FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Maciejewski, ML Liu, CF Kavee, AL Olsen, MK AF Maciejewski, Matthew L. Liu, Chuan-Fen Kavee, Andrew L. Olsen, Maren K. TI HOW PRICE RESPONSIVE IS THE DEMAND FOR SPECIALTY CARE? SO HEALTH ECONOMICS LA English DT Article DE costs; longitudinal; mixed model; random effects; health econometrics; zero-inflated data; specialty care; co-payment; cost sharing ID HEALTH MAINTENANCE ORGANIZATION; OFFICE VISIT COPAYMENTS; RISK ADJUSTMENT; PREVENTIVE SERVICES; EMERGENCY; OUTCOMES; IMPACT; COSTS; COINSURANCE; PERFORMANCE AB Objectives Outpatient visit co-payments have increased in recent years. We estimate the patient response to a price change for specialty care, based on a co-payment increase from $15 to $50 per visit for veterans with hypertension. Design, Setting, and Patients A retrospective cohort of veterans required to pay co-payments was compared with veterans exempt from co-payments whose nonequivalence was reduced via propensity score matching. Specialty care expenditures in 20002003 were estimated via a two-part mixed model to account for the correlation of the use and level outcomes over time, and results from this correlated two-part model were compared with an uncorrelated two-part model and a correlated random intercept two-part mixed model. Results A $35 specialty visit co-payment increase had no impact on the likelihood of seeking specialty care but induced lower specialty expenditures over time among users who were required to pay co-payments. The log ratio of price responsiveness (semi-elasticity) for specialty care increased from -0.25 to -0.31 after the co-payment increase. Estimates were similar across the three models. Conclusion A significant increase in specialty visit co-payments reduced specialty expenditures among patients obtaining medications at the Veterans Affairs medical centers. Longitudinal expenditure analysis may be improved using recent advances in two-part model methods. Published 2011. This article is a US Government work and is in the public domain in the USA. C1 [Maciejewski, Matthew L.; Kavee, Andrew L.; Olsen, Maren K.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Maciejewski, Matthew L.] Duke Univ, Div Gen Internal Med, Durham, NC USA. [Liu, Chuan-Fen] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Liu, Chuan-Fen] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Olsen, Maren K.] Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA. RP Maciejewski, ML (reprint author), Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, 205 Fulton St, Durham, NC USA. EM mlm34@duke.edu FU Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs [IIR 03-200]; Department of Veterans Affairs [RCS 10-391]; Novartis; Takeda Pharmaceuticals; Surgical Review Corporation FX This work was supported by the Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs, project number IIR 03-200. Dr Maciejewski was also supported by a Research Career Scientist award from the Department of Veterans Affairs (RCS 10-391). The authors are grateful for the helpful comments from the editor, two reviewers, Jim Burgess, Steve Pizer, Anirban Basu, Courtney Van Houtven, Santanu Datta, Valerie Smith, and the seminar participants at the ASA Health Policy Statistics meeting in 2008. Dr Maciejewski has received consultation funds from Novartis, Takeda Pharmaceuticals, Surgical Review Corporation, and owns a stock in Amgen. The views expressed are those of the authors and do not reflect the views of the Department of Veterans Affairs, the Duke University, or the University of Washington. NR 44 TC 3 Z9 3 U1 1 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9230 J9 HEALTH ECON JI Health Econ. PD AUG PY 2012 VL 21 IS 8 BP 902 EP 912 DI 10.1002/hec.1759 PG 11 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 967KT UT WOS:000305907400002 PM 21755570 ER PT J AU McDermott, PJ Baicu, CF Wahl, SR Van Laer, AO Zile, MR AF McDermott, Paul J. Baicu, Catalin F. Wahl, Shaun R. Van Laer, An O. Zile, Michael R. TI In vivo measurements of the contributions of protein synthesis and protein degradation in regulating cardiac pressure overload hypertrophy in the mouse SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE Myocardium; Amino acids; Infusion; Inbred C57BL mice ID MYOSIN HEAVY-CHAIN; VENTRICULAR HYPERTROPHY; VOLUME OVERLOAD; MICE; TURNOVER; CANINE; HEART; DYSFUNCTION; MECHANISMS; PROTEASOME AB Cardiac hypertrophy is generated in response to hemodynamic overload by altering steady-state protein metabolism such that the rate of protein synthesis exceeds the rate of protein degradation. To determine the relative contributions of protein synthesis and degradation in regulating cardiac hypertrophy in mice, a continuous infusion strategy was developed to measure myocardial protein synthesis rates in vivo. Osmotic mini-pumps were implanted in the abdominal cavity to infuse radiolabeled leucine in mice that are conscious and ambulatory. Protein synthesis rates were calculated by measuring incorporation of leucine into myocardial protein over 24 h prior to each time point and dividing by the specific radioactivity of plasma leucine. Compared to sham-operated controls, fractional rates of protein synthesis (K (s)) increased significantly at days 1 and 3 of TAC, but was lower on day 7 and returned to control values by day 14. These changes coincided with the curvilinear increase in LV mass that characterizes the hypertrophic response. Fractional rates of protein degradation (K (d)) were calculated by subtracting the rate of myocardial growth from the corresponding K (s) value. K (d) fell at days 1 and 3 of TAC, increased at day 7 and returned to control on day 14. Thus, the increase in LV mass generated in response to pressure overload is caused by acceleration of K (s) and suppression of K (d). As the growth rate slows, a new steady-state is achieved once the hypertrophic response is completed. C1 [McDermott, Paul J.; Baicu, Catalin F.; Wahl, Shaun R.; Van Laer, An O.; Zile, Michael R.] Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Charleston, SC 29403 USA. [McDermott, Paul J.; Baicu, Catalin F.; Wahl, Shaun R.; Van Laer, An O.; Zile, Michael R.] Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. RP McDermott, PJ (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Strom Thurmond Biomed Res Bldg,Room 303,114 Dough, Charleston, SC 29403 USA. EM mcdermp@musc.edu FU Department of Veterans Affairs FX We thank Daisy Dominick and Dr. Harinath Kasiganesan for their excellent technical assistance, and Dr. Francis G. Spinale for his help using osmotic mini-pumps. This work was supported by Merit Review Awards (P. J. McDermott and M. R. Zile) from the Health Services Research and Development Program of the Department of Veterans Affairs. NR 24 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD AUG PY 2012 VL 367 IS 1-2 BP 205 EP 213 DI 10.1007/s11010-012-1334-7 PG 9 WC Cell Biology SC Cell Biology GA 964GX UT WOS:000305683100021 PM 22610791 ER PT J AU Zile, MR Baicu, CF Gottdiener, JS Hetzel, SJ McMurray, JJ Komajda, M McKelvie, R Massie, BM Carson, PE AF Zile, Michael R. Baicu, Catalin F. Gottdiener, John S. Hetzel, Scott J. McMurray, John J. Komajda, Michel McKelvie, Robert Massie, Barry M. Carson, Peter E. CA I-PRESERVE Investigators TI Response to Letters Regarding Article, "Prevalence and Significance of Alterations in Cardiac Structure and Function in Patients With Heart Failure and a Preserved Ejection Fraction" SO CIRCULATION LA English DT Letter C1 [Zile, Michael R.; Baicu, Catalin F.] RHJ Dept Vet Affairs Med Ctr, Charleston, SC USA. [Zile, Michael R.; Baicu, Catalin F.] Med Univ S Carolina, Charleston, SC 29425 USA. [Gottdiener, John S.] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. [Hetzel, Scott J.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [McMurray, John J.] Univ Glasgow, British Heart Fdn, Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Komajda, Michel] Univ Paris 06, Pitie Salpetriere Hosp, Paris, France. [McKelvie, Robert] McMaster Univ, Hamilton, ON, Canada. [Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Carson, Peter E.; I-PRESERVE Investigators] Georgetown Univ, Washington, DC USA. [Carson, Peter E.] VAMC, Washington, DC USA. RP Zile, MR (reprint author), RHJ Dept Vet Affairs Med Ctr, Charleston, SC USA. OI mcmurray, john/0000-0002-6317-3975 NR 7 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 31 PY 2012 VL 126 IS 5 BP E64 EP E65 DI 10.1161/CIRCULATIONAHA.112.110809 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 981OK UT WOS:000306977500008 ER PT J AU Eccles, MP Foy, R Sales, A Wensing, M Mittman, B AF Eccles, Martin P. Foy, Robbie Sales, Anne Wensing, Michel Mittman, Brian TI Implementation Science six years on-our evolving scope and common reasons for rejection without review SO IMPLEMENTATION SCIENCE LA English DT Editorial Material AB Implementation Science has been published for six years and over that time has gone from receiving 100 articles in 2006 to receiving 354 in 2011; our impact factor has risen from 2.49 in June 2010 to 3.10 in June 2012. Whilst our article publication rate has also risen, it has risen much less slowly than our submission rate-we published 29 papers in 2006 and 134 papers in 2011 and we now publish only around 40 % of submissions. About one-half of submitted manuscripts are rejected without being sent out for peer review; it has become clear that there are a number of common issues that result in manuscripts being rejected at this stage. We hope that by publishing this editorial on our common reasons for rejection without peer review we can help authors to better judge the relevance of their papers to Implementation Science. C1 [Eccles, Martin P.] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE2 4AX, Tyne & Wear, England. [Foy, Robbie] Univ Leeds, Leeds Inst Hlth Sci, Leeds LS2 9LJ, W Yorkshire, England. [Wensing, Michel] Radboud Univ Nijmegen, Med Ctr, Sci Inst Qual Healthcare, NL-6525 ED Nijmegen, Netherlands. [Mittman, Brian] VA Greater Los Angeles Healthcare Syst, VA Ctr Implementat Practice & Res Support, Sepulveda, CA 91343 USA. [Sales, Anne] Ann Arbor VA HSR&D Ctr Excellence, VA Inpatient Evaluat Ctr, Ann Arbor, MI USA. RP Eccles, MP (reprint author), Newcastle Univ, Inst Hlth & Soc, Baddiley Clark Bldg,Richardson Rd, Newcastle Upon Tyne NE2 4AX, Tyne & Wear, England. EM martin.eccles@ncl.ac.uk RI Wensing, Michel/H-8113-2014 OI Sales, Anne/0000-0001-9360-3334 NR 6 TC 15 Z9 15 U1 0 U2 8 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 JUL 27 PY 2012 VL 7 AR 71 DI 10.1186/1748-5908-7-71 PG 6 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 011HK UT WOS:000309155500001 PM 22839967 ER PT J AU Rettig, M Trinidad, K Pezeshkpour, G Frost, P Sharma, S Moatamed, F Tamanoi, F Mortazavi, F AF Rettig, Matthew Trinidad, Kenny Pezeshkpour, G. Frost, Patrick Sharma, Sherven Moatamed, Farhad Tamanoi, Fuyuhiko Mortazavi, Fariborz TI PAK1 Kinase Promotes Cell Motility and Invasiveness through CRK-II Serine Phosphorylation in Non-Small Cell Lung Cancer Cells SO PLOS ONE LA English DT Article ID ACTIVATED PROTEIN-KINASE; EPIDERMAL-GROWTH-FACTOR; RHO-FAMILY GTPASES; P120 CATENIN; ADAPTER PROTEINS; P21-ACTIVATED-KINASE-1 PAK1; CADHERIN EXPRESSION; ONCOGENE PRODUCT; P120-CATENIN; APOPTOSIS AB The role of c-Crk (CRK) in promoting metastasis is well described however the role of CRK phosphorylation and the corresponding signaling events are not well explained. We have observed CRK-II serine 41 phosphorylation is inversely correlated with p120-catenin and E-cadherin expressions in non-small cell lung cancer (NSCLC) cells. Therefore, we investigated the role of CRK-II serine 41 phosphorylation in the down-regulation of p120-catenin, cell motility and cell invasiveness in NSCLC cells. For this purpose, we expressed phosphomimetic and phosphodeficient CRK-II serine 41 mutants in NSCLC cells. NSCLC cells expressing phosphomimetic CRK-II seine 41 mutant showed lower p120-catenin level while CRK-II seine 41 phosphodeficient mutant expression resulted in higher p120-catenin. In addition, A549 cells expressing CRK-II serine 41 phosphomimetic mutant demonstrated more aggressive behavior in wound healing and invasion assays and, on the contrary, expression of phosphodeficient CRK-II serine 41 mutant in A549 cells resulted in reduced cell motility and invasiveness. We also provide evidence that PAK1 mediates CRK-II serine 41 phosphorylation. RNAi mediated silencing of PAK1 increased p120-catenin level in A549 and H157 cells. Furthermore, PAK1 silencing decreased cell motility and invasiveness in A549 cells. These effects were abrogated in A549 cells expressing phosphomimetic CRK-II serine 41. In summary, these data provide evidence for the role of PAK1 in the promotion of cell motility, cell invasiveness and the down regulation of p120-catenin through CRK serine 41 phosphorylation in NSCLC cells. C1 [Rettig, Matthew; Trinidad, Kenny; Frost, Patrick; Mortazavi, Fariborz] W Los Angeles VA, Div Hematol Oncol, Los Angeles, CA USA. [Rettig, Matthew; Sharma, Sherven; Mortazavi, Fariborz] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Rettig, Matthew; Tamanoi, Fuyuhiko; Mortazavi, Fariborz] Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. [Pezeshkpour, G.; Moatamed, Farhad] W Los Angeles VA, Dept Pathol, Los Angeles, CA USA. [Sharma, Sherven] W Los Angeles VA, Div Mol Med, Los Angeles, CA USA. [Tamanoi, Fuyuhiko] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA. RP Rettig, M (reprint author), W Los Angeles VA, Div Hematol Oncol, Los Angeles, CA USA. EM fredmortazavi@ucla.edu OI Frost, Patrick/0000-0003-3348-5983 NR 49 TC 22 Z9 22 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 27 PY 2012 VL 7 IS 7 AR e42012 DI 10.1371/journal.pone.0042012 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 981ER UT WOS:000306950200146 PM 22848689 ER PT J AU Tokhtaeva, E Clifford, RJ Kaplan, JH Sachs, G Vagin, O AF Tokhtaeva, Elmira Clifford, Rebecca J. Kaplan, Jack H. Sachs, George Vagin, Olga TI Subunit Isoform Selectivity in Assembly of Na,K-ATPase alpha-beta Heterodimers SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; CENTRAL-NERVOUS-SYSTEM; NA+-K+-ATPASE; ADHESION MOLECULE; CELL-ADHESION; EXPRESSION; ISOZYMES; IDENTIFICATION; EPILEPSY; GLIA AB To catalyze ion transport, the Na,K-ATPase must contain one alpha and one beta subunit. When expressed by transfection in various expression systems, each of the four alpha subunit isoforms can assemble with each of the three beta subunit isoforms and form an active enzyme, suggesting the absence of selective alpha-beta isoform assembly. However, it is unknown whether in vivo conditions the alpha-beta assembly is random or isoform-specific. The alpha(2)-beta(2) complex was selectively immunoprecipitated by both anti-alpha(2) and anti-beta(2) antibodies from extracts of mouse brain, which contains cells co-expressing multiple Na,K-ATPase isoforms. Neither alpha(1)-beta(2) nor alpha(2)-beta(1) complexes were detected in the immunoprecipitates. Furthermore, in MDCK cells co-expressing alpha(1), beta(1), and beta(2) isoforms, a greater fraction of the beta(2) subunits was unassembled with alpha(1) as compared with that of the beta(1) subunits, indicating preferential association of the alpha(1) isoform with the beta(1) isoform. In addition, the alpha(1)-beta(2) complex was less resistant to various detergents than the alpha(1)-beta(1) complex isolated from MDCK cells or the alpha(2)-beta(2) complex isolated from mouse brain. Therefore, the diversity of the alpha-beta Na,K-ATPase heterodimers in vivo is determined not only by cell-specific co-expression of particular isoforms, but also by selective association of the alpha and beta subunit isoforms. C1 [Tokhtaeva, Elmira; Sachs, George; Vagin, Olga] Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. [Tokhtaeva, Elmira; Sachs, George; Vagin, Olga] Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. [Clifford, Rebecca J.; Kaplan, Jack H.] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA. RP Vagin, O (reprint author), VAG LAHS W LA, 11301 Wilshire Blvd,Bldg 113,Rm 324, Los Angeles, CA 90073 USA. EM olgav@ucla.edu OI Kaplan, Jack/0000-0002-7048-6574 FU National Institutes of Health [DK077149, DK058333, GM39500] FX This work was supported, in whole or in part, by National Institutes of Health Grants DK077149 (to O. V.), DK058333 (to G. S.), and GM39500 (to J. H. K.). NR 58 TC 24 Z9 24 U1 0 U2 7 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 JUL 27 PY 2012 VL 287 IS 31 BP 26115 EP 26125 DI 10.1074/jbc.M112.370734 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 980TN UT WOS:000306916300039 PM 22696220 ER PT J AU Ramos, FJ Chen, SC Garelick, MG Dai, DF Liao, CY Schreiber, KH MacKay, VL An, EH Strong, R Ladiges, WC Rabinovitch, PS Kaeberlein, M Kennedy, BK AF Ramos, Fresnida J. Chen, Steven C. Garelick, Michael G. Dai, Dao-Fu Liao, Chen-Yu Schreiber, Katherine H. MacKay, Vivian L. An, Elroy H. Strong, Randy Ladiges, Warren C. Rabinovitch, Peter S. Kaeberlein, Matt Kennedy, Brian K. TI Rapamycin Reverses Elevated mTORC1 Signaling in Lamin A/C-Deficient Mice, Rescues Cardiac and Skeletal Muscle Function, and Extends Survival SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID GENETICALLY HETEROGENEOUS MICE; GIRDLE MUSCULAR-DYSTROPHY; DILATED CARDIOMYOPATHY; PRESSURE-OVERLOAD; HEART-FAILURE; SINGLE BOUT; LIFE-SPAN; IN-VIVO; P70 S6; AUTOPHAGY AB Mutations in LMNA, the gene that encodes A-type lamins, cause multiple diseases including dystrophies of the skeletal muscle and fat, dilated cardiomyopathy, and progeria-like syndromes (collectively termed laminopathies). Reduced A-type lamin function, however, is most commonly associated with skeletal muscle dystrophy and dilated cardiomyopathy rather than lipodystrophy or progeria. The mechanisms underlying these diseases are only beginning to be unraveled. We report that mice deficient in Lmna, which corresponds to the human gene LMNA, have enhanced mTORC1 (mammalian target of rapamycin complex 1) signaling specifically in tissues linked to pathology, namely, cardiac and skeletal muscle. Pharmacologic reversal of elevated mTORC1 signaling by rapamycin improves cardiac and skeletal muscle function and enhances survival in mice lacking A-type lamins. At the cellular level, rapamycin decreases the number of myocytes with abnormal desmin accumulation and decreases the amount of desmin in both muscle and cardiac tissue of Lmna(-/-) mice. In addition, inhibition of mTORC1 signaling with rapamycin improves defective autophagic-mediated degradation in Lmna(-/-) mice. Together, these findings point to aberrant mTORC1 signaling as a mechanistic component of laminopathies associated with reduced A-type lamin function and offer a potential therapeutic approach, namely, the use of rapamycin-related mTORC1 inhibitors. C1 [Chen, Steven C.; Garelick, Michael G.; MacKay, Vivian L.; Kennedy, Brian K.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Ramos, Fresnida J.; Dai, Dao-Fu; An, Elroy H.; Rabinovitch, Peter S.; Kaeberlein, Matt] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Liao, Chen-Yu; Schreiber, Katherine H.; Kennedy, Brian K.] Buck Inst Res Aging, Novara, CA 94945 USA. [Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Strong, Randy] S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX 78284 USA. [Strong, Randy] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78284 USA. [Ladiges, Warren C.] Univ Washington, Dept Comparat Med, Seattle, WA 98195 USA. RP Kennedy, BK (reprint author), Univ Washington, Dept Biochem, Seattle, WA 98195 USA. EM kaeber@uw.edu; bkennedy@buckinstitute.org FU National Institute on Aging [R01 AG024287, R01 AG033373, U01 AG022307]; NIH [T32AG000057, T32 HL007312] FX This study was supported by National Institute on Aging grants R01 AG024287 and R01 AG033373 (to B. K. K.) and U01 AG022307 (to R. S.). F.J.R. and M. G. G. are supported by NIH training grant T32AG000057. S. C. C. is supported by the cardiovascular and pathology training grant NIH T32 HL007312. M. K. is an Ellison Medical Foundation New Scholar in Aging. NR 63 TC 91 Z9 92 U1 3 U2 12 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JUL 25 PY 2012 VL 4 IS 144 AR 144ra103 DI 10.1126/scitranslmed.3003802 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 981LC UT WOS:000306968700006 PM 22837538 ER PT J AU Patel, A Zhu, YH Kuzhikandathil, EV Banks, WA Siegel, A Zalcman, SS AF Patel, Ankur Zhu, Youhua Kuzhikandathil, Eldo V. Banks, William A. Siegel, Allan Zalcman, Steven S. TI Soluble Interleukin-6 Receptor Induces Motor Stereotypies and Co-Localizes with Gp130 in Regions Linked to Cortico-Striato-Thalamo-Cortical Circuits SO PLOS ONE LA English DT Article ID BETA-PROTEIN ANTIBODY; BLOOD-BRAIN-BARRIER; IL-6 RECEPTOR; RHEUMATOID-ARTHRITIS; ALZHEIMERS-DISEASE; MULTIPLE-MYELOMA; CYTOKINE NETWORK; MOUSE MODEL; SCHIZOPHRENIA; AMPHETAMINE AB Soluble cytokine receptors are normal constituents of body fluids that regulate peripheral cytokine and lymphoid activity and whose levels are increased in states of immune activation. Soluble interleukin-6 receptor (sIL-6R) levels positively correlate with disease progression in some autoimmune conditions and psychiatric disorders. Particularly strong links between levels of sIL-6R and the severity of psychotic symptoms occur in schizophrenia, raising the possibility that sIL-6R is involved in this disease. However, there is no evidence that peripheral sIL-6R induces relevant behavioral disturbances. We showed that single subcutaneous injections of sIL-6R (0-1 mu g), stimulated novelty stress-induced exploratory motor behaviors in male Balb/c mice within 20-40-min of injection. A progressive increase in vertical stereotypies was observed 40-80 min post injection, persisting for the remainder of the test session. Paralleling these stimulant-like effects, sIL-6R pretreatment significantly enhanced stereotypy scores following challenge with GBR 12909. We found that peripherally administered sIL-6R crossed the blood-brain barrier, localizing in brain regions associated with cortico-striatal-thalamo-cortical (CSTC) circuits, which are putative neuroanatomical substrates of disorders associated with repetitive stereotypies. Peripherally administered sIL-6R co-localized with gp130, a transmembrane protein involved in IL-6 trans-signaling, in the nucleus accumbens, caudate-putamen, motor and infralimbic cortices, and thalamic nuclei, but not with gp130 in the ventral tegmental area, substantia nigra, or sensorimotor cortex,. The results suggest that peripheral sIL-6R can act as a neuroimmune messenger, crossing the blood brain barrier (BBB) to selectively target CSTC circuits rich in IL-6 trans-signaling protein, and inducing repetitive stereotypies. As such sIL-6R may represent a novel therapeutic agent for relevant psychiatric disorders. C1 [Patel, Ankur; Siegel, Allan] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol & Neurosci, Newark, NJ 07103 USA. [Zhu, Youhua; Zalcman, Steven S.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Psychiat, Newark, NJ 07103 USA. [Kuzhikandathil, Eldo V.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Physiol & Pharmacol, Newark, NJ 07103 USA. [Banks, William A.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Div Gerontol & Geriatr Med, Dept Med,Geriatr Res Educ & Clin Ctr, Seattle, WA 98195 USA. RP Patel, A (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol & Neurosci, 185 S Orange Ave, Newark, NJ 07103 USA. EM dr.ankur@yahoo.com FU National Institutes of Health [R01 MH74689, T32 5A74309] FX This work was supported by National Institutes of Health Grant R01 MH74689 (SSZ) and National Institutes of Health Training Fellowship T32 5A74309 (AP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 TC 12 Z9 12 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 23 PY 2012 VL 7 IS 7 AR e41623 DI 10.1371/journal.pone.0041623 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 977TM UT WOS:000306687700127 PM 22911828 ER PT J AU Bao, YR Dalrymple, L Chertow, GM Kaysen, GA Johansen, KL AF Bao, Yeran Dalrymple, Lorien Chertow, Glenn M. Kaysen, George A. Johansen, Kirsten L. TI Frailty, Dialysis Initiation, and Mortality in End-Stage Renal Disease SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PHYSICAL-ACTIVITY; HEMODIALYSIS; HARMFUL; ADULTS; OLDER AB Background: In light of the recent trend toward earlier dialysis initiation and its association with mortality among patients with end-stage renal disease, we hypothesized that frailty is associated with higher estimated glomerular filtration rate (eGFR) at dialysis start and may confound the relation between earlier dialysis initiation and mortality. Methods: We examined frailty among participants of the Comprehensive Dialysis Study (CDS), a special study of the US Renal Data System, which enrolled incident patients from September 1, 2005, through June 1, 2007. Patients were followed for vital status through September 30, 2009, and for time to first hospitalization through December 31, 2008. We used multivariate logistic regression to model the association of frailty with eGFR at dialysis start and proportional hazards regression to assess the outcomes of death or hospitalization. Results: Among 1576 CDS participants included, the prevalence of frailty was 73%. In multivariate analysis, higher eGFR at dialysis initiation was associated with higher odds of frailty (odds ratio [OR], 1.44 [95% CI, 1.23-1.68] per 5 mL/min/1.73 m(2); P<.001). Frailty was independently associated with mortality (hazard ratio [HR], 1.57 [95% CI, 1.25-1.97]; P<.001) and time to first hospitalization (HR, 1.26 [95% CI, 1.09-1.45]; P < .001). While higher eGFR at dialysis initiation was associated with mortality (HR, 1.12 [95% CI, 1.02-1.23] per 5 mL/min/1.73 m2; P=.02), the association was no longer statistically significant after frailty was accounted for (HR, 1.08 [95% CI, 0.98-1.19] per 5 mL/min/1.73 m(2); P=.11). Conclusions: Frailty is extremely common among patients starting dialysis in the United States and is associated with higher eGFR at dialysis initiation. Recognition of signs and symptoms of frailty by clinicians may prompt earlier initiation of dialysis and may explain, at least in part, the well-described association between eGFR at dialysis initiation and mortality. 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. [Dalrymple, Lorien; Kaysen, George A.] Univ Calif Davis, Div Nephrol, Davis, CA 95616 USA. [Chertow, Glenn M.] Stanford Univ, Sch Med, Div Nephrol, Palo Alto, CA 94304 USA. [Chertow, Glenn M.; Kaysen, George A.; Johansen, Kirsten L.] 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,A550,Box 1222, San Francisco, CA 94143 USA. EM yeran.bao@ucsf.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [N01-DK-7-0005]; Graduate Medical Education funding through the VA [69734]; National Institutes of Health [T32 2T32DK007418-31]; National Center for Research Resources [UL1 RR024146]; NIDDK [1K24DK085153] FX This work was supported through contracts N01-DK-7-0005 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Dr Bao's effort was supported by grant No. 69734 from the Graduate Medical Education funding through the VA and by T32 2T32DK007418-31 from the National Institutes of Health. Dr Dalrymple's effort was supported by grant No. UL1 RR024146 from the National Center for Research Resources. A portion of Dr Johansen's effort was supported by 1K24DK085153 from the NIDDK. NR 21 TC 81 Z9 81 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 23 PY 2012 VL 172 IS 14 BP 1071 EP 1077 DI 10.1001/archinternmed.2012.3020 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 976JY UT WOS:000306582000005 PM 22733312 ER PT J AU Perissinotto, CM Cenzer, IS Covinsky, KE AF Perissinotto, Carla M. Cenzer, Irena Stijacic Covinsky, Kenneth E. TI Loneliness in Older Persons A Predictor of Functional Decline and Death SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DEPRESSIVE SYMPTOMS; SOCIAL SUPPORT; ADULTS; HEALTH; PEOPLE; ASSOCIATION; IMPAIRMENT; MORTALITY; LIFE AB Background: Loneliness is a common source of distress, suffering, and impaired quality of life in older persons. We examined the relationship between loneliness, functional decline, and death in adults older than 60 years in the United States. Methods: This is a longitudinal cohort study of 1604 participants in the psychosocial module of the Health and Retirement Study, a nationally representative study of older persons. Baseline assessment was in 2002 and follow-up assessments occurred every 2 years until 2008. Subjects were asked if they (1) feel left out, (2) feel isolated, or (3) lack companionship. Subjects were categorized as not lonely if they responded hardly ever to all 3 questions and lonely if they responded some of the time or often to any of the 3 questions. The primary outcomes were time to death over 6 years and functional decline over 6 years on the following 4 measures: difficulty on an increased number of activities of daily living (ADL), difficulty in an increased number of upper extremity tasks, decline in mobility, or increased difficulty in stair climbing. Multivariate analyses adjusted for demographic variables, socioeconomic status, living situation, depression, and various medical conditions. Results: The mean age of subjects was 71 years. Fifty-nine percent were women; 81% were white, 11%, black, and 6%, Hispanic; and 18% lived alone. Among the elderly participants, 43% reported feeling lonely. Loneliness was associated with all outcome measures. Lonely subjects were more likely to experience decline in ADL (24.8% vs 12.5%; adjusted risk ratio [RR], 1.59; 95% CI, 1.23-2.07); develop difficulties with upper extremity tasks (41.5% vs 28.3%; adjusted RR, 1.28; 95% CI, 1.08-1.52); experience decline in mobility (38.1% vs 29.4%; adjusted RR, 1.18; 95% CI, 0.99-1.41); or experience difficulty in climbing (40.8% vs 27.9%; adjusted RR, 1.31; 95% CI, 1.10-1.57). Loneliness was associated with an increased risk of death (22.8% vs 14.2%; adjusted HR, 1.45; 95% CI, 1.11-1.88). Conclusion: Among participants who were older than 60 years, loneliness was a predictor of functional decline and death. C1 [Perissinotto, Carla M.; Cenzer, Irena Stijacic; Covinsky, Kenneth E.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94143 USA. [Covinsky, Kenneth E.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Perissinotto, CM (reprint author), Univ Calif San Francisco, Dept Med, Div Geriatr, 3333 Calif St,Ste 380, San Francisco, CA 94143 USA. EM carla.perissinotto@ucsf.edu FU National Institute on Aging [5R01AG028481-03, 1K24AG029812-01A1]; Geriatric Academic Career Award, Health Resources and Services Administration [K01HP20489] FX This project was supported by grant 5R01AG028481-03 (Depressive Symptoms, Aging, Disability and Health Outcomes) from the National Institute on Aging. Dr Perissinotto is also supported in part by the Geriatric Academic Career Award, Health Resources and Services Administration (K01HP20489). Dr Covinsky is supported in part by grant 1K24AG029812-01A1 (Mid-career Mentoring Award for Patient-Oriented Research in Aging) from the National Institute on Aging. NR 27 TC 129 Z9 135 U1 1 U2 63 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 23 PY 2012 VL 172 IS 14 BP 1078 EP 1083 DI 10.1001/archinternined.2012.1993 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 976JY UT WOS:000306582000006 PM 22710744 ER PT J AU Caverly, TJ Al-Khatib, SM Kutner, JS Masoudi, FA Matlock, DD AF Caverly, Tanner J. Al-Khatib, Sana M. Kutner, Jean S. Masoudi, Frederick A. Matlock, Daniel D. TI LESS IS MORE Patient Preference in the Decision to Place Implantable Cardioverter-Defibrillators SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter ID HEART-FAILURE; CONSEQUENCES C1 [Matlock, Daniel D.] Univ Colorado, Div Gen Internal Med, Dept Med, Sch Med,Acad Off 1, Aurora, CO 80045 USA. [Caverly, Tanner J.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Al-Khatib, Sana M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Duke Cardiovasc Ctr Educ & Res Therapeut, Durham, NC USA. [Al-Khatib, Sana M.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA. [Masoudi, Frederick A.; Matlock, Daniel D.] Colorado Cardiovasc Outcomes Res Inst, Denver, CO USA. [Masoudi, Frederick A.; Matlock, Daniel D.] Kaiser Permanente, Colorado Inst Hlth Res, Denver, CO USA. RP Matlock, DD (reprint author), Univ Colorado, Div Gen Internal Med, Dept Med, Sch Med,Acad Off 1, 12631 E 17th Ave,Campus Box B-180, Aurora, CO 80045 USA. EM Daniel.Matlock@ucdenver.edu FU AHRQ HHS [U18 HS016964, U18HS016964]; NCRR NIH HHS [UL1 RR025780, UL1RR025780]; NIA NIH HHS [K23 AG040696, K23 AG040696-01]; PHS HHS [T32HP1006] NR 8 TC 9 Z9 9 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 23 PY 2012 VL 172 IS 14 BP 1104 EP 1105 DI 10.1001/archinternmed.2012.2177 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 976JY UT WOS:000306582000013 PM 22688654 ER PT J AU Grady, D Redberg, RF AF Grady, Deborah Redberg, Rita F. TI A Different Perspective Regarding Prostate-Specific Antigen Testing In reply SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter C1 [Grady, Deborah; Redberg, Rita F.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94115 USA. [Grady, Deborah] San Francisco VA Med Ctr, San Francisco, CA USA. RP Grady, D (reprint author), Univ Calif San Francisco, Dept Med, 1635 Divisadero St,Ste 600, San Francisco, CA 94115 USA. NR 1 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 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 23 PY 2012 VL 172 IS 14 BP 1111 EP 1111 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 976JY UT WOS:000306582000019 PM 22825065 ER PT J AU Durant, RW Parmar, G Shuaib, F Le, A Brown, TM Roth, DL Hovater, M Halanych, JH Shikany, JM Prineas, RJ Samdarshi, TJ Safford, MM AF Durant, Raegan W. Parmar, Gaurav Shuaib, Faisal Le, Anh Brown, Todd M. Roth, David L. Hovater, Martha Halanych, Jewell H. Shikany, James M. Prineas, Ronald J. Samdarshi, Tandaw J. Safford, Monika M. TI Awareness and management of chronic disease, insurance status, and health professional shortage areas in the REasons for Geographic And Racial Differences in Stroke (REGARDS): a cross-sectional study SO BMC HEALTH SERVICES RESEARCH LA English DT Article ID NUTRITION EXAMINATION SURVEY; PRIMARY-CARE; CARDIOVASCULAR-DISEASE; NATIONAL-HEALTH; US ADULTS; MEDICARE BENEFICIARIES; MYOCARDIAL-INFARCTION; RISK-FACTORS; HYPERTENSION; PREVALENCE AB Background: Limited financial and geographic access to primary care can adversely influence chronic disease outcomes. We examined variation in awareness, treatment, and control of hypertension, diabetes, and hyperlipidemia according to both geographic and financial access to care. Methods: We analyzed data on 17,458 participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study with either hypertension, hyperlipidemia, or diabetes and living in either complete Health Professional Shortage Area (HPSA) counties or non-HPSA counties in the U. S. All analyses were stratified by insurance status and adjusted for sociodemographics and health behaviors. Results: 2,261 residents lived in HPSA counties and 15,197 in non-HPSA counties. Among the uninsured, HPSA residents had higher awareness of both hypertension (adjusted OR 2.30, 95% CI 1.08, 4.89) and hyperlipidemia (adjusted OR 1.50, 95% CI 1.01, 2.22) compared to non-HPSA residents. Also among the uninsured, HPSA residents with hypertension had lower blood pressure control (adjusted OR 0.45, 95% CI 0.29, 0.71) compared with non-HPSA residents. Similar differences in awareness and control according to HPSA residence were absent among the insured. Conclusions: Despite similar or higher awareness of some chronic diseases, uninsured HPSA residents may achieve control of hypertension at lower rates compared to uninsured non-HPSA residents. Federal allocations in HPSAs should target improved quality of care as well as increasing the number of available physicians. C1 [Durant, Raegan W.; Parmar, Gaurav; Shuaib, Faisal; Brown, Todd M.; Halanych, Jewell H.; Shikany, James M.; Safford, Monika M.] Univ Alabama Birmingham, Med Sch Birmingham, Birmingham, AL 35294 USA. [Durant, Raegan W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. [Le, Anh; Roth, David L.; Hovater, Martha] Univ Alabama Birmingham, Birmingham Sch Publ Hlth, Birmingham, AL 35294 USA. [Prineas, Ronald J.] Wake Forest Univ, Sch Med, Winston Salem, NC 27157 USA. [Samdarshi, Tandaw J.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. RP Durant, RW (reprint author), Univ Alabama Birmingham, Med Sch Birmingham, 1717 11th Ave S, Birmingham, AL 35294 USA. EM rdurant@dopm.uab.edu FU National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Service [U01 NS041588]; National Heart, Lung and Blood Institute [R01 HL80477, R01 HL080477-02 S1] FX This research project is supported by a cooperative agreement U01 NS041588 from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Service. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke or the National Institutes of Health. Representatives of the funding agency have been involved in the review of the manuscript but not directly involved in the collection, management, analysis or interpretation of the data. The authors thank the other investigators, the staff, and the participants of the REGARDS study for their valuable contributions. A full list of participating REGARDS investigators and institutions can be found at http://www.regardsstudy.org. Additional funding was provided by an investigator-initiated grant R01 HL80477 and a supplemental grant R01 HL080477-02 S1 from the National Heart, Lung and Blood Institute. NR 47 TC 5 Z9 5 U1 3 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD JUL 20 PY 2012 VL 12 AR 208 DI 10.1186/1472-6963-12-208 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 088DJ UT WOS:000314813700001 PM 22818296 ER PT J AU Srivastava, MK Zhu, L Harris-White, M Kar, U Huang, M Johnson, MF Lee, JM Elashoff, D Strieter, R Dubinett, S Sharma, S AF Srivastava, Minu K. Zhu, Li Harris-White, Marni Kar, Upendra Huang, Min Johnson, Ming F. Lee, Jay M. Elashoff, David Strieter, Robert Dubinett, Steven Sharma, Sherven TI Myeloid Suppressor Cell Depletion Augments Antitumor Activity in Lung Cancer SO PLOS ONE LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; MHC CLASS-I; BONE-MARROW; TUMOR-ANTIGENS; DENDRITIC CELLS; NK CELLS; TOLERANCE; INDUCTION; MECHANISM; ANERGY AB Background: Myeloid derived suppressor cells (MDSC) are important regulators of immune responses. We evaluated the mechanistic role of MDSC depletion on antigen presenting cell (APC), NK, T cell activities and therapeutic vaccination responses in murine models of lung cancer. Principal Findings: Individual antibody mediated depletion of MDSC (anti-Gr1 or anti-Ly6G) enhanced the antitumor activity against lung cancer. In comparison to controls, MDSC depletion enhanced the APC activity and increased the frequency and activity of the NK and T cell effectors in the tumor. Compared to controls, the anti-Gr1 or anti-Ly6G treatment led to increased: (i) CD8 T cells, (ii) NK cells, (iii) CD8 T or NK intracytoplasmic expression of IFN gamma, perforin and granzyme (iv) CD3 T cells expressing the activation marker CD107a and CXCR3, (v) reduced CD8 T cell IL-10 production in the tumors (vi) reduced tumor angiogenic (VEGF, CXCL2, CXCL5, and Angiopoietin1& 2) but enhanced anti-angiogenic (CXCL9 and CXCL10) expression and (vii) reduced tumor staining of endothelial marker Meca 32. Immunocytochemistry of tumor sections showed reduced Gr1 expressing cells with increased CD3 T cell infiltrates in the anti-Gr1 or anti-Ly6G groups. MDSC depletion led to a marked inhibition in tumor growth, enhanced tumor cell apoptosis and reduced migration of the tumors from the primary site to the lung compared to controls. Therapeutic vaccination responses were enhanced in vivo following MDSC depletion with 50% of treated mice completely eradicating established tumors. Treated mice that rejected their primary tumors acquired immunological memory against a secondary tumor challenge. The remaining 50% of mice in this group had 20 fold reductions in tumor burden compared to controls. Significance: Our data demonstrate that targeting MDSC can improve antitumor immune responses suggesting a broad applicability of combined immune based approaches against cancer. This multifaceted approach may prove useful against tumors where MDSC play a role in tumor immune evasion. C1 [Srivastava, Minu K.; Zhu, Li; Lee, Jay M.; Elashoff, David; Dubinett, Steven; Sharma, Sherven] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Lung Canc Res Program, Dept Med, Los Angeles, CA 90095 USA. [Lee, Jay M.; Elashoff, David; Dubinett, Steven; Sharma, Sherven] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Kar, Upendra] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. [Srivastava, Minu K.; Zhu, Li; Harris-White, Marni; Huang, Min; Johnson, Ming F.; Dubinett, Steven; Sharma, Sherven] Vet Affairs Greater Los Angeles Healthcare Syst, Mol Gene Med Lab, Los Angeles, CA USA. [Strieter, Robert] Univ Virginia, Dept Med, Charlottesville, VA USA. RP Srivastava, MK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, UCLA Lung Canc Res Program, Dept Med, Los Angeles, CA 90095 USA. EM ssharma@mednet.ucla.edu FU University of California Los Angeles Lung Cancer Program; Department of Veterans Affairs Medical Research Funds; National Institutes of Health (NIH) [RO1 CA95686, RO1 CA126944, P50 CA90388]; National Center for Advancing Translational Sciences [UL1TR000124]; Tobacco Related Disease Program Award Program of University of California [15RT-0207, 20FT0082] FX This work was supported by the University of California Los Angeles Lung Cancer Program, Department of Veterans Affairs Medical Research Funds, National Institutes of Health (NIH) Grants (RO1 CA95686, RO1 CA126944 and P50 CA90388), National Center for Advancing Translational Sciences, Grant UL1TR000124, and Tobacco Related Disease Program Award Program of University of California (15RT-0207 and 20FT0082). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 60 Z9 60 U1 2 U2 16 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 JUL 16 PY 2012 VL 7 IS 7 AR e40677 DI 10.1371/journal.pone.0040677 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 974VS UT WOS:000306466100054 PM 22815789 ER PT J AU Yates-Binder, CC Rodgers, M Jaynes, J Wells, A Bodnar, RJ Turner, T AF Yates-Binder, Cecelia C. Rodgers, Margaret Jaynes, Jesse Wells, Alan Bodnar, Richard J. Turner, Timothy TI An IP-10 (CXCL10)-Derived Peptide Inhibits Angiogenesis SO PLOS ONE LA English DT Article ID CHEMOKINE RECEPTOR CXCR3; PROTEIN-KINASE-A; INDUCIBLE PROTEIN-9; CELL MOTILITY; GROWTH-FACTOR; MICE LACKING; WOUND REPAIR; CALPAIN; KERATINOCYTES; ACTIVATION AB Angiogenesis plays a critical role in processes such as organ development, wound healing, and tumor growth. It requires well-orchestrated integration of soluble and matrix factors and timely recognition of such signals to regulate this process. Previous work has shown that newly forming vessels express the chemokine receptor CXC receptor 3 (CXCR3) and, activation by its ligand IP-10 (CXCL10), both inhibits development of new vasculature and causes regression of newly formed vessels. To identify and develop new therapeutic agents to limit or reverse pathological angiogenesis, we identified a 21 amino acid fragment of IP-10, spanning the a-helical domain residues 77-98, that mimic the actions of the whole IP-10 molecule on endothelial cells. Treatment of the endothelial cells with the 22 amino acid fragment referred to as IP-10p significantly inhibited VEGF-induced endothelial motility and tube formation in vitro, properties critical for angiogenesis. Using a Matrigel plug assay in vivo, we demonstrate that IP-10p both prevented vessel formation and induced involution of nascent vessels. CXCR3 neutralizing antibody was able to block the inhibitory effects of the IP-10p, demonstrating specificity of the peptide. Inhibition of endothelial function by IP-10p was similar to that described for IP-10, secondary to CXCR3-mediated increase in cAMP production, activation of PKA inhibiting cell migration, and inhibition of VEGF-mediated m-calpain activation. IP-10p provides a novel therapeutic agent that inhibits endothelial cell function thus, allowing for the modulation of angiogenesis. C1 [Yates-Binder, Cecelia C.; Jaynes, Jesse; Wells, Alan; Turner, Timothy] Tuskegee Univ, Ctr Canc Res, Tuskegee, AL 36088 USA. [Yates-Binder, Cecelia C.; Wells, Alan; Bodnar, Richard J.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. [Yates-Binder, Cecelia C.; Rodgers, Margaret; Wells, Alan; Bodnar, Richard J.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Yates-Binder, CC (reprint author), Tuskegee Univ, Ctr Canc Res, Tuskegee, AL 36088 USA. EM cey4@pitt.edu; Rjb8@pitt.edu OI Wells, Alan/0000-0002-1637-8150 FU National Center on Minority Health and Health Disparities, National Institute of General Medical Science of the National Institutes of Health [R01GM063569] FX These studies were supported by grants from the National Center on Minority Health and Health Disparities, National Institute of General Medical Science of the National Institutes of Health (R01GM063569) and in kind support from the Pittsburgh VA Medical Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 16 Z9 17 U1 0 U2 3 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 JUL 16 PY 2012 VL 7 IS 7 AR e40812 DI 10.1371/journal.pone.0040812 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 974VS UT WOS:000306466100073 PM 22815829 ER PT J AU Agassandian, M Chen, BB Pulijala, R Kaercher, L Glasser, JR Mallampalli, RK AF Agassandian, Marianna Chen, Bill B. Pulijala, Roopa Kaercher, Leah Glasser, Jennifer R. Mallampalli, Rama K. TI Calcium-calmodulin kinase I cooperatively regulates nucleocytoplasmic shuttling of CCT alpha by accessing a nuclear export signal SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CTP-PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE; PHOSPHATIDYLCHOLINE SYNTHESIS; TRANSCRIPTION FACTOR; DEPENDENT PATHWAYS; PROTEIN; ACTIVATION; CRM1; LOCALIZATION; PURIFICATION; SPECIFICITY AB We identified a new calmodulin kinase I (CaMKI) substrate, cytidyltransferase (CCT alpha), a crucial enzyme required for maintenance of cell membranes. CCT alpha becomes activated with translocation from the cytoplasm to the nuclear membrane, resulting in increased membrane phospholipids. Calcium-activated CCT alpha nuclear import is mediated by binding of its C-terminus to 14-3-3 zeta, a regulator of nuclear trafficking. Here CaMK1 phosphorylates residues within this C-terminus that signals association of CCT alpha with 14-3-3 zeta to initiate calcium-induced nuclear entry. CaMKI docks within the CCT alpha membrane-binding domain (residues 290-299), a sequence that displays similarities to a canonical nuclear export signal (NES) that also binds CRM1/exportin 1. Expression of a CFP-CCT alpha mutant lacking residues 290-299 in cells results in cytosolically retained enzyme. CRM1/exportin 1 was required for CCT alpha nuclear export, and its overexpression in cells was partially sufficient to trigger CCT alpha nuclear export despite calcium stimulation. An isolated CFP-290-299 peptide remained in the nucleus in the presence of leptomycin B but was able to target to the cytoplasm with farnesol. Thus CaMKI vies with CRM1/exportin 1 for access to a NES, and assembly of a CaMKI-14-3-3.-CCT alpha complex is a key effector mechanism that drives nuclear CCTa translocation. C1 [Agassandian, Marianna; Chen, Bill B.; Pulijala, Roopa; Kaercher, Leah; Glasser, Jennifer R.; Mallampalli, Rama K.] Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. RP Mallampalli, RK (reprint author), Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, 930 Scaife Hall, Pittsburgh, PA 15213 USA. EM mallampallirk@upmc.edu FU Merit Review Award from the U.S. Department of Veterans Affairs and National Institutes of Health [HL096376, HL097376, HL098174]; U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development FX We thank Jeffrey Brodsky for critical review of the manuscript. This material is based on work supported, in part, by the U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. This work was supported by a Merit Review Award from the U.S. Department of Veterans Affairs and National Institutes of Health RO1 Grants HL096376, HL097376, and HL098174 (to R.K.M.). The contents presented do not represent the views of the Department of Veterans Affairs of the United States Government. NR 45 TC 7 Z9 7 U1 1 U2 5 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUL 15 PY 2012 VL 23 IS 14 BP 2755 EP 2769 DI 10.1091/mbc.E11-10-0863 PG 15 WC Cell Biology SC Cell Biology GA 052SB UT WOS:000312217600014 PM 22621903 ER PT J AU Feng, S Shao, LJ Yu, WD Gavine, P Ittmann, M AF Feng, Shu Shao, Longjiang Yu, Wendong Gavine, Paul Ittmann, Michael TI Targeting Fibroblast Growth Factor Receptor Signaling Inhibits Prostate Cancer Progression SO CLINICAL CANCER RESEARCH LA English DT Article ID INTRAEPITHELIAL NEOPLASIA; INCREASED EXPRESSION; POTENTIAL TARGET; REACTIVE STROMA; TYROSINE KINASE; DOWN-REGULATION; PROLIFERATION; HYPERPLASIA; ACTIVATION; CARCINOMA AB Purpose: Extensive correlative studies in human prostate cancer as well as studies in vitro and in mouse models indicate that fibroblast growth factor receptor (FGFR) signaling plays an important role in prostate cancer progression. In this study, we used a probe compound for an FGFR inhibitor, which potently inhibits FGFR-1-3 and significantly inhibits FGFR-4. The purpose of this study is to determine whether targeting FGFR signaling from all four FGFRs will have in vitro activities consistent with inhibition of tumor progression and will inhibit tumor progression in vivo. Experimental Design: Effects of AZ8010 on FGFR signaling and invasion were analyzed using immortalized normal prostate epithelial (PNT1a) cells and PNT1a overexpressing FGFR-1 or FGFR-4. The effect of AZ8010 on invasion and proliferation in vitro was also evaluated in prostate cancer cell lines. Finally, the impact of AZ8010 on tumor progression in vivo was evaluated using a VCaP xenograft model. Results: AZ8010 completely inhibits FGFR-1 and significantly inhibits FGFR-4 signaling at 100 nmol/L, which is an achievable in vivo concentration. This results in marked inhibition of extracellular signal-regulated kinase (ERK) phosphorylation and invasion in PNT1a cells expressing FGFR-1 and FGFR-4 and all prostate cancer cell lines tested. Treatment in vivo completely inhibited VCaP tumor growth and significantly inhibited angiogenesis and proliferation and increased cell death in treated tumors. This was associated with marked inhibition of ERK phosphorylation in treated tumors. Conclusions: Targeting FGFR signaling is a promising new approach to treating aggressive prostate cancer. Clin Cancer Res; 18(14); 3880-8. (C)2012 AACR. C1 [Feng, Shu; Shao, Longjiang; Yu, Wendong; Ittmann, Michael] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Feng, Shu; Shao, Longjiang; Yu, Wendong; Ittmann, Michael] Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. [Gavine, Paul] Astra Zeneca Res & Dev, Innovat Ctr China, Shanghai, Peoples R China. RP Ittmann, M (reprint author), Baylor Coll Med, Dept Pathol & Immunol, 1 Baylor Plaza, Houston, TX 77030 USA. EM mittmann@bcm.tmc.edu FU Department of Veterans Affairs; Prostate Cancer Foundation; NIH [U01CA141497] FX This work was supported by the Department of Veterans Affairs Merit Review program (to M. Ittmann), the Prostate Cancer Foundation (to M. Ittmann), and the NIH U01 Mouse Models of Human Cancer (U01CA141497; to M. Ittmann), and by the use of the facilities of the Michael E. DeBakey VAMC. NR 40 TC 23 Z9 23 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 15 PY 2012 VL 18 IS 14 BP 3880 EP 3888 DI 10.1158/1078-0432.CCR-11-3214 PG 9 WC Oncology SC Oncology GA 988PN UT WOS:000307503100018 PM 22573348 ER PT J AU Liu, QL Rehman, H Krishnasamy, Y Ramshesh, VK Theruvath, TP Chavin, KD Schnellmann, RG Lemasters, JJ Zhong, Z AF Liu, Qinlong Rehman, Hasibur Krishnasamy, Yasodha Ramshesh, Venkat K. Theruvath, Tom P. Chavin, Kenneth D. Schnellmann, Rick G. Lemasters, John J. Zhong, Zhi TI Role of inducible nitric oxide synthase in mitochondrial depolarization and graft injury after transplantation of fatty livers SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE ALCOHOL; Inos; Liver; Transplantation; Mitochondrial; Depolarization; Steatosis ID N-TERMINAL KINASE; PERMEABILITY TRANSITION; REPERFUSION INJURY; HEPATIC STEATOSIS; MOUSE-LIVER; ISCHEMIA/REPERFUSION INJURY; STORAGE/REPERFUSION INJURY; UNCOUPLING PROTEIN-2; OXIDATIVE DAMAGE; RAT HEPATOCYTES AB This study investigated the role of inducible nitric oxide synthase (iNOS) in failure of ethanol-induced fatty liver grafts. Rat livers were explanted 20 h after gavaging with ethanol (5 g/kg) and storing in UW solution for 24 h before implantation. Hepatic oil red O staining-positive areas increased from similar to 2 to similar to 33% after ethanol treatment, indicating steatosis. iNOS expression increased similar to 8-fold after transplantation of lean grafts (LG) and 25-fold in fatty grafts (FG). Alanine aminotransferase release, total bilirubin, hepatic necrosis, TUNEL-positive cells, and cleaved caspase-3 were higher in FG than LG. A specific iNOS inhibitor 1400W (5 mu M in the cold-storage solution) blunted these alterations by > 42% and increased survival of fatty grafts from 25 to 88%. Serum nitrite/nitrate and hepatic nitrotyrosine adducts increased to a greater extent after transplantation of FG than LG, indicating reactive nitrogen species (RNS) overproduction. Phospho-c-Jun and phospho-c-Jun N-terminal kinase-1/2 (JNK1/2) were higher in FG than in LG, indicating more JNK activation in fatty grafts. RNS formation and JNK activation were blunted by 1400W. Mitochondrial polarization and cell death were visualized by intravital multiphoton microscopy of rhodamine 123 and propidium iodide, respectively. After implantation, viable cells with depolarized mitochondria were 3-fold higher in FG than in LG and 1400W decreased mitochondrial depolarization in FG to the levels of LG. Taken together, iNOS is upregulated after transplantation of FG, leading to excessive RNS formation, JNK activation, mitochondrial dysfunction, and severe graft injury. The iNOS inhibitor 1400W could be an effective therapy for primary nonfunction of fatty liver grafts. (C) 2012 Elsevier Inc. All rights reserved. C1 [Liu, Qinlong; Rehman, Hasibur; Krishnasamy, Yasodha; Theruvath, Tom P.; Schnellmann, Rick G.; Lemasters, John J.; Zhong, Zhi] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA. [Liu, Qinlong] Dalian Med Univ, Affiliated Hosp 2, Dept Gen Surg, Dalian, Peoples R China. [Ramshesh, Venkat K.; Schnellmann, Rick G.; Lemasters, John J.; Zhong, Zhi] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Chavin, Kenneth D.] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson VA Med Ctr, Charleston, SC 29403 USA. [Lemasters, John J.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. RP Zhong, Z (reprint author), Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM zhong@musc.edu RI Ji, Haofeng/G-6206-2012 FU National Institutes of Health [DK70844, DK70844S1, AA017756, DK84632, DK37034, 1P30 CA138313] FX This study was supported, in part, by Grants DK70844, DK70844S1, AA017756, DK84632, and DK37034 from the National Institutes of Health. We thank the Cell & Molecular Imaging Core of the Hollings Cancer Center at the Medical University of South Carolina supported by NIH Grant 1P30 CA138313 for providing instrumentation and assistance for confocal/multiphoton microscopy. NR 76 TC 10 Z9 10 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JUL 15 PY 2012 VL 53 IS 2 BP 250 EP 259 DI 10.1016/j.freeradbiomed.2012.05.012 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 977PS UT WOS:000306677500008 PM 22609250 ER PT J AU Smith, MA Covington, MD Schnellmann, RG AF Smith, Matthew A. Covington, Marisa D. Schnellmann, Rick G. TI Loss of calpain 10 causes mitochondrial dysfunction during chronic hyperglycemia SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE Calpain 10; Kidney; Hyperglycemia; siRNA; Mitochondria; Dysfunction ID TYPE-2 DIABETES-MELLITUS; OXIDATIVE STRESS; LON PROTEASE; BETA-CELLS; EXPRESSION; MECHANISM; PARKIN; KIDNEY; INJURY; RATS AB We showed that renal calpain 10, a mitochondrial and cytosolic Ca2+-regulated cysteine protease, is specifically decreased in kidneys of diabetic rats and mice, and is associated with diabetic nephropathy. The goals of this study were to examine renal calpain 10 and mitochondrial dysfunction in streptozotocin-induced hyperglycemic rats and determine the effects of siRNA-mediated knock down of renal calpain 10 on mitochondrial function. Four weeks after streptozotocin injection, calpain 10 protein and mRNA were decreased and calpain 10 substrates accumulated. We detected increased state 2 respiration in isolated renal mitochondria and increased markers of mitochondrial fission and mitophagy. All changes were prevented by daily insulin injection. Compared to scrambled siRNA, calpain 10 siRNA resulted in a marked decrease in renal calpain 10 at 2,5 and 7 days. In concert with the loss of renal calpain 10, calpain 10 substrates accumulated, mitochondrial fusion decreased, mitochondrial fission and mitophagy increased. In summary, insulin-sensitive hyperglycemia induced loss of renal calpain 10 is correlated with renal mitochondrial dysfunction, fission and mitophagy, and specific depletion of renal calpain 10 produces similar mitochondria! defects. These results provide evidence that diabetes-induced renal mitochondrial dysfunction and renal injury may directly result from the loss of renal calpain 10. Published by Elsevier Inc. C1 [Smith, Matthew A.; Covington, Marisa D.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Ctr Cell Death Injury & Regenerat, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Ctr Cell Death Injury & Regenerat, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM schnell@musc.edu FU NIH [GM 084147, C06 RR-015455]; NIEHS [ES-012239]; NIH/NIEHS [T32ES012878HS] FX This study was supported by NIH Grant [GM 084147], the NIEHS Grant [ES-012239], the NIH/NIEHS Training Program in Environmental Stress Signaling [T32ES012878HS Training Program in Environmental Stress Sig and Development Program of the Department of Veterans Affairs. Animal facilities were funded by NIH grant [C06 RR-015455]. NR 42 TC 7 Z9 9 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 EI 1096-0384 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL 15 PY 2012 VL 523 IS 2 BP 161 EP 168 DI 10.1016/j.abb.2012.04.020 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 959HR UT WOS:000305304000004 PM 22568896 ER PT J AU Watkins, GR Wang, N Mazalouskas, MD Gomez, RJ Guthrie, CR Kraemer, BC Schweiger, S Spiller, BW Wadzinski, BE AF Watkins, Guy R. Wang, Ning Mazalouskas, Matthew D. Gomez, Rey J. Guthrie, Chris R. Kraemer, Brian C. Schweiger, Susann Spiller, Benjamin W. Wadzinski, Brian E. TI Monoubiquitination Promotes Calpain Cleavage of the Protein Phosphatase 2A (PP2A) Regulatory Subunit alpha 4, Altering PP2A Stability and Microtubule-associated Protein Phosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID E3 UBIQUITIN LIGASE; OPITZ-SYNDROME; ALZHEIMERS-DISEASE; BINDING; TAU; ENZYME; MID1; DEGRADATION; PROTEOLYSIS; RESOLUTION AB Multiple neurodegenerative disorders are linked to aberrant phosphorylation of microtubule-associated proteins (MAPs). Protein phosphatase 2A (PP2A) is the major MAP phosphatase; however, little is known about its regulation at microtubules. alpha 4 binds the PP2A catalytic subunit (PP2Ac) and the microtubule-associated E3 ubiquitin ligase MID1, and through unknown mechanisms can both reduce and enhance PP2Ac stability. We show MID1-dependent monoubiquitination of alpha 4 triggers calpain-mediated cleavage and switches alpha 4's activity from protective to destructive, resulting in increased Tau phosphorylation. This regulatory mechanism appears important in MAP-dependent pathologies as levels of cleaved alpha 4 are decreased in Opitz syndrome and increased in Alzheimer disease, disorders characterized by MAP hypophosphorylation and hyperphosphorylation, respectively. These findings indicate that regulated inter-domain cleavage controls the dual functions of alpha 4, and dysregulation of alpha 4 cleavage may contribute to Opitz syndrome and Alzheimer disease. C1 [Watkins, Guy R.; Wang, Ning; Mazalouskas, Matthew D.; Gomez, Rey J.; Spiller, Benjamin W.; Wadzinski, Brian E.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. [Guthrie, Chris R.; Kraemer, Brian C.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Kraemer, Brian C.] Univ Washington, Div Gerontol & Geriatr Med, Dept Med, Seattle, WA 98104 USA. [Schweiger, Susann] Univ Dundee, Sch Med, Med Res Inst, Div Neurosci, Dundee DD1 SY9, Scotland. RP Wadzinski, BE (reprint author), Vanderbilt Univ, Med Ctr, Dept Pharmacol, 424 RRB, Nashville, TN 37232 USA. EM brian.wadzinski@vanderbilt.edu FU National Institutes of Health [DK070787, GM051366, NS064131, T32 GM07628]; American Cancer Society [IRG-58-009-49]; Department of Veterans Affairs Merit Review Grant [114891]; Ataxia UK; Tenovus Scotland FX This work was supported by National Institutes of Health Grants DK070787 and GM051366 (to B. E. W.), NS064131 (to B. C. K.), and T32 GM07628 (to G. R. W.); American Cancer Society IRG-58-009-49 (to B. W. S.); Department of Veterans Affairs Merit Review Grant 114891 (to B. C. K.); and Ataxia UK and Tenovus Scotland (to S. S.). NR 36 TC 17 Z9 22 U1 0 U2 5 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 JUL 13 PY 2012 VL 287 IS 29 BP 24207 EP 24215 DI 10.1074/jbc.M112.368613 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 977IQ UT WOS:000306651100015 PM 22613722 ER PT J AU Bensing, BA Yen, YT Seepersaud, R Sullam, PM AF Bensing, Barbara A. Yen, Yihfen T. Seepersaud, Ravin Sullam, Paul M. TI A Specific Interaction between SecA2 and a Region of the Preprotein Adjacent to the Signal Peptide Occurs during Transport via the Accessory Sec System SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BINDING PROTEIN-GSPB; STREPTOCOCCUS-PNEUMONIAE ADHESIN; SURFACE GLYCOPROTEIN GSPB; STAPHYLOCOCCUS-AUREUS; HUMAN PLATELETS; ATPASE SECA; GORDONII; EXPORT; GLYCOSYLATION; TRANSLOCATION AB The accessory Sec systems of streptococci and staphylococci mediate the transport of a family of large, serine-rich glycoproteins to the bacterial cell surface. These systems are comprised of SecA2, SecY2, and three core accessory Sec proteins (Asp1-3). In Streptococcus gordonii, transport of the serine-rich glycoprotein GspB requires both a unique 90-residue N-terminal signal peptide and an adjacent 24-residue segment (the AST domain). We used in vivo site-specific photo-cross-linking to identify proteins that interact with the AST domain during transport. To facilitate this analysis, the entire accessory Sec system of S. gordonii was expressed in Escherichia coli. The determinants of GspB trafficking to the accessory Sec system in E. coli matched those in S. gordonii, establishing the validity of this approach. When the photo-cross-linker was placed within the AST domain, the preprotein was found to cross-link to SecA2. Importantly, no cross-linking to SecA was detected. Cross-linking of the N-terminal end of the AST domain to SecA2 occurred regardless of whether Asp1-3 were present. However, cross-linking to the C-terminal end was dependent on the Asps. The combined results indicate that full engagement of the AST domain by SecA2 is modulated by one or more of the Asps, and suggest that this process is important for initiating transport. C1 San Francisco VA Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94121 USA. RP Sullam, PM (reprint author), VA Med Ctr, Div Infect Dis, 111W,4150 Clement St, San Francisco, CA 94121 USA. EM paul.sullam@ucsf.edu FU National Institutes of Health [RO1AI41513]; Dept. of Veterans Affairs; VA Merit Review program; Northern California Institute for Research and Education; American Heart Association FX This work was supported, in whole or in part, by the National Institutes of Health Grant RO1AI41513 (to P. S.), the Dept. of Veterans Affairs, and the VA Merit Review program, the Northern California Institute for Research and Education, and by a Postdoctoral Fellowship Award from the American Heart Association (to Y. Y.). NR 42 TC 7 Z9 7 U1 0 U2 3 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 JUL 13 PY 2012 VL 287 IS 29 BP 24438 EP 24447 DI 10.1074/jbc.M112.378059 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 977IQ UT WOS:000306651100037 PM 22654116 ER PT J AU Ramos, TN Darley, MM Weckbach, S Stahel, PF Tomlinson, S Barnum, SR AF Ramos, Theresa N. Darley, Meghan M. Weckbach, Sebastian Stahel, Philip F. Tomlinson, Stephen Barnum, Scott R. TI The C5 Convertase Is Not Required for Activation of the Terminal Complement Pathway in Murine Experimental Cerebral Malaria SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EXPERIMENTAL SIMIAN MALARIA; C6 DEFICIENCY; TARGETED EXPRESSION; PLASMINOGEN-BINDING; FACTOR-B; MICE; COAGULATION; COMPONENT; C3; SUSCEPTIBILITY AB Cerebral malaria (CM) is the most severe manifestation of clinical malaria syndromes and has a high fatality rate especially in the developing world. Recent studies demonstrated that C5(-/-) mice are resistant to experimental CM (ECM) and that protection was due to the inability to form the membrane attack complex. Unexpectedly, we observed that C4(-/-) and factor B-/- mice were fully susceptible to disease, indicating that activation of the classical or alternative pathways is not required for ECM. C3(-/-) mice were also susceptible to ECM, indicating that the canonical C5 convertases are not required for ECM development and progression. Abrogation of ECM by treatment with anti-C9 antibody and detection of C5a in serum of C3(-/-) mice confirmed that C5 activation occurs in ECM independent of C5 convertases. Our data indicate that activation of C5 in ECM likely occurs via coagulation enzymes of the extrinsic protease pathway. C1 [Ramos, Theresa N.; Darley, Meghan M.; Barnum, Scott R.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. [Ramos, Theresa N.; Darley, Meghan M.; Barnum, Scott R.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Weckbach, Sebastian; Stahel, Philip F.] Univ Colorado, Dept Orthoped Surg, Denver, CO 80204 USA. [Weckbach, Sebastian; Stahel, Philip F.] Univ Colorado, Dept Neurosurg, Denver, CO 80204 USA. [Tomlinson, Stephen] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Tomlinson, Stephen] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Barnum, SR (reprint author), Univ Alabama Birmingham, Dept Microbiol, 845 19th St S,BBRB-842, Birmingham, AL 35294 USA. EM sbarnum@uab.edu FU National Institutes of Health [T32 AI07051, NS077811, AI08382, HL82485]; Veterans Affairs Grant [NURC-051-10F]; German Research Foundation FX This work was supported, in whole or in part, by National Institutes of Health Grants T32 AI07051 and NS077811 (to T. N. R.), AI08382 (to S. R. B.), and HL82485 (to S. T.). This work was also supported by Veterans Affairs Grant NURC-051-10F (to S. T.) and a research fellowship from the German Research Foundation (to S. W.). NR 44 TC 16 Z9 16 U1 0 U2 2 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 JUL 13 PY 2012 VL 287 IS 29 BP 24734 EP 24738 DI 10.1074/jbc.C112.378364 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 977IQ UT WOS:000306651100066 PM 22689574 ER PT J AU Kar, UK Jiang, JN Champion, CI Salehi, S Srivastava, M Sharma, S Rabizadeh, S Niazi, K Kickhoefer, V Rome, LH Kelly, KA AF Kar, Upendra K. Jiang, Janina Champion, Cheryl I. Salehi, Sahar Srivastava, Minu Sharma, Sherven Rabizadeh, Shahrooz Niazi, Kayvan Kickhoefer, Valerie Rome, Leonard H. Kelly, Kathleen A. TI Vault Nanocapsules as Adjuvants Favor Cell-Mediated over Antibody-Mediated Immune Responses following Immunization of Mice SO PLOS ONE LA English DT Article ID IN-VIVO; ANTIGEN PRESENTATION; CROSS-PRESENTATION; DELIVERY-SYSTEMS; DNA VACCINES; T-CELLS; PROTEIN; VIRUS; NANOPARTICLES; LOCALIZATION AB Background: Modifications of adjuvants that induce cell-mediated over antibody-mediated immunity is desired for development of vaccines. Nanocapsules have been found to be viable adjuvants and are amenable to engineering for desired immune responses. We previously showed that natural nanocapsules called vaults can be genetically engineered to elicit Th1 immunity and protection from a mucosal bacterial infection. The purpose of our study was to characterize immunity produced in response to OVA within vault nanoparticles and compare it to another nanocarrier. Methodology and Principal Findings: We characterized immunity resulting from immunization with the model antigen, ovalbumin (OVA) encased in vault nanocapsules and liposomes. We measured OVA responsive CD8(+) and CD4(+) memory T cell responses, cytokine production and antibody titers in vitro and in vivo. We found that immunization with OVA contain in vaults induced a greater number of anti-OVA CD8(+) memory T cells and production of IFN gamma plus CD4(+) memory T cells. Also, modification of the vault body could change the immune response compared to OVA encased in liposomes. Conclusions/Significance: These experiments show that vault nanocapsules induced strong anti-OVA CD8(+) and CD4(+) T cell memory responses and modest antibody production, which markedly differed from the immune response induced by liposomes. We also found that the vault nanocapsule could be modified to change antibody isotypes in vivo. Thus it is possible to create a vault nanocapsule vaccine that can result in the unique combination of immunogen-responsive CD8(+) and CD4(+) T cell immunity coupled with an IgG1 response for future development of vault nanocapsule-based vaccines against antigens for human pathogens and cancer. C1 [Kar, Upendra K.; Kickhoefer, Valerie; Rome, Leonard H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. [Jiang, Janina; Champion, Cheryl I.; Salehi, Sahar; Kelly, Kathleen A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Srivastava, Minu; Sharma, Sherven] Vet Affairs Greater Los Angeles Healthcare Syst, Mol Med Lab, Los Angeles, CA USA. [Rabizadeh, Shahrooz; Niazi, Kayvan] Univ Calif Los Angeles, Samueli Sch Engn, Dept Bioengn, Los Angeles, CA USA. [Rabizadeh, Shahrooz; Niazi, Kayvan; Kickhoefer, Valerie; Rome, Leonard H.; Kelly, Kathleen A.] Univ Calif Los Angeles, Calif NanoSyst Inst, Los Angeles, CA USA. RP Kar, UK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. EM kkelly@mednet.ucla.edu RI Rome, Leonard/E-8786-2016 OI Rome, Leonard/0000-0002-1236-2063; Kickhoefer, Valerie/0000-0002-0048-0580 FU National Institutes of Health [AI026328]; Abraxis Bioscience, Inc [20090918] FX These studies were supported by the National Institutes of Health, AI026328 (Dr. Kelly), sponsored research award from Abraxis Bioscience, Inc (Dr. Kelly) and 20090918. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 11 Z9 11 U1 0 U2 18 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 JUL 11 PY 2012 VL 7 IS 7 AR e38553 DI 10.1371/journal.pone.0038553 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 973LU UT WOS:000306362400003 PM 22808011 ER PT J AU Kupersmith, J Eisen, S AF Kupersmith, Joel Eisen, Seth TI A New Approach to Health Services Research SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material C1 [Kupersmith, Joel; Eisen, Seth] US Dept Vet Affairs, Off Res & Dev, Washington, DC 20420 USA. [Eisen, Seth] US Dept Vet Affairs, Hlth Serv Res & Dev Serv, Washington, DC 20420 USA. RP Kupersmith, J (reprint author), US Dept Vet Affairs, Off Res & Dev, 810 Vermont Ave NW, Washington, DC 20420 USA. EM Joel.Kupersmith@va.gov NR 3 TC 5 Z9 5 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 9 PY 2012 VL 172 IS 13 BP 1033 EP 1034 DI 10.1001/archinternmed.2012.2004 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 971FP UT WOS:000306189500013 PM 22664894 ER PT J AU Stickrath, C Druck, J Hensley, N Maddox, TM Richlie, D AF Stickrath, Chad Druck, Jeffrey Hensley, Nathan Maddox, Thomas M. Richlie, Daniel TI Patient and Health Care Provider Discussions About the Risks of Medical Imaging: Not Ready for Prime Time SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter ID INCIDENTAL FINDINGS; RADIATION; BENEFITS C1 [Stickrath, Chad; Richlie, Daniel] Univ Colorado, Div Gen Internal Med, Denver Sch Med, Denver, CO 80202 USA. [Maddox, Thomas M.] Univ Colorado, Div Cardiol, Denver Sch Med, Denver, CO 80202 USA. [Druck, Jeffrey] Univ Colorado, Dept Med, Dept Emergency Med, Denver Sch Med, Denver, CO 80202 USA. [Hensley, Nathan] Univ Colorado, Dept Radiol, Denver Sch Med, Denver, CO 80202 USA. [Stickrath, Chad; Hensley, Nathan; Maddox, Thomas M.; Richlie, Daniel] Denver VA Med Ctr, Denver, CO 80220 USA. RP Stickrath, C (reprint author), Denver VA Med Ctr, 1055 Clermont St 111, Denver, CO 80220 USA. EM Chad.stickrath@va.gov NR 6 TC 7 Z9 7 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 9 PY 2012 VL 172 IS 13 BP 1037 EP 1038 DI 10.1001/archinternmed.2012.1791 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 971FP UT WOS:000306189500015 PM 22664652 ER PT J AU Asch, DA Muller, RW Volpp, KG AF Asch, David A. Muller, Ralph W. Volpp, Kevin G. TI Automated Hovering in Health Care - Watching Over the 5000 Hours SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID FINANCIAL INCENTIVES C1 [Asch, David A.; Volpp, Kevin G.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Asch, David A.; Muller, Ralph W.; Volpp, Kevin G.] Univ Penn, Hlth Syst Ctr Innovat Hlth Care Financing, Philadelphia, PA 19104 USA. [Asch, David A.; Volpp, Kevin G.] Univ Penn, Penn CMU Roybal Ctr Behav Econ & Hlth P30, Philadelphia, PA 19104 USA. [Asch, David A.; Muller, Ralph W.; Volpp, Kevin G.] Univ Penn, Ctr Hlth Incent & Behav Econ, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Asch, David A.; Volpp, Kevin G.] Univ Penn, Perelman Sch, Philadelphia, PA 19104 USA. [Asch, David A.; Volpp, Kevin G.