FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Gillman, J Davila, J Sansgiry, S Parkinson-Windross, D Miertschin, N Mitts, B Henley, C Giordano, TP AF Gillman, Jason Davila, Jessica Sansgiry, Shubhada Parkinson-Windross, Diana Miertschin, Nancy Mitts, Beau Henley, Charles Giordano, Thomas P. TI The Effect of Conspiracy Beliefs and Trust on HIV Diagnosis, Linkage, and Retention in Young MSM with HIV SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE HIV/AIDS; adolescent; race/ethnicity; linkage to care; retention in care ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL ADHERENCE; CARE PROVIDERS; HIV/AIDS; ADOLESCENTS; PREVENTION; GOVERNMENT; INFECTION; BARRIER; ADULTS AB Conspiracy beliefs about HIV may result in delayed diagnosis, medication non-adherence, and low retention in care. The impact of such beliefs is not well described for minority youth. We assessed conspiracy beliefs, trust in physicians, and trust in the health care system in 47 HIV-infected, minority, adolescent men who have sex with men (MSM). We identified correlations of these factors with two intermediate outcomes (general self-efficacy and medication attitudes) and with three clinical outcomes (CD4 cell count at diagnosis, linkage to care, and retention in care). Greater conspiracy beliefs were associated with negative medication attitudes (r = -0.37, p = .01), while trust in physicians was correlated with positive medication attitudes (r = 0.42, p = .003). Neither conspiracy beliefs nor trust was correlated with self-efficacy, nor were they correlated with any of the three clinical outcomes. Conspiracy beliefs and lack of trust did not predict delayed diagnosis or poor linkage and retention in this population of young, minority MSM. C1 [Gillman, Jason] Baylor Univ, Methodist Hosp, Dept Med, Houston, TX 77030 USA. [Davila, Jessica; Sansgiry, Shubhada; Giordano, Thomas P.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Davila, Jessica; Sansgiry, Shubhada; Giordano, Thomas P.] Michael E DeBakey VA Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. [Parkinson-Windross, Diana; Miertschin, Nancy; Giordano, Thomas P.] Harris Cty Hosp Dist, Thomas St Hlth Ctr, Houston, TX USA. [Mitts, Beau] City Houston Dept Hlth & Human Serv, Houston, TX USA. [Henley, Charles] Harris Cty Publ Hlth & Environm Serv, Houston, TX USA. RP Giordano, TP (reprint author), Michael E DeBakey VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM tpg@bcm.tmc.edu FU PHS HHS [H97HA03786] NR 22 TC 5 Z9 5 U1 2 U2 10 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD FEB PY 2013 VL 24 IS 1 BP 36 EP 45 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 087AZ UT WOS:000314734900008 PM 23377715 ER PT J AU Kim, DS Burt, AA Crosslin, DR Robertson, PD Ranchalis, JE Boyko, EJ Nickerson, DA Furlong, CE Jarvik, GP AF Kim, Daniel S. Burt, Amber A. Crosslin, David R. Robertson, Peggy D. Ranchalis, Jane E. Boyko, Edward J. Nickerson, Deborah A. Furlong, Clement E. Jarvik, Gail P. TI Novel common and rare genetic determinants of paraoxonase activity: FTO, SERPINA12, and ITGAL SO JOURNAL OF LIPID RESEARCH LA English DT Article DE exome chip; atherosclerosis; diabetes ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; LOW-DENSITY-LIPOPROTEIN; GENOME-WIDE ASSOCIATION; CAROTID-ARTERY-DISEASE; SERUM PARAOXONASE; PARKINSONS-DISEASE; MISSING HERITABILITY; ADIPOSE-TISSUE; PON1 STATUS; CARDIOVASCULAR-DISEASE AB HDL-associated paraoxonase 1 (PON1) activity is associated with cardiovascular and other human diseases. As the role of genetic variants outside of the PON gene cluster on PON1 activity is unknown, we sought to identify common and rare variants in such loci. We typed 33,057 variants on the CVD chip in 1,362 subjects to test for their effects on adjusted-PON1 activity. Three novel genes (FTO, ITGAL, and SERPINA12) and the PON gene cluster had SNPs associated with PON1 arylesterase (AREase) activity. These loci were carried forward for rare-variant analysis using Exome chip genotypes in an overlapping subset of 1,051 subjects using sequence kernel association testing. PON1 (P = 2.24 x 10=(-4)), PON3 (P = 0.022), FTO (P = 0.019), and SERPINA12 (P = 0.039) had both common and rare variants associated with PON1 AREase. ITGAL variants were associated with PON1 activity when using weighted sequence kernel association testing (SKAT) analysis (P = 2.63 x 10(-3)). When adjusting for the initial common variants, SERPINA12 became marginally significant (P = 0.09), whereas all other findings remained significant (P < 0.05), suggesting independent rare-variant effects. We present novel findings that common and rare variants in FTO, SERPINA12, and ITGAL predict PON1 activity. These results further link PON1 to diabetes and inflammation and may inform the role of HDL in human disease.-Kim, D. S., A. A. Burt, D. R. Crosslin, P. D. Robertson, J. E. Ranchalis, E. J. Boyko, D. A. Nickerson, C. E. Furlong, and G. P. Jarvik. Novel common and rare genetic determinants of paraoxonase activity: FTO, SERPINA12, and ITGAL. J. Lipid Res. 2013. 54: 552-560. C1 [Kim, Daniel S.; Burt, Amber A.; Crosslin, David R.; Ranchalis, Jane E.; Furlong, Clement E.; Jarvik, Gail P.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Kim, Daniel S.; Crosslin, David R.; Robertson, Peggy D.; Nickerson, Deborah A.; Furlong, Clement E.; Jarvik, Gail P.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. RP Jarvik, GP (reprint author), Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. EM pair@u.washington.edu RI Jarvik, Gail/N-6476-2014 OI Jarvik, Gail/0000-0002-6710-8708; Boyko, Edward/0000-0002-3695-192X FU National Institutes of Health [RO1 HL-67406]; State of Washington Life Sciences Discovery Award; Sarnoff Cardiovascular Research Fellowship for Medical Students Award; Veteran Affairs Epidemiologic Research and Information Center Award [CSP 701S] FX This work was funded by National Institutes of Health Grant RO1 HL-67406 and a State of Washington Life Sciences Discovery Award to the Northwest Institute of Genetic Medicine. D.S.K. was supported in part by a Sarnoff Cardiovascular Research Fellowship for Medical Students Award. This work utilized resources of National Heart, Lung, and Blood Institute (NHLBI) Program for Genomic Applications, SeattleSNPs, Seattle, WA (http://pga.gs.washington.edu). Past work in this cohort and specifically E.J.B.'s involvement, was supported in part by resources from the VA Puget Sound Health Care System, Seattle, WA, including the Veteran Affairs Epidemiologic Research and Information Center Award CSP 701S. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. NR 75 TC 12 Z9 12 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD FEB PY 2013 VL 54 IS 2 BP 552 EP 560 DI 10.1194/jlr.P033266 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 088ZH UT WOS:000314876400026 PM 23160181 ER PT J AU Pessarakli, MM Phan, RT AF Pessarakli, M. M. Phan, R. T. TI Association between Methylenetetrahydrofolate Reductase (MTHFR) Gene Variants and Hyperhomocysteinemia in United States Veterans SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 USC, Keck Sch Med, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2013 VL 93 SU 1 MA 1853 BP 444A EP 445A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 087UL UT WOS:000314789302468 ER PT J AU Blue-Howells, JH Clark, SC van den Berk-Clark, C McGuire, JF AF Blue-Howells, Jessica H. Clark, Sean C. van den Berk-Clark, Carissa McGuire, James F. TI The US Department of Veterans Affairs Veterans Justice Programs and the Sequential Intercept Model: Case Examples in National Dissemination of Intervention for Justice-Involved Veterans SO PSYCHOLOGICAL SERVICES LA English DT Article DE veterans justice programs; criminal justice intervention; Sequential Intercept Model; community psychology; program implementation ID SUBSTANCE USE DISORDERS; SERIOUS MENTAL-ILLNESS AB Veterans are a significant subpopulation in criminal justice populations, comprising between 9% and 10% of arrestee, jail, prison, and community-supervision populations. In order to address the needs of justice-involved veterans, the U.S. Department of Veterans Affairs (VA) Veterans Justice Programs (VJP) offer services to veterans at multiple points in their involvement in the criminal justice system. Within the context of the VA's national mandate to develop VJP, this article presents best practice case examples using the Sequential Intercept Model as the intervention frame, and discusses each in context of a community psychology framework for innovation dissemination. The case examples demonstrate how central program guidance is adapted locally to meet the national mandate using strategies that fit the local environment, illustrating the innovations in action orientation, boundary spanning, and flexibility of organizations. This review provides examples of creative reinvention that expand on the mandate and work to meet local needs. To optimize services to veterans released from custody or supervised in the community, future study of the implementation of this national mandate should examine all VJP sites to identify the full range of best practices in local program implementation. C1 [Blue-Howells, Jessica H.; Clark, Sean C.; van den Berk-Clark, Carissa; McGuire, James F.] US Dept Vet Affairs, Vet Hlth Adm, Homeless Programs Off, Washington, DC USA. RP Blue-Howells, JH (reprint author), Hlth Care Reentry Vet Program, 11301 Wilshire Blvd,Mail Code W10H5, Los Angeles, CA 90073 USA. EM Jessica.Blue-Howells@va.gov OI van den Berk-Clark, Carissa/0000-0001-7712-3787 NR 21 TC 13 Z9 13 U1 2 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 J9 PSYCHOL SERV JI Psychol. Serv. PD FEB PY 2013 VL 10 IS 1 BP 48 EP 53 DI 10.1037/a0029652 PG 6 WC Psychology, Clinical SC Psychology GA 090TI UT WOS:000315002500005 PM 22924802 ER PT J AU Weaver, CM Joseph, D Dongon, SN Fairweather, A Ruzek, JI AF Weaver, Christopher M. Joseph, David Dongon, Shara N. Fairweather, Amy Ruzek, Josef I. TI Enhancing Services Response to Crisis Incidents Involving Veterans: A Role for Law Enforcement and Mental Health Collaboration SO PSYCHOLOGICAL SERVICES LA English DT Article DE veterans; offending; police; PTSD; crisis ID POSTTRAUMATIC-STRESS-DISORDER; POLICE OFFICERS; INTERVENTION; IRAQ; COMBAT; RISK; WAR; AGGRESSION; DIVERSION; HOSTILITY AB When crisis situations involving veterans occur, responding police officers find themselves playing an important role in the spectrum of health and mental health services for those veterans. Crisis response training can help officers respond in a manner that increases safety and optimizes outcomes for all people involved. Yet, current crisis response police training models are only accessible to select officers. Nor do they emphasize the unique challenges and strengths that impact veterans who experience acute symptoms of mental illness. In the current study, we report the results from the first generation of training, collaboratively designed to enhance officers' (a) knowledge of relevant topics, including posttraumatic stress disorder and traumatic brain injury, (b) attitudes about veterans, and (c) and skills helpful in identifying and deescalating veterans and referring them to treatment Officers completed in-class evaluations (N = 314), and a subsample (n = 53) completed 3-month follow-up evaluations. Pre- versus posttest comparisons indicated significant improvements in total score, and individually in knowledge, attitudes, and skills. Consistent with previous literature, the specific in-class gains were not retained on follow-up. However, responding officers widely endorsed use of de-escalation techniques during, and a positive impact of the training on, their interactions with veterans in the 3 months following the training. Implications for future training and policy are discussed. C1 [Weaver, Christopher M.; Dongon, Shara N.] Palo Alto Univ, Clin Psychol PhD Program, Palo Alto, CA 94143 USA. [Weaver, Christopher M.] Vet Affairs Palo Alto Hlth Care Syst, Natl Ctr Postraumat Stress Disorder, Palo Alto, CA USA. [Joseph, David] US Dept Vet Affairs, No Calif Hlth Care Syst, Oakland, CA USA. [Fairweather, Amy] Swords Plowshares, Coalit Iraq & Afghanistan Vet, San Francisco, CA USA. [Ruzek, Josef I.] Vet Affairs Palo Alto Hlth Care Syst, Natl Ctr PTSD, Palo Alto, CA USA. RP Weaver, CM (reprint author), Palo Alto Univ, Forens Psychol Program, 1791 Arastradero Rd, Palo Alto, CA 94143 USA. EM cweaver@paloaltou.edu NR 26 TC 0 Z9 0 U1 4 U2 20 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 J9 PSYCHOL SERV JI Psychol. Serv. PD FEB PY 2013 VL 10 IS 1 BP 66 EP 72 DI 10.1037/a0029651 PG 7 WC Psychology, Clinical SC Psychology GA 090TI UT WOS:000315002500007 PM 23088401 ER PT J AU Davies, TF AF Davies, Terry F. TI Is Thyroid Transplantation on the Distant Horizon? SO THYROID LA English DT Editorial Material ID PLURIPOTENT STEM-CELLS; DIFFERENTIATION; PRESERVATION; GENERATION; ORGANOIDS; MOUSE; GLAND C1 [Davies, Terry F.] Icahn Sch Med Mt Sinai, Dept Med, Thyroid Res Unit, New York, NY USA. [Davies, Terry F.] James J Peters Vet Adm Med Ctr, Dept Med, New York, NY USA. RP Davies, TF (reprint author), Mt Sinai Med Ctr, Box 1055,I Gustave L Levy Pl, New York, NY 10029 USA. EM terry.davies@mssm.edu FU NIDDK NIH HHS [DK080459, DK069713, DK052464] NR 17 TC 1 Z9 1 U1 0 U2 4 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 FEB PY 2013 VL 23 IS 2 BP 139 EP 141 DI 10.1089/thy.2013.2302.ed2 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 088WB UT WOS:000314867300004 PM 23398160 ER PT J AU Tsai, M Mori, AM Forsberg, CW Waiss, N Sporleder, JL Smith, NL Goldberg, J AF Tsai, Melyssa Mori, Alaina M. Forsberg, Christopher W. Waiss, Nicole Sporleder, Jennifer L. Smith, Nicholas L. Goldberg, Jack TI The Vietnam Era Twin Registry: A Quarter Century of Progress SO TWIN RESEARCH AND HUMAN GENETICS LA English DT Article DE twins; Veterans; Vietnam; aging; repository; epidemiology; genetics AB Now celebrating its 26th year of existence, the Vietnam Era Twin Registry continues to be one of the largest national samples of adult twins in the United States. The Registry twin member population is composed of 7,369 US male-male twin pair Veterans (14,738 total individuals) who served on active duty in the military during the Vietnam conflict (1964-1975). The Registry also maintains a register, data repository, and a biospecimen repository. Details on the operations of the Registry are described, as well as an overview of specific studies. Registry maintenance activities are also described, including the updating of contact information and vital status. Future plans include expanding the biospecimen repository and obtaining input from twins about study methods and diseases and conditions they would like to see investigated. C1 [Tsai, Melyssa; Mori, Alaina M.; Forsberg, Christopher W.; Waiss, Nicole; Sporleder, Jennifer L.; Smith, Nicholas L.; Goldberg, Jack] Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, VET Registry, Seattle, WA USA. [Smith, Nicholas L.; Goldberg, Jack] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Smith, Nicholas L.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA. RP Mori, AM (reprint author), VA Puget Sound Hlth Care Syst, VET Registry, VA MS S-152-E,1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM Alaina.Mori@va.gov FU Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs; National Institutes of Health [DA14363, DA014363, MH60426, AA11667, AA016402, AG018386, AG022381, AA010586, AG18384, MH054636, MH055704, AA010339, AA11822, DA04604, DA009447, HL068630, HL078224, AG022982]; VA Merit Review funding; VA Cooperative Studies [256, 569]; Seattle Epidemiologic Research and Information Center; Medical College of Pennsylvania FX The Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. All statements, opinions, or views are solely of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States Government.; The authors acknowledge the work of the following people: (1) VET Registry staff; (2) Current and past VET Registry Scientific Ethics and Oversight Committee members: J. C. Breitner, MD, MPH; E. F. Coccaro, MD; T. Colton, ScD, MS; P. Concannon, PhD; J. Harris, PhD; W. E. Nance, MD, PhD; W. True, PhD, MPH; J. S. Dorman, PhD; R. S. Paffenbarger, Jr., MD, PhD; M. M. Weissman, PhD; R. R. Williams, MD; G. Chase, PhD; and A. Bearn, MD; and (3) the many research investigators who have helped expand the VET Registry repositories. In particular, we want to acknowledge DA14363, DA014363, MH60426, AA11667, AA016402, AG018386, AG022381, AA010586, AG18384, MH054636, MH055704, AA010339, AA11822, DA04604, DA009447, HL068630, HL078224, AG022982 from the National Institutes of Health; VA Merit Review funding awarded to Drs J. Douglas Bremner, Mark Gilbertson, and Theodore Jacob; VA Cooperative Studies funding of protocols #256 and #569, and core funding for the Seattle Epidemiologic Research and Information Center; and Medical College of Pennsylvania funding awarded Dr Emil F. Coccaro. NR 9 TC 5 Z9 5 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1832-4274 J9 TWIN RES HUM GENET JI Twin Res. Hum. Genet. PD FEB PY 2013 VL 16 IS 1 BP 429 EP 436 DI 10.1017/thg.2012.122 PG 8 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 087YD UT WOS:000314799700064 PM 23177374 ER PT J AU Graff, JN Drake, CG Beer, TM AF Graff, Julie N. Drake, Charles G. Beer, Tomasz M. TI Complete Biochemical (Prostate-specific Antigen) Response to Sipuleucel-T With Enzalutamide in Castration-resistant Prostate Cancer: A Case Report With Implications for Future Research SO UROLOGY LA English DT Article ID COMBINATION THERAPY; CELL INFILTRATION; IMMUNOTHERAPY; MITOXANTRONE; PREDNISONE; DOCETAXEL; VACCINE AB OBJECTIVE To describe the case of a patient with castration-resistant, metastatic prostate cancer who achieved a complete and durable biochemical response after treatment with sipuleucel-T while continuing with enzalutamide and to explore the immunologic basis for such a response. MATERIALS AND METHODS We obtained serial prostate-specific antigen (PSA) measurements and bone scans to assess the patient's response to enzalutamide followed by the addition of sipuleucel-T. Using preclinical and clinical data, we describe his response through known immunobiologic mechanisms. RESULTS This patient's PSA level became undetectable during treatment with enzalutamide and began to increase again after 14 months. He opted for treatment with sipuleucel-T, while continuing with the enzalutamide. This resulted in another complete PSA response 6 months after exposure to sipuleucel-T. CONCLUSION Sipuleucel-T typically does not produce significant PSA reductions, and, to the best of our knowledge, only 1 previous report of a durable complete PSA response in a patient with metastatic disease has been published. The timing of this response supports an immune mechanism. The biologic rationale for the combination, coupled with the clinical result observed in our patient, provides a basis for studies of the combination of sipuleucel-T and enzalutamide. UROLOGY 81: 381-383, 2013. Published by Elsevier Inc. C1 [Graff, Julie N.] Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Dept Oncol, Baltimore, MD USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Dept Urol, Baltimore, MD USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Dept Immunol, Baltimore, MD USA. RP Graff, JN (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,MC P3CHEMO, Portland, OR 97239 USA. EM graffj@ohsu.edu FU Dendreon, the maker of sipuleucel-T FX T. M. Beer is a consultant to and receives funding from Dendreon, the maker of sipuleucel-T; C. G. Drake is a consultant to Dendreon. NR 14 TC 12 Z9 12 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD FEB PY 2013 VL 81 IS 2 BP 381 EP 383 DI 10.1016/j.urology.2012.10.044 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 086LT UT WOS:000314686000056 PM 23374810 ER PT J AU O'Neil, ML Beckwith, LE Kincaid, CL Rasmussen, DD AF O'Neil, Meghan L. Beckwith, Lauren E. Kincaid, Carrie L. Rasmussen, Dennis D. TI The 1-Adrenergic Receptor Antagonist, Doxazosin, Reduces Alcohol Drinking in Alcohol-Preferring (P) Rats SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Noradrenergic; Doxazosin; Alcohol; Alcohol-Preferring; P Rats ID POSITIVE REINFORCING PROPERTIES; DOPAMINE-BETA-HYDROXYLASE; ALPHA-1-ADRENOCEPTOR ANTAGONIST; NORADRENERGIC MEDIATION; STARTLE RESPONSE; LABORATORY RATS; DEPENDENCE; PRAZOSIN; NEURONS; ETHANOL AB Background Evidence supports a role for the noradrenergic system in alcohol drinking in animals and humans. Our previous studies demonstrated the efficacy of prazosin, an 1-adrenergic antagonist, in decreasing alcohol drinking in rat models of alcohol dependence. Prazosin has also been shown to decrease alcohol drinking in treatment-seeking alcohol-dependent men. Clinically, the use of prazosin is limited by the requirement for multiple daily administrations, whereas doxazosin, a structurally similar 1-adrenergic antagonist, requires only once-daily dosing. In this study, we tested the hypothesis that doxazosin, like prazosin, would decrease alcohol drinking in rats selectively bred for alcohol preference (P line). Methods Adult male P rats were given 2h/d scheduled access to a 2-bottle choice (15% v/v alcohol vs. water) session 5d/wk (MF), with food and water available ad libitum 24h/d. Rats were injected with doxazosin (0 to 10mg/kg, IP) 40minutes prior to initiation of the alcohol access session in 3 trials (of 3, 5, and 5 consecutive days) each separated by 5 to 8weeks. The third trial included 1day without alcohol access (for locomotor testing), and 1day of a single hour of alcohol access (for plasma alcohol determination). Results Doxazosin significantly reduced alcohol intake in all 3 trials. The 5mg/kg dose consistently reduced alcohol intake, increased water drinking, did not affect locomotor activity, and resulted in lower plasma alcohol concentrations, suggesting that the doxazosin-induced reduction in alcohol drinking was not dependent on a motor impairment or an alteration in alcohol clearance. Conclusions Doxazosin decreases voluntary alcohol consumption by male alcohol-preferring (P) rats, supporting a role for the noradrenergic system in alcohol drinking in P rats and suggesting that doxazosin could potentially be an effective once-daily pharmacotherapeutic agent for the treatment of alcohol use disorders. C1 [O'Neil, Meghan L.; Beckwith, Lauren E.; Kincaid, Carrie L.; Rasmussen, Dennis D.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [O'Neil, Meghan L.; Beckwith, Lauren E.; Kincaid, Carrie L.; Rasmussen, Dennis D.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Rasmussen, Dennis D.] VISN 20 Mental Illness Res, Educ & Clin Ctr, Seattle, WA USA. RP Rasmussen, DD (reprint author), VA Puget Sound Hlth Care Syst, Med Ctr, MIRECC 116, 1660 S Columbian Way, Seattle, WA 98108 USA. EM drasmuss@u.washington.edu FU NIH [P20 AA017839, R24 AA015512] FX This material is based upon work supported in part by resources from the VA Puget Sound Health Care System, Seattle, Washington, and by NIH Grant P20 AA017839. P rats were provided by the Indiana Alcohol Research Resource Center, supported by NIH Grant R24 AA015512. NR 48 TC 11 Z9 11 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2013 VL 37 IS 2 BP 202 EP 212 DI 10.1111/j.1530-0277.2012.01884.x PG 11 WC Substance Abuse SC Substance Abuse GA 083ON UT WOS:000314474400005 PM 22758213 ER PT J AU Rice, IM Pohlig, RT Gallagher, JD Boninger, ML AF Rice, Ian M. Pohlig, Ryan T. Gallagher, Jerri D. Boninger, Michael. L. TI Handrim Wheelchair Propulsion Training Effect on Overground Propulsion Using Biomechanical Real-Time Visual Feedback SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT Washington University Program in Occupational Therapy CY JUL 06, 2010 CL St Louis, MO DE Biomechanics; Feedback; Kinetics; Rehabilitation; Wheelchairs ID SPINAL-CORD-INJURY; CARPAL-TUNNEL SYNDROME; UPPER EXTREMITY; MECHANICAL EFFICIENCY; PUSHRIM BIOMECHANICS; PARAPLEGIC PATIENTS; EXTERNAL-FOCUS; AXLE POSITION; SHOULDER PAIN; 2 SPEEDS AB Objective: To compare the effects of 2 manual wheelchair propulsion training programs on handrim kinetics, contact angle, and stroke frequency collected during overground propulsion. Design: Randomized controlled trial comparing handrim kinetics between 3 groups: a control group that received no training, an instruction-only group that reviewed a multimedia presentation, and a feedback group that reviewed the multimedia presentation and real-time visual feedback. Setting: Research laboratory. Participants: Full-time manual wheelchair users (N=27) with spinal cord injury living in the Pittsburgh area. Interventions: Propulsion training was given 3 times over 3 weeks, and data were collected at baseline, immediately after training, and at 3 months. Main Outcome Measures: Contact angle, stroke frequency, peak resultant force, and peak rate of rise of resultant force. Results: Both feedback and instruction-only groups improved their propulsion biomechanics across all surfaces (carpet, tile, and ramp) at both target and self-selected speeds compared with the control group. While controlling for velocity, both intervention groups showed long-term reductions in the peak rate or rise of resultant force, stroke frequency, and increased contact angle. Conclusions: Long-term wheelchair users in both intervention groups significantly improved many aspects of their propulsion technique immediately after training and 3 months from baseline. Furthermore, training with a low-cost instructional video and slide presentation was an effective training tool alone. Archives of Physical Medicine and Rehabilitation 2013;94:256-63 (C) 2013 by the American Congress of Rehabilitation Medicine C1 [Rice, Ian M.] Univ Illinois, Dept Kinesiol & Community Hlth, Champaign, IL 61820 USA. [Pohlig, Ryan T.; Gallagher, Jerri D.] Univ Pittsburgh, Dept Educ Psychol, Pittsburgh, PA USA. [Boninger, Michael. L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs, Pittsburgh, PA USA. [Boninger, Michael. L.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Boninger, Michael. L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Boninger, Michael. L.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. RP Rice, IM (reprint author), Univ Illinois, Coll Appl Hlth Sci, Dept Kinesiol & Community Hlth, Huff Hall,1206 S 4th St, Champaign, IL 61820 USA. EM ianrice@illinois.edu OI Boninger, Michael/0000-0001-6966-919X FU NICHD NIH HHS [1-R03-HD049735-01A1] NR 45 TC 10 Z9 10 U1 2 U2 17 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD FEB PY 2013 VL 94 IS 2 BP 256 EP 263 DI 10.1016/j.apmr.2012.09.014 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 084TZ UT WOS:000314563300005 PM 23022092 ER PT J AU Mitchell, T Chacko, B Ballinger, SW Bailey, SM Zhang, JH Darley-Usmar, V AF Mitchell, Tanecia Chacko, Balu Ballinger, Scott W. Bailey, Shannon M. Zhang, Jianhua Darley-Usmar, Victor TI Convergent mechanisms for dysregulation of mitochondrial quality control in metabolic disease: implications for mitochondrial therapeutics SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article DE alcoholic liver disease; cellular bioenergetics; diabetes; metabolic syndrome; mitochondria; mitoquinone (MitoQ); reserve respiratory capacity; steatosis ID ALCOHOLIC LIVER-DISEASE; ANTIOXIDANT MITOQ PROTECTS; HEPATOCELLULAR-CARCINOMA; REACTIVE OXYGEN; NITRIC-OXIDE; RAT-LIVER; DEPENDENT HEPATOTOXICITY; SIGNAL-TRANSDUCTION; OXIDATIVE STRESS; RISK-FACTORS AB Mitochondrial dysfunction is associated with a broad range of pathologies including diabetes, ethanol toxicity, metabolic syndrome and cardiac failure. It is now becoming clear that maintaining mitochondrial quality through a balance between biogenesis, reserve capacity and mitophagy is critical in determining the response to metabolic or xenobiotic stress. In diseases associated with metabolic stress, such as Type II diabetes and non-alcoholic and alcoholic steatosis, the mitochondria are subjected to multiple 'hits' such as hypoxia and oxidative and nitrative stress, which can overwhelm the mitochondrial quality control pathways. In addition, the underlying mitochondrial genetics that evolved to accommodate high-energy demand, low-calorie supply environments may now be maladapted to modern lifestyles (low-energy demand, high-calorie environments). The pro-oxidant and pro-inflammatory environment of a sedentary western lifestyle has been associated with modified redox cell signalling pathways such as steatosis, hypoxic signalling, inflammation and fibrosis. These data suggest that loss of mitochondrial quality control is intimately associated with the aberrant activation of redox cell signalling pathways under pathological conditions. In the present short review, we discuss evidence from alcoholic liver disease supporting this concept, the insights obtained from experimental models and the application of bioenergetic-based therapeutics in the context of maintaining mitochondrial quality. C1 [Mitchell, Tanecia; Chacko, Balu; Ballinger, Scott W.; Bailey, Shannon M.; Zhang, Jianhua; Darley-Usmar, Victor] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Mitchell, Tanecia; Chacko, Balu; Ballinger, Scott W.; Bailey, Shannon M.; Zhang, Jianhua; Darley-Usmar, Victor] Univ Alabama Birmingham, Ctr Free Radical Biol, Birmingham, AL 35294 USA. [Zhang, Jianhua] Univ Alabama Birmingham, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Darley-Usmar, V (reprint author), Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. EM darley@uab.edu FU National Institutes of Health [T32 DK007545, HL 94518, HL 103859, DK073775, AA015172, AA018841, NS064090, AA13395]; VA merit award FX This work was supported by National Institutes of Health [grant numbers T32 DK007545 (to T. M.), HL 94518 and HL 103859 (to S. B.), DK073775, AA015172 and AA018841 (to S. B.), NS064090 (to J.Z.), and AA13395 (to V.D.-U.)]. J.Z. was supported, in part, by a VA merit award. NR 61 TC 23 Z9 24 U1 2 U2 10 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD FEB PY 2013 VL 41 BP 127 EP 133 DI 10.1042/BST20120231 PN 1 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 080EB UT WOS:000314222900020 PM 23356271 ER PT J AU Lill, M Costa, LJ Yeh, RF Lim, S Stuart, R Waller, EK Shore, T Craig, M Freytes, CO Shea, TC Rodriguez, TE Flinn, IW Comeau, T Yeager, AM Pulsipher, MA Bence-Bruckler, I Laneuville, P Bierman, PJ Chen, AI Yu, LH Patil, S Sun, YP Armstrong, E Smith, A Elekes, A Kato, K Vaughan, W AF Lill, Michael Costa, Luciano J. Yeh, Rosa F. Lim, Stephen Stuart, Robert Waller, Edmund K. Shore, Tsiporah Craig, Michael Freytes, Cesar O. Shea, Thomas C. Rodriguez, Tulio E. Flinn, Ian W. Comeau, Terrance Yeager, Andrew M. Pulsipher, Michael A. Bence-Bruckler, Isabelle Laneuville, Pierre Bierman, Philip J. Chen, Andy I. Yu, Louie H. Patil, Shiva Sun, Yiping Armstrong, Elizabeth Smith, Angela Elekes, Agnes Kato, Kazunobu Vaughan, William TI Pharmacokinetic-Directed Dose Adjustment Is Essential for Intravenous Busulfan Exposure Optimization: Findings From a Multi-Center Phase II Study of Autologous Hematopoietic Stem Cell Transplantation for Lymphoma in North America SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Lill, Michael; Lim, Stephen] Cedars Sinai Med Ctr, Blood & Marrow Transplant Program, Los Angeles, CA 90048 USA. [Costa, Luciano J.; Stuart, Robert] Med Univ S Carolina, Charleston, SC 29425 USA. [Yeh, Rosa F.; Yu, Louie H.] Seattle Canc Care Alliance, Seattle, WA USA. [Waller, Edmund K.] Emory Univ, Bone Marrow & Stem Cell Transplant Program, Atlanta, GA 30322 USA. [Shore, Tsiporah] Cornell Univ, Weill Med Coll, Bone Marrow & Stem Cell Transplantat Program, New York, NY 10021 USA. [Shore, Tsiporah] New York Presbyterian Hosp, New York, NY USA. [Craig, Michael] W Virginia Univ, Osborn Heme Malignancy & Transplant Serv, Morgantown, WV 26506 USA. [Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, Hematopoiet Stem Cell Transplant Program, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Shea, Thomas C.] Univ N Carolina, Dept Med, UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. [Rodriguez, Tulio E.] Loyola Univ, Chicago Med Ctr, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. [Flinn, Ian W.] Sarah Cannon Sarah Cannon Res Inst, Nashville, TN USA. [Comeau, Terrance] New Brunswick Stem Cell Transplant Program, St John, NB, Canada. [Yeager, Andrew M.] Blood & Marrow Transplantat Program, Tucson, AZ USA. [Pulsipher, Michael A.] Univ Utah, Sch Med, Huntsman Canc Inst, Div Hematol & Hematol Malignancies,Primary Childr, Salt Lake City, UT USA. [Bence-Bruckler, Isabelle] Univ Ottawa, Ottawa Hosp, Ottawa, ON, Canada. [Laneuville, Pierre] McGill Univ, Royal Victoria Hosp, Ctr Hlth, Montreal, PQ H3A 1A1, Canada. [Bierman, Philip J.] Univ Nebraska Med Ctr, Dept Internal Med, BMT, Omaha, NE USA. [Chen, Andy I.] Oregon Hlth & Sci, Hematol Malignancies, Portland, OR USA. [Patil, Shiva; Sun, Yiping; Armstrong, Elizabeth; Smith, Angela; Elekes, Agnes; Kato, Kazunobu] Otsuka Pharmaceutical Dev & Commercializat Inc, Princeton, NJ USA. [Vaughan, William] Univ Alabama Birmingham, Bone Marrow Transplantat Program, Birmingham, AL USA. NR 0 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 41 BP S132 EP S132 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900042 ER PT J AU Ratanatharathorn, V Stadtmauer, EA Yeh, RF Freytes, CO Toro, JJ Akpek, G Sahovic, E Tricot, GJ Shaughnessy, PJ White, DJ Rodriguez, TE Solomon, SR Yu, LH Patil, S Sun, YP Armstrong, E Smith, A Elekes, A Kato, K Reece, DE AF Ratanatharathorn, Voravit Stadtmauer, Edward A. Yeh, Rosa F. Freytes, Cesar O. Toro, Juan J. Akpek, Gorgun Sahovic, Entezam Tricot, Guido J. Shaughnessy, Paul J. White, Darrell J. Rodriguez, Tulio E. Solomon, Scott R. Yu, Louie H. Patil, Shiva Sun, Yiping Armstrong, Elizabeth Smith, Angela Elekes, Agnes Kato, Kazunobu Reece, Donna E. TI Safety and Efficacy From Intravenous Busulfan with PLC-Directed Dosed Adjustment and Bortezomib Conditioning Regimen in Relapsed Multiple Myeloma Patients Undergoing a Second Autologous Hematopoietic Stem Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Ratanatharathorn, Voravit] Karmanos Canc Inst, Detroit, MI USA. [Stadtmauer, Edward A.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Yeh, Rosa F.; Yu, Louie H.] Seattle Canc Care Alliance, Seattle, WA USA. [Freytes, Cesar O.; Toro, Juan J.] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Akpek, Gorgun] Univ Maryland, Med Ctr, Med Greenebaum Canc Ctr BMT, Baltimore, MD 21201 USA. [Sahovic, Entezam] Western Pennsylvania Canc Inst, Pittsburgh, PA USA. [Tricot, Guido J.] Univ Utah, Sch Med, Div Hematol, BMT & Myeloma Program, Salt Lake City, UT USA. [Shaughnessy, Paul J.] Texas Transplant Inst, San Antonio, TX USA. [White, Darrell J.] Queen Elizabeth 2 Hlth Sci Ctr, Dept Med, Div Hematol, Halifax, NS, Canada. [White, Darrell J.] Dalhousie Univ, Halifax, NS B3H 3J5, Canada. [Rodriguez, Tulio E.] Loyola Univ Chicago, Med Ctr, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. [Solomon, Scott R.] Northside Hosp, Blood & Marrow Transplant Program, Atlanta, GA USA. [Patil, Shiva; Sun, Yiping; Armstrong, Elizabeth; Smith, Angela; Elekes, Agnes; Kato, Kazunobu] Otsuka Pharmaceut Dev & Commercializat Inc, Princeton, NJ USA. [Reece, Donna E.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 146 BP S186 EP S187 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900146 ER PT J AU Toro, JJ Schneider, D Lee, S Smith, GM Gushiken, F Haile, DJ Freytes, CO AF Toro, Juan J. Schneider, Deanna Lee, Shuko Smith, Gregory M. Gushiken, Francisco Haile, David J. Freytes, Cesar O. TI Is Edentulism Associated with Lower Bacteremia and Transplant-Associated Toxicities in Patients with Multiple Myeloma? SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 13-17, 2013 CL Salt Lake City, UT C1 [Toro, Juan J.; Schneider, Deanna; Lee, Shuko; Smith, Gregory M.; Gushiken, Francisco; Haile, David J.; Freytes, Cesar O.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 SU 2 MA 322 BP S272 EP S272 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DC UT WOS:000314441900320 ER PT J AU Mascaux, C Feser, WJ Lewis, MT Baron, AE Coldren, CD Merrick, DT Kennedy, TC Eckelberger, JI Rozeboom, LM Franklin, WA Minna, JD Bunn, PA Miller, YE Keith, RL Hirsch, FR AF Mascaux, Celine Feser, William J. Lewis, Marina T. Baron, Anna E. Coldren, Christopher D. Merrick, Daniel T. Kennedy, Timothy C. Eckelberger, John I. Rozeboom, Leslie M. Franklin, Wilbur A. Minna, John D. Bunn, Paul A. Miller, York E. Keith, Robert L. Hirsch, Fred R. TI Endobronchial miRNAs as Biomarkers in Lung Cancer Chemoprevention SO CANCER PREVENTION RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; MICRORNA EXPRESSION; DNA HYPERMETHYLATION; COLORECTAL-CANCER; GENE-EXPRESSION; CIGARETTE-SMOKE; CARCINOGENESIS; ADENOCARCINOMA; METHYLATION; METASTASIS AB Lung cancers express lower levels of prostacyclin than normal lung tissues. Prostacyclin prevents lung cancer in a variety of mouse models. A randomized phase II trial comparing oral iloprost (a prostacyclin analog) with placebo in high-risk subjects showed improvement in bronchial histology in former, but not current, smokers. This placebo-controlled study offered the opportunity for investigation of other potential intermediate endpoint and predictive biomarkers to incorporate into chemoprevention trials. Matched bronchial biopsies were obtained at baseline and at 6-month follow-up from 125 high-risk individuals who completed the trial: 31/29 and 37/28 current/former smokers in the iloprost and placebo arm, respectively. We analyzed the expression of 14 selected miRNAs by Real Time PCR in 496 biopsies. The expression of seven miRNAs was significantly correlated with histology at baseline. The expression of miR-34c was inversely correlated with histology at baseline (P < 0.0001) and with change in histology at follow-up (P = 0.0003), independent of treatment or smoking status. Several miRNAs were also found to be differentially expressed in current smokers as compared with former smokers. In current smokers, miR-375 was upregulated at baseline (P < 0.0001) and downregulated after treatment with iloprost (P = 0.0023). No miRNA at baseline reliably predicted a response to iloprost. No biomarker predictive of response to iloprost was found. MiR-34c was inversely correlated with baseline histology and with histology changes. Mir-34c changes at follow-up could be used as a quantitative biomarker that parallels histologic response in formalin-fixed bronchial biopsies in future lung cancer chemoprevention studies. Cancer Prev Res; 6(2); 100-8. (C)2012 AACR. C1 [Mascaux, Celine; Eckelberger, John I.; Rozeboom, Leslie M.; Bunn, Paul A.; Hirsch, Fred R.] Colorado Sch Publ Hlth, Dept Med, Div Med Oncol, Aurora, CO USA. [Feser, William J.] Colorado Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO USA. [Lewis, Marina T.; Baron, Anna E.; Merrick, Daniel T.; Franklin, Wilbur A.; Hirsch, Fred R.] Colorado Sch Publ Hlth, Dept Pathol, Aurora, CO USA. [Coldren, Christopher D.; Kennedy, Timothy C.; Miller, York E.; Keith, Robert L.] Colorado Sch Publ Hlth, Div Pulm Sci & Crit Care Med, Aurora, CO USA. Univ Colorado, Sch Med, Aurora, CO USA. [Merrick, Daniel T.; Miller, York E.; Keith, Robert L.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Coldren, Christopher D.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Minna, John D.] Univ Texas SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dept Internal Med, Dallas, TX USA. [Minna, John D.] Univ Texas SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dept Pharmacol, Dallas, TX USA. RP Mascaux, C (reprint author), Univ Colorado Denver, Div Med Oncol, 12801 E 17th Ave,Mail Stop 8177, Aurora, CO 80045 USA. EM celinejmmascaux@gmail.com FU Specialized Program of Research Excellence (SPORE) Career Development Award; Lung Cancer Biomarkers and Chemoprevention Consortium (LCBCC); International Association for the Study of Lung Cancer (IASLC); Louisiana Chapter of the National Lung Cancer Partnership (NLCP); Gary L. and Thelissa Zollinger Early Detection of Lung Cancer Endowment Fund; Colorado SPORE in Lung Cancer [NCI P50 CA58187, NCI RO1 CA164780]; Texas SPORE in Lung Cancer [P50 CA070907]; Department of Veterans Affairs Merit Review Program FX This work was financially supported by a Specialized Program of Research Excellence (SPORE) Career Development Award (C. Mascaux) and by Lung Cancer Biomarkers and Chemoprevention Consortium (LCBCC) funds (C. Mascaux and F.R. Hirsch). C. Mascaux was also supported by a fellowship from the International Association for the Study of Lung Cancer (IASLC), a grant from the Louisiana Chapter of the National Lung Cancer Partnership (NLCP), and a grant from the Gary L. and Thelissa Zollinger Early Detection of Lung Cancer Endowment Fund. Additional support was provided from the Colorado SPORE in Lung Cancer NCI P50 CA58187, NCI RO1 CA164780, Texas SPORE in Lung Cancer (P50 CA070907), Department of Veterans Affairs Merit Review Program (to R.L. Keith). NR 36 TC 6 Z9 6 U1 0 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD FEB PY 2013 VL 6 IS 2 BP 100 EP 108 DI 10.1158/1940-6207.CAPR-12-0382 PG 9 WC Oncology SC Oncology GA 086IF UT WOS:000314676600005 PM 23268837 ER PT J AU Heinz, AJ Peters, EN Boden, MT Bonn-Miller, MO AF Heinz, Adrienne J. Peters, Erica N. Boden, Matthew T. Bonn-Miller, Marcel O. TI A Comprehensive Examination of Delay Discounting in a Clinical Sample of Cannabis-Dependent Military Veterans Making a Self-Guided Quit Attempt SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE marijuana; Cannabis; cessation; delay discounting; impulsivity; relapse ID ADULTS SEEKING TREATMENT; SUBSTANCE-USE DISORDERS; ALCOHOL-USE DISORDERS; TIMELINE FOLLOW-BACK; MARIJUANA USE; BEHAVIORAL ECONOMICS; TREATMENT SEEKERS; MONEY MANAGEMENT; DRUG-DEPENDENCE; REPORTED USE AB Delay discounting (DD), an index of impulsivity, reflects individuals' preference for smaller immediate rewards to larger delayed rewards. The current study examined (a) relations between DD and quantity, frequency, and severity of Cannabis use, as well as several other measures of co-occurring substance use and clinical severity, and (b) whether DD predicted Cannabis-cessation outcomes. Cannabis-dependent United States (U. S.) veterans (N = 72; 95% male) who were interested in making serious self-quit attempts were evaluated prior to their cessation attempts, during which they completed a computerized DD task, and were followed throughout six months postattempt. Results indicated that higher DD was significantly correlated with higher compulsive craving for Cannabis (rho = .29, p < .05), younger age of first Cannabis use (r = -.32, p < .01), earlier commencement of regular Cannabis smoking (r = -.25, p < .05), and seeking professional help for a previous Cannabis quit attempt (rho = -.27, p < .05). DD did not significantly predict any Cannabis-cessation outcomes in the first week postattempt or during the 6-month follow-up. These results add to the literature on DD, which has focused on users of tobacco, alcohol, opioids, and cocaine, by demonstrating that DD is sensitive to developmental trajectories of Cannabis dependence, but does not reliably predict cessation outcomes. Results also suggest that DD may carry less relevance for Cannabis than for other substances of abuse. C1 [Heinz, Adrienne J.; Boden, Matthew T.; Bonn-Miller, Marcel O.] Vet Affairs Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Palo Alto, CA USA. [Heinz, Adrienne J.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Peters, Erica N.] Friends Res Inst, Baltimore, MD USA. [Peters, Erica N.] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Bonn-Miller, Marcel O.] Vet Affairs Palo Alto Hlth Care Syst, Natl Ctr Posttraumat Stress Disorder, Palo Alto, CA USA. [Bonn-Miller, Marcel O.] Philadelphia Vet Affairs Med Ctr, Ctr Excellence Subst Abuse Treatment & Educ, Philadelphia, PA USA. RP Heinz, AJ (reprint author), 795 Willow Rd,MPD 152, Menlo Pk, CA 94025 USA. EM aheinz@stanford.edu FU United States Department Veterans Affairs (VA); VA Health Services Research and Development Service funds FX Support for this research was provided by a United States Department Veterans Affairs (VA) Clinical Science Research and Development Career Development Award, Level 2, granted to Dr. Bonn-Miller, and VA Health Services Research and Development Service funds were provided to Dr. Heinz. These funding sources played no roles other than financial support. The expressed views do not necessarily represent those of the VA. The authors thank Neha Mitragotri, Johnna Medina, Meggan Bucossi, Nicole Short, and Jessica Galang for their assistance with data collection and management. All authors contributed in a significant way to the manuscript and all authors have read and approved the final manuscript. NR 91 TC 13 Z9 13 U1 6 U2 27 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 EI 1936-2293 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD FEB PY 2013 VL 21 IS 1 BP 55 EP 65 DI 10.1037/a0031192 PG 11 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 084KG UT WOS:000314537400007 PM 23379614 ER PT J AU Furuya, H Wada, M Shimizu, Y Yamada, PM Hannun, YA Obeid, LM Kawamori, T AF Furuya, Hideki Wada, Masayuki Shimizu, Yoshiko Yamada, Paulette M. Hannun, Yusuf A. Obeid, Lina M. Kawamori, Toshihiko TI Effect of sphingosine kinase 1 inhibition on blood pressure SO FASEB JOURNAL LA English DT Article DE sphingolipids; cardiovascular functions; chemoprevention; prostacyclin; COX-2; mPGES-1 ID PROSTAGLANDIN-E SYNTHASE-1; II-INDUCED HYPERTENSION; ANGIOTENSIN-II; CYCLOOXYGENASE-2 INHIBITOR; COLON CARCINOGENESIS; OXIDATIVE STRESS; ENDOTHELIAL-CELLS; E-2 PROTECTS; TNF-ALPHA; 1-PHOSPHATE AB Accumulating evidence suggests that sphingosine kinase 1 (SphK1) plays a key role in carcinogenesis by regulating cyclooxygenase-2 (COX-2) expression. Recent clinical studies have revealed that COX-2 inhibitors cause adverse cardiovascular side effects, likely due to inhibition of prostacyclin (PGI(2)). In this work, we investigated the roles of SphK1 inhibition on blood pressure (BP). The results show that lack of SphK1 expression did not exacerbate angiotensin II (Ang II)-induced acute hypertension, whereas celecoxib, a COX-2 inhibitor, augmented and sustained higher BP in mice. Interestingly, SphK1-knockout mice inhibited prostaglandin E-2 (PGE(2)) but not PGI(2) production in response to Ang II, whereas celecoxib blocked both PGE(2) and PGI(2) production. Mechanistically, SphK1 down-regulation by siRNA in human umbilical vein endothelial cells decreased cytokine-induced PGE(2) production primarily through inhibition of microsomal PGE synthase-1 (mPGES-1), not COX-2. SphK1 downregulation also decreased MKK6 expression, which phosphorylates and activates P38 MAPK, which, in turn, regulates early growth response-1 (Egr-1), a transcription factor of mPGES-1. Together, these data indicate that SphK1 regulates PGE(2) production by mPGES-1 expression via the p38 MAPK pathway, independent of COX-2 signaling, in endothelial cells, suggesting that SphK1 inhibition may be a promising strategy for cancer chemoprevention with lack of the adverse cardiovascular side effects associated with coxibs.-Furuya, H., Wada, M., Shimizu, Y., Yamada, P. M., Hannun, Y. A., Obeid, L. M., Kawamori, T. Effect of sphingosine kinase 1 inhibition on blood pressure. FASEB J. 27, 656-664 (2013). www.fasebj.org C1 [Furuya, Hideki; Shimizu, Yoshiko; Yamada, Paulette M.; Kawamori, Toshihiko] Univ Hawaii, Ctr Canc, Honolulu, HI 96813 USA. [Furuya, Hideki; Wada, Masayuki; Kawamori, Toshihiko] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Hannun, Yusuf A.; Obeid, Lina M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Obeid, Lina M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Shimizu, Yoshiko; Kawamori, Toshihiko] Univ Hawaii Manoa, Dept Mol Biosci & Bioengn, Honolulu, HI 96822 USA. [Obeid, Lina M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Kawamori, T (reprint author), Univ Hawaii, Ctr Canc, 651 Ilalo St,BSB 222H, Honolulu, HI 96813 USA. EM kawamori@cc.hawaii.edu OI obeid, lina/0000-0002-0734-0847 FU U.S. National Institutes of Health (NIH) [R01CA124687, P20RR17677, P01CA97132]; Hollings Cancer Center, MUSC; NIH Extramural Research Facilities Program of the National Center for Research Resources [C06RR015455] FX The authors thank the Lipidomics Core Facility and Animal Carcinogenesis Core, Hollings Cancer Center, Medical University of South Carolina (MUSC), and Animal Carcinogenesis Shared Resource, University of Hawaii Cancer Center. This work was supported by U.S. National Institutes of Health (NIH) grants (R01CA124687 and P20RR17677 to T. K., P01CA97132 to T. K., Y.A.H., and L.M.O.) and a seed grant to T. K. from the Hollings Cancer Center, MUSC. This work was conducted in a facility constructed with support from the NIH Extramural Research Facilities Program of the National Center for Research Resources (C06RR015455). NR 52 TC 9 Z9 9 U1 0 U2 4 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 FEB PY 2013 VL 27 IS 2 BP 656 EP 664 DI 10.1096/fj.12-219014 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 081YG UT WOS:000314358000024 PM 23109673 ER PT J AU Ho, L Ferruzzi, MG Janle, EM Wang, J Gong, B Chen, TY Lobo, J Cooper, B Wu, QL Talcott, ST Percival, SS Simon, JE Pasinetti, GM AF Ho, Lap Ferruzzi, Mario G. Janle, Elsa M. Wang, Jun Gong, Bing Chen, Tzu-Ying Lobo, Jessica Cooper, Bruce Wu, Qing Li Talcott, Stephen T. Percival, Susan S. Simon, James E. Pasinetti, Giulio Maria TI Identification of brain-targeted bioactive dietary quercetin-3-O-glucuronide as a novel intervention for Alzheimer's disease SO FASEB JOURNAL LA English DT Article DE polyphenol bioavailability; cognitive deterioration; neuroplasticity ID LONG-TERM POTENTIATION; RED WINE; TRANSGENIC MICE; MOUSE MODEL; IN-VIVO; LIQUID-CHROMATOGRAPHY; VARIETAL DIFFERENCES; SYNAPTIC PLASTICITY; OXIDATIVE STRESS; VITIS-VINIFERA AB Epidemiological and preclinical studies indicate that polyphenol intake from moderate consumption of red wines may lower the relative risk for developing Alzheimer's disease (AD) dementia. There is limited information regarding the specific biological activities and cellular and molecular mechanisms by which wine polyphenolic components might modulate AD. We assessed accumulations of polyphenols in the rat brain following oral dosage with a Cabernet Sauvignon red wine and tested brain-targeted polyphenols for potential beneficial AD disease-modifying activities. We identified accumulations of select polyphenolic metabolites in the brain. We demonstrated that, in comparison to vehicle-control treatment, one of the brain-targeted polyphenol metabolites, quercetin-3-O-glucuronide, significantly reduced the generation of beta-amyloid (A beta\) peptides by primary neuron cultures generated from the Tg2576 AD mouse model. Another brain-targeted metabolite, malvidin-3-O-glucoside, had no detectable effect on A beta generation. Moreover, in an in vitro analysis using the photo-induced cross-linking of unmodified proteins (PICUP) technique, we found that quercetin-3-O-glucuronide is also capable of interfering with the initial protein-protein interaction of A beta(1-40) and A beta(1-42) that is necessary for the formation of neurotoxic oligomeric A beta species. Lastly, we found that quercetin-3-O-glucuronide treatment, compared to vehicle-control treatment, significantly improved AD-type deficits in hippocampal formation basal synaptic transmission and long-term potentiation, possibly through mechanisms involving the activation of the c-Jun N-terminal kinases and the mitogen-activated protein kinase signaling pathways. Brain-targeted quercetin-3-O-glucuronide may simultaneously modulate multiple independent AD disease-modifying mechanisms and, as such, may contribute to the benefits of dietary supplementation with red wines as an effective intervention for AD.-Ho, L., Ferruzzi, M. G., Janle, E. M., Wang, J., Gong, B., Chen, T.-Y., Lobo, J., Cooper, B., Wu, Q. L., Talcott, S. T., Percival, S. S., Simon, J. E., Pasinetti, G. M. Identification of brain-targeted bioactive dietary quercetin-3-O-glucuronide as a novel intervention for Alzheimer's disease. FASEB J. 27, 769-781 (2013). www.fasebj.org C1 [Ho, Lap; Wang, Jun; Gong, Bing; Pasinetti, Giulio Maria] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. [Ferruzzi, Mario G.; Lobo, Jessica] Purdue Univ, Dept Food Sci, W Lafayette, IN 47907 USA. [Ferruzzi, Mario G.; Janle, Elsa M.; Chen, Tzu-Ying] Purdue Univ, Dept Nutr Sci, W Lafayette, IN 47907 USA. [Cooper, Bruce] Purdue Univ, Bindley Biosci Ctr, W Lafayette, IN 47907 USA. [Wu, Qing Li; Simon, James E.] Rutgers State Univ, Dept Plant Biol & Plant Pathol, New Brunswick, NJ 08903 USA. [Talcott, Stephen T.] Texas A&M Univ, Dept Nutr & Food Sci, College Stn, TX USA. [Percival, Susan S.] Univ Florida, Dept Food Sci & Human Nutr, Gainesville, FL USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Neurol, 1468 Madison Ave,Annenberg Bldg,Rm 20-02, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu FU U.S. National Institutes of Health [National Center for Complementary and Alternative Medicine (NCCAM)] [PO1 AT004511] FX These studies were supported by the U.S. National Institutes of Health [grant PO1 AT004511; National Center for Complementary and Alternative Medicine (NCCAM) Project 1 to L. H. and Project 3 to G. M. P.]. The authors thank Dr. Kenjiro Ono (Kanazawa University Graduate School of Medical Science, Takara-Machi, Kanazawa, Japan), for valuable assistance and support with the PICUP analysis. NR 80 TC 54 Z9 57 U1 1 U2 51 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB PY 2013 VL 27 IS 2 BP 769 EP 781 DI 10.1096/fj.12-212118 PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 081YG UT WOS:000314358000035 PM 23097297 ER PT J AU Saunders, JE Beeson, CC Schnellmann, RG AF Saunders, Janet E. Beeson, Craig C. Schnellmann, Rick G. TI Characterization of functionally distinct mitochondrial subpopulations SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE Mitochondria; Heterogeneity; Flow cytometry; Kidney; Subpopulations ID SKELETAL-MUSCLE MITOCHONDRIA; FLOW-CYTOMETRIC ANALYSIS; RAT CARDIAC-MUSCLE; INTERMYOFIBRILLAR MITOCHONDRIA; OXIDATIVE-PHOSPHORYLATION; PERMEABILITY TRANSITION; LIVER-MITOCHONDRIA; LIGHT SCATTER; INTERFIBRILLAR MITOCHONDRIA; HEART-MITOCHONDRIA AB Mitochondrial stress results in changes in mitochondrial function, morphology and homeostasis (biogenesis, fission/fusion, mitophagy) and may lead to changes in mitochondrial subpopulations. While flow cytometric techniques have been developed to quantify features of individual mitochondria related to volume, Ca2+ concentration, mtDNA content, respiratory capacity and oxidative damage, less information is available concerning the identification and characterization of mitochondrial subpopulations, particularly in epithelial cells. Mitochondria from rabbit kidneys were stained with molecular probes for cardiolipin content (nonyl acridine orange, NAO) and membrane potential (tetramethylrhodamine, TMRM) and analyzed using flow cytometry. We validated that side scatter was a better indicator of volume and that as side scatter (SSC) decreased mitochondrial volume increased. Furthermore, those mitochondria with the highest NAO content had greater side scattering and were most highly charged. Mitochondria with average NAO content were of average side scattering and maintained an intermediate charge. Those mitochondria with low NAO content had minimal side scattering and exhibited minimal charge. Upon titration with the uncoupler carbonylcyanide-4-(trifluoromethoxy)-phenylhydrazone (FCCP), it was found that the high NAO content subpopulations were more resistant to uncoupling than lower NAO content populations. Ca2+-induced swelling of mitochondria was evaluated using probability binning (PB) analyses of SSC. Interestingly, only 30 % of the mitochondria showed changes in response to Ca2+, which was blocked by cyclosporine A. In addition, the small, high NAO content mitochondria swelled differentially in response to Ca2+ over time. Our results demonstrate that flow cytometry can be used to identify mitochondrial subpopulations based on high, mid and low NAO content and/or volume/complexity. These subpopulations showed differences in membrane potential, volume, and responses to uncoupling and Ca2+-induced swelling. C1 [Saunders, Janet E.; Beeson, Craig C.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Ctr Cell Death Injury & Regenerat, Charleston, SC 29425 USA. [Beeson, Craig C.] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Beeson, CC (reprint author), Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM beesonc@musc.edu FU NIH [GM 084147, C06 RR-015455]; NIM/NIEHS [T32ES012878-05]; NIH/NHLBI [T32HL007260-34]; Department of Veterans Affairs FX This study was supported by NIH Grant GM 084147, the NIM/NIEHS Training Program in Environmental Stress Signaling T32ES012878-05 and NIH/NHLBI Training to Improve Cardiovascular Therapies T32HL007260-34, and by the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs. Animal facilities were funded by NIH grant C06 RR-015455 NR 43 TC 6 Z9 6 U1 0 U2 22 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD FEB PY 2013 VL 45 IS 1-2 BP 87 EP 99 DI 10.1007/s10863-012-9478-4 PG 13 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA 089GR UT WOS:000314899500008 PM 23080405 ER PT J AU Perron, NR Beeson, C Rohrer, B AF Perron, Nathan R. Beeson, Craig Rohrer, Barbel TI Early alterations in mitochondrial reserve capacity; a means to predict subsequent photoreceptor cell death SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE Mitochondrial respiration; Cell death; Photoreceptors; Retinitis pigmentosa ID RETINAL MULLER CELLS; ACID PROTEIN ASSAY; OXIDATIVE STRESS; BICINCHONINIC ACID; ENERGY-METABOLISM; ROD PHOTORECEPTORS; DEGENERATION; CALCIUM; SUPEROXIDE; MECHANISMS AB Although genetic and environmental factors contribute to neurodegenerative disease, the underlying etiology common to many diseases might be based on metabolic demand. Mitochondria are the main producer of ATP, but are also the major source of reactive oxygen species. Under normal conditions, these oxidants are neutralized; however, under environmental insult or genetic susceptibility conditions, oxidative stress may exceed cellular antioxidant capacities, leading to degeneration. We tested the hypothesis that loss in mitochondrial reserve capacity plays a causative role in neuronal degeneration and chose a cone photoreceptor cell line as our model. 661W cells were exposed to agents that mimic oxidant stress or calcium overload. Real-time changes in cellular metabolism were assessed using the multi-well Seahorse Biosciences XF24 analyzer that measures oxygen consumption (OCR) and extracellular acidification rates (ECAR). Cellular stress resulted in an early loss of mitochondrial reserve capacity, without affecting basal respiration; and ECAR was increased, representing a compensatory shift of ATP productions toward glycolysis. The degree of change in energy metabolism was correlated with the amount of subsequent cell death 24-hours post-treatment, the concentration-dependent loss in mitochondrial reserve capacity correlated with the number of live cells. Our data suggested first, that loss in mitochondrial reserve capacity is a major contributor in disease pathogenesis; and second, that the XF24 assay might represent a useful surrogate assay amenable to the screening of agents that protect against loss of mitochondrial reserve capacity. In future experiments, we will explore these concepts for the development of neuroprotective agents. C1 [Rohrer, Barbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. [Perron, Nathan R.; Beeson, Craig] Med Univ S Carolina, Dept Pharmaceut Sci, Charleston, SC 29425 USA. [Rohrer, Barbel] Ralph H Johnson VA Med Ctr, Dept Res Serv, Charleston, SC 29425 USA. [Beeson, Craig] Med Univ S Carolina, Coll Pharm Pharmaceut & Biomed Sci, Charleston, SC 29425 USA. RP Rohrer, B (reprint author), Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave,SEI 511, Charleston, SC 29425 USA. EM beesonc@musc.edu; rohrer@musc.edu FU National Institutes of Health [EY013520, EY019320]; Department for Veterans Affairs [RX000444]; Foundation Fighting Blindness; Research to Prevent Blindness (RPB), New York, NY FX This work was supported in part by National Institutes of Health grant EY013520, EY019320 (B.R.), a Department for Veterans Affairs merit award RX000444 (B.R.), the WG-TRAP award by Foundation Fighting Blindness (B.R. and C.B.), and an unrestricted grant to MUSC from Research to Prevent Blindness (RPB), New York, NY. B.R. is a RPB Olga Keith Wiess Scholar. NR 56 TC 11 Z9 11 U1 0 U2 16 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD FEB PY 2013 VL 45 IS 1-2 BP 101 EP 109 DI 10.1007/s10863-012-9477-5 PG 9 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA 089GR UT WOS:000314899500009 PM 23090843 ER PT J AU Ransom, CB Tao, WC Wu, YM Spain, WJ Richerson, GB AF Ransom, Christopher B. Tao, Wucheng Wu, Yuanming Spain, William J. Richerson, George B. TI Rapid regulation of tonic GABA currents in cultured rat hippocampal neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE tonic inhibition; gamma-aminobutyric acid receptor type A; gamma-aminobutyric acid transporter type 1; seizure ID CEREBELLAR GRANULE CELLS; ACTIVITY-DEPENDENT DISINHIBITION; CHLORIDE ACCUMULATION; DENTATE GYRUS; DELTA-SUBUNIT; MOUSE MODEL; IONIC BASIS; RECEPTORS; INHIBITION; TRANSPORTER AB Ransom CB, Tao W, Wu Y, Spain WJ, Richerson GB. Rapid regulation of tonic GABA currents in cultured rat hippocampal neurons. J Neurophysiol 109: 803-812, 2013. First published October 31, 2012; doi:10.1152/jn.00460.2012.-Subacute and chronic changes in tonic GABAergic inhibition occur in human and experimental epilepsy. Less is known about how tonic inhibition is modulated over shorter time frames (seconds). We measured endogenous tonic GABA currents from cultured rat hippocampal neurons to evaluate how they are affected by 1) transient increases in extracellular GABA concentration ([GABA]), 2) transient postsynaptic depolarization, and 3) depolarization of presynaptic cells. Transient increases in [GABA] (1 mu M) reduced tonic currents; this reduction resulted from GABA-induced shifts in the reversal potential for GABA currents (E-GABA). Transient depolarization of postsynaptic neurons reversed the effects of exogenous GABA and potentiated tonic currents. The voltage-dependent potentiation of tonic GABA currents was independent of E-GABA shifts and represented postdepolarization potentiation (PDP), an intrinsic GABA(A) receptor property (Ransom CB, Wu Y, Richerson GB. J Neurosci 30: 7672-7684, 2010). Inhibition of vesicular GABA release with concanamycin A (ConA) did not affect tonic currents. In ConA-treated cells, transient application of 12 mM K+ to depolarize presynaptic neurons and glia produced a persistent increase in tonic current amplitude. The K+-induced increase in tonic current was reversibly inhibited by SKF89976a (40 mu M), indicating that this was caused by nonvesicular GABA release from GABA transporter type 1 (GAT1). Nonvesicular GABA release due to GAT1 reversal also occurred in acute hippocampal brain slices. Our results indicate that tonic GABA currents are rapidly regulated by GABA-induced changes in intracellular Cl- concentration, PDP of extrasynaptic GABA(A) receptors, and nonvesicular GABA release. These mechanisms may influence tonic inhibition during seizures when neurons are robustly depolarized and extracellular GABA and K+ concentrations are elevated. C1 [Ransom, Christopher B.; Spain, William J.] Vet Affairs Puget Sound Hlth Care Syst, Epilepsy Ctr Excellence, Seattle, WA USA. [Ransom, Christopher B.; Spain, William J.] Univ Washington, Dept Neurol, Seattle, WA 98105 USA. [Tao, Wucheng; Spain, William J.] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98105 USA. [Wu, Yuanming; Richerson, George B.] Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA. [Richerson, George B.] Univ Iowa, Dept Mol Physiol & Biophys, Iowa City, IA USA. RP Ransom, CB (reprint author), Univ Washington, Epilepsy Ctr Excellence, VA Puget Sound Hlth Care Syst, Dept Neurol, Seattle, WA 98105 USA. EM cbr5@u.washington.edu FU Department of Veterans Affairs Health Administration; National Institutes of Health; National Epifellows Foundation FX This work was supported by the Department of Veterans Affairs Health Administration (C. B. Ransom, W. J. Spain), the National Institutes of Health (G. B. Richerson), and the National Epifellows Foundation (C. B. Ransom). NR 60 TC 9 Z9 10 U1 2 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 2013 VL 109 IS 3 BP 803 EP 812 DI 10.1152/jn.00460.2012 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 085TI UT WOS:000314636800019 PM 23114210 ER PT J AU Kumar, N Garg, N Bailey, A AF Kumar, Nilay Garg, Neetika Bailey, Amos TI Opiate Receptor Antagonists for Treatment of Severe Pruritus Associated with Advanced Cholestatic Liver Disease SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Letter ID DOUBLE-BLIND C1 [Kumar, Nilay] Univ Alabama Birmingham, Dept Internal Med, Birmingham, AL 35294 USA. [Garg, Neetika] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Bailey, Amos] Birmingham VA Med Ctr, Div Palliat Care & Hosp Med, Birmingham, AL USA. RP Kumar, N (reprint author), Univ Alabama Birmingham, Dept Internal Med, BDB 327,1530 3rd Ave S, Birmingham, AL 35294 USA. EM nkumar@uab.edu OI Garg, Neetika/0000-0002-7001-2168 NR 6 TC 3 Z9 3 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD FEB PY 2013 VL 16 IS 2 BP 122 EP 123 DI 10.1089/jpm.2012.0452 PG 2 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 088FB UT WOS:000314818100003 PM 23391399 ER PT J AU de Boer, IH Sachs, M Hoofnagle, AN Utzschneider, KM Kahn, SE Kestenbaum, B Himmelfarb, J AF de Boer, Ian H. Sachs, Michael Hoofnagle, Andrew N. Utzschneider, Kristina M. Kahn, Steven E. Kestenbaum, Bryan Himmelfarb, Jonathan TI Paricalcitol does not improve glucose metabolism in patients with stage 3-4 chronic kidney disease SO KIDNEY INTERNATIONAL LA English DT Article DE chronic kidney disease; clinical trial; insulin resistance; metabolism; vitamin D ID FIBROBLAST GROWTH FACTOR-23; RANDOMIZED CONTROLLED-TRIAL; GLOMERULAR-FILTRATION-RATE; FGF23 GENE-EXPRESSION; VITAMIN-D THERAPY; INSULIN-RESISTANCE; SECONDARY HYPERPARATHYROIDISM; HEMODIALYSIS-PATIENTS; 1,25-DIHYDROXYVITAMIN D-3; INTRAVENOUS CALCITRIOL AB Patients with chronic kidney disease are often insulin resistant and glucose intolerant abnormalities that promote cardiovascular disease. Administration of 1,25-dihydroxyvitamin D (calcitriol) has improved glucose metabolism in patients with end-stage renal disease. We conducted a randomized, placebo-controlled clinical trial to test whether paricalcitol, a 1,25-dihydroxyvitamin D analog, changes glucose tolerance in earlier stages of chronic kidney disease. In a crossover design, 22 nondiabetic patients with estimated glomerular filtration rates of stage 3-4 chronic kidney disease and fasting plasma glucose of 100-125 mg/dl were given daily oral paricalcitol for 8 weeks and matching placebo for 8 weeks, separated by an 8-week washout period. The order of interventions was random and blinded to both participants and investigators. Paricalcitol significantly reduced serum concentrations of parathyroid hormone, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D while significantly increasing serum concentrations of fibroblast growth factor-23 and 24,25-dihydroxyvitamin D. Paricalcitol, however, had no significant effect on glucose tolerance (the primary outcome measure), insulin sensitivity, beta-cell insulin response, plasma free fatty acid suppression, or urinary F2-isoprostane excretion. Thus, despite substantial effects on vitamin D metabolism, paricalcitol did not improve glucose metabolism in nondiabetic patients with stage 3-4 chronic kidney disease. Kidney International (2013) 83, 323-330; doi:10.1038/ki.2012.311; published online 22 August 2012 C1 [de Boer, Ian H.; Sachs, Michael; Kestenbaum, Bryan; Himmelfarb, Jonathan] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98104 USA. [de Boer, Ian H.; Sachs, Michael; Kestenbaum, Bryan; Himmelfarb, Jonathan] Univ Washington, Dept Med, Kidney Res Inst, Seattle, WA 98104 USA. [de Boer, Ian H.; Kestenbaum, Bryan] Univ Washington, Dept Epidemiol, Seattle, WA 98104 USA. [Hoofnagle, Andrew N.] Univ Washington, Dept Lab Med, Seattle, WA 98104 USA. [Utzschneider, Kristina M.; Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Utzschneider, Kristina M.; Kahn, Steven E.] Univ Washington, Seattle, WA 98104 USA. RP de Boer, IH (reprint author), Univ Washington, Dept Med, Div Nephrol, Box 359606,325 9th Ave, Seattle, WA 98104 USA. EM deboer@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU Abbott Laboratories; National Institutes of Health [1R01DK087726, 1R01HL096875, 5R01HL070938, 5KL2RR025015, P30DK035816, 5P30DK017047, UL1RR025014]; Veterans Affairs Puget Sound Health Care System, Seattle, WA FX This work was supported by an investigator-initiated grant from Abbott Laboratories and by grants 1R01DK087726, 1R01HL096875, 5R01HL070938, 5KL2RR025015, P30DK035816, 5P30DK017047, and UL1RR025014 from the National Institutes of Health. This material is the result of work supported in part by resources from the Veterans Affairs Puget Sound Health Care System, Seattle, WA. We thank the study participants for their generous dedication and Laura Curtin, BS, Alexandra Flynn, MD, Aparna Lakshman, BA, and the staff of the University of Washington Investigational Drug Services and Clinical Research Center for their hard work. NR 52 TC 14 Z9 14 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 2013 VL 83 IS 2 BP 323 EP 330 DI 10.1038/ki.2012.311 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 085NM UT WOS:000314621500022 PM 22913981 ER PT J AU Royall, DR AF Royall, Donald R. TI Fortress Brain SO MEDICAL HYPOTHESES LA English DT Article ID SIMPLEX-VIRUS TYPE-1; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; PARKINSONS-DISEASE; PERINEURONAL NETS; FOLLOW-UP; EXPRESSION; TAU; DISORDERS AB Neurodegenerative diseases are associated with neuronal inclusions, comprised of protein aggregates. In Alzheimer's Disease (AD) and Lewy Body Disease (LBD) such lesions are distributed in a hierarchical retrograde transynaptic spatial pattern. This implies a retrograde transynaptic temporal propagation as well. There can be few explanations for this other than infectious agents (prions and viruses). This suggests that AD and LBD (at least) may have infectious origins. Transynaptic infiltration of the CNS along cranial nerve or other major projections, by one or more infectious agents has important implications. The clinical syndrome and natural history of each neurodegenerative disorder will reflect its portal of entry. There may be a different neurodegenerative syndrome for each cranial nerve or other portal of entry, and not all may manifest as "dementia". Each syndrome may be associated with more than one pathological lesion. Each pathology may be associated with several clinical syndromes. Host-parasite interactions are species specific. This may explain the rarity of AD-like pathology in most other older mammals. Over evolutionary timescales, the human brain should be adapted to predation by neurotropic agents. Viewed from this perspective, the prion-like pro-inflammatory and pro-apoptotic properties of beta-amyloid and other proteins may be adaptive, and anti-microbial. Reductions in synaptic density may slow the progress of invading pathogens, while perineuronal nets and other structures may guard the gates. This suggests a defense in depth of a structure, the brain, that is inherently vulnerable to invasion along its neural networks. (c) 2012 Elsevier Ltd. All rights reserved. C1 [Royall, Donald R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Royall, Donald R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Royall, Donald R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Royall, Donald R.] S Texas Vet Hlth Syst, Audie L Murphy Div, GRECC, San Antonio, TX USA. RP Royall, DR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. EM royall@uthscsa.edu NR 48 TC 1 Z9 1 U1 0 U2 9 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD FEB PY 2013 VL 80 IS 2 BP 118 EP 121 DI 10.1016/j.mehy.2012.11.005 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 083SO UT WOS:000314485700004 PM 23265350 ER PT J AU Pessarakli, MM Phan, RT AF Pessarakli, M. M. Phan, R. T. TI Association between Methylenetetrahydrofolate Reductase (MTHFR) Gene Variants and Hyperhomocysteinemia in United States Veterans SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 USC, Keck Sch Med, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1853 BP 444A EP 445A PG 2 WC Pathology SC Pathology GA 083EB UT WOS:000314444402478 ER PT J AU Mendez, MF Joshi, A Tassniyom, K Teng, E Shapira, JS AF Mendez, Mario F. Joshi, Aditi Tassniyom, Kanida Teng, Edmond Shapira, Jill S. TI Clinicopathologic differences among patients with behavioral variant frontotemporal dementia SO NEUROLOGY LA English DT Article ID CENTER NACC DATABASE; UNIFORM DATA SET; LOBAR DEGENERATION; ALZHEIMER-DISEASE; DIAGNOSTIC-CRITERIA; CONSORTIUM; CONSENSUS; FEATURES AB Objective: To characterize the presenting symptoms and signs of patients clinically diagnosed with behavioral variant frontotemporal dementia (bvFTD) and who had different neuropathologic findings on autopsy. Methods: This study reviewed all patients entered as clinical bvFTD in the National Alzheimer's Coordinating Center's database and who had both clinical and neuropathologic data from 2005 to 2011. Among the 107 patients identified, 95 had unambiguous pathologic findings, including 74 with frontotemporal lobar degeneration (bvFTD-FTLD) and 21 with Alzheimer disease (bvFTD-AD). The patients with bvFTD-FTLD were further subdivided into tau-positive (n = 23) or tau-negative (n = 51) histopathology subgroups. Presenting clinical signs and symptoms were compared between these neuropathologic groups. Results: The patients with bvFTD-FTLD were significantly more likely than patients with bvFTD-AD to have initially predominant personality changes and poor judgment/decision-making. In contrast, patients with bvFTD-AD were more likely than patients with bvFTD-FTLD to have memory difficulty and delusions/hallucinations and agitation. Within the bvFTD-FTLD group, the tau-positive subgroup had more patients with initial behavioral problems and personality change than the tau-negative subgroup, who, in turn, had more patients with initial cognitive impairment and speech problems. Conclusion: During life, patients with AD pathology may be misdiagnosed with bvFTD if they have an early age at onset and prominent neuropsychiatric features despite having greater memory difficulties and more intact personality and executive functions than patients with bvFTD-FTLD. Among those with FTLD pathology, patients with tau-positive bvFTD were likely to present with behavior/personality changes. These findings offer clues for antemortem recognition of neuropathologic subtypes of bvFTD. Neurology (R) 2013;80:561-568 C1 [Mendez, Mario F.; Joshi, Aditi; Teng, Edmond; Shapira, Jill S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Mendez, Mario F.; Teng, Edmond] VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. [Tassniyom, Kanida] Khon Kaen Univ, Dept Psychiat, Khon Kaen, Thailand. RP Mendez, MF (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. EM mmendez@ucla.edu FU NIA [R01AG034499-03]; VA Merit Review; Alzheimer's Disease Research Center Grant [NIA P50 AG-16570]; NACC [UO1 AG016976] FX Supported by NIA grant #R01AG034499-03 (M.F. Mendez), a VA Merit Review (A. Joshi, M.F. Mendez), Alzheimer's Disease Research Center Grant NIA P50 AG-16570 (M.F. Mendez), and the NACC grant (UO1 AG016976). NR 27 TC 29 Z9 32 U1 0 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 2013 VL 80 IS 6 BP 561 EP 568 DI 10.1212/WNL.0b013e3182815547 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 086OD UT WOS:000314693800014 PM 23325909 ER PT J AU Sibila, O Restrepo, MI AF Sibila, Oriol Restrepo, Marcos I. TI Corticosteroids for pneumonia: Are we there yet? SO RESPIROLOGY LA English DT Editorial Material DE community-acquired pneumonia; corticosteroid; length of stay; pneumonia ID COMMUNITY-ACQUIRED PNEUMONIA; CONTROLLED-TRIAL; CLINICAL-COURSE; GLUCOCORTICOIDS C1 [Sibila, Oriol] Hosp Santa Creu & Sant Pau, Serv Pneumol, Barcelona, Spain. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Restrepo, Marcos I.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Restrepo, Marcos I.] Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. RP Sibila, O (reprint author), Hosp Santa Creu & Sant Pau, Serv Pneumol, Barcelona, Spain. RI Restrepo, Marcos/H-4442-2014 FU NHLBI NIH HHS [K23 HL096054, K23HL096054] NR 12 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1323-7799 J9 RESPIROLOGY JI Respirology PD FEB PY 2013 VL 18 IS 2 BP 199 EP 200 DI 10.1111/resp.12012 PG 2 WC Respiratory System SC Respiratory System GA 078RH UT WOS:000314116500001 PM 23134329 ER PT J AU Kring, AM Gur, RE Blanchard, JJ Horan, WP Reise, SP AF Kring, Ann M. Gur, Raquel E. Blanchard, Jack J. Horan, William P. Reise, Steven P. TI The Clinical Assessment Interview for Negative Symptoms (CAINS): Final Development and Validation SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PSYCHIATRIC RATING-SCALE; RESEARCH DOMAIN CRITERIA; ITEM RESPONSE THEORY; SCHIZOPHRENIA; ANHEDONIA; PERSPECTIVE; DEFICITS; EMOTION; RELIABILITY; REWARD AB Objective: A major barrier to developing treatments for negative symptoms has been measurement concerns with existing assessment tools. Fulfilling the top recommendation of the National Institute of Mental Health's Consensus Development Conference on Negative Symptoms, the Clinical Assessment Interview for Negative Symptoms (CAINS) was developed-using an iterative, empirical approach, and includes items assessing motivation, pleasure, and emotion expression. The authors employed multiple analytic techniques to develop the CAINS and here provide final development and validation results. Method: The CAINS structure, interrater agreement, test-retest reliability, and convergent and discriminant validity were assessed in a large and diverse sample of 162 outpatients with schizophrenia or schizo-affective disorder recruited from four sites. Results: Three items with poor psychometric properties were removed, resulting in a 13-item CAINS. The CAMS factor structure was replicated, demonstrating two modestly correlated scales: expression (four items) and motivation/pleasure (nine items). The scales demonstrated good internal consistency, test-retest stability, and interrater agreement. Strong convergent validity was demonstrated by linkages with other negative symptom measures, self-report scales of sociality, pleasure, and motivation, and coded facial expressions. Discriminant validity was shown by independence from depression, medication side effects, and cognition. Notably, the CAINS scales were related to real-world vocational, independent living, and social/familial functioning. Conclusions: The CAINS is an empirically developed and evaluated measure of negative symptoms. Findings indicate that the CAINS is brief yet comprehensive and employable across a wide range of research and clinical contexts. (Am J Psychiatry 2013; 170:165-172) C1 [Kring, Ann M.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Kring, AM (reprint author), Univ Calif Berkeley, Dept Psychol, 3210 Tolman Hall, Berkeley, CA 94720 USA. EM akring@berkeley.edu FU Pfizer; AstraZeneca; NIH [1R01MH082890, 1R01MH082783, 1R01MH082839, 1R01MH082782] FX Dr. Gur has received investigator-initiated grants from Pfizer and AstraZeneca. Dr. Blanchard has received honoraria and travel support from Merck and Genentech for consulting. The other authors report no competing interests.; Supported in part by NIH grant 1R01MH082890 to Dr. Kring, grant 1R01MH082783 to Dr. Gur, grant 1R01MH082839 to Dr. Blanchard, and grant 1R01MH082782 to Dr. Horan. NR 44 TC 131 Z9 132 U1 4 U2 23 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2013 VL 170 IS 2 BP 165 EP 172 DI 10.1176/appi.ajp.2012.12010109 PG 8 WC Psychiatry SC Psychiatry GA 079VY UT WOS:000314201500008 PM 23377637 ER PT J AU Maramattom, LV Hari, PN Burns, LJ Carreras, J Arcese, W Cairo, MS Costa, LJ Fenske, TS Lill, M Freytes, CO Gale, RP Gross, TG Hale, GA Hamadani, M Holmberg, LA Hsu, JW Inwards, DJ Lazarus, HM Marks, DI Maloney, DG Maziarz, RT Montoto, S Rizzieri, DA Wirk, B Gajewski, JL AF Maramattom, Leena V. Hari, Parameswaran N. Burns, Linda J. Carreras, Jeanette Arcese, William Cairo, Mitchell S. Costa, Luciano J. Fenske, Timothy S. Lill, Michael Freytes, Cesar O. Gale, Robert Peter Gross, Thomas G. Hale, Gregory A. Hamadani, Mehdi Holmberg, Leona A. Hsu, Jack W. Inwards, David J. Lazarus, Hillard M. Marks, David I. Maloney, David G. Maziarz, Richard T. Montoto, Silvia Rizzieri, David A. Wirk, Baldeep Gajewski, James L. TI Autologous and Allogeneic Transplantation for Burkitt Lymphoma Outcomes and Changes in Utilization: A Report from the Center for International Blood and Marrow Transplant Research SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE AlloHCT; AutoHCT; Burkitt lymphoma ID ADULT BURKITT; LEUKEMIA; CHEMOTHERAPY; RADIATION; THERAPY AB Trends in utilization and outcomes after autologous or allogeneic hematopoietic cell transplantation (HCT) for Burkitt lymphoma were analyzed in 241 recipients reported to the Center for International Blood and Marrow Transplant Research between 1985 and 2007. The autologous HCT cohort had a higher proportion of chemotherapy-sensitive disease, peripheral blood grafts, and HCT in first complete remission (CR1). The use of autologous HCT has declined over time, with only 19% done after 2001. Overall survival at 5 years for the autologous cohort was 83% for those in CR1 and 31% for those not in CR1. Corresponding progression-free survival (PFS) was 78% and 27%, respectively. After allogeneic HCT, overall survival at 5 years was 53% and 20% for the CR1 and non-CR1 cohorts, whereas PFS was 50% and 19%, respectively. The most common cause of death was progressive lymphoma. Allogeneic HCT performed in a higher-risk subset (per National Comprehensive Cancer Network guidelines) resulted in a 5-year PFS of 27%. Autologous HCT resulted in a 5-year PFS of 44% in those undergoing transplantation in the second CR. (C) 2013 American Society for Blood and Marrow Transplantation. C1 [Maramattom, Leena V.; Hari, Parameswaran N.; Fenske, Timothy S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Hari, Parameswaran N.; Fenske, Timothy S.] Med Coll Wisconsin, Dept Med, Div Hematol Oncol, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Burns, Linda J.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Carreras, Jeanette] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Arcese, William] Univ Roma Tor Vergata, Rome Transplant Network, Rome, Italy. [Cairo, Mitchell S.] New York Med Coll, Valhalla, NY 10595 USA. [Costa, Luciano J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Lill, Michael] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Freytes, Cesar O.] S Vet Hlth Care Syst, San Antonio, TX USA. [Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Gale, Robert Peter] Celgene Cord Blood Bank, Cedar Knolls, NJ USA. [Gross, Thomas G.] Nationwide Childrens Hosp, Columbus, OH USA. [Hale, Gregory A.] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA. [Hamadani, Mehdi] W Virginia Univ Hosp Inc, Morgantown, WV USA. [Holmberg, Leona A.; Maloney, David G.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Hsu, Jack W.; Wirk, Baldeep] Shands HealthCare, Gainesville, FL USA. [Hsu, Jack W.] Univ Florida, Gainesville, FL USA. [Inwards, David J.] Mayo Clin Rochester, Rochester, MN USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Marks, David I.] Bristol Childrens Hosp, Bristol, Avon, England. [Maziarz, Richard T.; Gajewski, James L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Montoto, Silvia] Queen Mary Univ London, Barts Canc Inst, London, England. [Rizzieri, David A.] Duke Univ, Med Ctr, Durham, NC USA. RP Hari, PN (reprint author), Med Coll Wisconsin, POB 26509, Milwaukee, WI 53226 USA. EM phari@mcw.edu OI Hari, Parameswaran/0000-0002-8800-297X; Hamadani, Mehdi/0000-0001-5372-510X FU Public Health Service from the National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung and Blood Institute (NHLBI) [5U01HL069294]; National Institute of Allergy and Infectious Diseases (NIAID); NCI; Resources and Services Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos, Inc.; Amgen, Inc.; Angioblast; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma; Leukemia & Lymphoma Society; Medical College of Wisconsin; Merck Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; THERAKOS, Inc.; Wellpoint, Inc. FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); two grants N00014-06-1-0704 and. N00014-08-1-0058 from the Office of Naval Research; and grants from Allos, Inc.; Amgen, Inc.; Angioblast; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; THERAKOS, Inc.; and Wellpoint, Inc. 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, or any other agency of the US Government. NR 14 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 BP 173 EP 179 DI 10.1016/j.bbmt.2012.11.016 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DA UT WOS:000314441700004 PM 23200705 ER PT J AU Liu, YH Malin, JL Diamant, AL Thind, A Maly, RC AF Liu, Yihang Malin, Jennifer L. Diamant, Allison L. Thind, Amardeep Maly, Rose C. TI Adherence to adjuvant hormone therapy in low-income women with breast cancer: the role of provider-patient communication SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Hormone therapy adherence; Low-income women ID MEDICALLY UNDERSERVED WOMEN; POSTMENOPAUSAL WOMEN; PHYSICIAN COMMUNICATION; MEDICATION NONADHERENCE; RACIAL DISPARITIES; TAMOXIFEN THERAPY; ENDOCRINE THERAPY; OLDER PATIENTS; CARE; DISCONTINUATION AB To assess the impact of patient-provider communication on adherence to tamoxifen (TAM) and aromatase inhibitors (AIs) 36 months after breast cancer (BC) diagnosis in a low-income population of women. California statewide surveys were conducted among 921 low-income women with BC at 6, 18, and 36 months after BC diagnosis. A subset of 303 women with stage I-III BC who initiated hormone treatment after diagnosis was identified. Bivariate and multivariate logistic regression analyses were performed, and adjusted adherence rates were calculated. The main outcome measure was self-reported hormone use at 36 months after BC diagnosis and the chief independent variables were patient-centered communication after diagnosis by patient report as measured by the Consumer Assessment of Healthcare Providers and Systems (CAHPS) and patients' self-efficacy in patient-physician interactions (PEPPI). Overall adherence to TAM/AI was relatively high (88 %). Adjusted rates of adherence were 59 and 94 % for patients with the lowest versus highest scores on the CAHPS communication scale (AOR = 1.22, P = 0.006) and 72 versus 91 % for patients with the lowest and highest rating of PEPPI (AOR = 1.04, P = 0.04). Having at least one comorbid condition also increased the odds of adherence to hormonal therapy (AOR = 3.14, P = 0.03). Having no health insurance and experiencing side-effects from hormone treatment were barriers for adherence (AOR = 0.12, P = 0.001; AOR = 0.26, P = 0.003, respectively). Patient-centered communication and perceived self-efficacy in patient-physician interaction were significantly associated with patient adherence to ongoing TAM/AI therapy among low-income women with BC. Interventions on patient-provider communication may provide opportunities to improve patient outcomes in this vulnerable population. C1 [Liu, Yihang; Maly, Rose C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Family Med, Los Angeles, CA 90024 USA. [Malin, Jennifer L.] VA Greater Los Angeles Healthcare Syst, Div Hematol Oncol, Los Angeles, CA USA. [Diamant, Allison L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Thind, Amardeep] Univ Western Ontario, Dept Family Med & Epidemiol & Biostat, London, ON, Canada. RP Maly, RC (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Family Med, 10880 Wilshire Blvd Ste 1800, Los Angeles, CA 90024 USA. EM rmaly@mednet.ucla.edu FU American Cancer Society [TURSG-02-081]; California Breast Cancer Research Program [7PB-0070]; National Cancer Institute [R01CA119197-01A1, R01CA140481-01A1] FX This study was funded by the American Cancer Society (# TURSG-02-081), the California Breast Cancer Research Program (# 7PB-0070), and the National Cancer Institute (#R01CA119197-01A1). Dr. Maly was additionally supported by the National Cancer Institute (#R01CA140481-01A1). NR 58 TC 32 Z9 32 U1 2 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD FEB PY 2013 VL 137 IS 3 BP 829 EP 836 DI 10.1007/s10549-012-2387-8 PG 8 WC Oncology SC Oncology GA 076GN UT WOS:000313944600017 PM 23263740 ER PT J AU Saxon, AJ Ling, W Hillhouse, M Thomas, C Hasson, A Ang, A Doraimani, G Tasissa, G Lokhnygina, Y Leimberger, J Bruce, RD McCarthy, J Wiest, K McLaughlin, P Bilangi, R Cohen, A Woody, G Jacobs, P AF Saxon, Andrew J. Ling, Walter Hillhouse, Maureen Thomas, Christie Hasson, Albert Ang, Alfonso Doraimani, Geetha Tasissa, Gudaye Lokhnygina, Yuliya Leimberger, Jeff Bruce, R. Douglas McCarthy, John Wiest, Katharina McLaughlin, Paul Bilangi, Richard Cohen, Allan Woody, George Jacobs, Petra TI Buprenorphine/Naloxone and methadone effects on laboratory indices of liver health: A randomized trial SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Liver function; Buprenorphine; Methadone; Treatment outcome ID OPIOID DEPENDENCE; MAINTENANCE; HEPATITIS; ABUSE AB Background: Buprenorphine/naloxone (BUP) and methadone (MET) are efficacious treatments for opioid dependence, although concerns about a link between BUP and drug-induced hepatitis have been raised. This study compares the effects of BUP and MET on liver health in opioid-dependent participants. Methods: This was a randomized controlled trial of 1269 opioid-dependent participants seeking treatment at 8 federally licensed opioid treatment programs and followed for up to 32 weeks between May 2006 and August 2010; 731 participants met "evaluable" criteria defined as completing 24 weeks of medication and providing at least 4 blood samples for transaminase testing. Participants were randomly assigned to receive BUP or MET for 24 weeks. Shift table analysis determined how many evaluable participants moved between categories of low and elevated transaminase levels. Predictors of moving from low to high transaminase levels were identified. Results: Changes in transaminase levels did not differ by medication condition. Baseline infection with hepatitis C or B was the only significant predictor of moving from low to elevated transaminase levels; 9 BUP and 15 MET participants showed extreme liver test elevations and were more likely than those without extreme elevations to have seroconverted to both hepatitis B and C during the study, or to use illicit drugs during the first 8 weeks of treatment. MET participants were retained longer in treatment than BUP participants. Conclusions: This study demonstrated no evidence of liver damage during the initial 6 months of treatment in either condition. Physicians can prescribe either medication without major concern for liver injury. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Saxon, Andrew J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Ling, Walter; Hillhouse, Maureen; Thomas, Christie; Hasson, Albert; Ang, Alfonso; Doraimani, Geetha] Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA 90025 USA. [Tasissa, Gudaye; Lokhnygina, Yuliya; Leimberger, Jeff] Duke Clin Res Inst, Durham, NC 27705 USA. [Bruce, R. Douglas] Yale Univ, Sch Med, New Haven, CT 06510 USA. [McCarthy, John] Bivalley Med Clin Inc, Carmichael, CA 95838 USA. [Wiest, Katharina] CODA Inc, Portland, OR 97214 USA. [McLaughlin, Paul] Hartford Dispensary, Manchester, CT 06040 USA. [Bilangi, Richard] Connecticut Counseling Ctr, Danbury, CT 06810 USA. [Cohen, Allan] Bay Area Addict Res & Treatment, Sherman Oaks, CA 91403 USA. [Woody, George] Univ Penn, Sch Med, Philadelphia, PA 19106 USA. [Jacobs, Petra] NIDA, Clin Trials Network, Bethesda, MD 20892 USA. RP Hillhouse, M (reprint author), Univ Calif Los Angeles, Integrated Subst Abuse Programs, 1640 S Sepulveda Blvd,Suite 120, Los Angeles, CA 90025 USA. EM hillhous@ucla.edu FU Gilead Sciences, Inc; Merck Co; Bristol Myers Squibb; Boehringer Ingelheim; Reckitt Benckiser Pharmaceuticals; Abbott Laboratories; Pfizer, Inc FX Authors disclosing relevant financial interests, activities, relationships, and affiliations are: Andrew Saxon: Paid consultant to Reckitt Benckiser Pharmaceuticals; Walter Ling: Paid consultant to Reckitt Benckiser Pharmaceuticals; R. Douglas Bruce: Research grant support from Gilead Sciences, Inc., Merck & Co., Bristol Myers Squibb, Boehringer Ingelheim, Reckitt Benckiser Pharmaceuticals, Abbott Laboratories, Pfizer, Inc., and honorarium from Reckitt Benckiser Pharmaceuticals; Yuliya Lokhnygina: Paid consultant to Johnson & Johnson. All other authors report no financial or other possible conflicts of interest. NR 19 TC 25 Z9 25 U1 2 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD FEB 1 PY 2013 VL 128 IS 1-2 BP 71 EP 76 DI 10.1016/j.drugalcdep.2012.08.002 PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 081OO UT WOS:000314331700011 PM 22921476 ER PT J AU Ho, JM Blevins, JE AF Ho, Jacqueline M. Blevins, James E. TI Coming Full Circle: Contributions of Central and Peripheral Oxytocin Actions to Energy Balance SO ENDOCRINOLOGY LA English DT Review ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; CONDITIONED PLACE PREFERENCE; RECEPTOR GENE-EXPRESSION; C-FOS EXPRESSION; FOOD-INTAKE; BRAIN-STEM; GASTRIC DISTENSION; DEFICIENT MICE; NEUROHYPOPHYSEAL HORMONES; INTRACELLULAR CALCIUM AB The neuropeptide oxytocin has emerged as an important anorexigen in the regulation of energy balance. Its effects on food intake have largely been attributed to limiting meal size through interactions in key regulatory brain regions such as the hypothalamus and hindbrain. Pharmacologic and pair-feeding studies indicate that its ability to reduce body mass extends beyond that of food intake, affecting multiple factors that determine energy balance such as energy expenditure, lipolysis, and glucose regulation. Systemic administration of oxytocin recapitulates many of its effects when administered centrally, raising the questions of whether and to what extent circulating oxytocin contributes to energy regulation. Its therapeutic potential to treat metabolic conditions remains to be determined, but data from diet-induced and genetically obese rodent models as well as application of oxytocin in humans in other areas of research have revealed promising results thus far. (Endocrinology 154: 589-596, 2013) C1 [Ho, Jacqueline M.] Vet Affairs Puget Sound Hlth Care Syst, Off Res & Dev, Med Res Serv, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. RP Ho, JM (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Off Res & Dev, Med Res Serv, 1660 S Columbian Way, Seattle, WA 98108 USA. EM jmh529@uw.edu FU Office of Research and Development, Medical Research Service, Department of Veterans Affairs; Department of Veterans Affairs; National Institutes of Health [T32DK007247-35] FX This work was supported by resources from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, including the Department of Veterans Affairs Merit Review Research Program. Funding for this manuscript was provided by the Department of Veterans Affairs Merit Review Research Program (to J.E.B.) and a Trainee Fellowship under National Institutes of Health grant T32DK007247-35 (to J.M.H.). NR 99 TC 20 Z9 22 U1 2 U2 14 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 2013 VL 154 IS 2 BP 589 EP 596 DI 10.1210/en.2012-1751 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 076ME UT WOS:000313959800004 PM 23270805 ER PT J AU Nuzzo, E Shensa, A Kim, KH Fine, MJ Barnett, TE Cook, R Primack, BA AF Nuzzo, Erin Shensa, Ariel Kim, Kevin H. Fine, Michael J. Barnett, Tracey E. Cook, Robert Primack, Brian A. TI Associations between hookah tobacco smoking knowledge and hookah smoking behavior among US college students SO HEALTH EDUCATION RESEARCH LA English DT Article ID HIGH-SCHOOL-STUDENTS; WATER-PIPE; CIGARETTE SMOKERS; CARBON-MONOXIDE; PREVALENCE; UNIVERSITY; NICOTINE; SUSCEPTIBILITY; CONSEQUENCES; NONRESPONSE AB Hookah tobacco smoking is increasing among US college students, including those who would not otherwise use tobacco. Part of hookah's appeal is attributed to the perception that hookah is less harmful than cigarettes. The aims of this study were to assess knowledge of harmful exposures associated with hookah smoking relative to cigarette smoking and to determine associations between this knowledge and hookah smoking outcomes. Students (N = 852) at the University of Florida were randomly sampled via e-mail to obtain information on demographics, hookah smoking behavior and knowledge of five exposures (e.g. tar and nicotine). Multivariable logistic regression models assessed independent associations between knowledge and hookah smoking outcomes. Of the five factual knowledge items asked, 475 (55.8%) of the respondents answered none correctly. In multivariable models, correct responses to any knowledge items were not associated with lower odds of hookah smoking or susceptibility to hookah smoking in the future. Although college students are largely unaware of the toxicant exposures associated with hookah smoking, there is little association between knowledge and hookah smoking behavior. C1 [Nuzzo, Erin; Shensa, Ariel; Fine, Michael J.; Primack, Brian A.] Univ Pittsburgh, Sch Educ, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. [Kim, Kevin H.] Univ Pittsburgh, Sch Educ, Dept Educ Psychol, Pittsburgh, PA 15260 USA. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15213 USA. [Barnett, Tracey E.] Univ Florida, Dept Behav Sci & Community Hlth, Gainesville, FL 32610 USA. [Cook, Robert] Univ Florida, Dept Epidemiol, Gainesville, FL 32610 USA. [Primack, Brian A.] Univ Pittsburgh, Sch Med, Dept Pediat, Div Adolescent Med, Pittsburgh, PA 15213 USA. RP Primack, BA (reprint author), Univ Pittsburgh, Sch Educ, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. EM bprimack@pitt.edu FU NCI NIH HHS [K07 CA114315, R01 CA140150, R01-CA140150] NR 38 TC 23 Z9 23 U1 2 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD FEB PY 2013 VL 28 IS 1 BP 92 EP 100 DI 10.1093/her/cys095 PG 9 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 079EF UT WOS:000314152400009 PM 22987864 ER PT J AU Richter, LL Miller, RM Hillman, JD Chiu, MW AF Richter, Laura L. Miller, Robert M. Hillman, Joseph D. Chiu, Melvin W. TI Bilateral thick crusts on the legs SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Editorial Material ID DERMATITIS NEGLECTA AB What is your diagnosis? C1 [Chiu, Melvin W.] Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Dept Med,Ctr Hlth Sci 52 121, Los Angeles, CA 90095 USA. [Hillman, Joseph D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Miller, Robert M.; Chiu, Melvin W.] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. RP Chiu, MW (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Dept Med,Ctr Hlth Sci 52 121, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM mchiu@mednet.ucla.edu NR 10 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD FEB PY 2013 VL 52 IS 2 BP 133 EP 135 DI 10.1111/j.1365-4632.2012.05678.x PG 3 WC Dermatology SC Dermatology GA 077ZW UT WOS:000314068900002 PM 23347299 ER PT J AU Wasse, H Zhang, R Johansen, KL Kutner, N AF Wasse, Haimanot Zhang, Rebecca Johansen, Kirsten L. Kutner, Nancy TI ESRD patients using permanent vascular access report greater physical activity compared with catheter users SO INTERNATIONAL UROLOGY AND NEPHROLOGY LA English DT Article DE Dialysis vascular access; Physical function ID STAGE RENAL-DISEASE; AMBULATORY PATIENTS; DIALYSIS PATIENTS; HEMODIALYSIS; MORTALITY; SURVIVAL; EXERCISE; WAVE-2 AB Low levels of physical activity among end-stage renal disease (ESRD) patients are associated with increased risk of hospitalization and mortality, and contributors to low activity levels are important to identify. Among hemodialysis (HD) patients, use of a central venous catheter (CVC) might impede physical activity due to factors such as infection or patient fear of catheter dislodgement. This Comprehensive Dialysis Study surveyed patients who had recently started regular dialysis. Physical activity level was ascertained using responses to the Human Activity Profile (HAP) provided by 1,458 HD participants. We examined the association of vascular access type with patients' scores on HAP subscales measuring self-care and leg effort, two dimensions that are especially important for daily living. 32.6% of patients used an arteriovenous fistula (AVF), 11.5% used an arteriovenous graft, 51.8% used a CVC, and 4.1% used a CVC with another maturing access. Patients' self-care and leg effort scores differed by vascular access type and receipt of early nephrology care, and the mean self-care score of AVF users who received early care was similar to the mean score reported for healthy adults. Reported levels of self-care and leg effort activity were higher among incident HD patients using an AVF compared to those using a CVC. Future research should examine whether reinforcing the importance of regular physical activity in the pre-dialysis period, as well as wider early use of AVF in the HD population, may improve physical activity levels among ESRD patients. C1 [Wasse, Haimanot] Emory Univ, Sch Med, Div Nephrol, WMB, Atlanta, GA 30322 USA. [Wasse, Haimanot; Zhang, Rebecca; Johansen, Kirsten L.; Kutner, Nancy] Emory Univ, Rehabil Qual Life Special Studies Ctr, US Renal Data Syst, Atlanta, GA 30322 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA. RP Wasse, H (reprint author), Emory Univ, Sch Med, Div Nephrol, WMB, Room 338,1639 Pierce Dr, Atlanta, GA 30322 USA. EM hwasse@emory.edu FU National Institutes of Health [K23 DK65634, HHSN267200715004C, N01-DK-7-5004] FX The human activity profile was reproduced for use in the CDS with permission of the author, David Daughton. This work was supported in part by a National Institutes of Health Career Development Award K23 DK65634 (Haimanot Wasse) and by National Institutes of Health contract HHSN267200715004C, ADB No. N01-DK-7-5004. NR 15 TC 1 Z9 1 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0301-1623 J9 INT UROL NEPHROL JI Int. Urol. Nephrol. PD FEB PY 2013 VL 45 IS 1 BP 199 EP 205 DI 10.1007/s11255-012-0137-9 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 081CD UT WOS:000314292500030 PM 22350837 ER PT J AU Aston-Mourney, K Zraika, S Udayasankar, J Subramanian, SL Green, PS Kahn, SE Hull, RL AF Aston-Mourney, Kathryn Zraika, Sakeneh Udayasankar, Jayalakshmi Subramanian, Shoba L. Green, Pattie S. Kahn, Steven E. Hull, Rebecca L. TI Matrix Metalloproteinase-9 Reduces Islet Amyloid Formation by Degrading Islet Amyloid Polypeptide SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-CELL APOPTOSIS; DIABETES-MELLITUS; TRANSGENIC MOUSE; PANCREATIC-ISLETS; FIBRIL FORMATION; HUMAN AMYLIN; PEPTIDE; MICE; INSULIN; HYPERGLYCEMIA AB Deposition of islet amyloid polypeptide ( IAPP) as amyloid is a pathological hallmark of the islet in type 2 diabetes, which is toxic to beta-cells. We previously showed that the enzyme neprilysin reduces islet amyloid deposition and thereby reduces beta-cell apoptosis, by inhibiting fibril formation. Two other enzymes, matrix metalloproteinase ( MMP)-2 and MMP-9, are extracellular gelatinases capable of degrading another amyloidogenic peptide, A beta, the constituent of amyloid deposits in Alzheimer disease. We therefore investigated whether MMP-2 and MMP-9 play a role in reducing islet amyloid deposition. MMP-2 and MMP-9 mRNA were present in mouse islets but only MMP-9 activity was detectable. In an islet culture model where human IAPP ( hIAPP) transgenic mouse islets develop amyloid but nontransgenic islets do not, a broad spectrum MMP inhibitor ( GM6001) and an MMP-2/9 inhibitor increased amyloid formation and the resultant beta-cell apoptosis. In contrast, a specific MMP-2 inhibitor had no effect on either amyloid deposition or beta-cell apoptosis. Mass spectrometry demonstrated that MMP-9 degraded amyloidogenic hIAPP but not nonamyloidogenic mouse IAPP. Thus, MMP-9 constitutes an endogenous islet protease that limits islet amyloid deposition and its toxic effects via degradation of hIAPP. Because islet MMP-9 mRNA levels are decreased in type 2 diabetic subjects, islet MMP-9 activity may also be decreased in human type 2 diabetes, thereby contributing to increased islet amyloid deposition and beta-cell loss. Approaches to increase islet MMP-9 activity could reduce or prevent amyloid deposition and its toxic effects in type 2 diabetes. C1 [Aston-Mourney, Kathryn; Zraika, Sakeneh; Udayasankar, Jayalakshmi; Subramanian, Shoba L.; Green, Pattie S.; Kahn, Steven E.; Hull, Rebecca L.] Vet Affairs Puget Sound Hlth Care Syst, Washington, WA 98108 USA. [Aston-Mourney, Kathryn; Zraika, Sakeneh; Udayasankar, Jayalakshmi; Subramanian, Shoba L.; Green, Pattie S.; Kahn, Steven E.; Hull, Rebecca L.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Aston-Mourney, Kathryn] Deakin Univ, Sch Med, Metab Res Unit, Waurn Ponds, Vic 3216, Australia. RP Hull, RL (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way 151, Seattle, WA 98108 USA. EM rhull@u.washington.edu OI Aston-Mourney, Kathryn/0000-0003-1412-6715; Kahn, Steven/0000-0001-7307-9002; Hull, Rebecca/0000-0001-9690-4087 FU Department of Veterans Affairs, Veterans Affairs Puget Sound Health Care System (Seattle, WA); National Institutes of Health [DK-075998, DK-074404, DK-080945, DK-017047, DK-007247]; American Diabetes Association Mentor-Based fellowship; University of Washington McAbee fellowship; Deakin University Alfred Deakin Postdoctoral research fellowship; Juvenile Diabetes Research Foundation FX This work was supported, in whole or in part, by the Department of Veterans Affairs, Veterans Affairs Puget Sound Health Care System (Seattle, WA) and National Institutes of Health Grants DK-075998 (to S. E. K.), DK-074404 (to R. L. H.), DK-080945 (to S. Z.), DK-017047 (to the Cellular and Molecular Imaging Core of the University of Washington Diabetes Research Center), and DK-007247.; Supported by an American Diabetes Association Mentor-Based fellowship, the University of Washington McAbee fellowship, and a Deakin University Alfred Deakin Postdoctoral research fellowship.; Supported by a Juvenile Diabetes Research Foundation postdoctoral fellowship. NR 36 TC 12 Z9 13 U1 0 U2 22 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 1 PY 2013 VL 288 IS 5 BP 3553 EP 3559 DI 10.1074/jbc.M112.438457 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 082NE UT WOS:000314397900060 PM 23229548 ER PT J AU Bloch, MJ Basile, JN AF Bloch, Michael J. Basile, Jan N. TI Analysis of Recent Papers in Hypertension Treatment of Obstructive Sleep Apnea With Continuous Positive Airway Pressure Appears to Decrease the Incidence of Incident Hypertension SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article ID ASSOCIATION C1 [Bloch, Michael J.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Seinsheimer Cardiovasc Hlth Program, Div Gen Internal Med Geriatr, Charleston, SC 29425 USA. [Bloch, Michael J.] Univ Nevada, Sch Med, MedSch Associates N, Dept Internal Med, Reno, NV 89520 USA. RP Bloch, MJ (reprint author), Univ Nevada, Sch Med, MedSch Associates N, Dept Internal Med, 1500 E 2nd St,Suite 302, Reno, NV 89520 USA. EM mbloch@aol.com NR 4 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD FEB PY 2013 VL 15 IS 2 BP 85 EP 87 DI 10.1111/jch.12041 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 075PX UT WOS:000313900100001 PM 23339724 ER PT J AU Wiederhold, NP Najvar, LK Bocanegra, R Kirkpatrick, WR Patterson, TF Thornton, CR AF Wiederhold, Nathan P. Najvar, Laura K. Bocanegra, Rosie Kirkpatrick, William R. Patterson, Thomas F. Thornton, Christopher R. TI Interlaboratory and Interstudy Reproducibility of a Novel Lateral-Flow Device and Influence of Antifungal Therapy on Detection of Invasive Pulmonary Aspergillosis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID GALACTOMANNAN ENZYME-IMMUNOASSAY; NEUTROPENIC PATIENTS; RAPID SERODIAGNOSIS; MURINE MODEL; DIAGNOSIS; ASSAY; HIV; ANTIBODIES; FUMIGATUS AB Interest in lateral-flow devices (LFDs) as potential point-of-care assays for the diagnosis of infectious diseases has increased. Our objective was to evaluate the interlaboratory and interstudy reproducibility and the effects of antifungal therapy on an LFD developed for invasive pulmonary aspergillosis (IPA) detection. An established neutropenic guinea pig model of IPA caused by Aspergillus fumigatus was used. At predetermined time points (1 h and 3, 5, and 7 days postinoculation), blood and bronchoalveolar lavage (BAL) fluid were collected from infected and uninfected animals. In a separate experiment, guinea pigs were treated with posaconazole (10 mg/kg of body weight orally [p.o.] twice a day [BID]), voriconazole (10 mg/kg p.o. BID), liposomal amphotericin B (10 mg/kg intraperitoneally [i.p.] once a day [QD]), or caspofungin (2 mg/kg i.p. QD), and samples were collected on days 7 and 11. Each laboratory independently evaluated the IgG monoclonal antibody-based LFD. Galactomannan and (1 -> 3)-beta-D-glucan were also measured using commercially available kits. Good interlaboratory agreement was observed with the LFD, as the results for 97% (32/33) of the serum and 78.8% (26/33) of the BAL fluid samples from infected animals were in agreement. Good interstudy agreement was also observed. The serum sensitivity of each surrogate-marker assay was reduced in animals treated with antifungals. In contrast, these markers remained elevated within the BAL fluids of treated animals, which was consistent with the fungal burden and histopathology results. These results demonstrate that the LFD assay is reproducible between different laboratories and studies. However, the sensitivity of this assay and other markers of IPA may be reduced with serum in the presence of antifungal therapy. C1 [Wiederhold, Nathan P.; Najvar, Laura K.; Bocanegra, Rosie; Kirkpatrick, William R.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Wiederhold, Nathan P.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Najvar, Laura K.; Bocanegra, Rosie; Kirkpatrick, William R.; Patterson, Thomas F.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Thornton, Christopher R.] Univ Exeter, Exeter, Devon, England. RP Wiederhold, NP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. EM wiederholdn@uthscsa.edu OI Wiederhold, Nathan/0000-0002-2225-5122 FU National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) [N01-AI-30041, HHSN272201000038I/HHSN27200002-task order A05, R21AI085393]; Pfizer; Schering-Plough; Merck; Basilea; Astellas FX This work was supported by contracts from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID; contract numbers N01-AI-30041 and HHSN272201000038I/HHSN27200002-task order A05) to T. F. Patterson and NIH/NIAID grant R21AI085393 to N. P. Wiederhold and C. R. Thornton.; N.P.W. has received research support from Pfizer, Schering-Plough, Merck, Basilea, and Astellas and has served on advisory boards for Merck, Astellas, Toyama, and Viamet. T.F.P. has received research grants to the UT Health Science Center at San Antonio from Astellas, Basilea, Merck, and Pfizer and has served as a consultant for Astellas, Basilea, Merck, Pfizer, and Toyama. C.R.T. has received support from Pfizer. None of the other authors has a conflict of interest. NR 26 TC 28 Z9 30 U1 0 U2 14 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD FEB PY 2013 VL 51 IS 2 BP 459 EP 465 DI 10.1128/JCM.02142-12 PG 7 WC Microbiology SC Microbiology GA 078OH UT WOS:000314108000012 PM 23175252 ER PT J AU Egede, LE Lynch, CP Gebregziabher, M Hunt, KJ Echols, C Gilbert, GE Mauldin, PD AF Egede, Leonard E. Lynch, Cheryl P. Gebregziabher, Mulugeta Hunt, Kelly J. Echols, Carrae Gilbert, Gregory E. Mauldin, Patrick D. TI Differential Impact of Longitudinal Medication Non-Adherence on Mortality by Race/Ethnicity among Veterans with Diabetes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE medication non-adherence; veterans; diabetes; mortality; race/ethnicity ID RACIAL-DIFFERENCES; ADHERENCE; ADULTS; HEALTH; POPULATION; COHORT; HOSPITALIZATION; PREVALENCE; MELLITUS; US AB To examine the differential effect of medication non-adherence over time on all-cause mortality by race/ethnicity. Data on a longitudinal cohort of veterans with type 2 diabetes was examined. The main outcome was time to death. Primary independent variables were race/ethnicity and mean medication possession ratio (MPR) categorized into quintiles over the study period. Cox regression was used to model the association between time to death and MPR quintiles and race/ethnicity, adjusting for relevant covariates. The cohort of 629,563 veterans was followed for 5 years. After adjusting for all covariates, the hazard ratios (HR) for subjects in the lowest versus highest MPR quintile was 12.21 (95 % CI 11.89, 12.55) for non-Hispanic white (NHW), 10.01 (95 % CI 9.18, 10.91) for non-Hispanic black (NHB), 12.65 (95 % CI 11.10, 14.43) for Hispanic and 10.41 (95 % CI 9.06, 11.96) for Other race veterans. Furthermore, type of diabetes therapy (oral versus insulin) maintained a significant relationship with mortality that varied by racial/ethnic group. This study demonstrates the differential impact of medication non-adherence on mortality by race. It also demonstrates that type of diabetes therapy (insulin with or without oral agents) is associated with mortality and varies by racial/ethnic group. C1 [Egede, Leonard E.; Lynch, Cheryl P.; Gebregziabher, Mulugeta; Hunt, Kelly J.; Echols, Carrae; Gilbert, Gregory E.] Ralph H Johnson Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC 29425 USA. [Egede, Leonard E.; Lynch, Cheryl P.; Mauldin, Patrick D.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta; Hunt, Kelly J.] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Mauldin, Patrick D.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Mauldin, Patrick D.] Div Gen Internal Med & Geriatr, Charleston, SC USA. RP Egede, LE (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, POB 250593, Charleston, SC 29425 USA. EM Egedel@musc.edu RI Gilbert, Gregory/C-7735-2016 OI Gilbert, Gregory/0000-0003-0879-5496; Gebregziabher, Mulugeta/0000-0002-4826-481X FU VHA Health Services Research and Development (HSRD) program [IIR-06-219] FX This study was supported by grant #IIR-06-219 funded by the VHA Health Services Research and Development (HSR&D) program. The funding agency did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The manuscript represents the views of the authors and not those of the VA or HSR&D. All authors had access to the data and contributed to the manuscript NR 22 TC 13 Z9 13 U1 2 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2013 VL 28 IS 2 BP 208 EP 215 DI 10.1007/s11606-012-2200-8 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 077ZM UT WOS:000314067900011 PM 22948932 ER PT J AU Barnes, DE Mehta, KM Boscardin, WJ Fortinsky, RH Palmer, RM Kirby, KA Landefeld, CS AF Barnes, Deborah E. Mehta, Kala M. Boscardin, W. John Fortinsky, Richard H. Palmer, Robert M. Kirby, Katharine A. Landefeld, C. Seth TI Prediction of Recovery, Dependence or Death in Elders Who Become Disabled During Hospitalization SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE functional status; disability; mortality; hospitalization; prognosis ID ACUTE MEDICAL ILLNESS; FUNCTIONAL DECLINE; OLDER-ADULTS; PROGNOSTIC INDEX; 1-YEAR MORTALITY; SCREENING TOOLS; ACUTE-CARE; RISK; VALIDATION; OUTCOMES AB Many older adults become dependent in one or more activities of daily living (ADLs: dressing, bathing, transferring, eating, toileting) when hospitalized, and their prognosis after discharge is unclear. To develop a prognostic index to estimate one-year probabilities of recovery, dependence or death in older hospitalized patients who are discharged with incident ADL dependence. Retrospective cohort study. 449 adults aged a parts per thousand yen 70 years hospitalized for acute illness and discharged with incident ADL dependence. Potential predictors included demographics (age, sex, race, education, marital status), functional measures (ADL dependencies, instrumental activities of daily living [IADL] dependencies, walking ability), chronic conditions (e.g., congestive heart failure, dementia, cancer), reason for admission (e.g., neurologic, cardiovascular), and laboratory values (creatinine, albumin, hematocrit). Multinomial logistic regression was used to develop a prognostic index for estimating the probabilities of recovery, disability or death over 1 year. Discrimination of the index was assessed for each outcome based on the c statistic. During the year following hospitalization, 36 % of patients recovered, 27 % remained dependent and 37 % died. Key predictors of recovery, dependence or death were age, sex, number of IADL dependencies 2 weeks prior to admission, number of ADL dependencies at discharge, dementia, cancer, number of other chronic conditions, reason for admission, and creatinine levels. The final prognostic index had good to excellent discrimination for all three outcomes based on the c statistic (recovery: 0.81, dependence: 0.72, death: 0.78). This index accurately estimated the probabilities of recovery, dependence or death in adults aged 70 years or older who were discharged with incident disability following hospitalization. This tool may be useful in clinical settings to guide care discussions and inform decision-making related to post-hospitalization care. C1 [Barnes, Deborah E.; Boscardin, W. John; Kirby, Katharine A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Barnes, Deborah E.; Boscardin, W. John; Kirby, Katharine A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Mehta, Kala M.] Stanford Univ, Stanford, CA 94305 USA. [Fortinsky, Richard H.] Univ Connecticut, Sch Med, Farmington, CT USA. [Palmer, Robert M.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Landefeld, C. Seth] Univ Alabama Birmingham, Birmingham, AL USA. RP Barnes, DE (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. EM Deborah.barnes@ucsf.edu FU National Institutes of Health (Landefeld) [R01 AG029233, AG10418]; S. D. Bechtel, Jr. Foundation FX Support for this study was provided by the National Institutes of Health (Landefeld: R01 AG029233, AG10418) and the S. D. Bechtel, Jr. Foundation. NR 44 TC 19 Z9 19 U1 2 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2013 VL 28 IS 2 BP 261 EP 268 DI 10.1007/s11606-012-2226-y PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 077ZM UT WOS:000314067900018 PM 23054919 ER PT J AU Eckstrom, E Feeny, DH Walter, LC Perdue, LA Whitlock, EP AF Eckstrom, Elizabeth Feeny, David H. Walter, Louise C. Perdue, Leslie A. Whitlock, Evelyn P. TI Individualizing Cancer Screening in Older Adults: A Narrative Review and Framework for Future Research SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE older adults; cancer screening; patient preferences ID SERVICES TASK-FORCE; QUALITY-OF-LIFE; CLINICAL DECISION-MAKING; COLORECTAL-CANCER; BREAST-CANCER; MAMMOGRAPHY; WOMEN; PREVENTION; GUIDELINES; SURVIVAL AB Older adults often have multiple chronic conditions that may decrease additional life expectancy. Research evaluating the benefits and harms of screening must include consideration of competing morbidities and patient heterogeneity (beyond age), potentially increased harms of screening, and patient preferences. Other areas in need of additional research include the lack of evidence for older adults on the harms of screening tests; the overdiagnosis of disease; the burden of disease labeling; the effects of inaccurate test results; the harms of disease treatment; and harms related to prioritization of healthcare (e.g., for a particular patient, lifestyle counseling may be more important than screening). Nontraditional outcomes, such as the effects on family caregivers, are also relevant. Studies comparing trajectories of quality-adjusted survival with and without screening to assess net benefit are typically lacking. There is little evidence on the preferences of older adults for deciding whether to be screened, the process of being screened, and the health states associated with being or not being screened. To enhance the quality and quantity of evidence, older adults need to be enrolled in screening trials and clinical studies. Measures of functional status and health-related quality of life (HRQL) need to be included in trials, registries, and cohort studies. This article addresses these challenges, and presents a framework for what research is needed to better inform screening decisions in older adults. C1 [Eckstrom, Elizabeth] Oregon Hlth & Sci Univ, Dept Med, Div Gen Internal Med & Geriatr, Portland, OR 97201 USA. [Feeny, David H.; Perdue, Leslie A.; Whitlock, Evelyn P.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. [Walter, Louise C.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [Walter, Louise C.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Eckstrom, E (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Gen Internal Med Geriatr, 3181 SW Sam Jackson Pk Rd,L475, Portland, OR 97239 USA. EM eckstrom@ohsu.edu FU Agency for Health Care Research; National Cancer Institute; National Cancer Institute [R01 CA134425]; National Institute on Aging [K24AG041180] FX Agency for Health Care Research; National Cancer Institute (Dr. Eckstrom, Dr. Feeny, and Ms. Perdue). Dr. Walter's effort was supported by the National Cancer Institute (grant number R01 CA134425) and the National Institute on Aging (grant number K24AG041180). NR 44 TC 7 Z9 7 U1 0 U2 19 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2013 VL 28 IS 2 BP 292 EP 298 DI 10.1007/s11606-012-2227-x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 077ZM UT WOS:000314067900021 PM 23054920 ER PT J AU Chiovaro, J AF Chiovaro, Joe TI Haunted by the Unread SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 Portland VA Med Ctr, Div Hosp Med, Dept Med, Portland, OR 97239 USA. RP Chiovaro, J (reprint author), Portland VA Med Ctr, Div Hosp Med, Dept Med, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM jchiovaro@gmail.com 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2013 VL 28 IS 2 BP 326 EP 327 DI 10.1007/s11606-012-2143-0 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 077ZM UT WOS:000314067900029 PM 22752590 ER PT J AU Hirachan, P Polnaszek, NM Martinez, M Wagner, B AF Hirachan, P. Polnaszek, N. M. Martinez, M. Wagner, B. TI ACUTE KIDNEY INJURY FOLLOWING RETROGRADE PYELOGRAM SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 21-23, 2013 CL New Orleans, LA SP Amer Federat Med Res, So Reg C1 [Hirachan, P.; Polnaszek, N. M.; Martinez, M.; Wagner, B.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Wagner, B.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2013 VL 61 IS 2 MA 258 BP 445 EP 446 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 079FO UT WOS:000314156100273 ER PT J AU Sewell, J Wagner, B AF Sewell, J. Wagner, B. TI NEPHROGENIC SYSTEMIC FIBROSIS: REDOX SENSITIVITY, DERMAL CCR7-EXPRESSING FIBROCYTES, AND EVIDENCE OF PULMONARY INVOLVEMENT IN A RAT MODEL SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 21-23, 2013 CL New Orleans, LA SP Amer Federat Med Res, So Reg C1 [Sewell, J.; Wagner, B.] Univ Texas Hlth Care Syst San Antonio, San Antonio, TX USA. [Wagner, B.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2013 VL 61 IS 2 MA 271 BP 449 EP 449 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 079FO UT WOS:000314156100286 ER PT J AU Jessee, R Weaver, F Chin, A Burns, S Svircev, J Hoenig, H Heggeness, M Carbone, L AF Jessee, R. Weaver, F. Chin, A. Burns, S. Svircev, J. Hoenig, H. Heggeness, M. Carbone, L. TI MANAGEMENT OF LOWER EXTREMITY FRACTURES IN MEN WITH SPINAL CORD INJURIES SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 21-23, 2013 CL New Orleans, LA SP Amer Federat Med Res, So Reg C1 [Jessee, R.; Carbone, L.] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA. [Weaver, F.; Chin, A.] Jr VA Hosp, Hines, IL USA. [Weaver, F.] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. [Burns, S.; Svircev, J.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Burns, S.; Svircev, J.] Univ Washington, Seattle, WA 98195 USA. [Hoenig, H.] Durham VAMC, Durham, NC USA. [Heggeness, M.] VA Med Ctr, Houston, TX USA. [Heggeness, M.] Baylor Coll Med, Houston, TX 77030 USA. [Carbone, L.] Memphis VA Med Ctr, Memphis, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2013 VL 61 IS 2 MA 297 BP 456 EP 456 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 079FO UT WOS:000314156100312 ER PT J AU Sewell, J Wagner, B AF Sewell, J. Wagner, B. TI NEPHROGENIC SYSTEMIC FIBROSIS: REDOX SENSITIVITY, DERMAL CCR7-EXPRESSING FIBROCYTES, AND EVIDENCE OF PULMONARY INVOLVEMENT IN A RAT MODEL SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 21-23, 2013 CL New Orleans, LA SP Amer Federat Med Res C1 [Sewell, J.; Wagner, B.] Univ Texas Hlth Care Syst San Antonio, San Antonio, TX USA. [Wagner, B.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2013 VL 61 IS 2 MA 393 BP 484 EP 484 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 079FO UT WOS:000314156100408 ER PT J AU Alge, J Karakala, N Neely, B Janech, M Arthur, J AF Alge, J. Karakala, N. Neely, B. Janech, M. Arthur, J. TI URINARY ANGIOTENSINOGEN: A PROGNOSTIC BIOMARKER OF ACUTE KIDNEY INJURY SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 21-23, 2013 CL New Orleans, LA SP Amer Federat Med Res, So Reg C1 [Alge, J.; Karakala, N.; Neely, B.; Janech, M.; Arthur, J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Janech, M.; Arthur, J.] Ralph H Johnson VAMC, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2013 VL 61 IS 2 MA 504 BP 516 EP 516 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 079FO UT WOS:000314156100519 ER PT J AU Bhensdadia, N Hunt, K Lopes-Virella, M Tucker, M Neely, B Janech, M Arthur, J AF Bhensdadia, N. Hunt, K. Lopes-Virella, M. Tucker, M. Neely, B. Janech, M. Arthur, J. TI URINE HAPTOGLOBIN TO CREATININE RATIO PREDICTS WORSENING RENAL FUNCTIONS IN PATIENTS WITH TYPE 2 DIABETES SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 21-23, 2013 CL New Orleans, LA SP Amer Federat Med Res, So Reg C1 [Bhensdadia, N.; Hunt, K.; Lopes-Virella, M.; Tucker, M.; Neely, B.; Janech, M.; Arthur, J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Lopes-Virella, M.; Janech, M.; Arthur, J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2013 VL 61 IS 2 MA 506 BP 517 EP 517 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 079FO UT WOS:000314156100521 ER PT J AU Davis, B Stewart, EH Clemans-Taylor, BL Centor, R Estrada, C AF Davis, B. Stewart, E. H. Clemans-Taylor, B. L. Centor, R. Estrada, C. TI A META-ANALYSIS OF THE RAPID ANTIGEN STREPTOCOCCUS TEST SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 21-23, 2013 CL New Orleans, LA SP Amer Federat Med Res, So Reg C1 [Davis, B.; Stewart, E. H.; Clemans-Taylor, B. L.; Centor, R.; Estrada, C.] Univ Alabama Birmingham, Birmingham, AL USA. [Estrada, C.] Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2013 VL 61 IS 2 MA 527 BP 523 EP 523 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 079FO UT WOS:000314156100542 ER PT J AU Bryan, T Snyder, E Estrada, C Castiglioni, A AF Bryan, T. Snyder, E. Estrada, C. Castiglioni, A. TI EDUCATION IN DELIVERING PATIENT-CENTERED CARE: PROVIDER COMFORT LEVEL IN COUNSELING WOMEN AGES 40-49 REGARDING BREAST CANCER SCREENING OPTIONS SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 21-23, 2013 CL New Orleans, LA SP Amer Federat Med Res, So Reg C1 [Bryan, T.; Snyder, E.; Estrada, C.] Univ Alabama Birmingham, Birmingham, AL USA. [Castiglioni, A.] Univ Cent Florida, Coll Med, Tampa, FL USA. [Bryan, T.; Snyder, E.; Estrada, C.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2013 VL 61 IS 2 MA 528 BP 524 EP 524 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 079FO UT WOS:000314156100543 ER PT J AU Miller, AN Barei, DP Iaquinto, JM Ledoux, WR Beingessner, DM AF Miller, Anna N. Barei, David P. Iaquinto, Joseph M. Ledoux, William R. Beingessner, Daphne M. TI Iatrogenic Syndesmosis Malreduction via Clamp and Screw Placement SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE Ankle; syndesmosis; iatrogenic; malreduction ID ANKLE FRACTURES; OPERATIVE TREATMENT; FIXATION; STABILIZATION; INJURIES; REMOVAL AB Objectives: The purpose of this study was to assess the impact of variations in angulation of clamp placement to hold syndesmotic reduction and how subsequent syndesmotic screw placement affects malreduction of the syndesmosis. We hypothesized that an anatomic syndesmosis reduction cannot be reliably achieved with a clamp alone; and, inaccurate placement of intraoperative clamps and trans-syndesmotic screws after reduction can malreduce the ankle syndesmosis. Methods: After computed tomography scanning of the intact limbs, 14 cadaver legs were dissected; the syndesmosis was completely disrupted in all. Using planned drill holes, clamps were first placed at 0 degrees, 15 degrees, and 30 degrees angles from the fibula, then separate posterolateral, followed by lateral, screws were placed. After each intervention, the limb had a computed tomography scan so the fibular reduction could be evaluated precisely. Results: Clamps placed at 15 degrees and 30 degrees significantly displaced the fibula in external rotation and caused significant overcompression of the syndesmosis. Thirty-degree lateral screws caused significant anteromedial displacement, external rotation, and overcompression of the syndesmosis. The 15 degrees posterolateral screws also caused significant external rotation and overcompression of the syndesmosis. Conclusions: Our study demonstrates that intraoperative clamping and fixation can cause statistically significant malreduction of the syndesmosis. This article should alert clinicians that clamp and screw placement can cause iatrogenic malreduction of the syndesmosis and make them aware that these dangers occur with specific clamp and screw angles in particular. C1 [Miller, Anna N.] Wake Forest Univ, Bowman Gray Sch Med, Dept Orthopaed Surg, Winston Salem, NC 27157 USA. [Barei, David P.; Beingessner, Daphne M.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [Barei, David P.; Ledoux, William R.; Beingessner, Daphne M.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. [Iaquinto, Joseph M.; Ledoux, William R.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Seattle, WA USA. [Ledoux, William R.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. RP Miller, AN (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Orthopaed Surg, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM anmiller@wakehealth.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714; Miller, Anna/0000-0002-7056-8502 FU University of Washington Department of Orthopaedic Surgery; Department of Veterans Affairs Rehabilitation Research and Development Center of Excellence FX Supported by the University of Washington Department of Orthopaedic Surgery and the Department of Veterans Affairs Rehabilitation Research and Development Center of Excellence. NR 22 TC 22 Z9 24 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD FEB PY 2013 VL 27 IS 2 BP 100 EP 106 DI 10.1097/BOT.0b013e31825197cb PG 7 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 077VV UT WOS:000314058300013 PM 22549032 ER PT J AU Hosain, GMM Latini, DM Kauth, M Goltz, HH Helmer, DA AF Hosain, G. M. Monawar Latini, David M. Kauth, Michael Goltz, Heather Honore Helmer, Drew A. TI Sexual Dysfunction among Male Veterans Returning from Iraq and Afghanistan: Prevalence and Correlates SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE Sexual Dysfunction; Veterans; Post-Traumatic Stress Disorder; Prevalence; Male; Young ID POSTTRAUMATIC-STRESS-DISORDER; MALE ERECTILE DYSFUNCTION; DEPRESSIVE SYMPTOMS; UNITED-STATES; INTIMATE-RELATIONSHIPS; WAR VETERANS; MEN; HYPERTENSION; SATISFACTION; PREDICTORS AB Introduction. Sexual dysfunction (SD) is not well described in the Iraq/Afghanistan veteran population despite high prevalence of multiple risk factors for this issue. Aim. To estimate the prevalence and examine the association of various sociodemographic, mental health, comorbid conditions and life style factors with sexual dysfunction in Iraq/Afghanistan veterans. Methods. This exploratory cross-sectional study was conducted using data from the VA administrative database. A total of 4,755 Iraq/Afghanistan veterans were identified who sought treatment from the Michael E. DeBakey Veterans Affairs Medical Center inpatient and outpatient clinic between September 2007 and August 2009. Main Outcome Measures. Sexual dysfunction was determined by ICD9-CM codes related to sexual health issues and/or by specific medications, primarily phosphodiesterase-5 inhibitors (PDE5i), prescribed for erectile dysfunction. Results. The overall prevalence of sexual dysfunction was 5.5% (N = 265). By age category, it was 3.6% (N = 145) for Iraq/Afghanistan veterans aged 1840 years and 15.7% (N = 120) for Iraq/Afghanistan veterans aged > 40 years, respectively. A multivariate logistic-regression model revealed that annual income, marital status, post-traumatic stress disorder, and hypertension were significant risk factors of SD (all P < 0.05) among younger Iraq/Afghanistan veterans, whereas among the older Iraq/Afghanistan veterans, being African American and having PTSD and hypertension were significant risk factors of SD (all P < 0.05). There was marked discrepancy between documented erectile dysfunction and prescription of a PDE5i. Conclusions. These data demonstrate that a significant proportion of Iraq/Afghanistan veterans have SD and that the risk factors differ between younger and older veterans. Our findings also suggest that SD is likely under-coded. To better identify the scope of the problem, systematic screening for sexual dysfunction may be appropriate perhaps as part of an initial post-deployment health evaluation. Hosain GMM, Latini DM, Kauth M, Goltz HH, and Helmer DA. Sexual dysfunction among male veterans returning from Iraq and Afghanistan: Prevalence and correlates. J Sex Med 2013;10:516-523. C1 [Hosain, G. M. Monawar; Latini, David M.; Kauth, Michael; Goltz, Heather Honore] Michael E DeBakey Vet Affairs Med Ctr 152, Houston VA HSR&D Ctr Excellence, Houston, TX 77030 USA. [Hosain, G. M. Monawar; Latini, David M.] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. [Kauth, Michael] S Cent Mental Illness Res Educ & Clin Ctr, Houston, TX USA. [Kauth, Michael] Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Goltz, Heather Honore] Univ Houston Downtown, Houston, TX USA. [Helmer, Drew A.] VA RRD Ctr Excellence & PrimeCare, Houston, TX USA. [Helmer, Drew A.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Hosain, GMM (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, Houston VA HSR&D Ctr Excellence, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM monawarhosain@gmail.com OI Latini, David/0000-0002-6161-4861; Goltz, Heather/0000-0002-2875-7764 FU NIH [K12 DK0083014] FX G. M. Monawar Hosain is working as an NIDDK K-12 scholar (NIH Grant K12 DK0083014). This work was also supported in part by the facilities and resources of the Houston VA HSR&D Center of Excellence (HFP90-020). The views expressed reflect those of the authors and not necessarily those of the Department of Veterans Affairs/Baylor College of Medicine. The NIH had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. NR 37 TC 21 Z9 21 U1 1 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD FEB PY 2013 VL 10 IS 2 BP 516 EP 523 DI 10.1111/j.1743-6109.2012.02978.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 078OC UT WOS:000314107400024 PM 23088675 ER PT J AU Fett, NM Teng, J Longley, BJ AF Fett, Nicole M. Teng, Joyce Longley, B. Jack TI Familial Urticaria Pigmentosa: Report of a Family and Review of the Role of KIT Mutations SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Review DE mastocytosis; urticarial pigmentosa; c-kit protooncogene; KIT tyrosine kinase ID GASTROINTESTINAL STROMAL TUMORS; C-KIT; GERMLINE MUTATION; PEDIATRIC MASTOCYTOSIS; CUTANEOUS MASTOCYTOSIS; DOMAIN MUTATIONS; DISEASE AB Cutaneous mastocytosis is a rare clinically heterogeneous disorder characterized by mast cell infiltration. Mastocytosis affects both children and adults and has been reported to occur in families. Recent data suggest that mutations in the c-kit protooncogene are causative of mastocytosis not only in adults but in children and familial cases as well; however, mutation analysis other than D816V is not widely available, making detection of causative mutations problematic. We present the case of a 33-year-old man with a 30-year history of persistent urticaria pigmentosa and his 2 affected children. Sequencing of KIT exons 8, 10, 11, and 17 was carried out on a skin biopsy specimen and mucosal swabs of the incident case and was negative for known KIT mutations. Additional work-up was deferred by the family. Presentation of this familial case of urticaria pigmentosa demonstrates the complexity of genetic evaluation in clinical settings. It suggests that mutations other than those reported in exons 8, 10, 11, and 17 may also result in familial mastocytosis. Presentation of this case also allows for review of the mechanism of action of causative KIT mutations and the recent literature supporting KIT mutations in childhood and familial mastocytosis. C1 [Fett, Nicole M.] Philadelphia VA Med Ctr, Dept Dermatol, Philadelphia, PA USA. [Fett, Nicole M.] Univ Penn, Dept Dermatol, Perelman Ctr Adv Med, Sch Med, Philadelphia, PA 19104 USA. [Teng, Joyce; Longley, B. Jack] Univ Wisconsin, Hosp & Clin, Dept Dermatol, Madison, WI 53792 USA. RP Fett, NM (reprint author), Univ Penn, Dept Dermatol, Perelman Ctr Adv Med, Sch Med, Suite 1-330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM nicole.fett@uphs.upenn.edu NR 22 TC 9 Z9 9 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD FEB PY 2013 VL 35 IS 1 BP 113 EP 116 DI 10.1097/DAD.0b013e31826330bf PG 4 WC Dermatology SC Dermatology GA 078MR UT WOS:000314103600024 PM 22892471 ER PT J AU Chlebicki, MP Safdar, N O'Horo, JC Maki, DG AF Chlebicki, Maciej Piotr Safdar, Nasia O'Horo, John Charles Maki, Dennis G. TI Preoperative chlorhexidine shower or bath for prevention of surgical site infection: A meta-analysis SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Review DE Antiseptic; Systematic review; Clean; Clean-contaminated ID WHOLE-BODY DISINFECTION; WOUND-INFECTION; CONTROLLED-TRIAL; PRISMA STATEMENT; POVIDONE-IODINE; CLINICAL-TRIALS; SURGERY; GLUCONATE; DETERGENT; PROPHYLAXIS AB Background: Chlorhexidine showering is frequently recommended as an important preoperative measure to prevent surgical site infection (SSI). However, the efficacy of this approach is uncertain. Methods: A search of electronic databases was undertaken to identify prospective controlled trials evaluating whole-body preoperative bathing with chlorhexidine versus placebo or no bath for prevention of SSI. Summary risk ratios were calculated using a DerSimonian-Laird random effects model and a Mantel-Haenzel dichotomous effects model. Results: Sixteen trials met inclusion criteria with a total of 17,932 patients: 7,952 patients received a chlorhexidine bath, and 9,980 patients were allocated to various comparator groups. Overall, 6.8% of patients developed SSI in the chlorhexidine group compared with 7.2% of patients in the comparator groups. Chlorhexidine bathing did not significantly reduce overall incidence of SSI when compared with soap, placebo, or no shower or bath (relative risk, 0.90; 95% confidence interval: 0.77-1.05, P = .19). Conclusions: Meta-analysis of available clinical trials suggests no appreciable benefit of preoperative whole-body chlorhexidine bathing for prevention of SSI. However, most studies omitted details of chlorhexidine application. Better designed trials with a specified duration and frequency of exposure to chlorhexidine are needed to determine whether preoperative whole-body chlorhexidine bathing reduces SSI. Copyright (C) 2013 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. C1 [Chlebicki, Maciej Piotr] Singapore Gen Hosp, Dept Infect Dis, Singapore, Singapore. [Safdar, Nasia] Univ Wisconsin, MFCB, Infect Dis Sect, Dept Med,Med Sch, Madison, WI 53705 USA. [Safdar, Nasia; Maki, Dennis G.] Univ Wisconsin Hosp & Clin, Infect Control Dept, Madison, WI 53792 USA. [Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [O'Horo, John Charles] Aurora Healthcare, Dept Grad Med Educ, Milwaukee, WI USA. RP Safdar, N (reprint author), Univ Wisconsin, MFCB, Infect Dis Sect, Dept Med,Med Sch, 1685 Highland Ave, Madison, WI 53705 USA. EM ns2@medicine.wisc.edu RI O'Horo, John/A-8787-2013; O'Horo, John/N-8681-2013 OI O'Horo, John/0000-0002-0880-4498; O'Horo, John/0000-0002-0880-4498 NR 42 TC 33 Z9 33 U1 0 U2 30 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD FEB PY 2013 VL 41 IS 2 BP 167 EP 173 DI 10.1016/j.ajic.2012.02.014 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 078NJ UT WOS:000314105500018 PM 22722008 ER PT J AU Ahmed, A Rich, MW Zile, M Sanders, PW Patel, K Zhang, Y Aban, IB Love, TE Fonarow, GC Aronow, WS Allman, RM AF Ahmed, Ali Rich, Michael W. Zile, Michael Sanders, Paul W. Patel, Kanan Zhang, Yan Aban, Inmaculada B. Love, Thomas E. Fonarow, Gregg C. Aronow, Wilbert S. Allman, Richard M. TI Renin-Angiotensin Inhibition in Diastolic Heart Failure and Chronic Kidney Disease SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Angiotensin-converting enzyme inhibitors; Angiotensin receptor blockers; Chronic kidney disease; Diastolic heart failure ID FUNCTIONAL RENAL-INSUFFICIENCY; CONVERTING-ENZYME-INHIBITION; PRESERVED EJECTION FRACTION; OLDER-ADULTS; SYSTOLIC FUNCTION; PROPENSITY SCORE; ATRIAL-FIBRILLATION; PRACTICE GUIDELINES; OUTCOMES; ASSOCIATION AB BACKGROUND: The role of renin-angiotensin inhibition in older patients with diastolic heart failure and chronic kidney disease remains unclear. METHODS: Of the 1340 patients (age >= 65 years) with diastolic heart failure (ejection fraction >= 45%) and chronic kidney disease (estimated glomerular filtration rate < 60 mL/min/1.73 m(2)), 717 received angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Propensity scores for the use of these drugs, estimated for each of the 1340 patients, were used to assemble a cohort of 421 pairs of patients, receiving and not receiving these drugs, who were balanced on 56 baseline characteristics. RESULTS: During more than 8 years of follow-up, all-cause mortality occurred in 63% and 69% of matched patients with chronic kidney disease receiving and not receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, respectively (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.70-0.97; P = .021). There was no association with heart failure hospitalization (HR, 0.98; 95% CI, 0.82-1.18; P = .816). Similar mortality reduction (HR, 0.81; 95% CI, 0.66-0.995; P = .045) occurred in a subgroup of matched patients with an estimated glomerular filtration rate less than 45 mL/min/1.73 m2. Among 207 pairs of propensity-matched patients without chronic kidney disease, the use of these drugs was not associated with mortality (HR, 1.03; 95% CI, 0.80-1.33; P = .826) or heart failure hospitalization (HR, 0.99; 95% CI, 0.76-1.30; P = .946). CONCLUSIONS: A discharge prescription for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with a significant reduction in all-cause mortality in older patients with diastolic heart failure and chronic kidney disease, including those with more advanced chronic kidney disease. Published by Elsevier Inc. The American Journal of Medicine (2013) 126, 150-161 C1 [Ahmed, Ali; Sanders, Paul W.; Patel, Kanan; Zhang, Yan; Aban, Inmaculada B.; Allman, Richard M.] Univ Alabama Birmingham, Birmingham, AL USA. [Ahmed, Ali; Sanders, Paul W.; Allman, Richard M.] Vet Affairs Med Ctr, Birmingham, AL USA. [Rich, Michael W.] Washington Univ, St Louis, MO USA. [Zile, Michael] Med Univ S Carolina, Charleston, SC 29425 USA. [Zile, Michael] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Love, Thomas E.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Aronow, Wilbert S.] New York Med Coll, Valhalla, NY 10595 USA. RP Ahmed, A (reprint author), UAB Ctr Aging, CH19,Ste 219,1720 2nd Ave S, Birmingham, AL 35294 USA. EM aahmed@uab.edu OI Sanders, Paul/0000-0002-2915-5714 FU National Heart, Lung, and Blood Institute (NHLBI)/National Institutes of Health (NIH) [R01-HL085561, R01-HL085561-S]; NIH/NHLBI [R01-HL097047]; NIH/National Center for Research Resources [5UL1 RR025777]; NIH/National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK46199]; Department of Veterans Affairs FX The project was supported by Grant Numbers R01-HL085561 and R01-HL085561-S from the National Heart, Lung, and Blood Institute (NHLBI)/National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NHLBI or NIH. Dr Ahmed also is supported by NIH/NHLBI Grant R01-HL097047 and a generous gift from Jean B. Morris of Birmingham, Alabama. Dr Allman is supported by NIH/National Center for Research Resources Grant 5UL1 RR025777. Dr Sanders is supported by NIH/National Institute of Diabetes and Digestive and Kidney Diseases Grant R01-DK46199 and funding from the Department of Veterans Affairs. NR 41 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD FEB PY 2013 VL 126 IS 2 BP 150 EP 161 DI 10.1016/j.amjmed.2012.06.031 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 072WP UT WOS:000313704500022 PM 23331442 ER PT J AU Hunt, KJ Gebregziabher, M Lynch, CP Echols, C Mauldin, PD Egede, LE AF Hunt, Kelly J. Gebregziabher, Mulugeta Lynch, Cheryl P. Echols, Carrae Mauldin, Patrick D. Egede, Leonard E. TI Impact of diabetes control on mortality by race in a national cohort of veterans SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Type 2 diabetes; Race; Hemoglobin A1c; Retrospective cohort; Medication adherence; Mortality ID ALL-CAUSE MORTALITY; MEDICATION ADHERENCE; HEMOGLOBIN A(1C); CARDIOVASCULAR-DISEASE; LONGITUDINAL COHORT; RACIAL-DIFFERENCES; GLUCOSE CONTROL; DRUG-THERAPY; TYPE-2; MELLITUS AB Purpose: The association between glycated hemoglobin (HbA1c), medication use/adherence, and mortality stratified by race/ethnicity was examined in a national cohort of veterans with type 2 diabetes. Methods: A total of 892,223 veterans with diabetes in 2002 were followed through 2006. HbA1c category was the main exposure (i.e., HbA1c <7%, HbA1c 7%-8% [reference], HbA1c 8%-9%, and HbA1c >9%). Covariates included age, sex, marital status, rural/urban residence, geographic region, number of comorbidities, and diabetes medication use/adherence (i.e., adherent, medication possession ratio >= 80%; nonadherent; and nonusers). HbA1c and medication use/adherence varied over time, and Cox regression models accounting for time-varying variables were used. Results: In nonmedication users, HbA1c greater than 9% predicted higher mortality risk relative to HbA1c of 7%-8% in non-Hispanic whites (hazard ratio [HR], 1.55; 95% confidence interval [95% CI], 1.43-1.69), non-Hispanic blacks (NHB) (HR, 1.58; 95% CI, 1.34-1.87), and Hispanics (HR, 2.22; 95% CI, 1.75-2.82). In contrast, in nonadherent medication users, HbA1c less than 7% predicted higher mortality risk in NHB (HR, 1.12; 95% CI, 1.05-1.20), whereas HbA1c greater than 9% only predicted mortality in non-Hispanic whites (HR, 1.11; 95% CI, 1.06-1.16). In adherent medication users, HbA1c less than 7% predicted higher mortality in NHB (HR, 1.18; 95% CI, 1.07-1.31), whereas HbA1c greater than 9.0% predicted higher mortality risk across all race/ethnic groups. Conclusion: We found evidence for racial/ethnic differences in the association between glycemic control and mortality, which varied by medication use/adherence. (c) 2013 Elsevier Inc. All rights reserved. C1 [Hunt, Kelly J.; Gebregziabher, Mulugeta; Lynch, Cheryl P.; Echols, Carrae; Mauldin, Patrick D.; Egede, Leonard E.] Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Ralph H Johnson Dept, Charleston, SC 29403 USA. [Hunt, Kelly J.; Gebregziabher, Mulugeta] Med Univ S Carolina, Dept Med, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Hunt, Kelly J.; Lynch, Cheryl P.; Echols, Carrae; Mauldin, Patrick D.; Egede, Leonard E.] Med Univ S Carolina, Dept Med, Div Gen Internal Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Dept Med, Div Gen Internal Med, Ctr Hlth Dispar Res, 135 Rutledge Ave,MSC 593, Charleston, SC 29425 USA. EM egedel@musc.edu OI Gebregziabher, Mulugeta/0000-0002-4826-481X FU VHA Health Services Research and Development program; [IIR-06-219] FX This study was supported by grant IIR-06-219 funded by the VHA Health Services Research and Development program. The funding agency did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 39 TC 6 Z9 6 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 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD FEB PY 2013 VL 23 IS 2 BP 74 EP 79 DI 10.1016/j.annepidem.2012.11.002 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 074WO UT WOS:000313846000007 PM 23238350 ER PT J AU Wiederhold, NP Najvar, LK Bocanegra, R Kirkpatrick, WR Sorrell, TC Patterson, TF AF Wiederhold, Nathan P. Najvar, Laura K. Bocanegra, Rosie Kirkpatrick, William R. Sorrell, Tania C. Patterson, Thomas F. TI Limited Activity of Miltefosine in Murine Models of Cryptococcal Meningoencephalitis and Disseminated Cryptococcosis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INDIAN VISCERAL LEISHMANIASIS; WORLD CUTANEOUS LEISHMANIASIS; AMPHOTERICIN-B; FUNGICIDAL ACTIVITY; ORAL MILTEFOSINE; IN-VITRO; MENINGITIS; FLUCONAZOLE; HEXADECYLPHOSPHOCHOLINE; FLUCYTOSINE AB Miltefosine is an alkyl phosphocholine with good oral bioavailability and in vitro activity against Cryptococcus species that has gained interest as an additional agent for cryptococcal infections. Our objective was to further evaluate the in vivo efficacy of miltefosine in experimental in vivo models of cryptococcal meningoencephalitis and disseminated cryptococcosis. Mice were infected intracranially or intravenously with either C. neoformans USC1597 or H99. Miltefosine treatment (1.8 to 45 mg/kg of body weight orally once daily) began at either 1 h or 1 day postinoculation. Fluconazole (10 mg/kg orally twice daily) or amphotericin B deoxycholate (3 mg/kg intraperitoneally once daily) served as positive controls. In our standard models, miltefosine did not result in significant improvements in survival or reductions in fungal burden against either C. neoformans isolate. There was a trend toward improved survival with miltefosine at 7.2 mg/kg against disseminated cryptococcosis with the H99 strain but only at a low infecting inoculum. In contrast, both fluconazole and amphotericin B significantly improved survival in mice with cryptococcal meningoencephalitis and disseminated cryptococcosis due to USC1597. Amphotericin B also improved survival against both cryptococcal infections caused by H99. Combination therapy with miltefosine demonstrated neither synergy nor antagonism in both models. These results demonstrate limited efficacy of miltefosine and suggest caution with the potential use of this agent for the treatment of C. neoformans infections. C1 [Wiederhold, Nathan P.; Najvar, Laura K.; Bocanegra, Rosie; Kirkpatrick, William R.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Wiederhold, Nathan P.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Najvar, Laura K.; Bocanegra, Rosie; Kirkpatrick, William R.; Patterson, Thomas F.] S Texas Vet Hlth Care Adm, San Antonio, TX USA. [Sorrell, Tania C.] Sydney Emerging Infect & Biosecur Inst, Sydney, NSW, Australia. [Sorrell, Tania C.] Univ Sydney, Sydney, NSW 2006, Australia. [Sorrell, Tania C.] Westmead Millennium Inst, Sydney, NSW, Australia. RP Wiederhold, NP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. EM wiederholdn@uthscsa.edu OI Wiederhold, Nathan/0000-0002-2225-5122 FU National Institutes of Health/National Institute of Allergy and Infectious Diseases [N01-AI-25475]; Pfizer; Schering-Plough; Merck; Basilea; Astellas FX This work was supported by a contract from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (N01-AI-25475) to T.F.P. T.C.S. is a Sydney Medical School Foundation Fellow.; N.P.W. has received research support from Pfizer, Schering-Plough, Merck, Basilea, and Astellas and has served on advisory boards for Merck, Astellas, Toyama, and Viamet. T.F.P. has received research grants to UT Health Science Center San Antonio from Astellas, Basilea, Merck, and Pfizer and has been a consultant for Astellas, Basilea, Merck, Pfizer, and Toyama. We have no other conflicts of interest. NR 30 TC 10 Z9 10 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 2013 VL 57 IS 2 BP 745 EP 750 DI 10.1128/AAC.01624-12 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 075ON UT WOS:000313896500008 PM 23165465 ER PT J AU Halford, C Gonzalez, R Campuzano, S Hu, B Babbitt, JT Liu, J Wang, J Churchill, BM Haake, DA AF Halford, Colin Gonzalez, Rodrigo Campuzano, Susana Hu, Bo Babbitt, Jane T. Liu, Jun Wang, Joseph Churchill, Bernard M. Haake, David A. TI Rapid Antimicrobial Susceptibility Testing by Sensitive Detection of Precursor rRNA Using a Novel Electrochemical Biosensing Platform SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CLINICAL URINE SPECIMENS; AMBIENT-TEMPERATURE; UROPATHOGENS; HYBRIDIZATION AB Precursor rRNA (pre-rRNA) is an intermediate stage in the formation of mature rRNA and is a useful marker for cellular metabolism and growth rate. We developed an electrochemical sensor assay for Escherichia coli pre-rRNA involving hybridization of capture and detector probes with tail sections that are spliced away during rRNA maturation. A ternary self-assembled monolayer (SAM) prepared on gold electrode surfaces by coassembly of thiolated capture probes with hexanedithiol and posttreatment with 6-mercapto-1-hexanol minimized the background signal and maximized the signal-to-noise ratio. Inclusion of internal calibration controls allowed accurate estimation of the pre-rRNA copy number per cell. As expected, the ratio of pre-rRNA to mature rRNA was low during stationary phase and high during log phase. Pre-rRNA levels were highly dynamic, ranging from 2 copies per cell during stationary phase to similar to 1,200 copies per cell within 60 min of inoculation into fresh growth medium. Specificity of the assay for pre-rRNA was validated using rifampin and chloramphenicol, which are known inhibitors of pre-rRNA synthesis and processing, respectively. The DNA gyrase inhibitor, ciprofloxacin, was found to act similarly to rifampin; a decline in pre-rRNA was detectable within 15 min in ciprofloxacin-susceptible bacteria. Assays for pre-rRNA provide insight into cellular metabolism and are promising predictors of antibiotic susceptibility. C1 [Halford, Colin; Gonzalez, Rodrigo; Babbitt, Jane T.; Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Halford, Colin; Churchill, Bernard M.; Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Babbitt, Jane T.; Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. [Campuzano, Susana; Wang, Joseph] Univ Calif San Diego, Dept Nanoengn, La Jolla, CA 92093 USA. [Hu, Bo; Liu, Jun] Univ Texas Med Sch Houston, Dept Pathol & Lab Med, Houston, TX USA. RP Haake, DA (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. EM dhaake@ucla.edu RI Campuzano Ruiz, Susana/C-6448-2011; Wang, Joseph/C-6175-2011 FU National Institute of Allergy and Infectious Diseases [AI075565]; Wendy and Ken Ruby Fund for Excellence in Pediatric Urology Research; Welch Foundation [AU-1714] FX This study was supported by Cooperative Agreement Award AI075565 (to D.A.H.) from the National Institute of Allergy and Infectious Diseases and by the Wendy and Ken Ruby Fund for Excellence in Pediatric Urology Research. B.M.C. is the Judith and Robert Winston Chair in Pediatric Urology. B.H. and J.L. were supported by a grant from Welch Foundation (AU-1714). NR 18 TC 4 Z9 4 U1 0 U2 19 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 2013 VL 57 IS 2 BP 936 EP 943 DI 10.1128/AAC.00615-12 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 075ON UT WOS:000313896500033 PM 23229486 ER PT J AU Saremi, A Schwenke, DC Buchanan, TA Hodis, HN Mack, WJ Banerji, M Bray, GA Clement, SC Henry, RR Kitabchi, AE Mudaliar, S Ratner, RE Stentz, FB Musi, N Tripathy, D DeFronzo, RA Reaven, PD AF Saremi, Aramesh Schwenke, Dawn C. Buchanan, Thomas A. Hodis, Howard N. Mack, Wendy J. Banerji, MaryAnn Bray, George A. Clement, Stephen C. Henry, Robert R. Kitabchi, Abbas E. Mudaliar, Sunder Ratner, Robert E. Stentz, Frankie B. Musi, Nicolas Tripathy, Devjit DeFronzo, Ralph A. Reaven, Peter D. TI Pioglitazone Slows Progression of Atherosclerosis in Prediabetes Independent of Changes in Cardiovascular Risk Factors SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE carotid atherosclerosis progression; impaired glucose tolerance; insulin resistance; inflammation; pioglitazone ID IMPAIRED GLUCOSE-TOLERANCE; TYPE-2 DIABETES-MELLITUS; ACTIVATED-RECEPTOR-GAMMA; INTIMA-MEDIA THICKNESS; RANDOMIZED CONTROLLED-TRIAL; SMOOTH-MUSCLE-CELLS; PPAR-GAMMA; INSULIN SENSITIVITY; SUBCLINICAL ATHEROSCLEROSIS; CORONARY ATHEROSCLEROSIS AB Objective-To determine whether changes in standard and novel risk factors during the Actos Now for Prevention of Diabetes trial explained the slower rate of carotid intima media thickness (CIMT) progression with pioglitazone treatment in persons with prediabetes. Methods and Results-CIMT was measured in 382 participants at the beginning and up to 3 additional times during follow-up of the Actos Now for Prevention of Diabetes trial. During an average follow-up of 2.3 years, the mean unadjusted annual rate of CIMT progression was significantly (P=0.01) lower with pioglitazone treatment (4.76x10(-3) mm/year; 95% CI: 2.39x10(-3)-7.14x10(-3) mm/year) compared with placebo (9.69x10(-3) mm/year; 95% CI: 7.24x10(-3)-12.15x10(-3) mm/year). High-density lipoprotein cholesterol, fasting and 2-hour glucose, HbA(1c), fasting insulin, Matsuda insulin sensitivity index, adiponectin, and plasminogen activator inhibitor-1 levels improved significantly with pioglitazone treatment compared with placebo (P<0.001). However, the effect of pioglitazone on CIMT progression was not attenuated by multiple methods of adjustment for traditional, metabolic, and inflammatory risk factors and concomitant medications, and was independent of changes in risk factors during pioglitazone treatment. Conclusion-Pioglitazone slowed progression of CIMT, independent of improvement in hyperglycemia, insulin resistance, dyslipidemia, and systemic inflammation in prediabetes. These results suggest a possible direct vascular benefit of pioglitazone. (Arterioscler Thromb Vasc Biol. 2013;33:393-399.) C1 [Saremi, Aramesh; Schwenke, Dawn C.; Reaven, Peter D.] Phoenix Vet Affair VA Hlth Care Syst, Phoenix, AZ USA. [Buchanan, Thomas A.; Hodis, Howard N.; Mack, Wendy J.] Univ So Calif, Sch Med, Los Angeles, CA USA. [Banerji, MaryAnn] SUNY Hlth Sci Ctr, Brooklyn, NY USA. [Bray, George A.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Clement, Stephen C.] Georgetown Univ, Washington, DC USA. [Henry, Robert R.; Mudaliar, Sunder] San Diego VA Hlth Care Syst, San Diego, CA USA. [Henry, Robert R.; Mudaliar, Sunder] Univ San Diego, San Diego, CA 92110 USA. [Kitabchi, Abbas E.; Stentz, Frankie B.] Univ Tennessee, Memphis, TN USA. [Ratner, Robert E.] Medstar Res Inst, Hyattsville, MD USA. [Musi, Nicolas; Tripathy, Devjit; DeFronzo, Ralph A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Musi, Nicolas] S Texas Vet Healthcare Syst, San Antonio, TX USA. RP Reaven, PD (reprint author), Carl T Hayden VAMC 111E, Diabet Program, 650 E Indian Sch Rd, Phoenix, AZ 85012 USA. EM Peter.Reaven@va.gov FU Takeda Pharmaceuticals [NCT00220961]; office of Research and Development, Medical Research Service, Department of Veterans Affairs; BMS; Novartis; Boehringer Ingelheim; Sanofi-Aventis; Merck; Roche; Takeda; Amylin; Eli Lilly; Daiichi-Sankyo; NovoNordisk; Genentech-Roche; GlaxoSmithKline; Bayhill; Halozyme; Integrium; Takeda Pharmaceuticals FX This investigator-initiated study was supported by a grant from Takeda Pharmaceuticals. (ClinicalTrial.gov number, NCT00220961). This work was supported in part by the office of Research and Development, Medical Research Service, Department of Veterans Affairs. We are grateful to ACT NOW study participants, study staff, and investigators. The contents of this article do not repre-sent the views of the Department of Veterans Affairs or the U.S. Government.; Dr Banerji reports receiving consulting fees from BMS, Novartis, Boehringer Ingelheim, Sanofi-Aventis, Merck, and Roche, and lecture fees from Merck and Sanofi-Aventis; Dr Buchanan reports receiving consulting fees and lecture fees from Takeda and reports that the University of Southern California Keck School of Medicine has received grant support from Takeda; Dr DeFronzo reports receiving payments for board membership from Amylin, Takeda, ISIS, and Boehringer Ingelheim and reports that the University of Texas Health Science Center at San Antonio has received grant support from Takeda, Amylin, and Eli Lilly; Dr Henry reports receiving consulting fees, lecture fees, and payment for expert testimony from Takeda; Dr Musi reports receiving consulting fees from Merck, Daiichi-Sankyo, Takeda, and Novartis; Dr Ratner reports that the Medstar Research Institute has received consulting fees from Amylin, NovoNordisk, Sanofi-Aventis, and Genentech-Roche and grant support from Amylin, NovoNordisk, GlaxoSmithKline, Bayhill, Halozyme, and Integrium; Dr Reaven reports receiving consulting fees from BMS and Gilead, lecture fees from Merck and Amylin, and payment for the development of educational presentations from Amylin, and that the Carl T. Hayden Veterans Affairs Medical Center has received grant support from Amylin; and Dr Tripathy reports receiving grant support from Takeda Pharmaceuticals. No other potential conflict of interest relevant to this article was reported. NR 40 TC 36 Z9 36 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD FEB PY 2013 VL 33 IS 2 BP 393 EP + DI 10.1161/ATVBAHA.112.300346 PG 16 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 073MS UT WOS:000313747700035 PM 23175674 ER PT J AU Anzueto, A Restrepo, MI Pugh, MJV Wilson, BZ Mortensen, EM AF Anzueto, Antonio Restrepo, Marcos I. Pugh, Mary Jo V. Wilson, Bryan Z. Mortensen, Eric M. TI Severe Community-Acquired Pneumonia: Don't Get Rid of Fluoroquinolone reply SO CRITICAL CARE MEDICINE LA English DT Letter C1 [Anzueto, Antonio; Restrepo, Marcos I.; Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, VERDICT S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol, San Antonio, TX 78229 USA. [Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biostat, San Antonio, TX 78229 USA. [Wilson, Bryan Z.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Mortensen, Eric M.] VA N Texas Hlth Care Syst, Dallas, TX USA. [Mortensen, Eric M.] Univ Texas SW, Dallas, TX USA. RP Anzueto, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, VERDICT S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RI Restrepo, Marcos/H-4442-2014 FU NHLBI NIH HHS [K23 HL096054] NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 2013 VL 41 IS 2 BP E16 EP E17 DI 10.1097/CCM.0b013e318277103a PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 078NO UT WOS:000314106000006 PM 23353969 ER PT J AU Erqou, S Lee, CTC Suffoletto, M Echouffo-Tcheugui, JB de Boer, RA van Melle, JP Adler, AI AF Erqou, Sebhat Lee, Chee-Tin Christine Suffoletto, Matthew Echouffo-Tcheugui, Justin B. de Boer, Rudolf A. van Melle, Joost P. Adler, Amanda I. TI Association between glycated haemoglobin and the risk of congestive heart failure in diabetes mellitus: systematic review and meta-analysis SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Review DE Heart failure; Diabetes; Epidemiology; HbA(1c); Hyperglycaemia; Meta-analysis; Risk factor; Systematic review ID GLYCEMIC CONTROL; ATHEROSCLEROSIS RISK; TASK-FORCE; TYPE-2; DISEASE; GLUCOSE; HOSPITALIZATION; CARDIOMYOPATHY; COLLABORATION; COMPLICATIONS AB Clinical trials to date have not provided definitive evidence regarding the effects of glucose lowering on the incidence of congestive heart failure (CHF). We synthesized available prospective epidemiological data on the association between glycaemia measured by haemoglobin A(1c) (HbA(1c)) and incident CHF in individuals with diabetes. We searched electronic databases and reference lists of selected articles for relevant prospective epidemiological studies. We abstracted data from relevant studies using standardized forms and obtained additional data from investigators when required. We pooled study-specific relative risk estimates using random-effects model meta-analysis. Of the 1044 citations identified, we included 10 studies comprising 178 929 participants with diabetes and 14 176 incident CHF cases. Five studies included only patients with type 2 diabetes, four studies had predominantly patients with type 2 diabetes, and one study included only patients with type 1 diabetes. All studies except one showed an increased risk of CHF with higher HbA(1c). The overall adjusted risk ratio (RR) for CHF was 1.15 [95 confidence interval (CI) 1.101.21] for each percentage point higher HbA(1c). There was substantial heterogeneity across the 10 studies (I-2: 83; 95 CI 6991; P 0.001) not explained by available study-level characteristics such as study design or average HbA(1c) level. In seven studies reporting RRs with more than one degree of adjustment, the association was minimally altered after adjustment for several cardiovascular risk factors. In observational studies of individuals with diabetes, a higher HbA(1c) level was associated with a significantly increased incidence of CHF. C1 [Erqou, Sebhat] Univ Pittsburgh, Med Ctr, Dept Internal Med, Pittsburgh, PA 15213 USA. [Lee, Chee-Tin Christine] Univ Toronto, Dept Nutr Sci, Toronto, ON M5S 1A1, Canada. [Suffoletto, Matthew] Vet Affairs Pittsburgh Hlth Care Syst, Dept Cardiol, Pittsburgh, PA USA. [Echouffo-Tcheugui, Justin B.] Emory Univ, Rollins Sch Publ Hlth, Dept Global Hlth, Atlanta, GA 30322 USA. [de Boer, Rudolf A.; van Melle, Joost P.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 AB Groningen, Netherlands. [Adler, Amanda I.] Addenbrookes Hosp, Inst Metab Sci, Cambridge, England. RP Erqou, S (reprint author), Univ Pittsburgh, Med Ctr, Dept Internal Med, Pittsburgh, PA 15213 USA. EM sebhaterqou@googlemail.com NR 40 TC 17 Z9 17 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD FEB PY 2013 VL 15 IS 2 BP 185 EP 193 DI 10.1093/eurjhf/hfs156 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 074RV UT WOS:000313831900010 PM 23099356 ER PT J AU Chirinos, JA Segers, P Rietzschel, ER De Buyzere, ML Raja, MW Claessens, T De Bacquer, D Sutton, MSJ Gillebert, TC AF Chirinos, Julio A. Segers, Patrick Rietzschel, Ernst R. De Buyzere, Marc L. Raja, Muhammad W. Claessens, Tom De Bacquer, Dirk Sutton, Martin St. John Gillebert, Thierry C. CA Asklepios Investigators TI Early and Late Systolic Wall Stress Differentially Relate to Myocardial Contraction and Relaxation in Middle-Aged Adults The Asklepios Study SO HYPERTENSION LA English DT Article DE afterload; diastolic function; loading sequence; myocardial function; myocardial wall stress; systolic function; tissue Doppler imaging ID LEFT-VENTRICULAR RELAXATION; WAVE REFLECTION MAGNITUDE; INTACT CANINE HEART; LOADING SEQUENCE; DEPENDENT RELAXATION; CARDIAC-MUSCLE; ARTERIAL LOAD; PRESSURE FALL; DETERMINANTS; VELOCITY AB Experimental studies implicate late systolic load as a determinant of impaired left-ventricular relaxation. We aimed to assess the relationship between the myocardial loading sequence and left-ventricular contraction and relaxation. Time-resolved central pressure and time-resolved left-ventricular geometry were measured with carotid tonometry and speckle-tracking echocardiography, respectively, for computation of time-resolved ejection-phase myocardial wall stress (EP-MWS) among 1214 middle-aged adults without manifest cardiovascular disease from the general population. Early diastolic annular velocity and systolic annular velocities were measured with tissue Doppler imaging, and segment-averaged longitudinal strain was measured with speckle-tracking echocardiography. After adjustment for age, sex, and potential confounders, late EP-MWS was negatively associated with early diastolic mitral annular velocity (standardized beta=-0.25; P<0.0001) and mitral inflow propagation velocity (standardized beta=-0.13; P=0.02). In contrast, early EP-MWS was positively associated with early diastolic mitral annular velocity (standardized beta=0.18; P<0.0001) and mitral inflow propagation velocity (standardized beta=0.22; P<0.0001). A higher late EP-MWS predicted a lower systolic mitral annular velocity (standardized beta=-0.31; P<0.0001) and lesser myocardial longitudinal strain (standardized beta=0.32; P<0.0001), whereas a higher early EP-MWS was associated with a higher systolic mitral annular velocity (standardized beta=0.16; P=0.002) and greater longitudinal strain (standardized beta=-0.24; P=0.002). The loading sequence remained independently associated with early diastolic mitral annular velocity after adjustment for systolic mitral annular velocity or systolic longitudinal strain. In the context of available experimental data, our findings support the role of the myocardial loading sequence as a determinant of left-ventricular systolic and diastolic function. A loading sequence characterized by prominent late systolic wall stress was associated with lower longitudinal systolic function and diastolic relaxation. (Hypertension. 2013;61:296-303.). circle Online Data Supplement C1 [Chirinos, Julio A.; Raja, Muhammad W.; Sutton, Martin St. John] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Chirinos, Julio A.; Raja, Muhammad W.; Sutton, Martin St. John] Univ Penn, Philadelphia, PA 19104 USA. [Segers, Patrick; Claessens, Tom] Univ Ghent, Inst Biomed Technol, B-9000 Ghent, Belgium. [Rietzschel, Ernst R.; De Bacquer, Dirk] Univ Ghent, Dept Publ Hlth, B-9000 Ghent, Belgium. [Rietzschel, Ernst R.; De Buyzere, Marc L.; Gillebert, Thierry C.] Ghent Univ Hosp, Dept Cardiovasc Dis, Ghent, Belgium. [Claessens, Tom] Univ Coll Ghent, Dept Mech, Ghent, Belgium. RP Chirinos, JA (reprint author), 3800 Woodland Ave,Rm 8B111, Philadelphia, PA 19104 USA. EM Julio.chirinos@uphs.upenn.edu RI Claessens, Tom/B-2737-2009 OI Claessens, Tom/0000-0002-3182-6820; Gillebert, Thierry/0000-0002-3832-919X FU Fonds voor Wetenschappelijk Onderzoek Vlaanderen [G.0.838.10]; Edna G. Kynett Memorial Foundation; National Institutes of Health; American Heart Association FX This study was supported by Fonds voor Wetenschappelijk Onderzoek Vlaanderen grant G.0.838.10 and Edna G. Kynett Memorial Foundation (Dr Chirinos).; Dr Chirinos has received significant (>$ 10 000) grants from the National Institutes of Health and the American Heart Association for research studies related to arterial hemodynamics and has received minor support (equipment loans) from Atcor Medical, Cardiodynamics, and APC cardiovascular. NR 38 TC 33 Z9 33 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD FEB PY 2013 VL 61 IS 2 BP 296 EP 303 DI 10.1161/HYPERTENSIONAHA.111.00530 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 073JU UT WOS:000313740100026 PM 23283359 ER PT J AU Reeves, RM Ong, FR Matheny, ME Denny, JC Aronsky, D Gobbel, GT Montella, D Speroff, T Brown, SH AF Reeves, Ruth M. Ong, Ferdo R. Matheny, Michael E. Denny, Joshua C. Aronsky, Dominik Gobbel, Glenn T. Montella, Diane Speroff, Theodore Brown, Steven H. TI Detecting temporal expressions in medical narratives SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS LA English DT Article DE Event sequence; TimeML; Temporal reasoning; Narration; Natural language processing ID DISCHARGE SUMMARIES; CLASSIFICATION; ARCHITECTURE; INFORMATION; KNOWLEDGE; SYSTEM; TEXT AB Background: Clinical practice and epidemiological information aggregation require knowing when, how long, and in what sequence medically relevant events occur. The Temporal Awareness and Reasoning Systems for Question Interpretation (TARSQI) Toolkit (TTK) is a complete, open source software package for the temporal ordering of events within narrative text documents. TTK was developed on newspaper articles. We extended TTK to support medical notes using veterans' affairs (VA) clinical notes and compared it to TTK. Methods: We used a development set consisting of 200 VA clinical notes to modify and append rules to TTK's time tagger, creating Med-TTK. We then evaluated the performances of TTK and Med-TTK on an independent random selection of 100 clinical notes. Evaluation tasks were to identify and classify time-referring expressions as one of four temporal classes (DATE, TIME, DURATION, and SET). The reference standard for this test set was generated by dual human manual review with disagreements resolved by a third reviewer. Outcome measures included recall and precision for each class, and inter-rater agreement scores. Results: There were 3146 temporal expressions in the reference standard. TTK identified 1595 temporal expressions. Recall was 0.15 (95% confidence interval [CI] 0.12-0.15) and precision was 0.27 (95% CI 0.25-0.29) for TTK. Med-TTK identified 3174 expressions. Recall was 0.86 (95% CI 0.84-0.87) and precision was 0.85 (95% CI 0.84-0.86) for Med-TTK. Conclusion: The algorithms for identifying and classifying temporal expressions in medical narratives developed within Med-TTK significantly improved performance compared to TTK. Natural language processing applications such as Med-TTK provide a foundation for meaningful longitudinal mapping of patient history events among electronic health records. The tool can be accessed at the following site: http://code.google.com/p/med-ttk/. (c) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Reeves, Ruth M.; Matheny, Michael E.; Gobbel, Glenn T.; Speroff, Theodore; Brown, Steven H.] Tennessee Valley Healthcare Syst, Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, Nashville, TN USA. [Reeves, Ruth M.; Ong, Ferdo R.; Matheny, Michael E.; Denny, Joshua C.; Aronsky, Dominik; Gobbel, Glenn T.; Montella, Diane; Brown, Steven H.] Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA. [Matheny, Michael E.; Speroff, Theodore] Vanderbilt Univ, Sch Med, Dept Med, Div Gen Internal Med, Nashville, TN 37212 USA. [Matheny, Michael E.; Speroff, Theodore] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN USA. [Montella, Diane; Brown, Steven H.] Vet Hlth Adm, Dept Vet Affairs, Off Informat & Analyt, Nashville, TN USA. RP Reeves, RM (reprint author), US Dept Vet Affairs, Tennessee Valley Healthcare Syst, 1310 24th Ave S, Nashville, TN 37212 USA. EM ruth.reeves2@va.gov OI Matheny, Michael/0000-0003-3217-4147 FU VA Medical Informatics Fellowship, Office of Academic Affiliations; Veterans Health Administration HSR&D Career Development Award [CDA-08-020]; Veterans Health Consortium for Health Informatics Research (CHIR) [HIR 09-001, HIR 09-003]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development FX The research reported here began with the 2009 Medical Informatics Master's Thesis of Dr. Ferdo Ong who initiated his research with an interest in adapting TTK for eventual clinical usage. This thesis entitled "The Tarsqi Toolkit's Recognition of Temporal Expressions within Medical Documents" is available at http://etd.library.vanderbilt.edu/available/etd-05242010-101636/. Drs. Reeves, Montella and Ong were supported by VA Medical Informatics Fellowship, Office of Academic Affiliations. Dr. Matheny is supported by the Veterans Health Administration HSR&D Career Development Award CDA-08-020. Drs. Matheny and Speroff and Gobbel are supported by the Veterans Health Consortium for Health Informatics Research (CHIR) awards HIR 09-001 and HIR 09-003.; This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development with resources and the use of facilities at the VA Tennessee Valley Healthcare System. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 54 TC 12 Z9 12 U1 0 U2 15 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1386-5056 J9 INT J MED INFORM JI Int. J. Med. Inform. PD FEB PY 2013 VL 82 IS 2 BP 118 EP 127 DI 10.1016/j.ijmedinf.2012.04.006 PG 10 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 078RJ UT WOS:000314116700006 PM 22595284 ER PT J AU Ohning, GV AF Ohning, Gordon V. TI Intestinal Mucins The First Line of Defense SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Editorial Material ID INFLAMMATORY-BOWEL-DISEASE; MECHANISMS C1 Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, W Los Angeles VA Healthcare Ctr, Los Angeles, CA 90073 USA. RP Ohning, GV (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, W Los Angeles VA Healthcare Ctr, Bld 115,Rm 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gordon.ohning@va.gov NR 10 TC 0 Z9 0 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD FEB PY 2013 VL 47 IS 2 BP 104 EP 105 DI 10.1097/MCG.0b013e3182713185 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 075UP UT WOS:000313912700005 PM 23314666 ER PT J AU Kar, HL O'Leary, KD AF Kar, Heidi L. O'Leary, K. Daniel TI Patterns of Psychological Aggression, Dominance, and Jealousy within Marriage SO JOURNAL OF FAMILY VIOLENCE LA English DT Article DE Emotional abuse; Intimate-partner violence; Partner aggression; Control; Bilateral aggression ID RISK YOUNG COUPLES; PHYSICAL AGGRESSION; DOMESTIC VIOLENCE; PARTNER VIOLENCE; GENDER; CONFLICT; DEPRESSION; FREQUENCY; EMOTIONS; SYMMETRY AB Few empirical studies with representative samples have focused on the gendered aspect of psychological aggression and its sub-constructs of dominance and jealousy. Those that do report on gender differences, often fail to report on important dyadic factors such as whether the aggression is unilateral or bilateral in nature. Differences in psychological aggression, dominance, and jealousy constructs were assessed in a representative sample of 453 married parents. Overall, women had significantly higher dominance, jealousy, and psychological aggression scores. Both male and female respondents in relationships where there was bi-directional severe psychological aggression demonstrated higher mean levels of severe psychological aggression, dominance, and jealousy than did their counterparts who were unilaterally severely aggressive. This is the first study to demonstrate that bilateral psychological aggression is associated with higher mean levels of psychological aggression, dominance, and jealousy scores for both male and female partners than unilateral aggression. Contrary to our hypothesis, there was no differential impact of severe psychological aggression by gender. C1 [Kar, Heidi L.] San Francisco VA Med Ctr, Psychol Serv 116B, San Francisco, CA 94121 USA. [O'Leary, K. Daniel] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. RP Kar, HL (reprint author), San Francisco VA Med Ctr, Psychol Serv 116B, 4150 Clement St, San Francisco, CA 94121 USA. EM Heidi.Kar@va.gov NR 72 TC 2 Z9 2 U1 4 U2 55 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 J9 J FAM VIOLENCE JI J. Fam. Violence PD FEB PY 2013 VL 28 IS 2 BP 109 EP 119 DI 10.1007/s10896-012-9492-7 PG 11 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 077LL UT WOS:000314029100001 ER PT J AU Gupta, PK Ramanan, B MacTaggart, JN Sundaram, A Fang, X Gupta, H Johanning, JM Pipinos, II AF Gupta, Prateek K. Ramanan, Bala MacTaggart, Jason N. Sundaram, Abhishek Fang, Xiang Gupta, Himani Johanning, Jason M. Pipinos, Iraklis I. TI Risk index for predicting perioperative stroke, myocardial infarction, or death risk in asymptomatic patients undergoing carotid endarterectomy SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-College-of-Surgeons CY OCT 03, 2012 CL Chicago, IL SP Amer Coll Surg ID CARDIAC RISK; ARTERIAL-DISEASE; LOWER-EXTREMITY; BYPASS-SURGERY; SURGICAL CARE; YOUNG-ADULTS; MORTALITY; VALIDATION; ADJUSTMENT; QUALITY AB Objective: The latest guidelines recommend performance of carotid endarterectomy (CEA) on asymptomatic patients with high-grade carotid stenosis, only if the combined perioperative stroke, myocardial infarction (MI), or death risk is <= 3%. Our objective was to develop and validate a risk index to estimate the combined risk of perioperative stroke, MI, or death in asymptomatic patients undergoing elective CEA. Methods: Asymptomatic patients who underwent an elective CEA (n = 17,692) were identified from the 2005-2010 National Surgical Quality Improvement Program, a multicenter, prospective database. Multivariable logistic regression analysis was performed with primary outcome of interest being the composite of any stroke, MI, or death during the 30-day periprocedural period. Bootstrapping was used for internal validation. A risk index was created by assigning weighted points to each predictor using the beta-coefficients from the regression analysis. Results: Fifty-eight percent of the patients were men with a median age of 72 years. Thirty-day incidences of stroke, MI, and death were 0.9% (n = 167), 0.6% (n = 108), and 0.4% (n = 72), respectively. The combined 30-day stroke, MI, or death incidence was 1.8%(n = 324). On multivariable analysis, six independent predictors were identified and a risk index created by assigning weighted points to each predictor using the b-coefficients from the regression analysis. The predictors included age in years (<60: 0 point; 60-69: -1 point; 70-79: -1 point; >= 80: 2 points), dyspnea (2 points), chronic obstructive pulmonary disease (3 points), previous peripheral revascularization or amputation (3 points), recent angina within 1 month (4 points), and dependent functional status (5 points). Patients were classified as low(<3%), intermediate (3%-6%), or high (>6%) risk for combined 30-day stroke, MI, or death, based on a total point score of <4, 4-7, and >7, respectively. There were 15,249 patients (86.2%) in the low-risk category, 2233 (12.6%) in the intermediate-risk category, and 210 (1.2%) in the high-risk category. Conclusions: The validated risk index can help identify asymptomatic patients who are at greatest risk for 30-day stroke, MI, and death after CEA, thereby aiding patient selection. (J Vasc Surg 2013; 57: 318-26.) C1 [Gupta, Prateek K.] Univ Wisconsin Hosp & Clin, Dept Surg, Madison, WI 53792 USA. [Gupta, Himani] William S Middleton Mem Vet Adm Med Ctr, Dept Med, Madison, WI USA. [Ramanan, Bala; Sundaram, Abhishek] Creighton Univ, Dept Surg, Omaha, NE 68178 USA. [MacTaggart, Jason N.; Johanning, Jason M.; Pipinos, Iraklis I.] Univ Nebraska, Med Ctr, Dept Surg, Omaha, NE 68154 USA. [MacTaggart, Jason N.; Johanning, Jason M.; Pipinos, Iraklis I.] VA Nebraska & Western Iowa Hlth Care Syst, Omaha, NE 68154 USA. [Fang, Xiang] Creighton Univ, Biostat Core, Omaha, NE 68178 USA. RP Pipinos, II (reprint author), Univ Nebraska, Med Ctr, Dept Surg, Omaha, NE 68154 USA. EM ipipinos@unmc.edu FU NIA NIH HHS [R01 AG034995] NR 34 TC 19 Z9 20 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 2013 VL 57 IS 2 BP 318 EP 326 DI 10.1016/j.jvs.2012.08.116 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 073NX UT WOS:000313750800003 PM 23159474 ER PT J AU Epstein, AJ Busch, SH Busch, AB Asch, DA Barry, CL AF Epstein, Andrew J. Busch, Susan H. Busch, Alisa B. Asch, David A. Barry, Colleen L. TI Does Exposure to Conflict of Interest Policies in Psychiatry Residency Affect Antidepressant Prescribing? SO MEDICAL CARE LA English DT Article DE drug utilization; pharmaceutical policy; physician practice patterns; psychiatry ID ACADEMIC MEDICAL-CENTERS; PHARMACEUTICAL REPRESENTATIVES; NATIONAL-SURVEY; PRESCRIPTION DRUGS; PHYSICIANS; INDUSTRY; ATTITUDES; BEHAVIOR; INFORMATION AB Background: Academic medical institutions have instituted conflict of interest (COI) policies in response to concerns about pharmaceutical industry influence. Objective: To determine whether exposure to COI policies during psychiatry residency training affects psychiatrists' antidepressant prescribing patterns after graduation. Research Design: We used 2009 physician-level national administrative prescribing data from IMS Health for 1652 psychiatrists from 162 residency programs. We used difference-in-differences estimation to compare antidepressant prescribing based on graduation before (2001) or after (2008) COI policy adoption across residency program groups with maximally, moderately, and minimally restrictive COI policies. The primary outcomes were shares of psychiatrists' prescribing of heavily promoted, brand reformulated, and brand antidepressants. Results: Rates of prescribing heavily promoted, brand reformulated, and brand antidepressants in 2009 were lower among post-COI graduates than pre-COI graduates at all levels of COI restrictiveness. However, differences between pre-COI and post-COI graduates' prescribing of heavily promoted medications were larger for maximally restrictive programs than both minimally restrictive programs [- 4.3 percentage points; 95% confidence interval (CI), - 7.0, - 1.6] and moderately restrictive programs (- 3.6 percentage points; 95% CI, - 6.2, - 1.1). The difference in prescribing reformulations was larger for maximally restrictive programs than minimally restrictive programs (- 3.0 percentage points; 95% CI, - 5.3, - 0.7). Results were consistent for prescribing of brand drugs. Conclusions: This study provides the first empirical evidence of the effects of COI policies. Our results suggest that COI policies can help inoculate physicians against persuasive aspects of pharmaceutical promotion. Further research should assess whether these policies affect other drug classes and physician specialties similarly. C1 [Epstein, Andrew J.; Asch, David A.] Univ Penn, Dept Vet Affairs, Ctr Hlth Equ Res & Promot, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Epstein, Andrew J.; Asch, David A.] Univ Penn, Dept Med, Div Gen Internal Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Epstein, Andrew J.; Asch, David A.; Barry, Colleen L.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Busch, Susan H.] Yale Univ, Sch Publ Hlth, Dept Hlth Policy & Adm, New Haven, CT USA. [Busch, Alisa B.] McLean Hosp, Belmont, MA 02178 USA. [Busch, Alisa B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Barry, Colleen L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. RP Epstein, AJ (reprint author), Univ Penn, Dept Med, Div Gen Internal Med, Perelman Sch Med, 423 Guardian Dr, Philadelphia, PA 19104 USA. EM eandrew@mail.med.upenn.edu OI Asch, David/0000-0002-7970-286X NR 32 TC 23 Z9 23 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD FEB PY 2013 VL 51 IS 2 BP 199 EP 203 DI 10.1097/MLR.0b013e318277eb19 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 078LW UT WOS:000314101400014 PM 23142772 ER PT J AU Gesty-Palmer, D Yuan, L Martin, B Wood, WH Lee, MH Janech, MG Tsoi, LC Zheng, WJ Luttrell, LM Maudsley, S AF Gesty-Palmer, Diane Yuan, Ling Martin, Bronwen Wood, William H., III Lee, Mi-Hye Janech, Michael G. Tsoi, Lam C. Zheng, W. Jim Luttrell, Louis M. Maudsley, Stuart TI beta-Arrestin-Selective G Protein-Coupled Receptor Agonists Engender Unique Biological Efficacy in Vivo SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PARATHYROID-HORMONE PTH; SIGNALING PATHWAYS; BONE-FORMATION; ACTIVATION; BETA-ARRESTIN-2; MICE; KINASE; CELLS; BINDING; CANCER AB Biased G protein-coupled receptor agonists are orthosteric ligands that possess pathway-selective efficacy, activating or inhibiting only a subset of the signaling repertoire of their cognate receptors. In vitro, D-Trp(12), Tyr(34)-bPTH(7-34) [bPTH(7-34)], a biased agonist for the type 1 PTH receptor, antagonizes receptor-G protein coupling but activates arrestin-dependent signaling. In vivo, both bPTH(7-34) and the conventional agonist hPTH(1-34) stimulate anabolic bone formation. To understand how two PTH receptor ligands with markedly different in vitro efficacy could elicit similar in vivo responses, we analyzed transcriptional profiles from calvarial bone of mice treated for 8 wk with vehicle, bPTH(7-34) or hPTH(1-34). Treatment of wild-type mice with bPTH(7-34) primarily affected pathways that promote expansion of the osteoblast pool, notably cell cycle regulation, cell survival, and migration. These responses were absent in beta-arrestin2-null mice, identifying them as downstream targets of beta-arrestin2-mediated signaling. In contrast, hPTH(1-34) primarily affected pathways classically associated with enhanced bone formation, including collagen synthesis and matrix mineralization. hPTH(1-34) actions were less dependent on beta-arrestin2, as might be expected of a ligand capable of G protein activation. In vitro, bPTH(7-34) slowed the rate of preosteoblast proliferation, enhanced osteoblast survival when exposed to an apoptotic stimulus, and stimulated cell migration in wild-type, but not beta-arrestin2-null, calvarial osteoblasts. These results suggest that bPTH(7-34) and hPTH(1-34) affect bone mass in vivo through predominantly separate genomic mechanisms created by largely distinct receptor-signaling networks and demonstrate that functional selectivity can be exploited to change the quality of G protein-coupled receptor efficacy. (Molecular Endocrinology 27: 296-314, 2013) C1 [Gesty-Palmer, Diane; Yuan, Ling] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Martin, Bronwen; Maudsley, Stuart] NIA, NIH, Receptor Pharmacol Unit, Baltimore, MD 21224 USA. [Wood, William H., III] NIA, NIH, Gene Express & Genom Unit, Baltimore, MD 21224 USA. [Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. [Tsoi, Lam C.; Zheng, W. Jim; Luttrell, Louis M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Janech, Michael G.; Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Luttrell, LM (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, 96 Jonathan Lucas St,Suite 816 CSB,MSC 624, Charleston, SC 29425 USA. EM luttrell@musc.edu OI Janech, Michael/0000-0002-3202-4811 FU National Institutes of Health [DK64353, DK55524, HD043446]; Arthritis Foundation; Research Services of the Charleston, South Carolina; Research Services of the Charleston, Durham; North Carolina Veterans Affairs Medical Centers; Neph-cure Young Investigator; Department of Veterans Affairs Career Development Awards; National Institute on Aging Intramural Research Program of the NIH FX This work was supported by National Institutes of Health Grants DK64353 (to L.M.L./D.G.-P.), DK55524 (to L.M.L.), HD043446 (to D.G.-P.), the Arthritis Foundation (to D.G.-P.), and the Research Services of the Charleston, South Carolina and Durham, North Carolina Veterans Affairs Medical Centers (to L.M.L., M.G.J., and D.G.-P.). M.G.J. was supported by Neph-cure Young Investigator and Department of Veterans Affairs Career Development Awards. This work was supported in part by the National Institute on Aging Intramural Research Program of the NIH (to S.M., B.M., and W.W.). NR 68 TC 28 Z9 28 U1 1 U2 11 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD FEB PY 2013 VL 27 IS 2 BP 296 EP 314 DI 10.1210/me.2012-1091 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 078RK UT WOS:000314116900010 PM 23315939 ER PT J AU Fu, MY Brewer, S Olafsen, T Wu, AM Gordon, LK Said, J Braun, J Wadehra, M AF Fu, Maoyong Brewer, Sarah Olafsen, Tove Wu, Anna M. Gordon, Lynn K. Said, Jonathan Braun, Jonathan Wadehra, Madhuri TI Positron Emission Tomography Imaging of Endometrial Cancer Using Engineered Anti-EMP2 Antibody Fragments SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE Epithelial membrane protein-2; Endometrial cancer; PET imaging; Minibody; Copper-64 ID EPITHELIAL MEMBRANE PROTEIN-2; IN-VIVO; SURFACE EXPRESSION; EMP2; COMPLEXES; PET; ANTIGEN; TUMORIGENICITY; XENOGRAFTS; PROSTATE AB As imaging of the cell surface tetraspan protein epithelial membrane protein-2 (EMP2) expression in malignant tumors may provide important prognostic and predictive diagnostic information, the goal of this study is to determine if antibody fragments to EMP2 may be useful for imaging EMP2 positive tumors. The normal tissue distribution of EMP2 protein expression was evaluated by immunohistochemistry and found to be discretely expressed in both mouse and human tissues. To detect EMP2 in tumors, a recombinant human anti-EMP2 minibody (scFv-hinge-C(H)3 dimer; 80 kDa) was designed to recognize a common epitope in mice and humans and characterized. In human tumor cell lines, the antibody binding induced EMP2 internalization and degradation, prompting the need for a residualizing imaging strategy. Following conjugation to DOTA (1,4,7,10-tetraazacyclododecane-N,N',N',N'aEuro(3)-tetraacetic acid), the minibody was radiolabeled with Cu-64 (t (1/2) = 12.7 h) and evaluated in mice as a positron emission tomography (PET) imaging agent for human EMP2-expressing endometrial tumor xenografts. The residualizing agent, Cu-64-DOTA anti-EMP2 minibody, achieved high uptake in endometrial cancer xenografts overexpressing EMP2 (10.2 +/- 2.6, percent injected dose per gram (%ID/g) +/- SD) with moderate uptake in wild-type HEC1A tumors (6.0 +/- 0.1). In both cases, precise tumor delineation was observed from the PET images. In contrast, low uptake was observed with anti-EMP2 minibodies in EMP2-negative tumors (1.9 +/- 0.5). This new immune-PET agent may be useful for preclinical assessment of anti-EMP2 targeting in vivo. It may also have value for imaging of tumor localization and therapeutic response in patients with EMP2-positive malignancies. C1 [Fu, Maoyong; Brewer, Sarah; Said, Jonathan; Braun, Jonathan; Wadehra, Madhuri] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Olafsen, Tove; Wu, Anna M.; Braun, Jonathan] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Wu, Anna M.; Said, Jonathan; Braun, Jonathan; Wadehra, Madhuri] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Gordon, Lynn K.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Gordon, Lynn K.] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Surg, Los Angeles, CA 90099 USA. RP Wadehra, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. EM mwadehra@mednet.ucla.edu OI Braun, Jonathan/0000-0003-1646-2974 FU NIH [HD48540, R21 CA131756, CA016042, R24 CA86307] FX This work was supported by NIH grants HD48540 (J. Braun), R21 CA131756 (M. Wadehra), CA016042 (University of California at Los Angeles Jonsson Comprehensive Cancer Center flow cytometry core), and R24 CA86307 (Production of 64Cu at Washington University School of Medicine). A.M.W., J.S., J.B., and M.W. are members of the Jonsson Comprehensive Cancer Center. We are especially grateful to Dr. David Ho and Arye Lipman in ImaginAb, Inc. for the assistance with minibody KS83 construction and Dr. David Stout and Waldemar Ladno at the Crump Institute for Molecular Imaging at UCLA (U24 CA092865) for the assistance with the small animal PET/CT scans. NR 43 TC 4 Z9 5 U1 0 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD FEB PY 2013 VL 15 IS 1 BP 68 EP 78 DI 10.1007/s11307-012-0558-y PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 077MY UT WOS:000314033000009 PM 22585360 ER PT J AU Zhang, XY Chen, DC Xiu, MH De Yang, F Tan, YL He, SC Kosten, TA Kosten, TR AF Zhang, Xiang Yang Chen, Da Chun Xiu, Mei Hong De Yang, Fu Tan, Yun Long He, Shuchang Kosten, Therese A. Kosten, Thomas R. TI Thioredoxin, a novel oxidative stress marker and cognitive performance in chronic and medicated schizophrenia versus healthy controls SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Cognition; Oxidative stress; Psychopathology ID FREE-RADICAL PATHOLOGY; SUPEROXIDE-DISMUTASE; 1ST-EPISODE SCHIZOPHRENIA; NEUROPSYCHOLOGICAL STATUS; PLASMA THIOREDOXIN; REPEATABLE BATTERY; TARDIVE-DYSKINESIA; LIPID-PEROXIDATION; DIFFERENT FORMS; PSYCHOSIS AB Oxidative stress-induced damage to neurons may contribute to cognitive deficits during aging and in neuro-degenerative disorders. Schizophrenia has a range of cognitive deficits that may evolve from oxidative stress. Thioredoxin (TRX), a redox-regulating protein with antioxidant activity recognized as an oxidative-stress marker has recently been found to be involved in pathogenesis and psychopathology of schizophrenia. The aim of this study was to examine the association of TRX with cognitive deficits in schizophrenia. We recruited 45 chronic schizophrenic patients and 66 healthy control subjects and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum TRX in both groups. Schizophrenic symptoms were assessed using the positive and negative syndrome scale (PANSS). We found no significant difference in TRX levels between patients and healthy controls. Cognitive scores on the RBANS and four of its five subscales (all p<0.001) except for the Visuospatial/Constructional index (p>0.05) were significantly lower in schizophrenic patients than normal controls. For the patients, TRX was inversely associated with the Attention domain of cognitive deficits in schizophrenia; however, TRX was positively associated with Attention in controls. The significantly lower TRX levels in attention impaired schizophrenia compared to controls suggest that oxidative stress may be involved in the cognitive impairment, especially attention in schizophrenia. The differential association of TRX and cognitive performance in schizophrenia and controls may be related to the impaired oxidative stress status of schizophrenia patients. (C) 2012 Elsevier B. V. All rights reserved. C1 [Zhang, Xiang Yang; Kosten, Therese A.; Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Zhang, Xiang Yang; Kosten, Therese A.; Kosten, Thomas R.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Zhang, Xiang Yang; Chen, Da Chun; Xiu, Mei Hong; De Yang, Fu; Tan, Yun Long; Kosten, Thomas R.] Peking Univ, Beijing HuiLongGuan Hosp, Beijing 100871, Peoples R China. [He, Shuchang] Peking Univ, Dept Psychol, Beijing 100871, Peoples R China. RP Zhang, XY (reprint author), VA Med Ctr, Res Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. EM xyzhang@bcm.edu; kosten@bcm.edu FU Stanley Medical Research Institute [03T-459, 05T-726]; Department of Veterans Affairs; VISN 16; Mental Illness Research, Education and Clinical Center (MIRECC); United States National Institute of Health [K05-DA0454, P50-DA18827, U01-MH79639] FX Funding for this study was provided by grants from the Stanley Medical Research Institute (03T-459 and 05T-726), the Department of Veterans Affairs, VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC), and United States National Institute of Health (K05-DA0454, P50-DA18827 and U01-MH79639). These sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 62 TC 17 Z9 18 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 2013 VL 143 IS 2-3 BP 301 EP 306 DI 10.1016/j.schres.2012.11.017 PG 6 WC Psychiatry SC Psychiatry GA 072GX UT WOS:000313659000011 PM 23238053 ER PT J AU Jahshan, C Wynn, JK Green, MF AF Jahshan, Carol Wynn, Jonathan K. Green, Michael F. TI Relationship between auditory processing and affective prosody in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Auditory processing; Affective prosody; Mismatch negativity; P300 ID FACIAL AFFECT RECOGNITION; MISMATCH NEGATIVITY; SENSORY CONTRIBUTIONS; VOCAL EXPRESSION; COGNITION; PERCEPTION; DEFICITS; DISCRIMINATION; COMMUNICATION; METAANALYSIS AB Patients with schizophrenia have well-established deficits in their ability to identify emotion from facial expression and tone of voice. In the visual modality, there is strong evidence that basic processing deficits contribute to impaired facial affect recognition in schizophrenia. However, few studies have examined the auditory modality for mechanisms underlying affective prosody identification. In this study, we explored links between different stages of auditory processing, using event-related potentials (ERPs), and affective prosody detection in schizophrenia. Thirty-six schizophrenia patients and 18 healthy control subjects received tasks of affective prosody, facial emotion identification, and tone matching, as well as two auditory oddball paradigms, one passive for mismatch negativity (MMN) and one active for P300. Patients had significantly reduced MMN and P300 amplitudes, impaired auditory and visual emotion recognition, and poorer tone matching performance, relative to healthy controls. Correlations between ERP and behavioral measures within the patient group revealed significant associations between affective prosody recognition and both MMN and P300 amplitudes. These relationships were modality specific, as MMN and P300 did not correlate with facial emotion recognition. The two ERP waves accounted for 49% of the variance in affective prosody in a regression analysis. Our results support previous suggestions of a relationship between basic auditory processing abnormalities and affective prosody dysfunction in schizophrenia, and indicate that both relatively automatic pre-attentive processes (MMN) and later attention-dependent processes (P300) are involved with accurate auditory emotion identification. These findings provide support for bottom-up (e. g., perceptually based) cognitive remediation approaches. Published by Elsevier B.V. C1 VA Greater Los Angeles Healthcare Syst, Sierra Pacific Mental Illness Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. RP Jahshan, C (reprint author), VA Greater Los Angeles Healthcare Syst, MIRECC, Bldg 210,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM caroljahshan@hotmail.com RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU Department of Veterans Affairs Sierra Pacific Mental Illness Research, Education and Clinical Center (MIRECC); National Institute of Mental Health [MH065707]; Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment FX Funding for this study was provided by grants from the Department of Veterans Affairs Sierra Pacific Mental Illness Research, Education and Clinical Center (MIRECC) and the National Institute of Mental Health (MH065707 to MFG). The MIRECC and NIH had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.; Writing of this manuscript was supported by the Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment. The authors would like to thank Crystal Gibson, Cory Tripp, Katie Weiner, Mark McGee, Christen Waldon and Amanda Bender for their assistance with recruitment and testing. The authors would also like to thank Petri Laukka, Ph.D. and David I. Leitman, Ph.D. for providing the affective prosody task and tone matching task, respectively. NR 42 TC 17 Z9 17 U1 0 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 2013 VL 143 IS 2-3 BP 348 EP 353 DI 10.1016/j.schres.2012.11.025 PG 6 WC Psychiatry SC Psychiatry GA 072GX UT WOS:000313659000018 PM 23276478 ER PT J AU Mavandadi, S Rook, KS Newsom, JT Oslin, DW AF Mavandadi, Shahrzad Rook, Karen S. Newsom, Jason T. Oslin, David W. TI Suicidal ideation and social exchanges among at-risk veterans referred for a behavioral health assessment SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article DE Suicide; Positive social exchanges; Negative social exchanges; Mental health; Veterans ID PSYCHOLOGICAL DISTRESS; RELATIVE IMPORTANCE; COMMUNITY SAMPLE; DEPRESSION; POPULATION; AFFAIRS; SUPPORT; STRESS; ADULTS; LIFE AB The current study examined the independent association between positive (e.g., emotional and instrumental support) and negative (e.g., insensitive behavior, unwanted advice from others) social exchanges and suicidal ideation among veterans referred for a behavioral health assessment. The sample included 606 veterans [mean age = 54.96 (SD = 14.96)] referred by primary care for a clinical mental health/substance abuse (MH/SA) assessment following a positive MH/SA screen. Data on sociodemographics, MH/SA conditions (e.g., depression, PTSD, anxiety, and alcohol abuse), the self-reported frequency of positive and negative social exchanges, and suicidal ideation were extracted from clinical interviews and evaluated. Veterans were primarily male, non-married, and had adequate financial resources, and approximately half were White. 74.4 and 20.3 % met criteria for a MH/SA condition and suicidal ideation, respectively. Multiple logistic regression analyses revealed that, adjusting for sociodemographics, physical functioning, and comorbid MH/SA conditions, veterans reporting more frequent negative exchanges with network members were significantly more likely to report suicidal ideation. Positive exchanges, in contrast, were not significantly related to the outcome. Inadequate finances and MH/SA conditions also were significantly related to suicidal ideation. Findings highlight the value of exploring the quality of social exchanges among veterans in primary care who screen positive for behavioral health issues, as such information has the potential to inform screening and intervention efforts aimed at reducing suicidal ideation. C1 [Mavandadi, Shahrzad; Oslin, David W.] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. [Mavandadi, Shahrzad; Oslin, David W.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Rook, Karen S.] Univ Calif Irvine, Sch Social Ecol, Dept Psychol & Social Behav, Irvine, CA 92697 USA. [Newsom, Jason T.] Portland State Univ, Sch Community Hlth, Inst Aging, Portland, OR 97207 USA. RP Mavandadi, S (reprint author), Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, 3900 Woodland Ave,B215, Philadelphia, PA 19104 USA. EM Shahrzad.Mavandadi@va.gov FU VISN 4 Mental Illness Research, Education, and Clinical Center (MIRECC) at the Philadelphia Veterans Affairs Medical Center (PVAMC); VA Office of Research and Development FX This work was supported by the VISN 4 Mental Illness Research, Education, and Clinical Center (MIRECC) at the Philadelphia Veterans Affairs Medical Center (PVAMC) and VA Office of Research and Development. The content of this article does not reflect the views of the VHA or of the Government. NR 58 TC 6 Z9 6 U1 3 U2 26 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0933-7954 EI 1433-9285 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD FEB PY 2013 VL 48 IS 2 BP 233 EP 243 DI 10.1007/s00127-012-0534-5 PG 11 WC Psychiatry SC Psychiatry GA 074LR UT WOS:000313814500007 PM 22722536 ER PT J AU Richards, A Cheng, EM AF Richards, Adam Cheng, Eric M. TI Stroke Risk Calculators in the Era of Electronic Health Records Linked to Administrative Databases SO STROKE LA English DT Review DE cardiovascular disease; database management systems; electronic health records; epidemiology; risk assessment; stroke ID CORONARY-HEART-DISEASE; GLOBAL CARDIOVASCULAR RISK; TRANSIENT ISCHEMIC ATTACK; ATRIAL-FIBRILLATION; PRIMARY-CARE; SOCIOECONOMIC-STATUS; NATIONWIDE COHORT; VALIDATION; PREDICTION; SCORES C1 [Richards, Adam; Cheng, Eric M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Cheng, Eric M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Cheng, EM (reprint author), VA Greater Los Angeles, Dept Neurol, 11301 Wilshire Blvd,ML 127, Los Angeles, CA 90073 USA. EM eric.cheng@va.gov FU National Institutes of Health/National Institute of Neurological Disorders and Stroke [K23NS058571]; UCLA Outcomes Research Center; American Heart Association Pharmaceutical Roundtable FX Dr Cheng is supported by a Career Development Award from National Institutes of Health/National Institute of Neurological Disorders and Stroke (K23NS058571). Drs Cheng and Richards are supported by the UCLA Outcomes Research Center, funded through the American Heart Association Pharmaceutical Roundtable and David and Stevie Spina. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 40 TC 2 Z9 3 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 BP 564 EP 569 DI 10.1161/STROKEAHA.111.649798 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 073PK UT WOS:000313754800059 PM 23204057 ER PT J AU Yaffe, K Ackerson, L Hoang, TD Go, AS Maguire, MG Ying, GS Daniel, E Bazzano, LA Coleman, M Cohen, DL Kusek, JW Ojo, A Seliger, S Xie, DW Grunwald, JE AF Yaffe, Kristine Ackerson, Lynn Hoang, Tina D. Go, Alan S. Maguire, Maureen G. Ying, Gui-Shuang Daniel, Ebenezer Bazzano, Lydia A. Coleman, Martha Cohen, Debbie L. Kusek, John W. Ojo, Akinlolu Seliger, Stephen Xie, Dawei Grunwald, Juan E. CA CRIC Study Investigators TI Retinopathy and Cognitive Impairment in Adults With CKD SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Chronic kidney disease; cognitive impairment; retinopathy ID RETINAL MICROVASCULAR ABNORMALITIES; CHRONIC KIDNEY-DISEASE; SMALL-VESSEL DISEASE; GLOMERULAR-FILTRATION-RATE; CARDIOVASCULAR HEALTH; ATHEROSCLEROSIS RISK; ELDERLY POPULATION; RENAL-DISEASE; OLDER-ADULTS; FOLLOW-UP AB Background: Retinal microvascular abnormalities have been associated with cognitive impairment, possibly serving as a marker of cerebral small-vessel disease. This relationship has not been evaluated in persons with chronic kidney disease (CKD), a condition associated with increased risk of both retinal pathology and cognitive impairment. Study Design: Cross-sectional study. Setting & Participants: 588 participants 52 years or older with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study. Predictor: Retinopathy graded using the Early Treatment Diabetic Retinopathy Study severity scale and diameters of retinal vessels. Outcomes: Neuropsychological battery of 6 cognitive tests. Measurements: Logistic regression models were used to evaluate the association of retinopathy, individual retinopathy features, and retinal vessel diameters with cognitive impairment (<= 1 SD from the mean), and linear regression models were used to compare cognitive test scores across levels of retinopathy, adjusting for age, race, sex, education, and medical comorbid conditions. Results: The mean age of the cohort was 65.3 +/- 5.6 (SD) years, 51.9% were nonwhite, and 52.6% were men. The prevalence of retinopathy was 30.1%, and the prevalence of cognitive impairment was 14.3%. Compared with those without retinopathy, participants with retinopathy had an increased likelihood of cognitive impairment on executive function (35.1% vs 11.5%; OR, 3.4 [ 95% CI, 2.0-6.0]), attention (26.7% vs 7.3%; OR, 3.0 [ 95% CI, 1.8-4.9]), and naming (26.0% vs 10.0%; OR, 2.1 [ 95% CI, 1.2-3.4]) after multivariable adjustment. Increased level of retinopathy also was associated with lower cognitive performance on executive function and attention. Microaneurysms were associated with cognitive impairment on some domains, but there were no significant associations with other retinal measures after multivariable adjustment. Limitations: Unknown temporal relationship between retinopathy and impairment. Conclusions: In adults with CKD, retinopathy is associated with poor performance on several cognitive domains, including executive function and attention. Evaluation of retinal microvascular abnormalities may be a promising tool for identifying patients with CKD who are at increased risk of cognitive impairment. Am J Kidney Dis. 61(2): 219-227. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94121 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Ackerson, Lynn; Go, Alan S.] Kaiser Permanente, Div Res, Oakland, CA USA. [Hoang, Tina D.] No Calif Inst Res & Educ, San Francisco, CA USA. [Maguire, Maureen G.; Ying, Gui-Shuang; Daniel, Ebenezer; Grunwald, Juan E.] Univ Penn, Dept Ophthalmol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Bazzano, Lydia A.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA. [Coleman, Martha] Univ Hosp Cleveland, Cleveland Clin Fdn, Cleveland, OH 44106 USA. [Cohen, Debbie L.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kusek, John W.] NIDDKD, Div Kidney Urol & Hematol Dis, Bethesda, MD USA. [Ojo, Akinlolu] Univ Michigan Hlth Syst, Dept Internal Med, Ann Arbor, MI USA. [Ojo, Akinlolu] Univ Michigan Hlth Syst, Dept Nephrol, Ann Arbor, MI USA. [Seliger, Stephen] Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA. [Xie, Dawei] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM kristine.yaffe@ucsf.edu OI Daniel, Ebenezer/0000-0002-2027-2316 FU National Institutes of Health (NIH) [U01 DK060980, U01 DK060902, U01 DK060963, U01 DK060984, U01 DK060990, U01 DK061021, U01 DK061022]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [UL1 RR-024134, UL1 RR-025005, MO1 RR-16500, UL1 RR-024989, MO1 RR-000042, UL1 RR-024986, UL1 RR-029879, UL1 RR-024131]; NIDDK grant [R01 DK069406]; NIH [R01 DK74151]; Vivian S. Lasko Research Fund; Nina C. Mackall Trust, and Research to Prevent Blindness FX The CRIC Study is funded by National Institutes of Health (NIH) grants U01 DK060980, U01 DK060902, U01 DK060963, U01 DK060984, U01 DK060990, U01 DK061021, and U01 DK061022 and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants UL1 RR-024134, UL1 RR-025005, MO1 RR-16500, UL1 RR-024989, MO1 RR-000042, UL1 RR-024986, UL1 RR-029879, and UL1 RR-024131. The ancillary studies also were supported by NIDDK grant R01 DK069406, which was administered by the Northern California Institute for Research and Education and with resources of the Veterans Affairs Medical Center, San Francisco, CA, and by NIH R01 DK74151, Vivian S. Lasko Research Fund, Nina C. Mackall Trust, and Research to Prevent Blindness. NR 47 TC 9 Z9 10 U1 0 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD FEB PY 2013 VL 61 IS 2 BP 219 EP 227 DI 10.1053/j.ajkd.2012.10.006 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 071KP UT WOS:000313591800008 PM 23206534 ER PT J AU La Fountaine, MF Rivera, DR Radulovic, M Bauman, WA AF La Fountaine, Michael F. Rivera, Dwindally Rosado Radulovic, Miroslav Bauman, William A. TI The Hemodynamic Actions of Insulin Are Blunted in the Sublesional Microvasculature of Healthy Persons with Spinal Cord Injury SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Iontophoresis; Insulin; Autonomic; Laser Doppler Flowmetry; Skin Blood Flow ID SKELETAL-MUSCLE VASODILATION; NITRIC-OXIDE RELEASE; CARDIOVASCULAR-DISEASE; ENDOTHELIAL FUNCTION; GLUCOSE-INTOLERANCE; BLOOD-FLOW; SKIN; RESISTANCE; HUMANS; RISK AB La Fountaine MF, Rivera DR, Radulovic M, Bauman WA: The hemodynamic actions of insulin are blunted in the sublesional microvasculature of healthy persons with spinal cord injury. Am J Phys Med Rehabil 2013;92:127-135. Objective: The aim of this study was to gain a better understanding of the hemodynamic actions of insulin on cutaneous microcirculation in persons with spinal cord injury (SCI). Design: A prospective, open-label, nonrandomized, placebo-controlled investigation was performed in an otherwise healthy cohort of persons with SCI (n = 10) and in an age- and sex-matched cohort of control subjects whose neurologic function is intact (n = 10). Laser Doppler flowmetry characterized the peak blood perfusion unit (BPU) response (percent change from baseline) to insulin or placebo iontophoresis above and below the neurologic level of injury. Results: Placebo iontophoresis did not result in any statistically significant changes in BPU. In the arm, insulin iontophoresis resulted in a 20% mean increase in BPU (P < 0.05) in the control group and a 9% mean increase in the SCI group (P = 0.14). In the leg, insulin iontophoresis resulted in an 81% (P < 0.01) mean increase in BPU in the control group and a 29% (P < 0.001) mean increase in BPU in the SCI group. The relative effect of insulin on the lower extremity BPU response was significantly greater (P < 0.05) in the control group compared with the SCI group (77% vs. 35%, respectively). Conclusions: The hemodynamic actions of insulin are markedly blunted in the sublesional microvasculature of persons with SCI, most likely as a result of impaired sublesional sympathetic nervous system control. C1 [La Fountaine, Michael F.; Rivera, Dwindally Rosado; Radulovic, Miroslav; Bauman, William A.] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. [La Fountaine, Michael F.; Radulovic, Miroslav; Bauman, William A.] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA. [La Fountaine, Michael F.; Bauman, William A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Radulovic, Miroslav] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. [La Fountaine, Michael F.] Seton Hall Univ, Dept Phys Therapy, Sch Hlth & Med Sci, S Orange, NJ 07079 USA. RP La Fountaine, MF (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU Veterans Affairs Rehabilitation Research & Development National Center of Excellence for the Medical Consequences of Spinal Cord Injury [B9212-C]; James J. Peters VA Medical Center; James J. Peters VA Medical Center, Bronx, NY; Department of Veterans Affairs Rehabilitation Research & Development Service FX Funded by the Veterans Affairs Rehabilitation Research & Development National Center of Excellence for the Medical Consequences of Spinal Cord Injury (#B9212-C) and James J. Peters VA Medical Center.; The authors thank James J. Peters VA Medical Center, Bronx, NY, and the Department of Veterans Affairs Rehabilitation Research & Development Service for their support. NR 31 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD FEB PY 2013 VL 92 IS 2 BP 127 EP 135 DI 10.1097/PHM.0b013e31827d63ee PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 072KA UT WOS:000313668600004 PM 23328885 ER PT J AU Elias, JA Morgenroth, DC AF Elias, Joseph Abraham Morgenroth, David Crespi TI Amputee Care Education in Physical Medicine and Rehabilitation Residency Programs SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Residency; Amputee; Education; Physical Medicine and Rehabilitation ID LOWER-LIMB AMPUTATIONS; MUSCULOSKELETAL EDUCATION; INPATIENT REHABILITATION; UNITED-STATES; BACK-PAIN; PREVALENCE; OSTEOARTHRITIS; SERVICES; KNEE AB Elias JA, Morgenroth DC: Amputee care education in physical medicine and rehabilitation residency programs. Am J Phys Med Rehabil 2013;92:157-162. Objective: The aim of this study was to assess amputee care-related educational offerings and barriers to further educational opportunities in United States physical medicine and rehabilitation residency programs. Design: A two-part survey was distributed to all United States physical medicine and rehabilitation residency program directors. Part 1 assessed the use of educational tools in amputee education. Part 2 assessed the potential barriers to amputee care-related education. Results: Sixty-nine percent of the program directors responded. Seventy-five percent or more of the programs that responded have didactic lectures; grand rounds; reading lists; self-assessment exam review; gait analysis training; training with prosthetists; faculty with amputee expertise; and amputee care during inpatient, outpatient, and consult rotations. Less than 25% of the programs use intranet resources. No more than 14% of the programs said any one factor was a major barrier. However, some of the most prominent major barriers were limited faculty number, finances, and patient volume. The factors many of the programs considered somewhat of a barrier included lack of national standardized resources for curriculum, resident time, and faculty time. Conclusions: This study identified the most commonly used amputee educational opportunities and methods in physical medicine and rehabilitation residencies as well as the barriers to furthering resident amputee education. Developing Web-based resources on amputee care and increasing awareness of physiatrists as perioperative consultants could improve resident amputee education and have important implications toward optimizing care of individuals with amputation. C1 [Elias, Joseph Abraham; Morgenroth, David Crespi] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Morgenroth, David Crespi] Dept Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Morgenroth, DC (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way,RCS-117, Seattle, WA 98108 USA. OI Morgenroth, David/0000-0002-0226-7775 NR 24 TC 1 Z9 1 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD FEB PY 2013 VL 92 IS 2 BP 157 EP 162 DI 10.1097/PHM.0b013e318269d7c8 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 072KA UT WOS:000313668600008 PM 23334616 ER PT J AU Bowden, MG Woodbury, ML Duncan, PW AF Bowden, Mark G. Woodbury, Michelle L. Duncan, Pamela W. TI Promoting neuroplasticity and recovery after stroke: future directions for rehabilitation clinical trials SO CURRENT OPINION IN NEUROLOGY LA English DT Review DE neuroplasticity; recovery; rehabilitation; stroke ID DIRECT-CURRENT STIMULATION; CONSTRAINT-INDUCED MOVEMENT; RANDOMIZED CONTROLLED-TRIAL; NONINVASIVE CORTICAL STIMULATION; ADULT SQUIRREL-MONKEYS; MOTOR CORTEX; NEURAL PLASTICITY; AMBULATORY FUNCTION; DC-STIMULATION; BRAIN-INJURY AB Purpose of review The purpose is to establish a theoretical framework by which new interventions for poststroke rehabilitation may be developed incorporating knowledge of neuroplasticity and the critical ingredients of rehabilitation. Recent findings Large phase III randomized controlled trials (RCTs) are rare in neurorehabilitation, and the results of those that have been completed are perplexing because the experimental and control treatments were not different when matched for activity level. In addition, the outcome measures used to define treatment effects reflected behavioral endpoints, but did not reveal how neuroplastic mechanisms or other mechanistic factors may have contributed to the treatment response. Knowledge of both the neurophysiologic basis of recovery and key elements of interventions that drive motor learning, such as intensity and task progression, are critical for optimizing future poststroke motor rehabilitation clinical trials. Summary Future neurorehabilitation RCTs require a better understanding of the interaction of interventions and neurophysiological recovery in order to target interventions at specific neurophysiologic substrates, develop a more clear understanding of the impact of intervention parameters (e.g. dose, intensity), and advance discussions regarding optimal ways to partner medical and rehabilitation interventions in order to improve outcomes. C1 [Bowden, Mark G.; Woodbury, Michelle L.