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. RP Asch, DA (reprint author), Univ Penn, Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. OI Asch, David/0000-0002-7970-286X NR 5 TC 46 Z9 46 U1 2 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 JUL 5 PY 2012 VL 367 IS 1 BP 1 EP 3 DI 10.1056/NEJMp1203869 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 968KJ UT WOS:000305979400014 PM 22716935 ER PT J AU Eccles, MP Grimshaw, JM Shekelle, P Schunemann, HJ Woolf, S AF Eccles, Martin P. Grimshaw, Jeremy M. Shekelle, Paul Schuenemann, Holger J. Woolf, Steven TI Developing clinical practice guidelines: target audiences, identifying topics for guidelines, guideline group composition and functioning and conflicts of interest SO IMPLEMENTATION SCIENCE LA English DT Article ID RAPID ADVICE GUIDELINES; INDUSTRY; QUALITY; POLICY; INVOLVEMENT; SOCIETIES; APPRAISAL AB Clinical practice guidelines are one of the foundations of efforts to improve health care. In 1999, we authored a paper about methods to develop guidelines. Since it was published, the methods of guideline development have progressed both in terms of methods and necessary procedures and the context for guideline development has changed with the emergence of guideline clearing houses and large scale guideline production organisations (such as the UK National Institute for Health and Clinical Excellence). It therefore seems timely to, in a series of three articles, update and extend our earlier paper. In this first paper we discuss: the target audience(s) for guidelines and their use of guidelines; identifying topics for guidelines; guideline group composition (including consumer involvement) and the processes by which guideline groups function and the important procedural issue of managing conflicts of interest in guideline development. C1 [Eccles, Martin P.] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE2 4AX, Tyne & Wear, England. [Grimshaw, Jeremy M.] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. [Grimshaw, Jeremy M.] Univ Ottawa, Dept Med, Ottawa, ON, Canada. [Shekelle, Paul] RAND Corp, Santa Monica, CA 90407 USA. [Shekelle, Paul] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Schuenemann, Holger J.] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Schuenemann, Holger J.] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Woolf, Steven] Virginia Commonwealth Univ, Dept Family Med, Richmond, VA USA. [Woolf, Steven] Virginia Commonwealth Univ, Ctr Human Needs, Richmond, VA USA. RP Shekelle, P (reprint author), RAND Corp, Santa Monica, CA 90407 USA. EM shekelle@rand.org RI Grimshaw, Jeremy/D-8726-2013 OI Grimshaw, Jeremy/0000-0001-8015-8243 NR 47 TC 54 Z9 58 U1 1 U2 14 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 JUL 4 PY 2012 VL 7 AR 60 DI 10.1186/1748-5908-7-60 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 066EZ UT WOS:000313204500001 PM 22762776 ER PT J AU Shekelle, P Woolf, S Grimshaw, JM Schunemann, HJ Eccles, MP AF Shekelle, Paul Woolf, Steven Grimshaw, Jeremy M. Schuenemann, Holger J. Eccles, Martin P. TI Developing clinical practice guidelines: reviewing, reporting, and publishing guidelines; updating guidelines; and the emerging issues of enhancing guideline implementability and accounting for comorbid conditions in guideline development SO IMPLEMENTATION SCIENCE LA English DT Article ID QUALITY; CARE; FRAMEWORK AB Clinical practice guidelines are one of the foundations of efforts to improve health care. In 1999, we authored a paper about methods to develop guidelines. Since it was published, the methods of guideline development have progressed both in terms of methods and necessary procedures and the context for guideline development has changed with the emergence of guideline clearing houses and large scale guideline production organisations (such as the UK National Institute for Health and Clinical Excellence). It therefore seems timely to, in a series of three articles, update and extend our earlier paper. In this third paper we discuss the issues of: reviewing, reporting, and publishing guidelines; updating guidelines; and the two emerging issues of enhancing guideline implementability and how guideline developers should approach dealing with the issue of patients who will be the subject of guidelines having co-morbid conditions. C1 [Shekelle, Paul] RAND Corp, Santa Monica, CA 90407 USA. [Shekelle, Paul] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Woolf, Steven] Virginia Commonwealth Univ, Dept Family Med, Richmond, VA USA. [Woolf, Steven] Virginia Commonwealth Univ, Ctr Human Needs, Richmond, VA USA. [Grimshaw, Jeremy M.] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. [Grimshaw, Jeremy M.] Univ Ottawa, Dept Med, Ottawa, ON, Canada. [Schuenemann, Holger J.] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Schuenemann, Holger J.] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Eccles, Martin P.] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE2 4AX, Tyne & Wear, England. RP Shekelle, P (reprint author), RAND Corp, Santa Monica, CA 90407 USA. EM shekelle@rand.org RI Grimshaw, Jeremy/D-8726-2013 OI Grimshaw, Jeremy/0000-0001-8015-8243 NR 23 TC 58 Z9 60 U1 1 U2 11 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 JUL 4 PY 2012 VL 7 AR 62 DI 10.1186/1748-5908-7-62 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 044MJ UT WOS:000311623400001 PM 22762242 ER PT J AU Woolf, S Schunemann, HJ Eccles, MP Grimshaw, JM Shekelle, P AF Woolf, Steven Schuenemann, Holger J. Eccles, Martin P. Grimshaw, Jeremy M. Shekelle, Paul TI Developing clinical practice guidelines: types of evidence and outcomes; values and economics, synthesis, grading, and presentation and deriving recommendations SO IMPLEMENTATION SCIENCE LA English DT Article ID SERVICES TASK-FORCE; SHARED DECISION-MAKING; HEALTH-CARE CONSUMERS; QUALITY; STRENGTH; MEDICINE; PREFERENCES; CONSENSUS; NUMBERS; SYMBOLS AB Clinical practice guidelines are one of the foundations of efforts to improve healthcare. In 1999, we authored a paper about methods to develop guidelines. Since it was published, the methods of guideline development have progressed both in terms of methods and necessary procedures and the context for guideline development has changed with the emergence of guideline clearinghouses and large scale guideline production organisations (such as the UK National Institute for Health and Clinical Excellence). It therefore seems timely to, in a series of three articles, update and extend our earlier paper. In this second paper, we discuss issues of identifying and synthesizing evidence: deciding what type of evidence and outcomes to include in guidelines; integrating values into a guideline; incorporating economic considerations; synthesis, grading, and presentation of evidence; and moving from evidence to recommendations. C1 [Shekelle, Paul] RAND Corp, Santa Monica, CA 90407 USA. [Shekelle, Paul] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Woolf, Steven] Virginia Commonwealth Univ, Dept Family Med, Richmond, VA USA. [Woolf, Steven] Virginia Commonwealth Univ, Ctr Human Needs, Richmond, VA USA. [Schuenemann, Holger J.] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Schuenemann, Holger J.] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Eccles, Martin P.] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE2 4AX, Tyne & Wear, England. [Grimshaw, Jeremy M.] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. [Grimshaw, Jeremy M.] Univ Ottawa, Dept Med, Ottawa, ON, Canada. RP Shekelle, P (reprint author), RAND Corp, Santa Monica, CA 90407 USA. EM shekelle@rand.org RI Grimshaw, Jeremy/D-8726-2013 OI Grimshaw, Jeremy/0000-0001-8015-8243 NR 64 TC 35 Z9 39 U1 2 U2 13 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 JUL 4 PY 2012 VL 7 AR 61 DI 10.1186/1748-5908-7-61 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 001NG UT WOS:000308466800001 PM 22762158 ER PT J AU Zhang, J Xie, FL Delzell, E Chen, L Winthrop, KL Lewis, JD Saag, KG Baddley, JW Curtis, JR AF Zhang, Jie Xie, Fenglong Delzell, Elizabeth Chen, Lang Winthrop, Kevin L. Lewis, James D. Saag, Kenneth G. Baddley, John W. Curtis, Jeffrey R. TI Association Between Vaccination for Herpes Zoster and Risk of Herpes Zoster Infection Among Older Patients With Selected Immune-Mediated Diseases SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RHEUMATOID-ARTHRITIS; UNITED-STATES; ADMINISTRATIVE DATABASE; VARICELLA; RECOMMENDATIONS; CHILDREN; THERAPY; SAFETY; AGENTS; ADULTS AB Context Based on limited data, the live attenuated herpes zoster (HZ) vaccine is contraindicated in patients taking anti-tumor necrosis factor (anti-TNF) therapies or other biologics commonly used to treat immune-mediated diseases. The safety and effectiveness of the vaccine are unclear for these patients. Objective To examine the association between HZ vaccination and HZ incidence within and beyond 42 days after vaccination in patients with selected immune-mediated diseases and in relation to biologics and other therapies used to treat these conditions. Design, Setting, and Patients Retrospective cohort study of 463 541 Medicare beneficiaries 60 years and older with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, or inflammatory bowel disease using Medicare claims data from January 1, 2006, through December 31, 2009. Main Outcome Measures Herpes zoster incidence rate within 42 days after vaccination (a safety concern) and beyond 42 days; hazard ratios estimated using Cox proportional hazards models for HZ comparing vaccinated vs unvaccinated patients. Results Median duration of follow-up was 2.0 years (interquartile range, 0.8-3.0); 4.0% of patients received HZ vaccine. The overall crude HZ incidence rate was 7.8 cases per 1000 person-years (95% CI, 3.7-16.5) within 42 days after vaccination. The rate among the unvaccinated was 11.6 cases per 1000 person-years (95% CI, 11.4-11.9). Among 633 patients exposed to biologics at the time of vaccination or within the subsequent 42 days, no case of HZ or varicella occurred. After multivariable adjustment, HZ vaccination was associated with a hazard ratio of 0.61 (95% CI, 0.52-0.71) for HZ risk after 42 days. Conclusions Receipt of HZ vaccine was not associated with a short-term increase in HZ incidence among Medicare beneficiaries with selected immune-mediated diseases, including those exposed to biologics. The vaccine was associated with a lower HZ incidence over a median of 2 years of follow-up. JAMA. 2012; 308(1):43-49 www.jama.com C1 [Zhang, Jie; Delzell, Elizabeth; Curtis, Jeffrey R.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Xie, Fenglong; Chen, Lang; Saag, Kenneth G.; Curtis, Jeffrey R.] Univ Alabama Birmingham, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Baddley, John W.] Univ Alabama Birmingham, Div Infect Dis, Birmingham, AL 35294 USA. [Winthrop, Kevin L.] Oregon Hlth & Sci Univ, Dept Med, Div Infect Dis, Portland, OR 97201 USA. [Lewis, James D.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Baddley, John W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Curtis, JR (reprint author), Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, FOT 805D,510 20th St S, Birmingham, AL 35294 USA. EM jcurtis@uab.edu FU Amgen; Pfizer; UCB; Abbott; Centocor; Takeda; Shire; Merck; Genentech/Roche; BMS; Agency for Healthcare Research and Quality (AHRQ) [R01 HS018517, T32HS013852]; National Institutes of Health [AR 053351] FX Dr Zhang reported having received research support from Amgen. Dr Delzell reported having received research support from Amgen. Dr Winthrop reported having received consulting fees from Pfizer, Amgen, UCB, and Abbott and grants from Pfizer. Dr Lewis reported having received research grants from Centocor, Takeda, and Shire and having served as a consultant for Amgen, Abbott, Pfizer, and Millennium Pharmaceuticals. Dr Saag is the chair of the American College of Rheumatology Quality of Care Committee and reported having received consulting fees from Merck. Dr Baddley reported having received consulting fees from Abbott and Merck. Dr Curtis reported having received research grants and consulting fees from Amgen, UCB, Abbott, Genentech/Roche, Centocor, BMS, and Merck. No other disclosures were reported.; This project was supported by the Agency for Healthcare Research and Quality (AHRQ) (R01 HS018517). Dr Zhang received support from the AHRQ (T32HS013852), and Dr Curtis received support from the National Institutes of Health (AR 053351). NR 23 TC 110 Z9 111 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 4 PY 2012 VL 308 IS 1 BP 43 EP 49 DI 10.1001/jama.2012.7304 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 971DD UT WOS:000306183000022 PM 22760290 ER PT J AU Qaseem, A Humphrey, LL Shekelle, P AF Qaseem, Amir Humphrey, Linda L. Shekelle, Paul TI Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Qaseem, Amir] Amer Coll Physicians, Philadelphia, PA 19106 USA. [Humphrey, Linda L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Shekelle, Paul] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Qaseem, A (reprint author), Amer Coll Physicians, Philadelphia, PA 19106 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 3 PY 2012 VL 157 IS 1 BP 76 EP 77 DI 10.7326/0003-4819-157-1-201207030-00019 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 992NS UT WOS:000307784900013 ER PT J AU Zhang, XY Chen, DC Xiu, MH Yang, FD Haile, CN Kosten, TA Kosten, TR AF Zhang, Xiang Yang Chen, Da Chun Xiu, Mei Hong Yang, Fu De Haile, Colin N. Kosten, Therese A. Kosten, Thomas R. TI Gender Differences in Never-Medicated First-Episode Schizophrenia and Medicated Chronic Schizophrenia Patients SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID 1ST EPISODE PSYCHOSIS; SEX-DIFFERENCES; CHINESE SCHIZOPHRENIA; VERBAL MEMORY; ONSET; AGE; SMOKING; PREVALENCE; DISORDERS; ILLNESS AB Background: Schizophrenia shows gender differences in patients' clinical presentation, neurocognitive impairment, course, and treatment outcome. The aims of this study were to compare gender differences in clinical features and cognitive functioning in first-episode and chronic schizophrenia among Han Chinese inpatients. Method: We compared gender differences in 262 unmedicated first-episode schizophrenia and 960 chronic schizophrenia inpatients (diagnosed according to DSM-IV) to 804 matched healthy controls on sociodemographic characteristics, smoking behavior, and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Patients were also rated on the Positive and Negative Syndrome Scale. The study was conducted from December 2006 to May 2008. Results: Schizophrenia first occurred in both first-episode and chronic schizophrenia patients at a significantly earlier age in male than female patients (P < .05 and P < .001, respectively). The paranoid subtype of schizophrenia was more common in female patients only in chronic schizophrenia, not first-episode patients. Further, cigarette smoking was more common in male than female patients from both patient groups, and, among men, more chronic schizophrenia patients than controls smoked, while among women, fewer chronic schizophrenia patients than controls smoked. Female chronic schizophrenia patients had more severe positive and general psychopathological symptoms, whereas male patients had more severe negative symptoms. By contrast, first-episode schizophrenia patients showed no gender differences in symptoms and severity. Both first-episode and chronic schizophrenia patients performed worse than controls on most of the cognitive tasks. RBANS attention, delayed memory, and immediate memory were less impaired in female than male chronic schizophrenia patients, and first-episode schizophrenia patients showed no gender differences. Conclusions: Chronic schizophrenia patients have notable gender differences in the age at onset, smoking, symptom severity, and cognitive function favoring women, but first-episode schizophrenia patients show few gender differences. J Clin Psychiatry 2012;73(7):1025-1033 (c) Copyright 2012 Physicians Postgraduate Press, Inc. C1 [Zhang, Xiang Yang; Haile, Colin N.; Kosten, Therese A.; Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Chen, Da Chun; Xiu, Mei Hong; Yang, Fu De] Beijing HuiLongGuan Hosp, Ctr Psychiat Res, Beijing, 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 OI Haile, Colin/0000-0001-8293-7291 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 Institutes of Health [K05-DA0454, P50-DA18827, U01-MH79639] FX This study was funded by 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 Institutes of Health (K05-DA0454, P50-DA18827, and U01-MH79639). NR 42 TC 33 Z9 34 U1 3 U2 33 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 JUL PY 2012 VL 73 IS 7 BP 1025 EP 1033 DI 10.4088/JCP.11m07422 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 090SL UT WOS:000315000200017 PM 22901352 ER PT J AU Riegel, B Lee, CS Ratcliffe, SJ De Geest, S Potashnik, S Patey, M Sayers, SL Goldberg, LR Weintraub, WS AF Riegel, Barbara Lee, Christopher S. Ratcliffe, Sarah J. De Geest, Sabina Potashnik, Sheryl Patey, Megan Sayers, Steven L. Goldberg, Lee R. Weintraub, William S. TI Predictors of Objectively Measured Medication Nonadherence in Adults With Heart Failure SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; medication adherence; patient compliance; self-care; sleep; World Health Organization ID SELF-CARE; ADHERENCE; ASSOCIATION; MIXTURE; HEALTH; QUESTIONNAIRE; SLEEPINESS; REGIMENS; NUMBER; TRIAL AB Background-Medication nonadherence rates are high. The factors predicting nonadherence in heart failure remain unclear. Methods and Results-A sample of 202 adults with heart failure was enrolled from the northeastern United States and followed for 6 months. Specific aims were to describe the types of objectively measured medication adherence (eg, taking, timing, dosing, drug holidays) and to identify contributors to nonadherence 6 months after enrollment. Latent growth mixture modeling was used to identify distinct trajectories of adherence. Indicators of the 5 World Health Organization dimensions of adherence (socioeconomic, condition, therapy, patient, and healthcare system) were tested to identify contributors to nonadherence. Two distinct trajectories were identified and labeled persistent adherence (77.8%) and steep decline (22.3%). Three contributors to the steep decline in adherence were identified. Participants with lapses in attention (adjusted OR, 2.65; P=0.023), those with excessive daytime sleepiness (OR, 2.51; P=0.037), and those with >= 2 medication dosings per day (OR, 2.59; P=0.016) were more likely to have a steep decline in adherence over time than to have persistent adherence. Conclusions-Two distinct patterns of adherence were identified. Three potentially modifiable contributors to nonadherence have been identified. (Circ Heart Fail. 2012; 5: 430-436.) C1 [Riegel, Barbara] Univ Penn, Sch Nursing, Biobehav Res Ctr, Philadelphia, PA 19104 USA. [Lee, Christopher S.] Oregon Hlth & Sci Univ, Sch Nursing, Portland, OR 97201 USA. [Ratcliffe, Sarah J.; Goldberg, Lee R.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [De Geest, Sabina] Univ Basel, Inst Nursing Sci, Basel, Switzerland. [Sayers, Steven L.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Weintraub, William S.] Christiana Care Hlth Syst, Dept Cardiol, Newark, DE USA. RP Riegel, B (reprint author), Univ Penn, Sch Nursing, Biobehav Res Ctr, Claire M Fagin Hall,418 Curie Blvd, Philadelphia, PA 19104 USA. EM briegel@nursing.upenn.edu OI Goldberg, Lee/0000-0002-7906-9638 FU National Heart, Lung & Blood Institute [RO1 HL084394-01A1]; Philadelphia Veterans Affairs Medical Center, VISN 4 Mental Illness Research, Education, and Clinical Center (MIREC) FX This work was funded by the National Heart, Lung & Blood Institute (RO1 HL084394-01A1) and by the Philadelphia Veterans Affairs Medical Center, VISN 4 Mental Illness Research, Education, and Clinical Center (MIREC). NR 41 TC 24 Z9 25 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JUL PY 2012 VL 5 IS 4 BP 430 EP 436 DI 10.1161/CIRCHEARTFAILURE.111.965152 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071GJ UT WOS:000313578100012 PM 22647773 ER PT J AU Nahab, FB Handforth, A Brown, T Shin, C Quesada, A Dong, CH Haubenberger, D Hallett, M AF Nahab, Fatta B. Handforth, Adrian Brown, Tyler Shin, Christopher Quesada, Arnulfo Dong, Chuanhui Haubenberger, Dietrich Hallett, Mark TI Octanoic Acid Suppresses Harmaline-Induced Tremor in Mouse Model of Essential Tremor SO NEUROTHERAPEUTICS LA English DT Article DE 1-octanol; Octanoic acid; Essential tremor; Harmaline; Therapeutics ID OPEN-LABEL; 1-OCTANOL AB Recent work exploring the use of high-molecular weight alcohols to treat essential tremor (ET) has identified octanoic acid as a potential novel tremor-suppressing agent. We used an established harmaline-based mouse model of ET to compare tremor suppression by 1-octanol and octanoic acid. The dose-related effect on digitized motion power within the tremor bandwidth as a fraction of overall motion power was analyzed. Both 1-octanol and octanoic acid provided significant reductions in harmaline tremor. An 8-carbon alkyl alcohol and carboxylic acid each suppress tremor in a pre-clinical mouse model of ET. Further studies are warranted to determine the safety and efficacy of such agents in humans with ET. C1 [Nahab, Fatta B.; Brown, Tyler; Dong, Chuanhui] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Handforth, Adrian] Vet Affairs Greater Los Angeles Healthcare Syst, Neurol Serv, Los Angeles, CA 90073 USA. [Shin, Christopher; Quesada, Arnulfo] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. [Quesada, Arnulfo] Univ Calif Los Angeles, Dept Neurobiol, David Geffen Sch Med, Los Angeles, CA 90073 USA. [Haubenberger, Dietrich] Med Univ Vienna, Dept Neurol, Vienna, Austria. [Brown, Tyler; Haubenberger, Dietrich; Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, Bethesda, MD 20892 USA. RP Nahab, FB (reprint author), Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. EM fnahab@med.miami.edu FU Intramural division of the National Institute of Neurological Disorders and Stroke; Ariston Pharmaceuticals FX This work was supported by the Intramural division of the National Institute of Neurological Disorders and Stroke and a collaborative research and development agreement with Ariston Pharmaceuticals. NR 16 TC 6 Z9 6 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JUL PY 2012 VL 9 IS 3 BP 635 EP 638 DI 10.1007/s13311-012-0121-1 PG 4 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 006NV UT WOS:000308826800014 PM 22454323 ER PT J AU Bradley, SM Maynard, C Bryson, CL AF Bradley, Steven M. Maynard, Charles Bryson, Chris L. TI Appropriateness of Percutaneous Coronary Interventions in Washington State SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE appropriateness criteria; percutaneous coronary intervention; utilization; quality improvement; health services research ID CARDIOVASCULAR DATA REGISTRY; INTRAVENOUS THROMBOLYTIC THERAPY; ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED-TRIALS; METAANALYSIS; DISEASE; RISK; ANGIOPLASTY; STRATEGIES; OUTCOMES AB Background-In anticipation of applying Appropriate Use Criteria for percutaneous coronary intervention (PCI) quality improvement, we determined the prevalence of appropriate, uncertain, and inappropriate PCIs stratified by indication for all PCIs performed in the state of Washington. Methods and Results-Within the Clinical Outcomes Assessment Program, we assigned appropriateness ratings to all PCIs performed in 2010 in accordance with published Appropriate Use Criteria. Of 13 291 PCIs, we successfully mapped the clinical scenario to the Appropriate Use Criteria in 9924 (75%) cases. Of the 3367 PCIs not classified, common failures to map to the criteria included nonacute PCI without prior noninvasive stress results (n = 1906; 57%) and unstable angina without high-risk features (n = 902; 27%). Of mapped PCIs, 8010 (71%) were for acute indications, with 7887 (98%) rated as appropriate, 39 (<1%) as uncertain, and 84 (1%) as inappropriate. Of 1914 mapped nonacute indications, 847 (44%) were rated as appropriate, 748 (39%) as uncertain, and 319 (17%) as inappropriate. Assuming results for noninvasive stress tests when data were missing, in the best-case scenario, 319 (8%) of nonacute PCIs were classified as inappropriate compared with 1459 (38%) in the worst-case scenario. Variation in inappropriate PCIs by facility was greatest for mapped nonacute indications (median = 14%; 25th to 75th percentiles = 9% to 24%) and nonacute indications with missing data precluding appropriateness classification (median = 54%; 25th to 75th percentiles = 35% to 66%). Conclusions-In a complete cohort of PCIs performed in Washington state, 1% of PCIs for acute indications and 17% of PCIs for nonacute indications were classified as inappropriate. Missing data on noninvasive stress tests present a challenge in the application of the criteria for quality improvement. (Circ Cardiovasc Qual Outcomes. 2012; 5: 445-453.) C1 [Bradley, Steven M.] VA Eastern Colorado Hlth Care Syst, Dept Vet Affairs, Denver, CO 80220 USA. [Bradley, Steven M.] Univ Colorado, Denver, CO 80202 USA. [Maynard, Charles; Bryson, Chris L.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev NW Ctr Excellence, Seattle, WA USA. [Maynard, Charles; Bryson, Chris L.] Univ Washington, Seattle, WA 98195 USA. [Maynard, Charles; Bryson, Chris L.] Fdn Hlth Care Qual, Clin Outcomes Assessment Program, Seattle, WA USA. RP Bradley, SM (reprint author), VA Eastern Colorado Hlth Care Syst, Dept Vet Affairs, 1055 Clermont St 111B, Denver, CO 80220 USA. EM Steven.Bradley@va.gov RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 FU Health Services Research and Development Service; Health Services Research and Development QuERI Program, Department of Veterans Affairs [RRP 09-040]; VA Health Services Research and Development [1 IK2 HX000779-01] FX This material is based upon work supported by Health Services Research and Development Service and the Health Services Research and Development QuERI Program, Department of Veterans Affairs (Project No.: RRP 09-040). Dr. Steven Bradley is a Career Development Grant Awardee (1 IK2 HX000779-01, funding pending) from VA Health Services Research and Development. NR 24 TC 23 Z9 24 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JUL PY 2012 VL 5 IS 4 BP 445 EP 453 DI 10.1161/CIRCOUTCOMES.111.964320 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 002PO UT WOS:000308544500008 PM 22570356 ER PT J AU Keyhani, S Cheng, E Arling, G Li, XL Myers, L Ofner, S Williams, LS Phipps, M Ordin, D Bravata, DM AF Keyhani, Salomeh Cheng, Eric Arling, Greg Li, Xinli Myers, Laura Ofner, Susan Williams, Linda S. Phipps, Michael Ordin, Diana Bravata, Dawn M. TI Does the Inclusion of Stroke Severity in a 30-Day Mortality Model Change Standardized Mortality Rates at Veterans Affairs Hospitals? SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE stroke; outcome assessment (health care); hospital mortality ID ISCHEMIC-STROKE; SCALE; OUTCOMES; SCORE; RISK AB Background-The Centers for Medicare and Medicaid Services is considering developing a 30-day ischemic stroke hospital-level mortality model using administrative data. We examined whether inclusion of the National Institutes of Health Stroke Scale (NIHSS), a measure of stroke severity not included in administrative data, would alter 30-day mortality rates in the Veterans Health Administration. Methods and Results-A total of 2562 veterans admitted with ischemic stroke to 64 Veterans Health Administration Hospitals in the fiscal year 2007 were included. First, we examined the distribution of unadjusted mortality rates across the Veterans Health Administration. Second, we estimated 30-day all-cause, risk standardized mortality rates (RSMRs) for each hospital by adjusting for age, sex, and comorbid conditions using hierarchical models with and without the inclusion of the NIHSS. Finally, we examined whether adjustment for the NIHSS significantly changed RSMRs for each hospital compared with other hospitals. The median unadjusted mortality rate was 3.6%. The RSMR interquartile range without the NIHSS ranged from 5.1% to 5.6%. Adjustment with the NIHSS did not change the RSMR interquartile range (5.1%-5.6%). Among veterans >= 65 years, the RSMR interquartile range without the NIHSS ranged from 9.2% to 10.3%. With adjustment for the NIHSS, the RSMR interquartile range changed from 9.4% to 10.0%. The plot of 30-day RSMRs estimated with and without the inclusion of the NIHSS in the model demonstrated overlapping 95% confidence intervals across all hospitals, with no hospital significantly below or above the mean-unadjusted 30-day mortality rate. The 30-day mortality measure did not discriminate well among hospitals. Conclusion-The impact of the NIHSS on RSMRs was limited. The small number of stroke admissions and the narrow range of 30-day stroke mortality rates at the facility level in the Veterans Health Administration cast doubt on the value of using 30-day RSMRs as a means of identifying outlier hospitals based on their stroke care quality. (Circ Cardiovasc Qual Outcomes. 2012; 5: 508-513.) C1 [Keyhani, Salomeh] Univ Calif San Francisco, San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA 94121 USA. [Keyhani, Salomeh] Univ Calif San Francisco, San Francisco VA Med Ctr HSR& REAP, San Francisco, CA 94121 USA. [Cheng, Eric] VA Greater Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA USA. [Cheng, Eric] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Li, Xinli; Myers, Laura; Williams, Linda S.; Bravata, Dawn M.] Richard L Roudebush VA Med Ctr, VHA HSR & Ctr Excellence Implementing Evidence Ba, Indianapolis, IN USA. [Ofner, Susan] Indiana Univ Sch Med, Div Biostat, Indianapolis, IN USA. [Cheng, Eric; Arling, Greg; Myers, Laura; Ofner, Susan; Williams, Linda S.; Bravata, Dawn M.] VHA HSR & Stroke Qual Enhancement Res Initiat Pro, Indianapolis, IN USA. [Arling, Greg; Williams, Linda S.] Indiana Univ Sch Med, Indiana Univ Ctr Aging Res, Indianapolis, IN USA. [Williams, Linda S.; Bravata, Dawn M.] Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN USA. [Myers, Laura; Bravata, Dawn M.] Indiana Univ Sch Med, Dept Internal Med, Indianapolis, IN USA. [Arling, Greg; Williams, Linda S.; Bravata, Dawn M.] Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. [Phipps, Michael] Yale Univ, Sch Med, Robert Wood Johnson Fdn Clin Scholars Program, New Haven, CT USA. [Phipps, Michael] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. RP Keyhani, S (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Div Gen Internal Med, 4150 Clement 111A1, San Francisco, CA 94121 USA. EM salomeh.keyhani@va.gov OI Phipps, Michael/0000-0001-8398-5404 FU Department of Veterans Affairs; Veterans Health Administration; Office of Quality and Performance and Health Services Research; Development Service Quality Enhancement Research Initiative [RRP 09-184]; VA HSRD FX The Department of Veterans Affairs, Veterans Health Administration, Office of Quality and Performance and Health Services Research, and Development Service Quality Enhancement Research Initiative (RRP 09-184) supported this project. Dr Bravata is the principal investigator of this project at the Richard L. Roudebush VA Medical Center (Indianapolis, IN). Dr Keyhani is currently supported by a VA HSR&D career development award. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 15 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JUL PY 2012 VL 5 IS 4 BP 508 EP 513 DI 10.1161/CIRCOUTCOMES.111.962936 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 002PO UT WOS:000308544500016 PM 22787062 ER PT J AU Lambert-Kerzner, A Del Giacco, EJ Fahdi, IE Bryson, CL Melnyk, SD Bosworth, HB Davis, R Mun, H Weaver, J Barnett, C Radcliff, T Hubbard, A Bosket, KD Carey, E Virchow, A Mihalko-Corbitt, R Kaufman, A Marchant-Miros, K Ho, PM AF Lambert-Kerzner, Anne Del Giacco, Eric J. Fahdi, Ibrahim E. Bryson, Chris L. Melnyk, S. Dee Bosworth, Hayden B. Davis, Ryan Mun, Howard Weaver, Jennifer Barnett, Casey Radcliff, Tiffany Hubbard, Amanda Bosket, Kevin D. Carey, Evan Virchow, Allison Mihalko-Corbitt, Renee Kaufman, Amy Marchant-Miros, Kathy Ho, P. Michael CA Multifaceted Intervention Improve TI Patient-Centered Adherence Intervention After Acute Coronary Syndrome Hospitalization SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE acute coronary syndromes; adherence; medication adherence; cost-effectiveness; treatment effectiveness ID ACUTE MYOCARDIAL-INFARCTION; SECONDARY PREVENTION; MEDICATION; CARE; THERAPY; OUTCOMES; DISCONTINUATION; PREVALENCE; PREDICTORS; MORTALITY AB Background-Adherence to cardioprotective medications in the year after acute coronary syndrome hospitalization is generally poor and is associated with increased risk of rehospitalization and mortality. Few interventions have specifically targeted this high-risk patient population to improve medication adherence. We hypothesize that a multifaceted patient-centered intervention could improve adherence to cardioprotective medications. Methods and Results-To evaluate this intervention, we propose enrolling 280 patients with a recent acute coronary syndrome event into a multicenter randomized, controlled trial. The intervention comprises4 main components: (1) pharmacist-led medication reconciliation and tailoring; (2) patient education; (3) collaborative care between pharmacist and primary care provider/cardiologist; and (4) 2 types of voice messaging (educational and medication refill reminder calls). Patients in the intervention arm will visit with the study pharmacist approximate to 1 week post-hospital discharge. The pharmacist will work with the patient and collaborate with providers to reconcile medication issues. Voice messages will augment the educational process and remind patients to refill their cardioprotective medications. The study will compare the intervention versus usual care for 12 months. The primary outcome of interest is adherence using the ReComp method. Secondary and tertiary outcomes include achievement of targets for blood pressure and low-density lipoprotein, and reduction in the combined cardiovascular end points of myocardial infarction hospitalization, coronary revascularization, and all-cause mortality. Finally, we will also evaluate the cost-effectiveness of the intervention compared with usual care. Conclusions-If the intervention is effective in improving medication adherence and demonstrating a lower cost, the intervention has the potential to improve cardiovascular outcomes in this high-risk patient population. (Circ Cardiovasc Qual Outcomes. 2012; 5: 571-576.) C1 [Lambert-Kerzner, Anne; Davis, Ryan; Radcliff, Tiffany; Carey, Evan; Virchow, Allison; Multifaceted Intervention Improve] Denver VA Med Ctr, Denver, CO USA. [Del Giacco, Eric J.; Fahdi, Ibrahim E.; Weaver, Jennifer; Barnett, Casey; Hubbard, Amanda; Mihalko-Corbitt, Renee; Marchant-Miros, Kathy] Little Rock VA Med Ctr, Little Rock, AR USA. [Bryson, Chris L.; Mun, Howard; Bosket, Kevin D.] Puget Sound VA Med Ctr, Seattle, WA USA. [Melnyk, S. Dee; Bosworth, Hayden B.; Kaufman, Amy] Durham VA Med Ctr, Durham, NC USA. RP Lambert-Kerzner, A (reprint author), 1055 Clermont St, Denver, CO 80220 USA. EM anne.lambert-kerzner@va.gov FU Veterans Administration Health Services Research and Development Grant [IIR 08-302]; VA HSR&D Career Development Award; VA HSR&D Career Scientist Award [RCS 08-027] FX The study is being funded by Veterans Administration Health Services Research and Development Grant contract number IIR 08-302.; Dr Ho is supported by a VA HSR&D Career Development Award.5-26 Dr Bosworth was supported by a VA HSR&D Career Scientist Award (RCS 08-027). NR 32 TC 13 Z9 14 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JUL PY 2012 VL 5 IS 4 BP 571 EP 576 DI 10.1161/CIRCOUTCOMES.111.962290 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 002PO UT WOS:000308544500024 PM 22811499 ER PT J AU De La Garza, BH Li, G Shih, YYI Duong, TQ AF De La Garza, Bryan H. Li, Guang Shih, Yen-Yu I. Duong, Timothy Q. TI Layer-Specific Manganese-Enhanced MRI of the Retina in Light and Dark Adaptation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID CHOROIDAL BLOOD-FLOW; OPTICAL COHERENCE TOMOGRAPHY; RAT RETINA; FUNCTIONAL MRI; OUTER RETINA; IN-VIVO; OXYGEN DISTRIBUTION; GLUCOSE-METABOLISM; CAT RETINA; CONSUMPTION AB PURPOSE. To employ functional manganese-enhanced MRI (MEMRI) to image layer-specific changes in calcium-dependent activities in the rat retina during light versus dark adaptation. METHODS. Functional MEMRI at 203203700 mu m was used to study light and dark adaptation in the same animals (N = 10) in which one eye was covered and the fellow eye was not. The activity encoding of the light and dark adaptation was achieved in awake conditions and imaged under anesthesia. T-1-weighted MRI at 11.7 tesla (T) was performed using two identical radiofrequency transceiver coils to allow interleaved MRI acquisitions of the two eyes. An intravascular contrast agent was also used to verify layer assignments. RESULTS. MEMRI detected contrasts among the inner retina, outer retina, and choroid. Independent confirmation of the vascular layers and boundaries between layers was documented with an intravascular contrast agent. The retinal layer thicknesses agreed with published data. The outer retina had lower MEMRI activity in light compared with dark adaption (P < 0.001), consistent with the increased metabolic demand associated with the "dark current." The inner retina had higher MEMRI activity in light compared with dark adaption (P < 0.05). The choroid MEMRI activity was not statistically different between light and dark adaptation (P > 0.05). CONCLUSIONS. This study demonstrated a high-resolution MEMRI protocol to image functional activities among different layers of the retinas in awake animals during light and dark adaptation. This approach could have potential applications in animal models of retinal dysfunction. (Invest Ophthalmol Vis Sci. 2012;53:4352-4358) DOI:10.1167/iovs.11-8826 C1 [De La Garza, Bryan H.; Li, Guang; Shih, Yen-Yu I.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008; Li, Guang/C-9539-2011 OI Li, Guang/0000-0002-7648-0464; Shih, Yen-Yu Ian/0000-0001-6529-911X FU NIH/NEI [R01 EY014211, EY018855]; MERIT Award from the Department of Veterans Affairs FX Supported in part by NIH/NEI Grants R01 EY014211 and EY018855 and a MERIT Award from the Department of Veterans Affairs. NR 50 TC 11 Z9 11 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2012 VL 53 IS 8 BP 4352 EP 4358 DI 10.1167/iovs.11-8826 PG 7 WC Ophthalmology SC Ophthalmology GA 983DA UT WOS:000307096400004 PM 22669725 ER PT J AU Wilson, R Anzueto, A Miravitlles, M Arvis, P Alder, J Haverstock, D Trajanovic, M Sethi, S AF Wilson, Robert Anzueto, Antonio Miravitlles, Marc Arvis, Pierre Alder, Jeff Haverstock, Daniel Trajanovic, Mila Sethi, Sanjay TI Moxifloxacin versus amoxicillin/clavulanic acid in outpatient acute exacerbations of COPD: MAESTRAL results SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE Acute exacerbations of chronic obstructive pulmonary disease; amoxicillin/clavulanic acid; antibiotic; clinical trial design; exacerbation; moxifloxacin ID OBSTRUCTIVE PULMONARY-DISEASE; GEORGES RESPIRATORY QUESTIONNAIRE; ACUTE BACTERIAL EXACERBATIONS; LONG-TERM OUTCOMES; CHRONIC-BRONCHITIS; ANTIBIOTIC-TREATMENT; TRACT INFECTION; LUNG-FUNCTION; HEALTH-STATUS; FREE INTERVAL AB Bacterial infections causing acute exacerbations of chronic obstructive pulmonary disease (AECOPD) frequently require antibacterial treatment. More evidence is needed to guide antibiotic choice. The Moxifloxacin in Acute Exacerbations of Chronic Bronchitis TriaL (MAESTRAL) was a multiregional, randomised, double-blind non-inferiority outpatient study. Patients were aged >= 60 yrs, with an Anthonisen type I exacerbation, a forced expiratory volume in 1 s <60% predicted and two or more exacerbations in the last year. Following stratification by steroid use patients received moxifloxacin 400 mg p.o.q.d. (5 days) or amoxicillin/clavulanic acid 875/125 mg p.o. b.i.d. (7 days). The primary end-point was clinical failure 8 weeks post-therapy in the per protocol population. Moxifloxacin was noninferior to amoxicillin/clavulanic acid at the primary end-point (111 (20.6%) out of 538, versus 114 (22.0%) out of 518, respectively; 95% CI -5.89-3.83%). In patients with confirmed bacterial AECOPD, moxifloxacin led to significantly lower clinical failure rates than amoxicillin/clavulanic acid (in the intent-to-treat with pathogens, 62 (19.0%) out of 327 versus 85 (25.4%) out of 335, respectively; p=0.016). Confirmed bacterial eradication at end of therapy was associated with higher clinical cure rates at 8 weeks post-therapy overall (p=0.0014) and for moxifloxacin (p=0.003). Patients treated with oral corticosteroids had more severe disease and higher failure rates. The MAESTRAL study showed that moxifloxacin was as effective as amoxicillin/clavulanic acid in the treatment of outpatients with AECOPD. Both therapies were well tolerated. C1 [Wilson, Robert] Royal Brompton Hosp, Host Def Unit, London SW3 6NP, England. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Alder, Jeff; Haverstock, Daniel] Bayer HealthCare Pharmaceut, Montville, NJ USA. [Sethi, Sanjay] SUNY Buffalo, Div Pulm Crit Care & Sleep Med, Buffalo, NY 14260 USA. [Miravitlles, Marc] Hosp Clin Barcelona, Ciber Enfermedades Resp CIBERES, IDIBAPS, Barcelona, Spain. [Arvis, Pierre] Bayer HealthCare, Loos, France. [Trajanovic, Mila] Bayer Inc, Toronto, ON, Canada. RP Wilson, R (reprint author), Royal Brompton Hosp, Host Def Unit, Sydney St, London SW3 6NP, England. EM r.wilson@rbht.nhs.uk OI Miravitlles, Marc/0000-0002-9850-9520 FU Bayer HealthCare Pharmaceuticals AG, Berlin, Germany; NIHR Respiratory Disease Biomedical Research Unit; Bayer HealthCare FX This study was sponsored by Bayer HealthCare Pharmaceuticals AG, Berlin, Germany. R. Wilson was supported by the NIHR Respiratory Disease Biomedical Research Unit.; Highfield Communication Consultancy, Oxford, UK, funded by Bayer HealthCare, provided editorial support in the development of this paper. All analyses were carried out by the study sponsor and the Data Review Committee was responsible for validating all clinical failure data. The authors thank G. Farago (Bayer Inc., Toronto, ON, Canada), study manager, for excellent and dedicated support throughout the trial and R. Kay (RK Statistics Ltd, Bakewell, UK) for independent statistical assessment. They are also grateful to all physicians who enrolled patients in the study; a full list is given in the online supplementary material. NR 52 TC 33 Z9 36 U1 1 U2 3 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 EI 1399-3003 J9 EUR RESPIR J JI Eur. Resp. J. PD JUL PY 2012 VL 40 IS 1 BP 17 EP 27 DI 10.1183/09031936.00090311 PG 11 WC Respiratory System SC Respiratory System GA 985RS UT WOS:000307287500007 PM 22135277 ER PT J AU Thase, ME AF Thase, Michael E. TI Social Skills Training for Depression and Comparative Efficacy Research: A 30-Year Retrospective SO BEHAVIOR MODIFICATION LA English DT Article DE social skills training; depression; major depressive disorder; comparative efficacy ID COGNITIVE-BEHAVIOR THERAPY; UNIPOLAR DEPRESSION; MAJOR DEPRESSION; PHARMACOTHERAPY; PSYCHOTHERAPY AB By the late 1970s it was clear that cognitive and behavioral therapies were promising alternatives to antidepressant medications for treatment of depressed outpatients. One such model of therapy, Social Skills Training, was developed by Michel Hersen and his colleagues specifically for treatment of depressed women. Professor Hersen and his colleagues obtained funding from the National Institute of Mental Health to conduct the first well-controlled randomized trial of this intervention, contrasting Social Skills Training, in combination with either placebo or active amitriptyline, against two active standards: amitriptyline alone and time-limited, psychodynamic psychotherapy in combination with placebo. The results of this study suggested that Social Skills Training (plus placebo) was at least as effective as amitriptyline alone or psychodynamic psychotherapy (plus placebo), with superior mode-specific effects on measures of social skill. The current narrative, which provides an autobiographical perspective of four critical years (1980-1984) in the early career of the author that were intertwined with the conduct and completion of this clinical trial, is an homage to Professor Hersen's talents as a supervisor, researcher, and mentor. C1 [Thase, Michael E.] Univ Penn, Perelman Sch Med, Mood & Anxiety Sect, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Thase, Michael E.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. RP Thase, ME (reprint author), Univ Penn, Perelman Sch Med, Mood & Anxiety Sect, 3535 Market St,Suite 670, Philadelphia, PA 19104 USA. EM thase@mail.med.upenn.edu NR 20 TC 1 Z9 2 U1 2 U2 15 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-4455 J9 BEHAV MODIF JI Behav. Modificat. PD JUL PY 2012 VL 36 IS 4 SI SI BP 545 EP 557 DI 10.1177/0145445512445610 PG 13 WC Psychology, Clinical SC Psychology GA 986IO UT WOS:000307335500009 PM 22718283 ER PT J AU Gros, DF Price, M Strachan, M Yuen, EK Milanak, ME Acierno, R AF Gros, Daniel F. Price, Matthew Strachan, Martha Yuen, Erica K. Milanak, Melissa E. Acierno, Ron TI Behavioral Activation and Therapeutic Exposure: An Investigation of Relative Symptom Changes in PTSD and Depression During the Course of Integrated Behavioral Activation, Situational Exposure, and Imaginal Exposure Techniques SO BEHAVIOR MODIFICATION LA English DT Article DE behavioral activation and therapeutic exposure; BA-TE; depression; PTSD; comorbidity; transdiagnostic ID POSTTRAUMATIC-STRESS-DISORDER; PROLONGED EXPOSURE; MAJOR DEPRESSION; RANDOMIZED-TRIAL; PRIMARY-CARE; COMORBIDITY; PREVALENCE; COMMUNITY; VETERANS; VICTIMS AB Effectiveness of exposure therapy for posttraumatic stress disorder (PTSD) may be adversely influenced by comorbid disorders. The present study investigated behavioral activation and therapeutic exposure (BA-TE), a new integrated treatment designed specifically for comorbid symptoms of PTSD and depression. Combat veterans with PTSD (N = 117) completed eight sessions of BA-TE that included two phases of treatment: (a) behavioral activation (BA) in which some activities involved situational exposures and (b) BA and situational exposures with imaginal exposures. Findings supported improvements in symptoms of PTSD, and overlapping symptoms of PTSD and depression, but not in nonoverlapping symptoms of depression. The findings also demonstrated a relatively consistent rate of change in PTSD and depression symptoms during BA-TE, despite the addition of imaginal exposures midway through the treatment. Together, these findings provide preliminary support for BA-TE as a treatment for PTSD and depression, and highlight the utility of transdiagnostic treatments in addressing comorbidity and symptom overlap. C1 [Gros, Daniel F.] Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv 116, Charleston, SC 29401 USA. [Milanak, Melissa E.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Natl Crime Victims Ctr, Charleston, SC USA. [Acierno, Ron] Ralph H Johnson Vet Affairs Med Ctr, Posttraumat Stress Disorder Clin Team, Charleston, SC 29401 USA. RP Gros, DF (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu FU NIDA NIH HHS [R01 DA030143] NR 54 TC 27 Z9 28 U1 7 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-4455 J9 BEHAV MODIF JI Behav. Modificat. PD JUL PY 2012 VL 36 IS 4 SI SI BP 580 EP 599 DI 10.1177/0145445512448097 PG 20 WC Psychology, Clinical SC Psychology GA 986IO UT WOS:000307335500011 PM 22679240 ER PT J AU Volpe, EM Hardie, TL Cerulli, C AF Volpe, Ellen M. Hardie, Thomas L. Cerulli, Catherine TI Associations among Depressive Symptoms, Dating Violence, and Relationship Power in Urban, Adolescent Girls SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING LA English DT Article DE dating violence; depression; relationship power; adolescent; aggression ID INTIMATE PARTNER VIOLENCE; PHYSICAL HEALTH CONSEQUENCES; SEXUAL RELATIONSHIP POWER; ROMANTIC RELATIONSHIPS; GENDER SYMMETRY; UNITED-STATES; MENTAL-HEALTH; CES-D; RISK; AGGRESSION AB Objective To explore the associations among dating violence (DV), aggression, relationship power, and depressive symptoms. Design A cross-sectional survey secondary analysis. Setting An urban, school based health center, October, 2009 through May, 2009. Participants Low income, adolescent girls (n = 155), ages 1418. Methods Descriptive and bivariate analyses were conducted to illustrate patterns and associations among variables. Key variables included depressive symptoms, DV victimization and aggression, and relationship power. We used mediation analyses to determine the direct and indirect effects among variables. Results Both DV victimization and aggression were reported frequently. Furthermore, DV victimization had a significant direct effect on depression and an indirect effect through relationship power. Depressive symptoms and relationship power were associated with DV aggression. Although relationship power did have a significant inverse effect on depressive symptoms, it was not through DV aggression. Conclusions Complex associations remain between mental health and DV; however, relationship power partially accounts for DV victimization's effect on depressive symptoms. Depressive symptoms are associated with DV victimization and aggression; therefore, nurses should address relationship power in clinical and community interventions. C1 [Volpe, Ellen M.] Univ Penn, Ctr Hlth Equ Res, Sch Nursing, Philadelphia, PA 19104 USA. [Volpe, Ellen M.] Univ Penn, Ctr Global Womans Hlth, Sch Nursing, Philadelphia, PA 19104 USA. Univ Penn, Ctr Hlth Equ Res, Sch Nursing, Philadelphia, PA 19104 USA. [Hardie, Thomas L.] Drexel Univ, Coll Nursing & Hlth Profess, Philadelphia, PA 19104 USA. [Cerulli, Catherine] Univ Rochester, Med Ctr, Dept Psychiat, Lab Interpersonal Violence & Victimizat, Rochester, NY 14642 USA. RP Volpe, EM (reprint author), Univ Penn, Ctr Hlth Equ Res, Sch Nursing, 418 Curie Blvd,233L, Philadelphia, PA 19104 USA. EM evolpe@nursing.upenn.edu RI Hardie, Thomas/J-7776-2012 OI Hardie, Thomas/0000-0002-4547-7991 FU National Institutes of Health [F31MH082646-01A2]; National Institute of Nursing Research [T32NR 007100]; Sigma Theta Tau; Epsilon Xi Chapter; Susan B. Anthony Institute FX Supported in part by grants from the National Institutes of Health, the National Institutes of Mental Health (F31MH082646-01A2), the National Institute of Nursing Research (T32NR 007100), Sigma Theta Tau, Epsilon Xi Chapter, and Susan B. Anthony Institute. The authors thank Drs. Morrison-Beedy, Tuttle, Fals-Stewart, and Sommers. NR 73 TC 7 Z9 7 U1 2 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-2175 J9 JOGNN-J OBST GYN NEO JI JOGNN PD JUL-AUG PY 2012 VL 41 IS 4 BP 506 EP 518 DI 10.1111/j.1552-6909.2012.01384.x PG 13 WC Nursing; Obstetrics & Gynecology SC Nursing; Obstetrics & Gynecology GA 974ZN UT WOS:000306476300007 PM 22697267 ER PT J AU Li, CY Zeliadt, SB Hall, IJ Smith, JL Ekwueme, DU Moinpour, CM Penson, DF Thompson, IM Keane, TE Ramsey, SD AF Li, Chunyu Zeliadt, Steven B. Hall, Ingrid J. Smith, Judith Lee Ekwueme, Donatus U. Moinpour, Carol M. Penson, David F. Thompson, Ian M. Keane, Thomas E. Ramsey, Scott D. TI Willingness to Pay for Prostate Cancer Treatment among Patients and Their Family Members at 1 Year After Diagnosis SO VALUE IN HEALTH LA English DT Article DE family member; patient; prostate cancer; side effect; willingness to pay ID QUALITY-OF-LIFE; TREATMENT DECISION-MAKING; SEER-MEDICARE DATA; CARE; COSTS; TIME; MEN; SURGERY; COUPLES AB Objectives: To explore an alternative approach to quantifying the burden of side effects at 1 year after treatment for prostate cancer among both patients and their partners. Methods: We analyzed data from 75 couples in the Family and Cancer Therapy Selection study. Paired patients and family members were independently asked about their willingness to pay (WTP) for a hypothetical new treatment that cures prostate cancer without side effects if they could reconsider their treatment decision by indicating the maximum amount they would be willing to pay given 11 separate "bids" ranging from $0 to $1500 per month. Descriptive and regression analyses were conducted for patients and family members controlling for sociodemographic characteristics and health status; Spearman correlations were also examined. Results: Among 75 couples analyzed, the income-adjusted mean WTP estimates per month were $400.8 (standard error [SE] $54.3) for patients and $650.2 (SE 72.2) for family members. The WTP between patients and family members was correlated (Pearson rho 0.30; P = 0.01). After adjusting for covariates, the adjusted mean WTP per month was $588.1 (SE 65.77) for patients and $819.4 (SE 74.33) for family members. Wanting to avoid side effects at baseline predicted higher WTP for patients (P = 0.010). Experiencing sexual side effects was predictive of higher WTP for family members (P = 0.047). Conclusions: Fairly high WTP amounts for a hypothetical treatment without side effects suggests that patients and their partners are experiencing important burdens 1 year after treatment. The higher amounts partners are willing to pay and the correlation with sexual side effects suggest that they are perceptive of significant treatment burdens. C1 [Li, Chunyu; Hall, Ingrid J.; Smith, Judith Lee; Ekwueme, Donatus U.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. [Zeliadt, Steven B.; Moinpour, Carol M.; Ramsey, Scott D.] Fred Hutchinson Canc Res Ctr, Publ Hlth Serv Div, Seattle, WA 98104 USA. [Zeliadt, Steven B.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. [Penson, David F.] Vanderbilt Univ, Med Ctr, Vanderbilt Inst Med & Publ Hlth, Nashville, TN USA. [Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Keane, Thomas E.] Med Univ S Carolina, Urol Serv, Charleston, SC 29425 USA. RP Li, CY (reprint author), Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Highway NE,MS K-55, Atlanta, GA 30341 USA. EM Cli11@cdc.gov FU Centers for Disease Control and Prevention, Prevention Research Centers Program, through the University of Washington Health Promotion Research Center [SIP 25-04 1-U48-DP-000050] FX This study was supported by Cooperative Agreement Number SIP 25-04 1-U48-DP-000050 from the Centers for Disease Control and Prevention, Prevention Research Centers Program, through the University of Washington Health Promotion Research Center. The findings and conclusions in this study are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. NR 35 TC 4 Z9 4 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD JUL-AUG PY 2012 VL 15 IS 5 BP 716 EP 723 DI 10.1016/j.jval.2012.03.003 PG 8 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 986AH UT WOS:000307311100015 PM 22867781 ER PT J AU Duvvuri, U Shiwarski, DJ Xiao, D Bertrand, C Huang, X Edinger, RS Rock, JR Harfe, BD Henson, BJ Kunzelmann, K Schreiber, R Seethala, RS Egloff, AM Chen, X Lui, VW Grandis, JR Gollin, SM AF Duvvuri, Umamaheswar Shiwarski, Daniel J. Xiao, Dong Bertrand, Carol Huang, Xin Edinger, Robert S. Rock, Jason R. Harfe, Brian D. Henson, Brian J. Kunzelmann, Karl Schreiber, Rainer Seethala, Raja S. Egloff, Ann Marie Chen, Xing Lui, Vivian W. Grandis, Jennifer R. Gollin, Susanne M. TI TMEM16A Induces MAPK and Contributes Directly to Tumorigenesis and Cancer Progression SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; ACTIVATED CHLORIDE CHANNEL; CA2+-ACTIVATED CL-CHANNELS; TRANSMEMBRANE CONDUCTANCE REGULATOR; GASTROINTESTINAL STROMAL TUMORS; ORAL-CANCER; TRANSCRIPTOME ANALYSIS; INTERSTITIAL-CELLS; EPITHELIAL-CELLS; 11Q13 AMPLICON AB Frequent gene amplification of the receptor-activated calcium-dependent chloride channel TMEM16A (TAOS2 or ANO1) has been reported in several malignancies. However, its involvement in human tumorigenesis has not been previously studied. Here, we show a functional role for TMEM16A in tumor growth. We found TMEM16A overexpression in 80% of head and neck squamous cell carcinoma (SCCHN), which correlated with decreased overall survival in patients with SCCHN. TMEM16A overexpression significantly promoted anchorage-independent growth in vitro, and loss of TMEM16A resulted in inhibition of tumor growth both in vitro and in vivo. Mechanistically, TMEM16A-induced cancer cell proliferation and tumor growth were accompanied by an increase in extracellular signal-regulated kinase (ERK) 1/2 activation and cyclin D1 induction. Pharmacologic inhibition of MEK/ERK and genetic inactivation of ERK1/2 (using siRNA and dominant-negative constructs) abrogated the growth effect of TMEM16A, indicating a role for mitogen-activated protein kinase (MAPK) activation in TMEM16A-mediated proliferation. In addition, a developmental small-molecule inhibitor of TMEM16A, T16A-inh01 (A01), abrogated tumor cell proliferation in vitro. Together, our findings provide a mechanistic analysis of the tumorigenic properties of TMEM16A, which represents a potentially novel therapeutic target. The development of small-molecule inhibitors against TMEM16A may be clinically relevant for treatment of human cancers, including SCCHN. Cancer Res; 72(13); 3270-81. (C) 2012 AACR. C1 [Duvvuri, Umamaheswar; Shiwarski, Daniel J.; Xiao, Dong; Egloff, Ann Marie; Chen, Xing; Lui, Vivian W.; Grandis, Jennifer R.; Gollin, Susanne M.] Univ Pittsburgh, Med Ctr, Dept Otolaryngol, Pittsburgh, PA 15213 USA. [Bertrand, Carol] Univ Pittsburgh, Med Ctr, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. [Seethala, Raja S.; Gollin, Susanne M.] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA 15213 USA. [Grandis, Jennifer R.] Univ Pittsburgh, Med Ctr, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA. [Edinger, Robert S.] Univ Pittsburgh, Med Ctr, Renal & Electrolyte Div, Pittsburgh, PA 15213 USA. [Huang, Xin] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA. [Huang, Xin] Univ Pittsburgh, Med Ctr, Magee Womens Res Inst, Pittsburgh, PA 15213 USA. [Duvvuri, Umamaheswar] Vet Affairs Pittsburgh Hlth Syst, Pittsburgh, PA USA. [Henson, Brian J.; Gollin, Susanne M.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. [Henson, Brian J.; Gollin, Susanne M.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Rock, Jason R.] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. [Harfe, Brian D.] Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL USA. [Harfe, Brian D.] Univ Florida, Genet Inst, Gainesville, FL USA. [Kunzelmann, Karl; Schreiber, Rainer] Univ Regensburg, Dept Physiol, Regensburg, Germany. RP Duvvuri, U (reprint author), Univ Pittsburgh, Med Ctr, Dept Otolaryngol, 200 Lothrop St,W948 Biomed Sci Tower, Pittsburgh, PA 15213 USA. EM duvvuriu@upmc.edu RI Lui, Vivian/I-5458-2016 OI Kunzelmann, Karl/0000-0002-4583-7037; Shiwarski, Daniel/0000-0001-6978-303X FU Head and Neck Cancer SPORE grant [NIH P50CA097190]; Department of Otolaryngology; Deutsche Krebshilfe Projekt [109438]; CPPF; [P30CA047904] FX This work was supported by the Head and Neck Cancer SPORE grant (NIH P50CA097190 J.R. Grandis), through a Veterans Administration CDA; CPPF (U. Duvvuri) and start-up funds from the Department of Otolaryngology (U. Duvvuri). The molecular cytogenetic studies were carried out in the University of Pittsburgh Cancer Institute Cytogenetics Facility, supported in part by P30CA047904 to N.E. Davidson/R.B. Herberman/S.M. Gollin. KK was supported by Deutsche Krebshilfe Projekt 109438. NR 48 TC 96 Z9 102 U1 1 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2012 VL 72 IS 13 BP 3270 EP 3281 DI 10.1158/0008-5472.CAN-12-0475-T PG 12 WC Oncology SC Oncology GA 986OB UT WOS:000307350700017 PM 22564524 ER PT J AU Krassner, A Dhaliwal, G Baudendistel, TE AF Krassner, Alexander Dhaliwal, Gurpreet Baudendistel, Thomas E. TI Overcome by weakness SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID NOCARDIOSIS C1 [Krassner, Alexander; Baudendistel, Thomas E.] Kaiser Oakland Med Ctr, Dept Med, Oakland, CA 94611 USA. [Dhaliwal, Gurpreet] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. RP Krassner, A (reprint author), Kaiser Oakland Med Ctr, Dept Med, 280 W MacArthur Blvd, Oakland, CA 94611 USA. EM alexander.d.krassner@kp.org NR 7 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD JUL-AUG PY 2012 VL 7 IS 6 BP 513 EP 516 DI 10.1002/jhm.1930 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 982NW UT WOS:000307053200010 PM 22407607 ER PT J AU Camacho-Soto, A Sowa, GA Perera, S Weiner, DK AF Camacho-Soto, Alejandra Sowa, Gwendolyn A. Perera, Subashan Weiner, Debra K. TI Fear Avoidance Beliefs Predict Disability in Older Adults With Chronic Low Back Pain SO PM&R LA English DT Article ID GAIT SPEED; PHYSICAL FUNCTION; RISK-FACTORS; QUESTIONNAIRE; PEOPLE; PREVALENCE; DEPRESSION; SURVIVAL; DECLINE; SCALE AB Objectives: To determine whether fear avoidance beliefs (FABs) in older adults with chronic low back pain (CLBP) are significantly associated with gait speed decline and/or self-report of greater disability. Design: Cross-sectional analysis. Setting: An academic medical center (single site). Participants: Two hundred English-speaking participants aged 65 years and older with CLBP every day or almost every day of moderate or greater intensity for >= 3 months. Main Outcome Measurements: The physical activity portion of the FAB questionnaire assessed FABs. Disability was measured with gait speed and the Roland Morris Questionnaire. Covariates measured included age, gender, body mass index, chronic disease (Cumulative Illness Rating Scale), depression (Geriatric Depression Scale), and pain (McGill Pain Questionnaire Short Form). Results: FABs were significantly associated with the Roland Morris Questionnaire (P < .0001) and gait speed (P = .002) after controlling for all covariates. Conclusion: FABs related to physical activity in older adults with CLBP were significantly associated with both self-reported and performance-based disability after controlling for known confounders. Previous studies have reported similar associations between self-reported measures of disabling back pain and FABs. Ours is the first study to examine the relationship between FAB and gait speed, a powerful predictor of morbidity and mortality. Future work should examine whether targeting fear avoidance in addition to other psychosocial measures in older adults with CLBP improves gait speed and functional independence. PM R 2012;4:493-497 C1 [Camacho-Soto, Alejandra; Sowa, Gwendolyn A.] Univ Pittsburgh, Sch Med, Dept Med & Phys Med & Rehabil, Pittsburgh, PA USA. [Perera, Subashan] Univ Pittsburgh, Sch Med, Dept Biostat & Med, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA. [Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Camacho-Soto, A (reprint author), 333 E Ontario 18048, Chicago, IL 60611 USA. EM acamachosoto@gmail.com RI Perera, Subashan/D-7603-2014 FU Pittsburgh Claude D. Pepper Older Americans Independence Center [AG024827]; National Center for Complementary and Alternative Medicine [R01 AT000985]; National Institute on Aging, National Institutes of Health, Pitt Clinical Research Training Geriatrics/Gerontology [AG21885] FX Research support: Pittsburgh Claude D. Pepper Older Americans Independence Center, AG024827, grant R01 AT000985 from the National Center for Complementary and Alternative Medicine and the National Institute on Aging, National Institutes of Health, Pitt Clinical Research Training Geriatrics/Gerontology, AG21885 NR 31 TC 13 Z9 13 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD JUL PY 2012 VL 4 IS 7 BP 493 EP 497 DI 10.1016/j.pmrj.2012.01.017 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 981RR UT WOS:000306987800005 PM 22516436 ER PT J AU Schmidt, MG Attaway, HH Sharpe, PA John, J Sepkowitz, KA Morgan, A Fairey, SE Singh, S Steed, LL Cantey, JR Freeman, KD Michels, HT Salgado, CD AF Schmidt, Michael G. Attaway, Hubert H. Sharpe, Peter A. John, Joseph, Jr. Sepkowitz, Kent A. Morgan, Andrew Fairey, Sarah E. Singh, Susan Steed, Lisa L. Cantey, J. Robert Freeman, Katherine D. Michels, Harold T. Salgado, Cassandra D. TI Sustained Reduction of Microbial Burden on Common Hospital Surfaces through Introduction of Copper SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; ACUTE-CARE HOSPITALS; ENVIRONMENTAL CONTAMINATION; CLOSTRIDIUM-DIFFICILE; INFECTION; SURVIVAL; RISK; ACQUISITION; HYGIENE; UNIT AB The contribution of environmental surface contamination with pathogenic organisms to the development of health care-associated infections (HAI) has not been well defined. The microbial burden (MB) associated with commonly touched surfaces in intensive care units (ICUs) was determined by sampling six objects in 16 rooms in ICUs in three hospitals over 43 months. At month 23, copper-alloy surfaces, with inherent antimicrobial properties, were installed onto six monitored objects in 8 of 16 rooms, and the effect that this application had on the intrinsic MB present on the six objects was assessed. Census continued in rooms with and without copper for an additional 21 months. In concert with routine infection control practices, the average MB found for the six objects assessed in the clinical environment during the preintervention phase was 28 times higher (6,985 CFU/100 cm(2); n = 3,977 objects sampled) than levels proposed as benign immediately after terminal cleaning (< 250 CFU/100 cm(2)). During the intervention phase, the MB was found to be significantly lower for both the control and copper-surfaced objects. Copper was found to cause a significant (83%) reduction in the average MB found on the objects (465 CFU/100 cm(2); n = 2714 objects) compared to the controls (2,674 CFU/100 cm(2); n = 2,831 objects [P < 0.0001]). The introduction of copper surfaces to objects formerly covered with plastic, wood, stainless steel, and other materials found in the patient care environment significantly reduced the overall MB on a continuous basis, thereby providing a potentially safer environment for hospital patients, health care workers (HCWs), and visitors. C1 [Schmidt, Michael G.; Attaway, Hubert H.; Morgan, Andrew; Fairey, Sarah E.] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Sharpe, Peter A.] Irwin P Sharpe & Associates, W Orange, NJ USA. [John, Joseph, Jr.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Sepkowitz, Kent A.; Singh, Susan] Mem Sloan Kettering Canc Ctr, Dept Med, Div Infect Dis, New York, NY 10021 USA. [Steed, Lisa L.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Cantey, J. Robert; Salgado, Cassandra D.] Med Univ S Carolina, Dept Med, Div Infect Dis, Charleston, SC 29425 USA. [Freeman, Katherine D.] Yeshiva Univ, Albert Einstein Coll Med, Montefiore Med Ctr, Dept Epidemiol & & Populat Hlth, Bronx, NY USA. [Michels, Harold T.] Copper Dev Assoc, New York, NY USA. RP Schmidt, MG (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. EM schmidtm@musc.edu OI Schmidt, Michael G/0000-0002-7794-7265 FU U.S. Army Material Command [W81XWH-07-C-0053] FX This work was supported by the U.S. Army Material Command (contract W81XWH-07-C-0053). NR 40 TC 56 Z9 56 U1 2 U2 21 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 JUL PY 2012 VL 50 IS 7 BP 2217 EP 2223 DI 10.1128/JCM.01032-12 PG 7 WC Microbiology SC Microbiology GA 986RB UT WOS:000307360800008 PM 22553242 ER PT J AU O'Horo, JC Jones, A Stemke, M Harper, C Safdar, N AF O'Horo, John C. Jones, Amy Stemke, Matthew Harper, Christopher Safdar, Nasia TI Molecular Techniques for Diagnosis of Clostridium difficile Infection: Systematic Review and Meta-analysis SO MAYO CLINIC PROCEEDINGS LA English DT Review ID REAL-TIME PCR; POLYMERASE-CHAIN-REACTION; MEDIATED ISOTHERMAL AMPLIFICATION; TOXIN-B GENE; STOOL SAMPLES; ENZYME-IMMUNOASSAY; RAPID DETECTION; PROSPECTIVE MULTICENTER; LABORATORY DIAGNOSIS; TESTING ALGORITHMS AB Objective: To assess the usefulness of 2 rapid molecular diagnostic techniques, polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP), in Clostridium difficile infection (CDI). Methods: We conducted a systematic review and meta-analysis to evaluate the accuracy of PCR and LAMP in diagnosis of CDI, including studies that used toxigenic culture or cytotoxicity assay as reference standard. Results: A search of PubMed and CinAHL medical databases yielded 25 PCR studies, including 11,801 samples that met inclusion criteria and 6 heterogeneous studies that evaluated LAMP. With toxigenic culture as a standard, pooled sensitivity was 0.92 (95% confidence interval [Cl], 0.91-0.94); specificity, 0.94 (95% Cl, 0.94-0.95); and diagnostic odds ratio, 378 (95% Cl, 260-547). With cytotoxicity as a standard, pooled sensitivity was 0.87 (95% Cl, 0.84-0.90); specificity, 0.97 (95% Cl, 0.97-0.98); and diagnostic odds ratio, 370 (95% Cl, 226-606). Conclusion: Polymerase chain reaction is a highly accurate test for identifying CDI. Heterogeneity in LAMP studies did not allow meta-analysis; however, further research into this promising method is warranted. (C) 2012 Mayo Foundation for Medical Education and Research Mayo Clin Proc. 2012:87(7):643-651 C1 [Safdar, Nasia] Univ Wisconsin Hosp & Clin, Sect Infect Dis, Dept Med, Madison, WI 53705 USA. [O'Horo, John C.] Aurora UW Med Grp, Dept Grad Med Educ, Milwaukee, WI USA. [Safdar, Nasia] Univ Wisconsin, Sch Med & Publ Hlth, William S Middleton Mem Vet Hosp, Madison, WI USA. RP Safdar, N (reprint author), Univ Wisconsin Hosp & Clin, Sect Infect Dis, Dept Med, MFCB 5221, 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 64 TC 29 Z9 31 U1 0 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JUL PY 2012 VL 87 IS 7 BP 643 EP 651 DI 10.1016/j.mayocp.2012.02.024 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 980DC UT WOS:000306872800007 PM 22766084 ER PT J AU Ruff, RL Rutecki, P AF Ruff, Robert L. Rutecki, Paul TI Faster, slower, but never better Mutations of the skeletal muscle acetylcholine receptor SO NEUROLOGY LA English DT Editorial Material ID NICOTINIC RECEPTOR; AGONIST BINDING; SUBUNIT C1 [Ruff, Robert L.] Case Western Reserve Univ, Dept Neurol, Neurol Serv, Louis Stokes Cleveland Dept Vet Affairs Med Ctr, Cleveland, OH 44106 USA. [Rutecki, Paul] Univ Wisconsin, Dept Neurol, William S Middleton Mem Vet Hosp, Neurol Serv, Madison, WI 53706 USA. RP Ruff, RL (reprint author), Case Western Reserve Univ, Dept Neurol, Neurol Serv, Louis Stokes Cleveland Dept Vet Affairs Med Ctr, Cleveland, OH 44106 USA. EM robert.ruff1@va.gov NR 10 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 2012 VL 79 IS 5 BP 404 EP 405 DI 10.1212/WNL.0b013e31825b5bee PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 984AY UT WOS:000307161100009 PM 22592368 ER PT J AU Mohr, DC Lovera, J Brown, T Cohen, B Neylan, T Henry, R Siddique, J Jin, L Daikh, D Pelletier, D AF Mohr, David C. Lovera, Jesus Brown, Ted Cohen, Bruce Neylan, Thomas Henry, Roland Siddique, Juned Jin, Ling Daikh, David Pelletier, Daniel TI A randomized trial of stress management for the prevention of new brain lesions in MS SO NEUROLOGY LA English DT Article ID TELEPHONE-ADMINISTERED PSYCHOTHERAPY; COGNITIVE-BEHAVIORAL THERAPY; REMITTING MULTIPLE-SCLEROSIS; PSYCHOLOGICAL STRESS; DOUBLE-BLIND; LIFE EVENTS; DEPRESSION; METAANALYSIS; DISABILITY; SYMPTOMS AB Objectives: This trial examined the efficacy of a stress management program in reducing neuroimaging markers of multiple sclerosis (MS) disease activity. Methods: A total of 121 patients with relapsing forms of MS were randomized to receive stress management therapy for MS (SMT-MS) or a wait-list control condition. SMT-MS provided 16 individual treatment sessions over 24 weeks, followed by a 24-week post-treatment follow-up. The primary outcome was the cumulative number of new gadolinium-enhancing (Gd+) brain lesions on MRI at weeks 8, 16, and 24. Secondary outcomes included new or enlarging T2 MRI lesions, brain volume change, clinical exacerbation, and stress. Results: SMT-MS resulted in a reduction in cumulative Gd+ lesions (p = 0.04) and greater numbers of participants remained free of Gd+ lesions during the treatment (76.8% vs 54.7%, p = 0.02), compared to participants receiving the control treatment. SMT-MS also resulted in significantly reduced numbers of cumulative new T2 lesions (p = 0.005) and a greater number of participants remaining free of new T2 lesions (69.5% vs 42.7%, p = 0.006). These effects were no longer detectable during the 24-week post-treatment follow-up period. Conclusions: This trial indicates that SMT-MS may be useful in reducing the development of new MRI brain lesions while patients are in treatment. Classification of evidence: This study provides Class I evidence that SMT-MS, a manualized stress management therapy program, reduced the number of Gd+ lesions in patients with MS during a 24-week treatment period. This benefit was not sustained beyond 24 weeks, and there were no clinical benefits. C1 [Mohr, David C.; Cohen, Bruce; Siddique, Juned; Jin, Ling] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Lovera, Jesus] Louisiana State Univ, Hlth Sci Ctr, Sch Med, New Orleans, LA USA. [Brown, Ted] Evergreen Hosp Med Ctr, Seattle, WA USA. [Neylan, Thomas; Henry, Roland; Daikh, David; Pelletier, Daniel] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Neylan, Thomas; Daikh, David] San Francisco VA Med Ctr, San Francisco, CA USA. RP Mohr, DC (reprint author), Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. EM d-mohr@northwestern.edu FU NIH; Lilly Inc.; Acorda; Teva Neuroscience; Northwestern University from Biogen-Idec; EMD Serono; Novartis; Roche; CME program (through Northwestern University) from Teva Neuroscience; Actelion; Glaxo Smith Kline; National Institutes of Health, NINDS [R01NS062885]; NICHD [R01-HD043323] FX D. Mohr receives research funding from the NIH. J. Lovera has honoraria for consulting and speaking from Biogen Idec, Serono, and Teva. T. Brown has served as a consultant for Acorda, Biogen, EMD Serono, and Teva Neuroscience and has received honoraria from Acorda, Pfizer, and Teva and has been funded by research grants from Lilly Inc., Acorda, and Teva Neuroscience. B. Cohen has received payments for consulting or speaking honoraria from Accorda, Astellis, Bayer, Biogen-Idec, EMD Serono, Genentech, Novartis, Pfizer, and Teva Neuroscience. He has received research support through Northwestern University from Biogen-Idec, EMD Serono, Novartis, Roche, and an Unrestricted Educational Grant in support of a CME program (through Northwestern University) from Teva Neuroscience. T. Neylan has received research support (supply of investigative medication) from Actelion and Glaxo Smith Kline. R. Henry, J. Siddique, L. Jin, and D. Daikh report no disclosures. D. Pelletier receives research support from the National Institutes of Health, NINDS (R01NS062885). Go to Neurology.org for full disclosures.; This study was funded by NICHD grant R01-HD043323. NR 33 TC 34 Z9 34 U1 5 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 2012 VL 79 IS 5 BP 412 EP 419 DI 10.1212/WNL.0b013e3182616ff9 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 984AY UT WOS:000307161100011 PM 22786596 ER PT J AU Even, C Weintraub, D AF Even, Christian Weintraub, Daniel TI Is depression in Parkinson's Disease (PD) a specific entity? SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Review DE Depression; Parkinson's Disease; Mood disorders ID SEROTONIN TRANSPORTER GENE; PLACEBO-CONTROLLED TRIAL; MAJOR DEPRESSION; FUNCTIONAL POLYMORPHISM; STRIATAL DOPAMINE; ALLELIC VARIATION; INCREASED RISK; DOUBLE-BLIND; LATE-LIFE; SYMPTOMS AB Background: Clinical lore and research have suggested for a long time that depression and PD are closely related. We examined the validity of depression associated with PD (dPD) as a specific subtype of depression according to face validity, descriptive validity, construct validity and predictive validity. Methods: The English literature was reviewed after searching the MEDLINE database up to June 2010. Results: There appears to be three possible subtypes of comorbid depression: 1) patients who would have been depressed even if they had no PD (nonspecific-casual comorbid dPD), 2) patients who would have been depressed if they had had another disabling medical illness (nonspecific-reactive comorbid dPD) 3) those for which depression is directly related to the underlying pathophysiology of PD (specific comorbid dPD). These latter patients may more often present with particular clinical characteristics (descriptive validity): absence of history of depression or only within 5 years prior to onset of PD, absence of guilty thoughts and self-blame, absence of suicidal behavior, right-sided onset. However, dPD is only partly responsive to dopamine replacement and cannot be solely explained by dopamine deficiency. Other neurotransmitter systems are affected in PD and are involved in the pathophysiology of dPD. Their relative involvement however may differ from that in idiopathic depression (i.e.: lesser involvement of serotonergic systems). Limitations: Therapeutic data are limited to few controlled trials. Conclusions: Further research may allow differential diagnosis between dPD subtypes (i.e.: those who do and do not result from the underlying pathophysiological process of PD) and help inform treatment choice. (C) 2011 Elsevier B.V. All rights reserved. C1 [Even, Christian] Ctr Hosp St Anne, Clin Malad Mentales & Encephale, F-75674 Paris 14, France. [Even, Christian] Univ Paris 05, INSERM, U894, Ctr Psychiat & Neurosci, Paris, France. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr PADRECC, Philadelphia, PA USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. RP Even, C (reprint author), Ctr Hosp St Anne, Clin Malad Mentales & Encephale, 100 Rue Sante, F-75674 Paris 14, France. EM c.even@ch-sainte-anne.fr FU Sanofi-Synthelabo; Novartis; Boehringer-Ingelheim FX Dr Weintraub has received grants and honoraria from Sanofi-Synthelabo, Novartis and Boehringer-Ingelheim. NR 119 TC 7 Z9 7 U1 5 U2 23 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. PD JUL PY 2012 VL 139 IS 2 BP 103 EP 112 DI 10.1016/j.jad.2011.07.002 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 975TV UT WOS:000306535300001 PM 21794923 ER PT J AU Cunningham, MA Naga, OS Eudaly, JG Scott, JL Gilkeson, GS AF Cunningham, Melissa A. Naga, Osama S. Eudaly, Jackie G. Scott, Jennifer L. Gilkeson, Gary S. TI Estrogen receptor alpha modulates toll-like receptor signaling in murine lupus SO CLINICAL IMMUNOLOGY LA English DT Article DE Estrogen receptor alpha; Systemic lupus erythematosus; Dendritic cells; Toll-like receptors ID DENDRITIC CELL-DIFFERENTIATION; ANTIGEN-PRESENTING CELLS; BONE-MARROW; AUTOANTIBODY PRODUCTION; NEUROPSYCHIATRIC LUPUS; CEREBROSPINAL-FLUID; ERYTHEMATOSUS; EXPRESSION; PROMOTES; DISEASE AB Systemic lupus erythematosus (SLE) is a disease that disproportionately affects females. Despite significant research effort, the mechanisms underlying the female predominance in this disease are largely unknown. Previously, we showed that estrogen receptor alpha knockout (ER alpha KO) lupus prone female mice had significantly less pathologic renal disease and proteinuria, and significantly prolonged survival. Since autoantibody levels and number and percentage of BIT cells were not significantly impacted by ER alpha genotype, we hypothesized that the primary benefit of ERa deficiency in lupus nephritis was via modulation of the innate immune response. Using BMDCs and spleen cells/B cells from female wild-type or ER alpha KO mice, we found that ER alpha KO-derived cells have a significantly reduced inflammatory response after stimulation with TLR agonists. Our results indicate that the inflammatory response to TLR ligands is significantly impacted by the presence of ER alpha despite the absence of estradiot, and may partially explain the protective effect of ER alpha deficiency in lupus-prone animals. (C) 2012 Published by Elsevier Inc. C1 Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Hosp, Charleston, SC 29425 USA. RP Gilkeson, GS (reprint author), 96 Jonathan Lucas St,Suite 912,MSC637, Charleston, SC 29425 USA. EM gilkeson@musc.edu OI Cunningham, Melissa/0000-0002-9207-1986 FU NIAMS NIH HHS [T32 AR050958] NR 44 TC 13 Z9 13 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUL PY 2012 VL 144 IS 1 BP 1 EP 12 DI 10.1016/j.clim.2012.04.001 PG 12 WC Immunology SC Immunology GA 977PX UT WOS:000306678000001 PM 22659029 ER PT J AU Jacobs, RL Harper, N He, WJ Andrews, CP Rather, CG Ramirez, DA Ahuja, SK AF Jacobs, Robert L. Harper, Nathan He, Weijing Andrews, Charles P. Rather, Cynthia G. Ramirez, Daniel A. Ahuja, Sunil K. TI Responses to ragweed pollen in a pollen challenge chamber versus seasonal exposure identify allergic rhinoconjunctivitis endotypes SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Allergic diseases; environmental chamber; ragweed; endotypes ID VALIDATION; NASAL; RHINITIS; ASTHMA; ONSET; UNIT AB Background: The level of concordance between allergic symptoms induced on exposure to pollen in a pollen challenge chamber (PCC) versus the natural season is unknown. Objective: We sought to test the hypothesis that the symptom levels of allergic rhinoconjunctivitis elicited after out-of-season exposure to short ragweed in a PCC and during the natural season for giant ragweed pollen are highly correlated. Methods: Thirty-one ragweed-sensitive participants recorded symptoms for 15 days during the natural giant ragweed season in San Antonio, Texas. Twenty-six of these participants were challenged to short ragweed pollen in a PCC for 3 hours per day for up to 4 days. Results: In the PCC participants were dichotomized into those in whom low versus high levels of symptoms developed slowly or rapidly (ie, slow/low vs rapid/high). Each successive exposure visit associated with a progressive increase in symptom levels that approximated those experienced during the natural season. Hierarchic clustering identified 3 endotypes: endotypes I and II reflected concordantly low (n = 7) versus high (n = 14) total symptom scores (TSSs) in both the natural season and the PCC, respectively. Accordingly, the correlation between the TSSs recorded in the natural season and in the PCC for these 21 participants was very high. Although participants with endotype III (n = 5) had greater TSSs in the natural season than in the PCC, the degree of correlation between the TSSs remained high. Conclusions: Our findings affirm our hypothesis, underscore the high cross-reactivity between distinct pollens, and highlight the utility of the PCC to identify novel allergy endotypes that might have contrasting mechanistic underpinnings and potentially therapeutic responses. (J Allergy Clin Immunol 2012;130:122-7.) C1 [Jacobs, Robert L.; Andrews, Charles P.; Rather, Cynthia G.; Ramirez, Daniel A.] Biogen Res Chamber LLC, San Antonio, TX 78229 USA. [Harper, Nathan; He, Weijing; Ahuja, Sunil K.] S Texas Vet Hlth Care Syst, Vet Adm Ctr Personalized Med, San Antonio, TX USA. [Harper, Nathan; He, Weijing; 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. RP Jacobs, RL (reprint author), Biogen Res Chamber LLC, 8299 Fredericksburg Rd, San Antonio, TX 78229 USA. EM robert.jacobs7025@sbcglobal.net OI Andrews, Charles/0000-0002-8944-8404; Jacobs, Robert/0000-0002-2831-9086 FU Doris Duke Distinguished Clinical Scientist Award; Burroughs Wellcome Clinical Scientist in Translational Research Award; Max and Minnie Tomerlin Voelcker Scholar Award; Center for Personalized Medicine at the South Texas Veterans Health Care System; National Institutes of Health FX S.K.A. received support from the following grants: the Doris Duke Distinguished Clinical Scientist Award, the Burroughs Wellcome Clinical Scientist in Translational Research Award, the Max and Minnie Tomerlin Voelcker Scholar Award, and the Center for Personalized Medicine at the South Texas Veterans Health Care System.; Disclosure of potential conflict of interest: R. L. Jacobs is the owner of the Biogenics Research Chamber and Biogenics Research Institute. C. P. Andrews is a partner in the Biogenics Research Chamber and Director of Clinical Research at the Diagnostics Research Group. C. G. Rather is Executive Director of the Biogenics Research Chamber. D. A. Ramirez is a partner in the Biogenics Research Chamber. S. K. Ahuja has received research support from the National Institutes of Health. The rest of the authors declare that they have no relevant conflicts of interest. NR 20 TC 24 Z9 24 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 2012 VL 130 IS 1 BP 122 EP + DI 10.1016/j.jaci.2012.03.031 PG 14 WC Allergy; Immunology SC Allergy; Immunology GA 977GN UT WOS:000306644800017 PM 22554707 ER PT J AU Smith, T Capitulo, KL Griffin, MTQ Fitzpatrick, JJ AF Smith, Thomas Capitulo, Kathleen Leask Griffin, Mary T. Quinn Fitzpatrick, Joyce J. TI Structural empowerment and anticipated turnover among behavioural health nurses SO JOURNAL OF NURSING MANAGEMENT LA English DT Article DE anticipated turnover; behavioural health nurse; registered nurse; structural empowerment; workforce retention ID WORK ENVIRONMENTS; SATISFACTION; STAFF; SETTINGS; MODEL; PERCEPTIONS; WORKPLACE; INTENT; IMPACT; LEAVE AB smith t., capitulo k.l., quinn griffin m.t. & fitzpatrick j.j. (2012) Journal of Nursing Management similar to 20, 679684 Structural empowerment and anticipated turnover among behavioural health nurses Aim The aim of this pilot study was to examine the relationship between structural empowerment and anticipated turnover among behavioural health nurses. Background There have been several studies relating structural empowerment to a range of organizational characteristics and personal attributes of nurses themselves. There are also previous studies linking the key variables in the present study, but no previous research of behavioural health nurses was available. Methods A quantitative design was used for this cross-sectional pilot study. All registered nurses (RN) working on inpatient units in the study facility were invited to participate (n = 97). An anonymous survey was sent to all potential participants. Results The response rate was 53% (n = 50). The majority of participants perceived themselves as moderately empowered. There was a significant negative correlation between empowerment and anticipated turnover. Conclusion The results of this pilot study among behavioural health nurses are similar to the results among nurses working in other clinical areas. Implications for nursing management Nurse managers should be cognizant of the factors that enhance nurses perceptions of empowerment, particularly related to issues of retention and anticipated turnover among behavioural health nurses. C1 [Griffin, Mary T. Quinn; Fitzpatrick, Joyce J.] Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, Cleveland, OH 44106 USA. [Smith, Thomas] Maimonides Hosp, Brooklyn, NY 11219 USA. [Capitulo, Kathleen Leask] James J Peters VA Med Ctr, Bronx, NY USA. RP Fitzpatrick, JJ (reprint author), Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, Cleveland, OH 44106 USA. EM joyce.fitzpatrick@case.edu NR 25 TC 5 Z9 5 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0966-0429 J9 J NURS MANAGE JI J. Nurs. Manag. PD JUL PY 2012 VL 20 IS 5 SI SI BP 679 EP 684 DI 10.1111/j.1365-2834.2012.01384.x PG 6 WC Management; Nursing SC Business & Economics; Nursing GA 977IE UT WOS:000306649300013 PM 22823224 ER PT J AU Robinson, TN Wu, DS Pointer, LF Dunn, CL Moss, M AF Robinson, Thomas N. Wu, Daniel S. Pointer, Lauren F. Dunn, Christina L. Moss, Marc TI Preoperative Cognitive Dysfunction Is Related to Adverse Postoperative Outcomes in the Elderly SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 119th Scientific Session of the Western-Surgical-Association CY NOV, 2011 CL Tucson, AZ SP Western Surg Assoc ID INTENSIVE-CARE-UNIT; MECHANICALLY VENTILATED PATIENTS; CONFUSION ASSESSMENT METHOD; MINI-COG; DISCHARGE INSTITUTIONALIZATION; GERIATRIC-PATIENT; DELIRIUM; DEMENTIA; POPULATION; FRAILTY AB BACKGROUND: Preoperative risk stratification is commonly performed by assessing end-organ function (such as cardiac and pulmonary) to define postoperative risk. Little is known about impaired preoperative cognition and outcomes. The purpose of this study was to evaluate the impact of baseline impaired cognition on postoperative outcomes in geriatric surgery patients. STUDY DESIGN: Subjects 65 years and older undergoing a planned elective operation requiring postoperative ICU admission were recruited prospectively. Preoperative baseline cognition was assessed using the validated Mini-Cog test. Impaired cognition was defined as a Mini-Cog score of <= 3. Delirium was assessed using the Confusion Assessment Method-ICU by a trained research team. Adverse outcomes were defined using the Veterans Affairs Surgical Quality Improvement Program definitions. RESULTS: One hundred and eighty-six subjects were included, with a mean age of 73 +/- 6 years. Eighty-two subjects (44%) had baseline impaired cognition. The impaired cognition group had the following unadjusted outcomes: increased incidence of 1 or more postoperative complications (41% vs 24%; p = 0.011), higher incidence of delirium (78% vs 37%; p < 0.001), longer hospital stays (15 +/- 14 vs 9 +/- 9 days; p = 0.001), higher rate of discharge institutionalization (42% vs 18%; p = 0.001), and higher 6-month mortality (13% vs 5%; p = 0.040). Adjusting for potential confounders determined by univariate analysis, logistic regression found impaired cognition was still associated with the occurrence of 1 or more postoperative complications (odds ratio = 2.401; 95% CI, 1.185 +/- 4.865; p = 0.015). Kaplan-Meier survival analysis revealed higher mortality in the impaired cognition group (log-rank p = 0.008). CONCLUSIONS: Baseline cognitive impairment in older adults undergoing major elective operations is related to adverse postoperative outcomes including increased complications, length of stay, and long-term mortality. Improved understanding of baseline cognition and surgical outcomes can aid surgical decision making in older adults. (J Am Coll Surg 2012; 215: 12-18. (C) 2012 by the American College of Surgeons) C1 [Robinson, Thomas N.; Wu, Daniel S.; Dunn, Christina L.] Univ Colorado, Denver Sch Med, Dept Surg, Aurora, CO 80045 USA. [Moss, Marc] Univ Colorado, Denver Sch Med, Dept Med, Aurora, CO USA. [Robinson, Thomas N.; Wu, Daniel S.] Denver Vet Affairs Med Ctr, Dept Surg, Denver, CO USA. [Pointer, Lauren F.] Denver Vet Affairs Med Ctr, Dept Biostat, Denver, CO USA. RP Robinson, TN (reprint author), Univ Colorado, Denver Sch Med, Dept Surg, 12631 E 17th Ave,MS C313, Aurora, CO 80045 USA. EM thomas.robinson@ucdenver.edu FU NHLBI NIH HHS [K24 HL089223, K24-HL-089223]; NIA NIH HHS [K23 AG034632, K23AG034632] NR 28 TC 44 Z9 45 U1 3 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUL PY 2012 VL 215 IS 1 BP 12 EP 17 DI 10.1016/j.jamcollsurg.2012.02.007 PG 6 WC Surgery SC Surgery GA 977GE UT WOS:000306643900002 PM 22626912 ER PT J AU Hussar, DA Hallinan, SE AF Hussar, Daniel A. Hallinan, Sarah E. TI Clobazam, ezogabine, and tafluprost SO JOURNAL OF THE AMERICAN PHARMACISTS ASSOCIATION LA English DT News Item C1 [Hussar, Daniel A.] Univ Sci, Philadelphia Coll Pharm, Philadelphia, PA 19104 USA. [Hallinan, Sarah E.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Hussar, DA (reprint author), Univ Sci, Philadelphia Coll Pharm, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER PHARMACEUTICAL ASSOC PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA SN 1544-3191 J9 J AM PHARM ASSOC JI J. Am. Pharm. Assoc. PD JUL-AUG PY 2012 VL 52 IS 4 BP 546 EP 550 DI 10.1331/JAPhA.2012.12529 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 977GG UT WOS:000306644100019 PM 22825237 ER PT J AU Penson, DF Lange, PH AF Penson, David F. Lange, Paul H. TI Systemic therapy and the urologic oncologist: A unique opportunity for the specialty to provide comprehensive care that ultimately benefits the patient SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Systemic therapy; Urologic cancers; Practice models ID CANCER AB The changing healthcare environment will demand greater integration and coordination of care for patients. By incorporating systemic therapies into the practice of urologic oncology, our specialty has the opportunity to take the lead in this initiative. By learning how to deliver these therapies to patients in need, urologic oncologists likely will improve communication and trust, as patients often will already have a long and positive relationship with their urologist. In turn, this will likely lead to increased satisfaction with care and possibly improved outcomes. The development of comprehensive urologic oncology practices that include the administration of systemic therapy will maintain the relevance of the specialty and ultimately benefit our patients. (C) 2012 Elsevier Inc. All rights reserved. C1 [Penson, David F.] Vanderbilt Univ, Dept Urol Surg, Nashville, TN 37203 USA. [Penson, David F.] VA Tennessee Valley Geriatr Res Educ & Clin Ctr G, Nashville, TN 37203 USA. [Lange, Paul H.] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [Lange, Paul H.] VA Puget Sound Healthcare Syst, Seattle, WA 98195 USA. RP Penson, DF (reprint author), Vanderbilt Univ, Dept Urol Surg, Nashville, TN 37203 USA. EM david.penson@vanderbilt.edu NR 4 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JUL-AUG PY 2012 VL 30 IS 4 SU S BP S2 EP S4 DI 10.1016/j.urolonc.2011.04.008 PG 3 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 977EI UT WOS:000306638800002 PM 22795076 ER PT J AU Baicu, CF Zhang, YH Van Laer, AO Renaud, L Zile, MR Bradshaw, AD AF Baicu, Catalin F. Zhang, Yuhua Van Laer, An O. Renaud, Ludivine Zile, Michael R. Bradshaw, Amy D. TI Effects of the absence of procollagen C-endopeptidase enhancer-2 on myocardial collagen accumulation in chronic pressure overload SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE procollagen; procollagen C-proteinase enhancer-2; fibrosis; hypertrophy ID BONE MORPHOGENETIC PROTEIN-1; FRIZZLED-RELATED PROTEIN-2; DIASTOLIC HEART-FAILURE; FIBRILLAR COLLAGEN; LEFT-VENTRICLE; RAT-HEART; EXPRESSION; GENE; INFARCTION; FIBROSIS AB Baicu CF, Zhang Y, Van Laer AO, Renaud L, Zile MR, Bradshaw AD. Effects of the absence of procollagen C-endopeptidase enhancer-2 on myocardial collagen accumulation in chronic pressure overload. Am J Physiol Heart Circ Physiol 303: H234-H240, 2012. First published May 18, 2012; doi:10.1152/ajpheart.00227.2012.-Cardiac interstitial fibrillar collagen accumulation, such as that associated with chronic pressure overload (PO), has been shown to impair left ventricular diastolic function. Therefore, insight into cellular mechanisms that mediate excessive collagen deposition in the myocardium is pivotal to this important area of research. Collagen is secreted as a soluble procollagen molecule with NH2- and COOH (C)-terminal propeptides. Cleavage of these propeptides is required for collagen incorporation to insoluble collagen fibrils. The C-procollagen proteinase, bone morphogenic protein 1, cleaves the C-propeptide of procollagen. Procollagen C-endopeptidase enhancer (PCOLCE) 2, an enhancer of bone morphogenic protein-1 activity in vitro, is expressed at high levels in the myocardium. However, whether the absence of PCOLCE2 affects collagen content at baseline or after PO induced by transverse aortic constriction (TAC) has never been examined. Accordingly, in vivo procollagen processing and deposition were examined in wild-type (WT) and PCOLCE2-null mice. No significant differences in collagen content or myocardial stiffness were detected in non-TAC (control) PCOLCE2-null versus WT mice. After TAC-induced PO, PCOLCE2-null hearts demonstrated a lesser collagen content (PCOLCE2-null TAC collagen volume fraction, 0.41% +/- 0.07 vs. WT TAC, 1.2% +/- 0.3) and lower muscle stiffness compared with WT PO hearts [PCOLCE2-null myocardial stiffness (beta), 0.041 +/- 0.002 vs. WT myocardial stiffness, 0.065 +/- 0.001]. In addition, in vitro, PCOLCE2-null cardiac fibroblasts exhibited reductions in efficiency of C-propeptide cleavage, as demonstrated by increases in procollagen alpha 1(I) and decreased levels of processed collagen alpha 1(I) versus WT cardiac fibroblasts. Hence, PCOLCE2 is required for efficient procollagen processing and deposition of fibrillar collagen in the PO myocardium. These results support a critical role for procollagen processing in the regulation of collagen deposition in the heart. C1 [Bradshaw, Amy D.] Med Univ S Carolina, Dept Med, Div Cardiol, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. RP Bradshaw, AD (reprint author), Med Univ S Carolina, Dept Med, Div Cardiol, Gazes Cardiac Res Inst, 114 Doughty St,Rm 223 Gazes Strom Thurmond Res Bl, Charleston, SC 29425 USA. EM bradshad@musc.edu FU Research Service of the Department of Veterans Affairs; National Institutes of Health [PO1-HL-48788, HL-094517, P20-RR-017696] FX This study was supported by the Research Service of the Department of Veterans Affairs (to M. R. Zile and A. D. Bradshaw) and National Institutes of Health Grants PO1-HL-48788 (to M. R. Zile), HL-094517 (to A. D. Bradshaw), and P20-RR-017696 (to A. D. Bradshaw). NR 27 TC 17 Z9 17 U1 0 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUL PY 2012 VL 303 IS 2 BP H234 EP H240 DI 10.1152/ajpheart.00227.2012 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 974JD UT WOS:000306429900011 PM 22610170 ER PT J AU Scheuner, MT Hilborne, L Brown, J Lubin, IM AF Scheuner, Maren T. Hilborne, Lee Brown, Julie Lubin, Ira M. CA RAND Mol Genetic Test Report Advis TI A Report Template for Molecular Genetic Tests Designed to Improve Communication Between the Clinician and Laboratory SO GENETIC TESTING AND MOLECULAR BIOMARKERS LA English DT Article ID CANCER-RISK; MEDICINE; GUIDELINES; PHYSICIANS; ERRORS; EXPERIENCE; DISEASE; HEALTH AB Aim: Errors are most likely to occur during the pre- and postanalytic phases of the genetic testing process, which can contribute to underuse, overuse, and misuse of genetic tests. To mitigate these errors, we created a template for molecular genetic test reports that utilizes the combined features of synoptic reporting and narrative interpretation. Methods: A variation of the Delphi consensus process with an expert panel was used to create a draft report template, which was further informed by focus group discussions with primary care physicians. Results: There was agreement that molecular genetic test reports should present information in groupings that flow in a logical manner, and most participants preferred the following order of presentation: patient and physician information, test performed, test results and interpretation, guidance on next steps, and supplemental information. We define data elements for the report as "required," "optional," "possible," and "not necessary"; provide recommendations regarding the grouping of these data elements; and describe the ideal design of the report template, including the preferred order of the report sections, formatting of data, and length of the report. Discussion: With input from key stakeholders and building upon prior work, we created a template for molecular genetic test reports designed to improve clinical decision making at the point of care. The template design should lead to more effective communication between the laboratory and ordering clinician. Studies are needed to assess the usefulness and effectiveness of molecular genetic test reports generated using this template. C1 [Scheuner, Maren T.] Greater Los Angeles Healthcare Syst, Dept Vet Affairs, Los Angeles, CA USA. [Scheuner, Maren T.; Hilborne, Lee; Brown, Julie] RAND Corp, Santa Monica, CA USA. [Scheuner, Maren T.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Hilborne, Lee] Quest Diagnost, Canoga Pk, CA USA. [Hilborne, Lee] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Lubin, Ira M.] Ctr Dis Control & Prevent, Div Lab Sci & Stand, Atlanta, GA USA. RP Scheuner, MT (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 500,Room 3218, Los Angeles, CA 90073 USA. EM maren.scheuner@va.gov OI Weck, Karen/0000-0002-8516-333X NR 28 TC 14 Z9 15 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1945-0265 J9 GENET TEST MOL BIOMA JI Genet. Test. Mol. Biomark. PD JUL PY 2012 VL 16 IS 7 BP 761 EP 769 DI 10.1089/gtmb.2011.0328 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 974ZB UT WOS:000306475100021 PM 22731646 ER PT J AU Uomoto, JM AF Uomoto, Jay M. TI Best Practices in Veteran Traumatic Brain Injury Care Preface SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Editorial Material ID POSTTRAUMATIC-STRESS-DISORDER C1 US Dept Vet Affairs, Off Mental Hlth Serv, Washington, DC USA. RP Uomoto, JM (reprint author), US Dept Vet Affairs, Off Mental Hlth Serv, Washington, DC USA. NR 9 TC 1 Z9 1 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-9701 J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JUL-AUG PY 2012 VL 27 IS 4 BP 241 EP 243 DI 10.1097/HTR.0b013e31825ee26a PG 3 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 975PJ UT WOS:000306523000001 PM 22767071 ER PT J AU Williams, RM Bambara, J Turner, AP AF Williams, Rhonda M. Bambara, Jennifer Turner, Aaron P. TI A Scoping Study of One-to-One Peer Mentorship Interventions and Recommendations for Application With Veterans With Postdeployment Syndrome SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE mutual support; OIF/OEF; peer mentorship; polytrauma; postdeployment syndrome; Veterans ID RANDOMIZED CONTROLLED-TRIAL; TRAUMATIC BRAIN-INJURY; QUALITY-OF-LIFE; SELF-EFFICACY; PROVIDED SERVICES; MENTORING PROGRAM; SUPPORT PROGRAM; SOCIAL SUPPORT; BREAST-CANCER; CARE AB Background: We employ the term postdeployment syndrome (PDS) to characterize the combinations of physical, psychological, and social difficulties frequently encountered by Veterans returning from combat. Objectives: To conduct a scoping review to identify and describe one-to-one peer mentorship (PM) interventions, identify elements associated with positive outcome and of relevance to Veterans with PDS, and summarize current practice in a way that informs the development of such interventions for this population. Methods: Scoping review methodology was used to identify and summarize key practices and concepts in the one-to-one PM literature between 1980 and 2012. Of 196 articles initially identified, 33 were retained for further examination. Eighteen met full-study criteria and were retained in the analyses. Three reviewers reached consensus on articles to include, and 2 coders independently extracted information from each article. Results: A range of populations was targeted in the interventions. Most identified the provision of support as the primary goal, although some also included other educational and behavioral goals. Most employed selection and training strategies for their mentors and offered ongoing supervision and consultation. Most studies indicated that participants found PM to be beneficial. Conclusions: This review supports the application in this population and proposes next steps for the development and systematic evaluation of PM interventions. C1 [Williams, Rhonda M.] VA Puget Sound Hlth Care Syst, Dept Rehabil Med, Rehabil Care Serv, Seattle, WA 98108 USA. [Williams, Rhonda M.; Turner, Aaron P.] Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA. RP Williams, RM (reprint author), VA Puget Sound Hlth Care Syst, Dept Rehabil Med, Rehabil Care Serv, S-117 RCS,1660 S Columbian Way, Seattle, WA 98108 USA. EM Rhonda.Williams1@va.gov OI Turner, Aaron/0000-0001-6897-8003 FU US Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Polytrauma and Blast-Related QUERI [07-289, 09-134]; Langeloth Foundation; US Department of Veterans Affairs, Office of Research and Development, Rehabilitation Research and Development [B4927W] FX This material is based upon the work supported by the US Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Polytrauma and Blast-Related QUERI (RRP # 07-289 and RRP # 09-134; Dr Williams, PI), the Langeloth Foundation, and by the US Department of Veterans Affairs, Office of Research and Development, Rehabilitation Research and Development (Career Development Award B4927W; Dr Turner, PI). NR 53 TC 4 Z9 4 U1 5 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-9701 J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JUL-AUG PY 2012 VL 27 IS 4 BP 261 EP 273 DI 10.1097/HTR.0b013e3182585cb6 PG 13 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 975PJ UT WOS:000306523000004 PM 22767074 ER PT J AU Lyddon, R Navarrett, S Dracheva, S AF Lyddon, Rebecca Navarrett, Scott Dracheva, Stella TI Ionotropic glutamate receptor mRNA editing in the prefrontal cortex: no alterations in schizophrenia or bipolar disorder SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE LA English DT Article ID SEROTONIN 2C RECEPTOR; MOLECULAR DETERMINANT; KINETIC-PROPERTIES; KAINATE RECEPTORS; 5-HT2C RECEPTOR; MOTOR-NEURONS; AMPA; EPILEPSY; CHANNELS; GLUR2 AB Background: Dysfunction of glutamate neurotransmission has been implicated in the pathology of schizophrenia and bipolar disorder, and one mechanism by which glutamate signalling can be altered is through RNA editing of ionotropic glutamate receptors (iGluRs). The objectives of the present study were to evaluate the editing status of iGluRs in the human prefrontal cortex, determine whether iGluR editing is associated with psychiatric disease or suicide and evaluate a potential association between editing and alternative splicing in the a-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) iGluR subunits' pre-mRNA. Methods: We studied specimens derived from patients with antemortem diagnoses of bipolar disorder (n = 31) or schizophrenia (n = 34) who died by suicide or other causes, and from psychiatrically healthy controls (n = 34) who died from causes other than suicide. The RNA editing at all 8 editing sites within AMPA (GluA2-4 subunits) and kainate (GluK1-2 subunits) iGluRs was analyzed using a novel real-time quantitative polymerase chain reaction assay. Results: No differences in editing were detected among schizophrenia, bipolar or control groups or between suicide completers and patients who died from causes other than suicide. The editing efficiency was significantly higher in the flop than in the flip splicoforms of GluA3-4 AMPA subunits (all p < 0.001). Limitations: The study is limited by the near absence of specimens from medicationnaive psychiatric patients and considerable variation in medication regimens among individuals, both of which introduce considerable uncertainty into the analysis of potential medication effects. Conclusion: We found that iGluR RNA editing status was not associated with bipolar disorder, schizophrenia or suicide. Differences in editing between flip and flop splicoforms suggest that glutamate sensitivity of receptors containing GluA3 and/or GluA4 flop subunits is moderated as a result of increased editing. C1 [Lyddon, Rebecca; Navarrett, Scott; Dracheva, Stella] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Navarrett, Scott; Dracheva, Stella] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Dracheva, S (reprint author), Bronx VA Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Stella.Dracheva@mssm.edu FU Department of Veterans Affairs (VA), Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; VA Merit award; NIMH/NIH [MH090352]; American Foundation for Suicide Prevention; VISN3 Mental Illness Research and Education Clinical Center; Stanley Medical Research Institute FX This study was supported by the Department of Veterans Affairs (VA), Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development, by a VA Merit award (S. Dracheva), NIMH/NIH grant MH090352 (S. Dracheva), a grant from the American Foundation for Suicide Prevention (S. Dracheva) and by the VISN3 Mental Illness Research and Education Clinical Center (S. Dracheva). Postmortem brain tissue was donated by The Stanley Medical Research Institute. NR 43 TC 5 Z9 5 U1 0 U2 2 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 5W8, CANADA SN 1180-4882 J9 J PSYCHIATR NEUROSCI JI J. Psychiatry Neurosci. PD JUL PY 2012 VL 37 IS 4 BP 267 EP 272 DI 10.1503/jpn.110107 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 974LV UT WOS:000306437800008 PM 22469055 ER PT J AU Fryer, SL AF Fryer, Susanna L. TI Another Step Forward in Relating Facial and Brain Dysmorphologies Associated with Prenatal Alcohol Exposure SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID SPECTRUM DISORDERS; CORPUS-CALLOSUM; CHILDREN; ADULTS; FMRI C1 Univ Calif San Francisco, Dept Psychiat, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Fryer, SL (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco VA Med Ctr, Psychiat Serv 116D,4150 Clement St, San Francisco, CA 94121 USA. EM susanna.fryer@ucsf.edu FU [T32MH089920] FX This work was funded by T32MH089920. NR 13 TC 0 Z9 0 U1 0 U2 4 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 JUL PY 2012 VL 36 IS 7 BP 1131 EP 1133 DI 10.1111/j.1530-0277.2012.01849.x PG 3 WC Substance Abuse SC Substance Abuse GA 971QR UT WOS:000306219400003 PM 22780985 ER PT J AU Carrillo, MC Bain, LJ Frisoni, GB Weiner, MW AF Carrillo, Maria C. Bain, Lisa J. Frisoni, Giovanni B. Weiner, Michael W. TI Worldwide Alzheimer's Disease Neuroimaging Initiative SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Neuroimaging; Biomarkers ID ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; RECOMMENDATIONS; DISCOVERY; MILD AB The Alzheimer's Disease Neuroimaging Initiative (ADNI) was launched in 2003 to speed drug development by validating imaging and blood/cerebrospinal fluid biomarkers for Alzheimer's disease clinical treatment trials. ADNI is a naturalistic (nontreatment) multisite longitudinal study. A true public private partnership, the first phase of ADNI (ADNI 1) set a new standard for data sharing without embargo. In addition, it has been extended to 2017 by additional funding (North American-ADNI Grand Opportunities and ADNI 2) as well as multiple projects around the world, collectively known as Worldwide ADNI (WW-ADNI). The goal of WW-ADNI is to harmonize projects and results across different geographical sites and to encourage and harmonize data management and availability to investigators around the world. WW-ADNI projects are currently underway in North America, Europe, Japan, Australia, Korea, Taiwan, and Argentina, with a nascent program in China and a possible future program in Brazil. (C) 2012 The Alzheimer's Association. All rights reserved. C1 [Carrillo, Maria C.] Alzheimers Assoc, Med cfc Sci Relat, Chicago, IL USA. [Frisoni, Giovanni B.] IRCCS, Ctr San Giovanni Dio Fatebenefratelli, Lab Neuroimaging, Brescia, Italy. [Weiner, Michael W.] San Francisco VA Med Ctr, No Calif Inst Res, San Francisco, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. RP Carrillo, MC (reprint author), Alzheimers Assoc, Med cfc Sci Relat, Chicago, IL USA. EM Maria.Carrillo@alz.org RI Frisoni, Giovanni B/K-1360-2016 OI Frisoni, Giovanni B/0000-0002-6419-1753 FU National Institute on Aging of the National Institutes of Health [U01-AG024904]; Alzheimer's Association; PharmaCog from the European Commission's Innovative Medicine Initiative [115009]; grant Programma Strategico [RF07.39.2]; grant Programma Strategico 2007, conv. PS39 [RF07.39.2] FX NA-ADNI was supported with a grant (U01-AG024904) from the National Institute on Aging of the National Institutes of Health. The pilot E-ADNI was funded by the Alzheimer's Association. E-ADNI is funded through PharmaCog from the European Commission's Innovative Medicine Initiative under grant agreement number 115009 (Prediction of cognitive properties of new drug candidates for neurodegenerative diseases in early clinical development, PharmaCog). Italian ADNI has been funded by the grant Programma Strategico 2007 (RF07.39.2), conv. PS39. NR 14 TC 43 Z9 44 U1 4 U2 12 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 JUL PY 2012 VL 8 IS 4 BP 337 EP 342 DI 10.1016/j.jalz.2012.04.007 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 973XW UT WOS:000306394900010 PM 22748939 ER PT J AU Schopfer, DW Whooley, MA Stamos, TD AF Schopfer, David W. Whooley, Mary A. Stamos, Thomas D. TI Hospital compliance with performance measures and 30-day outcomes in patients with heart failure SO AMERICAN HEART JOURNAL LA English DT Article ID QUALITY-OF-CARE; OPTIMIZE-HF; MORTALITY; ASSOCIATION; SURVIVAL; DEFIBRILLATOR; MORBIDITY; ENALAPRIL; PROGRAM; TRIAL AB Background In 2005, the American College of Cardiology/American Heart Association published performance measures to provide a standard of care for hospitalized patients with heart failure ( HF). Despite increasing compliance with these measures, hospital mortality and readmission rates remain stagnant. Whether compliance with HF performance measures improves patient outcomes at the hospital level is unclear. Methods We evaluated compliance with HF performance measures at 3,655 US hospitals. Patients admitted with a diagnosis of HF in 2008 were identified using the US Department of Health and Human Services Hospital Compare database. Compliance with 4 specific performance measures was examined: evaluation of left ventricular systolic function, administration of angiotensin-converting enzyme inhibitor I or angiotensin-receptor blocker for left ventricular systolic dysfunction, offering smoking cessation advice and counseling, and providing discharge instructions. Thirty-day mortality and readmission rate were recorded. Results Hospitals reporting greater compliance with the 4 performance measures had significantly lower 30-day mortality rates. However, these hospitals were also located in areas of higher socioeconomic status and treated higher volumes of patients with HF. After adjusting for socioeconomic and hospital factors, only evaluation of left ventricular systolic function was associated with lower 30-day mortality, and evaluation of left ventricular systolic function and smoking cessation counseling were associated with lower readmission rates. Conclusions We found that socioeconomic factors and hospital volume were stronger predictors of mortality than compliance with HF performance measures. After adjusting for socioeconomic factors and hospital volume, only 1 of the 4 performance measures was associated with lower 30-day mortality and 2 were associated with lower readmissions. (Am Heart J 2012;164:80-6.) C1 [Schopfer, David W.; Stamos, Thomas D.] Univ Illinois, Coll Med, Cardiol Sect, Chicago, IL USA. [Whooley, Mary A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Whooley, Mary A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Schopfer, DW (reprint author), 4150 Clement St,111A1, San Francisco, CA 94121 USA. EM david.schopfer@ucsf.edu NR 31 TC 4 Z9 4 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUL PY 2012 VL 164 IS 1 BP 80 EP 86 DI 10.1016/j.ahj.2012.04.017 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 973NM UT WOS:000306366900012 PM 22795286 ER PT J AU Ingraham, AM Haas, B Cohen, ME Ko, CY Nathens, AB AF Ingraham, Angela M. Haas, Barbara Cohen, Mark E. Ko, Clifford Y. Nathens, Avery B. TI Comparison of Hospital Performance in Trauma vs Emergency and Elective General Surgery Implications for Acute Care Surgery Quality Improvement SO ARCHIVES OF SURGERY LA English DT Article ID SURGICAL CARE; RISK; MARKER AB Hypotheses: As emergency general surgery (EMGS) and trauma care are increasingly being provided by the same personnel with overlapping resources, we postulated that the quality of care provided to EMGS and trauma patients would be similar. We also evaluated the relationship between trauma and elective general surgery (ELGS) care, believing that performance would be similar across these services as it reflects institutional culture. Design: Retrospective cohort study comparing hospital performance in trauma and EMGS care and in trauma and ELGS care. Regression models for mortality and serious morbidity were constructed for trauma, EMGS, and ELGS hospitals contributing to both the National Trauma Data Bank (2007) and American College of Surgeons National Surgical Quality Improvement Program (2005-2008). Setting: Forty - six hospitals. Main Outcome Measures: Correlations of observed to expected ratios were examined. Outlier status (hospitals with CIs of observed to expected ratios excluding 1.0) was compared using weighted kappa. Results: There was no significant relationship between trauma and EMGS mortality (r=-0.01, P=.94; kappa=-0.10, P=.61) or between trauma and ELGS mortality (r=0.23, P=.12; kappa=0.07, P=.62). There was no significant relationship between trauma and EMGS morbidity (r=0.21, P=.17; kappa=0.04, P=.63) or between trauma and ELGS morbidity (r=0.16, P=.30; kappa=0.11, P=.37). No hospitals were consistently low or high outliers across all 3 groups. Conclusions: Trauma performance improvement programs are well established compared with those for EMGS. Although EMGS patients use similar structures and processes as trauma patients, there is a lack of correlation between the quality of care provided to trauma and EMGS patients; EMGS should be incorporated into trauma performance improvement programs. C1 [Ingraham, Angela M.] Univ Cincinnati, Dept Surg, Coll Med, Cincinnati, OH 45267 USA. [Ingraham, Angela M.; Cohen, Mark E.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Haas, Barbara; Nathens, Avery B.] Inst St Michaels Hosp, Div Surg & Trauma, Keenan Res Ctr Li Ka Shing Knowledge, Toronto, ON, Canada. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. RP Ingraham, AM (reprint author), Univ Cincinnati, Dept Surg, Coll Med, Mail Locat 0558,231 Albert Sabin Way,Room 1586, Cincinnati, OH 45267 USA. EM angieingraham@gmail.com FU Clinical Scholars in Residence Program at the ACS; Canadian Institutes of Health Research; Canada Research Chair in Systems of Trauma Care FX Dr Ingraham is supported by the Clinical Scholars in Residence Program at the ACS. Dr Haas is supported by a Canadian Institutes of Health Research fellowship. Dr Nathens is supported by a Canada Research Chair in Systems of Trauma Care. NR 20 TC 9 Z9 9 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD JUL PY 2012 VL 147 IS 7 BP 591 EP 598 DI 10.1001/archsurg.2012.71 PG 8 WC Surgery SC Surgery GA 974GB UT WOS:000306417900004 PM 22430094 ER PT J AU Maciejewski, ML Livingston, EH Smith, VA Kahwati, LC Henderson, WG Arterburn, DE AF Maciejewski, Matthew L. Livingston, Edward H. Smith, Valerie A. Kahwati, Leila C. Henderson, William G. Arterburn, David E. TI Health Expenditures Among High-Risk Patients After Gastric Bypass and Matched Controls SO ARCHIVES OF SURGERY LA English DT Article ID MORBIDLY OBESE-PATIENTS; LONG-TERM MORTALITY; BARIATRIC SURGERY; COST-EFFECTIVENESS; MEDICAL EXPENDITURES; PROPENSITY SCORE; SELECTION BIAS; WEIGHT-LOSS; CARE COSTS; ADJUSTMENT AB Objective: To determine whether bariatric surgery is associated with reduced health care expenditures in a multisite cohort of predominantly older male patients with a substantial disease burden. Design: Retrospective cohort study of bariatric surgery. Outpatient, inpatient, and overall health care expenditures within Department of Veterans Affairs (VA) medical centers were examined via generalized estimating equations in the propensity-matched cohorts. Setting: Bariatric surgery programs in VA medical centers. Participants: Eight hundred forty-seven veterans who were propensity matched to 847 nonsurgical control subjects from the same 12 VA medical centers. Intervention: Bariatric surgical procedures. Main Outcome Measure: Health expenditures through December 2006. Results: Outpatient, inpatient, and total expenditures trended higher for bariatric surgical cases in the 3 years leading up to the procedure and then converged back to the lower expenditure levels of nonsurgical controls in the 3 years after the procedure. Conclusions: Based on analyses of a cohort of predominantly older men, bariatric surgery does not appear to be associated with reduced health care expenditures 3 years after the procedure. C1 [Maciejewski, Matthew L.; Smith, Valerie A.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. [Maciejewski, Matthew L.] Duke Univ, Dept Med, Div Gen Internal Med, Durham, NC USA. [Kahwati, Leila C.] Vet Hlth Adm, Natl Ctr Hlth Promot & Dis Prevent, Off Patient Care Serv, Durham, NC USA. [Livingston, Edward H.] Univ Texas SW Med Ctr Dallas, Div Gastrointestinal & Endocrine Surg, Dallas, TX 75390 USA. [Livingston, Edward H.] VA N Texas Hlth Care Syst, Dallas, TX USA. [Livingston, Edward H.] Univ Texas Arlington, Biomed Engn Grad Program, Arlington, TX USA. [Henderson, William G.] Denver VA Med Ctr, Denver, CO USA. [Henderson, William G.] Univ Colorado, Dept Biostat, Sch Publ Hlth, Aurora, CO USA. [Henderson, William G.] Univ Colorado, Colorado Hlth Outcomes Program, Aurora, CO USA. [Arterburn, David E.] Univ Washington, Grp Hlth Res Inst, Seattle, WA 98195 USA. [Arterburn, David E.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA USA. RP Maciejewski, ML (reprint author), Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Mail Stop 152,411 W Chapel Hill St,Ste 600, Durham, NC 27705 USA. EM matthew.maciejewski@va.gov FU Takeda Pharmaceuticals, Novartis; Surgical Review Corporation; Texas Instruments; Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs [IIR 05-201, SHP 08-137]; Department of Veterans Affairs [RCS 10-391] FX Dr Maciejewski has received consultation funds from Takeda Pharmaceuticals, Novartis, and the Surgical Review Corporation and owns stock in Amgen. Dr Livingston has received consulting funds from Texas Instruments and serves as a contributing editor to JAMA. Dr Arterburn receives research funding and has received salary support as a medical editor for the not-for-profit (501[c][3]) Foundation for Informed Medical Decision Making (http://www.fimdm.org), which develops content for patient education programs. The Foundation has an arrangement with a for-profit company, Health Dialog, to coproduce and market these programs to health care organizations. Dr Arterburn was formerly with the Cincinnati VA, and Dr Livingston was formerly with the Dallas VA.; This study was supported by grants IIR 05-201 and SHP 08-137 from the Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs, and by Research Career Scientist award RCS 10-391 from the Department of Veterans Affairs (Dr Maciejewski). NR 37 TC 26 Z9 26 U1 5 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD JUL PY 2012 VL 147 IS 7 BP 633 EP 640 PG 8 WC Surgery SC Surgery GA 974GB UT WOS:000306417900014 PM 22802057 ER PT J AU Marshall, DT Savage, SJ Garrett-Mayer, E Keane, TE Hollis, BW Horst, RL Ambrose, LH Kindy, MS Gattoni-Celli, S AF Marshall, David T. Savage, Stephen J. Garrett-Mayer, Elizabeth Keane, Thomas E. Hollis, Bruce W. Horst, Ronald L. Ambrose, Linda H. Kindy, Mark S. Gattoni-Celli, Sebastiano TI Vitamin D-3 Supplementation at 4000 International Units Per Day for One Year Results in a Decrease of Positive Cores at Repeat Biopsy in Subjects with Low-Risk Prostate Cancer under Active Surveillance SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CONSERVATIVE MANAGEMENT; SOLAR-RADIATION; LEUKEMIA-CELLS; DOUBLE-BLIND; LNCAP CELLS; MORTALITY; TRIAL; APOPTOSIS; CALCIUM; WOMEN AB Context: We wanted to investigate vitamin D in low-risk prostate cancer. Objectives: The objective of the study was to determine whether vitamin D-3 supplementation at 4000 IU/d for 1 yr is safe and would result in a decrease in serum levels of prostate-specific antigen (PSA) or in the rate of progression. Design: In this open-label clinical trial (Investigational New Drug 77,839), subjects were followed up until repeat biopsy. Setting: All subjects were enrolled through the Medical University of South Carolina and the Ralph H. Johnson Veterans Affairs Medical Center, both in Charleston, SC. Patients and Other Participants: All subjects had a diagnosis of low-risk prostate cancer. Fifty-two subjects were enrolled in the study, 48 completed 1 yr of supplementation, and 44 could be analyzed for both safety and efficacy objectives. Intervention: The intervention included vitamin D-3 soft gels (4000 IU). Main Outcome Measures: Adverse events were monitored throughout the study. PSA serum levels were measured at entry and every 2 months for 1 yr. Biopsy procedures were performed before enrollment (for eligibility) and after 1 yr of supplementation. Results: No adverse events associated with vitamin D-3 supplementation were observed. No significant changes in PSA levels were observed. However, 24 of 44 subjects (55%) showed a decrease in the number of positive cores or decrease in Gleason score; five subjects (11%) showed no change; 15 subjects (34%) showed an increase in the number of positive cores or Gleason score. Conclusion: Patients with low-risk prostate cancer under active surveillance may benefit from vitamin D-3 supplementation at 4000 IU/d. (J Clin Endocrinol Metab 97: 2315-2324, 2012) C1 [Marshall, David T.; Ambrose, Linda H.; Gattoni-Celli, Sebastiano] Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29425 USA. [Savage, Stephen J.; Keane, Thomas E.] Med Univ S Carolina, Dept Urol, Charleston, SC 29425 USA. [Garrett-Mayer, Elizabeth] Med Univ S Carolina, Dept Med Biostat, Charleston, SC 29425 USA. [Hollis, Bruce W.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Kindy, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Savage, Stephen J.; Kindy, Mark S.; Gattoni-Celli, Sebastiano] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Horst, Ronald L.] Iowa State Univ, Dept Anim Sci, Ames, IA 50011 USA. RP Gattoni-Celli, S (reprint author), Strom Thurmond Biomed Res Bldg,Room 338C,114 Doug, Charleston, SC 29403 USA. EM gattonis@musc.edu FU Gateway for Cancer Research Grant [G-06-068]; Health Services Research and Development Program of the Department of Veterans Affairs, Veterans Affairs Merit Award [CX000163]; Biostatistics Shared Resource, Hollings Cancer Center's Support Grant [P30 CA138313]; National Institutes of Health/National Center for Research Resources [UL1 RR029881]; South Carolina Clinical and Translational Research Institute [UL1 RR029882] FX This work was supported in part by Gateway for Cancer Research Grant G-06-068), the Health Services Research and Development Program of the Department of Veterans Affairs, Veterans Affairs Merit Award CX000163, the Biostatistics Shared Resource, Hollings Cancer Center's Support Grant P30 CA138313 (National Institutes of Health/National Center for Research Resources Grant UL1 RR029881), and South Carolina Clinical and Translational Research Institute Grant UL1 RR029882. NR 40 TC 38 Z9 38 U1 0 U2 0 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 JUL PY 2012 VL 97 IS 7 BP 2315 EP 2324 DI 10.1210/jc.2012-1451 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 972OJ UT WOS:000306286100054 PM 22508710 ER PT J AU Ingram, KH Hill, H Moellering, DR Hill, BG Lara-Castro, C Newcomer, B Brandon, LJ Ingalls, CP Penumetcha, M Rupp, JC Garvey, WT AF Ingram, Katherine H. Hill, Helliner Moellering, Douglas R. Hill, Bradford G. Lara-Castro, Cristina Newcomer, Bradley Brandon, L. Jerome Ingalls, Christopher P. Penumetcha, Meera Rupp, Jeffrey C. Garvey, W. Timothy TI Skeletal Muscle Lipid Peroxidation and Insulin Resistance in Humans SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID OXIDATIVE STRESS; BIOMARKERS; ALDEHYDES; EXERCISE; OBESITY; DISEASE; PLASMA AB Objective: The relationships among skeletal muscle lipid peroxidation, intramyocellular lipid content (IMCL), and insulin sensitivity were evaluated in nine insulin-sensitive (IS), 13 insulin-resistant (IR), and 10 adults with type 2 diabetes (T2DM). Design: Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp [ glucose disposal rate (GDR)]. Lipid peroxidation was assessed by 4-hydroxynonenal (HNE)-protein adducts and general oxidative stress by protein carbonyl content. All patients were sedentary. Results: Protein-HNE adducts were elevated 1.6-fold in T2DM compared with IS adults, whereas IR showed intermediate levels of HNE-modified proteins. Protein-HNE adducts correlated with GDR, waist circumference, and body mass index. IMCL was increased by 4.0- and 1.9-fold in T2DM and IR patients, respectively, compared with IS, and was correlated with GDR and waist circumference but not BMI. Protein carbonyls were not different among groups and did not correlate with any of the measured variables. Correlations were detected between IMCL and protein-HNE. Conclusion: Our data show for the first time that skeletal muscle protein-HNE adducts are related to the severity of insulin resistance in sedentary adults. These results suggest that muscle lipid peroxidation could be involved in the development of insulin resistance. (J Clin Endocrinol Metab 97: E1182-E1186, 2012) C1 [Ingram, Katherine H.; Moellering, Douglas R.; Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Newcomer, Bradley] Univ Alabama Birmingham, Dept Clin & Diagnost Sci, Birmingham, AL 35294 USA. [Hill, Helliner] Novo Nordisk, Dept Field Med Affairs, Div Diabet, Princeton, NJ 08540 USA. [Hill, Bradford G.] Univ Louisville, Inst Mol Cardiol, Louisville, KY 40202 USA. [Lara-Castro, Cristina] Univ S Carolina, Sch Med, Dept Internal Med, Columbia, SC 29208 USA. [Brandon, L. Jerome; Ingalls, Christopher P.] Georgia State Univ, Dept Kinesiol & Hlth, Atlanta, GA 30302 USA. [Rupp, Jeffrey C.] Life Univ, Marietta, GA 30060 USA. [Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. [Penumetcha, Meera] Georgia State Univ, Dept Nutr, Atlanta, GA 30302 USA. RP Ingram, KH (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, 232 Webb Nutr Sci Bldg,1675 Univ Blvd, Birmingham, AL 35294 USA. EM khingram@uab.edu RI Hill, Bradford/F-9228-2011; Hill, Bradford/I-4154-2013 OI Hill, Bradford/0000-0001-5332-8286 FU National Institutes of Health [DK-038765, DK-083562, PO1 HL-55782]; T32 Training Grant "UAB Obesity Training Program" [HL-079888]; Department of Veterans Affairs; Gatorade Sports Science Institute; UAB Center for Clinical and Translational Science [UL1 RR025777]; Nutrition and Obesity Research Center [P30 DK56336]; Diabetes Research and Training Center [P60 DK079626] FX This work was supported by Grants DK-038765, DK-083562, and PO1 HL-55782 from the National Institutes of Health; T32 Training Grant (HL-079888) entitled "UAB Obesity Training Program"; the Merit Review program of the Department of Veterans Affairs; and the Gatorade Sports Science Institute (dissertation grant). We also acknowledge support from the UAB Center for Clinical and Translational Science (Grant UL1 RR025777), the Nutrition and Obesity Research Center (Grant P30 DK56336), and the Diabetes Research and Training Center (Grant P60 DK079626). NR 19 TC 14 Z9 15 U1 0 U2 7 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 JUL PY 2012 VL 97 IS 7 BP E1182 EP E1186 DI 10.1210/jc.2011-2963 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 972OJ UT WOS:000306286100013 PM 22496506 ER PT J AU Dixon, CE Yan, HQ Jenkins, LW Ma, XC Li, YM Shin, SS Dixon, CE AF Dixon, C. Edward Yan, Hong Q. Jenkins, Larry W. Ma, Xiecheng Li, Youming Shin, Samuel S. Dixon, C. Edward TI THE EFFECTS OF TBI ON HIPPOCAMPAL SNARE-COMPLEX ASSEMBLY AND ATTENUATION BY CHRONIC LITHIUM THERAPY SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 30th Annual National Neurotrauma Symposium CY JUL 22-25, 2012 CL Phoenix, AZ DE TBI; vesicles; lithium; hippocampus C1 [Shin, Samuel S.] Univ Pittsburgh, Sch Med, Ctr Neurosci & Neurosurg, Pittsburgh, PA 15260 USA. [Dixon, C. Edward] VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL PY 2012 VL 29 IS 10 BP A22 EP A23 PG 2 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 971YV UT WOS:000306244400034 ER PT J AU Crittenden, DB Lehmann, RA Schneck, L Keenan, RT Shah, B Greenberg, JD Cronstein, BN Sedlis, SP Pillinger, MH AF Crittenden, Daria B. Lehmann, R. Aaron Schneck, Laura Keenan, Robert T. Shah, Binita Greenberg, Jeffrey D. Cronstein, Bruce N. Sedlis, Steven P. Pillinger, Michael H. TI Colchicine Use Is Associated with Decreased Prevalence of Myocardial Infarction in Patients with Gout SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE GOUT; COLCHICINE; MYOCARDIAL INFARCTION; MORTALITY; C-REACTIVE PROTEIN ID C-REACTIVE PROTEIN; FAMILIAL MEDITERRANEAN FEVER; CORONARY-ARTERY-DISEASE; ENDOTHELIAL-CELLS; HUMAN LEUKOCYTES; ORAL COLCHICINE; T-LYMPHOCYTES; L-SELECTIN; INFLAMMATION; ATHEROSCLEROSIS AB Objective. The ability of antiinflammatory strategies to alter cardiovascular risk has not been rigorously examined. Colchicine is an antiinflammatory agent that affects macrophages, neutrophils, and endothelial cells, all of which are implicated in the pathogenesis of cardiovascular disease. We examined whether colchicine use was associated with a reduced risk of myocardial infarction (MI) in patients with gout. Methods. We conducted a retrospective, cross-sectional study of all patients with an International Classification of Diseases, 9th ed, code for gout in the electronic medical record (EMR) of the New York Harbor Healthcare System Veterans Affairs network and 1 hospital visit between August 2007 and August 2008. Hospital pharmacy data were used to identify patients who had filled at least 1 colchicine prescription versus those who had not. Demographics and CV comorbidities were collected by EMR review. The primary outcome was diagnosis of MI. Secondary outcomes included all-cause mortality and C-reactive protein (CRP) level. Results. In total. 1288 gout patients were identified. Colchicine (n = 576) and no colchicine (n = 712) groups had similar baseline demographics and serum urate levels. Prevalence of MI was 1.2% in the colchicine versus 2.6% in the no-colchicine group (p = 0.03). Colchicine users also had fewer deaths and lower CRP levels, although these did not achieve statistical significance. Colchicine effects persisted when allopurinol users were excluded from the analysis. Conclusion. In this hypothesis-generating study, gout patients who took colchicine had a significantly lower prevalence of MI and exhibited trends toward reduced all-cause mortality and lower CRP level versus those who did not take colchicine. (First Release June 1 2012; J Rheumatol 2012;39:1458-64; doi:10.3899/jrheum.111533) C1 NYU, Div Rheumatol, Crystal Dis Study Grp, Sch Med, New York, NY 10003 USA. NYU, Div Cardiol, Sch Med, New York, NY 10003 USA. US Dept Vet Affairs, Dept Med, New York Harbor Healthcare Syst, New York, NY USA. Duke Univ, Med Ctr, Div Rheumatol, Durham, NC USA. [Shah, Binita; Greenberg, Jeffrey D.; Cronstein, Bruce N.] NYU, Clin & Translat Sci Inst, Sch Med, New York, NY 10003 USA. RP Crittenden, DB (reprint author), NYU, Hosp Joint Dis, Div Rheumatol, 301 E 17th St,Room 1410, New York, NY 10003 USA. EM daria.crittenden@nyumc.org OI Sedlis, Steven/0000-0002-8194-8017; Pillinger, Michael/0000-0003-3168-1542 FU US National Institutes of Health [5T32AR007176] FX Drs. Keenan and Lehmann were supported by US National Institutes of Health T32 training grant 5T32AR007176. NR 59 TC 44 Z9 45 U1 0 U2 8 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 2012 VL 39 IS 7 BP 1458 EP 1464 DI 10.3899/jrheum.111533 PG 7 WC Rheumatology SC Rheumatology GA 973VQ UT WOS:000306388300024 PM 22660810 ER PT J AU Shastri, S Katz, R Rifkin, DE Fried, LF Odden, MC Peralta, CA Chonchol, M Siscovick, D Shlipak, MG Newman, AB Sarnak, MJ AF Shastri, Shani Katz, Ronit Rifkin, Dena E. Fried, Linda F. Odden, Michelle C. Peralta, Carmen A. Chonchol, Michel Siscovick, David Shlipak, Michael G. Newman, Anne B. Sarnak, Mark J. TI Kidney Function and Mortality in Octogenarians: Cardiovascular Health Study All Stars SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE octogenarians; kidney function; mortality ID SERUM CYSTATIN-C; GLOMERULAR-FILTRATION-RATE; OLDER-ADULTS; ELDERLY PERSONS; HEART-FAILURE; RISK-FACTOR; DISEASE; PREVALENCE; CREATININE; OUTCOMES AB Objectives To examine the association between kidney function and all-cause mortality in octogenarians. Design Retrospective analysis of prospectively collected data. Setting Community. Participants Serum creatinine and cystatin C were measured in 1,053 Cardiovascular Health Study (CHS) All Stars participants. Measurements Estimated glomerular filtration rate (eGFR) was determined using the Chronic Kidney Disease Epidemiology Collaboration creatinine (eGFRCR) and cystatin C one-variable (eGFRCYS) equations. The association between quintiles of kidney function and all-cause mortality was analyzed using unadjusted and adjusted Cox proportional hazards models. Results Mean age of the participants was 85, 64% were female, 66% had hypertension, 14% had diabetes mellitus, and 39% had prevalent cardiovascular disease. There were 154 deaths over a median follow-up of 2.6 years. The association between eGFRCR and all-cause mortality was U-shaped. In comparison with the reference quintile (6475 mL/min per 1.73 m2), the highest (=75 mL/min per 1.73 m2) and lowest (=43 mL/min per 1.73 m2) quintiles of eGFRCR were independently associated with mortality (hazard ratio (HR) = 2.49, 95% confidence interval (CI) = 1.364.55; HR = 2.28, 95% CI = 1.264.10, respectively). The association between eGFRCYS and all-cause mortality was linear in those with eGFRCYS of less than 60 mL/min per 1.73 m2, and in the multivariate analyses, the lowest quintile of eGFRCYS (<52 mL/min per 1.73 m2) was significantly associated with mortality (HR = 2.04, 95% CI = 1.123.71) compared with the highest quintile (>0.88 mL/min per 1.73 m2). Conclusion Moderate reduction in kidney function is a risk factor for all-cause mortality in octogenarians. The association between eGFRCR and all-cause mortality differed from that observed with eGFRCYS; the relationship was U-shaped for eGFRCR, whereas the risk was primarily present in the lowest quintile for eGFRCYS. C1 [Shastri, Shani] Univ Texas SW, Div Nephrol, Dallas, TX USA. [Katz, Ronit] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Rifkin, Dena E.] Univ Calif San Diego, Div Nephrol, San Diego, CA 92103 USA. [Fried, Linda F.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Fried, Linda F.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Odden, Michelle C.] Oregon State Univ, Sch Biol & Populat Hlth Sci, Dept Epidemiol, Corvallis, OR 97331 USA. [Peralta, Carmen A.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Chonchol, Michel] Univ Colorado, Div Renal Dis & Hypertens, Denver, CO 80202 USA. [Siscovick, David] Univ Washington, Dept Med & Epidemiol, Seattle, WA 98195 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Newman, Anne B.] Univ Pittsburgh, Sch Med, Div Geriatr Med, Dept Epidemiol, Pittsburgh, PA USA. [Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Boston, MA USA. RP Shastri, S (reprint author), UT SW, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Shani.Shastri@UTSouthwestern.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU National Institute on Aging (NIA) [AG-023629]; National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133]; NHLBI [HL080295]; Department of Veterans Affairs, Veterans Integrated Service Network 4 from the National Heart, Lung and Blood Institute [R01 HL-075366]; University of Pittsburgh Claude. D. Pepper Older Americans Independence Center [P30-AG-024827]; [K24 DK078204] FX The research reported in this article was supported by National Institute on Aging (NIA) Grant AG-023629. CHS was supported by National Heart, Lung, and Blood Institute (NHLBI) Contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, and N01-HC-45133 and NHLBI Grant HL080295, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the NIA. A full list of principal CHS investigators and institutions can be found at http://www.chsnhlbi.org/pi.htm. This material is also based on work supported in part by the Department of Veterans Affairs, Veterans Integrated Service Network 4, R01 HL-075366 from the National Heart, Lung and Blood Institute, and the University of Pittsburgh Claude. D. Pepper Older Americans Independence Center P30-AG-024827. Dr. Sarnak is supported by K24 DK078204. NR 27 TC 19 Z9 19 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 2012 VL 60 IS 7 BP 1201 EP 1207 DI 10.1111/j.1532-5415.2012.04046.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 972WJ UT WOS:000306311600001 PM 22724391 ER PT J AU Gellad, WF Good, CB Amuan, ME Marcum, ZA Hanlon, JT Pugh, MJV AF Gellad, Walid F. Good, Chester B. Amuan, Megan E. Marcum, Zachary A. Hanlon, Joseph T. Pugh, Mary Jo V. TI Facility-Level Variation in Potentially Inappropriate Prescribing for Older Veterans SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE potentially inappropriate prescribing; HEDIS measures; quality of care; pharmacoepidemiology ID ADVERSE DRUG-REACTIONS; RISK-ADJUSTED MORTALITY; MEDICATION USE; BEERS CRITERIA; EXPLICIT CRITERIA; ELDERLY PEOPLE; ADULTS; OUTCOMES; QUALITY; CARE AB Objectives To describe facility-level variation in two measures of potentially inappropriate prescribing prevalent in Veterans Affairs (VA) facilitiesexposure to high-risk medications in elderly adults (HRME) and drugdisease interactions (Rx-DIS)and to identify facility characteristics associated with high-quality prescribing. Design Cross-sectional. Setting VA Healthcare System. Participants Veterans aged 65 and older with at least one inpatient or outpatient visit in 20052006 (N = 2,023,477; HRME exposure) and a subsample with a history of falls or hip fractures, dementia, or chronic renal failure (n = 305,059; Rx-DIS exposure). Measurements Incident use of any HRME (iHRME) and incident Rx-DIS (iRx-DIS) and facility-level rates and facility-level predictors of iHRME and iRx-DIS exposure, adjusting for differences in patient characteristics. Results Overall, 94,692 (4.7%) veterans had iHRME exposure. At the facility level, iHRME exposure ranged from 1.6% at the lowest facility to 12.8% at the highest (median 4.7%). In the subsample, 9,803 (3.2%) veterans had iRx-DIS exposure, with a facility-level range from 1.3% to 5.8% (median 3.2%). In adjusted analyses, veterans seen in facilities with formal geriatric education had lower odds of iHRME (odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.770.96) and iRx-DIS (OR = 0.95, 95% CI = 0.881.01). Patients seen in facilities caring for fewer older veterans had greater odds of iHRME (OR = 1.54, 95% CI = 1.351.75) and iRx-DIS exposure (OR = 1.22, 95% CI = 1.111.33). Conclusion Substantial variation in the quality of prescribing for older adults exists across VA facilities, even after adjusting for patient characteristics. Higher-quality prescribing is found in facilities caring for a larger number of older veterans and facilities with formal geriatric education. C1 [Gellad, Walid F.; Good, Chester B.; Hanlon, Joseph T.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Gellad, Walid F.; Good, Chester B.] Univ Pittsburgh, Div Gen Med, Pittsburgh, PA USA. [Gellad, Walid F.; Hanlon, Joseph T.] Univ Pittsburgh, Div Geriatr Pharmaceut, Pittsburgh, PA USA. [Gellad, Walid F.; Hanlon, Joseph T.] Univ Pittsburgh, Geroinformat Res & Training Program, Pittsburgh, PA USA. [Gellad, Walid F.] RAND Corp, Pittsburgh, PA USA. [Good, Chester B.] Dept Vet Affairs, Pharm Benefits Management Serv, Hines, IL USA. [Amuan, Megan E.] Edith Nourse Rogers Mem Vet Hosp, Vet Affairs Ctr Hlth Qual, Bedford, MA USA. [Marcum, Zachary A.; Hanlon, Joseph T.] Univ Pittsburgh, Dept Med, Div Geriatr, Pittsburgh, PA USA. [Hanlon, Joseph T.] Pittsburgh Vet Affairs, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Pugh, Mary Jo V.] S Texas Vet Healthcare Syst, Vet Evidence Based Res Disseminat & Implementat C, Res Enhancement Award Program, San Antonio, TX USA. [Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Geriatr & Gerontol, San Antonio, TX 78229 USA. RP Gellad, WF (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM walid.gellad@va.gov OI Pugh, Mary Jo/0000-0003-4196-7763 FU VA Career Development Award CDA [09-207]; VA Health Services Research and Development Grant [IIR 06-062]; National Institute on Aging [P30AG024827, T32 AG021885, K07AG033174, R01AG034056, R56AG027017]; National Institute of Nursing Research [R01 NR010135]; Agency for Healthcare Research and Quality [R01 HS017695, R01 HS018721, K12 HS019461]; VA HSRD DHI [09-237]; VA HSRD [IIR-06-062, SDR-07-042, IIR-05-121, IAF-06-080, IIR-09-335, SHP 08-140, TRX 01-091]; VA HSR D IIR [08-274]; Department of Defense CDMRP [09090014]; National Institutes of Health [R01-NR010828]; Kelsey Seybold Research Foundation FX Conflict of Interest: All authors are employed by the VA. This study was supported by VA Career Development Award CDA 09-207 and a VA Health Services Research and Development Grant (IIR 06-062); National Institute on Aging Grants P30AG024827, T32 AG021885, K07AG033174, R01AG034056, and R56AG027017; National Institute of Nursing Research Grant R01 NR010135; and Agency for Healthcare Research and Quality Grants R01 HS017695, R01 HS018721, and K12 HS019461. Dr. Pugh has received research funding from VA HSR&D DHI 09-237 (PI); VA HSR&D IIR-06-062 PI, Epilepsy Foundation PI, VA HSR&D PPO 09-295 PI, VA HSR&D IIR 02-274 PI. Pugh as co-I: VA HSR&D IIR 08-274, VA HSR&D SDR-07-042, IIR-05-121, IAF-06-080, IIR-09-335, SHP 08-140, TRX 01-091 Department of Defense CDMRP 09090014, National Institutes of Health R01-NR010828, Pugh Speaker Honoraria: 2009 Kelsey Seybold Research Foundation $ 400. NR 42 TC 11 Z9 11 U1 0 U2 5 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 JUL PY 2012 VL 60 IS 7 BP 1222 EP 1229 DI 10.1111/j.1532-5415.2012.04042.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 972WJ UT WOS:000306311600004 PM 22726206 ER PT J AU Spira, AP Covinsky, K Rebok, GW Stone, KL Redline, S Yaffe, K AF Spira, Adam P. Covinsky, Kenneth Rebok, George W. Stone, Katie L. Redline, Susan Yaffe, Kristine TI Objectively Measured Sleep Quality and Nursing Home Placement in Older Women SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE sleep; actigraphy; nursing home; placement; women ID ELDERLY PERSONS; DEPRESSION; INFLAMMATION; VARIABILITY; DURATION; DISEASE AB Objectives To determine the association between objectively measured sleep and subsequent placement in a nursing home or a personal care home. Design Prospective cohort. Setting Participants' homes and sites of the Study of Osteoporotic Fractures. Participants One thousand six hundred sixty-four community-dwelling women with a mean age of 83 +/- 4. Measurements At baseline, participants completed an average of 4 nights of wrist actigraphy; they provided data on place of residence at baseline and at follow-up, 5 years later. Results At baseline, participants had a mean total sleep time of 408 +/- 72 minutes, mean wake after sleep onset of 71 +/- 43 minutes, and mean sleep efficiency of 79 +/- 11%. At follow-up, 71 (4%) were residing in a nursing home, and 127 (8%) were in a personal care home. Women with the most wake after sleep onset (by quartile) had more than twice the odds as those with the least of placement in a nursing home (adjusted odds ratio (AOR) = 2.94, 95% confidence interval (CI) = 1.346.44) or a personal care home (AOR = 2.33, 95% CI = 1.264.30). Similarly, women with the lowest sleep efficiency had more than three times the odds as those with the highest of nursing home placement (AOR = 3.25, 95% CI = 1.35, 7.82) and more than twice the odds of placement in a personal care home (AOR = 2.38, 95% CI = 1.33, 4.24). There was no association between sleep duration and placement. Conclusion In very old community-dwelling women, greater wake after sleep onset and lower sleep efficiency are risk factors for placement in a nursing home or personal care home. Sleep duration alone does not appear to increase the risk of placement in these long-term care settings. C1 [Spira, Adam P.; Rebok, George W.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Covinsky, Kenneth] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94143 USA. [Covinsky, Kenneth] San Francisco VA Med Ctr, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Stone, Katie L.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Redline, Susan] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Sleep Med, Boston, MA USA. [Redline, Susan] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Spira, AP (reprint author), 624 N Broadway,Hampton House,Rm 794, Baltimore, MD 21205 USA. EM aspira@jhsph.edu FU National Institutes of Health (NIH) [R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG026720, R01 AG027574, R01 AG027576, R01 AG005394]; Alzheimer's Association [IIRG-08-88872]; National Institute on Aging (NIA) [K01AG033195, K24AG031155]; NIH, National Heart, Lung, and Blood Institute; ResMed Foundation; NIH; National Institute of Mental Health; National Institute of Diabetes and Digestive and Kidney Diseases; Department of Defense; Department of Veterans Affairs; Alzheimer's Association FX Conflict of Interest: Supported by National Institutes of Health (NIH) Grants R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG026720, R01 AG027574, R01 AG027576, and R01 AG005394 and Alzheimer's Association Award IIRG-08-88872. Dr. Spira is supported by Mentored Research Scientist Development Award K01AG033195 from the National Institute on Aging (NIA). Dr. Yaffe is partially supported by Midcareer Investigator Award in Patient-Oriented Research K24AG031155 from the NIA. Dr. Spira received honoraria while serving as a clinical editor for the International Journal of Sleep and Wakefulness-Primary Care, which receives pharmaceutical company support, and from a private sleep medicine practice for a continuing education presentation on adverse outcomes of late-life sleep disturbance. Drs. Covinsky and Rebok are supported by grants from the National Institute on Aging. Dr. Redline is supported by grants from the NIH, National Heart, Lung, and Blood Institute and has received a subcontract from California Pacific Medical Center for work on this study. She also has received a research grant from ResMed Foundation to support ancillary data collection for an NIHfunded clinical trial. She is a member of the Board of Directors for the American Academy of Sleep Medicine and is the first incumbent of an endowed professorship donated to the Harvard Medical School by Dr. Peter Farrell, the founder and Board Chairman of ResMed, through a charitable remainder trust instrument, with annual support equivalent to the endowment payout provided to the Harvard Medical School during Dr. Farrell's lifetime by the ResMed Company through an irrevocable gift agreement. Dr. Stone reports that NIH funding has been obtained for this work. Dr. Yaffe has received grants from the NIA, National Institute of Mental Health, National Institute of Diabetes and Digestive and Kidney Diseases, Department of Defense, Department of Veterans Affairs, the Alzheimer's Association, and an anonymous donor. She has served on data safety monitoring bards for Pfizer and Medivation, and received honoraria from Novartis as an advisory board member. She is a member of the boards of the Beeson Program; National Institute of Mental Health; and National Heart, Lung, and Blood Institute. NR 22 TC 11 Z9 11 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 2012 VL 60 IS 7 BP 1237 EP 1243 DI 10.1111/j.1532-5415.2012.04044.