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. [Bowden, Mark G.; Woodbury, Michelle L.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Bowden, Mark G.] Med Univ S Carolina, Div Phys Therapy, Charleston, SC 29425 USA. [Woodbury, Michelle L.] Med Univ S Carolina, Div Occupat Therapy, Charleston, SC 29425 USA. [Duncan, Pamela W.] Wake Forest Baptist Med Ctr, Dept Neurol, Winston Salem, NC USA. RP Bowden, MG (reprint author), Med Univ S Carolina, Ralph H Johnson VA Med Ctr, 77 President St,MSC 700, Charleston, SC 29425 USA. EM bowdenm@musc.edu FU Ralph H. Johnson Veterans Affairs Medical Center; Department of Veterans Affairs Office of Research and Development [B-7177M, B-6332W]; South Carolina Clinical and Translational Research Institute Discovery Grant; American Heart Association Innovative Research Grant FX This work was supported in part by the Ralph H. Johnson Veterans Affairs Medical Center and the Department of Veterans Affairs Office of Research and Development, Rehabilitation Research and Development; Career Development-1 Award (B-7177M), PI: M. G. Bowden; Career Development-2 Award (B-6332W), PI: M.L. Woodbury.; None of the authors has a conflict of interest with this manuscript. Dr Duncan has been involved with private industry, notably she has received honorarium for consulting with Allergan to develop a post stroke disability measures and with Glaxo to design phase 2 trials to enhance stroke recovery. The authors are supported by the following grants: South Carolina Clinical and Translational Research Institute Discovery Grant; American Heart Association Innovative Research Grant. NR 57 TC 20 Z9 22 U1 1 U2 51 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD FEB PY 2013 VL 26 IS 1 BP 37 EP 42 DI 10.1097/WCO.0b013e32835c5ba0 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 070XI UT WOS:000313547000005 PM 23254556 ER PT J AU Van Houtven, CH Thorpe, JM Chestnutt, D Molloy, M Boling, JC Davis, LL AF Van Houtven, Courtney Harold Thorpe, Joshua M. Chestnutt, Deborah Molloy, Margory Boling, John C. Davis, Linda Lindsey TI Do Nurse-Led Skill Training Interventions Affect Informal Caregivers' Out-of-Pocket Expenditures? SO GERONTOLOGIST LA English DT Article DE Cost analysis; Intervention study; Nurses/midwives/nursing; Alzheimer's disease; Parkinson's disease; Average treatment effect ID RANDOMIZED CONTROLLED-TRIAL; ALZHEIMERS-DISEASE; HOME PLACEMENT; CARE; DEMENTIA; COST; BURDEN; CANCER; METAANALYSIS AB Purpose of the Study: This paper is a report of a study of the Assistance, Support, and Self-health Initiated through Skill Training (ASSIST) randomized control trial. The aim of this paper is to understand whether participating in ASSIST significantly changed the out-of-pocket (OOP) costs for family caregivers of Alzheimer's disease (AD) or Parkinson's disease (PD) patients. Design and Methods: Secondary analysis of randomized control trial data, calculating average treatment effects of the intervention on OOP costs. Enrollment in the ASSIST trial occurred between 2002 and 2007 at 2 sites: Durham, North Carolina, and Birmingham, Alabama. We profile OOP costs for caregivers who participated in the ASSIST study and use 2-part expenditure models to examine the average treatment effect of the intervention on caregiver OOP expenditures. Results: ASSIST-trained AD and PD caregivers reported monthly OOP expenditures that averaged $500-$600. The intervention increased the likelihood of caregivers spending any money OOP by 26 percentage points over usual care, but the intervention did not significantly increase overall OOP costs. Implications: The ASSIST intervention was effective and inexpensive to the caregiver in direct monetary outlays; thus, there are minimal unintended consequences of the trial on caregiver financial well-being. C1 [Van Houtven, Courtney Harold] Durham VA, Ctr Excellence Hlth Serv Res Primary Care, Durham, NC 27705 USA. [Van Houtven, Courtney Harold] Duke Univ, Dept Med, Durham, NC USA. [Thorpe, Joshua M.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA 15260 USA. [Thorpe, Joshua M.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Chestnutt, Deborah] Ralph H Johnson Charleston Vet Adm Hosp, VA Nurse Acad, Charleston, SC USA. [Molloy, Margory] Duke Univ, Sch Nursing, Ctr Nursing Discovery, Durham, NC USA. RP Van Houtven, CH (reprint author), Durham VA, Ctr Excellence Hlth Serv Res Primary Care, 508 Fulton St, Durham, NC 27705 USA. EM courtney.vanhoutven@duke.edu RI Thorpe, Joshua/C-1188-2013 FU NINR NIH HHS [R01 NR 008285, R01 NR008285] NR 36 TC 3 Z9 3 U1 2 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 2013 VL 53 IS 1 BP 60 EP 70 DI 10.1093/geront/gns045 PG 11 WC Gerontology SC Geriatrics & Gerontology GA 071RV UT WOS:000313612800007 PM 22459694 ER PT J AU Liu, WM Luo, YC Dunn, JH Norris, DA Dinarello, CA Fujita, M AF Liu, Weimin Luo, Yuchun Dunn, Jeffrey H. Norris, David A. Dinarello, Charles A. Fujita, Mayumi TI Dual Role of Apoptosis-Associated Speck-Like Protein Containing a CARD (ASC) in Tumorigenesis of Human Melanoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID KAPPA-B ACTIVATION; ABERRANT METHYLATION; TMS1/ASC; CANCER; CELLS; INFLAMMASOME; ADAPTER; FAMILY; GENE AB Apoptosis-associated Speck-like protein containing a CARD (caspase recruitment domain) (ASC) was originally named because it triggered apoptosis in certain tumors. More recently, however, ASC was found to be a central adaptor protein of inflammasome, which mediates the secretion of protumorigenic inflammation. Here we examined the role of ASC in tumorigenesis of human melanoma. Compared with primary melanoma, ASC protein expression was generally downregulated in metastatic melanoma. Although overexpressing ASC in metastatic melanoma showed no effects on cell viability, silencing ASC with short hairpin RNA induced Cl cell cycle arrest, reduced cell viability, and suppressed tumorigenesis in metastatic melanoma. On the other hand, silencing ASC in primary melanoma reduced cell death, increased cell viability, and enhanced tumorigenesis. In primary and metastatic melanoma cells, ASC knockdown inhibited inflammasome-mediated caspase-1 activity and IL-1 beta secretion. However, phosphorylated I kappa B kinase (IKK)alpha/beta expression and NF-kappa B activity were suppressed in metastatic melanoma and enhanced in primary melanoma after ASC knockdown. These findings suggest stage-dependent dual roles of ASC in tumorigenesis. ASC expression in primary melanoma inhibits tumorigenesis by reducing IKK alpha/beta phosphorylation and inhibiting NF-kappa B activity. In metastatic melanoma, on the other hand, this inhibitory effect is diminished, and ASC induces tumorigenic pathways through enhanced NF-kappa B activity and inflammasome-mediated IL-1 beta secretion. Journal of Investigative Dermatology (2013) 133, 518-527; doi:10.1038/jid.2012.317; published online 30 August 2012 C1 [Liu, Weimin; Luo, Yuchun; Dunn, Jeffrey H.; Norris, David A.; Fujita, Mayumi] Univ Colorado Denver, Dept Dermatol, Sch Med, Aurora, CO 80045 USA. [Norris, David A.; Fujita, Mayumi] Denver Vet Affairs Med Ctr, Denver, CO USA. [Dinarello, Charles A.] Univ Colorado Denver, Dept Med, Sch Med, Aurora, CO 80045 USA. RP Fujita, M (reprint author), Univ Colorado Denver, Dept Dermatol, Sch Med, Mail Stop 8127,12801 E 17th Ave,RC-1 S,Room 4124, Aurora, CO 80045 USA. EM mayumi.fujita@ucdenver.edu RI Luo, Yuchun/B-8683-2014 FU Veterans Affairs Merit Review Award; US National Institutes of Health [P30CA046934, P30AR057212]; Dermatology Foundation; Wendy Will Case Cancer Fund grant; Cancer League of Colorado; Tadamitsu Cancer Research Fund FX We thank the University of Colorado Denver (UCD) melanoma tissue bank for providing human melanoma samples, the University of Colorado Cancer Center (UCCC) and the Skin Disease Research Center (SDRC) flow core (Alistaire S. Acosta and Karen Helm) for helping with FACS, and IHCtech LLC for helping with immunohistochemical staining. We also thank Xianzhong Meng, MD, PhD (Department of Surgery, UCD), and Advance Light Microscopy Core Facility of UCD for technical support of microscopic analysis, and Manjinder Kaur, PhD (Department of Dermatology, UCD), for critically reviewing the manuscript. This work was supported, in whole or in part, by a Veterans Affairs Merit Review Award (to M.F.), US National Institutes of Health grants P30CA046934 (Flow Core of the UCCC) and P30AR057212 (Flow Core of the SDRC), Dermatology Foundation (to M.F.), Wendy Will Case Cancer Fund grant (to M.F.), Cancer League of Colorado (to M.F.), and Tadamitsu Cancer Research Fund (to M.F.). The funders had no role in study design, data collection, analysis and interpretation, manuscript preparation, or decision to submit the manuscript. NR 17 TC 23 Z9 23 U1 0 U2 9 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 FEB PY 2013 VL 133 IS 2 BP 518 EP 527 DI 10.1038/jid.2012.317 PG 10 WC Dermatology SC Dermatology GA 072JU UT WOS:000313668000031 PM 22931929 ER PT J AU Fok, WC Zhang, YQ Salmon, AB Bhattacharya, A Gunda, R Jones, D Ward, W Fisher, K Richardson, A Perez, VI AF Fok, Wilson C. Zhang, Yiqiang Salmon, Adam B. Bhattacharya, Arunabh Gunda, Rakesh Jones, Dean Ward, Walter Fisher, Kathleen Richardson, Arlan Perez, Viviana I. TI Short-Term Treatment With Rapamycin and Dietary Restriction Have Overlapping and Distinctive Effects in Young Mice SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Rapamycin; Dietary restriction; mTOR; Autophagy; Gene expression ID GLUTATHIONE REDOX STATE; GENETICALLY HETEROGENEOUS MICE; EXTENDS LIFE-SPAN; CELL-CYCLE ARREST; CALORIE RESTRICTION; OXIDATIVE STRESS; RAT HEPATOCYTES; MTOR INHIBITION; UREA CYCLE; LONGEVITY AB Because rapamycin, an inhibitor of the nutrient sensor mammalian target of rapamycin, and dietary restriction both increase life span of mice, it has been hypothesized that they act through similar mechanisms. To test this hypothesis, we compared various biological parameters in dietary restriction mice (40% food restriction) and mice fed rapamycin (14 ppm). Both treatments led to a significant reduction in mammalian target of rapamycin signaling and a corresponding increase in autophagy. However, we observed striking differences in fat mass, insulin sensitivity, and expression of cell cycle and sirtuin genes in mice fed rapamycin compared with dietary restriction. Thus, although both treatments lead to significant downregulation of mammalian target of rapamycin signaling, these two manipulations have quite different effects on other physiological functions suggesting that they might increase life span through a common pathway as well as pathways that are altered differently by dietary restriction and rapamycin. C1 [Fok, Wilson C.; Richardson, Arlan; Perez, Viviana I.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Zhang, Yiqiang; Salmon, Adam B.; Bhattacharya, Arunabh; Gunda, Rakesh; Ward, Walter; Fisher, Kathleen; Richardson, Arlan; Perez, Viviana I.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Zhang, Yiqiang; Ward, Walter; Fisher, Kathleen] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Salmon, Adam B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Salmon, Adam B.; Richardson, Arlan] S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX USA. [Jones, Dean] Emory Univ, Sch Med, Dept Med,Clin Biomarkers Lab, Div Pulm Allergy & Crit Care Med, Atlanta, GA USA. RP Perez, VI (reprint author), Oregon State Univ, Dept Biochem & Biophys, Linus Pauling Inst, Linus Pauling Sci Ctr 307, Corvallis, OR 97331 USA. EM viviana.perez@oregonstate.edu OI Fok, Wilson Chun Yim/0000-0003-3289-2093 FU San Antonio Nathan Shock Aging Center [1P30-AG-13319]; National Institutes of Health (NIH) [AG036613]; NIH [AG021890]; Ellison Medical Foundation FX Financial support was provided by The San Antonio Nathan Shock Aging Center (1P30-AG-13319 to A.R.), National Institutes of Health (NIH) RC2 Grand Opportunity grant (AG036613 to A.R.), NIH T32 Training Grant (AG021890 to W.C.F.), and The Ellison Medical Foundation (to V.I.P.). NR 55 TC 21 Z9 21 U1 1 U2 23 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD FEB PY 2013 VL 68 IS 2 BP 108 EP 116 DI 10.1093/gerona/gls127 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 069YW UT WOS:000313474000002 PM 22570137 ER PT J AU Baddley, JW Andes, DR Marr, KA Kauffman, CA Kontoyiannis, DP Ito, JI Schuster, MG Brizendine, KD Patterson, TF Lyon, GM Boeckh, M Oster, RA Chiller, T Pappas, PG AF Baddley, John W. Andes, David R. Marr, Kieren A. Kauffman, Carol A. Kontoyiannis, Dimitrios P. Ito, James I. Schuster, Mindy G. Brizendine, Kyle D. Patterson, Thomas F. Lyon, G. Marshall Boeckh, Michael Oster, Robert A. Chiller, Tom Pappas, Peter G. TI Antifungal therapy and length of hospitalization in transplant patients with invasive aspergillosis SO MEDICAL MYCOLOGY LA English DT Article DE aspergillosis; combination therapy; voriconazole; Aspergillus ID HEMATOPOIETIC STEM-CELL; SURVEILLANCE NETWORK TRANSNET; FUNGAL-INFECTIONS; IMMUNOCOMPROMISED PATIENTS; UNITED-STATES; AMPHOTERICIN-B; MORTALITY; RECIPIENTS; OUTCOMES; COSTS AB The impact of antifungal therapy on economic outcomes in patients with invasive aspergillosis (IA) needs further exploration. The purpose of this study was to describe antifungal therapy and factors associated with hospital length of stay (LOS) in transplant patients with IA. Patients were enrolled from March 2001 to October 2005 and IA cases identified through March 2006 from a sub-group of patients in the Transplant Associated Infection Surveillance Network (TRANSNET). Factors associated with hospital LOS were determined by logistic regression analysis. Of 361 patients, the mean age was 49 years, 60.7% were male, and 63% were hematopoietic stem cell transplantation (HSCT) recipients. Primary monotherapy was used in 233 (64.5%) patients, of which voriconazole (93/233, 39.9%) was most commonly used antifungal. Primary combination therapy was used in 128 (35.4%) of 361 patients, with voriconazole plus caspofungin (81/361, 22.4%) the most frequently employed. Mean duration of therapy was 115 days (HSCT 109.7; solid organ transplant [SOT] 125.3). Mean hospital LOS was 35.3 days (HSCT 38.7; SOT 29.7). Regression analysis identified disseminated IA, neutropenia, malnutrition and length of ICU stay as factors associated with increased hospital LOS. Initial voriconazole use was associated with decreased LOS. Further investigation on impact of antifungal therapy on economic outcomes is needed. C1 [Baddley, John W.] Univ Alabama Birmingham, Div Infect Dis, Dept Med, Birmingham, AL 35294 USA. [Baddley, John W.; Brizendine, Kyle D.; Oster, Robert A.; Pappas, Peter G.] Birmingham VA Med Ctr, Birmingham, AL USA. [Andes, David R.] Univ Wisconsin, Dept Med, Madison, WI USA. [Marr, Kieren A.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Kauffman, Carol A.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Kauffman, Carol A.] Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Dept Med, Houston, TX 77030 USA. [Ito, James I.] City Hope Natl Med Ctr, Dept Med, Los Angeles, CA USA. [Schuster, Mindy G.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Patterson, Thomas F.] S Texas Vet Healthcare Syst, San Antonio, TX USA. [Lyon, G. Marshall] Emory Univ, Dept Med, Atlanta, GA 30322 USA. [Boeckh, Michael] Fred Hutchinson Canc Res Ctr, Dept Med, Seattle, WA 98104 USA. [Chiller, Tom] Ctr Dis Control, Mycot Dis Branch, Atlanta, GA 30333 USA. RP Baddley, JW (reprint author), Univ Alabama Birmingham, Div Infect Dis, Dept Med, 1900 Univ Blvd,229 Tinsley Harrison Tower, Birmingham, AL 35294 USA. EM jbaddley@uab.edu FU Centers for Disease Control (CDC); Astellas; Pfizer; Merck; Schering Plough; NIH [K23AI064613, K24AI085118]; Schering-Plough; Astella Pharma Inc.; Enzon Pharmaceuticals; Merck and Co., Inc.; Basilea; Qiagen; T2 Biosystems FX TRANSNET was sponsored by the Centers for Disease Control (CDC), Astellas, Pfizer, Merck, and Schering Plough. Pfizer sponsored additional treatment data collection. The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the Centers of Disease Control and Prevention.; JWB was sponsored in part by NIH K23AI064613. He is on the advisory board or consulting for Pfizer and Merck. DRA receives research grants from Merck, Astellas and Pfizer and is a consultant for Astellas, Novartis, Merck, Schering Plough. KAM is sponsored in part by NIH K24AI085118 and receives research grants from Merck, Astellas and Pfizer. He is on the advisory board or consulting for Astellas, Basilea, Merck, Pfizer, Schering Plough. CAK receives research grants from Merck and is on the data adjudication Board, Pfizer, and the Data Safety Monitoring Board, Merck. DPK has received research support and honoraria from Schering-Plough, Pfizer, Astella Pharma Inc., Enzon Pharmaceuticals, and Merck and Co., Inc. JII is on the speakers' bureaux for Astellas, Enzon, Merck, Pfizer, Schering-Plough and is a consultant for Enzon, Sigma Tau. TFP receives research grants from Astellas, Basilea, Merck, Pfizer and Schering-Plough and is on the advisory boards or consulting for Astellas, Basilea, Merck, Pfizer and Toyoma. GML is on the advisory board for Merck and receives research funding from Pfizer, Astellas and Qiagen. PGP receives research support and is an ad hoc advisor for Merck, Pfizer, Astellas, Basilea and T2 Biosystems. The remaining authors have no conflicts of interest for this subject matter. The authors alone are responsible for the content and writing of the paper. NR 20 TC 13 Z9 14 U1 2 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD FEB PY 2013 VL 51 IS 2 BP 128 EP 135 DI 10.3109/13693786.2012.690108 PG 8 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 072MQ UT WOS:000313676100003 PM 22680976 ER PT J AU Schacht, JP Anton, RF Voronin, KE Randall, PK Li, XB Henderson, S Myrick, H AF Schacht, Joseph P. Anton, Raymond F. Voronin, Konstantin E. Randall, Patrick K. Li, Xingbao Henderson, Scott Myrick, Hugh TI Interacting Effects of Naltrexone and OPRM I and DAT I Variation on the Neural Response to Alcohol Cues SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE alcoholism; opioid antagonist; functional neuroimaging; SNP; VNTR ID OPIOID RECEPTOR GENE; DOPAMINE TRANSPORTER GENE; CLINICAL LABORATORY PARADIGM; NUCLEUS-ACCUMBENS; VENTRAL STRIATUM; 3'-UNTRANSLATED REGION; DEPENDENT SUBJECTS; SOCIAL DRINKERS; VARIABLE NUMBER; HEAVY DRINKERS AB Variation at a single nucleotide polymorphism in the mu-opioid receptor gene (OPRM I), Al 18G (Asn40Asp), may moderate naltrexone (NTX) effects in alcohol dependence. Both NTX and Al 18G variation have also been reported to affect alcohol cue-elicited brain activation. This study investigated whether sub-acute NTX treatment and Al 18G genotype interacted in their effects on cue-elicited activation of the ventral striatum (VS), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC). Secondarily, variation at a variable number tandem repeat polymorphism in the dopamine transporter gene (DAT I/SLC6A3), which has been associated with increased reward-related activation in VS, was analyzed as a moderator of medication and Al 18G effects. Seventy-four non-treatment-seeking alcohol-dependent individuals, half preselected to carry at least one copy of the Al 18G G (Asp) allele, were randomized to NTX (50 mg) or placebo for 7 days, and performed an fMRI alcohol cue reactivity task on day 6. Region-of-interest analyses indicated no main effects of medication or Al 18G genotype. However, these factors interacted in their effects on OFC activation, such that, among NTX-treated individuals, G-allele carriers had less activation than A-allele homozygotes. DAT I variation also moderated medication/Al 18G effects. There was a three-way interaction between medication and Al 18G and DAT I genotypes on VS activation, such that, among G-allele carriers who received NTX, DATI 10-repeat-allele (10R) homozygotes had less activation than 9-repeat-allele (9R) carriers. Further, IOR homozygotes who received NIX had less mPFC activation than 9R carriers. Polymorphic variation in OPRM I and DATI should be considered in future studies of NTX, particularly regarding its effects on reward processing. Neuropsychopharmacology (2013) 38, 414-422; doi:10.1038/npp.2012.195; published online 3 October 2012 C1 [Schacht, Joseph P.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Ctr Drug & Alcohol Programs, Charleston, SC 29425 USA. [Myrick, Hugh] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Schacht, JP (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Ctr Drug & Alcohol Programs, MSC 861, Charleston, SC 29425 USA. EM schacht@musc.edu FU National Institute on Alcohol Abuse and Alcoholism (the Charleston Alcohol Research Center) [P50 AA010761, T32 AA007474, K05 AA017435]; Eli Lilly; Schering Plough; Lundbeck; Alkermes; GlaxoSmithKline; Johnson Johnson; Abbott Laboratories; Merck; NIDA FX This work was supported by grants from the National Institute on Alcohol Abuse and Alcoholism: P50 AA010761 (the Charleston Alcohol Research Center), T32 AA007474 (to Dr Schacht), and K05 AA017435 (to Dr Anton). Portions were presented in a symposium at the 35th Annual Meeting of the Research Society on Alcoholism (June, 2012, San Francisco, CA).; Dr Anton reports as being a consultant or on the scientific advisory board for Eli Lilly, GlaxoSmithKline, Alkermes, Lundbeck, and Roche for the past 3 years. Additionally, as part of the Alcohol Clinical Trials Initiative workgroup (ACTIVE), he has received support from Eli Lilly, Schering Plough, Lundbeck, Alkermes, GlaxoSmithKline, Johnson & Johnson, and Abbott Laboratories. He has also received research contracts/grants from Eli Lilly and Merck. He is a stockholder in Alcomed, which has received Small Business Technology Transfer Research support from NIDA. Dr Myrick reports serving on speakers' bureaus for Bristol-Myers Squibb and Alkermes. All other authors declare no conflict of interest. NR 65 TC 34 Z9 34 U1 5 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 2013 VL 38 IS 3 BP 414 EP 422 DI 10.1038/npp.2012.195 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 073VK UT WOS:000313771000005 PM 23032071 ER PT J AU Theodoroff, SM Folmer, RL AF Theodoroff, Sarah M. Folmer, Robert L. TI Repetitive Transcranial Magnetic Stimulation as a Treatment for Chronic Tinnitus: A Critical Review SO OTOLOGY & NEUROTOLOGY LA English DT Review DE Repetitive transcranial magnetic stimulation; Tinnitus; Transcranial magnetic stimulation ID POSTTRAUMATIC-STRESS-DISORDER; DORSAL COCHLEAR NUCLEUS; LOW-FREQUENCY RTMS; AUDITORY-CORTEX; PREMOTOR CORTEX; NEURAL ACTIVITY; MOTOR CORTEX; FOLLOW-UP; SUPPRESSION; DEPRESSION AB Objective: Because chronic tinnitus is a condition that negatively impacts the quality of life for millions of people worldwide, a safe and effective treatment for tinnitus has been sought for decades. However, a true "cure'' for the most common causes of tinnitus remains elusive. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive procedure, has shown potential for reducing patients' perception or severity of tinnitus. This article provides background information about rTMS and reviews studies that investigated rTMS as a treatment for chronic tinnitus. Data Sources: PubMed and Medline databases (National Center for Biotechnology Information, U.S. National Library of Medicine) were searched for the terms repetitive transcranial magnetic stimulation, tinnitus, TMS, and rTMS in articles published from 1980 to 2012. Study Selection: Articles included in this review were selected to represent a sampling of rTMS methodologies that have been used with tinnitus patients. Data Extraction: Data extraction included sample size, TMS stimulation frequency, TMS stimulation intensity, number of pulses administered per session, number of TMS sessions, and method of tinnitus assessment. Data Synthesis: Because of the heterogeneity of the studies reviewed, most of which had small populations of subjects, it was not appropriate to perform a meta-analysis. A systematic review of the literature was conducted to summarize and critique published research results. Conclusion: Although optimism for the clinical use of rTMS as an effective treatment for tinnitus remains high among many researchers, clinicians, and patients, several key questions and procedural issues remain unresolved. Suggestions for improving rTMS research protocols are described and discussed. C1 [Theodoroff, Sarah M.; Folmer, Robert L.] Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR 97239 USA. [Theodoroff, Sarah M.; Folmer, Robert L.] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. RP Folmer, RL (reprint author), Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, 3710 SWUS Vet Hosp Rd NCRAR, Portland, OR 97239 USA. EM Robert.Folmer@va.gov FU U.S. Department of Veterans Affairs Rehabilitation Research and Development (RRD) Service; National Center for Rehabilitative Auditory Research at Portland VA Medical Center FX This research was supported by a grant from the U.S. Department of Veterans Affairs Rehabilitation Research and Development (RR&D) Service. Additional support was provided by the National Center for Rehabilitative Auditory Research at Portland VA Medical Center. NR 78 TC 20 Z9 24 U1 6 U2 39 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD FEB PY 2013 VL 34 IS 2 BP 199 EP 208 DI 10.1097/MAO.0b013e31827b4d46 PG 10 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 073YH UT WOS:000313778500004 PM 23444467 ER PT J AU Hawkins, K Donihi, AC Korytkowski, MT AF Hawkins, Kara Donihi, Amy C. Korytkowski, Mary T. TI Glycemic Management in Medical and Surgical Patients in the Non-ICU Setting SO CURRENT DIABETES REPORTS LA English DT Article DE Type 1 diabetes; Type 2 diabetes; Hyperglycemia; Inpatients; Insulin; Perioperative care; Continuity of patient care; Glycemic management; Medical and surgical patients; Non-ICU setting ID INTENSIVE INSULIN THERAPY; CRITICALLY-ILL PATIENTS; HOSPITALIZED-PATIENTS; RANDOMIZED-TRIAL; GLUCOSE CONTROL; PUMP THERAPY; INPATIENT; CARE; HYPERGLYCEMIA; HYPOGLYCEMIA AB Hyperglycemia is commonly observed in hospitalized patients with and without previously known diabetes and is associated with adverse outcomes. For this reason, measurement of blood glucose (BG) is recommended for all patients at admission. Measurement of an A1C identifies patients with either newly recognized diabetes or uncontrolled diabetes. Current guidelines advise fasting and premeal BG < 140 mg/dl, with maximal random BG < 180 mg/dl for the majority of noncritically ill patients. Rational use of basal bolus insulin (BBI) regimens is effective in achieving these glycemic goals, with low risk for hypoglycemia. The safety of BBI relies upon provider knowledge for initiation and adjustment of insulin doses for changes in nutritional status or use of medications affecting glucose metabolism. Smooth transition of care to the outpatient setting is facilitated by providing oral and written instructions regarding timing and dosing of insulin, as well as education in basic skills for home management. C1 [Hawkins, Kara] VA Pittsburgh Healthcare Syst, Div Endocrinol, Dept Med, Pittsburgh, PA USA. [Donihi, Amy C.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA. [Korytkowski, Mary T.] Univ Pittsburgh, Dept Med, Med Ctr, Div Endocrinol, Pittsburgh, PA 15213 USA. RP Korytkowski, MT (reprint author), Univ Pittsburgh, Dept Med, Med Ctr, Div Endocrinol, Room 560,3601 5th Ave, Pittsburgh, PA 15213 USA. EM mtk7@pitt.edu FU Sanofi-Aventis FX K. Hawkins, none; A. C. Donihi, none; M. T. Korytkowski has a board membership with the American Diabetes Association (volunteer position), was a consultant for Regeneron, and has received grant support and honoraria from Sanofi-Aventis. NR 49 TC 6 Z9 6 U1 0 U2 13 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD FEB PY 2013 VL 13 IS 1 BP 96 EP 106 DI 10.1007/s11892-012-0340-1 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 069LJ UT WOS:000313437300014 PM 23100037 ER PT J AU Adler, A Wegscheider, K Lieberman, D Aminalai, A Aschenbeck, J Drossel, R Mayr, M Mross, M Scheel, M Schroder, A Gerber, K Stange, G Roll, S Gauger, U Wiedenmann, B Altenhofen, L Rosch, T AF Adler, Andreas Wegscheider, Karl Lieberman, David Aminalai, Alireza Aschenbeck, Jens Drossel, Rolf Mayr, Michael Mross, Michael Scheel, Mathias Schroeder, Andreas Gerber, Katharina Stange, Gabriela Roll, Stephanie Gauger, Ulrich Wiedenmann, Bertram Altenhofen, Lutz Rosch, Thomas TI Factors determining the quality of screening colonoscopy: a prospective study on adenoma detection rates, from 12 134 examinations (Berlin colonoscopy project 3, BECOP-3) SO GUT LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HIGH-DEFINITION; WIDE-ANGLE; PROSPECTIVE MULTICENTER; COLORECTAL NEOPLASIA; SURGICAL MORTALITY; HOSPITAL VOLUME; WITHDRAWAL TIME; POLYP DETECTION; UNITED-STATES AB Background Screening colonoscopy (SC) outcome quality is best determined by the adenoma detection rate (ADR). The substantial variability in the ADRs between endoscopists may reflect different skills, experience and/or equipment. Objective To analyse the potential factors that may influence ADR variance, including case volume. Design 12 134 consecutive SCs (mean age 64.5 years, 47% men) from 21 Berlin private-practice colonoscopists were prospectively studied during 18 months. The data were analysed using a two-level mixed linear model to adequately address the characteristics of patients and colonoscopists. The ADR was regressed after considering the following factors: sex, age, bowel cleanliness, NSAID intake, annual SC case volume, lifetime experience, instrument withdrawal times, instrument generations used, and the number of annual continuing medical education (CME) meetings attended by the physician. The case volume was also retrospectively analysed from the 2007 national SC registry data (312 903 colonoscopies and 1004 colonoscopists). Results The patient factors that correlated with the ADR were sex, age (p<0.001) and low quality of bowel preparation (p=0.005). The factors that were related to the colonoscopists were the number of CME meetings attended (p=0.012) and instrument generation (p=0.001); these factors accounted for approximately 40% of the interphysician variability. Within a narrow range (6-11 min), the withdrawal time was not correlated with the ADR. Annual screening case volume did not correlate with the ADR, and this finding was confirmed by the German registry data. Conclusions The outcome quality of screening colonoscopies is mainly influenced by individual colonoscopist factors (ie, CME activities) and instrument quality. C1 [Adler, Andreas; Stange, Gabriela] Charite, Campus Virchow Hosp, D-13353 Berlin, Germany. [Wegscheider, Karl] Univ Hosp Hamburg Eppendorf, Dept Med Biometry & Epidemiol, D-20246 Hamburg, Germany. [Lieberman, David] Portland VA Med Ctr, Div Gastroenterol, Portland, OR USA. [Gerber, Katharina; Rosch, Thomas] Univ Hosp Hamburg Eppendorf, Dept Interdisciplinary Endoscopy, Berlin Study Grp Off, D-20246 Hamburg, Germany. [Roll, Stephanie] Charite, Campus Mitte Hosp, Inst Social Med Epidemiol & Hlth Econ, D-13353 Berlin, Germany. [Gauger, Ulrich] Berlin Stat Off, Berlin, Germany. [Wiedenmann, Bertram] Charite, Campus Virchow Klinikum, MED KLIN MS Hepatol U Gastroenterol, D-13353 Berlin, Germany. [Altenhofen, Lutz] Cent Res Inst Ambulatory Hlth Care, Berlin, Germany. RP Rosch, T (reprint author), Univ Hosp Hamburg Eppendorf, Dept Interdisciplinary Endoscopy, Berlin Study Grp Off, Martinistr 52, D-20246 Hamburg, Germany. EM t.roesch@uke.de FU Deutsche Krebshilfe e.V. [108166]; Olympus; Pentax; Falk Companies FX The Berlin Colonoscopy Screening Study was supported by a grant from Deutsche Krebshilfe e.V. (no. 108166) and by unrestricted grants from Olympus, Pentax and Falk Companies. There was no influence on study design, performance, data analysis or the writing of the manuscript. NR 33 TC 79 Z9 80 U1 1 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD FEB PY 2013 VL 62 IS 2 BP 236 EP 241 DI 10.1136/gutjnl-2011-300167 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 067AQ UT WOS:000313264400009 PM 22442161 ER PT J AU Slade, EP McCarthy, JF Valenstein, M Visnic, S Dixon, LB AF Slade, Eric P. McCarthy, John F. Valenstein, Marcia Visnic, Stephanie Dixon, Lisa B. TI Cost Savings from Assertive Community Treatment Services in an Era of Declining Psychiatric Inpatient Use SO HEALTH SERVICES RESEARCH LA English DT Article DE Assertive community treatment; inpatient use; serious mental illness ID CRITICAL TIME INTERVENTION; MENTAL-HOSPITAL TREATMENT; INSTRUMENTAL VARIABLES; CAUSAL INFERENCE; BEHAVIORAL-MODEL; HEALTH TREATMENT; MEDICAL-CARE; ILLNESS; HOMELESSNESS; PROGRAM AB Objective To assess, during a period of decreasing psychiatric inpatient utilization, cost savings from Assertive Community Treatment (ACT) programs for individuals with severe mental illnesses. Data Source U.S. Department of Veterans Affairs' (VA) national administrative data for entrants into ACT programs. Study Design An observational study of the effects of ACT enrollment on mental health inpatient utilization and costs in the first 12 months following enrollment. ACT enrollees (N = 2010) were propensity score matched to ACT-eligible non-enrollees (N = 4020). An instrumental variables generalized linear regression approach was used to estimate enrollment effects. Results Instrumental variables estimates indicate that between FY2001 and FY2004, entry into ACT resulted in a net increase of $4529 in VA costs. Trends in inpatient use among ACT program entrants suggest this effect remained stable after FY2004. However, eligibility for ACT declined 37 percent, because fewer patients met an eligibility standard based on high prior psychiatric inpatient use. Conclusions Savings from ACT programs depend on new enrollees' intensity of psychiatric inpatient utilization prior to entering the ACT program. Although a program eligibility standard based on prior psychiatric inpatient use helped to sustain the savings from VA ACT programs, over time, it also resulted in an unintended narrowing of program eligibility. C1 [Slade, Eric P.; Dixon, Lisa B.] US Dept Vet Affairs, VA Capitol Healthcare Network VISN 5, Mental Illness Res Educ & Clin Ctr, Baltimore, MD 21201 USA. [Slade, Eric P.; Dixon, Lisa B.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [McCarthy, John F.; Valenstein, Marcia] US Dept Vet Affairs, VA Serious Mental Illness Treatment Resource & Ev, Ann Arbor, MI USA. [McCarthy, John F.; Valenstein, Marcia] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI 48109 USA. [Visnic, Stephanie] US Dept Vet Affairs, Serious Mental Illness Treatment Resource & Evalu, Ann Arbor, MI USA. RP Slade, EP (reprint author), US Dept Vet Affairs, VA Capitol Healthcare Network VISN 5, Mental Illness Res Educ & Clin Ctr, 737 W Lombard St,Room 526, Baltimore, MD 21201 USA. EM eslade@psych.umaryland.edu FU U.S. Department of Veterans Affairs (VA) Health Services Research & Development Service [IIR-06-115] FX This project was supported by grant IIR-06-115 from the U.S. Department of Veterans Affairs (VA) Health Services Research & Development Service. Data for this project were generously provided by the VA New England Performance Evaluation Center (NEPEC), the VA Serious Mental Illness Treatment Resource and Evaluation Center (SMITREC), and the VA Health Economics Resource Center (HERC). The authors also thank Rosalinda Ignacio, Deborah Welsh, and Lan Li for outstanding data analysis; Alan Bellack at the VA VISN5 MIRECC and Frederic Blow at the VA SMITREC for their leadership and support of this project; and Robert Rosenheck at the VA NEPEC for many helpful suggestions on an earlier version of the manuscript. None of the authors has a financial or other conflict. NR 59 TC 6 Z9 6 U1 2 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD FEB PY 2013 VL 48 IS 1 BP 195 EP 217 DI 10.1111/j.1475-6773.2012.01420.x PG 23 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 066WT UT WOS:000313253100011 PM 22594523 ER PT J AU Molis, MR Diedesch, A Gallun, F Leek, MR AF Molis, Michelle R. Diedesch, Anna Gallun, Frederick Leek, Marjorie R. TI Vowel Identification by Amplitude and Phase Contrast SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE spectral contrast; formants; hearing impairment; frequency selectivity; phase; vowel identification ID HEARING-IMPAIRED LISTENERS; SPECTRAL CONTRAST; COMPONENT PHASE; ENHANCEMENT; NOISE; MODEL; INTELLIGIBILITY; PERCEPTION; FREQUENCY; SPEECH AB Vowel identification is largely dependent on listeners' access to the frequency of two or three peaks in the amplitude spectrum. Earlier work has demonstrated that, whereas normal-hearing listeners can identify harmonic complexes with vowel-like spectral shapes even with very little amplitude contrast between "formant" components and remaining harmonic components, listeners with hearing loss require greater amplitude differences. This is likely the result of the poor frequency resolution that often accompanies hearing loss. Here, we describe an additional acoustic dimension for emphasizing formant versus non-formant harmonics that may supplement amplitude contrast information. The purpose of this study was to determine whether listeners were able to identify "vowel-like" sounds using temporal (component phase) contrast, which may be less affected by cochlear loss than spectral cues, and whether overall identification improves when congruent temporal and spectral information are provided together. Five normal-hearing and five hearing-impaired listeners identified three vowels over many presentations. Harmonics representing formant peaks were varied in amplitude, phase, or a combination of both. In addition to requiring less amplitude contrast, normal-hearing listeners could accurately identify the sounds with less phase contrast than required by people with hearing loss. However, both normal-hearing and hearing-impaired groups demonstrated the ability to identify vowel-like sounds based solely on component phase shifts, with no amplitude contrast information, and they also showed improved performance when congruent phase and amplitude cues were combined. For nearly all listeners, the combination of spectral and temporal information improved identification in comparison to either dimension alone. C1 [Molis, Michelle R.; Diedesch, Anna; Gallun, Frederick; Leek, Marjorie R.] Portland VA Med Ctr, VA RR&D Natl Ctr Rehabilitat Auditory Res NCRAR, Portland, OR 97207 USA. [Molis, Michelle R.; Gallun, Frederick; Leek, Marjorie R.] Oregon Hlth & Sci Univ, Oregon Hearing Res Ctr, Portland, OR 97239 USA. RP Molis, MR (reprint author), Portland VA Med Ctr, VA RR&D Natl Ctr Rehabilitat Auditory Res NCRAR, 3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. EM michelle.molis@va.gov RI Gallun, Frederick/G-3792-2012 OI Gallun, Frederick/0000-0002-4145-2199 FU NIDCD [R01 DC 00626, T35 DC008764]; Department of Veterans Affairs Rehabilitation Research & Development Service [C6116W, C4963W]; Senior Research Career Scientist [C4042L] FX This research was supported by grant no. R01 DC 00626 [PI: Leek] from the NIDCD. Diedesch was supported by T35 DC008764 [PI: Leek], also from the NIDCD. Support was also provided by the Department of Veterans Affairs Rehabilitation Research & Development Service [Career Development grants C6116W (Molis) and C4963W (Gallun), and Senior Research Career Scientist award C4042L ( Leek)]. The work was supported with resources and the use of facilities at the Portland VA Medical Center. The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government. NR 23 TC 0 Z9 0 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD FEB PY 2013 VL 14 IS 1 BP 125 EP 137 DI 10.1007/s10162-012-0352-1 PG 13 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 068LZ UT WOS:000313369500010 PM 23007720 ER PT J AU Guyatt, GH Oxman, AD Santesso, N Helfand, M Vist, G Kunz, R Brozek, J Norris, S Meerpohl, J Djulbegovic, B Alonso-Coello, P Post, PN Busse, JW Glasziou, P Christensen, R Schunemann, HJ AF Guyatt, Gordon H. Oxman, Andrew D. Santesso, Nancy Helfand, Mark Vist, Gunn Kunz, Regina Brozek, Jan Norris, Susan Meerpohl, Joerg Djulbegovic, Ben Alonso-Coello, Pablo Post, Piet N. Busse, Jason W. Glasziou, Paul Christensen, Robin Schuenemann, Holger J. TI GRADE guidelines: 12. Preparing Summary of Findings tables-binary outcomes SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE GRADE; Summary of findings; Evidence profile; Confidence in estimates; Quality of evidence; Systematic reviews ID SULFONYLUREA-INDUCED HYPOGLYCEMIA; NATURAL FREQUENCIES; COCHRANE REVIEWS; CLINICAL-TRIALS; QUALITY; METAANALYSIS; OCTREOTIDE; DIFFERENCE AB (SoF) tables present, for each of the seven (or fewer) most important outcomes, the following: the number of studies and number of participants; the confidence in effect estimates (quality of evidence); and the best estimates of relative and absolute effects. Potentially challenging choices in preparing SoF table include using direct evidence (which may have very few events) or indirect evidence (from a surrogate) as the best evidence for a treatment effect. If a surrogate is chosen, it must be labeled as substituting for the corresponding patient-important outcome. Another such choice is presenting evidence from low-quality randomized trials or high-quality observational studies. When in doubt, a reasonable approach is to present both sets of evidence; if the two bodies of evidence have similar quality but discrepant results, one would rate down further for inconsistency. For binary outcomes, relative risks (RRs) are the preferred measure of relative effect and, in most instances, are applied to the baseline or control group risks to generate absolute risks. Ideally, the baseline risks come from observational studies including representative patients and identifying easily measured prognostic factors that define groups at differing risk. In the absence of such studies, relevant randomized trials provide estimates of baseline risk. When confidence intervals (CIs) around the relative effect include no difference, one may simply state in the absolute risk column that results fail to show a difference, omit the point estimate and report only the CIs, or add a comment emphasizing the uncertainty associated with the point estimate. (C) 2013 Elsevier Inc. All rights reserved. C1 [Guyatt, Gordon H.; Santesso, Nancy; Brozek, Jan; Busse, Jason W.; Schuenemann, Holger J.] McMaster Univ, Dept Clin Epidemiol & Biostat, W Hamilton, ON L8N 3Z5, Canada. [Guyatt, Gordon H.; Santesso, Nancy; Brozek, Jan; Busse, Jason W.; Schuenemann, Holger J.] McMaster Univ, Dept Med, W Hamilton, ON L8N 3Z5, Canada. [Oxman, Andrew D.; Vist, Gunn] Norwegian Knowledge Ctr Hlth Serv, N-0130 Oslo, Norway. [Helfand, Mark] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Oregon Evidence Based Practice Ctr, Portland, OR 97201 USA. [Kunz, Regina] Univ Basel Hosp, Basel Inst Clin Epidemiol, CH-4031 Basel, Switzerland. [Norris, Susan] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. [Meerpohl, Joerg] Univ Med Ctr Freiburg, Inst Med Biometry & Med Informat, German Cochrane Ctr, D-79104 Freiburg, Germany. [Meerpohl, Joerg] Univ Med Ctr Freiburg, Dept Pediat & Adolescent Med, Div Pediat Hematol & Oncol, D-79106 Freiburg, Germany. [Djulbegovic, Ben] Univ S Florida, Ctr Evidence Based Med & Hlth Outcomes Res, Tampa, FL 33612 USA. [Djulbegovic, Ben] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Hematol, Tampa, FL 33612 USA. [Djulbegovic, Ben] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Hlth Outcomes & Behav, Tampa, FL 33612 USA. [Alonso-Coello, Pablo] CIBRESP IIB St Pau, Iberoamer Cochrane Ctr, Barcelona 08041, Spain. [Alonso-Coello, Pablo] Hosp St Pau Creu & St Pau, Epidemiol & Publ Hlth CIBER CIBERESP, Barcelona 08041, Spain. [Post, Piet N.] Dutch Inst Healthcare Improvement CBO, Utrecht, Netherlands. [Busse, Jason W.] Inst Work & Hlth, Toronto, ON M5G 2E9, Canada. [Glasziou, Paul] Bond Univ, Fac Hlth Sci, Ctr Res Evidence Based Practice, Gold Coast, Qld 4229, Australia. [Christensen, Robin] Copenhagen Univ Hosp, Parker Inst, Musculoskeletal Stat Unit, Frederiksberg, Denmark. RP Guyatt, GH (reprint author), McMaster Univ, CLAR Res Grp, Dept Clin Epidemiol, Room 2C12,1200 Main St, W Hamilton, ON L8N 3Z5, Canada. EM guyatt@mcmaster.ca RI Djulbegovic, Benjamin/I-3661-2012; Meerpohl, Joerg/J-4224-2013; Glasziou, Paul/A-7832-2008 OI Djulbegovic, Benjamin/0000-0003-0671-1447; Meerpohl, Joerg/0000-0002-1333-5403; Glasziou, Paul/0000-0001-7564-073X; Busse, Jason/0000-0002-0178-8712 NR 38 TC 128 Z9 132 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD FEB PY 2013 VL 66 IS 2 BP 158 EP 172 DI 10.1016/j.jclinepi.2012.01.012 PG 15 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 068PK UT WOS:000313378500007 PM 22609141 ER PT J AU Wight, RG Aneshensel, CS Barrett, C Ko, M Chodosh, J Karlamangla, AS AF Wight, Richard G. Aneshensel, Carol S. Barrett, Christopher Ko, Michelle Chodosh, Joshua Karlamangla, Arun S. TI Urban neighbourhood unemployment history and depressive symptoms over time among late middle age and older adults SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID HEALTH; RETIREMENT AB Background Little is known about how a neighbourhood's unemployment history may set the stage for depressive symptomatology. This study examines the effects of urban neighbourhood unemployment history on current depressive symptoms and subsequent symptom trajectories among residentially stable late middle age and older adults. Contingent effects between neighbourhood unemployment and individual-level employment status (ie, cross-level interactions) are also assessed. Methods Individual-level survey data are from four waves (2000, 2002, 2004 and 2006) of the original cohort of the nationally representative US Health and Retirement Study. Neighbourhoods are operationalised with US Census tracts for which historical average proportion unemployed between 1990 and 2000 and change in proportion unemployed between 1990 and 2000 are used to characterise the neighbourhood's unemployment history. Hierarchical linear regressions estimate three-level (time, individual and neighbourhood) growth models. Results Symptoms in 2000 are highest among those residing in neighbourhoods characterised by high historical average unemployment beginning in 1990 and increasing unemployment between 1990 and 2000, net of a wide range of socio-demographic controls including individual-level employment status. These neighbourhood unemployment effects are not contingent upon individual-level employment status in 2000. 6-year trajectories of depressive symptoms decrease over time on average but are not significantly influenced by the neighbourhood's unemployment history. Conclusions Given the current US recession, future studies that do not consider historical employment conditions may underestimate the mental health impact of urban neighbourhood context. The findings suggest that exposure to neighbourhood unemployment earlier in life may be consequential to mental health later in life. C1 [Wight, Richard G.; Aneshensel, Carol S.; Barrett, Christopher] Univ Calif Los Angeles, Dept Community Hlth Sci, Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA. [Ko, Michelle] Univ Calif Los Angeles, Dept Hlth Serv, Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA. [Chodosh, Joshua; Karlamangla, Arun S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. [Chodosh, Joshua] VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. RP Wight, RG (reprint author), Univ Calif Los Angeles, Dept Community Hlth Sci, Fielding Sch Publ Hlth, 650 Charles Young Dr,Box 951772, Los Angeles, CA 90095 USA. EM rwight@ucla.edu OI Chodosh, Joshua/0000-0001-7784-4306 FU National Institute on Aging [R01AG022537] FX The project described was supported by award number R01AG022537 (CSA, Principal Investigator) from the National Institute on Aging. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Aging or the National Institutes of Health. NR 31 TC 12 Z9 12 U1 1 U2 28 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD FEB PY 2013 VL 67 IS 2 BP 153 EP 158 DI 10.1136/jech-2012-201537 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 068AC UT WOS:000313335900007 PM 22918896 ER PT J AU Anderson, CB Penson, DF Ni, SH Makarov, DV Barocas, DA AF Anderson, Christopher B. Penson, David F. Ni, Shenghua Makarov, Danil V. Barocas, Daniel A. TI Centralization of Radical Prostatectomy in the United States SO JOURNAL OF UROLOGY LA English DT Article DE prostatectomy; prostatic neoplasms; trends; robotics ID HOSPITAL VOLUME; OPERATIVE MORTALITY; POTENTIAL BENEFITS; SURGERY; CANCER; TRENDS; ASSOCIATION; TECHNOLOGY; PATTERNS; OUTCOMES AB Purpose: Radical prostatectomy is a common treatment for organ confined prostate cancer and its use is increasing. We examined how the increased volume is being distributed and what hospital characteristics are associated with increasing volume. Materials and Methods: We identified all men age 40 to less than 80 years who underwent radical prostatectomy for prostate cancer from 2000 to 2008 in the NIS (Nationwide Inpatient Sample) (586,429). Ownership of a surgical robot was determined using the 2007 AHA (American Hospital Association) Annual Survey. The association between hospital radical prostatectomy volume and hospital characteristics, including ownership of a robot, was explored using multivariate linear regression. Results: From 2000 to 2008 there was a 74% increase in the number of radical prostatectomies performed (p = 0.05) along with a 19% decrease in the number of hospitals performing radical prostatectomy (p < 0.001), resulting in an increase in annual hospital radical prostatectomy volume (p = 0.009). Several hospital variables were associated with greater radical prostatectomy volume including teaching status, urban location, large bed size and ownership of a robot in 2007. On multivariate analysis the year, teaching status, large bed size, urban location and presence of a robot were associated with higher hospital radical prostatectomy volume. Conclusions: Use of radical prostatectomy increased significantly between 2000 and 2008, most notably after 2005. The increase in radical prostatectomy resulted in centralization to select hospitals, particularly those in the top radical prostatectomy volume quartile and those investing in robotic technology. Our findings support the hypothesis that hospitals with the greatest volume increases are specialty centers already performing a high volume of radical prostatectomy procedures. C1 [Anderson, Christopher B.; Penson, David F.; Ni, Shenghua; Barocas, Daniel A.] Vanderbilt Univ, Med Ctr, Dept Urol Surg, Nashville, TN 37232 USA. [Penson, David F.; Barocas, Daniel A.] Vanderbilt Univ, Med Ctr, Ctr Surg Qual & Outcomes Res, Nashville, TN 37232 USA. [Penson, David F.] Tennessee Valley Geriatr Res Educ & Clin Ctr DFP, US Dept Vet Affairs, Nashville, TN USA. [Makarov, Danil V.] NYU, Sch Med, Dept Urol, New York, NY 10003 USA. [Makarov, Danil V.] New York Harbor Healthcare Syst, US Dept Vet Affairs, New York, NY USA. RP Anderson, CB (reprint author), Vanderbilt Univ, Med Ctr, Dept Urol Surg, A-1302 Med Ctr N, Nashville, TN 37232 USA. EM c.anderson@vanderbilt.edu RI Ni, Shenghua/E-7300-2013 OI Ni, Shenghua/0000-0002-8411-9126; Makarov, Danil/0000-0002-0565-9272 FU Agency for Healthcare Research and Quality [1 R01 HS019356-01] FX Supported by Grant 1 R01 HS019356-01 from the Agency for Healthcare Research and Quality (DFP) NR 28 TC 15 Z9 15 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 2013 VL 189 IS 2 BP 500 EP 506 DI 10.1016/j.juro.2012.10.012 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 069VI UT WOS:000313464800027 PM 23069384 ER PT J AU Hakimi, K Spanier, D AF Hakimi, Kevin Spanier, David TI Electrodiagnosis of Cervical Radiculopathy SO PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA LA English DT Article DE Cervical; Radiculopathy; Electrodiagnosis; Electromyography ID FLEXOR CARPI RADIALIS; ASYMPTOMATIC SUBJECTS; H-REFLEX; UTILITY; ROOT; ELECTROMYOGRAPHY; EPIDEMIOLOGY; MYELOGRAPHY; DIAGNOSIS; STENOSIS AB Cervical radiculopathy is a common diagnosis with a peak onset in the fifth decade. The most commonly affected nerve root is C7, C6, and C8. The etiology is often compressive, but may arise from noncompressive sources. Patients commonly complain of pain, weakness, numbness, and/or tingling. Examination may reveal sensory or motor disturbance in-a dermatomal/myotomal distribution. Neural compression and tension signs may be positive. Diagnostic tests include imaging and electrodiagnostic study. Electrodiagnostic study serves as an extension of the neurologic examination. Electrodiagnostic findings can be useful for patients with atypical symptoms, potential pain-mediated weakness, and nonfocal imaging findings. C1 [Hakimi, Kevin; Spanier, David] VA Puget Sound, Rehabil Care Serv RCS 117, Dept Rehabil Med, Rehabil Care Serv, Seattle, WA 98108 USA. RP Hakimi, K (reprint author), VA Puget Sound, Rehabil Care Serv RCS 117, Dept Rehabil Med, Rehabil Care Serv, 1660 S Columbian Way, Seattle, WA 98108 USA. EM khakimi@uw.edu NR 24 TC 5 Z9 5 U1 3 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1047-9651 J9 PHYS MED REH CLIN N JI Phys. Med. Rehabil. Clin. N. Am. PD FEB PY 2013 VL 24 IS 1 BP 1 EP + DI 10.1016/j.pmr.2012.08.012 PG 13 WC Rehabilitation SC Rehabilitation GA 065KA UT WOS:000313146000003 PM 23177027 ER PT J AU Brooks-Worrell, BM Palmer, JP AF Brooks-Worrell, B. M. Palmer, J. P. TI Attenuation of islet-specific T cell responses is associated with C-peptide improvement in autoimmune type 2 diabetes patients SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE autoimmunity; PPAR-; rosiglitazone; T cells; type 2 diabetes ID PROLIFERATOR-ACTIVATED-RECEPTOR; PPAR-GAMMA AGONISTS; PROGRESSIVE MULTIPLE-SCLEROSIS; TRANSCRIPTION FACTOR; IMMUNE-RESPONSES; INTERLEUKIN-12; ENCEPHALOMYELITIS; INFLAMMATION; LYMPHOCYTES; DISEASES AB The clinical efficacy of peroxisome proliferator-activated receptor gamma (PPAR-?) agonists in cell-mediated autoimmune diseases results from down-regulation of inflammatory cytokines and autoimmune effector cells. T cell islet autoimmunity has been demonstrated to be common in patients with phenotypic type 2 diabetes mellitus (T2DM) and islet-specific T cells (T+) to be correlated positively with more severe beta cell dysfunction. We hypothesized that the beneficial effects of the PPAR-? agonist, rosiglitazone, therapy in autoimmune T2DM patients is due, in part, to the immunosuppressive properties on the islet-specific T cell responses. Twenty-six phenotypic T2DM patients positive for T cell islet autoimmunity (T+) were identified and randomized to rosiglitazone (n?=?12) or glyburide (n?=?14). Beta cell function, islet-specific T cell responses, interleukin (IL)-12 and interferon (IFN)-? responses and islet autoantibodies were followed for 36 months. Patients treated with rosiglitazone demonstrated significant (P? 90 consecutive days). Results: During the study year, 35% of the sample received an opioid prescription and 5% received COT. Most first opioid prescriptions were written by primary care clinicians. Veterans prescribed COT were younger, had greater pain intensity, and high rates of psychiatric and substance use disorders compared with veterans in the other 2 groups. Among patients receiving COT, 29% were prescribed long-acting opioids, 37% received 1 or more urine drug screens, and 24% were prescribed benzodiazepines. Adjusting for age, sex, and baseline pain intensity, major depression [odds ratio 1.24 (1.10-1.39); 1.48 (1.14-1.93)], and nicotine dependence [1.34 (1.17-1.53); 2.02 (1.53-2.67)] were associated with receiving any opioid prescription and with COT, respectively. Discussion: Opioid initiations are common among veterans with persistent pain, but most veterans are not prescribed opioids long-term. Psychiatric disorders and substance use disorders are associated with receiving COT. Many Veterans receiving COT are concurrently prescribed benzodiazepines and many do not receive urine drug screening; additional study regarding practices that optimize safety of COT in this population is indicated. C1 [Dobscha, Steven K.; Morasco, Benjamin J.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA. [Dobscha, Steven K.; Morasco, Benjamin J.; Macey, Tara] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Ctr Occupat & Environm Toxicol, Portland, OR 97201 USA. [Dobscha, Steven K.; Morasco, Benjamin J.; Duckart, Jonathan P.] Portland VA Med Ctr, Ctr Study Chron Comorbid Mental & Phys Disorders, Portland, OR USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97201 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Internal Med, Portland, OR 97201 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Deyo, Richard A.] Kaiser Permanente Ctr Hlth Res, Portland, OR 90034 USA. RP Dobscha, SK (reprint author), Portland VA Med Ctr P3MHADM, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM steven.dobscha@va.gov FU National Institute on Drug Abuse, Bethesda, MD [K23DA023467]; VA Health Services Research and Development Service, Portland, OR [REA 06-174] FX Supported with resources and the use of facilities at the Portland VA Medical Center, Portland, OR. B.J.M. received support from award K23DA023467 from the National Institute on Drug Abuse, Bethesda, MD. J.P.D. was supported by grant REA 06-174 from the VA Health Services Research and Development Service, Portland, OR. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs or the National Institutes of Health. The authors declare no conflict of interest. NR 43 TC 37 Z9 38 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-8047 J9 CLIN J PAIN JI Clin. J. Pain PD FEB PY 2013 VL 29 IS 2 BP 102 EP 108 DI 10.1097/AJP.0b013e3182490bdb PG 7 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 063VK UT WOS:000313029900003 PM 23269280 ER PT J AU Hwang, U Platts-Mills, TF AF Hwang, Ula Platts-Mills, Timothy F. TI Acute Pain Management in Older Adults in the Emergency Department SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Pain; Geriatrics; Emergency medicine; Pain assessment; Analgesics ID RANDOMIZED CONTROLLED-TRIAL; POSTOPERATIVE PAIN; HIP FRACTURE; PHARMACOLOGICAL MANAGEMENT; MUSCULOSKELETAL PAIN; COMPARATIVE SAFETY; COPING SKILLS; CARE; MEDICATION; ANALGESIA AB Effective treatment of acute pain in older patients is a common challenge faced by emergency providers. Because older adults are at increased risk for adverse events associated with systemic analgesics, pain treatment must proceed cautiously. Essential elements to quality acute pain care include an early initial assessment for the presence of pain, selection of an analgesic based on patient-specific risks and preferences, and frequent reassessments and retreatments as needed. This article describes current knowledge regarding the assessment and treatment of acute pain in older adults. C1 [Hwang, Ula] Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA. [Hwang, Ula] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Hwang, Ula] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Platts-Mills, Timothy F.] Univ N Carolina, Dept Emergency Med, Chapel Hill, NC USA. [Platts-Mills, Timothy F.] Univ N Carolina, Dept Anesthesiol, Chapel Hill, NC USA. RP Hwang, U (reprint author), Mt Sinai Sch Med, Dept Emergency Med, 1 Gustave L Levy Pl,Box 1620, New York, NY 10029 USA. EM ula.hwang@mountsinai.org FU National Institute on Aging [AG031218, AG040734]; National Center for Research Resources through North Carolina Translational and Clinical Science Institute [KL2 TR000084, UL1 TR000083] FX Ula Hwang is supported by a K23 (AG031218) and R21 (AG040734) from the National Institute on Aging to study pain care for older adults in the ED setting. Dr Platts-Mills is supported by Award Number KL2 TR000084 and UL1 TR000083 from the National Center for Research Resources through the North Carolina Translational and Clinical Science Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources, the National Institutes of Health, or the North Carolina Translational and Clinical Science Institute. NR 71 TC 8 Z9 8 U1 3 U2 17 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 EI 1879-8853 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD FEB PY 2013 VL 29 IS 1 BP 151 EP + DI 10.1016/j.cger.2012.10.006 PG 15 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 058HK UT WOS:000312624500009 PM 23177605 ER PT J AU Lo, AX Harada, CN AF Lo, Alexander X. Harada, Caroline N. TI Geriatric Dizziness Evolving Diagnostic and Therapeutic Approaches for the Emergency Department SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Dizziness; Geriatrics; Vertigo; Stroke ID PAROXYSMAL POSITIONAL VERTIGO; NATIONALLY REPRESENTATIVE SAMPLE; TRANSIENT ISCHEMIC ATTACK; ACUTE VESTIBULAR SYNDROME; CROSS-SECTIONAL ANALYSIS; PRIMARY-CARE; PERSISTENT DIZZINESS; ELDERLY-PATIENTS; EPLEY MANEUVER; DIZZY PATIENT AB Dizziness affects one in five people over the age of 65 years and is associated with substantial healthcare costs. Serious causes of dizziness are found in 20% of patients over 50 years. The approach to the patient with dizziness is challenging as physical exam and diagnostic tests have suboptimal sensitivities. The risk of vascular events is higher in the first 30 days than after, suggesting some missed diagnoses. Medications and vestibular rehabilitation may serve as treatment options for dizziness, but data on their efficacy in older patients is lacking. C1 [Lo, Alexander X.] Univ Alabama Birmingham, Dept Emergency Med, Birmingham, AL 35249 USA. [Harada, Caroline N.] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. [Harada, Caroline N.] Univ Alabama Birmingham, Dept Med, Div Gerontol Geriatr & Palliat Care, Birmingham, AL 35249 USA. RP Lo, AX (reprint author), Univ Alabama Birmingham, Dept Emergency Med, OHB 251,619 19th St S, Birmingham, AL 35249 USA. EM alexanderlo@uabmc.edu FU John Hartford Foundation FX Supported by a grant from the John Hartford Foundation. NR 107 TC 3 Z9 6 U1 4 U2 14 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD FEB PY 2013 VL 29 IS 1 BP 181 EP + DI 10.1016/j.cger.2012.10.004 PG 25 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 058HK UT WOS:000312624500011 PM 23177607 ER PT J AU Breslau, N Troost, JP Bohnert, K Luo, Z AF Breslau, N. Troost, J. P. Bohnert, K. Luo, Z. TI Influence of predispositions on post-traumatic stress disorder: does it vary by trauma severity? SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Epidemiology; post-traumatic stress disorder; predispositions; sexual assault; trauma ID NATIONAL COMORBIDITY SURVEY; SEX-DIFFERENCES; YOUNG-ADULTS; DSM-IV; EXPOSURE; RISK; COMMUNITY; EVENTS; PTSD; INTELLIGENCE AB Background. Only a minority of trauma victims (< 10%) develops post-traumatic stress disorder (PTSD), suggesting that victims vary in predispositions to the PTSD response to traumas. It is assumed that the influence of predispositions is inversely related to trauma severity : when trauma is extreme predispositions are assumed to play a secondary role. This assumption has not been tested. We estimate the influence of key predispositions on PTSD induced by an extreme trauma - associated with a high percentage of PTSD - (sexual assault), relative to events of lower magnitude (accidents, disaster, and unexpected death of someone close). Method. The National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) is representative of the adult population of the USA. A total of 34 653 respondents completed the second wave in which lifetime PTSD was assessed. We conducted three series of multinomial logistic regressions, comparing the influence of six predispositions on the PTSD effect of sexual assault with each comparison event. Three pre-existing disorders and three parental history variables were examined. Results. Predispositions predicted elevated PTSD risk among victims of sexual assault as they did among victims of comparison events. We detected no evidence that the influence of predispositions on PTSD risk was significantly lower when the event was sexual assault, relative to accidents, disasters and unexpected death of someone close. Conclusions. Important predispositions increase the risk of PTSD following sexual assault as much as they do following accidents, disaster, and unexpected death of someone close. Research on other predispositions and alternative classifications of event severity would be illuminating. Received 13 March 2012; Revised 25 April 2012; Accepted 30 April 2012; First published online 18 June 2012 C1 [Breslau, N.; Troost, J. P.; Luo, Z.] Michigan State Univ, Coll Human Med, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Bohnert, K.] US Dept Vet Affairs, Serious Mental Illness Treatment Resource & Evalu, Ann Arbor, MI USA. RP Breslau, N (reprint author), Michigan State Univ, Coll Human Med, Dept Epidemiol & Biostat, B645 W Fee Hall, E Lansing, MI 48824 USA. EM breslau@epi.msu.edu FU National Institutes of Health, in Bethesda, MD [MH44586, MH071395, MH092737] FX This study was supported by grants no. MH44586 (N.B.), no. MH071395 (N.B.) and no. MH092737 (Z.L.) from the National Institutes of Health, in Bethesda, MD. NR 37 TC 11 Z9 11 U1 1 U2 36 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD FEB PY 2013 VL 43 IS 2 BP 381 EP 390 DI 10.1017/S0033291712001195 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 064IB UT WOS:000313066400014 PM 22703614 ER PT J AU Rahimy, E Law, SK AF Rahimy, Ehsan Law, Simon K. TI Orbital inflammation after zoledronate infusion: an emerging complication SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE LA English DT Letter ID BISPHOSPHONATES; DISEASE C1 [Rahimy, Ehsan; Law, Simon K.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Law, Simon K.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Law, SK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. EM law@jsei.ucla.edu NR 5 TC 2 Z9 2 U1 0 U2 1 PU CANADIAN OPHTHAL SOC PI OTTAWA PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA SN 0008-4182 EI 1715-3360 J9 CAN J OPHTHALMOL JI Can. J. Opthalmol.-J. Can. Opthalmol. PD FEB PY 2013 VL 48 IS 1 BP E11 EP E12 DI 10.1016/j.jcjo.2012.09.011 PG 3 WC Ophthalmology SC Ophthalmology GA AA5NR UT WOS:000331147200008 PM 23419305 ER PT J AU Beadling, C Patterson, J Justusson, E Nelson, D Pantaleo, MA Hornick, JL Chacon, M Corless, CL Heinrich, MC AF Beadling, Carol Patterson, Janice Justusson, Emily Nelson, Dylan Pantaleo, Maria A. Hornick, Jason L. Chacon, Matias Corless, Christopher L. Heinrich, Michael C. TI Gene expression of the IGF pathway family distinguishes subsets of gastrointestinal stromal tumors wild type for KIT and PDGFRA SO CANCER MEDICINE LA English DT Article DE Gastrointestinal stromal tumor; IGF1R; wild type AB Gastrointestinal stromal tumors (GISTs) arise from the interstitial cells of Cajal (ICCs) and are the most common mesenchymal neoplasm of the gastrointestinal tract. While the majority of GISTs harbor activating mutations in either the v-kit Hardy-Zuckerman feline sarcoma viral oncogene homolog (KIT) or platelet-derived growth factor receptor alpha (PDGFRA) tyrosine kinases, approximately 10-15% of adult GISTs and 85% of pediatric GISTs lack such mutations. These "wild-type" GISTs have been reported to express high levels of the insulin-like growth factor 1 receptor (IGF1R), and IGF1R-targeted therapy of wild-type GISTs is being evaluated in clinical trials. However, it is not clear that all wild-type GISTs express IGF1R, because studies to date have predominantly focused on a particular subtype of gastric wild-type GIST that is deficient in the mitochondrial succinate dehydrogenase (SDH) complex. This study of a series of 136 GISTs, including 72 wild-type specimens, was therefore undertaken to further characterize wild-type GIST subtypes based on the relative expression of transcripts encoding IGF1R. Additional transcripts relevant to GIST biology were also evaluated, including members of the IGF-signaling pathway (IGF1, IGF2, and insulin receptor [INSR]), neural markers (CDH2 [CDH: Cadherin], neurofilament, light polypeptide, LHX2 [LHX: LIM homeobox], and KIRREL3 [KIRREL: kin of IRRE like]), KIT, PDGFRA, CD34, and HIF1A. Succinate dehydrogenase complex, subunit B protein expression was also assessed as a measure of SDH complex integrity. In addition to the previously described SDH-deficient, IGF1R high wild-type GISTs, other SDH-intact wild-type subpopulations were defined by high relative expression of IGF1R, neural markers, IGF1 and INSR, or low IGF1R coupled with high IGF2. These results underscore the complexity and heterogeneity of wild-type GISTs that will need to be factored into molecularly-targeted therapeutic strategies. C1 [Beadling, Carol; Patterson, Janice; Justusson, Emily; Nelson, Dylan; Corless, Christopher L.; Heinrich, Michael C.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Beadling, Carol; Heinrich, Michael C.] Oregon Hlth & Sci Univ, Div Hematol & Oncol, Portland, OR 97201 USA. [Pantaleo, Maria A.] Univ Bologna, Dept Hematol & Oncol Sci, S Orsola Malpighi Hosp, I-40126 Bologna, Italy. [Hornick, Jason L.] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Chacon, Matias] GATE D, Buenos Aires, DF, Argentina. [Corless, Christopher L.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [Heinrich, Michael C.] Portland VA Med Ctr, Portland, OR USA. RP Heinrich, MC (reprint author), 3710 SW US Vet Hosp Rd,R&D 19, Portland, OR 97239 USA. EM Heinrich@ohsu.edu OI Patterson, Janice/0000-0002-8969-2933; PANTALEO, MARIA ABBONDANZA/0000-0002-0177-6957 FU GIST Cancer Research Fund; BP Lester Foundation; Life Raft Group; VA Merit Review Grant FX This study was supported, in part, by funds from the GIST Cancer Research Fund, the BP Lester Foundation, and the Life Raft Group (M. C. H. and C. L. C.). M. C. H. is a recipient of a VA Merit Review Grant. NR 45 TC 12 Z9 14 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 FEB PY 2013 VL 2 IS 1 BP 21 EP 31 DI 10.1002/cam4.57 PG 11 WC Oncology SC Oncology GA V36KH UT WOS:000209210500003 PM 24133624 ER PT J AU Bischoff, D Zhu, JH Makhijani, N Yamaguchi, D AF Bischoff, David Zhu, Jian-hua Makhijani, Nalini Yamaguchi, Dean TI Induction of CXC Chemokines in Human Mesenchymal Stem Cells (hMSCs) by Stimulation with Secreted Frizzled-Related Proteins (sFRPs) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Bischoff, David; Zhu, Jian-hua; Makhijani, Nalini; Yamaguchi, Dean] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 FEB PY 2013 VL 28 SU 1 MA SU0153 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035804219 ER PT J AU LaRue, A Parthiban, B Cumbee, JL Borke, J Ogawa, M Mehrotra, M AF LaRue, Amanda Parthiban, Beneta Cumbee, Jasper L. Borke, James Ogawa, Makio Mehrotra, Meenal TI Contribution of Hematopoietic Stem Cells to Dental Tissues SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [LaRue, Amanda] Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 USA. [Parthiban, Beneta; Cumbee, Jasper L.; Ogawa, Makio] MUSC, Charleston, SC USA. [Borke, James] Western Univ Hlth Sci, Pomona, CA USA. [Mehrotra, Meenal] Med Univ South Carolina & Res Serv, Ralph H Johnson VAMC, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0105 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035803037 ER PT J AU Liu, XH Kang, H Dang, A Kim, H Nissenson, R Halloran, B AF Liu, Xuhui Kang, Heejae Dang, Alexis Kim, Hubert Nissenson, Robert Halloran, Bernard TI A Novel Mouse Model of Heterotopic Ossification with Spinal Cord Injury SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Liu, Xuhui; Dang, Alexis; Kim, Hubert; Nissenson, Robert] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Kang, Heejae] San Francisco VA Med Ctr, San Francisco, CA USA. [Nissenson, Robert] VA Med Ctr, Portland, VA USA. [Halloran, Bernard] VA Med Ctr, Portland, VA 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0191 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035801225 ER PT J AU Mcnabb, B Vittinghoff, E Eastell, R Schwartz, A Bauer, D Ensrud, K Barrett-Connor, E Black, D AF Mcnabb, Brian Vittinghoff, Eric Eastell, Richard Schwartz, Ann Bauer, Douglas Ensrud, Kristine Barrett-Connor, Elizabeth Black, Dennis TI Post-Alendronate DXA Monitoring Strategy Based on 5-year Changes in BMD SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Mcnabb, Brian] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Vittinghoff, Eric; Schwartz, Ann; Bauer, Douglas; Black, Dennis] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Eastell, Richard] Univ Sheffield, Sheffield S10 2TN, S Yorkshire, England. [Ensrud, Kristine] Univ Minnesota, Minneapolis, MN 55455 USA. [Ensrud, Kristine] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA. [Barrett-Connor, Elizabeth] Univ Calif San Diego, San Diego, CA 92103 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA LB-MO21 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800222 ER PT J AU Nielson, C Srikanth, P Zmuda, J Shen, J Klein, R Orwoll, E AF Nielson, Carrie Srikanth, Priya Zmuda, Joseph Shen, Jian Klein, Robert Orwoll, Eric TI Gene by genome-wide interactions on femoral neck BMD in MrOS and SOF: a synergistic effect of polymorphisms in the alkaline phosphatase (ALPL) and lecithin retinol acyltransferase (LRAT) genes SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Nielson, Carrie; Srikanth, Priya; Shen, Jian; Orwoll, Eric] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Zmuda, Joseph] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Klein, Robert] Portland VA Med Ctr, Portland, OR 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0337 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035802070 ER PT J AU Wang, YM Menendez, A Fong, C Bikle, D AF Wang, Yongmei Menendez, Alicia Fong, Chak Bikle, Daniel TI EphrinB2/EphB4 Mediates the Actions of IGF-I Signaling in Regulating Vascularization during Endochondral Bone Formation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Wang, Yongmei; Menendez, Alicia; Fong, Chak] Univ Calif San Francisco, Endocrine Unit, San Francisco VA Med Ctr, San Francisco, CA USA. [Bikle, Daniel] Div Endocrinol UCSF, Endocrine Res Unit, San Francisco, CA USA. [Bikle, Daniel] VAMC, Portland, OR 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0156 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035803078 ER PT J AU Ye, S Park, BH Song, KJ Kim, JR Jang, KY Park, HS Bae, JS Brochmann, EJ Wang, JC Murray, SS Lee, KB AF Ye, Shuai Park, Byung-Hyun Song, Kyung-Jin Kim, Jung-Ryul Jang, Kyu-Yun Park, Ho-Sung Bae, Jun Sang Brochmann, Elsa J. Wang, Jeffrey C. Murray, Samuel S. Lee, Kwang-Bok TI In Vivo Inhibition of Bone Morphogenetic Protein-2 on Breast Cancer Cell Growth SO SPINE LA English DT Article DE BMP2; breast cancer; cell line MDA-MB-231; cell cycle ID PROSTATE-CANCER; EXPRESSION; TUMORIGENICITY; ENHANCEMENT; ANTAGONISTS; MATRIGEL; PATHWAY; LESIONS; KINASE; BMP-2 AB Study Design. In vitro and in vivo study. Objective. To evaluate the role of recombinant human bone morphogenetic protein-2 (rhBMP2) on breast cancer cell (MDA-MB-231 cells) growth. Summary of Background Data. Bone morphogenetic proteins (BMPs) are expressed in a variety of human carcinoma cell lines and are known to promote tumor invasion and metastasis. However, their roles in tumor progression have not been fully clarified. In addition, there is no in vivo study regarding the inhibitory effect of BMP2 on breast cancer cell proliferation. Method. Cell proliferation was determined by BrdU incorporation assay and flow cytometry. BMP2 signal transduction pathways were estimated on Western blot. Fifteen animals were divided into 2 groups; 1 (control = 5) was breast cancer cells alone, while the other (experiment = 5) was rhBMP2 + breast cancer cells. Cancer cells were injected into 2 sites (subcutaneous and femur) of nude mice with or without BMP2. Tumor size was determined by direct measurements for subcutaneous tumor formation and by femur radiographs. Histological and immunohistochemical analyses were performed. Results. RhBMP2 inhibited the proliferation of MDA-MB-231 cells in vitro. Inhibition was associated with changes in both the Smad and Wnt signaling pathways and was ultimately mediated through effects on various cell cycle proteins. Furthermore, rhBMP2 inhibited the growth of MDA-MB-231 cells injected both subcutaneously and intrafemorally. Conclusion. In this model using human breast adenocarcinoma cell line, rhBMP2 has no stimulatory effect of tumor growth. Therefore, we can provide the basic science data to support the utilization in the management of patients with spine tumor in the future. C1 [Ye, Shuai; Song, Kyung-Jin; Kim, Jung-Ryul; Lee, Kwang-Bok] Chonbuk Natl Univ, Sch Med, Dept Orthopaed Surg, Jeonju 561756, Jeonbuk, South Korea. [Park, Byung-Hyun] Chonbuk Natl Univ, Sch Med, Dept Biochem, Jeonju 561756, Jeonbuk, South Korea. [Jang, Kyu-Yun; Park, Ho-Sung; Bae, Jun Sang] Chonbuk Natl Univ, Sch Med, Dept Pathol, Jeonju 561756, Jeonbuk, South Korea. [Lee, Kwang-Bok] Chonbuk Natl Univ, Sch Med, Res Inst Clin Med, Biomed Res Inst,Chonbuk Natl Univ Hosp, Jeonju 561756, Jeonbuk, South Korea. [Wang, Jeffrey C.] Univ Calif Los Angeles, Dept Orthopaed Surg, Los Angeles, CA USA. [Brochmann, Elsa J.; Murray, Samuel S.] VA Greater Los Angeles, Geriatr Res Educ & Clin Ctr, Hlth Care Syst, Sepulveda, CA USA. [Brochmann, Elsa J.; Murray, Samuel S.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Wang, Jeffrey C.; Murray, Samuel S.] Univ Calif Los Angeles, Biomed Engn Interdept Program, Los Angeles, CA USA. RP Lee, KB (reprint author), Chonbuk Natl Univ, Sch Med, Dept Orthopaed Surg, 567 Baekje Daero, Jeonju 561756, Jeonbuk, South Korea. EM osdr2815@naver.com FU Biomedical Research Institute, Chonbuk National University Hospital FX This article was supported by the Biomedical Research Institute, Chonbuk National University Hospital. NR 21 TC 8 Z9 10 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD FEB 1 PY 2013 VL 38 IS 3 BP E143 EP E150 DI 10.1097/BRS.0b013e31827db4c6 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA AD1WD UT WOS:000333023500004 PM 23169070 ER PT J AU Arnold, CW Love, A El-Saden, S Liebeskind, DS Andrada, L Saver, J Bui, AA AF Arnold, Corey W. Love, Alexa El-Saden, Suzie Liebeskind, David S. Andrada, Lewellyn Saver, Jeffery Bui, Alex A. TI A Bayesian Network for Reasoning on Acute Ischemic Stroke Intervention SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Computer C1 [Arnold, Corey W.; Love, Alexa; Liebeskind, David S.; Andrada, Lewellyn; Saver, Jeffery; Bui, Alex A.] Univ Calif Los Angeles, Los Angeles, CA USA. [El-Saden, Suzie] VA Greater Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201057 ER PT J AU Damush, T Myers, L Anderson, J Yu, Z Ofner, S Schmid, A Williams, L AF Damush, Teresa Myers, Laura Anderson, Jane Yu, Zhangsheng Ofner, Susan Schmid, Arlene Williams, Linda TI Implementation of a Secondary Stroke Prevention Program: Effect on Medication Adherence SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Prevention; Behavioral medicine; Risk factors C1 [Damush, Teresa; Williams, Linda] Indiana Univ, Sch Med, VA Stroke QUERI Cntr, Indianapolis, IN 46204 USA. [Myers, Laura] Roudebush VAMC, Indianapolis, IN USA. [Anderson, Jane] Houston VAMC, Houston, TX USA. [Yu, Zhangsheng; Ofner, Susan] Indiana Univ, Sch Med, Dept Biostat, Indianapolis, IN 46204 USA. [Schmid, Arlene] Indiana Univ, VA Stroke QUERI Cntr, Indianapolis, IN 46204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201088 ER PT J AU Koyama, A Stone, K Yaffe, K AF Koyama, Alain Stone, Katie Yaffe, Kristine TI Serum oxidized low-density lipoprotein level and risk of cognitive impairment in older women SO NEUROBIOLOGY OF AGING LA English DT Article DE Dementia; Alzheimer's disease; Oxidized LDL; Inflammation; Oxidative stress ID ALZHEIMERS-DISEASE; DEMENTIA; LDL; INFLAMMATION AB We investigated the association between serum level of oxidized low-density lipoprotein (oxLDL) and risk of cognitive impairment (dementia or mild cognitive impairment) among 572 nondemented community-dwelling women from a prospective cohort study of aging. After 5 years of follow-up, 228 (39.9%) developed cognitive impairment; and this did not differ by tertile of baseline oxLDL level (highest compared with lowest tertile 38.2% vs. 39.5%; odds ratio, 0.90; 95% confidence interval, 0.63-1.43). Multivariate adjustment produced similar results (odds ratio, 0.91; 95% confidence interval, 0.60-1.39). These findings suggest that increased levels of serum oxLDL are not associated with a greater risk of incident cognitive impairment in older women. (C) 2013 Elsevier Inc. All rights reserved. C1 [Koyama, Alain] No Calif Inst Res & Educ, San Francisco, CA USA. [Koyama, Alain; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Stone, Katie] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Koyama, A (reprint author), 4150 Clement St,VAMC 116H, San Francisco, CA 94121 USA. EM alain.koyama@va.gov FU National Institute of Aging [K24 AG 031155, R01 AG 026720]; Alzheimer's Association [IIRG-08-88872]; National Institutes of Health; National Institute on Aging (NIA) [R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576] FX This study was supported in part by grants K24 AG 031155 and R01 AG 026720 from the National Institute of Aging and grant IIRG-08-88872 from the Alzheimer's Association. The Study of Osteoporotic Fractures (SOF) is supported by the National Institutes of Health. The National Institute on Aging (NIA) provides support under the following grant numbers: R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, and R01 AG027576. NR 15 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD FEB PY 2013 VL 34 IS 2 BP 634 EP U293 DI 10.1016/j.neurobiolaging.2012.02.030 PG 4 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 053HX UT WOS:000312263200025 PM 22483339 ER PT J AU Wong, MH Johnson, MD AF Wong, Mandi H. Johnson, Meshell D. TI Differential Response of Primary Alveolar Type I and Type II Cells to LPS Stimulation SO PLOS ONE LA English DT Article ID SURFACTANT-PROTEIN-D; NF-KAPPA-B; ACUTE LUNG INJURY; EPITHELIAL-CELLS; PULMONARY SURFACTANT; PNEUMOCOCCAL PNEUMONIA; GENE-EXPRESSION; PRIMARY CULTURE; HOST-DEFENSE; TNF-ALPHA AB The alveolar epithelium serves as a barrier between organism and environment and functions as the first line of protection against potential respiratory pathogens. Alveolar type II (TII) cells have traditionally been considered the immune cells of the alveolar epithelium, as they possess immunomodulatory functions; however, the precise role of alveolar type I (TI) cells, which comprise similar to 95% of the alveolar epithelial surface area, in lung immunity is not clear. We sought to determine if there was a difference in the response of TI and TII cells to lung injury and if TI cells could actively participate in the alveolar immune response. TI cells isolated via fluorescence activated cell sorting (FACS) from LPS-injured rats demonstrated greater fold-induction of multiple inflammatory mediators than TII cells isolated in the same manner from the same animals. Levels of the cytokines TNF-alpha, IL-6 and IL-1 beta from cultured primary rat TI cells after LPS stimulation were significantly increased compared to similarly studied primary rat TII cells. We found that contrary to published reports, cultured TII cells produce relatively small amounts of TNF-alpha, IL-6 and IL-1 beta after LPS treatment; the higher levels of cytokine expression from cultured TII cells reported in the literature were likely from macrophage contamination due to traditional non-FACS TII cell isolation methods. Co-culture of TII cells with macrophages prior to LPS stimulation increased TNF-alpha and IL-6 production to levels reported by other investigators for TII cells, however, co-culture of TI cells and macrophages prior to LPS treatment resulted in marked increases in TNF-alpha and IL-6 production. Finally, exogenous surfactant blunted the IL-6 response to LPS in cultured TI cells. Taken together, these findings advocate a role for TI cells in the innate immune response and suggest that both TI and TII cells are active players in host defense mechanisms in the lung. C1 [Wong, Mandi H.; Johnson, Meshell D.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Wong, Mandi H.; Johnson, Meshell D.] No Calif Inst Res & Educ, San Francisco, CA USA. [Johnson, Meshell D.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Johnson, MD (reprint author), San Francisco VA Med Ctr, San Francisco, CA 94121 USA. EM meshell.johnson@ucsf.edu FU Department of Veterans Affairs [CDA2]; Northern California Institute for Research and Education FX This work was supported by grants from the Department of Veterans Affairs (CDA2) and the Northern California Institute for Research and Education (www.ncire.org). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 13 Z9 15 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 31 PY 2013 VL 8 IS 1 AR e55545 DI 10.1371/journal.pone.0055545 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 085JH UT WOS:000314610600124 PM 23383221 ER PT J AU Hirata, H Ueno, K Shahryari, V Deng, GR Tanaka, Y Tabatabai, ZL Hinoda, Y Dahiya, R AF Hirata, Hiroshi Ueno, Koji Shahryari, Varahram Deng, Guoren Tanaka, Yuichiro Tabatabai, Z. Laura Hinoda, Yuji Dahiya, Rajvir TI MicroRNA-182-5p Promotes Cell Invasion and Proliferation by Down Regulating FOXF2, RECK and MTSS1 Genes in Human Prostate Cancer SO PLOS ONE LA English DT Article ID SUPPRESSOR GENE; TARGETING RECK; METASTASIS; CARCINOMA; MIR-182; PROGRESSION; EXPRESSION; METALLOPROTEINASE; OVEREXPRESSION; AGGRESSIVENESS AB Recently miR-182 has been reported to be over-expressed in prostate cancer (PC) tissues, however detailed functional analysis of miR-182-5p has not been carried out. The purpose of this study was to: 1. analyze the function of miR-182-5p in prostate cancer, 2. assess its usefulness as a tumor marker, 3. identify miR-182-5p target genes in PC, 4. investigate the potential for miR-182-5p inhibitor to be used in PC treatment. Initially we found that miR-182-5p expression was significantly higher in prostate cancer tissues and cell lines compared to normal prostate tissues and cells. Moreover high miR-182-5p expression was associated with shorter overall survival in PC patients. To study the functional significance of miR-182-5p, we knocked down miR-182-5p with miR-182-5p inhibitor. After miR-182-5p knock-down, prostate cancer cell proliferation, migration and invasion were decreased. We identified FOXF2, RECK and MTSS1 as potential target genes of miR-182-5p using several algorithms which was confirmed by 3'UTR luciferase assay and Western analysis. Knock-down of miR-182-5p also significantly decreased in vivo prostate tumor growth. In conclusion this is the first report documenting that over-expression of miR-182-5p is associated with prostate cancer progression and potentially useful as a prognostic biomarker. Also knock down of miR-182-5p in order to increase expression of tumor suppressor genes FOXF2, RECK and MTSS1 may be of therapeutic benefit in prostate cancer treatment. C1 [Hirata, Hiroshi; Ueno, Koji; Shahryari, Varahram; Deng, Guoren; Tanaka, Yuichiro; Dahiya, Rajvir] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA USA. [Hirata, Hiroshi; Ueno, Koji; Shahryari, Varahram; Deng, Guoren; Tanaka, Yuichiro; Tabatabai, Z. Laura; Dahiya, Rajvir] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Tabatabai, Z. Laura] San Francisco VA Med Ctr, Dept Pathol, San Francisco, CA USA. [Hinoda, Yuji] Yamaguchi Univ, Dept Oncol & Lab Med, Grad Sch Med, Yamaguchi, Japan. RP Dahiya, R (reprint author), San Francisco VA Med Ctr, Dept Urol, San Francisco, CA USA. EM rdahiya@urology.ucsf.edu FU National Center for Research Resources of the National Institutes of Health [RO1CA138642, RO1CA130860, RO1CA160079]; VA Merit Review grants; VA Program Project; Yamada Science Foundation FX This study was supported by National Center for Research Resources of the National Institutes of Health through Grant Number RO1CA138642, RO1CA130860, RO1CA160079, VA Merit Review grants, VA Program Project and Yamada Science Foundation. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 56 Z9 60 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 30 PY 2013 VL 8 IS 1 AR e55502 DI 10.1371/journal.pone.0055502 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 098QM UT WOS:000315563800161 PM 23383207 ER PT J AU Predina, J Eruslanov, E Judy, B Kapoor, V Cheng, GJ Wang, LC Sun, J Moon, EK Fridlender, ZG Albelda, S Singhal, S AF Predina, Jarrod Eruslanov, Evgeniy Judy, Brendan Kapoor, Veena Cheng, Guanjun Wang, Liang-Chuan Sun, Jing Moon, Edmund K. Fridlender, Zvi Gregorio Albelda, Steven Singhal, Sunil TI Changes in the local tumor microenvironment in recurrent cancers may explain the failure of vaccines after surgery SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material C1 [Predina, Jarrod; Eruslanov, Evgeniy; Judy, Brendan; Kapoor, Veena; Cheng, Guanjun; Singhal, Sunil] Univ Penn, Sch Med, Dept Surg, Thorac Surg Res Lab, Philadelphia, PA 19104 USA. [Wang, Liang-Chuan; Sun, Jing; Moon, Edmund K.; Fridlender, Zvi Gregorio; Albelda, Steven] Univ Penn, Sch Med, Dept Med, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA. [Singhal, Sunil] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA 19104 USA. RP Singhal, S (reprint author), Univ Penn, Sch Med, Dept Surg, Thorac Surg Res Lab, Philadelphia, PA 19104 USA. EM sunil.singhal@uphs.upenn.edu NR 0 TC 0 Z9 0 U1 1 U2 4 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 JAN 29 PY 2013 VL 110 IS 5 BP 1582 EP 1583 DI 10.1073/pnas.1211850110 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 084RZ UT WOS:000314558100011 ER PT J AU Predina, J Eruslanov, E Judy, B Kapoor, V Cheng, GJ Wang, LC Sun, J Moon, EK Fridlender, ZG Albelda, S Singhal, S AF Predina, Jarrod Eruslanov, Evgeniy Judy, Brendan Kapoor, Veena Cheng, Guanjun Wang, Liang-Chuan Sun, Jing Moon, Edmund K. Fridlender, Zvi Gregorio Albelda, Steven Singhal, Sunil TI Changes in the local tumor microenvironment in recurrent cancers may explain the failure of vaccines after surgery SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE immunology; tumor macrophages; T regulatory cells ID ADJUVANT IMMUNOTHERAPY; CELLS; CYTOREDUCTION; MACROPHAGES; INDUCTION; MECHANISM; CARCINOMA; RESECTION; ANTIGEN; GROWTH AB Each year, more than 700,000 people undergo cancer surgery in the United States. However, more than 40% of those patients develop recurrences and have a poor outcome. Traditionally, the medical community has assumed that recurrent tumors arise from selected tumor clones that are refractory to therapy. However, we found that tumor cells have few phenotypical differences after surgery. Thus, we propose an alternative explanation for the resistance of recurrent tumors. Surgery promotes inhibitory factors that allow lingering immunosuppressive cells to repopulate small pockets of residual disease quickly. Recurrent tumors and draining lymph nodes are infiltrated with M2 (CD11b(+)F4/80(hi)CD206(hi) and CD11b+F4/80(hi)CD124(hi)) macrophages and CD4(+)Foxp3(+) regulatory T cells. This complex network of immunosuppression in the surrounding tumor microenvironment explains the resistance of tumor recurrences to conventional cancer vaccines despite small tumor size, an intact antitumor immune response, and unaltered cancer cells. Therapeutic strategies coupling antitumor agents with inhibition of immunosuppressive cells potentially could impact the outcomes of more than 250,000 people each year. C1 [Predina, Jarrod; Eruslanov, Evgeniy; Judy, Brendan; Kapoor, Veena; Cheng, Guanjun; Singhal, Sunil] Univ Penn, Sch Med, Dept Surg, Thorac Surg Res Lab, Philadelphia, PA 19104 USA. [Wang, Liang-Chuan; Sun, Jing; Moon, Edmund K.; Fridlender, Zvi Gregorio; Albelda, Steven] Univ Penn, Sch Med, Dept Med, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA. [Singhal, Sunil] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA 19104 USA. RP Singhal, S (reprint author), Univ Penn, Sch Med, Dept Surg, Thorac Surg Res Lab, Philadelphia, PA 19104 USA. EM sunil.singhal@uphs.upenn.edu FU National Institutes of Health; Lavin Family Foundation; American Foundation for Cancer Research; National Lung Cancer Partnership FX We thank Theresa Busch and Cory Rice for their assistance in performing TGF-beta assays. S.S. is the recipient of a National Institutes of Health Paul Calabresi Scholarship. Further funding came from the Lavin Family Foundation (S.S.), the American Foundation for Cancer Research (S.S.), and the National Lung Cancer Partnership (S.S.). NR 32 TC 44 Z9 44 U1 1 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 JAN 29 PY 2013 VL 110 IS 5 BP E415 EP E424 DI 10.1073/pnas.1211850110 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 130VG UT WOS:000317947600014 PM 23271806 ER PT J AU Lin, CT McKenzie, M Pell, J Caplan, L AF Lin, Chen-Tan McKenzie, Marlene Pell, Jonathan Caplan, Liron TI Health Care Provider Satisfaction With a New Electronic Progress Note Format: SOAP vs APSO Format SO JAMA INTERNAL MEDICINE LA English DT Letter ID INFORMATION C1 [Lin, Chen-Tan; McKenzie, Marlene; Pell, Jonathan] Univ Colorado, Sch Med, Dept Med, Div Gen Internal Med, Aurora, CO 80045 USA. [Caplan, Liron] Univ Colorado, Sch Med, Dept Med, Div Rheumatol, Aurora, CO 80045 USA. [Caplan, Liron] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Lin, CT (reprint author), Univ Colorado, Sch Med, Dept Med, Div Gen Internal Med, 12631 E 17th Ave,Box B-180,Acad Off Bldg 1,Room 8, Aurora, CO 80045 USA. EM ct.lin@ucdenver.edu NR 8 TC 6 Z9 6 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN 28 PY 2013 VL 173 IS 2 BP 160 EP 162 DI 10.1001/2013.jamainternmed.474 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 121JO UT WOS:000317239700019 PM 23403939 ER PT J AU Beatty, AL Schiller, NB Whooley, MA AF Beatty, Alexis L. Schiller, Nelson B. Whooley, Mary A. TI Moderate Exercise for Improvement in 6-Minute Walk Test Performance in Stable Coronary Heart Disease Reply SO JAMA INTERNAL MEDICINE LA English DT Letter ID CARDIAC REHABILITATION PROGRAM C1 [Beatty, Alexis L.; Schiller, Nelson B.; Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Whooley, Mary A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Whooley, Mary A.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Beatty, AL (reprint author), Univ Calif San Francisco, Dept Med, 505 Parnassus Ave,Box 0124, San Francisco, CA 94143 USA. EM alexis.beatty@ucsf.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN 28 PY 2013 VL 173 IS 2 BP 169 EP 169 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 121JO UT WOS:000317239700029 PM 23358843 ER PT J AU Robinson, CP Schwarz, EM Sternberg, PW AF Robinson, Carmie Puckett Schwarz, Erich M. Sternberg, Paul W. TI Identification of DVA Interneuron Regulatory Sequences in Caenorhabditis elegans SO PLOS ONE LA English DT Article ID C-ELEGANS; NERVOUS-SYSTEM; TRANSCRIPTION FACTORS; GENE-EXPRESSION; DNA-SEQUENCE; NEURON; DIFFERENTIATION; CELL; SPECIFICATION; CONSERVATION AB Background: The identity of each neuron is determined by the expression of a distinct group of genes comprising its terminal gene battery. The regulatory sequences that control the expression of such terminal gene batteries in individual neurons is largely unknown. The existence of a complete genome sequence for C. elegans and draft genomes of other nematodes let us use comparative genomics to identify regulatory sequences directing expression in the DVA interneuron. Methodology/Principal Findings: Using phylogenetic comparisons of multiple Caenorhabditis species, we identified conserved non-coding sequences in 3 of 10 genes (fax-1, nmr-1, and twk-16) that direct expression of reporter transgenes in DVA and other neurons. The conserved region and flanking sequences in an 85-bp intronic region of the twk-16 gene directs highly restricted expression in DVA. Mutagenesis of this 85 bp region shows that it has at least four regions. The central 53 bp region contains a 29 bp region that represses expression and a 24 bp region that drives broad neuronal expression. Two short flanking regions restrict expression of the twk-16 gene to DVA. A shared GA-rich motif was identified in three of these genes but had opposite effects on expression when mutated in the nmr-1 and twk-16 DVA regulatory elements. Conclusions/Significance: We identified by multi-species conservation regulatory regions within three genes that direct expression in the DVA neuron. We identified four contiguous regions of sequence of the twk-16 gene enhancer with positive and negative effects on expression, which combined to restrict expression to the DVA neuron. For this neuron a single binding site may thus not achieve sufficient specificity for cell specific expression. One of the positive elements, an 8-bp sequence required for expression was identified in silico by sequence comparisons of seven nematode species, demonstrating the potential resolution of expanded multi-species phylogenetic comparisons. C1 [Robinson, Carmie Puckett; Schwarz, Erich M.; Sternberg, Paul W.] CALTECH, Div Biol, Pasadena, CA 91125 USA. [Robinson, Carmie Puckett; Schwarz, Erich M.; Sternberg, Paul W.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA. [Robinson, Carmie Puckett] Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. [Robinson, Carmie Puckett] Univ So Calif, Keck Sch Med, VA Greater Angeles Healthcare Syst, Los Angeles, CA 90033 USA. RP Sternberg, PW (reprint author), CALTECH, Div Biol, Pasadena, CA 91125 USA. EM pws@caltech.edu OI Schwarz, Erich/0000-0003-3151-4381 FU Howard Hughes Medical Insitute; National Institutes of Health [GM084389] FX Funding: Howard Hughes Medical Insitute, with which PWS is an investigator; National Institutes of Health GM084389 (to PWS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 1 Z9 5 U1 1 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 JAN 28 PY 2013 VL 8 IS 1 AR e54971 DI 10.1371/journal.pone.0054971 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093SF UT WOS:000315211500042 ER PT J AU Meissner, HI Glasgow, RE Vinson, CA Chambers, D Brownson, RC Green, LW Ammerman, AS Weiner, BJ Mittman, B AF Meissner, Helen I. Glasgow, Russell E. Vinson, Cynthia A. Chambers, David Brownson, Ross C. Green, Lawrence W. Ammerman, Alice S. Weiner, Bryan J. Mittman, Brian TI The US training institute for dissemination and implementation research in health SO IMPLEMENTATION SCIENCE LA English DT Article DE Training; Dissemination; Implementation ID KNOWLEDGE TRANSLATION; SCIENCE; FRAMEWORK AB Background: The science of dissemination and implementation (D&I) is advancing the knowledge base for how best to integrate evidence-based interventions within clinical and community settings and how to recast the nature or conduct of the research itself to make it more relevant and actionable in those settings. While the field is growing, there are only a few training programs for D&I research; this is an important avenue to help build the field's capacity. To improve the United States' capacity for D&I research, the National Institutes of Health and Veterans Health Administration collaborated to develop a five-day training institute for postdoctoral level applicants aspiring to advance this science. Methods: We describe the background, goals, structure, curriculum, application process, trainee evaluation, and future plans for the Training in Dissemination and Implementation Research in Health (TIDIRH). Results: The TIDIRH used a five-day residential immersion to maximize opportunities for trainees and faculty to interact. The train-the-trainer-like approach was intended to equip participants with materials that they could readily take back to their home institutions to increase interest and further investment in D&I. The TIDIRH curriculum included a balance of structured large group discussions and interactive small group sessions. Thirty-five of 266 applicants for the first annual training institute were accepted from a variety of disciplines, including psychology (12 trainees); medicine (6 trainees); epidemiology (5 trainees); health behavior/health education (4 trainees); and 1 trainee each from education & human development, health policy and management, health services research, public health studies, public policy and social work, with a maximum of two individuals from any one institution. The institute was rated as very helpful by attendees, and by six months after the institute, a follow-up survey (97% return rate) revealed that 72% had initiated a new grant proposal in D&I research; 28% had received funding, and 77% had used skills from TIDIRH to influence their peers from different disciplines about D&I research through building local research networks, organizing formal presentations and symposia, teaching and by leading interdisciplinary teams to conduct D&I research. Conclusions: The initial TIDIRH training was judged successful by trainee evaluation at the conclusion of the week's training and six-month follow-up, and plans are to continue and possibly expand the TIDIRH in coming years. Strengths are seen as the residential format, quality of the faculty and their flexibility in adjusting content to meet trainee needs, and the highlighting of concrete D&I examples by the local host institution, which rotates annually. Lessons learned and plans for future TIDIRH trainings are summarized. C1 [Meissner, Helen I.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Glasgow, Russell E.; Vinson, Cynthia A.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA. [Chambers, David] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [Brownson, Ross C.] Washington Univ, Sch Med, St Louis, MO USA. [Green, Lawrence W.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA USA. [Ammerman, Alice S.] Univ N Carolina, Gillings Sch Publ Hlth, Ctr Hlth Promot & Dis Prevent, Chapel Hill, NC USA. [Weiner, Bryan J.] Univ N Carolina, Dept Hlth Policy & Management, Gillings Sch Publ Hlth, Chapel Hill, NC USA. [Mittman, Brian] VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. RP Meissner, HI (reprint author), NIH, Off Behav & Social Sci Res, Bldg 10, Bethesda, MD 20892 USA. EM meissneh@od.nih.gov OI Mittman, Brian/0000-0003-3589-9178 FU NIDDK NIH HHS [P30 DK092950] NR 14 TC 34 Z9 34 U1 4 U2 22 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD JAN 24 PY 2013 VL 8 AR 12 DI 10.1186/1748-5908-8-12 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 137DC UT WOS:000318414200003 PM 23347882 ER PT J AU Roychaudhuri, R Yang, MF Deshpande, A Cole, GM Frautschy, S Lomakin, A Benedek, GB Teplow, DB AF Roychaudhuri, Robin Yang, Mingfeng Deshpande, Atul Cole, Gregory M. Frautschy, Sally Lomakin, Aleksey Benedek, George B. Teplow, David B. TI C-Terminal Turn Stability Determines Assembly Differences between A beta 40 and A beta 42 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article ID AMYLOID-BETA-PROTEIN; ALZHEIMERS-DISEASE; A-BETA; CROSS-LINKING; SECONDARY STRUCTURE; SENILE PLAQUES; FIBRILS; OLIGOMERIZATION; PEPTIDES; NMR AB Oligomerization of the amyloid beta-protein (A beta) is a seminal event in Alzheimer's disease. A beta 42, which is only two amino acids longer than A beta 40, is particularly pathogenic. Why this is so has not been elucidated fully. We report here results of computational and experimental studies revealing a C-terminal turn at Val36-Gly37 in A beta 42 that is not present in A beta 40. The dihedral angles of residues 36 and 37 in an Ile31-Ala42 peptide were consistent with beta-turns, and a beta-hairpin-like structure was indeed observed that was stabilized by hydrogen bonds and by hydrophobic interactions between residues 31-35 and residues 38-42. In contrast, A beta(31-40) mainly existed as a statistical coil. To study the system experimentally, we chemically synthesized A beta peptides containing amino acid substitutions designed to stabilize or destabilize the hairpin. The triple substitution Gly33Val-Va136Pro-Gly38Val ("VPV") facilitated A beta 42 hexamer and nonamer formation, while inhibiting formation of classical amyloid-type fibrils. These assemblies were as toxic as were assemblies from wild-type A beta 42. When substituted into A beta 40, the VPV substitution caused the peptide to oligomerize similarly to A beta 42. The modified A beta 40 was significantly more toxic than A beta 40. The double substitution D-Pro36-L-Pro37 abolished hexamer and dodecamer formation by A beta 42 and produced an oligomer size distribution similar to that of A beta 40. Our data suggest that the Va136-Gly37 turn could be the sine qua non of A beta 42. If true, this structure would be an exceptionally important therapeutic target. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Roychaudhuri, Robin; Yang, Mingfeng] Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Deshpande, Atul; Cole, Gregory M.; Frautschy, Sally] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. [Deshpande, Atul; Cole, Gregory M.; Frautschy, Sally] Greater Los Angeles Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Ctr, Sepulveda, CA 91343 USA. [Lomakin, Aleksey; Benedek, George B.] MIT, Ctr Mat Sci & Engn, Cambridge, MA 02139 USA. [Lomakin, Aleksey; Benedek, George B.] MIT, Dept Phys, Cambridge, MA 02139 USA. [Teplow, David B.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. [Teplow, David B.] Univ Calif Los Angeles, Inst Mol Biol, David Geffen Sch Med, Mary S Easton Ctr Alzheimers Dis Res, Los Angeles, CA 90095 USA. [Teplow, David B.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. RP Teplow, DB (reprint author), Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. EM dteplow@ucla.edu FU State of California Alzheimer's Disease Research Fund [07-65806]; UCLA Faculty Research Fund; National Institutes of Health [AG027818, NS038328]; Jim Easton Consortium for Alzheimer's Drug Discovery and Biomarkers FX We thank Margaret Condron for synthesizing all the peptides used here. We gratefully acknowledge grants from the State of California Alzheimer's Disease Research Fund (No. 07-65806), UCLA Faculty Research Fund, the National Institutes of Health (AG027818, NS038328), and the Jim Easton Consortium for Alzheimer's Drug Discovery and Biomarkers. NR 66 TC 30 Z9 31 U1 1 U2 46 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 23 PY 2013 VL 425 IS 2 BP 292 EP 308 DI 10.1016/j.jmb.2012.11.006 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 095AA UT WOS:000315305700008 PM 23154165 ER PT J AU Ma, LL Borwankar, AU Willsey, BW Yoon, KY Tam, JO Sokolov, KV Feldman, MD Milner, TE Johnston, KP AF Ma, L. L. Borwankar, A. U. Willsey, B. W. Yoon, K. Y. Tam, J. O. Sokolov, K. V. Feldman, M. D. Milner, T. E. Johnston, K. P. TI Growth of textured thin Au coatings on iron oxide nanoparticles with near infrared absorbance SO NANOTECHNOLOGY LA English DT Article ID MAGNETIC NANOPARTICLES; GOLD NANOPARTICLES; OPTICAL-PROPERTIES; SHELL NANOPARTICLES; FE OXIDE; SIZE; CORE; NANOCRYSTALS; REDUCTION; NANOSHELLS AB A homologous series of Au coated iron oxide nanoparticles with hydrodynamic diameters smaller than 60 nm was synthesized with very low Au-to-iron mass ratios, as low as 0.15. The hydrodynamic diameter was determined by dynamic light scattering and the composition by atomic absorption spectroscopy and energy dispersive x-ray spectroscopy. Unusually low Au precursor supersaturation levels were utilized to nucleate and grow Au coatings on iron oxide relative to the formation of pure Au nanoparticles. This approach produced unusually thin coatings by lowering autocatalytic growth of Au on Au, as shown by transmission electron microscopy. Nearly all of the nanoparticles were attracted by a magnet, indicating a minimal number of pure Au particles. The coatings were sufficiently thin to shift the surface plasmon resonance to the near infrared with large extinction coefficients, despite the small particle hydrodynamic diameters observed from dynamic light scattering to be less than 60 nm. C1 [Ma, L. L.; Borwankar, A. U.; Willsey, B. W.; Yoon, K. Y.; Johnston, K. P.] Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA. [Ma, L. L.; Feldman, M. D.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Tam, J. O.; Sokolov, K. V.; Milner, T. E.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. [Sokolov, K. V.] Univ Texas MD Anderson Canc Ctr, Dept Biomed Engn, Houston, TX 77030 USA. [Sokolov, K. V.] Univ Texas MD Anderson Canc Ctr, Dept Imaging Phys, Houston, TX 77030 USA. [Feldman, M. D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Cardiol, San Antonio, TX 78229 USA. RP Ma, LL (reprint author), Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA. EM kpj@che.utexas.edu OI Sokolov, Konstantin/0000-0002-0198-2005; Ma, Li/0000-0002-0959-5616 FU STC Program of the National Science Foundation [CHE-9876674]; Welch Foundation [F-1319]; NIH [RO1 EB008821-01, NIH RO1 CA 143663]; NSF [CBET-0968038]; Veterans Hospital Administration Merit Grant; National Natural Science Foundation of China [81000113] FX This work is supported in part by the STC Program of the National Science Foundation under Agreement CHE-9876674, Welch Foundation (F-1319), NIH RO1 EB008821-01, NIH RO1 CA 143663, NSF CBET-0968038 and Veterans Hospital Administration Merit Grant. Dr Li Leo Ma acknowledges partial support from the National Natural Science Foundation of China (81000113). NR 72 TC 4 Z9 4 U1 0 U2 75 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0957-4484 EI 1361-6528 J9 NANOTECHNOLOGY JI Nanotechnology PD JAN 18 PY 2013 VL 24 IS 2 AR 025606 DI 10.1088/0957-4484/24/2/025606 PG 14 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Science & Technology - Other Topics; Materials Science; Physics GA 057UF UT WOS:000312588800017 PM 23238021 ER PT J AU Le, T Wright, EJ Smith, DM He, WJ Catano, G Okulicz, JF Young, JA Clark, RA Richman, DD Little, SJ Ahuja, SK AF Le, Tuan Wright, Edwina J. Smith, Davey M. He, Weijing Catano, Gabriel Okulicz, Jason F. Young, Jason A. Clark, Robert A. Richman, Douglas D. Little, Susan J. Ahuja, Sunil K. TI Enhanced CD4+T-Cell Recovery with Earlier HIV-1 Antiretroviral Therapy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LYMPHOID-TISSUE STRUCTURE; SOCIETY-USA PANEL; T-CELLS; PRIMARY INFECTION; AIDS; SEROCONVERSION; CD4; RECOMMENDATIONS; RECONSTITUTION AB Background The relationship between the timing of the initiation of antiretroviral therapy (ART) after infection with human immunodeficiency virus type 1 (HIV-1) and the recovery of CD4+ T-cell counts is unknown. Methods In a prospective, observational cohort of persons with acute or early HIV-1 infection, we determined the trajectory of CD4+ counts over a 48-month period in partially overlapping study sets: study set 1 included 384 participants during the time window in which they were not receiving ART and study set 2 included 213 participants who received ART soon after study entry or sometime thereafter and had a suppressed plasma HIV viral load. We investigated the likelihood and rate of CD4+ T-cell recovery to 900 or more cells per cubic millimeter within 48 months while the participants were receiving viral-load-suppressive ART. Results Among the participants who were not receiving ART, CD4+ counts increased spontaneously, soon after HIV-1 infection, from the level at study entry (median, 495 cells per cubic millimeter; interquartile range, 383 to 622), reached a peak value (median, 763 cells per cubic millimeter; interquartile range, 573 to 987) within approximately 4 months after the estimated date of infection, and declined progressively thereafter. Recovery of CD4+ counts to 900 or more cells per cubic millimeter was seen in approximately 64% of the participants who initiated ART earlier (<= 4 months after the estimated date of HIV infection) as compared with approximately 34% of participants who initiated ART later (>4 months) (P<0.001). After adjustment for whether ART was initiated when the CD4+ count was 500 or more cells per cubic millimeter or less than 500 cells per cubic millimeter, the likelihood that the count would increase to 900 or more cells per cubic millimeter was lower by 65% (odds ratio, 0.35), and the rate of recovery was slower by 56% (rate ratio, 0.44), if ART was initiated later rather than earlier. There was no association between the plasma HIV RNA level at the time of initiation of ART and CD4+ T-cell recovery. Conclusions A transient, spontaneous restoration of CD4+ T-cell counts occurs in the 4-month time window after HIV-1 infection. Initiation of ART during this period is associated with an enhanced likelihood of recovery of CD4+ counts. (Funded by the National Institute of Allergy and Infectious Diseases and others.) C1 [Le, Tuan; He, Weijing; Catano, Gabriel; Clark, Robert A.; Ahuja, Sunil K.] S Texas Vet Hlth Care Syst, Vet Affairs Res Ctr AIDS & HIV Infect 1, San Antonio, TX 78229 USA. [Le, Tuan; He, Weijing; Catano, Gabriel; Clark, Robert A.; Ahuja, Sunil K.] S Texas Vet Hlth Care Syst, Ctr Personalized Med, San Antonio, TX USA. [Le, Tuan; He, Weijing; Catano, Gabriel; Clark, Robert A.; Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Okulicz, Jason F.] San Antonio Mil Med Ctr, Infect Dis Serv, Ft Sam Houston, TX USA. [Wright, Edwina J.] Monash Univ, Alfred Hosp, Dept Infect Dis, Burnet Inst, Melbourne, Vic 3181, Australia. [Wright, Edwina J.] Monash Univ, Dept Infect Dis, Melbourne, Vic 3004, Australia. [Smith, Davey M.; Richman, Douglas D.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. [Smith, Davey M.; Young, Jason A.; Richman, Douglas D.; Little, Susan J.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Richman, Douglas D.] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. RP Ahuja, SK (reprint author), S Texas Vet Hlth Care Syst, Vet Affairs Res Ctr AIDS & HIV Infect 1, San Antonio, TX 78229 USA. EM slittle@ucsd.edu; ahujas@uthscsa.edu FU Veterans Affairs (VA) Center for AIDS and HIV Infection; VA Center for Personalized Medicine of the South Texas Veterans Health Care System; National Institutes of Health (NIH) [UL1TR000149, R37 AI046326]; NIH [AI43638, AI69432, MH62512, AI74621, MH083552, AI077304, AI007384, AI080193, AI096113]; International AIDS Vaccine Initiative [DMS0714991]; California HIV/AIDS Research Program [RN07-SD-702]; VA Career Development Award-2; National Health and Medical Research Council of Australia; Doris Duke Distinguished Clinical Scientist Award, a VA MERIT; Elizabeth Glaser Pediatric AIDS Foundation; Burroughs Welcome Clinical Scientist Award in Translational Research; Senior Scholar Award from the Max and Minnie Tomerlin Voelcker Fund FX Supported by the Veterans Affairs (VA) Center for AIDS and HIV Infection and VA Center for Personalized Medicine of the South Texas Veterans Health Care System and a MERIT grant (R37 AI046326) and a Clinical and Translational Science Award (UL1TR000149) from the National Institutes of Health (NIH) (all for the work at San Antonio) and by grants from the NIH (AI43638, AI69432, MH62512, AI74621, MH083552, AI077304, AI007384, AI080193, and AI096113), the International AIDS Vaccine Initiative (DMS0714991), and the California HIV/AIDS Research Program (RN07-SD-702) (all for the work at San Diego). Dr. Le was supported by a VA Career Development Award-2, Dr. Wright by an Early Career Fellowship from the National Health and Medical Research Council of Australia, and Dr. Ahuja by the Doris Duke Distinguished Clinical Scientist Award, a VA MERIT award, the Elizabeth Glaser Pediatric AIDS Foundation, the Burroughs Welcome Clinical Scientist Award in Translational Research, and the Senior Scholar Award from the Max and Minnie Tomerlin Voelcker Fund. NR 33 TC 146 Z9 147 U1 0 U2 22 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 17 PY 2013 VL 368 IS 3 BP 218 EP 230 DI 10.1056/NEJMoa1110187 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 070YG UT WOS:000313549900006 PM 23323898 ER PT J AU Casson, L Howell, L Mathews, LA Ferrer, M Southall, N Guha, R Keller, JM Thomas, C Siskind, LJ Beverly, LJ AF Casson, Lavona Howell, Lauren Mathews, Lesley A. Ferrer, Marc Southall, Noel Guha, Rajarshi Keller, Jonathan M. Thomas, Craig Siskind, Leah J. Beverly, Levi J. TI Inhibition of Ceramide Metabolism Sensitizes Human Leukemia Cells to Inhibition of BCL2-Like Proteins SO PLOS ONE LA English DT Article ID DAUNORUBICIN-INDUCED APOPTOSIS; ACUTE LYMPHOBLASTIC-LEUKEMIA; BCL-2 FAMILY PROTEINS; BH3 MIMETIC ABT-737; GLUCOSYLCERAMIDE SYNTHASE; SPHINGOSINE KINASE; MYELOID-LEUKEMIA; CARCINOMA-CELLS; IN-VITRO; PATHWAY AB The identification of novel combinations of effective cancer drugs is required for the successful treatment of cancer patients for a number of reasons. First, many "cancer specific" therapeutics display detrimental patient side-effects and second, there are almost no examples of single agent therapeutics that lead to cures. One strategy to decrease both the effective dose of individual drugs and the potential for therapeutic resistance is to combine drugs that regulate independent pathways that converge on cell death. BCL2-like family members are key proteins that regulate apoptosis. We conducted a screen to identify drugs that could be combined with an inhibitor of anti-apoptotic BCL2-like proteins, ABT-263, to kill human leukemia cells lines. We found that the combination of D,L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) hydrochloride, an inhibitor of glucosylceramide synthase, potently synergized with ABT-263 in the killing of multiple human leukemia cell lines. Treatment of cells with PDMP and ABT-263 led to dramatic elevation of two pro-apoptotic sphingolipids, namely ceramide and sphingosine. Furthermore, treatment of cells with the sphingosine kinase inhibitor, SKi-II, also dramatically synergized with ABT-263 to kill leukemia cells and similarly increased ceramides and sphingosine. Data suggest that synergism with ABT-263 requires accumulation of ceramides and sphingosine, as AMP-deoxynojirimycin, (an inhibitor of the glycosphingolipid pathway) did not elevate ceramides or sphingosine and importantly did not sensitize cells to ABT-263 treatment. Taken together, our data suggest that combining inhibitors of anti-apoptotic BCL2-like proteins with drugs that alter the balance of bioactive sphingolipids will be a powerful combination for the treatment of human cancers. C1 [Casson, Lavona; Beverly, Levi J.] Univ Louisville, James Graham Brown Canc Ctr, Dept Med, Div Hematol & Oncol, Louisville, KY 40292 USA. [Howell, Lauren; Siskind, Leah J.] Med Sch S Carolina, S Carolina Coll Pharm, Dept Drug Discovery & Biomed Sci, Charleston, SC USA. [Mathews, Lesley A.; Ferrer, Marc; Southall, Noel; Guha, Rajarshi; Keller, Jonathan M.; Thomas, Craig] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Siskind, Leah J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Beverly, Levi J.] NHGRI, Canc Biol & Genet Sect, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Siskind, LJ (reprint author), Med Sch S Carolina, S Carolina Coll Pharm, Dept Drug Discovery & Biomed Sci, Charleston, SC USA. EM Siskind@MUSC.edu; Levi.Beverly@Louisville.edu RI Southall, Noel/H-8991-2012 OI Southall, Noel/0000-0003-4500-880X FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [R01DK093462]; Cancer Center Support Grant [P30 CA138313]; NIH/NCRR COBRE in Lipidomics and Pathobiology [P20 RR17677]; National Institutes of Health, Molecular Targets COBRE [8P20GM103482-10]; Wendy Will Case Cancer Fund [GB220413]; Kosair Pediatric Cancer Research Program award; NIH Common Fund Molecular Libraries and Imaging Program [U54 MH084681] FX Research reported in this publication was supported by: National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, R01DK093462 (to LJS), the Lipidomics Shared Resource of the Hollings Cancer Center at the Medical University of South Carolina supported by a Cancer Center Support Grant (P30 CA138313), pilot project (to LJS) from the NIH/NCRR P20 RR17677 COBRE in Lipidomics and Pathobiology, National Institutes of Health, Molecular Targets COBRE, 8P20GM103482-10 (to LJB), Wendy Will Case Cancer Fund, GB220413 (to LJB), Kosair Pediatric Cancer Research Program award (to LJB). This research was partly supported by the NIH Common Fund Molecular Libraries and Imaging Program, Grant U54 MH084681. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 15 Z9 15 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 16 PY 2013 VL 8 IS 1 AR e54525 DI 10.1371/journal.pone.0054525 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 072OV UT WOS:000313682700122 PM 23342165 ER PT J AU Rahnama, R Wang, MQ Dang, AC Kim, HT Kuo, AC AF Rahnama, Ruyan Wang, Miqi Dang, Alexis C. Kim, Hubert T. Kuo, Alfred C. TI Cytotoxicity of Local Anesthetics on Human Mesenchymal Stem Cells SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID ARTICULAR CHONDROCYTES; IN-VITRO; BUPIVACAINE; ARTHROSCOPY; CARTILAGE; CHONDROGENESIS; CHONDROLYSIS; ROPIVACAINE; LIDOCAINE; CATHETER AB Background: Local anesthetics are frequently delivered intra-articularly to provide perioperative pain control. Previous studies have shown that the commonly used drugs lidocaine, ropivacaine, and bupivacaine can be toxic to human chondrocytes. The present study was conducted to determine whether the toxic effects of local anesthetics on human chondrocytes also extend to human mesenchymal stem cells. Methods: Human mesenchymal stem cells from three healthy donors were grown in tissue culture and exposed to the following anesthetic treatments for sixty minutes: (1) 1% lidocaine, (2) 2% lidocaine, (3) 0.25% bupivacaine, (4) 0.5% bupivacaine, (5) 0.2% ropivacaine, and (6) 0.5% ropivacaine. The cells were then allowed to recover for twenty-four hours in regular growth media, and viability was measured with use of fluorescent staining for live cells or a luminescence assay for ATP content. Results: The live cell counts and ATP content were correlated (r(2) = 0.79), and 2% lidocaine was found to be significantly more toxic than all doses of bupivacaine and ropivacaine. Treatment with 1% lidocaine resulted in significantly fewer live cells (49%) compared with the control, and the live cell count was also significantly less than that for the other anesthetics. However, the ATP level in the 1% lidocaine group was not significantly lower than those in the other groups. Bupivacaine and ropivacaine did not exhibit significant differences in toxicity compared with the control or with each other. Conclusions: Ropivacaine and bupivacaine had limited toxicity in human mesenchymal stem cells. However, lidocaine could significantly decrease mesenchymal stem cell viability. Since other studies have shown ropivacaine to be less toxic to chondrocytes than bupivacaine, ropivacaine may be a safer intra-articular anesthetic. C1 [Rahnama, Ruyan] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Orthopaed Surg, San Francisco, CA 94121 USA. RP Rahnama, R (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Orthopaed Surg, 4150 Clement St,Box 112, San Francisco, CA 94121 USA. FU Department of Orthopaedic Surgery of the University of California San Francisco FX This work was performed with funding from the Department of Orthopaedic Surgery of the University of California San Francisco and with resources of the Veterans Affairs Medical Center, San Francisco, California. There was no external funding source. NR 27 TC 19 Z9 21 U1 0 U2 7 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JAN 16 PY 2013 VL 95A IS 2 BP 132 EP 137 DI 10.2106/JBJS.K.01291 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 076BO UT WOS:000313931700007 PM 23324960 ER PT J AU Roxburgh, RH Smith, CO Lim, JG Bachman, DF Byrd, E Bird, TD AF Roxburgh, Richard H. Smith, Corrie O. Lim, Jung G. Bachman, David F. Byrd, Erica Bird, Thomas D. TI The unique co-occurrence of spinocerebellar ataxia type 10 (SCA10) and Huntington disease SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE Spinocerebellar ataxia; Huntington disease; Trinucleotide repeat; Neurogenetics ID ATTCT REPEAT EXPANSION; BRAZILIAN FAMILIES; PHENOTYPE; GENE; HOMOZYGOSITY; MUTATIONS; ORIGIN; ONSET; SIGNS AB We present a unique thirty-nine year old woman with both Huntington's disease (HD) and spinocerebellar ataxia type 10 (SCA10). She has 48 CAG repeats in the HD gene and 2511 ATTCT repeats in the ATX10 gene. Although both conditions are repeat expansion diseases they are thought to have quite different pathogenic mechanisms. The symptomatic age of onset in this patient (mid30s) is within the expected range for her repeat expansion sizes for each condition, but we discuss the evidence that the two conditions may interact to produce a more severe cognitive phenotype than would be expected for either of the conditions independently. The subject has Amerindian background on the maternal side from Colombia, South America, thus adding a 5th country expressing SCA10, all with Amerindian ancestry. (C) 2012 Elsevier B.V. All rights reserved. C1 [Roxburgh, Richard H.] Auckland City Hosp, Dept Neurol, Auckland, New Zealand. [Roxburgh, Richard H.] Univ Auckland, Ctr Brain Res, Auckland 1, New Zealand. [Smith, Corrie O.; Byrd, Erica; Bird, Thomas D.] Univ Washington, Dept Med Med Genet & Neurol, Seattle, WA 98195 USA. [Lim, Jung G.] Lourdes Med Ctr, Pasco, WA 99301 USA. [Bird, Thomas D.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. RP Bird, TD (reprint author), Univ Washington, Box 356465, Seattle, WA 98195 USA. EM tomnroz@uw.edu OI Roxburgh, Richard/0000-0002-8930-7003 FU Athena Diagnostics, Inc. FX TDB receives licensing fees from Athena Diagnostics, Inc. NR 21 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD JAN 15 PY 2013 VL 324 IS 1-2 BP 176 EP 178 DI 10.1016/j.jns.2012.09.030 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 088RT UT WOS:000314855500035 PM 23083689 ER PT J AU Kartalija, M Ovrutsky, AR Bryan, CL Pott, GB Fantuzzi, G Thomas, J Strand, MJ Bai, XY Ramamoorthy, P Rothman, MS Nagabhushanam, V McDermott, M Levin, AR Frazer-Abel, A Giclas, PC Korner, J Iseman, MD Shapiro, L Chan, ED AF Kartalija, Marinka Ovrutsky, Alida R. Bryan, Courtney L. Pott, Gregory B. Fantuzzi, Giamila Thomas, Jacob Strand, Matthew J. Bai, Xiyuan Ramamoorthy, Preveen Rothman, Micol S. Nagabhushanam, Vijaya McDermott, Michael Levin, Adrah R. Frazer-Abel, Ashley Giclas, Patricia C. Korner, Judith Iseman, Michael D. Shapiro, Leland Chan, Edward D. TI Patients with Nontuberculous Mycobacterial Lung Disease Exhibit Unique Body and Immune Phenotypes SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE leptin; adiponectin; pectus excavatum; scoliosis; Marfan syndrome ID COMPLEX PULMONARY-DISEASE; NECROSIS-FACTOR-ALPHA; GROWTH-FACTOR-BETA; AVIUM COMPLEX; INTERFERON-GAMMA; MARFAN-SYNDROME; LEPTIN CONCENTRATIONS; CYTOKINE PRODUCTION; PECTUS EXCAVATUM; TGF-BETA AB Rationale: Among patients with nontuberculous mycobacterial lung disease is a subset of previously healthy women with a slender body morphotype, often with scoliosis and/or pectus excavatum. We hypothesize that unidentified factors predispose these individuals to pulmonary nontuberculous mycobacterial disease. Objectives: To compare body morphotype, serum adipokine levels, and whole-blood cytokine responses of patients with pulmonary nontuberculous mycobacteria (pNTM) with contemporary control subjects who are well matched demographically. Methods: We enrolled 103 patients with pNTM and 101 uninfected control subjects of similar demographics. Body mass index and body fat were quantified. All patients with pNTM and a subset of control subjects were evaluated for scoliosis and pectus excavatum. Serum leptin and adiponectin were measured. Specific cytokines important to host-defense against mycobacteria were measured in whole blood before and after stimulation. Measurements and Main Results: Patients with pNTM and control subjects were well matched for age, gender, and race. Patients with pNTM had significantly lower body mass index and body fat and were significantly taller than control subjects. Scoliosis and pectus excavatum were significantly more prevalent in patients with pNTM. The normal relationships between the adipokines and body fat were lost in the patients with pNTM, a novel finding. IFN-gamma and IL-10 levels were significantly suppressed in stimulated whole blood of patients with pNTM. Conclusions: This is the first study to comprehensively compare body morphotype, adipokines, and cytokine responses between patients with NTM lung disease and demographically matched controls. Our findings suggest a novel, predisposing immunophenotype that should be mechanistically defined. C1 [Kartalija, Marinka; Bryan, Courtney L.; Pott, Gregory B.; Iseman, Michael D.; Shapiro, Leland] Univ Colorado Denver, Div Infect Dis, Aurora, CO USA. [Thomas, Jacob; Strand, Matthew J.] Univ Colorado Denver, Dept Biostat, Aurora, CO USA. [Bai, Xiyuan; Iseman, Michael D.; Chan, Edward D.] Univ Colorado Denver, Div Pulm Sci & Crit Care Med, Aurora, CO USA. [Rothman, Micol S.; McDermott, Michael] Univ Colorado Denver, Div Endocrinol, Aurora, CO USA. [Ovrutsky, Alida R.; Bai, Xiyuan; Ramamoorthy, Preveen; Nagabhushanam, Vijaya; Levin, Adrah R.; Iseman, Michael D.; Chan, Edward D.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. [Ovrutsky, Alida R.; Bai, Xiyuan; Ramamoorthy, Preveen; Nagabhushanam, Vijaya; Levin, Adrah R.; Iseman, Michael D.; Chan, Edward D.] Natl Jewish Hlth, Dept Acad Affairs, Denver, CO 80206 USA. [Strand, Matthew J.] Natl Jewish Hlth, Div Biostat, Denver, CO 80206 USA. [Frazer-Abel, Ashley; Giclas, Patricia C.] Natl Jewish Hlth, Complement Lab, Denver, CO 80206 USA. [Bryan, Courtney L.; Pott, Gregory B.; Shapiro, Leland; Chan, Edward D.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Fantuzzi, Giamila] Univ Illinois, Dept Kinesiol & Nutr, Chicago, IL USA. [Korner, Judith] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. RP Chan, ED (reprint author), Natl Jewish Hlth, Dept Med, D509,Neustadt Bldg,1400 Jackson St, Denver, CO 80206 USA. EM chane@njhealth.org RI Fantuzzi, Giamila/A-1758-2009 OI Fantuzzi, Giamila/0000-0001-5334-0082 FU Fern and Phil Leitman of Non-tuberculous Mycobacteria Info and Research (NTMir) of Miami, Florida; National Institutes of Health/National Center for Research Resources Colorado CTSI [UL1 RR025780]; Denver Veterans Affairs Medical Center FX This work was supported by Fern and Phil Leitman of Non-tuberculous Mycobacteria Info and Research (NTMir) of Miami, Florida and by National Institutes of Health/National Center for Research Resources Colorado CTSI grant no. UL1 RR025780.; The authors thank Dr. Leonid Heifets for providing the M. intracellulare isolate used in the ex vivo experiments, Eric Schonteich for help with some of the assays, and Dr. Mary Bessesen for providing Dr. Kartalija with a Training Grant from the Denver Veterans Affairs Medical Center. NR 63 TC 53 Z9 54 U1 1 U2 7 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 15 PY 2013 VL 187 IS 2 BP 197 EP 205 DI 10.1164/rccm.201206-1035OC PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 075YY UT WOS:000313924600016 PM 23144328 ER PT J AU Iqbal, FM Al Jaroudi, W Sanam, K Sweeney, A Heo, J Iskandrian, AE Hage, FG AF Iqbal, Fahad M. Al Jaroudi, Wael Sanam, Kumar Sweeney, Aaron Heo, Jaekyeong Iskandrian, Ami E. Hage, Fadi G. TI Reclassification of Cardiovascular Risk in Patients With Normal Myocardial Perfusion Imaging Using Heart Rate Response to Vasodilator Stress SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID DIABETES-MELLITUS; PROGNOSTIC VALUE; DISEASE; SCORE; REGADENOSON; ADENOSINE; MORTALITY; PREDICTION; SPECT AB Previous studies have shown that patients with normal vasodilator myocardial perfusion imaging (MPI) findings remain at a greater risk of future cardiac events than patients with normal exercise MPI findings. The aim was to assess improvement in risk classification provided by the heart rate response (HRR) in patients with normal vasodilator MPI findings when added to traditional risk stratification. We retrospectively studied 2,000 patients with normal regadenoson or adenosine MPI findings. Risk stratification was performed using Adult Treatment Panel III framework. Patients were stratified by HRR (percentage of increase from baseline) into tertiles specific to each vasodilator. All-cause mortality and cardiac death/nonfatal myocardial infarction (MI) <= 2 years from the index MPI were recorded. During follow-up, 11.8% patients died and 2.7% patients experienced cardiac death/nonfatal MI in the adenosine and regadenoson groups, respectively. The patients who died had a greater Framingham risk score (12 +/- 4 vs 11 +/- 4, p = 0.009) and lower HRR (22 16 vs 32 21, p <0.0001). In an adjusted Cox model, the lowest tertile HRR was associated with an increased risk of mortality (hazard ratio 2.1) and cardiac death/nonfatal MI (hazard ratio 2.9; p <0.01). Patients in the highest HRR tertile, irrespective of the Adult Treatment Panel III category, were at low risk. When added to the Adult Treatment Panel III categories, the HRR resulted in net reclassification improvement in mortality of 18% and cardiac death/nonfatal MI of 22%. In conclusion, a blunted HRR to vasodilator stress was independently associated with an increased risk of cardiac events and overall mortality in patients with normal vasodilator MPI findings. The HRR correctly reclassified a substantial proportion of these patients in addition to the traditional risk classification models and identified patients with normal vasodilator MPI findings, who had a truly low risk of events. (C) 2013 Published by Elsevier Inc. (Am J Cardiol 2013;111:190-195) C1 [Iqbal, Fahad M.; Sweeney, Aaron] Tulane Univ, Inst Heart & Vasc, New Orleans, LA 70118 USA. [Al Jaroudi, Wael] Cleveland Clin, Div Cardiovasc Med, Sect Cardiac Imaging, Inst Heart & Vasc, Cleveland, OH 44106 USA. [Sanam, Kumar; Heo, Jaekyeong; Iskandrian, Ami E.; Hage, Fadi G.] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Div Cardiol, Birmingham, AL USA. RP Iqbal, FM (reprint author), Tulane Univ, Inst Heart & Vasc, New Orleans, LA 70118 USA. EM fiqbal1@tulane.edu OI Hage, Fadi/0000-0002-1397-4942 FU Astellas Pharma FX Dr. Iskandrian is a consultant for Gilead Sciences and Astellas Pharma; and Dr. Hage is the recipient of an investigator initiated grant from Astellas Pharma. The remaining authors have no conflicts of interest to disclose. NR 26 TC 13 Z9 13 U1 0 U2 4 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 2013 VL 111 IS 2 BP 190 EP 195 DI 10.1016/j.amjcard.2012.09.013 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071PQ UT WOS:000313607100007 PM 23111139 ER PT J AU Kumar, V Venkataraman, R Aljaroudi, W Osorio, J Heo, J Iskandrian, AE Hage, FG AF Kumar, Vineet Venkataraman, Rajesh Aljaroudi, Wael Osorio, Jose Heo, Jaekyeong Iskandrian, Arni E. Hage, Fadi G. TI Implications of Left Bundle Branch Block in Patient Treatment SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIAC-RESYNCHRONIZATION THERAPY; ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY-DISEASE; CHRONIC HEART-FAILURE; ELECTROCARDIOGRAPHIC DIAGNOSIS; STRESS ECHOCARDIOGRAPHY; COMPUTED-TOMOGRAPHY; RANDOMIZED-TRIALS; NATURAL-HISTORY; QRS MORPHOLOGY AB Left bundle branch block (LBBB) causes an abnormal pattern of cardiac activation and affects regional myocardial function. Although recognition of LBBB on the surface electrocardiogram is straightforward, dissecting its effect on patient treatment and outcome can be more challenging. The altered pattern of cardiac activation in LBBB causes electrical and mechanical ventricular dyssynchrony, influences ischemia detection on the surface electrocardiogram, and affects stress testing and imaging modalities dependent on wall motion and thickening. Restoration of synchrony by biventricular pacing can improve symptoms and longevity in carefully selected patients. The diagnostic, prognostic, and therapeutic implications of LBBB across this spectrum are discussed in this review. (C) 2013 Elsevier Inc. All rights reserved. (Am J Cardiol 2013;111:291-300) C1 [Kumar, Vineet; Venkataraman, Rajesh; Osorio, Jose; Heo, Jaekyeong; Iskandrian, Arni E.; Hage, Fadi G.] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Aljaroudi, Wael] Cleveland Clin, Cleveland, OH 44106 USA. [Osorio, Jose; Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, AL USA. RP Hage, FG (reprint author), Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI Hage, Fadi/0000-0002-1397-4942 NR 74 TC 11 Z9 13 U1 0 U2 9 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 2013 VL 111 IS 2 BP 291 EP 300 DI 10.1016/j.amjcard.2012.09.029 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071PQ UT WOS:000313607100023 PM 23111137 ER PT J AU Metra, M Cotter, G Davison, BA Felker, GM Filippatos, G Greenberg, BH Ponikowski, P Unemori, E Voors, AA Adams, KF Dorobantu, MI Grinfeld, L Jondeau, G Marmor, A Masip, J Pang, PS Werdan, K Prescott, MF Edwards, C Teichman, SL Trapani, A Bush, CA Saini, R Schumacher, C Severin, T Teerlink, JR AF Metra, Marco Cotter, Gad Davison, Beth A. Felker, G. Michael Filippatos, Gerasimos Greenberg, Barry H. Ponikowski, Piotr Unemori, Elaine Voors, Adriaan A. Adams, Kirkwood F., Jr. Dorobantu, Maria I. Grinfeld, Liliana Jondeau, Guillaume Marmor, Alon Masip, Josep Pang, Peter S. Werdan, Karl Prescott, Margaret F. Edwards, Christopher Teichman, Sam L. Trapani, Angelo Bush, Christopher A. Saini, Rajnish Schumacher, Christoph Severin, Thomas Teerlink, John R. CA RELAX-AHF Investigators TI Effect of Serelaxin on Cardiac, Renal, and Hepatic Biomarkers in the Relaxin in Acute Heart Failure (RELAX-AHF) Development Program Correlation With Outcomes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE congestion; heart failure; organ protection; RELAX-AHF; serelaxin ID 3RD UNIVERSAL DEFINITION; MYOCARDIAL-INFARCTION; TROPONIN ELEVATION; EUROPEAN-SOCIETY; TASK-FORCE; ASSOCIATION; HOSPITALIZATION; PROTECT; CARE; PREVALENCE AB Objectives The aim of this study was to assess the effects of serelaxin on short-term changes in markers of organ damage and congestion and relate them to 180-day mortality in patients with acute heart failure. Background Hospitalization for acute heart failure is associated with high post-discharge mortality, and this may be related to organ damage. Methods The Pre-RELAX-AHF (Relaxin in Acute Heart Failure) phase II study and RELAX-AHF phase III study were international, multicenter, double-blind, placebo-controlled trials in which patients hospitalized for acute heart failure were randomized within 16 h to intravenous placebo or serelaxin. Each patient was followed daily to day 5 or discharge and at days 5, 14, and 60 after enrollment. Vital status was assessed through 180 days. In RELAX-AHF, laboratory evaluations were performed daily to day 5 and at day 14. Plasma levels of biomarkers were measured at baseline and days 2, 5, and 14. All-cause mortality was assessed as a safety endpoint in both studies. Results Serelaxin reduced 180-day mortality, with similar effects in the phase II and phase III studies (combined studies: N = 1,395; hazard ratio: 0.62; 95% confidence interval: 0.43 to 0.88; p = 0.0076). In RELAX-AHF, changes in markers of cardiac (high-sensitivity cardiac troponin T), renal (creatinine and cystatin-C), and hepatic (aspartate transaminase and alanine transaminase) damage and of decongestion (N-terminal pro-brain natriuretic peptide) at day 2 and worsening heart failure during admission were associated with 180-day mortality. Serelaxin administration improved these markers, consistent with the prevention of organ damage and faster decongestion. Conclusions Early administration of serelaxin was associated with a reduction of 180-day mortality, and this occurred with fewer signs of organ damage and more rapid relief of congestion during the first days after admission. (J Am Coll Cardiol 2013; 61: 196-206) (C) 2013 by the American College of Cardiology Foundation C1 [Metra, Marco] Univ Brescia, Dept Med & Surg Specialties Radiol Sci & Publ Hlt, Brescia, Italy. [Metra, Marco] Spedali Civil Brescia, I-25123 Brescia, Italy. [Cotter, Gad; Davison, Beth A.; Edwards, Christopher] Momentum Res Inc, Durham, NC USA. [Felker, G. Michael] Duke Univ, Sch Med, Durham, NC USA. [Felker, G. Michael] Duke Univ, Med Ctr, Duke Heart Ctr, Durham, NC 27710 USA. [Filippatos, Gerasimos] Athens Univ Hosp, Athens, Greece. [Greenberg, Barry H.] Univ Calif San Diego, San Diego, CA 92103 USA. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Unemori, Elaine; Teichman, Sam L.] Corthera Inc, San Carlos, CA USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Adams, Kirkwood F., Jr.] Univ N Carolina, Chapel Hill, NC USA. [Dorobantu, Maria I.] Floreasca Emergency Clin Hosp, Bucharest, Romania. [Grinfeld, Liliana] Univ Buenos Aires, Sch Med, Cardiovasc Physiopathol Inst, Buenos Aires, DF, Argentina. [Jondeau, Guillaume] Univ Paris 07, Hop Bichat, Paris, France. [Marmor, Alon] Ziv Med Ctr, Safed, Israel. [Masip, Josep] Univ Barcelona, Consorci Sanitari Integral, Barcelona, Spain. [Pang, Peter S.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Werdan, Karl] Univ Halle Wittenberg, D-06108 Halle, Germany. [Prescott, Margaret F.; Trapani, Angelo; Bush, Christopher A.; Saini, Rajnish] Novartis Pharmaceut, E Hanover, NJ USA. [Schumacher, Christoph; Severin, Thomas] Novartis Pharma AG, Basel, Switzerland. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Metra, M (reprint author), Spedali Civil Brescia, Piazza Spedali Civili 1, I-25123 Brescia, Italy. EM metramarco@libero.it RI Lainscak, Mitja/F-3237-2015; Ponikowski, Piotr/O-6454-2015 OI Ponikowski, Piotr/0000-0002-3391-7064; Metra, Marco/0000-0001-6691-8568; Davison, Beth/0000-0003-2374-6449 FU Corthera, Inc. (a Novartis AG affiliate company); Novartis; Amgen; Corthera; Merck; Roche Diagnostics; Duke Clinical Research Unit; Momentum Research; Medpace; Otsuka; Trevena; BG Medicine; NHLBI; Nanosphere; European Union; Abbott Vascular; Bayer; Abbott; PDL BioPharma; Cardio3 Bioscience; Cytokinetics; Takeda; Teva; Alere; Cardio3Biosciences; Celladon; Ceva; European Commission; Dutch Heart Foundation; Servier; Torrent; Vifor FX The Relaxin in Acute Heart Failure study is supported by Corthera, Inc. (a Novartis AG affiliate company). Dr. Adams has received research grants from Novartis, Amgen, Corthera, Merck, Roche Diagnostics, and the Duke Clinical Research Unit and has received consulting fees from Corthera, Merck, Roche Diagnostics, the Duke Clinical Research Unit, and Momentum Research. Dr. Felker has received consulting income from Novartis, Medpace, Amgen, Otsuka, Trevena, Roche Diagnostics, Merck, BG Medicine, Medtronic, and St Jude and grant funding from Amgen, Otsuka, Roche Diagnostics, and NHLBI. Dr. Filippatos is a consultant to Corthera, Bayer, Cardiorentis, and has received research grants from Amgen, Nanosphere, European Union. Dr. Greenberg served as a consultant for Corthera and Novartis. Dr. Metra has received consulting income from Abbott Vascular, Bayer, Corthera, and Novartis, and travel support and honoraria from Servier and Novartis. Dr. Ponikowski was a consultant for Astellas, Bayer, EKR Therapeutics, J&J, the Medicines Company, Medtronic, Novartis, Otsuka, Palatin Technologies, PDL BioPharma, Pericor Therapeutics, SigmaTau, Solvay Pharmaceuticals, and Trevena; has received honoraria from Alere, Beckman-Coulter, BiogenIdec, Corthera, Ikaria, Nile Therapeutics, Momentum Research, and Overcome; has received research support from Abbott, Merck and PDL BioPharma; and has received travel support from MyLife and equipment support from Sonosite. Dr. Teerlink has received research grants or consulting fees from Amgen, Bayer, Corthera, Cardio3 Bioscience, Cytokinetics, Merck, Novartis, Takeda, Teva and Trevena. Dr. Dorobantu, Grinfeld, Joundeau, Marmor, Masip and Verdan have received research grants from Corthera (a Novartis affiliate company). Dr. Unemori is employed and Dr. Teichman was employed by the sponsor, Corthera. Drs. Bush, Prescott, Saini, and Trapani are employees and shareholders of Novartis Pharmaceuticals Corporation. Drs. Schumacher and Severin are employees and shareholders of Novartis Pharma AG. Drs. Davison and Cotter and Mr. Edwards are employees of Momentum Research, which has provided consulting and trial management services to NovaCardia, Merck, Corthera, Novartis, Nile Therapeutics, Bioheart, Cardio3 Biosciences, Amgen, Celadon, Targegen, Trevena, Sorbent Therapeutics, and NIH. Dr. Pang has been consultant for Astellas, Bayer, EKR Therapeutics, J& J, the Medicines Company, Medtronic, Novartis, Otsuka, Palatin Technologies, PDL BioPharma, Pericor Therapeutics, SigmaTau, Solvay Pharmaceuticals, Trevena and has received honoraria from Alere, Beckman-Coulter, BiogenIdec, Corthera, Ikaria, Nile Therapeutics, Momentum Research, Overcome and research support from Abbott, Merck and PDL BioPharma, travel support from MyLife and equipment support from Sonosite. Dr. Voorshas received consultancy fees and/or research grants from Alere, Bayer, Cardio3Biosciences, Celladon, Ceva, European Commission, Dutch Heart Foundation, Novartis, Servier, Torrent, and Vifor. Dr. Werdan received honorarium for patient enrolment and for national coordinatorship of RELAX-AHF trial and received honoraria for lectures from Servier, Biotest, Maquet, Brahms Company. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 39 TC 169 Z9 174 U1 2 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 15 PY 2013 VL 61 IS 2 BP 196 EP 206 DI 10.1016/j.jacc.2012.11.005 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 065PZ UT WOS:000313162200015 PM 23273292 ER PT J AU Barsic, B Dickerman, S Krajinovic, V Pappas, P Altclas, J Carosi, G Casabe, JH Chu, VH Delahaye, F Edathodu, J Fortes, CQ Olaison, L Pangercic, A Patel, M Rudez, I Tamin, SS Vincelj, J Bayer, AS Wang, A AF Barsic, Bruno Dickerman, Stuart Krajinovic, Vladimir Pappas, Paul Altclas, Javier Carosi, Giampiero Casabe, Jose H. Chu, Vivian H. Delahaye, Francois Edathodu, Jameela Fortes, Claudio Querido Olaison, Lars Pangercic, Ana Patel, Mukesh Rudez, Igor Tamin, Syahidah Syed Vincelj, Josip Bayer, Arnold S. Wang, Andrew CA Int Collaboration Endocarditis-Pro TI Influence of the Timing of Cardiac Surgery on the Outcome of Patients With Infective Endocarditis and Stroke SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE endocarditis; stroke; surgery ID CEREBROVASCULAR COMPLICATIONS; NEUROLOGIC COMPLICATIONS; PROSPECTIVE MULTICENTER; BACTERIAL-ENDOCARDITIS; CARDIOEMBOLIC STROKE; VALVE-REPLACEMENT; PROGNOSTIC VALUE; BRAIN-DAMAGE; DIAGNOSIS; ECHOCARDIOGRAPHY AB Background. The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. Methods. Data were obtained from the International Collaboration on Endocarditis-Prospective Cohort Study of 4794 patients with definite IE who were admitted to 64 centers from June 2000 through December 2006. Multivariate logistic regression and Cox regression analyses were performed to estimate the impact of early surgery on hospital and 1-year mortality after adjustments for other significant covariates. Results. Of the 857 patients with IE complicated by ischemic stroke syndromes, 198 who underwent valve replacement surgery poststroke were available for analysis. Overall, 58 (29.3%) patients underwent early surgical treatment vs 140 (70.7%) patients who underwent late surgical treatment. After adjustment for other risk factors, early surgery was not significantly associated with increased in-hospital mortality rates (odds ratio, 2.308; 95% confidence interval [CI], .942-5.652). Overall, probability of death after 1-year follow-up did not differ between 2 treatment groups (27.1% in early surgery and 19.2% in late surgery group, P = .328; adjusted hazard ratio, 1.138; 95% CI, .802-1.650). Conclusions. There is no apparent survival benefit in delaying surgery when indicated in IE patients after ischemic stroke. Further observational analyses that include detailed pre- and postoperative clinical neurologic findings and advanced imaging data (eg, ischemic stroke size), may allow for more refined recommendations on the optimal timing of valvular surgery in patients with IE and recent stroke syndromes. C1 [Barsic, Bruno; Krajinovic, Vladimir] Hosp Infect Dis, Sch Med, Zagreb, Croatia. [Dickerman, Stuart] NYU, Sch Med, New York, NY USA. [Pappas, Paul; Chu, Vivian H.; Wang, Andrew] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Altclas, Javier] Barcelona Ctr Int Hlth Res, Barcelona, Spain. [Carosi, Giampiero] Univ Brescia, I-25121 Brescia, Italy. [Casabe, Jose H.] Fdn Favaloro, Buenos Aires, DF, Argentina. [Delahaye, Francois] Hop Louis Pradel, Lyon, France. [Edathodu, Jameela] King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia. [Fortes, Claudio Querido] Clementino Fraga Filho Hosp, Rio De Janeiro, Brazil. [Olaison, Lars] Sahlgrens Univ Hosp, Gothenburg, Sweden. [Pangercic, Ana] Univ Hosp Ctr Sestre Milosrdnice, Zagreb, Croatia. [Patel, Mukesh] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Rudez, Igor; Vincelj, Josip] Dubrava Univ Hosp, Zagreb, Croatia. [Tamin, Syahidah Syed] Inst Jantung Negara, Kuala Lumpur, Malaysia. [Bayer, Arnold S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Barsic, B (reprint author), Hosp Infect Dis, Sch Med, Zagreb, Croatia. EM bbarsic@bfm.hr RI ; Toniolo, Antonio/B-4103-2015; Munoz, Patricia/E-9431-2017; Bouza, Emilio/D-8661-2014 OI Sfeir, Jad/0000-0003-1576-1534; Falces, Carlos/0000-0002-3483-3786; Selton-Suty, Christine/0000-0003-4129-5784; Post, Jeffrey/0000-0003-1475-9272; Toniolo, Antonio/0000-0003-3008-2126; Munoz, Patricia/0000-0001-5706-5583; Bouza, Emilio/0000-0001-6967-9267; Vincelj, Josip/0000-0003-0064-9128; Athan, Eugene/0000-0001-9838-6471 FU Cubist; Astellas; Polymedix Inc; Trius; Duke University Center; Gilead Sciences; Edward Lifesciences; Abbott Vascular FX B. B. is a consultant for Pfizer and Pliva Pharmaceuticals and has also participated as a speaker for MSD, Pfizer, and Pliva. A. S. B. has received grants from Cubist, Astellas, Polymedix Inc, and Trius, and is receiving payments for lectures from Duke University Center (ID Grand Rounds). A. W. has provided expert testimony for Young Moore and Henderson, has received grants from Gilead Sciences, Edward Lifesciences, and Abbott Vascular, and has received honoraria from American Physician, Springer, and the American College of Cardiology Foundation. All other authors report no potential conflicts. NR 31 TC 40 Z9 44 U1 1 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 15 PY 2013 VL 56 IS 2 BP 209 EP 217 DI 10.1093/cid/cis878 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 058AJ UT WOS:000312606100011 PM 23074311 ER PT J AU Case, BG Bertollo, DN Laska, EM Price, LH Siegel, CE Olfson, M Marcus, SC AF Case, Brady G. Bertollo, David N. Laska, Eugene M. Price, Lawrence H. Siegel, Carole E. Olfson, Mark Marcus, Steven C. TI Declining Use of Electroconvulsive Therapy in United States General Hospitals SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Electroconvulsive therapy (ECT); general hospitals; hospital psychiatry; mental health services; recurrent major depression; somatic therapy ID COMMUNITY HOSPITALS; ECT; DEPRESSION; ATTITUDES; PSYCHIATRISTS; EFFICACY; TRENDS AB Background: Falling duration of psychiatric inpatient stays over the past 2 decades and recent recommendations to tighten federal regulation of electroconvulsive therapy (ECT) devices have focused attention on trends in ECT use, but current national data have been unavailable. Methods: We calculated the annual number of inpatient stays involving ECT and proportion of general hospitals conducting the procedure at least once in the calendar year with a national sample of discharges from 1993 to 2009. We estimated adjusted probabilities that in patients with severe recurrent major depression (n = 465,646) were treated in a hospital that conducts ECT and, if so, received the procedure. Results: The annual number of stays involving ECT fell from 12.6 to 7.2/100,000 adult US residents, driven by dramatic declines among elderly persons, whereas the percentage of hospitals conducting ECT decreased from 14.8% to 10.6%. The percentage of stays for severe recurrent major depression in hospitals that conducted ECT fell from 70.5% to 44.7%, whereas receipt of ECT where conducted declined from 12.9% to 10.5%. For depressed inpatients, the adjusted probability that the treating hospital conducts ECT fell 34%, whereas probability of receiving ECT was unchanged for patients treated in facilities that conducted the procedure. Adjusted declines were greatest for elderly persons. Throughout the period inpatients from poorer neighborhoods or who were publicly insured or uninsured were less likely to receive care from hospitals conducting ECT. Conclusions: Electroconvulsive therapy use for severely depressed inpatients has fallen markedly, driven exclusively by a decline in the probability that their hospital conducts ECT. C1 [Case, Brady G.] Emma Pendleton Bradley Hosp, Hlth Serv Res Program, E Providence, RI 02915 USA. [Case, Brady G.; Price, Lawrence H.] Brown Univ, Dept Psychiat & Human Behav, Albert Med Sch, Providence, RI 02912 USA. [Price, Lawrence H.] Butler Hosp, Providence, RI 02906 USA. [Case, Brady G.; Bertollo, David N.; Laska, Eugene M.; Siegel, Carole E.] Nathan S Kline Inst Psychiat Res, Dept Stat, Orangeburg, NY 10962 USA. [Case, Brady G.; Bertollo, David N.; Laska, Eugene M.; Siegel, Carole E.] Nathan S Kline Inst Psychiat Res, Div Res Serv, Orangeburg, NY 10962 USA. [Case, Brady G.; Laska, Eugene M.; Siegel, Carole E.] NYU, Sch Med, Dept Psychiat, New York, NY 10003 USA. [Olfson, Mark] Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, New York, NY USA. [Marcus, Steven C.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Case, BG (reprint author), Emma Pendleton Bradley Hosp, Hlth Serv Res Program, 1011 Vet Mem Pkwy, E Providence, RI 02915 USA. EM brady_case@brown.edu RI Case, Brady/M-1879-2015 OI Case, Brady/0000-0001-9512-0416; Laska, Eugene/0000-0001-6799-1361; Siegel, Carole/0000-0002-7460-788X FU Leon Levy Foundation; American Academy of Child and Adolescent Psychiatry Eli Lilly Pilot Research Award; American Psychiatric Association Astra Zeneca Young Mindsin Psychiatry Award; Medtronic; Neuronetics; Cyberonics; NeoSync; Eli Lilly and Company; Ortho-McNeil Janssen; Forest Research Institute; [K12 DA000357-11] FX This work was supported in part by K12 DA000357-11 (BGC) and the Leon Levy Foundation (BGC). The views and information presented do not necessarily state or reflect those of supporting organizations. We gratefully acknowledge the editorial comments of Christopher F. Koller and the clinical guidance of Patrick Ying.; Dr. Case has received support from the American Academy of Child and Adolescent Psychiatry Eli Lilly Pilot Research Award and the American Psychiatric Association Astra Zeneca Young Mindsin Psychiatry Award. In the past 3 years, Dr. Price has served as an investigator on research supported by Medtronic, Neuronetics, Cyberonics, and NeoSync, none of which involved electroconvulsive therapy. Only the research supported by NeoSync was active during the time of his involvement with this project, and he has received no direct support or compensation for any of this work. Dr. Price has served on the advisory panels of Abbott and AstraZeneca and has consulted for Abbott and AstraZeneca. Dr. Olfson has received a research grant to Columbia University from Eli Lilly and Company. Dr. Marcus has received grant support from Ortho-McNeil Janssen and Forest Research Institute and has served as a consultant to AstraZeneca. All other authors report no biomedical financial interests or potential conflicts of interest. BGC is currently affiliated with the Department of Health Services, Policy, and Practice, Public Health Program of Brown University, Providence, Rhode Island. NR 35 TC 18 Z9 18 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 15 PY 2013 VL 73 IS 2 BP 119 EP 126 DI 10.1016/j.biopsych.2012.09.005 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 053JF UT WOS:000312266800008 PM 23059049 ER PT J AU Townsend, JD Torrisi, SJ Lieberman, MD Sugar, CA Bookheimer, SY Altshuler, LL AF Townsend, Jennifer D. Torrisi, Salvatore J. Lieberman, Matthew D. Sugar, Catherine A. Bookheimer, Susan Y. Altshuler, Lori L. TI Frontal-Amygdala Connectivity Alterations During Emotion Downregulation in Bipolar I Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Amygdala; bipolar disorder; emotion regulation; functional connectivity; functional neuroimaging; vlPFC ID MEDIAL PREFRONTAL CORTEX; FUNCTIONAL CONNECTIVITY; NEGATIVE EMOTION; VOLUNTARY SUPPRESSION; ANTERIOR CINGULATE; COGNITIVE CONTROL; AFFECTIVE STIMULI; MOOD REGULATION; RESTING STATE; DEFAULT MODE AB Background: The symptoms of bipolar disorder suggest dysfunction of emotion regulatory networks. In healthy control populations, downregulation of emotional responses activates the ventral lateral prefrontal cortex (vlPFC) and dampens amygdala activation. This study investigated frontal and limbic function and connectivity during emotion downregulation in euthymic subjects with bipolar I disorder (BPI) and healthy control subjects. Methods: Thirty BPI and 26 control subjects underwent functional magnetic resonance imaging scanning while performing an emotion processing task with passive viewing and emotion downregulation conditions. Contrasts were made for each group comparing the downregulation and passive viewing conditions, and these were entered into a between-group random effects analysis to assess group differences in activation. Psychophysiological interaction analyses were conducted to test for significant group differences in functional connectivity between the amygdala and inhibitory frontal regions (i.e., vlPFC). Results: Control subjects showed the expected robust bilateral activation of frontal and limbic regions during passive viewing and emotion downregulation tasks. Between-group analyses revealed similar activation of BPI and control subjects during passive viewing but significantly decreased activation in bilateral vlPFC, bilateral anterior and posterior cingulate, medial frontal gyrus, and bilateral dorsal lateral prefrontal cortex during emotion downregulation in subjects with BPI. Connectivity analysis demonstrated that control subjects had significantly greater negative functional connectivity between the left amygdala and bilateral vlPFC compared with subjects with BPI. Conclusions: This study provides evidence that dysfunction in the neural networks responsible for emotion regulation, including the prefrontal cortex, cingulate, and subcortical structures, are present in BPI subjects, even while euthymic. C1 [Altshuler, Lori L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Lieberman, Matthew D.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Psychol, Los Angeles, CA 90095 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Sch Publ Hlth, Jane & Terry Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA. [Altshuler, Lori L.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. RP Altshuler, LL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, 300 UCLA Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu FU Furlotti Family Foundation; Swift Family Foundation; National Institutes of Health; National Institute of Mental Health [R01 MH084955, K24 MH001848, R21 MH075944]; National Center for Research Resources [RR012169, RR013642, RR00865]; Abbott Laboratories FX For financial support of this study, we gratefully acknowledge the Furlotti Family Foundation, the Swift Family Foundation, and the following two components of the National Institutes of Health: the National Institute of Mental Health (R01 MH084955 [LLA], K24 MH001848 [LLA], R21 MH075944 [LLA]) and the National Center for Research Resources (RR012169, RR013642, and RR00865). Contents of this report are solely the responsibility of the authors and do not necessarily represent the official views of any sponsoring organization. For generous support, we also thank the Brain Mapping Medical Research Organization, Brain Mapping Support Foundation, Pierson-Lovelace Foundation, The Ahmanson Foundation, William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation, Tamkin Foundation, Jennifer Jones-Simon Foundation, Capital Group Companies Charitable Foundation, Robson Family, and Northstar Fund. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.; Dr. Altshuler, Dr. Bookheimer, Dr. Lieberman, Mr. Torrisi, Dr. Sugar, and Ms. Townsend had full access to all study data and take responsibility for its integrity and the accuracy of data analysis. Dr. Altshuler has received past (and potential future) funding from Abbott Laboratories (research support and consulting honoraria); Forest Laboratories (consulting and speakers bureau honoraria); Glaxo-SmithKline (speakers bureau honoraria); and no past, but potential future honoraria from Astra-Zeneca (speakers bureau) and Merck and Co. (consulting). Ms. Townsend, Mr. Torrisi, Dr. Lieberman, Dr. Sugar, and Dr. Bookheimer report no biomedical financial interests or potential conflicts of interest. NR 85 TC 54 Z9 55 U1 5 U2 34 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 15 PY 2013 VL 73 IS 2 BP 127 EP 135 DI 10.1016/j.biopsych.2012.06.030 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 053JF UT WOS:000312266800009 PM 22858151 ER PT J AU Adams, AS Uratsu, C Dyer, W Magid, D O'Connor, P Beck, A Butler, M Ho, PM Schmittdiel, JA AF Adams, Alyce S. Uratsu, Connie Dyer, Wendy Magid, David O'Connor, Patrick Beck, Arne Butler, Melissa Ho, P. Michael Schmittdiel, Julie A. TI Health System Factors and Antihypertensive Adherence in a Racially and Ethnically Diverse Cohort of New Users SO JAMA INTERNAL MEDICINE LA English DT Article ID MAIL-ORDER PHARMACY; ISOLATED SYSTOLIC HYPERTENSION; MEDICATION ADHERENCE; AFRICAN-AMERICANS; BLOOD-PRESSURE; UNITED-STATES; CARDIOVASCULAR-DISEASE; INTERVENTIONS; TRENDS; DISPARITIES AB Background: The purpose of this study was to identify potential health system solutions to suboptimal use of antihypertensive therapy in a diverse cohort of patients initiating treatment. Methods: Using a hypertension registry at Kaiser Permanente Northern California, we conducted a retrospective cohort study of 44 167 adults (age, >= 18 years) with hypertension who were new users of antihypertensive therapy in 2008. We used multivariate logistic regression analysis to model the relationships between race/ethnicity, specific health system factors, and early non-persistence (failing to refill the first prescription within 90 days) and nonadherence (<80% of days covered during the 12 months following the start of treatment), respectively, controlling for sociodemographic and clinical risk factors. Results: More than 30% of patients were early nonpersistent and 1 in 5 were nonadherent to therapy. Nonwhites were more likely to exhibit both types of suboptimal medication-taking behavior compared with whites. In logistic regression models adjusted for sociodemographic, clinical, and health system factors, nonwhite race was associated with early nonpersistence (black: odds ratio, 1.56 [95% CI, 1.43-1.70]; Asian: 1.40 [1.29-1.51]; Hispanic: 1.46 [1.35-1.57]) and nonadherence (black: 1.55 [1.37-1.77]; Asian: 1.13 [1.00-1.28]; Hispanic: 1.46 [1.31-1.63]). The likelihood of early nonpersistence varied between Asians and Hispanics by choice of first-line therapy. In addition, racial and ethnic differences in nonadherence were appreciably attenuated when medication co-payment and mail-order pharmacy use were accounted for in the models. Conclusions: Racial/ethnic differences in medication-taking behavior occur early in the course of treatment. However, health system strategies designed to reduce patient co-payments, ease access to medications, and optimize the choice of initial therapy may be effective tools in narrowing persistent gaps in the use of these and other clinically effective therapies. JAMA Intern Med. 2013;173(1):54-61. Published online December 10, 2012. doi:10.1001/2013.jamainternmed.955 C1 [Adams, Alyce S.; Uratsu, Connie; Dyer, Wendy; Schmittdiel, Julie A.] Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [Magid, David; Beck, Arne; Ho, P. Michael] Kaiser Permanente, Inst Res, Denver, CO USA. [O'Connor, Patrick] HealthPartners Res Fdn, Minneapolis, MN USA. [Butler, Melissa] Kaiser Permanente, Ctr Hlth Res Southeast, Atlanta, GA USA. [Ho, P. Michael] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Adams, AS (reprint author), Kaiser Permanente, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM Alyce.S.Adams@kp.org FU National Heart, Lung, and Blood Institute [3U19HL091179-04S1]; National Institute for Mental Health; Health Delivery Systems Center for Diabetes Translational Research [P30DK092924]; National Institute for Diabetes and Digestive and Kidney Diseases FX This study was funded by 3U19HL091179-04S1 (National Heart, Lung, and Blood Institute) and the National Institute for Mental Health as a supplement to the Health Maintenance Organization Research Network Cardiovascular Disease Network. Additional support for Drs Adams, O'Connor, and Schmittdiel was provided by P30DK092924 (Health Delivery Systems Center for Diabetes Translational Research), funded by the National Institute for Diabetes and Digestive and Kidney Diseases. NR 44 TC 16 Z9 16 U1 2 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN 14 PY 2013 VL 173 IS 1 BP 54 EP 61 DI 10.1001/2013.jamainternmed.955 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 121JF UT WOS:000317238800013 PM 23229831 ER PT J AU Trautner, BW AF Trautner, Barbara W. TI New Perspectives on Urinary Tract Infection in Men SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID CLINICAL-PRACTICE GUIDELINES; ASYMPTOMATIC BACTERIURIA; DISEASES-SOCIETY; AMERICA; DIAGNOSIS; ADULTS; WOMEN C1 Baylor Coll Med, Infect Dis Sect, Hlth Serv Res Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Trautner, BW (reprint author), Baylor Coll Med, Infect Dis Sect, Hlth Serv Res Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM trautner@bcm.edu NR 9 TC 1 Z9 1 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN 14 PY 2013 VL 173 IS 1 BP 68 EP 70 DI 10.1001/jamainternmed.2013.1783 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 121JF UT WOS:000317238800015 PM 23212451 ER PT J AU Bao, YR Johansen, KL AF Bao, Yeran Johansen, Kirsten L. TI Frailty in Dialysis-Dependent Patients With End-Stage Renal Disease Reply SO JAMA INTERNAL MEDICINE LA English DT Letter ID WOMENS HEALTH; PHENOTYPE; OLDER C1 [Bao, Yeran] Univ Calif San Francisco, Div Endocrinol, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, USRDS Nutr Special Studies Ctr, San Francisco, CA USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA. [Johansen, Kirsten L.] USRDS Rehabil Qual Life Special Studies Ctr, Atlanta, GA USA. RP Bao, YR (reprint author), Univ Calif San Francisco, Div Endocrinol, 400 Parnassus Ave,Ste A550,Box 1222, San Francisco, CA 94143 USA. EM yeranbao@gmail.com NR 5 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN 14 PY 2013 VL 173 IS 1 BP 79 EP 79 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 121JF UT WOS:000317238800022 PM 23318592 ER PT J AU Shi, Y Frost, P Hoang, B Yang, Y Fukunaga, R Gera, J Lichtenstein, A AF Shi, Y. Frost, P. Hoang, B. Yang, Y. Fukunaga, R. Gera, J. Lichtenstein, A. TI MNK kinases facilitate c-myc IRES activity in rapamycin-treated multiple myeloma cells SO ONCOGENE LA English DT Article DE multiple myeloma; rapamycin; mTOR inhibitors; c-myc; IRES activity; MNK kinases ID INTERNAL RIBOSOME ENTRY; INITIATION-FACTOR 4E; MAMMALIAN TARGET; CYCLIN D1; ENHANCED SENSITIVITY; PROTEIN-SYNTHESIS; BINDING-PROTEIN; SITE FUNCTION; AKT ACTIVITY; N-TERMINI AB When mTOR inhibitor rapalogs prevent cap-dependent translation of cell-cycle proteins like c-myc, continuing tumor cell growth depends on cap-independent translation, which is mediated by internal ribosome entry sites (IRESes) located in the 5'-UTR (untranslated region) of transcripts. To investigate if rapalog-induced activation of MNK kinases had a role in such IRES activity, we studied multiple myeloma (MM) cells. Rapamycin (RAP)-activated MNK1 kinase activity in MM cell lines and primary specimens by a mitogen-activated protein kinase-dependent mechanism. Pharmacological inhibition of MNK activity or genetic silencing of MNK1 prevented a rapalog-induced upregulation of c-myc IRES activity. Although RAP, used alone, had little effect on myc protein expression, when combined with a MNK inhibitor, myc protein expression was abrogated. In contrast, there was no inhibition of myc RNA, consistent with an effect on myc translation. In a RAP-resistant MM cell lines as well as a resistant primary MM specimen, co-exposure to a MNK inhibitor or MNK1 knockdown significantly sensitized cells for RAP-induced cytoreduction. Studies in MNK-null murine embryonic fibroblasts additionally supported a role for MNK kinases in RAP-induced myc IRES stimulation. These results indicate that MNK kinase activity has a critical role in the fail-safe mechanism of IRES-dependent translation when mTOR is inhibited. As kinase activity also regulated sensitivity to RAP, the data also provide a rationale for therapeutically targeting MNK kinases for combined treatment with mTOR inhibitors. Oncogene (2013) 32, 190-197; doi:10.1038/onc.2012.43; published online 27 February 2012 C1 [Shi, Y.; Frost, P.; Hoang, B.; Yang, Y.; Fukunaga, R.; Gera, J.; Lichtenstein, A.] Univ Calif Los Angeles, Med Ctr, Dept Med, Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA 90024 USA. [Shi, Y.; Frost, P.; Hoang, B.; Yang, Y.; Fukunaga, R.; Gera, J.; Lichtenstein, A.] Univ Calif Los Angeles, Med Ctr, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Shi, Y.; Frost, P.; Hoang, B.; Yang, Y.; Fukunaga, R.; Gera, J.; Lichtenstein, A.] Osaka Univ Pharmaceut Sci, Dept Biochem, Biochem Lab, Takatsuki, Osaka, Japan. RP Lichtenstein, A (reprint author), W LA VA Hosp, W111H,11301 Wilshire Blvd,Bldg 500,Rm 4237, Los Angeles, CA 90073 USA. EM alan.lichtenstein@med.va.gov OI Frost, Patrick/0000-0003-3348-5983 FU Veteran's Administration; Multiple Myeloma Research Foundation; Department of Defense; NIH [RO1 CA109312, RO1 CA111448] FX We thank the UCLA Jonsson Comprehensive Cancer Center vector core lab for assistance in generating the lentiviral shRNA vectors. This work was supported by research funds of the Veteran's Administration, the Multiple Myeloma Research Foundation and the Department of Defense and NIH Grants RO1 CA109312 and RO1 CA111448. NR 32 TC 12 Z9 14 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 10 PY 2013 VL 32 IS 2 BP 190 EP 197 DI 10.1038/onc.2012.43 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 078CK UT WOS:000314075500007 PM 22370634 ER PT J AU Wu, DM Kraut, JA Abraham, WM AF Wu, Dongmei Kraut, Jeffrey A. Abraham, William M. TI Sabiporide Improves Cardiovascular Function, Decreases the Inflammatory Response and Reduces Mortality in Acute Metabolic Acidosis in Pigs SO PLOS ONE LA English DT Article ID EXTRACELLULAR ACIDOSIS; EXCHANGE INHIBITION; SODIUM-BICARBONATE; LACTIC-ACIDOSIS; MECHANISMS; CONTRACTILITY; MYOCARDIUM; ACTIVATION; MANAGEMENT; DIAGNOSIS AB Introduction: Acute metabolic acidosis impairs cardiovascular function and increases the mortality of critically ill patients. However, the precise mechanism(s) underlying these effects remain unclear. We hypothesized that targeting pH-regulatory protein, Na+/H+ exchanger (NHE1) could be a novel approach for the treatment of acute metabolic acidosis. The aim of the present study was to examine the impact of a novel NHE1 inhibitor, sabiporide, on cardiovascular function, blood oxygen transportation, and inflammatory response in an experimental model of metabolic acidosis produced by hemorrhage-induced hypovolemia followed by an infusion of lactic acid. Methods and Results: Anesthetized pigs were subjected to hypovolemia for 30 minutes. The animals then received a bolus infusion of sabiporide (3 mg/kg) or vehicle, followed by an infusion of lactic acid for 2 hours. The animals were continuously monitored for additional 3 hours. Hypovolemia followed by a lactic acid infusion resulted in a severe metabolic acidosis with blood pH falling to 6.8. In association with production of the acidemia, there was an excessive increase in pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR). Treatment with sabiporide significantly attenuated the increase in PAP by 38% and PVR by 67%, as well as significantly improved cardiac output by 51%. Sabiporide treatment also improved mixed venous blood oxygen saturation (55% in sabiporide group vs. 28% in control group), and improved systemic blood oxygen delivery by 36%. In addition, sabiporide treatment reduced plasma levels of TNF-alpha (by 33%), IL-6 (by 63%), troponin-I (by 54%), ALT (by 34%), AST (by 35%), and urea (by 40%). Conclusion: These findings support the possible beneficial effects of sabiporide in the treatment of acute metabolic acidosis and could have implications for the treatment of metabolic acidosis in man. C1 [Wu, Dongmei] Mt Sinai Med Ctr, Dept Res, Div Neonatol, Miami Beach, FL 33140 USA. [Abraham, William M.] Mt Sinai Med Ctr, Div Pulm & Crit Care Med, Miami Beach, FL 33140 USA. [Wu, Dongmei] Chonbuk Natl Univ, Dept BIN Fus Technol, Jeonju, South Korea. [Kraut, Jeffrey A.] Vet Adm Greater Angeles Healthcare Syst, Div Nephrol Med & Res Serv, Los Angeles, CA USA. [Kraut, Jeffrey A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Wu, DM (reprint author), Mt Sinai Med Ctr, Dept Res, Div Neonatol, Miami Beach, FL 33140 USA. EM dongmeiwu@bellsouth.net FU USAMRMC [W81XWH-06-1-0719]; Ministry of Education, Science and Technology [R31-20029, 2012007331]; National Research Foundation of Korea (NRF); honbuk National University, Korea FX This work was supported by a USAMRMC grant W81XWH-06-1-0719 (to DW); and in part by the World Class University Program (R31-20029) funded by the Ministry of Education, Science and Technology; by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012007331); and by New Faculty funding from Chonbuk National University, Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 7 Z9 8 U1 0 U2 21 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 JAN 10 PY 2013 VL 8 IS 1 AR e53932 DI 10.1371/journal.pone.0053932 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 070YV UT WOS:000313552400061 PM 23326542 ER PT J AU Kudo, M Soltani, SMAK Sakuma, SA McKleroy, W Lee, TH Woodruff, PG Lee, JW Huang, K Chen, C Arjomandi, M Huang, XZ Atabai, K AF Kudo, Makoto Soltani, S. M. Amin Khalifeh Sakuma, Stephen A. McKleroy, William Lee, Ting-Hein Woodruff, Prescott G. Lee, Jae Woo Huang, Katherine Chen, Chun Arjomandi, Mehrdad Huang, Xiaozhu Atabai, Kamran TI Mfge8 suppresses airway hyperresponsiveness in asthma by regulating smooth muscle contraction SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE calcium sensitivity; lactadherin ID ACUTE LUNG INJURY; APOPTOTIC CELLS; T-CELLS; ALLERGIC-ASTHMA; INTEGRIN; MICE; DISEASE; HYPERREACTIVITY; INTERLEUKIN-13; SENSITIZATION AB Airway obstruction is a hallmark of allergic asthma and is caused primarily by airway smooth muscle (ASM) hypercontractility. Airway inflammation leads to the release of cytokines that enhance ASM contraction by increasing ras homolog gene family, member A (RhoA) activity. The protective mechanisms that prevent or attenuate the increase in RhoA activity have not been well studied. Here, we report that mice lacking the gene that encodes the protein Milk Fat Globule-EGF factor 8 (Mfge8(-/-)) develop exaggerated airway hyperresponsiveness in experimental models of asthma. Mfge8(-/-) ASM had enhanced contraction after treatment with IL-13, IL-17A, or TNF-alpha. Recombinant Mfge8 reduced contraction in murine and human ASM treated with IL-13. Mfge8 inhibited IL-13-induced NF-kappa B activation and induction of RhoA. Mfge8 also inhibited rapid activation of RhoA, an effect that was eliminated by an inactivating point mutation in the RGD integrin-binding site in recombinant Mfge8. Human subjects with asthma had decreased Mfge8 expression in airway biopsies compared with healthy controls. These data indicate that Mfge8 binding to integrin receptors on ASM opposes the effect of allergic inflammation on RhoA activity and identify a pathway for specific inhibition of ASM hypercontractility in asthma. C1 [Kudo, Makoto; Huang, Katherine; Chen, Chun; Arjomandi, Mehrdad; Huang, Xiaozhu; Atabai, Kamran] Univ Calif San Francisco, Lung Biol Ctr, San Francisco, CA 94143 USA. [Kudo, Makoto] Yokohama City Univ, Grad Sch Med, Dept Internal Med & Clin Immunol, Yokohama, Kanagawa 2360004, Japan. [Soltani, S. M. Amin Khalifeh; Sakuma, Stephen A.; McKleroy, William; Lee, Ting-Hein; Atabai, Kamran] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Soltani, S. M. Amin Khalifeh; Sakuma, Stephen A.; McKleroy, William; Lee, Ting-Hein; Woodruff, Prescott G.; Huang, Katherine; Chen, Chun; Huang, Xiaozhu; Atabai, Kamran] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Lee, Jae Woo] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. [Arjomandi, Mehrdad] San Francisco VA Med Ctr, Pulm Res Grp, San Francisco, CA 94121 USA. RP Atabai, K (reprint author), Univ Calif San Francisco, Lung Biol Ctr, San Francisco, CA 94143 USA. EM kamran.atabai@ucsf.edu FU National Institutes of Health (NIH) [HL083985, AI081988]; Sandler Program in Basic Sciences; NIH [K23 HL083099]; NIH/National Center for Research Resources, Office of the Director [KL2 RR024130] FX This work was supported by National Institutes of Health (NIH) Grants HL083985 and AI081988 (to K. A.), a grant from the Sandler Program in Basic Sciences (to K. A.), NIH Grant K23 HL083099 (to M. A.), and NIH/National Center for Research Resources, Office of the Director Grant KL2 RR024130 to the UCSF Clinical and Translational Science Institute. NR 47 TC 14 Z9 14 U1 0 U2 17 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 JAN 8 PY 2013 VL 110 IS 2 BP 660 EP 665 DI 10.1073/pnas.1216673110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 075SK UT WOS:000313906600058 PM 23269839 ER PT J AU Pinne, M Haake, DA AF Pinne, Marija Haake, David A. TI LipL32 Is a Subsurface Lipoprotein of Leptospira interrogans: Presentation of New Data and Reevaluation of Previous Studies SO PLOS ONE LA English DT Article ID OUTER-MEMBRANE PROTEIN; SURFACE-EXPOSED LIPOPROTEIN; PATHOGENIC LEPTOSPIRA; MONOCLONAL-ANTIBODIES; MOLECULAR-CLONING; SEQUENCE-ANALYSIS; INFECTION; FIBRONECTIN; EPIDEMIC; ANTIGEN AB The agents of leptospirosis, a zoonosis with worldwide distribution, are pathogenic spirochetes belonging to the genus Leptospira. The leptospiral life cycle involves transmission via fresh water and colonization of the renal tubules of their reservoir hosts. Infection of accidental hosts, including humans, may result in life-threatening sequelae. Bacterial outer membrane proteins (OMPs), particularly those with surface-exposed regions, play crucial roles in pathogen virulence mechanisms and adaptation to environmental conditions, including those found in the mammalian host. Therefore, elucidation and characterization of the surface-exposed OMPs of Leptospira spp. is of great interest in the leptospirosis field. A thorough, multi-pronged approach for assessing surface exposure of leptospiral OMPs is essential. Herein, we present evidence for a sub-surface location for most or all of the major leptospiral lipoprotein, LipL32, based on surface immunofluorescence utilizing three different types of antibodies and four different permeabilization methods, as well as surface proteolysis of intact and lysed leptospires. We reevaluate prior evidence presented in support of LipL32 surface-exposure and present a novel perspective on a protein whose location has been misleading researchers, due in large part to its extraordinary abundance in leptospiral cells. C1 [Pinne, Marija] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. [Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. [Pinne, Marija; Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA. RP Pinne, M (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. EM mpinne@ucla.edu FU VA Medical Research Funds; National Institute of Allergy and Infectious Diseases [AI-034431] FX This study was supported by VA Medical Research Funds (to D. A. H.) and grant AI-034431 (to D. A. H.) from the National Institute of Allergy and Infectious Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 21 Z9 22 U1 0 U2 8 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 JAN 8 PY 2013 VL 8 IS 1 AR e51025 DI 10.1371/journal.pone.0051025 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 069IY UT WOS:000313429800006 PM 23323152 ER PT J AU Lee, SJ Boscardin, WJ Stijacic-Cenzer, I Conell-Price, J O'Brien, S Walter, LC AF Lee, Sei J. Boscardin, W. John Stijacic-Cenzer, Irena Conell-Price, Jessamyn O'Brien, Sarah Walter, Louise C. TI Time lag to benefit after screening for breast and colorectal cancer: meta-analysis of survival data from the United States, Sweden, United Kingdom, and Denmark SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID FECAL-OCCULT-BLOOD; RANDOMIZED CONTROLLED-TRIAL; SERVICES TASK-FORCE; FOLLOW-UP; RECOMMENDATION STATEMENT; OLDER-ADULTS; AGE 40; MORTALITY; MAMMOGRAPHY; SIGMOIDOSCOPY AB Objectives To determine a pooled, quantitative estimate of the length of time needed after breast or colorectal cancer screening before a survival benefit is observed. Design Meta-analysis of survival data from population based, randomized controlled trials comparing populations screened and not screened for breast or colorectal cancer. Trials were identified as high quality by reviews from the Cochrane Collaboration and United States Preventive Services Task Force. Setting Trials undertaken in the United States, Denmark, United Kingdom, and Sweden. Population Screened patients older than 40 years. Primary outcome measures Time to death from breast or colorectal cancer in screened and control populations. Interventions Fecal occult blood testing for colorectal cancer screening, mammography for breast cancer screening. Results Our study included five and four eligible trials of breast and colorectal cancer screening, respectively. For breast cancer screening, 3.0 years (95% confidence interval 1.1 to 6.3) passed before one death from breast cancer was prevented for every 5000 women screened. On average across included studies, it took 10.7 years (4.4 to 21.6) before one death from breast cancer was prevented for 1000 women screened. For colorectal cancer screening, 4.8 years (2.0 to 9.7) passed before one death from colorectal cancer was prevented for 5000 patients screened. On average across included studies, it took 10.3 years (6.0 to 16.4) before one death from colorectal cancer was prevented for 1000 patients screened. Conclusions Our results suggest that screening for breast and colorectal cancer is most appropriate for patients with a life expectancy greater than 10 years. Incorporating time lag estimates into screening guidelines would encourage a more explicit consideration of the risks and benefits of screening for breast and colorectal cancer. C1 [Lee, Sei J.; Stijacic-Cenzer, Irena; Walter, Louise C.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Geriatr, San Francisco, CA 94121 USA. [Boscardin, W. John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Conell-Price, Jessamyn] Univ Calif San Francisco & Berkeley, Joint Med Program, San Francisco, CA USA. [O'Brien, Sarah] Univ Calif San Francisco, AIDS Educ & Training Evaluat Ctr, San Francisco, CA 94121 USA. RP Lee, SJ (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Geriatr, San Francisco, CA 94121 USA. EM sei.lee@ucsf.edu FU Veterans Affairs Medical Center, San Francisco, CA; San Francisco Veterans Affairs Medical Center; Division of Geriatrics, University of California, San Francisco; Hartford Geriatrics Health Outcomes Research Scholars Award; Hellman Family Award for Early Career Faculty at University of California (San Francisco); American Federation of Aging Research and National Institute on Aging [K23AG040779]; National Center for Research Resources, National Institutes of Health [KL2RR024130]; National Institute on Aging [K24AG041180]; National Cancer Institute [R01CA134425] FX This work was supported by the Veterans Affairs Medical Center, San Francisco, CA. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.; All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: support from the San Francisco Veterans Affairs Medical Center and Division of Geriatrics, University of California, San Francisco for the submitted work; SJL was supported by Hartford Geriatrics Health Outcomes Research Scholars Award, the Hellman Family Award for Early Career Faculty at University of California (San Francisco), K23AG040779 from the American Federation of Aging Research and National Institute on Aging, and KL2RR024130 from the National Center for Research Resources, a component of the National Institutes of Health; LCW was supported by R01CA134425 from the National Cancer Institute and K24AG041180 from the National Institute on Aging administered by the Northern California Institute for Research and Education; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. NR 43 TC 43 Z9 45 U1 1 U2 13 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 JAN 8 PY 2013 VL 346 AR e8441 DI 10.1136/bmj.e8441 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 070ZH UT WOS:000313553800014 PM 23299842 ER PT J AU Teerlink, JR Cotter, G Davison, BA Felker, GM Filippatos, G Greenberg, BH Ponikowski, P Unemori, E Voors, AA Adams, KF Dorobantu, MI Grinfeld, LR Jondeau, G Marmor, A Masip, J Pang, PS Werdan, K Teichman, SL Trapani, A Bush, CA Saini, R Schumacher, C Severin, TM Metra, M AF Teerlink, John R. Cotter, Gad Davison, Beth A. Felker, G. Michael Filippatos, Gerasimos Greenberg, Barry H. Ponikowski, Piotr Unemori, Elaine Voors, Adriaan A. Adams, Kirkwood F., Jr. Dorobantu, Maria I. Grinfeld, Liliana R. Jondeau, Guillaume Marmor, Alon Masip, Josep Pang, Peter S. Werdan, Karl Teichman, Sam L. Trapani, Angelo Bush, Christopher A. Saini, Rajnish Schumacher, Christoph Severin, Thomas M. Metra, Marco CA RELAXin Acute Heart Failure RELAX- TI Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial SO LANCET LA English DT Article ID RENAL-FUNCTION; PROTECT; DYSPNEA; HOSPITALIZATION; ROLOFYLLINE; ANTAGONIST; OUTCOMES; ASSOCIATION; MORTALITY; LEVOSIMENDAN AB Background Serelaxin, recombinant human relaxin-2, is a vasoactive peptide hormone with many biological and haemodynamic effects. In a pilot study, serelaxin was safe and well tolerated with positive clinical outcome signals in patients with acute heart failure. The RELAX-AHF trial tested the hypothesis that serelaxin-treated patients would have greater dyspnoea relief compared with patients treated with standard care and placebo. Methods RELAX-AHF was an international, double-blind, placebo-controlled trial, enrolling patients admitted to hospital for acute heart failure who were randomly assigned (1:1) via a central randomisation scheme blocked by study centre to standard care plus 48-h intravenous infusions of placebo or serelaxin (30 mu g/kg per day) within 16 h from presentation. All patients had dyspnoea, congestion on chest radiograph, increased brain natriuretic peptide (BNP) or N-terminal prohormone of BNP, mild-to-moderate renal insufficiency, and systolic blood pressure greater than 125 mm Hg. Patients, personnel administering study drug, and those undertaking study-related assessments were masked to treatment assignment. The primary endpoints evaluating dyspnoea improvement were change from baseline in the visual analogue scale area under the curve (VAS AUC) to day 5 and the proportion of patients with moderate or marked dyspnoea improvement measured by Likert scale during the first 24 h, both analysed by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00520806. Findings 1161 patients were randomly assigned to serelaxin (n=581) or placebo (n=580). Serelaxin improved the VAS AUC primary dyspnoea endpoint (448 mm x h, 95% CI 120-775; p=0.007) compared with placebo, but had no significant effect on the other primary endpoint (Likert scale; placebo, 150 patients [26%]; serelaxin, 156 [27%]; p=0.70). No significant effects were recorded for the secondary endpoints of cardiovascular death or readmission to hospital for heart failure or renal failure (placebo, 75 events [60-day Kaplan-Meier estimate, 13.0%]; serelaxin, 76 events [13.2%]; hazard ratio [HR] 1.02 [0.74-1.41], p=0.89] or days alive out of the hospital up to day 60 (placebo, 47.7 [SD 12.1] days; serelaxin, 48.3 [11.6]; p=0.37). Serelaxin treatment was associated with significant reductions of other prespecified additional endpoints, including fewer deaths at day 180 (placebo, 65 deaths; serelaxin, 42; HR 0.63, 95% CI 0.42-0.93; p=0.019). Interpretation Treatment of acute heart failure with serelaxin was associated with dyspnoea relief and improvement in other clinical outcomes, but had no effect on readmission to hospital. Serelaxin treatment was well tolerated and safe, supported by the reduced 180-day mortality. C1 [Teerlink, John R.] San Francisco VA Med Ctr, Div Cardiol, San Francisco, CA 94121 USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Cotter, Gad; Davison, Beth A.] Momentum Res, Durham, NC USA. [Felker, G. Michael] Duke Univ, Sch Med, Durham, NC USA. [Felker, G. Michael] Duke Univ, Med Ctr, Duke Heart Ctr, Durham, NC 27710 USA. [Filippatos, Gerasimos] Athens Univ Hosp, Athens, Greece. [Greenberg, Barry H.] Univ Calif San Diego, San Diego, CA 92103 USA. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Unemori, Elaine; Teichman, Sam L.] Corthera, San Carlos, CA USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Gronignen, Groningen, Netherlands. [Adams, Kirkwood F., Jr.] Univ N Carolina, Chapel Hill, NC USA. [Dorobantu, Maria I.] Floreasca Emergency Clin Hosp, Bucharest, Romania. [Grinfeld, Liliana R.] Univ Buenos Aires, Buenos Aires, DF, Argentina. [Jondeau, Guillaume] Univ Paris 07, Hop Bichat, Paris, France. [Marmor, Alon] Ziv Med Ctr, Safed, Israel. [Masip, Josep] Univ Barcelona, Consorci Sanitari Integral, Barcelona, Spain. [Pang, Peter S.] Northwestern Univ, Chicago, IL 60611 USA. [Werdan, Karl] Univ Halle Wittenberg, Halle, Saale, Germany. [Trapani, Angelo; Bush, Christopher A.; Saini, Rajnish] Novartis Pharmaceut, E Hanover, NJ USA. [Schumacher, Christoph; Severin, Thomas M.] Novartis Pharmaceut, Basel, Switzerland. [Metra, Marco] Univ Brescia, Brescia, Italy. RP Teerlink, JR (reprint author), San Francisco VA Med Ctr, Div Cardiol, San Francisco, CA 94121 USA. EM john.teerlink@ucsf.edu RI Lainscak, Mitja/F-3237-2015; Ponikowski, Piotr/O-6454-2015 OI Ponikowski, Piotr/0000-0002-3391-7064; Metra, Marco/0000-0001-6691-8568; Davison, Beth/0000-0003-2374-6449 FU Corthera; Amgen; Bayer; Cardio3 Bioscience; Cytokinetics; Merck; Novartis; Takeda; Teva; Trevena; Otsuka; Roche Diagnostics; NHLBI; Nanosphere; European Union; Abbott; PDL BioPharma; Alere; Cardio3Biosciences; Celladon; Ceva; European Committee; Dutch Heart Foundation; Servier; Torrent; Vifor; Duke Clinical Research Institute; Momentum Research; Abbott Vascular FX JRT has received research grants or consulting fees from Amgen, Bayer, Corthera, Cardio3 Bioscience, Cytokinetics, Merck, Novartis, Takeda, Teva, and Trevena. GC and BAD are employees of Momentum Research, which has provided consulting and trial management services to NovaCardia, Merck, Corthera, Novartis, Nile Therapeutics, Bioheart, Cardio3 Biosciences, Amgen, Celadon, Targegen, Trevena, Sorbent Therapeutics, and NIH. GMF reports consulting income from Novartis, Medpace, Amgen, Otsuka, Trevena, Roche Diagnostics, Merck, BG Medicine, Medtronic, and St Judes and grant fundings from Amgen, Otsuka, Roche Diagnostics, and NHLBI. GF is an executive committee member and consultant to Corthera (a Novartis company), Bayer, Cardiorentis, and has received research grants from Amgen, Nanosphere, European Union. BHG served as a consultant for Corthera and Novartis. PP was a consultant for Astellas, Bayer, EKR Therapeutics, J&J, the Medicines Company, Medtronic, Novartis, Otsuka, Palatin Technologies, PDL BioPharma, Pericor Therapeutics, SigmaTau, Solvay Pharmaceuticals, and Trevena; has received honoraria from Alere, Beckman-Coulter, BiogenIdec, Corthera, Ikaria, Nile Therapeutics, Momentum Research, and Overcome; has received research support from Abbott, Merck and PDL BioPharma; and has received travel support from MyLife and equipment support from Sonosite. EU is employed by the sponsor, Corthera (a Novartis company). AAV has received consultancy fees and/or research grants from Alere, Bayer, Cardio3Biosciences, Celladon, Ceva, European Committee, Dutch Heart Foundation, Novartis, Servier, Torrent, and Vifor. KFA has received research grants and consulting fees from Corthera, Merck, Roche Diagnostics, and Duke Clinical Research Institute; research grants from Novartis and Amgen; and consulting fees from Momentum Research. MID, LRG, JG, AM, JM, and KW have received research grants from Corthera (a Novartis affiliate company). KW received personal support for travel to meetings for the RELAX-AHF trial. KW's institution received honorarium for patient enrolment in the RELAX-AHF trial and honorarium for national coordinatorship of KW for the RELAX-AHF trial. PSP has been a consultant for Astellas, Bayer, EKR Therapeutics, J&J, the Medicines Company, Medtronic, Novartis, Otsuka, Palatin Technologies, PDL BioPharma, Pericor Therapeutics, SigmaTau, Solvay Pharmaceuticals, Trevena; received honoraria from Alere, Beckman-Coulter, BiogenIdec, Corthera, Ikaria, Nile Therapeutics, Momentum Research, and Overcome; received research support from Abbott, Merck, and PDL BioPharma; and received travel support from MyLife and equipment support from Sonosite. SLT was an employee of the sponsor, Corthera (a Novartis affiliate company). AT, CAB, RS, CS, and TMS are Novartis employees and receive salary, benefits, and stock options from Novartis Pharmaceuticals Corporation (CAB, RS, AT) or Novartis Pharma (CS, TS). MM has received consulting income from Abbott Vascular, Bayer, Corthera, and Novartis, as well as travel support and honoraria from Servier and Novartis. NR 43 TC 328 Z9 345 U1 4 U2 51 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JAN 5 PY 2013 VL 381 IS 9860 BP 29 EP 39 DI 10.1016/S0140-6736(12)61855-8 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 064AW UT WOS:000313044300024 PM 23141816 ER PT J AU Snider, AJ Ruiz, P Obeid, LM Oates, JC AF Snider, Ashley J. Ruiz, Phillip Obeid, Lina M. Oates, Jim C. TI Inhibition of Sphingosine Kinase-2 in a Murine Model of Lupus Nephritis SO PLOS ONE LA English DT Article ID RENAL THROMBOXANE PRODUCTION; MRL/LPR MICE; ERYTHEMATOSUS; SURVIVAL; FTY720; SPHINGOSINE-1-PHOSPHATE; DISEASE; CYCLOOXYGENASE-2; INFLAMMATION; ASSOCIATION AB Sphingosine-1-phosphate (S1P), a potent bioactive lipid, is emerging as a central mediator in inflammation and immune responses. We have previously implicated S1P and its synthetic enzyme sphingosine kinase (SK) in inflammatory and autoimmune disorders, including inflammatory bowel disease and rheumatoid arthritis. Generation of S1P requires phosphorylation of sphingosine by SK, of which there are two isoforms. Numerous studies have implicated SK1 in immune cell trafficking, inflammation and autoimmune disorders. In this study, we set out to determine the role of SK and S1P in lupus nephritis (LN). To this end, we examined S1P and dihydro-S1P (dh-S1P) levels in serum and kidney tissues from a mouse model of LN. Interestingly dh-S1P was significantly elevated in serum and kidney tissue from LN mice, which is more readily phosphorylated by SK2. Therefore, we employed the use of the specific SK2 inhibitor, ABC294640 in our murine model of LN. Treatment with ABC294640 did not improve vascular or interstitial pathology associated with LN. However, mice treated with the SK2 inhibitor did demonstrate decreases in glomerular pathology and accumulation of B and T cells in the spleen these were not statistically different from lpr mice treated with vehicle. LN mice treated with ABC294640 did not have improved urine thromboxane levels or urine proteinuria measurements. Both S1P and dh-S1P levels in circulation were significantly reduced with ABC294640 treatment; however, dh-S1P was actually elevated in kidneys from LN mice treated with ABC294640. Together these data demonstrate a role for SKs in LN; however, they suggest that inhibition of SK1 or perhaps both SK isoforms would better prevent elevations in S1P and dh-S1P and potentially better protect against LN. C1 [Snider, Ashley J.; Obeid, Lina M.; Oates, Jim C.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Snider, Ashley J.; Obeid, Lina M.; Oates, Jim C.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Ruiz, Phillip] Univ Miami, Miller Sch Med, Dept Pathol, Div Immunopathol, Miami, FL 33136 USA. [Obeid, Lina M.] Med Univ S Carolina, Dept Mol & Cellular Biol & Pathobiol, Charleston, SC 29425 USA. RP Oates, JC (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. EM oatesjc@musc.edu OI obeid, lina/0000-0002-0734-0847 FU Alliance for Lupus Research; Veterans Affairs Merit Award; Career Development Award FX This work was supported by a grant from the Alliance for Lupus Research (JCO), Veterans Affairs Merit Award (LMO) and Career Development Award (AJS). Lipid analyses provided by the Lipidomics Shared Resource, Hollings Cancer Center, Medical University of South Carolina (P30 CA138313) and the Lipidomics Core in the SC Lipidomics and Pathobiology COBRE, Department Biochemistry, MUSC (P20 RR017677). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 10 Z9 10 U1 0 U2 33 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 JAN 3 PY 2013 VL 8 IS 1 AR e53521 DI 10.1371/journal.pone.0053521 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 070BE UT WOS:000313480000063 PM 23301082 ER PT J AU Leng, SY Nallamothu, BK Saint, S Appleman, LJ Bump, GM AF Leng, Siyang Nallamothu, Brahmajee K. Saint, Sanjay Appleman, Leonard J. Bump, Gregory M. TI Simple and Complex SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MYELOPROLIFERATIVE DISORDERS; ESSENTIAL THROMBOCYTHEMIA; POLYCYTHEMIA-VERA; MYELOFIBROSIS; THROMBOSIS; DIAGNOSIS; NEOPLASMS; RUXOLITINIB; MANAGEMENT; DISEASE C1 [Leng, Siyang; Appleman, Leonard J.; Bump, Gregory M.] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA USA. [Appleman, Leonard J.] Univ Pittsburgh, Med Ctr, Div Hematol Oncol, Pittsburgh, PA USA. [Nallamothu, Brahmajee K.; Saint, Sanjay] VA Ann Arbor Healthcare Syst, Dept Internal Med, Ann Arbor, MI USA. [Nallamothu, Brahmajee K.] VA Ann Arbor Healthcare Syst, Div Cardiol, Ann Arbor, MI USA. Univ Michigan Hlth Syst, Ann Arbor, MI USA. RP Leng, SY (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr 130-U, Pittsburgh, PA 15240 USA. EM siyang.leng@gmail.com OI Appleman, Leonard/0000-0003-4951-7388 NR 16 TC 1 Z9 1 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 3 PY 2013 VL 368 IS 1 BP 65 EP 71 DI 10.1056/NEJMcps1202256 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 062PA UT WOS:000312930600008 PM 23281978 ER PT J AU Singh, J AF Singh, Jasvinder TI FOLIC ACID SUPPLEMENTATION FOR RHEUMATOID ARTHRITIS PATIENTS ON METHOTREXATE: THE GOOD GETS BETTER SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Editorial Material DE Rheumatology ID LOW-DOSE METHOTREXATE; MODIFYING ANTIRHEUMATIC DRUGS; RECOMMENDATIONS; TRIAL C1 [Singh, Jasvinder] Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. [Singh, Jasvinder] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA. [Singh, Jasvinder] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, J (reprint author), Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. EM jasvinder.md@gmail.com NR 11 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2013 IS 7 AR ED000063 DI 10.1002/14651858.ED000063 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AQ8AY UT WOS:000343044400002 PM 24151647 ER PT S AU Benton, RG Choubey, S Clark, DG Johnsten, T Raghavan, VV AF Benton, Ryan G. Choubey, Suresh Clark, David G. Johnsten, Tom Raghavan, Vijay V. BE Imamura, K Usui, S Shirao, T Kasamatsu, T Schwabe, L Zhong, N TI Diagnosis and Grading of Alzheimer's Disease via Automatic Classification of FDG-PET Scans SO BRAIN AND HEALTH INFORMATICS SE Lecture Notes in Artificial Intelligence LA English DT Proceedings Paper CT International Conference on Brain and Health Informatics (BHI) CY OCT 29-31, 2013 CL Maebashi, JAPAN SP Web Intelligence Consortium, IEEE Computat Intelligence Soc Task Force on Brain Informat, Maebashi Inst Technol, Gunma Prefecture Govt, Maebashi City Govt, Maebashi Convent Bur, Web Intelligence Lab Inc, Mitsuba Gakki Co Ltd, GCC Inc, Japan High Comm, Kuribara Med Instruments, Yamato Inc DE Alzheimer's Disease; PET; Mild Cognitive Impairment ID DEMENTIA AB Clinical trials for interventions that seek to delay the onset of Alzheimer's disease (AD) are hampered by inadequate methods for selecting study subjects who are at risk, and who may therefore benefit from the interventions being studied. Automated monitoring tools may facilitate clinical research and thereby reduce the impact of AD on individuals, caregivers, society at large, and government healthcare infrastructure. We studied the 18F-deoxyglucose positron emission tomography (FDG-PET) scans of research subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI), using a Machine Learning technique. Three hundred ninety-four FDG-PET scans were obtained from the ADNI database. An automated procedure was used to extract measurements from 31 regions of each PET surface projection. These data points were used to evaluate the sensitivity and specificity of support vector machine (SVM) classifiers and to compare both Linear and Radial-Basis SVM techniques against a classic thresholding method used in earlier work. C1 [Benton, Ryan G.; Raghavan, Vijay V.] Univ Louisiana Lafayette, Ctr Adv Comp Studies, Lafayette, LA 70504 USA. [Choubey, Suresh] Qual Operat GE Healthcare, Birmingham, AL USA. [Clark, David G.] Birmingham VA Med Ctr, Birmingham, AL USA. [Clark, David G.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL USA. [Johnsten, Tom] Univ S Alabama, Sch Comp, Mobile, AL USA. RP Benton, RG (reprint author), Univ Louisiana Lafayette, Ctr Adv Comp Studies, Lafayette, LA 70504 USA. EM rbenton@cacs.louisiana.edu; suresh.choubey@ge.com; dgclark@gmail.com; tjohnsten@southalabama.edu; vijay@cacs.louisiana.edu FU Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health [U01 AG024904] FX Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI data are disseminated by the Laboratory for Neuro- Imaging at the University of California, Los Angeles. NR 15 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-02753-1; 978-3-319-02752-4 J9 LECT NOTES ARTIF INT PY 2013 VL 8211 BP 266 EP 276 PG 11 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BB3HY UT WOS:000342795600027 ER PT J AU Clancy, CM AF Clancy, Carolyn M. TI Creating a Healing Environment SO HERD-HEALTH ENVIRONMENTS RESEARCH & DESIGN JOURNAL LA English DT Editorial Material ID DESIGN RP Clancy, CM (reprint author), US Dept Vet Affairs, Washington, DC 20420 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU VENDOME GROUP LLC PI NEW YORK PA 6 EAST 32 ST, 8 FLOOR, NEW YORK, NY 10016 USA SN 1937-5867 EI 2167-5112 J9 HERD-HEALTH ENV RES JI Herd-Health Env. Res. Des. J. PY 2013 VL 7 SU S SI SI BP 5 EP 7 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AN9MP UT WOS:000340931300001 ER PT S AU Wasterlain, CG Gloss, DS Niquet, J Wasterlain, AS AF Wasterlain, Claude G. Gloss, David S. Niquet, Jerome Wasterlain, Amy S. BE Dulac, O Lassonde, M Sarnat, HB TI Epileptogenesis in the developing brain SO PEDIATRIC NEUROLOGY, PT I SE Handbook of Clinical Neurology LA English DT Article; Book Chapter ID DEVELOPING RAT-BRAIN; TEMPORAL-LOBE EPILEPSY; DELAYED NEURONAL DEATH; EARLY-LIFE SEIZURES; INFLAMMATORY CELL RESPONSE; PROLONGED FEBRILE SEIZURES; INDUCED STATUS EPILEPTICUS; LONG-TERM CONSEQUENCES; ANTIEPILEPTIC DRUGS; IMMATURE BRAIN C1 [Wasterlain, Claude G.; Gloss, David S.; Niquet, Jerome; Wasterlain, Amy S.] VA Greater Los Angeles Hlth Care Syst, Dept Neurol, Los Angeles, CA USA. [Wasterlain, Claude G.; Gloss, David S.; Niquet, Jerome; Wasterlain, Amy S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Wasterlain, CG (reprint author), West LA VA Med Ctr 127, Dept Neurol, 11301 Wilshire Blvd, West Los Angeles, CA 90073 USA. EM wasterla@ucla.edu FU BLRD VA [I01 BX000273]; NINDS NIH HHS [U01 NS074926, NS13515, NS059704] NR 125 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0072-9752 BN 978-0-444-62698-1; 978-0-444-52891-9 J9 HAND CLINIC PY 2013 VL 111 BP 427 EP 439 PG 13 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA BA6KF UT WOS:000337167000048 PM 23622191 ER PT S AU Meyerhoff, DJ Durazzo, TC Ende, G AF Meyerhoff, Dieter J. Durazzo, Timothy C. Ende, Gabriele BE Sommer, WH Spanagel, R TI Chronic Alcohol Consumption, Abstinence and Relapse: Brain Proton Magnetic Resonance Spectroscopy Studies in Animals and Humans SO BEHAVIORAL NEUROBIOLOGY OF ALCOHOL ADDICTION SE Current Topics in Behavioral Neurosciences LA English DT Article; Book Chapter DE Alcoholism; Alcohol use disorders; Magnetic resonance spectroscopy; Neuroimaging; Brain metabolites; Recovery; Relapse; Nicotine; Smoking ID CHRONIC CIGARETTE-SMOKING; GAMMA-AMINOBUTYRIC-ACID; N-ACETYL-ASPARTATE; DSM-IV ALCOHOL; NATIONAL EPIDEMIOLOGIC SURVEY; CORTICAL GABA LEVELS; SHORT-TERM RECOVERY; IN-VIVO; RAT-BRAIN; MR SPECTROSCOPY AB This chapter summarizes the peer-reviewed literature of proton magnetic resonance spectroscopy (H-1 MRS) studies on the effects of chronic and excessive alcohol consumption in both the animal and human brain. After a brief summary of the neuropathology of alcohol use disorders (AUD), we describe the primary brain metabolites measured by in vivo H-1 MRS. We then focus on published MRS studies of animal models of alcohol dependence and of treatment-seeking humans with AUD. We also summarize the scant MRS research on the much larger fraction of treatment-naive individuals with AUD and the similarities and discrepancies relative to treatment-seekers. It is exceedingly apparent that premorbid and/or comorbid disorders/conditions, especially chronic smoking, among individuals with AUD contribute to the considerable variability in the pattern and magnitude of neurobiological and neurocognitive abnormalities in AUD. Therefore, we also review studies on the neurobiological consequences of the combined effects of chronic drinking and smoking in AUD. Finally, as AUD is characterized by a chronically relapsing/remitting course over lifetime and identification of those at greatest risk for relapse is important, we review H-1 MRS studies on brain spectroscopic measures that contribute to the prediction of relapse in AUD. We conclude with an overall assessment of the MRS research literature on brain alcohol effects, the role of animal and human studies in understanding the disease, and discuss the need of widely integrative MRS studies of cohorts that include individuals with comorbidies that are reflective of the general population with AUD. C1 [Meyerhoff, Dieter J.; Durazzo, Timothy C.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. [Meyerhoff, Dieter J.; Durazzo, Timothy C.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Ende, Gabriele] Cent Inst Mental Hlth, Dept Neuroimaging, Mannheim, Germany. RP Meyerhoff, DJ (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. EM dieter.meyerhoff@ucsf.edu FU NIAAA NIH HHS [R01 AA10788]; NIDA NIH HHS [K01 DA24136] NR 151 TC 15 Z9 16 U1 1 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1866-3370 BN 978-3-642-28720-6; 978-3-642-28719-0 J9 CURR TOP BEHAV NEURO JI Cur. Top. Behav. Neurosci. PY 2013 VL 13 BP 511 EP 540 DI 10.1007/7854_2011_131 D2 10.1007/978-3-642-28720-6 PG 30 WC Substance Abuse; Neurosciences SC Substance Abuse; Neurosciences & Neurology GA BA9NA UT WOS:000339611900018 PM 21688208 ER PT B AU Ma, QL Yang, FS Frautschy, SA Cole, GM AF Ma, Qiu-Lan Yang, Fusheng Frautschy, Sally A. Cole, Greg M. BE Maruta, H TI PAK1 in Alzheimer's and Huntington's Diseases SO PAKS, RAC/CDC42 (P21)-ACTIVATED KINASES: TOWARDS THE CURE OF CANCER AND OTHER PAK-DEPENDENT DISEASES SE Elsevier Insights LA English DT Article; Book Chapter ID DENDRITIC SPINE MORPHOGENESIS; D-ASPARTATE RECEPTOR; SRC FAMILY KINASES; A-BETA OLIGOMERS; AMYLOID-BETA; MUTANT HUNTINGTIN; IN-VIVO; SYNAPTIC PLASTICITY; ACTIN CYTOSKELETON; MENTAL-RETARDATION C1 [Ma, Qiu-Lan; Yang, Fusheng; Frautschy, Sally A.; Cole, Greg M.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Ma, Qiu-Lan; Yang, Fusheng; Frautschy, Sally A.; Cole, Greg M.] West Angeles Med Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Geriatr Res & Clin Ctr, Los Angeles, CA USA. RP Ma, QL (reprint author), Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. NR 87 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-407210-7; 978-0-12-407198-8 J9 ELSEV INSIGHT PY 2013 BP 107 EP 124 DI 10.1016/B978-0-12-407198-8.00006-0 PG 18 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BA4GB UT WOS:000335640300006 ER PT S AU Warren, T Dickey, M AF Warren, T. Dickey, M. BE Hamilton, AC TI The influence of event-related knowledge on verb-argument processing in aphasia SO 51ST ACADEMY OF APHASIA PROCEEDINGS SE Procedia Social and Behavioral Sciences LA English DT Proceedings Paper CT 51st Conference of the Academy-of-Aphasia CY OCT 20-22, 2013 CL Lucerne, SWITZERLAND SP Acad Aphasia C1 [Warren, T.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Dickey, M.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Warren, T (reprint author), Univ Pittsburgh, Pittsburgh, PA 15260 USA. EM mdickey@pitt.edu OI Dickey, Michael Walsh/0000-0002-9068-3313 FU National Institutes of Health [R01DC011520]; [UL1TR000005] FX This research was supported by the National Institutes of Health through Grant number R01DC011520 to the authors and by Grant number UL1TR000005 to the Clinical and Translational Science Institute of the University of Pittsburgh. It is the result of work supported with resources and the use of facilities at the VA Pittsburgh Healthcare System. Thanks are due to Minas Abovyan, Amanda Fryd, Emily Kosenske, Molly Lane, Evelyn Milburn, Hannah Rosenberg, Hyunsoo Yoo, and Lidia Zacharczuk for help running participants, to Alice Proverbio and Federica Riva for sharing their picture stimuli from Proverbio and Riva (2009), and to audiences at the 2012 and 2013 CUNY Sentence Processing Conference and the 2013 Academy of Aphasia meeting for comments and suggestions. Special thanks are due to the adults with aphasia who participated in these studies. A preliminary version of this work was published as Warren and Dickey (2013). NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-0428 J9 PROCD SOC BEHV PY 2013 VL 94 BP 194 EP + DI 10.1016/j.sbspro.2013.09.095 PG 2 WC Psychology, Clinical SC Psychology GA BA4IF UT WOS:000335774400094 ER PT S AU Dickey, M Yoo, H AF Dickey, M. Yoo, H. BE Hamilton, AC TI Acquisition versus generalization in sentence production treatment in aphasia: Dose-response relationships SO 51ST ACADEMY OF APHASIA PROCEEDINGS SE Procedia Social and Behavioral Sciences LA English DT Proceedings Paper CT 51st Conference of the Academy-of-Aphasia CY OCT 20-22, 2013 CL Lucerne, SWITZERLAND SP Acad Aphasia C1 [Dickey, M.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. [Yoo, H.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Dickey, M (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. EM mdickey@pitt.edu OI Dickey, Michael Walsh/0000-0002-9068-3313 NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-0428 J9 PROCD SOC BEHV PY 2013 VL 94 BP 281 EP + DI 10.1016/j.sbspro.2013.09.141 PG 2 WC Psychology, Clinical SC Psychology GA BA4IF UT WOS:000335774400140 ER PT S AU Holers, VM Rohrer, B Tomlinson, S AF Holers, V. Michael Rohrer, Baerbel Tomlinson, Stephen BE Lambris, JD Holers, VM Ricklin, D TI CR2-Mediated Targeting of Complement Inhibitors: Bench-to-Bedside Using a Novel Strategy for Site-Specific Complement Modulation SO COMPLEMENT THERAPEUTICS SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; EPSTEIN-BARR-VIRUS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; PATHWAY-MEDIATED DISEASES; CD21 LIGAND-BINDING; MACULAR DEGENERATION; ALTERNATIVE PATHWAY; REPERFUSION INJURY; FACTOR-H; CHOROIDAL NEOVASCULARIZATION AB Recent approval of the first human complement pathway-directed therapeutics, along with high-pro file genetic association studies, has catalyzed renewed biopharmaceutical interest in developing drugs that modulate the complement system. Substantial challenges remain, however, that must be overcome before widespread application of complement inhibitors in inflammatory and autoimmune diseases becomes possible. Among these challenges are the following: (1) defining the complement pathways and effector mechanisms that cause tissue injury in humans and determining whether the relative importance of each varies by disease, (2) blocking or modulating, using traditional small molecule or biologic approaches, the function of complement proteins whose circulating levels are very high and whose turnover rates are relatively rapid, especially in the setting of acute and chronic autoimmune diseases, and (3) avoiding infectious complications or impairment of other important physiological functions of complement when using systemically active complement-blocking agents. This chapter will review data that address these challenges to therapeutic development, with a focus on the development of a novel strategy of blocking specific complement pathways by targeting inhibitors using a recombinant portion of the human complement receptor type 2 (CR2/CD21) which specifically targets to sites of local complement C3 activation where C3 fragments are covalently fixed. Recently, the first of these CR2-targeted proteins has entered human phase I studies in the human disease paroxysmal nocturnal hemoglobinuria. The results of murine translational studies using CR2-targeted inhibitors strongly suggest that a guiding principle going forward in complement therapeutic development may well be to focus on developing strategies to modulate the pathway as precisely as possible by physically localizing therapeutic inhibitory effects. C1 [Holers, V. Michael] Univ Colorado, Sch Med, Dept Med, Aurora, CO 80045 USA. [Holers, V. Michael] Univ Colorado, Sch Med, Dept Immunol, Aurora, CO USA. [Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. [Rohrer, Baerbel; Tomlinson, Stephen] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Tomlinson, Stephen] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Holers, VM (reprint author), Univ Colorado, Sch Med, Dept Med, Aurora, CO 80045 USA. EM michael.holers@ucdenver.edu FU NEI NIH HHS [R01 EY019320]; NHLBI NIH HHS [R01 HL082485, HL086576]; NIAMS NIH HHS [R01 AR51749] NR 106 TC 27 Z9 28 U1 0 U2 10 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-4117-5; 978-1-4614-4118-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2013 VL 735 BP 137 EP 154 DI 10.1007/978-1-4614-4118-2_9 D2 10.1007/978-1-4614-4118-2 PG 18 WC Immunology; Microbiology SC Immunology; Microbiology GA BA2RJ UT WOS:000333837700010 PM 23402024 ER PT J AU Tapp, A Wood, A Sylvers, P Kilzieh, N Saxon, A AF Tapp, A. Wood, A. Sylvers, P. Kilzieh, N. Saxon, A. TI QUETIAPINE FOR THE TREATMENT OF COCAINE DEPENDENCE SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 [Tapp, A.; Wood, A.; Sylvers, P.; Kilzieh, N.] VA Puget Sound Hlth Care Syst, Psychiat, Tacoma, WA USA. [Saxon, A.] VA Puget Sound Hlth Care Syst, Psychiat, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 EI 1778-3585 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 2013 VL 28 SU 1 MA 2733 PG 1 WC Psychiatry SC Psychiatry GA AG5LN UT WOS:000335460602138 ER PT J AU Kearns, W Jasiewicz, JM Fozard, JL Webster, P Scott, S Craighead, J Bowen, ME McCarthy, J AF Kearns, William Jasiewicz, Jan M. Fozard, James L. Webster, Paul Scott, Steven Craighead, Jeffrey Bowen, Mary E. McCarthy, Joseph TI Temporo-spacial prompting for persons with cognitive impairment using smart wrist-worn interface SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Editorial Material ID TECHNOLOGY; ACCEPTANCE C1 [Kearns, William; Jasiewicz, Jan M.; Fozard, James L.; Scott, Steven; Craighead, Jeffrey] James A Haley Vet Hosp, Vet Integrated Serv Network 8, Ctr Innovat Disabil & Rehabil Res, Tampa, FL 33612 USA. [Kearns, William] Univ S Florida, Coll Behav & Community Sci, Dept Rehabil & Mental Hlth Counseling, Tampa, FL USA. [Fozard, James L.] Univ S Florida, Coll Behav & Community Sci, Sch Aging Studies, Tampa, FL USA. [Webster, Paul; McCarthy, Joseph] Ubisense, Cambridge, England. [Scott, Steven] James A Haley Vet Hosp, Phys Med & Rehabil Serv, Tampa, FL 33612 USA. [Bowen, Mary E.] W Chester Univ, Dept Hlth, W Chester, PA 19380 USA. [Bowen, Mary E.