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 972WJ UT WOS:000306311600006 PM 22702839 ER PT J AU Holmes, HM Luo, R Hanlon, JT Elting, LS Suarez-Almazor, M Goodwin, JS AF Holmes, Holly M. Luo, Ruili Hanlon, Joseph T. Elting, Linda S. Suarez-Almazor, Maria Goodwin, James S. TI Ethnic Disparities in Adherence to Antihypertensive Medications of Medicare Part D Beneficiaries SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE medication adherence; ethnic disparities; Medicare Part D ID D PROGRAMS; NONADHERENCE; IMPACT; PREDICTORS; DIAGNOSIS; SURVIVAL; OUTCOMES; BENEFIT; BREAST; CANCER AB Objectives To determine the level of adherence to medications and characteristics of Part D beneficiaries associated with higher levels of antihypertensive medication adherence. Design Retrospective cohort study. Setting Medicare claims and Part D event files. Participants Medicare Part D enrollees with prevalent uncomplicated hypertension who filled at least one antihypertensive prescription in 2006 and two prescriptions in 2007. Measurements Medication adherence was defined as an average medication possession ratio of 80% or greater. Potential factors associated with adherence evaluated were age, sex, race or ethnicity, socioeconomic factors, comorbidity, medication use, copayments, being in the coverage gap, and number of unique prescribers. Results Overall adherence was 79.5% of 168,522 Medicare Part D enrollees with prevalent uncomplicated hypertension receiving antihypertensive medicines in 2007. In univariate analysis, adherence varied significantly according to most patient factors. In multivariable analysis, lower odds of adherence persisted for blacks (odds ratio (OR) = 0.53, 95% confidence interval (CI) = 0.510.55), Hispanics (OR = 0.58, 95% CI = 0.550.61), and other non-white races (OR = 0.80 95% CI = 0.750.85) than for whites. Greater comorbidity and concurrent medication use were also associated with poorer adherence. Adherence was significantly different across several geographic regions. Conclusion A number of associations were identified between patient factors and adherence to antihypertensive drugs, with significant differences in adherence according to ethnicity. Improving adherence could have significant public health implications and could improve outcomes specific to hypertension, as well as improving cost and healthcare utilization. C1 [Holmes, Holly M.; Luo, Ruili; Suarez-Almazor, Maria] UT MD Anderson Canc Ctr, Dept Gen Internal Med, Houston, TX 77030 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Dept Pharm & Therapeut, Div Geriatr Med, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Dept Epidemiol, Div Geriatr Med, Pittsburgh, PA 15261 USA. [Hanlon, Joseph T.] Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Elting, Linda S.] UT MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Goodwin, James S.] Univ Texas Med Branch, Dept Internal Med, Galveston, TX USA. [Goodwin, James S.] Univ Texas Med Branch, Sealy Ctr Aging, Galveston, TX USA. RP Holmes, HM (reprint author), UT MD Anderson Canc Ctr, Dept Gen Internal Med, 1515 Holcombe Blvd,Unit 1465, Houston, TX 77030 USA. EM hholmes@mdanderson.org FU Hartford Geriatrics Health Outcomes Research Scholars Award; National Institute on Aging [K23AG038476, R56AG 0207017, P30AG024827, T32 AG021885, K07AG033174, R01AG034056, 3U01 AG012553]; National Institute of Mental Health [R34 MH082682]; National Institute of Nursing Research [R01 NR010135]; Agency for Healthcare Research and Quality [R01 HS017695, K12 HS019461, R01HS018721]; Veterans Affairs Health Services Research [IIR-06062]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [K24 AR053593]; Cancer Prevention and Research Institute of Texas [RP 101207]; National Cancer Institute [K05 CA134923] FX Conflict of Interest: Dr. Holmes was supported by a Hartford Geriatrics Health Outcomes Research Scholars Award and by a grant from the National Institute on Aging (K23AG038476). Dr. Hanlon was supported in part by National Institute on Aging grants and contracts (R56AG 0207017, P30AG024827, T32 AG021885, K07AG033174, R01AG034056, 3U01 AG012553), a National Institute of Mental Health grant (R34 MH082682), a National Institute of Nursing Research grant (R01 NR010135), Agency for Healthcare Research and Quality grants (R01 HS017695, K12 HS019461, R01HS018721), and a Veterans Affairs Health Services Research grant (IIR-06062). Dr. Suarez-Almazor is supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (K24 AR053593). Drs. Elting, Suarez-Almazor, and Goodwin are supported by a grant from the Cancer Prevention and Research Institute of Texas (RP 101207). Dr. Goodwin was supported by an Established Investigator Grant from the National Cancer Institute (K05 CA134923). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 30 TC 22 Z9 22 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 2012 VL 60 IS 7 BP 1298 EP 1303 DI 10.1111/j.1532-5415.2012.04037.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 972WJ UT WOS:000306311600015 PM 22702464 ER PT J AU Zhang, YA Benmohamed, R Zhang, W Kim, J Edgerly, CK Zhu, YQ Morimoto, RI Ferrante, RJ Kirsch, DR Silverman, RB AF Zhang, Yinan Benmohamed, Radhia Zhang, Wei Kim, Jinho Edgerly, Christina K. Zhu, Yaoqiu Morimoto, Richard I. Ferrante, Robert J. Kirsch, Donald R. Silverman, Richard B. TI Chiral Cyclohexane 1,3-Diones as Inhibitors of Mutant SOD1-Dependent Protein Aggregation for the Treatment of ALS SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Cyclohexane 1,3-diones; superoxide dismutase 1 (SOD1); protein aggregation; amyotrophic lateral sclerosis (ALS); mutant SOD1; PC-12 cells; cortical neurons ID AMYOTROPHIC-LATERAL-SCLEROSIS; POTENTIAL APPLICATION; RILUZOLE; TOXICITY; DESIGN AB Cyclohexane 1,3-diones were identified as a class of molecules exhibiting a protective effect against mutant SOD1 induced toxicity in PC-12 cells, but an optimized analogue had little or no effect on life extension in the G93A SOD1 mouse model for amyotrophic lateral sclerosis (ALS). Additional testing showed that these compounds were inactive in neurons, and further analogue synthesis was carried out to identify compounds with neuronal activity. Starting from two racemic derivatives that were active in cortical neurons, two potent analogues (1b and 2b) were resolved, which were protective against mutant SOD1 induced toxicity in PC 12 cells. Both compounds were found to be active in cortical neurons and presented good ADME profiles in vitro. On the basis of these results, an ALS mouse trial with 1b was carried out, which showed slightly greater life extension than the FDA approved ALS drug riluzole, thereby validating cyclohexane 1,3-diones as a novel therapeutic class for the treatment of ALS. C1 [Zhang, Yinan; Zhang, Wei; Silverman, Richard B.] Northwestern Univ, Dept Chem, Chem Life Proc Inst,Ctr Mol Innovat & Drug Discov, Dept Mol Biosci, Evanston, IL 60208 USA. [Benmohamed, Radhia; Kirsch, Donald R.] Cambria Pharmaceut, Cambridge, MA 02142 USA. [Kim, Jinho; Edgerly, Christina K.; Ferrante, Robert J.] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15213 USA. [Kim, Jinho; Edgerly, Christina K.; Ferrante, Robert J.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Kim, Jinho; Edgerly, Christina K.; Ferrante, Robert J.] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA 15213 USA. [Kim, Jinho; Edgerly, Christina K.; Ferrante, Robert J.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr 00 GR H, Pittsburgh, PA 15206 USA. [Zhu, Yaoqiu] MetabQuest Res & Consulting, Beijing 100871, Peoples R China. [Morimoto, Richard I.] Northwestern Univ, Rice Inst Biomed Res, Dept Mol Biosci, Evanston, IL 60208 USA. RP Silverman, RB (reprint author), Northwestern Univ, Dept Chem, Chem Life Proc Inst,Ctr Mol Innovat & Drug Discov, Dept Mol Biosci, 2145 Sheridan Rd, Evanston, IL 60208 USA. EM Agman@chem.northwestern.edu RI Zhu, Yaoqiu/D-4624-2013; Zhang, Yinan/D-5769-2016 OI Zhang, Yinan/0000-0002-0362-1473 FU National Institutes of Health [1R43NS057849] FX We thank the National Institutes of Health (Grant 1R43NS057849), the ALS Association (TREAT program), and the Department of Defense (AL093052), for their generous support of this research. NR 19 TC 6 Z9 6 U1 1 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD JUL PY 2012 VL 3 IS 7 BP 584 EP 587 DI 10.1021/ml3000963 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 972GP UT WOS:000306265600014 PM 22837812 ER PT J AU Jensen, J Tantiwong, P Stuenaes, JT Molina-Carrion, M DeFronzo, RA Sakamoto, K Musi, N AF Jensen, Jorgen Tantiwong, Puntip Stuenaes, Jorid T. Molina-Carrion, Marjorie DeFronzo, Ralph A. Sakamoto, Kei Musi, Nicolas TI Effect of acute exercise on glycogen synthase in muscle from obese and diabetic subjects SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE insulin resistance ID HUMAN SKELETAL-MUSCLE; GLUCOSE-UPTAKE; INSULIN-RESISTANCE; EPITROCHLEARIS MUSCLES; SYNTHETASE ACTIVITY; ACTIVITY CONTRIBUTE; KINETIC-PROPERTIES; UDP-GLUCOSE; PHOSPHORYLATION; ACTIVATION AB Jensen J, Tantiwong P, Stuenaes JT, Molina-Carrion M, DeFronzo RA, Sakamoto K, Musi N. Effect of acute exercise on glycogen synthase in muscle from obese and diabetic subjects. Am J Physiol Endocrinol Metab 303: E82-E89, 2012. First published April 17, 2012; doi: 10.1152/ajpendo.00658.2011.-Insulin stimulates glycogen synthase (GS) through dephosphorylation of serine residues, and this effect is impaired in skeletal muscle from insulin-resistant [obese and type 2 diabetic (T2DM)] subjects. Exercise also increases GS activity, yet it is not known whether the ability of exercise to affect GS is impaired in insulin-resistant subjects. The objective of this study was to examine the effect of acute exercise on GS phosphorylation and enzyme kinetic properties in muscle from insulin-resistant individuals. Lean normal glucose-tolerant (NGT), obese NGT, and obese T2DM subjects performed 40 min of moderate-intensity cycle exercise (70% of Vo(2max)). GS kinetic properties and phosphorylation were measured in vastus lateralis muscle before exercise, immediately after exercise, and 3.5 h postexercise. In lean subjects, GS fractional activity increased twofold after 40 min of exercise, and it remained elevated after the 3.5-h rest period. Importantly, exercise also decreased GS K-m for UDP-glucose from approximate to 0.5 to approximate to 0.2 mM. In lean subjects, exercise caused significant dephosphorylation of GS by 50-70% (Ser(641), Ser(645), and Ser(645,649,653,657)), and phosphorylation of these sites remained decreased after 3.5 h; Ser(7) phosphorylation was not regulated by exercise. In obese NGT and T2DM subjects, exercise increased GS fractional activity, decreased K-m for UDP-glucose, and decreased GS phosphorylation as effectively as in lean NGT subjects. We conclude that the molecular regulatory process by which exercise promotes glycogen synthesis in muscle is preserved in insulin-resistant subjects. C1 [Jensen, Jorgen] Norwegian Sch Sport Sci, Dept Phys Performance, Oslo, Norway. [Jensen, Jorgen; Stuenaes, Jorid T.] Natl Inst Occupat Hlth, Dept Work Related Musculoskeletal Disorders, Oslo, Norway. [Tantiwong, Puntip; Molina-Carrion, Marjorie; DeFronzo, Ralph A.; Musi, Nicolas] Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, San Antonio, TX 78229 USA. [Tantiwong, Puntip; Molina-Carrion, Marjorie; DeFronzo, Ralph A.; Musi, Nicolas] Texas Diabet Inst, San Antonio, TX USA. [Sakamoto, Kei] Univ Dundee, Coll Life Sci, MRC, Prot Phosphorylat Unit, Dundee, Scotland. [Musi, Nicolas] S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. RP Musi, N (reprint author), Audie L Murphy VA Hosp, GRECC 182,7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM musi@uthscsa.edu RI Jensen, Jorgen/O-2245-2013 FU American Diabetes Association; National Institutes of Health [AG-030979, DK-80157, DK-089229, DK-24092]; San Antonio Nathan Shock Center; South Texas Health Research Center; US Department of Veterans Affairs; Novo Nordisk Foundation; United Kingdom (UK) Medical Research Council; Diabetes UK; Dundee and District of Diabetes UK Volunteer Group FX This study was supported by grants from the American Diabetes Association (N. Musi and R. A. DeFronzo), the National Institutes of Health (AG-030979, DK-80157, and DK-089229 to N. Musi and DK-24092 to R. A. DeFronzo), the San Antonio Nathan Shock Center (N. Musi), the South Texas Health Research Center (N. Musi), the US Department of Veterans Affairs (R. A. DeFronzo), the Novo Nordisk Foundation (J. Jensen), the United Kingdom (UK) Medical Research Council (K. Sakamoto), Diabetes UK (K. Sakamoto), and the Dundee and District of Diabetes UK Volunteer Group (K. Sakamoto). NR 45 TC 4 Z9 4 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUL PY 2012 VL 303 IS 1 BP E82 EP E89 DI 10.1152/ajpendo.00658.2011 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 974EG UT WOS:000306412000007 PM 22510711 ER PT J AU Separovic, D Breen, P Joseph, N Bielawski, J Pierce, JS Van Buren, E Gudz, TI AF Separovic, Duska Breen, Paul Joseph, Nicholas Bielawski, Jacek Pierce, Jason S. Van Buren, Eric Gudz, Tatyana I. TI siRNA-Mediated Down-regulation of Ceramide Synthase 1 Leads to Apoptotic Resistance in Human Head and Neck Squamous Carcinoma Cells after Photodynamic Therapy SO ANTICANCER RESEARCH LA English DT Article DE Apoptosis; ceramide; ceramide synthase 1; dihydroceramide; PDT; sphingolipids; head and neck squamous carcinomas cells UM-SCC-22A ID LONGEVITY ASSURANCE GENE-1; DE-NOVO SPHINGOLIPIDS; PHOTOSENSITIZED CELLS; FAMILY-MEMBERS; ACCUMULATION; 1-PHOSPHATE; SPECIFICITY; INHIBITION; GROWTH; DEATH AB Background: The effectiveness of photodynamic therapy (PDT) for cancer treatment correlates with apoptosis. We previously observed that the knockdown of ceramide synthase 6, an enzyme from the de novo sphingolipid biosynthesis pathway, is associated with marked reduction in C18-dihydroceramide and makes cells resistant to apoptosis post-PDT. Down-regulation of ceramide synthase 1 (CERS1) can also render cells resistant to anticancer drugs. Aim: To explore the impact of CERS1 knockdown on apoptosis and the sphingolipid profile, post-PDT, with the silicone phthalocyanine Pc 4, in a human head and neck squamous carcinoma cell line. Materials and Methods: Besides siRNA transfection and PDT treatment, the following methods were used: immunoblotting for protein expression, mass spectrometry for sphingolipid analysis, spectroflurometry and flow cytometry for apoptosis detection, and trypan blue assay for cell viability evaluation. Results: CERS1 knockdown led to inhibition of PDT-induced caspase 3-like (DEVDase) activation, of apoptosis and cell death. CERS1 knockdown was associated with global and selective decreases in ceramides and dihydroceramides, in particular C18-, C18:1- and C20-ceramide post-PDT. Conclusion: Our novel findings are consistent with the notion that CERS1 regulates apoptotic resistance to PDT, partly via C18- and C20-ceramide, and that CERS1 is a molecular target for controlling resistance to PDT. C1 [Separovic, Duska; Breen, Paul; Joseph, Nicholas] Wayne State Univ, Dept Pharmaceut Sci, Eugene Applebaum Coll Pharm & Hlth Sci, Detroit, MI 48201 USA. [Separovic, Duska; Van Buren, Eric] Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48201 USA. [Bielawski, Jacek; Pierce, Jason S.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Gudz, Tatyana I.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Gudz, Tatyana I.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. RP Separovic, D (reprint author), Wayne State Univ, Dept Pharmaceut Sci, Eugene Applebaum Coll Pharm & Hlth Sci, 259 Mack Ave, Detroit, MI 48201 USA. EM dseparovic@wayne.edu FU U.S. Public Health Service from the National Cancer Institute, National Institutes of Health [R01 CA77475]; Veterans Administration; NCI [IPO1CA097132, P30 CA 138313]; NIH/NCRR SC COBRE [P20 RR017677]; NIH; Extramural Research Facilities Program of the National Center for Research Resources [C06 RR018823] FX This work was supported by U.S. Public Health Service Grant R01 CA77475 from the National Cancer Institute, National Institutes of Health (DS) and the Veterans Administration Merit Awards from RR&D and BLRD programs (TIG). The MS-related work was performed by the Lipidomics Shared Resource (Medical University of South Carolina), supported by NCI grants: IPO1CA097132 and P30 CA 138313 and NIH/NCRR SC COBRE Grant P20 RR017677. Laboratory space for the Lipidomics Shared Resource was supported by the NIH, grant C06 RR018823 from the Extramural Research Facilities Program of the National Center for Research Resources. We thank Drs. Besim Ogretmen and Can Emre Senkal for helpful discussions over the manuscript. NR 29 TC 9 Z9 9 U1 0 U2 4 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JUL PY 2012 VL 32 IS 7 SI SI BP 2479 EP 2485 PG 7 WC Oncology SC Oncology GA 972CO UT WOS:000306254300010 PM 22753704 ER PT J AU Khan, BA Guzman, O Campbell, NL Walroth, T Tricker, JL Hui, SL Perkins, A Zawahiri, M Buckley, JD Farber, MO Ely, EW Boustani, MA AF Khan, Babar A. Guzman, Oscar Campbell, Noll L. Walroth, Todd Tricker, Jason L. Hui, Siu L. Perkins, Anthony Zawahiri, Mohammed Buckley, John D. Farber, Mark O. Ely, E. Wesley Boustani, Malaz A. TI Comparison and Agreement Between the Richmond Agitation-Sedation Scale and the Riker Sedation-Agitation Scale in Evaluating Patients' Eligibility for Delirium Assessment in the ICU SO CHEST LA English DT Article ID INTENSIVE-CARE-UNIT; MECHANICALLY VENTILATED PATIENTS; CRITICALLY-ILL PATIENTS; CONFUSION ASSESSMENT METHOD; MONITORING SEDATION; ADULT; RELIABILITY; VALIDITY; EFFICACY; PROTOCOL AB Background: Delirium evaluation in patients in the ICU requires the use of an arousal/sedation assessment tool prior to assessing consciousness. The Richmond Agitation-Sedation Scale (BASS) and the Riker Sedation-Agitation Scale (SAS) are well-validated arousal/sedation tools. We sought to assess the concordance of BASS and SAS assessments in determining eligibility of patients in the ICU for delirium screening using the confusion assessment method for the ICU (CAM-ICU). Methods: We performed a prospective cohort study in the adult medical, surgical, and progressive (step-down) ICUs of a tertiary care, university-affiliated, urban hospital in Indianapolis, Indiana. The cohort included 975 admissions to the ICU between January and October 2009. Results: The outcome measures of interest were the correlation and agreement between RASS and SAS measurements. In 2,469 RASS and SAS paired screens, the rank correlation using the Spearman correlation coefficient was 0.91, and the agreement between the two screening tools for assessing CAM-ICU eligibility as estimated by the K coefficient was 0.93. Analysis showed that 70.1% of screens were eligible for CAM-ICU assessment using BASS (7.1% sedated [BASS -3 to -1]; 62.6% calm [0]; and 0.4% restless, agitated [+1 to +3]), compared with 72.1% using SAS (5% sedated [SAS 3]; 66.5% calm [4]; and 0.6% anxious, agitated [5, 6]). In the mechanically ventilated subgroup, RASS identified 19.1% CAM-ICU eligible patients compared with 24.6% by SAS. The correlation coefficient in this subgroup was 0.70 and the agreement was 0.81. Conclusion: Both SAS and BASS led to similar rates of delirium assessment using the CAM-ICU. CHEST 2012; 142(1):48-54 C1 [Khan, Babar A.; Hui, Siu L.; Buckley, John D.; Farber, Mark O.; Boustani, Malaz A.] Indiana Univ Sch Med, Indianapolis, IN USA. [Guzman, Oscar] Westchester Cty Med Ctr, Dept Pharm, Westchester, NY USA. [Khan, Babar A.; Campbell, Noll L.; Hui, Siu L.; Perkins, Anthony; Zawahiri, Mohammed; Boustani, Malaz A.] Regenstrief Inst Inc, Indianapolis, IN USA. [Walroth, Todd; Tricker, Jason L.] Wishard Hlth Serv, Indianapolis, IN USA. [Khan, Babar A.; Campbell, Noll L.; Hui, Siu L.; Boustani, Malaz A.] Indiana Univ, Ctr Aging Res, Indianapolis, IN 46204 USA. [Campbell, Noll L.] Purdue Univ, Coll Pharm, Dept Pharm Practice, W Lafayette, IN 47907 USA. [Ely, E. Wesley] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Ely, E. Wesley] US Dept Vet Affairs, Tennessee Valley Geriatr Res Educ Clin Ctr, Nashville, TN USA. RP Khan, BA (reprint author), 410 W 10th St,Ste 2000, Indianapolis, IN 46202 USA. EM bakhan@iupui.edu FU National Institute on Aging [R01AG034205-01A1]; National Institutes of Health; Forest Pharmaceuticals; Novartis FX The study was supported by a grant from the National Institute on Aging [Grant R01AG034205-01A1].; Financial/nonfinancial disclosures: Dr Boustani has received grant funds from the National Institute on Aging and the National Institutes of Health, grant funds from Forest Pharmaceuticals and Novartis, and serves on the speakers' bureau for Pfizer Inc and an advisory board for Eli Lilly and Company. All other authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. NR 34 TC 16 Z9 19 U1 3 U2 12 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2012 VL 142 IS 1 BP 48 EP 54 DI 10.1378/chest.11-2100 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 971NE UT WOS:000306209800013 PM 22539644 ER PT J AU Leung, JM Udris, EM Uman, J Au, DH AF Leung, Janice M. Udris, Edmunds M. Uman, Jane Au, David H. TI The Effect of End-of-Life Discussions on Perceived Quality of Care and Health Status Among Patients With COPD SO CHEST LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; LUNG-CANCER; COMMUNICATION; VENTILATION; PREFERENCES; CLINICIAN; PROGNOSIS; INSIGHTS; BARRIERS; DEATH AB Background: Despite strong preferences for discussions about end-of-life care, patients with COPD do not often have these discussions with their providers. Our objective was to determine whether patients who reported having end-of-life discussions also reported higher perceived markers of quality of care and health status. Methods: A cross-sectional study of data collected at baseline for a trial to improve the occurrence and quality of end-of-life communication in patients with COPD was conducted. The primary exposure was self-reported acknowledgment of having discussions about end-of-life planning with their physicians. The primary outcome measures were patient-reported quality of care and satisfaction with care, which were dichotomized as best imaginable quality of care vs other ratings of quality and highest satisfaction vs other ratings of satisfaction. We adjusted for confounding factors, including patient and provider characteristics, using logistic regression clustered by provider. Results: Three hundred seventy-six patients were enrolled, of whom 55 (14.6%) reported having end-of-life discussions. Individuals who reported having end-of-life discussions with their physicians were significantly more likely to rate their quality of care as the best imaginable (OR, 2.07; 95% CI, 1.05-4.09) and to be very satisfied with their medical care (OR, 1.98; 95% CI, 1.10-3.55). Discussions were more likely to have occurred among patients with worse health status as measured by St. George Respiratory Questionnaire total and impact scores. Conclusions: Patients who reported having end-of-life care discussions with their physicians had higher perceived quality of care and satisfaction with their physicians. Discussing end-of-life care with patients who have COPD may improve their perceived overall quality of and satisfaction with care. CHEST 2012; 142(1):128-133 C1 [Leung, Janice M.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Leung, Janice M.; Au, David H.] Univ Washington, Dept Med, Div Pulm & Crit Care Med, Seattle, WA USA. [Udris, Edmunds M.; Uman, Jane; Au, David H.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. RP Leung, JM (reprint author), 10 Ctr Dr,2C145, Bethesda, MD 20892 USA. EM Janice.Leung@nih.gov FU Department of Veterans Affairs [IIR-0292]; Department of Veterans Affairs; National Heart, Lung, and Blood Institute; Agency of Healthcare Research and Quality; Gilead Sciences FX This study was supported by the Department of Veterans Affairs [IIR-0292].; Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Au is a research advisor for Bosch. He receives research funding from the Department of Veterans Affairs; the National Heart, Lung, and Blood Institute; Agency of Healthcare Research and Quality; and Gilead Sciences. Dr Leung, Mr Udris, and Ms Uman have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. NR 24 TC 11 Z9 11 U1 0 U2 13 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2012 VL 142 IS 1 BP 128 EP 133 DI 10.1378/chest.11-2222 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 971NE UT WOS:000306209800022 PM 22241761 ER PT J AU Rodriguez, RA AF Rodriguez, Rudolph A. TI Dialysis and Mortality: Does It Matter Where You Live? SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID PERITONEAL-DIALYSIS; KIDNEY-TRANSPLANTATION; UNITED-STATES; REMOTE C1 [Rodriguez, Rudolph A.] Puget Sound VA Med Ctr, Nephrol & Renal Dialysis Unit, Seattle, WA 98108 USA. [Rodriguez, Rudolph A.] Univ Washington, Seattle, WA 98195 USA. [Rodriguez, Rudolph A.] VA Puget Sound Healthcare Syst, Seattle, WA 98195 USA. RP Rodriguez, RA (reprint author), Puget Sound VA Med Ctr, Nephrol & Renal Dialysis Unit, Bldg 100,Room 5B113,1660 S Columbian Way, Seattle, WA 98108 USA. EM rudyrod@u.washington.edu NR 10 TC 1 Z9 1 U1 1 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUL PY 2012 VL 7 IS 7 BP 1055 EP 1057 DI 10.2215/CJN.05410512 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 970QX UT WOS:000306148500001 PM 22723448 ER PT J AU Yenchek, RH Ix, JH Shlipak, MG Bauer, DC Rianon, NJ Kritchevsky, SB Harris, TB Newman, AB Cauley, JA Fried, LF AF Yenchek, Robert H. Ix, Joachim H. Shlipak, Michael G. Bauer, Douglas C. Rianon, Nahiof J. Kritchevsky, Stephen B. Harris, Tamara B. Newman, Anne B. Cauley, Jane A. Fried, Linda F. CA Hlth Aging & Body Composition Stud TI Bone Mineral Density and Fracture Risk in Older Individuals with CKD SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; HEMODIALYSIS-PATIENTS; HIP FRACTURE; DIALYSIS PATIENTS; OSTEOPOROTIC FRACTURE; RENAL OSTEODYSTROPHY; DIABETES-MELLITUS; HOMOCYSTEINE; ULTRASOUND AB Background and objectives Kidney Disease Improving Global Outcomes guidelines recommend against bone mineral density (BMD) screening in CKD patients with mineral bone disease, due to a lack of association of BMD with fractures in cross-sectional studies in CKD. We assessed whether BMD is associated with fractures in participants with and without CKD in the Health, Aging, and Body Composition study, a prospective study of well functioning older individuals. Design, setting, participants, & measurements Hip BMD was measured by dual-energy x-ray absorptiometry. Osteoporosis was defined as a femoral neck BMD (FNBMD) T score below -2.5 and CKD as an estimated GFR <60 ml/min per 1.73 m(2). The association of BMD with incident nonspine, fragility fractures to study year 11 was analyzed using Cox proportional hazards analyses, adjusting for age, race, sex, body mass index, hyperparathyroidism, low vitamin D level, and CKD. Interaction terms were used to assess whether the association of BMD with fracture differed in those with and without CKD. Results There were 384 incident fractures in 2754 individuals (mean age 73.6 years). Lower FNBMD was associated with greater fracture, regardless of CKD status. After adjustment, the hazard ratios (95% confidence intervals) were 2.74 (1.99, 3.77) and 2.15 (1.80, 2.57) per lower SD FNBMD for those with and without CKD, respectively (interaction P=0.68), and 2.10 (1.23, 3.59) and 1.63 (1.18, 2.23) among those with osteoporosis in patients with and without CKD, respectively (interaction P=0.75). Conclusions BMD provides information on risk for fracture in older individuals with or without moderate CKD. Clin J Am Soc Nephrol 7: 1130-1136, 2012. doi: 10.2215/CJN.12871211 C1 [Yenchek, Robert H.] Univ Pittsburgh, Dept Med, Renal Electrolyte Div, Sch Med, Pittsburgh, PA 15213 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. [Ix, Joachim H.] Univ Calif San Diego, Sch Med, Dept Med, San Diego, CA 92103 USA. [Ix, Joachim H.] Univ Calif San Diego, Sch Med, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Shlipak, Michael G.; Bauer, Douglas C.] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA USA. [Rianon, Nahiof J.] Univ Texas Houston, Sch Med, Dept Family & Community Med, Houston, TX USA. [Kritchevsky, Stephen B.] Wake Forest Sch Med, Stricht Ctr Aging, Wake Forest, NC USA. [Harris, Tamara B.] NIA, NIH, Bethesda, MD 20892 USA. [Newman, Anne B.; Cauley, Jane A.; Fried, Linda F.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Fried, Linda F.] Vet Affairs Pittsburgh Hlth Care Syst, Renal Sect, Pittsburgh, PA USA. RP Yenchek, RH (reprint author), Univ Pittsburgh, Dept Med, Renal Electrolyte Div, Sch Med, 200 Lothrop St,C1100 PUH, Pittsburgh, PA 15213 USA. EM yenchekrh@upmc.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781; Cauley, Jane A/0000-0003-0752-4408 FU Intramural Research Program of the National Institutes of Health; National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050, R01-AG029364]; National Institute of Nursing Research [R01-NR012459]; NIDDK [T32DK061296] FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, as well as the National Institute on Aging (Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; and Grants R01-AG028050 and R01-AG029364) and the National Institute of Nursing Research (Grant R01-NR012459). R.H.Y. is supported by NIDDK Grant T32DK061296. NR 32 TC 52 Z9 54 U1 1 U2 5 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUL PY 2012 VL 7 IS 7 BP 1130 EP 1136 DI 10.2215/CJN.12871211 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 970QX UT WOS:000306148500012 PM 22516286 ER PT J AU Hernandez-Tejada, MA Campbell, JA Walker, RJ Smalls, BL Davis, KS Egede, LE AF Hernandez-Tejada, Melba A. Campbell, Jennifer A. Walker, Rebekah J. Smalls, Brittany L. Davis, Kimberly S. Egede, Leonard E. TI Diabetes Empowerment, Medication Adherence and Self-Care Behaviors in Adults with Type 2 Diabetes SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID EDUCATION-PROGRAM; MANAGEMENT; KNOWLEDGE; SCALE AB Background: Evidence suggests that empowerment is an important factor to address everyday aspects of dealing with a chronic disease. This study evaluated the effect of diabetes empowerment on medication adherence and self-care behaviors in adults with type 2 diabetes. Subjects and Methods: Data on 378 subjects with type 2 diabetes recruited from two primary care clinics in the southeastern United States were examined. Previously validated scales were used to measure diabetes empowerment, medication adherence, diabetes knowledge, and diabetes self-care behaviors (including diet, physical activity, blood sugar testing, and foot care). Multiple linear regression was used to assess the independent effect of diabetes empowerment on medication adherence and self-care behaviors controlling for relevant covariates. Results: Eighty-three percent were non-Hispanic blacks, 69% were women, 22% were 65 years or older, 68% were not married, 26% had less than high school education, 60% were unemployed, 39% were uninsured, and 47% had a yearly income <$10,000. Empowerment had significant correlations with medication adherence (r = 0.17, P < 0.003), diabetes knowledge (r = 0.16, P = 0.007), diet (r = 0.24, P < 0.001), exercise (r = 0.25, P < 0.001), blood sugar testing (r = 0.12, P = 0.043), and foot care (r = 0.18, P = 0.002). In the regression model, diabetes empowerment was significantly associated with medication adherence (beta = -0.04, P = 0.001), diabetes knowledge (beta = 0.09, P = 0.012), diet (beta = 0.09, P < 0.001), exercise (beta = 0.10, P < 0.001), blood sugar testing (beta = 0.07, P = 0.016), and foot care (beta = 0.08, P = 0.001). Conclusions: In this sample, diabetes empowerment was related to better diabetes knowledge, medication adherence and improved self-care behaviors. Emphasis on empowerment and self-efficacy is relevant to improve outcomes in the management of diabetes. C1 [Hernandez-Tejada, Melba A.; Campbell, Jennifer A.; Walker, Rebekah J.; Smalls, Brittany L.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Davis, Kimberly S.; Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Dept Med, Charleston, SC 29425 USA. [Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston VA REAP, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280G,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu FU National Institute for Diabetes and Digestive and Kidney Diseases [T35DK007431] FX This work was supported by grant T35DK007431 from the National Institute for Diabetes and Digestive and Kidney Diseases. NR 28 TC 16 Z9 17 U1 1 U2 20 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD JUL PY 2012 VL 14 IS 7 BP 630 EP 634 DI 10.1089/dia.2011.0287 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 971ZF UT WOS:000306245600014 PM 22524548 ER PT J AU Hawkins, EJ Malte, CA Imel, ZE Saxon, AJ Kivlahan, DR AF Hawkins, Eric J. Malte, Carol A. Imel, Zac E. Saxon, Andrew J. Kivlahan, Daniel R. TI Prevalence and trends of benzodiazepine use among Veterans Affairs patients with posttraumatic stress disorder, 2003-2010 SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Trends in benzodiazepine use; Posttraumatic stress disorder; Opioid analgesics use ID SUBSTANCE USE DISORDERS; CHRONIC NONCANCER PAIN; MENTAL-HEALTH; PHARMACOLOGICAL-TREATMENT; ADMINISTRATIVE DATA; ANXIETY DISORDERS; OPIOID OVERDOSE; ALCOHOL-USE; RISK; ASSOCIATION AB Background: Although the Veterans Affairs and Department of Defense (VA/DoD) clinical guidelines for management of posttraumatic stress disorder (PTSD) recommend against routine benzodiazepine use, little is known about the trends and clinical and prescription profiles of benzodiazepine use since these guidelines were released in 2004. Methods: This retrospective study included 64,872 patients with a PTSD diagnosis received from care at facilities in VA Northwest Veterans Integrated Service Network (VISN 20) during 2003-2010. Annual prevalence of any use was defined as any prescription for benzodiazepines, and long-term use was defined as >90 days' supply, in a year. Gender-specific logistic regressions were fit to estimate any and long-term benzodiazepine use, test for linear trends over 8-years and explore factors associated with trends. Results: The trend of age-adjusted benzodiazepine use over 8-years rose significantly from 25.0 to 26.8% among men and 31.2 to 38.8% among women. Long-term use in men and women increased from 15.4 to 16.4% and 18.0 to 22.7%, respectively. Comorbid psychiatric and alcohol use disorders (AUD) were associated with a greater increase in long-term use of benzodiazepines. In 2010, 61% of benzodiazepine users received >90 days' supply. Among those prescribed benzodiazepines long-term, 11% had AUD and 47% were also prescribed opioids long-term. Conclusion: Despite VA/DoD clinical guidelines recommending against routine use of benzodiazepines for PTSD, the adjusted prevalence of long-term use increased among men and women with PTSD in VISN 20. Widespread concomitant use of benzodiazepines and opioids suggests risk management systems and research on the efficacy and safety of these medications are needed. Published by Elsevier Ireland Ltd. C1 [Hawkins, Eric J.] VA Puget Sound Hlth Care Syst, Seattle Div S116ATC, Hlth Serv Res & Dev, Seattle, WA 98108 USA. [Hawkins, Eric J.; Malte, Carol A.; Saxon, Andrew J.; Kivlahan, Daniel R.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. [Saxon, Andrew J.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Hawkins, Eric J.; Kivlahan, Daniel R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Imel, Zac E.] Univ Utah, Dept Educ Psychol, Salt Lake City, UT 84112 USA. RP Hawkins, EJ (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div S116ATC, Hlth Serv Res & Dev, 1660 S Columbian Way, Seattle, WA 98108 USA. EM Eric.Hawkins@va.gov OI imel, zachary/0000-0001-9645-7184 FU VA Puget Sound Health Care System, Center of Excellence in Substance Abuse Treatment & Education, Seattle, WA FX This material is the result of work supported by resources from the VA Puget Sound Health Care System, Center of Excellence in Substance Abuse Treatment & Education, Seattle, WA. Supporting organizations had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. 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 University of Washington. NR 52 TC 21 Z9 21 U1 2 U2 11 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 JUL 1 PY 2012 VL 124 IS 1-2 BP 154 EP 161 DI 10.1016/j.drugalcdep.2012.01.003 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 969IJ UT WOS:000306048600021 PM 22305658 ER PT J AU Smalls, BL Walker, RJ Hernandez-Tejada, MA Campbell, JA Davis, KS Egede, LE AF Smalls, Brittany L. Walker, Rebekah J. Hernandez-Tejada, Melba A. Campbell, Jennifer A. Davis, Kimberly S. Egede, Leonard E. TI Associations between coping, diabetes knowledge, medication adherence and self-care behaviors in adults with type 2 diabetes SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Coping; Medication adherence; Self-care; Diabetes ID EMOTIONAL APPROACH; MANAGEMENT; SCALE AB Background: Few studies have examined the emotional approach to coping on diabetes outcomes. This study examined the relationship between emotional coping and diabetes knowledge, medication adherence and self-care behaviors in adults with type 2 diabetes. Methods: Data on 378 subjects with type 2 diabetes recruited from two primary care clinics in the southeastern United States were examined. Previously validated scales were used to measure coping, medication adherence, diabetes knowledge and diabetes self-care behaviors (including diet, physical activity, blood sugar testing and foot care). Multiple linear regression was used to assess the independent effect of coping through emotional approach on medication adherence and self-care behaviors while controlling for relevant covariates. Results: Significant correlations were observed between emotional coping [as measured by emotional expression (EE) and emotional processing (EP)] and self-care behaviors. In the linear regression model, EP was significantly associated with medication adherence [beta -0.17, 95% confidence interval (CI) -0.32 to -0.015], diabetes knowledge (beta 0.76, 95% CI 0.29 to 1.24), diet (beta 0.52, 95% CI 0.24 to 0.81), exercise (beta 0.51, 95% CI 0.19 to 0.82), blood sugar testing (beta 0.54, 95% CI 0.16 to 0.91) and foot care (beta 0.32, 95% CI -0.02 to 0.67). On the other hand, EE was associated with diet (beta 0.38, 95% CI 0.13 to 0.64), exercise (beta 0.54, 95% CI 0.27 to 0.82), blood sugar testing (beta 0.42, 95% CI 0.09 to 0.76) and foot care (beta 0.36, 95% CI 0.06 to 0.66), but it was not associated with diabetes knowledge. Conclusion: These findings indicate that coping through an emotional approach is significantly associated with behaviors that lead to positive diabetes outcomes. (C) 2012 Elsevier Inc. All rights reserved. C1 [Smalls, Brittany L.; Walker, Rebekah J.; Hernandez-Tejada, Melba A.; Campbell, Jennifer A.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Davis, Kimberly S.; Egede, Leonard E.] Med Univ S Carolina, Dept Med, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. [Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Charleston VA REAP, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, POB 250593 Charleston, Charleston, SC 29425 USA. EM egedel@musc.edu FU National Institute for Diabetes, Digestive and Kidney Disease [T35DK007431] FX Supported by grant no. T35DK007431 from the National Institute for Diabetes, Digestive and Kidney Disease. NR 19 TC 13 Z9 13 U1 2 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JUL-AUG PY 2012 VL 34 IS 4 BP 385 EP 389 DI 10.1016/j.genhosppsych.2012.03.018 PG 5 WC Psychiatry SC Psychiatry GA 972TI UT WOS:000306302700009 PM 22554428 ER PT J AU Collins, EG O'Connell, S McBurney, C Jelinek, C Butler, J Reda, D Gerber, BS Hurt, C Grabiner, M AF Collins, Eileen G. O'Connell, Susan McBurney, Conor Jelinek, Christine Butler, Jolene Reda, Domenic Gerber, Ben S. Hurt, Christopher Grabiner, Mark TI Comparison of Walking With Poles and Traditional Walking for Peripheral Arterial Disease Rehabilitation SO JOURNAL OF CARDIOPULMONARY REHABILITATION AND PREVENTION LA English DT Article DE peripheral arterial disease; rehabilitation; walking exercise ID INTERMITTENT CLAUDICATION; NORDIC WALKING; PHYSIOLOGICAL-RESPONSES; ENERGY-EXPENDITURE; EXERCISE; PAIN AB PURPOSE: The purpose of this study was to compare the effects of a 24-week walking with poles rehabilitation program with a traditional 24-week walking program on physical function in patients with peripheral arterial disease (PAD). METHODS: Patients with PAD (n = 103, age = 69.7 +/- 8.9 years, ankle-brachial index < 0.90 or evidence of calcified vessels) were randomized into a rehabilitation program of traditional walking (n = 52) or walking with poles (n = 51). Patients exercised 3 times per week for 24 weeks. Exercise endurance was measured by time walked on a constant work rate treadmill test at 6, 12, and 24 weeks. Perceived physical function was measured by the Medical Outcomes Study Short Form-36 and Walking Impairment Questionnaire. Tissue oxygenation was measured using near-infrared spectroscopy. RESULTS: Patients assigned to the traditional walking group walked longer at 24 weeks than those assigned to the pole walking group (21.10 +/- 17.07 minutes and 15.02 +/- 12.32 minutes, respectively, P = .037). There were no differences between the groups in tissue oxygenation. However, there was a significant lengthening of time for which it took to reach minimum tissue oxygenation values (P < .001) within the groups on the constant work rate test. There were no differences between the groups in perceived physical function as measured by the Physical Function subscale on the Medical Outcomes Study Short Form-36 or perceived walking distance as measured by the Walking Distance subscale on the Walking Impairment Scale. CONCLUSIONS: Traditional walking was superior to walking with poles in increasing walking endurance on a constant work rate treadmill test for patients with PAD. C1 [Collins, Eileen G.; O'Connell, Susan; McBurney, Conor; Jelinek, Christine; Butler, Jolene; Gerber, Ben S.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care, Dept Vet Affairs, Hines, IL 60141 USA. [Reda, Domenic] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Cooperat Studies Program, Dept Vet Affairs, Hines, IL 60141 USA. [Collins, Eileen G.] Univ Illinois, Dept Biobehav Hlth Sci, Coll Nursing, Chicago, IL 60612 USA. [Gerber, Ben S.] Univ Illinois, Sect Hlth Promot Res, Dept Med, Chicago, IL 60612 USA. [Hurt, Christopher; Grabiner, Mark] Univ Illinois, Dept Kinesiol & Nutr, Chicago, IL 60612 USA. RP Collins, EG (reprint author), Univ Illinois, Dept Biobehav Hlth Sci, Coll Nursing MC802, 845 S Damen Ave, Chicago, IL 60612 USA. EM ecollins@uic.edu OI Gerber, Ben/0000-0003-4367-6396 FU National Institute of Nursing Research [RO1 NR008877-01]; Research Career Scientist Award, Rehabilitation Research & Development, Department of Veterans Affairs FX This work was supported by a grant from the National Institute of Nursing Research (RO1 NR008877-01) and a Research Career Scientist Award (Collins), Rehabilitation Research & Development, Department of Veterans Affairs. The contents of this article do not represent the views of the National Institutes of Health, the Department of Veterans Affairs, or the US Government. The authors have no affiliation with Exerstrider. NR 23 TC 8 Z9 8 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-7501 J9 J CARDIOPULM REHABIL JI J. Cardiopulm. Rehabil. Prev. PD JUL-AUG PY 2012 VL 32 IS 4 BP 210 EP 218 DI 10.1097/HCR.0b013e31825828f4 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 970GF UT WOS:000306115400007 PM 22595894 ER PT J AU Roth, CP Ganz, DA Nickels, L Martin, D Beckman, R Wenger, NS AF Roth, Carol P. Ganz, David A. Nickels, Lorraine Martin, David Beckman, Robin Wenger, Neil S. TI Nurse Care Manager Contribution to Quality of Care in a Dual-Eligible Special Needs Plan SO JOURNAL OF GERONTOLOGICAL NURSING LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; URINARY-INCONTINENCE; OLDER-PATIENTS; VULNERABLE ELDERS; DEMENTIA; HEALTH; FALLS; MODEL; INTERVENTIONS; DEPRESSION AB We evaluated the quality of care provided to older patients with complex needs in a dual-eligible, community-based Medicare Special Needs Plan that used a nurse care manager model. Care provided by physicians was substantially supplemented by nurse care managers, as measured by Assessing Care of Vulnerable Elders quality indicators. We describe selected nurse care manager activities for six geriatric conditions (falls, dementia, depression, nutrition, urinary incontinence, and end-of-life care) during provision of patient care coordination and management for patients in the highest decile of clinical complexity. We identify areas of high nurse performance (i.e., falls screening, functional assessment, behavioral interventions for dementia problems, advance care planning) and areas of potential missed opportunities (i.e., follow up for new memory problems, targeted dementia counseling, nutrition, and behavioral approaches to urinary incontinence). Increasing the collaborative interaction between nurses providing care in this model and physicians has the potential to enhance nurses' contributions to primary care for vulnerable older adults. C1 [Roth, Carol P.; Ganz, David A.; Beckman, Robin; Wenger, Neil S.] RAND Hlth, Santa Monica, CA 90407 USA. [Nickels, Lorraine] UnitedHealthcare, Clin Qual Improvement, Minnetonka, MN USA. [Martin, David] UnitedHealthcare Medicare & Retirement, Clin Innovat, Minnetonka, MN USA. [Ganz, David A.] VA Greater Los Angeles Healthcare Syst, Hlth Serv Res & Dev Serv, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Wenger, Neil S.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Roth, CP (reprint author), RAND Hlth, 1776 Main St, Santa Monica, CA 90407 USA. EM roth@rand.org FU UnitedHealthcare FX Ms. Roth, Dr. Ganz, Ms. Beckman, and Dr. Wenger have disclosed no potential conflicts of interest, financial or otherwise. Ms. Nickels and Dr. Martin disclose that they are United Healthcare shareholders. This project was supported by a contract from UnitedHealthcare to the RAND Corporation. NR 42 TC 3 Z9 3 U1 3 U2 10 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0098-9134 J9 J GERONTOL NURS JI J. Gerontol. Nurs. PD JUL PY 2012 VL 38 IS 7 BP 44 EP 54 DI 10.3928/00989134-20120606-10 PG 11 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA 971OH UT WOS:000306213200007 PM 22833891 ER PT J AU Saldarriaga, OA Travi, BL Choudhury, GG Melby, PC AF Saldarriaga, Omar A. Travi, Bruno L. Choudhury, Goutam Ghosh Melby, Peter C. TI Identification of hamster inducible nitric oxide synthase (iNOS) promoter sequences that influence basal and inducible iNOS expression SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE C/EBP-beta; transcriptional regulation; NF-IL-6; NOS2 ID BINDING PROTEIN BETA; FACTOR-KAPPA-B; INTERFERON-GAMMA; ALVEOLAR MACROPHAGES; SPECIES-DIFFERENCES; MOUSE MACROPHAGES; RESPONSE ELEMENT; REACTIVE OXYGEN; ENDOTOXIC-SHOCK; MESSENGER-RNA AB IFN-gamma/LPS-activated hamster (Mesocricetus auratus) macrophages express significantly less iNOS (NOS2) than activated mouse macrophages, which contributes to the hamster's susceptibility to intracellular pathogens. We determined a mechanism responsible for differences in iNOS promoter activity in hamsters and mice. The HtPP (1.2 kb) showed low basal and inducible promoter activity when compared with the mouse, and sequences within a 100-bp region (-233 to -133) of the mouse and hamster promoters influenced this activity. Moreover, within this 100 bp, we identified a smaller region (44 bp) in the mouse promoter, which recovered basal promoter activity when swapped into the hamster promoter. The mouse homolog (100-bp region) contained a cis-element for NF-IL-6 (-153/-142), which was absent in the hamster counterpart. EMSA and supershift assays revealed that the hamster sequence did not support the binding of NF-IL-6. Introduction of a functional NF-IL-6 binding sequence into the hamster promoter or its alteration in the mouse promoter revealed the critical importance of this transcription factor for full iNOS promoter activity. Furthermore, the binding of NF-IL-6 to the iNOS promoter (-153/-142) in vivo was increased in mouse cells but was reduced in hamster cells after IFN-gamma/LPS stimulation. Differences in the activity of the iNOS promoters were evident in mouse and hamster cells, so they were not merely a result of species-specific differences in transcription factors. Thus, we have identified unique DNA sequences and a critical transcription factor, NF-IL-6, which contribute to the overall basal and inducible expression of hamster iNOS. J. Leukoc. Biol. 92: 205-218; 2012. C1 [Saldarriaga, Omar A.; Travi, Bruno L.; Choudhury, Goutam Ghosh; Melby, Peter C.] S Texas Vet Hlth Care Syst, Res Serv, Dept Vet Affairs Med Ctr, San Antonio, TX USA. [Saldarriaga, Omar A.; Travi, Bruno L.; Choudhury, Goutam Ghosh; Melby, Peter C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Saldarriaga, Omar A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. RP Melby, PC (reprint author), Univ Texas Med Branch, Dept Internal Med, Div Infect Dis, 301 Univ Blvd,Rte 0435, Galveston, TX 77555 USA. EM pcmelby@utmb.edu FU U.S. National Institutes of Health (NIH) [AI61624]; U.S. NIH [RO1 DK 50,190]; VA Merit Review; JDRF [1-2008-185]; U.S. Department of Veterans Affairs FX This work was supported by U.S. National Institutes of Health (NIH) grant AI61624 (P. C. M.). G. G. C. is supported by U.S. NIH RO1 DK 50,190, VA Merit Review, and JDRF 1-2008-185 grants. G. G. C. is a recipient of a Senior Research Career Scientists award from the U.S. Department of Veterans Affairs. We thank Dr. Sunil Ahuja and Dr. Srinivas Mummidi for their scientific input and Sheela Rani for her advice with the ChiP assays. NR 46 TC 7 Z9 7 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUL PY 2012 VL 92 IS 1 BP 205 EP 218 DI 10.1189/jlb.1010568 PG 14 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 966KS UT WOS:000305837100022 PM 22517919 ER PT J AU Arcenas, RC Spadoni, S Mohammad, A Kiechle, FL Walker, K Fader, RC Perdreau-Remington, F Osiecki, J Liesenfeld, O Hendrickson, S Rao, A AF Arcenas, Rodney C. Spadoni, Stacey Mohammad, Amin Kiechle, Frederick L. Walker, Kimberly Fader, Robert C. Perdreau-Remington, Francoise Osiecki, John Liesenfeld, Oliver Hendrickson, Shelby Rao, Arundhati TI Multicenter Evaluation of the LightCycler MRSA Advanced Test, the Xpert MRSA Assay, and MRSASelect Directly Plated Culture with Simulated Workflow Comparison for the Detection of Methicillin-Resistant Staphylococcus aureus in Nasal Swabs SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID REAL-TIME PCR; CHROMAGAR MRSA; SURVEILLANCE CULTURES; CHROMOGENIC MEDIA; MOLECULAR ASSAYS; RAPID DETECTION; EPIDEMIOLOGY; INFECTIONS; RISK; IDENTIFICATION AB Rapid detection of nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) followed by appropriate infection control procedures reduces MRSA infection and transmission. We compared the performance and workflow of two Food and Drug Administration-approved nucleic acid amplification assays, the LightCycler MRSA Advanced Test and the Xpert MRSA test, with those of directly plated culture (MRSASelect) using 1202 nasal swabs collected at three U.S. sites. The sensitivity of the LightCycler test (95.2%; 95% CI, 89.1% to 98.4%) and Xpert assay (99%; 95% CI, 94.8% to 100%) did not differ compared with that of culture; the specificity of the two assays was identical (95.5%; 95% CI, 94.1% to 96.7%) compared with culture. However, sequencing performed on 71 samples with discordant results among the three methods confirmed the presence of MRSA in 40% of samples that were positive by both molecular methods but negative by culture. Workflow analysis from all sites including batch runs revealed average hands-on sample preparation times of 1.40, 2.35, and 1.44 minutes per sample for the LightCycler, Xpert, and MRSASelect methods, respectively. Discrete event simulation analysis of workflow efficiencies revealed that the LightCycler test used less hands-on time for the assay when greater than eight batched samples were run. The high sensitivity and specificity, low hands-on time, and efficiency gains using hatching capabilities make the LightCycler test suitable for rapid batch screening of MRSA colonization. (J Mol Diagn 2012, 14: 367-375; http://dx.doi.org/10.1016/j.jmoldx.2012.01.015) C1 [Mohammad, Amin; Walker, Kimberly; Fader, Robert C.; Hendrickson, Shelby; Rao, Arundhati] Scott & White Healthcare, Texas A&M Hlth Sci Ctr, Dept Pathol, Temple, TX 76508 USA. [Arcenas, Rodney C.; Kiechle, Frederick L.] Mem Reg Hosp S, Dept Pathol, Hollywood, FL USA. [Spadoni, Stacey] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Pathol, Hines, IL 60141 USA. [Perdreau-Remington, Francoise] Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA USA. [Osiecki, John] Roche Diagnost Corp, Med & Sci Affairs, Indianapolis, IN USA. [Liesenfeld, Oliver] Roche Mol Diagnost, Med & Sci Affairs, Pleasanton, CA USA. RP Rao, A (reprint author), Scott & White Healthcare, Texas A&M Hlth Sci Ctr, Dept Pathol, 2401 S 31st St, Temple, TX 76508 USA. EM arao@swmail.sw.org FU Roche Diagnostics Corp. FX Supported in part by Roche Diagnostics Corp. NR 34 TC 4 Z9 4 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD JUL PY 2012 VL 14 IS 4 BP 367 EP 375 DI 10.1016/j.jmoldx.2012.01.015 PG 9 WC Pathology SC Pathology GA 972AC UT WOS:000306247900009 PM 22584139 ER PT J AU Craft, S Foster, TC Landfield, PW Maier, SF Resnick, SM Yaffe, K AF Craft, Suzanne Foster, Thomas C. Landfield, Philip W. Maier, Steven F. Resnick, Susan M. Yaffe, Kristine TI Session III: Mechanisms of Age-Related Cognitive Change and Targets for Intervention: Inflammatory, Oxidative, and Metabolic Processes SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Aging; Cognition; Inflammation; Oxidative stress; Metabolism ID ALZHEIMER-DISEASE; IMPAIRMENT; DECLINE; MEMORY; RISK; HIPPOCAMPUS; PREVALENCE; DEMENTIA; LATINOS; PROTEIN AB There is increasing evidence from basic science and human epidemiological studies that inflammation, oxidative stress, and metabolic abnormalities are associated with age-related cognitive decline and impairment. This article summarizes selected research on these topics presented at the Cognitive Aging Summit II. Speakers in this session presented evidence highlighting the roles of these processes and pathways on age-related cognitive decline, pointing to possible targets for intervention in nondemented older adults. Specific areas discussed included age differences in the production of cytokines following injury or infection, mechanisms underlying oxidative stress-induced changes in memory consolidation, insulin effects on brain signaling and memory, and the association between metabolic syndrome and cognitive decline in older adults. These presentations emphasize advances in our understanding of mechanisms and modifiers of age-related cognitive decline and provide insights into potential targets to promote cognitive health in older adults. C1 [Resnick, Susan M.] NIA, Lab Behav Neurosci, BRC, Baltimore, MD 21224 USA. [Craft, Suzanne] Univ Washington, Dept Psychiat & Behav Sci, Geriatr Res Educ & Clin Ctr, Seattle, WA 98195 USA. [Foster, Thomas C.] Univ Florida, Dept Neurosci, Evelyn F & William L McKnight Brain Inst, Gainesville, FL 32610 USA. [Landfield, Philip W.] Univ Kentucky, Dept Mol & Biomed Pharmacol, Coll Med, Lexington, KY 40506 USA. [Maier, Steven F.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. [Maier, Steven F.] Univ Colorado, Dept Neurosci, Boulder, CO 80309 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. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Resnick, SM (reprint author), NIA, Lab Behav Neurosci, BRC, Room 4B335,251 Bayview Blvd, Baltimore, MD 21224 USA. EM susan.resnick@nih.gov FU Intramural NIH HHS [ZIA AG000191-15]; NCATS NIH HHS [UL1 TR000064]; NIA NIH HHS [R01 AG014979, P30 AG028740, R01 AG034605, R37 AG036800] NR 26 TC 29 Z9 30 U1 1 U2 9 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 JUL PY 2012 VL 67 IS 7 BP 754 EP 759 DI 10.1093/gerona/gls112 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 970PD UT WOS:000306143700008 PM 22570133 ER PT J AU Craft, S AF Craft, Suzanne TI Insulin resistance and AD-extending the translational path SO NATURE REVIEWS NEUROLOGY LA English DT Editorial Material ID TRANSGENIC MOUSE MODEL; ALZHEIMERS-DISEASE; AMYLOIDOSIS; OLIGOMERS; BRAIN AB Two recent studies have carefully characterized amyloid-related brain insulin resistance in animal models of, and patients with, Alzheimer disease (AD). The researchers show that exendin-4, a glucagon-like peptide 1 receptor agonist, ameliorates pathology and symptoms in a mouse model of AD, suggesting a novel therapeutic approach to this disease. C1 Vet Affairs Puget Sound, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. RP Craft, S (reprint author), Vet Affairs Puget Sound, Geriatr Res Educ & Clin Ctr, S-182,1660 S Columbian Way, Seattle, WA 98108 USA. EM scraft@u.washington.edu NR 9 TC 46 Z9 47 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD JUL PY 2012 VL 8 IS 7 BP 360 EP 362 DI 10.1038/nrneurol.2012.112 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 970BU UT WOS:000306103900002 PM 22710630 ER PT J AU Delgado-Escueta, AV AF Delgado-Escueta, Antonio V. TI Lafora progressive myoclonus epilepsy Glycogen storage disease vs neurodegenerative disease SO NEUROLOGY LA English DT Editorial Material ID MALIN; MICE C1 [Delgado-Escueta, Antonio V.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Delgado-Escueta, Antonio V.] VA Greater Los Angeles Healthcare Syst, VA Epilepsy Ctr Excellence, Los Angeles, CA USA. RP Delgado-Escueta, AV (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. EM escueta@ucla.edu OI Delgado-Escueta, Antonio V./0000-0002-1581-6999 FU NINDS NIH HHS [R01 NS042376] NR 10 TC 3 Z9 3 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 2012 VL 79 IS 1 BP 21 EP 22 DI 10.1212/WNL.0b013e31825dcea6 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 971BE UT WOS:000306176000008 PM 22622859 ER PT J AU Weaver, FM Follett, KA Stern, M Luo, P Harris, CL Hur, K Marks, WJ Rothlind, J Sagher, O Moy, C Pahwa, R Burchiel, K Hogarth, P Lai, EC Duda, JE Holloway, K Samii, A Horn, S Bronstein, JM Stoner, G Starr, PA Simpson, R Baltuch, G De Salles, A Huang, GD Reda, DJ AF Weaver, Frances M. Follett, Kenneth A. Stern, Matthew Luo, Ping Harris, Crystal L. Hur, Kwan Marks, William J., Jr. Rothlind, Johannes Sagher, Oren Moy, Claudia Pahwa, Rajesh Burchiel, Kim Hogarth, Penelope Lai, Eugene C. Duda, John E. Holloway, Kathryn Samii, Ali Horn, Stacy Bronstein, Jeff M. Stoner, Gatana Starr, Philip A. Simpson, Richard Baltuch, Gordon De Salles, Antonio Huang, Grant D. Reda, Domenic J. CA CSP 468 Study Grp TI Randomized trial of deep brain stimulation for Parkinson disease Thirty-six-month outcomes SO NEUROLOGY LA English DT Article ID QUALITY-OF-LIFE; 5-YEAR FOLLOW-UP; PALLIDAL STIMULATION; GLOBUS-PALLIDUS; SUBTHALAMIC NUCLEUS; MOTOR FLUCTUATIONS; MEDICAL THERAPY; MULTICENTER; VALIDATION; EFFICACY AB Objectives: Our objective was to compare long-term outcomes of deep brain stimulation (DBS) of the globus pallidus interna (GPi) and subthalamic nucleus (STN) for patients with Parkinson disease (PD) in a multicenter randomized controlled trial. Methods: Patients randomly assigned to GPi (n = 89) or STN DBS (n = 70) were followed for 36 months. The primary outcome was motor function on stimulation/off medication using the Unified Parkinson's Disease Rating Scale motor subscale. Secondary outcomes included quality of life and neurocognitive function. Results: Motor function improved between baseline and 36 months for GPi (41.1 to 27.1; 95% confidence interval [CI] -16.4 to -10.8; p < 0.001) and STN (42.5 to 29.7; 95% CI -15.8 to -9.4; p < 0.001); improvements were similar between targets and stable over time (p = 0.59). Health-related quality of life improved at 6 months on all subscales (all p values significant), but improvement diminished over time. Mattis Dementia Rating Scale scores declined faster for STN than GPi patients (p = 0.01); other neurocognitive measures showed gradual decline overall. Conclusions: The beneficial effect of DBS on motor function was stable and comparable by target over 36 months. Slight declines in quality of life following initial gains and gradual decline in neurocognitive function likely reflect underlying disease progression and highlight the importance of nonmotor symptoms in determining quality of life. Classification of Evidence: This study provides Class III evidence that improvement of motor symptoms of PD by DBS remains stable over 3 years and does not differ by surgical target. Neurology (R) 2012; 79:55-65 C1 [Weaver, Frances M.] Hines VA Hosp, Ctr Management Complex Chron Care, Hines, IL USA. [Weaver, Frances M.] Loyola Univ Stritch Sch Med, Maywood, IL USA. [Follett, Kenneth A.] Iowa City VA Med Ctr, Iowa City, IA USA. [Follett, Kenneth A.] Univ Nebraska Med Ctr, Omaha, NE USA. [Stern, Matthew; Horn, Stacy; Baltuch, Gordon] Univ Penn Hlth Syst, Philadelphia, PA USA. [Luo, Ping; Hur, Kwan; Reda, Domenic J.] Hines VA Hosp, Cooperat Studies Coordinating Ctr, Hines, IL USA. [Harris, Crystal L.] VA Cooperat Studies Program, Albuquerque, NM USA. [Marks, William J., Jr.; Rothlind, Johannes; Starr, Philip A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Marks, William J., Jr.; Rothlind, Johannes; Starr, Philip A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Sagher, Oren] Univ Michigan Med Ctr, Ann Arbor, MI USA. [Moy, Claudia] NINDS, Rockville, MD USA. [Pahwa, Rajesh] Univ Kansas Med Ctr, Kansas City, KS USA. [Burchiel, Kim] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Burchiel, Kim; Hogarth, Penelope] Portland VA Med Ctr, Portland, OR USA. [Lai, Eugene C.; Simpson, Richard] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Lai, Eugene C.; Simpson, Richard] Methodist Neurol Inst, Houston, TX USA. [Stern, Matthew; Duda, John E.; Baltuch, Gordon] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Holloway, Kathryn] Richmond VA Med Ctr, Richmond, VA USA. [Samii, Ali] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Bronstein, Jeff M.; De Salles, Antonio] W Los Angeles VA Med Ctr, Los Angeles, CA USA. [Bronstein, Jeff M.; De Salles, Antonio] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Stoner, Gatana] Univ Iowa Hlth Care, Iowa City, IA USA. [Huang, Grant D.] US Dept Vet Affairs, Cooperat Studies Program, Cent Off, Washington, DC USA. RP Weaver, FM (reprint author), Hines VA Hosp, Ctr Management Complex Chron Care, Hines, IL USA. EM Frances.Weaver@va.gov FU Medtronic Neurological, Inc.; Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development; NINDS; Teva; Ipsen; Medtronic; Adamas Pharma; Schering-Plough; GSK; GE Healthcare; EMD Serono; Boehringer Ingelheim; St Jude Medical; Impax Pharma; Novartis; Biogen; Xenoport; Solvay; Eisai; NIH/NINDS; NPF; Allon; Acadia; Valeant; Kyowa; Johnson Johnson; Schering; Santhera FX Medtronic Neurological, Inc. provided financial support. The Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, provided financial support and contributed to the study design. NINDS provided financial support and contributed to the design of the study.; F. Weaver reports no disclosures relevant to the manuscript. K. Follett reports serving as a consultant for Medtronic Neurological (safety monitoring panel). M. Stern reports receiving consulting fees from Teva, Ipsen, Medtronic, Adamas Pharma, Schering-Plough, payment for speakers bureaus from Teva, Novartis, and the Movement Disorder Society, payment for development of educational presentations from Teva and Medtronic. P. Luo, C. Harris, and K. Hur report no disclosures relevant to the manuscript. W. Marks reports receiving consulting fees from Medtronic and lecture fees from Medtronic. J. Rothlind, O. Sagher, and C. Moy report no disclosures relevant to the manuscript. R. Pahwa reports receiving consulting fees from Teva, GSK, GE Healthcare, EMD Serono, Boehringer Ingelheim, Medtronic, St Jude Medical, Impax Pharma, Novartis, Adamas Pharma, and Biogen, providing expert testimony, grants/grants pending from Teva, Novartis, Xenoport, Impax Pharma, Boehringer Ingelheim, Solvay, EMD Serono, Eisai, NIH/NINDS, NPF, Allon, Acadia, GSK, Valeant, Kyowa, Johnson & Johnson, Santhera, and Schering, payment for lectures from Teva, GSK, and Medtronic, royalties from Oxford Press and Informa Healthcare, payment for development of educational presentations from Medscape, Co-Editor in Chief International Journal of Neuroscience, and DSMB member (Ceregene). K. Burchiel reports grants/grants pending from Medtronic, and owning stock/stock options in Medtronic. P. Hogarth, E. Lai, and J. Duda report no disclosures relevant to the manuscript. K. Holloway reports receiving consulting fees and grant/grants pending from Medtronic. A. Samii reports receiving payment for lectures from Teva, Ipsen, and Boehringer Ingelheim. S. Horn, J. Bronstein, and G. Stoner report no disclosures relevant to the manuscript. P. Starr reports receiving consulting fees from Medtronic. R. Simpson reports participating on advisory board and receiving consulting fees from Medtronic, and providing expert testimony. G. Baltuch, A. DeSalles, G. Huang, and D. Reda report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures. NR 30 TC 114 Z9 118 U1 2 U2 24 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 2012 VL 79 IS 1 BP 55 EP 65 DI 10.1212/WNL.0b013e31825dcdc1 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 971BE UT WOS:000306176000014 PM 22722632 ER PT J AU Cheng, EM Keyhani, S Ofner, S Williams, LS Hebert, PL Ordin, DL Bravata, DM AF Cheng, Eric M. Keyhani, Salomeh Ofner, Susan Williams, Linda S. Hebert, Paul L. Ordin, Diana L. Bravata, Dawn M. TI Lower use of carotid artery imaging at minority-serving hospitals SO NEUROLOGY LA English DT Article ID ASSOCIATION/AMERICAN STROKE ASSOCIATION; HEALTH-CARE PROFESSIONALS; ETHNIC DISPARITIES; ISCHEMIC-STROKE; ENDARTERECTOMY; AMERICAN; RACE; QUALITY; MODELS; SYSTEM AB Objective: We determined whether site of care explains a previously identified racial disparity in carotid artery imaging. Methods: In this retrospective cohort study, data were obtained from a chart review of veterans hospitalized with ischemic stroke at 127 Veterans Administration hospitals in 2007. Extensive exclusion criteria were applied to obtain a sample who should have received carotid artery imaging. Minority-serving hospitals were defined as the top 10% of hospitals ranked by the proportion of stroke patients who were black. Population level multivariate logistic regression models with adjustment for correlation of patients in hospitals were used to calculate predictive probabilities of carotid artery imaging by race and minority-service hospital status. Bootstrapping was used to obtain 95% confidence intervals (CIs). Results: The sample consisted of 1,534 white patients and 628 black patients. Nearly 40% of all black patients were admitted to 1 of 13 minority-serving hospitals. No racial disparity in receipt of carotid artery imaging was detected within nonminority serving hospitals. However, the predicted probability of receiving carotid artery imaging for white patients at nonminority-serving hospitals (89.7%, 95% CI [87.3%, 92.1%]) was significantly higher than both white patients (78.0% [68.3%, 87.8%] and black patients (70.5% [59.3%, 81.6%]) at minority-serving hospitals. Conclusions: Underuse of carotid artery imaging occurred most often among patients hospitalized at minority-serving hospitals. Further work is required to explore why site of care is a mechanism for racial disparities in this clinically important diagnostic test. Neurology (R) 2012;79:138-144 C1 [Cheng, Eric M.] VA Greater Los Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA USA. [Cheng, Eric M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Keyhani, Salomeh] UCSF, Div Gen Internal Med, Dept Med, San Francisco, CA USA. [Keyhani, Salomeh] San Francisco VA Med Ctr, Res Enhancement Award Program, San Francisco, CA USA. [Ofner, Susan] Indiana Univ Sch Med, Div Biostat, Indianapolis, IN USA. [Williams, Linda S.] Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN USA. [Bravata, Dawn M.] Indiana Univ Sch Med, Dept Internal Med, Indianapolis, IN USA. [Williams, Linda S.; Ordin, Diana L.; Bravata, Dawn M.] Richard L Roudebush VA Med Ctr, HSR & D Ctr Implementing Evidence Based Practice, Indianapolis, IN USA. [Williams, Linda S.] Richard L Roudebush VA Med Ctr, Dept Neurol, Indianapolis, IN USA. [Hebert, Paul L.] Puget Sound Med Ctr, Ctr Excellence, VA HSR & D NW Ctr Outcomes Res Older Adults, Seattle, WA USA. [Ordin, Diana L.] Dept Vet Affairs, Off Informat & Analyt, Washington, DC USA. RP Cheng, EM (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA USA. EM eric.cheng@va.gov FU Veterans Administration [RRP 09-184, RRP 09-185]; VHA HSR&D Center of Excellence on Implementing Evidence-Based Practice (CIEBP); Richard L. Roudebush VA Medical Center, Indianapolis; VHA HSR&D Stroke Quality Enhancement Research Initiative (QUERI) Program, Indianapolis, IN; Career Development Award from NIH/NINDS [K23NS058571]; Project EXPORT (NCMHD) [P20MD000182]; UCLA Outcomes Research Center; American Heart Association Pharmaceutical Roundtable and David and Stevie Spina; Career Development Award from the Veterans Administration FX Supported by Veterans Administration RRP 09-184 (PI: Dr. Bravata) and RRP 09-185 (PI: Dr. Keyhani) and by the VHA HSR&D Center of Excellence on Implementing Evidence-Based Practice (CIEBP), Richard L. Roudebush VA Medical Center, Indianapolis, and the VHA HSR&D Stroke Quality Enhancement Research Initiative (QUERI) Program, Indianapolis, IN. Dr. Cheng is supported by a Career Development Award from NIH/NINDS (K23NS058571), by Project EXPORT (NCMHD grants P20MD000182), and by the UCLA Outcomes Research Center, funded through the American Heart Association Pharmaceutical Roundtable and David and Stevie Spina. Dr. Keyhani is supported by a Career Development Award from the Veterans Administration. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 34 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 2012 VL 79 IS 2 BP 138 EP 144 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 971XV UT WOS:000306241000011 PM 22700815 ER PT J AU Yeh, BM Yee, J AF Yeh, Benjamin M. Yee, Judy TI State-of-the-Art PET/CT of the Pancreas: Current Role and Emerging Indications Invited Commentary SO RADIOGRAPHICS LA English DT Editorial Material ID CT C1 [Yeh, Benjamin M.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Yee, Judy] San Francisco VA Med Ctr, Dept Radiol, San Francisco, CA USA. RP Yeh, BM (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JUL-AUG PY 2012 VL 32 IS 4 BP 1158 EP 1160 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 972OE UT WOS:000306285600018 ER PT J AU Bauman, WA Biering-Sorensen, F Krassioukov, A AF Bauman, W. A. Biering-Sorensen, F. Krassioukov, A. TI International spinal cord injury endocrine and metabolic basic data set (version 1.2) SO SPINAL CORD LA English DT Letter C1 [Bauman, W. A.] James J Peters Vet Affairs Med Ctr, Vet Affairs Rehabil Res & Dev Ctr Excellence Med, Bronx, NY USA. [Biering-Sorensen, F.] Univ Copenhagen, Rigshosp, Clin Spinal Cord Injuries, Ctr Neurosci, DK-2100 Copenhagen, Denmark. [Biering-Sorensen, F.] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark. [Krassioukov, A.] Univ British Columbia, Dept Med, ICORD, Vancouver, BC, Canada. [Krassioukov, A.] Vancouver Coastal Hlth, Vancouver, BC, Canada. RP Bauman, WA (reprint author), James J Peters Vet Affairs Med Ctr, Vet Affairs Rehabil Res & Dev Ctr Excellence Med, Bronx, NY USA. EM william.bauman@va.gov NR 1 TC 4 Z9 4 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD JUL PY 2012 VL 50 IS 7 BP 567 EP 567 DI 10.1038/sc.2012.37 PG 1 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 972NB UT WOS:000306282700021 PM 22508533 ER PT J AU Shea, JA Weissman, A McKinney, S Silber, JH Volpp, KG AF Shea, Judy A. Weissman, Arlene McKinney, Sean Silber, Jeffrey H. Volpp, Kevin G. TI Internal Medicine Trainees' Views of Training Adequacy and Duty Hours Restrictions in 2009 SO ACADEMIC MEDICINE LA English DT Article ID WORK-HOURS; RESIDENTS PERCEPTIONS; ACCREDITATION-COUNCIL; SURGICAL RESIDENTS; HOURS REGULATIONS; SLEEP; MORTALITY; REFORM; IMPACT; REQUIREMENTS AB Purpose To gauge internal medicine (IM) trainees' perceptions regarding aspects of their inpatient rotations, including supervision, educational opportunities, the perceived effect of duty hours regulations on quality of patient care, the causes of medical errors, and sleep. Method The authors analyzed the results of questionnaires administered to trainees following the October 2009 in-training examinations (ITE). Results Of the 21,768 IM trainees in postgraduate years 1 through 3 who took the IM-ITE, 18,272 (83.9%) responded. The majority of these trainees (87.7%) reported that supervision was adequate, and nearly half (46.3%) reported insufficient or minimal time to participate in learning activities. Two-thirds or more thought that specific work regulations such as limited shift length and more time off after nights and extended shifts would at least "occasionally," if not "usually" or "always," improve patient care. IM trainees at least "occasionally" attributed errors to workload (68.8% of respondents), fatigue (66.9%), inexperience or lack of knowledge (61.0%), incomplete handoffs (60.2%), and insufficient ancillary staff (53.5%). IM trainees' sleep hours were limited during extended and overnight shifts. Conclusions IM trainees agree that limited educational opportunities are the weakest part of the average inpatient rotation. Few have complaints about the adequacy of supervision. These trainees' optimism regarding the positive influence of potential work hours restrictions on patient care and their views of likely causes of medical errors suggest the need for innovative patient care schedules and education curricula. C1 [Shea, Judy A.; Silber, Jeffrey H.; Volpp, Kevin G.