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Kearns, W (reprint author), James A Haley Vet Hosp, Vet Integrated Serv Network 8, Ctr Innovat Disabil & Rehabil Res, Tampa, FL 33612 USA. EM kearns@usf.edu RI Kearns, William/F-9810-2015 OI Kearns, William/0000-0002-0241-814X NR 13 TC 3 Z9 3 U1 0 U2 3 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2013 VL 50 IS 10 BP VII EP XIII DI 10.1682/JRRD.2013.12.0261 PG 7 WC Rehabilitation SC Rehabilitation GA AE0LR UT WOS:000333658300001 PM 24699980 ER PT J AU Gebrosky, B Pearlman, J Cooper, RA Cooper, R Kelleher, A AF Gebrosky, Benjamin Pearlman, Jonathan Cooper, Rory A. Cooper, Rosemarie Kelleher, Annmarie TI Evaluation of lightweight wheelchairs using ANSI/RESNA testing standards SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE ANSI/RESNA; depot wheelchair; double drum; durability; fatigue tests; lightweight wheelchair; manual wheelchair; wheelchair; wheelchair comparison; wheelchair testing ID SPINAL-CORD-INJURY; MANUAL WHEELCHAIRS; ADVERSE CONSEQUENCES; REPAIRS; PEOPLE AB Lightweight wheelchairs are characterized by their low cost and limited range of adjustment. Our study evaluated three different folding lightweight wheelchair models using the American National Standards Institute/Rehabilitation Engineering Society of North America (ANSI/RESNA) standards to see whether quality had improved since the previous data were reported. On the basis of reports of increasing breakdown rates in the community, we hypothesized that the quality of these wheelchairs had declined. Seven of the nine wheelchairs tested failed to pass the multidrum test durability requirements. An average of 194,502 +/- 172,668 equivalent cycles was completed, which is similar to the previous test results and far below the 400,000 minimum required to pass the ANSI/RESNA requirements. This was also significantly worse than the test results for aluminum ultralight folding wheelchairs. Overall, our results uncovered some disturbing issues with these wheelchairs and suggest that manufacturers should put more effort into this category to improve quality. To improve the durability of lightweight wheelchairs, we suggested that stronger regulations be developed that require wheelchairs to be tested by independent and certified test laboratories. We also proposed a wheelchair rating system based on the National Highway Transportation Safety Administration vehicle crash ratings to assist clinicians and end users when comparing the durability of different wheelchairs. C1 [Gebrosky, Benjamin; Pearlman, Jonathan; Cooper, Rory A.; Cooper, Rosemarie; Kelleher, Annmarie] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs VA, Rehabil Res & Dev Serv, Pittsburgh, PA 15206 USA. [Pearlman, Jonathan; Cooper, Rosemarie] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Cooper, Rory A.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Cooper, Rory A.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Cooper, Rosemarie; Kelleher, Annmarie] Univ Pittsburgh, Med Ctr, Ctr Assist Technol, Pittsburgh, PA USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151R B, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu OI Pearlman, Jon/0000-0003-0830-9136 FU Center for Excellence for Wheelchairs and Associated Rehabilitation Engineering [B6789C] FX This material was based on work supported by the Center for Excellence for Wheelchairs and Associated Rehabilitation Engineering (grant B6789C). NR 22 TC 3 Z9 3 U1 2 U2 6 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2013 VL 50 IS 10 BP 1373 EP 1389 DI 10.1682/JRRD.2012.08.0155 PG 17 WC Rehabilitation SC Rehabilitation GA AE0LR UT WOS:000333658300009 PM 24699973 ER PT J AU Tobin, MJ AF Tobin, Martin J. TI Probing with the ventilator SO CRITICAL CARE LA English DT Editorial Material ID MECHANICAL VENTILATION; TRIALS AB Neurally adjusted ventilatory assist operates through recordings of electrical activity of the diaphragm (EAdi). Barwing and colleagues found increases in EAdi in weaning-failure patients, although the values were not significantly different from weaning-success patients. Future studies will need to carefully control for the considerable biological noise evident in EAdi recordings. C1 [Tobin, Martin J.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. [Tobin, Martin J.] Loyola Univ, Chicago Stritch Sch Med, Hines, IL 60141 USA. RP Tobin, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. EM mtobin2@lumc.edu NR 7 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 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2013 VL 17 IS 5 AR 198 DI 10.1186/cc13038 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA AB1HA UT WOS:000331540900099 PM 24090345 ER PT J AU Wang, LS Jiao, Y Huang, Y Liu, XY Gibson, G Bennett, B Hamre, KM Li, DW Zhao, HY Gelernter, J Kranzler, HR Farrer, LA Lu, L Wang, YJ Gu, WK AF Wang, L. S. Jiao, Y. Huang, Y. Liu, X. Y. Gibson, G. Bennett, B. Hamre, K. M. Li, D. W. Zhao, H. Y. Gelernter, J. Kranzler, H. R. Farrer, L. A. Lu, L. Wang, Y. J. Gu, W. K. TI Critical evaluation of transcription factor Atf2 as a candidate modulator of alcohol preference in mouse and human populations SO GENETICS AND MOLECULAR RESEARCH LA English DT Article DE Alcohol preference; Atf2; Candidate; QTL; Gene expression ID GENETIC DISSECTION; ETHANOL; TRAIT; EXPRESSION; STRAINS; METABOLISM; DEPENDENCE; KINASE AB In prior work, congenic strains carrying the DBA/2Igb (D2) region of chromosome 2 (Chr2) for alcohol preference were bred onto a C57BL/6Ibg (B6) background and as predicted were found to reduce voluntary consumption. Subsequently, interval-specific congenic recombinant strains (ISCRS) were generated and also tested. These ISCRS strains reduced the quantitative trait loci (QTL) interval to a comparatively small 3.4 Mb region. Here, we have exploited an integrative approach using both murine and human populations to critically evaluate candidate genes within this region. First, we used bioinformatics tools to search for genes relevant to alcohol preference within the QTL region. Second, we searched for single nucleotide polymorphisms (SNPs) within exons of every gene in this region. Third, we conducted follow-up microarray analyses to identify differentially expressed genes between the B6 and ISCRS strains in mice from each group. Fourth, we analyzed correlations between the expression level of candidate genes and phenotypes of alcohol preference in a large family of BXD recombinant inbred strains derived from B6 and D2. Finally, we evaluated SNP segregation in both BXD mouse strains and in humans who were heavy alcohol drinkers or non-drinkers. Among several potential candidate genes in this region, we identified activating transcription factor 2 (Atf2) as the most plausible gene that would influence alcohol preference. However, the candidacy of Atf2 was only weakly supported when we used a genetic network approach and by focused reanalysis of genome-wide association study data from European-American and African-American populations. Thus, we cannot conclude that Atf2 plays a role in the regulation of the QTL of mouse Chr2. C1 [Wang, L. S.; Jiao, Y.; Huang, Y.; Liu, X. Y.; Gibson, G.; Gu, W. K.] Univ Tennessee, Ctr Hlth Sci, Campbell Clin, Dept Orthopaed Surg & BioMed Engn, Memphis, TN 38163 USA. [Bennett, B.] Univ Colorado Denver, Sch Pharm, Aurora, CO USA. [Hamre, K. M.; Lu, L.] Univ Tennessee, Ctr Hlth Sci, Dept Anat & Neurobiol, Memphis, TN 38163 USA. [Li, D. W.; Gelernter, J.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Zhao, H. Y.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Zhao, H. Y.; Gelernter, J.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Gelernter, J.] VA Connecticut Healthcare Ctr, West Haven, CT USA. [Gelernter, J.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA. [Kranzler, H. R.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Kranzler, H. R.] Philadelphia VA Med Ctr, VISN MIRECC 4, Philadelphia, PA USA. [Farrer, L. A.] Boston Univ, Sch Med, Dept Med Biomed Genet, Boston, MA 02118 USA. [Farrer, L. A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Farrer, L. A.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. [Farrer, L. A.] Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA. [Farrer, L. A.] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. [Farrer, L. A.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA. [Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Med Biomed Genet, Boston, MA USA. [Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Neurol, Boston, MA USA. [Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Ophthalmol, Boston, MA USA. [Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Genet & Genom, Boston, MA USA. [Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Wang, Y. J.] Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, Beijing, Peoples R China. RP Gu, WK (reprint author), Univ Tennessee, Ctr Hlth Sci, Campbell Clin, Dept Orthopaed Surg & BioMed Engn, Memphis, TN 38163 USA. EM wgu@uthsc.edu RI Li, Dawei/A-3466-2011 OI Farrer, Lindsay/0000-0001-5533-4225 FU National Institutes of Health, United States [AA016342, DA12849, DA12690, AA017535, AA12870, AA11330]; National Institutes of Health [N01-HG-65403]; Alkermes; Lilly; Lundbeck; Pfizer; Roche; Eli Lilly; Janssen; Schering Plough; GlaxoSmithKline; Abbott; Johnson Johnson FX Research supported by the National Institutes of Health, United States (research grants #AA016342, #DA12849, #DA12690, #AA017535, #AA12870, and #AA11330). Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (contract #N01-HG-65403). Authors thank Dr. Robert Williams for his great assistance on the analysis of data in GeneNetwork and kindly reviewing of the manuscript.; Dr. Kranzler has been a paid consultant for Alkermes, Lilly, Lundbeck, Pfizer, and Roche. He also reports associations with Eli Lilly, Janssen, Schering Plough, Lundbeck, Alkermes, GlaxoSmithKline, Abbott, and Johnson & Johnson, as these companies provide support to the ACNP Alcohol Clinical Trials Initiative (ACTIVE) and Dr. Kranzler has received honoraria from ACTIVE. The other authors report no financial interests or potential conflicts of interest. NR 23 TC 3 Z9 2 U1 0 U2 1 PU FUNPEC-EDITORA PI RIBEIRAO PRETO PA RUA FLORIANO PEIXOTO 2444, ALTO DA BOA VISTA, RIBEIRAO PRETO, SP 00000, BRAZIL SN 1676-5680 J9 GENET MOL RES JI Genet. Mol. Res. PY 2013 VL 12 IS 4 BP 5992 EP 6005 DI 10.4238/2013.November.26.9 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AB2FG UT WOS:000331608000188 PM 24338393 ER PT J AU Liao, W Jordaan, G Srivastava, MK Dubinett, S Sharma, S Sharma, S AF Liao, Wei Jordaan, Gwen Srivastava, Minu K. Dubinett, Steven Sharma, Sherven Sharma, Sanjai TI Effect of epigenetic histone modifications on E-cadherin splicing and expression in lung cancer SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Article DE E-cadherin; splicing; histone modifications; HDAC; HDAC inhibitor; Zeb1; EMT ID EPITHELIAL-MESENCHYMAL TRANSITION; MESSENGER-RNA DECAY; C-TERMINAL DOMAIN; TUMOR PROGRESSION; CHROMATIN MODIFICATIONS; CELL-LINES; GENE; METHYLATION; DISEASE; GROWTH AB We have identified an alternatively spliced, non-functional aberrant E-cadherin transcript that lacks exon 11 and is over expressed in malignant cells as compared to the normal non-malignant cells. This increase in the aberrant transcript is a mechanism of loss of E-cadherin gene expression as it is rapidly degraded by the nonsense mediated decay pathway. To study the mechanism of this gene missplicing we analyzed the role of histone epigenetic modifications in lung cancer cell lines. The treatment of low E-cadherin lung cancer cell lines with histone deacetylase inhibitor (HDACi, MS-275) resulted in the preferential expression of the correctly spliced transcripts in the low E-cadherin expressing cell lines only. Chromatin immunoprecipitation (ChIP) assays revealed that the histone hypoacetylation levels correlate with aberrant exon 11 splicing as there is more aberrant splicing in cell lines with E-cadherin promoter hypoacetylation. Inactivation of histone deacetylases (HDAC) 1, 2 and 3 resulted in an increase in E-cadherin expression and an increase in the ratio of the correctly spliced E-cadherin transcript. As transcription of the gene is closely linked to splicing, we considered the possibility that change in E-cadherin transcription correlates with splicing. The Zeb1 epithelial-mesenchymal transformation (EMT) inducer silences E-cadherin expression and could also alter the splicing of this exon. Inhibition of the E-cadherin promoter transcription with Zeb1 expression increases aberrant splicing and the reverse is observed when Zeb1 is knocked down. The role of HDAC inhibitors was also studied in vivo in a immunodeficient mouse xenograft model. Exposure of mice to HDACi resulted in growth inhibition, increase in E-cadherin expression, alteration of aberrant splicing and the reversal of EMT in mouse tumors. The findings support the modulation of E-cadherin exon 11 inclusion or exclusion by histone epigenetic modifications as they change the overall chromatin structure. The results provide an interesting link between epigenetic alterations in cancer cells and gene splicing in addition to their effect on gene silencing. C1 [Liao, Wei; Jordaan, Gwen; Srivastava, Minu K.; Dubinett, Steven; Sharma, Sherven; Sharma, Sanjai] UCLA West Los Angeles Vet Med Ctr, Div Hematol Oncol, Los Angeles, CA 90073 USA. [Srivastava, Minu K.; Dubinett, Steven; Sharma, Sherven] Vet Affairs Greater Los Angeles Healthcare Syst, Mol Med Lab, Los Angeles, CA USA. [Dubinett, Steven; Sharma, Sherven] Univ Calif Los Angeles, Div Pulm & Crit Care Med, Los Angeles, CA USA. RP Sharma, S (reprint author), UCLA West Los Angeles Vet Med Ctr, 11301 Wilshire Blvd,Bldg 304,Rm E1-115, Los Angeles, CA 90073 USA. EM sasharma@mednet.ucla.edu FU Flight Attendants Medical Research Institute (FAMRI); ASCO Foundation; VA Merit Research award; NIH [RO1 CA95686, RO1 CA126944, P50 CA90388]; UCLA Lung Cancer Program; VA Medical Research Funds; Tobacco Related Disease Program Award Program of University of California FX SS is a recipient of a grant from Flight Attendants Medical Research Institute (FAMRI), ASCO Foundation Young Investigator Award and a VA Merit Research award. Steven Dubinett and Sherven Sharma are supported by NIH Grants (RO1 CA95686, RO1 CA126944 and P50 CA90388), UCLA Lung Cancer Program, VA Medical Research Funds and Tobacco Related Disease Program Award Program of University of California. NR 54 TC 6 Z9 7 U1 0 U2 2 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 2156-6976 J9 AM J CANCER RES JI Am. J. Cancer Res. PY 2013 VL 3 IS 4 BP 374 EP 389 PG 16 WC Oncology SC Oncology GA AA4MJ UT WOS:000331069400004 PM 23977447 ER PT J AU Gollapudi, K Galet, C Grogan, T Zhang, H Said, JW Huang, J Elashoff, D Freedland, SJ Rettig, M Aronson, WJ AF Gollapudi, Kiran Galet, Colette Grogan, Tristan Zhang, Hong Said, Jonathan W. Huang, Jiaoti Elashoff, David Freedland, Stephen J. Rettig, Matthew Aronson, William J. TI Association between tumor-associated macrophage infiltration, high grade prostate cancer, and biochemical recurrence after radical prostatectomy SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Article DE Biochemical recurrence; cancer development; prostate; tumor associated macrophages; tissue microarray ID BREAST-CANCER; EXPRESSION; INFLAMMATION; CELLS; ANGIOGENESIS; PROGRESSION; METASTASIS; PROGNOSIS; CARCINOMA; DENSITY AB Background: Tumor-associated macrophages (TAMs) are a key component of the inflammatory microenvironment. Their role in prostate cancer development and progression remains unclear. We examined whether the amount of TAMs in prostate cancer is: 1) higher than prostatic intraepithelial neoplasia (PIN) and benign tissue 2) associated with poorly differentiated disease, and 3) predictive of biochemical recurrence among surgically treated men. Methods: A tissue microarray (TMA) of prostatectomy specimens from 332 patients was stained for CD68, a TAM marker. A separate TMA was used for validation. Associations between mean TAMs in cancer cores and PSA recurrence were determined by Cox proportional hazards models after adjusting for age, preoperative PSA, race, body mass index, pathologic Gleason sum, seminal vesicle invasion, extracapsular extension, and margin status. Results: Mean TAM number was higher in cancer versus PIN and benign tissue (p<0.0001). Mean TAM number was higher in Gleason grade 4 cores vs. Gleason grade 3 cores (p=0.003). On multivariable analysis, no association was observed between mean TAM number per cancer core and biochemical recurrence in either cohort. Conclusion: Mean TAM number was higher in cancer cores vs. PIN and benign tissue, and higher in high grade prostate cancer supporting the potential role of TAMs in prostate cancer development. However, TAMs were not associated with biochemical recurrence after radical prostatectomy suggesting TAM counts do not provide independent prognostic value among surgically treated men. Further studies are required to elucidate the functional significance of TAMs in the prostate cancer microenvironment. C1 [Gollapudi, Kiran; Galet, Colette; Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Grogan, Tristan; Elashoff, David] Univ Calif Los Angeles, Sch Med, Dept Med Stat Core, Los Angeles, CA 90095 USA. [Zhang, Hong; Said, Jonathan W.; Huang, Jiaoti] Univ Calif Los Angeles, Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. [Freedland, Stephen J.] Duke Univ, Med Ctr, Durham Vet Affairs Med Ctr, Dept Surg, Durham, NC USA. [Freedland, Stephen J.] Duke Univ, Med Ctr, Div Urol Surg, Durham, NC USA. [Freedland, Stephen J.] Duke Univ, Med Ctr, Duke Prostate Ctr, Dept Surg, Durham, NC USA. [Freedland, Stephen J.] Duke Univ, Med Ctr, Duke Prostate Ctr, Dept Pathol, Durham, NC USA. [Rettig, Matthew] VA Greater Angeles Healthcare Syst, Dept Med, Div Hematol Oncol, Los Angeles, CA USA. [Aronson, William J.] VA Greater Angeles Healthcare Syst, Dept Surg, Urol Sect, Los Angeles, CA USA. RP Aronson, WJ (reprint author), Univ Calif Los Angeles, Sch Med, Dept Urol, Box 951738, Los Angeles, CA 90095 USA. EM kgollapudi@mednet.ucla.edu; waron-son@ucla.edu FU National Cancer Institute (NCI) [P50CA92131, 1K24CA160653-01]; Department of Veterans Affairs; Department of Defense [PC030686]; CTSI NIH [UL1TR000124]; UCLA Cancer Center [P30CA16042] FX We thank Dr Gholamhossein Pezeshkpour for his assistance in creating the WLA tissue microarray. We also thank Leah Gerber for her assistance in retrieving all necessary information from the WLA and Durham databases. This study was supported by National Cancer Institute (NCI) Grant Number P50CA92131 (WJA) and Grant Number 1K24CA160653-01 (SJF), The Department of Veterans Affairs (WJA), the Department of Defense Grant Number PC030686 (MR) and the CTSI NIH Grant Number UL1TR000124 (TG and DE) and UCLA Cancer Center (P30CA16042) (TG and DE). NR 25 TC 18 Z9 19 U1 0 U2 4 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 2156-6976 J9 AM J CANCER RES JI Am. J. Cancer Res. PY 2013 VL 3 IS 5 BP 523 EP 529 PG 7 WC Oncology SC Oncology GA AA4MK UT WOS:000331069500009 PM 24224130 ER PT J AU Singh, JA AF Singh, Jasvinder A. TI Veterans Affairs databases are accurate for gout-related health care utilization: a validation study SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID QUALITY-OF-LIFE; POPULATION; DIAGNOSES; COSTS; COMORBIDITIES; ARTHRITIS; PATTERNS; COHORT; FLARES AB Introduction: The aim of this study was to assess the accuracy of Veterans Affairs (VA) databases for gout-related health care utilization. Methods: This retrospective study utilized VA administrative and clinical databases. A random sample of gout patients with visits (outpatient, inpatient or emergent/urgent care) with or without the diagnosis of gout (International Classification of Diseases, ninth revision, common modification ICD-9-CM code of 274.x or 274.xx) at the Birmingham VA hospital was selected. A blinded abstractor performed a review of VA electronic health records for the documentation of gout or gout-related terms (gouty arthritis, tophaceous gout, tophus/tophi, acute gout, chronic gout, podagra, urate stones, urate or uric acid crystals and so on) in the chief complaint, history of present illness or assessment and plan for the visit; this constituted the gold standard for gout-related utilization. The accuracy of database-derived gout-related claims was assessed by calculating sensitivity, specificity, and positive and negative predictive values (PPV and NPV). Results: Of 108 potential visits, 85 outpatient, inpatient or urgent care/emergency room visits to a health care provider (85 patients: 84 men and 1 woman with a mean age of 63 years) and retrievable data from medical records constituted the analyzed dataset. Administrative claims for gout-related utilization with ICD-9 code for gout were accurate with a PPV of 86%, specificity of 95%, sensitivity of 86% and NPV of 95%. Conclusions: VA databases are accurate for gout-related visits. These findings support their use for studies of health services and outcome studies. It remains to be seen if these findings are generalizable to other settings and databases. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. EM Jasvinder.md@gmail.com FU Takeda Pharmaceuticals USA, Inc.; National Institutes of Arthritis, Musculoskeletal and Skin Diseases (NIAMS); National Institutes of Aging (NIA); National Cancer Institute (NCI); Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs) FX I thank Michael Conner, BS from Birmingham VA Medical Center, for creating a random sample of gout and non-gout visits. Takeda Pharmaceuticals USA, Inc. funded this investigator-initiated study, but had no contribution to the study design, analytic plan, data collection, analyses or the decision to submit the study. The study author (Dr. Singh) developed study protocol, performed data collection and data analyses, prepared the manuscript and made the decision to submit the manuscript. An internal review committee at Takeda Pharmaceuticals reviewed a draft of the manuscript and provided comments to the author. The decision to or not to incorporate these comments was made by the author (Dr. Singh). Dr. Singh is also supported by research grants from the National Institutes of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Aging (NIA), National Cancer Institute (NCI) and the Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs), and the resources and use of facilities at the Birmingham VA Medical Center. NR 18 TC 9 Z9 9 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2013 VL 15 IS 6 AR R224 DI 10.1186/ar4425 PG 5 WC Rheumatology SC Rheumatology GA 302TW UT WOS:000330628800050 PM 24377421 ER PT J AU Arnardottir, ES Janson, C Bjornsdottir, E Benediktsdottir, B Juliusson, S Kuna, ST Pack, AI Gislason, T AF Arnardottir, Erna Sif Janson, Christer Bjornsdottir, Erla Benediktsdottir, Bryndis Juliusson, Sigurdur Kuna, Samuel T. Pack, Allan I. Gislason, Thorarinn TI Nocturnal sweating - a common symptom of obstructive sleep apnoea: the Icelandic sleep apnoea cohort SO BMJ OPEN LA English DT Article ID NIGHT SWEATS; GASTROESOPHAGEAL-REFLUX; CARE PATIENTS; LUNG-FUNCTION; PREVALENCE; OKPRN; EPIDEMIOLOGY; ASSOCIATIONS; RELIABILITY; PRESSURE AB Objectives: To estimate the prevalence and characteristics of frequent nocturnal sweating in obstructive sleep apnoea (OSA) patients compared with the general population and evaluate the possible changes with positive airway pressure (PAP) treatment. Nocturnal sweating can be very bothersome to the patient and bed partner. Design: Case-control and longitudinal cohort study. Setting: Landspitali-The National University Hospital, Iceland. Participants: The Icelandic Sleep Apnea Cohort consisted of 822 untreated patients with OSA, referred for treatment with PAP. Of these, 700 patients were also assessed at a 2-year follow-up. The control group consisted of 703 randomly selected subjects from the general population. Intervention: PAP therapy in the OSA cohort. Main outcome measures: Subjective reporting of nocturnal sweating on a frequency scale of 1-5: (1) never or very seldom, (2) less than once a week, (3) once to twice a week, (4) 3-5 times a week and (5) every night or almost every night. Full PAP treatment was defined objectively as the use for = 4 h/day and = 5 days/week. Results: Frequent nocturnal sweating (= 3x a week) was reported by 30.6% of male and 33.3% of female OSA patients compared with 9.3% of men and 12.4% of women in the general population (p<0.001). This difference remained significant after adjustment for demographic factors. Nocturnal sweating was related to younger age, cardiovascular disease, hypertension, sleepiness and insomnia symptoms. The prevalence of frequent nocturnal sweating decreased with full PAP treatment (from 33.2% to 11.5%, p<0.003 compared with the change in non-users). Conclusions: The prevalence of frequent nocturnal sweating was threefold higher in untreated OSA patients than in the general population and decreased to general population levels with successful PAP therapy. Practitioners should consider the possibility of OSA in their patients who complain of nocturnal sweating. C1 [Arnardottir, Erna Sif; Bjornsdottir, Erla; Benediktsdottir, Bryndis; Gislason, Thorarinn] Natl Univ Hosp Iceland, Landspitali, Dept Resp Med & Sleep, Reykjavik, Iceland. [Arnardottir, Erna Sif; Bjornsdottir, Erla; Benediktsdottir, Bryndis; Gislason, Thorarinn] Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland. [Janson, Christer] Uppsala Univ, Dept Med Sci Resp Med & Allergol, Uppsala, Sweden. [Juliusson, Sigurdur] Natl Univ Hosp Iceland, Landspitali, Dept Otolaryngol, Reykjavik, Iceland. [Kuna, Samuel T.] Univ Penn, Sch Med, Dept Med, Div Sleep Med,Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA. [Kuna, Samuel T.] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. RP Gislason, T (reprint author), Natl Univ Hosp Iceland, Landspitali, Dept Resp Med & Sleep, Reykjavik, Iceland. EM thorarig@landspitali.is FU NIH [HL72067, HL94307]; University of Iceland; Landspitali University Hospital Research Fund FX NIH grant HL72067 for "A Family Linkage Study of Obstructive Sleep Apnoea" and HL94307 for "Endophenotypes of Sleep Apnea and Role of Obesity", the Eimskip fund of the University of Iceland and the Landspitali University Hospital Research Fund. NR 36 TC 5 Z9 5 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2013 VL 3 IS 5 AR e002795 DI 10.1136/bmjopen-2013-002795 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 301NF UT WOS:000330538300081 ER PT J AU Bortnik, KE Horner, MD Bachman, DL AF Bortnik, Kirsty E. Horner, Michael David Bachman, David L. TI Performance on Standard Indexes of Effort Among Patients with Dementia SO APPLIED NEUROPSYCHOLOGY-ADULT LA English DT Article DE dementia; effort; geriatric; symptom validity testing ID SYMPTOM VALIDITY TEST; MEMORY MALINGERING TOMM; NEUROPSYCHOLOGICAL STATUS RBANS; DIAGNOSTIC-CRITERIA; REPEATABLE BATTERY; CLASSIFICATION ACCURACY; INTERNATIONAL WORKSHOP; COGNITIVELY INTACT; VASCULAR DEMENTIA; GERIATRIC SAMPLE AB Assessment of response validity is an integral part of neuropsychological practice. Although many studies have demonstrated the efficacy of stand alone and embedded effort measures in a variety of medical and compensation-seeking contexts, much less is known about the robustness of these measures in elderly populations, particularly in patients with dementia. Although older adults may be viewed as less likely to intentionally feign symptoms for an external gain, there are a variety of other factors that could result in suboptimal effort, including fatigue, lack of interest or cooperation in the testing process, or failure to fully appreciate the implications of the assessment on treatment care and outcome. The current study examined the clinical utility of several stand alone and embedded effort measures including the Repeatable Battery for the Assessment of Neuropsychological Status Effort Index, Trail-Making Test Ratio, Rey 15-Item Test, and the Test of Memory Malingering in a sample of patients with dementia. Results found that the majority of effort indexes demonstrated unacceptably high false-positive error rates with specificity levels as high as 83%. These findings demonstrate the need for caution in interpreting effort measure performance in dementia samples due to the fact that despite their best effort, many patients with dementia fail effort measures and are at risk for being misclassified. C1 [Bortnik, Kirsty E.] Med Univ S Carolina, Fuller Grad Sch Psychol, Charleston, SC 29425 USA. [Bortnik, Kirsty E.; Horner, Michael David; Bachman, David L.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Horner, Michael David; Bachman, David L.] Med Univ S Carolina, Neuropsychol Clin, Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Bortnik, KE (reprint author), Columbia Univ, Med Ctr, Neurol Inst, 710 W 168th St, New York, NY 10032 USA. EM kbortnik@gmail.com NR 60 TC 8 Z9 8 U1 3 U2 9 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0908-4282 EI 1532-4826 J9 APPL NEUROPSYCH-ADUL JI Appl. Neuropsychol.-Adult PY 2013 VL 20 IS 4 BP 233 EP 242 DI 10.1080/09084282.2012.695757 PG 10 WC Clinical Neurology; Psychology SC Neurosciences & Neurology; Psychology GA 298ST UT WOS:000330345400001 ER PT J AU Singh, JA Hawn, M Campagna, EJ Henderson, WG Richman, J Houston, TK AF Singh, Jasvinder A. Hawn, Mary Campagna, Elizabeth J. Henderson, William G. Richman, Joshua Houston, Thomas K. TI Mediation of smoking-associated postoperative mortality by perioperative complications in veterans undergoing elective surgery: data from Veterans Affairs Surgical Quality Improvement Program (VASQIP)-a cohort study SO BMJ OPEN LA English DT Article DE Epidemiology ID CARDIAC RISK-ASSESSMENT; PULMONARY COMPLICATIONS; NONCARDIAC SURGERY; QUIT RATES; CESSATION PROGRAM; ABDOMINAL-SURGERY; EUROPEAN-SOCIETY; UNITED-STATES; GUIDELINES; PREVALENCE AB Objective To assess the mediation of smoking-associated postoperative mortality by postoperative complications. Design Observational cohort study. Setting Using data from the Veterans Affairs (VA) Surgical Quality Improvement Programme, a quality assurance programme for major surgical procedures in the VA healthcare system, we assessed the association of current smoking at the time of the surgery with 6-month and 1-year mortality. Primary and secondary outcome measures Using mediation analyses, we calculated the relative contribution of each smoking-associated complication to smoking-associated postoperative mortality, both unadjusted and adjusted for age, race/ethnicity, work relative value unit of the operation, surgeon specialty, American Society of Anesthesiologists class and year of surgery. Smoking-associated complications included surgical site infection (SSI), cardiovascular complications (myocardial infarction, cardiac arrest and/or stroke) and pulmonary complications (pneumonia, failure to wean and/or reintubation). Results There were 186632 never smokers and 135741 current smokers. The association of smoking and mortality was mediated by smoking-related complications with varying effects. In unadjusted analyses, the proportions of mediation of smoking to 6-month mortality explained by the complications were as follows: SSIs 22%, cardiovascular complications 12% and pulmonary complications 89%. In adjusted analyses, the per cents mediated by each complication were as follows: SSIs 2%, cardiovascular complications 4% and pulmonary complications 22%. In adjusted analyses for 1-year mortality, respective per cents mediated were 2%, 3% and 16%. Conclusions Pulmonary complications, followed by cardiovascular complications and SSIs were mediators of smoking-associated 6-month and 1-year mortality. Interventions targeting smoking cessation and prevention and early treatment of pulmonary complications has the likelihood of reducing postoperative mortality after elective surgery. C1 [Singh, Jasvinder A.; Hawn, Mary; Richman, Joshua] Univ Alabama Birmingham, Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Hawn, Mary; Richman, Joshua] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Hawn, Mary] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. [Campagna, Elizabeth J.; Henderson, William G.] Univ Colorado Denver, Colorado Hlth Outcomes Program, Aurora, CO USA. [Campagna, Elizabeth J.] VA Med Ctr, Denver, CO USA. [Houston, Thomas K.] Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Houston, Thomas K.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU Veterans Affairs Research Grant [VA IIR IAB 06-038-2] FX Veterans Affairs Research Grant - VA IIR IAB 06-038-2. NR 37 TC 4 Z9 4 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2013 VL 3 IS 4 AR e002157 DI 10.1136/bmjopen-2012-002157 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 291DZ UT WOS:000329809200016 ER PT J AU Shah, RC Kamphuis, PJ Leurgans, S Swinkels, SH Sadowsky, CH Bongers, A Rappaport, SA Quinn, JF Wieggers, RL Scheltens, P Bennett, DA AF Shah, Raj C. Kamphuis, Patrick J. Leurgans, Sue Swinkels, Sophie H. Sadowsky, Carl H. Bongers, Anke Rappaport, Stephen A. Quinn, Joseph F. Wieggers, Rico L. Scheltens, Philip Bennett, David A. TI The S-Connect study: results from a randomized, controlled trial of Souvenaid in mild-to-moderate Alzheimer's disease SO ALZHEIMERS RESEARCH & THERAPY LA English DT Article ID DEMENTIA RATING CDR; NATIONAL INSTITUTE; CLINICAL-TRIALS; NORMATIVE DATA; MEDICAL FOOD; SYNAPSE LOSS; EFFICACY; GUIDELINES; BRAIN; SCALE AB Introduction: Souvenaid r containing Fortasyn r Connect is a medical food designed to support synapse synthesis in persons with Alzheimer's disease (AD). Fortasyn Connect includes precursors (uridine monophosphate; choline; phospholipids; eicosapentaenoic acid; docosahexaenoic acid) and cofactors (vitamins E, C, B12, and B6; folic acid; selenium) for the formation of neuronal membranes. Whether Souvenaid slows cognitive decline in treated persons with mild-to-moderate AD has not been addressed. Methods: In a 24-week, double-masked clinical trial at 48 clinical centers, 527 participants taking AD medications [52% women, mean age 76.7 years (Standard Deviation, SD = 8.2), and mean Mini-Mental State Examination score 19.5 (SD = 3.1, range 14-24)] were randomized 1: 1 to daily, 125-mL (125 kcal), oral intake of the active product (Souvenaid) or an iso-caloric control. The primary outcome of cognition was assessed by the 11-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog). Compliance was calculated from daily diary recordings of product intake. Statistical analyses were performed using mixed models for repeated measures. Results: Cognitive performance as assessed by ADAS-cog showed decline over time in both control and active study groups, with no significant difference between study groups (difference = 0.37 points, Standard Error, SE = 0.57, p = 0.513). No group differences in adverse event rates were found and no clinically relevant differences in blood safety parameters were noted. Overall compliance was high (94.1% [active] and 94.5% [control]), which was confirmed by significant changes in blood (nutritional) biomarkers. Conclusions: Add-on intake of Souvenaid during 24 weeks did not slow cognitive decline in persons treated for mild-to-moderate AD. Souvenaid was well tolerated in combination with standard care AD medications. C1 [Shah, Raj C.; Leurgans, Sue; Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Kamphuis, Patrick J.; Swinkels, Sophie H.; Bongers, Anke; Wieggers, Rico L.] Nutricia Res, Nutricia Adv Med Nutr, NL-3584 TC Utrecht, Netherlands. [Swinkels, Sophie H.] Nutricia Res, NL-3584 TC Utrecht, Netherlands. [Sadowsky, Carl H.] Nova SE Univ, Dept Neurol, W Palm Beach, FL USA. [Rappaport, Stephen A.] Agewell Hlth, Indianapolis, IN USA. [Quinn, Joseph F.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Quinn, Joseph F.] Portland VA Med Ctr, Portland, OR 97201 USA. [Scheltens, Philip] Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, NL-1007 MB Amsterdam, Netherlands. RP Shah, RC (reprint author), Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, 600 South Paulina,Suite 1022, Chicago, IL 60612 USA. EM Raj_C_Shah@rush.edu NR 29 TC 23 Z9 23 U1 3 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-9193 J9 ALZHEIMERS RES THER JI Alzheimers Res. Ther. PY 2013 VL 5 IS 6 AR 59 DI 10.1186/alzrt224 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 292NQ UT WOS:000329909300007 PM 24280255 ER PT J AU Khorsan, R Cohen, AB Lisi, AJ Smith, MM Delevan, D Armstrong, C Mittman, BS AF Khorsan, Raheleh Cohen, Angela B. Lisi, Anthony J. Smith, Monica M. Delevan, Deborah Armstrong, Courtney Mittman, Brian S. TI Mixed-Methods Research in a Complex Multisite VA Health Services Study: Variations in the Implementation and Characteristics of Chiropractic Services in VA SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article ID ALTERNATIVE MEDICINE USE; EVALUATING QUALITY; MILITARY VETERANS; UNITED-STATES; TEAM SCIENCE; CARE-SYSTEM; CASE SERIES; COMPLEMENTARY; TRENDS; MANAGEMENT AB Maximizing the quality and benefits of newly established chiropractic services represents an important policy and practice goal for the US Department of Veterans Affairs' healthcare system. Understanding the implementation process and characteristics of new chiropractic clinics and the determinants and consequences of these processes and characteristics is a critical first step in guiding quality improvement. This paper reports insights and lessons learned regarding the successful application of mixed methods research approaches-insights derived from a study of chiropractic clinic implementation and characteristics, Variations in the Implementation and Characteristics of Chiropractic Services in VA (VICCS). Challenges and solutions are presented in areas ranging from selection and recruitment of sites and participants to the collection and analysis of varied data sources. The VICCS study illustrates the importance of several factors in successful mixed-methods approaches, including (1) the importance of a formal, fully developed logic model to identify and link data sources, variables, and outcomes of interest to the study's analysis plan and its data collection instruments and codebook and (2) ensuring that data collection methods, including mixed-methods, match study aims. Overall, successful application of a mixed-methods approach requires careful planning, frequent trade-offs, and complex coding and analysis. C1 [Khorsan, Raheleh; Cohen, Angela B.; Smith, Monica M.; Delevan, Deborah; Mittman, Brian S.] VA Greater Los Angeles Healthcare Syst, VA Ctr Implementat Practice & Res Support, Los Angeles, CA 91343 USA. [Khorsan, Raheleh] Samueli Inst, Mil Med Res Program, Corona Del Mar, CA USA. [Lisi, Anthony J.] Vet Hlth Adm, Patient Care Serv, Chiropract Program, Washington, DC USA. [Lisi, Anthony J.] VA Connecticut Healthcare Syst, Chiropract Serv, West Haven, CT USA. [Armstrong, Courtney] RAND Corp, Boston, MA USA. RP Mittman, BS (reprint author), VA Greater Los Angeles Healthcare Syst, VA Ctr Implementat Practice & Res Support, 16111 Plummer St, Los Angeles, CA 91343 USA. EM brian.mittman@va.gov OI Cohen, Angela B./0000-0002-0620-1909 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research Development Service; Samueli Institute; US Army Medical Research and Materiel Command [W81XWH-06-1-0279]; National Institutes of Health National Center for Complementary and Alternative Medicine (NIH-NCCAM) [K01-AT002391] FX The authors would like to acknowledge Joan A. Walter, J.D., P. A., and Rick Welton, M. D., for their support and contributions to the project. They would also like to acknowledge the members of the project advisory board: Lucille Beck, Ph.D.; Charles Burgar, M. D.; A. Lucile Burgo-Black, M. D.; Ian Coulter, Ph.D.; Paul Shekelle, M. D., Ph.D.; Joan Walter, J.D., P. A. Oral presentations by (1) Khorsan R, Cohen A, Smith M, Lisi A, Mittman B, Coulter I, and Walter J. Integrative Chiropractic Services in VA: A Pilot Study (VICCS). American Public Health Association (APHA) 140th Annual Meeting and Exposition, Session: 3418.0 Policy, regulation, comparative and cost effectiveness research: San Francisco, CA. Monday, October 29, 2012: 5: 15 p. m. (Abstract no. 269497); (2) Cohen A, Smith M, Khorsan R, Lisi A, Mittman B, Jenkins D, and Armstrong C. Methodological and logistical challenges to conducting multi-site partnered research in the VA healthcare system. American Public Health Association (APHA) 140th Annual Meeting and Exposition, Session: 3323.0 Chiropractic Research: Current status and updates: San Francisco, CA. Monday, October 29, 2012: 3: 00 PM. (Abstract no. 268597); (3) Smith M, Cohen A, Khorsan R, Jenkins D, Armstrong C, Lisi A, and Mittman B. Tracking VA's chiropractic program: Implementation timelines and variations across selected facilities. American Public Health Association (APHA) 140th Annual Meeting and Exposition, Session: 4133.1 Veteran's Health Care and Health Risks: San Francisco, CA. Tuesday, October 30, 2012: 11: 30 PM. (Abstract no. 265497); (4) Lisi A, Mittman B, Khorsan R, Smith S, Cohen A, Armstrong C, MacGregor C, Carucci M, and Jenkins DM. Variations in the Implementation and Characteristics of Chiropractic Services in VA: A Pilot Study. Association of Chiropractic Colleges (ACC) and Research Agenda Conference (RAC): Las Vegas, NV. March 20-21, 2012; (5) Lisi A, Mittman B, Khorsan R, Smith S, Cohen A, Armstrong C, MacGregor C, Carucci M, and Jenkins DM. Studying the introduction, integration, and effectiveness of chiropractic services within the VA healthcare system: A novel clinical/research collaboration. Association of Chiropractic Colleges (ACC) and Research Agenda Conference (RAC): Las Vegas, NV. March 19-21, 2011; and (6) Lisi A, Mittman B, Khorsan R, Smith S, Cohen A, Armstrong C, MacGregor C, Carucci M, and Jenkins DM. Variations in the implementation and characteristics of chiropractic services in VA Association of Chiropractic Colleges (ACC) and Research Agenda Conference (RAC): Las Vegas, NV. March 19-21, 2011. This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research Development Service. The views expressed in this paper are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. In addition, this work was supported, in part, by a grant to Brian S. Mittman by the Samueli Institute. This grant is supported by the US Army Medical Research and Materiel Command under Award no. W81XWH-06-1-0279. The views, opinions, and/or findings contained in this report are those of the author(s) and should not be construed as an official position, policy, or decision of Department of the Army unless so designated by other documentation.; Also, the views, opinions, and/or findings contained in this report are those of the author(s) and should not be construed as the opinion or policy of the Samueli Institute. In the conduct of research where humans are the subjects, the investigator(s) adhered to the policies regarding the protection of human subjects as prescribed by Code of Federal Regulations (CFR) Title 45, Volume 1, Part 46; Title 32, Chapter 1, Part 219; and Title 21, Chapter 1, Part 50 (Protection of Human Subjects). Monica M. Smith was supported in this work by Grant no. K01-AT002391, a grant from National Institutes of Health National Center for Complementary and Alternative Medicine (NIH-NCCAM). Study findings and conclusions are those of the authors and do not represent the opinion or position of NIH or NCCAM. Institutional review board (IRB) approvals were by VA Greater Los Angeles Healthcare System (IRB of record), VA Connecticut Healthcare System(IRB for Co-PI), Western IRB (IRB for Samueli Institute), and US Army Medical Research and Materiel Command (IRB for Department of Defense). NR 55 TC 2 Z9 2 U1 3 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1741-427X EI 1741-4288 J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PY 2013 AR 701280 DI 10.1155/2013/701280 PG 10 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 289XI UT WOS:000329715500001 ER PT J AU Caswell, JL Kerlikowske, K Shepherd, JA Cummings, SR Hu, DL Huntsman, S Ziv, E AF Caswell, Jennifer L. Kerlikowske, Karla Shepherd, John A. Cummings, Steven R. Hu, Donglei Huntsman, Scott Ziv, Elad TI High mammographic density in women of Ashkenazi Jewish descent SO BREAST CANCER RESEARCH LA English DT Article ID BREAST-CANCER RISK; X-RAY ABSORPTIOMETRY; EUROPEAN AMERICANS; DIGITAL MAMMOGRAMS; POPULATION HISTORY; MUTATION CARRIERS; FAMILY-HISTORY; UNITED-STATES; ASSOCIATION; HERITABILITY AB Introduction: Percent mammographic density (PMD) adjusted for age and body mass index is one of the strongest risk factors for breast cancer and is known to be approximately 60% heritable. Here we report a finding of an association between genetic ancestry and adjusted PMD. Methods: We selected self-identified Caucasian women in the California Pacific Medical Center Research Institute Cohort whose screening mammograms placed them in the top or bottom quintiles of age-adjusted and body mass index-adjusted PMD. Our final dataset included 474 women with the highest adjusted PMD and 469 with the lowest genotyped on the Illumina 1 M platform. Principal component analysis(PCA) and identity-by-descent analyses allowed us to infer the women's genetic ancestry and correlate it with adjusted PMD. Results: Women of Ashkenazi Jewish ancestry, as defined by the first principal component of PCA and identity-bydescent analyses, represented approximately 15% of the sample. Ashkenazi Jewish ancestry, defined by the first principal component of PCA, was associated with higher adjusted PMD(P = 0.004). Using multivariate regression to adjust for epidemiologic factors associated with PMD, including age at parity and use of postmenopausal hormone therapy, did not attenuate the association. Conclusions: Women of Ashkenazi Jewish ancestry, based on genetic analysis, are more likely to have high age-adjusted and body mass index-adjusted PMD. Ashkenazi Jews may have a unique set of genetic variants or environmental risk factors that increase mammographic density. C1 [Caswell, Jennifer L.; Hu, Donglei; Huntsman, Scott; Ziv, Elad] Univ Calif San Francisco, Dept Med, Helen Diller Family Comprehens Canc Ctr, Inst Human Genet,Div Gen Internal Med, San Francisco, CA 94143 USA. [Kerlikowske, Karla] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Med, Gen Internal Med Sect 111A1, San Francisco, CA 94121 USA. [Kerlikowske, Karla] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Epidemiol & Biostat, Gen Internal Med Sect 111A1, San Francisco, CA 94121 USA. [Shepherd, John A.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, MRSC AC122, San Francisco, CA 94143 USA. [Cummings, Steven R.] Calif Pacific Med Ctr Res Inst, San Francisco Coordinating Ctr, San Francisco, CA 94107 USA. RP Ziv, E (reprint author), Univ Calif San Francisco, Dept Med, Helen Diller Family Comprehens Canc Ctr, Inst Human Genet,Div Gen Internal Med, 1450 3rd St, San Francisco, CA 94143 USA. EM elad.ziv@ucsf.edu RI Ziv, Elad/L-5396-2014 OI Caswell-Jin, Jennifer/0000-0002-5711-8355 FU National Institutes of Health [HHSN268200782096C, HHSN268201100011I]; NCI [U01CA63740] FX The authors are grateful to Alice Larocca and Viktoriya Kopvak for assistance with database management and for retrieving the samples. They are grateful to Noah Rosenberg, Doron Behar, and Karl Skorecki for helpful discussions about the results of the analysis. Genotyping was supported by the National Institutes of Health HHSN268200782096C and HHSN268201100011I, and was completed at the Johns Hopkins University Center for Inherited Disease Research. Support for analysis was provided by R01CA120120 and K24169004 to EZ. Support for sample collection was provided by the DaCosta International Fund for Prevention of Breast Cancer, the Eli Lilly Foundation, and the California Pacific Medical Center CRCLE Program. The San Francisco Mammography Registry is supported by an NCI-funded Breast Cancer Surveillance Consortium cooperative agreement (U01CA63740). NR 56 TC 2 Z9 2 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2013 VL 15 IS 3 AR R40 DI 10.1186/bcr3424 PG 9 WC Oncology SC Oncology GA 279CQ UT WOS:000328937600004 PM 23668689 ER PT J AU Hayden, MR Banks, WA Shah, GN Gu, Z Sowers, JR AF Hayden, M. R. Banks, W. A. Shah, G. N. Gu, Z. Sowers, J. R. TI Cardiorenal Metabolic Syndrome and Diabetic Cognopathy SO CARDIORENAL MEDICINE LA English DT Article DE Diabetic cognopathy; Alzheimer's disease; Type 2 diabetes mellitus; Ultrastructure; Remodeling; Neurovascular unit; Blood-brain barrier ID BLOOD-BRAIN-BARRIER; RENIN-ANGIOTENSIN SYSTEM; CALCIFIC UREMIC ARTERIOLOPATHY; CHRONIC KIDNEY-DISEASE; ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; OXIDATIVE STRESS; COGNITIVE DYSFUNCTION; MELLITUS; PERICYTES AB The prevalence of the cardiorenal metabolic syndrome (CRS) is increasing in parallel with obesity, type 2 diabetes mellitus, Alzheimer's disease, and other forms of dementia. Along with metabolic, inflammatory, and immunological abnormalities, there is maladaptive structural remodeling of the heart, kidney, and brain. The term 'diabetic cognopathy' (DC) may be used when discussing functional and structural changes in the brain of the diabetic patient. DC likely represents an advanced form of these changes in the brain that evolve with increasing duration of the CRS and subsequent clinical diabetes. We posit that DC develops due to a convergence of aging, genetic and lifestyle abnormalities (overnutrition and lack of exercise), which result in multiple injurious metabolic and immunologic toxicities such as dysfunctional immune responses, oxidative stress, inflammation, insulin resistance, and dysglycemia (systemically and in the brain). These converging abnormalities may lead to endothelial blood-brain barrier tight junction/adherens junction (TJ/AJ) complex remodeling and microglia activation, which may result in neurodegeneration, impaired cognition, and dementia. Herein, we describe the brain ultrastructural changes evolving from a normal state to maladaptive remodeling in rodent models of CRS including microglia activation/polarization and attenuation and/or loss of the TJ/AJ complexes, pericytes and astrocytes of the neurovascular unit. Further, we discuss the potential relationship between these structural changes and the development of DC, potential therapeutic strategies, and future directions. (C) 2013 S. Karger AG, Basel C1 [Hayden, M. R.; Sowers, J. R.] Univ Missouri, Dept Internal Med, Div Endocrinol Diabet & Metab, Columbia, MO 65212 USA. [Hayden, M. R.; Gu, Z.; Sowers, J. R.] Univ Missouri, Diabet & Cardiovasc Res Lab, Columbia, MO 65212 USA. [Sowers, J. R.] Univ Missouri, Dept Med Pharmacol & Physiol, Columbia, MO 65212 USA. [Sowers, J. R.] Harry S Truman Mem Vet Hosp, Columbia, MO 65201 USA. [Banks, W. A.] Univ Washington, Dept Med, Div Geriatr Med, Vet Affairs Puget Sound Hlth Care Syst,Geriat Res, Seattle, WA USA. [Shah, G. N.] St Louis Univ, Dept Internal Med, Div Endocrinol, St Louis, MO 63103 USA. RP Hayden, MR (reprint author), Univ Missouri, D109 Diabet Ctr HSC,1 Hosp Dr, Columbia, MO 65212 USA. EM mrh29@usmo.com FU NIH [R01 HL73101-01A1, R01 HL107910-01]; Veterans Affairs Merit System [0018] FX The authors would like to acknowledge Tommi White, PhD, of the University of Missouri Electron Microscopic Core Facility, Columbia, Mo., USA, for preparing and staining the transmission electron microscopic images for viewing. We wish to acknowledge Brenda Hunter for her editorial assistance. The work presented is supported by the NIH (R01 HL73101-01A1 and R01 HL107910-01), Veterans Affairs Merit System 0018 (J.R. Sowers). NR 65 TC 4 Z9 4 U1 2 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1664-3828 EI 1664-5502 J9 CARDIORENAL MED JI CardioRenal Med. PY 2013 VL 3 IS 4 BP 265 EP 282 DI 10.1159/000357113 PG 18 WC Cardiac & Cardiovascular Systems; Urology & Nephrology SC Cardiovascular System & Cardiology; Urology & Nephrology GA 278UL UT WOS:000328915300007 PM 24474955 ER PT J AU Yu, MK Katon, W Young, BA AF Yu, Margaret K. Katon, Wayne Young, Bessie A. TI Diabetes Self-Care, Major Depression, and Chronic Kidney Disease in an Outpatient Diabetic Population SO NEPHRON CLINICAL PRACTICE LA English DT Article DE Chronic kidney disease; Depression; Diabetes mellitus; Self-care ID MEDICATION ADHERENCE; AFRICAN-AMERICANS; TYPE-2; PREVALENCE; MORTALITY; PATHWAYS; HOSPITALIZATION; METAANALYSIS; DIALYSIS; MELLITUS AB Background/Aims: The associations between major depression and chronic kidney disease (CKD) in patients with diabetes are incompletely characterized. Depressed patients with diabetes are known to have worse diabetes self-care, but it is not known whether this mediates the association between depression and CKD in this population. Methods: We conducted a cross-sectional study of the associations between major depressive symptoms and CKD in the Pathways Study (n = 4,082), an observational cohort of ambulatory diabetic patients from a managed care setting. Depression status was ascertained using the Patient Health Questionnaire-9 (PHQ-9). Stepwise logistic regression models examined the associations between depression and impaired estimated glomerular filtration rate (<60 ml/min/1.73 m(2)) or microalbuminuria, after adjustment for demographics, CKD risk factors, and diabetes self-care variables. Results: Clinically significant depression symptoms (PHQ-9 >= 10) were associated with a greater risk of microalbuminuria after adjustment for demographic variables (OR 1.54, 95% CI 1.21-1.95) and traditional CKD risk factors (OR 1.36, 95% CI 1.04-1.77); this association persisted after additional adjustment for diabetes self-care (OR 1.34, 95% CI 1.02-1.75). Depression was not associated with impaired estimated glomerular filtration rate in any of the models. Conclusion: In this cohort of diabetic subjects, clinically significant depression symptoms were associated with microalbuminuria, which could not be entirely explained by differences in diabetes self-care. (C) 2013 S. Karger AG, Basel C1 [Yu, Margaret K.; Young, Bessie A.] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [Yu, Margaret K.; Young, Bessie A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Katon, Wayne] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. [Young, Bessie A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Yu, Margaret K.; Young, Bessie A.] Vet Affairs Puget Sound Hlth Care Syst, Kidney Res Inst, Seattle, WA USA. [Young, Bessie A.] Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. RP Yu, MK (reprint author), Univ Washington, Box 356521,1959 NE Pacific St, Seattle, WA 98195 USA. EM mkyu@uw.edu FU National Institutes of Health [RO1 DK 079745, T32 DK007467, MH41739, MH01643]; American Kidney Fund Clinical Scientist in Nephrology Fellowship Program FX This study was supported by grants from the National Institutes of Health (RO1 DK 079745, T32 DK007467, MH41739, MH01643) and the American Kidney Fund Clinical Scientist in Nephrology Fellowship Program. We also thank Dr. Noel Weiss for reviewing the manuscript and the other investigators of the Pathways Study, without whom this research would not be possible. NR 33 TC 8 Z9 8 U1 4 U2 10 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2110 J9 NEPHRON CLIN PRACT JI Nephron. Clin. Pract. PY 2013 VL 124 IS 1-2 BP 106 EP 112 DI 10.1159/000355551 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 275UZ UT WOS:000328704800016 PM 24192760 ER PT J AU Peterson, AL Murchison, C Zabetian, C Leverenz, JB Watson, GS Montine, T Carney, N Bowman, GL Edwards, K Quinn, JF AF Peterson, Amie L. Murchison, Charles Zabetian, Cyrus Leverenz, James B. Watson, G. Stennis Montine, Thomas Carney, Natasha Bowman, Gene L. Edwards, Karen Quinn, Joseph F. TI Memory, Mood, and Vitamin D in Persons with Parkinson's Disease SO JOURNAL OF PARKINSONS DISEASE LA English DT Article DE Parkinson's disease; vitamin D; dementia; depression; cognition ID MILD COGNITIVE IMPAIRMENT; SERUM 25-HYDROXYVITAMIN D; D SUPPLEMENTATION; DOUBLE-BLIND; D DEFICIENCY; POPULATION; DEPRESSION; PREVALENCE; DEMENTIA; BRAIN AB Background: Research in recent years has suggested a role of vitamin D in the central nervous system. The final converting enzyme and the vitamin D receptor are found throughout the human brain. From animal studies vitamin D appears important in neurodevelopment, up-regulation of neurotrophic factors, stabilization of mitochondrial function, and antioxidation. Objective: To examine the relationship between serum vitamin D and neuropsychiatric function in persons with Parkinson's disease (PD). Methods: This is an add-on study to a longitudinal study following neuropsychiatric function in persons with PD. Baseline neuropsychiatric performance and serum 25-hydroxyvitamin D were examined for 286 participants with PD. Measures of global cognitive function (MMSE, MOCA, Mattis Dementia Scale), verbal memory (Hopkins Verbal Learning Test), fluency (animals, vegetables, and FAS words), visuospatial function (Benton Line Orientation), executive function (Trails Making Test and Digit-Symbol Substitution), PD severity (Hoehn & Yahr and Unified Parkinson's Disease Rating Scale) and depression (Geriatric Depression Scale (GDS)) were administered. Multivariate linear regression assessed the association between vitaminD concentration and neuropsychiatric function, in the entire cohort as well as the non-demented and demented subsets. Results: Using a multivariate model, higher vitamin D concentrations were associated with better performance on numerous neuropsychiatric tests in the non-demented subset of the cohort. Significant associations were specifically found between vitamin D concentration and verbal fluency and verbal memory (t = 4.31, p < 0.001 and t = 3.04, p = 0.0083). Vitamin D concentrations also correlated with depression scores (t=-3.08, p = 0.0083) in the non-demented subset. Conclusions: Higher plasma vitamin D is associated with better cognition and better mood in this sample of PD patients without dementia. Determination of causation will require a vitamin D intervention study. C1 [Peterson, Amie L.; Carney, Natasha; Quinn, Joseph F.] Portland VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr PADRECC, Portland, OR USA. [Zabetian, Cyrus; Leverenz, James B.] VA Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr PADRECC, Seattle, WA USA. [Zabetian, Cyrus; Leverenz, James B.; Watson, G. Stennis] VA Puget Sound Hlth Care Syst, Geriat Res Educ & Clin Ctr GRECC, Seattle, WA USA. [Leverenz, James B.] VA Puget Sound Hlth Care Syst, MIRECC, Seattle, WA USA. [Peterson, Amie L.; Murchison, Charles; Bowman, Gene L.; Quinn, Joseph F.] Oregon Hlth & Sci Univ, Portland, OR USA. [Zabetian, Cyrus; Leverenz, James B.; Watson, G. Stennis; Montine, Thomas; Edwards, Karen] Univ Washington, Seattle, WA 98195 USA. RP Peterson, AL (reprint author), Mail Code OP32,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM peterami@ohsu.edu OI Zabetian, Cyrus/0000-0002-7739-4306 FU Department of Veterans Affairs Office of Research and Development CDA2 Award - The Effects of Vitamin D on Balance in Parkinson's Disease; Parkinson Study Group; Parkinson's Disease Foundation's Advancing Parkinson's Treatments Innovations Grant; Pacific Northwest Udall Center [P50 NS062684]; Oregon Clinical and Translation Research Institute (OCTRI) from the National Center for Research Resources (NCRR) of the National Institutes of Health (NIH) [UL1 RR024140]; NIH Roadmap for Medical Research, NeuroNext [5U10NS077350-02]; NINDS [R01 NS065070]; Paul and Elizabeth Duffy Family Trust FX This research was made possible with support from the Department of Veterans Affairs Office of Research and Development CDA2 Award - The Effects of Vitamin D on Balance in Parkinson's Disease. Also from the Mentored Clinical Research Award Supported by the Parkinson Study Group and the Parkinson's Disease Foundation's Advancing Parkinson's Treatments Innovations Grant; the Pacific Northwest Udall Center (P50 NS062684); and the Oregon Clinical and Translation Research Institute (OCTRI), grant number UL1 RR024140 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research, NeuroNext (5U10NS077350-02) funded via NINDS, grant number R01 NS065070, and the Paul and Elizabeth Duffy Family Trust. NR 44 TC 10 Z9 12 U1 3 U2 11 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1877-7171 EI 1877-718X J9 J PARKINSON DIS JI J. Parkinsons Dis. PY 2013 VL 3 IS 4 BP 547 EP 555 DI 10.3233/JPD-130206 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 270PY UT WOS:000328332100007 PM 24081441 ER PT J AU Alge, JL Karakala, N Neely, BA Janech, MG Velez, JCQ Arthur, JM AF Alge, Joseph L. Karakala, Nithin Neely, Benjamin A. Janech, Michael G. Velez, Juan Carlos Q. Arthur, John M. CA SAKInet Investigators TI Urinary angiotensinogen predicts adverse outcomes among acute kidney injury patients in the intensive care unit SO CRITICAL CARE LA English DT Article ID GELATINASE-ASSOCIATED LIPOCALIN; CRITICALLY-ILL PATIENTS; ACUTE-RENAL-FAILURE; FRACTIONAL EXCRETION; CARDIAC-SURGERY; AKI DIAGNOSIS; BIOMARKERS; RISK; UREA; DEFINITION AB Introduction: Acute kidney injury (AKI) is commonly observed in the intensive care unit (ICU), where it can be caused by a variety of factors. The objective of this study was to evaluate the prognostic value of urinary angiotensinogen, a candidate prognostic AKI biomarker identified in post-cardiac surgery patients, in this heterogeneous population. Methods: Urinary angiotensinogen was measured by ELISA and corrected for urine creatinine in 45 patients who developed AKI in the ICU. Patients were grouped by AKI etiology, and the angiotensinogen-to-creatinine ratio (uAnCR) was compared among the groups using the Kruskal-Wallis test. The ability of uAnCR to predict the following endpoints was tested using the area under the ROC curve (AUC): the need for renal replacement therapy (RRT) or death, increased length of stay (defined as hospital discharge > 7 days or death <= 7 days from sample collection), and worsening AKI (defined as an increase in serum creatinine > 0.3 mg/dL after sample collection or RRT). Results: uAnCR was significantly elevated in patients who met the composite outcome RRT or death (89.4 vs 25.4 ng/mg; P = 0.01), and it was a strong predictor of this outcome (AUC = 0.73). Patients with uAnCR values above the median for the cohort (55.21 ng/mg) had increased length of stay compared to patients with uAnCR = 55.21 ng/mg (22 days vs 7 days after sample collection; P = 0.01). uAnCR was predictive of the outcome increased length of stay (AUC = 0.77). uAnCR was also a strong predictor of worsening of AKI (AUC = 0.77). The uAnCR of patients with pre-renal AKI was lower compared to patients with AKI of other causes (median uAnCR 11.3 vs 80.2 ng/mg; P = 0.02). Conclusions: Elevated urinary angiotensinogen is associated with adverse events in AKI patients in the ICU. It could be used to identify high risk patients who would benefit from timely intervention that could improve their outcomes. C1 [Alge, Joseph L.; Karakala, Nithin; Neely, Benjamin A.; Janech, Michael G.; Velez, Juan Carlos Q.; Arthur, John M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Arthur, John M.] Ralph H Johnson VA Med Ctr, Med Serv, Charleston, SC 29401 USA. RP Arthur, JM (reprint author), Med Univ S Carolina, Dept Med, 96 Jonathan Lucas St, Charleston, SC 29425 USA. EM arthurj@musc.edu RI Velez, Juan Carlos/N-3782-2016 OI Neely, Benjamin/0000-0001-6120-7695; Alge, Joseph/0000-0002-2491-1066; Janech, Michael/0000-0002-3202-4811 FU NIH [R01 DK080234, UL1 RR029882]; Merit Review award from the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs FX This study was supported by NIH grant numbers R01 DK080234 and UL1 RR029882 and by a Merit Review award from the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs. The contents do not necessarily represent the views of the Department of Veterans Affairs or the United States Government. NR 32 TC 8 Z9 8 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2013 VL 17 IS 2 AR R69 DI 10.1186/cc12612 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 264OG UT WOS:000327887300034 PM 23587112 ER PT J AU Ibanez, GE Levi-Minzi, MA Rigg, KK Mooss, AD AF Ibanez, Gladys E. Levi-Minzi, Maria A. Rigg, Khary K. Mooss, Angela D. TI Diversion of Benzodiazepines Through Healthcare Sources SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE benzodiazepines; dependence; diversion; prescription drug ID PRESCRIPTION OPIOID ABUSE; METHADONE-MAINTENANCE TREATMENT; NONMEDICAL USE; DRUG-ABUSE AB Benzodiazepines (BZ) are often diverted from legal sources to illicit markets at various points in the distribution process beginning with a pharmaceutical manufacturer, followed by healthcare providers, and finally, to the intended users. Little is known about the extent of BZ diversion involving distribution points directly related to healthcare sources versus points further down the distribution chain. The present study examines the scope of BZ diversion, and the association between BZ dependence and the direct utilization of particular healthcare-related diversion sources among a diverse sample of prescription drug abusers in South Florida. Cross-sectional data were collected from five different groups of drug users: methadone-maintenance clients (n = 247), street drug users (n = 238), public-pay treatment clients (n = 245), private-pay treatment clients (n = 228), and stimulant-using men who have sex with men (MSM; n = 249). Findings suggest that those who are ages 26 to 35 years old, non-Hispanic White participants, private-pay treatment clients, those who are insured, and those with higher incomes had higher odds of utilizing healthcare diversion sources. Those who reported BZ dependence had 2.5 times greater odds of using a healthcare source to obtain BZs than those who did not meet criteria for dependence. C1 [Ibanez, Gladys E.; Mooss, Angela D.] Behav Sci Res Inst, Coral Gables, FL USA. [Levi-Minzi, Maria A.] Nova SE Univ, Ctr Appl Res Subst Use & Hlth Dispar, Miami, FL 33137 USA. [Rigg, Khary K.] Philadelphia VA Med Ctr, Ctr Hlth Equi Res & Promot, Philadelphia, PA USA. RP Levi-Minzi, MA (reprint author), Nova SE Univ, 2 NE 40th St,Suite 404, Miami, FL 33137 USA. EM ms2007@nova.edu FU NIDA NIH HHS [R01 DA021330] NR 32 TC 5 Z9 5 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0279-1072 EI 2159-9777 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD JAN-MAR PY 2013 VL 45 IS 1 BP 48 EP 56 DI 10.1080/02791072.2013.764232 PG 9 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 265HN UT WOS:000327941300006 PM 23662331 ER PT J AU Crytzer, TM Dicianno, BE Fairman, AD AF Crytzer, Theresa M. Dicianno, Brad E. Fairman, Andrea D. TI Effectiveness of an Upper Extremity Exercise Device and Text Message Reminders to Exercise in Adults with Spina Bifida: A Pilot Study SO ASSISTIVE TECHNOLOGY LA English DT Article DE arm ergometry; cognition; exercise; exercise test; hydrocephalus; myelomeningocele; physical activity; spina bifida; upper extremity ID QUALITY-OF-LIFE; EVERYDAY PHYSICAL-ACTIVITY; YOUNG-ADULTS; CEREBRAL-PALSY; METABOLIC SYNDROME; CORD DYSFUNCTION; AEROBIC FITNESS; POCKET-COMPUTER; GMFCS LEVEL; HEALTH-CARE AB Obesity, deconditioning, cognitive impairment, and poor exercise tolerance are health issues concerning adults with spina bifida (SB). Our aim is to describe exercise participation and identify motivating tactics and exercise devices that increase participation. In a quasi-experimental randomized crossover design, the GameCycle was compared to a Saratoga Silver I arm ergometer. Personalized free or low-cost text/voice message reminders to exercise were sent. Nineteen young adults with SB were assigned to either the GameCycle or Saratoga exercise group. Within each group, participants were randomized to receive reminders to exercise, or no reminders, then crossed over to the opposite message group after eight weeks. Before and after a 16-week exercise program anthropometric, metabolic, exercise testing and questionnaire data, and recorded participation were collected. Miles traveled by the GameCycle group were significantly higher than the Saratoga exercise groups. No significant differences were found in participation between the message reminder groups. Low participation rates were seen overall. Those using the GameCycle traveled more miles. Barriers to exercise participation may have superseded ability to motivate adults with SB to exercise even with electronic reminders. Support from therapists to combat deconditioning and develop coping skills may be needed. C1 [Crytzer, Theresa M.; Dicianno, Brad E.] Vet Affairs Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Crytzer, Theresa M.; Dicianno, Brad E.; Fairman, Andrea D.] Univ Pittsburgh, Sch Hlth & Rehabil Sci, Pittsburgh, PA USA. [Dicianno, Brad E.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Fairman, Andrea D.] Philadelphia Univ, Dept Occupat Therapy, Philadelphia, PA USA. RP Dicianno, BE (reprint author), Kaufmann Med Bldg,3471 5th Ave, Pittsburgh, PA 15213 USA. EM dicianno@pitt.edu FU NICHD NIH HHS [T32 HD049307, T32HD049307] NR 78 TC 1 Z9 1 U1 0 U2 9 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 EI 1949-3614 J9 ASSIST TECHNOL JI Assist. Technol. PY 2013 VL 25 IS 4 BP 181 EP 193 DI 10.1080/10400435.2012.747572 PG 13 WC Rehabilitation SC Rehabilitation GA 257OM UT WOS:000327394300001 PM 24620701 ER PT J AU Pearlman, J Cooper, R Duvall, J Livingston, R AF Pearlman, Jonathan Cooper, Rory Duvall, Jonathan Livingston, Ryan TI Pedestrian Pathway Characteristics and Their Implications on Wheelchair Users SO ASSISTIVE TECHNOLOGY LA English DT Article DE accessible; pathway; roughness; whole-body vibrations ID WHOLE-BODY VIBRATION; LOW-BACK-PAIN; SURFACES AB Individuals who use wheelchairs (WCs) frequently navigate over pathways with obstacles (e.g., bumps or curb descents) or terrain that is extremely rough. Surface characteristics such as roughness can have an effect on comfort and variables associated with bodily injury. Understanding these relationships can be helpful to ensure safe and comfortable access to all public and private pathways. This article reviews existing research related to the topics of surface roughness effects on WC user's bodies, surface roughness measurement techniques, and design guidelines and exposure limits that attempt to ensure pathways are safe and passable. These findings are discussed along with opportunities to improve them. Using a broad literature search, it was found that several measurement and analysis techniques exist to characterize surface roughness related to automobile roadways, but they have not been systematically applied to WC use over pedestrian pathways. The roughness measurement approach that appears most relevant and adaptable for sidewalks are rolling profilers. Commercially available devices could be recalibrated or adapted to measure pedestrian pathways. IRI and ride-quality analysis techniques appear most relevant and could also be adapted. Any analysis technique that uses profiles of surfaces should focus on frequencies and wavelengths that are most applicable to WC riders. C1 [Pearlman, Jonathan; Cooper, Rory; Duvall, Jonathan; Livingston, Ryan] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Rehabil Res & Dev Ctr Excellence Wheelchairs &, Pittsburgh, PA 15206 USA. [Pearlman, Jonathan; Cooper, Rory; Duvall, Jonathan; Livingston, Ryan] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Pearlman, Jonathan; Cooper, Rory; Duvall, Jonathan; Livingston, Ryan] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Pearlman, Jonathan; Cooper, Rory; Duvall, Jonathan; Livingston, Ryan] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. RP Pearlman, J (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15206 USA. EM jlp46@pitt.edu OI Pearlman, Jon/0000-0003-0830-9136 NR 26 TC 1 Z9 1 U1 0 U2 1 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 EI 1949-3614 J9 ASSIST TECHNOL JI Assist. Technol. PY 2013 VL 25 IS 4 BP 230 EP 239 DI 10.1080/10400435.2013.778915 PG 10 WC Rehabilitation SC Rehabilitation GA 257OM UT WOS:000327394300006 PM 24620706 ER PT J AU Wortzel, HS Shura, RD Brenner, LA AF Wortzel, Hal S. Shura, Robert D. Brenner, Lisa A. TI Chronic Traumatic Encephalopathy and Suicide: A Systematic Review SO BIOMED RESEARCH INTERNATIONAL LA English DT Review ID FOOTBALL-LEAGUE PLAYER; BRAIN-INJURY AB Traumatic brain injury (TBI) is a global health concern, and the recent literature reports that a single mild TBI can result in chronic traumatic encephalopathy (CTE). It has been suggested that CTE may lead to death by suicide, raising important prevention, treatment, and policy implications. Thus, we conducted a systematic review of the medical literature to answer the key question: What is the existing evidence in support of a relationship between CTE and suicide? Systematic searches of CTE and suicide yielded 85 unique abstracts. Seven articles were identified for full text review. Only two case series met inclusion criteria and included autopsies from 17 unique cases, 5 of whom died by suicide. Neither studies used blinding, control cases, or systematic data collection regarding TBI exposure and/or medical/neuropsychiatric history. The identified CTE literature revealed divergent opinions regarding neuropathological elements of CTE and heterogeneity regarding clinical manifestations. Overall quality of evidence regarding a relationship between CTE and suicide was rated as very low using Grading of Recommendations Assessment, Development and Evaluation Working Group (GRADE) criteria. Further studies of higher quality and methodological rigor are needed to determine the existence and nature of any relationship between CTE and suicide. C1 [Wortzel, Hal S.; Shura, Robert D.; Brenner, Lisa A.] Denver Vet Affairs Med Ctr, Res Educ & Clin Ctr, VISN, Dept Psychiat, Denver, CO 80220 USA. [Wortzel, Hal S.; Shura, Robert D.; Brenner, Lisa A.] Denver Vet Affairs Med Ctr, Res Educ & Clin Ctr, VISN, Dept Neurol, Denver, CO 80220 USA. [Wortzel, Hal S.; Shura, Robert D.; Brenner, Lisa A.] Denver Vet Affairs Med Ctr, Res Educ & Clin Ctr, VISN, Dept Phys Med & Rehabil, Denver, CO 80220 USA. [Wortzel, Hal S.; Brenner, Lisa A.] Univ Colorado, Sch Med, Dept Psychiat, Denver, CO 80045 USA. [Wortzel, Hal S.; Brenner, Lisa A.] Univ Colorado, Sch Med, Dept Neurol, Denver, CO 80045 USA. [Shura, Robert D.] Marshall Univ, Dept Psychol, Huntington, WV 25755 USA. RP Wortzel, HS (reprint author), Denver Vet Affairs Med Ctr, Res Educ & Clin Ctr, VISN, Dept Psychiat, 19 Mental Illness, Denver, CO 80220 USA. EM hal.wortzel@ucdenver.edu OI Shura, Robert/0000-0002-9505-0080 FU Department of Veterans Affairs FX This paper is based on work supported, in part, by the Department of Veterans Affairs but does not necessarily represent the views of the Department of Veterans Affairs or the United States Government. NR 24 TC 12 Z9 12 U1 3 U2 5 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2013 AR 424280 DI 10.1155/2013/424280 PG 6 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 261ED UT WOS:000327646100001 ER PT J AU Fung, CH Martin, JL Dzierzewski, JM Jouldjian, S Josephson, K Park, M Alessi, C AF Fung, Constance H. Martin, Jennifer L. Dzierzewski, Joseph M. Jouldjian, Stella Josephson, Karen Park, Michelle Alessi, Cathy TI Prevalence and Symptoms of Occult Sleep Disordered Breathing among Older Veterans with Insomnia SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE Sleep disordered breathing; prevalence; risk factors; older adults; comorbid insomnia ID COMORBID INSOMNIA; APNEA SYNDROME; ASSOCIATION; POPULATION; COMMUNITY; ADULTS; PATIENT; HEALTH; DEVICE; SAMPLE AB Study Objectives: To determine the prevalence of occult sleep disordered breathing (SDB) and describe the relationship between classic SDB symptoms (e. g., loud snoring) and occult SDB in older veterans with insomnia. Methods: We analyzed baseline survey and in-home sleep study data for 435 veterans (mean age = 72.0 years [SD 8.0]) who had no known history of SDB, met International Classification of Sleep Disorders 2nd Edition criteria for insomnia, and were enrolled in a behavioral intervention trial for insomnia. Variables of interest included apnea-hypopnea index (AHI) >= 15, age, race/ethnicity, marital status, body mass index (BMI), insomnia subtype (i.e., onset, maintenance, or terminal), self-reported excessive daytime sleepiness, snoring, and witnessed breathing pause items from the Berlin Questionnaire. We computed the frequency of AHI = 15 and assessed whether each classic SDB symptom was associated with an AHI = 15 in 4 separate multivariate logistic regression models. Results: Prevalence of AHI >= 15 was 46.7%. Excessive daytime sleepiness (adjusted odds ratio 1.63, 95% CI 1.02, 2.60, p = 0.04), but not snoring loudness, snoring frequency, or witnessed breathing pauses was associated with occult SDB (AHI >= 15). Insomnia subtypes were not significantly associated with occult SDB (p > 0.38). Conclusions: In our sample of older veterans with insomnia, nearly half had occult SDB, which was characterized by reported excessive daytime sleepiness, but not loud or frequent snoring or witnessed breathing pauses. Insomnia subtype was unrelated to the presence of occult SDB. C1 [Fung, Constance H.; Martin, Jennifer L.; Dzierzewski, Joseph M.; Jouldjian, Stella; Josephson, Karen; Alessi, Cathy] Vet Adm Greater Los Angeles Healthcare Syst, GRECC, Los Angeles, CA USA. [Fung, Constance H.; Martin, Jennifer L.; Dzierzewski, Joseph M.; Alessi, Cathy] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Park, Michelle] Western Univ Hlth Sci, Pomana, CA USA. RP Fung, CH (reprint author), VA Greater Los Angeles Healthcare Syst, 16111 Plummer St, North Hills, CA 91343 USA. EM Connie.Fung@va.gov FU Department of Veterans Affairs Advanced Geriatrics Fellowship Program; Veterans Administration Health Services Research and Development [IIR 08-295]; American Sleep Medicine Foundation Physician Scientist Training Award; Veterans Administration Greater Los Angeles Geriatric Research, Education and Clinical Center, American Federation for Aging Research; Medical Student Training in Aging Research Program, National Institute on Aging [T35AG026736]; John A. Hartford Foundation; MetLife Foundation; Lillian R. Gleitsman Foundation FX Funded by the Department of Veterans Affairs Advanced Geriatrics Fellowship Program (Fung, Dzierzewski), Veterans Administration Health Services Research and Development (Alessi IIR 08-295), the American Sleep Medicine Foundation Physician Scientist Training Award (Fung), Veterans Administration Greater Los Angeles Geriatric Research, Education and Clinical Center, American Federation for Aging Research (Fung), Medical Student Training in Aging Research Program, National Institute on Aging (Park T35AG026736), the John A. Hartford Foundation (Fung, Park), the MetLife Foundation (Park), and the Lillian R. Gleitsman Foundation (Park). The authors have indicated no financial conflicts of interest. All work was completed at VA Greater Los Angeles Healthcare System. This study did not involve any off-label or investigational use. NR 38 TC 6 Z9 7 U1 1 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 EI 1550-9397 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2013 VL 9 IS 11 BP 1173 EP 1178 DI 10.5664/jcsm.3162 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 256PZ UT WOS:000327327300009 PM 24235899 ER PT J AU Watkins, ML Wilcox, TK Tabberer, M Brooks, JM Donohue, JF Anzueto, A Chen, WH Crim, C AF Watkins, Michael L. Wilcox, Teresa K. Tabberer, Maggie Brooks, Jean M. Donohue, James F. Anzueto, Antonio Chen, Wen-Hung Crim, Courtney TI Shortness of Breath with Daily Activities questionnaire: validation and responder thresholds in patients with chronic obstructive pulmonary disease SO BMJ OPEN LA English DT Article DE THORACIC MEDICINE; RESPIRATORY MEDICINE (see Thoracic Medicine) ID QUALITY-OF-LIFE; COPD AB Objectives To test the reliability, validity and responsiveness of the 13-item Shortness of Breath with Daily Activities (SOBDA) questionnaire, and determine the threshold for response and minimal important difference (MID). Design 6week, randomised, double-blind, placebo-controlled study. Setting 40 centres in the USA between 29 October 2009 and 1 July 2010. Primary and secondary outcome measures 547 patients with chronic obstructive pulmonary disease (COPD) were enrolled and 418 entered the 2-week run-in period. Data from the run-in period were collected to test internal consistency, test-retest reliability, convergent validity and known-groups validity of the SOBDA. Three hundred and sixty six patients were randomised 2:2:1 to fluticasone propionate/salmeterol 250/50 mu g, salmeterol 50 mu g or placebo, twice daily. Results from the SOBDA questionnaire, Patient Global Assessment of Change Question, modified Medical Research Council Dyspnoea Scale (mMRC), Clinician Global Impression of Dysponea Severity (CGI-S), Clinician Global Impression of Change Question and Chronic Respiratory Disease Questionnaire self-administered standardised version (CRQ-SAS) were evaluated; spirometry and safety parameters were measured. Study endpoints were selected to investigate the cross-sectional and longitudinal validity of the SOBDA questionnaire in relation to the clinical criteria. Results Internal consistency of the SOBDA questionnaire (Cronbach ) was 0.89. Test-retest reliability (intraclass correlation) was 0.94. The SOBDA weekly scores correlated with the patient-reported and clinician-reported mMRC, CGI-S and CRQ-SAS dyspnoea domain scores (0.29, 0.24, 0.24 and -0.68, respectively). The SOBDA weekly scores differentiated between the responders and the non-responders as rated by the patients and the clinicians. Anchor-based and supportive distribution-based analyses produced a range of the potential values for the threshold for the responders and MID. Conclusions The 13-item SOBDA questionnaire is reliable, valid and responsive to change in patients with COPD. On using anchor-based methods, the proposed responder threshold shows a -0.1 to -0.2 score change. A specific threshold value will be identified as more data are generated from future clinical trials. Trial registration NCT00984659; GlaxoSmithKline study number: ASQ112989. C1 [Watkins, Michael L.; Crim, Courtney] GlaxoSmithKline, Resp Med Dev Ctr, Res Triangle Pk, NC 27709 USA. [Wilcox, Teresa K.; Chen, Wen-Hung] Evidera, United BioSource Corp, Bethesda, MD USA. [Tabberer, Maggie; Brooks, Jean M.] GlaxoSmithKline, Resp Med Dev Ctr, Uxbridge, Middx, England. [Donohue, James F.] Univ N Carolina, Div Pulm & Crit Care Med, Chapel Hill, NC USA. [Anzueto, Antonio] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Watkins, ML (reprint author), GlaxoSmithKline, Resp Med Dev Ctr, Res Triangle Pk, NC 27709 USA. EM michael.l.watkins@gsk.com FU GlaxoSmithKline FX The SOBDA development programme, including this ASQ112989 study, was funded by GlaxoSmithKline. GlaxoSmithKline and Evidera (formerly United BioSource Corporation) developed the instrument. GlaxoSmithKline had a role in the study design, data collection and analyses, decision to publish and in the preparation of all study reporting including this manuscript. NR 16 TC 9 Z9 9 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2013 VL 3 IS 10 AR e003048 DI 10.1136/bmjopen-2013-003048 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 250UY UT WOS:000326882800005 PM 24154513 ER PT J AU Rosendorff, C AF Rosendorff, C. TI Treatment of hypertension with CAD: AHA guidelines SO CARDIOLOGY LA English DT Meeting Abstract C1 [Rosendorff, C.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY USA. [Rosendorff, C.] James J Peters VA Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2013 VL 126 SU 2 BP 240 EP 240 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 245CR UT WOS:000326437200234 ER PT J AU Thase, ME AF Thase, Michael E. TI The Multifactorial Presentation of Depression in Acute Care SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SEASONAL AFFECTIVE-DISORDER; STAR-ASTERISK-D; BEHAVIORAL-ANALYSIS SYSTEM; MAJOR DEPRESSION; NONANXIOUS DEPRESSION; ATYPICAL DEPRESSION; UNIPOLAR DEPRESSION; PREVALENCE; FEATURES; BIPOLAR AB Depression is by its very nature a heterogeneous disorder; 2 patients with the same diagnosis (ie, major depressive disorder) may have few symptoms in common. This heterogeneity is evidenced by the fact that depression presents in a wide variety forms related to polarity (unipolar vs bipolar), symptoms (melancholic, atypical, psychotic, or anxious), onset (specific events, seasons, or age), recurrence, and severity. These diagnostic specifiers and subgroups can guide treatment decisions in several ways. For example, recognizing a specific depressive subtype in a patient can help the clinician select an appropriate treatment based on that patient's particular presentation. These subtypes can also guide treatment by helping the clinician and patient to identify and discuss factors that help or hinder the achievement of remission and recovery. Although depression specifiers and subtypes are subject to revision and change, many of them provide helpful information about recognition and treatment. C1 [Thase, Michael E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Thase, Michael E.] Univ Penn, Dept Psychiat, Sch Med, Philadelphia Vet Affairs Med Ctr, Pittsburgh, PA USA. [Thase, Michael E.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Philadelphia, PA USA. [Thase, Michael E.] Univ Pittsburgh, Dept Psychiat, Med Ctr, Pittsburgh, PA USA. RP Thase, ME (reprint author), 3535 Market St,Ste 670, Philadelphia, PA 19104 USA. EM thase@mail.med.upenn.edu FU AHRQ Eli Lilly; Forest; NIMH; Otsuka FX Dr Thase is an advisor/consultant for Alkermes, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Dey, Forest, Gerson Lehman, GlaxoSmithKline, Guidepoint Global, Lundbeck, MedAvante, Merck, Neuronetics, Ortho-McNeil, Otsuka, Pamlab, Pfizer, Roche, Shire, Sunovion, Takeda, and Transcept; has received grant/research support from AHRQ Eli Lilly, Forest, NIMH, and Otsuka; has received honoraria from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck, and Pfizer; has equity holdings in MedAvante; and has received royalties from the American Psychiatric Foundation, Guilford Publications, Herald House, and W.W. Norton & Company; his spouse/partner is employed by Peloton Advantage. NR 43 TC 3 Z9 3 U1 0 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2013 VL 74 SU 2 BP 3 EP 8 DI 10.4088/JCP.12084su1c.01 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 243KV UT WOS:000326316200001 PM 24191971 ER PT S AU Namura, S Ooboshi, H Liu, JL Yenari, MA AF Namura, Shobu Ooboshi, Hiroaki Liu, Jialing Yenari, Midori A. GP Annals NY Acad Sci TI Neuroprotection after cerebral ischemia SO ANNALS MEETING REPORTS SE Annals of the New York Academy of Sciences LA English DT Article DE stroke; cerebral ischemia; cerebrovascular disease; neurovascular unit; cell therapy; repair; immune response ID EXPERIMENTAL STROKE; BRAIN; RECOVERY; INJURY; CELLS AB Cerebral ischemia, a focal or global insufficiency of blood flow to the brain, can arise through multiple mechanisms, including thrombosis and arterial hemorrhage. Ischemia is a major driver of stroke, one of the leading causes of morbidity and mortality worldwide. While the general etiology of cerebral ischemia and stroke has been known for some time, the conditions have only recently been considered treatable. This report describes current research in this field seeking to fully understand the pathomechanisms underlying stroke; to characterize the brain's intrinsic injury, survival, and repair mechanisms; to identify putative drug targets as well as cell-based therapies; and to optimize the delivery of therapeutic agents to the damaged cerebral tissue. C1 [Namura, Shobu] Morehouse Sch Med, Inst Neurosci, Dept Neurobiol, Atlanta, GA 30310 USA. [Ooboshi, Hiroaki] Med & Dent Hosp, Fukuoka Dent Coll, Dept Internal Med, Fukuoka, Japan. [Liu, Jialing] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94121 USA. [Yenari, Midori A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yenari, Midori A.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Yenari, MA (reprint author), Univ Calif San Francisco, Dept Neurol, 4150 Clement St, San Francisco, CA 94121 USA. EM yenari@alum.mit.edu RI Liu, Jialing/A-8627-2012 OI Liu, Jialing/0000-0003-4420-4382 FU NIH through the U.S.-Japan Brain Research Cooperative Program [3R01 NS040516-11S1]; Japan-U.S. Science and Technology Cooperation Program; Brain Research Division FX This meeting was funded by an NIH R13 Grant through the U.S.-Japan Brain Research Cooperative Program (3R01 NS040516-11S1) to Midori A. Yenari; and from the Japan-U.S. Science and Technology Cooperation Program, Brain Research Division, to Hiroaki Ooboshi, Genentech (a member of the Roche Group), and Peter R. MacLeish (Neuroscience Institute, Morehouse School of Medicine). Grant funds were administered by the Northern California Institute for Research and Education. The organizers of the "Trans-Pacific Workshop on Stroke" thank the presenters and attendees for their contributions and lively and insightful discussions. The attendees dedicated the meeting to the memory of Akira Arimura, an American scientist at Tulane University with beginnings in Japan, whose remarkable career included many U.S.-Japan collaborations. NR 19 TC 3 Z9 6 U1 0 U2 7 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2013 VL 1278 BP 25 EP 32 DI 10.1111/nyas.12087 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BHO53 UT WOS:000326100700003 PM 23488559 ER PT J AU Santiago, M Cui, Y Adams, A Carrel, A Allen, D Delgado, A Gonzalez, M Schoeller, D LaRowe, T AF Santiago, M. Cui, Y. Adams, A. Carrel, A. Allen, D. Delgado, A. Gonzalez, M. Schoeller, D. LaRowe, T. TI INDIVIDUAL AND FAMILIAL DIETARY PREDICTORS OF OBESITY AMONG HISPANIC CHILDREN FROM AN URBAN COMMUNITY IN THE US SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract DE Obesity; sugar-sweetened beverages; home food environment; Hispanic children C1 [Santiago, M.; Adams, A.; Carrel, A.; Allen, D.; Schoeller, D.; LaRowe, T.] Univ Wisconsin, Madison, WI USA. [Cui, Y.] Univ Maryland, Natl Ctr Smart Growth Res & Educ, College Pk, MD 20742 USA. [Delgado, A.] Univ So Calif, Inst Hlth Promot & Dis Prevent Res IPR, Alhambra, CA USA. [Gonzalez, M.] US Dept Vet Affairs, RORC, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 EI 1421-9697 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2013 VL 63 SU 1 BP 356 EP 356 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 219YR UT WOS:000324548201731 ER PT J AU Pelluru, D Konadhode, R Blanco-Centurion, C Liu, M Shiromani, PJ AF Pelluru, Dheeraj Konadhode, RodaRani Blanco-Centurion, Carlos Liu, Meng Shiromani, Priyattam J. BA Shaw, P Tafti, M Thorpy, M BF Shaw, P Tafti, M Thorpy, M TI Gene therapy for sleep disorders SO GENETIC BASIS OF SLEEP AND SLEEP DISORDERS LA English DT Article; Book Chapter ID X-LINKED ADRENOLEUKODYSTROPHY; OREXIN KNOCKOUT MICE; PHASE SYNDROME; DORSOLATERAL PONS; HUMAN NARCOLEPSY; RAT-BRAIN; NEURONS; EXPRESSION; MUTATION; HYPOTHALAMUS C1 [Pelluru, Dheeraj; Konadhode, RodaRani; Blanco-Centurion, Carlos; Liu, Meng; Shiromani, Priyattam J.] Ralph H Johnson VA, Charleston, SC USA. [Pelluru, Dheeraj; Konadhode, RodaRani; Blanco-Centurion, Carlos; Liu, Meng; Shiromani, Priyattam J.] Med Univ S Carolina, Charleston, SC 29425 USA. RP Pelluru, D (reprint author), Ralph H Johnson VA, Charleston, SC USA. NR 41 TC 0 Z9 0 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-04125-7 PY 2013 BP 375 EP 380 D2 10.1017/CBO9781139649469 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA BHL19 UT WOS:000325766000037 ER PT J AU Brown, CJ Bearden, DM AF Brown, Cynthia J. Bearden, Donna M. BE Williams, BC Malani, PN Wesorick, DH TI FALLS AND MOBILITY DURING HOSPITALIZATION SO HOSPITALISTS' GUIDE TO THE CARE OF OLDER PATIENTS SE Hospital Medicine-Current Concepts LA English DT Article; Book Chapter ID OLDER-ADULTS; EARLY MOBILIZATION; RANDOMIZED-TRIAL; PREVENTING FALLS; INPATIENT FALLS; CARE; PROGRAM; NONPAYMENT; DISCHARGE; MEDICARE C1 [Brown, Cynthia J.; Bearden, Donna M.] Univ Alabama Birmingham, Div Gerontol Geriatr & Palliat Care, Birmingham, AL 35294 USA. [Brown, Cynthia J.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Brown, CJ (reprint author), Univ Alabama Birmingham, Div Gerontol Geriatr & Palliat Care, Birmingham, AL 35294 USA. NR 39 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-12792-6 J9 HOSP MED-CURR CONCEP PY 2013 BP 165 EP 179 D2 10.1002/9781118674963 PG 15 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA BHQ14 UT WOS:000326288000010 ER PT J AU Farook, VS Coletta, DK Puppala, S Schneider, J Chittoor, G Hu, SL Winnier, DA Norton, L Dyer, TD Arya, R Cole, SA Carless, M Goring, HH Almasy, L Mahaney, MC Comuzzie, AG Curran, JE Blangero, J Duggirala, R Lehman, DM Jenkinson, CP DeFronzo, RA AF Farook, Vidya S. Coletta, Dawn K. Puppala, Sobha Schneider, Jennifer Chittoor, Geetha Hu, Shirley L. Winnier, Deidre A. Norton, Luke Dyer, Thomas D. Arya, Rector Cole, Shelley A. Carless, Melanie Goering, Harald H. Almasy, Laura Mahaney, Michael C. Comuzzie, Anthony G. Curran, Joanne E. Blangero, John Duggirala, Ravindranath Lehman, Donna M. Jenkinson, Christopher P. DeFronzo, Ralph A. TI Linkage of Type 2 Diabetes on Chromosome 9p24 in Mexican Americans: Additional Evidence from the Veterans Administration Genetic Epidemiology Study (VAGES) SO HUMAN HEREDITY LA English DT Article DE Type 2 diabetes; Linkage; Chromosome 9p24; Mexican Americans; VAGES ID GENOME-WIDE ASSOCIATION; DENSITY-LIPOPROTEIN-CHOLESTEROL; QUANTITATIVE TRAIT LOCI; SUSCEPTIBILITY LOCI; INSULIN-RESISTANCE; RISK LOCI; TRIGLYCERIDE LEVELS; GLUCOSE-TOLERANCE; GLYCEMIC TRAITS; STARR COUNTY AB Objective: Type 2 diabetes (T2DM) is a complex metabolic disease and is more prevalent in certain ethnic groups such as the Mexican Americans. The goal of our study was to perform a genome-wide linkage (GWL) analysis to localize T2DM susceptibility loci in Mexican Americans. Methods: We used the phenotypic and genotypic data from 1,122 Mexican-American individuals (307 families) who participated in the Veterans Administration Genetic Epidemiology Study (VAGES). GWL analysis was performed using the variance components approach. Data from 2 additional Mexican-American family studies, the San Antonio Family Heart Study (SAFHS) and the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), were combined with the VAGES data to test for improved linkage evidence. Results: After adjusting for covariate effects, T2DM was found to be under significant genetic influences (h(2) = 0.62, p = 2.7 x 10(-6)). The strongest evidence for linkage of T2DM occurred between markers D9S1871 and D9S2169 on chromosome 9p24.2-p24.1 CLOD = 1.8). Given that we previously reported suggestive evidence for linkage of T2DM at this region also in SAFDGS, we found the significant and increased linkage evidence (LOD = 4.3, empirical p = 1.0 x 10(-5), genome-wide p = 1.6 x 10(-3)) for T2DM at the same chromosomal region, when we performed a GWL analysis of the VAGES data combined with the SAFHS and SAFDGS data. Conclusion: Significant T2DM linkage evidence was found on chromosome 9p24 in Mexican Americans. Importantly, the chromosomal region of interest in this study overlaps with several recent genome-wide association studies involving T2DM-related traits. Given its overlap with such findings and our own initial T2DM association findings in the 9p24 chromosomal region, high throughput sequencing of the linked chromosomal region could identify the potential causal T2DM genes. (C) 2013 S. Karger AG, Basel C1 [Farook, Vidya S.; Puppala, Sobha; Schneider, Jennifer; Chittoor, Geetha; Dyer, Thomas D.; Cole, Shelley A.; Carless, Melanie; Goering, Harald H.; Almasy, Laura; Mahaney, Michael C.; Comuzzie, Anthony G.; Curran, Joanne E.; Blangero, John; Duggirala, Ravindranath; Jenkinson, Christopher P.] SW Fdn Biomed Res, San Antonio, TX 78284 USA. [Coletta, Dawn K.] Arizona State Univ, Ctr Metab Biol, Phoenix, AZ USA. [Hu, Shirley L.; Jenkinson, Christopher P.; DeFronzo, Ralph A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Winnier, Deidre A.; Norton, Luke; Jenkinson, Christopher P.; DeFronzo, Ralph A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Diabet, San Antonio, TX 78229 USA. [Lehman, Donna M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Clin Epidemiol, San Antonio, TX 78229 USA. [Arya, Rector] Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, Div Endocrinol & Diabet, San Antonio, TX 78229 USA. RP DeFronzo, RA (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Diabet, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM albarado@uthscsa.edu RI Coletta, Dawn/G-6382-2016 OI Coletta, Dawn/0000-0001-5819-5152; Norton, Luke/0000-0002-0231-5722 FU Veterans Administration; National Institutes of Health [DK42273, DK47482, DK53889, DK70746, HD41111, MH59490] FX We thank Marcel J. Fourcaudot and Lenore M. Rodriguez for their excellent technical assistance. We thank our nurses, James King, John Kincaid, Rose Kaminski-Graham, and Norma Diaz, for their excellent care of the participants throughout the study. This work was supported by a Veterans Administration Epidemiologic grant to R.A.D. This study was also supported in part by grants from the National Institutes of Health (DK42273, DK47482, DK53889, DK70746, HD41111, and MH59490). We thank the CIDR for providing genome scans using the VAGES and SAFDGS data sets, respectively. We thank the participants of VAGES, SAFHS, and SAFDGS, and are grateful for their generous partaking and cooperation. NR 64 TC 3 Z9 3 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 EI 1423-0062 J9 HUM HERED JI Hum. Hered. PY 2013 VL 76 IS 1 BP 36 EP 46 DI 10.1159/000354849 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 239FX UT WOS:000326009100005 PM 24060607 ER PT J AU Wells, JM Dransfield, MT AF Wells, J. Michael Dransfield, Mark T. TI Pathophysiology and clinical implications of pulmonary arterial enlargement in COPD SO INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Review DE pulmonary artery enlargement; aorta; ratio; pulmonary hypertension; chronic obstructive pulmonary disease; computed tomography ID OBSTRUCTIVE SLEEP-APNEA; VENTRICULAR DIASTOLIC FUNCTION; EXPERT CONSENSUS DOCUMENTS; AMERICAN-HEART-ASSOCIATION; FOUNDATION TASK-FORCE; NITRIC-OXIDE SYNTHASE; LUNG-DISEASE; COMPUTED-TOMOGRAPHY; ECHOCARDIOGRAPHIC EVALUATION; CARDIOVASCULAR DEATH AB Chronic obstructive pulmonary disease (COPD) is a complex condition defined by progressive airflow limitation in response to noxious stimuli, inflammation, and vascular changes. COPD exacerbations are critical events in the natural history of the disease, accounting for the majority of disease burden, cost, and mortality. Pulmonary vascular disease is an important risk factor for disease progression and exacerbation risk. Relative pulmonary artery enlargement on computed tomography scan, defined by a pulmonary artery to aortic (PA:A) ratio >1, has been evaluated as a marker of pulmonary vascular disease. The PA: A ratio can be measured reliably independent of electrocardiographic gating or the use of contrast, and in healthy patients a PA:A ratio >0.9 is considered to be abnormal. The PA:A ratio has been compared with invasive hemodynamic parameters, primarily mean pulmonary artery pressure in various disease conditions and is more strongly correlated with mean pulmonary artery pressure in obstructive as compared with interstitial lung disease. In patients without known cardiac or pulmonary disease, the PA:A ratio is predictive of mortality, while in COPD, an elevated PA:A ratio is correlated with increased exacerbation risk, outperforming other well established predictors of these events. Future studies should be aimed at determining the stability of the metric over time and evaluating the utility of the PA:A ratio in guiding specific therapies. C1 Univ Alabama Birmingham, Dept Med, Div Pulm Allergy & Crit Care, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Wells, JM (reprint author), Univ Alabama Birmingham, Dept Med, 1900 Univ Blvd,THT 422, Birmingham, AL 35294 USA. EM jmwells@uab.edu FU National Institutes of Health; Aeris; Astra Zeneca; Boehringer Ingelheim; Boston Scientific; Centocor; Forest; GlaxoSmithKline; Ikaria; Medimmune; Olmstead Medical Center; Otsuka; Pfizer; Pulmonx FX JMW has no conflicts of interest to declare. MTD has served as a consultant to Boehringer Ingelheim, GlaxoSmithKline, and Ikaria and his institution has received research support from the National Institutes of Health, Aeris, Astra Zeneca, Boehringer Ingelheim, Boston Scientific, Centocor, Forest, GlaxoSmithKline, Ikaria, Medimmune, Olmstead Medical Center, Otsuka, Pfizer, and Pulmonx. NR 102 TC 10 Z9 11 U1 1 U2 7 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1176-9106 EI 1178-2005 J9 INT J CHRONIC OBSTR JI Int. J. Chronic Obstr. Pulm. Dis. PY 2013 VL 8 BP 509 EP 521 DI 10.2147/COPD.S52204 PG 13 WC Respiratory System SC Respiratory System GA 241EV UT WOS:000326150100001 PM 24235822 ER PT J AU Stern, SL Donahue, DA Allison, S Hatch, JP Lancaster, CL Benson, TA Johnson, AL Jeffreys, MD Pride, D Moreno, C Peterson, AL AF Stern, Stephen L. Donahue, D. Allen Allison, Sybil Hatch, John P. Lancaster, Cynthia L. Benson, Trisha A. Johnson, Allegro L. Jeffreys, Matthew D. Pride, Denise Moreno, Carlos Peterson, Alan L. TI Potential Benefits of Canine Companionship for Military Veterans with Posttraumatic Stress Disorder (PTSD) SO SOCIETY & ANIMALS LA English DT Article DE anxiety; canine companionship; nonhuman animal; posttraumatic stress disorder (PTSD); veteran ID COGNITIVE PROCESSING THERAPY; PET OWNERSHIP; BLOOD-PRESSURE; PROLONGED EXPOSURE; US VETERANS; HEALTH; SYMPTOMS; TRIAL; DOG; AFGHANISTAN AB Investigators surveyed 30 U.S. military veterans with PTSD who reported having benefited from living with a dog. The subject population included men and women aged 34 to 67, with a mean of 56.9 years (SD = 8.1), who were being treated at two Department of Veterans Affairs (VA) outpatient clinics. Participants received a questionnaire packet designed to assess aspects of their mental and physical health and relationship with a canine companion, which they completed at home and returned either in person or by mail. The packet consisted of the PTSD ChecklistMilitary Version (PCL-M); Beck Depression Inventory, Second Edition (BDI-II); Veterans Short Form Health Survey and Health Behaviors Questionnaire (SF-36); Dog Information Sheet; Dog Relationship Questionnaire; and Lexington Attachment to Pets Scale. Respondents indicated that since adopting their dog they had experienced improvement in several areas, including feeling calmer, less lonely, less depressed, and less worried about their and their family's safety. These results suggest that living with a companion dog may help relieve some of the psychological distress associated with PTSD in some veterans. C1 [Stern, Stephen L.; Jeffreys, Matthew D.] South Texas Vet Hlth Care Syst, Psychiat Serv, San Antonio, TX USA. [Stern, Stephen L.; Donahue, D. Allen; Allison, Sybil; Hatch, John P.; Benson, Trisha A.; Jeffreys, Matthew D.; Peterson, Alan L.] Univ Texas San Antonio, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX USA. [Lancaster, Cynthia L.] Univ Texas Austin, Lab Study Anxiety Disorders, Austin, TX 78712 USA. [Johnson, Allegro L.] South Texas Vet Hlth Care Syst, Psychol Serv, Kerrville, TX USA. [Pride, Denise] San Antonio Mil Med Ctr, Dept Psychiat, San Antonio, TX USA. [Moreno, Carlos] South Texas Vet Hlth Care Syst, Nursing Serv, San Antonio, TX USA. RP Stern, SL (reprint author), South Texas Vet Hlth Care Syst, Psychiat Serv, San Antonio, TX USA. NR 42 TC 3 Z9 3 U1 10 U2 91 PU BRILL ACADEMIC PUBLISHERS PI LEIDEN PA PLANTIJNSTRAAT 2, P O BOX 9000, 2300 PA LEIDEN, NETHERLANDS SN 1063-1119 J9 SOC ANIM JI Soc. Anim. PY 2013 VL 21 IS 6 BP 568 EP 581 DI 10.1163/15685306-12341286 PG 14 WC Sociology; Veterinary Sciences SC Sociology; Veterinary Sciences GA 235VT UT WOS:000325749800004 ER PT J AU Kar, HL O'Leary, KD AF Kar, Heidi Lary O'Leary, K. Daniel TI Emotional Intimacy Mediates the Relationship Between Posttraumatic Stress Disorder and Intimate Partner Violence Perpetration in OEF/OIF/OND Veterans SO VIOLENCE AND VICTIMS LA English DT Article DE aggression; path analysis; couples; mental health ID MALE VIETNAM VETERANS; MARITAL SATISFACTION; MILITARY SERVICE; FIT INDEXES; ADJUSTMENT; COMBAT; FAMILY; INTERVENTIONS; METAANALYSIS; AGGRESSION AB Veterans with posttraumatic stress disorder (PTSD) are at elevated risk for perpetrating intimate partner violence (IPV). Little research exists on the link between PTSD and physical IPV in Operational Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) veterans. A sample of 110 male participants was recruited from the Northport Veterans Affairs Medical Center (VAMC). Three separate models were compared to determine which best explained the relationships between PTSD, IPV, emotional intimacy, and relationship satisfaction. Constructs were assessed via a battery of standardized, self-report instruments. Thirty-three percent of veterans had clinically elevated PTSD scores, and 31% of the men reported that they engaged in physical IPV in the past year. Poor emotional intimacy mediated the association between PTSD symptoms and perpetration of physical IPV. Past predeployment IPV perpetration was shown to be a predictor for current postdeployment physical IPV perpetration. C1 [Kar, Heidi Lary] San Francisco VA Med Ctr, San Francisco, CA USA. [O'Leary, K. Daniel] SUNY Stony Brook, Stony Brook, NY USA. RP Kar, HL (reprint author), Northport Vet Affairs Med Ctr, Psychol Serv, Northport, NY 11768 USA. EM Heidi.Kar@va.gov NR 44 TC 1 Z9 1 U1 1 U2 9 PU SPRINGER PUBLISHING CO PI NEW YORK PA 11 WEST 42ND STREET, NEW YORK, NY 10036 USA SN 0886-6708 EI 1945-7073 J9 VIOLENCE VICTIMS JI Violence Vict. PY 2013 VL 28 IS 5 BP 790 EP 803 DI 10.1891/0886-6708.VV-D-12-00080 PG 14 WC Criminology & Penology SC Criminology & Penology GA 237VM UT WOS:000325899000003 PM 24364123 ER PT J AU Rodriguez, RA Hotchkiss, JR O'Hare, AM AF Rodriguez, Rudolph A. Hotchkiss, John R. O'Hare, Ann M. TI Geographic information systems and chronic kidney disease: racial disparities, rural residence and forecasting SO JOURNAL OF NEPHROLOGY LA English DT Article DE Chronic kidney disease; Geography; Geospatial analysis; Racial disparities; Rural health ID STAGE RENAL-DISEASE; UNITED-STATES; NEIGHBORHOOD POVERTY; HEALTH DISPARITIES; MYOCARDIAL-INFARCTION; PACIFIC-ISLANDERS; GEOCODING PROJECT; SOCIAL-CLASS; CARE; US AB The dynamics of health and health care provision in the United States vary substantially across regions, and there is substantial regional heterogeneity in population density, age distribution, disease prevalence, race and ethnicity, poverty and the ability to access care. Geocoding and geographic information systems (GIS) are important tools to link patient or population location to information regarding these characteristics. In this review, we provide an overview of basic GIS concepts and provide examples to illustrate how GIS techniques have been applied to the study of kidney disease, and in particular to understanding the interplay between race, poverty, rural residence and the planning of renal services for this population. The interplay of socioeconomic status and renal disease outcomes remains an important area for investigation and recent publications have explored this relationship utilizing GIS techniques to incorporate measures of socioeconomic status and racial composition of neighborhoods. In addition, there are many potential challenges in providing care to rural patients with chronic kidney disease including long travel times and sparse renal services such as transplant and dialysis centers. Geospatially fluent analytic approaches can also inform system level analyses of health care systems and these approaches can be applied to identify an optimal distribution of dialysis facilities. GIS analysis could help untangle the complex interplay between geography, socioeconomic status, and racial disparities in chronic kidney disease, and could inform policy decisions and resource allocation as the population ages and the prevalence of renal disease increases. C1 [Rodriguez, Rudolph A.; O'Hare, Ann M.] Univ Washington, Seattle, WA 98195 USA. [Rodriguez, Rudolph A.; O'Hare, Ann M.] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. [Hotchkiss, John R.] Univ Pittsburgh, Pittsburgh, PA USA. [Hotchkiss, John R.] Vet Engn Resource Ctr, Pittsburgh, PA USA. RP Rodriguez, RA (reprint author), Puget Sound Vet Affairs Med Ctr, Nephrol & Renal Dialysis Unit, Bldg 100 Room 5B113 1660 S Columbian Way, Seattle, WA 98108 USA. EM rudy.rodriguez@va.gov FU Chief Business Office, Veteran's Healthcare Administration; CDC; NIA [U01 AG006781]; UpToDate FX J.R. Hotchkiss: Chief Business Office, Veteran's Healthcare Administration. A.M. O'Hare: interagency agreement with the CDC and NIA (U01 AG006781 Larson) and receives Royalties from UpToDate. R.A. Rodriguez: none. NR 76 TC 8 Z9 8 U1 2 U2 17 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 1121-8428 EI 1724-6059 J9 J NEPHROL JI J. Nephrol. PD JAN-FEB PY 2013 VL 26 IS 1 BP 3 EP 15 DI 10.5301/jn.5000225 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 235AI UT WOS:000325686000002 PM 23065915 ER PT S AU Anstead, GM Cadena, J Javeri, H AF Anstead, Gregory M. Cadena, Jose Javeri, Heta BE Ji, Y TI Treatment of Infections Due to Resistant Staphylococcus aureus SO METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (MRSA) PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE MRSA; Vancomycin; Linezolid; Daptomycin; Oritavancin; Dalbavancin; Tigecycline; Telavancin; Ceftaroline; Clindamycin; Minocycline; Rifampin; Doxycycline; Trimethoprim-sulfamethoxazole; Fusidic acid; Fosfomycin; Pristinamycin; Dalbavancin; Oritavancin; Omadacycline; Delafl oxacin; Tidezolid; JNJ-Q2 ID SKIN-STRUCTURE INFECTIONS; SOFT-TISSUE INFECTIONS; GRAM-POSITIVE INFECTIONS; HIGH-DOSE DAPTOMYCIN; IN-VITRO ACTIVITY; INDUCIBLE CLINDAMYCIN RESISTANCE; MINIMUM INHIBITORY CONCENTRATION; SIMULATED ENDOCARDIAL VEGETATIONS; VENTILATOR-ASSOCIATED PNEUMONIA; BROAD-SPECTRUM CEPHALOSPORIN AB This chapter reviews data on the treatment of infections caused by drug-resistant Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA). This review covers findings reported in the English language medical literature up to January of 2013. Despite the emergence of resistant and multidrug-resistant S. aureus, we have seven effective drugs in clinical use for which little resistance has been observed: vancomycin, quinupristin-dalfopristin, linezolid, tigecycline, telavancin, ceftaroline, and daptomycin. However, vancomycin is less effective for infections with MRSA isolates that have a higher MIC within the susceptible range. Linezolid is probably the drug of choice for the treatment of complicated MRSA skin and soft tissue infections (SSTIs); whether it is drug of choice in pneumonia remains debatable. Daptomycin has shown to be non-inferior to either vancomycin or beta-lactams in the treatment of staphylococcal SSTIs, bacteremia, and right-sided endocarditis. Tigecycline was also non-inferior to comparator drugs in the treatment of SSTIs, but there is controversy about whether it is less effective than other therapeutic options in the treatment of more serious infections. Telavancin has been shown to be non-inferior to vancomycin in the treatment of SSTIs and pneumonia, but has greater nephrotoxicity. Ceftaroline is a broad-spectrum cephalosporin with activity against MRSA; it is non-inferior to vancomycin in the treatment of SSTIs. Clindamycin, trimethoprim-sulfamethoxazole, doxycycline, rifampin, moxifloxacin, and minocycline are oral anti-staphylococcal agents that may have utility in the treatment of SSTIs and osteomyelitis, but the clinical data for their efficacy is limited. There are also several drugs with broad-spectrum activity against Gm-positive organisms that have reached the phase II and III stages of clinical testing that will hopefully be approved for clinical use in the upcoming years: oritavancin, dalbavancin, omadacycline, tedizolid, delafloxacin, and JNJ-Q2. Thus, there are currently many effective drugs to treat resistant S. aureus infections and many promising agents in the pipeline. Nevertheless, S. aureus remains a formidable adversary, and despite our deep bullpen of potential therapies, there are still frequent treatment failures and unfortunate clinical outcomes. The following discussion summarizes the clinical challenges presented by MRSA, the clinical experience with our current anti-MRSA antibiotics, and the gaps in our knowledge on how to use these agents to most effectively combat MRSA infections. C1 [Anstead, Gregory M.; Cadena, Jose] South Texas Vet Hlth Care Syst, Med Serv, San Antonio, TX USA. [Anstead, Gregory M.; Cadena, Jose; Javeri, Heta] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. RP Anstead, GM (reprint author), South Texas Vet Hlth Care Syst, Med Serv, San Antonio, TX USA. NR 205 TC 0 Z9 0 U1 1 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-663-4; 978-1-62703-664-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 185 BP 259 EP 309 DI 10.1007/978-1-62703-664-1_16 D2 10.1007/978-1-62703-664-1 PG 51 WC Microbiology SC Microbiology GA BHK36 UT WOS:000325709200017 ER PT S AU Dionne, KR Tyler, KL AF Dionne, Kalen R. Tyler, Kenneth L. BE Amini, S White, MK TI Slice Culture Modeling of Central Nervous System (CNS) Viral Infection SO NEURONAL CELL CULTURE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Organotypic; Ex vivo; Brain slice; Spinal cord slice; Virus; Encephalitis; Myelitis; Cytokine; Apoptosis; Caspase ID ORGANOTYPIC HIPPOCAMPAL CULTURES; ACTIVATED PROTEIN-KINASE; NEURONAL CELL-DEATH; IN-VITRO; SYNAPTIC PLASTICITY; BRAIN; INJURY; DISEASE; TISSUE; FIBER AB The complexity of the central nervous system (CNS) is not recapitulated in cell culture models. Thin slicing and subsequent culture of CNS tissue has become a valued means to study neuronal and glial biology within the context of the physiologically relevant tissue milieu. Modern membrane-interface slice culturing methodology allows straightforward access to both CNS tissue and feeding medium, enabling experimental manipulations and analyses that would otherwise be impossible in vivo. CNS slices can be successfully maintained in culture for up to several weeks for investigation of evolving pathology and long-term intervention in models of chronic neurologic disease. Herein, membrane-interface slice culture models for studying viral encephalitis and myelitis are detailed, with emphasis on the use of these models for investigation of pathogenesis and evaluation of novel treatment strategies. We describe techniques to (1) generate brain and spinal cord slices from rodent donors, (2) virally infect slices, (3) assess virally induced injury/apoptosis, (4) characterize "CNS-specific" cytokine production, and (5) treat slices with cytokines/pharmaceuticals. Although our focus is on CNS viral infection, we anticipate that the described methods can be adapted to address a wide range of investigations within the fields of neuropathology, neuroimmunology, and neuropharmacology. C1 [Dionne, Kalen R.; Tyler, Kenneth L.] Denver Vet Affairs Med Ctr, Dept Neurol, Aurora, CO USA. RP Dionne, KR (reprint author), Denver Vet Affairs Med Ctr, Dept Neurol, Aurora, CO USA. OI Tyler, Kenneth/0000-0003-3294-5888 FU NIAID NIH HHS [R21AI01064]; NIGMS NIH HHS [T32GM008497]; NINDS NIH HHS [R01 NS050138, F30NS071630, R01 NS051403, R01NS076512] NR 46 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-640-5; 978-1-62703-639-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1078 BP 97 EP 117 DI 10.1007/978-1-62703-640-5_9 D2 10.1007/978-1-62703-640-5 PG 21 WC Neurosciences SC Neurosciences & Neurology GA BHJ26 UT WOS:000325612600010 PM 23975824 ER PT J AU Mangale, D Kariuki, SN Chrabot, BS Kumabe, M Kelly, JA Harley, JB James, JA Sivils, KL Niewold, TB AF Mangale, Dorothy Kariuki, Silvia N. Chrabot, Beverly S. Kumabe, Marissa Kelly, Jennifer A. Harley, John B. James, Judith A. Sivils, Kathy L. Niewold, Timothy B. TI Familial Aggregation of High Tumor Necrosis Factor Alpha Levels in Systemic Lupus Erythematosus SO CLINICAL & DEVELOPMENTAL IMMUNOLOGY LA English DT Article ID DISEASE RISK VARIANT; INTERFERON-ALPHA; AUTOIMMUNE-DISEASE; I INTERFERON; IFN-ALPHA; JUVENILE DERMATOMYOSITIS; INCREASED SENSITIVITY; ASSOCIATION; AUTOANTIBODIES; POLYMORPHISMS AB Systemic lupus erythematosus (SLE) patients frequently have high circulating tumor necrosis factor alpha (TNF-alpha) levels. We explored circulating TNF-alpha levels in SLE families to determine whether high levels of TNF-alpha were clustered in a heritable pattern. We measured TNF-alpha in 242 SLE patients, 361 unaffected family members, 23 unaffected spouses of SLE patients, and 62 unrelated healthy controls. Familial correlations and relative recurrence risk rates for the high TNF-alpha trait were assessed. SLE-affected individuals had the highest TNF-alpha levels, and TNF-alpha was significantly higher in unaffected first degree relatives than healthy unrelated subjects (P = 0.0025). No Mendelian patterns were observed, but 28.4% of unaffected first degree relatives of SLE patients had high TNF-alpha levels, resulting in a first degree relative recurrence risk of 4.48 (P = 2.9 x 10(-5)). Interestingly, the median TNF-alpha value in spouses was similar to that of the first degree relatives. Concordance of the TNF-alpha trait (high versus low) in SLE patients and their spouses was strikingly high at 78.2%. These data support a role for TNF-alpha in SLE pathogenesis, and TNF-alpha levels may relate with heritable factors. The high degree of concordance in SLE patients and their spouses suggests that environmental factors may also play a role in the observed familial aggregation. C1 [Mangale, Dorothy; Kariuki, Silvia N.; Chrabot, Beverly S.; Kumabe, Marissa] Univ Chicago, Rheumatol Sect, Chicago, IL 60637 USA. [Mangale, Dorothy; Kariuki, Silvia N.; Chrabot, Beverly S.; Kumabe, Marissa] Univ Chicago, Gwen Knapp Ctr Lupus & Immunol Res, Chicago, IL 60637 USA. [Kelly, Jennifer A.; James, Judith A.; Sivils, Kathy L.] Oklahoma Med Res Fdn, Arthritis & Clin Immunol Program, Oklahoma City, OK 73104 USA. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Ctr Autoimmune Genom & Etiol, Cincinnati, OH 45229 USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH 45229 USA. [Niewold, Timothy B.] Mayo Clin, Div Rheumatol, Rochester, MN 55905 USA. [Niewold, Timothy B.] Mayo Clin, Dept Immunol, Rochester, MN 55905 USA. RP Niewold, TB (reprint author), Mayo Clin, Div Rheumatol, 200 1st St SW,Guggenheim Bldg 3-42, Rochester, MN 55905 USA. EM niewold.timothy@mayo.edu OI Niewold, Timothy/0000-0003-3532-6660 FU Katen Scholarship at University of Chicago; US Department of Veterans Affairs; US Department of Defense [PR094002]; NIH [N01AR62277, R37AI024717, R01AR042460, P01AI083194, P20RR020143, P01AR049084, U01HG006828, P30AR053483, P30GM103510, U01AI101934, U19AI082714, R01AR04327, R01AR060861, K08AI083790, L30AI071651, UL1RR024999]; Lupus Research Institute Novel Research Grant; Alliance for Lupus Research Target Identification in Lupus Grant FX Dorothy Mangale received the Katen Scholarship at University of Chicago. John B. Harley Harley acknowledges the US Department of Veterans Affairs, the US Department of Defense (PR094002), NIH grants N01AR62277, R37AI024717, R01AR042460, P01AI083194, P20RR020143, P01AR049084, and U01HG006828. Judith A. James received the NIH grants P30AR053483, P30GM103510, U01AI101934, U19AI082714. Kathy L. Sivils received the NIH grants P01AI083194 and R01AR043274. Timothy B. Niewold received the NIH grants R01AR060861, K08AI083790, L30AI071651, and UL1RR024999, Lupus Research Institute Novel Research Grant, and an Alliance for Lupus Research Target Identification in Lupus Grant. NR 41 TC 6 Z9 6 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1740-2522 J9 CLIN DEV IMMUNOL JI Clin. Dev. Immunol. PY 2013 AR 267430 DI 10.1155/2013/267430 PG 6 WC Immunology SC Immunology GA 230WC UT WOS:000325373000001 ER PT J AU Thase, ME AF Thase, Michael E. BE Mann, JJ McGrath, PJ Roose, SP TI Cognitive behavior therapy SO CLINICAL HANDBOOK FOR THE MANAGEMENT OF MOOD DISORDERS LA English DT Article; Book Chapter ID RANDOMIZED CONTROLLED-TRIAL; COLLABORATIVE RESEARCH-PROGRAM; MENTAL-HEALTH TREATMENT; RECURRENT DEPRESSION; MAJOR DEPRESSION; UNIPOLAR DEPRESSION; NATIONAL-INSTITUTE; RELAPSE-PREVENTION; BIPOLAR DISORDERS; PRIMARY-CARE C1 Philadelphia VA Med Ctr, Dept Psychiat, Mood & Anxiety Disorders Treatment & Res Program, Philadelphia, PA USA. RP Thase, ME (reprint author), Philadelphia VA Med Ctr, Dept Psychiat, Mood & Anxiety Disorders Treatment & Res Program, Philadelphia, PA USA. NR 49 TC 0 Z9 0 U1 2 U2 2 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-02463-2 PY 2013 BP 258 EP 269 D2 10.1017/CBO9781139175869 PG 12 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BGN18 UT WOS:000323552500019 ER PT J AU McCaffery, JM Papandonatos, GD Huggins, GS Peter, I Erar, B Kahn, SE Knowler, WC Lipkin, EW Kitabchi, AE Wagenknecht, LE Wing, RR AF McCaffery, Jeanne M. Papandonatos, George D. Huggins, Gordon S. Peter, Inga Erar, Bahar Kahn, Steven E. Knowler, William C. Lipkin, Edward W. Kitabchi, Abbas E. Wagenknecht, Lynne E. Wing, Rena R. CA Genetic Subgrp Look AHEAD Look AHEAD Res Grp TI Human Cardiovascular Disease IBC Chip-Wide Association with Weight Loss and Weight Regain in the Look AHEAD Trial SO HUMAN HEREDITY LA English DT Article DE Type 2 diabetes; Obesity; Weight loss; Diet; Genetics ID DIABETES PREVENTION PROGRAM; SALT EXPORT PUMP; BODY-MASS INDEX; FAMILIAL INTRAHEPATIC CHOLESTASIS; LIFE-STYLE INTERVENTION; OBESITY-RELATED TRAITS; ADIPOSE-TISSUE; CLINICAL-TRIAL; RISK-FACTORS; GENE AB Background/Aims:The present study identified genetic predictors of weight change during behavioral weight loss treatment. Methods: Participants were 3,899 overweight/obese individuals with type 2 diabetes from Look AHEAD, a randomized controlled trial to determine the effects of intensive lifestyle intervention (ILI), including weight loss and physical activity, relative to diabetes support and education, on cardiovascular outcomes. Analyses focused on associations of single nucleotide polymorphisms (SNPs) on the Illumina CARe iSelect (IBC) chip (minor allele frequency >5%; n = 31,959) with weight change at year 1 and year 4, and weight regain at year 4, among individuals who lost at year 1. Results: Two novel regions of significant chip-wide association with year-1 weight loss in ILI were identified (p < 2.96E-06). ABCB11 rs484066 was associated with 1.16 kg higher weight per minor allele at year 1, whereas TNFRSF11A, or RANK, rs17069904 was associated with 1.70 kg lower weight per allele at year 1. Conclusions: This study, the largest to date on genetic predictors of weight loss and regain, indicates that SNPs within ABCB11, related to bile salt transfer, and TNFRSF11A, implicated in adipose tissue physiology, predict the magnitude of weight loss during behavioral intervention. These results provide new insights into potential biological mechanisms and may ultimately inform weight loss treatment. (C) 2013 S. Karger AG, Basel C1 [McCaffery, Jeanne M.; Wing, Rena R.] Brown Univ, Miriam Hosp, Weight Control & Diabet Res Ctr, Dept Psychiat & Human Behav, Providence, RI USA. [McCaffery, Jeanne M.; Wing, Rena R.] Brown Univ, Brown Med Sch, Providence, RI 02912 USA. [Papandonatos, George D.; Erar, Bahar] Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. [Huggins, Gordon S.] Mol Cardiol Res Inst, MCRI Ctr Translat Genom, Tufts Med Ctr, Boston, MA USA. [Peter, Inga] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Lipkin, Edward W.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Knowler, William C.] Natl Inst Diabet & Digest & Kidney Dis, Phoenix, AZ USA. [Kitabchi, Abbas E.] Univ Tennessee, Ctr Hlth Sci, Div Endocrinol Diabet & Metab, Memphis, TN 38163 USA. [Wagenknecht, Lynne E.] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA. RP McCaffery, JM (reprint author), Miriam Hosp, Weight Control & Diabet Res Ctr, 196 Richmond St, Providence, RI 02903 USA. EM jeanne_mccaffery@brown.edu RI Papandonatos, George/J-2328-2014 OI Papandonatos, George/0000-0001-6770-932X; Kahn, Steven/0000-0001-7307-9002 FU Department of Health and Human Services through National Institutes of Health [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992]; Johns Hopkins Medical Institutions Bayview General Clinical Research Center [M01RR02719]; Massachusetts General Hospital Mallinckrodt General Clinical Research Center and the Massachusetts Institute of Technology General Clinical Research Center [M01RR01066]; University of Colorado Health Sciences Center General Clinical Research Center [M01RR00051]; Clinical Nutrition Research Unit [P30 DK48520]; University of Tennessee at Memphis General Clinical Research Center [M01RR0021140]; University of Pittsburgh General Clinical Research Center (GCRC) [M01RR000056]; Clinical Translational Research Center (CTRC); Clinical and Translational Science Award [UL1 RR 024153]; NIH [DK 046204]; VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; Frederic C. Bartter General Clinical Research Center [M01RR01346] FX This study was supported by the Department of Health and Human Services through the following cooperative agreements from the National Institutes of Health: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135 and DK56992. The following federal agencies have contributed support: National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; NIH Office of Research on Women's Health, and the Centers for Disease Control and Prevention. This research was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The Indian Health Service (IHS) provided personnel, medical oversight, and use of facilities. The opinions expressed in this paper are those of the authors and do not necessarily reflect the views of the IHS or other funding sources.; Additional support was received from The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (M01RR02719); the Massachusetts General Hospital Mallinckrodt General Clinical Research Center and the Massachusetts Institute of Technology General Clinical Research Center (M01RR01066); the University of Colorado Health Sciences Center General Clinical Research Center (M01RR00051) and Clinical Nutrition Research Unit (P30 DK48520); the University of Tennessee at Memphis General Clinical Research Center (M01RR0021140); the University of Pittsburgh General Clinical Research Center (GCRC) (M01RR000056); the Clinical Translational Research Center (CTRC) funded by the Clinical and Translational Science Award (UL1 RR 024153) and NIH grant (DK 046204); the VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs, and the Frederic C. Bartter General Clinical Research Center (M01RR01346). NR 67 TC 8 Z9 8 U1 0 U2 16 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2013 VL 75 IS 2-4 BP 160 EP 174 DI 10.1159/000353181 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 229BE UT WOS:000325236000011 PM 24081232 ER PT J AU Ellis, C Focht, KL Grubaugh, AL AF Ellis, Charles Focht, Kendrea L. Grubaugh, Anouk L. TI Perceptions of stroke recovery: An exclusion of communication and cognition SO NEUROREHABILITATION LA English DT Article DE Stroke; recovery; cognition; communication ID PERSPECTIVES; HEALTH; APHASIA; CARE AB BACKGROUND: Perceptions of stroke recovery can differ substantially between stroke survivors and their healthcare providers. Concordance between the two is important for collaborative goal setting to facilitate optimal outcomes. OBJECTIVE: To explore stroke survivors' perceptions of their own recovery and residual impairments with specific emphasis on communication and cognition. METHODS AND PROCEDURES: A qualitative analytic approach was used in the study. Nine stroke survivors participated in a focus group discussion as part of a larger study designed to examine post-stroke outcomes. RESULTS: Early in the focus group proceedings, a discussion emphasizing how stroke survivors perceive their overall recovery emerged. Six of the nine participants (67%) perceived their overall stroke recovery to be greater than 90%, and only physical impairments were reported. Later in the course of the interview, eight of the nine participants (89%) reported either word retrieval or memory loss deficits which negatively influenced their daily functional activities. CONCLUSIONS: Stroke survivors in this sample did not include communication and cognitive deficits in their perception of their overall recovery despite later reporting these symptoms and related impairment. Failure of patients to include such persisting deficits in their reports of recovery can cause a mismatch between stroke survivor and healthcare provider goals. C1 [Ellis, Charles; Grubaugh, Anouk L.] Ralph H Johnson VA Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. [Ellis, Charles; Focht, Kendrea L.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Grubaugh, Anouk L.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Ellis, C (reprint author), Med Univ S Carolina, Dept Hlth Sci & Res, 77 President St,302, Charleston, SC 29425 USA. EM ellisc@musc.edu FU Veterans Health Administration Health Services Research and Development program FX The first author was supported by a career development award from the Veterans Health Administration Health Services Research and Development program. NR 28 TC 1 Z9 1 U1 3 U2 6 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1053-8135 J9 NEUROREHABILITATION JI Neurorehabilitation PY 2013 VL 33 IS 2 BP 233 EP 239 DI 10.3233/NRE-130950 PG 7 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 228IO UT WOS:000325179600007 PM 23949059 ER PT S AU Quinn, JF AF Quinn, Joseph F. BE Perry, G Zhu, X Smith, MA Sorensen, A Avila, J TI Biomarkers for Alzheimer's Disease: Showing the Way or Leading Us Astray? SO ALZHEIMER'S DISEASE: ADVANCES FOR A NEW CENTURY SE Advances in Alzheimers Disease LA English DT Article; Book Chapter DE Alzheimer's disease; biomarkers; clinical trials ID MILD COGNITIVE IMPAIRMENT; GAMMA-SECRETASE INHIBITOR; DECLINE; TRIAL; ACID AB The indolent nature of Alzheimer's disease, coupled with burgeoning interest in a "presymptomatic" stage of disease, has motivated efforts to identify, validate, and exploit surrogate disease markers for trials of disease-modifying or preventive strategies. Many of these efforts have been productive, and biomarkers are now routinely applied in selection of study subjects and evaluation of outcomes in clinical trials. On the other hand, biomarkers also have the capacity to lead to bad therapeutic outcomes when they determine "go-no go" decisions in early drug development. This paper reviews several reports of biomarker studies which illustrate the great potential, for both good and ill, of biomarkers of Alzheimer's disease. C1 [Quinn, Joseph F.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Quinn, Joseph F.] Portland VA Med Ctr, Portland, OR USA. RP Quinn, JF (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Mail Code CR-131,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM quinnj@ohsu.edu NR 15 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 2210-5727 BN 978-1-61499-154-0 J9 ADV ALZH DIS PY 2013 VL 3 BP 371 EP 376 DI 10.3233/978-1-61499-154-0-371 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BGV89 UT WOS:000324325100035 ER PT J AU Pullicino, PM Thompson, JLP Sacco, RL Sanford, AR Qian, M Teerlink, JR Haddad, H Diek, M Freudenberger, RS Labovitz, AJ Di Tullio, MR Lok, DJ Ponikowski, P Anker, SD Graham, S Mann, DL Mohr, JP Homma, S AF Pullicino, Patrick M. Thompson, John L. P. Sacco, Ralph L. Sanford, Alexandra R. Qian, Min Teerlink, John R. Haddad, Haissam Diek, Monika Freudenberger, Ronald S. Labovitz, Arthur J. Di Tullio, Marco R. Lok, Dirk J. Ponikowski, Piotr Anker, Stefan D. Graham, Susan Mann, Douglas L. Mohr, J. P. Homma, Shunichi CA WARCEF Investigators TI Stroke in Heart Failure in Sinus Rhythm: The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction Trial SO CEREBROVASCULAR DISEASES LA English DT Article DE Aspirin; Cardiac embolism; Heart failure; Stroke prevention ID ACUTE ISCHEMIC-STROKE; ATRIAL-FIBRILLATION; CARDIOMYOPATHY; FREQUENCY; THERAPY AB Background: The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial found no difference between warfarin and aspirin in patients with low ejection fraction in sinus rhythm for the primary outcome: first to occur of 84 incident ischemic strokes (IIS), 7 intracerebral hemorrhages or 531 deaths. Prespecified secondary analysis showed a 48% hazard ratio reduction (p = 0.005) for warfarin in IIS. Cardioembolism is likely the main pathogenesis of stroke in heart failure. We examined the IIS benefit for warfarin in more detail in post hoc secondary analyses. Methods: We subtyped IIS into definite, possible and noncardioembolic using the Stroke Prevention in Atrial Fibrillation method. Statistical tests, stratified by prior ischemic stroke or transient ischemic attack, were the conditional binomial for independent Poisson variables for rates, the Cochran-Mantel-Haenszel test for stroke subtype and the van Elteren test for modified Rankin Score (mRS) and National Institute of Health Stroke Scale (NIHSS) distributions, and an exact test for proportions. Results: Twenty-nine of 1,142 warfarin and 55 of 1,163 aspirin patients had IIS. The warfarin IIS rate (0.727/100 patient-years, PY) was lower than for aspirin (1.36/100 PY, p = 0.003). Definite cardioembolic IIS was less frequent on warfarin than aspirin (0.22 vs. 0.55/100 PY, p = 0.012). Possible cardioembolic IIS tended to be less frequent on warfarin than aspirin (0.37 vs. 0.67/100 PY, p = 0.063) but noncardioembolic IIS showed no difference: 5 (0.12/100 PY) versus 6 (0.15/100 PY, p = 0.768). Among patients experiencing IIS, there were no differences by treatment arm in fatal IIS, baseline mRS, mRS 90 days after IIS, and change from baseline to post-IIS mRS. The warfarin arm showed a trend to a lower proportion of severe nonfatal IIS [mRS 3-5; 3/23 (13.0%) vs. 16/48 (33.3%), p = 0.086]. There was no difference in NIHSS at the time of stroke (p = 0.825) or in post-IIS mRS (p = 0.948) between cardioembolic, possible cardioembolic and noncardioembolic stroke including both warfarin and aspirin groups. Conclusions: The observed benefits in the reduction of IIS for warfarin compared to aspirin are most significant for cardioembolic IIS among patients with low ejection fraction in sinus rhythm. This is supported by trends to lower frequencies of severe IIS and possible cardioembolic IIS in patients on warfarin compared to aspirin. Copyright (c) 2013 S. Karger AG, Basel C1 [Pullicino, Patrick M.] Univ Kent, Canterbury CT2 7NZ, Kent, England. [Thompson, John L. P.; Sanford, Alexandra R.; Qian, Min; Di Tullio, Marco R.; Mohr, J. P.; Homma, Shunichi] Columbia Univ, Med Ctr, New York, NY USA. [Graham, Susan] SUNY Buffalo, Buffalo, NY 14260 USA. [Sacco, Ralph L.] Univ Miami, Miami, FL USA. [Labovitz, Arthur J.] Univ S Florida, Tampa, FL USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Freudenberger, Ronald S.] Lehigh Valley Hosp, Allentown, PA USA. [Mann, Douglas L.] Washington Univ, St Louis, MO USA. [Haddad, Haissam] Univ Ottawa, Ottawa, ON K1N 6N5, Canada. [Diek, Monika; Anker, Stefan D.] Charite, Campus Virchow Klinikum, D-13353 Berlin, Germany. [Lok, Dirk J.] Hosp Deventer, Deventer, Netherlands. [Ponikowski, Piotr] Mil Hosp, Dept Heart Dis, Wroclaw, Poland. [Anker, Stefan D.] IRCCS San Raffaele, Ctr Clin & Basic Res, Rome, Italy. RP Pullicino, PM (reprint author), Univ Kent, Canterbury CT2 7NZ, Kent, England. EM P.Pullicino@kent.ac.uk RI Ponikowski, Piotr/O-6454-2015 OI Ponikowski, Piotr/0000-0002-3391-7064; Mann, Douglas /0000-0002-2516-0145 FU National Institute of Neurological Diseases and Stroke [U01-NS-043975, U01-NS-039143] FX Funding was offered by U01-NS-043975 (S. Homma) and U01-NS-039143 (J.L.P. Thompson) from the National Institute of Neurological Diseases and Stroke. Warfarin and warfarin placebo were provided by Taro Pharmaceuticals USA Inc., Hawthorne, N.Y., USA, and aspirin and aspirin placebo by Bayer HealthCare LLC, Morristown, N.J., USA. NR 11 TC 4 Z9 5 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 36 IS 1 BP 74 EP 78 DI 10.1159/000352058 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 219WZ UT WOS:000324543600011 PM 23921215 ER PT J AU Goodrich, GL Martinsen, GL Flyg, HM Kirby, J Asch, SM Brahm, KD Brand, JM Cajamarca, D Cantrell, JL Chong, T Dziadul, JA Hetrick, BJ Huang, MA Ihrig, C Ingalla, SP Meltzer, BR Rakoczy, CM Rone, A Schwartz, E Shea, JE AF Goodrich, Gregory L. Martinsen, Gary L. Flyg, Heidi M. Kirby, Jennine Asch, Steven M. Brahm, Karen D. Brand, John M. Cajamarca, Diana Cantrell, Jenette L. Chong, Theresa Dziadul, John A. Hetrick, Barbara J. Huang, Michael A. Ihrig, Carolyn Ingalla, Shanida P. Meltzer, Bradley R. Rakoczy, Chrystyna M. Rone, Ashley Schwartz, Elliot Shea, Jane E. TI Development of a mild traumatic brain injury-specific vision screening protocol: A Delphi study SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE accommodation; binocular vision; consensus; convergence insufficiency; Delphi method; mild traumatic brain injury; oculomotor; optometrist; traumatic brain injury; visual symptoms ID POST-CONCUSSION SYNDROME; POLYTRAUMA NETWORK SITE; CONVERGENCE INSUFFICIENCY; PHYSICAL-EXAMINATION; VISUAL FUNCTION; REHABILITATION; POPULATION; PREVALENCE; GUIDELINES; DIAGNOSIS AB Although traumatic brain injury (TBI) can happen to anyone at any time, the wars in Iraq and Afghanistan have brought it renewed attention. Fortunately, most cases of TBI from the recent conflicts are mild TBI (mTBI). Still, many physical, psychological, and social problems are associated with mTBI. Among the difficulties encountered are oculomotor and vision problems, many of which can impede daily activities such as reading. Therefore, correct diagnosis and treatment of these mTBI-related vision problems is an important part of patient recovery. Numerous eye care providers in the Department of Veterans Affairs, in military settings, and in civilian practices specialize and are proficient in examining patients who have a history of TBI. However, many do not have this level of experience working with and treating patients with mTBI. Recognizing this, we used a modified Delphi method to derive expert opinions from a panel of 16 optometrists concerning visual examination of the patient with mTBI. This process resulted in a clinical tool containing 17 history questions and 7 examination procedures. This tool provides a set of clinical guidelines that can be used as desired by any eye care provider either as a screening tool or adjunct to a full eye examination when seeing a patient with a history of mTBI. The 757 goal of this process was to provide optimal and uniform vision care for the patient with mTBI. C1 [Goodrich, Gregory L.; Martinsen, Gary L.; Flyg, Heidi M.; Kirby, Jennine; Asch, Steven M.; Ingalla, Shanida P.] Dept Vet Affairs VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Brahm, Karen D.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Brand, John M.] VA Salt Lake City Hlth Care Syst, Salt Lake City, UT USA. [Cajamarca, Diana] West Palm Beach VA Med Ctr VAMC, W Palm Beach, FL USA. [Cantrell, Jenette L.] Bay Pines VA Healthcare Syst, Bay Pines, FL USA. [Chong, Theresa] VA Southern Nevada Healthcare Syst, North Las Vegas, NV USA. [Dziadul, John A.] Viera VA Outpatient Clin, Viera, FL USA. [Hetrick, Barbara J.] Jonathan M Wainwright Mem VAMC, Walla Walla, WA USA. [Huang, Michael A.] VA Mission Valley Clin, San Diego, CA USA. [Ihrig, Carolyn] VA Western New York Healthcare Syst, Buffalo, NY USA. [Meltzer, Bradley R.] Northport VAMC, Northport, NY USA. [Rakoczy, Chrystyna M.] James A Haley Vet Hosp, Tampa, FL 33612 USA. [Rone, Ashley] Lexington VAMC, Lexington, KY USA. [Schwartz, Elliot] VA New York Harbor Healthcare Syst, New York, NY USA. [Shea, Jane E.] VA St Louis Hlth Care Syst, St Louis, MO USA. RP Goodrich, GL (reprint author), VA Palo Alto Hlth Care Syst, 795 Willow Rd,Bldg T-365, Menlo Pk, CA 94025 USA. EM Gregorv.Goodrich@va.gov FU VA Health Services Research & Development QUERI [RRP 11-008] FX This material was based on work supported by a VA Health Services Research & Development QUERI (grant RRP 11-008). NR 51 TC 8 Z9 8 U1 3 U2 18 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2013 VL 50 IS 6 BP 757 EP 768 DI 10.1682/JRRD.2012.10.0184 PG 12 WC Rehabilitation SC Rehabilitation GA 217HJ UT WOS:000324350200005 PM 24203539 ER PT J AU Burdick, DJ Leverenz, JB AF Burdick, Daniel J. Leverenz, James B. BE Aarsland, D Cummings, J Weintraub, D Chaudhuri, KR TI Parkinson's disease: pathology, anatomy, and behavior SO NEUROPSYCHIATRIC AND COGNITIVE CHANGES IN PARKINSON'S DISEASE AND RELATED MOVEMENT DISORDERS: DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID IMPULSE CONTROL DISORDERS; CORTICAL LEWY BODIES; VISUAL HALLUCINATIONS; ALPHA-SYNUCLEIN; ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; POSITRON EMISSION; BODY DISEASE; DEMENTIA; DEPRESSION C1 [Burdick, Daniel J.] Evergreen Hosp, Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. [Leverenz, James B.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Leverenz, James B.] VA Puget Sound Hlth Care Syst, Mental Illnes Res Educ & Clin Ctr, Seattle, WA USA. [Leverenz, James B.] VA Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. [Leverenz, James B.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Leverenz, James B.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Burdick, DJ (reprint author), Evergreen Hosp, Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. NR 88 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-03922-3 PY 2013 BP 14 EP 24 D2 10.1017/CBO9781139856669 PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BGY95 UT WOS:000324630200003 ER PT J AU Weintraub, D Rektorova, I AF Weintraub, Daniel Rektorova, Irena BE Aarsland, D Cummings, J Weintraub, D Chaudhuri, KR TI Impulse control disorders and related behaviors SO NEUROPSYCHIATRIC AND COGNITIVE CHANGES IN PARKINSON'S DISEASE AND RELATED MOVEMENT DISORDERS: DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID HEDONISTIC HOMEOSTATIC DYSREGULATION; SUBTHALAMIC NUCLEUS STIMULATION; STRIATAL DOPAMINE RELEASE; DISEASE-RATING-SCALE; PARKINSONS-DISEASE; COMPULSIVE BEHAVIORS; CLINICAL-FEATURES; SEEKING BEHAVIOR; AGONIST THERAPY; FOLLOW-UP C1 [Weintraub, Daniel] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [Rektorova, Irena] Masaryk Univ, Dept Neurol 1, Sch Med, Brno, Czech Republic. [Rektorova, Irena] Masaryk Univ, St Annes Hosp, Brno, Czech Republic. [Rektorova, Irena] CEITEC MU, Cent European Inst Technol, Brno, Czech Republic. RP Weintraub, D (reprint author), Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. NR 105 TC 1 Z9 1 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-03922-3 PY 2013 BP 140 EP 152 D2 10.1017/CBO9781139856669 PG 13 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BGY95 UT WOS:000324630200014 ER PT J AU Smith, M Murphy, D Laxmisan, A Sittig, D Reis, B Esquivel, A Singh, H AF Smith, M. Murphy, D. Laxmisan, A. Sittig, D. Reis, B. Esquivel, A. Singh, H. TI Developing Software to "Track and Catch" Missed Follow-up of Abnormal Test Results in a Complex Sociotechnical Environment SO APPLIED CLINICAL INFORMATICS LA English DT Article DE Diagnostic errors; patient safety; test results; care delays; health information technology ID HEALTH INFORMATION-TECHNOLOGY; ELECTRONIC-MEDICAL-RECORDS; CANCER-DIAGNOSIS; TASK-ANALYSIS; ORDER ENTRY; CARE; SAFETY; SYSTEMS; DESIGN; ERRORS AB Background: Abnormal test results do not always receive timely follow-up, even when providers are notified through electronic health record (EHR)-based alerts. High workload, alert fatigue, and other demands on attention disrupt a provider's prospective memory for tasks required to initiate follow-up. Thus, EHR-based tracking and reminding functionalities are needed to improve follow-up. Objectives: The purpose of this study was to develop a decision-support software prototype enabling individual and system-wide tracking of abnormal test result alerts lacking follow-up, and to conduct formative evaluations, including usability testing. Methods: We developed a working prototype software system, the Alert Watch And Response Engine (AWARE), to detect abnormal test result alerts lacking documented follow-up, and to present context-specific reminders to providers. Development and testing took place within the VA's EHR and focused on four cancer-related abnormal test results. Design concepts emphasized mitigating the effects of high workload and alert fatigue while being minimally intrusive. We conducted a multifaceted formative evaluation of the software, addressing fit within the larger socio-technical system. Evaluations included usability testing with the prototype and interview questions about organizational and workflow factors. Participants included 23 physicians, 9 clinical information technology specialists, and 8 quality/safety managers. Results: Evaluation results indicated that our software prototype fit within the technical environment and clinical workflow, and physicians were able to use it successfully. Quality/safety managers reported that the tool would be useful in future quality assurance activities to detect patients who lack documented follow-up. Additionally, we successfully installed the software on the local facility's "test" EHR system, thus demonstrating technical compatibility. Conclusion: To address the factors involved in missed test results, we developed a software prototype to account for technical, usability, organizational, and workflow needs. Our evaluation has shown the feasibility of the prototype as a means of facilitating better follow-up for cancer-related abnormal test results. C1 [Smith, M.; Murphy, D.; Laxmisan, A.; Reis, B.; Singh, H.] Baylor Coll Med, Houston VA HSR&D Ctr Excellence, Houston, TX 77030 USA. [Smith, M.; Murphy, D.; Laxmisan, A.; Reis, B.; Singh, H.] Baylor Coll Med, Ctr Inquiry Improve Outpatient Safety Effect Elec, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Smith, M.; Murphy, D.; Laxmisan, A.; Reis, B.; Singh, H.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Sittig, D.] Univ Texas Houston, Sch Biomed Informat, Houston, TX USA. [Sittig, D.] UT Mem Hermann Ctr Healthcare Qual & Safety, Houston, TX USA. [Esquivel, A.] St Lukes Episcopal Hlth Syst, Dept Clin Effectiveness & Performance Measurement, Houston, TX USA. RP Smith, M (reprint author), VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM ms6@bcm.edu FU VA Innovation Initiative [XNV 33-124]; VA National Center of Patient Safety; Houston VA HSR&D Center of Excellence [HFP90-020] FX The authors wish to acknowledge the expert contributions of: Dana Douglas, Mark Becker, and Dick Horst of UserWorks, Inc.; Bryan Campbell and Angela Schmeidel Randall of Normal Modes, LLC; and Ignacio Valdes and Fred Trotter of Astronaut Contracting, LLC. Additional thanks to Velma Payne, Varsha Modi, Kathy Taylor, Roxie Pierce, Pawan Gulati, and George Welch. Project supported by the VA Innovation Initiative (XNV 33-124), VA National Center of Patient Safety and in part by the Houston VA HSR&D Center of Excellence (HFP90-020). The views expressed in this article are those of the author(s) and do not necessarily represent the views of the Department of Veterans Affairs. There are no conflicts of interest for any authors. NR 59 TC 8 Z9 8 U1 2 U2 11 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 1869-0327 J9 APPL CLIN INFORM JI Appl. Clin. Inform. PY 2013 VL 4 IS 3 BP 359 EP 375 DI 10.4338/ACI-2013-04-RA-0019 PG 17 WC Medical Informatics SC Medical Informatics GA 215TZ UT WOS:000324234800004 PM 24155789 ER PT J AU Huber, BR Meabon, JS Martin, TJ Mourad, PD Bennett, R Kraemer, BC Cernak, I Petrie, EC Emery, MJ Swenson, ER Mayer, C Mehic, E Peskind, ER Cook, DG AF Huber, Bertrand R. Meabon, James S. Martin, Tobin J. Mourad, Pierre D. Bennett, Raymond Kraemer, Brian C. Cernak, Ibolja Petrie, Eric C. Emery, Michael J. Swenson, Erik R. Mayer, Cynthia Mehic, Edin Peskind, Elaine R. Cook, David G. TI Blast Exposure Causes Early and Persistent Aberrant Phospho- and Cleaved-Tau Expression in a Murine Model of Mild Blast-Induced Traumatic Brain Injury SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Blast-induced neurotrauma; brain trauma; cerebellum; mitochondrial oxidative stress; neurodegeneration; tauopathy ID HEAD-INJURY; CASPASE ACTIVATION; MOUSE MODEL; ENCEPHALOPATHY; DISEASE; STRESS; HYPERPHOSPHORYLATION; OVERPRESSURE; AFGHANISTAN; INVOLVEMENT AB Mild traumatic brain injury (mTBI) is considered the 'signature injury' of combat veterans that have served during the wars in Iraq and Afghanistan. This prevalence of mTBI is due in part to the common exposure to high explosive blasts in combat zones. In addition to the threats of blunt impact trauma caused by flying objects and the head itself being propelled against objects, the primary blast overpressure (BOP) generated by high explosives is capable of injuring the brain. Compared to other means of causing TBI, the pathophysiology of mild-to-moderate BOP is less well understood. To study the consequences of BOP exposure in mice, we employed a well-established approach using a compressed gas-driven shock tube that recapitulates battlefield-relevant open-field BOP. We found that 24 hours post-blast a single mild BOP provoked elevation of multiple phospho- and cleaved-tau species in neurons, as well as elevating manganese superoxide-dismutase (MnSOD or SOD2) levels, a cellular response to oxidative stress. In hippocampus, aberrant tau species persisted for at least 30 days post-exposure, while SOD2 levels returned to sham control levels. These findings suggest that elevated phospho- and cleaved-tau species may be among the initiating pathologic processes induced by mild blast exposure. These findings may have important implications for efforts to prevent blast-induced insults to the brain from progressing into long-term neurodegenerative disease processes. C1 [Huber, Bertrand R.; Petrie, Eric C.; Mayer, Cynthia; Peskind, Elaine R.] Vet Affairs Puget Sound Hlth Care Syst, Northwest Network Mental Illness Res Educ & Clin, Seattle, WA USA. [Meabon, James S.; Petrie, Eric C.; Peskind, Elaine R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Meabon, James S.; Martin, Tobin J.; Kraemer, Brian C.; Cook, David G.] Vet Affairs Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. [Mourad, Pierre D.] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. [Mourad, Pierre D.] Univ Washington, Appl Phys Lab, Seattle, WA 98105 USA. [Mourad, Pierre D.; Mehic, Edin] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. [Bennett, Raymond] Baker Engn & Risk Consultants, San Antonio, TX USA. [Kraemer, Brian C.; Cook, David G.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. [Cernak, Ibolja] Univ Alberta, Fac Rehabil Med, Edmonton, AB T6G 2M7, Canada. [Emery, Michael J.; Swenson, Erik R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Swenson, Erik R.] Univ Washington, Div Pulm & Crit Care Med, Dept Med, Seattle, WA USA. [Cook, David G.] Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA. RP Cook, DG (reprint author), 1660 S Columbian Way, Seattle, WA 98108 USA. EM dgcook@u.washington.edu FU Department of Veterans Affairs Office of Research and Development Medical Research Service; University of Washington Friends of Alzheimer's Research; University of Washington Royalty Research Fund; Northwest Network Mental Illness Research, Education and Clinical Center; Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs; NIH [T32 AG000258] FX This work was supported by the Department of Veterans Affairs Office of Research and Development Medical Research Service (DGC, ERP, BCK), University of Washington Friends of Alzheimer's Research (DGC, ERP), University of Washington Royalty Research Fund (DGC); Northwest Network Mental Illness Research, Education and Clinical Center (ERP), Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs (BRH); NIH T32 AG000258 (JSM); None of the authors have financial or other potential conflicts of interest regarding this report. NR 47 TC 36 Z9 36 U1 5 U2 23 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2013 VL 37 IS 2 BP 309 EP 323 DI 10.3233/JAD-130182 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 217EA UT WOS:000324338400006 PM 23948882 ER PT J AU Spindler, M Gooneratne, NS Siderowf, A Duda, JE Cantor, C Dahodwala, N AF Spindler, Meredith Gooneratne, Nalaka S. Siderowf, Andrew Duda, John E. Cantor, Charles Dahodwala, Nabila TI Daytime Sleepiness is Associated with Falls in Parkinson's Disease SO JOURNAL OF PARKINSONS DISEASE LA English DT Article DE Parkinson's disease; falls; sleepiness; depression; cognitive impairment ID MINI-MENTAL-STATE; DOPAMINERGIC TREATMENT; OLDER-PEOPLE; FATIGUE; DISORDERS; DEPRESSION; FREQUENCY; DEMENTIA; INSOMNIA; QUALITY AB Falls are frequent in Parkinson's disease (PD), and may be influenced by daytime sleepiness. We reviewed the records of 120 men with PD. Mean Epworth Sleepiness Scale (ESS) values were significantly different between non-fallers and fallers (6.0 vs. 9.7, p < 0.01). In multivariate analysis, ESS remained significantly associated with falls (OR 1.2, 95% CI 1.1-1.4, p = 0.02), along with cognitive impairment (OR 4.4 95% CI 1.0-18.7, p = 0.04) and postural instability/gait dysfunction (OR 1.6 95% CI 1.0-2.4, p = 0.03) in non-depressed patients. In conclusion, non-depressed PD patients are 20% more likely to fall for every one unit increase in the ESS measure of sleepiness. C1 [Spindler, Meredith; Duda, John E.; Cantor, Charles; Dahodwala, Nabila] Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA 19107 USA. [Spindler, Meredith; Duda, John E.] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [Gooneratne, Nalaka S.] Univ Penn, Perelman Sch Med, Dept Med, Div Geriatr Med, Philadelphia, PA 19107 USA. [Gooneratne, Nalaka S.; Cantor, Charles] Univ Penn, Perelman Sch Med, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19107 USA. [Gooneratne, Nalaka S.; Cantor, Charles] Univ Penn, Perelman Sch Med, Div Sleep Med, Philadelphia, PA 19107 USA. [Siderowf, Andrew] Avid Radiopharmaceut Inc, Philadelphia, PA USA. RP Dahodwala, N (reprint author), Univ Penn, Sch Med, Parkinsons Dis & Movement Disorders Ctr, 330S 9th St, Philadelphia, PA 19107 USA. EM dahodwan@mail.med.upenn.edu FU Parkinson's Disease Research, Education and Clinical Center of the Philadelphia Veterans Affairs Medical Center; NIH [K23 AG034236] FX Funding for this project has been provided by the following: 1) Pilot Project Award from the Parkinson's Disease Research, Education and Clinical Center of the Philadelphia Veterans Affairs Medical Center; 2) NIH grant K23 AG034236 (Dahodwala). The information contained in this paper does not necessarily reflect the position or the policy of the United States Government, and no official endorsement should be inferred. NR 43 TC 0 Z9 1 U1 2 U2 8 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1877-7171 J9 J PARKINSON DIS JI J. Parkinsons Dis. PY 2013 VL 3 IS 3 BP 387 EP 391 DI 10.3233/JPD-130184 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 218AN UT WOS:000324405000014 PM 23948992 ER PT S AU Garcia-Bellmunt, L Sibila, O Restrepo, MI Anzueto, A AF Garcia-Bellmunt, Laia Sibila, Oriol Restrepo, Marcos I. Anzueto, Antonio BE Blasi, F Miravitlles, M Welte, T TI Chronic bronchitis: a risk factor for bronchial infection SO SPECTRUM OF BRONCHIAL INFECTION SE European Respiratory Monograph LA English DT Article; Book Chapter DE Acute exacerbation; airway inflammation; bronchial infection; chronic bronchitis; chronic obstructive pulmonary disease; host factors ID OBSTRUCTIVE PULMONARY-DISEASE; AIR-FLOW OBSTRUCTION; QUALITY-OF-LIFE; NONTYPABLE HAEMOPHILUS-INFLUENZAE; CHRONIC MUCUS HYPERSECRETION; LOWER RESPIRATORY-TRACT; PSEUDOMONAS-AERUGINOSA; BACTERIAL-COLONIZATION; ACUTE EXACERBATIONS; COPD EXACERBATIONS AB Chronic bronchitis is a clinical entity characterised by chronic bronchial mucus hypersecretion. It is frequently associated with chronic obstructive pulmonary disease (COPD) and it is related to worse outcomes. COPD patients with chronic bronchitis experienced accelerated lung function decline and an increased risk of exacerbations. Chronic mucus hypersecretion is also associated with acute or chronic bacterial bronchial infection, and increased airway and systemic inflammation. In addition, different antibiotic and anti-inflammatory treatments have been tested in these patients, with conflicting results. Mechanisms to explain the relationship between chronic bronchitis and infection are not well established, although host factors have been identified as key factors in the pathogenesis of bronchial infection. This chapter discusses the association of chronic bronchitis and the risk of bronchial infection, and the infection mechanisms that are responsible for this association, potential antibiotic and anti-inflammatory treatment. C1 [Garcia-Bellmunt, Laia; Sibila, Oriol] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Restrepo, Marcos I.; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Restrepo, Marcos I.; Anzueto, Antonio] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Restrepo, Marcos I.] Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. RP Anzueto, A (reprint author), South Texas Vet Hlth Care Syst, Audie L Murphy Div San Antonio, 7400 Merton Minter Blvd 11C6, San Antonio, TX 78229 USA. EM anzueto@uthscsa.edu NR 80 TC 0 Z9 0 U1 0 U2 0 PU EUROPEAN RESPIRATORY SOCIETY PI SHEFFIELD PA 442 GLOSSOP ROAD, SHEFFIELD, S10 2PX, ENGLAND SN 2075-6674 BN 978-1-84984-035-4; 978-1-84984-034-7 J9 EUR RESPIR MONOGR PY 2013 IS 60 BP 18 EP 26 DI 10.1183/1025448x.10017012 PG 9 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA BGW46 UT WOS:000324380900004 ER PT J AU Goldstein, G Oakes, H Lovejoy, D Holdnack, JA AF Goldstein, Gerald Oakes, Howard Lovejoy, David Holdnack, James A. BE Holdnack, JA Weiss, LG Iverson, GL TI Assessing Individual's with Psychiatric and Developmental Disorders SO WAIS-IV, WMS-IV, AND ACS: ADVANCED CLINICAL INTERPRETATION SE Practical Resources for the Mental Health Professional LA English DT Article; Book Chapter ID HIGH-FUNCTIONING AUTISM; ASPERGER-SYNDROME; COGNITIVE FUNCTION; SOCIAL-PERCEPTION; SCHIZOPHRENIA; INTELLIGENCE; ADOLESCENTS; MEMORY; ADULTS; BRAIN C1 [Goldstein, Gerald] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Oakes, Howard; Lovejoy, David] Hartford Hosp, Hartford, CT USA. [Lovejoy, David] Univ Connecticut, Sch Med, Farmington, CT USA. [Holdnack, James A.] Pearson Assessment, San Antonio, TX USA. RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 55 TC 0 Z9 0 U1 2 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-386953-1 J9 PRACT RESOUR MENT PY 2013 BP 545 EP 599 DI 10.1016/B978-0-12-386934-0.00011-0 PG 55 WC Psychology, Clinical SC Psychology GA BGQ37 UT WOS:000323772000012 ER PT B AU Chandler, L AF Chandler, Laura BE Dasgupta, A Sepulveda, JL TI Challenges in Clinical Microbiology Testing SO ACCURATE RESULTS IN THE CLINICAL LABORATORY: A GUIDE TO ERROR DETECTION AND CORRECTION LA English DT Article; Book Chapter ID BLOOD CULTURE CONTAMINATION; BRUCELLA-MELITENSIS; MISIDENTIFICATION; SUSCEPTIBILITY C1 [Chandler, Laura] Univ Penn, Dept Pathol & Lab Med, Philadelphia VA Med Ctr, Philadelphia, PA USA. [Chandler, Laura] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Chandler, L (reprint author), Univ Penn, Dept Pathol & Lab Med, Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 29 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-415858-0 PY 2013 BP 315 EP 326 DI 10.1016/B978-0-12-415783-5.00020-7 PG 12 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA BGG75 UT WOS:000322877800022 ER PT B AU Chandler, L AF Chandler, Laura BE Dasgupta, A Sepulveda, JL TI Sources of Errors in Molecular Testing SO ACCURATE RESULTS IN THE CLINICAL LABORATORY: A GUIDE TO ERROR DETECTION AND CORRECTION LA English DT Article; Book Chapter ID POLYMERASE-CHAIN-REACTION; NUCLEIC-ACID AMPLIFICATION; PHENOL-CHLOROFORM EXTRACTION; THERMOSTABLE DNA-POLYMERASE; BOVINE SERUM-ALBUMIN; SINGLE-STEP METHOD; VIRUS TYPE-1 RNA; NEISSERIA-GONORRHOEAE; GENOMIC MEDICINE; DIAGNOSTIC PCR C1 [Chandler, Laura] Univ Penn, Dept Pathol & Lab Med, Philadelphia VA Med Ctr, Philadelphia, PA USA. [Chandler, Laura] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Chandler, L (reprint author), Univ Penn, Dept Pathol & Lab Med, Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 57 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-415858-0 PY 2013 BP 327 EP 341 DI 10.1016/B978-0-12-415783-5.00021-9 PG 15 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA BGG75 UT WOS:000322877800023 ER PT S AU Findlay, VJ Larue, AC Turner, DP Watson, PM Watson, DK AF Findlay, Victoria J. LaRue, Amanda C. Turner, David P. Watson, Patricia M. Watson, Dennis K. BE Tew, KD Fisher, PB TI Understanding the Role of ETS-Mediated Gene Regulation in Complex Biological Processes SO ADVANCES IN CANCER RESEARCH, VOL 119 SE Advances in Cancer Research LA English DT Review; Book Chapter ID HUMAN BREAST-CANCER; SYSTEMIC-LUPUS-ERYTHEMATOSUS; TRANSCRIPTION FACTOR FLI1; HUMAN DERMAL FIBROBLASTS; EPIDERMAL-GROWTH-FACTOR; EPITHELIAL-MESENCHYMAL TRANSITION; PUTATIVE TUMOR-SUPPRESSOR; MAMMARY-GLAND DEVELOPMENT; PROTEIN-ASSOCIATED FACTOR; HEMATOPOIETIC STEM-CELLS AB Ets factors are members of one of the largest families of evolutionarily conserved transcription factors, regulating critical functions in normal cell homeostasis, which when perturbed contribute to tumor progression. The well-documented alterations in ETS factor expression and function during cancer progression result in pleiotropic effects manifested by the downstream effect on their target genes. Multiple ETS factors bind to the same regulatory sites present on target genes, suggesting redundant or competitive functions. The anti- and prometastatic signatures obtained by examining specific ETS regulatory networks will significantly improve our ability to accurately predict tumor progression and advance our understanding of gene regulation in cancer. Coordination of multiple ETS gene functions also mediates interactions between tumor and stromal cells and thus contributes to the cancer phenotype. As such, these new insights may provide a novel view of the ETS gene family as well as a focal point for studying the complex biological control involved in tumor progression. One of the goals of molecular biology is to elucidate the mechanisms that contribute to the development and progression of cancer. Such an understanding of the molecular basis of cancer will provide new possibilities for: (1) earlier detection, as well as better diagnosis and staging of disease; (2) detection of minimal residual disease recurrences and evaluation of response to therapy; (3) prevention; and (4) novel treatment strategies. Increased understanding of ETS-regulated biological pathways will directly impact these areas. C1 [Findlay, Victoria J.; LaRue, Amanda C.; Turner, David P.; Watson, Dennis K.] Med Univ S Carolina, Dept Pathol & Lab Med, Hollings Canc Ctr, Charleston, SC 29425 USA. [LaRue, Amanda C.] Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC USA. [Watson, Patricia M.] Med Univ S Carolina, Dept Med, Hollings Canc Ctr, Charleston, SC 29425 USA. [Watson, Dennis K.] Med Univ S Carolina, Dept Biochem & Mol Biol, Hollings Canc Ctr, Charleston, SC 29425 USA. RP Watson, DK (reprint author), Med Univ S Carolina, Dept Pathol & Lab Med, Hollings Canc Ctr, Charleston, SC 29425 USA. EM watsondk@musc.edu NR 256 TC 13 Z9 14 U1 1 U2 13 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-230X BN 978-0-12-407190-2 J9 ADV CANCER RES JI Adv.Cancer Res. PY 2013 VL 119 BP 1 EP 61 DI 10.1016/B978-0-12-407190-2.00001-0 PG 61 WC Oncology SC Oncology GA BGK69 UT WOS:000323354400001 PM 23870508 ER PT J AU Morasco, BJ AF Morasco, Benjamin J. BE Miller, PM TI Psychological Treatments for Pathological Gambling SO INTERVENTIONS FOR ADDICTION: COMPREHENSIVE ADDICTIVE BEHAVIORS AND DISORDERS, VOL 3 LA English DT Article; Book Chapter ID COGNITIVE-BEHAVIORAL THERAPY; GAMBLERS; COMORBIDITY; ALCOHOL C1 [Morasco, Benjamin J.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA. [Morasco, Benjamin J.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. RP Morasco, BJ (reprint author), Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA. NR 10 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398363-3 PY 2013 BP 227 EP 233 DI 10.1016/B978-0-12-398338-1.00024-5 PG 7 WC Psychology, Clinical; Substance Abuse; Psychiatry; Psychology SC Psychology; Substance Abuse; Psychiatry GA BGI00 UT WOS:000323055000025 ER PT B AU Chakravorty, S AF Chakravorty, Subhajit BE Miller, PM TI The Treatment of Insomnia in Substance-Abusing Patients SO INTERVENTIONS FOR ADDICTION: COMPREHENSIVE ADDICTIVE BEHAVIORS AND DISORDERS, VOL 3 LA English DT Article; Book Chapter C1 Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Chakravorty, S (reprint author), Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398363-3 PY 2013 BP 517 EP 525 DI 10.1016/B978-0-12-398338-1.00055-5 PG 9 WC Psychology, Clinical; Substance Abuse; Psychiatry; Psychology SC Psychology; Substance Abuse; Psychiatry GA BGI00 UT WOS:000323055000056 ER PT J AU Balsam, KF Molina, Y Lehavot, K AF Balsam, Kimberly F. Molina, Yamile Lehavot, Keren BE Miller, PM Blume, AW Kavanagh, DJ Kampman, KM Bates, ME Larimer, ME Petry, NM DeWitte, P Ball, SA TI Alcohol and Drug Use in Lesbian, Gay, Bisexual, and Transgender (LGBT) Youth and Young Adults SO PRINCIPLES OF ADDICTION: COMPREHENSIVE ADDICTIVE BEHAVIORS AND DISORDERS, VOL 1 LA English DT Article; Book Chapter ID SEXUAL ORIENTATION; SUBSTANCE USE; TRAJECTORIES; DEPENDENCE C1 [Balsam, Kimberly F.] Palo Alto Univ, Palo Alto, CA USA. [Molina, Yamile] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Lehavot, Keren] VA Puget Sound Healthcare Syst, Seattle, WA USA. RP Balsam, KF (reprint author), Palo Alto Univ, Palo Alto, CA USA. NR 10 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398361-9 PY 2013 BP 563 EP 573 DI 10.1016/B978-0-12-398336-7.00058-9 PG 11 WC Substance Abuse SC Substance Abuse GA BGG51 UT WOS:000322841800059 ER PT S AU Yenari, MA Han, HS AF Yenari, M. A. Han, H. S. BE Naritomi, H Krieger, DW TI Influence of Therapeutic Hypothermia on Regeneration after Cerebral Ischemia SO CLINICAL RECOVERY FROM CNS DAMAGE SE Frontiers of Neurology and Neuroscience LA English DT Article; Book Chapter ID TRAUMATIC BRAIN-INJURY; ENDOTHELIAL GROWTH-FACTOR; NEUROTROPHIC FACTOR; MILD HYPOTHERMIA; CARDIAC-ARREST; ADULT NEUROGENESIS; GLOBAL-ISCHEMIA; RAT HIPPOCAMPUS; ANGIOGENESIS; CELLS AB The protective effect of therapeutic hypothermia in cerebral ischemia is well accepted in experimental models, and some clinical studies show that there is benefit in humans as well. Long-term observations in animal and clinical studies have documented recovery of neurological function following hypothermia treatment. Diminished damage by hypothermic protection should contribute to the recovery in many ways, but hypothermia appears to enhance regeneration of brain tissue as well. Since regeneration of the brain after damage initiates within hours and is active days and weeks after stroke, prolonged hypothermia might affect regenerative processes which have been documented to occur in these time frames. As there is a lack of data at the basic and clinical levels, the mechanism of neuroregeneration by hypothermia is unclear. Yet, we speculate that hypothermia enhances regeneration by positively influencing neurogenesis, angiogenesis, gliogenesis and synapse/circuit formation after stroke. In this chapter, we will provide up-to-date data from experimental studies and clinical reports on the effect of therapeutic hypothermia on neuroregeneration, with perspectives on future research. Copyright (C) 2013 S. Karger AG, Basel C1 [Yenari, M. A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yenari, M. A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Han, H. S.] Kyungpook Natl Univ, Sch Med, Dept Physiol, Taegu, South Korea. RP Yenari, MA (reprint author), Univ Calif San Francisco, Dept Neurol, 4150 Clement St, San Francisco, CA 94121 USA. EM yenari@alum.mit.edu FU NINDS NIH HHS [R01 NS040516] NR 33 TC 6 Z9 6 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1660-4431 BN 978-3-318-02309-1 J9 FRONT NEUROL NEUROSC JI Front. Neurol. Neurosci. PY 2013 VL 32 BP 122 EP 128 DI 10.1159/000346428 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA BGG55 UT WOS:000322844300015 PM 23859971 ER PT B AU Walker, RH AF Walker, Ruth H. BE Fernandez, HH Merello, M TI Chorea in a Man With Peripheral Neuropathy and Hepatomegaly: The Diagnosis Can Make a Difference! SO MOVEMENT DISORDERS: UNFORGETTABLE CASES AND LESSONS FROM THE BEDSIDE LA English DT Article; Book Chapter C1 James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY USA. RP Walker, RH (reprint author), James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-9362-8728-4 PY 2013 BP 155 EP 157 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BGI25 UT WOS:000323088600045 ER PT B AU Walker, RH AF Walker, Ruth H. BE Fernandez, HH Merello, M TI Speech and Gait Problems in a Patient Being Treated for Schizophrenia: A Lesson on Psychiatric Comorbidity From an Afro-Caribbean Man SO MOVEMENT DISORDERS: UNFORGETTABLE CASES AND LESSONS FROM THE BEDSIDE LA English DT Article; Book Chapter ID CEREBELLAR DEGENERATION C1 James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY USA. RP Walker, RH (reprint author), James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-9362-8728-4 PY 2013 BP 240 EP 242 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BGI25 UT WOS:000323088600072 ER PT J AU Haney, EM Calarge, C Bliziotes, MM AF Haney, Elizabeth M. Calarge, Chadi Bliziotes, M. Michael BE Karsenty, G TI Clinical Implications of Serotonin Regulation of Bone Mass SO TRANSLATIONAL ENDOCRINOLOGY OF BONE: REPRODUCTION, METABOLISM, AND THE CENTRAL NERVOUS SYSTEM LA English DT Article; Book Chapter ID SYSTEM-ACTIVE MEDICATIONS; NURSING-HOME RESIDENTS; REUPTAKE INHIBITOR USE; MINERAL DENSITY; DEPRESSIVE SYMPTOMS; FRACTURE RISK; OLDER WOMEN; HIP FRACTURE; POSTMENOPAUSAL WOMEN; PSYCHOTROPIC MEDICATIONS C1 [Haney, Elizabeth M.; Bliziotes, M. Michael] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Calarge, Chadi] Univ Iowa, Iowa City, IA USA. [Bliziotes, M. Michael] Portland VA Med Ctr, Portland, OR USA. RP Haney, EM (reprint author), Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 94 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-415859-7 PY 2013 BP 189 EP 198 DI 10.1016/B978-0-12-415784-2.00016-6 PG 10 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA BGH26 UT WOS:000322959600017 ER PT J AU Raven, EP Lu, PH Tishler, TA Heydari, P Bartzokis, G AF Raven, Erika P. Lu, Po H. Tishler, Todd A. Heydari, Panthea Bartzokis, George TI Increased Iron Levels and Decreased Tissue Integrity in Hippocampus of Alzheimer's Disease Detected in vivo with Magnetic Resonance Imaging SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; chelation; dementia; ferritin; field dependent relaxation rate increase (FDRI); iron; magnetic resonance imagining (MRI); myelin; prevention; treatment ID BRAIN FERRITIN IRON; MATTER STRUCTURAL INTEGRITY; OLIGODENDROCYTE CELL-DEATH; MILD COGNITIVE IMPAIRMENT; AMYLOID PRECURSOR PROTEIN; POPULATION-BASED COHORTS; NON-HAEMIN IRON; PARKINSONS-DISEASE; WHITE-MATTER; OXIDATIVE DAMAGE AB Background: Iron can catalyze damaging free radical reactions. With age, iron accumulates in brain gray matter regions and may contribute to the risk of developing age-related diseases such as Alzheimer's disease (AD). Prior MRI studies demonstrated increased iron deposits in basal ganglia regions; however, the hippocampus (Hipp), which is heavily damaged in AD, and comparator regions that are resistant to AD damage, such as thalamus (Th), have rarely been examined. Objective: To assess iron levels and evidence of tissue damage in Hipp and Th of AD subjects and healthy controls. Methods: Thirty-one AD and sixty-eight healthy control subjects participated in this study. High-and low-field strength MRI instruments were used in combination to quantify iron content of ferritin molecules (ferritin iron) using the field dependent relaxation rate increase (FDRI) method. Decreased transverse relaxation rate (R-2) was used as an index of tissue damage. Results: Compared with healthy controls, AD subjects had increased ferritin iron in Hipp (p = 0.019) but not Th (p = 0.637), and significantly decreased R-2 in Hipp (p < 0.001) but not Th (p = 0.37). In the entire sample, FDRI and R-2 were negatively correlated. Conclusion: The data shows that in AD, Hipp damage occurs in conjunction with ferritin iron accumulation. Prospective studies are needed to evaluate how increasing iron levels may influence the trajectory of tissue damage and cognitive and pathologic manifestations of AD. C1 [Raven, Erika P.; Tishler, Todd A.; Heydari, Panthea; Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Lu, Po H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Bartzokis, George] Univ Calif Los Angeles, Dept Neurol, Div Brain Mapping, Lab Neuroimaging, Los Angeles, CA 90024 USA. [Bartzokis, George] Greater Los Angeles VA Healthcare Syst, Dept Psychiat, West Los Angeles, CA USA. RP Bartzokis, G (reprint author), 300 UCLA Med Plaza,Suite 2200, Los Angeles, CA 90095 USA. EM gbar@ucla.edu RI Bartzokis, George/K-2409-2013 FU NIH [MH 0266029, AG027342, T32 NS041231]; RCS Alzheimer's Foundation FX This work was supported in part by NIH grants (MH 0266029; AG027342; T32 NS041231) and the RCS Alzheimer's Foundation. NR 106 TC 46 Z9 47 U1 2 U2 21 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2013 VL 37 IS 1 BP 127 EP 136 DI 10.3233/JAD-130209 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 206AJ UT WOS:000323487300013 PM 23792695 ER PT J AU Belter, JT Segil, JL Dollar, AM Weir, RF AF Belter, Joseph T. Segil, Jacob L. Dollar, Aaron M. Weir, Richard F. TI Mechanical design and performance specifications of anthropomorphic prosthetic hands: A review SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Review DE amputee; grasping; grippers; hands; iLimb Hand; manipulation; Michelangelo Hand; rehabilitation; robotics; terminal devices AB In this article, we set forth a detailed analysis of the mechanical characteristics of anthropomorphic prosthetic hands. We report on an empirical study concerning the performance of several commercially available myoelectric prosthetic hands, including the Vincent, iLimb, iLimb Pulse, Bebionic, Bebionic v2, and Michelangelo hands. We investigated the finger design and kinematics, mechanical joint coupling, and actuation methods of these commercial prosthetic hands. The empirical findings are supplemented with a compilation of published data on both commercial and prototype research prosthetic hands. We discuss numerous mechanical design parameters by referencing examples in the literature. Crucial design trade-offs are highlighted, including number of actuators and hand complexity, hand weight, and grasp force. Finally, we offer a set of rules of thumb regarding the mechanical design of anthropomorphic prosthetic hands. C1 [Belter, Joseph T.; Dollar, Aaron M.] Yale Univ, Dept Mech Engn & Mat Sci, New Haven, CT 06511 USA. [Segil, Jacob L.] Univ Colorado, Dept Mech Engn, Boulder, CO 80309 USA. [Weir, Richard F.] Denver VA Med Ctr, Dept Vet Affairs VA Eastern Colorado Healthcare, Biomechatron Dev Lab, Denver, CO USA. [Weir, Richard F.] Univ Colorado Denver, Coll Engn & Appl Sci, Dept Bioengn, Denver, CO USA. RP Belter, JT (reprint author), Yale Univ, Dept Mech Engn & Mat Sci, 10 Hillhouse Ave, New Haven, CT 06511 USA. EM joseph.belter@yale.edu FU Gustavus and Louise Pfeiffer Research Foundation; Department of Veterans Affairs (VA) Rehabilitation Research and Development Service; U.S. Department of Defense [W81XWH-10-1-0921] FX This material was based on work supported by the Gustavus and Louise Pfeiffer Research Foundation; Department of Veterans Affairs (VA) Rehabilitation Research and Development Service, administered through the VA Colorado Eastern Healthcare System; and a U.S. Department of Defense award (grant W81XWH-10-1-0921). NR 47 TC 72 Z9 73 U1 11 U2 71 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2013 VL 50 IS 5 BP 599 EP 617 DI 10.1682/JRRD.2011.10.0188 PG 19 WC Rehabilitation SC Rehabilitation GA 202RO UT WOS:000323237500003 PM 24013909 ER PT J AU Cholerton, B Larson, EB Baker, LD Craft, S Crane, PK Millard, SP Sonnen, JA Montine, TJ AF Cholerton, Brenna Larson, Eric B. Baker, Laura D. Craft, Suzanne Crane, Paul K. Millard, Steven P. Sonnen, Joshua A. Montine, Thomas J. TI Neuropathologic Correlates of Cognition in a Population-Based Sample SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; brain; cerebrovascular disorders; cognition; dementia; Lewy bodies; pathologic processes ID ALZHEIMERS ASSOCIATION GUIDELINES; MINI-MENTAL-STATE; PARKINSONS-DISEASE; OLDER-ADULTS; NATIONAL INSTITUTE; DEMENTIA; IMPAIRMENT; COMMUNITY; PERFORMANCE; AUTOPSY AB Many cognitively normal older adults have underlying neuropathologic changes of Alzheimer's disease (AD), vascular brain injury (VBI), or Lewy body disease (LBD), which confer an increased risk of dementia. The current study focused on the association between multiple neuropathologic indices and performance on specific cognitive domains in a community sample of older adults. Of 438 participants in the Adult Changes in Thought population-based study of brain aging who were autopsied, 363 subjects had cognitive testing at their final study visit and were included. Associations were measured between performance on the Cognitive Abilities Screening Instrument prior to death and neuropathologic endpoints, including AD neuropathologic changes, LBD, cerebral amyloid angiopathy, and measures of VBI. Braak stage for neurofibrillary tangles, lower brain weight, and VBI as measured by cerebral cortical microvascular lesions (mu VBI) explained a significant proportion of the variance associated with global cognitive test performance (R-2 = 0.31, p < 0.0001) both in the entire sample and when analysis was restricted to non-demented subjects (R-2 = 0.23, p < 0.0001). Specific cognitive domains were differentially related to neuropathologic lesion type: memory and executive function with AD pathologic changes and cortical mu VBI, executive function with subcortical mu VBI, and visuospatial construction with LBD. Thus, neuropathologic lesions of LBD and mu VBI are associated with poorer cognitive performance over and above AD neuropathologic changes in subjects without dementia in this cohort. These findings underscore that cognitive impairment is a complex convergent trait that has important implications for clinical investigation and medical management of older adults. C1 [Cholerton, Brenna] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Millard, Steven P.] Vet Affairs Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA USA. [Cholerton, Brenna] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Larson, Eric B.; Crane, Paul K.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Sonnen, Joshua A.; Montine, Thomas J.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Larson, Eric B.] Grp Hlth Res Inst, Seattle, WA USA. [Baker, Laura D.; Craft, Suzanne] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27103 USA. RP Cholerton, B (reprint author), VA Puget Sound Hlth Care Syst GRECC A 182, 9600 Vet Dr SW, Tacoma, WA 98493 USA. EM bchol@u.washington.edu RI Crane, Paul/C-8623-2014; Sonnen, 37382016/H-3738-2016 OI Sonnen, 37382016/0000-0001-9267-8705; Crane, Paul/0000-0003-4278-7465 FU Group Health Research Institute; Nancy and Buster Alvord Endowment; Department of Veterans Affairs; [NS062684]; [AG006781]; [AG024180] FX This research was supported by NS062684, AG006781, AG024180, the Group Health Research Institute, the Nancy and Buster Alvord Endowment, and the Department of Veterans Affairs. The funding sources did not provide scientific input for the study. NR 53 TC 14 Z9 14 U1 1 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2013 VL 36 IS 4 BP 699 EP 709 DI 10.3233/JAD-130281 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 195XV UT WOS:000322738000008 PM 23666176 ER PT J AU Nedjat-Haiem, FR Carrion, IV Lorenz, KA Ell, K Palinkas, L AF Nedjat-Haiem, Frances R. Carrion, Iraida V. Lorenz, Karl A. Ell, Kathleen Palinkas, Lawrence TI PSYCHOSOCIAL CONCERNS AMONG LATINAS WITH LIFE-LIMITING ADVANCED CANCERS SO OMEGA-JOURNAL OF DEATH AND DYING LA English DT Article ID BREAST-CANCER; HISPANIC PATIENTS AB Research has demonstrated that limited dialogue in end-of-life (EOL) care can negatively impact decision-making and place of death. Furthermore, when vulnerable populations are faced with EOL cancer care, they experience issues resulting from previous gaps in services attributed to sociocultural and economic issues that influence EOL care. These conditions place an additional burden on disadvantaged populations which can cause distress, especially as disparate conditions continue to persist. Little is known about Latinos' psychosocial concerns that lead to distress in EOL care. The objective of this study is to explore Latinas' experiences with life-limiting cancer conditions to identify the EOL care concerns that impact their dying experience. This study used a phenomenological approach to explore the EOL care concerns of 24 Latinas receiving treatment for metastatic cancers in a public sector healthcare system in Los Angeles, California. In-depth interviews were recorded and transcribed, and qualitative analysis was performed using Atlas.ti software. C1 [Nedjat-Haiem, Frances R.; Lorenz, Karl A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Nedjat-Haiem, Frances R.; Carrion, Iraida V.; Ell, Kathleen; Palinkas, Lawrence] Univ So Calif, Pacific Palisades, CA 90272 USA. RP Nedjat-Haiem, FR (reprint author), Univ So Calif, 17165 Ave Santa Ynez, Pacific Palisades, CA 90272 USA. EM nedjatha@usc.edu OI Carrion, Iraida/0000-0003-4076-6644 FU NCI NIH HHS [R25CA110454] NR 17 TC 3 Z9 3 U1 2 U2 5 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, PO BOX 337, AMITYVILLE, NY 11701 USA SN 0030-2228 J9 OMEGA-J DEATH DYING JI Omega-J. Death Dying PY 2013 VL 67 IS 1-2 SI SI BP 167 EP 174 DI 10.2190/OM.67.1-2.t PG 8 WC Psychology, Multidisciplinary; Social Sciences, Biomedical SC Psychology; Biomedical Social Sciences GA 195CZ UT WOS:000322681200021 PM 23977793 ER PT J AU Yoder, MS Lozano, B Center, KB Miller, A Acierno, R Tuerk, PW AF Yoder, Matthew S. Lozano, Brian Center, Kristy B. Miller, Aaron Acierno, Ron Tuerk, Peter W. TI EFFECTIVENESS OF PROLONGED EXPOSURE FOR PTSD IN OLDER VETERANS SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE LA English DT Article DE PTSD; older adults; exposure therapy; veterans ID POSTTRAUMATIC-STRESS-DISORDER; COMBAT VETERANS; RAPE VICTIMS; THERAPY; SCALE; TRIAL AB Exposure-based therapy is an effective treatment for PTSD, including combat-related PTSD. However, questions remain within PTSD treatment literature and among front-line clinicians about the appropriateness of exposure-based therapies for older adults. The current study examined the effectiveness of Prolonged Exposure (PE) in reducing PTSD and depression symptoms in a sample of 65 Veterans age 60 and older who were diagnosed with PTSD via structured clinical interview. In addition to within-subject repeated measure analyses, the entire intent to treat sample was compared to treatment completers. Within group d-type effect sizes across both groups were large (1.13-1.90) and the retention rate was high (85%). Importantly, no adverse medical or psychiatric events were reported over the course of the study. Results are discussed and limitations, along with future directions, are presented. C1 Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. Med Univ S Carolina, Charleston, SC USA. RP Yoder, MS (reprint author), RHJ VAMC, Mental Hlth 116,109 Bee St, Charleston, SC 29401 USA. EM yoderm@musc.edu FU Department of Veteran Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development [CDA-2] FX Dr. Tuerk's contribution to this manuscript was partially supported by Career Development Award (CDA-2) from the Department of Veteran Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development (PI: Tuerk). NR 37 TC 7 Z9 7 U1 2 U2 8 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, PO BOX 337, AMITYVILLE, NY 11701 USA SN 0091-2174 J9 INT J PSYCHIAT MED JI Int. J. Psychiatr. Med. PY 2013 VL 45 IS 2 BP 111 EP 124 DI 10.2190/PM.45.2.b PG 14 WC Psychiatry SC Psychiatry GA 195GA UT WOS:000322689100002 PM 23977816 ER PT J AU Tuerk, PW Hall, B Nagae, N McCauley, JL Yoder, M Rauch, SAM AF Tuerk, Peter W. Hall, Brian Nagae, Nobukazu McCauley, Jenna L. Yoder, Matthew Rauch, Sheila A. M. TI FORTY DAYS AFTER THE GREAT EAST JAPAN EARTHQUAKE: FIELD RESEARCH INVESTIGATING COMMUNITY ENGAGEMENT AND TRAUMATIC STRESS SCREENING IN A POST-DISASTER COMMUNITY MENTAL HEALTH TRAINING SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE LA English DT Article DE PTSD; disaster; community mental health; Japan ID HANSHIN-AWAJI EARTHQUAKE; POSTTRAUMATIC-STRESS; PSYCHOLOGICAL DISTRESS; HURRICANE-ANDREW; SYMPTOMS; DISASTER; IMPACT; PTSD; RELIABILITY; MORBIDITY AB The current article describes the results of posttraumatic stress educational outreach and screening offered to 141 citizens of Japan who attended a public-service mental health training regarding post-disaster coping 40 days after a 6.8 Richter Scale earthquake, local and regional deaths, and an ongoing nuclear radiation threat. Attendees were given access to anonymous questionnaires that were integrated into the training as a tool to help enhance mental health literacy and bridge communication gaps. Questionnaires were turned in by a third of those in attendance. Among respondents, multiple exposures to potentially-traumatic events were common. More than a quarter of respondents met criteria for probable PTSD. Physical health and loss of sense of community were related to PTSD symptoms. Associations and diagnosis rates represented in these data are not generalizable to the population as a whole or intended for epidemiological purposes; rather, they are evidence of a potentially useful approach to post-disaster clinical screening, education, and engagement. Results are presented in the context of previous findings in Japan and ecologically-supportive post-disaster field research is discussed. C1 [Tuerk, Peter W.; Yoder, Matthew] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. [Tuerk, Peter W.; McCauley, Jenna L.; Yoder, Matthew] Med Univ S Carolina, Charleston, SC USA. [Hall, Brian] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Nagae, Nobukazu] Fukuoka Univ, Fukuoka, Japan. [Rauch, Sheila A. M.] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Rauch, Sheila A. M.] Univ Michigan, Sch Med, Ann Arbor, MI USA. RP Tuerk, PW (reprint author), RHJ VAMC, Mental Hlth 116,109 Bee St, Charleston, SC 29401 USA. EM Tuerk@musc.edu RI Rauch, Sheila/K-4450-2015 OI Rauch, Sheila/0000-0001-9686-4011; Hall, Brian/0000-0001-9358-2377 FU Department of Veteran Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development [CDA-2]; NIMH [T32MH014592-35, T32MH018869-24] FX Drs. Tuerk's and Rauch's contribution to this article was partially supported by Career Development Awards (CDA-2) from the Department of Veteran Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development (PI: Tuerk, PI: Rauch). Dr. Hall's contribution to this work was supported by NIMH training grants T32MH014592-35 (PI: Zandi) and T32MH018869-24 (PI: Kilpatrick). NR 46 TC 5 Z9 6 U1 2 U2 10 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, PO BOX 337, AMITYVILLE, NY 11701 USA SN 0091-2174 J9 INT J PSYCHIAT MED JI Int. J. Psychiatr. Med. PY 2013 VL 45 IS 2 BP 159 EP 174 DI 10.2190/PM.45.2.e PG 16 WC Psychiatry SC Psychiatry GA 195GA UT WOS:000322689100005 PM 23977819 ER PT J AU Thames, AD Arentoft, A Rivera-Mindt, M Hinkin, CH AF Thames, April D. Arentoft, Alyssa Rivera-Mindt, Monica Hinkin, Charles H. TI Functional disability in medication management and driving among individuals with HIV: A 1-year follow-up study SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article DE HIV; Instrumental activities of daily living; Cognitive function; Medication management; Driving ID PERFORMANCE-BASED MEASURES; NEUROPSYCHOLOGICAL IMPAIRMENT; NEUROCOGNITIVE DISORDERS; PHYSICAL PERFORMANCE; ALZHEIMER-DISEASE; OLDER ADULTS; INFECTION; ADHERENCE; HIV/AIDS; PREDICTORS AB Approximately 50% of individuals with HIV report cognitive deficits that can affect social or occupational functioning. The present study used a longitudinal design (1 year) to examine the relationship between cognitive factors and incidental functional deficits in medication management and driving ability among a cohort of 101 HIV+ participants. Participants were classified into groups of functionally stable and disabled for each laboratory-based functional task (i.e., Medication Management Task-Revised, MMT-R, and PC-based driving simulator). We hypothesized that participants who exhibited a functional deficit in either MMT-R or driving at follow-up assessment would demonstrate significantly poorer baseline cognitive performance at study entry than participants who remained functionally stable. As hypothesized, participants who demonstrated significantly lower baseline performance in learning/memory and executive functioning also demonstrated functional disability on the MMT-R at follow-up when compared to functionally stable participants. Poor baseline performance in speed of information processing was associated with a deficit in driving ability at follow-up assessment. Our results suggest that lower baseline cognitive functioning predicts downstream functional disability, and that deficits in learning/memory and information processing speed are particularly predictive of deficits in medication management and driving ability. C1 [Thames, April D.; Arentoft, Alyssa; Hinkin, Charles H.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Sch Med, Los Angeles, CA 90095 USA. [Arentoft, Alyssa; Hinkin, Charles H.] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Rivera-Mindt, Monica] Fordham Univ, Dept Psychol, New York, NY 10023 USA. [Rivera-Mindt, Monica] Mt Sinai Sch Med, Dept Neurol & Psychiat, New York, NY USA. RP Thames, AD (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 740 Westwood Plaza C8-746, Los Angeles, CA 90095 USA. EM athames@mednet.ucla.edu RI Thames, April/K-1964-2014 OI Thames, April/0000-0001-8414-7189; Arentoft, Alyssa/0000-0002-4235-4638 FU VA Merit Review; National Institute of Mental Health [T32 19535] FX We would like to acknowledge the following funding sources: VA Merit Review awarded to Charles Hinkin, PhD and National Institute of Mental Health training grant (T32 19535; PI: C. Hinkin). NR 45 TC 9 Z9 9 U1 3 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD JAN 1 PY 2013 VL 35 IS 1 BP 49 EP 58 DI 10.1080/13803395.2012.747596 PG 10 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 189YL UT WOS:000322304100006 PM 23237014 ER PT J AU Allen, RS Guadagno, RE Parmelee, P Minney, JA Hilgeman, MM Tabb, KD McNeal, SF Houston, T Kertesz, S Davis, L AF Allen, R. S. Guadagno, R. E. Parmelee, P. Minney, J. A. Hilgeman, M. M. Tabb, K. D. McNeal, S. F. Houston, T. Kertesz, S. Davis, L. TI Internet connectivity among rural Alabama veterans: baseline findings from the Alabama Veterans Rural Health Initiative Project SO RURAL AND REMOTE HEALTH LA English DT Article DE aging; healthcare disparities; internet; rural population; USA; veterans' health ID OLDER-ADULTS; CARE; TECHNOLOGY; ACCESS; ATTITUDES; DISPARITIES; EDUCATION; MILITARY AB Introduction: The purpose of this secondary data analysis was to characterize the Internet usage of rural veterans (n=201) who had either never enrolled, or had previously enrolled but not accessed, Veterans Affairs (VA) health services in at least 2 years. The VA Office of Rural Health (ORH)(ie part of the United States Government Department of Veterans Affairs) is a government agency with the mission to improve access and quality of care for enrolled rural and highly rural US veterans. The ORH seeks to use evidence-based policies and innovative practices to support the unique needs of enrolled veterans residing in geographically remote areas. These individuals represent a population considered to experience health disparities secondary to reduced health care access. Methods: This study explored the role of the Internet in providing health information and information regarding VA services to rural Caucasian and African American veterans in the southeastern USA. African Americans were significantly younger (50.32 years, SD=13.50, range 22-85 years) than Caucasian rural veterans (58.50 years, SD=13.82, range 21-85 years). Results: A small majority of veterans (n=107; 53.23%) reported 'going on-line to use the Internet or World Wide Web, or to send and receive e-mail'. Among Internet users, multivariate logistic regression showed that neither age nor race/ethnicity predicted using the Internet to access health information or information regarding VA services. Conclusion: In comparison with population norms, rural veterans displayed lower usage of the Internet; however, there were few practical age differences between young, middle-aged and older rural veterans in use of the Internet for seeking health information. These results suggest a tremendous potential for online outreach efforts to rural veterans seeking health information and information regarding VA services and benefits. The US Federal Government's VA Office of Rural Health is investing in technology-based services and will need to disseminate information regarding the availability of these services to rural veterans. C1 [Allen, R. S.; Guadagno, R. E.; Parmelee, P.; Minney, J. A.] Univ Alabama, Tuscaloosa, AL 35487 USA. [Hilgeman, M. M.; Davis, L.] Tuscaloosa Vet Affairs Med Ctr, Tuscaloosa, AL USA. [Tabb, K. D.; McNeal, S. F.; Kertesz, S.] Birmingham Vet Affairs Med Ctr, Alabama Vet Rural Hlth Initiat, Birmingham, AL USA. [Houston, T.] Edith Nourse Rogers Mem Vet Hosp, EHlth Qual Enhancement Res Initiat, Bedford, MA USA. RP Allen, RS (reprint author), Univ Alabama, Tuscaloosa, AL 35487 USA. FU VA Health Services Research and Development Office (eHealth QUERI grant) [EHQ 10-190]; VA Office of Rural Health FX The authors acknowledge the support of the VA Health Services Research and Development Office (eHealth QUERI grant number EHQ 10-190) and the VA Office of Rural Health. NR 17 TC 1 Z9 1 U1 1 U2 7 PU AUSTRALIAN RURAL HEALTH EDUC NETWORK PI DEAKIN WEST PA PO BOX 242, DEAKIN WEST, ACT 2600, AUSTRALIA SN 1445-6354 J9 RURAL REMOTE HEALTH JI Rural Remote Health PD JAN-MAR PY 2013 VL 13 IS 1 AR 2138 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 190TY UT WOS:000322364800020 PM 23331256 ER PT S AU Guillory, B Splenser, A Garcia, J AF Guillory, Bobby Splenser, Andres Garcia, Jose BE Litwack, G TI The Role of Ghrelin in Anorexia-Cachexia Syndromes SO ANOREXIA SE Vitamins and Hormones LA English DT Review; Book Chapter ID GROWTH-HORMONE SECRETAGOGUE; DES-ACYL GHRELIN; OBSTRUCTIVE PULMONARY-DISEASE; CHRONIC HEART-FAILURE; LEAN BODY-MASS; UBIQUITIN-PROTEASOME PATHWAY; FOXO TRANSCRIPTION FACTORS; MUSCLE PROTEIN BREAKDOWN; PLACEBO-CONTROLLED TRIAL; O-ACYLTRANSFERASE GOAT AB Anorexia, sarcopenia, and cachexia are common complications of many chronic conditions including cancer, rheumatoid arthritis, HIV infection, aging, and chronic lung, heart, or kidney disease. Currently, there is no effective treatment for muscle atrophy or wasting conditions although they typically take a significant toll on the quality of life of patients and are associated with poor prognosis and decreased survival. Ghrelin affects multiple key pathways in the regulation of body weight, body composition, and appetite in the setting of cachexia that may lead to an increase in appetite and growth hormone secretion and a reduction in energy expenditure and inflammation. The net effect is increased lean body mass and fat mass preservation. In this chapter, we review the mechanisms of action of ghrelin and present the available data in animal models and human trials using ghrelin or ghrelin mimetics in different settings of cachexia. C1 [Guillory, Bobby; Splenser, Andres; Garcia, Jose] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Div Diabet Endocrinol & Metab, Houston, TX 77030 USA. [Garcia, Jose] Baylor Coll Med, Huffington Ctr Aging, Dept Mol & Cell Biol, Houston, TX 77030 USA. RP Garcia, J (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Div Diabet Endocrinol & Metab, Houston, TX 77030 USA. EM jgarcia1@bcm.edu FU NIA NIH HHS [AG040583, T32AG000183] NR 225 TC 8 Z9 9 U1 0 U2 11 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0083-6729 BN 978-0-12-410473-0 J9 VITAM HORM JI Vitam. Horm. PY 2013 VL 92 BP 61 EP 106 DI 10.1016/B978-0-12-410473-0.00003-9 PG 46 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Psychology SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Psychology GA BFP64 UT WOS:000320892700004 PM 23601421 ER PT J AU Broyles, LM Gordon, AJ Rodriguez, KL Hanusa, BH Kengor, C Kraemer, KL AF Broyles, Lauren M. Gordon, Adam J. Rodriguez, Keri L. Hanusa, Barbara H. Kengor, Caroline Kraemer, Kevin L. TI Evaluation of a Pilot Training Program in Alcohol Screening, Brief Intervention, and Referral to Treatment for Nurses in Inpatient Settings SO JOURNAL OF ADDICTIONS NURSING LA English DT Article DE alcohol consumption; brief intervention; counseling; curriculum; education; inpatients; nurses; referral and consultation; screening ID PRIMARY-CARE; EMERGENCY-DEPARTMENT; IMPLEMENTATION-RESEARCH; MEDICAL-EDUCATION; TREATMENT SBIRT; ATTITUDES; EXPERIENCE; CURRICULUM; IMPACT; AAPPQ AB Alcohol screening, brief intervention, and referral to treatment (SBIRT) is a set of clinical strategies for reducing the burden of alcohol-related injury, disease, and disability. SBIRT is typically considered a physician responsibility but calls for interdisciplinary involvement requiring basic SBIRT knowledge and skills training for all healthcare disciplines. The purpose of this pilot study was to design, implement, and evaluate a theory-driven SBIRT training program for nurses in inpatient settings (RN-SBIRT) that was developed through an interdisciplinary collaboration of nursing, medical, and public health professionals and tailored for registered nurses in the inpatient setting. In this three-phase study, we evaluated (1) RN-SBIRT's effectiveness for changing nurses' alcohol-related knowledge, clinical practice, and attitudes and (2) the feasibility of implementing the inpatient curriculum. In a quasi-experimental design, two general medical units at our facility were randomized to receive RN-SBIRT or a self-directed Web site on alcohol-related care. We performed a formative evaluation of RN-SBIRT, guided by the RE-AIM implementation framework. After training, nurses in the experimental condition had significant increases in Role Adequacy for working with drinkers and reported increased performance and increased competence for a greater number of SBIRT care tasks. Despite some scheduling challenges for the nurses to attend RN-SBIRT, nurse stakeholders were highly satisfied with RN-SBIRT. Results suggest that with adequate training and ongoing role support, nurses in inpatient settings could play active roles in interdisciplinary initiatives to address unhealthy alcohol use among hospitalized patients. C1 [Broyles, Lauren M.; Gordon, Adam J.; Rodriguez, Keri L.; Hanusa, Barbara H.; Kengor, Caroline] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Broyles, Lauren M.; Gordon, Adam J.; Hanusa, Barbara H.] Vet Affairs Pittsburgh Healthcare Syst, Vet Integrated Serv Network Mental Illness Res Ed, Pittsburgh, PA 15206 USA. [Broyles, Lauren M.; Gordon, Adam J.; Rodriguez, Keri L.; Kraemer, Kevin L.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Broyles, Lauren M.; Gordon, Adam J.; Rodriguez, Keri L.; Kraemer, Kevin L.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. RP Broyles, LM (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr,Bldg 2,Rm 4020W 151C-H, Pittsburgh, PA 15206 USA. EM lauren.broyles@va.gov FU Veterans Affairs Quality Enhancement Research Initiative Program [RRP 09-064]; Health Services Research and Development service of the U.S. Department of Veterans Affairs [CDA 10-014] FX Funding for this study was provided by Veterans Affairs Quality Enhancement Research Initiative Program (RRP 09-064, Principal Investigator, L. M. Broyles). The funding body played no role in the design; data collection, analysis, and interpretation of the data; the writing of the manuscript; nor the decision to submit the manuscript for publication. Dr. Broyles is currently supported by a Career Development Award (CDA 10-014) from the Health Services Research and Development service of the U.S. Department of Veterans Affairs. The material is the result of work supported with resources and the use of facilities at the Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the U. S. government. NR 53 TC 8 Z9 9 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1088-4602 J9 J ADDICT NURS JI J. Addict. Nurs. PD JAN-MAR PY 2013 VL 24 IS 1 BP 8 EP 19 DI 10.1097/JAN.0b013e31828767ef PG 12 WC Substance Abuse; Nursing SC Substance Abuse; Nursing GA 185LZ UT WOS:000321970800004 PM 24622525 ER PT J AU Broyles, LM Conley, JW Harding, JD Gordon, AJ AF Broyles, Lauren M. Conley, James W. Harding, John D., Jr. Gordon, Adam J. TI A Scoping Review of Interdisciplinary Collaboration in Addictions Education and Training SO JOURNAL OF ADDICTIONS NURSING LA English DT Review DE Alcohol-related disorders; collaboration; cooperative behavior; curriculum; drug use disorders; education; interdisciplinary; interdisciplinary communication; interprofessional relations; substance abuse; substance addiction ID HEALTH-PROFESSIONAL STUDENTS; SUBSTANCE-ABUSE; BRIEF INTERVENTION; TREATMENT SBIRT; MODEL; MULTIDISCIPLINARITY; TRANSDISCIPLINARITY; CURRICULUM; PROVIDERS; SERVICES AB Developing a workforce of multidisciplinary healthcare professionals equipped with the knowledge and skills to collaboratively address the public health crisis of alcohol and other drug (AOD) use is critical for effectively identifying, preventing, and managing AOD conditions and their sequelae. Despite general enthusiasm for interdisciplinary education and training, little is known overall about the nature and outcomes of interdisciplinary collaboration in addictions education and training. We conducted a five-stage scoping review of the literature to provide an eight domain overview of the state of interdisciplinary collaboration in addictions education (ICAE). In our final review of 30 articles, we identified a lack of conceptual and terminological clarity around ICAE but a wide range of learners and professional collaborators in ICAE initiatives, which focused on a variety of AOD topics and used a constellation of didactic, interactive, and service-learning teaching strategies and formats. Although we found limited substantive educational or practice-oriented outcomes available for ICAE initiatives, learner and faculty feedback reflected high enthusiasm for ICAE and widespread perceptions of benefit for improved clinical care. Facilitators and barriers to the implementation of ICAE initiatives occurred at the level of the individual and the institution and ranged from pragmatic to conceptual. Emerging trends in ICAE initiatives included increased application of learning and implementation theory and extension of ICAE into research training. We conclude with recommendations to support ICAE as a new paradigm for addictions education for all health professionals. C1 [Broyles, Lauren M.; Harding, John D., Jr.; Gordon, Adam J.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Broyles, Lauren M.; Conley, James W.; Gordon, Adam J.] Vet Affairs Pittsburgh Healthcare Syst, Vet Integrated Serv Network Mental Illness Res Ed, Pittsburgh, PA 15206 USA. [Broyles, Lauren M.; Gordon, Adam J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Broyles, Lauren M.; Gordon, Adam J.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. RP Broyles, LM (reprint author), Vet Affairs Pittsburgh Healthcare Syst, 7180 Highland Dr,Bldg 2,Rm 4020W 151C-H, Pittsburgh, PA 15206 USA. EM Lauren.Broyles@va.gov FU Health Services Research & Development Service of the U.S. Department of Veterans Affairs [CDA 10-014] FX The authors have no conflicts of interest to declare. Dr. Broyles is currently supported by a Career Development Award (CDA 10-014) from the Health Services Research & Development Service of the U. S. Department of Veterans Affairs. The material is the result of work supported with resources and the use of facilities at the VAPHS, Pittsburgh, PA. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the U. S. government. NR 40 TC 0 Z9 0 U1 3 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1088-4602 J9 J ADDICT NURS JI J. Addict. Nurs. PD JAN-MAR PY 2013 VL 24 IS 1 BP 29 EP 36 DI 10.1097/JAN.0b013e318282751e PG 8 WC Substance Abuse; Nursing SC Substance Abuse; Nursing GA 185LZ UT WOS:000321970800006 PM 24622527 ER PT S AU Akl, TJ Wilson, MA Ericson, MN Cote, GL AF Akl, Tony J. Wilson, Mark A. Ericson, M. Nance Cote, Gerard L. BE Cote, GL TI Optical Modeling toward Optimizing Monitoring of Intestinal Perfusion in Trauma Patients SO OPTICAL DIAGNOSTICS AND SENSING XIII: TOWARD POINT-OF-CARE DIAGNOSTICS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Diagnostics and Sensing XIII - Toward Point-of-Care Diagnostics CY FEB 06, 2013 CL San Francisco, CA SP SPIE DE Perfusion monitoring; Photoplethysmography; Trauma; Oximetry; Telemetry ID TISSUE; RESUSCITATION; PENETRATION; DEPTH; SHOCK AB Trauma is the number one cause of death for people between the ages 1 and 44 years in the United States. In addition, according to the Centers of Disease Control and Prevention, injury results in over 31 million emergency department visits annually. Minimizing the resuscitation period in major abdominal injuries increases survival rates by correcting impaired tissue oxygen delivery. Optimization of resuscitation requires a monitoring method to determine sufficient tissue oxygenation. Oxygenation can be assessed by determining the adequacy of tissue perfusion. In this work, we present the design of a wireless perfusion and oxygenation sensor based on photoplethysmography. Through optical modeling, the benefit of using the visible wavelengths 470, 525 and 590nm (around the 525nm hemoglobin isobestic point) for intestinal perfusion monitoring is compared to the typical near infrared (NIR) wavelengths (805nm isobestic point) used in such sensors. Specifically, NIR wavelengths penetrate through the thin intestinal wall (similar to 4mm) leading to high background signals. However, these visible wavelengths have two times shorter penetration depth that the NIR wavelengths. Monte-Carlo simulations show that the transmittance of the three selected wavelengths is lower by 5 orders of magnitude depending on the perfusion state. Due to the high absorbance of hemoglobin in the visible range, the perfusion signal carried by diffusely reflected light is also enhanced by an order of magnitude while oxygenation signal levels are maintained. In addition, short source-detector separations proved to be beneficial for limiting the probing depth to the thickness of the intestinal wall. C1 [Akl, Tony J.; Cote, Gerard L.] Texas A&M Univ, Dept Biomed Engn, College Stn, TX 77843 USA. [Wilson, Mark A.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15260 USA. [Wilson, Mark A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. [Cote, Gerard L.] Oak Ridge Natl Lab, Oak Ridge, TN USA. RP Akl, TJ (reprint author), Texas A&M Univ, Dept Biomed Engn, College Stn, TX 77843 USA. RI Ericson, Milton/H-9880-2016 OI Ericson, Milton/0000-0002-6628-4865 FU NIH [5R01-GM077150] FX This research was funded by a bioengineering research partnership (BRP) grant from NIH, (#5R01-GM077150). NR 21 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9360-6 J9 PROC SPIE PY 2013 VL 8591 AR 859106 DI 10.1117/12.2003352 PG 6 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BFX14 UT WOS:000321740300006 ER PT J AU Hussey, SE Liang, HY Costford, SR Klip, A DeFronzo, RA Sanchez-Avila, A Ely, B Musi, N AF Hussey, Sophie E. Liang, Hanyu Costford, Sheila R. Klip, Amira DeFronzo, Ralph A. Sanchez-Avila, Alicia Ely, Brian Musi, Nicolas TI TAK-242, a small-molecule inhibitor of Toll-like receptor 4 signalling, unveils similarities and differences in lipopolysaccharide- and lipid-induced inflammation and insulin resistance in muscle cells SO BIOSCIENCE REPORTS LA English DT Article DE endotoxin; mitogen-activated protein kinase (MAPK); nuclear factor kappa B (NF-kappa B); saturated non-esterified fatty acid (NEFA); Toll-like receptor 4 (TLR4). ID SATURATED FATTY-ACIDS; NECROSIS-FACTOR-ALPHA; DIET-INDUCED OBESITY; KAPPA-B KINASE; SKELETAL-MUSCLE; PROTEIN-KINASE; GLUT4 TRANSLOCATION; 3-KINASE ACTIVITY; INNATE IMMUNITY; GLUCOSE-UPTAKE AB Emerging evidence suggests that TLR (Toll-like receptor) 4 and downstream pathways [MAPKs (mitogen-activated protein kinases) and NF-kappa B (nuclear factor kappa B)] play an important role in the pathogenesis of insulin resistance. LPS (lipopolysaccharide) and saturated NEFA (non-esterified fatty acids) activate TLR4, and plasma concentrations of these TLR4 ligands are elevated in obesity and Type 2 diabetes. Our goals were to define the role of TLR4 on the insulin resistance caused by LPS and saturated NEFA, and to dissect the independent contribution of LPS and NEFA to the activation of TLR4-driven pathways by employing TAK-242, a specific inhibitor of TLR4. LPS caused robust activation of the MAPK and NF-kappa B pathways in L6 myotubes, along with impaired insulin signalling and glucose transport. TAK-242 completely prevented the inflammatory response (MAPK and NF-kappa B activation) caused by LPS, and, in turn, improved LPS-induced insulin resistance. Similar to LPS, stearate strongly activated MAPKs, although stimulation of the NF-kappa B axis was modest. As seen with LPS, the inflammatory response caused by stearate was accompanied by impaired insulin action. TAK-242 also blunted stearate-induced inflammation; yet, the protective effect conferred by TAK-242 was partial and observed only on MAPKs. Consequently, the insulin resistance caused by stearate was only partially improved by TAK-242. In summary, TAK-242 provides complete and partial protection against LPS- and NEFA-induced inflammation and insulin resistance, respectively. Thus, LPS-induced insulin resistance depends entirely on TLR4, whereas NEFA works through TLR4-dependent and -independent mechanisms to impair insulin action. C1 [Hussey, Sophie E.; Liang, Hanyu; DeFronzo, Ralph A.; Ely, Brian; Musi, Nicolas] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Diabet Div, San Antonio, TX 78229 USA. [Hussey, Sophie E.; Liang, Hanyu; DeFronzo, Ralph A.; Sanchez-Avila, Alicia] Texas Diabet Inst, San Antonio, TX 78207 USA. [Costford, Sheila R.; Klip, Amira] Hosp Sick Children, Cell Biol Program, Toronto, ON M5G 1X8, Canada. [Musi, Nicolas] Univ Texas Hlth Sci Ctr San Antonio, Ctr Hlth Aging, San Antonio, TX 78229 USA. [Musi, Nicolas] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Musi, N (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Diabet Div, San Antonio, TX 78229 USA. EM musi@uthscsa.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [RO1-DK80157, RO1-DK089229, RO1-DK24092]; Canadian Institutes of Health Research [MT12601] FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [grant numbers RO1-DK80157 and RO1-DK089229 (to N.M.), and RO1-DK24092 (to R.A.D.)] and the Canadian Institutes of Health Research [grant number MT12601 (to A.K.)]. NR 49 TC 15 Z9 20 U1 1 U2 13 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0144-8463 J9 BIOSCIENCE REP JI Biosci. Rep. PY 2013 VL 33 BP 37 EP U56 AR UNSP e00004 DI 10.1042/BSR20120098 PN 1 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 175PJ UT WOS:000321242600004 PM 23050932 ER PT J AU Kepe, V Bordelon, Y Boxer, A Huang, SC Liu, J Thiede, FC Mazziotta, JC Mendez, MF Donoghue, N Small, G Barrio, JR AF Kepe, Vladimir Bordelon, Yvette Boxer, Adam Huang, Sung-Cheng Liu, Jie Thiede, Frederick C. Mazziotta, John C. Mendez, Mario F. Donoghue, Natacha Small, Garyw. Barrio, Jorge R. TI PET Imaging of Neuropathology in Tauopathies: Progressive Supranuclear Palsy SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE FDDNP; neuropathology; Parkinson's disease; positron emission tomography; progressive supranuclear palsy; tauopathy ID ALZHEIMERS-DISEASE; NEURODEGENERATIVE TAUOPATHIES; LIVING BRAIN; TAU; PROTEIN; PATHOLOGY; FILAMENTS; DEPOSITS; CRITERIA AB Objective: Currently [F-18] FDDNP is the only PET imaging probe with the ability to visualize hyperphosphorylated tau fibrillar aggregates in living subjects. In this work, we evaluate in vivo [F-18] FDDNP labeling of brain neuropathology, primarily tau fibrillar aggregates, in patients with progressive supranuclear palsy (PSP), a human tauopathy usually lacking amyloid-beta deposits. Methods: Fifteen patients with PSP received [F-18] FDDNP PET scanning. [F-18] FDDNP distribution volume ratios, in reference to cerebellar gray matter, were determined for cortical and subcortical areas and compared with those of patients with Parkinson's disease with short disease duration, and age-matched control subjects without neurodegenerative disorders. Results: [F-18] FDDNP binding was present in subcortical areas (e.g., striatum, thalamus, subthalamic region, midbrain, and cerebellar white matter) regardless of disease severity, with progressive subcortical and cortical involvement as disease severity increased. Brain patterns of [F-18] FDDNP binding were entirely consistent with the known pathology distribution for PSP. High midbrain and subthalamic region [F-18] FDDNP binding was distinctive for PSP subjects and separated them from controls and patients with Parkinson's disease. Conclusions: These results provide evidence that [F-18] FDDNP is a sensitive in vivo PET imaging probe to map and quantify the dynamic regional localization of tau fibrillar aggregates in PSP. Furthermore, [F-18] FDDNP PET may provide a tool to detect changes in tau pathology distribution either associated with disease progression or as a treatment biomarker for future tau-specific therapies. Patterns of [F-18] FDDNP binding may also be useful in diagnosis early in disease presentation when clinical distinction among neurodegenerative disorders is often difficult. C1 [Kepe, Vladimir; Huang, Sung-Cheng; Liu, Jie; Barrio, Jorge R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Bordelon, Yvette; Thiede, Frederick C.; Mazziotta, John C.; Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Mendez, Mario F.; Donoghue, Natacha; Small, Garyw.