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weissman, Arlene] Amer Coll Physicians, Res Ctr, Philadelphia, PA USA. [McKinney, Sean] Amer Coll Physicians, Self Assessment Programs, Philadelphia, PA USA. [Silber, Jeffrey H.; Volpp, Kevin G.] Univ Penn, Wharton Sch Business, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Philadelphia Vet Affairs Med Ctr, CHERP, Philadelphia, PA 19104 USA. RP Shea, JA (reprint author), Univ Penn, Perelman Sch Med, 1223 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM sheaja@mail.med.upenn.edu FU NHLBI [1R01HL094593] FX The work was supported by NHLBI grant #1R01HL094593: Work Hour Regulation for Physician Trainees: Educational and Clinical Outcomes (Volpp). NR 30 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD JUL PY 2012 VL 87 IS 7 BP 889 EP 894 DI 10.1097/ACM.0b013e3182582583 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 967HL UT WOS:000305897400017 PM 22622211 ER PT J AU Shea, JA Willett, LL Borman, KR Itani, KMF McDonald, FS Call, SA Chaudhry, S Adams, M Chacko, KM Volpp, KG Arora, VM AF Shea, Judy A. Willett, Lisa L. Borman, Karen R. Itani, Kamal M. F. McDonald, Furman S. Call, Stephanie A. Chaudhry, Saima Adams, Michael Chacko, Karen M. Volpp, Kevin G. Arora, Vineet M. TI Anticipated Consequences of the 2011 Duty Hours Standards: Views of Internal Medicine and Surgery Program Directors SO ACADEMIC MEDICINE LA English DT Article ID RESIDENCY PROGRAM; ACCREDITATION COUNCIL; SURGICAL RESIDENTS; NATIONAL-SURVEY; HOURS REFORM; IMPACT; ACGME; REGULATIONS; EDUCATION; MORTALITY AB Purpose To assess internal medicine (IM) and surgery program directors' views of the likely effects of the 2011 Accreditation Council for Graduate Medical Education duty hours regulations. Method In fall 2010, investigators surveyed IM and surgery program directors, assessing their views of the likely impact of the 2011 duty hours standards on learning environment, workload, education opportunities, program administration, and patient outcomes. Results Of 381 IM program directors, 287 (75.3%) responded; of 225 surgery program directors, 118 (52.4%) responded. Significantly more surgeons than internists indicated that the new regulations would likely negatively impact learning climate, including faculty morale and residents' relationships (P < .001). Most leaders in both specialties (80.8% IM, 80.2% surgery) felt that the regulations would likely increase faculty workload (P = .73). Both IM (82.2%) and surgery (96.6%) leaders most often rated, of all education opportunities, first-year resident clinical experience to be adversely affected (P < .001). Respondents from both specialties indicated that they will hire more nonphysician/midlevel providers (59.5% IM, 89.0% surgery, P < .001) and use more nonteaching services (66.8% IM, 70.1% surgery, P = .81). Respondents expect patient safety (45.1% IM, 76.9% surgery, P < .001) and continuity of care (83.6% IM across all training levels, 97.5% surgery regarding first-year residents) to decrease. Conclusions IM and surgery program directors agree that the 2011 duty hours regulations will likely negatively affect the quality of the learning environment, workload, education opportunities, program administration, and patient outcomes. Careful evaluation of actual impact is important. C1 [Shea, Judy A.; Volpp, Kevin G.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Willett, Lisa L.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Borman, Karen R.] Abington Mem Hosp, Philadelphia, PA USA. [Borman, Karen R.] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [Itani, Kamal M. F.] Vet Affairs Boston Hlth Care Syst, Surg Serv, Boston, MA USA. [Itani, Kamal M. F.] Boston Univ, Boston, MA 02215 USA. [McDonald, Furman S.] Mayo Clin Internal Med Residency, Rochester, MN USA. [Call, Stephanie A.] Virginia Commonwealth Univ, Richmond, VA USA. [Chaudhry, Saima] Hofstra N Shore LIJ Sch Med, Residency Program Internal Med, Hempstead, NY USA. [Adams, Michael] MedStar Georgetown Univ Hosp, Washington, DC USA. [Chacko, Karen M.] Univ Colorado, Primary Care Internal Med Residency Training Prog, Denver, CO 80202 USA. [Volpp, Kevin G.] Univ Penn, CHERP, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Wharton Sch Business, Philadelphia, PA 19104 USA. [Arora, Vineet M.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Shea, JA (reprint author), Univ Penn, Perelman Sch Med, 1223 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM sheaja@mail.med.upenn.edu OI Arora, Vineet/0000-0002-4745-7599 FU National Heart, Lung, and Blood Institute [1R01HL094593] FX The work was supported by National Heart, Lung, and Blood Institute grant no. 1R01HL094593: Work Hour Regulation for Physician Trainees: Educational and Clinical Outcomes (Volpp). NR 32 TC 21 Z9 21 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD JUL PY 2012 VL 87 IS 7 BP 895 EP 903 DI 10.1097/ACM.0b013e3182584118 PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 967HL UT WOS:000305897400018 PM 22622221 ER PT J AU Hauer, KE Carney, PA Chang, A Satterfield, J AF Hauer, Karen E. Carney, Patricia A. Chang, Anna Satterfield, Jason TI Behavior Change Counseling Curricula for Medical Trainees: A Systematic Review SO ACADEMIC MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; PATIENT-CENTERED APPROACH; FAMILY-PRACTICE RESIDENTS; SEXUAL HISTORY INQUIRY; PRIMARY-CARE PRACTICE; SMOKING-CESSATION; STANDARDIZED PATIENTS; HEALTH-CARE; UNITED-STATES; EDUCATION RESEARCH AB Purpose Unhealthy behaviors contribute to half of U. S. deaths. However, physicians lack sufficient skill in counseling patients to change behaviors. Characterizing effective published curricular interventions for behavior change counseling for medical trainees would inform educators toward improved training. Method The authors conducted a systematic literature search of studies published between 1965 and 2011 evaluating curricula on behavior change counseling for medical trainees. Included studies described behavior change counseling, teaching interventions for medical trainees, and assessment of interventions. The authors extracted eligible articles, rated outcomes for learners and patients using Kirkpatrick's hierarchy, and determined study quality. Results Of 2,788 identified citations, 109 met inclusion criteria. Most studies were performed in the United States (98), 93 at a single institution, and 81 in primary care settings. Curricular topics for counseling included smoking (67 studies), nutrition (30), alcohol/drug use (26), and exercise (22). Although most studies did not include theoretical frameworks, 39 used the Transtheoretical Model of Change. Sixty-two studies involved eight or fewer hours of curricular time, and 51 spanned four or fewer weeks. The studies with highest-level outcomes and quality employed multiple curricular techniques and included practice of counseling techniques in either simulated or actual clinical settings. Conclusions Existing literature suggests that trainees learn behavior change counseling through active, realistic practice and implementation of reminder and feedback systems within actual clinical practice settings. Multiinstitutional medical education research on methods of teaching behavior change counseling that influence patients' health outcomes are needed to ensure trainees' clinical competence and improve patient care. C1 [Hauer, Karen E.; Satterfield, Jason] Univ Calif San Francisco, Dept Med, Sch Med, San Francisco, CA 94143 USA. [Carney, Patricia A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Chang, Anna] Dept Med, Div Geriatr, San Francisco, CA USA. [Chang, Anna] San Francisco VA Med Ctr, San Francisco, CA USA. RP Hauer, KE (reprint author), Univ Calif San Francisco, Dept Med, Sch Med, 505 Parnassus Ave,M1078,Box 0120, San Francisco, CA 94143 USA. EM karen.hauer@ucsf.edu FU NIH/NCCAM [K07 AT003131]; NIH.NCI [CA121457]; University of California, San Francisco Department of Medicine; Haile T. Debas Academy of Medical Educators FX This study was funded in part by NIH/NCCAM (K07 AT003131-Drs. Satterfield, Hauer), the Gold-Headed Cane Endowed Education Chair in Internal Medicine (University of California, San Francisco Department of Medicine and the Haile T. Debas Academy of Medical Educators) (Dr. Hauer), and NIH.NCI CA121457 (Dr. Carney). NR 86 TC 20 Z9 20 U1 2 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUL PY 2012 VL 87 IS 7 BP 956 EP 968 DI 10.1097/ACM.0b013e31825837be PG 13 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 967HL UT WOS:000305897400026 PM 22622220 ER PT J AU McBane, S Thomas, T Karr, S Kelley, KW AF McBane, Sarah Thomas, Tyan Karr, Samantha Kelley, Kristi W. TI Serving as a student preceptor: Focus on emerging challenges SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material ID EDUCATION C1 [McBane, Sarah] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Thomas, Tyan] Univ Sci Philadelphia, Philadelphia Coll Pharm, Philadelphia, PA USA. [Thomas, Tyan] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Karr, Samantha] Midwestern Univ, Coll Pharm Glendale, Glendale, AZ USA. [Kelley, Kristi W.] Auburn Univ, Harrison Sch Pharm, Auburn, AL 36849 USA. [Kelley, Kristi W.] Baptist Hlth Syst Inc, Continu Clin, Trinity Med Ctr, Birmingham, AL USA. RP McBane, S (reprint author), Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, 9500 Gilman Dr,MC 0719, La Jolla, CA 92093 USA. EM smcbane@ucsd.edu NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD JUL 1 PY 2012 VL 69 IS 13 BP 1110 EP 1111 DI 10.2146/ajhp110291 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 969EB UT WOS:000306037400013 PM 22722589 ER PT J AU Singh, RP Waldron, RT Hahn, BH AF Singh, Ram P. Waldron, Richard T. Hahn, Bevra H. TI Genes, tolerance and systemic autoimmunity SO AUTOIMMUNITY REVIEWS LA English DT Review DE Autoimmunity; Systemic lupus erythematosus; Genes; Tolerance; CD8(+)Ti ID REGULATORY T-CELLS; VERSUS-HOST-DISEASE; GENERATED EX-VIVO; COMPLEMENTARITY-DETERMINING REGION-1; INTERFERON-INDUCIBLE GENE; LUPUS-LIKE DISEASE; MURINE LUPUS; MEDIATED SUPPRESSION; SUSCEPTIBILITY GENE; PROGRAMMED DEATH-1 AB The characterization of functional CD8(+) inhibitory or regulatory T cells and their gene regulation remains a critical challenge in the field of tolerance and autoimmunity. Investigating the genes induced in regulatory cells and the regulatory networks and pathways that underlie mechanisms of immune resistance and prevent apoptosis in the CD8(+) T cell compartment are crucial to understanding tolerance mechanisms in systemic autoimmunity. Little is currently known about the genetic control that governs the ability of CD8(+) Ti or regulatory cells to suppress anti-DNA Ab production in B cells. Silencing genes with siRNA or shRNA and overexpression of genes with lentiviral cDNA transduction are established approaches to identifying and understanding the function of candidate genes in tolerance and immunity. Elucidation of interactions between genes and proteins, and their synergistic effects in establishing cell-cell cross talk, including receptor modulation/antagonism, are essential for delineating the roles of these cells. In this review, we will examine recent reports which describe the modulation of cells from lupus prone mice or lupus patients to confer anti-inflammatory and protective gene expression and novel associated phenotypes. We will highlight recent findings on the role of selected genes induced by peptide tolerance in CD8(+) Ti. (C) 2011 Elsevier B.V. All rights reserved. C1 [Singh, Ram P.] Univ Calif Los Angeles, David Geffen Sch Med, Div Rheumatol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Pancreat Res Grp, VA Greater Los Angeles Healthcare Syst,Dept Med,D, Los Angeles, CA 90095 USA. RP Singh, RP (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Rheumatol, Los Angeles, CA 90095 USA. EM rpsingh@mednet.ucla.edu FU NIH [AR54034, AI083894, AI65645]; UCLA Clinical Translational Seed Grant (CTSG); American Autoimmune Related Disease Association grant (AARDA); TEVA Pharmaceuticals; UCLA Senate Core Grant FX RPS is supported by NIH grants AR54034, AI083894, AI65645, UCLA Clinical Translational Seed Grant (CTSG) and the American Autoimmune Related Disease Association grant (AARDA). BHH is supported by an award from TEVA Pharmaceuticals. BHH and RPS are also supported by UCLA Senate Core Grant. NR 114 TC 15 Z9 15 U1 2 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-9972 J9 AUTOIMMUN REV JI Autoimmun. Rev. PD JUL PY 2012 VL 11 IS 9 BP 664 EP 669 DI 10.1016/j.autrev.2011.11.017 PG 6 WC Immunology SC Immunology GA 967TU UT WOS:000305931500010 PM 22155015 ER PT J AU El-Serag, HB AF El-Serag, Hashem B. TI The New Board of Editors for Clinical Gastroenterology and Hepatology: Our Vision and Plans SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material C1 Baylor Coll Med, Houston VA Med Ctr, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Baylor Coll Med, Houston VA Med Ctr, Houston, TX 77030 USA. EM hasheme@bcm.edu 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 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JUL PY 2012 VL 10 IS 7 BP 690 EP 691 DI 10.1016/j.cgh.2012.05.001 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 969QA UT WOS:000306069300003 PM 22721437 ER PT J AU Ezra, N Hamid, O Behroozan, D AF Ezra, Navid Hamid, Omid Behroozan, Daniel TI Eruptive Squamous Cell Carcinomas Associated with BRAF-Inhibitor Therapy in a Patient with Metastatic Melanoma SO DERMATOLOGIC SURGERY LA English DT Editorial Material ID RAF INHIBITORS; RAS/RAF/MEK/ERK PATHWAY; ACTINIC KERATOSES; GENE MUTATION; MAPK PATHWAY; HUMAN SKIN; CANCER; SORAFENIB; KERATOACANTHOMAS; PROGRESSION C1 [Behroozan, Daniel] Dermatol Inst So Calif, Santa Monica, CA 90405 USA. [Ezra, Navid; Behroozan, Daniel] Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Dept Med, Los Angeles, CA 90095 USA. [Hamid, Omid] Angeles Clin & Res Inst, Los Angeles, CA USA. [Behroozan, Daniel] W Los Angeles Vet Adm Med Ctr, Dept Dermatol, Los Angeles, CA USA. RP Behroozan, D (reprint author), Dermatol Inst So Calif, 2221 Lincoln Blvd,Suite 100, Santa Monica, CA 90405 USA. EM db@dermsurgery.net NR 39 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1076-0512 EI 1524-4725 J9 DERMATOL SURG JI Dermatol. Surg. PD JUL PY 2012 VL 38 IS 7 BP 1086 EP 1090 DI 10.1111/j.1524-4725.2012.02396.x PN 1 PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA 967XC UT WOS:000305940400022 PM 22563699 ER PT J AU Sosenko, JM Skyler, JS Mahon, J Krischer, JP Beam, CA Boulware, DC Greenbaum, CJ Rafkin, LE Cowie, C Cuthbertson, D Palmer, JP AF Sosenko, Jay M. Skyler, Jay S. Mahon, Jeffrey Krischer, Jeffrey P. Beam, Craig A. Boulware, David C. Greenbaum, Carla J. Rafkin, Lisa E. Cowie, Catherine Cuthbertson, David Palmer, Jerry P. CA Type 1 Diabet TrialNet & Diabet Pr TI The Application of the Diabetes Prevention Trial-Type 1 Risk Score for Identifying a Preclinical State of Type 1 Diabetes SO DIABETES CARE LA English DT Article ID BETA-CELL FUNCTION; GLUCOSE-TOLERANCE; INSULIN; ONSET; TRIAL-TYPE-1; MELLITUS; PARTICIPANTS; PROGRESSION; ANTIBODIES AB OBJECTIVE-We assessed the utility of the Diabetes Prevention Trial Type 1 Risk Score (DPTRS) for identifying individuals who are highly likely to progress to type 1 diabetes (T ID) within 2 years. RESEARCH DESIGN AND METHODS-The DPTRS was previously developed from Diabetes Prevention Trial Type 1 (DPT-1) data and was subsequently validated in the TrialNet Natural History Study (TNNHS). DPTRS components included C-peptide and glucose indexes from oral glucose tolerance testing, along with age and BM1. The cumulative incidence of T ID was determined after DPTRS thresholds were first exceeded and after the first occurrences of glucose abnormalities. RESULTS-The 2-year risks after the 9.00 DPTRS threshold was exceeded were 0.88 and 0.77 in DPT-1 (n = 90) and the TNNHS (n = 69), respectively. In DPT-1, the 2-year risks were much lower after dysglycemia first occurred (0.37; n = 306) and after a 2-h glucose value between 190 and 199 mg/dL was first reached (0.64; n = 59). Among those who developed T1D in DPT-1, the 9.00 threshold was exceeded 0.81 +/- 0.53 years prior to the conventional diagnosis. Post-challenge C-peptide levels were substantially higher (P = 0.001 for 30 min; P < 0.001 for other time points) when the 9.00 threshold was first exceeded compared with the levels at diagnosis. CONCLUSIONS-A DPTRS threshold of 9.00 identifies individuals who are very highly likely to progress to the conventional diagnosis of T ID within 2 years and, thus, are essentially in a preclinical diabetic state. The 9.00 threshold is exceeded well before diagnosis, when stimulated C-peptide levels are substantially higher. Diabetes Care 35:1552-1555,2012 C1 [Sosenko, Jay M.; Skyler, Jay S.; Rafkin, Lisa E.] Univ Miami, Div Endocrinol, Miami, FL 33136 USA. [Mahon, Jeffrey] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada. [Krischer, Jeffrey P.; Beam, Craig A.; Boulware, David C.] Univ S Florida, Div Informat & Biostat, Tampa, FL USA. [Greenbaum, Carla J.] Benaroya Res Inst Virginia Mason, Seattle, WA USA. [Cowie, Catherine] NIDDK, NIH, Bethesda, MD USA. [Cuthbertson, David] Univ S Florida, Pediat Epidemiol Ctr, Tampa, FL USA. [Palmer, Jerry P.] Univ Washington, VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. RP Sosenko, JM (reprint author), Univ Miami, Div Endocrinol, Miami, FL 33136 USA. EM jsosenko@med.miami.edu RI Skyler, Jay/F-4211-2016 FU National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute for Child Health and Human Development; National Center for Research Resources; Juvenile Diabetes Research Foundation International; American Diabetes Association FX This work was funded by the National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute for Child Health and Human Development, and the National Center for Research Resources; by the Juvenile Diabetes Research Foundation International; and by the American Diabetes Association. NR 20 TC 17 Z9 17 U1 0 U2 1 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 JUL PY 2012 VL 35 IS 7 BP 1552 EP 1555 DI 10.2337/dc12-0011 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962MJ UT WOS:000305548900026 PM 22547092 ER PT J AU Machado-Salas, J Avila-Costa, MR Guevara, P Guevara, J Duron, RM Bai, DS Tanaka, M Yamakawa, K Delgado-Escueta, AV AF Machado-Salas, Jesus Rosa Avila-Costa, Maria Guevara, Patricia Guevara, Jorge Duron, Reyna M. Bai, Dongsheng Tanaka, Miyabi Yamakawa, Kazuhiro Delgado-Escueta, Antonio V. TI Ontogeny of Lafora bodies and neurocytoskeleton changes in Laforin-deficient mice SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Lafora body disease; Laforin protein; Mouse; Cytoskeleton ID PROGRESSIVE MYOCLONUS EPILEPSY; GLYCOGEN-SYNTHASE KINASE-3; POLYGLUCOSAN BODIES; BIELSCHOWSKY BODIES; INCLUSION-BODIES; NERVOUS-SYSTEM; TAU-PROTEIN; EPM2A GENE; AGED DOGS; DISEASE AB Lafora disease (LD) is an autosomal recessive, always fatal progressive myoclonus epilepsy with rapid cognitive and neurologic deterioration. One of the pathological hallmarks of LD is the presence of cytoplasmic PAS + polyglucosan inclusions called Lafora bodies (LBs). Current clinical and neuropathological views consider LBs to be the cause of neurological derangement of patients. A systematic study of the ontogeny and structural features of the LBs has not been done in the past. Therefore, we undertook a detailed microscopic analysis of the neuropile of a Laforin-deficient (epm2a-/-) mouse model. Wild type and epm2a-/- mice were sacrificed at different ages and their encephalon processed for light microscopy. Luxol-fast-blue, PAS, Bielschowski techniques, as well as immunocytochemistry (TUNEL, Caspase-3, Apaf-1, Cytochrome-C and Neurofilament L antibodies) were used. Young null mice (11 days old) showed necrotic neuronal death in the absence of LBs. Both cell death and LBs showed a progressive increment in size and number with age. Type I LBs emerged at two weeks of age and were distributed in somata and neurites. Type 11 LBs appeared around the second month of age and always showed a complex architecture and restricted to neuronal somata. Their number was considerably less than type I LBs. Bielschowski method showed neurofibrillary degeneration and senile-like plaques. These changes were more prominent in the hippocampus and ventral pons. Neurofibrillary tangles were already present in 11 days-old experimental animals, whereas senile-like plaques appeared around the third to fourth month of life. The encephalon of null mice was not uniformly affected: Diencephalic structures were spared, whereas cerebral cortex, basal ganglia, pons, hippocampus and cerebellum were notoriously affected. This uneven distribution was present even within the same structure, i.e., hippocampal sectors. Of special relevance, was the observation of the presence of immunoreactivity to neurofilament L on the external rim of type II LBs. Perhaps, type II LB is not the end point of a metabolic abnormality. Instead, we suggest that type II LB is a highly specialized structural and functional entity that emerges as a neuronal response to major carbohydrate metabolism impairment. Early necrotic cell death, neurocytoskeleton derangement, different structural and probably functional profiles for both forms of LBs, a potential relationship between the external rim of the LB type II and the cytoskeleton and an uneven distribution of these abnormalities indicate that LD is both a complex neurodegenerative disease and a glycogen metabolism disorder. Our findings are critical for future studies on disease mechanisms and therapies for LD. Interestingly, the neurodegenerative changes observed in this LD model can also be useful for understanding the process of dementia. (C) 2012 Elsevier Inc. All rights reserved. C1 [Machado-Salas, Jesus; Duron, Reyna M.; Bai, Dongsheng; Tanaka, Miyabi; Delgado-Escueta, Antonio V.] VA Greater Los Angeles Healthcare Syst, W Los Angeles Med Ctr, Epilepsy Ctr Excellence Neurol & Res Serv, Epilepsy Genet Genom Labs, Los Angeles, CA USA. [Rosa Avila-Costa, Maria] Univ Nacl Autonoma Mexico, UNAM, Neurosci Dept FES Iztacala, Mexico City, DF, Mexico. [Guevara, Patricia] Natl Inst Neurol & Neurosurg Manuel Velasco Suare, Mexico City, DF, Mexico. [Guevara, Jorge] Univ Nacl Autonoma Mexico, UNAM, Fac Med, Dept Biochem, Mexico City, DF, Mexico. [Yamakawa, Kazuhiro] RIKEN Brain Sci Inst, Saitama, Japan. [Machado-Salas, Jesus; Duron, Reyna M.; Bai, Dongsheng; Tanaka, Miyabi; Delgado-Escueta, Antonio V.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Machado-Salas, J (reprint author), VA Greater Los Angeles Healthcare Syst, Epilepsy Genet Genom Labs, Los Angeles, CA 90073 USA. EM msmdphd@hotmail.com RI Yamakawa, Kazuhiro/N-5050-2015 OI Duron, Reyna M./0000-0002-9425-2289; Delgado-Escueta, Antonio V./0000-0002-1581-6999 FU National Institutes of Health [1RO1NS055057]; Chelsea's Hope Foundation for Lafora Disease; Programa de Apoyo a Proyectos de Investigacion e Innovacion Tecnologica-DGAPA UNAM [IN214609, 1220111, PAPCA 2010-2011] FX This work was supported by the grants from: National Institutes of Health [1RO1NS055057], Chelsea's Hope Foundation for Lafora Disease, Programa de Apoyo a Proyectos de Investigacion e Innovacion Tecnologica-DGAPA UNAM [IN214609, 1220111 and PAPCA 2010-2011]. NR 51 TC 2 Z9 2 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD JUL PY 2012 VL 236 IS 1 BP 131 EP 140 DI 10.1016/j.expneurol.2012.04.008 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 959IM UT WOS:000305306100015 PM 22542948 ER PT J AU De Costa, AMA Justis, DN Schuyler, CA Young, MRI AF De Costa, Anna-Maria A. Justis, Danielle N. Schuyler, Corinne A. Young, M. Rita I. TI Administration of a vaccine composed of dendritic cells pulsed with premalignant oral lesion lysate to mice bearing carcinogen-induced premalignant oral lesions stimulates a protective immune response SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE HNSCC; Premalignant; Immunotherapy; Dendritic cell vaccination ID NECK-CANCER; TH17 CELLS; T-CELLS; HEAD; SUPPRESSION; GENERATION; REACTIVITY; CYTOKINES AB The use of dendritic cell (DC) vaccines as treatment for malignancy is complicated by immune evasion tactics often employed by carcinomas such as head and neck squamous cell carcinoma (HNSCC). The present study aims to determine if an immune response can be elicited by administering a DC vaccine during the premalignant stages of HNSCC, prior to development of immune escape. Mice treated with the carcinogen 4-nitroquinoline 1-oxide (4NQO) in drinking water develop premalignant oral lesions that progress to HNSCC. As previous studies demonstrated that premalignant lesions and HNSCC overexpress common tumor antigens, bone marrow-derived DCs were pulsed with premalignant lesion lysate (DCpm) and administered to 4NQO-treated mice exhibiting premalignant lesions. Lesion progression was tracked through endoscopy. which revealed that DCpm vaccination and control vaccination with dendritic cells pulsed with normal tongue epithelium lysate (DCnt) significantly decreased lesion burden at 8 weeks. Analysis of lymph node cells revealed that while DCnt vaccination resulted in a rapid increase in total lymphocyte count, levels of activated conventional CD4(+) T cells and Th1, Tc1, Th17, Tc17, and Th2 cells, DCpm vaccination results in a delayed, yet substantial, increase in these immune effector mechanisms. This suggests that dendritic cell vaccination may have a beneficial effect on clinical outcome regardless of type of antigenic stimulation. Also, pulsing DCs with premalignant lysate rather than normal tongue epithelium lysate affects the dendritic cells in a way that delays the immune effector response upon vaccination of premalignant lesion-bearing mice. Published by Elsevier B.V. C1 [De Costa, Anna-Maria A.; Schuyler, Corinne A.; Young, M. Rita I.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA. [De Costa, Anna-Maria A.; Justis, Danielle N.; Young, M. Rita I.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29401 USA. [De Costa, Anna-Maria A.; Justis, Danielle N.; Young, M. Rita I.] Med Univ S Carolina, Dept Med, Charleston, SC 29401 USA. RP Young, MRI (reprint author), Ralph H Johnson VA Med Ctr, Res Serv 151, Charleston, SC 29401 USA. EM rita.young@va.gov FU Biomedical Laboratory and Clinical Sciences Programs of the Department of Veterans Affairs; National Institute of Health (MRIY) [101-CX000100, R01-CA128837, R01-DE018268] FX This work has been supported by awards from the Biomedical Laboratory and Clinical Sciences Programs of the Department of Veterans Affairs and by grants from the National Institute of Health (MRIY, 101-CX000100, R01-CA128837 and R01-DE018268). NR 26 TC 6 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD JUL PY 2012 VL 13 IS 3 BP 322 EP 330 DI 10.1016/j.intimp.2012.05.004 PG 9 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 969EC UT WOS:000306037500014 PM 22609090 ER PT J AU High, KP Brennan-Ing, M Clifford, DB Cohen, MH Currier, J Deeks, SG Deren, S Effros, RB Gebo, K Goronzy, JJ Justice, AC Landay, A Levin, J Miotti, PG Munk, RJ Nass, H Rinaldo, CR Shlipak, MG Tracy, R Valcour, V Vance, DE Walston, JD Volberding, P AF High, Kevin P. Brennan-Ing, Mark Clifford, David B. Cohen, Mardge H. Currier, Judith Deeks, Steven G. Deren, Sherry Effros, Rita B. Gebo, Kelly Goronzy, Joerg J. Justice, Amy C. Landay, Alan Levin, Jules Miotti, Paolo G. Munk, Robert J. Nass, Heidi Rinaldo, Charles R., Jr. Shlipak, Michael G. Tracy, Russell Valcour, Victor Vance, David E. Walston, Jeremy D. Volberding, Paul CA OAR Working Grp HIV Aging TI HIV and Aging: State of Knowledge and Areas of Critical Need for Research. A Report to the NIH Office of AIDS Research by the HIV and Aging Working Group SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE aging; HIV/AIDS; co-morbidity; research priorities ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC KIDNEY-DISEASE; OLDER-ADULTS; CARDIOVASCULAR-DISEASE; INFECTED PATIENTS; IMMUNE-SYSTEM; COHORT; BIOMARKERS; RISK; INFLAMMATION AB HIV risk behaviors, susceptibility to HIV acquisition, progression of disease after infection, and response to antiretroviral therapy all vary by age. In those living with HIV, current effective treatment has increased the median life expectancy to >70 years of age. Biologic, medical, individual, social, and societal issues change as one ages with HIV infection, but there has been only a small amount of research in this field. Therefore, the Office of AIDS Research of the National Institutes of Health commissioned a working group to develop an outline of the current state of knowledge and areas of critical need for research in HIV and Aging; the working groups' findings and recommendations are summarized in this report. Key overarching themes identified by the group included the following: multimorbidity, polypharmacy, and the need to emphasize maintenance of function; the complexity of assessing HIV versus treatment effects versus aging versus concurrent disease; the inter-related mechanisms of immune senescence, inflammation, and hypercoagulability; the utility of multivariable indices for predicting outcomes; a need to emphasize human studies to account for complexity; and a required focus on issues of community support, caregivers, and systems infrastructure. Critical resources are needed to enact this research agenda and include expanded review panel expertise in aging, functional measures, and multimorbidity, and facilitated use and continued funding to allow long-term follow-up of cohorts aging with HIV. C1 [High, Kevin P.] Wake Forest Univ, Baptist Med Ctr, Infect Dis Sect, Dept Internal Med,Wake Forest Sch Med, Winston Salem, NC 27157 USA. [Brennan-Ing, Mark] ACRIA Ctr HIV & Aging, New York, NY USA. [Clifford, David B.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Cohen, Mardge H.] Rush Univ, Dept Internal Med, WIHS, Chicago, IL 60612 USA. [Currier, Judith; Effros, Rita B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Currier, Judith; Effros, Rita B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Deren, Sherry] NYU, Coll Nursing, New York, NY USA. [Gebo, Kelly] Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA. [Goronzy, Joerg J.] Stanford Univ, Sch Med, Dept Immunol & Rheumatol, Stanford, CA 94305 USA. [Justice, Amy C.] Yale Univ, Dept Med, Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA. [Landay, Alan] Rush Univ, Med Ctr, Dept Immunol & Microbiol, Chicago, IL 60612 USA. [Levin, Jules] Natl AIDS Treatment Advocacy Project, Off AIDS Res, New York, NY USA. [Miotti, Paolo G.] NIH, Off AIDS Res, DHHS, Rockville, MD USA. [Munk, Robert J.] AIDS InfoNet, Arroyo Seco, NM USA. [Rinaldo, Charles R., Jr.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, Vet Affairs Med Ctr, San Francisco, CA USA. [Tracy, Russell] Univ Vermont, Coll Med, Dept Pathol & Biochem, Colchester, VT USA. [Valcour, Victor] Univ Calif San Francisco, Dept Neurol, Div Geriatr Med, Memory & Aging Ctr, San Francisco, CA USA. [Vance, David E.] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL USA. [Volberding, Paul] Univ Calif San Francisco, Dept Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. [Walston, Jeremy D.] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA. RP High, KP (reprint author), Wake Forest Univ, Baptist Med Ctr, Infect Dis Sect, Dept Internal Med,Wake Forest Sch Med, 100 Med Ctr Blvd, Winston Salem, NC 27157 USA. EM khigh@wakehealth.edu FU Office of AIDS Research, National Institutes of Health FX Supported by the Office of AIDS Research, National Institutes of Health. NR 88 TC 160 Z9 162 U1 5 U2 22 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUL 1 PY 2012 VL 60 SU 1 BP S1 EP S18 PG 18 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 968ZH UT WOS:000306024400001 PM 22688010 ER PT J AU Dille, MF Wilmington, D McMillan, GP Helt, W Fausti, SA Konrad-Martin, D AF Dille, Marilyn F. Wilmington, Debra McMillan, Garnett P. Helt, Wendy Fausti, Stephen A. Konrad-Martin, Dawn TI Development and Validation of a Cisplatin Dose-Ototoxicity Model SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Article DE Cisplatin; ototoxicity; ototoxicity monitoring; Veterans ID PRODUCT OTOACOUSTIC EMISSIONS; TESTICULAR CANCER; HEARING-LOSS; RISK-FACTORS; CHEMOTHERAPY; SENSITIVITY; TOXICITY; CHILDREN; TINNITUS; PROTOCOL AB Background: Cisplatin is effective in the treatment of several cancers but is a known ototoxin resulting in shifts to hearing sensitivity in up to 50-60% of patients. Cisplatin-induced hearing shifts tend to occur first within an octave of a patient's high frequency hearing limit, termed the sensitive range for ototoxicity (SRO), and progress to lower frequencies. While it is currently not possible to know which patients will experience ototoxicity without testing their hearing directly, monitoring the SRO provides an early indication of damage. A tool to help forecast susceptibility to ototoxic-induced changes in the SRO in advance of each chemotherapy treatment visit may prove useful for ototoxicity monitoring efforts, patient counseling, and therapeutic planning. Purpose: This project was designed to (1) establish pretreatment risk curves that quantify the probability that a new patient will suffer hearing loss within the SRO during treatment with cisplatin and (2) evaluate the accuracy of these predictions in an independent sample of Veterans receiving cisplatin for the treatment of cancer. Study Sample: Two study samples were used. The Developmental sample contained 23 subjects while the Validation sample consisted of 12 subjects. Data Collection and Analysis: Risk curve predictions for SRO threshold shifts following cisplatin exposure were developed using a Developmental sample comprised of data from a total of 155 treatment visits obtained in 45 ears of 23 Veterans. Pure-tone thresholds were obtained within each subject's SRO at each treatment visit and compared with baseline measures. The risk of incurring an SRO shift was statistically modeled as a function of factors related to chemotherapy treatment (cisplatin dose, radiation treatment, doublet medication) and patient status (age, pre-exposure hearing, cancer location and stage). The model was reduced so that only statistically significant variables were included. Receiver-operating characteristic (ROC) curve analyses were then used to determine the accuracy of the risk curve predictions in an independent Validation sample of observations from over 62 treatment visits obtained in 24 ears of 12 Veterans. Results: Only cumulative cisplatin dose and pre-exposure hearing were found to be significantly related to the risk for hearing shift. The dose-ototoxicity risk curve predictions developed from the Developmental sample yielded area under the ROC curve accuracy estimates of 0.85 when applied to an independent Validation sample. Conclusions: Cumulative cisplatin dose in combination with pre-exposure hearing provides an indication of whether hearing will shift in the SRO in advance of cisplatin administration. The validated dose-ototoxicity risk curves described herein can be used before and during treatment to anticipate hearing loss. While having such a tool would not replace serial hearing testing, it would be of great benefit to an ototoxicity monitoring program. It would promote relevant pretreatment counseling. Furthermore, for those found to be at risk of SRO shifts within the speech frequencies, the oncology treatment plan could incorporate anticipated dosing adjustments-that could stave off the impact that ototoxicity might bring. C1 [Dille, Marilyn F.; Wilmington, Debra; McMillan, Garnett P.; Helt, Wendy; Fausti, Stephen A.; Konrad-Martin, Dawn] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, VA RR&D Natl Ctr Rehabil Auditory Res, Portland, OR 97201 USA. [Dille, Marilyn F.; Wilmington, Debra; Fausti, Stephen A.; Konrad-Martin, Dawn] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA. [McMillan, Garnett P.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. RP Dille, MF (reprint author), Portland VA Med Ctr, VA RR&D Natl Ctr Rehabil Auditory Res NCRAR, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Marilyn.Dille@va.gov FU Department of Veterans Affairs RRD Service [C4183R, C7113N]; VA RR&D National Center for Rehabilitative Auditory Research, Portland, OR; Office of Rehabilitation Research and Development (RR&D) Service, Department of Veterans Affairs [C4183R, C4447K] FX Work supported by the Department of Veterans Affairs RR&D Service (grants C4183R and C7113N) and the VA RR&D National Center for Rehabilitative Auditory Research, Portland, OR.; This work was supported by the Office of Rehabilitation Research and Development (RR&D) Service, Department of Veterans Affairs (Grants C4183R and C4447K) and the VA RR&D National Center for Rehabilitative Auditory Research, Portland, OR. NR 44 TC 8 Z9 8 U1 1 U2 5 PU AMER ACAD AUDIOLOGY PI RESTON PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA SN 1050-0545 J9 J AM ACAD AUDIOL JI J. Am. Acad. Audiol. PD JUL-AUG PY 2012 VL 23 IS 7 BP 510 EP 521 DI 10.3766/jaaa.23.7.3 PG 12 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 969HI UT WOS:000306045900003 PM 22992258 ER PT J AU Rodriguez-Ortiz, ME Lopez, I Munoz-Castaneda, JR Martinez-Moreno, JM Ramirez, AP Pineda, C Canalejo, A Jaeger, P Aguilera-Tejero, E Rodriguez, M Felsenfeld, A Almaden, Y AF Rodriguez-Ortiz, Maria E. Lopez, Ignacio Munoz-Castaneda, Juan R. Martinez-Moreno, Julio M. Peralta Ramirez, Alan Pineda, Carmen Canalejo, Antonio Jaeger, Philippe Aguilera-Tejero, Escolastico Rodriguez, Mariano Felsenfeld, Arnold Almaden, Yolanda TI Calcium Deficiency Reduces Circulating Levels of FGF23 SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; VITAMIN-D METABOLISM; GROWTH-FACTOR 23; SECONDARY HYPERPARATHYROIDISM; TRANSPLANT RECIPIENTS; PARATHYROID-HORMONE; RECEPTOR 1; EXPRESSION; PHOSPHATE; KLOTHO AB Fibroblast growth factor (FGF) 23 inhibits calcitriol production, which could exacerbate calcium deficiency or hypocalcemia unless calcium itself modulates FGF23 in this setting. In Wistar rats with normal renal function fed a diet low in both calcium and vitamin D, the resulting hypocalcemia was associated with low FGF23 despite high parathyroid hormone (PTH) and high calcitriol levels. FGF23 correlated positively with calcium and negatively with PTH. Addition of high dietary phosphorus to this diet increased FGF23 except in rats with hypocalcemia despite high PTH levels. In parathyroidectomized rats, an increase in dietary calcium for 10 days increased serum calcium, with an associated increase in FGF23, decrease in calcitriol, and no change in phosphorus. Also in parathyroidectomized rats, FGF23 increased significantly 6 hours after administration of calcium gluconate. Taken together, these results suggest that hypocalcemia reduces the circulating concentrations of FGF23. This decrease in FGF23 could be a response to avoid a subsequent reduction in calcitriol, which could exacerbate hypocalcemia. C1 [Rodriguez, Mariano] Hosp Univ Reina Sofia, Unidad Invest, Serv Nefrol, IMIBIC, Cordoba 14004, Spain. [Rodriguez-Ortiz, Maria E.; Munoz-Castaneda, Juan R.; Martinez-Moreno, Julio M.; Almaden, Yolanda] Hosp Univ Reina Sofia, IMIBIC, Res Unit, Cordoba 14004, Spain. [Lopez, Ignacio; Pineda, Carmen; Aguilera-Tejero, Escolastico] Univ Cordoba, Dept Med & Cirugia Anim, Cordoba, Spain. [Canalejo, Antonio] Univ Huelva, Dept Biol Ambiental & Salud Publ, Huelva, Spain. [Jaeger, Philippe] UCL, Ctr Nephrol, London, England. [Felsenfeld, Arnold] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Felsenfeld, Arnold] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Rodriguez, M (reprint author), Hosp Univ Reina Sofia, Unidad Invest, Serv Nefrol, IMIBIC, Avda Menendez Pidal S-N, Cordoba 14004, Spain. EM juanm.rodriguez.sspa@juntadeandalucia.es RI Canalejo, Antonio/L-8407-2014 OI Canalejo, Antonio/0000-0003-2098-8960; Pineda Martos, Carmen Maria/0000-0002-3664-8699 FU Instituto Carlos III [FIS 07/0287, FIS 07/0315, 010/1311]; Consejeria de Salud [JA 0127/2008]; UE Grant from Framework Programme 7 Syskid (FP7) [241544]; Consejeria de Innovacion, Ciencia y Empresa of Junta de Andalucia [CTS-5205, CTS-170]; Fundacion Progreso y Salud, Consejeria de Salud (Junta de Andalucia); Amgen; Fresenius; Abbott; Shire FX This study was supported by Instituto Carlos III (FIS 07/0287, FIS 07/0315, 010/1311), Consejeria de Salud (JA 0127/2008), a UE Grant from Framework Programme 7 Syskid (FP7-241544), and Consejeria de Innovacion, Ciencia y Empresa (CTS-5205 and CTS-170) of Junta de Andalucia. Y.A. is a senior researcher supported by the Fundacion Progreso y Salud, Consejeria de Salud (Junta de Andalucia).; M.R. has received research grants from Amgen and Fresenius and lecture fees from the following companies: Amgen, Abbott, Shire, and Fresenius. NR 25 TC 82 Z9 84 U1 1 U2 31 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 2012 VL 23 IS 7 BP 1190 EP 1197 DI 10.1681/ASN.2011101006 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 968ZZ UT WOS:000306026800012 PM 22581996 ER PT J AU Reilly, LM Rapp, JH Grenon, SM Hiramoto, JS Sobel, J Chuter, TAM AF Reilly, Linda M. Rapp, Joseph H. Grenon, S. Marlene Hiramoto, Jade S. Sobel, Julia Chuter, Timothy A. M. TI Efficacy and durability of endovascular thoracoabdominal aortic aneurysm repair using the caudally directed cuff technique SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID STENT-GRAFTS; HYBRID PROCEDURES; SURGICAL REPAIR; UNITED-STATES; EXPERIENCE; MORTALITY; ENDOGRAFTS; MORBIDITY; OUTCOMES; IV AB Purpose: This study determined early and intermediate results of multibranched endovascular thoracoabdominal (TAAA) and pararenal aortic aneurysm (PRAA) repair using a uniform operative technique. Methods: Eighty-one patients (mean age, 73 +/- 8 years, 19 [23.5%] women) underwent endovascular TAAA repair in a prospective trial using self-expanding covered stents connecting axially oriented, caudally directed cuffs to target aortic branches. Mean aneurysm diameter was 67 +/- 10 mm. Thirty-nine TAAA (48.1%) were Crawford type II, III, or V; 42 (51.9%) were type IV or pararenal. Thirty-three procedures (40.7%) were staged. The insertion approach was femoral for aortic components and brachial for branch components. Follow-up assessments were performed at 1, 6, and 12 months, and yearly thereafter. Results: All devices (n = 81) and branches (n = 306) were successfully inserted and deployed, with no conversions to open repair. Overall mortality was 6.2% (n = 5), including three perioperative (3.7%) and two late treatment-related deaths (2.5%). Permanent paraplegia occurred in three patients (3.7%), and transient paraplegia/paraparesis occurred in 16 (19.8%). Four patients (4.9%) required dialysis postoperatively, three permanently and one transiently. Women accounted for 67% of the paraplegia, 75% of the perioperative dialysis, and 60% of the perioperative or treatment-related deaths. During a mean follow-up of 21.2 months, no aneurysms ruptured, but four (4.9%) enlarged: two were successfully treated, one was unsuccessfully treated, and one was not treated. No late onset spinal cord ischemia symptoms developed. Of the five patients starting dialysis during follow-up, two resulted from renal branch occlusion. Sixteen branches occluded (nine renal, two celiac) or developed stenoses (four renal, one superior mesenteric artery), requiring stenting. Primary patency was 94.8%, and primary-assisted patency was 95.1%. Thirty-two patients (39.5%) underwent 42 reinterventions. Of 25 early reinterventions (<= 45 days), 10 were to treat access or insertion complications, and 5 were for endoleak. Of 17 late reinterventions, eight were for endoleak and five were for branch stenosis/occlusion. New endoleaks developed in two patients during follow-up. Overall, 73 of 81 patients (90.1%) were treated without procedure-related death, dialysis, paralysis, aneurysm rupture, or conversion to open repair. Conclusions: Total endovascular TAAA/PRAA repair using caudally directed cuffs is safe, effective, and durable in the intermediate term. The most common form of late failure, renal artery occlusion, rarely had a clinically significant consequence (dialysis). The trend toward worse outcome in women needs further study. (J Vasc Surg 2012;) C1 [Reilly, Linda M.; Hiramoto, Jade S.; Sobel, Julia; Chuter, Timothy A. M.] Univ Calif San Francisco, Div Vasc & Endovasc Surg, San Francisco, CA 94143 USA. [Rapp, Joseph H.; Grenon, S. Marlene] San Francisco VA Med Ctr, Vasc Surg Sect, San Francisco, CA USA. RP Reilly, LM (reprint author), Univ Calif San Francisco, Div Vasc Surg, Rm A-581,400 Parnassus Ave, San Francisco, CA 94143 USA. EM linda.reilly@ucsfmedctr.org FU Cook Medical, Inc FX Dr Chuter receives royalties from licensed patents, travel expenses and research funding from Cook Medical, Inc, the manufacturer of the multibranched thoracoabdominal stent graft. NR 44 TC 40 Z9 40 U1 0 U2 2 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 JUL PY 2012 VL 56 IS 1 BP 53 EP 64 DI 10.1016/j.jvs.2012.01.006 PG 13 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 968GJ UT WOS:000305965000010 PM 22560233 ER PT J AU Zhu, S Pan, W Song, XY Liu, Y Shao, XR Tang, YJ Liang, D He, DY Wang, HL Liu, WJ Shi, YF Harley, JB Shen, N Qian, YC AF Zhu, Shu Pan, Wen Song, Xinyang Liu, Yan Shao, Xinrui Tang, Yuanjia Liang, Dong He, Dongyi Wang, Honglin Liu, Wenjun Shi, Yufang Harley, John B. Shen, Nan Qian, Youcun TI The microRNA miR-23b suppresses IL-17-associated autoimmune inflammation by targeting TAB2, TAB3 and IKK-alpha SO NATURE MEDICINE LA English DT Article ID CD4(+) T-CELLS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; KAPPA-B-ZETA; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS; IMMUNE-RESPONSES; MESSENGER-RNA; EXPRESSION; RECEPTOR; DISEASE AB Inflammatory cytokines such as interleukin-17 (IL-17) promote inflammatory autoimmune diseases. Although several microRNAs (miRNAs) have been shown to regulate autoimmune pathogenesis by affecting lymphocyte development and function, the role of miRNAs in resident cells present in inflammatory lesions remains unclear. Here we show that miR-23b is downregulated in inflammatory lesions of humans with lupus or rheumatoid arthritis, as well as in the mouse models of lupus, rheumatoid arthritis or multiple sclerosis. IL-17 downregulates miR-23b expression in human fibroblast-like synoviocytes, mouse primary kidney cells and astrocytes and is essential for the downregulation of miR-23b during autoimmune pathogenesis. In turn, miR-23b suppresses IL-17-, tumor necrosis factor alpha (TNF-alpha)- or IL-1 beta-induced NF-kappa B activation and inflammatory cytokine expression by targeting TGF-beta-activated kinase 1/MAP3K7 binding protein 2 (TAB2), TAB3 and inhibitor of nuclear factor kappa-B kinase subunit alpha (IKK-alpha) and, consequently, represses autoimmune inflammation. Thus, IL-17 contributes to autoimmune pathogenesis by suppressing miR-23b expression in radio-resident cells and promoting proinflammatory cytokine expression. C1 [Zhu, Shu; Pan, Wen; Song, Xinyang; Liu, Yan; Shao, Xinrui; Shi, Yufang; Shen, Nan; Qian, Youcun] Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Stem Cell Biol, Inst Hlth Sci, Shanghai 200031, Peoples R China. [Tang, Yuanjia; Shen, Nan] Shanghai Jiao Tong Univ, Sch Med, Shanghai Renji Hosp, Shanghai Inst Rheumatol, Shanghai 200030, Peoples R China. [Liang, Dong; Harley, John B.; Shen, Nan] Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH USA. [Liang, Dong; Harley, John B.; Shen, Nan] Cincinnati Childrens Hosp Med Ctr, CAGE, Cincinnati, OH USA. [Wang, Honglin] Shanghai Jiao Tong Univ, Sch Med, Inst Med Sci, Shanghai Inst Immunol, Shanghai 200030, Peoples R China. [He, Dongyi] Guanghua Rheumatol Hosp, Shanghai, Peoples R China. [Liu, Wenjun] Univ Manitoba, Dept Biochem & Med Genet, Winnipeg, MB, Canada. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. RP Qian, YC (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Stem Cell Biol, Inst Hlth Sci, Shanghai 200031, Peoples R China. EM nanshensibs@gmail.com; ycqian@sibs.ac.cn RI Pan, Wen/I-9965-2016 FU National Natural Science Foundation of China and 973 program [30930084, 2010CB529705, 91029708, 30871298]; Chinese Academy of Sciences [KSCX2-YW-R-146]; Science and Technology Commission of Shanghai Municipality [10JC1416600]; National Natural Science Foundation of China [30971632, 81025016]; Chinese Ministry of Health [201202008]; Program of the Shanghai Commission of Science and Technology [10JC1409300] FX We thank R. Flavell (Yale University) for providing Pi 17a-deficient mice. This work is supported by grants from National Natural Science Foundation of China and 973 program (30930084, 2010CB529705, 91029708 and 30871298), Chinese Academy of Sciences (KSCX2-YW-R-146) and the Science and Technology Commission of Shanghai Municipality (10JC1416600) to Y.Q.; as well as National Natural Science Foundation of China (30971632 and 81025016), Chinese Ministry of Health (201202008) and the Program of the Shanghai Commission of Science and Technology (10JC1409300) to N. S. NR 58 TC 151 Z9 166 U1 1 U2 35 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2012 VL 18 IS 7 BP 1077 EP + DI 10.1038/nm.2815 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 970IM UT WOS:000306121600037 PM 22660635 ER PT J AU Pellegrini, CN AF Pellegrini, Cara N. TI Can AV Node Ablation Help Save AV Conduction? SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Editorial Material ID SLOW PATHWAY ABLATION; REENTRANT TACHYCARDIA; RADIOFREQUENCY ABLATION; ATRIOVENTRICULAR-BLOCK; JUNCTIONAL TACHYCARDIA; KOCHS TRIANGLE; PREDICTS; ECTOPY; RISK C1 [Pellegrini, Cara N.] VA Med Ctr, Cardiol Sect, San Francisco, CA USA. [Pellegrini, Cara N.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Pellegrini, CN (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Cardiol 111C, San Francisco, CA 94121 USA. EM pellegrinic@medicine.ucsf.edu NR 12 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD JUL PY 2012 VL 35 IS 7 BP 785 EP 786 DI 10.1111/j.1540-8159.2012.03390.x PG 2 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 967HM UT WOS:000305897500015 PM 22519423 ER PT J AU Beidas, RS Edmunds, JM Marcus, SC Kendall, PC AF Beidas, Rinad S. Edmunds, Julie M. Marcus, Steven C. Kendall, Philip C. TI Training and Consultation to Promote Implementation of an Empirically Supported Treatment: A Randomized Trial SO PSYCHIATRIC SERVICES LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; PSYCHOTHERAPY-RESEARCH; DISSEMINATION; CLINICIAN; MODEL AB Objective: The study evaluated the efficacy of three training modalities and the impact of ongoing consultation after training. Cognitive-behavioral therapy (CBT) for anxiety among youths, an empirically supported treatment, was used as the exemplar. Participants were randomly assigned to one of three one-day workshops to examine the efficacy of training modality: routine training (training as usual), computer training (computerized version of training as usual), and augmented training (training that emphasized active learning). After training, all participants received three months of ongoing consultation that included case consultation, didactics, and problem solving. Methods: Participants were 115 community therapists (mean age of 35.9 years; 90% were women). Outcome measures included the Adherence and Skill Checklist, used to rate a performance-based role-play; a knowledge test; and the Training Satisfaction Bating Scale. Results: All three training modalities resulted in limited gains in therapist adherence, skill, and knowledge. There was no significant effect of modality on adherence, skill, or knowledge from pretraining to posttraining. Participants were more satisfied with augmented and routine training than with Computer training. Most important, number of consultation hours after training significantly predicted higher therapist adherence and skill at the three-month follow-up. Conclusions: The findings suggest that training alone did not result in therapist behavior change. The inclusion of ongoing consultation was critical to influencing therapist adherence and skill. Implications for implementation science and mental health services research are discussed. (Psychiatric Services 63:660-665, 2012; doi: 10.1176/appi.ps.201100401) C1 [Beidas, Rinad S.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Edmunds, Julie M.; Kendall, Philip C.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. [Marcus, Steven C.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Beidas, RS (reprint author), Univ Penn, Dept Psychiat, 3535 Market St,Room 3015, Philadelphia, PA 19104 USA. EM rbeidas@upenn.edu FU National Institute of Mental Health [F31-MH083333]; Shipley Research Prize; Ortho-McNeil Janssen; Forest Research Institute FX This study was funded by grant F31-MH083333 from the National Institute of Mental Health and by the Shipley Research Prize awarded to Dr. Beidas. The authors thank Robert Fauber, Ph.D., Philip Hineline, Ph.D., and David Mandell, Sc.D., for comments on drafts of this article. The authors thank the following individuals for their help as consultants: Kathleen Carroll, Ph.D., Wench Cross, Ph.D., and Kimberly Hoagwood, Ph.D. The authors thank the following research assistants: Stacey Austin, Kayla Brehm, Mamatha Chary, Margaret Downey, Philip Fizur, Kyle Peer, and Anna Slavachevskaya.; Dr. Marcus has received grant support from Ortho-McNeil Janssen and Forest Research Institute and has served as a consultant to Astra-Zeneca. Dr. Kendall reports receiving royalties from sales of materials related to the treatment of anxiety among youths. The other authors report no competing interests. NR 28 TC 73 Z9 73 U1 0 U2 16 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JUL PY 2012 VL 63 IS 7 BP 660 EP 665 DI 10.1176/appi.ps.201100401 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 967TY UT WOS:000305931900008 PM 22549401 ER PT J AU Harris, AHS Oliva, E Bowe, T Humphreys, KN Kivlahan, DR Trafton, JA AF Harris, Alex H. S. Oliva, Elizabeth Bowe, Thomas Humphreys, Keith N. Kivlahan, Daniel R. Trafton, Jodie A. TI Pharmacotherapy of Alcohol Use Disorders by the Veterans Health Administration: Patterns of Receipt and Persistence SO PSYCHIATRIC SERVICES LA English DT Article ID MEDICATION COMPLIANCE; NALTREXONE; DEFINITIONS; TRENDS; CARE AB Objective: This study assessed changes since 2007 at Veterans Health Administration (VHA) facilities (N=129) in use of the medications approved by the U.S. Food and Drug Administration for treatment of alcohol use disorders. Methods: VHA data from fiscal years (FYs) 2008 and 2009 were used to identify patients with a diagnosis of an alcohol use disorder who received oral or extended-release naltrexone, disulfiram, or acamprosate as well as the proportion of days covered (PDC) in the 180 days after initiation and the time to first ten-day gap in possession (persistence) for each medication. Multilevel, mixed-effects logistic regression models examined the association between patient and facility characteristics and use of medications. Results: Nationally, 3.4% of VHA patients with an alcohol use disorder received medications in FY 2009 (11,165 of 331,635 patients), up from 3.0% in FY 2007. Use of medications by patients at the facilities ranged from 0% to 12%. In fully adjusted analyses, facilities offering evening and weekend services had higher rates of medication receipt, but other facility characteristics, such as having prescribers on the addiction program's staff or using medication to treat opioid or tobacco dependence, were unrelated to medication receipt. The mean PDC of acamprosate was significantly lower than mean PDCs of the other medications (p<.05), and persistence in use of naltrexone was significantly greater than use of acamprosate and significantly less than use of disulfiram (p<.05). Conclusions: Use of these medications is increasing but remains variable across the VHA system. Interventions are needed to optimize initiation of and persistence in use of these medications. (Psychiatric Services 63: 679-685, 2012; doi: 10.1176/appi.ps.201000553) C1 [Harris, Alex H. S.; Oliva, Elizabeth; Bowe, Thomas; Humphreys, Keith N.; Kivlahan, Daniel R.; Trafton, Jodie A.] US Dept Vet Affairs VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA. [Harris, Alex H. S.; Oliva, Elizabeth; Bowe, Thomas; Humphreys, Keith N.; Kivlahan, Daniel R.; Trafton, Jodie A.] Stanford Univ, Sch Med, Menlo Pk, CA 94025 USA. [Kivlahan, Daniel R.] Univ Washington, Sch Med, Seattle, WA USA. [Kivlahan, Daniel R.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Harris, AHS (reprint author), US Dept Vet Affairs VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, 795 Willow Rd,152-MPD, Menlo Pk, CA 94025 USA. EM alexander.harris2@va.gov NR 19 TC 26 Z9 26 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JUL PY 2012 VL 63 IS 7 BP 679 EP 685 DI 10.1176/appi.ps.201000553 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 967TY UT WOS:000305931900011 PM 22549276 ER PT J AU Bradley, KA Rubinsky, AD Sun, HL Blough, DK Tonnesen, H Hughes, G Beste, LA Bishop, MJ Hawn, MT Maynard, C Harris, ASH Hawkins, EJ Bryson, CL Houston, TK Henderson, WG Kivlahan, DR AF Bradley, Katharine A. Rubinsky, Anna D. Sun, Haili Blough, David K. Tonnesen, Hanne Hughes, Grant Beste, Lauren A. Bishop, Michael J. Hawn, Mary T. Maynard, Charles Harris, Alex S. H. Hawkins, Eric J. Bryson, Chris L. Houston, Thomas K. Henderson, William G. Kivlahan, Daniel R. TI Prevalence of alcohol misuse among men and women undergoing major noncardiac surgery in the Veterans Affairs health care system SO SURGERY LA English DT Article ID DISORDERS IDENTIFICATION TEST; PROSTATE-CANCER; SCREENING SCORES; AUDIT-C; RISK; CONSUMPTION; QUALITY; COMPLICATIONS; ASSOCIATION; MORBIDITY AB Background. Patients who screen positive for alcohol misuse on the Alcohol Use Disorder Identification Test Consumption Questionnaire (AUDIT-C >= 5 points) have significantly increased postoperative complications. Severe alcohol misuse (AUDIT-C >= 9 points) is associated with increased postoperative health care use; however, little is known about the prevalence of alcohol misuse in demographic and clinical subgroups of surgical patients. Methods. The prevalence of alcohol misuse was evaluated among 10,284 patients (9,771 men and 513 women) who underwent major noncardiac surgery in Veterans Affairs (VA) hospitals during the fiscal years 2004 to 2006 and completed the AUDIT-C. Sex-stratified analyses evaluated prevalence rates of alcohol misuse (AUDIT-C >= 5) and severe misuse (AUDIT-C >= 9) across demographic and clinical subgroups. Results. Overall, 1,607(16%) men and 24 (5%) women screened positive for alcohol misuse (AUDIT-C >= 5) in the year before operation, with 4% and 2% screening positive for severe misuse (AUDIT-C >= 9), respectively. Alcohol misuse was more common among men who were <60 years of age, divorced or separated, current smokers, or American Stoke Association class 1 or 2, and those with cirrhosis/hepatitis or substance use disorders. Among patients with alcohol misuse, 36% of men and 58% of women were American Society Of Anesthesiologists class I or 2, and most did not have diagnoses that were commonly associated with alcohol misuse. Conclusion. Alcohol misuse is relatively common in male surgical patients. Moreover, surgical patients undergoing operation who screen positive for alcohol misuse are often relatively healthy, without health problems that might alert providers to their alcohol misuse in the absence of screening. (Surgery 2012;152:69-81.) C1 [Bradley, Katharine A.] Univ Washington, Grp Hlth Res Inst, Seattle, WA 98101 USA. [Bradley, Katharine A.; Hawkins, Eric J.; Kivlahan, Daniel R.] Univ Washington, Dept Vet Affairs Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98101 USA. [Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA 98101 USA. [Bradley, Katharine A.; Rubinsky, Anna D.; Beste, Lauren A.; Maynard, Charles] Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA. [Blough, David K.] Univ Washington, Dept Pharm, Seattle, WA 98101 USA. [Tonnesen, Hanne] Bispebjerg Hosp, World Hlth Org Collaborating Ctr Evidence Based H, Copenhagen, Denmark. [Hughes, Grant; Henderson, William G.] Dept Vet Affairs Eastern Colorado Healthcare Syst, Denver, CO USA. [Bryson, Chris L.] Univ Washington, Dept Vet Affairs Puget Sound Hlth Care Syst, Gen Med Serv, Seattle, WA 98101 USA. [Hawn, Mary T.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA. [Hawn, Mary T.] Birmingham Vet Affairs Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Harris, Alex S. H.] Dept Vet Affairs Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA USA. [Houston, Thomas K.] Bedford Vet Affairs Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Houston, Thomas K.] Univ Massachusetts, Sch Med, Div Hlth Informat & Implementat Sci, Dept Quantitat Hlth Sci, Worcester, MA USA. [Henderson, William G.] Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. RP Bradley, KA (reprint author), Univ Washington, Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM bradley.k@ghc.org RI Houston, Thomas/F-2469-2013; Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development and Health Services Research and Development (HSRD) [IAC 06-021]; US Department of Veterans Affairs, Office of Research and Development FX Supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development and Health Services Research and Development (HSR & D; project IAC 06-021). Dr Bradley was an investigator at the Veterans Affairs Northwest HSR&D Center of Excellence and at the Center of Excellence in Substance Abuse Treatment and Education, VA Puget Sound Health Care System, Seattle, WA, while this work was conducted.; This material is based upon work supported by the US Department of Veterans Affairs, Office of Research and Development. 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 38 TC 9 Z9 9 U1 2 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD JUL PY 2012 VL 152 IS 1 BP 69 EP 81 DI 10.1016/j.surg.2012.02.007 PG 13 WC Surgery SC Surgery GA 966QZ UT WOS:000305853800011 PM 22503319 ER PT J AU Yin, XM Latif, R Bahn, R Davies, TF AF Yin, Xiaoming Latif, Rauf Bahn, Rebecca Davies, Terry F. TI Genetic Profiling in Graves' Disease: Further Evidence for Lack of a Distinct Genetic Contribution to Graves' Ophthalmopathy SO THYROID LA English DT Article ID AUTOIMMUNE THYROID-DISEASE; INTERLEUKIN-23 RECEPTOR GENE; T-LYMPHOCYTE ANTIGEN-4; THYROTROPIN RECEPTOR; RHEUMATOID-ARTHRITIS; FUNCTIONAL VARIANTS; SUSCEPTIBILITY GENE; TSH-RECEPTOR; ASSOCIATION; CTLA-4 AB Background: Graves' disease (GD), including Graves' ophthalmopathy or orbitopathy (GO), is an autoimmune disease with an environmental and genetic component to its etiology. The genetic contribution to the GO clinical phenotype remains unclear. Previous data from our laboratory and others have suggested that GO has no specific genetic component distinct from GD itself, while other reports have occasionally appeared suggesting that polymorphisms in genes such as CTLA4 and IL23R specifically increase the risk for GO. One of the criticisms of all these reports has been the clinical definition of the GO phenotype as distinct from hyperthyroid GD devoid of clinically significant eye involvement. The objective of this study was to take advantage of a phenotypically pure group of GD patients with GO and examine a series of genes associated with GD to determine if any were more definitively associated with GO rather than Graves' thyroid disease itself. Methods: To further examine whether specific susceptibility genes are associated with GO, we have performed further genetic association studies using highly characterized GO patients, many of whom had undergone orbital decompression surgery for their exophthalmos. We genotyped HLA, CTLA4, IL23R, and TSHR genes in a group of 256 Caucasian patients with severe GO (n = 199) and less severe GO (n = 57), and 90 patients with GD but no clinically apparent GO. Results: We found that the allele and genotype frequencies were not statistically different between GO and non-GO patients for any of the genes and gene combinations assessed. Conclusions: These results provide further evidence that patients with GO do not have a distinct genetic susceptibility to their eye disease and again suggest that environmental and/or epigenetic influences are at play. C1 [Yin, Xiaoming; Latif, Rauf; Davies, Terry F.] James J Peters VA Med Ctr, Mt Sinai Sch Med, Thyroid Res Unit, New York, NY 10468 USA. [Bahn, Rebecca] Mayo Clin, Sch Med, Div Endocrinol, Rochester, MN USA. RP Yin, XM (reprint author), James J Peters VA Med Ctr, Mt Sinai Sch Med, Thyroid Res Unit, Room 2F-26,130 W Kingsbridge Rd, New York, NY 10468 USA. EM xiaoming.yin@mssm.edu OI latif, rauf/0000-0002-4226-3728 FU NIH-NIDDK the David Owen Segal Endowment [DK052464, DK69713]; James J. Peters VAMC; VA Merit Award program FX This work was supported in part by DK052464 and DK69713 from NIH-NIDDK the David Owen Segal Endowment, the James J. Peters VAMC, and the VA Merit Award program. We thank our colleague Dr. Yaron Tomer for his help and advice. NR 58 TC 16 Z9 18 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD JUL PY 2012 VL 22 IS 7 BP 730 EP 736 DI 10.1089/thy.2012.0007 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 968JE UT WOS:000305974400011 PM 22663548 ER PT J AU Fischer, MJ Xie, DW Jordan, N Kop, WJ Krousel-Wood, M Tamura, MK Kusek, JW Ford, V Rosen, LK Strauss, L Teal, VL Yaffe, K Powe, NR Lash, JP AF Fischer, Michael J. Xie, Dawei Jordan, Neil Kop, Willem J. Krousel-Wood, Marie Tamura, Manjula Kurella Kusek, John W. Ford, Virginia Rosen, Leigh K. Strauss, Louise Teal, Valerie L. Yaffe, Kristine Powe, Neil R. Lash, James P. CA CRIC Study Grp Investigators TI Factors Associated With Depressive Symptoms and Use of Antidepressant Medications Among Participants in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC Studies SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Depression; chronic kidney disease; disparities; antidepressants ID CHRONIC KIDNEY-DISEASE; QUALITY-OF-LIFE; NATIONAL COMORBIDITY SURVEY; BASE-LINE CHARACTERISTICS; HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS; PRIMARY-CARE; AFRICAN-AMERICANS; MAJOR DEPRESSION; COMMUNITY SAMPLE AB Background: Depressive symptoms are correlated with poor health outcomes in adults with chronic kidney disease (CKD). The prevalence, severity, and treatment of depressive symptoms and potential risk factors, including level of kidney function, in diverse populations with CKD have not been well studied. Study Design: Cross-sectional analysis. Settings & Participants: Participants at enrollment into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies. CRIC enrolled Hispanics and non-Hispanics at 7 centers in 2003-2007, and H-CRIC enrolled Hispanics at the University of Illinois in 2005-2008. Measurement: Depressive symptoms measured by Beck Depression Inventory (BDI). Predictors: Demographic and clinical factors. Outcomes: Elevated depressive symptoms (BDI score >= 11) and antidepressant medication use. Results: Of 3,853 participants, 27.4% had evidence of elevated depressive symptoms and 18.2% were using antidepressant medications; 31.0% of persons with elevated depressive symptoms were using antidepressants. The prevalence of elevated depressive symptoms varied by level of kidney function: 23.6% for participants with estimated glomerular filtration rate (eGFR) >= 60 mL/min/1.73 m(2) and 33.8% of those with eGFR <30 mL/min/1.73 m(2). Lower eGFR (OR per 10-mL/min/1.73 m(2) decrease, 1.10; 95% CI, 1.04-1.17), and non-Hispanic black race (OR, 1.42; 95% CI, 1.16-1.74) were each associated with increased odds of elevated depressive symptoms after controlling for other factors. In regression analyses incorporating BDI score, whereas female sex was associated with greater odds of antidepressant use, Hispanic ethnicity, non-Hispanic black race, and higher urine albumin levels were associated with decreased odds of antidepressant use (P < 0.05 for each). Limitations: Absence of clinical diagnosis of depression and use of nonpharmacologic treatments. Conclusions: Although elevated depressive symptoms were common in individuals with CKD, use of antidepressant medications is low. Individuals of racial and ethnic minority background and with more advanced CKD had a greater burden of elevated depressive symptoms and lower use of antidepressant medications. Am J Kidney Dis. 60(1): 27-38. 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 [Fischer, Michael J.; Lash, James P.] Univ Illinois, Med Ctr, Chicago, IL USA. [Fischer, Michael J.; Lash, James P.] Jesse Brown VA Med Ctr, Chicago, IL USA. [Xie, Dawei; Ford, Virginia; Rosen, Leigh K.; Teal, Valerie L.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Jordan, Neil] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Kop, Willem J.] Univ Maryland, Baltimore, MD 21201 USA. [Kop, Willem J.] Tilburg Univ, NL-5000 LE Tilburg, Netherlands. [Krousel-Wood, Marie] Tulane Univ, New Orleans, LA 70118 USA. [Krousel-Wood, Marie] Ochsner Clin Fdn, Ctr Hlth Res, New Orleans, LA USA. [Tamura, Manjula Kurella] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Kusek, John W.] NIDDK, NIH, Bethesda, MD USA. [Strauss, Louise] Univ Hosp Cleveland, Case Med Ctr, Cleveland, OH 44106 USA. [Yaffe, Kristine; Powe, Neil R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Powe, Neil R.] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Fischer, Michael J.; Jordan, Neil] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. RP Fischer, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care, 5000 S 5th Ave 151H, Hines, IL 60141 USA. EM fischerm@uic.edu RI Krousel-Wood, Marie Antoinette/D-4718-2011; Kurella Tamura, Manjula/C-8284-2014 OI Kurella Tamura, Manjula/0000-0001-5227-2479 FU National Institute of Diabetes and Digestive and Kidney Diseases [5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028, 5U01DK60980, 5U01DK060963, 5U01DK060902, R01 DK072231]; Clinical Translational Science Awards (CTSA); National Institutes of Health (NIH) Johns Hopkins University [UL1 RR-025005]; National Institutes of Health (NIH) University of Maryland GRCR [M01 RR-16500]; National Institutes of Health (NIH) Case Western Reserve University Clinical and Translational Science Collaborative (University Hospitals of Cleveland, Cleveland Clinic Foundation, and MetroHealth) [UL1 RR-024989]; National Institutes of Health (NIH) University of Michigan GCRC [M01 RR-000042, CTSA UL1 RR-024986]; National Institutes of Health (NIH) University of Illinois at Chicago Clinical Research Center [M01 RR-013987-06]; National Institutes of Health (NIH) Tulane/LSU/Charity Hospital General Clinical Research Center [RR-05096]; National Institutes of Health (NIH) Kaiser NIH/National Center for Research Resources UCSF-CTSI [UL1 RR-024131, 5K24DK002651] FX In addition to funding under a cooperative agreement from the National Institute of Diabetes and Digestive and Kidney Diseases (5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028, 5U01DK60980, 5U01DK060963, and 5U01DK060902) and R01 DK072231 (H-CRIC), this work was supported in part by the following institutional Clinical Translational Science Awards (CTSA) and other National Institutes of Health (NIH) grants: Johns Hopkins University UL1 RR-025005, University of Maryland GRCR M01 RR-16500, Case Western Reserve University Clinical and Translational Science Collaborative (University Hospitals of Cleveland, Cleveland Clinic Foundation, and MetroHealth) UL1 RR-024989, University of Michigan GCRC M01 RR-000042, CTSA UL1 RR-024986, University of Illinois at Chicago Clinical Research Center, M01 RR-013987-06, Tulane/LSU/Charity Hospital General Clinical Research Center RR-05096, and Kaiser NIH/National Center for Research Resources UCSF-CTSI UL1 RR-024131, 5K24DK002651. Additional support provided by the National Center for Minority Health and Health Disparities, NIH, and Department of Veterans Affairs Health Services Research and Development Service (Career Development Award to Dr Fischer). NR 49 TC 9 Z9 10 U1 1 U2 5 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 JUL PY 2012 VL 60 IS 1 BP 27 EP 38 DI 10.1053/j.ajkd.2011.12.033 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 960RJ UT WOS:000305406200007 PM 22497791 ER PT J AU Choi, JC Bakaeen, FG Cornwell, LD Dao, TK Coselli, JS LeMaire, SA Chu, D AF Choi, Justin C. Bakaeen, Faisal G. Cornwell, Lorraine D. Dao, Tam K. Coselli, Joseph S. LeMaire, Scott A. Chu, Danny TI Morbid Obesity Is Associated With Increased Resource Utilization in Coronary Artery Bypass Grafting SO ANNALS OF THORACIC SURGERY LA English DT Article ID BODY-MASS INDEX; AMERICAN-HEART-ASSOCIATION; QUALITY-OF-LIFE; CARDIOVASCULAR-DISEASE; CARDIAC-SURGERY; UNITED-STATES; PHYSICAL-ACTIVITY; OPERATING-ROOM; WEIGHT-LOSS; RISK-FACTOR AB Background. Studies have shown good outcomes for morbidly obese patients who undergo cardiac surgery. However, little is known about how much additional resource utilization treating these challenging patients requires. We hypothesized that morbidly obese patients (body mass index >= 40 kg/m(2)) undergoing coronary artery bypass grafting needed longer operating room times and had longer hospital and intensive care unit stays than non-morbidly obese patients. Methods. We reviewed data from all morbidly obese patients (n = 56, body mass index = 42.7 +/- 2.6 kg/m(2)) who underwent coronary artery bypass grafting at our institution between 1999 and 2009. These patients' outcomes were compared with those of non-morbidly obese patients (n = 168, body mass index = 30.0 +/- 2.8 kg/m(2)) who were propensity-matched 3: 1 with the morbidly obese patients. Results. Of the 14 preoperative characteristics examined, only 1, creatinine level, differed significantly between the two groups (p = 0.02). Intraoperative and postoperative complication rates and the mortality rate were similar between groups (p > 0.09). However, morbidly obese patients had longer operating times (449 +/- 70 versus 420 +/- 59 minutes; p = 0.002), intensive care unit stays (5.2 versus 3.3 days; p < 0.005), and postoperative hospital stays (14.2 versus 9.5 days; p < 0.005) than the non-morbidly obese patients. Conclusions. Although good outcomes can be achieved for morbidly obese patients who undergo coronary artery bypass grafting, these patients require considerably more resource utilization in the operating room and intensive care unit, and they spend more time in the hospital after surgery. At a cardiac surgical operating room cost of approximately $50 per minute and $4,500 per intensive care unit day, the financial implications for morbidly obese patients who need coronary artery bypass grafting are not insignificant. C1 [Chu, Danny] Baylor Coll Med, Texas Heart Inst, Michael E DeBakey Vet Affairs Med Ctr, Dept Surg,Div Cardiothorac Surg, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX 77030 USA. St Lukes Episcopal Hosp, Texas Heart Inst, Div Cardiovasc Surg, Houston, TX USA. Univ Houston, Dept Educ Psychol, Houston, TX USA. RP Chu, D (reprint author), Baylor Coll Med, Texas Heart Inst, Michael E DeBakey Vet Affairs Med Ctr, Dept Surg,Div Cardiothorac Surg, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA. EM dchu@bcm.edu NR 39 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 2012 VL 94 IS 1 BP 23 EP 28 DI 10.1016/j.athoracsur.2012.03.036 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 965XS UT WOS:000305801600014 PM 22607785 ER PT J AU Schumacher, HR AF Schumacher, H. Ralph, Jr. TI The need to compare rilonacept against active treatment for prevention of gout flares: comment on the article by Schumacher et al Reply SO ARTHRITIS AND RHEUMATISM LA English DT Letter ID ARTHRITIS C1 [Schumacher, H. Ralph, Jr.] Univ Penn, Philadelphia, PA 19104 USA. [Schumacher, H. Ralph, Jr.