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. [Donoghue, Natacha] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Boxer, Adam] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA. [Mendez, Mario F.] VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. RP Barrio, JR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, CHS B2-086A,694817,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM jbarrio@mednet.ucla.edu FU National Institutes of Health [P01AG025831, R01AG038791, R01AG031278, R01AG034499, P50AG16570]; Tau Research Consortium; Elizabeth and Thomas Plott Endowment in Gerontology FX Supported by the National Institutes of Health (P01AG025831, R01AG038791, R01AG031278, R01AG034499, P50AG16570) and by the Tau Research Consortium. JRB gratefully acknowledges support from the Elizabeth and Thomas Plott Endowment in Gerontology. No company provided support of any kind for this study. Special thanks also to Dr. N. Satyamurthy and cyclotron staff and J. Williams and the Nuclear Medicine Clinic staff for their support with the scanning protocols. NR 35 TC 38 Z9 39 U1 1 U2 11 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2013 VL 36 IS 1 BP 145 EP 153 DI 10.3233/JAD-130032 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 159FJ UT WOS:000320030200013 PM 23579330 ER PT J AU Collins, MP Liu, CF Taylor, L Souza, PE Yueh, B AF Collins, Margaret P. Liu, Chuan-Fen Taylor, Leslie Souza, Pamela E. Yueh, Bevan TI Hearing aid effectiveness after aural rehabilitation: Individual versus group trial results SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE education; group visits; health resources; health services research; hearing aids; hearing loss; outcome assessment; patient satisfaction; rehabilitation of hearing impaired; Veterans ID HEALTH MAINTENANCE ORGANIZATION; BEHAVIORAL TREATMENT APPROACH; RANDOMIZED CONTROLLED-TRIAL; BASE-LINE CHARACTERISTICS; CHRONIC CARE CLINICS; 2-YEAR FOLLOW-UP; AUDIOLOGICAL REHABILITATION; COMMUNICATION COURSE; AUDITORY IMPAIRMENT; GROUP VISITS AB We designed this noninferiority randomized trial to determine (1) if group hearing aid fitting visits and group hearing aid follow-up visits were at least as effective as individual visits in terms of hearing-related function (measured with the Inner Effectiveness of Auditory Rehabilitation [EAR] scale) and adherence, and (2) if group visits were less costly over the 6 mo postfitting period. For 644 participants randomized to receive their hearing aid visits in an individual or group format at the Department of Veterans Affairs Puget Sound Health Care System, 6 mo outcomes showed no significant differences in Timer EAR scores between individual and group fitting (p = 0.53) or follow-up (p = 0.11), or in the number of hours per day hearing aids were worn between individual and group fitting (p = 0.90) or follow-up (p = 0.24). We found significantly higher cost for individual compared with group fitting (p < 0.001) and follow-up (p < 0.001). We conclude that outcomes for group hearing aid fitting and hearing aid follow-up visits were not inferior to individual hearing aid fitting and follow-up visits, with group fitting and follow-up visits yielding cost savings. C1 [Collins, Margaret P.; Liu, Chuan-Fen; Taylor, Leslie; Yueh, Bevan] Dept Vet Affairs VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. [Collins, Margaret P.; Yueh, Bevan] Univ Washington, Dept Med Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. [Liu, Chuan-Fen; Yueh, Bevan] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Souza, Pamela E.] Northwestern Univ, Dept Commun Sci & Disorders, Evanston, IL USA. [Souza, Pamela E.] Univ Washington, Dept Speech & Hearing Sci, Seattle, WA 98195 USA. [Yueh, Bevan] Univ Minnesota, Dept Otolaryngol Head & Neck Surg, Minneapolis, MN USA. [Yueh, Bevan] VA Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA 98101 USA. RP Collins, MP (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM margaret.collins@va.gov RI Liu, Chang/B-7249-2009 OI Yueh, Bevan/0000-0003-1380-1053 FU VA, Office of Research and Development, Health Services Research and Development [SLI 04-265] FX This material was based on work supported by VA, Office of Research and Development, Health Services Research and Development (project SLI 04-265). NR 40 TC 6 Z9 7 U1 3 U2 17 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2013 VL 50 IS 4 BP 585 EP 598 DI 10.1682/JRRD.2012.03.0049 PG 14 WC Rehabilitation SC Rehabilitation GA 179RS UT WOS:000321539600015 PM 23934877 ER PT S AU Luttrell, LM AF Luttrell, Louis M. BE Luttrell, LM TI PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE The Molecular Biology of Arrestins PREFACE SO MOLECULAR BIOLOGY OF ARRESTINS SE Progress in Molecular Biology and Translational Science LA English DT Editorial Material; Book Chapter C1 [Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Luttrell, Louis M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. RP Luttrell, LM (reprint author), Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-394440-5 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2013 VL 118 BP XV EP XV PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFY19 UT WOS:000321874600001 PM 23764066 ER PT S AU Luttrell, LM Miller, WE AF Luttrell, Louis M. Miller, William E. BE Luttrell, LM TI Arrestins as Regulators of Kinases and Phosphatases SO MOLECULAR BIOLOGY OF ARRESTINS SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID PROTEIN-COUPLED RECEPTOR; G-BETA-GAMMA; ANGIOTENSIN-II RECEPTOR; NUCLEAR EXPORT SIGNAL; KAPPA-B ACTIVATION; BETA(2)-ADRENERGIC RECEPTOR; C-SRC; TYROSINE-KINASE; ERK ACTIVATION; CLATHRIN ADAPTER AB The discovery that, in addition to mediating G protein-coupled receptor (GPCR) desensitization and endocytosis, arrestins bind to diverse catalytically active nonreceptor proteins and act as ligand-regulated signaling scaffolds led to a paradigm shift in the study of GPCR signal transduction. Research over the past decade has solidified the concept that arrestins confer novel GPCR-signaling capacity by recruiting protein and lipid kinase, phosphatase, phosphodiesterase, and ubiquitin ligase activity into receptor-based multiprotein "signalsome" complexes. Signalsomes regulate downstream pathways controlled by Sic family nonreceptor tyrosine kinases, mitogen-activated protein kinases, protein kinase B (AKT), glycogen synthase kinase 3, protein phosphatase 2A, nuclear factor-kappa B, and several others, imposing spatial and temporal control on their function. While many arrestin-bound kinases and phosphatases are involved in the control of cytoskeletal rearrangement, vesicle endocytosis, exocytosis, and cell migration, other signals reach into the nucleus, affecting cell proliferation, apoptosis, and survival. Indeed, the kinase/phosphatase network regulated by arrestins may be fully as diverse as that regulated by heterotrimeric G proteins. C1 [Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Luttrell, Louis M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. [Miller, William E.] Univ Cincinnati, Coll Med, Dept Mol Genet, Cincinnati, OH USA. RP Luttrell, LM (reprint author), Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. FU NCATS NIH HHS [UL1 TR000077]; NIDDK NIH HHS [DK55524] NR 120 TC 20 Z9 20 U1 2 U2 6 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-394440-5 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2013 VL 118 BP 115 EP 147 DI 10.1016/B978-0-12-394440-5.00005-X PG 33 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFY19 UT WOS:000321874600006 PM 23764052 ER PT S AU Luttrell, LM AF Luttrell, Louis M. BE Luttrell, LM TI Arrestin Pathways as Drug Targets SO MOLECULAR BIOLOGY OF ARRESTINS SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID PROTEIN-COUPLED RECEPTORS; RESONANCE ENERGY-TRANSFER; PARATHYROID-HORMONE PTH; GROWTH-FACTOR RECEPTOR; BETA-ARRESTIN; BETA(2)-ADRENERGIC RECEPTOR; BIASED-AGONISM; IN-VIVO; TYROSINE PHOSPHORYLATION; PHARMACOLOGICAL AGONISM AB Our growing appreciation of the pluridimensionality of G protein-coupled receptor (GPCR) efficacy, coupled with the phenomenon of orthosteric ligand "bias," offers the prospect of drugs that selectively modulate different aspects of GPCR function for therapeutic benefit. As the best-studied non-G protein effectors, arrestins have been shown to mediate a wide range of GPCR signals, and arrestin pathway-selective ligands have been identified for several receptors. When viewed from the perspective of short term in vitro assays, such "biased" agonists appear to activate a subset of the response profile produced by a conventional agonist. Yet, when examined in vivo, the limited data available suggest that biased ligand effects can diverge from their conventional counterparts in ways that cannot be predicted from their in vitro efficacy profile. While some widely conserved arrestin-regulated biological processes are becoming apparent, what is lacking at present is a rational framework for relating the in vitro efficacy of a "biased" agonist to its in vivo actions that will aid drug discovery programs in identifying "biased" ligands with the desired biological effects. C1 [Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Luttrell, Louis M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. RP Luttrell, LM (reprint author), Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. FU NIDDK NIH HHS [DK55524] NR 103 TC 12 Z9 12 U1 0 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-394440-5 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2013 VL 118 BP 469 EP 497 DI 10.1016/B978-0-12-394440-5.00018-8 PG 29 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFY19 UT WOS:000321874600019 PM 23764065 ER PT J AU Rosenberg, DE Turner, AP Littman, AJ Williams, RM Norvell, DC Hakimi, KM Czerniecki, JM AF Rosenberg, Dori E. Turner, Aaron P. Littman, Alyson J. Williams, Rhonda M. Norvell, Dan C. Hakimi, Kevin M. Czerniecki, Joseph M. TI Body mass index patterns following dysvascular lower extremity amputation SO DISABILITY AND REHABILITATION LA English DT Article DE Mobility disability; obesity; prosthesis ID LOWER-LIMB AMPUTATION; RISK-FACTORS; SELF-REPORT; OBESITY; AMPUTEES; ADULTS; PREVALENCE; OVERWEIGHT; WEIGHT; UNDERWEIGHT AB Purpose: Using preliminary data, we examined: (i) patterns of body mass index (BMI) over the year following amputation by amputation level and (ii) the association between BMI and mobility and prosthetic device use. Method: Patients from three medical centers undergoing dysvascular amputation (N = 87; M age = 62) participated in interviews pre-surgically and at 6 weeks, 4 months, and 12 months following amputation. The main outcome was self-reported BMI, adjusting for limb weight lost due to amputation. Additional outcomes were mobility and time spent using and walking in a prosthetic device. Results: Adjusted BMI slightly decreased at 6 weeks (pre-surgery M = 31.2; 6 weeks M = 30.3) and 4 months (M = 30.7) but exceeded baseline levels by 12 months (M = 31.7). There were no significant BMI differences by amputation level. In multivariable analyses, higher pre-surgical BMI was associated with fewer hours of prosthetic device walking at month 4 (beta = -0.49) and poorer overall mobility at month 12 (beta = -0.22). Conclusions: BMI increased at one year following amputation surgery. Higher pre-surgical BMI was associated with poorer mobility and prosthetic device use. Interventions are needed to prevent excess weight gain in the year following amputation. C1 [Rosenberg, Dori E.; Turner, Aaron P.; Williams, Rhonda M.; Hakimi, Kevin M.; Czerniecki, Joseph M.] VA Puget Sound Hlth Care Syst, Rehabil Care Serv, Seattle, WA 98108 USA. [Rosenberg, Dori E.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA. [Turner, Aaron P.; Williams, Rhonda M.; Hakimi, Kevin M.; Czerniecki, Joseph M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Littman, Alyson J.] Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Littman, Alyson J.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Norvell, Dan C.] Spectrum Res, Tacoma, WA USA. RP Turner, AP (reprint author), VA Puget Sound Hlth Care Syst, Rehabil Care Serv, 1660 S Columbian Way, Seattle, WA 98108 USA. EM aaron.turner@med.va.gov OI Turner, Aaron/0000-0001-6897-8003 FU US Department of Veterans Affairs, Office of Research and Development, Rehabilitation Research and Development Merit Review [A41241, CDA B4927W, CDA 6982]; NIH Kirschstein NRSA award [2T32HD007424-19] FX This material is based upon work supported by the US Department of Veterans Affairs, Office of Research and Development, Rehabilitation Research and Development Merit Review A41241 (Joseph Czerniecki, PI), CDA B4927W (Aaron Turner, PI) CDA 6982 (Alyson Littman, PI) and NIH Kirschstein NRSA award (2T32HD007424-19) for Dori Rosenberg. NR 29 TC 8 Z9 8 U1 0 U2 14 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0963-8288 J9 DISABIL REHABIL JI Disabil. Rehabil. PY 2013 VL 35 IS 15 BP 1269 EP 1275 DI 10.3109/09638288.2012.726690 PG 7 WC Rehabilitation SC Rehabilitation GA 169VM UT WOS:000320808700003 PM 23094934 ER PT J AU Faestel, PM Littell, CT Vitiello, MV Forsberg, CW Littman, AJ AF Faestel, Paul M. Littell, Christopher T. Vitiello, Michael V. Forsberg, Christopher W. Littman, Alyson J. TI Perceived Insufficient Rest or Sleep among Veterans: Behavioral Risk Factor Surveillance System 2009 SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE Insufficient sleep; Veterans health; Behavior Risk Factor Surveillance System ID POSTTRAUMATIC-STRESS-DISORDER; UNITED-STATES; DURATION; DISTURBANCES; AFGHANISTAN; TRANSITION; DISABILITY; DEPLOYMENT; WORK; LIFE AB Study Objectives: Sleep problems are of particular concern among the active duty military population as factors such as inconsistent work hours and deployment may compromise adequate sleep and adversely impact performance. However, few prior studies have investigated whether the prevalence of sleep problems differ between Veterans and demographically similar non-Veterans. The purpose of this study is to investigate whether self-reported insufficient rest or sleep varies in relation to Veteran status and to identify high-risk groups of Veterans. Methods: This study used data from the 2009 Behavioral Risk Factor Surveillance System (analyzed in 2011), a state based national telephone survey of non-institutionalized US adults. Insufficient rest was assessed in 411,313 adults aged 21 and older, of whom 55,361 were Veterans. Sleep duration was assessed in 6 states (n = 4,936 Veterans and 30,983 non-Veterans). Model-based direct rate adjustment was used to estimate the prevalence of insufficient rest or sleep while controlling for confounding. Multivariable logistic regression was used to estimate odds ratios of insufficient sleep or rest in subgroups of Veterans. Results: After multivariable adjustment, insufficient rest or sleep (22.7% vs. 21.1%, p < 0.001) and short sleep duration (< 7 h/night, 34.9% vs. 31.3%, p = 0.026) were more common among Veterans than non-Veterans. When the Veteran group was further divided among newly transitioned (<= 12 months) and longer-term Veterans (> 12 months), the overall test for a difference was not statistically significant between groups, mainly because there was little difference in sleep between the two groups of Veterans. High-risk Veteran subgroups included those who were 21-44 years of age (vs. 65-74), women, non-whites, current smokers, obese, unable to work, and those in poor health. Conclusions: This study suggests that Veterans have a high burden of sleep problems and identifies subgroups that should be targeted to receive interventions and enhanced education regarding insufficient sleep. C1 [Faestel, Paul M.; Littell, Christopher T.] Madigan Healthcare Syst, Dept Prevent Med, Tacoma, WA USA. [Vitiello, Michael V.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Forsberg, Christopher W.; Littman, Alyson J.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Littman, Alyson J.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Faestel, PM (reprint author), MEDDAC, Dept Prevent Med, Mt Belvedere Dr,Bldg 10720, Ft Drum, NY 13602 USA. EM paul.faestel@us.army.mil OI Vitiello, Michael/0000-0002-9776-0473 FU Cooperative Studies Program, Department of Veterans Affairs; Puget Sound VA Medical Center; VA Rehabilitation Research and Development Career Development Award [6982] FX The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of Defense or the Department of Veterans Affairs. This material is the result of work partly supported with resources and the use of facilities from the Cooperative Studies Program, Department of Veterans Affairs, and the Puget Sound VA Medical Center. Dr. Littman was supported by a VA Rehabilitation Research and Development Career Development Award (#6982). Institution at which work was performed: Madigan Healthcare System, Tacoma, WA. NR 35 TC 14 Z9 14 U1 0 U2 4 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2013 VL 9 IS 6 BP 577 EP 584 DI 10.5664/jcsm.2754 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 164UP UT WOS:000320436000009 PM 23772191 ER PT J AU Hill, M Mor, MK Travis, L Ward, T Palevsky, PM Ramkumar, M Weisbord, SD AF Hill, Marlene Mor, Maria K. Travis, Lesli Ward, Tina Palevsky, Paul M. Ramkumar, Mohan Weisbord, Steven D. TI Renal function following fistulography in patients with advanced chronic kidney disease SO RENAL FAILURE LA English DT Article DE Acute kidney injury; contrast; dialysis access; fistulogram; glomerular filtration rate ID CONTRAST-INDUCED NEPHROPATHY; CORONARY-ANGIOGRAPHY; ARTERIOVENOUS-FISTULA; RISK; MORTALITY; RADIOCONTRAST; INTERVENTION; OUTCOMES; INJURY; HEMODIALYSIS AB Background/aims: Contrast-induced acute kidney injury (CIAKI) is associated with an accelerated progression of underlying chronic kidney disease (CKD). We sought to characterize the rate of loss of kidney function following fistulography in patients with advanced CKD. Materials/methods: We identified all patients with stage 4 or 5 non-dialysis-dependent CKD who underwent fistulography with iodinated contrast for non-maturing arteriovenous fistulae between 1 January 2010 and 30 November 2011. We recorded all eGFR values measured during the 6 months prior to and 6 months following the procedure, the volume and type of contrast, use of intravenous fluid and N-acetylcysteine (NAC), and timing of dialysis initiation following the procedure. We used mixed linear regression with random effects to compare the composite slope of decline in eGFR prior to and following fistulography. Results: Overall, 27 patients underwent a total of 44 fistulograms. The mean age of the patients was 66 years and mean baseline eGFR was 16.7 +/- 5 mL/min/1.73m(2). Patients received a median volume of contrast of 12 mL [IQR 10-20]. None of the patients initiated acute dialysis within weeks following the procedure. In unadjusted analyses, there was no statistically significant change in the rate of decline in eGFR following fistulography compared to pre-procedure (0.14 mL/min/month versus -0.14 mL/min/month, p = 0.11). In analyses that adjusted for procedural, demographic and clinical variables, the decline in eGFR following fistulography was not statistically different than before the procedure (0.15 mL/min/month versus -0.14 mL/min/month, p = 0.11). Conclusions: Fistulography with small volumes of iodinated contrast in patients with advanced CKD does not result in more rapid progression of underlying CKD. C1 [Hill, Marlene; Travis, Lesli; Ward, Tina; Palevsky, Paul M.; Ramkumar, Mohan; Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Renal Sect, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. [Mor, Maria K.; Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Palevsky, Paul M.; Ramkumar, Mohan; Weisbord, Steven D.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, 7E Room 120,111F-U, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 NR 25 TC 0 Z9 0 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0886-022X J9 RENAL FAILURE JI Ren. Fail. PY 2013 VL 35 IS 6 BP 791 EP 795 DI 10.3109/0886022X.2013.794432 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 161MS UT WOS:000320197800001 PM 23713575 ER PT J AU La Fountaine, MF Wecht, JM Cirnigliaro, CM Kirshblum, SC Spungen, AM Bauman, WA AF La Fountaine, Michael F. Wecht, Jill M. Cirnigliaro, Christopher M. Kirshblum, Steven C. Spungen, Ann M. Bauman, William A. TI Testosterone Replacement Therapy Improves QTaVI in Hypogonadal Men with Spinal Cord Injury SO NEUROENDOCRINOLOGY LA English DT Article DE Spinal cord injury; Hypogonadism; Testosterone; QT interval; Autonomic nervous system; QT variance ID AUTONOMIC NERVOUS-SYSTEM; QT INTERVAL VARIABILITY; VENTRICULAR REPOLARIZATION; HEART-RATE; CARDIOVASCULAR-DISEASE; HEALTHY-MEN; RISK; TETRAPLEGIA; EXPRESSION; MORTALITY AB Aim: To determine the effect of a 12-month intent-to-treat testosterone (T) replacement therapy (TRT) trial on QTa interval variability (QTaVI) in hypogonadal (HG) men with spinal cord injury (SCI). Method: A prospective, controlled 12-month TRT trial was completed in 22 healthy, chronic, nonambulatory men with SCI. Based on serum T concentration, subjects were designated as HG (<= 11.3 nmol/l) or eugonadal (EG >= 11.4 nmol/l). Digital 3-lead electrocardiograms were performed. Heart rate (RR), heart rate variability [including total power (TPRR), low frequency (LFRR) and high frequency (HFRR)], QTa, QTe, and RT intervals, QTC (Bazett formula), QTVN, and QTaVI were calculated and evaluated at baseline and at 12 months. Lipoprotein profiles (triglycerides, total cholesterol, low-density and high-density lipoproteins) were obtained at the respective time points. Results: Based on serum T concentration, 13 subjects were designated as HG and 11 as EG. During the trial, there were no group differences for RR, QTa, QTe or RT intervals, QTC, TPRR, HFRR, or lipoproteins. The HG group was older (p < 0.05) and their LFRR was lower (p < 0.05) at baseline. At baseline, QTaVI was significantly greater in the HG group compared to the EG group [-0.17 (0.92) vs. -1.07 (0.90); p < 0.05]. After TRT, this group difference was no longer present [-0.44 (0.87) vs. -0.65 (0.85)] and the change in the HG group was significant (p < 0.05). Conclusion: Hypogonadism in men with SCI was associated with elevated QTaVI at baseline. After 12 months of physiological TRT, the QTaVI improved in association with raising T into the normal range. These findings occurred independently of the prolongation of the QT interval. Copyright (C) 2013 S. Karger AG, Basel C1 [La Fountaine, Michael F.; Wecht, Jill M.; Cirnigliaro, Christopher M.; Spungen, Ann M.; Bauman, William A.] James J Peters VA Med Ctr, VA RR&D Ctr Excellence Med Consequences Spinal Co, Bronx, NY 10468 USA. [La Fountaine, Michael F.; Wecht, Jill M.; Spungen, Ann M.; Bauman, William A.] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA. [La Fountaine, Michael F.; Spungen, Ann M.; Bauman, William A.] Mt Sinai Hosp, Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Wecht, Jill M.; Spungen, Ann M.; Bauman, William A.] Mt Sinai Hosp, Mt Sinai Sch Med, Dept Rehabil Med, New York, NY 10029 USA. [La Fountaine, Michael F.] Seton Hall Univ, Sch Hlth & Med Sci, Dept Phys Therapy, S Orange, NJ 07079 USA. [Kirshblum, Steven C.] Kessler Inst Rehabil, W Orange, NJ USA. [Kirshblum, Steven C.] Univ Med & Dent New Jersey, Dept Phys Med & Rehabil, Newark, NJ 07103 USA. RP La Fountaine, MF (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Room 7A-13,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM michael.lafountaine@va.gov NR 31 TC 1 Z9 1 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2013 VL 97 IS 4 BP 341 EP 346 DI 10.1159/000347070 PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 161BV UT WOS:000320166900007 PM 23343764 ER PT J AU Whelan, SP Zuckerbraun, BS AF Whelan, Sean P. Zuckerbraun, Brian S. TI Mitochondrial Signaling: Forwards, Backwards, and In Between SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY LA English DT Review ID UNFOLDED PROTEIN RESPONSE; INDUCED ROS RELEASE; RETROGRADE RESPONSE; SACCHAROMYCES-CEREVISIAE; STRESS RESPONSES; GENE-EXPRESSION; RNA-POLYMERASE; CELL-DEATH; ACTIVATION; YEAST AB Mitochondria are semiautonomous organelles that are a defining characteristic of almost all eukaryotic cells. They are vital for energy production, but increasing evidence shows that they play important roles in a wide range of cellular signaling and homeostasis. Our understanding of nuclear control of mitochondrial function has expanded over the past half century with the discovery of multiple transcription factors and cofactors governing mitochondrial biogenesis. More recently, nuclear changes in response to mitochondrial messaging have led to characterization of retrograde mitochondrial signaling, in which mitochondria have the ability to alter nuclear gene expression. Mitochondria are also integral to other components of stress response or quality control including ROS signaling, unfolded protein response, mitochondrial autophagy, and biogenesis. These avenues of mitochondrial signaling are discussed in this review. C1 [Zuckerbraun, Brian S.] Univ Pittsburgh, Dept Gen Surg, Pittsburgh, PA 15206 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. RP Zuckerbraun, BS (reprint author), Univ Pittsburgh, Dept Gen Surg, F1200 PUH,200 Lothrop St, Pittsburgh, PA 15206 USA. EM zuckerbraunbs@upmc.edu NR 85 TC 5 Z9 5 U1 0 U2 9 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1942-0900 EI 1942-0994 J9 OXID MED CELL LONGEV JI Oxidative Med. Cell. Longev. PY 2013 AR UNSP 351613 DI 10.1155/2013/351613 PG 10 WC Cell Biology SC Cell Biology GA 162FT UT WOS:000320251600001 ER PT J AU Claxton, A Baker, LD Wilkinson, CW Trittschuh, EH Chapman, D Watson, GS Cholerton, B Plymate, SR Arbuckle, M Craft, S AF Claxton, Amy Baker, Laura D. Wilkinson, Charles W. Trittschuh, Emily H. Chapman, Darla Watson, G. Stennis Cholerton, Brenna Plymate, Stephen R. Arbuckle, Matthew Craft, Suzanne TI Sex and ApoE Genotype Differences in Treatment Response to Two Doses of Intranasal Insulin in Adults with Mild Cognitive Impairment or Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; insulin; intranasal drug administration; mild cognitive impairment; randomized clinical trials ID APOLIPOPROTEIN-E GENOTYPE; AMYLOID PRECURSOR PROTEIN; CENTRAL-NERVOUS-SYSTEM; GLUCOSE-METABOLISM; RATING-SCALE; OLDER-ADULTS; MEMORY; BRAIN; SENSITIVITY; DEMENTIA AB A previous clinical trial demonstrated that four months of treatment with intranasal insulin improves cognition and function for patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI), but prior studies suggest that response to insulin treatment may differ by sex and ApoE epsilon 4 carriage. Thus, responder analyses using repeated measures analysis of covariance were completed on the trial's 104 participants with MCI or AD who received either placebo or 20 or 40 IU of insulin for 4 months, administered by a nasal delivery device. Results indicate that men and women with memory impairment responded differently to intranasal insulin treatment. On delayed story memory, men and women showed cognitive improvement when taking 20 IU of intranasal insulin, but only men showed cognitive improvement for the 40 IU dose. The sex difference was most apparent for ApoE epsilon 4 negative individuals. For the 40 IU dose, ApoE epsilon 4 negative men improved while ApoE epsilon 4 negative women worsened. Their ApoE epsilon 4 positive counterparts remained cognitively stable. This sex effect was not detected in functional measures. However, functional abilities were relatively preserved for women on either dose of intranasal insulin compared with men. Unlike previous studies with young adults, neither men nor women taking intranasal insulin exhibited a significant change in weight over 4 months of treatment. C1 [Claxton, Amy; Wilkinson, Charles W.; Trittschuh, Emily H.; Chapman, Darla; Watson, G. Stennis; Cholerton, Brenna; Plymate, Stephen R.; Arbuckle, Matthew] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Claxton, Amy; Wilkinson, Charles W.; Trittschuh, Emily H.; Chapman, Darla; Watson, G. Stennis; Cholerton, Brenna; Plymate, Stephen R.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Baker, Laura D.; Craft, Suzanne] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC 27157 USA. RP Craft, S (reprint author), Wake Forest Sch Med, Dept Internal Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM suzcraft@wakehealth.edu FU National Institute of Aging [AG027415, T32 AG000258]; Department of Veterans Affairs; Veterans Affairs Puget Sound Health Care System, Seattle, Washington FX This research was supported by National Institute of Aging grants AG027415 (to Dr. Craft) and T32 AG000258 (to Dr. Claxton), and the Department of Veterans Affairs. This material is the result of work supported in part by resources from the Veterans Affairs Puget Sound Health Care System, Seattle, Washington. NR 43 TC 37 Z9 38 U1 2 U2 14 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2013 VL 35 IS 4 BP 789 EP 797 DI 10.3233/JAD-122308 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 149TW UT WOS:000319345300012 PM 23507773 ER PT J AU Cholerton, BA Zabetian, CP Quinn, JF Chung, KA Peterson, A Espay, AJ Revilla, FJ Devoto, J Watson, GS Hu, SC Edwards, KL Montine, TJ Leverenz, JB AF Cholerton, Brenna A. Zabetian, Cyrus P. Quinn, Joseph F. Chung, Kathryn A. Peterson, Amie Espay, Alberto J. Revilla, Fredy J. Devoto, Johnna Watson, G. Stennis Hu, Shu-Ching Edwards, Karen L. Montine, Thomas J. Leverenz, James B. TI Pacific Northwest Udall Center of Excellence Clinical Consortium: Study Design and Baseline Cohort Characteristics SO JOURNAL OF PARKINSONS DISEASE LA English DT Article DE Cognition; cohort studies; dementia; mild cognitive impairment; movement disorders; Parkinson disease ID MILD COGNITIVE IMPAIRMENT; PARKINSONS-DISEASE; DIAGNOSTIC-CRITERIA; NORWEGIAN PARKWEST; ALZHEIMERS-DISEASE; GENDER-DIFFERENCES; DEMENTIA; PREVALENCE; INCIDENT; PROFILE AB Background: The substantial proportion of individuals with Parkinson's disease (PD) who have or are expected to develop concomitant cognitive impairment emphasizes the need for large, well-characterized participant cohorts to serve as a basis for research into the causes, manifestations, and potential treatments of cognitive decline in those with PD. Objective: To establish a multi-site clinical core that cognitively and clinically characterizes patients with PD by obtaining quality longitudinal clinical, neuropsychological, and validated biomarker data. Methods: Six hundred nineteen participants with idiopathic PD (68.0 +/- 9.1 years, 7.1 +/- 6.2 years since diagnosis, 70% males) were enrolled in the Pacific Northwest Udall Center (PANUC), one of the Morris K. Udall Centers of Excellence for Parkinson's Research, Clinical Consortium and underwent comprehensive clinical and neuropsychological assessment. Participants were diagnosed with no cognitive impairment (PD-NCI), mild cognitive impairment (PD-MCI), or dementia (PDD) at a diagnostic consensus conference. Results: A substantial proportion of the overall sample was diagnosed with cognitive impairment at baseline: 22% with PDD and 59% with PD-MCI. A higher rate of cognitive impairment was observed in men than women (87% vs. 68%, p < 0.0001), despite a higher level of education. Most patients older than 50 years at the time of diagnosis and with disease duration greater than 10 years were cognitively impaired or demented. Conclusions: The PANUC Clinical Consortium is a clinically and cognitively well-characterized cohort of patients with PD. Baseline cohort characteristics demonstrate a high rate of cognitive impairment in the sample, as well as potential sex differences with regard to cognitive diagnosis. The PANUC Clinical Consortium, with its access to biomarker, genetic, and autopsy data, provides an excellent foundation for detailed research related to cognitive impairment in PD. C1 [Cholerton, Brenna A.; Zabetian, Cyrus P.; Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Zabetian, Cyrus P.; Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. [Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Cholerton, Brenna A.; Watson, G. Stennis; Leverenz, James B.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Zabetian, Cyrus P.; Hu, Shu-Ching; Leverenz, James B.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Edwards, Karen L.] Univ Washington, Sch Med, Dept Epidemiol, Seattle, WA USA. [Montine, Thomas J.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Quinn, Joseph F.; Chung, Kathryn A.; Peterson, Amie] Portland VA Med Ctr, Portland, OR USA. [Quinn, Joseph F.; Chung, Kathryn A.; Peterson, Amie] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Espay, Alberto J.; Revilla, Fredy J.; Devoto, Johnna] Univ Cincinnati, Dept Neurol & Rehabil Med, Cincinnati, OH USA. RP Cholerton, BA (reprint author), VA Puget Sound Hlth Care Syst, GRECC A-182,9600 Vet Dr SW, Tacoma, WA 98493 USA. EM bchol@u.washington.edu OI Zabetian, Cyrus/0000-0002-7739-4306; Espay, Alberto/0000-0002-3389-136X FU Nancy and Buster Alvord Endowment; Department of Veterans Affairs; [NS062684]; [NS065070] FX This research was supported by NS062684 and NS065070, the Nancy and Buster Alvord Endowment, and the Department of Veterans Affairs. The funding sources did not provide scientific input for the study. NR 50 TC 16 Z9 16 U1 4 U2 13 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1877-7171 J9 J PARKINSON DIS JI J. Parkinsons Dis. PY 2013 VL 3 IS 2 BP 205 EP 214 DI 10.3233/JPD-130189 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 149SE UT WOS:000319340700011 PM 23938350 ER PT J AU Staton, LJ Estrada, C Panda, M Ortiz, D Roddy, D AF Staton, Lisa J. Estrada, Carlos Panda, Mukta Ortiz, David Roddy, Donna TI A multimethod approach for cross-cultural training in an internal medicine residency program SO MEDICAL EDUCATION ONLINE LA English DT Article DE cultural competence; residency education; community resources; web-based curriculum; racial disparities; internal medicine ID ETHNIC DISPARITIES; HEALTH-CARE; PREPAREDNESS; COMPETENCE; EDUCATION AB Background: Cultural competence training in residency is important to improve learners' confidence in cross-cultural encounters. Recognition of cultural diversity and avoidance of cultural stereotypes are essential for health care providers. Methods: We developed a multimethod approach for cross-cultural training of Internal Medicine residents and evaluated participants' preparedness for cultural encounters. The multimethod approach included (1) a conference series, (2) a webinar with a national expert, (3) small group sessions, (4) a multicultural social gathering, (5) a Grand Rounds presentation on cross-cultural training, and (6) an interactive, online case-based program. Results: The program had 35 participants, 28 of whom responded to the survey. Of those, 16 were white (62%), and residents comprised 71% of respondents (n = 25). Following training, 89% of participants were more comfortable obtaining a social history. However, prior to the course only 27% were comfortable caring for patients who distrust the US system and 35% could identify religious beliefs and customs which impact care. Most (71%) believed that the training would help them give better care for patients from different cultures, and 63% felt more comfortable negotiating a treatment plan following the course. Conclusions: Multimethod training may improve learners' confidence and comfort with cross-cultural encounters, as well as lay the foundation for ongoing learning. Follow-up is needed to assess whether residents' perceived comfort will translate into improved patient outcomes. C1 [Staton, Lisa J.; Panda, Mukta] Univ Tennessee, Coll Med Chattanooga, Dept Internal Med, Chattanooga, TN 37403 USA. [Estrada, Carlos] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Estrada, Carlos] Univ Alabama Birmingham, Dept Internal Med, Birmingham, AL USA. [Ortiz, David; Roddy, Donna] BlueCross BlueShield Tennessee, Chattanooga, TN USA. RP Staton, LJ (reprint author), Univ Tennessee, Coll Med Chattanooga, Dept Internal Med, 975 East 3rd,Box 94, Chattanooga, TN 37403 USA. EM lisa.staton@erlanger.org NR 12 TC 0 Z9 0 U1 2 U2 9 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 1087-2981 J9 MED EDUC ONLINE JI Med. Educ. Online PY 2013 VL 18 BP 1 EP 6 AR 20352 DI 10.3402/meo.v18i0.20352 PG 6 WC Education & Educational Research SC Education & Educational Research GA 147WA UT WOS:000319198700001 PM 23683845 ER PT J AU Vianna, VF Bonfim, DC Cavalcanti, AD Fernandes, MC Kahn, SA Casado, PL Lima, IC Murray, SS Murray, EJB Duarte, MEL AF Vianna, Veronica Fernandes Bonfim, Danielle Cabral Cavalcanti, Amanda dos Santos Fernandes, Marco Cury Kahn, Suzana Assad Casado, Priscila Ladeira Lima, Inaya Correa Murray, Samuel S. Murray, Elsa J. Brochmann Leite Duarte, Maria Eugenia TI Late Adherent Human Bone Marrow Stromal Cells Form Bone and Restore the Hematopoietic Microenvironment In Vivo SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID MESENCHYMAL STEM-CELLS; OSTEOGENESIS; FIBROBLASTS; ASSAYS; NICHE AB Bone marrow stromal cells (BMSCs) are a valuable resource for skeletal regenerative medicine because of their osteogenic potential. In spite of the very general term "stem cell," this population of cells is far from homogeneous, and different BMSCs clones have greatly different phenotypic properties and, therefore, potentially different therapeutic potential. Adherence to a culture flask surface is a primary defining characteristic of BMSCs. We hypothesized that based on the adherence time we could obtain an enriched population of cells with a greater therapeutic potential. We characterized two populations of bone marrow-derived cells, those that adhered by three days (R-cells) and those that did not adhere by three days but did by six days (L-cells). Clones derived from L-cells could be induced into adipogenic, chondrogenic, and osteogenic differentiation in vitro. L-cells appeared to have greater proliferative capacity, as manifested by larger colony diameter and clones with higher CD146 expression. Only clones from L-cells developed bone marrow stroma in vivo. We conclude that the use of late adherence of BMSCs is one parameter that can be used to enrich for cells that will constitute a superior final product for cell therapy in orthopedics. C1 [Vianna, Veronica Fernandes; Bonfim, Danielle Cabral; Cavalcanti, Amanda dos Santos; Fernandes, Marco Cury; Kahn, Suzana Assad; Casado, Priscila Ladeira; Leite Duarte, Maria Eugenia] Natl Inst Traumatol & Orthopaed, Clin & Basic Res Div, BR-20940070 Rio De Janeiro, RJ, Brazil. [Vianna, Veronica Fernandes; Bonfim, Danielle Cabral; Leite Duarte, Maria Eugenia] Univ Fed Rio de Janeiro, Inst Biomed Sci, BR-21941970 Rio De Janeiro, RJ, Brazil. [Lima, Inaya Correa] Univ Fed Rio de Janeiro, COPPE, Lab Nucl Instrumentat, BR-21941970 Rio De Janeiro, RJ, Brazil. [Murray, Samuel S.; Murray, Elsa J. Brochmann] VA Greater Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. [Murray, Samuel S.; Murray, Elsa J. Brochmann] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. RP Vianna, VF (reprint author), Natl Inst Traumatol & Orthopaed, Clin & Basic Res Div, Ave Brasil 500, BR-20940070 Rio De Janeiro, RJ, Brazil. EM vvianna@into.saude.gov.br NR 29 TC 1 Z9 1 U1 2 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 J9 BIOMED RES INT JI Biomed Res. Int. PY 2013 AR 790842 DI 10.1155/2013/790842 PG 11 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 141KW UT WOS:000318725100001 ER PT J AU Scheff, SW Price, DA Schmitt, FA Roberts, KN Ikonomovic, MD Mufson, EJ AF Scheff, Stephen W. Price, Douglas A. Schmitt, Frederick A. Roberts, Kelly N. Ikonomovic, Milos D. Mufson, Elliott J. TI Synapse Stability in the Precuneus Early in the Progression of Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; early onset; episodic memory; synapses; synaptic plasticity ID MILD COGNITIVE IMPAIRMENT; POSTERIOR PARIETAL CORTEX; VOXEL-BASED MORPHOMETRY; PITTSBURGH-COMPOUND-B; DEFAULT-MODE NETWORK; RHESUS-MONKEY; EPISODIC MEMORY; EMISSION-TOMOGRAPHY; FRONTAL-CORTEX; AMYLOID BURDEN AB Amnestic mild cognitive impairment (aMCI) is considered to be one of the early stages in the progression from no cognitive impairment (NCI) to Alzheimer's disease (AD). Individuals with aMCI have increased levels of AD-type neuropathology in multiple regions of the neocortex and hippocampus and demonstrate a loss of synaptic connectivity. Recent neuroimaging studies have reported increased levels of C-11-PiB (Pittsburgh, compound B) in regions of the neocortex including the precuneus region of the medial parietal lobe. This cortical region has been implicated in episodic memory, which is disrupted early in the progression of AD. In this study, unbiased stereology coupled with electron microscopy was used to quantify total synaptic numbers in lamina 3 of the precuneus from short postmortem autopsy tissue harvested from subjects who died at different cognitive stages during the progression of AD. Individuals with aMCI did not reveal a statistically significant decline in total synapses compared to the NCI cohort while the AD group did show a modest but significant decline. Synaptic numbers failed to correlate with several different cognitive tasks including the Mini-Mental State Examination scores and episodic memory scores. Although levels of [H-3] PiB binding were elevated in both the aMCI and AD groups, it did not strongly correlate with synaptic counts. These results support the idea that despite increased amyloid load, the precuneus region does not show early changes in synaptic decline during the progression of AD. C1 [Scheff, Stephen W.; Price, Douglas A.; Schmitt, Frederick A.; Roberts, Kelly N.] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Ikonomovic, Milos D.] Ctr Geriatr Res Educ & Clin, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Mufson, Elliott J.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. RP Scheff, SW (reprint author), Univ Kentucky, Ctr Aging, 101 Sanders Brown, Lexington, KY 40536 USA. EM sscheff@email.uky.edu FU National Institute of Health [P01 AG14449, P30 AG0283883, P01 AG025204R01, AG027219, AG025204]; Mansbach Chair in Alzheimer's Disease FX This work was supported by the National Institute of Health grants: P01 AG14449; P30 AG0283883; P01 AG025204R01; AG027219, AG025204 and the Mansbach Chair in Alzheimer's Disease. We are indebted to the altruism of the participants in the SBCOA and the Religious Orders Study. The pathological diagnosis was performed by M. R. Markesbery and P. T. Nelson (SBCOA) and J. A. Schneider (Rush University Medical Center). NR 91 TC 18 Z9 18 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2013 VL 35 IS 3 BP 599 EP 609 DI 10.3233/JAD-122353 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 140AY UT WOS:000318627800016 PM 23478309 ER PT J AU Atwood, CW AF Atwood, Charles W., Jr. TI Progress Toward a Clearer Understanding of the Role of Bilevel Positive Airway Pressure Therapy for Obstructive Sleep Apnea SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Editorial Material C1 [Atwood, Charles W., Jr.] VA Pittsburgh Healthcare Syst, Sleep Disorders Program, Pittsburgh, PA USA. [Atwood, Charles W., Jr.] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, UPMC Sleep Med Ctr, Pittsburgh, PA 15213 USA. [Atwood, Charles W., Jr.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Atwood, CW (reprint author), Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, 3459 5th Ave,NW628 MUH, Pittsburgh, PA 15213 USA. EM atwoodcw@upmc.edu NR 7 TC 4 Z9 4 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2013 VL 9 IS 4 BP 337 EP 338 DI 10.5664/jcsm.2582 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 139SI UT WOS:000318604100007 PM 23585748 ER PT J AU Lu, PH Mendez, MF Lee, GJ Leow, AD Lee, HW Shapira, J Jimenez, E Boeve, BB Caselli, RJ Graff-Radford, NR Jack, CR Kramer, JH Miller, BL Bartzokis, G Thompson, PM Knopman, DS AF Lu, Po H. Mendez, Mario F. Lee, Grace J. Leow, Alex D. Lee, Hyun-Woo Shapira, Jill Jimenez, Elvira Boeve, Bradley B. Caselli, Richard J. Graff-Radford, Neill R. Jack, Clifford R. Kramer, Joel H. Miller, Bruce L. Bartzokis, George Thompson, Paul M. Knopman, David S. TI Patterns of Brain Atrophy in Clinical Variants of Frontotemporal Lobar Degeneration SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Frontotemporal dementia; Primary progressive aphasia; Longitudinal study; Magnetic resonance imaging; Tensor-based morphometry; White matter ID TENSOR-BASED MORPHOMETRY; PRIMARY-PROGRESSIVE-APHASIA; VOXEL-BASED MORPHOMETRY; WHITE-MATTER CHANGES; ALZHEIMERS-DISEASE; DIAGNOSTIC-CRITERIA; SEMANTIC DEMENTIA; DIFFUSION; MRI; PATHOLOGY AB Background/Aims: The clinical syndromes of frontotemporal lobar degeneration include behavioral variant frontotemporal dementia (bvFTD) and semantic (SV-PPA) and nonfluent variants (NF-PPA) of primary progressive aphasia. Using magnetic resonance imaging (MRI), tensor-based morphometry (TBM) was used to determine distinct patterns of atrophy between these three clinical groups. Methods: Twenty-seven participants diagnosed with bvFTD, 16 with SV-PPA, and 19 with NF-PPA received baseline and follow-up MRI scans approximately 1 year apart. TBM was used to create three-dimensional Jacobian maps of local brain atrophy rates for individual subjects. Results: Regional analyses were performed on the three-dimensional maps and direct comparisons between groups (corrected for multiple comparisons using permutation tests) revealed significantly greater frontal lobe and frontal white matter atrophy in the bvFTD relative to the SV-PPA group (p < 0.005). The SV-PPA subjects exhibited significantly greater atrophy than the bvFTD in the fusiform gyrus (p = 0.007). The NF-PPA group showed significantly more atrophy in the parietal lobes relative to both bvFTD and SV-PPA groups (p < 0.05). Percent volume change in ventromedial prefrontal cortex was significantly associated with baseline behavioral symptomatology. Conclusion: The bvFTD, SV-PPA, and NF-PPA groups displayed distinct patterns of progressive atrophy over a 1-year period that correspond well to the behavioral disturbances characteristic of the clinical syndromes. More specifically, the bvFTD group showed significant white matter contraction and presence of behavioral symptoms at baseline predicted significant volume loss of the ventromedial prefrontal cortex. Copyright (C) 2013 S. Karger AG, Basel C1 [Lu, Po H.; Mendez, Mario F.; Lee, Grace J.; Shapira, Jill; Jimenez, Elvira; Thompson, Paul M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Leow, Alex D.; Bartzokis, George; Thompson, Paul M.] Univ Calif Los Angeles, David Geffen Sch Med, Lab Neuroimaging, Los Angeles, CA 90095 USA. [Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Mendez, Mario F.; Jimenez, Elvira] Greater Los Angeles VA Healthcare Syst, Neurobehav Unit, Los Angeles, CA USA. [Leow, Alex D.] Community Psychiat Associates, Sacramento, CA USA. [Kramer, Joel H.; Miller, Bruce L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Leow, Alex D.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Leow, Alex D.] Univ Illinois, Dept Bioengn, Chicago, IL USA. [Boeve, Bradley B.; Jack, Clifford R.; Knopman, David S.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Caselli, Richard J.] Mayo Clin, Dept Neurol, Scottsdale, AZ USA. [Graff-Radford, Neill R.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Lee, Hyun-Woo] McGill Univ, Dept Phys, Montreal, PQ, Canada. RP Lu, PH (reprint author), Mary S Easton Ctr Alzheimers Dis Res, 10911 Weyburn Ave,Suite 200, Los Angeles, CA 90095 USA. EM plu@mednet.ucla.edu RI Bartzokis, George/K-2409-2013; Leow, Alex/K-3236-2014; Jack, Clifford/F-2508-2010 OI Leow, Alex/0000-0002-5660-8651; Jack, Clifford/0000-0001-7916-622X FU National Institute of Health/National Institute of Aging (NIH/NIA) [K23-AG028727, R01-AG034499]; Alzheimer's Association [NIRG-07-60424]; NIH [P50 AG-16570, R01-AG023195, R01-AG11378, P50 AG-16574, P30-AG19610, R01-AG022983, P50-AG023501, U01 AG016976]; California Alzheimer's Disease Center; NIA, NIBIB; National Library of Medicine; National Center for Research Resources [AG016570, EB01651, LM05639, RR019771] FX This work was supported by grants K23-AG028727 and R01-AG034499 from the National Institute of Health/National Institute of Aging (NIH/NIA) and a grant from the Alzheimer's Association (NIRG-07-60424). Further support for this study came from NIH grants P50 AG-16570 (UCLA Alzheimer's Disease Research Center), R01-AG023195, R01-AG11378, P50 AG-16574 (Mayo Alzheimer's Disease Research Center), P30-AG19610 (Arizona Alzheimer Disease Center), R01-AG022983, P50-AG023501 (UCSF Alzheimer Disease Research Center) U01 AG016976 (National Alzheimer's Coordinating Center), and the California Alzheimer's Disease Center. Algorithm development for this study was also funded by the NIA, NIBIB, the National Library of Medicine, and the National Center for Research Resources (AG016570, EB01651, LM05639, RR019771 to PT). NR 68 TC 9 Z9 11 U1 2 U2 10 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2013 VL 35 IS 1-2 BP 34 EP 50 DI 10.1159/000345523 PG 17 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 130GB UT WOS:000317900400003 PM 23306166 ER PT J AU Knapp, H Anaya, HD AF Knapp, H. Anaya, H. D. TI Implementation science in the real world: a case study of HIV rapid testing SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Article DE implementation science; quality improvement; organizational change; process design/re-design/re-engineering; performance improvement models; HIV; diagnostic testing; rapid test ID NEEDLE PHOBIA; DIAGNOSIS; FRAMEWORK; RISK AB Implementation science theories offer technical principles for carrying out activities designed to create or improve systems; however, such theories tend not to provide pragmatic or streamlined guidance when it comes to executing the actual implementation. We assembled a streamlined and comprehensive six-step theory-based implementation science model (ADAPTS - Assessment, Deliverables, Activate, Pretraining, Training, Sustainability) derived from the methods we have used to successfully execute multiple self-sustaining implementation efforts within the Veteran's Affairs Healthcare System. This paper provides a case study of our ADAPTS implementation science model, using a complex multisite HIV rapid testing implementation project as an exemplar. C1 [Knapp, H.; Anaya, H. D.] VA Greater Los Angeles Healthcare Syst, Vet Affairs VA Qual Enhancement Res Initiat HIV &, Los Angeles, CA USA. [Knapp, H.; Anaya, H. D.] VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, VA Greater Los Angeles Hlth Serv Res & Dev HRS&D, Los Angeles, CA USA. [Anaya, H. D.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, Los Angeles, CA 90095 USA. RP Knapp, H (reprint author), 11301 Wilshire Blvd 111G,Bldg 500,Off 4681, Los Angeles, CA 90073 USA. EM Herschel.Knapp@va.gov NR 18 TC 2 Z9 2 U1 1 U2 7 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0956-4624 J9 INT J STD AIDS JI Int. J. STD AIDS PD JAN PY 2013 VL 24 IS 1 BP 5 EP 11 DI 10.1258/ijsa.2012.012140 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 134IJ UT WOS:000318203300001 PM 23427213 ER PT J AU Lei-Rivera, L Sutera, J Galatioto, JA Hujsak, BD Gurley, JM AF Lei-Rivera, Laura Sutera, John Galatioto, Jessica A. Hujsak, Bryan D. Gurley, James M. TI Special tools for the assessment of balance and dizziness in individuals with mild traumatic brain injury SO NEUROREHABILITATION LA English DT Article DE Vestibular rehabilitation; traumatic brain injury; concussion; outcomes measures ID ERROR SCORING SYSTEM; DWELLING OLDER-ADULTS; PAROXYSMAL POSITIONAL VERTIGO; FUNCTIONAL GAIT ASSESSMENT; SENSORY INTERACTION; POSTURAL STABILITY; FALL RISK; CLINICAL-TEST; FOLLOW-UP; CONCUSSION AB INTRODUCTION: Although a majority of patients following minor traumatic brain injury recover to their pre-morbid functional level, persistent activity and participation limitations can occur in the refractory patient. These long-term consequences of brain injury may only become apparent months to years after the injury. In order to quantify these long-term sequella, laboratory, clinical and functional outcome measures may not only identify needed areas of treatment, but may also assist in determining the impact of the treatment on the individuals function. PURPOSE: The aim of this manuscript is to review the clinical utility of vestibular laboratory testing and the bedside vestibular examination in patients following mild traumatic brain injury. In addition, the validity and inter-observer reliability of functional outcome measures commonly used in individuals with mTBI will also be reviewed. SUMMARY: Because of the diffuse pathology seen with mTBI, multiple tests are needed to determine the resultant impairment and their impact on the patient's activity level and participation level. Laboratory test and bedside tests of vestibular impairment are reviewed. Functional outcome measures including the Dynamic Gait Index, the Functional Gait Assessment, the Balance Error Scoring System, and Dual Task Performance are reviewed for their appropriateness in quantifying the effect of mTBI at activity level and participation level of the individual. CONCLUSION: TBI rehabilitation services are increasingly exemplified by the needs of patients, rather than by the underlying pathology or diagnosis. Basing treatment decisions and treatment timing on laboratory, clinical, and functional testing can optimize the rehabilitation outcome. C1 [Lei-Rivera, Laura; Sutera, John; Hujsak, Bryan D.] New York Eye & Ear Infirm, Vestibular Rehabil Dept, New York, NY USA. [Galatioto, Jessica A.] New York Eye & Ear Infirm, Ctr Hearing & Balance Disorders, New York, NY USA. [Gurley, James M.] Mercy Coll, Phys Therapy Program, Dobbs Ferry, NY 10522 USA. [Gurley, James M.] James J Peters VAMC, Dept Otololaryngol, Bronx, NY USA. RP Gurley, JM (reprint author), Mercy Coll, Phys Therapy Program, 555 Broadway, Dobbs Ferry, NY 10522 USA. EM jgurley@mercy.edu NR 61 TC 3 Z9 4 U1 2 U2 22 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1053-8135 J9 NEUROREHABILITATION JI Neurorehabilitation PY 2013 VL 32 IS 3 BP 463 EP 472 DI 10.3233/NRE-130869 PG 10 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 135DM UT WOS:000318266200005 PM 23648601 ER PT J AU Gurley, JM Hujsak, BD Kelly, JL AF Gurley, James M. Hujsak, Bryan D. Kelly, Jennifer L. TI Vestibular rehabilitation following mild traumatic brain injury SO NEUROREHABILITATION LA English DT Article DE Vestibular rehabilitation; traumatic brain injury; concussion ID PAROXYSMAL POSITIONAL VERTIGO; STABILITY FOLLOWING CONCUSSION; DIZZINESS HANDICAP INVENTORY; PREDICT PROTRACTED RECOVERY; SPORTS-RELATED CONCUSSION; HEART-RATE-VARIABILITY; VESTIBULOOCULAR REFLEX; POSTURAL-CONTROL; SMOOTH-PURSUIT; FOOTBALL PLAYERS AB INTRODUCTION: Vertigo, dizziness, and imbalance are a symptom complex that is commonly found following concussion. Early metabolic changes following concussion may lead to worsening of the injury and symptoms in individuals not properly managed from the outset. When symptoms do not recover spontaneously, skilled vestibular rehabilitation can be an effective modality in an attempt to normalize the individual's vestibular responses. PURPOSE: The purpose of this review is to appraise the current and accepted methods available to the skilled clinician in quantifying and treating vestibular dysfunction following concussion. Incidence and prognostic indicators will be reviewed along with common barriers to recovery. SUMMARY: Vestibular Rehabilitation following concussion utilizes similar tools and techniques employed when treating those solely with peripheral pathology. The clinician must not only have a solid understanding of when and why certain exercises are required, but also be willing to accept that less exercise may be indicated in this population. As injury to the system following mild traumatic brain injury can include both peripheral and central structures, the duration of therapy and the time to recovery may be prolonged. Co-morbidities including cognitive and behavioral issues, visual-perceptual dysfunction, metabolic dysfunction, and autonomic dysfunction may hamper the effectiveness of the traditional Vestibular Rehabilitation approach. As successful treatment does not occur in a vacuum, working closely with other disciplines well versed in treating these co-morbid issues will help the individual to obtain optimal recovery. CONCLUSION: Vestibular Rehabilitation is an effective modality for managing dizziness, vertigo, and imbalance following concussion. Careful consideration of the acuity of the injury, along with effective management of co-morbid conditions will optimize the result. C1 [Gurley, James M.] Mercy Coll, Phys Therapy Program, Dobbs Ferry, NY 10522 USA. [Gurley, James M.] James J Peters VAMC, Dept Otololaryngol, Bronx, NY USA. [Hujsak, Bryan D.; Kelly, Jennifer L.] New York Eye & Ear Infirm, Vestibular Rehabil Dept, New York, NY USA. RP Gurley, JM (reprint author), Mercy Coll, Phys Therapy Program, 555 Broadway, Dobbs Ferry, NY 10522 USA. EM jgurley@mercy.edu NR 79 TC 11 Z9 11 U1 3 U2 35 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1053-8135 J9 NEUROREHABILITATION JI Neurorehabilitation PY 2013 VL 32 IS 3 BP 519 EP 528 DI 10.3233/NRE-130874 PG 10 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 135DM UT WOS:000318266200010 PM 23648606 ER PT J AU Turner, TH Hinson, V AF Turner, Travis H. Hinson, Vanessa TI Mattis Dementia Rating Scale Cutoffs Are Inadequate for Detecting Dementia in Parkinson's Disease SO APPLIED NEUROPSYCHOLOGY-ADULT LA English DT Article DE cognition; diagnosis; geriatric; measurement; statistics; tests ID MILD COGNITIVE IMPAIRMENT; SCREENING DEMENTIA; DISORDER AB The Mattis Dementia Rating Scale (DRS) is widely used to assess cognition and screen for dementia in Parkinson's disease (PD). In 2008, Llebaria and colleagues reported excellent sensitivity and specificity detecting dementia in PD using a DRS total score cutoff of 123. However, this study used a sample with rather low mean educational achievement (8.9 years). The 123 cutoff score was cross-validated in a sample of 51 PD patients with a rather high mean educational achievement (14.84 years). A total score cutoff of 123 correctly classified 60.7% of the sample, with 20% sensitivity and 100% specificity. Use of age- and education-corrected scaled scores improved classification accuracy, but these cutoffs corresponded to the 25th percentile. Optimal classification of 82.4% accuracy was achieved using a raw total score cutoff of 133, corresponding roughly to the 16th percentile. Neither age nor education evinced a strong correlation to DRS total score in our sample. Results suggest caution in applying the DRS-2 total score cutoff of 123 and highlight the importance of comprehensive neuropsychological evaluations for clinical diagnosis of dementia in PD. C1 [Turner, Travis H.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. Ralph H Johnson VAMC, Mental Hlth Serv, Charleston, SC 29401 USA. RP Turner, TH (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM turnertr@musc.edu NR 28 TC 3 Z9 4 U1 1 U2 2 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0908-4282 J9 APPL NEUROPSYCH-ADUL JI Appl. Neuropsychol.-Adult PD JAN 1 PY 2013 VL 20 IS 1 BP 61 EP 65 DI 10.1080/09084282.2012.670168 PG 5 WC Clinical Neurology; Psychology SC Neurosciences & Neurology; Psychology GA 109PH UT WOS:000316380000009 PM 23373686 ER PT J AU Chang, AY Ghazi, E Okawa, J Werth, VP AF Chang, Aileen Y. Ghazi, Elizabeth Okawa, Joyce Werth, Victoria P. TI Quality of Life Differences Between Responders and Nonresponders in the Treatment of Cutaneous Lupus Erythematosus SO JAMA DERMATOLOGY LA English DT Letter ID INSTRUMENT; SEVERITY; CLASI C1 [Chang, Aileen Y.; Ghazi, Elizabeth; Okawa, Joyce; Werth, Victoria P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Chang, Aileen Y.; Ghazi, Elizabeth; Okawa, Joyce; Werth, Victoria P.] Univ Penn, Perelman Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. [Ghazi, Elizabeth] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA. RP Werth, VP (reprint author), Perelman Ctr Adv Med, Dept Dermatol, 3400 Civ Ctr Blvd,Ste 1-330S, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU Intramural NIH HHS; NIAMS NIH HHS [K24-AR 18 02207, K24 AR002207] NR 6 TC 8 Z9 8 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6068 J9 JAMA DERMATOL JI JAMA Dermatol. PD JAN PY 2013 VL 149 IS 1 BP 104 EP 106 DI 10.1001/2013.jamadermatol.467 PG 4 WC Dermatology SC Dermatology GA 127BB UT WOS:000317668000024 PM 23324773 ER PT J AU Holsinger, JW Scutchfield, FD AF Holsinger, James W., Jr. Scutchfield, F. Douglas BE Holsinger, JW TI History and Context of Public Health Care Introduction SO CONTEMPORARY PUBLIC HEALTH: PRINCIPLES, PRACTICE, AND POLICY LA English DT Editorial Material; Book Chapter ID EMERGENCY PREPAREDNESS; DISPARITIES C1 [Holsinger, James W., Jr.; Scutchfield, F. Douglas] Univ Kentucky, Coll Publ Hlth, Lexington, KY 40506 USA. [Holsinger, James W., Jr.] US Dept Vet Affairs, Washington, DC USA. [Holsinger, James W., Jr.] Univ Kentucky, Med Ctr, Lexington, KY 40506 USA. [Scutchfield, F. Douglas] San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. [Scutchfield, F. Douglas] Univ Kentucky, Sch Publ Hlth, Lexington, KY 40506 USA. RP Holsinger, JW (reprint author), Univ Kentucky, Coll Publ Hlth, Lexington, KY 40506 USA. NR 47 TC 1 Z9 1 U1 0 U2 0 PU UNIV PRESS KENTUCKY PI LEXINGTON PA 102 LAFFERTY HALL, UNIVERSITY OF KENTUCKY, LEXINGTON, KY 40506 USA BN 978-0-8131-4124-4 PY 2013 BP 1 EP 23 PG 23 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BDZ13 UT WOS:000315694300003 ER PT B AU Holsinger, JW AF Holsinger, James W., Jr. BE Holsinger, JW TI CONTEMPORARY PUBLIC HEALTH Principles, Practice, and Policy Preface SO CONTEMPORARY PUBLIC HEALTH: PRINCIPLES, PRACTICE, AND POLICY LA English DT Editorial Material; Book Chapter C1 [Holsinger, James W., Jr.] Univ Kentucky, Coll Publ Hlth, Lexington, KY 40506 USA. [Holsinger, James W., Jr.] US Dept Vet Affairs, Washington, DC USA. [Holsinger, James W., Jr.] Univ Kentucky, Med Ctr, Lexington, KY 40506 USA. RP Holsinger, JW (reprint author), Univ Kentucky, Coll Publ Hlth, Lexington, KY 40506 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV PRESS KENTUCKY PI LEXINGTON PA 102 LAFFERTY HALL, UNIVERSITY OF KENTUCKY, LEXINGTON, KY 40506 USA BN 978-0-8131-4124-4 PY 2013 BP XIII EP XIV PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BDZ13 UT WOS:000315694300002 ER PT B AU Keck, CW Scutchfield, FD Holsinger, JW AF Keck, C. William Scutchfield, F. Douglas Holsinger, James W., Jr. BE Holsinger, JW TI Future of Public Health Conclusion SO CONTEMPORARY PUBLIC HEALTH: PRINCIPLES, PRACTICE, AND POLICY LA English DT Editorial Material; Book Chapter ID SOCIAL DETERMINANTS; IMPACT ASSESSMENT; IMPROVING HEALTH; CARE C1 [Scutchfield, F. Douglas; Holsinger, James W., Jr.] Univ Kentucky, Coll Publ Hlth, Lexington, KY 40506 USA. [Scutchfield, F. Douglas] San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. [Scutchfield, F. Douglas] Univ Kentucky, Sch Publ Hlth, Lexington, KY 40506 USA. [Holsinger, James W., Jr.] US Dept Vet Affairs, Washington, DC USA. [Holsinger, James W., Jr.] Univ Kentucky, Med Ctr, Lexington, KY 40506 USA. NR 49 TC 0 Z9 0 U1 0 U2 0 PU UNIV PRESS KENTUCKY PI LEXINGTON PA 102 LAFFERTY HALL, UNIVERSITY OF KENTUCKY, LEXINGTON, KY 40506 USA BN 978-0-8131-4124-4 PY 2013 BP 251 EP 276 PG 26 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BDZ13 UT WOS:000315694300015 ER PT S AU Appleton, KM Lee, MH Alele, C Alele, C Luttrell, DK Peterson, YK Morinelli, TA Luttrell, LM AF Appleton, Kathryn M. Lee, Mi-Hye Alele, Christian Alele, Christine Luttrell, Deirdre K. Peterson, Yuri K. Morinelli, Thomas A. Luttrell, Louis M. BE Conn, PM TI Biasing the Parathyroid Hormone Receptor: Relating In Vitro Ligand Efficacy to In Vivo Biological Activity SO G PROTEIN COUPLED RECEPTORS: MODELING, ACTIVATION, INTERACTIONS AND VIRTUAL SCREENING SE Methods in Enzymology LA English DT Review; Book Chapter ID HUMAN PTH/PTHRP RECEPTOR; C ACTIVATION DOMAIN; BONE-FORMATION; 7-TRANSMEMBRANE RECEPTORS; AGONIST ACTIVITY; PHOSPHOLIPASE-C; PTH RECEPTOR; PROTEIN; PEPTIDE; CELLS AB Recent advances in our understanding of the pluridimensional nature of GPCR signaling have provided new insights into how orthosteric ligands regulate receptors, and how the phenomenon of functional selectivity or ligand "bias" might be exploited in pharmaceutical design. In contrast to the predictions of simple two-state models of GPCR function, where ligands affect all aspects of GPCR signaling proportionally, current models assume that receptors exist in multiple "active" conformations that differ in their ability to couple to different downstream effectors, and that structurally distinct ligands can bias signaling by preferentially stabilizing different active states. The type 1 parathyroid hormone receptor (PTH1R) offers unique insight into both the opportunities and challenges of exploiting ligand bias in pharmaceutical design, not only because numerous "biased" PTH analogs have been described but also because many of them have been characterized for biological activity in vivo. The PTH1R has pleiotropic signaling capacity, coupling to G(s), G(q/11), and G(i/o) family heterotrimeric G proteins, and binding arrestins, which mediate receptor desensitization and arrestin-dependent signaling. Here, we compare the activity of six different PTH1R ligands in a common HEK293 cell background using three readouts of receptor activation, cAMP production, intracellular calcium influx, and ERK1/2 activation, demonstrating the range of signal bias that can be experimentally observed in a "typical" screening program. When the in vitro activity profiles of these ligands are compared to their reported effects on bone mass in murine models, it is apparent that ligands activating cAMP production produce an anabolic response that does not correlate with the ability to also elicit calcium signaling. Paradoxically, one ligand that exhibits inverse agonism for cAMP production and arrestin-dependent ERK1/2 activation in vitro, (D-Trp(12), Tyr(34))-bPTH(7-34), reportedly produces an anabolic bone response in vivo despite an activity profile that is dramatically different from that of other active ligands. This underscores a major challenge facing efforts to rationally design "biased" GPCR ligands for therapeutic application. While it is clearly plausible to identify functionally selective ligands, the ability to predict how bias will affect drug response in vivo, is often lacking, especially in complex disorders. C1 [Appleton, Kathryn M.; Lee, Mi-Hye; Alele, Christian; Alele, Christine; Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. [Luttrell, Deirdre K.; Morinelli, Thomas A.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Appleton, Kathryn M.; Peterson, Yuri K.] Med Univ S Carolina, Coll Pharm, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA. [Morinelli, Thomas A.; Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. RP Luttrell, LM (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. EM luttrell@musc.edu FU NCRR NIH HHS [S10 RR027777]; NIDDK NIH HHS [R01 DK55524] NR 56 TC 12 Z9 12 U1 0 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-407865-9 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2013 VL 522 BP 229 EP 262 DI 10.1016/B978-0-12-407865-9.00013-3 PG 34 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BEL04 UT WOS:000317147300013 PM 23374189 ER PT J AU Profit, J Zupancic, JAF Gould, JB Pietz, K Kowalkowski, MA Draper, D Hysong, SJ Petersen, LA AF Profit, Jochen Zupancic, John A. F. Gould, Jeffrey B. Pietz, Kenneth Kowalkowski, Marc A. Draper, David Hysong, Sylvia J. Petersen, Laura A. TI Correlation of Neonatal Intensive Care Unit Performance Across Multiple Measures of Quality of Care SO JAMA PEDIATRICS LA English DT Article ID HOSPITAL QUALITY; MORTALITY-RATES; SAFETY CULTURE; HEALTH-CARE; INFECTIONS; INDICATORS; OUTCOMES; NETWORK; STATES; NICU AB Objectives: To examine whether high performance on one measure of quality is associated with high performance on others and to develop a data-driven explanatory model of neonatal intensive care unit (NICU) performance. Design: We conducted a cross-sectional data analysis of a statewide perinatal care database. Risk-adjusted NICU ranks were computed for each of 8 measures of quality selected based on expert input. Correlations across measures were tested using the Pearson correlation coefficient. Exploratory factor analysis was used to determine whether underlying factors were driving the correlations. Setting: Twenty-two regional NICUs in California. Patients: In total, 5445 very low-birth-weight infants cared for between January 1, 2004, and December 31, 2007. Main Outcomes Measures: Pneumothorax, growth velocity, health care-associated infection, antenatal corticosteroid use, hypothermia during the first hour of life, chronic lung disease, mortality in the NICU, and discharge on any human breast milk. Results: The NICUs varied substantially in their clinical performance across measures of quality. Of 28 unitlevel correlations, 6 were significant (rho < .05). Correlations between pairs of measures of quality of care were strong (rho >= .5) for 1 pair, moderate (range, rho >= .3 to rho < .5) for 8 pairs, weak (range, rho >= .1 to rho < .3) for 5 pairs, and negligible (rho < .1) for 14 pairs. Exploratory factor analysis revealed 4 underlying factors of quality in this sample. Pneumothorax, mortality in the NICU, and antenatal corticosteroid use loaded on factor 1; growth velocity and health care-associated infection loaded on factor 2; chronic lung disease loaded on factor 3; and discharge on any human breast milk loaded on factor 4. Conclusion: In this sample, the ability of individual measures of quality to explain overall quality of neonatal intensive care was modest. JAMA Pediatr. 2013;167(1):47-54. Published online November 12, 2012. doi:10.1001/jamapediatrics.2013.418 C1 [Profit, Jochen] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Profit, Jochen; Pietz, Kenneth; Kowalkowski, Marc A.; Hysong, Sylvia J.; Petersen, Laura A.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Profit, Jochen] Texas Childrens Hosp, Dept Pediat, Sect Neonatol, Houston, TX 77030 USA. [Profit, Jochen; Pietz, Kenneth; Kowalkowski, Marc A.; Hysong, Sylvia J.; Petersen, Laura A.] Michael E DeBakey VA Med Ctr, Houston Vet Affairs Hlth Serv Res & Dev Ctr Excel, Hlth Policy & Qual Program, Houston, TX 77030 USA. [Zupancic, John A. F.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Neonatol, Boston, MA 02215 USA. [Zupancic, John A. F.] Harvard Univ, Sch Med, Div Newborn Med, Boston, MA 02215 USA. [Gould, Jeffrey B.] Stanford Univ, Sch Med, Div Neonatol, Perinatal Epidemiol & Hlth Outcomes Res Unit, Palo Alto, CA 94304 USA. [Gould, Jeffrey B.] Lucile Packard Childrens Hosp, Palo Alto, CA USA. [Gould, Jeffrey B.] Calif Perinatal Qual Care Collaborat, Palo Alto, CA USA. [Draper, David] Univ Calif Santa Cruz, Dept Appl Math & Stat, Baskin Sch Engn, Santa Cruz, CA 95064 USA. RP Profit, J (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, Houston Vet Affairs Hlth Serv Res & Dev Ctr Excel, Hlth Policy & Qual Program, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM profit@bcm.edu RI Hysong, Sylvia/B-8420-2008 OI Hysong, Sylvia/0000-0002-9063-5207; Kowalkowski, Marc/0000-0003-2624-4209; Zupancic, John/0000-0003-1734-7193 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [1 K23 HD056298]; Department of Veterans Affairs Health Services Research and Development Program [CD2-07-0181]; Veterans Affairs Health Services Research and Development Center of Excellence grant [HFP90-20]; American Heart Association [0540043N] FX This study is supported in part by grants 1 K23 HD056298 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Dr Profit), CD2-07-0181 from the Department of Veterans Affairs Health Services Research and Development Program (Dr Hysong), Veterans Affairs Health Services Research and Development Center of Excellence grant HFP90-20 (Drs Hysong and Petersen), and American Heart Association Established Investigator Award 0540043N (Dr Petersen). NR 30 TC 9 Z9 9 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6203 J9 JAMA PEDIATR JI JAMA Pediatr. PD JAN PY 2013 VL 167 IS 1 BP 47 EP 54 DI 10.1001/jamapediatrics.2013.418 PG 8 WC Pediatrics SC Pediatrics GA 115FH UT WOS:000316797500010 PM 23403539 ER PT J AU Wisneski, AD Beyer, AT Shunk, KA AF Wisneski, Andrew D. Beyer, Anna T. Shunk, Kendrick A. TI An Unusual Case of Bilateral Subclavian-Carotid Artery Graft Occlusion With Coronary Steal Syndrome Managed in the Cath Lab SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Article DE carotid artery; chronic total occlusion ID STENOSIS AB A 65-year-old man, s/p coronary bypass surgery (CABG) with left internal mammary artery (LIMA) to the left anterior descending (LAD) artery 12 years previously, presented to his local hospital with left upper extremity pain, dizziness, falls, and chest pain. At the outside hospital, a proximal total left subclavian occlusion was found and the patient underwent left subclavian artery to common carotid artery (SCA-CCA) bypass surgery. Shortly thereafter, the patient developed right subclavian thrombosis, and underwent right SCA-CCA bypass surgery. Twenty days later, coronary steal symptoms recurred; troponin levels were elevated and ultrasound exam revealed bilateral SCA-CCA graft occlusion. The patient was then transferred to a tertiary care facility with a diagnosis of non-ST elevation myocardial infarct (NSTEMI). A successful endovascular procedure was performed in the cardiac catheterization laboratory with the use of coronary chronic total occlusion (CTO) devices, to treat the coronary steal syndrome. J INVASIVE CARDIOL 2013;25(1):E14-E16 C1 Univ Calif San Francisco, Dept Cardiol, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Shunk, KA (reprint author), San Francisco VA Med Ctr, Dept Cardiol, 111C,4150 Clement St, San Francisco, CA 94121 USA. EM Kendrick.Shunk@va.gov FU Gilead; InfraredX; Abbott Vascular; Siemens Medical Systems FX The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Shunk holds grants from Gilead, InfraredX, Abbott Vascular, and Siemens Medical Systems, and discloses stock ownership (divested) in Revascular Therapeutics, Inc. NR 8 TC 2 Z9 2 U1 0 U2 2 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1042-3931 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD JAN PY 2013 VL 25 IS 1 BP E14 EP E16 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 110AQ UT WOS:000316414600005 PM 23293182 ER PT J AU Mendez, MF Owens, EM Berenji, GR Peppers, DC Liang, LJ Licht, EA AF Mendez, Mario F. Owens, Emily M. Berenji, Gholam Reza Peppers, Dominique C. Liang, Li-Jung Licht, Eliot A. TI Mild traumatic brain injury from primary blast vs. blunt forces: Post-concussion consequences and functional neuroimaging SO NEUROREHABILITATION LA English DT Article DE Mild traumatic brain injury; blast forces; post-concussion; positron emission tomography imaging ID PERSISTENT POSTCONCUSSIVE SYMPTOMS; POSITRON EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE-METABOLISM; OIF/OEF SERVICE MEMBERS; IRAQ WAR VETERANS; HEAD-INJURY; POSTTRAUMATIC-STRESS; NEUROPSYCHOLOGICAL DEFICITS; MILITARY PERSONNEL; FDG-PET AB INTRODUCTION: Primary blast forces may cause dysfunction from mild traumatic brain injury (mTBI). OBJECTIVE: To investigate the effects of primary blast forces, independent of associated blunt trauma and post-traumatic stress disorder, on sensitive post-concussive measures. METHODS: This study investigated post-concussive symptoms, functional health and well-being, cognition, and positron emission tomography (PET) neuroimaging among 12 Iraq or Afghanistanwar veterans who sustained pure blast-force mTBI, compared to 12 who sustained pure blunt-force mTBI. RESULTS: Both groups had significantly lower scores than published norms on the Rivermead Post-Concussion Questionnaire (RPQ) and the SF36-V Health Survey. Compared to the Blunt Group, the Blast Group had poorer scores on the Paced Auditory Serial Addition Test (PASAT) and greater PET hypometabolism in the right superior parietal region. Only the Blast Group had significant correlations of their RPQ, SF36-V Mental Composite Score, and PASAT scores with specific regional metabolic changes. CONCLUSION: This pilot study suggests that pure blast force mTBI may have greater post-concussive sequelae including deficits in attentional control and regional brain metabolism, compared to blunt mTBI. A disturbance of a right parietal-frontal attentional network is one potential explanation for these findings. C1 [Mendez, Mario F.; Owens, Emily M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. [Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Mendez, Mario F.; Licht, Eliot A.] VA Greater Los Angeles Healthcare Ctr, Neurol Sect, Los Angeles, CA 90073 USA. [Berenji, Gholam Reza; Peppers, Dominique C.] VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA. [Liang, Li-Jung] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90024 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@UCLA.edu FU Veterans Affairs Administration FX No conflicts of interest. This research was made possible by a grant from the Veterans Affairs Administration. NR 70 TC 16 Z9 16 U1 4 U2 27 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1053-8135 J9 NEUROREHABILITATION JI Neurorehabilitation PY 2013 VL 32 IS 2 BP 397 EP 407 DI 10.3233/NRE-130861 PG 11 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 115ZT UT WOS:000316851900025 PM 23535805 ER PT J AU O'Donovan, A Slavich, GM Epel, ES Neylan, TC AF O'Donovan, Aoife Slavich, George M. Epel, Elissa S. Neylan, Thomas C. TI Exaggerated neurobiological sensitivity to threat as a mechanism linking anxiety with increased risk for diseases of aging SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE Anxiety; Attentional bias; Cellular aging; Diseases of aging; Hypothalamic-pituitary-adrenal axis; Inflammation; Information processing; Neurobiological; Parasympathetic nervous system; Psychoneuroimmunology; Sympathetic nervous system; Threat ID POSTTRAUMATIC-STRESS-DISORDER; C-REACTIVE PROTEIN; HEART-RATE-VARIABILITY; PREFRONTAL CORTICAL PROJECTIONS; URINARY CORTISOL EXCRETION; MENTAL-HEALTH DISORDERS; EXPLICIT MEMORY BIAS; QUALITY-OF-LIFE; GENERALIZED-ANXIETY; ATTENTIONAL BIAS AB Anxiety disorders increase risk for the early development of several diseases of aging. Elevated inflammation, a common risk factor across diseases of aging, may play a key role in the relationship between anxiety and physical disease. However, the neurobiological mechanisms linking anxiety with elevated inflammation remain unclear. In this review, we present a neurobiological model of the mechanisms by which anxiety promotes inflammation. Specifically we propose that exaggerated neurobiological sensitivity to threat in anxious individuals may lead to sustained threat perception, which is accompanied by prolonged activation of threat-related neural circuitry and threat-responsive biological systems including the hypothalamic-pituitary-adrenal (HPA) axis, autonomic nervous system (ANS), and inflammatory response. Over time, this pattern of responding can promote chronic inflammation through structural and functional brain changes, altered sensitivity of immune cell receptors, dysregulation of the HPA axis and ANS, and accelerated cellular aging. Chronic inflammation, in turn, increases risk for diseases of aging. Exaggerated neurobiological sensitivity to threat may thus be a treatment target for reducing disease risk in anxious individuals. (c) 2012 Elsevier Ltd. All rights reserved. C1 [O'Donovan, Aoife; Epel, Elissa S.; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [O'Donovan, Aoife; Neylan, Thomas C.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [O'Donovan, Aoife; Neylan, Thomas C.] Northern Calif Inst Res & Educ, San Francisco, CA USA. [Slavich, George M.] Univ Calif Los Angeles, Cousins Ctr Psychoneuroimmunol, Los Angeles, CA USA. [Slavich, George M.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP O'Donovan, A (reprint author), San Francisco VA Med Ctr, Psychiat Serv 116H, 4150 Clement St, San Francisco, CA 94121 USA. EM aoife.odonovan@ucsf.edu FU Society in Science - The Branco Weiss Fellowship FX Aoife O'Donovan and George M. Slavich were supported by Society in Science - The Branco Weiss Fellowship during the preparation of this review. We thank Joshua Woolley, Keely Muscatell, Kristen Nishimi, and Annika Rose for their helpful feedback on a previous version of this manuscript. NR 235 TC 31 Z9 31 U1 11 U2 37 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD JAN PY 2013 VL 37 IS 1 BP 96 EP 108 DI 10.1016/j.neubiorev.2012.10.013 PG 13 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 112IU UT WOS:000316586700007 PM 23127296 ER PT J AU Arar, N Delgado, E Lee, S Abboud, HE AF Arar, Nedal Delgado, Elizabeth Lee, Shuko Abboud, Hanna E. TI Improving learning about familial risks using a multicomponent approach: the GRACE program SO PERSONALIZED MEDICINE LA English DT Article DE familial risks assessment; family health history tool; genomics; learning; online Surgeon General ID PRIMARY-CARE; PUBLIC-HEALTH; HISTORY INFORMATION; COLORECTAL-CANCER; TOOL; HERITABILITY; DISEASES; SUPPORT; RECORD; BREAST AB Aim: To enhance learning (knowledge, attitudes and practices) about the importance of family health history (FHH) information and familial risks. Methods: A pre-post design with one group was employed in this study. Five learning sessions were conducted with a community-based sample (n = 75) recruited from five counties in Texas, USA. Each learning session included: a short online video; enactive instructions on how to use the online Surgeon General FHH tool; and a presentation on how to assess familial risks. Participants completed the pre-post knowledge, attitudes and practices questionnaires and the study's satisfaction survey, and participated in a short focus group interview. Results: Participants' average age was 48.1 +/- 13.3 years. Over half of the participants (79%) were female, and 55% described themselves as non-Hispanic White. Our findings showed significant changes (p < 0.05) in participants' specific knowledge about factors that affect their familial risks. Similarly, significant changes (p < 0.05) in participants' attitudes toward familial risks assessment for common disease complications and confidence in controlling these risks have been documented. Participants' reported a high level of satisfaction in using online FHH tools, yet no significant change (p > 0.05) was detected in their reported practices regarding sharing FHH information with their providers or relatives. Focus group interviews revealed that participants were uncertain about providers' or relatives' reactions to sharing FHH information. Conclusion: Using different learning styles may have a significant impact on improving knowledge and attitudes about familial risks. C1 [Arar, Nedal; Delgado, Elizabeth; Abboud, Hanna E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Arar, Nedal; Lee, Shuko; Abboud, Hanna E.] Audie L Murphy Mem Vet Adm Med Ctr, South Texas Vet Hlth Care System, San Antonio, TX 78284 USA. RP Arar, N (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. EM ararn@uthscsa.edu FU NIH [CTSA: UL1RR025767]; VHA-HSRD [DNA 08-129, PPO 09-241]; Area Health Education Center at South Texas FX This work was supported by NIH grant (CTSA: UL1RR025767) and the VHA-HSR&D (DNA 08-129 and PPO 09-241, principal investigator: N Arar) and Area Health Education Center at South Texas. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 40 TC 2 Z9 2 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD JAN PY 2013 VL 10 IS 1 BP 35 EP 44 DI 10.2217/PME.12.107 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 115FG UT WOS:000316797400010 PM 23682294 ER PT J AU Nordenstedt, H Graham, DY Kramer, JR Rugge, M Verstovsek, G Fitzgerald, S Alsarraj, A Shaib, Y Velez, ME Abraham, N Anand, B Md, RC El-Serag, HB AF Nordenstedt, Helena Graham, David Y. Kramer, Jennifer R. Rugge, Massimo Verstovsek, Gordana Fitzgerald, Stephanie Alsarraj, Abeer Shaib, Yasser Velez, Maria E. Abraham, Neena Anand, Bhupinderjit Cole, Rhonda El-Serag, Hashem B. TI Helicobacter pylori-Negative Gastritis: Prevalence and Risk Factors SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID EROSIVE ESOPHAGITIS; ERADICATION; INFECTION AB OBJECTIVES: Recent studies using histology alone in select patients have suggested that Helicobacter pylori negative gastritis may be common. The objective of this study was to investigate the prevalence of H. pylori among individuals with histologic gastritis. METHODS: Subjects between 40 and 80 years underwent elective esophagogastroduodenoscopy at a VA Medical Center. Gastric biopsies were mapped from seven prespecified sites (two antrum, four corpus, and one cardia) and graded by two gastrointestinal pathologists, using the Updated Sydney System. H. pylori-negative required four criteria: negative triple staining at all seven gastric sites, negative H. pylori culture, negative IgG H. pylori serology, and no previous treatment for H. pylori. Data regarding tobacco smoking, alcohol drinking, nonsteroidal anti-inflammatory drug, and proton pump inhibitor (PPI) use were obtained by questionnaire. RESULTS: Of the 491 individuals enrolled, 40.7 % (200) had gastritis of at least grade 2 in at least one biopsy site or grade 1 in at least two sites. Forty-one (20.5 %) had H. pylori-negative gastritis; most (30 or 73.2 %) had chronic gastritis, five (12.2 %) had active gastritis, and six (14.6 %) had both. H. pylori negative gastritis was approximately equally distributed in the antrum, corpus, and both antrum and corpus. Past and current PPI use was more frequent in H. pylori-negative vs. H. pylori-positive gastritis (68.2 % and 53.8 %; P = 0.06). CONCLUSIONS: We used multiple methods to define non-H. pylori gastritis and found it in 21 % of patients with histologic gastritis. While PPI use is a potential risk factor, the cause or implications of this entity are not known. Am J Gastroenterol 2013; 108:65-71; doi:10.1038/ajg.2012.372; published online 13 November 2012 C1 [Nordenstedt, Helena; Kramer, Jennifer R.; Fitzgerald, Stephanie; Alsarraj, Abeer; Abraham, Neena; El-Serag, Hashem B.] Houston VA HSR&D Ctr Excellence, Houston, TX USA. [Nordenstedt, Helena; Graham, David Y.; Rugge, Massimo; Shaib, Yasser; Velez, Maria E.; Abraham, Neena; Anand, Bhupinderjit; Cole, Rhonda; El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Gastroenterol Sect, Houston, TX 77030 USA. [Graham, David Y.; Shaib, Yasser; Velez, Maria E.; Abraham, Neena; Anand, Bhupinderjit; Cole, Rhonda; El-Serag, Hashem B.] Dept Med, Houston, TX USA. [Kramer, Jennifer R.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Rugge, Massimo] Univ Padua, Dept Diagnost Med Sci & Special Therapies, Surg Pathol & Cytopathol Unit, Padua, Italy. [Verstovsek, Gordana] Michael E DeBakey VA Med Ctr, Dept Pathol, Houston, TX USA. RP El-Serag, HB (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.edu RI Rugge, Massimo/K-7525-2016 FU VA HSR&D Houston Center of Excellence [HFP90-020]; NCI [R01 116845]; NIDDK [K24-04-107] FX This work was partly supported by the VA HSR&D Houston Center of Excellence (HFP90-020), Grant support : NCI R01 116845 and NIDDK K24-04-107. NR 11 TC 22 Z9 22 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2013 VL 108 IS 1 BP 65 EP 71 DI 10.1038/ajg.2012.372 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 107AI UT WOS:000316186600009 PM 23147524 ER PT J AU Garakani, A Martinez, JM Yehuda, R Gorman, JM AF Garakani, Amir Martinez, Jose M. Yehuda, Rachel Gorman, Jack M. TI Cerebrospinal fluid levels of glutamate and corticotropin releasing hormone in major depression before and after treatment SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Glutamine; Corticotropin releasing factor (CRF); Major depressive disorder (MDD); Venlafaxine; Antidepressant; Stress ID CSF; CITALOPRAM; SPECTROSCOPY; FLUOXETINE; DISORDERS; MOOD AB Background: Glutamate and corticotropin releasing hormone (CRH) are pro-stress neurotransmitters and may be altered in the plasma and cerebrospinal fluid (CSF) of persons with major depressive disorder (MDD). The goal of this study was to compare the CSF levels of glutamate, glutamine and CRH between patients with depression and healthy controls. Methods: Eighteen patients with MDD and 25 healthy controls underwent a lumbar puncture (LP); CSF samples were withdrawn and assays were done for glutamine, glutamate, and CRH. Patients with MDD underwent 8 weeks of treatment with the antidepressant venlafaxine and then had a repeat LP post treatment. Results: Patients had higher baseline scores on depression and suicide rating scales and those scales improved significantly post-treatment. Higher suicidal ratings at baseline were correlated with higher glutamate levels (p=0.016). There were no significant differences between the control and patient group in any baseline CSF measures of glutamate (p=0.761), glutamine (p=0.226) or CRH (p=0.675). Despite no significant change in glutamate (p=0.358) and CRH (p=0.331) in the treatment group, there was a post-treatment decrease in glutamine (p=0.045) in patients. Limitations: There was a small sample size, age discordance between patients and controls, lack of a follow-up LP in controls, absence of dexamethasone suppression testing, and fluctuating sample sizes among various measures. Conclusion: Although no significant differences were noted between patients and controls at baseline there was an association of high CSF glutamate and suicidal ideation and lower glutamine post-treatment which may be correlated with attenuation of dysfunction in the glutamatergic system after antidepressant treatment. (c) 2012 Elsevier B.V. All rights reserved. C1 [Garakani, Amir; Yehuda, Rachel] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Martinez, Jose M.] NYU, Med Ctr, New York, NY 10016 USA. [Yehuda, Rachel] James J Peters Vet Affairs, Bronx, NY USA. [Gorman, Jack M.] Franklin Behav Hlth Consultants, Bronx, NY USA. [Garakani, Amir] Silver Hill Hosp, New Canaan, CT USA. RP Garakani, A (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM amir.garakani@mssm.edu RI Garakani, Amir/A-3936-2013 FU National Institutes of Health (NIH) Grant [R01-MH58808, K08-MH6701] FX This work was supported by the National Institutes of Health (NIH) Grant nos. R01-MH58808 and K08-MH6701. NR 24 TC 8 Z9 8 U1 2 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PY 2013 VL 146 IS 2 BP 262 EP 265 DI 10.1016/j.jad.2012.06.037 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 106PC UT WOS:000316156000015 PM 22840611 ER PT J AU Bergman, BC Howard, D Schauer, IE Maahs, DM Snell-Bergeon, JK Clement, TW Eckel, RH Perreault, L Rewers, M AF Bergman, Bryan C. Howard, David Schauer, Irene E. Maahs, David M. Snell-Bergeon, Janet K. Clement, Timothy W. Eckel, Robert H. Perreault, Leigh Rewers, Marian TI The Importance of Palmitoleic Acid to Adipocyte Insulin Resistance and Whole-Body Insulin Sensitivity in Type 1 Diabetes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORONARY-ARTERY CALCIFICATION; SKELETAL-MUSCLE; ADIPOSE-TISSUE; GLUCOSE-METABOLISM; IMPAIRED BASAL; FATTY-ACIDS; IN-VIVO; MELLITUS; LIPOLYSIS; HUMANS AB Context: Type 1 diabetes is an insulin-resistant state, but it is less clear which tissues are affected. Our previous report implicated skeletal muscle and liver insulin resistance in people with type 1 diabetes, but this occurred independently of generalized, visceral, or ectopic fat. Objective: The aim of the study was to measure adipose tissue insulin sensitivity and plasma triglyceride composition in individuals with type 1 diabetes after overnight insulin infusion to lower fasting glucose. Design, Patients, and Methods: Fifty subjects (25 individuals with type 1 diabetes and 25 controls without) were studied. After 3 d of dietary control and overnight insulin infusion, we performed a three-stage hyperinsulinemic/euglycemic clamp infusing insulin at 4, 8, and 40 mU/m(2) . min. Infusions of [1,1,2,3,3-H-2(2)]glycerol and [1-C-13]palmitate were used to quantify lipid metabolism. Results: Basal glycerol and palmitate rates of appearance were similar between groups, decreased more in control subjects during the first two stages of the clamp, and similarly suppressed during the highest insulin dose. The concentration of insulin required for 50% inhibition of lipolysis was twice as high in individuals with type 1 diabetes. Plasma triglyceride saturation was similar between groups, but palmitoleic acid in plasma triglyceride was inversely related to adipocyte insulin sensitivity. Unesterified palmitoleic acid in plasma was positively related to insulin sensitivity in controls, but not in individuals with type 1 diabetes. Conclusions: Adipose tissue insulin resistance is a significant feature of type 1 diabetes. Palmitoleic acid is not related to insulin sensitivity in type 1 diabetes, as it was in controls, suggesting a novel mechanism for insulin resistance in this population. (J Clin Endocrinol Metab 98: E40-E50, 2013) C1 [Bergman, Bryan C.; Howard, David; Schauer, Irene E.; Clement, Timothy W.; Eckel, Robert H.; Perreault, Leigh] Univ Colorado Anschutz Med Campus, Div Endocrinol Metab & Diabet, Dept Med, Aurora, CO 80045 USA. [Maahs, David M.; Snell-Bergeon, Janet K.; Rewers, Marian] Univ Colorado Anschutz Med Campus, Sch Med, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80045 USA. [Schauer, Irene E.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Bergman, BC (reprint author), Univ Colorado Anschutz Med Campus, Div Endocrinol Metab & Diabet, POB 6511,MS 8106, Aurora, CO 80045 USA. EM Bryan.Bergman@ucdenver.edu OI Bergman, Bryan/0000-0002-9561-1052 FU National Institutes of Health (NIH) National Heart, Lung, and Blood Institute [R01 HL-61753, R01 HL-079611]; Clinical Translational Research Center at the University of Colorado Denver [M01 RR000051, RR-00036]; Barbara Davis Center for Childhood Diabetes in Denver; NIH Diabetes Endocrinology Research Center Clinical Investigation Core [P30 DK57516]; National Institute for Diabetes and Digestive and Kidney Diseases [K01 DK066219]; NIH Building Interdisciplinary Research Careers in Women's Health [K12, K23 DK075360]; American Diabetes Association junior faculty award [1-10-JF-50] FX This work was supported by the National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (Grants R01 HL-61753 and R01 HL-079611); the Clinical Translational Research Center at the University of Colorado Denver (Grants M01 RR000051 and RR-00036); as well as the Barbara Davis Center for Childhood Diabetes in Denver. Support was also provided by the NIH Diabetes Endocrinology Research Center Clinical Investigation Core (P30 DK57516), National Institute for Diabetes and Digestive and Kidney Diseases (K01 DK066219; to B. C. B.), NIH Building Interdisciplinary Research Careers in Women's Health (K12; to I. E. S.), K23 DK075360 (to D. M. M.), and the American Diabetes Association junior faculty award 1-10-JF-50 (to J.K.S.-B.). NR 41 TC 12 Z9 13 U1 0 U2 9 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2013 VL 98 IS 1 BP E40 EP E50 DI 10.1210/jc.2012-2892 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 107IT UT WOS:000316210300006 PM 23150678 ER PT J AU Tomer, Y Hasham, A Davies, TF Stefan, M Concepcion, E Keddache, M Greenberg, DA AF Tomer, Yaron Hasham, Alia Davies, Terry F. Stefan, Mihaela Concepcion, Erlinda Keddache, Mehdi Greenberg, David A. TI Fine Mapping of Loci Linked to Autoimmune Thyroid Disease Identifies Novel Susceptibility Genes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LINKAGE ANALYSIS; GRAVES-DISEASE; THYROGLOBULIN GENE; TSH RECEPTOR; ASSOCIATION; POLYMORPHISM; POPULATION; MECHANISMS; FAMILIES; JAPANESE AB Context: Genetic factors play a major role in the etiology of autoimmune thyroid disease (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT). We have previously identified three loci on chromosomes 10q, 12q, and 14q that showed strong linkage with AITD, HT, and GD, respectively. Objectives: The objective of the study was to identify the AITD susceptibility genes at the 10q, 12q, and 14q loci. Design and Participants: Three hundred forty North American Caucasian AITD patients and 183 healthy controls were studied. The 10q, 12q, and 14q loci were fine mapped by genotyping densely spaced single-nucleotide polymorphisms (SNPs) using the Illumina GoldenGate genotyping platform. Case control association analyses were performed using the UNPHASED computer package. Associated SNPs were reanalyzed in a replication set consisting of 238 AITD patients and 276 controls. Results: Fine mapping of the AITD locus, 10q, showed replicated association of the AITD phenotype (both GD and HT) with SNP rs6479778. This SNP was located within the ARID5B gene recently reported to be associated with rheumatoid arthritis and GD in Japanese. Fine mapping of the GD locus, 14q, revealed replicated association of the GD phenotype with two markers, rs12147587 and rs2284720, located within the NRXN3 and TSHR genes, respectively. Conclusions: Fine mapping of three linked loci identified novel susceptibility genes for AITD. The discoveries of new AITD susceptibility genes will engender a new understanding of AITD etiology. (J Clin Endocrinol Metab 98: E144-E152, 2013) C1 [Tomer, Yaron; Hasham, Alia; Davies, Terry F.; Stefan, Mihaela; Concepcion, Erlinda] Mt Sinai Sch Med, Div Endocrinol, Dept Med, New York, NY 10029 USA. [Keddache, Mehdi] Cincinnati Childrens Hosp Med Ctr, Genome Ctr, Cincinnati, OH 45229 USA. [Greenberg, David A.] Columbia Univ, Div Stat Genet, New York, NY 10032 USA. [Tomer, Yaron; Hasham, Alia; Davies, Terry F.; Stefan, Mihaela] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. RP Tomer, Y (reprint author), Mt Sinai Med Ctr, Div Endocrinol, Box 1055,1 Gustave L Levy Pl, New York, NY 10029 USA. EM yaron.tomer@mssm.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [DK061659, DK067555, DK073681, DK069713, DK052464, DK080459]; MADGC grant National Institutes of Health/National Institute of Allergy and Infectious Diseases [RO1-AI-68759]; Veterans Affairs Merit Award Program; [NS27941]; [NA61829]; [MH48858] FX This work was supported in part by Grants DK061659, DK067555, and DK073681 from the National Institute of Diabetes and Digestive and Kidney Diseases (to Y.T.); Grants DK069713, DK052464, and DK080459 from the National Institute of Diabetes and Digestive and Kidney Diseases (to T.F.D.); Grants NS27941, NA61829, and MH48858 (to D.A.G.); MADGC grant National Institutes of Health/National Institute of Allergy and Infectious Diseases Grant RO1-AI-68759 (to Peter Gregersen); and the Veterans Affairs Merit Award Program (to Y.T. and T.F.D.). NR 39 TC 19 Z9 19 U1 0 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2013 VL 98 IS 1 BP E144 EP E152 DI 10.1210/jc.2012-2408 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 107IT UT WOS:000316210300022 PM 23118423 ER PT J AU Virella, G Colglazier, J Chassereau, C Hunt, KJ Baker, NL Lopes-Virella, MF AF Virella, Gabriel Colglazier, Joan Chassereau, Charlyne Hunt, Kelly J. Baker, Nathaniel L. Lopes-Virella, Maria F. TI IMMUNOASSAY OF MODIFIED FORMS OF HUMAN LOW DENSITY LIPOPROTEIN IN ISOLATED CIRCULATING IMMUNE COMPLEXES SO JOURNAL OF IMMUNOASSAY & IMMUNOCHEMISTRY LA English DT Article DE diabetic complications; immune complexes; modified LDL capture assays; modified lipoproteins; oxidized LDL; risk factors ID CORONARY-ARTERY-DISEASE; INTIMA-MEDIA THICKNESS; OXIDIZED LDL; DIABETES-MELLITUS; ATHEROSCLEROSIS; ANTIBODIES; AUTOANTIBODIES; MACROPHAGES; PROGRESSION; CELLS AB Modified lipoproteins are able to induce inflammatory reactions through innate immunity pathways and are immunogenic, leading to an autoimmune response that results in the formation of proinflammatory immune complexes. The measurement of circulating oxidized lipoproteins and corresponding antibodies has, therefore, been proposed as an approach to assess the risk for complications in patients with diabetes and for the risk of cardiovascular disease in the general population. However, the majority of modified low density lipoprotein (LDL) in the peripheral circulation exists in the form of immune complexes, and this is a significant obstacle for the measurement of modified LDL and the corresponding antibodies. In this manuscript, we describe in detail the methodology developed by our group for isolation and fractionation of circulating immune complexes (IC), allowing the accurate assay of different LDL modifications. This approach has resulted in several studies showing that the levels of modified LDL are risk factors with a stronger association to diabetic retinopathy, nephropathy, and macrovascular disease. Ongoing research is focused on evaluating the predictive power of modified LDL levels for the development or progression of atherosclerotic cardiovascular disease in other patient populations and on the simplification of the assay to make it more applicable to diagnostic laboratories. C1 [Virella, Gabriel] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Colglazier, Joan; Chassereau, Charlyne; Lopes-Virella, Maria F.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Colglazier, Joan; Chassereau, Charlyne] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Hunt, Kelly J.; Baker, Nathaniel L.] Med Univ S Carolina, Charleston, SC 29425 USA. [Lopes-Virella, Maria F.] Ralph H Johnson VA Med Ctr, Dept Lab Serv, Charleston, SC USA. RP Virella, G (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, 173 Ashley Ave, Charleston, SC 29425 USA. EM virellag@musc.edu NR 40 TC 3 Z9 3 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1532-1819 J9 J IMMUNOASS IMMUNOCH JI J. Immunoass. Immunoch. PD JAN 1 PY 2013 VL 34 IS 1 BP 61 EP 74 DI 10.1080/15321819.2012.683500 PG 14 WC Biochemical Research Methods; Immunology; Medical Laboratory Technology SC Biochemistry & Molecular Biology; Immunology; Medical Laboratory Technology GA 105HH UT WOS:000316056800006 PM 23323982 ER PT J AU Brown, TJ Pittman, AL Monaco, GN Benscoter, BJ Mantravadi, AV Akst, LM Jones, KJ Foecking, EM AF Brown, Todd J. Pittman, Amy L. Monaco, Gina N. Benscoter, Brent J. Mantravadi, Avinash V. Akst, Lee M. Jones, Kathryn J. Foecking, Eileen M. TI Androgen treatment and recovery of function following recurrent laryngeal nerve injury in the rat SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Article DE Testosterone propionate; recurrent laryngeal nerve; vocal fold mobility; crush injury ID HAMSTER FACIAL MOTONEURONS; HUMAN VOCAL FOLD; GONADAL-STEROIDS; ELECTRICAL-STIMULATION; MESSENGER-RNA; SCIATIC-NERVE; REGENERATIVE PROPERTIES; INDUCED ACCELERATION; AXONAL REGENERATION; HORMONE-RECEPTORS AB Purpose: To investigate the effects of the androgen testosterone propionate (TP), on regeneration of the recurrent laryngeal nerve (RLN) after unilateral crush injury using assessment of vocal fold mobility (VFM) as a measure of behavioral recovery. Methods: 48 adult male rats underwent standardized crush injury of left RLN and received treatment in the form of 2 silastic capsules containing TP or controls receiving a blank capsule (untreated). Direct laryngoscopic assessment of vocal cord mobility was performed before, immediately following and 1, 2, 3, 4, 5 or 6 weeks post injury. Results: Treatment with TP enhanced the recovery of full VFM following crush injury of the RLN compared to controls. There was statistically significant improvement in VFM seen at the 1 and 2 week time points (p < 0.05). By 4 weeks TP-treated rats displayed a 100% recovery of VFM function, compared to only 50% by the control group. Conclusions: TP enhances RLN functional recovery following a crush injury, which further supports its potential general applicability as a therapeutic agent in peripheral nerve injury. C1 [Brown, Todd J.; Jones, Kathryn J.] Richard L Roudebush VA Med Ctr, R&D Serv, Indianapolis, IN USA. [Brown, Todd J.; Jones, Kathryn J.] Indiana Sch Med, Dept Cell Biol & Anat, Indianapolis, IN USA. [Pittman, Amy L.; Benscoter, Brent J.; Mantravadi, Avinash V.; Foecking, Eileen M.] Loyola Univ, Med Ctr, Dept Otolaryngol Head & Neck Surg, Proviso, IL USA. [Akst, Lee M.] Johns Hopkins Univ Hosp, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA. [Monaco, Gina N.] Loyola Univ Chicago, Stritch Sch Med, Cell Biol Neurobiol & Anat Program, Maywood, IL USA. [Foecking, Eileen M.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, R&D Serv, Hines, IL 60141 USA. RP Brown, TJ (reprint author), Richard L Roudebush VAMC, 1481W 10th St,Mail Code 151,Rm C-3074, Indianapolis, IN 46202 USA. EM tojobrow@iupui.edu FU Loyola RFC Grant [201299] FX The authors of this paper would like to acknowledge Keith Fargo, Ph.D. and Rena Meadows, B.S. for their invaluable help with statistical analysis and would also like to thank Piotr Tekiela for the technical work he contributed to this study. This work was supported by funds from Loyola RFC Grant #201299 and was performed in the labs of Dr. Kathryn Jones at Edward Hines, Jr. VA Hospital, Hines, IL. NR 44 TC 6 Z9 6 U1 0 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0922-6028 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PY 2013 VL 31 IS 2 BP 169 EP 176 DI 10.3233/RNN-120287 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 112SN UT WOS:000316613700006 PM 23247060 ER PT J AU Pandey, GS Tseng, SC Howard, TE Sauna, ZE AF Pandey, Gouri Shankar Tseng, Sandra C. Howard, Tom E. Sauna, Zuben E. TI Detection of Intracellular Factor VIII Protein in Peripheral Blood Mononuclear Cells by Flow Cytometry SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID HEMOPHILIA-A; MONOCLONAL-ANTIBODIES; GENE; INHIBITORS; EXPRESSION; COAGULATION AB Flow cytometry is widely used in cancer research for diagnosis, detection of minimal residual disease, as well as immune monitoring and profiling following immunotherapy. Detection of specific host proteins for diagnosis predominantly uses quantitative PCR and western blotting assays. In this study, we optimized a flow cytometry-based detection assay for Factor VIII protein in peripheral blood mononuclear cells (PBMCs). An indirect intracellular staining (ICS) method was standardized using monoclonal antibodies to different domains of human Factor VIII protein. The FVIII protein expression level was estimated by calculating the mean and median fluorescence intensities (MFI) values for each monoclonal antibody. ICS staining of transiently transfected cell lines supported the method's specificity. Intracellular FVIII protein expression was also detected by the monoclonal antibodies used in the study in PBMCs of five blood donors. In summary, our data suggest that intracellular FVIII detection in PBMCs of hemophilia A patients can be a rapid and reliable method to detect intracellular FVIII levels. C1 [Pandey, Gouri Shankar; Tseng, Sandra C.; Sauna, Zuben E.] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Howard, Tom E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA 90073 USA. RP Pandey, GS (reprint author), US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM gouri.pandey@fda.hhs.gov; zuben.sauna@fda.hhs.gov FU National Heart, Lung and Blood Institute; NIH [1RC2-HL101851, HL-71130, HL-72533]; Bayer Healthcare Corporation; Bayer Haemophilia Awards Program; Baxter Healthcare Corporation; Clinical Translational Science Institute at the University of Southern California's Keck School of Medicine FX The research conducted in the laboratory of Z. E. Sauna is funded by the Modernization of Science Program of the Center for Biologics Evaluation and Research, Food and Drug Administration. Research conducted in the laboratory of T. E. Howard is funded by Grants from the National Heart, Lung and Blood Institute, NIH, (1RC2-HL101851, HL-71130, and HL-72533) as well as from Bayer Healthcare Corporation, Bayer Haemophilia Awards Program, Baxter Healthcare Corporation, and the Clinical Translational Science Institute at the University of Southern California's Keck School of Medicine. NR 26 TC 2 Z9 2 U1 0 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 J9 BIOMED RES INT JI Biomed Res. Int. PY 2013 AR 793502 DI 10.1155/2013/793502 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 102YR UT WOS:000315881100001 ER PT J AU Ghazi, E Sontheimer, RD Werth, VP AF Ghazi, E. Sontheimer, R. D. Werth, V. P. TI The importance of including amyopathic dermatomyositis in the idiopathic inflammatory myositis spectrum SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Review DE amyopathic dermatomyositis; interstitial lung diseases; connective tissue disease ID INTERSTITIAL LUNG-DISEASE; SINE MYOSITIS; JAPANESE PATIENTS; GENE 5; POLYMYOSITIS; MYOPATHIES; AUTOANTIBODIES; MANIFESTATION; ASSOCIATION; DERMATOLOGY AB The objective of this review is to summarise the published evidence that supports the existence of amyopathic dermatomyositis (ADM) and its clinical significance including risk for rapidly progressive, fatal interstitial lung disease (ILD) and possible risk for internal malignancy. By establishing such inherent risks, we hope to establish the importance of formally recognising ADM as a subset of dermatomyositis (DM). Population-based epidemiologic studies have suggested that amyopathic DM might account for 20% of the total population of dermatomyositis (DM) patients (1). Patients presenting with ADM have been reported by investigators of multiple nationalities to be at risk for rapidly progressive, potentially fatal ILD (2-5). In addition, a new autoantibody, anti-CADM-140, has been reported to be a risk factor for the development of interstitial lung disease in CADM patients (6-9). It has been argued that ADM patients may be at increased risk of developing internal malignancy compared to the general population, though its rate in comparison to classic DM (CDM) needs further study (1, 10-12). In our population, 41% of CADM patients were previously classified as LE or UCTD. We conclude that ADM is a real entity that makes up a significant portion of the DM disease. It is important to formally recognise amyopathic DM as a subset of DM as it carries increased risk of ILD and possibly malignancy. Without appropriate disease classification, the opportunity for ILD and malignancy screening may be missed. C1 [Ghazi, E.; Werth, V. P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Ghazi, E.; Werth, V. P.] Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. [Ghazi, E.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. [Sontheimer, R. D.] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA. RP Werth, VP (reprint author), Perelman Ctr Adv Med, Dept Dermatol, Suite 1-330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU NIAMS NIH HHS [K24 AR002207] NR 55 TC 10 Z9 12 U1 0 U2 1 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD JAN-FEB PY 2013 VL 31 IS 1 BP 128 EP 134 PG 7 WC Rheumatology SC Rheumatology GA 101ER UT WOS:000315758500020 PM 23190767 ER PT J AU Yeh, CH Chien, LC Balaban, D Sponberg, R Primavera, J Morone, NE Glick, R Albers, KM Cohen, SM Ren, DX Huang, LC Suen, LKP AF Yeh, Chao Hsing Chien, Lung Chang Balaban, Devora Sponberg, Rebecca Primavera, Jaclyn Morone, Natalia E. Glick, Ronald Albers, Kathryn M. Cohen, Susan M. Ren, Dianxu Huang, Li Chun Suen, Lorna Kwai-Ping TI A Randomized Clinical Trial of Auricular Point Acupressure for Chronic Low Back Pain: A Feasibility Study SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article ID EVIDENCE-INFORMED MANAGEMENT; MORRIS DISABILITY QUESTIONNAIRE; PRIMARY DYSMENORRHEA; ACUPUNCTURE POINTS; AURICULOTHERAPY; PREVALENCE; SCALE; CARE AB Objectives. This prospective, randomized clinical trial (RCT) was designed to investigate the feasibility and effects of a 4-week auricular point acupressure (APA) for chronic low back pain (CLBP). Methods. Participants were randomized to either true APA (true acupoints with taped seeds on the designated ear points for CLBP) or sham APA (sham acupoints with taped seeds but on different locations than those designated for CLBP). The duration of treatment was four weeks. Participants were assessed before treatment, weekly during treatment, and 1 month following treatment. Results. Participants in the true APA group who completed the 4-week APA treatment had a 70% reduction in worst pain intensity, a 75% reduction in overall pain intensity, and a 42% improvement in disability due to back pain from baseline assessment. The reductions of worst pain and overall pain intensity in the true APA group were statistically greater than participants in the sham group (P < 0.01) at the completion of a 4-week APA and 1 month followup. Discussion. The preliminary findings of this feasibility study showed a reduction in pain intensity and improvement in physical function suggesting that APA may be a promising treatment for patients with CLBP. C1 [Yeh, Chao Hsing; Balaban, Devora; Sponberg, Rebecca; Primavera, Jaclyn; Cohen, Susan M.; Ren, Dianxu] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. [Chien, Lung Chang] Washington Univ, Dept Internal Med, St Louis, MO USA. [Morone, Natalia E.] Univ Pittsburgh, Sch Med, Dept Med, VA Pittsburgh Healthcare Syst,Geriatr Res Educ &, Pittsburgh, PA 15213 USA. [Glick, Ronald] Univ Pittsburgh, Sch Med, Med Ctr, Dept Psychiat Phys Med & Rehabil, Pittsburgh, PA USA. [Glick, Ronald] Univ Pittsburgh, Sch Med, Med Ctr, Dept Family Med, Pittsburgh, PA USA. [Albers, Kathryn M.