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Schumacher, HR (reprint author), Univ Penn, Philadelphia, PA 19104 USA. NR 2 TC 0 Z9 0 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD JUL PY 2012 VL 64 IS 7 BP 2416 EP 2416 DI 10.1002/art.34475 PG 1 WC Rheumatology SC Rheumatology GA 965CD UT WOS:000305742800041 ER PT J AU Liel, MS Greenberg, DL Recht, M Vanek, C Klein, RF Taylor, JA AF Liel, Meghan S. Greenberg, Daniel L. Recht, Michael Vanek, Chaim Klein, Robert F. Taylor, Jason A. TI Decreased bone density and bone strength in a mouse model of severe factor VIII deficiency SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE haemophilia; factor VIII; bone density; osteoporosis ID HEMOPHILIA; OSTEOPOROSIS; RISK C1 [Liel, Meghan S.; Greenberg, Daniel L.; Recht, Michael; Taylor, Jason A.] Oregon Hlth & Sci Univ, Hemophilia Ctr, Portland, OR 97201 USA. [Liel, Meghan S.; Klein, Robert F.; Taylor, Jason A.] Portland VA Med Ctr, Med Serv, Portland, OR USA. [Vanek, Chaim; Klein, Robert F.] Oregon Hlth & Sci Univ, Bone & Mineral Res Unit, Portland, OR 97201 USA. RP Liel, MS (reprint author), Oregon Hlth & Sci Univ, Hemophilia Ctr, Portland, OR 97201 USA. EM taylojas@ohsu.edu NR 10 TC 11 Z9 11 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 2012 VL 158 IS 1 BP 140 EP 143 DI 10.1111/j.1365-2141.2012.09101.x PG 4 WC Hematology SC Hematology GA 956ZC UT WOS:000305127100015 PM 22469061 ER PT J AU Kaunitz, JD AF Kaunitz, Jonathan D. TI Digestive Diseases and Sciences: Sadness, Satisfaction, and Sanguinity SO DIGESTIVE DISEASES AND SCIENCES LA English DT Editorial Material C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA 90095 USA. RP Kaunitz, JD (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA 90095 USA. EM Jonathan.Kaunitz@va.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUL PY 2012 VL 57 IS 7 BP 1742 EP 1744 DI 10.1007/s10620-012-2287-0 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 965DH UT WOS:000305746100002 ER PT J AU Kanwal, F Kramer, JR Buchanan, P Asch, SM Assioun, Y Bacon, BR Li, J El-Serag, HB AF Kanwal, Fasiha Kramer, Jennifer R. Buchanan, Paula Asch, Steven M. Assioun, Youssef Bacon, Bruce R. Li, Juan El-Serag, Hashem B. TI The Quality of Care Provided to Patients With Cirrhosis and Ascites in the Department of Veterans Affairs SO GASTROENTEROLOGY LA English DT Article DE SBP; Best Practices; Quality Measurement; Predictors ID SPONTANEOUS BACTERIAL PERITONITIS; CHRONIC HEPATITIS-C; LIVER-DISEASE; UNITED-STATES; MANAGEMENT; PROPHYLAXIS; MORTALITY; SURVIVAL; COHORT; PREDICT AB BACKGROUND & AIMS: Ascites are the most common complication of cirrhosis. Evidence-based guidelines define the criteria and standards of care for patients with cirrhosis and ascites. However, little is known about the extent to which patients with ascites meet these standards. METHODS: We evaluated the quality of ascites care, measured by 8 explicit Delphi panel-derived quality indicators, in 774 patients with cirrhosis and ascites, seen at 3 Veterans Affairs Medical Centers between 2000 and 2007. We also conducted a structured implicit review of patients' medical charts to determine whether patient refusal, outside care, or other justifiable exceptions to care processes account for nonadherence to the quality indicators. RESULTS: Quality scores (maximum 100%) varied among individual indicators, ranging from 30% for secondary prophylaxis of spontaneous bacterial peritonitis, to 90% for assays for cell number and type in the paracentesis fluid. In general, care targeted at treatment was more likely to meet standards than preventive care. Only 33.2% (95% confidence interval [CI]: 29.9% - 32.9%) of patients received all recommended care. Patients with no comorbidity (Deyo index 0 vs >3; odds ratio = 2.21; 95% CI: 1.43 - 3.43), who saw a gastroenterologist (odds ratio = 1.33; 95% CI, 1.01 - 1.74), or were seen in a facility with academic affiliation (odds ratio = 1.73; 95% CI: 1.29 - 2.35) received higher-quality care. Justifiable exceptions to indicated care, documented in charts, were common for patients with paracentesis after diagnosis with ascites, patients that received antibiotics for gastrointestinal bleeding, and patients that required diuretics. However, most patients did not have an explanation documented for nonadherence to recommended care. CONCLUSIONS: Health care quality, measured by whether patients received recommended services, was suboptimal for patients with cirrhosis-related ascites. Care that included gastroenterologists was associated with high quality. However, for some of the quality indicators, too many denominator exceptions existed to allow for accurate automated measurement. C1 [Kanwal, Fasiha] Michael E DeBakey VA Med Ctr, Dept Gastroenterol & Hepatol, Houston, TX 77030 USA. [Kanwal, Fasiha; Kramer, Jennifer R.; El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Buchanan, Paula] St Louis Univ, Sch Publ Hlth, St Louis, MO 63103 USA. [Asch, Steven M.] Greater Los Angeles VA Healthcare Syst, Dept Med, Los Angeles, CA USA. [Asch, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Assioun, Youssef; Bacon, Bruce R.; Li, Juan] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA. RP Kanwal, F (reprint author), Michael E DeBakey VA Med Ctr, Dept Gastroenterol & Hepatol, 2002 Holcombe Blvd,152, Houston, TX 77030 USA. EM fasiha.kanwal@va.gov FU American Society of Gastrointestinal Endoscopy Quality of Care Award; American College of Gastroenterology Clinical Research Award; Veteran's Affairs Health Services Research and Development (HSR&D) Investigator Initiated Research Award [IIR-07-111]; Houston VA HSR&D Center of Excellence [HFP90-020] FX This material is based upon work supported by the 2008 American Society of Gastrointestinal Endoscopy Quality of Care Award and by the 2009 American College of Gastroenterology Clinical Research Award. Dr Kanwal is supported by Veteran's Affairs Health Services Research and Development (HSR&D) Investigator Initiated Research Award IIR-07-111. This material is also supported in part by the Houston VA HSR&D Center of Excellence (HFP90-020). NR 26 TC 38 Z9 38 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2012 VL 143 IS 1 BP 70 EP 77 DI 10.1053/j.gastro.2012.03.038 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 965QE UT WOS:000305781500030 PM 22465432 ER PT J AU Gordon, PL Doyle, JW Johansen, KL AF Gordon, Patricia L. Doyle, Julie W. Johansen, Kirsten L. TI Association of 1,25-Dihydroxyvitamin D Levels With Physical Performance and Thigh Muscle Cross-sectional Area in Chronic Kidney Disease Stage 3 and 4 SO JOURNAL OF RENAL NUTRITION LA English DT Article ID CHRONIC-RENAL-FAILURE; QUALITY-OF-LIFE; VITAMIN-D INSUFFICIENCY; SKELETAL-MUSCLE; HEMODIALYSIS-PATIENTS; RESISTANCE EXERCISE; 25-HYDROXYVITAMIN D; BODY-COMPOSITION; CONTROLLED-TRIAL; 6-MINUTE WALK AB Background: Declines in 1,25-dihydroxyvitamin D (1,25(OH)(2)D) levels and physical functioning follow the course of chronic kidney disease (CKD). Although the molecular actions of vitamin D in skeletal muscle are well known, and muscle weakness and atrophy are observed in vitamin D-deficient states, there is little information regarding vitamin D and muscle function and size in CKD. Objective: To examine associations of vitamin D with physical performance (PF) and muscle size. Design: Cross-sectional. Setting: CKD clinic. Subjects: Twenty-six patients (61 +/- 13 years, 92% men) with CKD stage 3 or 4. Main Outcome Measures: Gait speed, 6-minute walk, sit-to-stand time, 1-legged balance, and thigh muscle cross-sectional area (MCSA), measured by magnetic resonance imaging (MRI). Results: Overall, 73% were 25-hydroxyvitamin D(25(OH)D) deficient (n = 10) or insufficient (n = 9) (Kidney Disease Outcomes Quality Initiative guidelines). 25(OH)D level was associated with normal gait speed only (r = 0.41, P = .04). Normal and fast gait speed, the distance walked in 6 minutes, and sit-to-stand time were best explained by 1,25(OH)(2)D and body mass index (P < .05 for all) and 1-legged stand by 1,25(OH)(2)D (r = 0.40, P < .05) only. There were no associations of age, estimated glomerular filtration rate (eGFR), intact parathyroid hormone (iPTH), or albumin with any PF measures. MCSA was associated with eGFR (r = 0.54, P < .01) only. Variance in MCSA was best explained by a model containing 1,25(OH)(2)D, plasma Ca2+, and daily physical activity (by accelerometry) (P < .05 for all). Once these variables were in the model, there was no contribution of eGFR. Conclusion: These results suggest that 1,25(OH)(2)D is a determinant of PF and muscle size in patients with stage 3 and 4 CKD. (C) 2012 by the National Kidney Foundation, Inc. All rights reserved. C1 [Gordon, Patricia L.] Univ Calif San Francisco, Div Nephrol, Dept Med, San Francisco, CA 94121 USA. [Gordon, Patricia L.; Doyle, Julie W.; Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA. RP Gordon, PL (reprint author), Univ Calif San Francisco, Div Nephrol, Dept Med, Box 111J,4150 Clement St, San Francisco, CA 94121 USA. EM patricia.gordon@ucsf.edu FU Abbott Laboratories FX This study was funded through investigator-initiated funding by Abbott Laboratories. P.L.G. and K.L.J. have received financial support for this study from Abbott Laboratories. NR 59 TC 4 Z9 5 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1051-2276 J9 J RENAL NUTR JI J. Renal Nutr. PD JUL PY 2012 VL 22 IS 4 BP 423 EP 433 DI 10.1053/j.jrn.2011.10.006 PG 11 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA 965DY UT WOS:000305748100008 PM 22227183 ER PT J AU Subramanian, A Timberlake, M Mittakanti, H Lara, M Brandt, ML AF Subramanian, Anuradha Timberlake, Matthew Mittakanti, Harsha Lara, Michael Brandt, Mary L. TI Novel Educational Approach for Medical Students: Improved Retention Rates Using Interactive Medical Software Compared with Traditional Lecture-Based Format SO JOURNAL OF SURGICAL EDUCATION LA English DT Article DE web-based; surgical education; interactive tool AB BACKGROUND: Mannequin and computer-based simulators are useful for the practice of patient management, physical procedures, and competency. However, they are ineffective in teaching clinical medicine. StepStone Interactive Medical Software (SS) is a web-based medical learning modality that provides the user with a highly focused set of evaluative and interventional tasks to treat memorable virtual patients in a visual case-based format. OBJECTIVE: To determine whether the SS learning modality is superior to traditional lecture format in medical student learning and retention. METHODS: After Institutional Review Board (IRB) approval was obtained and the consents were signed, 30 third-year medical students were assigned randomly to 2 groups of 15 students each: The control group received two 30-minute PowerPoint lectures (Microsoft Corporation, Redmond, Washington) about torsades de pointes (TdP) and pulseless electrical activity (PEA), and the SS group was given 1 hour to review 2 SS cases teaching TdP and PEA. A preintervention test was given to assess their baseline knowledge. An immediate postintervention test was given to both groups. Twenty-two days later, a long-term retention test was administered. The results were analyzed using a Student t test for continuous variables. RESULTS: The mean scores for the preintervention test in the control and SS groups were 44.9 +/- 3% and 44.1 +/- 2%, respectively (p = 0.41). The mean scores for the postintervention test in the control and SS groups were 61.7 +/- 2% and 86.7 +/- 2%, respectively (p < 0.001). Improvement from baseline knowledge was calculated, and the mean improvement was 16.8 +/- 3% in the control group and 42.5 +/- 2% in the SS group (p < 0.001). The long-term retention test revealed the mean scores of 55.8 +/- 3% in the control group and 70.1 +/- 3% in the SS group (p < 0.001). Long-term improvement from baseline knowledge was calculated and the control group improved by 10.9 +/- 4%, whereas the SS group improved by 26 +/- 3% (p = 0.002). CONCLUSIONS: The SS learning modality demonstrated a significant improvement in student learning retention compared to traditional didactic lecture format. SS is an effective web-based medical education tool. (J Surg 69:449-452. (C) 2012 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.) C1 [Subramanian, Anuradha] Baylor Coll Med, VA Med Ctr, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. RP Subramanian, A (reprint author), Baylor Coll Med, VA Med Ctr, Michael E DeBakey Dept Surg, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA. EM asubrama@bcm.edu NR 6 TC 14 Z9 14 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-7204 J9 J SURG EDUC JI J. Surg. Educ. PD JUL-AUG PY 2012 VL 69 IS 4 BP 449 EP 452 DI 10.1016/j.jsurg.2012.05.013 PG 4 WC Education, Scientific Disciplines; Surgery SC Education & Educational Research; Surgery GA 960CS UT WOS:000305366200003 PM 22677580 ER PT J AU Zhang, XY Liang, J Chen, DC Xiu, MH Yang, FD Kosten, TA Kosten, TR AF Zhang, Xiang Yang Liang, Jun Chen, Da Chun Xiu, Mei Hong Yang, Fu De Kosten, Therese A. Kosten, Thomas R. TI Low BDNF is associated with cognitive impairment in chronic patients with schizophrenia SO PSYCHOPHARMACOLOGY LA English DT Article DE Schizophrenia; Cognition; Brain-derived neurotrophic factor; Serum ID NEUROTROPHIC FACTOR LEVELS; LONG-TERM TREATMENT; LOW SERUM-LEVELS; BIPOLAR DISORDER; 1ST-EPISODE SCHIZOPHRENIA; NEUROPSYCHOLOGICAL STATUS; ATYPICAL ANTIPSYCHOTICS; VAL66MET POLYMORPHISM; TARDIVE-DYSKINESIA; REPEATABLE BATTERY AB Several lines of evidence suggest that brain-derived neurotrophic factor (BDNF) plays a critical role in activity-dependent neuroplasticity underlying learning and memory in the hippocampus. Schizophrenia has a range of cognitive deficits that may evolve from decreased BDNF, and this study examines this association of BDNF with cognitive deficits in schizophrenia. We recruited 251 chronic schizophrenic patients and 206 healthy control subjects and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum BDNF in both groups. Schizophrenic symptoms were assessed using the Positive and Negative Syndrome Scale. BDNF levels were significantly lower in patients than controls (p < 0.001). Cognitive scores on the RBANS and nearly all 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, BDNF was positively associated with immediate memory in schizophrenia. Our findings suggest that BDNF may be involved in the pathophysiology of schizophrenia, and its associated cognitive impairment, especially immediate memory. C1 [Zhang, Xiang Yang; Kosten, Thomas R.] VA Med Ctr, Houston, TX 77030 USA. [Chen, Da Chun; Xiu, Mei Hong; Yang, Fu De] Beijing HuiLongGuan Hosp, Beijing 100096, Peoples R China. [Liang, Jun] Peking Univ, Inst Mental Hlth, Beijing 100083, Peoples R China. [Zhang, Xiang Yang; Kosten, Therese A.; Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. 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 This study was funded by the Stanley Medical Research Institute (03T-459 and 05T-726), and the Department of Veterans Affairs, VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC), United States National Institute of Health K05-DA0454, P50-DA18827, and U01-MH79639. NR 55 TC 44 Z9 47 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 2012 VL 222 IS 2 BP 277 EP 284 DI 10.1007/s00213-012-2643-y PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 964GI UT WOS:000305681600009 PM 22274000 ER PT J AU Moschak, TM Stang, KA Phillips, TJ Mitchell, SH AF Moschak, Travis M. Stang, Katherine A. Phillips, Tamara J. Mitchell, Suzanne H. TI Behavioral inhibition in mice bred for high vs. low levels of methamphetamine consumption or sensitization SO PSYCHOPHARMACOLOGY LA English DT Article DE Inhibition; Go/no-go; Behavioral sensitization; Self-administration; Selected lines; Methamphetamine; Impulsivity ID REACTION-TIME-TASK; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; GO/NO-GO TASK; D-AMPHETAMINE; STOP-SIGNAL; RATS; PERFORMANCE; IMPULSIVITY; LESIONS; METHYLPHENIDATE AB Research indicates that genetics influence methamphetamine self-administration as well as sensitization to the psychomotor-stimulating effects of methamphetamine (MA). Other studies have suggested that heightened levels of impulsivity, including low levels of behavioral inhibition, are associated with the use of drugs, including MA. The current study examined whether lines of mice selected for traits associated with a heightened risk of developing MA dependence would also exhibit low levels of drug-na < ve inhibition and whether administration of MA would result in different levels of inhibition in animals selected to consume or respond more to MA. A go/no-go task was used to assess inhibition in male and female mice selected for low or high levels of MA consumption or selected for high or low levels of locomotor sensitization to repeated injections of MA. Mice selected for MA sensitization differed in false alarms, precue response rates (measures of behavioral inhibition), and also hits (measure of operant responding). Mice selected for MA consumption did not differ in measures of behavioral inhibition, though hits differed. When MA was administered prior to the task, false alarms, precue response rates, and hits decreased for mice from all selected lines. Female high drinking mice were particularly resistant to MA's effects on hits, but not precue response rate or false alarms. These data suggest a shared, but complex, genetic association between inhibition processes, general levels of operant responding, and MA sensitization or consumption. C1 [Moschak, Travis M.; Stang, Katherine A.; Phillips, Tamara J.; Mitchell, Suzanne H.] Oregon Hlth & Sci Univ, Dept Behav Neurosci L470, Portland, OR 97239 USA. [Mitchell, Suzanne H.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. [Phillips, Tamara J.; Mitchell, Suzanne H.] Oregon Hlth & Sci Univ, Methamphetamine Abuse Res Ctr, Portland, OR 97239 USA. [Phillips, Tamara J.] Portland VA Med Ctr, Portland, OR USA. RP Mitchell, SH (reprint author), Oregon Hlth & Sci Univ, Dept Behav Neurosci L470, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM mitchesu@ohsu.edu OI Mitchell, Suzanne/0000-0002-0225-7200 FU Methamphetamine Abuse Research Center [P50 DA018165]; Department of Veterans Affairs; Portland Alcohol Research Center [P60 AA10760]; NIAAA [AA007468] FX SHM and TJP designed the study, TMM and KAS collected the data with help from Noah Gubner and Ryan McLaughlin, data analysis was performed by TMM, KAS and SHM, all authors were involved in data interpretation and manuscript preparation. This research was supported by the Methamphetamine Abuse Research Center (P50 DA018165), the Department of Veterans Affairs, and the Portland Alcohol Research Center (P60 AA10760). TMM was supported by NIAAA T32 training grant AA007468. All research was conducted in compliance with laws in USA. NR 49 TC 7 Z9 7 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 2012 VL 222 IS 2 BP 353 EP 365 DI 10.1007/s00213-012-2650-z PG 13 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 964GI UT WOS:000305681600017 PM 22311384 ER PT J AU Yilmaz-Rastoder, E Gold, MS Hough, KA Gebhart, GF Williams, BA AF Yilmaz-Rastoder, Eser Gold, Michael S. Hough, Karen A. Gebhart, G. F. Williams, Brian A. TI Effect of Adjuvant Drugs on the Action of Local Anesthetics in Isolated Rat Sciatic Nerves SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Article ID PERIPHERAL BENZODIAZEPINE-RECEPTORS; PERINEURAL INFUSION; CLONIDINE; ROPIVACAINE; ANALGESIA; BLOCK; DEXAMETHASONE; NEUROTOXICITY; BUPIVACAINE; CONDUCTION AB Background and Objectives: There is increasing clinical use of adjuvant drugs to prolong the duration of local anesthetic-induced block of peripheral nerves. However, the mechanistic understanding regarding drug interactions between these compounds in the periphery is quite limited. Accordingly, we undertook this study to determine whether selected adjuvant drugs are efficacious in blocking action potential propagation in peripheral nerves at concentrations used clinically and whether these drugs influence peripheral nerve block produced by local anesthetics. Methods: Isolated rat sciatic nerves were used to assess (1) the efficacy of buprenorphine, clonidine, dexamethasone, or midazolam, alone and in combination, on action potential propagation; and (2) their influence on the blocking actions of local anesthetics ropivacaine and lidocaine. Compound action potentials (CAPs) from A- and C-fibers were studied before and after drug application. Results: At estimated clinical concentrations, neither buprenorphine nor dexamethasone affected either A- or C-waves of the CAP. Clonidine produced a small but significant attenuation of the C-wave amplitude. Midazolam attenuated both A- and C-wave amplitudes, but with greater potency on the C-wave. The combination of clonidine, buprenorphine, and dexamethasone had no influence on the potency or duration of local anesthetic- or midazolam-induced block of A- and C-waves of the CAP. Conclusions: These results suggest that the reported clinical efficacy of clonidine, buprenorphine, and dexamethasone influences the actions of local anesthetics via indirect mechanisms. Further identification of these indirect mechanisms may enable the development of novel approaches to achieve longer-duration, modality-specific peripheral nerve block. C1 [Yilmaz-Rastoder, Eser; Gold, Michael S.; Hough, Karen A.; Gebhart, G. F.; Williams, Brian A.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Ctr Pain Res, Pittsburgh, PA 15261 USA. [Williams, Brian A.] VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. RP Williams, BA (reprint author), Univ Pittsburgh, Sch Med, Dept Anesthesiol, Ctr Pain Res, W-1403 BST WR, Pittsburgh, PA 15261 USA. EM williamsba@anes.upmc.edu OI Gold, Michael/0000-0002-2083-6206 FU Department of Defense grant [OR090012] FX This research is supported by a Department of Defense grant (OR090012) to Drs. Williams, Gold, and Gebhart. The article review by Department of Defense grant coprincipal investigator Chester C. Buckenmaier, III, MD (Walter Reed Army Medical Center), is also acknowledged. NR 20 TC 18 Z9 18 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-7339 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD JUL-AUG PY 2012 VL 37 IS 4 BP 403 EP 409 DI 10.1097/AAP.0b013e3182485965 PG 7 WC Anesthesiology SC Anesthesiology GA 965QI UT WOS:000305781900008 PM 22430023 ER PT J AU Burke, LE Styn, MA Sereika, SM Conroy, MB Ye, L Glanz, K Sevick, MA Ewing, LJ AF Burke, Lora E. Styn, Mindi A. Sereika, Susan M. Conroy, Molly B. Ye, Lei Glanz, Karen Sevick, Mary Ann Ewing, Linda J. TI Using mHealth Technology to Enhance Self-Monitoring for Weight Loss A Randomized Trial SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID LIFE-STYLE MODIFICATION; LOSS MAINTENANCE; TREATMENT PREFERENCE; PHYSICAL-ACTIVITY; CLINICAL-TRIAL; MOBILE PHONE; OBESE ADULTS; PROGRAM; INTERVENTIONS; MANAGEMENT AB Background: Self-monitoring for weight loss has traditionally been performed with paper diaries. Technologic advances could reduce the burden of self-monitoring and provide feedback to enhance adherence. Purpose: To determine if self-monitoring diet using a PDA only or the PDA with daily tailored feedback ( PDA + feedback [FB]), was superior to using a paper diary on weight loss and maintenance. Design: The Self-Monitoring and Recording Using Technology (SMART) Trial was a 24-month randomized clinical trial; participants were randomly assigned to one of three self-monitoring groups. Setting/participants: From 2006 to 2008, a total of 210 overweight/obese adults (84.8% female, 78.1% white) were recruited from the community. Data were analyzed in 2011. Intervention: Participants received standard behavioral treatment for weight loss that included dietary and physical activity goals, encouraged the use of self-monitoring, and was delivered in group sessions. Main outcome measures: Percentage weight change at 24 months, adherence to self-monitoring over time. Results: Study retention was 85.6%. The mean percentage weight loss at 24 months was not different among groups (paper diary: -1.94%, 95% CI = -3.88, 0.01; PDA: -1.38%, 95% CI = -3.38, 0.62; PDA + FB: -2.32%, 95% CI = -4.29, -0.35); only the PDA + FB group (p = 0.02) demonstrated a significant loss. For adherence to self-monitoring, there was a time-by-treatment group interaction between the combined PDA groups and the paper diary group (p = 0.03) but no difference between PDA and PDA + FB groups (p = 0.49). Across all groups, weight loss was greater for those who were adherent >= 60% versus <30% of the time (p < 0.001). Conclusions: PDA + FB use resulted in a small weight loss at 24 months; PDAuse resulted in greater adherence to dietary self-monitoring over time. However, for sustained weight loss, adherence to self-monitoring is more important than the method used to self-monitor. A daily feedback message delivered remotely enhanced adherence and improved weight loss, which suggests that technology can play a role in improving weight loss. Trial registration: This study is registered at clinicaltrials. gov NCT00277771. (Am J Prev Med 2012;43(1):20-26) (C) 2012 American Journal of Preventive Medicine C1 [Burke, Lora E.; Styn, Mindi A.; Sereika, Susan M.; Ye, Lei] Univ Pittsburgh, Sch Nursing, Dept Hlth & Community Syst, Pittsburgh, PA 15261 USA. [Burke, Lora E.; Styn, Mindi A.; Sereika, Susan M.; Conroy, Molly B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Sereika, Susan M.; Ye, Lei] Univ Pittsburgh, Dept Biostat, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Conroy, Molly B.; Sevick, Mary Ann] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15261 USA. [Ewing, Linda J.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. [Sevick, Mary Ann] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Glanz, Karen] Univ Penn, Sch Med & Nursing, Philadelphia, PA 19104 USA. RP Burke, LE (reprint author), Univ Pittsburgh, Sch Nursing, Dept Hlth & Community Syst, 3500 Victoria St,415 Victoria Bldg, Pittsburgh, PA 15261 USA. EM lbu100@pitt.edu RI Emchi, Karma/Q-1952-2016 FU NIH [NIH/NIDDK R01-DK071817, R01-DK071817-04S1, R01-DK071817-05S1, NIH/NINR K24-NR010742]; Data Management Core of the Center for Research in Chronic Disorders at the University of Pittsburgh School of Nursing [NIH-NINR P30-NR03924]; General Clinical Research Center [NIH-NCRR-GCRC 5M01-RR000056]; Clinical Translational Research Center (NIH/NCRR/CTSA) at University of Pittsburgh [UL1 RR024153] FX This work was supported by NIH grants NIH/NIDDK R01-DK071817, R01-DK071817-04S1, R01-DK071817-05S1, and NIH/NINR K24-NR010742. The conduct of the study also was supported by the Data Management Core of the Center for Research in Chronic Disorders at the University of Pittsburgh School of Nursing (NIH-NINR P30-NR03924), the General Clinical Research Center (NIH-NCRR-GCRC 5M01-RR000056) and the Clinical Translational Research Center (NIH/NCRR/CTSA Grant UL1 RR024153) at the University of Pittsburgh. NR 32 TC 76 Z9 76 U1 9 U2 43 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL PY 2012 VL 43 IS 1 BP 20 EP 26 DI 10.1016/j.amepre.2012.03.016 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 959VJ UT WOS:000305344000003 PM 22704741 ER PT J AU Hale, GA Shrestha, S Le-Rademacher, J Burns, LJ Gibson, J Inwards, DJ Freytes, CO Bolwell, BJ Hsu, JW Slavin, S Isola, L Rizzieri, DA Gale, RP Laport, GG Montoto, S Lazarus, HM Hari, PN AF Hale, Gregory A. Shrestha, Smriti Le-Rademacher, Jennifer Burns, Linda J. Gibson, John Inwards, David J. Freytes, Cesar O. Bolwell, Brian J. Hsu, Jack W. Slavin, Shimon Isola, Luis Rizzieri, David A. Gale, Robert Peter Laport, Ginna G. Montoto, Silvia Lazarus, Hillard M. Hari, Parameswaran N. TI Alternate Donor Hematopoietic Cell Transplantation (HCT) in Non-Hodgkin Lymphoma Using Lower Intensity Conditioning: A Report from the CIBMTR SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Non-Hodgkin lymphoma; HCT ID ALLOGENEIC TRANSPLANTATION; MARROW-TRANSPLANTATION; RETROSPECTIVE ANALYSIS; HOST DISEASE; FOLLOW-UP; GRAFT; SURVIVAL; REGIMEN; LEUKEMIA; OUTCOMES AB We analyzed the outcomes of 248 (61% male) adult recipients of HLA-matched unrelated and HLA-mismatched related donor hematopoietic cell transplantation (HCT) for non-Hodgkin lymphoma (NHL) after reduced or lower intensity conditioning (RIC), reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 1997 to 2004. Median age was 52 (range: 18-72 years); 31% had a Karnofsky performance score <90. Follicular NHL (43%) was the major histology. Incidence of grades II-IV acute graft-versus-host disease (aGVHD) was 43% at 100 days; and chronic GVHD (cGVHD) was 44% at 3 years. Treatment-related mortality (TRM) at 100 days was 24%. Three-year overall survival (OS) and progression-free survival (PFS) were 41% and 32%, respectively. In multivariate analysis, use of antithymocyte globulin (ATG) and HLA mismatch were associated with increased TRM. High-grade histology, ATG use, and chemotherapy resistance were associated with lower PFS. Older age, shorter interval from diagnosis to HCT, non total body irridiation (TBI) conditioning regimens, ex vivo T cell depletion, and HLA-mismatched unrelated donors were associated with mortality. GVHD did not influence relapse or PFS. Older age, aggressive histology, and chemotherapy resistance correlated with poorer survival. For selected patients with NHL, lack of an available sibling donor should not be a barrier to allogeneic HCT. Biol Blood Marrow Transplant 18: 1036-1043 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Shrestha, Smriti; Le-Rademacher, Jennifer; Hari, Parameswaran N.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplantat Res, Milwaukee, WI 53226 USA. [Hale, Gregory A.] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA. [Burns, Linda J.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Gibson, John] Royal Prince Alfred Hosp, Inst Haematol, Camperdown, NSW 2050, Australia. [Inwards, David J.] Mayo Clin, Rochester, MN USA. [Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Bolwell, Brian J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Hsu, Jack W.] Univ Florida, Shands Hosp, Gainesville, FL USA. [Slavin, Shimon] Int Ctr Cell Therapy & Canc Immunotherapy, Tel Aviv, Israel. [Isola, Luis] Mt Sinai Hosp, New York, NY 10029 USA. [Rizzieri, David A.] Duke Univ, Med Ctr, Durham, NC USA. [Gale, Robert Peter] Celgene Corp, Summit, NJ USA. [Laport, Ginna G.] Stanford Hosp & Clin, Stanford, CA USA. [Montoto, Silvia] Queen Mary Univ London, Sch Med, London, England. [Lazarus, Hillard M.] Univ Hosp, Case Med Ctr, Cleveland, OH USA. RP Hari, PN (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplantat Res, 9200 W Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA. EM phari@mcw.edu OI Hari, Parameswaran/0000-0002-8800-297X FU National Cancer Institute (NCI) [U24-CA76518, 5U01HL069294]; National Heart, Lung and Blood Institute (NHLBI) [U24-CA76518, 5U01HL069294]; National Institute of Allergy and Infectious Diseases (NIAID) [U24-CA76518]; Health Resources and Services Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos, Inc.; Amgen, Inc.; Angioblast 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); 2 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; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; Swedish Orphan Biovitrum; THERAKOS, Inc.; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, or any other agency of the U.S. Government. NR 23 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 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUL PY 2012 VL 18 IS 7 BP 1036 EP 1043 DI 10.1016/j.bbmt.2011.11.026 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 964BE UT WOS:000305667900008 PM 22155506 ER PT J AU Merkow, RP Bilimoria, KY McCarter, MD Chow, WB Gordon, HS Stewart, AK Ko, CY Bentrem, DJ AF Merkow, Ryan P. Bilimoria, Karl Y. McCarter, Martin D. Chow, Warren B. Gordon, Howard S. Stewart, Andrew K. Ko, Clifford Y. Bentrem, David J. TI Effect of histologic subtype on treatment and outcomes for esophageal cancer in the United States SO CANCER LA English DT Article DE esophageal cancer; tumor histology; surgery; survival; hospital type; adenocarcinoma; squamous cell carcinoma; treatment utilization; outcomes ID PROPENSITY SCORE; SURGERY; CARCINOMA; CHEMORADIATION; ADENOCARCINOMA; PATTERNS; THERAPY; CARE AB BACKGROUND: Esophageal adenocarcinoma (AC) and squamous cell carcinoma (SCC) have distinct clinico-pathologic characteristics; however, it is unclear whether treatment patterns differ by histologic subtype. The objective of this study was to examine differences in treatment use and outcomes by histologic subtype for esophageal cancer in the United States. METHODS: From the National Cancer Data Base, patients with esophageal cancer were identified. Regression models were formulated to assess the influence of histologic subtype on treatment use and overall survival. RESULTS: From 1998 to 2007, 80,961 patients were identified with esophageal cancer in the United States. A higher percentage of patients with nonmetastatic AC underwent surgical resection compared with patients with nonmetastatic SCC (AC, 65.7%; SCC, 36.0%; P<.001), who were more often treated with chemoradiotherapy alone (AC, 25.7%; SCC, 54.1%; P<.001). High-volume academic centers used surgery more frequently for both AC and SCC than did other centers, yet even at high-volume academic centers, surgery was used much less often to treat SCC than AC (AC, 79.3%; SCC, 53.7%; P<.001). The likelihood of operative treatment for nonmetastatic disease was significantly lower in patients with SCC compared with patients with AC (P<.001). Overall survival was lower for patients with stage II/III disease of either histologic subtype treated with chemoradiotherapy alone compared with surgery plus chemoradiotherapy (P<.001). CONCLUSION: A large proportion of patients with esophageal cancer are being treated nonoperatively, and treatment use varies according to tumor histology, particularly by center type. Cancer 2011. (c) 2011 American Cancer Society. C1 [Merkow, Ryan P.; Bilimoria, Karl Y.; Bentrem, David J.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Bentrem, David J.] Jesse Brown VA Med Ctr, Dept Surg, Chicago, IL USA. [Merkow, Ryan P.; McCarter, Martin D.] Univ Colorado, Dept Surg, Sch Med, Aurora, CO USA. [Bilimoria, Karl Y.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Gordon, Howard S.] Univ Illinois, Coll Med, VA Ctr Management Complex Chron Care, Jesse Brown VA Med Ctr,Dept Med, Chicago, IL USA. [Stewart, Andrew K.] Amer Coll Surg, Canc Programs, Chicago, IL USA. [Chow, Warren B.; Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Chow, Warren B.; Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Bentrem, DJ (reprint author), 676 N St Clair St,Suite 650, Chicago, IL 60611 USA. EM dbentrem@nmff.org RI Gordon, Howard/E-4420-2010 OI Gordon, Howard/0000-0002-6712-5954 FU Health Services Research Division, Department of Veterans Affairs FX D.J.B. is supported by a Career Development Award from the Health Services Research Division, Department of Veterans Affairs. NR 32 TC 12 Z9 12 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JUL 1 PY 2012 VL 118 IS 13 BP 3268 EP 3276 DI 10.1002/cncr.26608 PG 9 WC Oncology SC Oncology GA 960LM UT WOS:000305389500011 PM 22006369 ER PT J AU Ahdout, J Kotlerman, J Elashoff, D Kim, J Chiu, MW AF Ahdout, J. Kotlerman, J. Elashoff, D. Kim, J. Chiu, M. W. TI Modifiable lifestyle factors associated with metabolic syndrome in patients with psoriasis SO CLINICAL AND EXPERIMENTAL DERMATOLOGY LA English DT Article ID DISEASE; PREVALENCE; RISK; EPIDEMIOLOGY; SMOKING; OBESITY; STRESS; DIET AB Background. Psoriasis is a chronic inflammatory skin disease, which is associated with obesity and with cardiovascular morbidity and mortality. Aim. To evaluate modifiable lifestyle factors including stress level, physical activity and nutrition, which may be associated with metabolic syndrome in patients with psoriasis. Methods. In total, 65 patients with psoriasis and 52 control subjects from our university dermatology clinic were enrolled in this casecontrol pilot study. The study questionnaire included the Perceived Stress Scale (PSS), the Godin Leisure-Time Exercise Questionnaire (GLTEQ) and the Rapid Eating Assessment for patients (REAP). For subjects with psoriasis, the Psoriasis Area and Severity Index (PASI) was measured. Results. Subjects with psoriasis (mean BMI 27.72) displayed a trend towards a higher BMI compared with controls (mean BMI 25.67). Subjects with psoriasis were not found to have an increased prevalence of self-reported metabolic syndrome-associated diseases including diabetes, heart disease, high cholesterol, hypertension or stroke compared with controls (P = 0.25, P = 0.46, P = 0.96, P = 0.26, and P = 0.16, respectively). There was no significant difference in exercise or stress between patients with psoriasis and controls (P = 0.06 and P = 0.26, respectively). However, compared with controls, subjects with psoriasis (mean REAP score = 2.23) did report poorer overall nutrition as assessed by the REAP score (mean = 2.38, P < 0.01). Among subjects with psoriasis, the factors of stress, smoking and systemic therapy were associated with increased PASI (r = 0.13, r = 3.47 and r = 3.19, respectively). Conclusions. Our study suggests that poor dietary and exercise habits may be factors contributing to obesity and metabolic syndrome in patients with psoriasis. Further studies with larger numbers are needed to confirm these results. C1 [Ahdout, J.] Univ Calif Irvine, Dept Dermatol, Irvine, CA 92697 USA. [Kotlerman, J.; Elashoff, D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med Stat Core, Los Angeles, CA 90095 USA. [Kim, J.; Chiu, M. W.] Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Dept Med, Los Angeles, CA 90095 USA. [Kim, J.; Chiu, M. W.] Greater Los Angeles Vet Affairs Healthcare Syst, Dermatol Serv, Los Angeles, CA USA. RP Ahdout, J (reprint author), Univ Calif Irvine, Dept Dermatol, C340 Med Sci 1, Irvine, CA 92697 USA. EM jahdout@gmail.com FU UCLA Department of Medicine, Division of Dermatology; Dermatologic Research Foundation of California FX This study was supported in part by the UCLA Department of Medicine, Division of Dermatology and the Dermatologic Research Foundation of California. The sponsors had no role in the design and conduct of the study, the collection, analysis and interpretation of the data, or in the preparation, review or approval of the manuscript. NR 25 TC 9 Z9 9 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0307-6938 J9 CLIN EXP DERMATOL JI Clin. Exp. Dermatol. PD JUL PY 2012 VL 37 IS 5 BP 477 EP 483 DI 10.1111/j.1365-2230.2012.04360.x PG 7 WC Dermatology SC Dermatology GA 961ZX UT WOS:000305509800003 PM 22712856 ER PT J AU Riegel, B Ratcliffe, SJ Weintraub, WS Sayers, SL Goldberg, LR Potashnik, S Weaver, TE Pressler, SJ AF Riegel, Barbara Ratcliffe, Sarah J. Weintraub, William S. Sayers, Steven L. Goldberg, Lee R. Potashnik, Sheryl Weaver, Terri E. Pressler, Susan J. TI Double jeopardy: the influence of excessive daytime sleepiness and impaired cognition on health-related quality of life in adults with heart failure SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Heart failure; Quality of life; Sleep; Cognition ID SYMPTOM BURDEN; APNEA; VALIDATION; QUESTIONNAIRE; DEPRESSION; INSOMNIA; PROGRAM; SYSTEM; IMPACT; CARE AB To determine how excessive daytime sleepiness (EDS) and impaired cognition contribute to health-related quality of life (HRQL) in heart failure (HF). Adults with chronic HF were enrolled into a prospective cohort study. Data were obtained from 280 subjects enrolled from three sites in the northeastern USA; 242 completed the 6-month study. At baseline, cohorts with and without EDS were identified using the Epworth Sleepiness Scale. Each EDS group was further subdivided into those with and without impaired cognition using a battery of five neuropsychological tests. Two disease-specific measures, the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Functional Outcomes of Sleep Questionnaire (FOSQ), were used to measure HRQL. General linear modelling of square-transformed variables was used to test the hypothesis that cohort membership was a significant predictor of HRQL. At 6 months the remaining sample was 62.5 [standard deviation (SD) 12] years old, mostly male (63), white (65), and functionally compromised [72 New York Heart Association (NYHA) class III/IV]. The cohort with both EDS and impaired cognition had the lowest KCCQ overall summary score (60.5 22.5) compared with the cohort without EDS or impaired cognition (74.6 17.4, P 0.001). A similar effect was seen on the FOSQ (16.0 2.8 vs. 18.5 2.2, P 0.001). Impaired cognition alone did not explain poor HRQL, but the addition of EDS poses a significant risk for poor HRQL. Interventions designed to influence EDS may improve HRQL in this population. C1 [Riegel, Barbara; Potashnik, Sheryl] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Ratcliffe, Sarah J.; Sayers, Steven L.; Goldberg, Lee R.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Weintraub, William S.] Christiana Care Hlth Syst, Newark, DE USA. [Sayers, Steven L.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Weaver, Terri E.] Univ Illinois, Coll Nursing, Chicago, IL USA. [Pressler, Susan J.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. RP Riegel, B (reprint author), Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. EM briegel@nursing.upenn.edu OI Goldberg, Lee/0000-0002-7906-9638; Ratcliffe, Sarah/0000-0002-6644-8284 FU National Heart, Lung, and Blood Institute at the National Institutes of Health [RO1 HL084394-01A1]; Philadelphia Veterans Affairs Medical Center; VISN 4 Mental Illness Research, Education, and Clinical Center (MIREC) FX The National Heart, Lung, and Blood Institute (RO1 HL084394-01A1) at the National Institutes of Health; the Philadelphia Veterans Affairs Medical Center; VISN 4 Mental Illness Research, Education, and Clinical Center (MIREC). NR 42 TC 6 Z9 6 U1 1 U2 7 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 JUL PY 2012 VL 14 IS 7 BP 730 EP 736 DI 10.1093/eurjhf/hfs054 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 963OT UT WOS:000305632300007 PM 22510422 ER PT J AU Chirinos, JA Segers, P Gillebert, TC Gupta, AK De Buyzere, ML De Bacquer, D St John-Sutton, M Rietzschel, ER AF Chirinos, Julio A. Segers, Patrick Gillebert, Thierry C. Gupta, Amit K. De Buyzere, Marc L. De Bacquer, Dirk St John-Sutton, Martin Rietzschel, Ernst R. CA Asklepios Investigators TI Arterial Properties as Determinants of Time-Varying Myocardial Stress in Humans SO HYPERTENSION LA English DT Article DE myocardial stress; arterial load; afterload; wave reflections; sex differences ID LEFT-VENTRICULAR HYPERTROPHY; SYSTOLIC PRESSURE; WAVE REFLECTION; HEART-FAILURE; IMPEDANCE; VOLUME AB Myocardial and arterial load are time-varying phenomena. Despite their importance in myocardial function, the arterial properties that determine time-resolved myocardial wall stress are unknown. We aimed to assess arterial properties as determinants of time-resolved myocardial stress among 1214 men and women enrolled in the Asklepios Study. Time-resolved central pressure, flow, and left ventricular geometry were measured with carotid tonometry, Doppler, and speckle-tracking echocardiography, respectively, for computation of arterial load and ejection-phase time-varying myocardial wall stress. For any given end-diastolic left ventricular geometry and cardiac output, peak myocardial stress correlated directly with systemic vascular resistance (standardized beta=1.12; P<0.0001) and aortic characteristic impedance (standardized beta=0.17; P<0.0001). The ejection-phase stress-time integral correlated with systemic vascular resistance (standardized beta=1.06; P<0.0001), lower total arterial compliance (standardized beta=-0.13; P=0.0008), and earlier return of wave reflections (standardized beta=-0.10; P<0.0001) but not with reflection magnitude, whereas end-systolic wall stress correlated with systemic vascular resistance (standardized beta=1.06; P<0.0001) and reflection magnitude (standardized beta=0.12; P<0.0001). After adjustment for age, all of the measured arterial properties, end-diastolic left ventricular geometry, and cardiac output, women demonstrated greater peak (534 versus 507 kdyne/cm(2); P<0.0001), end-systolic (335 versus 320 kdyne/cm(2); P<0.0001), and ejection-phase stress-time integral (157 versus 142 kdyne . s . cm(-2); P<0.0001). In conclusion, different arterial properties have selective effects on time-resolved ejection-phase myocardial wall stress, which are not apparent from single-time point measurements. Women demonstrate less efficient myocardial-arterial coupling, with higher wall stress development for any given left ventricular geometry, arterial properties, and flow output. These observations may relate to the differential susceptibility of women to heart failure. (Hypertension. 2012;60:64-70.). Online Data Supplement C1 [Chirinos, Julio A.; St John-Sutton, Martin] Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Segers, Patrick] Ghent Univ Hosp, Inst Biomed Technol, Ghent, Belgium. [Gillebert, Thierry C.; De Buyzere, Marc L.; Rietzschel, Ernst R.] Ghent Univ Hosp, Dept Cardiovasc Dis, Ghent, Belgium. [De Bacquer, Dirk; Rietzschel, Ernst R.] Ghent Univ Hosp, Dept Publ Hlth, Ghent, Belgium. [Gupta, Amit K.] Baylor Coll Med, Houston, TX 77030 USA. RP Chirinos, JA (reprint author), Room 8B111,5800 Woodland Ave, Philadelphia, PA 19143 USA. EM julio.chirinos@uphs.upenn.edu OI Gillebert, Thierry/0000-0002-3832-919X FU Fonds voor Wetenschappelijk Onderzoek Vlaanderen [G.0.838.10]; American Heart Association [0885031N]; National Institutes of Health FX This study was supported by Fonds voor Wetenschappelijk Onderzoek Vlaanderen grant G.0.838.10 and American Heart Association research award 0885031N.; J.A.C. has received significant (more than $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 16 TC 31 Z9 31 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 2012 VL 60 IS 1 BP 64 EP 70 DI 10.1161/HYPERTENSIONAHA.112.190710 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 962VF UT WOS:000305574200022 PM 22665121 ER PT J AU Holodniy, M Oda, G Schirmer, PL Lucero, CA Khudyakov, YE Xia, GL Lin, YL Valdiserri, R Duncan, WE Davey, VJ Cross, GM AF Holodniy, Mark Oda, Gina Schirmer, Patricia L. Lucero, Cynthia A. Khudyakov, Yury E. Xia, Guoliang Lin, Yulin Valdiserri, Ronald Duncan, William E. Davey, Victoria J. Cross, Gerald M. TI Results from a Large-Scale Epidemiologic Look-Back Investigation of Improperly Reprocessed Endoscopy Equipment SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID HEPATITIS-C VIRUS; GASTROINTESTINAL ENDOSCOPY; UNITED-STATES; DISEASE TRANSMISSION; FLEXIBLE ENDOSCOPY; INFECTION-CONTROL; BRITISH-SOCIETY; WORKING PARTY; DISINFECTION; RISK AB OBJECTIVE. To determine whether improper high-level disinfection practices during endoscopy procedures resulted in bloodborne viral infection transmission. DESIGN. Retrospective cohort study. SETTING. Four Veterans Affairs medical centers (VAMCs). PATIENTS. Veterans who underwent colonoscopy and laryngoscopy (ear, nose, and throat [ENT]) procedures from 2003 to 2009. METHODS. Patients were identified through electronic health record searches and serotested for human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV). Newly discovered case patients were linked to a potential source with known identical infection, whose procedure occurred no more than 1 day prior to the case patient's procedure. Viral genetic testing was performed for case/proximate pairs to determine relatedness. RESULTS. Of 10,737 veterans who underwent endoscopy at 4 VAMCs, 9,879 patients agreed to viral testing. Of these, 90 patients were newly diagnosed with 1 or more viral bloodborne pathogens (BBPs). There were no case/proximate pairings found for patients with either HIV or HBV; 24 HCV case/proximate pairings were found, of which 7 case patients and 8 proximate patients had sufficient viral load for further genetic testing. Only 2 of these cases, both of whom underwent laryngoscopy, and their 4 proximates agreed to further testing. None of the 4 remaining proximate patients who underwent colonoscopy agreed to further testing. Mean genetic distance between the 2 case patients and 4 proximate patients ranged from 13.5% to 19.1%. CONCLUSIONS. Our investigation revealed that exposure to improperly reprocessed ENT endoscopes did not result in viral transmission in those patients who had viral genetic analysis performed. Any potential transmission of BBPs from colonoscopy remains unknown. Infect Control Hosp Epidemiol 2012;33(7):649-656 C1 [Holodniy, Mark; Oda, Gina; Schirmer, Patricia L.; Lucero, Cynthia A.; Davey, Victoria J.] US Dept Vet Affairs, Off Publ Hlth, Washington, DC USA. [Holodniy, Mark] Stanford Univ, Dept Med, Div Infect Dis & Geog Med, Stanford, CA 94305 USA. [Khudyakov, Yury E.; Xia, Guoliang; Lin, Yulin] Ctr Dis Control & Prevent, Div Viral Hepatitis, Atlanta, GA USA. [Valdiserri, Ronald] US Dept HHS, Off HIV AIDS Policy, Washington, DC 20201 USA. [Duncan, William E.] US Dept Vet Affairs, Off Qual & Safety, Washington, DC USA. [Cross, Gerald M.] US Dept Vet Affairs, Off Patient Care Serv, Washington, DC USA. RP Holodniy, M (reprint author), Off Publ Hlth Surveillance & Res, 3801 Miranda Ave 132, Palo Alto, CA 94304 USA. EM mark.holodniy@va.gov FU Department of Veterans Affairs FX Financial support. This study was funded by intramural funds from the Department of Veterans Affairs. NR 39 TC 14 Z9 14 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JUL PY 2012 VL 33 IS 7 BP 649 EP 656 DI 10.1086/666345 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 955DW UT WOS:000304998300001 PM 22669224 ER PT J AU Kelley, AS Ettner, SL Morrison, RS Du, QL Sarkisian, CA AF Kelley, Amy S. Ettner, Susan L. Morrison, R. Sean Du, Qingling Sarkisian, Catherine A. TI Disability and Decline in Physical Function Associated with Hospital Use at End of Life SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE disability; end-of-life decisions; functional decline; Medicare; Medigap ID OLDER PERSONS PREFERENCES; LAST 6 MONTHS; TREATMENT INTENSITY; CARE; ILLNESS; OUTCOMES; ADULTS; DEATH; DETERMINANTS; MORTALITY AB Hospital use near the end of life is often undesirable to patients, represents considerable Medicare cost, and varies widely across regions. To concurrently examine regional and patient factors, including disability and functional decline, associated with end-of-life hospital use. We sampled decedents aged 65 and older (n = 2,493) from the Health and Retirement Study (2000-2006), and linked data from individual Medicare claims and the Dartmouth Atlas of Health Care. Two-part regression models estimated the relationship between total hospital days in the last 6 months and patient characteristics including physical function, while adjusting for regional resources and hospital care intensity (HCI). Median hospital days was 7 (range = 0-183). 53% of respondents had functional decline. Compared with decedents without functional decline, those with severe disability or decline had more regression-adjusted hospital days (range 3.47-9.05, depending on category). Dementia was associated with fewer days (-3.02); while chronic kidney disease (2.37), diabetes (2.40), stroke or transient ischemic attack (2.11), and congestive heart failure (1.74) were associated with more days. African Americans and Hispanics had more days (5.91 and 4.61, respectively). Those with family nearby had 1.62 fewer days and hospice enrollees had 1.88 fewer days. Additional hospital days were associated with urban residence (1.74) and residence in a region with more specialists (1.97) and higher HCI (2.27). Functional decline is significantly associated with end-of-life hospital use among older adults. To improve care and reduce costs, health care programs and policies should address specific needs of patients with functional decline and disability. C1 [Kelley, Amy S.; Morrison, R. Sean; Du, Qingling] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Ettner, Susan L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Morrison, R. Sean] James J Peters VA Med Ctr, Bronx, NY USA. [Sarkisian, Catherine A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Geriatr, Los Angeles, CA 90095 USA. [Sarkisian, Catherine A.] VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. RP Kelley, AS (reprint author), Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM amy.kelley@mssm.edu FU National Institute on Aging [K24 AG022345]; National Palliative Care Research Center; VA Greater Los Angeles Healthcare System Geriatric Research Education Clinical Center FX Dr. Kelley is a Brookdale Leadership in Aging Fellow. Dr. Morrison is the recipient of a Mid-Career Investigator Award in Patient-Oriented Research (K24 AG022345) from the National Institute on Aging and supported by the National Palliative Care Research Center. Dr. Sarkisian is supported by the VA Greater Los Angeles Healthcare System Geriatric Research Education Clinical Center. No sponsors or funders had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. NR 41 TC 11 Z9 11 U1 2 U2 15 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 JUL PY 2012 VL 27 IS 7 BP 794 EP 800 DI 10.1007/s11606-012-2013-9 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 962ET UT WOS:000305524400011 PM 22382455 ER PT J AU Kertesz, SG Khodneva, Y Richman, J Tucker, JA Safford, MM Jones, B Schumacher, J Pletcher, MJ AF Kertesz, Stefan G. Khodneva, Yulia Richman, Joshua Tucker, Jalie A. Safford, Monika M. Jones, Bobby Schumacher, Joseph Pletcher, Mark J. TI Trajectories of Drug Use and Mortality Outcomes Among Adults Followed Over 18 Years SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE opioids; stimulants; cocaine; trajectory; epidemiology; longitudinal data ID ARTERY RISK DEVELOPMENT; YOUNG-ADULTS; SCREENING-TEST; CARDIA; ALCOHOL; HEALTH; RECRUITMENT; MARIJUANA; SMOKING; DISEASE AB For adults in general population community settings, data regarding long-term course and outcomes of illicit drug use are sparse, limiting the formulation of evidence-based recommendations for drug use screening of adults in primary care. To describe trajectories of three illicit drugs (cocaine, opioids, amphetamines) among adults in community settings, and to assess their relation to all-cause mortality. Longitudinal cohort, 1987/88 - 2005/06. Community-based recruitment from four cities (Birmingham, Chicago, Oakland, Minneapolis). Healthy adults, balanced for race (black and white) and gender were assessed for drug use from 1987/88-2005/06, and for mortality through 12/31/2008 (n = 4301) Use of cocaine, amphetamines, and opioids (last 30 days) was queried in the following years: 1987/88, 1990/91, 1992/93, 1995/96, 2000/01, 2005/06. Survey-based assessment of demographics and psychosocial characteristics. Mortality over 18 years. Trajectory analysis identified four groups: Nonusers (n = 3691, 85.8%), Early Occasional Users (n = 340, 7.9%), Persistent Occasional Users (n = 160, 3.7%), and Early Frequent/Later Occasional Users (n = 110, 2.6%). Trajectories conformed to expected patterns regarding demographics, other substance use, family background and education. Adjusting for demographics, baseline health status, health behaviors (alcohol, tobacco), and psychosocial characteristics, Early Frequent/Later Occasional Users had greater all-cause mortality (Hazard Ratio, HR = 4.94, 95% CI = 1.58-15.51, p = 0.006). Study is restricted to three common drugs, and trajectory analyses represent statistical approximations rather than identifiable "types". Causal inferences are tentative. Four trajectories describe illicit drug use from young adulthood to middle age. Two trajectories, representing over one third of adult users, continued use into middle age. These persons were more likely to continue harmful risk behaviors such as smoking, and more likely to die. C1 [Kertesz, Stefan G.; Safford, Monika M.; Schumacher, Joseph] Univ Alabama Birmingham, Div Prevent Med, Sch Med, Birmingham, AL 35294 USA. [Jones, Bobby] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. [Pletcher, Mark J.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Richman, Joshua] Univ Alabama Birmingham, Sch Med, Dept Surg, Birmingham, AL 35294 USA. [Kertesz, Stefan G.; Khodneva, Yulia; Tucker, Jalie A.] Univ Alabama Birmingham, Dept Hlth Behav, Sch Publ Hlth, Birmingham, AL 35294 USA. [Kertesz, Stefan G.] Birmingham VA Med Ctr, Ctr Surg Med & Acute Care Res, Birmingham, AL USA. RP Kertesz, SG (reprint author), Univ Alabama Birmingham, Div Prevent Med, Sch Med, 1530 3rd Ave S,MT608, Birmingham, AL 35294 USA. EM skertesz@uab.edu FU [NIDA: R01-DA-025067]; [NHLBI: N01-HC-95095]; [NO1-HC-48047] FX Support: NIDA: R01-DA-025067; NHLBI: N01-HC-95095 AND NO1-HC-48047 NR 41 TC 17 Z9 17 U1 1 U2 12 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 JUL PY 2012 VL 27 IS 7 BP 808 EP 816 DI 10.1007/s11606-011-1975-3 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 962ET UT WOS:000305524400013 PM 22274889 ER PT J AU Madaras-Kelly, KJ Remington, RE Sloan, KL Fan, VS AF Madaras-Kelly, Karl J. Remington, Richard E. Sloan, Kevin L. Fan, Vincent S. TI Guideline-Based Antibiotics and Mortality in Healthcare-Associated Pneumonia SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE pneumonia; anti bacterial agents; guideline; methicillin resistant Staphylococcus aureus; Pseudomonas aeruginosa; healthcare-associated infection ID HOSPITAL-ACQUIRED PNEUMONIA; RESISTANT BACTERIA; THERAPY; OUTCOMES; INFECTION; ADMISSION; ACCURACY; UNIT AB Guidelines recommend administration of antibiotics with activity against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa for treatment of healthcare-associated pneumonia (HCAP). It is unclear if this therapy improves outcomes for patients with HCAP. To determine if administration of guideline-similar therapy (GST) was associated with a reduction in 30-day mortality for HCAP. Multi-center retrospective study. Thirteen hundred and eleven admissions for HCAP in six Veterans Affairs Medical Centers. Each admission was classified as receiving GST, anti-MRSA or anti-pseudomonal components of GST, or other non-HCAP therapy initiated within 48 hours of hospitalization. Association between 30-day mortality and GST was estimated with a logistic regression model that included GST, propensity to receive GST, probability of recovering an organism from culture resistant to antibiotics traditionally used to treat community-acquired pneumonia (CAP-resistance), and a GST by CAP-resistance probability interaction. Odds ratios and 95% confidence intervals [OR (95% CI)] of 30-day mortality for patients treated with GST and predicted probability of recovering a CAP-resistant organism, and ratio of odds ratios [ROR (95% CI)] for treatment by CAP-resistance probability interaction. Receipt of GST was associated with increased odds of 30-day mortality [OR = 2.11 (1.11, 4.04), P = 0.02)] as was the predicted probability of recovering a CAP-resistant organism [OR = 1.67 (1.26, 2.20), P < 0.001 for a 25% increase in probability]. An interaction between predicted probability of recovering a CAP-resistant organism and receipt of GST demonstrated lower mortality with GST at high probability of CAP resistance [ROR = 0.71(a parts per thousand currency sign1.00) for a 25% increase in probability, P = 0.05]. For HCAP patients with high probability of CAP-resistant organisms, GST was associated with lower mortality. Consideration of the magnitude of patient-specific risk for CAP-resistant organisms should be considered when selecting HCAP therapy. C1 [Madaras-Kelly, Karl J.] Vet Affairs Med Ctr, Clin Pharm Serv 119A, Boise, ID 83702 USA. [Remington, Richard E.] Vet Affairs Med Ctr, Res Serv, Boise, ID 83702 USA. [Fan, Vincent S.] Vet Affairs Puget Sound Hlth Care Syst, Med Serv, Seattle, WA USA. [Madaras-Kelly, Karl J.; Remington, Richard E.] Idaho State Univ, Dept Pharm Practice & Adm Sci, Coll Pharm, Meridian, ID USA. [Fan, Vincent S.] Univ Washington, Sch Med, Dept Pulm & Crit Care Med, Seattle, WA USA. RP Madaras-Kelly, KJ (reprint author), Vet Affairs Med Ctr, Clin Pharm Serv 119A, 500 W Ft St, Boise, ID 83702 USA. EM KMK@pharmacy.isu.edu FU National Institute of Allergy and Infectious Diseases [RO3AI074894-01A2]; Boise and Puget Sound Health Care System Veterans Affairs Medical Centers FX This study was supported through a grant from the National Institute of Allergy and Infectious Diseases (RO3AI074894-01A2). This work was supported in part with resources of the Boise and Puget Sound Health Care System Veterans Affairs Medical Centers. NR 26 TC 15 Z9 15 U1 0 U2 3 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 JUL PY 2012 VL 27 IS 7 BP 845 EP 852 DI 10.1007/s11606-012-2011-y PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 962ET UT WOS:000305524400018 PM 22396110 ER PT J AU Kim, JS Bashir, MM Werth, VP AF Kim, Jessica S. Bashir, Muhammad M. Werth, Victoria P. TI Gottron's Papules Exhibit Dermal Accumulation of CD44 Variant 7 (CD44v7) and Its Binding Partner Osteopontin: A Unique Molecular Signature SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; B-CELL ACTIVATION; AUTOIMMUNE-DISEASE; MONONUCLEAR-CELLS; INTERFERON-GAMMA; IMMUNE-RESPONSE; DENDRITIC CELLS; EXPRESSION; DERMATOMYOSITIS; SKIN AB The accumulated mucin in non-Gottron's dermatomyositis (DM) lesions is primarily chondroitin-4-sulfate (C4S), which is immunomodulatory in vitro. Gottron's papules are a particularly resistant manifestation of DM that often persist after other lesions have resolved with therapy. We examined non-Gottron's DM lesions and Gottron's papule skin biopsies for C4S, CD44 variant 7 (CD44v7), a chondroitin sulfate-binding isoform causally implicated in autoimmunity, and osteopontin (OPN), a CD44v7 ligand implicated in chronic inflammation. Gottron's papule dermis contained more C4S and CD44v7 than non-Gottron's lesions. Normal skin showed less CD44v7 over joints relative to Gottron's lesions. All DM dermis had increased OPN compared with healthy skin. Mechanically stretching cultured fibroblasts for 6 hours induced CD44v7 mRNA and protein, whereas IFN-gamma treatment induced OPN mRNA and protein. OPN alone did not induce CD44v7, but stretching dermal fibroblasts in the presence of OPN increased human acute monocytic leukemia cell line (THP-1) monocyte binding, which is blunted by anti-CD44v7 blocking antibody. C4S, CD44v7, and OPN are three molecules uniquely present in Gottron's papules that contribute to inflammation individually and in association with one another. We propose that stretch-induced CD44v7 over joints, in concert with dysregulated OPN levels in the skin of DM patients, increases local inflammatory cell recruitment and contributes to the pathogenesis and resistance of Gottron's papules. Journal of Investigative Dermatology (2012) 132, 1825-1832; doi:10.1038/jid.2012.54; published online 29 March 2012 C1 [Kim, Jessica S.; Bashir, Muhammad M.; Werth, Victoria P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Kim, Jessica S.] NYU, Sch Med, New York, NY USA. [Kim, Jessica S.; Bashir, Muhammad M.; Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Werth, VP (reprint author), Univ Penn, Dept Dermatol, 2 Maloney Bldg,36th & Spruce St, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU Lupus Foundation of America; Department of Veterans Affairs (Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development); National Institutes of Health [NIH K24-AR 02207] FX This material is based on the work supported by the Lupus Foundation of America and in part by a Merit Review Grant from the Department of Veterans Affairs (Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development) and by the National Institutes of Health (NIH K24-AR 02207) to VPW. The authors state no conflict of interest. NR 49 TC 6 Z9 7 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2012 VL 132 IS 7 BP 1825 EP 1832 DI 10.1038/jid.2012.54 PG 8 WC Dermatology SC Dermatology GA 961TR UT WOS:000305492900014 PM 22456539 ER PT J AU Valente, AJ Clark, RA Siddesha, JM Siebenlist, U Chandrasekar, B AF Valente, Anthony J. Clark, Robert A. Siddesha, Jalahalli M. Siebenlist, Ulrich Chandrasekar, Bysani TI CIKS (Act1 or TRAF3IP2) mediates Angiotensin-II-induced Interleukin-18 expression, and Nox2-dependent cardiomyocyte hypertrophy SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE RAAS; NADPH oxidase; Act1; TRAF3IP2; Fibrosis; Cardiac hypertrophy ID NF-KAPPA-B; INDUCED CARDIAC-HYPERTROPHY; NOX2-CONTAINING NADPH OXIDASE; HEART-FAILURE; SIGNALING PATHWAYS; GENE-EXPRESSION; PROTEIN-KINASE; IN-VIVO; ACTIVATION; REQUIREMENT AB Chronic elevation of angiotensin (Ang)-II can lead to myocardial inflammation, hypertrophy and cardiac failure. The adaptor molecule CIKS (connection to IKK and SAPK/JNK) activates the I kappa B kinase/nuclear factor (NF)-kappa B and JNK/activator protein (AP)-1 pathways in autoimmune and inflammatory diseases. Since Ang-II is a potent activator of NF-kappa B and AP-1, we investigated whether CIKS is critical in Ang-II-mediated cardiac hypertrophy. Here we report that Ang-II induced CIKS mRNA and protein expression, CIKS binding to IKK and JNK perhaps functioning as a scaffold protein, CIKS-dependent IKK/NF-kappa B and JNK/AP-1 activation, p65 and c-Jun phosphorylation and nuclear translocation, NF-kappa B- and AP-1-dependent IL-18 and MMP-9 induction, and hypertrophy of adult cardiomyocytes isolated from WT, but not CIKS-null mice. These results were recapitulated in WT-cardiomyocytes following CIKS knockdown. Infusion of Ang-II for 7 days induced cardiac hypertrophy, increased collagen content, and upregulated CIKS mRNA and protein expression in WT mice, whereas cardiac hypertrophy and collagen deposition were markedly attenuated in the CIKS-null mice, despite a similar increase in systolic blood pressure and DPI-inhibitable superoxide generation in both types of animals. Further, Ang-II-induced IKK/p65 and JNK/c-Jun phosphorylation, NF-kappa B and AP-1 activation, and IL-18 and MMP-9 expression were also markedly attenuated in CIKS-null mice. These results demonstrate that CIKS is critical in Ang-II-induced cardiomyocyte hypertrophy and fibrosis, and that CIKS is an important intermediate in Ang-II-induced redox signaling. CIKS is a potential therapeutic target in cardiac hypertrophy, fibrosis, and congestive heart failure. (c) 2012 Elsevier Ltd. All rights reserved. C1 [Siddesha, Jalahalli M.; Chandrasekar, Bysani] Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA. [Valente, Anthony J.; Clark, Robert A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Valente, Anthony J.; Clark, Robert A.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Siebenlist, Ulrich] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Chandrasekar, Bysani] SE Louisiana Vet Hlth Care Syst, Res Serv, New Orleans, LA 70161 USA. RP Chandrasekar, B (reprint author), Tulane Univ, Sch Med, Inst Heart & Vasc, 1430 Tulane Ave,SL-48, New Orleans, LA 70112 USA. EM bchandra@tulane.edu FU Veterans Affairs Office of Research and Development Biomedical Laboratory Research and Development Service Award [1IO1BX000246]; NIH/NHLBI [HL-86787] FX This work was supported by Veterans Affairs Office of Research and Development Biomedical Laboratory Research and Development Service Award 1IO1BX000246 and the NIH/NHLBI Grant HL-86787 (to BC). The contents of this report do not represent the views of the Department of Veterans Affairs or the United States Government. NR 45 TC 25 Z9 25 U1 0 U2 5 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUL PY 2012 VL 53 IS 1 BP 113 EP 124 DI 10.1016/j.yjmcc.2012.04.009 PG 12 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 963AI UT WOS:000305592100014 PM 22575763 ER PT J AU Wills, LP Trager, RE Beeson, GC Lindsey, CC Peterson, YK Beeson, CC Schnellmann, RG AF Wills, Lauren P. Trager, Richard E. Beeson, Gyda C. Lindsey, Christopher C. Peterson, Yuri K. Beeson, Craig C. Schnellmann, Rick G. TI The beta(2)-Adrenoceptor Agonist Formoterol Stimulates Mitochondrial Biogenesis SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PGC-1-ALPHA MESSENGER-RNA; PROXIMAL TUBULE CELLS; HUMAN SKELETAL-MUSCLE; REUPTAKE INHIBITORS; PROMOTES RECOVERY; GENE-EXPRESSION; RECEPTOR; METABOLISM; EXERCISE; CULTURE AB Mitochondrial dysfunction is a common mediator of disease and organ injury. Although recent studies show that inducing mitochondrial biogenesis (MB) stimulates cell repair and regeneration, only a limited number of chemicals are known to induce MB. To examine the impact of the beta-adrenoceptor (beta-AR) signaling pathway on MB, primary renal proximal tubule cells (RPTC) and adult feline cardiomyocytes were exposed for 24 h to multiple beta-AR agonists: isoproterenol (nonselective beta-AR agonist), (+/-)-(R*,R*)-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl] amino]propyl]phenoxy] acetic acid sodium hydrate (BRL 37344) (selective beta(3)-AR agonist), and formoterol (selective beta(2)-AR agonist). The Seahorse Biosciences (North Billerica, MA) extracellular flux analyzer was used to quantify carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP)-uncoupled oxygen consumption rate (OCR), a marker of maximal electron transport chain activity. Isoproterenol and BRL 37244 did not alter mitochondrial respiration at any of the concentrations examined. Formoterol exposure resulted in increases in both FCCP-uncoupled OCR and mitochondrial DNA (mtDNA) copy number. The effect of formoterol on OCR in RPTC was inhibited by the beta-AR antagonist propranolol and the beta(2)-AR inverse agonist 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol hydrochloride (ICI-118,551). Mice exposed to formoterol for 24 or 72 h exhibited increases in kidney and heart mtDNA copy number, peroxisome proliferator-activated receptor gamma coactivator 1 alpha, and multiple genes involved in the mitochondrial electron transport chain (F0 subunit 6 of transmembrane F-type ATP synthase, NADH dehydrogenase subunit 1, NADH dehydrogenase subunit 6, and NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8). Cheminformatic modeling, virtual chemical library screening, and experimental validation identified nisoxetine from the Sigma Library of Pharmacologically Active Compounds and two compounds from the ChemBridge DIVERSet that increased mitochondrial respiratory capacity. These data provide compelling evidence for the use and development of beta(2)-AR ligands for therapeutic MB. C1 [Wills, Lauren P.; Trager, Richard E.; Beeson, Gyda C.; Lindsey, Christopher C.; Peterson, Yuri K.; Beeson, Craig C.