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Huang, Li Chun] World Acad Auricular Med, Hoover, AL USA. [Suen, Lorna Kwai-Ping] Hong Kong Polytech Univ, Sch Nursing, Hong Kong, Hong Kong, Peoples R China. RP Yeh, CH (reprint author), Univ Pittsburgh, Sch Nursing, 3500 Victoria St,440 Victoria Bldg, Pittsburgh, PA 15261 USA. EM yehc@pitt.edu RI Suen, Lorna/F-5077-2014 OI Suen, Lorna/0000-0002-0126-6674; Albers, Kathryn/0000-0003-4597-9323 FU Center for Research and Evaluation Pilot/Feasibility Study Program, School of Nursing, University of Pittsburgh FX This study was supported by a grant to Dr. Yeh from Center for Research and Evaluation Pilot/Feasibility Study Program, School of Nursing, University of Pittsburgh. NR 51 TC 6 Z9 6 U1 1 U2 23 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1741-427X EI 1741-4288 J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PY 2013 AR 196978 DI 10.1155/2013/196978 PG 9 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 103EJ UT WOS:000315897200001 ER PT J AU Doba, N Tokuda, Y Tomiyama, H Goldstein, NE Kushiro, T Hinohara, S AF Doba, Nobutaka Tokuda, Yasuharu Tomiyama, Hirofumi Goldstein, Nathan E. Kushiro, Toshio Hinohara, Shigeaki TI Changes in Ankle Brachial Pulse Wave Velocity during a Five-Year Follow-up Period in Older Japanese Adults: Sub-analysis Results of the Health Research Volunteer Study in Japan SO INTERNAL MEDICINE LA English DT Article DE aging; arterial stiffness; antihypertensive medication; older adults; low hemoglobin ID ALL-CAUSE MORTALITY; ARTERIAL STIFFNESS; BLOOD-PRESSURE; BASE-LINE; CARDIOVASCULAR EVENTS; HYPERTENSION; FRAILTY; AGE; METAANALYSIS; TRIAL AB Objective Brachial-ankle pulse wave velocity (baPWV) is a measure of arterial stiffness. However, precisely how aging, hypertension and other factors influence this in progressively stiffening large arteries, especially in older adults, remains uncertain. We examined changes in arterial stiffness in a population of active older Japanese adults using a five-year follow-up cohort study. Methods Comprehensive geriatric assessments were performed in socially active adults over the age of 70 years at The Life Planning Center Clinic in Tokyo. Clinically acceptable baPWV measurements at baseline and at the end of the study were obtained in 257 individuals (115 men, baseline mean age of 78 +/- 4 years; 142 women, baseline mean age of 77 +/- 4 years) classified into four groups based on the use of antihypertensive interventions at the end of the study: Group 1 (112 normotensives), Group 2 (49 hypertensives without medication use), Group 3 (39 hypertensives with medication use initiated during the follow-up period) and Group 4 (57 hypertensives receiving medications throughout the follow-up period). Results During the follow-up period, Group 1 exhibited no changes in blood pressure with increases in baPWV. Group 2 exhibited increases in blood pressure and baPWV. Both Groups 3 and 4 exhibited decreases in blood pressure without any changes in baPWV. Other factors such as age, gender and the hemoglobin level could also have influenced baPWV. Conclusion Arterial stiffness increases with aging; however, antihypertensive medications were found to provide protective effects against the development of arterial stiffness during a five-year follow-up period. Other factors that modify baPWV were also identified. C1 [Doba, Nobutaka] Life Planning Ctr Fdn, Div Res & Educ, Tokyo, Japan. [Tokuda, Yasuharu] Univ Tsukuba, Inst Clin Med, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 305, Japan. [Tomiyama, Hirofumi] Tokyo Med Univ, Dept Internal Med 2, Tokyo 1608402, Japan. [Goldstein, Nathan E.] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY USA. [Goldstein, Nathan E.] James J Peters VA Med Ctr, Bronx, NY USA. [Kushiro, Toshio] Nihon Univ, Sch Med, Ctr Hlth Evaluat & Promot, Tokyo 102, Japan. RP Doba, N (reprint author), Life Planning Ctr Fdn, Div Res & Educ, Tokyo, Japan. EM doba@krd.biglobe.ne.jp FU Life Planning Center FX This work was supported by an institutional research fund from the Life Planning Center (a non-profit organization). We thank all the Healthy Research Volunteers who participated in this study, and we also express our gratitude to the other research members at the LPC for their professional and technical assistance with the study. NR 26 TC 3 Z9 5 U1 1 U2 1 PU JAPAN SOC INTERNAL MEDICINE PI TOKYO PA 34-3 3-CHOME HONGO BUNKYO-KU, TOKYO, 113, JAPAN SN 0918-2918 J9 INTERNAL MED JI Intern. Med. PY 2013 VL 52 IS 1 BP 21 EP 27 DI 10.2169/internalmedicine.52.8671 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 103YD UT WOS:000315954500005 PM 23291670 ER PT J AU Won, JS Kim, J Annamalai, B Shunmugavel, A Singh, I Singh, AK AF Won, Je-Seong Kim, Jinsu Annamalai, Balasubramaniam Shunmugavel, Anandakumar Singh, Inderjit Singh, Avtar K. TI Protective Role of S-Nitrosoglutathione (GSNO) Against Cognitive Impairment in Rat Model of Chronic Cerebral Hypoperfusion SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; amyloid-beta; bilateral common carotid artery occlusion; cerebral hypoperfusion; inflammation; S-nitrosylation; S-nitrosoglutathione ID NITRIC-OXIDE SYNTHASE; CHRONIC BRAIN HYPOPERFUSION; CAROTID-ARTERY OCCLUSION; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; LEARNING DYSFUNCTION; ENDOTHELIAL FUNCTION; NITROSO-GLUTATHIONE; EXPERIMENTAL STROKE; DOPAMINE NEURONS AB Chronic cerebral hypoperfusion (CCH), featuring in most of the Alzheimer's disease spectrum, plays a detrimental role in brain amyloid-beta (A beta) homeostasis, cerebrovascular morbidity, and cognitive decline; therefore, early management of cerebrovascular pathology is considered to be important for intervention in the impending cognitive decline. S-nitrosoglutathione (GSNO) is an endogenous nitric oxide carrier modulating endothelial function, inflammation, and neurotransmission. Therefore, the effect ofGSNOtreatment on CCH-associated neurocognitive pathologieswas determined in vivo by using rats with permanent bilateral common carotid artery occlusion (BCCAO), a rat model of chronic cerebral hypoperfusion. We observed that rats subjected to permanent BCCAO showed a significant decrease in learning/memory performance and increases in brain levels of A beta and vascular inflammatory markers. GSNO treatment (50 mu g/kg/day for 2 months) significantly improved learning and memory performance of BCCAO rats and reduced the A beta levels and ICAM-1/VCAM-1 expression in the brain. Further, in in vitro cell culture studies, GSNO treatment also decreased the cytokine-induced proinflammatory responses, such as activations of NF kappa B and STAT3 and expression of ICAM-1 and VCAM-1 in endothelial cells. In addition, GSNO treatment increased the endothelial and microglial A beta uptake. Additionally, GSNO treatment inhibited the beta-secretase activity in primary rat neuron cell culture, thus reducing secretion of A beta, suggesting GSNO mediated mechanisms in anti-inflammatory and anti-amyloidogenic activities. Taken together, these data document that systemic GSNO treatment is beneficial for improvement of cognitive decline under the conditions of chronic cerebral hypoperfusion and suggests a potential therapeutic use of GSNO for cerebral hypoperfusion associated mild cognitive impairment in Alzheimer's disease. C1 [Won, Je-Seong; Annamalai, Balasubramaniam; Singh, Avtar K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Kim, Jinsu; Shunmugavel, Anandakumar; Singh, Inderjit] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Singh, Avtar K.] Ralph H Johnson Vet Adm Med Ctr, Pathol & Lab Med Serv, Charleston, SC USA. RP Singh, AK (reprint author), Med Univ S Carolina, Charles P Darby Children Res Inst, Dept Pathol & Lab Med, 504D,173 Ashley Ave, Charleston, SC 29425 USA. EM avtar.singh@va.gov FU NIH; VA [NS072511, BX001062, NS037766, NS022576, BX001072] FX This work was supported by grants from NIH and VA (NS072511, BX001062, NS037766, NS022576 and BX001072). We also acknowledge Ms. Joyce Bryan and Ms. Chara Williams for their help in procurement of animals and supplies. NR 63 TC 16 Z9 19 U1 0 U2 7 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2013 VL 34 IS 3 BP 621 EP 635 DI 10.3233/JAD-121786 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 104KK UT WOS:000315991500006 PM 23254638 ER PT J AU Wang, LX Stengel, A Goebel-Stengel, M Shaikh, A Yuan, PQ Tache, Y AF Wang, Lixin Stengel, Andreas Goebel-Stengel, Miriam Shaikh, Almaas Yuan, Pu-Qing Tache, Yvette TI Intravenous injection of urocortin 1 induces a CRF2 mediated increase in circulating ghrelin and glucose levels through distinct mechanisms in rats SO PEPTIDES LA English DT Article DE Acyl ghrelin; Astressin(2)-B; CRF; Des-acyl ghrelin; Radioimmunoassay; Rat; Urocortin ID CORTICOTROPIN-RELEASING-FACTOR; ACYL GHRELIN; FOOD-INTAKE; FUNCTIONAL IMPLICATIONS; PERIPHERAL UROCORTIN; INTERNATIONAL-UNION; DESACYL GHRELIN; RECEPTORS; STOMACH; HORMONE AB Urocortins (Ucns) injected peripherally decrease food intake and gastric emptying through peripheral CRF2 receptors in rodents. However, whether Ucns influence circulating levels of the orexigenic and prokinetic hormone, ghrelin has been little investigated. We examined plasma levels of ghrelin and blood glucose after intravenous (iv) injection of Ucn 1, the CRF receptor subtype involved and underlying mechanisms in ad libitum fed rats equipped with a chronic iv cannula. Ucn 1 (10 mu g/kg, iv) induced a rapid onset and long lasting increase in ghrelin levels reaching 68% and 219% at 0.5 and 3 h post injection respectively and a 5-h hyperglycemic response. The selective CRF2 agonist, Ucn 2 (3 mu g/kg, iv) increased fasting acyl (3 h: 49%) and des-acyl ghrelin levels (3 h: 30%) compared to vehicle while the preferential agonist, CRF (3 mu g/kg, iv) had no effect. Ucn l's stimulatory actions were blocked by the selective CRF2 antagonist, astressin(2)-B (100 mu g/kg, iv). Hexamethonium (10 mg/kg, sc) prevented Ucn 1-induced rise in total ghrelin levels while not altering the hyperglycemic response. These data indicate that systemic injection of Ucns induces a CRF2-mediated increase in circulating ghrelin levels likely via indirect actions on gastric ghrelin cells that involves a nicotinic pathway independently from the hyperglycemic response. (C) 2012 Elsevier Inc. All rights reserved. C1 [Wang, Lixin; Stengel, Andreas; Goebel-Stengel, Miriam; Shaikh, Almaas; Yuan, Pu-Qing; Tache, Yvette] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA USA. [Wang, Lixin; Stengel, Andreas; Goebel-Stengel, Miriam; Shaikh, Almaas; Yuan, Pu-Qing; Tache, Yvette] Univ Calif Los Angeles, Dept Med, Div Digest Dis, Ctr Neurobiol Stress, Los Angeles, CA 90024 USA. [Wang, Lixin; Stengel, Andreas; Goebel-Stengel, Miriam; Shaikh, Almaas; Yuan, Pu-Qing; Tache, Yvette] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Wang, LX (reprint author), 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM lixinw@ucla.edu FU Veterans Administration Research Career Scientist Award; VA Merit Award; German Research Foundation [STE 1765/3-1]; Charite University Funding [UFF 89-441-176]; [NIH DK-41301]; [R01 NIH DX 33061] FX This work was supported by the Veterans Administration Research Career Scientist Award, VA Merit Award, Center Grant NIH DK-41301 (Animal Core) and R01 NIH DX 33061 (Y.T.), German Research Foundation STE 1765/3-1 (A.S.) and Charite University Funding UFF 89-441-176 (A.S.). We thank Dr. Jean Rivier (Clayton Foundation Laboratories, Salk Institute, La Jolla, CA) for the generous supply of peptides. We are grateful to Mrs. Honghui Liang for the excellent technical support and Ms. Eugenia Hu for her review of the manuscript. NR 55 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD JAN PY 2013 VL 39 BP 164 EP 170 DI 10.1016/j.peptides.2012.11.009 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 102IW UT WOS:000315839300025 PM 23183626 ER PT J AU Zhao, W Ho, L Varghese, M Yemul, S Dams-O'Connor, K Gordon, W Knable, L Freire, D Haroutunian, V Pasinetti, GM AF Zhao, Wei Ho, Lap Varghese, Merina Yemul, Shrishailam Dams-O'Connor, Kristen Gordon, Wayne Knable, Lindsay Freire, Daniel Haroutunian, Vahram Pasinetti, Giulio Maria TI Decreased Level of Olfactory Receptors in Blood Cells Following Traumatic Brain Injury and Potential Association with Tauopathy SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Biomarker; olfactory receptor; peripheral blood mononuclear cell; tauopathy; traumatic brain injury ID MILD ALZHEIMER-DISEASE; LOBE MEMORY SYSTEM; MOUSE MODEL; IN-VITRO; EXPRESSION; PROTEIN; TAU; PLASTICITY; DISCOVERY; SCLEROSIS AB Traumatic brain injury (TBI) is a leading cause of death and disability among children and young adults in the United States. In this study, we explored whether changes in the gene expression profile of peripheral blood mononuclear cells (PBMC) may provide a clinically assessable "window" into the brain, reflecting molecular alterations following TBI that might contribute to the onset and progression of TBI clinical complications. We identified three olfactory receptor (OR) TBI biomarkers that are aberrantly down-regulated in PBMC specimens from TBI subjects. Down-regulation of these OR biomarkers in PBMC was correlated with the severity of brain injury and TBI-specific symptoms. A two-biomarker panel comprised of OR11H1 and OR4M1 provided the best criterion for segregating the TBI and control cases with 90% accuracy, 83.3% sensitivity, and 100% specificity. We found that the OR biomarkers are ectopically expressed in multiple brain regions, including the entorhinal-hippocampus system known to play an important role in memory formation and consolidation. Activation of OR4M1 led to attenuation of abnormal tau phosphorylation, possibly through JNK signaling pathway. Our results suggested that addition of the two-OR biomarker model to current diagnostic criteria may lead to improved TBI detection for clinical trials, and decreased expression of OR TBI biomarkers might be associated with TBI-induced tauopathy. Future studies exploring the physiological relevance of OR TBI biomarkers in the normal brain and in the brain following TBI will provide a better understanding of the biological mechanisms underlying TBI and insights into novel therapeutic targets for TBI. C1 [Zhao, Wei; Ho, Lap; Varghese, Merina; Yemul, Shrishailam; Knable, Lindsay; Freire, Daniel; Pasinetti, Giulio Maria] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Dams-O'Connor, Kristen; Gordon, Wayne] Mt Sinai Sch Med, Dept Rehabil, New York, NY 10029 USA. [Haroutunian, Vahram; Pasinetti, Giulio Maria] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Yemul, Shrishailam; Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, GRECC, Bronx, NY USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Neurol, 1468 Madison Ave,Annenberg Bldg,Room 20-02, New York, NY 10029 USA. EM Giulio.Pasinetti@mssm.edu OI Varghese, Merina/0000-0002-1517-3903 FU National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [UL1RR029887] FX This study was supported in part by discretionary funding to GMP and in part from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) (UL1RR029887). NR 50 TC 11 Z9 11 U1 0 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2013 VL 34 IS 2 BP 417 EP 429 DI 10.3233/JAD-121894 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 095MF UT WOS:000315337900008 PM 23241557 ER PT J AU Tadros, NN Bland, L Legg, E Olyaei, A Conlin, MJ AF Tadros, Nicholas N. Bland, Lisa Legg, Edith Olyaei, Ali Conlin, Michael J. TI A single dose of a non-steroidal anti-inflammatory drug (NSAID) prevents severe pain after ureteric stent removal: a prospective, randomised, double-blind, placebo-controlled trial SO BJU INTERNATIONAL LA English DT Article DE ureteroscopy; stents; urolithiasis; NSAIDs ID IN-VITRO; SYMPTOMS; CONTRACTILITY; INHIBITORS AB Objectives To determine the incidence of severe pain after ureteric stent removal. To evaluate the efficacy of a single dose of a non-steroidal anti-inflammatory drug (NSAID) in preventing this complication. Patients and Methods A prospective, randomised, double-blind, placebo-controlled trial was performed at our institution. Adults with an indwelling ureteric stent after ureteroscopy were randomised to receive either a single dose of placebo or an NSAID (rofecoxib 50 mg) before ureteric stent removal. Pain was measured using a visual analogue scale (VAS) just before and 24 h after stent removal Pain medication use after ureteric stent removal was measured using morphine equivalents. Results In all, 22 patients were enrolled and randomised into the study before ending the study after interim analysis showed significant decrease in pain level in the NSAID group. The most common indication for ureteroscopy was urolithiasis (14 patients). The proportion of patients with severe pain (VAS score of >= 7) during the 24 h after ureteric stent removal was six of 11 (55%) in the placebo group and it was zero of 10 in the NSAID group (P < 0.01). There were no complications related to the use of rofecoxib. Conclusions We found a 55% incidence of severe pain after ureteric stent removal. A single dose of a NSAID before stent removal prevents severe pain after ureteric stent removal. C1 [Tadros, Nicholas N.; Bland, Lisa; Legg, Edith; Olyaei, Ali] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Conlin, Michael J.] Portland VA Med Ctr, Portland, OR USA. RP Conlin, MJ (reprint author), Oregon Hlth & Sci Univ, Div Urol & Renal Transplantat, CH 10U,3303 SW Bond Ave, Portland, OR 97239 USA. EM conlinm@ohsu.edu OI Tadros, Nick/0000-0002-2272-235X NR 11 TC 12 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD JAN PY 2013 VL 111 IS 1 BP 101 EP 105 DI 10.1111/j.1464-410X.2012.11214.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 092ZG UT WOS:000315160900021 PM 22578110 ER PT B AU Kline, AE Cheng, JP Dixon, CE AF Kline, Anthony E. Cheng, Jeffrey P. Dixon, C. Edward BE Zasler, ND Katz, DI Zafonte, RD TI Experimental Therapeutic Approaches for Traumatic Brain Injury SO BRAIN INJURY MEDICINE: PRINCIPLES AND PRACTICE, SECOND EDITION LA English DT Article; Book Chapter ID 5-HT1A RECEPTOR AGONIST; CONTROLLED CORTICAL IMPACT; FIBROBLAST-GROWTH-FACTOR; CALCIUM-CHANNEL BLOCKER; FLUID-PERCUSSION INJURY; IMPROVES FUNCTIONAL RECOVERY; EXPERIMENTAL HEAD-INJURY; VESICULAR ACETYLCHOLINE TRANSPORTER; ATTENUATES COGNITIVE DYSFUNCTION; AMPHETAMINE-INDUCED RECOVERY C1 [Kline, Anthony E.; Cheng, Jeffrey P.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. [Kline, Anthony E.] Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA USA. [Dixon, C. Edward] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA. [Dixon, C. Edward] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Kline, AE (reprint author), Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. NR 263 TC 0 Z9 0 U1 0 U2 1 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-27-7 PY 2013 BP 175 EP 192 PG 18 WC Clinical Neurology SC Neurosciences & Neurology GA BDJ25 UT WOS:000313536100014 ER PT B AU Cooper, RA McCue, M Schein, RM Cooper, R Sporner, ML Dodson, MB Reinsfelder, AM Yeager, AF Jinks, A LoPresti, E McClure, L Wang, HW Collinger, JL Hiremath, S Ding, D Lewis, A AF Cooper, Rory A. McCue, Michael Schein, Richard M. Cooper, Rosemarie Sporner, Michelle L. Dodson, Matthew B. Reinsfelder, Amanda M. Yeager, Arthur F. Jinks, Andrew LoPresti, Edmund McClure, Laura Wang, Hongwu Collinger, Jennifer L. Hiremath, Shivayogi Ding, Dan Lewis, Allen BE Zasler, ND Katz, DI Zafonte, RD TI Assistive Technology for People With Traumatic Brain Injuries SO BRAIN INJURY MEDICINE: PRINCIPLES AND PRACTICE, SECOND EDITION LA English DT Article; Book Chapter ID STAIRCASE-CLIMBING WHEELCHAIR; SPINAL-CORD INJURIES; OF-THE-ART; COGNITIVE IMPAIRMENTS; SMART HOMES; CLINICAL-APPLICATIONS; COMPUTER INTERFACES; PARAPLEGIC PATIENTS; PAGING SYSTEM; REHABILITATION C1 [Cooper, Rory A.; McCue, Michael; Schein, Richard M.; Cooper, Rosemarie; Sporner, Michelle L.; Jinks, Andrew; Wang, Hongwu; Hiremath, Shivayogi; Ding, Dan; Lewis, Allen] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. [Cooper, Rory A.] VA Pittsburgh Healthcare Syst, VA Rehabil Res & Dev Ctr Excellence, Pittsburgh, PA USA. [Cooper, Rosemarie] UPMC Ctr Assist Technol, Clin Serv, Pittsburgh, PA USA. [Dodson, Matthew B.] Walter Reed Natl Mil Med Ctr, TBI Sect, Occupat Therapy Dept, Bethesda, MD USA. [Reinsfelder, Amanda M.] Occupat Therapy Dept, TBI Sect, Bethesda, MD USA. [Yeager, Arthur F.] Walter Reed Natl Mil Med Ctr, Dept Orthoped & Rehabil, Bethesda, MD USA. [Jinks, Andrew] UPMC Ctr Assist Technol, Pittsburgh, PA USA. [LoPresti, Edmund] AT Sci LLC, Pittsburgh, PA USA. [McClure, Laura] Carle Fdn Hosp, Urbana, IL USA. [Collinger, Jennifer L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. RP Cooper, RA (reprint author), Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. NR 138 TC 0 Z9 0 U1 0 U2 4 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-27-7 PY 2013 BP 1178 EP 1199 PG 22 WC Clinical Neurology SC Neurosciences & Neurology GA BDJ25 UT WOS:000313536100071 ER PT J AU Yuan, BZ Feng, JQ Bowman, S Liu, Y Blank, RD Lindberg, I Drezner, MK AF Yuan, Baozhi Feng, Jian Q. Bowman, Stephen Liu, Ying Blank, Robert D. Lindberg, Iris Drezner, Marc K. TI Hexa-D-Arginine Treatment Increases 7B2 center dot PC2 Activity in hyp-Mouse Osteoblasts and Rescues the HYP Phenotype SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE X-LINKED HYPOPHOSPHATEMIA; hyp-Mouse; 7B2; SPC2; HEXA-d-ARGININE; fgf-23; BONE; RICKETS; OSTEOMALACIA ID LINKED HYPOPHOSPHATEMIC RICKETS; FAMILIAL TUMORAL CALCINOSIS; DENTIN MATRIX PROTEIN-1; RENAL 25-HYDROXYVITAMIN-D-1-ALPHA-HYDROXYLASE ACTIVITY; PROHORMONE CONVERTASE PC2; GROWTH-FACTOR 23; IN-VIVO; PEX GENE; PHOSPHATE HOMEOSTASIS; ENZYMATIC-ACTIVITY AB Inactivating mutations of the "phosphate regulating gene with homologies to endopeptidases on the X chromosome" (PHEX/Phex) underlie disease in patients with X-linked hypophosphatemia (XLH) and the hyp-mouse, a murine homologue of the human disorder. Although increased serum fibroblast growth factor 23 (FGF-23) underlies the HYP phenotype, the mechanism(s) by which PHEX mutations inhibit FGF-23 degradation and/or enhance production remains unknown. Here we show that treatment of wild-type mice with the proprotein convertase (PC) inhibitor, decanoyl-Arg-Val-Lys-Arg-chloromethyl ketone (Dec), increases serum FGF-23 and produces the HYP phenotype. Because PC2 is uniquely colocalized with PHEX in osteoblasts/bone, we examined if PC2 regulates PHEX-dependent FGF-23 cleavage and production. Transfection of murine osteoblasts with PC2 and its chaperone protein 7B2 cleaved FGF-23, whereas Signe1 (7B2) RNA interference (RNAi) transfection, which limited 7B2 protein production, decreased FGF-23 degradation and increased Fgf-23 mRNA and protein. The mechanism by which decreased 7B2 center dot PC2 activity influences Fgf-23 mRNA was linked to reduced conversion of the precursor to bone morphogenetic protein 1 (proBMP1) to active BMP1, which resulted in limited cleavage of dentin matrix acidic phosphoprotein 1 (DMP1), and consequent increased Fgf-23 mRNA. The significance of decreased 7B2 center dot PC2 activity in XLH was confirmed by studies of hyp-mouse bone, which revealed significantly decreased Sgne1 (7B2) mRNA and 7B2 protein, and limited cleavage of proPC2 to active PC2. The expected downstream effects of these changes included decreased FGF-23 cleavage and increased FGF-23 synthesis, secondary to decreased BMP1-mediated degradation of DMP1. Subsequent Hexa-D-Arginine treatment of hyp-mice enhanced bone 7B2 center dot PC2 activity, normalized FGF-23 degradation and production, and rescued the HYP phenotype. These data suggest that decreased PHEX-dependent 7B2 center dot PC2 activity is central to the pathogenesis of XLH. (C) 2013 American Society for Bone and Mineral Research. C1 [Yuan, Baozhi; Bowman, Stephen; Blank, Robert D.; Drezner, Marc K.] Univ Wisconsin, Dept Med, Madison, WI 53705 USA. [Yuan, Baozhi; Bowman, Stephen; Blank, Robert D.; Drezner, Marc K.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res & Educ Ctr, Madison, WI USA. [Feng, Jian Q.; Liu, Ying] Texas A&M Hlth Sci Ctr, Baylor Coll Dent, Dept Biomed Sci, Dallas, TX USA. [Lindberg, Iris] Univ Maryland, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. RP Drezner, MK (reprint author), Univ Wisconsin, Hlth Sci Learning Ctr 4246, Sch Med & Publ Hlth, 750 Highland Ave, Madison, WI 53705 USA. EM mkd@medicine.wisc.edu FU NIH [R01-AR27032, R01-SK65830, 1UL1RR025011, R01-DE018486, AR54753, DK049703]; Veterans Administration FX This work was funded by NIH grants (R01-AR27032, R01-SK65830, and 1UL1RR025011 to MKD; R01-DE018486 to JQF; AR54753 to RDB; and DK049703 to IL) and a Veterans Administration grant to RD Blank (Merit Award). The work reported in this article was conducted in the VAMC Geriatrics Research, Education, and Clinical Center, Madison, WI, USA. NR 71 TC 22 Z9 23 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JAN PY 2013 VL 28 IS 1 BP 56 EP 72 DI 10.1002/jbmr.1738 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 092EY UT WOS:000315103200007 PM 22886699 ER PT J AU Wilhelm, CJ Choi, D Huckans, M Manthe, L Loftis, JM AF Wilhelm, Clare J. Choi, Dongseok Huckans, Marilyn Manthe, Laura Loftis, Jennifer M. TI Adipocytokine signaling is altered in flinders sensitive line rats, and adiponectin correlates in humans with some symptoms of depression SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE Depression; Forced swim test; Hippocampus; Behavioral despair; Adipocytokine ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; GENETIC ANIMAL-MODEL; MAJOR DEPRESSION; HIPPOCAMPAL VOLUME; MOOD DISORDERS; PLASMA LEPTIN; INVENTORY-II; DSM-IV; SCHIZOPHRENIA; ANTIDEPRESSANT AB Major depression is a complex multi-factorial disorder with a lifetime diagnosis of nearly 1 out of 6. We used the Flinders Sensitive Line (FSL) of rats, a model of depression, and the parent Sprague-Dawley (SD) rats to identify genes, gene ontology categories and pathways associated with depression. Depression-like behavior was verified in the FSL line by forced swim testing, with FSL animals exhibiting greater immobility compared to SD rats. RNA samples from the hippocampus were isolated from a group of experimentally naive FSL and SD rats for microarray analysis. Microarray analysis yielded a total of 361 genes that were differentially regulated between FSL and SD rats, with catechol-O-methyltransferase (COMT) being the most up-regulated. The genes that were differentially regulated between FSL and SD rats were subjected to bioinformatic analysis using the Database for Annotation, Visualization and Integrated Discovery (DAVID), which yielded several gene ontology categories that were overrepresented. Subsequent pathway analysis indicated dysregulation of the adipocytokine signaling pathway. To test the translational impact of this pathway, metabolic factors and psychiatric symptoms were evaluated in a sample of human research participants. Results from our human subjects indicated that anxiety and a subset of depressive symptoms were correlated with adiponectin levels (but not leptin levels). Our results and those of others suggest that disruption of the adipocytokine signaling pathway may be a critical component of the depressive-like behaviors observed in the FSL rats and may also be an important indicator of depressive and anxiety symptoms in humans. Published by Elsevier Inc. C1 [Wilhelm, Clare J.; Huckans, Marilyn; Manthe, Laura; Loftis, Jennifer M.] Portland VA Med Ctr, Res & Dev Serv, Portland, OR USA. [Wilhelm, Clare J.; Huckans, Marilyn; Loftis, Jennifer M.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Choi, Dongseok] Oregon Hlth & Sci Univ, Dept Publ Hlth & Preventat Med, Portland, OR 97201 USA. RP Loftis, JM (reprint author), Portland VA Med Ctr R&D 16, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development and Clinical Sciences Research and Development FX This material is the result of work supported with resources and the use of facilities at the Portland Veterans Affairs Medical Center. JML, CJW and MH are supported by career development awards from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development and Clinical Sciences Research and Development. We thank Dr. Amir H. Rezvani, Department of Psychiatry, Duke University Medical Center for providing the Flinders Sensitive Line rats and Dr. David Overstreet, Department of Psychiatry, University of North Carolina at Chapel Hill, for review of this manuscript. We also thank Nikki Walter and the Portland Alcohol Research Center Molecular and Bioinformatics Core for technical assistance with the quantitative real-time PCR. NR 77 TC 11 Z9 11 U1 4 U2 14 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 JAN PY 2013 VL 103 IS 3 BP 643 EP 651 DI 10.1016/j.pbb.2012.11.001 PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 087VL UT WOS:000314792100029 PM 23153628 ER PT J AU Blondon, M Harrington, L Hoppe, KK Righini, M Boehlen, F Smith, NL Bounameaux, H AF Blondon, M. Harrington, L. Hoppe, K. K. Righini, M. Boehlen, F. Smith, N. L. Bounameaux, H. TI Risk of venous thrombosis after Cesarean sections: a meta-analysis SO THROMBOSIS RESEARCH LA English DT Meeting Abstract CT 5th International Symposiam on Womens Health Issues in Thrombosis and Haemostasis CY FEB 01-03, 2013 CL Vienna, AUSTRIA C1 [Blondon, M.; Harrington, L.; Smith, N. L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Hoppe, K. K.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Smith, N. L.] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA. [Smith, N. L.] US Dept Vet Affairs, Seattle Epidemiol Res & Informat Ctr, Off Res & Dev, Seattle, WA USA. [Blondon, M.; Righini, M.; Boehlen, F.; Bounameaux, H.] Univ Hosp Geneva, Div Angiol & Haemostasis, Dept Med, Geneva, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD JAN PY 2013 VL 131 SU 1 BP S97 EP S97 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 087AR UT WOS:000314734100120 ER PT J AU Blondon, M Wiggins, KL Harrington, L Li, G McKnight, B Psaty, BM Smith, NL AF Blondon, M. Wiggins, K. L. Harrington, L. Li, G. McKnight, B. Psaty, B. M. Smith, N. L. TI Interactions between genetic polymorphisms and oral hormone therapy on the risk of venous thrombosis SO THROMBOSIS RESEARCH LA English DT Meeting Abstract CT 5th International Symposiam on Womens Health Issues in Thrombosis and Haemostasis CY FEB 01-03, 2013 CL Vienna, AUSTRIA C1 [Blondon, M.; Harrington, L.; Psaty, B. M.; Smith, N. L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Wiggins, K. L.; Li, G.; Psaty, B. M.] Univ Washington, Dept Med, Seattle, WA USA. [McKnight, B.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Psaty, B. M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, B. M.; Smith, N. L.] Grp Hlth, Group Hlth Res Inst, Seattle, WA USA. [Smith, N. L.] US Dept Vet Affairs, Seattle Epidemiol Res & Informat Ctr, Off Res & Dev, Seattle, WA USA. [Blondon, M.] Univ Hosp Geneva, Dept Med, Geneva, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD JAN PY 2013 VL 131 SU 1 BP S97 EP S98 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 087AR UT WOS:000314734100121 ER PT J AU Vasquez, R Wang, D Tran, QP Adams-Huet, B Chren, MM Costner, MI Cohen, JB Werth, VP Chong, BF AF Vasquez, R. Wang, D. Tran, Q. P. Adams-Huet, B. Chren, M-M Costner, M. I. Cohen, J. B. Werth, V. P. Chong, B. F. TI A multicentre, cross-sectional study on quality of life in patients with cutaneous lupus erythematosus SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID HEALTH SURVEY SF-36; MEDICAL OUTCOMES; SEVERITY INDEX; SKIN-DISEASE; IMPACT; EPIDEMIOLOGY; INSTRUMENT; VALIDITY; SPECTRUM; AREA AB Background A study at the University of Pennsylvania (UPenn) Medical Center demonstrated that quality of life in patients with cutaneous lupus erythematosus (CLE) is negatively impacted. Whether patients with CLE in other geographic locations have similar quality of life is unknown. Objectives We sought to compare quality of life indicators between patients with CLE at the University of Texas Southwestern (UTSW) Medical Center at Dallas and those at UPenn. Methods Patients with CLE (total n = 248) at UTSW (n = 91) and UPenn (n = 157) completed the Skindex-29 + 3 and Short Form-36 (SF-36) surveys related to quality of life. Additional information, including demographics, presence of systemic lupus erythematosus (SLE) and disease severity, was collected from UTSW patients with CLE. Results Most Skindex-29 + 3 and SF-36 subdomain scores between UTSW and UPenn patients with CLE were similar. However, UTSW patients with CLE were significantly more affected in the functioning and lupus-specific Skindex-29 + 3 domains, and physical functioning, role-physical and general health SF-36 sub-scales than UPenn patients with CLE (P < 0.05). Factors related to poor quality of life in UTSW patients with CLE include sex, income, education, presence of SLE, and skin disease activity. Conclusions Most quality of life indicators were similar between the two CLE populations. Differences in psychosocial behaviour, and a larger proportion of patients with SLE and females in the UTSW group likely attributed to differences in a minority of Skindex-29 + 3 and SF-36 subdomains. Capturing data from CLE populations in different locations provides a more thorough picture of the quality of life that patients with CLE experience on a daily basis with special attention to quality of life issues in select patients with CLE. C1 [Vasquez, R.; Wang, D.; Tran, Q. P.; Costner, M. I.; Cohen, J. B.; Chong, B. F.] Univ Texas SW Med Ctr Dallas, Dept Dermatol, Dallas, TX 75390 USA. [Adams-Huet, B.] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Chren, M-M] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Werth, V. P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Werth, V. P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. RP Chong, BF (reprint author), Univ Texas SW Med Ctr Dallas, Dept Dermatol, Dallas, TX 75390 USA. EM ben.chong@utsouthwestern.edu FU NIH CTSA Grant [UL1 RR024982]; American College of Rheumatology/Arthritis Foundation Bridge Funding Grant; Celgene Corporation; Amgen Incorporated; Astion Pharma FX This project was funded in part by NIH CTSA Grant #UL1 RR024982 and the American College of Rheumatology/Arthritis Foundation Bridge Funding Grant (BFC).; V.P.W. is a consultant for Pfizer Incorporated, Medimmune, Genentech Incorporated, Novartis International AG, Celgene Corporation, Stiefel Laboratories, Incorporated, Rigel Pharmaceuticals, Amgen Incorporated, and Astion Pharma. V. P. W. has also received grants and honoraria from Celgene Corporation, Amgen Incorporated, and Astion Pharma. B. F. C. is an investigator for Celgene Corporation and Amgen Incorporated. NR 29 TC 8 Z9 9 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JAN PY 2013 VL 168 IS 1 BP 145 EP 153 DI 10.1111/j.1365-2133.2012.11106.x PG 9 WC Dermatology SC Dermatology GA 083MS UT WOS:000314469000051 PM 22708924 ER PT J AU DiGiovanna, JJ Mauro, T Milstone, LM Schmuth, M Toro, JR AF DiGiovanna, John J. Mauro, Theodora Milstone, Leonard M. Schmuth, Matthias Toro, Jorge R. TI Systemic retinoids in the management of ichthyoses and related skin types SO DERMATOLOGIC THERAPY LA English DT Review DE acitretin; ectropion; ichthyosis; isotretinoin; retinoid ID PITYRIASIS-RUBRA-PILARIS; HAILEY-HAILEY-DISEASE; RECESSIVE CONGENITAL ICHTHYOSIS; VITAMIN-A-DEFICIENCY; DARIERS-DISEASE; ERYTHROKERATODERMIA VARIABILIS; DOUBLE-BLIND; KID SYNDROME; EPIDERMOLYTIC HYPERKERATOSIS; GENETIC-HETEROGENEITY AB The term retinoid includes both natural and synthetic derivatives of vitamin A. Retinoid-containing treatments have been used since approximate to 1550BC by the early Egyptians. Treatment of ichthyosiform disorders with retinoids dates back at least to the 1930s. Early use of high-dose vitamin A demonstrated efficacy, but because vitamin A is stored in the liver, toxicity limited usefulness. Interest turned to synthetic retinoids in an effort to enhance efficacy and limit toxicity. Acetretin, isotretinoin and, in the past etretinate, have provided the most effective therapy for ichthyosiform conditions. They have been used for a variety of ages, including in newborns with severe ichthyosis and for decades in some patients. Careful surveillance and management of mucous membrane, laboratory, skeletal, and teratogenic side effects has made systemic retinoids the mainstay of therapy for ichthyosis and related skin types. C1 [DiGiovanna, John J.] NCI, DNA Repair Sect, Dermatol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Toro, Jorge R.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. [Mauro, Theodora] Univ Calif San Francisco, Dept Dermatol, San Francisco Vet Adm Med Ctr, San Francisco, CA 94143 USA. [Mauro, Theodora] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Milstone, Leonard M.] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA. [Schmuth, Matthias] Med Univ Innsbruck, Dept Dermatol & Venereol, A-6020 Innsbruck, Austria. [Toro, Jorge R.] Washington DC Vet Adm Med Ctr, Dept Dermatol, Washington, DC USA. RP DiGiovanna, JJ (reprint author), NCI, DNA Repair Sect, Dermatol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM jdigiova@mail.nih.gov OI Schmuth, Matthias/0000-0002-4064-1334 FU Intramural Research Program of the NCI, NIH, Medical Research Fund Tirol [MFF71, MFF153]; Austrian Science Fund [FWF J1901-MED, J2112-MED, P16990-B05]; European Cooperation in Science and Technology [COST Action BM0903] FX This research was supported in part by the Intramural Research Program of the NCI, NIH, Medical Research Fund Tirol (MFF71, MFF153), the Austrian Science Fund (FWF J1901-MED, J2112-MED, P16990-B05), the European Cooperation in Science and Technology (COST Action BM0903)" NR 101 TC 16 Z9 17 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1396-0296 J9 DERMATOL THER JI Dermatol. Ther. PD JAN-FEB PY 2013 VL 26 IS 1 BP 26 EP 38 DI 10.1111/j.1529-8019.2012.01527.x PG 13 WC Dermatology SC Dermatology GA 086CX UT WOS:000314661900003 PM 23384018 ER PT J AU Kahn, SE AF Kahn, Steven E. TI Quantifying beta-Cells in Health and Disease: The Past, the Present, and the Need SO DIABETES CARE LA English DT Editorial Material ID ENDOPLASMIC-RETICULUM STRESS; TYPE-2 DIABETES-MELLITUS; HUMAN PANCREATIC-ISLETS; AMYLOID DEPOSITION; APOPTOSIS; PATHOGENESIS; CONTRIBUTES; LANGERHANS C1 [Kahn, Steven E.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. RP Kahn, SE (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. EM skahn@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU BLRD VA [I01 BX001060]; NIDDK NIH HHS [P30 DK017047, R01 DK075998] NR 22 TC 5 Z9 5 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2013 VL 36 IS 1 BP 4 EP 5 DI 10.2337/dc12-1526 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083LP UT WOS:000314465700021 PM 23264284 ER PT J AU Vina, ER Green, SL Trivedi, T Kwoh, CK Utset, TO AF Vina, Ernest R. Green, Stephanie L. Trivedi, Tarak Kwoh, C. Kent Utset, Tammy O. TI Correlates of Sleep Abnormalities in Systemic Lupus A Cross-Sectional Survey in an Urban, Academic Center SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article DE systemic lupus erythematosus; sleep quality; depression; anxiety ID QUALITY-OF-LIFE; TRAIT ANXIETY INVENTORY; DISEASE-ACTIVITY; RHEUMATOID-ARTHRITIS; PSYCHOMETRIC PROPERTIES; DAYTIME SLEEPINESS; MEDICAL OUTCOMES; REPORTED SLEEP; HEALTH-STATUS; ERYTHEMATOSUS AB Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is associated with poor health-related quality-of-life outcomes. Objectives: The objectives of this study were to identify correlates of the domains of the Medical Outcomes Study (MOS) Sleep Scale in SLE and to determine the factors most associated with overall sleep quality. Methods: Sleep in 118 SLE patients was assessed using the self-administered MOS Sleep Scale. Bivariate correlations were determined between each of 6 MOS Sleep subscale scores and each sociodemographic, clinical, or psychological predictor variable. Serial hierarchical multiple regression analyses were computed to identify the variables associated with the individual sleep domains and the overall Sleep Problems Index. Results: The MOS Sleep Scale scores of patients with SLE were poorer than the US general population. Depression moderately correlated with 5 (all P < 0.01) and anxiety with 4 subscale scores (all P < 0.05). The SLE Disease Activity Index did not significantly correlate with any of the subscale scores. Results of a multivariate regression model showed that sleep adequacy and sleep disturbance were independently associated with depression (beta = -0.84; 95% confidence interval [CI], -1.37 to -0.32; and beta = 0.80; 95% CI, 0.15-1.45; respectively). Daytime somnolence was significantly associated with daily prednisone dosage (beta = 0.54; 95% CI, 0.29-0.80) and anxiety trait (beta = 0.81; 95% CI, 0.41-1.21). Snoring independently correlated with anxiety (beta = 1.64; 95% CI, 0.80-2.29). When demographic, clinical, and psychological variables were simultaneously regressed on the Sleep Problems Index, pain trended toward association with overall sleep problems (beta = 0.17; 95% CI, -0.02 to 0.36). Conclusions: Patients with SLE have greater sleep problems relative to the general population. Psychosocial factors, particularly depression and anxiety, are important determinants that are significantly associated with sleep abnormalities in SLE. C1 [Vina, Ernest R.; Kwoh, C. Kent] Univ Pittsburgh, Div Rheumatol & Clin Immunol, Pittsburgh, PA USA. [Vina, Ernest R.; Kwoh, C. Kent] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Green, Stephanie L.; Utset, Tammy O.] Univ Chicago, Rheumatol Sect, Dept Internal Med, Chicago, IL 60637 USA. [Trivedi, Tarak] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. RP Vina, ER (reprint author), Arthrit Res Ctr, 3347 Forbes Ave,Ste 220, Pittsburgh, PA 15213 USA. EM evina1@pitt.edu OI Vina, Ernest/0000-0001-8135-1731 NR 50 TC 8 Z9 8 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD JAN PY 2013 VL 19 IS 1 BP 7 EP 13 DI 10.1097/RHU.0b013e31827cd20d PG 7 WC Rheumatology SC Rheumatology GA 085LE UT WOS:000314615500002 PM 23319017 ER PT J AU Goldman, M Szucs-Reed, RP Jagannathan, K Ehrman, RN Wang, Z Li, Y Suh, JJ Kampman, K O'Brien, CP Childress, AR Franklin, TR AF Goldman, Marina Szucs-Reed, Regina P. Jagannathan, Kanchana Ehrman, Ronald N. Wang, Ze Li, Yin Suh, Jesse J. Kampman, Kyle O'Brien, Charles P. Childress, Anna Rose Franklin, Teresa R. TI Reward-related Brain Response and Craving Correlates of Marijuana Cue Exposure: A Preliminary Study in Treatment-seeking Marijuana-dependent Subjects SO JOURNAL OF ADDICTION MEDICINE LA English DT Article DE addiction; brain reward circuitry; cannabis; craving; marijuana cues; neuroimaging ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; LIMBIC ACTIVATION; CANNABIS WITHDRAWAL; CONTROLLED TRIAL; DRUG-ADDICTION; UNITED-STATES; DSM-IV; SMOKING; REACTIVITY; DOPAMINE AB Objective: Determining the brain substrates underlying the motivation to abuse addictive drugs is critical for understanding and treating addictive disorders. Laboratory neuroimaging studies have demonstrated differential activation of limbic and motivational circuitry (eg, amygdala, hippocampus, ventral striatum, insula, and orbitofrontal cortex) triggered by cocaine, heroin, nicotine, and alcohol cues. The literature on neural responses to marijuana cues is sparse. Thus, the goals of this study were to characterize the brain's response to marijuana cues, a major motivator underlying drug use and relapse, and determine whether these responses are linked to self-reported craving in a clinically relevant population of treatment-seeking marijuana-dependent subjects. Methods: Marijuana craving was assessed in 12 marijuana-dependent subjects using the Marijuana Craving Questionnaire-Short Form. Subsequently, blood oxygen level dependent functional magnetic resonance imaging data were acquired during exposure to alternating 20-second blocks of marijuana-related versus matched nondrug visual cues. Results: Brain activation during marijuana cue exposure was significantly greater in the bilateral amygdala and the hippocampus. Significant positive correlations between craving scores and brain activation were found in the ventral striatum and the medial and lateral orbitofrontal cortex (P < 0.0001). Conclusions: This study presents direct evidence for a link between reward-relevant brain responses to marijuana cues and craving and extends the current literature on marijuana cue reactivity. Furthermore, the correlative relationship between craving and brain activity in reward-related regions was observed in a clinically relevant sample (treatment-seeking marijuana-dependent subjects). Results are consistent with prior findings in cocaine, heroin, nicotine, and alcohol cue studies, indicating that the brain substrates of cue-triggered drug motivation are shared across abused substances. C1 [Goldman, Marina; Szucs-Reed, Regina P.; Jagannathan, Kanchana; Wang, Ze; Li, Yin; Suh, Jesse J.; Kampman, Kyle; O'Brien, Charles P.; Childress, Anna Rose; Franklin, Teresa R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ehrman, Ronald N.; Suh, Jesse J.; O'Brien, Charles P.; Childress, Anna Rose] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Ehrman, Ronald N.; Suh, Jesse J.; O'Brien, Charles P.; Childress, Anna Rose] VISN 4 Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. [Wang, Ze] Univ Penn, Dept Neurol, Ctr Funct Neuroimaging, Philadelphia, PA 19104 USA. RP Goldman, M (reprint author), Univ Penn, Dept Psychiat, 3900 Walnut St, Philadelphia, PA 19104 USA. EM marinag@mail.med.upenn.edu FU National Institute of Drug Abuse [5-P60-DA-05186, T32-DA-07241]; Philadelphia Veterans Affairs Medical Center and VISN 4 Mental Illness Research, Education & Clinical Center; Pennsylvania Department of Health; National Institute of Health/National Institute of NeurologicaI Disorders and Stroke [P30 NS045839] FX Supported by grants from the National Institute of Drug Abuse (Dr. O'Brien, principle investigator: 5-P60-DA-05186 and T32-DA-07241), the Philadelphia Veterans Affairs Medical Center and VISN 4 Mental Illness Research, Education & Clinical Center, the Pennsylvania Department of Health (Dr. Childress, principle investigator: CURE Center of Excellence: Brain Mechanisms of Relapse and Recovery), and imaging and infrastructure support for this work was kindly provided by the National Institute of Health/National Institute of NeurologicaI Disorders and Stroke (P30 NS045839). The funding agencies had no further role in the conduct of the research, preparation of the manuscript, study design, collection, analysis and interpretation of data, writing of the report, and the decision to submit the paper for publication. NR 56 TC 17 Z9 17 U1 3 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-0620 J9 J ADDICT MED JI J. Addict. Med. PD JAN-FEB PY 2013 VL 7 IS 1 BP 8 EP 16 DI 10.1097/ADM.0b013e318273863a PG 9 WC Substance Abuse SC Substance Abuse GA 088HP UT WOS:000314825100002 PM 23188041 ER PT J AU Kalapatapu, RK Campbell, A Aharonovich, E Hu, MC Levin, FR Nunes, EV AF Kalapatapu, Raj K. Campbell, Aimee Aharonovich, Efrat Hu, Mei-Chen Levin, Frances R. Nunes, Edward V. TI Demographic and Clinical Characteristics of Middle-aged Versus Younger Adults Enrolled in a Clinical Trial of a Web-delivered Psychosocial Treatment for Substance Use Disorders SO JOURNAL OF ADDICTION MEDICINE LA English DT Article DE addiction; aging; neurocognitive; Web-based treatment ID MILD COGNITIVE IMPAIRMENT; COCAINE-DEPENDENT PATIENTS; RANDOMIZED CONTROLLED-TRIAL; OLDER-ADULTS; LATE-LIFE; PSYCHOLOGICAL DISTRESS; NARCOTIC ADDICTION; ABUSE TREATMENT; DRUG-USE; ALCOHOL AB Objective: Evidence suggests that substance abuse is becoming more prevalent in middle-aged adults. The objective of this secondary analysis was to add to the growing empirical literature on the unique features of middle-aged substance abuse populations. Methods: We descriptively compared baseline demographic and clinical characteristics of middle-aged (age 45-62 years, n = 111) and younger (age 18-44 years, n = 395) substance abusers entering a Web-based psychosocial treatment study as part of the National Institute on Drug Abuse Clinical Trials Network. Results: A significantly greater percentage of middle-aged adults were nonwhite and had a marital status other than single/never married. There was a significant association between frequency of Internet use and the age group. Forty-six percent of middle-aged adults versus 21% of younger adults reported no Internet use in the prior 90 days. A significantly greater percentage of middle-aged adults used cocaine, and a significantly greater percentage of younger adults used marijuana and opioids. Clinically significant cognitive impairment (z < -1.0) was found for the average participant in both groups on logical association of familiar concepts. Conclusions: This secondary analysis of a National Institute on Drug Abuse Clinical Trials Network study provides additional information on the unique features of middle-aged substance abusers. Increasing knowledge of similarities and differences between younger and middle-aged substance abusers can help with potential age-specific substance abuse treatment planning. C1 [Kalapatapu, Raj K.] Univ Calif San Francisco, Dept Psychiat, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. [Campbell, Aimee; Aharonovich, Efrat; Hu, Mei-Chen; Levin, Frances R.; Nunes, Edward V.] Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY 10032 USA. [Campbell, Aimee; Aharonovich, Efrat; Hu, Mei-Chen; Levin, Frances R.; Nunes, Edward V.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. RP Kalapatapu, RK (reprint author), San Francisco VA Med Ctr, Bldg 8 Mental Hlth,Ground Floor,Room 4C,4150 Clem, San Francisco, CA 94121 USA. EM kalapatapu.raj.k@gmail.com FU NIDA [3U10DA013035-10S2, 5T32DA007294-19, R01DA020647, 5K24DA029647-02, 2K24DA022412-06]; Clinical/Research Fellowship in Psychiatry through the Veterans Affairs Medical Center FX Supported by the NIDA grant 3U10DA013035-10S2 (PI: Nunes). Dr. Kalapatapu was funded by the NIDA grant 5T32DA007294-19 (PI: Levin) while he was at Columbia University and is now funded by a Clinical/Research Fellowship in Psychiatry through the Veterans Affairs Medical Center. Dr. Aharonovich was funded by the NIDA grant R01DA020647 (PI: Aharonovich). Dr. Levin was funded by the NIDA grant 5K24DA029647-02 (PI: Levin). Dr. Nunes was funded by the NIDA grant 2K24DA022412-06 (PI: Nunes). NR 83 TC 3 Z9 3 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-0620 J9 J ADDICT MED JI J. Addict. Med. PD JAN-FEB PY 2013 VL 7 IS 1 BP 66 EP 72 DI 10.1097/ADM.0b013e31827e2d04 PG 7 WC Substance Abuse SC Substance Abuse GA 088HP UT WOS:000314825100010 PM 23340711 ER PT J AU Quinn, JF AF Quinn, Joseph F. TI Biomarkers for Alzheimer's Disease: Showing the Way or Leading Us Astray? SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Review DE Alzheimer's disease; biomarkers; clinical trials ID MILD COGNITIVE IMPAIRMENT; GAMMA-SECRETASE INHIBITOR; DECLINE; TRIAL; ACID AB The indolent nature of Alzheimer's disease, coupled with burgeoning interest in a "presymptomatic" stage of disease, has motivated efforts to identify, validate, and exploit surrogate disease markers for trials of disease-modifying or preventive strategies. Many of these efforts have been productive, and biomarkers are now routinely applied in selection of study subjects and evaluation of outcomes in clinical trials. On the other hand, biomarkers also have the capacity to lead to bad therapeutic outcomes when they determine "go- no go" decisions in early drug development. This paper reviews several reports of biomarker studies which illustrate the great potential, for both good and ill, of biomarkers of Alzheimer's disease. C1 [Quinn, Joseph F.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Quinn, Joseph F.] Portland VA Med Ctr, Portland, OR USA. RP Quinn, JF (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Mail Code CR-131,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM quinnj@ohsu.edu FU NIA NIH HHS [P30 AG008017] NR 15 TC 3 Z9 3 U1 1 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2013 VL 33 SU 1 SI SI BP S371 EP S376 DI 10.3233/JAD-2012-129022 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 083FH UT WOS:000314447600035 PM 22766735 ER PT J AU Keane, TM Chaudhry, B Docherty, JP Jesse, RL Lee, J McNurlen, J Zeller, E AF Keane, Terence M. Chaudhry, Basit Docherty, John P. Jesse, Robert L. Lee, Jennifer McNurlen, Jessica Zeller, Eileen TI Caring for Returning Veterans: Meeting Mental Health Needs SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material C1 [Keane, Terence M.] US Dept Vet Affairs, Natl Ctr PTSD, Behav Sci Div, Washington, DC USA. [Keane, Terence M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Chaudhry, Basit] IBM Res, Washington, DC USA. [Docherty, John P.] Weill Cornell Med Coll, Dept Psychiat, New York, NY USA. [Docherty, John P.] New York Presbyterian Hosp, New York, NY USA. [Jesse, Robert L.; Lee, Jennifer] US Dept Vet Affairs, Washington, DC USA. [McNurlen, Jessica] Mental Hlth Assoc Montgomery Cty, Rockville, MD USA. [Zeller, Eileen] SAMHSA, Ctr Mental Hlth Serv, Suicide Prevent Branch, Rockville, MD USA. RP Keane, TM (reprint author), US Dept Vet Affairs, Natl Ctr PTSD, Behav Sci Div, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JAN PY 2013 VL 74 IS 1 BP 23 EP + DI 10.4088/JCP.12071co1c PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 083UN UT WOS:000314490800004 PM 23419222 ER PT J AU Riddle, DL Singh, JA Harmsen, WS Schleck, CD Lewallen, DG AF Riddle, D. L. Singh, J. A. Harmsen, W. S. Schleck, C. D. Lewallen, D. G. TI Clinically important body weight gain following total hip arthroplasty: a cohort study with 5-year follow-up SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE Hip; Arthroplasty; Obesity ID KNEE ARTHROPLASTY; MASS INDEX; NONOBESE PATIENTS; UNITED-STATES; OLDER-ADULTS; RISK-FACTORS; US ADULTS; OBESITY; REPLACEMENT; POPULATION AB Objective: Literature examining the effects of total hip arthroplasty (THA) on subsequent body weight gain is inconclusive. Determining the extent to which clinically relevant weight gain occurs following THA has important public health implications. Design: We used multi-variable logistic regression to compare data from one of the largest US-based THA registries to a population-based control sample from the same geographic region. We also identified factors that increased risk of clinically important weight gain specifically among persons undergoing THA. The outcome measure of interest was weight gain of >= 5% of body weight up to 5 years following surgery. Results: The multi-variable adjusted [age, sex, body mass index (BMI), education, comorbidity and presurgical weight change] odds ratio for important weight gain was 1.7 [95% confidence interval (CI), 1.06, 2.6] for a person with THA as compared to the control sample. Additional arthroplasty procedures during the 5-year follow-up further increased odds for important weight gain (OR = 2.0, 95% CI, 1.4, 2.7) relative to the control sample. A patient with THA had increased risk of important post-surgical weight gain of 12% (OR = 1.12, 95% CI, 1.08, 1.16) for every kilogram of pre-operative weight loss. Conclusions: While findings should be interpreted with caution because of missing follow-up weight data, patients with THA appear to be at increased risk of clinically important weight gain following surgery as compared to peers. Patients less than 60 years and who have lost a substantial amount of weight prior to surgery appear to be at particularly high risk of important post-surgical weight gain. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 [Riddle, D. L.] Virginia Commonwealth Univ, Dept Phys Therapy, Richmond, VA 23298 USA. [Riddle, D. L.] Virginia Commonwealth Univ, Dept Orthopaed Surg, Richmond, VA 23298 USA. [Singh, J. A.] Univ Alabama Birmingham, Mayo Clin, Birmingham Vet Affairs Med Ctr, Rochester, MN USA. [Harmsen, W. S.; Schleck, C. D.; Lewallen, D. G.] Mayo Clin, Rochester, MN USA. RP Riddle, DL (reprint author), Virginia Commonwealth Univ, Dept Phys Therapy, POB 980224, Richmond, VA 23298 USA. EM dlriddle@vcu.edu; jasvinder.md@gmail.com; william.harmsen@mayo.edu; schleck@mayo.edu; lewallen.david@mayo.edu OI singh, jasvinder/0000-0003-3485-0006 FU Virginia Commonwealth University Presidential Research Initiative Program; Allergan; Takeda; Savient; Zimmer; DePuy; Stryker FX The study was funded by a grant from the Virginia Commonwealth University Presidential Research Initiative Program. The funding source played no role in the design, data collection or reporting of the study.; Dr. Singh has received grants from Allergan, Takeda, Savient and is a consultant with Allergan, Takeda, Savient, URL, Regeneron, Ardea and Novartis. Dr. Lewallen has received royalties/speaker fees from Zimmer, has been a paid consultant to Zimmer and has received institutional research funds from DePuy, Stryker and Zimmer. NR 51 TC 5 Z9 5 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD JAN PY 2013 VL 21 IS 1 BP 35 EP 43 DI 10.1016/j.joca.2012.09.010 PG 9 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 083QL UT WOS:000314480200006 PM 23047011 ER PT J AU Xu, C Wang, P Liu, Y Zhang, YZ Fan, WH Upton, MP Lohavanichbutr, P Houck, JR Doody, DR Futran, ND Zhao, LP Schwartz, SM Chen, C Mendez, E AF Xu, Chang Wang, Pei Liu, Yan Zhang, Yuzheng Fan, Wenhong Upton, Melissa P. Lohavanichbutr, Pawadee Houck, John R. Doody, David R. Futran, Neal D. Zhao, Lue Ping Schwartz, Stephen M. Chen, Chu Mendez, Eduardo TI Integrative Genomics in Combination with RNA Interference Identifies Prognostic and Functionally Relevant Gene Targets for Oral Squamous Cell Carcinoma SO PLOS GENETICS LA English DT Article ID GTPASE-ACTIVATING PROTEIN; BREAST-CANCER METASTASIS; LYMPH-NODE METASTASIS; DNA COPY NUMBER; OROPHARYNGEAL CANCER; EXPRESSION PROFILES; BINDING-PROTEIN; NECK-CANCER; P53 NETWORK; HEAD AB In oral squamous cell carcinoma (OSCC), metastasis to lymph nodes is associated with a 50% reduction in 5-year survival. To identify a metastatic gene set based on DNA copy number abnormalities (CNAs) of differentially expressed genes, we compared DNA and RNA of OSCC cells laser-microdissected from non-metastatic primary tumors (n = 17) with those from lymph node metastases (n = 20), using Affymetrix 250K Nsp single-nucleotide polymorphism (SNP) arrays and U133 Plus 2.0 arrays, respectively. With a false discovery rate (FDR)<5%, 1988 transcripts were found to be differentially expressed between primary and metastatic OSCC. Of these, 114 were found to have a significant correlation between DNA copy number and gene expression (FDR<0.01). Among these 114 correlated transcripts, the corresponding genomic regions of each of 95 transcripts had CNAs differences between primary and metastatic OSCC (FDR<0.01). Using an independent dataset of 133 patients, multivariable analysis showed that the OSCC-specific and overall mortality hazards ratio (HR) for patients carrying the 95-transcript signature were 4.75 (95% CI: 2.03-11.11) and 3.45 (95% CI: 1.84-6.50), respectively. To determine the degree by which these genes impact cell survival, we compared the growth of five OSCC cell lines before and after knockdown of over-amplified transcripts via a high-throughput siRNA-mediated screen. The expression-knockdown of 18 of the 26 genes tested showed a growth suppression >= 30% in at least one cell line (P<0.01). In particular, cell lines derived from late-stage OSCC were more sensitive to the knockdown of G3BP1 than cell lines derived from early-stage OSCC, and the growth suppression was likely caused by increase in apoptosis. Further investigation is warranted to examine the biological role of these genes in OSCC progression and their therapeutic potentials. C1 [Xu, Chang; Futran, Neal D.; Chen, Chu; Mendez, Eduardo] Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. [Xu, Chang; Mendez, Eduardo] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Wang, Pei; Liu, Yan; Zhang, Yuzheng; Fan, Wenhong; Lohavanichbutr, Pawadee; Houck, John R.; Doody, David R.; Zhao, Lue Ping; Schwartz, Stephen M.; Chen, Chu] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Wang, Pei; Zhao, Lue Ping] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Upton, Melissa P.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Schwartz, Stephen M.; Chen, Chu] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Mendez, Eduardo] VA Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA USA. RP Xu, C (reprint author), Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. EM edmendez@u.washington.edu OI Schwartz, Stephen/0000-0001-7499-8502 FU National Center for Research Resources, National Institutes of Health (NIH) [5KL2RR025015-03]; Robert Wood Johnson Foundation; Howard Hughes Medical Institute; National Cancer Institute, NIH [R01CA095419]; Institute of Translational Health Sciences, University of Washington; National Center for Research Resources, NIH [UL1RR025014]; Department of Otolaryngology-Head and Neck Surgery, University of Washington; VA Puget Sound Health Care System, Fred Hutchinson Cancer Research Center, University of Washington Medical Center; Harborview Medical Center, Seattle, Washington FX This work was supported in part by grants 5KL2RR025015-03 from National Center for Research Resources, National Institutes of Health (NIH); Amos Medical Faculty Development Program Award from The Robert Wood Johnson Foundation; Early Physician-Scientist Career Development Award from the Howard Hughes Medical Institute; R01CA095419 from the National Cancer Institute, NIH; Small Grants Translational Research Projects Award from the Institute of Translational Health Sciences, University of Washington, supported by grant UL1RR025014 from the National Center for Research Resources, NIH; center funds from the Department of Otolaryngology-Head and Neck Surgery, University of Washington; and by resources from and use of facilities at the VA Puget Sound Health Care System, Fred Hutchinson Cancer Research Center, University of Washington Medical Center and Harborview Medical Center, Seattle, Washington. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 5 Z9 5 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2013 VL 9 IS 1 AR e1003169 DI 10.1371/journal.pgen.1003169 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 085YZ UT WOS:000314651500022 PM 23341773 ER PT J AU Burguete, SR Maselli, DJ Fernandez, JF Levine, SM AF Burguete, Sergio R. Maselli, Diego J. Fernandez, Juan F. Levine, Stephanie M. TI Lung transplant infection SO RESPIROLOGY LA English DT Review DE Aspergillus; bacterial pneumonia; cytomegalovirus; immunosuppression; lung transplantation ID BRONCHIOLITIS-OBLITERANS-SYNDROME; RESPIRATORY VIRAL-INFECTIONS; INVASIVE FUNGAL-INFECTIONS; PNEUMOCYSTIS-CARINII-PNEUMONIA; BURKHOLDERIA-CEPACIA-COMPLEX; AEROSOLIZED AMPHOTERICIN-B; ANTI-THYMOCYTE GLOBULIN; CELL-MEDIATED-IMMUNITY; CYSTIC-FIBROSIS; RISK-FACTORS AB Lung transplantation has become an accepted therapeutic procedure for the treatment of end-stage pulmonary parenchymal and vascular disease. Despite improved survival rates over the decades, lung transplant recipients have lower survival rates than other solid organ transplant recipients. The morbidity and mortality following lung transplantation is largely due to infection-and rejection-related complications. This article will review the common infections that develop in the lung transplant recipient, including the general risk factors for infection in this population, and the most frequent bacterial, viral, fungal and other less frequent opportunistic infections. The epidemiology, diagnosis, prophylaxis, treatment and outcomes for the different microbial pathogens will be reviewed. The effects of infection on lung transplant rejection will also be discussed. C1 [Levine, Stephanie M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Pulm Dis & Crit Care Med, San Antonio, TX 78229 USA. S Texas Vet Healthcare Syst, San Antonio, TX USA. RP Levine, SM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Pulm Dis & Crit Care Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM levines@uthscsa.edu NR 161 TC 15 Z9 17 U1 2 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1323-7799 J9 RESPIROLOGY JI Respirology PD JAN PY 2013 VL 18 IS 1 BP 22 EP 38 DI 10.1111/j.1440-1843.2012.02196.x PG 17 WC Respiratory System SC Respiratory System GA 078RD UT WOS:000314116100005 PM 22591266 ER PT J AU Silvestrini, MT Yin, DL Coppes, VG Mann, P Martin, AJ Larson, PS Starr, PA Gupta, N Panter, SS Desai, TA Lim, DA AF Silvestrini, Matthew T. Yin, Dali Coppes, Valerie G. Mann, Preeti Martin, Alastair J. Larson, Paul S. Starr, Philip A. Gupta, Nalin Panter, S. Scott Desai, Tejal A. Lim, Daniel A. TI Radially Branched Deployment for More Efficient Cell Transplantation at the Scale of the Human Brain SO STEREOTACTIC AND FUNCTIONAL NEUROSURGERY LA English DT Article DE Radially branched deployment; Neural stem cell; Cell transplantation; Stereotactic surgery ID INTRACEREBRAL MICROINJECTION INSTRUMENT; FETAL STRIATAL TRANSPLANTATION; PARKINSONS-DISEASE; HUNTINGTONS-DISEASE; TECHNICAL NOTE; STEM-CELLS; HEMORRHAGIC COMPLICATIONS; NEURAL TRANSPLANTATION; AUTOMATED DELIVERY; IMPLANTATION AB Background: In preclinical studies, cell transplantation into the brain has shown great promise for the treatment of a wide range of neurological diseases. However, the use of a straight cannula and syringe for cell delivery to the human brain does not approximate cell distribution achieved in animal studies. This technical deficiency may limit the successful clinical translation of cell transplantation. Objective: To develop a stereotactic device that effectively distributes viable cells to the human brain. Our primary aims were to (1) minimize the number of transcortical penetrations required for transplantation, (2) reduce variability in cell dosing and (3) increase cell survival. Methods: We developed a modular cannula system capable of radially branched deployment (RBD) of a cell delivery catheter at variable angles from the longitudinal device axis. We also developed an integrated catheter-plunger system, eliminating the need for a separate syringe delivery mechanism. The RBD prototype was evaluated in vitro and in vivo with subcortical injections into the swine brain. Performance was compared to a 20G straight cannula with dual side ports, a device used in current clinical trials. Results: RBD enabled therapeutic delivery in a precise 'tree-like' pattern branched from a single initial trajectory, thereby facilitating delivery to a volumetrically large target region. RBD could transplant materials in a radial pattern up to 2.0 cm from the initial penetration tract. The novel integrated catheter-plunger system facilitated manual delivery of small and precise volumes of injection (1.36 +/- 0.13 mu l per cm of plunger travel). Both dilute and highly concentrated neural precursor cell populations tolerated transit through the device with high viability and unaffected developmental potential. While reflux of infusate along the penetration tract was problematic with the use of the 20G cannula, RBD was resistant to this source of cell dose variability in agarose. RBD enabled radial injections to the swine brain when used with a modern clinical stereotactic system. Conclusions: By increasing the total delivery volume through a single transcortical penetration in agarose models, RBD strategy may provide a new approach for cell transplantation to the human brain. Incorporation of RBD or selected aspects of its design into future clinical trials may increase the likelihood of successful translation of cell-based therapy to the human patient. Copyright (c) 2013 S. Karger AG, Basel C1 [Silvestrini, Matthew T.; Yin, Dali; Coppes, Valerie G.; Mann, Preeti; Larson, Paul S.; Starr, Philip A.; Gupta, Nalin; Panter, S. Scott; Lim, Daniel A.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Desai, Tejal A.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Martin, Alastair J.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Coppes, Valerie G.; Mann, Preeti; Panter, S. Scott; Lim, Daniel A.] San Francisco VA Med Ctr, Dept Surg, San Francisco, CA USA. [Lim, Daniel A.] Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA USA. RP Lim, DA (reprint author), Univ Calif San Francisco, Dept Neurol Surg, Ray & Dagmar Dolby Regenerat Med Bldg,35 Med Ctr, San Francisco, CA 94143 USA. EM LimD@neurosurg.ucsf.edu OI Lim, Daniel/0000-0001-7221-3425 FU California Institute for Regeneration Medicine [CIRM RT2-01975]; NIH grant [DP2-OD006505-01] FX This work was supported by a grant from the California Institute for Regeneration Medicine (CIRM RT2-01975) and NIH grant DP2-OD006505-01 to D.A.L. In addition, some aspects of this work were supported with resources and the use of facilities at the San Francisco Veterans Affairs Medical Center. NR 46 TC 7 Z9 7 U1 1 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-6125 J9 STEREOT FUNCT NEUROS JI Stereotact. Funct. Neurosurg. PY 2013 VL 91 IS 2 BP 92 EP 103 DI 10.1159/000343213 PG 12 WC Neurosciences; Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 086SO UT WOS:000314707500003 PM 23343609 ER PT J AU Kling, MA Trojanowski, JQ Wolk, DA Lee, VMY Arnold, SE AF Kling, Mitchel A. Trojanowski, John Q. Wolk, David A. Lee, Virginia M. Y. Arnold, Steven E. TI Vascular disease and dementias: Paradigm shifts to drive research in new directions SO ALZHEIMERS & DEMENTIA LA English DT Article DE Dementia; Vascular; Cerebrovascular; Pathophysiology; Risk factors; Metabolic syndrome; Magnetic resonance imaging; White matter hyperintensities; Obesity; Hypertension; Insulin resistance; Dyslipidemia ID MILD COGNITIVE IMPAIRMENT; CORONARY HEART-DISEASE; WHITE-MATTER LESIONS; CLINICAL DIAGNOSTIC-CRITERIA; CEREBRAL AMYLOID ANGIOPATHY; VISCERAL ADIPOSE-TISSUE; ALZHEIMERS-DISEASE; METABOLIC SYNDROME; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE AB Vascular disease was once considered the principal cause of aging-related dementia. More recently, however, research emphasis has shifted to studies of progressive neurodegenerative disease processes, such as those giving rise to neuritic plaques, neurofibrillary tangles, and Lewy bodies. Although these studies have led to critical insights and potential therapeutic strategies, interest in the role of systemic and cerebrovascular disease mechanisms waned and has received relatively less attention and research support. Recent studies suggest that vascular disease mechanisms play an important role in the risk for aging-related cognitive decline and disorders. Vascular disease frequently coexists with cognitive decline in aging individuals, shares many risk factors with dementias considered to be of the "Alzheimer type," and is observed more frequently than expected in postmortem material from individuals manifesting "specific" disease stigmata, such as abundant plaques and tangles. Considerable difficulties have emerged in attempting to classify dementias as being related to vascular versus neurodegenerative causes, and several systems of criteria have been used. Despite multiple attempts, a lack of consensus remains regarding the optimal means of incorporating vascular disease into clinical diagnostic, neurocognitive, or neuropathologic classification schemes for dementias. We propose here an integrative, rather than a strictly taxonomic, approach to the study and elucidation of how vascular disease mechanisms contribute to the development of dementias. We argue that, instead of discriminating between, for example, "Alzheimer's disease," "vascular dementia," and other diseases, there is a greater need to focus clinical and research efforts on elucidating specific pathophysiologic mechanisms that contribute to dementia phenotypes and neuropathologic outcomes. We outline a multitiered strategy, beginning with clinical and public health interventions that can be implemented immediately, enhancements to ongoing longitudinal studies to increase their informative value, and new initiatives to capitalize on recent advances in systems biology and network medicine. This strategy will require funding from multiple public and private sources to support collaborative and interdisciplinary research efforts to take full advantage of these opportunities and realize their societal benefits. (C) 2013 The Alzheimer's Association. All rights reserved. C1 [Kling, Mitchel A.; Arnold, Steven E.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kling, Mitchel A.] Philadelphia Vet Affairs Med Ctr, Behav Hlth Serv, Philadelphia, PA USA. [Trojanowski, John Q.; Lee, Virginia M. Y.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA. [Trojanowski, John Q.; Wolk, David A.; Lee, Virginia M. Y.; Arnold, Steven E.] Univ Penn, Inst Aging, Perelman Sch Med, Philadelphia, PA 19104 USA. [Wolk, David A.; Arnold, Steven E.] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Kling, MA (reprint author), Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. EM mitchel.kling@uphs.upenn.edu OI Kling, Mitchel/0000-0002-2232-1409 FU Alzheimer's Diseases Coordinating Center [NIH P30 AG010124]; Allen H. and Selma W. Berkman Charitable Trust FX This work was supported in part by funding from the Alzheimer's Diseases Coordinating Center (NIH P30 AG010124), and by a grant from the Allen H. and Selma W. Berkman Charitable Trust. NR 174 TC 45 Z9 48 U1 1 U2 31 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JAN PY 2013 VL 9 IS 1 BP 76 EP 92 DI 10.1016/j.jalz.2012.02.007 PG 17 WC Clinical Neurology SC Neurosciences & Neurology GA 078EO UT WOS:000314081400009 PM 23183137 ER PT J AU Murphey, P McLean, DJ McMahan, CA Walter, CA McCarrey, JR AF Murphey, Patricia McLean, Derek J. McMahan, C. Alex Walter, Christi A. McCarrey, John R. TI Enhanced Genetic Integrity in Mouse Germ Cells SO BIOLOGY OF REPRODUCTION LA English DT Article DE mutations; oogenesis; spermatogenesis; spermatogonial stem cells ID EMBRYONIC STEM-CELLS; INDUCED SPECIFIC-LOCUS; EXCISION-REPAIR ACTIVITY; MUTATION FREQUENCY; TRANSGENIC MICE; OLD MICE; IN-VIVO; SPERMATOGENIC CELLS; MUTANT FREQUENCIES; HETEROZYGOUS MICE AB Genetically based diseases constitute a major human health burden, and de novo germline mutations represent a source of heritable genetic alterations that can cause such disorders in offspring. The availability of transgenic rodent systems with recoverable, mutation reporter genes has been used to assess the occurrence of spontaneous point mutations in germline cells. Previous studies using the lacI mutation reporter transgenic mouse system showed that the frequency of spontaneous mutations is significantly lower in advanced male germ cells than in somatic cell types from the same individuals. Here we used this same mutation reporter transgene system to show that female germ cells also display a mutation frequency that is lower than that in corresponding somatic cells and similar to that seen in male germ cells, indicating this is a common feature of germ cells in both sexes. In addition, we showed that statistically significant differences in mutation frequencies are evident between germ cells and somatic cells in both sexes as early as mid-fetal stages in the mouse. Finally, a comparison of the mutation frequency in a general population of early type A spermatogonia with that in a population enriched for Thy-1-positive spermatogonia suggests there is heterogeneity among the early spermatogonial population such that a subset of these cells are predestined to form true spermatogonial stem cells. Taken together, these results support the disposable soma theory, which posits that genetic integrity is normally maintained more stringently in the germ line than in the soma and suggests that this is achieved by minimizing the initial occurrence of mutations in early germline cells and their subsequent gametogenic progeny relative to that in somatic cells. C1 [Murphey, Patricia; McCarrey, John R.] Univ Texas San Antonio, Dept Biol, San Antonio, TX 78249 USA. [McLean, Derek J.] Washington State Univ, Dept Anim Sci, Pullman, WA 99164 USA. [McMahan, C. Alex] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Walter, Christi A.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP McCarrey, JR (reprint author), Univ Texas San Antonio, Dept Biol, 1 UTSA Circle, San Antonio, TX 78249 USA. EM john.mccarrey@utsa.edu FU National Institutes of Health [HD42772, HD046521] FX Supported in part by National Institutes of Health grant HD42772 to J.R.M. and grant HD046521 to D.J.M. NR 58 TC 11 Z9 11 U1 0 U2 3 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JAN PY 2013 VL 88 IS 1 AR 6 DI 10.1095/biolreprod.112.103481 PG 8 WC Reproductive Biology SC Reproductive Biology GA 081YD UT WOS:000314357700005 PM 23153565 ER PT J AU Beard, AJ Hofer, TP Downs, JR Lucatorto, M Klamerus, ML Holleman, R Kerr, EA AF Beard, Ashley J. Hofer, Timothy P. Downs, John R. Lucatorto, Michelle Klamerus, Mandi L. Holleman, Rob Kerr, Eve A. CA Diabet Clinical Action Measures TI Assessing Appropriateness of Lipid Management Among Patients With Diabetes Mellitus Moving From Target to Treatment SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE cholesterol; performance measures; quality of care; diabetes mellitus; lipids ID CORONARY-HEART-DISEASE; INTENSIVE STATIN THERAPY; RANDOMIZED CONTROLLED-TRIALS; PLACEBO-CONTROLLED TRIAL; AVERAGE CHOLESTEROL LEVELS; RISK-FACTOR CONTROL; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; PERFORMANCE-MEASURES; LOWERING THERAPY AB Background-Performance measures that emphasize only a treat-to-target approach may motivate overtreatment with high-dose statins, potentially leading to adverse events and unnecessary costs. We developed a clinical action performance measure for lipid management in patients with diabetes mellitus that is designed to encourage appropriate treatment with moderate-dose statins while minimizing overtreatment. Methods and Results-We examined data from July 2010 to June 2011 for 964 818 active Veterans Affairs primary care patients >= 18 years of age with diabetes mellitus. We defined 3 conditions as successfully meeting the clinical action measure for patients 50 to 75 years old: (1) having a low-density lipoprotein (LDL) <100 mg/dL, (2) taking a moderate-dose statin regardless of LDL level or measurement, or (3) receiving appropriate clinical action (starting, switching, or intensifying statin therapy) if LDL is >= 100 mg/dL. We examined possible overtreatment for patients >= 18 years of age by examining the proportion of patients without ischemic heart disease who were on a high-dose statin. We then examined variability in measure attainment across 881 facilities using 2-level hierarchical multivariable logistic models. Of 668 209 patients with diabetes mellitus who were 50 to 75 years of age, 84.6% passed the clinical action measure: 67.2% with LDL <100 mg/dL, 13.0% with LDL >= 100 mg/dL and either on a moderate-dose statin (7.5%) or with appropriate clinical action (5.5%), and 4.4% with no index LDL on at least a moderate-dose statin. Of the entire cohort >= 18 years of age, 13.7% were potentially overtreated. Facilities with higher rates of meeting the current threshold measure (LDL <100 mg/dL) had higher rates of potential overtreatment (P<0.001). Conclusions-Use of a performance measure that credits appropriate clinical action indicates that almost 85% of diabetic veterans 50 to 75 years of age are receiving appropriate dyslipidemia management. However, many patients are potentially overtreated with high-dose statins. (Circ Cardiovasc Qual Outcomes. 2013; 6: 66-74.) C1 [Hofer, Timothy P.; Klamerus, Mandi L.; Holleman, Rob; Kerr, Eve A.] Dept Vet Affairs Ann Arbor Healthcare Syst, Ctr Clin Management Res, Ann Arbor, MI USA. [Beard, Ashley J.; Hofer, Timothy P.; Kerr, Eve A.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Hofer, Timothy P.; Kerr, Eve A.] Univ Michigan, Michigan Diabet Res & Training Ctr, Ann Arbor, MI 48109 USA. [Downs, John R.] S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat Implementat Ctr, San Antonio, TX USA. [Downs, John R.] Univ Texas Hlth Sci Ctr, Div Hosp Med, Dept Med, San Antonio, TX USA. [Lucatorto, Michelle] Dept Vet Affairs, Off Nursing Serv, Washington, DC USA. RP Kerr, EA (reprint author), VA Ctr Clin Management Res 152, 2215 Fuller Rd,POB 130170, Ann Arbor, MI 48113 USA. EM ekerr@umich.edu RI Kerr, Eve/I-3330-2013 FU VA QUERI RRP [09-111]; Veteran Affairs Diabetes Quality Enhancement Research Initiative [DIB 98-001]; Measurement Core of the Michigan Diabetes Research and Training Center (National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health] [P60 DK-20572] FX This study was funded by VA QUERI RRP 09-111. Additional support was provided by the Veteran Affairs Diabetes Quality Enhancement Research Initiative (DIB 98-001) and the Measurement Core of the Michigan Diabetes Research and Training Center (National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [P60 DK-20572]). NR 59 TC 14 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2013 VL 6 IS 1 BP 66 EP 74 DI 10.1161/CIRCOUTCOMES.112.966697 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071ZN UT WOS:000313637500013 PM 23233749 ER PT J AU Wong, LL Naugler, WE Schwartz, J Scott, DL Bhattacharya, R Reyes, J Orloff, SL AF Wong, Linda L. Naugler, Willscott E. Schwartz, Jonathan Scott, David L. Bhattacharya, Renuka Reyes, Jorge Orloff, Susan L. TI Impact of locoregional therapy and alpha-fetoprotein on outcomes in transplantation for liver cancer: a UNOS Region 6 pooled analysis SO CLINICAL TRANSPLANTATION LA English DT Article DE alpha-fetoprotein; chemoembolization; hepatocellular cancer; liver transplant; locoregional therapy ID HEPATOCELLULAR-CARCINOMA RECURRENCE; PROGNOSTIC-FACTORS; MICROVASCULAR INVASION; SELECTION CRITERIA; TUMOR RECURRENCE; RISK-FACTORS; SURVIVAL; LEVEL; HEPATECTOMY; PROGRESSION AB Liver transplantation (LT) provides optimal long-term disease-free survival for hepatocellular carcinoma (HCC). High pre-LT alpha-fetoprotein (AFP) has been associated with HCC recurrence, but it is unclear whether a drop in AFP or locoregional therapy impacts survival/recurrence after LT. LT-recipients transplanted for HCC in three centers (UNOS Region 6) were reviewed (20062009) for demographics, tumor characteristics, locoregional therapy, AFP, recurrence, and survival. Among 211 LT recipients (mean age 56.4 yr, 83% male, mean MELD 12.2), 94% met Milan criteria and 61% received locoregional therapy. Mean disease-free survival (DFS) was 1549.7 d, and 84% are currently alive. Factors affecting DFS included recurrence (RR, 0.074; 95% CI, 0.0380.14), normal peak AFP (29.6, 95% CI, 2.96296.3), peak AFP >400 (RR, 0.15; 95% CI, 0.030.73) and AFP at LT >400 (RR, 15.5; 95% CI, 2.4100.5). Twenty-one patients had recurrence and were more likely beyond Milan criteria (5/23(21%) vs. 8/220 (4%), p = 0.0038), with peak AFP >400 and AFP at LT >400 (p = 0.001). Locoregional therapy did not affect mean DFS (1458.0 vs. 1603.8 d, p = 0.05) or recurrence (12.5% vs. 6%). Predictors of recurrence were similar to previous studies, including high AFP and tumor outside Milan criteria. While locoregional therapy itself did not affect DFS/recurrence, a decrease in AFP pre-transplant appears to positively influence outcomes in those who received locoregional therapy. C1 [Wong, Linda L.] Hawaii Med Ctr E, Transplant Inst, Honolulu, HI USA. [Naugler, Willscott E.; Schwartz, Jonathan] Oregon Hlth & Sci Univ, Div Gastroenterol, Portland, OR 97201 USA. [Scott, David L.; Orloff, Susan L.] Oregon Hlth & Sci Univ, Div Abdominal Organ Transplantat, Portland, OR 97201 USA. [Scott, David L.; Orloff, Susan L.] Portland VA Med Ctr, Liver Transplant Program, Portland, OR USA. [Bhattacharya, Renuka; Reyes, Jorge] Univ Washington, Med Ctr, Transplant Serv, Seattle, WA 98195 USA. RP Wong, LL (reprint author), Queens Med Ctr, 550 S Beretania St,Suite 403, Honolulu, HI 96813 USA. EM hepatoma@aol.com NR 38 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0902-0063 J9 CLIN TRANSPLANT JI Clin. Transplant. PD JAN-FEB PY 2013 VL 27 IS 1 BP E72 EP E79 DI 10.1111/ctr.12056 PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 079YL UT WOS:000314208000019 PM 23278701 ER PT J AU Morasco, BJ Turk, DC Donovan, DM Dobscha, SK AF Morasco, Benjamin J. Turk, Dennis C. Donovan, Dennis M. Dobscha, Steven K. TI Risk for prescription opioid misuse among patients with a history of substance use disorder SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Prescription opioid misuse; Chronic pain; Substance use disorder; Aberrant medication-related behaviors; Quality of life ID CHRONIC NONCANCER PAIN; DRUG-RELATED BEHAVIORS; MEDICATION MISUSE; PRIMARY-CARE; HEPATITIS-C; ANXIETY DISORDERS; VALIDATION; ABUSE; PREVALENCE; VETERANS AB Background: History of substance use disorder (SUD) is associated with risk for prescription opioid misuse in chronic pain patients; however, little data are available regarding risk for prescription opioid misuse within the subgroup of patients with SUD histories. Methods: Participants with chronic pain, histories of SUD, and current opioid prescriptions were recruited from a single VA Medical Center. Participants (n = 80) completed measures of risk for prescription opioid misuse, pain severity, pain-related interference, pain catastrophizing, attitudes about managing pain, emotional functioning, and substance abuse. Results: Participants were divided into three groups based on risk for prescription opioid misuse, as assessed by the Pain Medication Questionnaire (PMQ). Participants in the High-PMQ group reported more pain severity, interference, catastrophizing, depressive symptoms, and lowest self-efficacy for managing pain, relative to the Low-PMQ group; the High-PMQ group and Moderate-PMQ group differed on measures of pain severity, catastrophizing, and psychiatric symptoms (all p-values <0.05). The High-PMQ group had the highest rates of current SUD (32% versus 20% and 0, p = 0.009). A regression analysis evaluated factors associated with PMQ scores: pain catastrophizing was the only variable significantly associated with risk for prescription opioid misuse. Conclusions: Among patients with SUD histories, those with higher risk for prescription opioid misuse reported more pain and impairment, symptoms of depression, and were more likely to have current SUD, relative to patients with lower risk for prescription opioid misuse. In adjusted analyses, pain catastrophizing was significantly associated with risk for prescription opioid misuse, but current SUD status was not a significant predictor. Published by Elsevier Ireland Ltd. C1 [Morasco, Benjamin J.; Dobscha, Steven K.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA. [Morasco, Benjamin J.; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Turk, Dennis C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Donovan, Dennis M.] Univ Washington, Alcohol & Drug Abuse Inst, Seattle, WA 98195 USA. [Dobscha, Steven K.] Portland VA Med Ctr, Ctr Study Chron Comorbid Med & Psychiat Disorders, Portland, OR USA. RP Morasco, BJ (reprint author), Portland VA Med Ctr R&D99, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM benjamin.morasco@va.gov FU National Institute on Drug Abuse (NIDA) [023467]; Endo; Johnson Johnson; Philips Respironics; National Institutes of Health; Eli Lilly; OrthoMcNeill-Janssen; Pfizer; SK LifeScience FX Funding for this study was provided in part by The National Institute on Drug Abuse (NIDA) grant 023467. NIDA had no further role in study design; in the collection, analysis or interpretation of data; in the writing of the manuscript; or in the decision to submit for publication.; Dr. Turk has received research support from Endo, Johnson & Johnson, Philips Respironics, and the National Institutes of Health, and consulting fees from Eli Lilly, OrthoMcNeill-Janssen, Pfizer, Philips Respironics, and SK LifeScience. He is also a Special Government Employee of the U.S. Food and Drug Administration. All other authors declare that they have no conflicts of interest. NR 49 TC 27 Z9 27 U1 4 U2 16 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 1 PY 2013 VL 127 IS 1-3 BP 193 EP 199 DI 10.1016/j.drugalcdep.2012.06.032 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 079VK UT WOS:000314200100028 PM 22818513 ER PT J AU Durant, RW Brown, QL Cherrington, AL Andreae, LJ Hardy, CM Scarinci, IC AF Durant, Raegan W. Brown, Qiana L. Cherrington, Andrea L. Andreae, Lynn J. Hardy, Claudia M. Scarinci, Isabel C. TI Social support among African Americans with heart failure: Is there a role for community health advisors? SO HEART & LUNG LA English DT Article DE African Americans; Community health advisors; Heart failure; Social support ID RANDOMIZED CONTROLLED-TRIAL; WORKER INTERVENTIONS; RACIAL-DIFFERENCES; BLOOD-PRESSURE; DIABETES CARE; SELF-CARE; DISPARITIES; OUTCOMES; POPULATION; HYPERTENSION AB Objective: The study had 2 objectives: (1) to gather the observations of community health advisors (CHAs) on the role of social support in the lives of African Americans; and (2) to develop a lay support intervention framework, on the basis of the existing literature and observations of CHAs, depicting how social support may address the needs of African American patients with heart failure. Methods: Qualitative data were collected in semistructured interviews among 15 CHAs working in African American communities in Birmingham, Alabama. Results: Prominent themes included the challenge of meeting clients' overlapping health care and general life needs, the variation in social support received from family and friends, and the opportunities for CHAs to provide multiple types of social support to clients. CHAs also believed that their, support activities could be implemented among populations with heart failure. Conclusion: The experience of CHAs with social support can inform a potential framework of a lay support intervention among African Americans with heart failure. Published by Elsevier Inc. C1 [Durant, Raegan W.; Cherrington, Andrea L.; Andreae, Lynn J.; Scarinci, Isabel C.] Univ Alabama Birmingham, Sch Med, Birmingham, AL 35294 USA. [Durant, Raegan W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Brown, Qiana L.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Hardy, Claudia M.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. RP Durant, RW (reprint author), Univ Alabama Birmingham, Sch Med, 1717 11th Ave S,MT 607, Birmingham, AL 35294 USA. EM rdurant@dopm.uab.edu FU National Institute on Aging (Deep Resource Center for Minority Aging Research) [P30AG031054]; National Cancer Institute (Deep South Network for Cancer Control [U01CA114619] FX This project was funded by grants from the National Institute on Aging (Deep Resource Center for Minority Aging Research, P30AG031054) and the National Cancer Institute (Deep South Network for Cancer Control, U01CA114619). NR 48 TC 2 Z9 2 U1 2 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-9563 J9 HEART LUNG JI Heart Lung PD JAN-FEB PY 2013 VL 42 IS 1 BP 19 EP 25 DI 10.1016/j.hrtlng.2012.06.007 PG 7 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA 083BB UT WOS:000314436600005 PM 22920609 ER PT J AU Chiu, MW Modlin, RL AF Chiu, Melvin W. Modlin, Robert L. TI RESIDENT ROUNDS: PART I Program Spotlight: The UCLA Division of Dermatology Residency Training Program SO JOURNAL OF DRUGS IN DERMATOLOGY LA English DT Editorial Material C1 [Chiu, Melvin W.; Modlin, Robert L.] Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Los Angeles, CA 90095 USA. [Chiu, Melvin W.] Greater Los Angeles Vet Adm Hlth Care Syst, Dermatol Serv, Los Angeles, CA USA. RP Chiu, MW (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Los Angeles, CA 90095 USA. EM mchiu@mednet.ucla.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOURNAL OF DRUGS IN DERMATOLOGY PI NEW YORK PA 377 PARK AVE SOUTH, 6TH FLOOR, NEW YORK, NY 10016 USA SN 1545-9616 J9 J DRUGS DERMATOL JI J. Drugs Dermatol. PD JAN PY 2013 VL 12 IS 1 BP 109 EP 110 PG 2 WC Dermatology SC Dermatology GA 081KC UT WOS:000314319900020 ER PT J AU Zarraga, IGE Kron, J AF Zarraga, Ignatius Gerardo E. Kron, Jack TI Oral Anticoagulation in Elderly Adults with Atrial Fibrillation: Integrating New Options with Old Concepts SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE anticoagulation; antithrombotic; atrial fibrillation; elderly ID WARFARIN-ASSOCIATED HEMORRHAGE; RANDOMIZED CONTROLLED-TRIAL; EURO HEART SURVEY; RE-LY TRIAL; PREDICTING STROKE; ANTITHROMBOTIC THERAPY; RISK STRATIFICATION; COST-EFFECTIVENESS; DABIGATRAN; ASPIRIN AB Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and the second most common cardiovascular condition in adults in the United States. It is prevalent in the elderly population and is an important risk factor for stroke. Oral anticoagulation offers significant protection against AF-related thromboembolic events, but several complex issues that contribute to its underuse in elderly adults surround it. To aid clinicians in their approach to these problems, a comprehensive PubMed-based search of the literature published in English from 1990 through July 2012 was conducted using the following terms or combination of terms: atrial fibrillation, elderly, antiplatelet, anticoagulation, stroke, bleeding, hemorrhage, and falls. Additional references were identified in a manual search of bibliographies in retrieved articles. The data were then synthesized to address the most relevant questions regarding anticoagulation in elderly adults, including fall risk, responsiveness to warfarin, physician perception of risks, and other barriers to the prescription of anticoagulants. Recently proposed risk-stratification schemes for stroke and hemorrhage that could refine the selection of antithrombotic therapy for AF are highlighted. Finally, available data on the use of antiplatelet therapy, warfarin, and new oral anticoagulants (direct thrombin inhibitor and factor Xa inhibitors) in AF are summarized. J Am Geriatr Soc 61:143-150, 2013. C1 [Zarraga, Ignatius Gerardo E.] Portland VA Med Ctr, Div Cardiol, Portland, OR 97239 USA. [Zarraga, Ignatius Gerardo E.; Kron, Jack] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Zarraga, IGE (reprint author), Portland VA Med Ctr, Div Cardiol, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Ignatius.Zarraga@va.gov FU Boehringer-Ingelheim Pharmaceuticals, Inc.; Johnson Johnson FX This work was supported by Boehringer-Ingelheim Pharmaceuticals, Inc. The authors received no compensation related to the development of the manuscript. The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. JK received a consulting fee from Johnson & Johnson in March 2011 and was a speaker for Biotronik. NR 40 TC 18 Z9 19 U1 1 U2 11 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 JAN PY 2013 VL 61 IS 1 BP 143 EP 150 DI 10.1111/jgs.12042 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 073AM UT WOS:000313715600025 PM 23252345 ER PT J AU Lipsky, BA Berendt, AR Cornia, PB Pile, JC Peters, EJG Armstrong, DG Deery, HG Embil, JM Joseph, WS Karchmer, AW Pinzur, MS Senneville, E AF Lipsky, Benjamin A. Berendt, Anthony R. Cornia, Paul B. Pile, James C. Peters, Edgar J. G. Armstrong, David G. Deery, H. Gunner Embil, John M. Joseph, Warren S. Karchmer, Adolf W. Pinzur, Michael S. Senneville, Eric TI 2012 Infectious Diseases Society of America Clinical Practice Guideline for the Diagnosis and Treatment of Diabetic Foot Infections (Reprinted from Clinical Infectious Diseases, vol 54, pg 132, 2012) SO JOURNAL OF THE AMERICAN PODIATRIC MEDICAL ASSOCIATION LA English DT Reprint AB Foot infections are a common and serious problem in persons with diabetes. Diabetic foot infections (DFIs) typically begin in a wound, most often a neuropathic ulceration. While all wounds are colonized with microorganisms, the presence of infection is defined by >= 2 classic findings of inflammation or purulence. Infections are then classified into mild (superficial and limited in size and depth), moderate (deeper or more extensive), or severe (accompanied by systemic signs or metabolic perturbations). This classification system, along with a vascular assessment, helps determine which patients should be hospitalized, which may require special imaging procedures or surgical interventions, and which will require amputation. Most DFIs are polymicrobial, with aerobic gram-positive cocci (GPC), and especially staphylococci, the most common causative organisms. Aerobic gram-negative bacilli are frequently copathogens in infections that are chronic or follow antibiotic treatment, and obligate anaerobes may be copathogens in ischemic or necrotic wounds. Wounds without evidence of soft tissue or bone infection do not require antibiotic therapy. For infected wounds, obtain a post-debridement specimen (preferably of tissue) for aerobic and anaerobic culture. Empiric antibiotic therapy can be narrowly targeted at GPC in many acutely infected patients, but those at risk for infection with antibiotic-resistant organisms or with chronic, previously treated, or severe infections usually require broader spectrum regimens. Imaging is helpful in most DFIs; plain radiographs may be sufficient, but magnetic resonance imaging is far more sensitive and specific. Osteomyelitis occurs in many diabetic patients with a foot wound and can be difficult to diagnose (optimally defined by bone culture and histology) and treat (often requiring surgical debridement or resection, and/or prolonged antibiotic therapy). Most DFIs require some surgical intervention, ranging from minor (debridement) to major (resection, amputation). Wounds must also be properly dressed and off-loaded of pressure, and patients need regular follow-up. An ischemic foot may require revascularization, and some nonresponding patients may benefit from selected adjunctive measures. Employing multidisciplinary foot teams improves outcomes. Clinicians and healthcare organizations should attempt to monitor, and thereby improve, their outcomes and processes in caring for DFIs. C1 [Lipsky, Benjamin A.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. [Berendt, Anthony R.] Oxford Univ Hosp NHS Trust, Nuffield Orthopaed Ctr, Bone Infect Unit, Oxford, England. [Cornia, Paul B.] Univ Washington, Veteran Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98195 USA. [Pile, James C.] MetroHlth Med Ctr, Div Hosp Med, Cleveland, OH USA. [Pile, James C.] Metrohlth Med Ctr, Div Infect Dis, Cleveland, OH USA. [Peters, Edgar J. G.] Vrije Univ Amsterdam, Med Ctr, Dept Internal Med, Amsterdam, Netherlands. [Armstrong, David G.] Univ Arizona, Dept Med, So Arizona Limb Salvage Alliance, Tucson, AZ USA. [Deery, H. Gunner] No Michigan Infect Dis, Petoskey, MI USA. [Embil, John M.] Univ Manitoba, Dept Med, Winnipeg, MB, Canada. [Joseph, Warren S.] Roxborough Mem Hosp, Dept Surg, Div Podiatr Surg, Philadelphia, PA USA. [Karchmer, Adolf W.] Harvard Univ, Sch Med, Dept Med,Div Infect Dis, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Pinzur, Michael S.] Loyola Univ, Med Ctr, Dept Orthopaed Surg & Rehabil, Maywood, IL 60153 USA. [Senneville, Eric] Dron Hosp, Dept Infect Dis, Tourcoing, France. RP Lipsky, BA (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM balipsky@uw.edu RI Peters, Edgar /B-7790-2014 OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 1 TC 21 Z9 22 U1 3 U2 30 PU AMER PODIATRIC MED ASSOC PI BETHESDA PA 9312 OLD GEORGETOWN ROAD, BETHESDA, MD 20814-1621 USA SN 8750-7315 J9 J AM PODIAT MED ASSN JI J. Am. Podiatr. Med. Assoc. PD JAN-FEB PY 2013 VL 103 IS 1 BP 2 EP 7 DI 10.1093/cid/cis346 PG 6 WC Orthopedics SC Orthopedics GA 081JU UT WOS:000314318600002 PM 23328846 ER PT J AU Nguyen, USDT Dufour, AB Positano, RG Dines, JS Dodson, CC Gagnon, DG Hillstrom, HJ Hannan, MT AF Nguyen, Uyen-Sa D. T. Dufour, Alyssa B. Positano, Rock G. Dines, Joshua S. Dodson, Christopher C. Gagnon, David G. Hillstrom, Howard J. Hannan, Marian T. TI The Occurrence of lpsilateral or Contra lateral Foot Disorders and Hand Dominance The Framingham Foot Study SO JOURNAL OF THE AMERICAN PODIATRIC MEDICAL ASSOCIATION LA English DT Article ID LEFT-HANDEDNESS; INJURY RISK; PREFERENCES; AGE; ADULTS; EYE AB Background: To our knowledge, hand dominance and side of foot disorders has not been described in the literature. We sought to evaluate whether hand dominance was associated with ipsilateral foot disorders in community-dwelling older men and women. Methods: Data were from the Framingham Foot Study (N = 2,089, examined 2002-2008). Hand preference for writing was used to classify hand dominance. Foot disorders and side of disorders were based on validated foot examination findings. Generalized linear models with generalized estimating equations were used to estimate odds ratios and 95% confidence intervals, accounting for intraperson variability. Results: Left-handed people were less likely to have foot pain or any foot disorders ipsilateral but were more likely to have hallux valgus ipsilateral to the left hand. Among right-handed people, the following statistically significant increased odds of having an ipsilateral versus contralateral foot disorder were seen: 30% for Morton's neuroma, 18% for hammer toes, 21% for lesser toe deformity, and a twofold increased odds of any foot disorder; there was a 17% decreased odds for Tailor's bunion and an 11% decreased odds for pes cavus. Conclusions: For the 2,089 study participants, certain forefoot disorders were shown to be ipsilateral and others were contralateral to the dominant hand. Future studies should examine whether the same biological mechanism that explains ipsilateral hand and foot preference may explain ipsilateral hand dominance and forefoot disorders. (J Am Podiatr Med Assoc 103(1): 16-23, 2013) C1 [Nguyen, Uyen-Sa D. T.] Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA. [Dufour, Alyssa B.; Hannan, Marian T.] Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA. [Dufour, Alyssa B.; Hannan, Marian T.] Harvard Univ, Sch Med, Boston, MA USA. [Positano, Rock G.] Hosp Special Surg, Nonsurg Foot & Ankle Serv, New York, NY 10021 USA. [Positano, Rock G.] Hosp Special Surg, Joe DiMaggio Sports Foot & Ankle Ctr, New York, NY 10021 USA. [Dines, Joshua S.] Hosp Special Surg, Sports Med & Shoulder Serv, New York, NY 10021 USA. [Dodson, Christopher C.] Thomas Jefferson Univ Hosp, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. [Gagnon, David G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Gagnon, David G.] US Dept Vet Affairs, Cooperat Studies Program, Boston, MA USA. [Hillstrom, Howard J.] Hosp Special Surg, MD Motion Anal Lab, New York, NY 10021 USA. RP Hannan, MT (reprint author), Hebrew SeniorLife, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA. EM Hannan@hsl.harvard.edu FU Non-surgical Foot and Ankle Service at the Hospital for Special Surgery; National Institutes of Health [R01-AR047853]; National Heart Lung and Blood Institute of the National Institutes of Health [N01-HC-25195]; Boston University School of Medicine; National Institutes of Health-National Institute on Aging supplement [3R01AG026316-03S1] FX This work was funded by an unrestricted research grant from the Non-surgical Foot and Ankle Service at the Hospital for Special Surgery and from the National Institutes of Health (R01-AR047853). This work was derived from the Framingham Heart Study, supported by the National Heart Lung and Blood Institute of the National Institutes of Health (contract No. N01-HC-25195) and Boston University School of Medicine. Dr. Hannan was supported by the National Institutes of Health-National Institute on Aging supplement 3R01AG026316-03S1. The sponsors played no role in the design and conduct of the study. NR 14 TC 1 Z9 1 U1 1 U2 6 PU AMER PODIATRIC MED ASSOC PI BETHESDA PA 9312 OLD GEORGETOWN ROAD, BETHESDA, MD 20814-1621 USA SN 8750-7315 J9 J AM PODIAT MED ASSN JI J. Am. Podiatr. Med. Assoc. PD JAN-FEB PY 2013 VL 103 IS 1 BP 16 EP 23 PG 8 WC Orthopedics SC Orthopedics GA 081JU UT WOS:000314318600004 PM 23328848 ER PT J AU Wang, GH Jiang, XY Pu, HJ Zhang, WT An, CR Hu, XM Liou, AKF Leak, RK Gao, YQ Chen, J AF Wang, Guohua Jiang, Xiaoyan Pu, Hongjian Zhang, Wenting An, Chengrui Hu, Xiaoming Liou, Anthony Kian-Fong Leak, Rehana K. Gao, Yanqin Chen, Jun TI Scriptaid, a Novel Histone Deacetylase Inhibitor, Protects Against Traumatic Brain Injury via Modulation of PTEN and AKT Pathway SO NEUROTHERAPEUTICS LA English DT Review DE TBI; Histone deacetylase inhibitor; CCI; Long-term protection; p-AKT; PTEN ID EXPERIMENTAL ANIMAL-MODELS; GLOBAL CEREBRAL-ISCHEMIA; ALZHEIMERS-DISEASE; TUMOR-SUPPRESSOR; H3 ACETYLATION; MOUSE MODEL; CELL-DEATH; RAT; NEURODEGENERATION; PHOSPHORYLATION AB Traumatic brain injury (TBI) is a leading cause of motor and cognitive deficits in young adults for which there is no effective therapy. The present study characterizes the protective effect of a new histone deacetylase inhibitor, Scriptaid (Sigma-Aldrich Corporation, St. Louis, MO), against injury from controlled cortical impact (CCI). Scriptaid elicited a dose-dependent decrease in lesion size at 1.5 to 5.5 mg/kg and a concomitant attenuation in motor and cognitive deficits when delivered 30 minutes postinjury in a model of moderate TBI. Comparable protection was achieved even when treatment was delayed to 12 h postinjury. Furthermore, the protection of motor and cognitive functions was long lasting, as similar improvements were detected 35 days postinjury. The efficacy of Scriptaid (Sigma-Aldrich Corporation) was manifested as an increase in surviving neurons, as well as the number/length of their processes within the CA3 region of the hippocampus and the pericontusional cortex. Consistent with other histone deacetylase inhibitors, Scriptaid treatment prevented the decrease in phospho-AKT (p-AKT) and phosphorylated phosphatase and tensin homolog deleted on chromosome 10 (p-PTEN) induced by TBI in cortical and CA3 hippocampal neurons. Notably, the p-AKT inhibitor LY294002 attenuated the impact of Scriptaid, providing mechanistic evidence that Scriptaid functions partly by modulating the prosurvival AKT signaling pathway. As Scriptaid offers long-lasting neuronal and behavioral protection, even when delivered 12 h after controlled cortical impact, it is an excellent new candidate for the effective clinical treatment of TBI. C1 [Wang, Guohua; Jiang, Xiaoyan; Pu, Hongjian; Zhang, Wenting; An, Chengrui; Gao, Yanqin; Chen, Jun] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China. [Wang, Guohua; Jiang, Xiaoyan; Pu, Hongjian; Zhang, Wenting; An, Chengrui; Gao, Yanqin; Chen, Jun] Fudan Univ, Inst Brain Sci, Shanghai 200032, Peoples R China. [Wang, Guohua; Hu, Xiaoming; Liou, Anthony Kian-Fong; Gao, Yanqin; Chen, Jun] Univ Pittsburgh, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. [Leak, Rehana K.] Duquesne Univ, Div Pharmaceut Sci, Mylan Sch Pharm, Pittsburgh, PA 15282 USA. [Wang, Guohua] Nantong Univ, Dept Neuropharmacol, Inst Naut Med, Nantong 226001, Jiangsu, Peoples R China. [Hu, Xiaoming; Liou, Anthony Kian-Fong; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. [Gao, Yanqin; Chen, Jun] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. RP Gao, YQ (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. EM yqgao@shmu.edu.cn; ChenJ2@upmc.edu RI Gao, Yanqin/I-6790-2016 OI Gao, Yanqin/0000-0002-4915-9819 FU Chinese Ministry of Science and Technology; National Institutes of Health/National Institute of Neurological Disorders and Stroke [NS36736, NS43802, NS45048]; Veterans Administration Merit Review; Chinese Natural Science Foundation [30870794, 81020108021, 81171149, 81150110494, 81000497] FX This research is supported in part by the Special Research Funds from the Chinese Ministry of Science and Technology to State Key Laboratories (to G. H. W, Y.G, and J.C); the National Institutes of Health/National Institute of Neurological Disorders and Stroke (grants NS36736, NS43802 and NS45048 to J.C.); the Veterans Administration Merit Review (grant to J.C.); and the Chinese Natural Science Foundation (grants No. 30870794, No. 81020108021, No. 81171149, No. 81150110494 to Y.G., and No. 81000497 to G. W.) The authors declare no conflict of interest. Full conflict of interest disclosures is available in the electronic supplementary material for this article. NR 65 TC 30 Z9 31 U1 4 U2 27 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2013 VL 10 IS 1 BP 124 EP 142 DI 10.1007/s13311-012-0157-2 PG 19 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 080WM UT WOS:000314274800014 PM 23132328 ER PT J AU Buckenmaier, CC Galloway, KT Polomano, RC McDuffie, M Kwon, N Gallagher, RM AF Buckenmaier, Chester C., III Galloway, Kevin T. Polomano, Rosemary C. McDuffie, Mary Kwon, Nancy Gallagher, Rollin M. TI Preliminary Validation of the Defense and Veterans Pain Rating Scale (DVPRS) in a Military Population SO PAIN MEDICINE LA English DT Article DE Validation Study; Pain Measurement; Pain Scales ID POLYTRAUMA CLINICAL TRIAD; RECEIVING PRIMARY-CARE; 5TH VITAL SIGN; IRAQI FREEDOM; CANCER PAIN; MANAGEMENT; INTERFERENCE; SEVERITY; VALIDITY; INJURY AB Background. The Army Surgeon General released the Pain Management Task Force final report in May 2010. Among military providers, concerns were raised that the standard numeric rating scale (NRS) for pain was inconsistently administered and of questionable clinical value. In response, the Defense and Veterans Pain Rating Scale (DVPRS) was developed. Methods. The instrument design integrates pain rating scale features to improve interpretability of incremental pain intensity levels, and to improve communication and documentation across all transitions of care. A convenience sample of 350 inpatient and outpatient active duty or retired military service members participated in the study at Walter Reed Army Medical Center. Participants completed the five-item DVPRSone pain intensity NRS with and without word descriptors presented in random order and four supplemental items measuring general activity, sleep, mood, and level of stress and the Brief Pain Inventory seven interference items. Using systematic sampling, a random sample was selected for a word descriptor validation procedure matching word phases to corresponding pain intensity on the NRS. Results. Parallel forms reliability and concurrent validity testing demonstrated a robust correlation. When the DVPRS was presented with the word descriptors first, the correlation between the two ratings was slightly higher, r?=?0.929 (N?=?171; P?