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Ctr Cell Death Injury & Regenerat, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Ctr Cell Death Injury & Regenerat, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM schnell@musc.edu FU National Institutes of Health National Cancer Institute [T32 CA119945-04]; National Institutes of Health National Institute of Environmental Health Sciences [F32 ES020103-01, ES012878]; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [DK062028, DK071997]; National Institutes of Health National Institute of General Medical Sciences [GM084147]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs; National Institutes of Health National Center for Research Resources [C06 RR-015455] FX L.P.W. is funded by the National Institutes of Health National Cancer Institute [Grant T32 CA119945-04] and the National Institutes of Health National Institute of Environmental Health Sciences [Grant F32 ES020103-01]. R.G.S. is funded by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grants DK062028, DK071997], the National Institutes of Health National Institute of Environmental Health Sciences [Grant ES012878], the National Institutes of Health National Institute of General Medical Sciences [Grant GM084147], and the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs. Animal facilities were funded by the National Institutes of Health National Center for Research Resources [Grant C06 RR-015455]. NR 42 TC 27 Z9 27 U1 0 U2 8 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUL PY 2012 VL 342 IS 1 BP 106 EP 118 DI 10.1124/jpet.112.191528 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 960NO UT WOS:000305395400012 PM 22490378 ER PT J AU Ellingson, LD Colbert, LH Cook, DB AF Ellingson, Laura D. Colbert, Lisa H. Cook, Dane B. TI Physical Activity Is Related to Pain Sensitivity in Healthy Women SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE ACCELEROMETER; VIGOROUS; PAIN RATINGS; PHYSICAL ACTIVITY RECOMMENDATIONS ID UNITED-STATES; SEDENTARY BEHAVIOR; EXERCISE; ACCELEROMETER; FIBROMYALGIA; NEUROANATOMY; CALIBRATION; RESPONSES; SAMPLE; ADULTS AB ELLINGSON, L. D., L. H. COLBERT, and D. B. COOK. Physical Activity Is Related to Pain Sensitivity in Healthy Women. Med. Sci. Sports Exerc., Vol. 44, No. 7, pp. 1401-1406, 2012. There are many benefits associated with meeting current physical activity recommendations. At present, it is unknown whether a reduced sensitivity to pain is included among these benefits. Purpose: The study's purpose was to assess the relationship between pain sensitivity and physical activity and sedentary behaviors in a sample of healthy women. Methods: Self-reported and accelerometer measures of physical activity and sedentary behavior were collected and compared with pain intensity and unpleasantness ratings to noxious thermal stimuli in a sample of 21 healthy women (age = 30.0 +/- 5.8 yr). On the basis of accelerometer data, participants were classified into two groups: meets recommendations (n = 12) and insufficiently active (n = 9). Independent-samples t-tests were conducted to compare pain ratings and physical activity behaviors between groups, and correlation coefficients (Spearman rho) were calculated between average minutes per day spent in moderate, vigorous, and sedentary behaviors, and average intensity and unpleasantness ratings. Results: Participants meeting physical activity recommendations had significantly lower unpleasantness ratings than their insufficiently active peers. Correlational analyses demonstrated a significant relationship between minutes spent in vigorous physical activity and both pain intensity and pain unpleasantness ratings. Relationships were not significant for moderate activity or sedentary behavior. Conclusions: These results provide preliminary evidence that meeting current physical activity recommendations may be beneficial for pain in women. Moreover, participation in vigorous activity seems to account for the decreased pain sensitivity. In our sample, sedentary behavior did not seem to have a deleterious effect on pain. Results from this study have many potential applications including aiding our understanding of why exercise functions as a treatment for those with chronic pain conditions and providing a rationale for including physical activity assessment in pain research. C1 [Cook, Dane B.] Univ Wisconsin Madison, Sch Educ, Dept Kinesiol, Unit Gymnasium Natatorium 2, Madison, WI 53706 USA. [Cook, Dane B.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Cook, DB (reprint author), Univ Wisconsin Madison, Sch Educ, Dept Kinesiol, Unit Gymnasium Natatorium 2, 2000 Observ Dr, Madison, WI 53706 USA. EM dcook@education.wisc.edu NR 32 TC 29 Z9 29 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JUL PY 2012 VL 44 IS 7 BP 1401 EP 1406 DI 10.1249/MSS.0b013e318248f648 PG 6 WC Sport Sciences SC Sport Sciences GA 961NX UT WOS:000305473200027 PM 22217571 ER PT J AU Zhao, J Wei, JX Mialki, RK Mallampalli, DF Chen, BB Coon, T Zou, CB Mallampalli, RK Zhao, YT AF Zhao, Jing Wei, Jianxin Mialki, Rachel K. Mallampalli, Daniel F. Chen, Bill B. Coon, Tiffany Zou, Chunbin Mallampalli, Rama K. Zhao, Yutong TI F-box protein FBXL19-mediated ubiquitination and degradation of the receptor for IL-33 limits pulmonary inflammation SO NATURE IMMUNOLOGY LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; AIRWAY INFLAMMATION; INDUCED ARTHRITIS; CELLS; INTERLEUKIN-33; EXPRESSION; ACTIVATION; CORTACTIN; GENE; INHIBITION AB The ST2L receptor for interleukin 33 (IL-33) mediates pulmonary inflammation and immune system-related disorders, such as asthma and rheumatoid arthritis. At present, very little is known about the molecular regulation of ST2L expression. Here we found that FBXL19, an 'orphan' member of the Skp1-Cullin-F-box family of E3 ubiquitin ligases, selectively bound to ST2L to mediate its polyubiquitination and elimination in the proteasome. Degradation of ST2L involved phosphorylation of ST2L at Ser442 catalyzed by the kinase GSK3 beta. Overexpression of FBXL19 abrogated the proapoptotic and inflammatory effects of IL-33 and lessened the severity of lung injury in mouse models of pneumonia. Our results suggest that modulation of the IL-33-ST2L axis by ubiquitin ligases might serve as a unique strategy for lessening pulmonary inflammation. C1 [Zhao, Jing; Wei, Jianxin; Mialki, Rachel K.; Mallampalli, Daniel F.; Chen, Bill B.; Coon, Tiffany; Zou, Chunbin; Mallampalli, Rama K.; Zhao, Yutong] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA. [Zhao, Jing; Wei, Jianxin; Mialki, Rachel K.; Mallampalli, Daniel F.; Chen, Bill B.; Coon, Tiffany; Zou, Chunbin; Mallampalli, Rama K.; Zhao, Yutong] Univ Pittsburgh, Sch Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA USA. [Mallampalli, Rama K.] Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA USA. RP Zhao, YT (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA. EM zhaoy3@upmc.edu RI Wei, Jianxin/P-5431-2016 FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; US Department of Veterans Affairs; US National Institutes of Health [R01 HL01916, R01 HL096376, R01 HL097376, R01 HL098174]; American Heart Association [12SDG9050005] FX We thank L. Wallace for technical assistance. This study is based on work supported in part by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. Supported by the US Department of Veterans Affairs (Merit Review Award), the US National Institutes of Health (R01 HL01916 to Y.Z. and R01 HL096376, R01 HL097376 and R01 HL098174 to R. K. M.) and the American Heart Association (12SDG9050005 to J.Z.). The contents presented do not represent the views of the Department of Veterans Affairs or the United States Government. NR 44 TC 45 Z9 50 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JUL PY 2012 VL 13 IS 7 BP 651 EP + DI 10.1038/ni.2341 PG 9 WC Immunology SC Immunology GA 961QZ UT WOS:000305483800010 PM 22660580 ER PT J AU Mackey, K Parchman, ML Leykum, LK Lanham, HJ Noel, PH Zeber, JE AF Mackey, Katherine Parchman, Michael L. Leykum, Luci K. Lanham, Holly J. Noel, Polly H. Zeber, John E. TI Impact of the Chronic Care Model on medication adherence when patients perceive cost as a barrier SO PRIMARY CARE DIABETES LA English DT Article DE Diabetes; Medication adherence; Chronic care delivery; Out-of-pocket cost ID CHRONIC ILLNESS CARE; CONCEPTUALLY BASED APPROACH; SELF-MANAGEMENT; BIPOLAR DISORDER; RANDOMIZED-TRIAL; NONADHERENCE; PRESCRIPTIONS; VALIDATION; PRESSURES; OUTCOMES AB Aims: Cost burdens represent a significant barrier to medication adherence among chronically ill patients, yet financial pressures may be mitigated by clinical or organizational factors, such as treatment aligned with the Chronic Care Model (CCM). This study examines how perceptions of chronic illness care attenuate the relationship between adherence and cost burden. Methods: Surveys were administered to patients at 40 small community-based primary care practices. Medication adherence was assessed using the 4-item Morisky scale, while five cost-related items documented recent pharmacy restrictions. CCM experiences were assessed via the 20-item Patient Assessment of Chronic Illness Care (PACIC). Nested random effects models determined if chronic care perceptions modified the association between medication adherence and cost-related burden. Results: Of 1823 respondents reporting diabetes and other chronic diseases, one-quarter endorsed intrapersonal adherence barriers, while 23% restricted medication due of cost. Controlling for age and health status, the relationship between medication cost and CCM with adherence was significant; including PACIC scores attenuated cost-related problems patients with adequate or problematic adherence behavior. Conclusions: Patients experiencing treatment more consistent with the CCM reported better adherence and lower cost-related burden. Fostering highly activated patients and shared clinical decision making may help alleviate medication cost pressures and improve adherence. Published by Elsevier Ltd on behalf of Primary Care Diabetes Europe. C1 [Zeber, John E.] Scott & White Healthcare, Ctr Appl Hlth Res, Temple, TX 76502 USA. [Mackey, Katherine; Parchman, Michael L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Parchman, Michael L.; Leykum, Luci K.; Lanham, Holly J.; Noel, Polly H.] S Texas Vet Hlth Care Syst VERDICT HSR&D, Dept Vet Affairs, San Antonio, TX USA. [Leykum, Luci K.; Lanham, Holly J.; Noel, Polly H.] Univ Texas Hlth Sci Ctr San Antonio, Dept Internal Med, San Antonio, TX 78229 USA. [Zeber, John E.] Cent Texas Vet Hlth Care Syst, Temple, TX USA. RP Zeber, JE (reprint author), Scott & White Healthcare, Ctr Appl Hlth Res, 2102 Birdcreek DriveTemple, Temple, TX 76502 USA. EM zeber@uthscsa.edu OI Parchman, Michael/0000-0001-7129-2889 FU National Institute of Diabetes and Digestive and Kidney Diseases [NIH/NIDDK R18DK075692] FX The authors would like to thank Nedal Arar, Raymond Palmer, and Laurel Copeland for additional suggestions and contributions to this manuscript. This project was supported by funding provided through award number NIH/NIDDK R18DK075692 from the National Institute of Diabetes and Digestive and Kidney Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Diabetes and Digestive and Kidney Diseases or the National Institutes of Health. NR 30 TC 9 Z9 11 U1 0 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1751-9918 EI 1878-0210 J9 PRIM CARE DIABETES JI Prim. Care Diabetes PD JUL PY 2012 VL 6 IS 2 BP 137 EP 142 DI 10.1016/j.pcd.2011.12.004 PG 6 WC Endocrinology & Metabolism; Primary Health Care SC Endocrinology & Metabolism; General & Internal Medicine GA 960HJ UT WOS:000305378300007 PM 22264426 ER PT J AU Shih, YYI Muir, ER Li, G De La Garza, BH Duong, TQ AF Shih, Yen-Yu I. Muir, Eric R. Li, Guang De La Garza, Bryan H. Duong, Timothy Q. TI High-Resolution 3D MR Microangiography of the Rat Ocular Circulation SO RADIOLOGY LA English DT Article ID RETINAL BLOOD-FLOW; SCANNING LASER OPHTHALMOSCOPY; FUNCTIONAL MRI; CARBON-DIOXIDE; OXYGEN; HYPEROXIA AB Purpose: To develop high-spatial-resolution magnetic resonance (MR) microangiography techniques to image the rat ocular circulation. Materials and Methods: Animal experiments were performed with institutional Animal Care Committee approval. MR microangiography (resolution, 84 x 84 x 84 mu m or 42 x 42 x 84 mu m) of the rat eye (eight rats) was performed by using a custom-made small circular surface coil with an 11.7-T MR unit before and after monocrystalline iron oxide nanoparticle (MION) injection. MR microangiography measurements were made during air, oxygen, and carbogen inhalation. From three-dimensional MR microangiography, the retina was virtually flattened to enable en face views of various retinal depths, including the retinal and choroidal vascular layers. Signal intensity changes within the retinal or choroidal arteries and veins associated with gas challenges were analyzed. Statistical analysis was performed by using paired t tests, with P < .05 considered to indicate a significant difference. Bonferroni correction was used to adjust for multiple comparisons. Results: The central retinal artery, long posterior ciliary arteries, and choroidal vasculature could be distinguished on MR microangiograms of the eye. With MR microangiography, retinal arteries and veins could be distinguished on the basis of blood oxygen level-dependent contrast. Carbogen inhalation-enhanced MR microangiography signal intensity in both the retina (P = .001) and choroid (P = .027) compared with oxygen inhalation. Carbogen inhalation showed significantly higher signal intensity changes in the retinal arteries (P = .001, compared with oxygen inhalation), but not in the veins (P = .549). With MION administration, MR microangiography depicted retinal arterial vasoconstriction when the animals were breathing oxygen (P = .02, compared with animals breathing air). Conclusion: MR microangiography of the eye allows depth-resolved imaging of small angiographic details of the ocular circulation. This approach may prove useful in studying microvascular pathologic findings and neurovascular dysfunction in the eye and retina. (C) RSNA, 2012 C1 [Shih, Yen-Yu I.] Univ N Carolina, Dept Neurol, Biomed Res Imaging Ctr, Chapel Hill, NC 27599 USA. [Shih, Yen-Yu I.; Muir, Eric R.; Li, Guang; De La Garza, Bryan H.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Shih, YYI (reprint author), Univ N Carolina, Dept Neurol, Biomed Res Imaging Ctr, 130 Mason Farm Rd,Bioinformat Bldg,CB 7513, Chapel Hill, NC 27599 USA. EM shihy@unc.edu RI Duong, Timothy/B-8525-2008; Li, Guang/C-9539-2011; Muir, Eric/H-8830-2013 OI Li, Guang/0000-0002-7648-0464; Shih, Yen-Yu Ian/0000-0001-6529-911X FU National Institutes of Health [5T32HL007446-29]; American Heart Association [10P0ST4290091]; Clinical Translational Science Award [UL1RR025767]; San Antonio Area Foundation; MERIT Award from the Department of Veterans Affairs and San Antonio Life Science Institute; National Eye Institute [R01 EY014211, EY018855]; National Institute of Neurological Disorders and Stroke [R01-NS45879] FX Y.Y.I.S. No potential conflicts of interest to disclose. E. R. M. Financial activities related to the present article: salary during some of the work has been partially paid by a stipend from the National Institutes of Health training grant 5T32HL007446-29. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. G. L. No potential conflicts of interest to disclose. B. H. D. L. G. No potential conflicts of interest to disclose. T. Q. D. No potential conflicts of interest to disclose.; From the Research Imaging Institute (Y.Y.I.S., E. R. M., G. L., B. H. D. L. G., T. Q. D.) and Departments of Ophthalmology, Radiology, and Physiology (T. Q. D.), University of Texas Health Science Center at San Antonio, San Antonio, Tex; and South Texas Veterans Health Care System, San Antonio, Tex (T. Q. D.). Received September 30, 2011; revision requested November 9; final revision received December 5; accepted December 29; final version accepted January 13, 2012. Supported in part by the American Heart Association (10P0ST4290091) and the Clinical Translational Science Award (parent grant UL1RR025767). Y.Y.I.S. supported in part by the San Antonio Area Foundation. E. R. M. supported in part by National Institutes of Health training grant T32HL007446-29. T. Q. D. supported in part by the MERIT Award from the Department of Veterans Affairs and San Antonio Life Science Institute.; This research was supported by the National Eye Institute (grants R01 EY014211, EY018855), the National Institute of Neurological Disorders and Stroke (grant R01-NS45879), and the National Institutes of Health (grant T32HL007446-29). NR 21 TC 14 Z9 14 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2012 VL 264 IS 1 BP 234 EP 241 DI 10.1148/radiol.12112033 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 963NA UT WOS:000305626500028 PM 22523323 ER PT J AU Ko, CY Merkow, RP AF Ko, Clifford Y. Merkow, Ryan P. TI Outcomes Research in Surgical Oncology Preface SO SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90095 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Ko, Clifford Y.; Merkow, Ryan P.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Merkow, Ryan P.] Northwestern Univ, Feinberg Sch Med, Dept Surg & Surg Outcomes, Chicago, IL 60611 USA. [Merkow, Ryan P.] Northwestern Univ, Feinberg Sch Med, Qual Improvement Ctr, Chicago, IL 60611 USA. [Merkow, Ryan P.] Univ Colorado, Sch Med, Dept Surg, Aurora, CO USA. RP Ko, CY (reprint author), Univ Calif Los Angeles, Dept Surg, 10833 LeConte Ave,72-215 CHS, Los Angeles, CA 90095 USA. EM CKo@mednet.ucla.edu; Ryan.Merkow@ucdenver.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1055-3207 J9 SURG ONCOL CLIN N AM JI Surg. Oncol. Clin. N. Am. PD JUL PY 2012 VL 21 IS 3 BP XV EP XVI DI 10.1016/j.soc.2012.04.001 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 959YS UT WOS:000305354700002 PM 22583999 ER PT J AU Rochefort, MM Tomlinson, JS AF Rochefort, Matthew M. Tomlinson, James S. TI Unexpected Readmissions After Major Cancer Surgery An Evaluation of Readmissions as a Quality-of-Care Indicator SO SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Surgery; Readmission; Rehospitalization; Oncology; Quality care ID VALIDATION; MORTALITY AB Readmissions following major oncologic operation are common affecting patient treatment, outcome, and hospital resources. The Center for Medicare and Medicaid Services mandates reporting of certain disease-specific readmissions and Congress is considering using individual hospital readmission rates as a performance measure. Studies using administrative data demonstrate that readmission rates following major cancer surgery are high. Administrative data cannot determine causes. Single-institution studies demonstrate length of hospital stay and comorbidities as risk factors. Discharge processes and outpatient healthcare utilization can be improved. Until studies on readmission rate are conducted, using readmission rates as a measure of quality should be pursued cautiously. C1 [Rochefort, Matthew M.; Tomlinson, James S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Tomlinson, James S.] Greater Los Angeles VA Med Ctr, Los Angeles, CA 90073 USA. RP Tomlinson, JS (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 Le Conte Ave,Room 54-140 CHS,Box 9511782, Los Angeles, CA 90095 USA. EM jtomlinson@mednet.ucla.edu NR 16 TC 12 Z9 12 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1055-3207 J9 SURG ONCOL CLIN N AM JI Surg. Oncol. Clin. N. Am. PD JUL PY 2012 VL 21 IS 3 BP 397 EP + DI 10.1016/j.soc.2012.03.004 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA 959YS UT WOS:000305354700006 PM 22583989 ER PT J AU Lawson, EH Gibbons, MM Ko, CY AF Lawson, Elise H. Gibbons, Melinda Maggard Ko, Clifford Y. TI Appropriate Use of Surgical Procedures for Patients with Cancer SO SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Cancer; Appropriateness method; Surgery; Overuse; Underuse ID CAROTID-ENDARTERECTOMY; CORONARY REVASCULARIZATION; MEDICAL PROCEDURES; PHYSICIAN RATINGS; PANEL; CARE; GUIDELINES; HYSTERECTOMY; NECESSITY; UNDERUSE AB With increasing focus on improving quality and promoting patient-centered care, ensuring that patients receive appropriate surgical procedures is paramount. The appropriateness method was developed to determine which patients should and should not undergo surgical intervention versus medical therapy. This method combines the best available evidence in the literature with expert opinion to produce explicit guidance for clinicians on the relative risks and benefits of a procedure for specific clinical indications. A coordinated effort to produce appropriateness criteria for surgical oncology could improve the quality of surgical care for patients with cancer if these criteria are integrated into routine clinical practice. C1 [Lawson, Elise H.] Univ Calif Los Angeles, Med Ctr, Dept Surg, Los Angeles, CA 90095 USA. [Lawson, Elise H.; Gibbons, Melinda Maggard; Ko, Clifford Y.] VA Greater Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. RP Lawson, EH (reprint author), Univ Calif Los Angeles, Med Ctr, Dept Surg, CHS 72-215,10833 LeConte Ave, Los Angeles, CA 90095 USA. EM elawson@mednet.ucla.edu NR 25 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1055-3207 J9 SURG ONCOL CLIN N AM JI Surg. Oncol. Clin. N. Am. PD JUL PY 2012 VL 21 IS 3 BP 479 EP + DI 10.1016/j.soc.2012.03.008 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 959YS UT WOS:000305354700012 PM 22583995 ER PT J AU Batki, SL Lasher, BA Herbst, E Prathikanti, S Metzler, T Tarasovsky, G Waldrop, A Neylan, TC Petrakis, I Coetzee, J AF Batki, Steven L. Lasher, Brooke A. Herbst, Ellen Prathikanti, Sridhar Metzler, Thomas Tarasovsky, Gary Waldrop, Angela Neylan, Thomas C. Petrakis, Ismene Coetzee, John TI Topiramate Treatment of Alcohol Dependence in Veterans with PTSD: Baseline Alcohol Use and PTSD Severity SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 UCSF, Dept Psychiat, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JUL-AUG PY 2012 VL 21 IS 4 MA 3 BP 382 EP 382 PG 1 WC Substance Abuse SC Substance Abuse GA 956XH UT WOS:000305122400015 ER PT J AU Meszaros, ZS Abdul-Malak, Y Dimmock, JA Wang, DL Batki, SL AF Meszaros, Zsuzsa Szombathyne Abdul-Malak, Ynesse Dimmock, Jacqueline A. Wang, Dongliang Batki, Steven L. TI Varenicline Treatment of Alcohol and Nicotine Dependence in Schizophrenia: Problems Encountered in a Pilot Trial SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Batki, Steven L.] SUNY Upstate Med Univ, Dept Psychiat, San Francisco VA Med Ctr, Syracuse, NY 13210 USA. [Wang, Dongliang] SUNY Upstate Med Univ, Dept Publ Hlth & Prevent Med, Syracuse, NY 13210 USA. [Batki, Steven L.] UCSF, Dept Psychiat, San Francisco, CA 94143 USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JUL-AUG PY 2012 VL 21 IS 4 MA 36 BP 393 EP 394 PG 2 WC Substance Abuse SC Substance Abuse GA 956XH UT WOS:000305122400044 ER PT J AU Lu, ZY Li, YC Jin, JF Zhang, XM Lopes-Virella, MF Huang, Y AF Lu, Zhongyang Li, Yanchun Jin, Junfei Zhang, Xiaoming Lopes-Virella, Maria F. Huang, Yan TI Toll-Like Receptor 4 Activation in Microvascular Endothelial Cells Triggers a Robust Inflammatory Response and Cross Talk With Mononuclear Cells via Interleukin-6 SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE endothelial cells; gene expression; inflammation; interleukin-6; toll-like receptor ID HUMAN ATHEROSCLEROSIS; CORONARY ATHEROSCLEROSIS; CHLAMYDIA-PNEUMONIAE; PLAQUE VULNERABILITY; ADHESION MOLECULE-1; EXPRESSION; NEOVASCULARIZATION; ANGIOGENESIS; PATHOGENESIS; MACROPHAGES AB Objective-It is known that toll-like receptor 4 (TLR4) plays an important role in atherosclerosis. Because both microvascular (MIC) and macrovascular (MAC) endothelial cells (ECs) are present in atherosclerotic lesions, the present study compared TLR4-triggered inflammatory response and cross talk with mononuclear cells between MIC and MAC ECs. Methods and Results-ELISA, real-time polymerase chain reaction, and gene expression profiling showed that TLR4 activation by lipopolysaccharide stimulated a much higher expression of inflammatory genes including cytokines, chemokines, growth factors, and adhesion molecules in MIC ECs than MAC ECs. Furthermore, coculture studies showed that TLR4 activation in MIC ECs, but not MAC ECs, induced a cross talk with U937 mononuclear cells through MIC EC-released interleukin-6 to upregulate matrix metalloproteinase-1 expression in U937 cells. To explore molecular mechanisms underlying the different responses to TLR4 activation between MIC and MAC ECs, we showed that MIC ECs had a higher expression of TLR4 and CD14 and a higher TLR4-mediated nuclear factor-kappaB activity than MAC ECs. Conclusion-The present study showed that TLR4 activation triggers a more robust inflammatory response in MIC ECs than MAC ECs. Given the importance of inflammatory cytokines and matrix metalloproteinases in plaque rupture, MIC ECs may play a key role in plaque destabilization through a TLR4-dependent mechanism. (Arterioscler Thromb Vasc Biol. 2012;32:1696-1706) C1 [Lopes-Virella, Maria F.; Huang, Yan] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA. [Lu, Zhongyang; Li, Yanchun; Jin, Junfei; Zhang, Xiaoming; Lopes-Virella, Maria F.; Huang, Yan] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29403 USA. RP Huang, Y (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, 114 Doughty St, Charleston, SC 29403 USA. EM huangyan@musc.edu FU Department of Veterans Affairs, National Institutes of Health [DE016353, DK081352] FX This work was supported by the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs, National Institutes of Health grant DE016353 (to Y. Huang) and DK081352 (to M.F. Lopes-Virella). NR 50 TC 19 Z9 21 U1 0 U2 1 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 JUL PY 2012 VL 32 IS 7 BP 1696 EP 1706 DI 10.1161/ATVBAHA.112.251181 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 959SK UT WOS:000305333100021 PM 22596222 ER PT J AU Postupna, N Rose, SE Bird, TD Gonzalez-Cuyar, LF Sonnen, JA Larson, EB Keene, CD Montine, TJ AF Postupna, Nadia Rose, Shannon E. Bird, Thomas D. Gonzalez-Cuyar, Luis F. Sonnen, Joshua A. Larson, Eric B. Keene, C. Dirk Montine, Thomas J. TI Novel Antibody Capture Assay for Paraffin-Embedded Tissue Detects Wide-Ranging Amyloid Beta and Paired Helical Filament-Tau Accumulation in Cognitively Normal Older Adults SO BRAIN PATHOLOGY LA English DT Article DE aging; Alzheimer's disease; ELISA; immunohistochemistry ID ALZHEIMERS-DISEASE; SYNAPTIC PROTEINS; NATIONAL-INSTITUTE; DEMENTIA; PATHOLOGY; IMPAIRMENT; DIAGNOSIS; RECOMMENDATIONS; NEUROPATHOLOGY; QUANTITATION AB Quantifying antigens in formalin-fixed tissue is challenging and limits investigation in population-based studies of brain aging. To address this major limitation, we have developed a new technique that we call Histelide: immunohistochemistry (HIST-) and enzyme-linked immunosorbent assay (ELISA) (-EL-) performed on a glass slide (-IDE). We validated Histelide in sections of prefrontal cortex from 20 selected cases: 12 subjects with clinically and neuropathologically diagnosed Alzheimer's disease (AD), either autosomal dominant or late-onset forms, and 8 clinical and neuropathologic controls. AD cases had significantly increased amyloid beta (A beta) peptide and paired helical filament (PHF-) tau per area of neocortex that was proteinase K-sensitive, and significantly decreased amount of synaptophysin. We next investigated prefrontal cortex from 81 consecutive cases of high-cognitive performers from the Adult Changes in Thought (ACT) study, a population-based study of brain aging and incident dementia. As expected, latent AD was common in this group; however, our results quantified widely individually varying levels of A beta peptides and PHF-tau among these high-cognitive performers. This novel approach obtains quantitative data from population-based studies, and our initial studies with high-cognitive performers provide important quantitative insights into latent AD that should help guide expectations from neuroimaging and prevention studies. C1 [Postupna, Nadia; Rose, Shannon E.; Gonzalez-Cuyar, Luis F.; Sonnen, Joshua A.; Keene, C. Dirk; Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98104 USA. [Bird, Thomas D.] Univ Washington, Dept Med, Seattle, WA 98104 USA. [Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA 98104 USA. [Bird, Thomas D.] VA Puget Sound Hlth Care Syst, Geriatr Res Clin & Educ Ctr, Seattle, WA USA. [Larson, Eric B.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. RP Montine, TJ (reprint author), Univ Washington, Dept Pathol, 300 9th Ave,Roomm 703, Seattle, WA 98104 USA. EM tmontine@uw.edu RI Sonnen, 37382016/H-3738-2016; Keene, Christopher/N-1806-2015 OI Sonnen, 37382016/0000-0001-9267-8705; FU NIH [AG05136, AG23801, AG006781, NS62684, T32AG000258, T32ES007032]; Nancy and Buster Alvord Endowment FX This work was supported by grants from the NIH (AG05136, AG23801, AG006781, NS62684, T32AG000258, T32ES007032), and the Nancy and Buster Alvord Endowment. We thank Dr. Kathy Montine for editorial assistance. NR 41 TC 7 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JUL PY 2012 VL 22 IS 4 BP 472 EP 484 DI 10.1111/j.1750-3639.2011.00542.x PG 13 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 958KH UT WOS:000305234900003 PM 21999410 ER PT J AU Armah, KA McGinnis, K Baker, J Gibert, C Butt, AA Bryant, KJ Goetz, M Tracy, R Oursler, KK Rimland, D Crothers, K Rodriguez-Barradas, M Crystal, S Gordon, A Kraemer, K Brown, S Gerschenson, M Leaf, DA Deeks, SG Rinaldo, C Kuller, LH Justice, A Freiberg, M AF Armah, Kaku A. McGinnis, Kathleen Baker, Jason Gibert, Cynthia Butt, Adeel A. Bryant, Kendall J. Goetz, Matthew Tracy, Russell Oursler, Krisann K. Rimland, David Crothers, Kristina Rodriguez-Barradas, Maria Crystal, Steve Gordon, Adam Kraemer, Kevin Brown, Sheldon Gerschenson, Mariana Leaf, David A. Deeks, Steven G. Rinaldo, Charles Kuller, Lewis H. Justice, Amy Freiberg, Matthew TI HIV Status, Burden of Comorbid Disease, and Biomarkers of Inflammation, Altered Coagulation, and Monocyte Activation SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID C-REACTIVE PROTEIN; APPARENTLY HEALTHY-MEN; T-CELL DEPLETION; MYOCARDIAL-INFARCTION; MICROBIAL TRANSLOCATION; DIABETES-MELLITUS; ANTIRETROVIRAL THERAPY; BLOOD-PRESSURE; SOLUBLE CD14; INFECTION AB Background. Biomarkers of inflammation, altered coagulation, and monocyte activation are associated with mortality and cardiovascular disease (CVD) in the general population and among human immunodeficiency virus (HIV)-infected people. We compared biomarkers for inflammation, altered coagulation, and monocyte activation between HIV-infected and uninfected people in the Veterans Aging Cohort Study (VACS). Methods. Biomarkers of inflammation (interleukin-6 [IL-6]), altered coagulation (D-dimer), and monocyte activation (soluble CD14 [sCD14]) were measured in blood samples from 1525 HIV-infected and 843 uninfected VACS participants. Logistic regression was used to determine the association between HIV infection and prevalence of elevated (>75th percentile) biomarkers, adjusting for confounding comorbidities. Results. HIV-infected veterans had less prevalent CVD, hypertension, diabetes, obesity, hazardous drinking, and renal disease, but more dyslipidemia, hepatitis C, and current smoking than uninfected veterans. Compared to uninfected veterans, HIV-infected veterans with HIV-1 RNA >= 500 copies/mL or CD4 count <200 cells/mu L had a significantly higher prevalence of elevated IL-6 (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.14-2.09; OR, 2.25; 95% CI, 1.60-3.16, respectively) and D-dimer (OR, 1.97; 95% CI, 1.44-2.71, OR, 1.68; 95% CI, 1.22-2.32, respectively) after adjusting for comorbidities. HIV-infected veterans with a CD4 cell count <200 cells/mu L had significantly higher prevalence of elevated sCD14 compared to uninfected veterans (OR, 2.60; 95% CI, 1.64-4.14). These associations still persisted after restricting the analysis to veterans without known confounding comorbid conditions. Conclusions. These data suggest that ongoing HIV replication and immune depletion significantly contribute to increased prevalence of elevated biomarkers of inflammation, altered coagulation, and monocyte activation. This contribution is independent of and in addition to the substantial contribution from comorbid conditions. C1 [Armah, Kaku A.; Kuller, Lewis H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Gordon, Adam] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Sch Med, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA 15260 USA. [Baker, Jason] Univ Minnesota, Dept Med, Hennepin Cty Med Ctr, Minneapolis, MN 55455 USA. [Gibert, Cynthia] VA Med Ctr, Washington, DC USA. [Gibert, Cynthia] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Butt, Adeel A.] Sheikh Khalifa Med City, Abu Dhabi, U Arab Emirates. [Bryant, Kendall J.] NIAAA, NIH, Bethesda, MD USA. [Goetz, Matthew; Leaf, David A.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Tracy, Russell] Univ Vermont, Dept Pathol, Coll Med, Burlington, VT 05405 USA. [Tracy, Russell] Univ Vermont, Dept Biochem, Coll Med, Burlington, VT 05405 USA. [Oursler, Krisann K.] Univ Maryland, Baltimore VA Med Ctr, Sch Med, Baltimore, MD USA. [Rimland, David] Emory Univ, Sch Med, VA Med Ctr, Atlanta, GA USA. [Crothers, Kristina] Univ Washington, Div Pulm & Crit Care, Dept Internal Med, Seattle, WA 98195 USA. [Rodriguez-Barradas, Maria] Baylor Coll Med, Houston, TX 77030 USA. [Rodriguez-Barradas, Maria] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Crystal, Steve] Rutgers State Univ, Ctr Pharmacotherapy Chron Dis Management & Outcom, Inst Hlth, New Brunswick, NJ 08903 USA. [Crystal, Steve] Rutgers State Univ, Sch Social Work, New Brunswick, NJ 08903 USA. [Gordon, Adam] Univ Pittsburgh, Sch Med, Ctr Hlth Equity Res & Promot, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. [Gordon, Adam] Univ Pittsburgh, Sch Med, Ctr Res Healthcare, Pittsburgh, PA 15260 USA. [Kraemer, Kevin] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. [Brown, Sheldon] Mt Sinai Med Ctr, Dept Internal Med, New York, NY 10029 USA. [Brown, Sheldon] Bronx Vet Affairs Med Ctr, New York, NY USA. [Gerschenson, Mariana] Univ Hawaii Manoa, Hawaii AIDS Clin Res Program, Dept Med, Honolulu, HI 96822 USA. [Gerschenson, Mariana] Univ Hawaii Manoa, John A Burns Sch Med, Honolulu, HI 96822 USA. [Deeks, Steven G.] San Francisco Gen Hosp, Dept Med, Posit Hlth Program, San Francisco, CA 94110 USA. [Rinaldo, Charles] Presbyterian Univ Hosp, Dept Microbiol, Dept Pathol, Pittsburgh, PA USA. [Justice, Amy] Yale Univ, Sch Med, Sect Gen Med, New Haven, CT USA. [Justice, Amy] VA Connecticut Healthcare Syst, West Haven, CT USA. [Freiberg, Matthew] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. RP Freiberg, M (reprint author), 230 McKee Pl,Ste 623, Pittsburgh, PA 15213 USA. EM freibergms@upmc.edu OI Goetz, Matthew/0000-0003-4542-992X FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Heart Lung and Blood Institute (NHLBI) at the National Institutes of Health (NIH) [K23AA015914-0651, R01HC095136-04, 5R01HC095126-04, U10AA013566-10]; NIH/NHLBI/NIAAA; Yale University; US Department of Veterans Affairs (VA) through the University of Pittsburgh FX This work was supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and National Heart Lung and Blood Institute (NHLBI) at the National Institutes of Health (NIH; grant numbers K23AA015914-0651, R01HC095136-04, 5R01HC095126-04 to M. F.; and U10AA013566-10 to A. J.).; K. A., K. A. O., A. G., K. K., S. B., S. D., A. J., and M. F. received NIH/NHLBI/NIAAA grant funding for this work. M. G. has received grant funding and support from Yale University for this work. R. T. has received grant funding from the US Department of Veterans Affairs (VA) through the University of Pittsburgh for this work. R. T. owns Haematologic Technologies and has received funding from Tibotec, Merck, and Abbott, none of which pertain to this work. All other authors report no potential conflicts. NR 37 TC 95 Z9 95 U1 1 U2 13 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 JUL 1 PY 2012 VL 55 IS 1 BP 126 EP 136 DI 10.1093/cid/cis406 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 956KM UT WOS:000305088500020 PM 22534147 ER PT J AU Richardson, J Tjoelker, R AF Richardson, Jeannette Tjoelker, Rita TI Beyond the Central Line-Associated Bloodstream Infection Bundle The Value of the Clinical Nurse Specialist in Continuing Evidence-Based Practice Changes SO CLINICAL NURSE SPECIALIST LA English DT Article DE catheter-related infections; evidence-based practice; quality improvement ID NETWORK NHSN REPORT; CRITICALLY-ILL PATIENTS; MORTALITY AB Purpose: The purpose of this project was to demonstrate the value of clinical nurse specialist (CNS)-led efforts to optimize patient outcomes through continued monitoring and management of a previously implemented evidence-based practice project. Background: Central line-associated bloodstream infections (CLABSIs) significantly impact patient morbidity/mortality and cost of care. In 2006, the critical care unit (CCU) of the Portland VA Medical Center implemented national recommendations for the prevention of CLABSIs through use of the Institute of Healthcare Improvement Central Line Bundle. This practice change was led by the CCU and infection control CNSs, and compliance in the completion of bundle items has remained consistently high (>90%). Although the CCU has maintained CLABSI rates below the national benchmark, it experienced a 4-month period of increased incidence in late 2008. Description: Clinical nurse specialists in CCU and infection control organized a "Hot Team" of nurses from multiple departments throughout the hospital to evaluate processes/data related to the recent increase in infections. Using national guidelines, the team focused on interdisciplinary implementation of strategies beyond the Central Line Bundle components. Consideration of cost and workflow patterns was critical to decision making. Outcome: Infection rates in CCU decreased from a high of 1.5 per 1000 line days down to 0 in June 2011, with the last CLABSI occurring in May 2010. Conclusion: The formation and efforts of a CNS-led team of nurses has been successful in decreasing infection rates through implementation of multiple innovative strategies. Implications: Clinical nurse specialist surveillance, management, and leadership following project implementation are valuable strategies for continued optimal patient outcomes. C1 [Richardson, Jeannette; Tjoelker, Rita] Portland VA Med Ctr, Portland, OR 97239 USA. RP Richardson, J (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM jeannette.richardson@va.gov NR 17 TC 8 Z9 10 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD JUL-AUG PY 2012 VL 26 IS 4 BP 205 EP 211 DI 10.1097/NUR.0b013e31825aebab PG 7 WC Nursing SC Nursing GA 958YU UT WOS:000305277700006 PM 22678186 ER PT J AU Kim, S Millard, SP Yu, CE Leong, L Radant, A Dobie, D Tsuang, DW Wijsman, EM AF Kim, Sulgi Millard, Steven P. Yu, Chang-En Leong, Lesley Radant, Allen Dobie, Dorcas Tsuang, Debby W. Wijsman, Ellen M. TI Inheritance Model Introduces Differential Bias in CNV Calls Between Parents and Offspring SO GENETIC EPIDEMIOLOGY LA English DT Article DE Schizophrenia; calling algorithm; family-based study; CNV burden ID COPY NUMBER VARIATION; BIPOLAR-DISORDER; INCREASE RISK; SCHIZOPHRENIA; ASSOCIATION; DELETIONS; DISEASE AB Copy Number Variation (CNV) is increasingly implicated in disease pathogenesis. CNVs are often identified by statistical models applied to data from single nucleotide polymorphism panels. Family information for samples provides additional information for CNV inference. Two modes of PennCNV (the Joint-call and Posterior-call), which are some of the most well-developed family-based CNV calling methods, use a Joint-model as a main component. This models all family members CNV states together with Mendelian inheritance. Methods based on the Joint-model are used to infer CNV calls of cases and controls in a pedigree, which may be compared to each other to test an association. Although benefits from the Joint-model have been shown elsewhere, equality of call rates in parents and offspring has not been evaluated previously. This can affect downstream analyses in studies that compare CNV rates in cases vs. controls in pedigrees. In this paper, we show that the Joint-model can introduce different CNV call rates among family members in the absence of a true difference. We show that the Joint-model may analytically introduce differential CNV calls because of asymmetry of the model. We demonstrate these differential call rates using single-marker simulations. We show that call rates using the two modes of PennCNV also differ between parents and offspring in one multimarker simulated dataset and two real datasets. Our results advise need for caution in use of the Joint-model calls in CNV association studies with family-based datasets. Genet. Epidemiol. 36:488-498, 2012. (C) 2012 Wiley Periodicals, Inc. C1 [Wijsman, Ellen M.] Univ Washington, Sch Med, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Millard, Steven P.; Tsuang, Debby W.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Yu, Chang-En] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Yu, Chang-En] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. [Leong, Lesley; Radant, Allen; Dobie, Dorcas; Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Wijsman, Ellen M.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Wijsman, Ellen M.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA. RP Wijsman, EM (reprint author), Univ Washington, Sch Med, Dept Med, Div Med Genet, Box 357720, Seattle, WA 98195 USA. EM wijsman@u.washington.edu RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894; Wijsman, Ellen/0000-0002-2725-6669 FU NIH [R01MH065558, R01MH065554]; U.S. Department of Veterans Affairs, Office of Research Development Biomedical Laboratory Research FX This work is supported by NIH: R01MH065558 and R01MH065554; the U.S. Department of Veterans Affairs, Office of Research Development Biomedical Laboratory Research: Merit Review; and VISN-20 MIRECC. We thank Jeremy Silverman and Larry Siever for contributing schizophrenia trios, and the NIMH Genetics Initiative on schizophrenia for providing DNA sample. The funding agencies did not play a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2012 VL 36 IS 5 BP 488 EP 498 DI 10.1002/gepi.21643 PG 11 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 956YP UT WOS:000305125800008 PM 22628073 ER PT J AU Zhang, XY Chen, DC Xiu, MH Haile, CN Luo, XG Xu, K Zhang, HP Zuo, LJ Zhang, ZJ Zhang, XR Kosten, TA Kosten, TR AF Zhang, Xiang Yang Chen, Da Chun Xiu, Mei Hong Haile, Colin N. Luo, Xingguang Xu, Ke Zhang, Hui Ping Zuo, Lingjun Zhang, Zhijun Zhang, Xiangrong Kosten, Therese A. Kosten, Thomas R. TI Cognitive and serum BDNF correlates of BDNF Val66Met gene polymorphism in patients with schizophrenia and normal controls SO HUMAN GENETICS LA English DT Article ID ACTIVITY-DEPENDENT SECRETION; NEUROTROPHIC FACTOR GENE; LONG-TERM-MEMORY; NEUROPSYCHOLOGICAL STATUS; REPEATABLE BATTERY; BIPOLAR DISORDER; CHINESE-HAN; MET ALLELE; BRAIN; ASSOCIATION AB Studies suggest that a functional polymorphism of the brain-derived neurotrophic factor gene (BDNF Val66Met) may mediate hippocampal-dependent cognitive functions. A few studies have reported its role in cognitive deficits in schizophrenia including its association with peripheral BDNF levels as a mediator of these cognitive deficits. We assessed 657 schizophrenic inpatients and 445 healthy controls on the repeatable battery for the assessment of neuropsychological status (RBANS), the presence of the BDNF Val66Met polymorphism and serum BDNF levels. We assessed patient psychopathology using the Positive and Negative Syndrome Scale. We showed that visuospatial/constructional abilities significantly differed by genotype but not genotype x diagnosis, and the Val allele was associated with better visuospatial/constructional performance in both schizophrenic patients and healthy controls. Attention performance showed a significant genotype by diagnosis effect. Met allele-associated attention impairment was specific to schizophrenic patients and not shown in healthy controls. In the patient group, partial correlation analysis showed a significant positive correlation between serum BDNF and the RBANS total score. Furthermore, the RBANS total score showed a statistically significant BDNF level x genotype interaction. We demonstrated an association between the BDNF Met variant and poor visuospatial/constructional performance. Furthermore, the BDNF Met variant may be specific to attentional decrements in schizophrenic patients. The association between decreased BDNF serum levels and cognitive impairment in schizophrenia is dependent on the BDNF Val66Met polymorphism. C1 [Zhang, Xiang Yang; Kosten, Thomas R.] VA Med Ctr, Houston, TX 77030 USA. [Zhang, Xiang Yang; Haile, Colin N.; Kosten, Therese A.; Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Chen, Da Chun; Xiu, Mei Hong] Beijing HuiLongGuan Hosp, Ctr Psychiat Res, Beijing, Peoples R China. [Luo, Xingguang; Xu, Ke; Zhang, Hui Ping; Zuo, Lingjun] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Zhang, Zhijun; Zhang, Xiangrong] Southeast Univ, Dept Neurol, Affiliated ZhongDa Hosp, Nanjing, 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 OI Haile, Colin/0000-0001-8293-7291 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 This study was funded by the Stanley Medical Research Institute (03T-459 and 05T-726), and the Department of Veterans Affairs, VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC), United States National Institute of Health K05-DA0454, P50-DA18827 and U01-MH79639. NR 51 TC 34 Z9 35 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUL PY 2012 VL 131 IS 7 BP 1187 EP 1195 DI 10.1007/s00439-012-1150-x PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 957VV UT WOS:000305195400017 PM 22362486 ER PT J AU Sonnenberg, A Walker, JT AF Sonnenberg, Amnon Walker, James T. TI Occupational mortality associated with inflammatory bowel disease in the United States 1984-1998 SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE Crohn's disease; environmental risk factors; epidemiology; industry; occupation; occupational mortality statistics; proportional mortality ratio; ulcerative colitis ID CROHNS-DISEASE; ULCERATIVE-COLITIS AB Background: The occurrence of Crohn's disease (CD) and ulcerative colitis (UC) is shaped by environmental influences. Many such environmental risk factors vary potentially with occupational exposure. We used a large national database to study the occupational variation of mortality associated with CD and UC. Methods: The National Occupational Mortality Surveillance database contains data from the death certificate linked with information about the occupation and industry of each deceased individual. Deaths were grouped by gender, ethnicity, disease type, occupation, and industry. Mortality by occupation and industry were expressed as age-adjusted proportional mortality ratio. Results: A total of 3110 inflammatory bowel disease (IBD) patients were included in the present analysis. IBD mortality was low among blue collar workers and high among white collar workers. It was low among farming occupations, manufacturing occupations, and manual laborers. It was high among secretaries, professionals, sales workers, homemakers, managerial occupations, and teachers. There was a strong correlation between the occupational distribution of CD and UC that applied to men and women alike. The overall distribution among different industries corroborated the patterns observed with respect to the occupational distribution. Conclusions: The correlations between the occupational distribution of CD and UC support the contention that environmental influences shape the occurrence of both diseases. Such influence must vary by occupation and, to a lesser extent, also by industry. It must be similar for both types of IBD. (Inflamm Bowel Dis 2011;) C1 [Sonnenberg, Amnon] Dept Vet Affairs Med Ctr, Portland, OR USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Walker, James T.] NIOSH, Cincinnati, OH 45226 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3 GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 17 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JUL PY 2012 VL 18 IS 7 BP 1249 EP 1253 DI 10.1002/ibd.21807 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 956IP UT WOS:000305083600010 PM 21710539 ER PT J AU Rubinow, KB Vaisar, T Tang, CR Matsumoto, AM Heinecke, JW Page, ST AF Rubinow, Katya B. Vaisar, Tomas Tang, Chongren Matsumoto, Alvin M. Heinecke, Jay W. Page, Stephanie T. TI Testosterone replacement in hypogonadal men alters the HDL proteome but not HDL cholesterol efflux capacity SO JOURNAL OF LIPID RESEARCH LA English DT Article DE cardiovascular disease; lipoproteins; lipids; atherosclerosis; androgens ID HIGH-DENSITY-LIPOPROTEIN; CORONARY-ARTERY-DISEASE; APOLIPOPROTEIN-A-I; CARDIOVASCULAR-DISEASE; HEPATIC LIPASE; APOC-I; ANTIINFLAMMATORY PROPERTIES; POSTMENOPAUSAL WOMEN; MASS-SPECTROMETRY; THERAPY AB The effects of androgens on cardiovascular disease (CVD) risk in men remain unclear. To better characterize the relationship between androgens and HDL, we investigated the effects of testosterone replacement on HDL protein composition and serum HDL-mediated cholesterol efflux in hypogonadal men. Twenty-three older hypogonadal men (ages 51-83, baseline testosterone < 280 ng/dl) were administered replacement testosterone therapy (1% transdermal gel) with or without the 5 alpha-reductase inhibitor dutasteride. At baseline and after three months of treatment, we determined fasting lipid concentrations, HDL protein composition, and the cholesterol efflux capacity of serum HDL. Testosterone replacement did not affect HDL cholesterol (HDL-C) concentrations but conferred significant increases in HDL-associated paraoxonase 1 (PON1) and fibrinogen alpha chain (FGA) (P = 0.022 and P = 0.023, respectively) and a decrease in apolipoprotein A-IV (apoA-IV) (P = 0.016). Exogenous testosterone did not affect the cholesterol efflux capacity of serum HDL. No differences were observed between men who received testosterone alone and those who also received dutasteride.(Jlr) Testosterone replacement in older hypogonadal men alters the protein composition of HDL but does not significantly change serum HDL-mediated cholesterol efflux. These effects appear independent of testosterone conversion to dihydrotestosterone. Further research is needed to determine how changes in HDL protein content affect CVD risk in men. Rubinow, K. B., T. Vaisar, C. Tang, A. M. Matsumoto, J. W. Heinecke, and S. T. Page. Testosterone replacement in hy C1 [Rubinow, Katya B.; Page, Stephanie T.] Univ Washington, Sch Med, Ctr Res Reprod & Contracept, Seattle, WA 98195 USA. [Vaisar, Tomas; Tang, Chongren; Heinecke, Jay W.] Univ Washington, Sch Med, Diabet & Obes Ctr Excellence, Seattle, WA USA. [Matsumoto, Alvin M.] Univ Washington, Sch Med, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Matsumoto, Alvin M.] Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. [Matsumoto, Alvin M.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. RP Rubinow, KB (reprint author), Univ Washington, Sch Med, Ctr Res Reprod & Contracept, Seattle, WA 98195 USA. EM rubinow@uw.edu FU National Institutes of Health [RO1-AG-037603, U54-HD-42454, P50-CA-097186, DK-017047, T32-DK-007247, P30-DK-035816, R01-HL-089504, P30-DK-017047, P01-HL-112625, R01-HL-086798, P01-HL-092969]; Department of Veterans Affairs Puget Sound Health Care System; American Heart Association [083-0231N] FX This work was supported by National Institutes of Health Grants RO1-AG-037603, U54-HD-42454, P50-CA-097186, DK-017047, T32-DK-007247 (K. B. R.), P30-DK-035816 (T. V.), R01-HL-089504 (T. V.), P30-DK-017047, P01-HL-112625 (J. W. H.), R01-HL-086798 (J. W. H.), and P01-HL-092969 (J. W. H.); by the Department of Veterans Affairs Puget Sound Health Care System (A. M. M.); and by American Heart Association Grant 083-0231N (T. V.). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. Transdermal placebo and testosterone gels were provided by Abbott Laboratories (formerly Solvay Pharmaceuticals), and dutasteride and oral placebo were provided by GlaxoSmithKline, neither of which had any input into the study design, analyses, or manuscript preparation. NR 47 TC 12 Z9 12 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 EI 1539-7262 J9 J LIPID RES JI J. Lipid Res. PD JUL PY 2012 VL 53 IS 7 BP 1376 EP 1383 DI 10.1194/jlr.P026005 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 957IZ UT WOS:000305156400014 PM 22504910 ER PT J AU Cardo, LF Coto, E de Mena, L Ribacoba, R Lorenzo-Betancor, O Pastor, P Samaranch, L Mata, IF Diaz, M Moris, G Menendez, M Corao, AI Alvarez, V AF Cardo, Lucia F. Coto, Eliecer de Mena, Lorena Ribacoba, Rene Lorenzo-Betancor, Oswaldo Pastor, Pau Samaranch, LLuis Mata, Ignacio F. Diaz, Marta Moris, German Menendez, Manuel Corao, Ana I. Alvarez, Victoria TI A Search for SNCA 3 ' UTR Variants Identified SNP rs356165 as a Determinant of Disease Risk and Onset Age in Parkinson's Disease SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Parkinson's disease; Alpha-synuclein; DNA polymorphisms; Genetic risk ID ALPHA-SYNUCLEIN GENE; GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY; MUTATION; POPULATION; EXPRESSION; REGIONS AB Alpha-synuclein gene (SNCA) polymorphisms have been associated with the common sporadic form of Parkinson's disease (PD). We searched for DNA variants at the SNCA 3' UTR through single strand conformation analysis and direct sequencing in a cohort of Spanish PD patients and controls. We have genotyped the rs356165 SNCA 3' UTR polymorphism in a total of 1,135 PD patients and 772 healthy controls from two Spanish cohorts (Asturias and Navarre). We identified six SNCA 3' UTR variants. Single nucleotide polymorphism (SNP) rs356165 was significantly associated with PD risk in the Spanish cohort (p = 0.0001; odd ratio = 1.37, 95%CI = 1.19-1.58). This SNP was also significantly associated with early age at onset of PD. Our work highlights rs356165 as an important determinant of the risk of developing PD and early age at onset and encourages future research to identify a functional effect on SNCA expression. C1 [Cardo, Lucia F.; Coto, Eliecer; de Mena, Lorena; Diaz, Marta; Corao, Ana I.; Alvarez, Victoria] Hosp Univ Cent Asturias, Genet Mol Lab Med, Oviedo 33006, Spain. [Ribacoba, Rene; Moris, German; Menendez, Manuel] Hosp Univ Cent Asturias, Asturias, Spain. [Lorenzo-Betancor, Oswaldo; Pastor, Pau; Samaranch, LLuis] Univ Navarra Clin, Ctr Appl Med Res, Div Neurosci, Neurogenet Lab, Pamplona, Spain. [Ribacoba, Rene; Moris, German; Menendez, Manuel] Alvarez Buylla Mieres, Asturias, Spain. [Coto, Eliecer] Univ Oviedo, Dept Med, Oviedo, Spain. [Lorenzo-Betancor, Oswaldo; Pastor, Pau] Univ Navarra Clin, Dept Neurol, Pamplona, Spain. [Mata, Ignacio F.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Mata, Ignacio F.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. RP Alvarez, V (reprint author), Hosp Univ Cent Asturias, Genet Mol Lab Med, Oviedo 33006, Spain. EM victoria.alvarez@sespa.princast.es RI Pastor, Pau/C-9834-2009 OI Pastor, Pau/0000-0002-7493-8777; Fernandez Mata, Ignacio/0000-0003-1198-0633; Moris, German/0000-0001-7608-2194 FU Fundacion Parkinson Asturias; Obra Social Cajastur; Spanish European Union [FIS-05/008, 08/0915]; FICYT-Principado de Asturias; Spanish Ministry of Science and Technology; European Social Fund; Spanish Ministry of Education and Science [SAF2006-10126]; Fundacio La Marato de TV3 [061131]; UTE, Spain FX Authors thank the "Fundacion Parkinson Asturias" and "Obra Social Cajastur" for their support. This work was supported by grants from the Spanish "Fondo de Investigaciones Sanitarias-Fondos FEDER" European Union (FIS-05/008 and 08/0915). LFC and LDM are predoctoral fellowships of FICYT-Principado de Asturias. LS held a "Torres Quevedo" fellowship from the Spanish Ministry of Science and Technology, co-financed by the European Social Fund. This study was supported by a grant from the Spanish Ministry of Education and Science (SAF2006-10126, 2006-2009) by the project 061131 from the "Fundacio La Marato de TV3" and by the UTE project FIMA, Spain to PP. NR 26 TC 14 Z9 17 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD JUL PY 2012 VL 47 IS 3 BP 425 EP 430 DI 10.1007/s12031-011-9669-1 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 958DV UT WOS:000305217600002 PM 22076805 ER PT J AU Wong, ES Piette, JD Liu, CF Perkins, M Maciejewski, ML Jackson, GL Blough, DK Fihn, SD Au, DH Bryson, CL AF Wong, Edwin S. Piette, John D. Liu, Chuan-Fen Perkins, Mark Maciejewski, Matthew L. Jackson, George L. Blough, David K. Fihn, Stephan D. Au, David H. Bryson, Chris L. TI Measures of Adherence to Oral Hypoglycemic Agents at the Primary Care Clinic Level The Role of Risk Adjustment SO MEDICAL CARE LA English DT Article DE risk adjustment; adherence; diabetes; organization of care; veterans ID MEDICATION ADHERENCE; PERFORMANCE-MEASURES; MEANINGFUL VARIATION; VETERANS-AFFAIRS; THERAPY; QUALITY; PERSISTENCE; MORTALITY; DISEASE; COSTS AB Background: Prior research found that in the Veterans Affairs health care system (VA), the proportion of patients adherent to oral hypoglycemic agents varies from 50% to 80% across primary care clinics. This study examined whether variation in patient and facility characteristics determined those differences. Methods: Retrospective cohort study of 444,418 VA primary care patients with diabetes treated in 559 clinics in fiscal year (FY) 2006-2007. Patients' adherence to each oral hypoglycemic agent was computed for the first 3 months of FY2007, and averaged across agents to produce an adherence score for the patient's overall regimen. Patients with an adherence score over 0.8 were defined as adherent. Risk adjustment used hierarchical logistic regression accounting for patient factors and facility effects by clustering patients within clinics and clinics within parent VA medical centers. We then assessed the influence of risk adjustment using observed-to-expected (O/E) ratios computed for each clinic. Results: The mean unadjusted proportion of adherent patients in clinics was 0.715 (interdecile range 0.559-0.826). The percent variation in patient's likelihood of being adherent explained at the patient, clinic, and parent VA medical center levels was 2.94%, 0.27%, and 0.76%, respectively. The mean clinic-level observed-to-expected ratio was 1.001 (interdecile range 0.975-1.027). Conclusions: The variation in the proportion of patients adherent across clinics remained large after risk adjustment. As patient and facility effects explained only 4% of the variance in adherence, comparing clinics based on unadjusted scores is a reasonable starting point unless more predictive patient, provider, and facility factors are identified. C1 [Wong, Edwin S.; Liu, Chuan-Fen; Perkins, Mark] VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, Seattle, WA 98101 USA. [Wong, Edwin S.; Liu, Chuan-Fen] Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Serv, Seattle, WA 98195 USA. [Piette, John D.] VA Ann Arbor Healthcare Syst, Vet Affairs Ctr Clin Management Res, Ann Arbor, MI USA. [Piette, John D.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Maciejewski, Matthew L.; Jackson, George L.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Maciejewski, Matthew L.; Jackson, George L.] Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, Durham, NC 27710 USA. [Blough, David K.] Univ Washington, Sch Pharm, Pharmaceut Outcomes Res & Policy Program, Seattle, WA 98195 USA. [Fihn, Stephan D.; Au, David H.; Bryson, Chris L.] Univ Washington, Dept Med, Seattle, WA USA. RP Wong, ES (reprint author), VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM eswong@uw.edu FU Department of Veterans Affairs, Health Services Research and Development [IIR 07-068-2]; VA Health Services Research and Development Postdoctoral Fellowship [TPP 61-024]; VA Career Development Award [03-177]; Gilead Sciences FX This research was supported by an Investigator Initiated Research Award (IIR 07-068-2) from the Department of Veterans Affairs, Health Services Research and Development. Dr Wong is supported by VA Health Services Research and Development Postdoctoral Fellowship TPP 61-024. Dr Bryson was supported by VA Career Development Award 03-177. An earlier version of this manuscript was presented as a poster at the Academy Health's Annual Research Meeting in Boston, MA in 2010.; Dr. Wong reports owning stock in Merck & Co., Inc. and the SPDR Health Care Select Sector Exchange Traded Fund. Dr. Fihn reports receiving travel/accomodations/meeting expenses from the Alliance for Academic Internal Medicine. Dr. Au reports serving as a consultant for Bosch Inc. and receiving grants from Gilead Sciences. All other authors declare no conflict of interest. NR 49 TC 11 Z9 11 U1 0 U2 4 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 JUL PY 2012 VL 50 IS 7 BP 591 EP 598 DI 10.1097/MLR.0b013e318249cb74 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 959DT UT WOS:000305292900006 PM 22354208 ER PT J AU Donohue, JF Anzueto, A Brooks, J Mehta, R Kalberg, C Crater, G AF Donohue, James F. Anzueto, Antonio Brooks, Jean Mehta, Rashmi Kalberg, Christopher Crater, Glenn TI A randomized, double-blind dose-ranging study of the novel LAMA GSK573719 in patients with COPD SO RESPIRATORY MEDICINE LA English DT Article DE Long-acting muscarinic receptor antagonist; Long-acting bronchodilator; Anticholinergic; Chronic obstructive pulmonary disease; G5K573719 ID OBSTRUCTIVE PULMONARY-DISEASE; MUSCARINIC ANTAGONIST; IPRATROPIUM; TIOTROPIUM; ACLIDINIUM AB Background: This study evaluated the dose-response and dosing interval of the novel long-acting muscarinic receptor antagonist (LAMA) GSK573719 in patients with COPD. Methods: This randomized, double-blind, placebo-controlled, 3-way cross-over, incomplete block study evaluated 5 once-daily doses of GSK573719 (62.5-1000 mu g), 3 twice-daily doses (62.5-250 mu g), and open-label tiotropium for 14 days in patients (N = 176) with COPD (FEV1 of 35-70% predicted). The primary endpoint was morning trough FEV1 at Day 15. Secondary endpoints included 0-24 h weighted mean FEV1 and serial FEV1 values over 28 h. Safety measures and pharmacokinetics were assessed. Results: All once-daily doses of GSK573719 significantly increased trough FEV1 at Day 15 with improvements ranging from 95 to 186 mL over placebo (p <= 0.006), from 79 to 172 mL with twice-daily dosing (p <= 0.03), and 105 mL with tiotropium (p = 0.003). No clear dose ordering was observed. Once-daily doses significantly (p < 0.001) increased 0-24 h weighted mean FEV1 at Day 14 by 131-143 mL over placebo, comparable to increases with the twice-daily doses (120-142 mL) and tiotropium (127 mL). Significant reductions in rescue albuterol use and improvements in FVC were also observed with once-daily dosing. Plasma C-max occurred within 5-15 min of dosing after which the drug was rapidly cleared and eliminated. GSK573719 was well tolerated, with no apparent treatment-related changes in vital signs, ECG and Hotter assessments, or clinical laboratory parameters. Conclusion: Once-daily dosing with GSK573719 in COPD provides clinically significant and sustained improvement in lung function over 24 h with similar efficacy to twice-daily dosing. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Donohue, James F.] Univ N Carolina, Coll Med, Dept Med, Chapel Hill, NC 27599 USA. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anzueto, Antonio] Audie L Murphy Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Brooks, Jean] GlaxoSmithKline, Resp Med Dev Ctr, Stockley Pk UB11 1BT, England. [Mehta, Rashmi; Kalberg, Christopher; Crater, Glenn] GlaxoSmithKline, Resp Med Dev Ctr, Res Triangle Pk, NC 27709 USA. RP Donohue, JF (reprint author), Univ N Carolina, Coll Med, Dept Med, 4125 Bioinformat Bldg, Chapel Hill, NC 27599 USA. EM james_donohue@med.unc.edu; Anzueto@uthscsa.edu; jean.2.brooks@gsk.com; rashmi.s.mehta@gsk.com; chris.j.kalberg@gsk.com; glenn.d.crater@gsk.com OI Crater, Glenn/0000-0002-1159-1323 FU Boehringer Ingelheim; GlaxoSmithKline; Novartis; NHLBI; Lilly; Pfizer; Pneuma pharmaceuticals FX J.F.D. has served as consultant to Almirall, AstraZeneca, Boehringer Ingelheim, Dey, Elevation Pharmaceuticals, Forest Laboratories, GlaxoSmithKline, Novartis, Pearl Pharmaceuticals, Pfizer and Sunovion; and has received research grants from Boehringer Ingelheim, GlaxoSmithKline and Novartis. A.A. is an advisor, consultant, and speaker for Boehringer Ingelheim, GlaxoSmithKline, Pfizer, Merck, Bayer-Schering Pharma, Dey Pharma, Forest laboratories and has investigational grants with the NHLBI, GlaxoSmithKline, Lilly, Pfizer, and Pneuma pharmaceuticals. J.B., R.M., C.K., G.C. are employees of and hold stocks/shares in GlaxoSmithKline. NR 16 TC 46 Z9 48 U1 0 U2 4 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD JUL PY 2012 VL 106 IS 7 BP 970 EP 979 DI 10.1016/j.rmed.2012.03.012 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 957LM UT WOS:000305164500008 PM 22498110 ER PT J AU Cecere, LM Williams, EC Sun, H Bryson, CL Clark, BJ Bradley, KA Au, DH AF Cecere, Laura M. Williams, Emily C. Sun, Haili Bryson, Chris L. Clark, Brendan J. Bradley, Katharine A. Au, David H. TI Smoking cessation and the risk of hospitalization for pneumonia SO RESPIRATORY MEDICINE LA English DT Article DE Pneumonia; Smoking cessation; COPD ID COMMUNITY-ACQUIRED PNEUMONIA; OBSTRUCTIVE PULMONARY-DISEASE; ALCOHOL SCREENING SCORES; UNITED-STATES; HEALTH-STATUS; OLDER-ADULTS; MORTALITY; CARE; POPULATION; VETERANS AB Background: Smoking increases the risk of hospitalization for pneumonia, yet it is unknown if smoking cessation changes this risk. We sought to determine if smoking cessation and the duration of abstinence from tobacco reduce the risk of pneumonia hospitalization. Methods: We performed secondary analysis of data collected from male United States Veterans participating in a randomized trial. We used Cox proportional-hazard models to estimate risk of hospitalization for pneumonia within one year of enrollment. We adjusted for confounders, including: demographics, comorbidity, alcohol use, prior pneumonia, inhaled corticosteroid use, and intensity of tobacco exposure. Among a restricted cohort excluding never smokers, we assessed for effect modification by a diagnosis of chronic obstructive pulmonary disease (COPD). Results: Of the 25,235 participants, we identified 6720 current, 13,625 former, and 4890 never smokers. Compared to current smokers, never smokers had a decreased (adjusted HR 0.48, 95% Cl 0.31-0.74), while former smokers had no difference in (adjusted HR 0.83, 95% Cl 0.63-1.09) risk of hospitalization for pneumonia. Among participants without COPD, former smokers had a lower risk of hospitalization (adjusted HR 0.65, 95% Cl 0.45-0.95). However, this lower risk was isolated to those who quit tobacco more than 10 years previously (adjusted HR 0.62, 95% CI 0.41-0.93). Among those with COPD, there was no difference in risk with smoking cessation or duration of remaining tobacco-free. Conclusions: Tobacco cessation is likely important in reducing hospital admissions for pneumonia, but its benefit depends on duration of smoking cessation and is likely attenuated in the presence of COPD. Published by Elsevier Ltd. C1 [Cecere, Laura M.; Williams, Emily C.; Sun, Haili; Bryson, Chris L.; Bradley, Katharine A.; Au, David H.] Puget Sound Hlth Care Syst, Dept Vet Affairs, NW Ctr Excellence, HSR&D, Seattle, WA USA. [Cecere, Laura M.; Au, David H.] Univ Washington, Div Pulm & Crit Care Med, Dept Med, Seattle, WA USA. [Williams, Emily C.; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Bryson, Chris L.; Bradley, Katharine A.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA USA. [Clark, Brendan J.] Univ Colorado Denver, Div Pulm Sci & Crit Care Med, Aurora, CO USA. [Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA USA. RP Cecere, LM (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM lcecere@uw.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSRD) [IAC 05-206-1]; VA HSRD [TPM 61-037]; Giliad Sciences FX This study was supported by a Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) grant [IAC 05-206-1]. Dr. Cecere is supported by a VA HSR&D fellowship [TPM 61-037]. 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.; Drs. Au and Bryson are co-investigators on a grant from Giliad Sciences for work which is unrelated to this manuscript. Dr. Au is a research consultant for Bosch LLC. Drs. Cecere, Williams, Sun, Clark, and Bradley have no potential conflicts of interest to disclose. NR 44 TC 5 Z9 6 U1 1 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD JUL PY 2012 VL 106 IS 7 BP 1055 EP 1062 DI 10.1016/j.rmed.2012.03.018 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 957LM UT WOS:000305164500018 PM 22541719 ER PT J AU Richman, JS Hosokawa, PW Min, SJ Tomeh, MG Neumayer, L Campbell, DA Henderson, WG Hawn, MT AF Richman, Joshua S. Hosokawa, Patrick W. Min, Sung-Joon Tomeh, Majed G. Neumayer, Leigh Campbell, Darrell A., Jr. Henderson, William G. Hawn, Mary T. TI Toward Prospective Identification of High-Risk Surgical Patients SO AMERICAN SURGEON LA English DT Article AB The purpose of this study was to explore the feasibility of prospectively identifying patients at high risk for surgical complications using automatable methods focused on patient characteristics. We used data from the Michigan Surgical Quality Collaborative (60,411 elective surgeries) performed between 2003 and 2008. Regression models for postoperative mortality, overall morbidity, cardiac, thromboembolic, pulmonary, renal, and surgical site infection complications were developed using preoperative patient and planned procedure data. Risk was categorized by quartiles of predicted probability: "low'' risk corresponding to the bottom quartile, "average'' to the middle two quartiles, and "high'' to the top quartile. C-indices were calculated to measure discrimination; model validity was assessed by cross-validation. Models were repeated using only patient characteristics. Risk category was closely related to event rates; 80 to 90 per cent of mortality and cardiac, renal, and pulmonary complications occurred among the 25 per cent of "high-risk" patients. Although thromboembolisms and surgical site infections were less predictable, 60 to 70 per cent of events occurred among high-risk patients. Cross-validation results were consistent and only slightly attenuated when predictors were restricted to patient characteristics alone. Adverse postoperative events are concentrated among patients identifiable preoperatively as high risk. Preoperative risk assessment could allow for efficient interventions targeted to high-risk patients. C1 [Richman, Joshua S.; Hawn, Mary T.] Birmingham Vet Affairs Med Ctr, C SMART, Birmingham, AL USA. [Richman, Joshua S.; Hawn, Mary T.] Univ Alabama Birmingham, Sch Med, Gastrointestinal Sect, Div Gen Surg, Birmingham, AL USA. [Hosokawa, Patrick W.; Min, Sung-Joon; Henderson, William G.] Univ Colorado, Sch Med, Colorado Hlth Outcomes Program, Denver, CO USA. [Tomeh, Majed G.] QCMetrix, Waltham, MA USA. [Neumayer, Leigh] Univ Utah, Salt Lake City, UT USA. [Campbell, Darrell A., Jr.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Henderson, William G.] Univ Colorado, Sch Publ Hlth, Dept Biostat & Informat, Denver, CO 80202 USA. RP Richman, JS (reprint author), BVAMC, 700 South 19th St,REAP Mail Stop 151, Birmingham, AL 35222 USA. EM jrichman@uab.edu NR 17 TC 5 Z9 5 U1 0 U2 2 PU SOUTHEASTERN SURGICAL CONGRESS PI CUMMING PA 115 SAMARITAN DR, #200, CUMMING, GA 30040-2354 USA SN 0003-1348 EI 1555-9823 J9 AM SURGEON JI Am. Surg. PD JUL PY 2012 VL 78 IS 7 BP 755 EP 760 PG 6 WC Surgery SC Surgery GA V32LX UT WOS:000208953800013 PM 22748533 ER PT J AU Goh, AC Kowalkowski, MA Bailey, DE Kazer, MW Knight, SJ Latini, DM AF Goh, Alvin C. Kowalkowski, Marc A. Bailey, Donald E., Jr. Kazer, Meredith W. Knight, Sara J. Latini, David M. TI Perception of cancer and inconsistency in medical information are associated with decisional conflict: a pilot study of men with prostate cancer who undergo active surveillance SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; decision-making; active surveillance; quality of life; uncertainty AB OBJECTIVE To understand the factors associated with decision-making, we conducted a telephone-based survey as part of a pilot study to develop a psychoeducational intervention for men with prostate cancer who undergo active surveillance. PATIENTS AND METHODS From 2007 to 2008, we conducted a cross-sectional study of 34 individuals on active surveillance for prostate cancer. We examined how specific mental health, quality of life and sociodemographic characteristics relate to decision-making. Five validated decision-making scales were used as primary outcomes reflecting the amount of satisfaction, regret and conflict a participant experienced about his decision to undergo active surveillance. A multivariate regression model was developed to identify specific psychosocial factors related to the decision-making outcomes. RESULTS Primary analyses focused on the decisional satisfaction and conflict measures, as the decisional regret measure showed poor reliability (alpha < 0.70) in this sample. Four psychosocial measures showed strong associations across the decision-making subscales, including the Fife Constructed Meaning Scale (Pearson r > 0.26), Mishel Uncertainty in Illness Scale - Inconsistency (r > 0.32), Mental Health Index-5 (r > 0.33), and Lepore self-efficacy for prostate symptom management scale (r > 0.33). Individuals with higher self-efficacy for prostate cancer symptom management (P = 0.02) and higher positive meaning for cancer (P = 0.03) were less likely to express decision-making conflict as the result of uncertainty. Individuals reporting higher positive meaning for cancer (P = 0.01) and less uncertainty in illness attributed to inconsistency (P = 0.02) were less likely to exhibit decision-making conflict related to the perceived effectiveness of treatment. CONCLUSIONS Men choosing active surveillance represent a patient group with unique vulnerabilities that require new psychoeducational interventions to provide information and support that will maintain and improve quality of life. We describe specific characteristics that may put patients at higher risk during the decision-making process and indicate their increased need for such interventions. C1 [Goh, Alvin C.; Latini, David M.] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. [Kowalkowski, Marc A.; Latini, David M.] Michael E DeBakey VA Med Ctr, VA Hlth Serv Res, Houston, TX USA. [Kowalkowski, Marc A.; Latini, David M.] Michael E DeBakey VA Med Ctr, Dev Ctr Excellence, Houston, TX USA. [Kowalkowski, Marc A.; Latini, David M.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Bailey, Donald E., Jr.] Duke Univ, Sch Nursing, Durham, NC USA. [Kazer, Meredith W.] Fairfield Univ, Fairfield, CT 06430 USA. [Knight, Sara J.] Univ Calif San Francisco, Dept Urol, San Francisco VA Med Ctr, San Francisco, CA USA. [Knight, Sara J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Latini, David M.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. RP Goh, AC (reprint author), Baylor Coll Med, Scott Dept Urol, 6620 Main St Ste 1325, Houston, TX 77030 USA. EM acg622@gmail.com OI Kowalkowski, Marc/0000-0003-2624-4209; Latini, David/0000-0002-6161-4861 FU American Cancer Society [06-083-01-CPPB] FX This material is partly the result of work supported with resources and the use of facilities at the Health Services Research & Development Center of Excellence (HFP90-020), Michael E. DeBakey Veterans Affairs Medical Center. Dr Latini is supported by Mentored Research Scholar Grant 06-083-01-CPPB from the American Cancer Society. The views expressed reflect those of the authors and not necessarily those of the Department of Veterans Affairs or Baylor College of Medicine. NR 25 TC 16 Z9 16 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD JUL PY 2012 VL 110 IS 2B BP E50 EP E56 DI 10.1111/j.1464-410X.2011.10791.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA V31JY UT WOS:000208881100008 PM 22145791 ER PT J AU Fernandez, JF Sibila, O Restrepo, MI AF Fernandez, Juan F. Sibila, Oriol Restrepo, Marcos I. TI Predicting ICU admission in community-acquired pneumonia: clinical scores and biomarkers SO EXPERT REVIEW OF CLINICAL PHARMACOLOGY LA English DT Article DE biomarkers; community-acquired infections; ICU; pneumonia; score; severity AB Community-acquired pneumonia (CAP) remains a common and serious worldwide health problem. Despite all the advances in therapy, significant interest has focused on the identification of patients with CAP who require intensive care unit admission to improve their outcomes. The severity assessment of CAP provides an important guide to clinicians in deciding the site of care and the use of empiric antibiotics and adjuvant therapy. For years, several clinical assessment scores have been suggested and validated to achieve this goal. The recent introduction of biomarkers as prognostic indicators of severe CAP, whether used alone or in conjunction with other clinical severity of illness scores, has been investigated. An objective scoring system with a high level of sensitivity and specificity to predict the severity of CAP and the need for high levels of care do not exist. Today, the addition of clinical scores and biomarkers to clinical judgment is the best approach to optimize the care of severe CAP. Future research will allow validation of these and newer tools to improve the prognosis of patients with CAP. C1 [Fernandez, Juan F.; Sibila, Oriol; Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm Crit Care Med, San Antonio, TX 78229 USA. [Sibila, Oriol] Hosp Santa Creu & Sant Pau, Serv Pneumol, Barcelona, Spain. [Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, Div Pulm Crit Care Med, San Antonio, TX 78229 USA. [Restrepo, Marcos I.] South Texas Vet Hlth Care Syst ALMD, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX 78229 USA. RP Restrepo, MI (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Pulm Crit Care Med, San Antonio, TX 78229 USA. EM restrepom@uthscsa.edu RI Restrepo, Marcos/H-4442-2014 FU National Heart, Lung and Blood Institute [K23HL096054]; Instituto de Salud Carlos III [BAE11/00102]; Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR); Societat Catalana de Pneumologia (SOCAP) FX MI Restrepo has participated in advisory boards for Ortho-McNeil-Janssen, Theravan, Forest Laboratories, Johnson & Johnson, Trius and Novartis. He is a former speaker for Covidien, BARD, Inc, Johnson & Johnson (Ortho-McNeil-Janssen) and Pfizer, and is also a consultant for Theravan, Trius and Pfizer (Wyeth). His time is partially protected by Award Number K23HL096054 from the National Heart, Lung and Blood Institute. O Sibila is supported by Instituto de Salud Carlos III (BAE11/00102), Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR) and Societat Catalana de Pneumologia (SOCAP). 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 119 TC 4 Z9 5 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1751-2441 J9 EXPERT REV CLIN PHAR JI Expert Rev. Clin. Pharmacol. PD JUL PY 2012 VL 5 IS 4 BP 445 EP 458 DI 10.1586/ECP.12.28 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V37PS UT WOS:000209288300016 PM 22943124 ER PT J AU Meyer, JD Stegner, AJ Natelson, BH Cook, DB AF Meyer, Jacob D. Stegner, Aaron J. Natelson, Benjamin H. Cook, Dane B. TI Psychobiological Response To Exercise Differs Between Chronic Fatigue Syndrome (CFS) And CFS With Comorbid Fibromyalgia SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Meyer, Jacob D.; Stegner, Aaron J.] Univ Wisconsin, Madison, WI USA. [Natelson, Benjamin H.] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Cook, Dane B.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. EM jdmeyer3@wisc.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 MA 1496 BP 325 EP 326 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142901253 ER PT J AU Ahluwalia, S AF Ahluwalia, Sangeeta TI IMPROVING THE STATE OF QUALITY MEASUREMENT: LESSONS FROM "DOWN UNDER" SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Ahluwalia, Sangeeta] Vet Adm Greater Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S226 EP S226 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900296 ER PT J AU Caverly, T Richlie, D Prochazka, AV Cook-Shimanek, MK Pawlak, M Woodward, J Stickrath, C AF Caverly, Tanner Richlie, Daniel Prochazka, Allan V. Cook-Shimanek, Margaret K. Pawlak, Mary Woodward, Jennifer Stickrath, Chad TI RISK-BENEFIT DISCUSSION PRIOR TO COMPUTED TOMOGRAPHY IMAGING - INFREQUENT AND INEFFECTIVE? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Caverly, Tanner; Prochazka, Allan V.; Cook-Shimanek, Margaret K.; Pawlak, Mary; Woodward, Jennifer; Stickrath, Chad] Univ Colorado, Denver, CO 80202 USA. [Caverly, Tanner; Richlie, Daniel; Prochazka, Allan V.; Stickrath, Chad] Denver Vet Affairs Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S302 EP S303 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900484 ER PT J AU Chang, E Rose, D Yano, EM Wells, K Lee, M Rubenstein, LV AF Chang, Evelyn Rose, Danielle Yano, Elizabeth M. Wells, Kenneth Lee, Martin Rubenstein, Lisa V. TI DETERMINANTS OF READINESS FOR PRIMARY CARE-MENTAL HEALTH INTEGRATION (PC-MHI) IN THE VA HEALTH CARE SYSTEM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Chang, Evelyn] VA Greater Los Angeles, Los Angeles, CA USA. [Rose, Danielle; Yano, Elizabeth M.; Lee, Martin; Rubenstein, Lisa V.] VA HSR&D Ctr Excellence Study Healthcare Provider, North Hills, CA USA. [Wells, Kenneth] Univ Calif Los Angeles, Los Angeles, CA USA. [Wells, Kenneth; Rubenstein, Lisa V.] RAND Corp, Santa Monica, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 JUL PY 2012 VL 27 SU 2 BP S158 EP S158 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900143 ER PT J AU Cordasco, KM Zephyrin, LC Canelo, I Kessler, C Mallard, M Rubenstein, LV Yano, EM AF Cordasco, Kristina M. Zephyrin, Laurie C. Canelo, Ismelda Kessler, Chad Mallard, Merri Rubenstein, Lisa V. Yano, Elizabeth M. TI 2011 VETERANS' HEALTH ADMINISTRATION EMERGENCY SERVICES FOR WOMEN (ESW) SURVEY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Cordasco, Kristina M.; Canelo, Ismelda; Rubenstein, Lisa V.; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Cordasco, Kristina M.; Rubenstein, Lisa V.] Univ Calif Los Angeles, David Geffin Sch Med, Los Angeles, CA USA. [Zephyrin, Laurie C.; Mallard, Merri] Vet Hlth Adm, Washington, DC USA. [Zephyrin, Laurie C.] VA New York Harbor Healthcare Syst, New York, NY USA. [Kessler, Chad] Jesse Brown VA Hosp, Chicago, IL USA. [Kessler, Chad] Univ Illinois, Chicago, IL USA. [Yano, Elizabeth M.] UCLA Sch Publ Hlth, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S99 EP S99 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900002 ER PT J AU Durant, RW Redmond, N You, ZY Hullett, S Sheppard, AR Scarinci, I AF Durant, Raegan W. Redmond, Nicole You, Zhiying Hullett, Sandral Sheppard, A. Robert Scarinci, Isabel TI RACIAL DIFFERENCES IN SELF-EFFICACY AMONG AFRICAN-AMERICANS AND WHITES WITH HEART FAILURE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Durant, Raegan W.; Redmond, Nicole; You, Zhiying; Sheppard, A. Robert; Scarinci, Isabel] Univ Alabama Birmingham, Birmingham, AL USA. [Durant, Raegan W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Redmond, Nicole; Hullett, Sandral] Cooper Green Mercy Hosp, Birmingham, AL USA. [Sheppard, A. Robert] DCH Reg Med Ctr, Tuscaloosa, AL USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S292 EP S292 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900457 ER PT J AU Edelman, EJ Gordon, KS Becker, W Goulet, JL Skanderson, M Gaither, JR Braden, JB Gordon, A Kerns, R Justice, AC Fiellin, DA AF Edelman, E. J. Gordon, Kirsha S. Becker, William Goulet, Joseph L. Skanderson, Melissa Gaither, Julie R. Braden, Jennifer B. Gordon, Adam Kerns, Robert Justice, Amy C. Fiellin, David A. TI HIV STATUS IS AN INDEPENDENT PREDICTOR OF RECEIVING OPIOID ANALGESICS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Edelman, E. J.; Becker, William; Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Med, New Haven, CT USA. [Gordon, Kirsha S.; Becker, William; Goulet, Joseph L.; Skanderson, Melissa; Kerns, Robert; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Gordon, Kirsha S.] Columbia Univ, Sch Publ Hlth, New York, NY USA. [Gaither, Julie R.] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Braden, Jennifer B.] Univ Washington, Seattle, WA 98195 USA. [Gordon, Adam] Univ Pittsburgh, Pittsburgh, PA USA. [Gordon, Adam] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S203 EP S204 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900247 ER PT J AU Kangovi, S Grande, D Ryan, DA Meehan, P Mitra, N Shannon, R Long, JA AF Kangovi, Shreya Grande, David Ryan, Daniel A. Meehan, Patricia Mitra, Nandita Shannon, Richard Long, Judith A. TI PERCEPTIONS OF READMITTED PATIENTS ON THE TRANSITION FROM HOSPITAL TO HOME SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Kangovi, Shreya; Long, Judith A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Kangovi, Shreya; Ryan, Daniel A.] Robert Wood Johnson Fdn Clin Scholars Program, Philadelphia, PA USA. [Grande, David; Shannon, Richard; Long, Judith A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Grande, David; Mitra, Nandita] Univ Penn, Philadelphia, PA 19104 USA. [Meehan, Patricia] Univ Penn Hlth Syst, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S271 EP S271 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900405 ER PT J AU Kertesz, S Pollio, DE Holt, C Steward, JL Gordon, A Kim, TW Stringfellow, E Austin, E Golden, J Johnson, N Davis, LL AF Kertesz, Stefan Pollio, David E. Holt, Cheryl Steward, Jocelyn L. Gordon, Adam Kim, Theresa W. Stringfellow, Erin Austin, Erika Golden, Joya Johnson, Nancy Davis, Lori L. TI COMPARISON OF TAILORED VERSUS MAINSTREAM PRIMARY CARE DELIVERY FOR HOMELESS PERSONS: A NEW, VALIDATED PATIENT ASSESSMENT TOOL SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Kertesz, Stefan; Austin, Erika; Johnson, Nancy] Birmingham VAMC, Homewood, AL USA. [Kertesz, Stefan; Pollio, David E.; Steward, Jocelyn L.; Davis, Lori L.] Univ Alabama Birmingham, Birmingham, AL USA. [Kim, Theresa W.; Stringfellow, Erin] Boston Hlth Care Homeless, Boston, MA USA. [Holt, Cheryl] Univ Maryland, Baltimore, MD 21201 USA. [Golden, Joya] VA Greater Los Angeles, Los Angeles, CA USA. [Gordon, Adam] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S147 EP S147 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900118 ER PT J AU Korthuis, T Marshall, R Beach, MC Saha, S Mori, T Loveless, MO Hibbard, JH Cohn, JA Sharp, VL AF Korthuis, Todd Marshall, Rebecca Beach, Mary Catherine Saha, Somnath Mori, Tomi Loveless, Mark O. Hibbard, Judith H. Cohn, Jonathan A. Sharp, Victoria L. TI PATIENT ACTIVATION AND IMPROVED OUTCOMES IN HIV-INFECTED PATIENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Korthuis, Todd; Marshall, Rebecca; Saha, Somnath; Mori, Tomi; Loveless, Mark O.; Hibbard, Judith H.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Beach, Mary Catherine] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Saha, Somnath] Portland VA Med Ctr, Portland, OR USA. [Hibbard, Judith H.] Univ Oregon, Eugene, OR 97403 USA. [Cohn, Jonathan A.] Wayne State Univ, Detroit, MI USA. [Sharp, Victoria L.] St Lukes Roosevelt Hosp, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S261 EP S262 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900381 ER PT J AU Kullgren, JT Loewenstein, G Troxel, AB Norton, L Wesby, L Zhu, JS Tao, YY Volpp, KG AF Kullgren, Jeffrey T. Loewenstein, George Troxel, Andrea B. Norton, Laurie Wesby, Lisa Zhu, Jingsan Tao, Yuanyuan Volpp, Kevin G. TI A RANDOMIZED CONTROLLED TRIAL OF FINANCIAL INCENTIVES TO PROMOTE WEIGHT LOSS AMONG OBESE EMPLOYEES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Kullgren, Jeffrey T.; Norton, Laurie; Volpp, Kevin G.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Kullgren, Jeffrey T.; Troxel, Andrea B.; Norton, Laurie; Wesby, Lisa; Zhu, Jingsan; Tao, Yuanyuan; Volpp, Kevin G.] Univ Penn, Philadelphia, PA 19104 USA. [Loewenstein, George] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. NR 0 TC 0 Z9 0 U1 1 U2 7 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 JUL PY 2012 VL 27 SU 2 BP S102 EP S103 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900010 ER PT J AU Lam, KD Miao, YH Steinman, MA AF Lam, Khoa D. Miao, Yinghui Steinman, Michael A. TI CUMULATIVE CHANGES IN USE OF CHRONIC MEDICATIONS: A NEW MEASURE OF PRESCRIBING INTENSITY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Lam, Khoa D.; Steinman, Michael A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Miao, Yinghui; Steinman, Michael A.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S151 EP S151 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900128 ER PT J AU Lawrence, V Noel, PH Yoder, LH Cornell, JE Johnson, AE Hsu, JR Wolf, SE AF Lawrence, Valerie Noel, Polly H. Yoder, Linda H. Cornell, John E. Johnson, Anthony E. Hsu, Joseph R. Wolf, Steven E. TI MENTAL HEALTH STATUS AND PHYSICAL FUNCTION OF COMBAT-INJURED MILITARY PERSONNEL AT HOSPITAL DISCHARGE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Lawrence, Valerie; Noel, Polly H.; Cornell, John E.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Lawrence, Valerie; Noel, Polly H.; Cornell, John E.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Yoder, Linda H.] Univ Texas Austin, Austin, TX 78712 USA. [Yoder, Linda H.; Hsu, Joseph R.] US Army Inst Surg Res, Ft Sam Houston, TX USA. [Johnson, Anthony E.; Hsu, Joseph R.] San Antonio Mil Med Ctr, Ft Sam Houston, TX USA. [Wolf, Steven E.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S246 EP S247 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900347 ER PT J AU Liu, CF Perkins, M Wong, E Bryson, CL AF Liu, Chuan-Fen Perkins, Mark Wong, Edwin Bryson, Christopher L. TI SURVEY RESPONSES AND MEDICATION ADHERENCE AMONG DIABETIC PATIENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Liu, Chuan-Fen; Perkins, Mark; Wong, Edwin; Bryson, Christopher L.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Liu, Chuan-Fen; Bryson, Christopher L.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S312 EP S312 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900507 ER PT J AU Lynch, CP Gebregziabher, M Hunt, KJ Echols, C Gilbert, G Egede, LE AF Lynch, Cheryl P. Gebregziabher, Mulugeta Hunt, Kelly J. Echols, Carrae Gilbert, Gregory Egede, Leonard E. TI IMPACT OF MEDICAL AND PSYCHIATRIC COMORBIDITY BURDEN AND MORTALITY IN VETERANS WITH TYPE 2 DIABETES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Lynch, Cheryl P.; Gebregziabher, Mulugeta; Hunt, Kelly J.; Echols, Carrae; Gilbert, Gregory; Egede, Leonard E.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Lynch, Cheryl P.; Gebregziabher, Mulugeta; Hunt, Kelly J.; Egede, Leonard E.] Med Univ S Carolina, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S219 EP S220 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900280 ER PT J AU Lynch, CP Gebregziabher, M Axon, RN Hunt, KJ Echols, C Egede, LE AF Lynch, Cheryl P. Gebregziabher, Mulugeta Axon, R. Neal Hunt, Kelly J. Echols, Carrae Egede, Leonard E. TI COMPARISON OF COMORBIDITY RISK ADJUSTMENT METHODS IN A NATIONAL COHORT OF VETERANS WITH DIABETES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Lynch, Cheryl P.; Gebregziabher, Mulugeta; Axon, R. Neal; Hunt, Kelly J.; Egede, Leonard E.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Lynch, Cheryl P.; Gebregziabher, Mulugeta; Axon, R. Neal; Hunt, Kelly J.; Echols, Carrae; Egede, Leonard E.] Med Univ S Carolina, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S146 EP S147 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900117 ER PT J AU Simonetti, JA Fine, MJ Simak, DM Chen, YF Hess, R AF Simonetti, Joseph A. Fine, Michael J. Simak, Deborah M. Chen, Yi-Fan Hess, Rachel TI RACIAL DISPARITIES IN INTERMEDIATE OUTCOMES OF DIABETES CARE IN A PATIENT-CENTERED MEDICAL HOME SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Simonetti, Joseph A.; Fine, Michael J.; Simak, Deborah M.; Hess, Rachel] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Chen, Yi-Fan] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S291 EP S291 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900455 ER PT J AU Snyder, E Castiglioni, A Estrada, C You, ZY Kertesz, S Schumacher, JE AF Snyder, Erin Castiglioni, Analia Estrada, Carlos You, Zhiying Kertesz, Stefan Schumacher, Joseph E. TI AN EDUCATIONAL INTERVENTION TO IMPROVE OPIATE PRESCRIBING PRACTICES IN RESIDENT CLINIC SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Snyder, Erin; Castiglioni, Analia; Estrada, Carlos; You, Zhiying; Kertesz, Stefan; Schumacher, Joseph E.] Univ Alabama Birmingham, Birmingham, AL USA. [Snyder, Erin; Castiglioni, Analia; Estrada, Carlos; Kertesz, Stefan] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S119 EP S120 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900050 ER PT J AU Stickrath, C Griffiths, M Prochazka, AV Aagaard, EM Anderson, M Deloughry, MN AF Stickrath, Chad Griffiths, Megan Prochazka, Allan V. Aagaard, Eva M. Anderson, Melver Deloughry, Melissa N. TI MAXIMIZING TEACHING EFFECTIVENESS: PREDICTORS OF LEARNER SATISFACTION WITH TEACHING ON ROUNDS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Stickrath, Chad; Prochazka, Allan V.; Anderson, Melver] Denver VA Med Ctr, Denver, CO USA. [Stickrath, Chad; Griffiths, Megan; Prochazka, Allan V.; Aagaard, Eva M.; Anderson, Melver; Deloughry, Melissa N.] Univ Colorado Denver, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S244 EP S244 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900341 ER PT J AU Volpp, KG Norton, L Shea, JA Zhu, JS Small, D Basner, M Ecker, A Dinges, D Mollicone, D Novak, C Bellini, L AF Volpp, Kevin G. Norton, Laurie Shea, Judy A. Zhu, Jingsan Small, Dylan Basner, Mathias Ecker, Adrian Dinges, David Mollicone, Daniel Novak, Cristina Bellini, Lisa TI A RANDOMIZED CONTROLLED TRIAL OF THE FEASIBILITY OF A PROTECTED SLEEP PERIOD FOR MEDICAL INTERNS IN THE HOSPITAL FOR PROLONGED DUTY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Volpp, Kevin G.; Norton, Laurie; Shea, Judy A.; Zhu, Jingsan; Small, Dylan; Basner, Mathias; Ecker, Adrian; Dinges, David; Novak, Cristina; Bellini, Lisa] Univ Penn, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Norton, Laurie; Novak, Cristina] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Mollicone, Daniel] Pulsar Informat, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S103 EP S103 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900011 ER PT J AU Wamsley, MA Batki, SL Dunlop, M Julian, K McCance-Katz, E O'Sullivan, PS Satterfield, J AF Wamsley, Maria A. Batki, Steven L. Dunlop, Miranda Julian, Katherine McCance-Katz, Elinore O'Sullivan, Patricia S. Satterfield, Jason TI A BRIEF CURRICULAR INTERVENTION TO IMPROVE SCREENING AND BRIEF INTERVENTIONS FOR SUBSTANCE ABUSE IN THE PRIMARY CARE SETTING DOES NOT IMPROVE PERFORMANCE ON A STANDARDIZED PATIENT ASSESSMENT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Wamsley, Maria A.; Batki, Steven L.; Dunlop, Miranda; Julian, Katherine; McCance-Katz, Elinore; O'Sullivan, Patricia S.; Satterfield, Jason] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Batki, Steven L.] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S100 EP S100 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900003 ER PT J AU Williams, B Ahalt, C AF Williams, Brie Ahalt, Cyrus TI PAYING THE PRICE: THE DEARTH OF PUBLICALLY AVAILABLE PRISON HEALTHCARE COST DATA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Williams, Brie; Ahalt, Cyrus] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Williams, Brie] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S269 EP S269 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900400 ER PT J AU Lam, J Simpson, PC Yang, PC Dash, R AF Lam, Justin Simpson, Paul C. Yang, Phillip C. Dash, Rajesh TI Synthesis of an In vivo MRI-detectable Apoptosis Probe SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Molecular Biology; Issue 65; Biomedical Engineering; conjugation; annexin; iron oxide; nanoparticle; MRI; molecular imaging AB Cellular apoptosis is a prominent feature of many diseases, and this programmed cell death typically occurs before clinical manifestations of disease are evident. A means to detect apoptosis in its earliest, reversible stages would afford a pre-clinical 'window' during which preventive or therapeutic measures could be taken to protect the heart from permanent damage. We present herein a simple and robust method to conjugate human Annexin V (ANX), which avidly binds to cells in the earliest, reversible stages of apoptosis, to superparamagnetic iron oxide (SPIO) nanoparticles, which serve as an MRI-detectable contrast agent. The conjugation method begins with an oxidation of the SPIO nanoparticles, which oxidizes carboxyl groups on the polysaccharide shell of SPIO. Purified ANX protein is then added in the setting of a sodium borate solution to facilitate covalent interaction of ANX with SPIO in a reducing buffer. A final reduction step with sodium borohydride is performed to complete the reduction, and then the reaction is quenched. Unconjugated ANX is removed from the mix by microcentrifuge filtration. The size and purity of the ANX-SPIO product is verified by dynamic light scattering (DLS). This method does not require addition to, or modification of, the polysaccharide SPIO shell, as opposed to cross-linked iron oxide particle conjugation methods or biotin-labeled nanoparticles. As a result, this method represents a simple, robust approach that may be extended to conjugation of other proteins of interest. C1 [Lam, Justin; Yang, Phillip C.; Dash, Rajesh] Stanford Univ, Med Ctr, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA. [Simpson, Paul C.] Univ Calif San Francisco, Dept Med, Div Cardiol, San Francisco, CA 94143 USA. [Simpson, Paul C.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Dash, R (reprint author), Stanford Univ, Med Ctr, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA. EM rdash@cvmed.stanford.edu FU National Institutes of Health, NHLBI; American Heart Association; Stanford University, VPUE Grant FX National Institutes of Health, NHLBI (RD, PY, PS).; American Heart Association (JL).; Stanford University, VPUE Grant (JL). NR 12 TC 1 Z9 1 U1 1 U2 2 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD JUL PY 2012 IS 65 AR UNSP e3775 DI 10.3791/3775 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36PJ UT WOS:000209223200011 ER PT J AU Maguen, S Lau, KM Madden, E Seal, K AF Maguen, Shira Lau, Karen M. Madden, Erin Seal, Karen TI Factors Associated With Completing Comprehensive Traumatic Brain Injury Evaluation SO MILITARY MEDICINE LA English DT Article AB This study examined factors associated with Iraq and Afghanistan Veterans following up with the Department of Veterans Affairs (VA) comprehensive traumatic brain injury (TBI) evaluation after a positive first-level VA TBI screen. Participants included 465 Iraq and Afghanistan Veterans at one VA Medical Center and its five affiliated community-based outpatient clinics, with a positive initial TBI screen between April 1, 2007 and June 1, 2010. We found that 75% of Veterans completed the comprehensive TBI evaluation. Women were three times less likely to complete the comprehensive TBI evaluation than men, and those who endorsed post-traumatic stress disorder avoidance symptoms were nearly two times less likely to complete the comprehensive TBI evaluation. In contrast, headaches, Hispanic ethnicity, and the season of the initial TBI screen (summer vs. winter) were positively associated with completing a comprehensive TBI evaluation. A substantial minority of Veterans who screen positive on the VA initial TBI screen fail to present for the comprehensive TBI evaluation. Addressing specific gender-related issues, avoidance, and the timing of referrals in the context of VA polytrauma programs may increase the likelihood that Veterans receive further assessment, education, and early intervention for TBI or other mental health problems to prevent chronic postdeployment disability. C1 [Maguen, Shira; Lau, Karen M.; Madden, Erin; Seal, Karen] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Maguen, Shira; Seal, Karen] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Maguen, Shira; Seal, Karen] Hlth Serv Res, Dev Res Enhancement Award Program, San Francisco, CA 94121 USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. FU Department of Defense Psychological Health and Traumatic Brain Injury (PH/TBI) Research Program [W81XWH-05-2-0094]; VA Health Sciences Research and Development Career Development Award [RCD06042A] FX We thank Gary Abrams, MD; Don Donati; Thomas Neylan, MD; Richard Pham, PhD; and Guiomar Scheid for their contributions. This research was supported by grants to Shira Maguen, PhD, by the Department of Defense Psychological Health and Traumatic Brain Injury (PH/TBI) Research Program (W81XWH-05-2-0094) and VA Health Sciences Research and Development Career Development Award (RCD06042A). NR 20 TC 3 Z9 3 U1 1 U2 1 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD JUL PY 2012 VL 177 IS 7 BP 797 EP 803 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA V33NZ UT WOS:000209026800007 PM 22808886 ER PT J AU Maguen, S Cohen, B Cohen, G Madden, E Bertenthal, D Seal, K AF Maguen, Shira Cohen, Beth Cohen, Greg Madden, Erin Bertenthal, Daniel Seal, Karen TI Eating Disorders and Psychiatric Comorbidity among Iraq and Afghanistan Veterans SO WOMENS HEALTH ISSUES LA English DT Article AB Objective: Individuals with mental health problems are at elevated risk for eating disorders. Veterans serving in support of the conflicts in Afghanistan and Iraq (OEF/OIF) have a high prevalence of deployment-related mental health problems, but little is known about their risk for eating disorders. Our aim was to determine rates of eating disorder diagnoses among OEF/OIF veterans with mental health problems, particularly among those with comorbid mental health problems. Methods: This retrospective, cross-sectional analysis of nationwide VA healthcare facilities used descriptive statistics and regression analyses to determine eating disorder rates in OEF/OIF veterans who were new users of VA healthcare from October 7, 2001 to December 31, 2010 (N = 593,739). Results: Although the prevalence of eating disorder diagnoses was 0.007% (n = 465) in women and <0.001% (n = 192) in men, veterans diagnosed with mental health problems were significantly more likely to have an eating disorder than those without mental health diagnoses. Eating disorders were significantly more common in women with depression, posttraumatic stress disorder, and alcohol and/or drug use disorders than in women veterans without these mental health disorders. Among men, the associations between eating disorder diagnoses and comorbid mental health diagnoses closely paralleled those observed in women. Conclusions: Rates of eating disorders are significantly higher among returning veterans with comorbid mental health problems compared with those without mental health diagnoses. Further research should examine methods to improve detection and treatment of eating disorders in this population. C1 [Maguen, Shira; Cohen, Beth; Cohen, Greg; Madden, Erin] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Bertenthal, Daniel] San Francisco VA Med Ctr, Mental Illness Res Educ & Clin Ctr, San Francisco, CA 94121 USA. [Seal, Karen] San Francisco VA Med Ctr, Iraq Afghanistan Vet Integrated Care Clin, San Francisco, CA 94121 USA. [Maguen, Shira; Cohen, Beth; Seal, Karen] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, 4150 Clement St,116-P, San Francisco, CA 94121 USA. EM Shira.Maguen@va.gov FU NHLBI NIH HHS [K23 HL 094765-01] NR 19 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2012 VL 22 IS 4 BP E403 EP E406 DI 10.1016/j.whi.2012.04.005 PG 4 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA V33SS UT WOS:000209039100009 PM 22749199 ER PT J AU Seo, SW Lee, JM Im, K Park, JS Kim, SH Kim, ST Ahn, HJ Chin, J Cheong, HK Weiner, MW Na, DL AF Seo, Sang Won Lee, Jong-Min Im, Kiho Park, Jun-Sung Kim, Sook-Hui Kim, Sung Tae Ahn, Hyun-Jung Chin, Juhee Cheong, Hae-Kwan Weiner, Michael W. Na, Duk L. TI Cortical thinning related to periventricular and deep white matter hyperintensities SO NEUROBIOLOGY OF AGING LA English DT Article DE White matter hyperintensities; Periventricle white matter hyperintensities; Deep white matter hyperintensities; Cortical thickness; Cognitive impairment; Dementia; Mild cognitive impairment ID MILD COGNITIVE IMPAIRMENT; SUBCORTICAL VASCULAR DEMENTIA; ALZHEIMERS-DISEASE; CEREBRAL MICROANGIOPATHY; CEREBROVASCULAR-DISEASE; CHOLINERGIC PATHWAYS; LESIONS; BRAIN; MRI; DECLINE AB Previous studies showed that white matter hyperintensities (WMH) are related to cognitive decline in patients with mild cognitive impairment (MCI) or dementia. Moreover, periventricular WMH (periventricular white matter hyperintensities (PWMH)) and deep WMH (deep white matter hyperintensities (DWMH)) may have different effects on cognition. The purpose of this study is to investigate the contributions of PWMH and DWMH to the topography of cortical thinning and to investigate the relationship among WMH, cortical thinning, and cognitive impairments. Participants included 226 patients with Alzheimer's disease or subcortical vascular dementia, and 135 patients with amnestic MCI or subcortical vascular MCI. Cortical thickness was measured using the surface based method. The topography of cortical thinning related to WMH was distributed in the frontal and perisylvian regions, which was similar to that of PWMH. In contrast, there were only small areas of cortical thinning inversely associated with DWMH, which were distributed in medial frontal and lingual gyrus. PWMH, but not DWMH, were associated with the frontal thinning and executive dysfunction; where both PWMH and frontal thinning were independently associated with executive dysfunction. Our results suggest that PWMH are associated with frontal thinning, which is further associated with frontal executive dysfunction. (C) 2012 Elsevier Inc. All rights reserved. C1 [Seo, Sang Won; Ahn, Hyun-Jung; Chin, Juhee; Na, Duk L.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Neurol, Seoul, South Korea. [Lee, Jong-Min] Hanyang Univ, Dept Biomed Engn, Seoul 133791, South Korea. [Im, Kiho; Park, Jun-Sung] Harvard Univ, Div Newborn Med, Childrens Hosp Boston, Sch Med, Cambridge, MA 02138 USA. [Kim, Sook-Hui] Konkuk Univ, Dept Neurol, Konkuk Univ Hosp, Sch Med, Seoul, South Korea. [Kim, Sung Tae] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Radiol, Seoul, South Korea. [Cheong, Hae-Kwan] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Social & Prevent Med, Seoul, South Korea. [Weiner, Michael W.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. RP Na, DL (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Neurol, Seoul, South Korea. EM dukna@skku.edu RI Na, Duk Lyul/C-9598-2011 OI Cheong, Hae-Kwan/0000-0003-2758-9399 FU Ministry for Health, Welfare and family Affairs, Republic of Korea [A050079]; Korean Science and Engineering Foundation (KOSEF) NRL; Korean government (MEST) [R0A-2007-000-20068-0]; Samsung Medical Center [CRL-108011, CRS 110-14-1] FX This study was supported by a grant from the Korean Healthcare Technology R&D Project, Ministry for Health, Welfare and family Affairs, Republic of Korea (A050079), a Korean Science and Engineering Foundation (KOSEF) NRL program grant funded by the Korean government (MEST; R0A-2007-000-20068-0), and a Samsung Medical Center Clinical Research Development Program grant (CRL-108011 and CRS 110-14-1). NR 55 TC 33 Z9 34 U1 1 U2 11 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 JUL PY 2012 VL 33 IS 7 BP 1156 EP + DI 10.1016/j.neurobiolaging.2010.12.003 PG 13 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 953GG UT WOS:000304854300006 PM 21316813 ER PT J AU Beeri, MS Schmeidler, J Lesser, GT Maroukian, M West, R Leung, S Wysocki, M Perl, DP Purohit, DP Haroutunian, V AF Beeri, Michal Schnaider Schmeidler, James Lesser, Gerson T. Maroukian, Maria West, Rebecca Leung, Stephanie Wysocki, Michael Perl, Daniel P. Purohit, Dushyant P. Haroutunian, Vahram TI Corticosteroids, but not NSAIDs, are associated with less Alzheimer neuropathology SO NEUROBIOLOGY OF AGING LA English DT Article DE Glucocorticoids; Corticosteroids; Nonsteroidal anti-inflammatory drugs (NSAIDs); Neuritic plaques; Neurofibrillary tangles ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE FUNCTION; P-GLYCOPROTEIN; CACHE COUNTY; DISEASE; BRAIN; INFLAMMATION; DEMENTIA; GLUCOCORTICOIDS; PREDNISOLONE AB The objective of this study was to test the hypothesis that corticosteroid and nonsteroidal anti-inflammatory drug (NSAID) medications are associated with less global and regional Alzheimer's disease (AD) neuropathology. This postmortem study was based on 694 brains of subjects from the Mount Sinai School of Medicine Brain Bank who did not have neuropathologies other than neuritic plaques (NPs), neurofibrillary tangles (NFTs), or cerebrovascular disease. Densities of NPs and of NFTs were assessed in several neocortical regions and in the hippocampus, entorhinal cortex, and amygdala. Counts of NPs in several neocortical regions were also assessed. For each neuropathology measure, analyses of covariance controlling for age at death and sex compared subjects who received only corticosteroids (n = 54) or those who received only NSAIDs (n = 56) to the same comparison group, subjects who received neither (n = 576). Subjects receiving corticosteroids had significantly lower ratings and counts of NPs for all neuropathological measures, and NFTs overall and in the cerebral cortex and amygdala. In contrast, no measures were significant for subjects who received NSAIDs. Use of corticosteroids was associated with approximately 50% fewer NPs and NFTs in most brain regions examined, compared with nonmedicated subjects. In contrast, use of NSAIDs was not substantially associated with the reductions in hallmark lesions of AD. Because corticosteroids have anti-inflammatory as well as a myriad of other neurobiological effects, more direct studies in model systems could reveal novel therapeutic targets and mechanisms for AD lesion reduction. (C) 2012 Elsevier Inc. All rights reserved. C1 [Beeri, Michal Schnaider; Schmeidler, James; Maroukian, Maria; West, Rebecca; Leung, Stephanie; Wysocki, Michael; Haroutunian, Vahram] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Lesser, Gerson T.] Jewish Home & Hosp, New York, NY USA. [Perl, Daniel P.; Purohit, Dushyant P.] Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA. [Haroutunian, Vahram] James J Peters VA Med Ctr, Bronx, NY USA. RP Beeri, MS (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave Levy Pl,Box 1230, New York, NY 10029 USA. EM michal.beeri@mssm.edu FU NIA [K01 AG023515-01, R01 AG034087, P01 AG02219]; Graubard Fund; Berkman Trust; Leir Foundation; ADRC [P50 AG05138] FX Study funding: supported by NIA grants K01 AG023515-01 and R01 AG034087 (MSB), P01 AG02219 (VH), and P50 AG05138 (ADRC- Dr. M. Sano), as well as by the Graubard Fund (MSB) and the Berkman Trust and Leir Foundation (VH). NR 43 TC 9 Z9 9 U1 2 U2 10 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 JUL PY 2012 VL 33 IS 7 BP 1258 EP 1264 DI 10.1016/j.neurobiolaging.2011.02.011 PG 7 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 953GG UT WOS:000304854300016 PM 21458888 ER PT J AU Ksiezak-Reding, H Ho, L Santa-Maria, I Diaz-Ruiz, C Wang, J Pasinetti, GM AF Ksiezak-Reding, Hanna Ho, Lap Santa-Maria, Ismael Diaz-Ruiz, Carmen Wang, Jun Pasinetti, Giulio Maria TI Ultrastructural alterations of Alzheimer's disease paired helical filaments by grape seed-derived polyphenols SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; Paired helical filaments; Tau protein; Ultrastructure; Grape seed polyphenols; Immunogold labeling ID AMYLOID FIBRIL FORMATION; CROSS-BETA-STRUCTURE; IN-VITRO; TAU AGGREGATION; NEUROFIBRILLARY TANGLES; CORE DOMAIN; PROTEIN-TAU; BINDING; INHIBITION; EXTRACT AB Abnormal folding of the microtubule-associated protein tau leads to aggregation of tau into paired helical filaments (PHFs) and neurofibrillary tangles, the major hallmark of Alzheimer's disease (AD). We have recently shown that grape seed polyphenol extract (GSPE) reduces tau pathology in the TMHT mouse model of tauopathy (Wang et al., 2010). In the present studies we assessed the impact of GSPE exposure on the ultrastructure of PHFs isolated from Alzheimer's disease brain. Transmission electron microscopy revealed that GSPE induced profound dose-and time-dependent alterations in the morphology of PHFs with partial disintegration of filaments. Filaments showed similar to 2-fold enlargement in width and displayed numerous protrusions and splayed ends consistent with unfolding of tau and diminished structural stability. In addition, GSPE induced a reduction in immunogold labeling with antibodies against the C-terminal half (12E8, PHF-1) and the middle region of tau (AT8, Tau5, pSer214 tau, and AT180) but not the C-terminal end (Tau46). In comparison, labeling of N-terminus (Alz50) was enhanced. It is unlikely that alterations in immunogold labeling were due to biochemical alterations, e. g., protein phosphatase or proteolytic activities potentially stimulated by GSPE, because western blotting studies have shown the preservation of full length polypeptides of tau and their phospho-epitopes in GSPE-treated samples. The GSPE mechanism may include a noncovalent interaction of polyphenols with proline residues in the proline-rich domain of tau, with Pin1 sites at P213 and P232 most seriously affected as judged by suppression of labeling. Collectively, our results suggest that GSPE has a significant potential for therapeutic development by neutralizing phospho-epitopes and disrupting fibrillary conformation leading to disintegration of PHFs. (C) 2012 Elsevier Inc. All rights reserved. C1 [Ksiezak-Reding, Hanna; Ho, Lap; Santa-Maria, Ismael; Diaz-Ruiz, Carmen; Wang, Jun; Pasinetti, Giulio Maria] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Ksiezak-Reding, Hanna; Ho, Lap; Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Santa-Maria, Ismael] Queen Sofia Fdn, CIEN Fdn, Alzheimer Dis Res Unit, Madrid, Spain. RP Ksiezak-Reding, H (reprint author), Mt Sinai Sch Med, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM hanna.reding@mssm.edu OI Diaz-Ruiz, Carmen/0000-0002-0112-0595 FU Society for Progressive Supranuclar Palsy; NIH [PO1 AT004511]; Veterans Administration FX The authors gratefully acknowledge the financial support from the Society for Progressive Supranuclar Palsy, NIH PO1 AT004511, and support in part from MERIT Review grant from Veterans Administration to GMP. NR 52 TC 22 Z9 25 U1 1 U2 24 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 JUL PY 2012 VL 33 IS 7 BP 1427 EP 1439 DI 10.1016/j.neurobiolaging.2010.11.006 PG 13 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 953GG UT WOS:000304854300033 PM 21196065 ER PT J AU Bedimo, R Kyriakides, T Brown, S Weidler, J Lie, Y Coakley, E Holodniy, M AF Bedimo, R. Kyriakides, T. Brown, S. Weidler, J. Lie, Y. Coakley, E. Holodniy, M. TI Predictive value of HIV-1 replication capacity and phenotypic susceptibility scores in antiretroviral treatment-experienced patients SO HIV MEDICINE LA English DT Article DE antiretroviral therapy; HIV; phenotypic susceptibility score; replication capacity; resistance ID HUMAN-IMMUNODEFICIENCY-VIRUS; DISEASE PROGRESSION; REVERSE-TRANSCRIPTASE; RESISTANCE MUTATIONS; VIROLOGICAL FAILURE; DRUG SUSCEPTIBILITY; INFECTED PATIENTS; CLINICAL-TRIAL; EX-VIVO; THERAPY AB Objectives The aim of the study was to determine the prognostic value of HIV replication capacity (RC) for subsequent antiretroviral (ARV) treatment response in ARV-experienced patients. Methods RC and phenotypic resistance testing were performed at baseline and week 12 on plasma samples from patients randomized to undergo a 12-week ARV drug-free period (ARDFP) or initiate immediate salvage therapy (no-ARDFP group) in the Options in Management with Antiretrovirals (OPTIMA) trial. Dichotomous and incremental phenotypic susceptibility scores (dPSSs and iPSSs, respectively) were calculated. The predictive value of RC and PSS for ARV therapy response and/or ARDFP was evaluated using multivariate regression analysis and Pearson correlations. Results In 146 no-ARDFP subjects, baseline RC (50.8%) did not change at week 12 and was not correlated with CD4 cell count or viral load changes at week 12 (P?=?0.33 and P?=?0.79, respectively) or at week 24 (P?=?0.96 and P?=?0.14, respectively). dPSS predicted virological but not CD4 cell count response to ARV therapy at weeks 12, 24 and 48 (P?=?0.002, P?c, Mr. Rene Costello, Dr. Omer Bonne, Dr. Gyorgy Csako, Dr. Alan Remaley, Dr. Alexander Neumeister, and Dr. Mitchel A. King have no conflicts to disclose. Dr. Wayne C. Drevets has reported that the research support for this project was provided entirely by the NIMH DIRP. Although Dr. Drevets has no financial conflicts that are relevant to the subject matter of the manuscript, during the past two years he has served as a consultant for the following companies: Pfizer, Eisai, Rules Based Medicine, Johnson and Johnson. Dr. Drevets also is named as co-inventor for a Use Patent filed by the NIMH for Scopolamine in the Treatment of Depression. Dr. Dennis S. Charney has reported that he and Mount Sinai School of Medicine have been named on a use patent of Ketamine for the treatment of depression. If Ketamine were shown to be effective in the treatment of depression and received approval from the Food and Drug Administration (FDA) for this indication, Dr. Charney and Mount Sinai School of Medicine could benefit financially. Dr. Charney has also disclosed that he is not currently engaged in any consulting activity and has had no activity for the past three years. NR 32 TC 7 Z9 7 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUN 27 PY 2012 VL 520 IS 1 BP 1 EP 5 DI 10.1016/j.neulet.2012.04.072 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 969AE UT WOS:000306027300001 PM 22579817 ER PT J AU Pietrzak, RH Tracy, M Galea, S Kilpatrick, DG Ruggiero, KJ Hamblen, JL Southwick, SM Norris, FH AF Pietrzak, Robert H. Tracy, Melissa Galea, Sandro Kilpatrick, Dean G. Ruggiero, Kenneth J. Hamblen, Jessica L. Southwick, Steven M. Norris, Fran H. TI Resilience in the Face of Disaster: Prevalence and Longitudinal Course of Mental Disorders following Hurricane Ike SO PLOS ONE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; NEUROPSYCHIATRIC INTERVIEW MINI; NATIONAL COMORBIDITY SURVEY; INTIMATE PARTNER VIOLENCE; MASS TRAUMATIC EVENT; IV ALCOHOL-ABUSE; DSM-IV; PTSD CHECKLIST; PSYCHOLOGICAL RESILIENCE; PSYCHOMETRIC PROPERTIES AB Objectives: Natural disasters may increase risk for a broad range of psychiatric disorders, both in the short-and in the medium-term. We sought to determine the prevalence and longitudinal course of posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD), depression, and suicidality in the first 18 months after Hurricane Ike. Methods: Six hundred fifty-eight adults representative of Galveston and Chambers Counties, Texas participated in a random, population-based survey. The initial assessment was conducted 2 to 5 months after Hurricane Ike struck Galveston Bay on September 13, 2008. Follow-up assessments were conducted at 5 to 9 and 14 to 18 months after Hurricane Ike. Results: Past-month prevalence of any mental disorder (20.6% to 10.9%) and hurricane-related PTSD (6.9% to 2.5%) decreased over time. Past-month prevalence of PTSD related to a non-disaster traumatic event (5.8% to 7.1%), GAD (3.1% to 1.8%), PD (0.8% to 0.7%), depression (5.0% to 5.6%), and suicidality (2.6% to 4.2%) remained relatively stable over time. Conclusions: PTSD, both due to the hurricane and due to other traumatic events, was the most prevalent psychiatric disorder 2 to 5 months after Hurricane Ike. Prevalence of psychiatric disorders declined rapidly over time, suggesting that the vast majority of individuals exposed to this natural disaster 'bounced back' and were resilient to long-term mental health consequences of this large-scale traumatic event. C1 [Pietrzak, Robert H.; Southwick, Steven M.] Vet Affairs Connecticut Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, West Haven, CT USA. [Pietrzak, Robert H.; Southwick, Steven M.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Pietrzak, Robert H.; Tracy, Melissa; Galea, Sandro; Kilpatrick, Dean G.; Ruggiero, Kenneth J.; Hamblen, Jessica L.; Southwick, Steven M.; Norris, Fran H.] Natl Ctr Disaster Mental Hlth Res, White River Jct, VT USA. [Tracy, Melissa; Galea, Sandro] Columbia Univ, Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Kilpatrick, Dean G.; Ruggiero, Kenneth J.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Kilpatrick, Dean G.; Ruggiero, Kenneth J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Hamblen, Jessica L.; Norris, Fran H.] White River Junct Vet Affairs Med Ctr, Natl Ctr Posttraumat Stress Disorder, White River Jct, VT USA. [Norris, Fran H.] Geisel Sch Med Dartmouth, Hanover, NH USA. RP Pietrzak, RH (reprint author), Vet Affairs Connecticut Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, West Haven, CT USA. EM robert.pietrzak@yale.edu FU National Center for Disaster Mental Health Research (National Institute of Mental Health) [5 P60 MH082598]; National Center for Posttraumatic Stress Disorder; Claude D. Pepper Older Americans Independence Center at Yale University School of Medicine (NIA) [P30AG21342] FX This research was supported by the National Center for Disaster Mental Health Research (National Institute of Mental Health Grant 5 P60 MH082598), Fran H. Norris, Center Director, Sandro Galea, Research Director. Preparation of this report was supported in part by the National Center for Posttraumatic Stress Disorder and a Research Career Development Award to Dr. Pietrzak from the Claude D. Pepper Older Americans Independence Center at Yale University School of Medicine (NIA Grant P30AG21342). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 23 Z9 23 U1 8 U2 26 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 JUN 26 PY 2012 VL 7 IS 6 AR e38964 DI 10.1371/journal.pone.0038964 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 966AK UT WOS:000305808700014 PM 22761716 ER PT J AU Dohgu, S Ryerse, JS Robinson, SM Banks, WA AF Dohgu, Shinya Ryerse, Jan S. Robinson, Sandra M. Banks, William A. TI Human Immunodeficiency Virus-1 Uses the Mannose-6-Phosphate Receptor to Cross the Blood-Brain Barrier SO PLOS ONE LA English DT Article ID MANNOSE 6-PHOSPHATE RECEPTOR; ENVELOPE GLYCOPROTEIN GP120; LYSOSOMAL-ENZYME; ADSORPTIVE ENDOCYTOSIS; MEDIATED TRANSPORT; ENDOTHELIAL-CELLS; SURFACE-PROTEINS; HIV-1 GP120; RAT-BRAIN; MOUSE AB HIV-1 circulates both as free virus and within immune cells, with the level of free virus being predictive of clinical course. Both forms of HIV-1 cross the blood-brain barrier (BBB) and much progress has been made in understanding the mechanisms by which infected immune cells cross the blood-brain barrier BBB. How HIV-1 as free virus crosses the BBB is less clear as brain endothelial cells are CD4 and galactosylceramide negative. Here, we found that HIV-1 can use the mannose-6 phosphate receptor (M6PR) to cross the BBB. Brain perfusion studies showed that HIV-1 crossed the BBB of all brain regions consistent with the uniform distribution of M6PR. Ultrastructural studies showed HIV-1 crossed by a transcytotic pathway consistent with transport by M6PR. An in vitro model of the BBB was used to show that transport of HIV-1 was inhibited by mannose, mannan, and mannose-6 phosphate and that enzymatic removal of high mannose oligosaccharide residues from HIV-1 reduced transport. Wheatgerm agglutinin and protamine sulfate, substances known to greatly increase transcytosis of HIV-1 across the BBB in vivo, were shown to be active in the in vitro model and to act through a mannose-dependent mechanism. Transport was also cAMP and calcium-dependent, the latter suggesting that the cation-dependent member of the M6PR family mediates HIV-1 transport across the BBB. We conclude that M6PR is an important receptor used by HIV-1 to cross the BBB. C1 [Dohgu, Shinya] Fukuoka Univ, Fac Pharmaceut Sci, Dept Pharmaceut Care & Hlth Sci, Fukuoka 81401, Japan. [Ryerse, Jan S.] St Louis Univ, Hlth Sci Ctr, Dept Pathol, St Louis, MO 63103 USA. [Robinson, Sandra M.] St Louis Univ, Sch Med, Div Geriatr Med, Dept Internal Med, St Louis, MO 63104 USA. [Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Banks, William A.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. RP Dohgu, S (reprint author), Fukuoka Univ, Fac Pharmaceut Sci, Dept Pharmaceut Care & Hlth Sci, 8-19-1 Nanakuma, Fukuoka 81401, Japan. EM wabanks1@u.washington.edu FU Veterans Affairs merit review; National Institutes of Health [RO-1 AG029839] FX The funders were Veterans Affairs merit review (http://www.research.va.gov/programs/csrd/merit_review.cfm) and National Institutes of Health RO-1 AG029839. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 14 Z9 14 U1 2 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 JUN 25 PY 2012 VL 7 IS 6 AR e39565 DI 10.1371/journal.pone.0039565 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 965QG UT WOS:000305781700049 PM 22761827 ER PT J AU Jutras-Aswad, D Jacobs, MM Yiannoulos, G Roussos, P Bitsios, P Nomura, Y Liu, X Hurd, YL AF Jutras-Aswad, Didier Jacobs, Michelle M. Yiannoulos, Georgia Roussos, Panos Bitsios, Panos Nomura, Yoko Liu, Xun Hurd, Yasmin L. TI Cannabis-Dependence Risk Relates to Synergism between Neuroticism and Proenkephalin SNPs Associated with Amygdala Gene Expression: Case-Control Study SO PLOS ONE LA English DT Article ID POPULATION-BASED SAMPLE; STOP SIGNAL INHIBITION; D2 RECEPTOR GENE; ENVIRONMENTAL-INFLUENCES; PRE-PROENKEPHALIN; NEGATIVE AFFECT; WORKING-MEMORY; SUBSTANCE USE; FEMALE TWINS; DRUG-USE AB Background: Many young people experiment with cannabis, yet only a subgroup progress to dependence suggesting individual differences that could relate to factors such as genetics and behavioral traits. Dopamine receptor D2 (DRD2) and proenkephalin (PENK) genes have been implicated in animal studies with cannabis exposure. Whether polymorphisms of these genes are associated with cannabis dependence and related behavioral traits is unknown. Methodology/Principal Findings: Healthy young adults (18-27 years) with cannabis dependence and without a dependence diagnosis were studied (N = 50/group) in relation to a priori-determined single nucleotide polymorphisms (SNPs) of the DRD2 and PENK genes. Negative affect, Impulsive Risk Taking and Neuroticism-Anxiety temperamental traits, positive and negative reward-learning performance and stop-signal reaction times were examined. The findings replicated the known association between the rs6277 DRD2 SNP and decisions associated with negative reinforcement outcomes. Moreover, PENK variants (rs2576573 and rs2609997) significantly related to Neuroticism and cannabis dependence. Cigarette smoking is common in cannabis users, but it was not associated to PENK SNPs as also validated in another cohort (N = 247 smokers, N = 312 non-smokers). Neuroticism mediated (15.3%-19.5%) the genetic risk to cannabis dependence and interacted with risk SNPs, resulting in a 9-fold increase risk for cannabis dependence. Molecular characterization of the postmortem human brain in a different population revealed an association between PENK SNPs and PENK mRNA expression in the central amygdala nucleus emphasizing the functional relevance of the SNPs in a brain region strongly linked to negative affect. Conclusions/Significance: Overall, the findings suggest an important role for Neuroticism as an endophenotype linking PENK polymorphisms to cannabis-dependence vulnerability synergistically amplifying the apparent genetic risk. C1 [Jutras-Aswad, Didier; Jacobs, Michelle M.; Yiannoulos, Georgia; Roussos, Panos; Nomura, Yoko; Liu, Xun; Hurd, Yasmin L.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Jacobs, Michelle M.] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY USA. [Bitsios, Panos; Hurd, Yasmin L.] Univ Crete, Fac Med, Dept Psychiat & Behav Sci, Iraklion, Crete, Greece. [Liu, Xun] Chinese Acad Sci, Inst Psychol, Beijing 100101, Peoples R China. [Nomura, Yoko] Queens Coll, Dept Psychol, Queens, NY USA. [Hurd, Yasmin L.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. [Hurd, Yasmin L.] James J Peters VA Med Ctr, New York, NY USA. RP Jutras-Aswad, D (reprint author), Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada. EM Yasmin.hurd@mssm.edu RI Liu, Xun/C-2400-2009; Roussos, Panos/J-7090-2013 OI Liu, Xun/0000-0003-1366-8926; Roussos, Panos/0000-0002-4640-6239 FU Mount Sinai School of Medicine Fund; Centre Hospitalier de l'Universite de Montreal Research Fellowship Award; National Institutes of Health [DA15446, T32 DA007135] FX This research was supported by Mount Sinai School of Medicine Fund (YLH), Centre Hospitalier de l'Universite de Montreal Research Fellowship Award (DJA) and National Institutes of Health [DA15446 (YLH), T32 DA007135 (MMJ)]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 15 Z9 16 U1 3 U2 12 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 JUN 22 PY 2012 VL 7 IS 6 AR e39243 DI 10.1371/journal.pone.0039243 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 964XV UT WOS:000305730900038 PM 22745721 ER PT J AU Elvington, M Huang, YX Morgan, BP Qiao, F van Rooijen, N Atkinson, C Tomlinson, S AF Elvington, Michelle Huang, Yuxiang Morgan, B. Paul Qiao, Fei van Rooijen, Nico Atkinson, Carl Tomlinson, Stephen TI Atargeted complement-dependent strategy to improve the outcome of mAb therapy, and characterization in a murine model of metastatic cancer SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CD20 MONOCLONAL-ANTIBODIES; DECAY-ACCELERATING FACTOR; IN-VIVO; TUMOR-CELLS; INHIBITORY PROTEINS; IMMUNE-RESPONSE; FACTOR-H; ACTIVATION; IMMUNOTHERAPY AB Complement inhibitors expressed on tumor cells provide an evasion mechanism against mAb therapy and may modulate the development of an acquired antitumor immune response. Here we investigate a strategy to amplify mAb-targeted complement activation on a tumor cell, independent of a requirement to target and block complement inhibitor expression or function, which is difficult to achieve in vivo. We constructed a murine fusion protein, CR2Fc, and demonstrated that the protein targets to C3 activation products deposited on a tumor cell by a specific mAb, and amplifies mAb-dependent complement activation and tumor cell lysis in vitro. In syngeneic models of metastatic lymphoma (EL4) and melanoma (B16), CR2Fc significantly enhanced the outcome of mAb therapy. Subsequent studies using the EL4 model with various genetically modified mice and macrophage-depleted mice revealed that CR2Fc enhanced the therapeutic effect of mAb therapy via both macrophage-dependent Fc gamma R-mediated antibody-dependent cellular cytotoxicity, and by direct complement-mediated lysis. Complement activation products can also modulate adaptive immunity, but we found no evidence that either mAb or CR2Fc treatment had any effect on an antitumor humoral or cellular immune response. CR2Fc represents a potential adjuvant treatment to increase the effectiveness of mAb therapy of cancer. (Blood. 2012; 119(25): 6043-6051) C1 [Elvington, Michelle; Huang, Yuxiang; Qiao, Fei; Atkinson, Carl; Tomlinson, Stephen] Med Univ S Carolina, Dept Microbiol & Immunol, Childrens Res Inst, Charleston, SC 29425 USA. [Morgan, B. Paul] Cardiff Univ, Dept Infect Immun & Biochem, Sch Med, Cardiff, S Glam, Wales. [van Rooijen, Nico] Free Univ Amsterdam, Dept Cell Biol & Immunol, Amsterdam, Netherlands. [Tomlinson, Stephen] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Tomlinson, S (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, Childrens Res Inst, 173 Ashley Ave,BSB 201, Charleston, SC 29425 USA. EM tomlinss@musc.edu FU National Institutes of Health [RO1CA158179]; Department of Defense [BC061523] FX This work was supported by the National Institutes of Health (grant RO1CA158179, S.T.) and the Department of Defense (BC061523 fellowship, M.E.). NR 44 TC 12 Z9 13 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 21 PY 2012 VL 119 IS 25 BP 6043 EP 6051 DI 10.1182/blood-2011-10-383232 PG 9 WC Hematology SC Hematology GA 987EG UT WOS:000307398700019 PM 22442351 ER PT J AU Seal, K Krebs, E Neylan, T AF Seal, Karen Krebs, Erin Neylan, Thomas TI Posttraumatic Stress Disorder and Opioid Use Among US Veterans Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID CHRONIC NONCANCER PAIN C1 [Seal, Karen; Neylan, Thomas] San Francisco VA Med Ctr, San Francisco, CA USA. [Krebs, Erin] Minneapolis Vet Affairs Hlth Care Syst, Minneapolis, MN USA. RP Seal, K (reprint author), San Francisco VA Med Ctr, San Francisco, CA USA. EM karen.seal@ucsf.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 20 PY 2012 VL 307 IS 23 BP 2485 EP 2486 DI 10.1001/jama.2012.6236 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 960MB UT WOS:000305391400014 ER PT J AU Maselli, DJ Anzueto, A AF Maselli, Diego J. Anzueto, Antonio TI The need to further understand who gets hospitalized for a COPD exacerbation SO MULTIDISCIPLINARY RESPIRATORY MEDICINE LA English DT Editorial Material ID OBSTRUCTIVE PULMONARY-DISEASE; MORTALITY; PREVENTION C1 [Maselli, Diego J.; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, Audie L Murphy Div, Dept Med,Div Pulm Crit Care Med, San Antonio, TX 78229 USA. RP Maselli, DJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, Audie L Murphy Div, Dept Med,Div Pulm Crit Care Med, San Antonio, TX 78229 USA. EM masellicacer@uthscsa.edu NR 12 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2049-6958 J9 MULTIDISCIP RESP MED JI Multidscip. Respir. Med. PD JUN 19 PY 2012 VL 7 AR 7 DI 10.1186/2049-6958-7-7 PG 2 WC Respiratory System SC Respiratory System GA 984YL UT WOS:000307229700002 PM 22958418 ER PT J AU Farbota, KD Bendlin, BB Alexander, AL Rowley, HA Dempsey, RJ Johnson, SC AF Farbota, Kimberly D. Bendlin, Barbara B. Alexander, Andrew L. Rowley, Howard A. Dempsey, Robert J. Johnson, Sterling C. TI Longitudinal diffusion tensor imaging and neuropsychological correlates in traumatic brain injury patients SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE traumatic brain injury; diffusion tensor imaging; longitudinal; neuropsychology; recovery; DTI; TBI ID CORPUS-CALLOSUM MICROSTRUCTURE; WHITE-MATTER INTEGRITY; AXONAL INJURY; DAMAGE; MODEL; MRI; ADOLESCENTS; ACTIVATION; PLASTICITY; FASCICULUS AB Traumatic brain injury (TBI) often involves focal cortical injury and white matter (WM) damage that can be measured shortly after injury. Additionally, slowly evolving WM change can be observed but there is a paucity of research on the duration and spatial pattern of long-term changes several years post-injury. The current study utilized diffusion tensor imaging to identify regional WM changes in 12 TBI patients and nine healthy controls at three time points over a four year period. Neuropsychological testing was also administered to each participant at each time point. Results indicate that TBI patients exhibit longitudinal changes to WM indexed by reductions in fractional anisotropy (FA) in the corpus callosum, as well as FA increases in bilateral regions of the superior longitudinal fasciculus (SLF) and portions of the optic radiation (OR). FA changes appear to be driven by changes in radial (not axial) diffusivity, suggesting that observed longitudinal FA changes may be related to changes in myelin rather than to axons. Neuropsychological correlations indicate that regional FA values in the corpus callosum and sagittal stratum (SS) correlate with performance on finger tapping and visuomotor speed tasks (respectively) in TBI patients, and that longitudinal increases in FA in the SS, SLF, and OR correlate with improved performance on the visuomotor speed (SS) task as well as a derived measure of cognitive control (SLF, OR). The results of this study showing progressive WM deterioration for several years post-injury contribute to a growing literature supporting the hypothesis that TBI should be viewed not as an isolated incident but as a prolonged disease state. The observations of long-term neurological and functional improvement provide evidence that some ameliorative change may be occurring concurrently with progressive degeneration. C1 [Farbota, Kimberly D.; Bendlin, Barbara B.; Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. [Farbota, Kimberly D.] Univ Wisconsin, Neurosci Training Program, Madison, WI 53705 USA. [Bendlin, Barbara B.; Johnson, Sterling C.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI 53705 USA. [Alexander, Andrew L.] Univ Wisconsin, Dept Med Phys, Sch Med & Publ Hlth, Madison, WI 53705 USA. [Rowley, Howard A.] Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53705 USA. [Dempsey, Robert J.] Univ Wisconsin, Dept Neurol Surg, Sch Med & Publ Hlth, Madison, WI 53705 USA. RP Johnson, SC (reprint author), Univ Wisconsin, William S Middleton Mem VA Hosp, Dept Med, 2500 Overlook Terrace, Madison, WI 53705 USA. EM scj@medicine.wisc.edu OI Bendlin, Barbara/0000-0002-0580-9875 FU Department of Veterans Affairs; NIH [MH65723, AG000213] FX This study was supported by a Merit Review Grant from the Department of Veterans Affairs, the NIH MH65723 (SCJ), NIH AG000213 and by the facilities and resources of the William S. Middleton Memorial Veterans Hospital. The assistance of Lisa Newman, Amy Hawley, Donald McLaren, and Erik Kastman is greatly appreciated. We would also like to acknowledge the support of researchers and staff at the Waisman Center , University of Wisconsin, Madison, where MR imaging took place . Finally, we thank all the patients who took part in this study . The contents of this report do not necessarily represent the views of the Department of Veterans Affairs or the United States Government. NR 59 TC 34 Z9 36 U1 1 U2 14 PU FRONTIERS RES FOUND PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD JUN 19 PY 2012 VL 6 AR 160 DI 10.3389/fnhum.2012.00160 PG 15 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 965SK UT WOS:000305787400001 PM 22723773 ER PT J AU Adachi, MS Taylor, AB Hart, PJ Fitzpatrick, PF AF Adachi, Mariya S. Taylor, Alexander B. Hart, P. John Fitzpatrick, Paul F. TI Mechanistic and Structural Analyses of the Role of His67 in the Yeast Polyarnine Oxidase Fmsl SO BIOCHEMISTRY LA English DT Article ID MONOMERIC SARCOSINE OXIDASE; AMINO-ACID OXIDASE; N-METHYLTRYPTOPHAN OXIDASE; OXYGEN ACTIVATION SITE; POLYAMINE OXIDASE; SUBSTRATE-SPECIFICITY; CRYSTAL-STRUCTURE; TRYPTOPHAN 2-MONOOXYGENASE; HETEROLOGOUS EXPRESSION; KINETIC MECHANISM AB The flavoprotein oxidase Fms1 from Saccharomyces cerevisiae catalyzes the oxidation of spermine and N-1-acetylspermine to spermidine and 3-aminopropanal or N-acetyl-3-aminopropanal. Within the active site of Fms1, His67 is positioned to form hydrogen bonds with the polyamine substrate. This residue is also conserved in other polyamine oxidases. The catalytic properties of H67Q, H67N, and H67A Fms1 have been characterized to evaluate the role of this residue in catalysis. With both spermine and N-1-acetylspermine as the amine substrate, the value of the first-order rate constant for flavin reduction decreases 2-3 orders of magnitude, with the H67Q mutation having the smallest effect and H67N the largest. The k(cat)/K-O2 value changes very little upon mutation with N-1-acetylspermine as the amine substrate and decreases only an order of magnitude with spermine. The k(cat)/K-M-pH profiles with N-1-acetylspermine are bell-shaped for all the mutants; the similarity to the profile of the wild-type enzyme rules out His67 as being responsible for either of the pK(a) values. The pH profiles for the rate constant for flavin reduction for all the mutant enzymes similarly show the same pK(a) as wild-type Fms1, about similar to 7.4; this pK(a) is assigned to the substrate N4. The k(cat)/K-O2-pH profiles for wild-type Fms1 and the H67A enzyme both show a pK(a) of about similar to 6.9; this suggests His67 is not responsible for this pH behavior. With the H67Q, H67N, and H67A enzymes the k(cat) value decreases when a single residue is protonated, as is the case with the wild-type enzyme. The structure of H67Q Fms1 has been determined at a resolution of 2.4 angstrom. The structure shows that the mutation disrupts a hydrogen bond network in the active site, suggesting that His67 is important both for direct interactions with the substrate and to maintain the overall active site structure. C1 [Adachi, Mariya S.; Taylor, Alexander B.; Hart, P. John; Fitzpatrick, Paul F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Hart, P. John] S Texas Vet Hlth Care Syst, Dept Vet Affairs, Audie Murphy Div, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Fitzpatrick, PF (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. EM fitzpatrick@biochem.uthscsa.edu FU NIH [GM058698]; The Welch Foundation [AQ-1399, AQ1245]; National Center for Research Resources [5P41RR015301-10]; National Institute of General Medical Sciences from the National Institutes of Health [8 P41 GM103403-10]; U.S. DOE [DE-AC02-06CH11357]; Department of Veterans Affairs; Veterans Health Administration; Office of Research Development; Biomedical Laboratory Research and Development; UTHSCSA Executive Research Committee; Cancer Therapy Research Center FX This work was supported in part by the NIH, grant GM058698 (to P.F.F.), and The Welch Foundation, grants AQ-1399 (to P.J.H.) and AQ1245 (to P.F.F.). This work is based upon research conducted at the Advanced Photon Source on the Northeastern Collaborative Access Team beamlines, which are supported by grants from the National Center for Research Resources (5P41RR015301-10) and the National Institute of General Medical Sciences (8 P41 GM103403-10) from the National Institutes of Health. Use of the Advanced Photon Source, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the U.S. DOE under Contract DE-AC02-06CH11357.; This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research Development, Biomedical Laboratory Research and Development. Support for the X-ray Crystallography Core Laboratory by the UTHSCSA Executive Research Committee and the Cancer Therapy Research Center is gratefully acknowledged. NR 44 TC 4 Z9 4 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 19 PY 2012 VL 51 IS 24 BP 4888 EP 4897 DI 10.1021/bi300517s PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 959NZ UT WOS:000305320800012 PM 22642831 ER PT J AU Abrol, R Edderkaoui, M Goddard, WA Pandol, SJ AF Abrol, Ravinder Edderkaoui, Mouad Goddard, William A., III Pandol, Stephen J. TI Molecular basis for the interplay of apoptosis and proliferation mediated by Bcl-xL:Bim interactions in pancreatic cancer cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Bcl-2 family; Mutagenesis; Apoptosis; Proliferation; Computational biochemistry ID INHIBITION; MODEL; EXPRESSION; BIOLOGY; BAX AB A major mechanism through which cancer cells avoid apoptosis is by promoting the association of antiapoptotic members of the pro-survival Bcl-2 protein family (like Bcl-2 and Bcl-xL) with BH3 domain-only proteins (like Bim and Bid). Apoptosis and cell proliferation have been shown to be linked for many cancers but the molecular basis for this link is far from understood. We have identified the Bcl-xL:Bim protein-protein interface as a direct regulator of proliferation and apoptosis in pancreatic cancer cells. We were able to predict and subsequently verify experimentally the effect of various Bcl-xL single-point mutants (at the position A142) on binding to Bim by structural analysis and computational modeling of the inter-residue interactions at the Bcl-xL:Bim protein-protein interface. The mutants A142N, A142Q and A142Y decreased binding of Bim to Bcl-xL and A142S increased this binding. The Bcl-xL mutants, with decreased affinity for Bim, caused an increase in apoptosis and a corresponding decrease in cell proliferation. However, we could prevent these effects by introducing a small interfering RNA (siRNA) targeted at Bim. These results show a novel role played by the Bcl-xL:Bim interaction in regulating proliferation of pancreatic cancer cells at the expense of apoptosis. This study presents a physiologically relevant model of the Bcl-xL:Bim interface that can be used for rational therapeutic design for the inhibition of proliferation and cancer cell resistance to apoptosis. (C) 2012 Elsevier Inc. All rights reserved. C1 [Abrol, Ravinder; Goddard, William A., III] CALTECH, Div Chem & Chem Engn, Mat & Proc Simulat Ctr, Pasadena, CA 91125 USA. [Edderkaoui, Mouad; Pandol, Stephen J.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Edderkaoui, Mouad; Pandol, Stephen J.] Univ Calif Los Angeles, Los Angeles, CA 90073 USA. RP Abrol, R (reprint author), CALTECH, Div Chem & Chem Engn, Mat & Proc Simulat Ctr, MC 139-74, Pasadena, CA 91125 USA. EM abrol@wag.caltech.edu; stephen.pandol@va.gov RI babakinejad, babak/G-2674-2012; Abrol, Ravinder/B-4980-2010 FU Department of Veterans Affairs; UCLA Center for Excellence in Pancreatic Diseases; National Center for Complementary and Alternative Medicine [1 P01 AT003960]; National Institute on Alcohol Abuse and Alcoholism [1K01AA019996] FX This work was supported by the Department of Veterans Affairs and the UCLA Center for Excellence in Pancreatic Diseases and National Center for Complementary and Alternative Medicine (1 P01 AT003960), National Institute on Alcohol Abuse and Alcoholism (1K01AA019996), and in part through gifts to the Materials and Process Simulation Center at Caltech. NR 27 TC 2 Z9 2 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 15 PY 2012 VL 422 IS 4 BP 596 EP 601 DI 10.1016/j.bbrc.2012.05.032 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 974NU UT WOS:000306443900012 PM 22609401 ER PT J AU Schepp-Berglind, J Atkinson, C Elvington, M Qiao, F Mannon, P Tomlinson, S AF Schepp-Berglind, Jennifer Atkinson, Carl Elvington, Michelle Qiao, Fei Mannon, Peter Tomlinson, Stephen TI Complement-Dependent Injury and Protection in a Murine Model of Acute Dextran Sulfate Sodium-Induced Colitis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; DECAY-ACCELERATING FACTOR; ULCERATIVE-COLITIS; CROHNS-DISEASE; ISCHEMIA/REPERFUSION INJURY; ALTERNATIVE PATHWAY; ACTIVATION; EXPRESSION; EPITHELIUM; RECEPTOR AB Complement plays a key role in the pathophysiology of many inflammatory diseases, and in this study, we investigated the role of complement in the pathogenesis of inflammatory bowel disease. Compared to wild-type mice, mice deficient in C3 or factor B were protected from acute dextran sulfate sodium (DSS)-induced colitis. C1q/mannose-binding lectin (MBL) double-deficient mice, however, exhibited more severe colitis than wild-type mice. When mice were allowed to recover after DSS treatment, all C1q/MBL-/- mice died by day 2 of recovery period, and, surprisingly, all C3(-/-) and factor B-/- mice died by day 5. Serum endotoxin levels were significantly increased in complement-deficient mice prior to death, particularly in C1q/MBL-/- mice, and antibiotic treatment prevented the lethal effect of DSS in all complement-deficient mice. In contrast to complement deficiency, targeted complement inhibition with either complement receptor 2 (CR2)-Crry (blocks all pathways at C3 activation) or CR2-factor H (blocks alternative pathway) was highly protective at treating established acute colitis. Endotoxin levels remained low in complement-inhibited mice, and complement inhibition also reduced inflammatory cytokines, leukocyte infiltration, and tissue injury while improving wound repair and mucosal healing. CR2-factor H provided more effective protection than CR2-Crry. Thus, complement has both pathogenic and protective roles in acute DSS-induced colitis, and whereas the alternative pathway appears to play a key role in tissue inflammation and injury, the classical/lectin pathway provides important protection in terms of host defense and wound repair. Targeted inhibition of the alternative pathway may represent a therapeutic modality for treating acute phases of inflammatory bowel disease. The Journal of Immunology, 2012, 188: 6309-6318. C1 [Schepp-Berglind, Jennifer; Atkinson, Carl; Elvington, Michelle; Qiao, Fei; Tomlinson, Stephen] Med Univ S Carolina, Dept Microbiol & Immunol, Childrens Res Inst, Charleston, SC 29425 USA. [Mannon, Peter] Univ Alabama Birmingham, Dept Gastroenterol & Hepatol, Birmingham, AL 35294 USA. [Tomlinson, Stephen] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Tomlinson, S (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, Childrens Res Inst, Charleston, SC 29425 USA. EM tomlinss@musc.edu FU Crohn's and Colitis Foundation of America; National Institutes of Health [T32 AR050958] FX This work was supported by a grant from the Crohn's and Colitis Foundation of America (to S.T.) and National Institutes of Health Training Grant T32 AR050958 (to J.S.-B.). NR 31 TC 20 Z9 21 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2012 VL 188 IS 12 BP 6309 EP 6318 DI 10.4049/jimmunol.1200553 PG 10 WC Immunology SC Immunology GA 956GK UT WOS:000305077900056 PM 22566568 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 SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID GRADE; RECOMMENDATIONS; CONSENSUS 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.; Cornia, Paul B.] 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. [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 Surg, 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, Beth Israel Deaconess Med Ctr, Sch Med, Div Infect Dis,Dept Med, Boston, MA 02215 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, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, 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 FU Infectious Diseases Society of America FX Support for these guidelines was provided by the Infectious Diseases Society of America. NR 6 TC 32 Z9 38 U1 0 U2 17 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 JUN 15 PY 2012 VL 54 IS 12 BP 1679 EP 1684 DI 10.1093/cid/cis460 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 948YT UT WOS:000304541000007 PM 22619239 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 SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; COLONY-STIMULATING FACTOR; SKIN-STRUCTURE INFECTIONS; PERIPHERAL ARTERIAL-DISEASE; TO-BONE TEST; PRESSURE WOUND THERAPY; RANDOMIZED CONTROLLED-TRIAL; LOWER-EXTREMITY INFECTIONS; HYPERBARIC-OXYGEN THERAPY; COMPLICATED SKIN 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.; Cornia, Paul B.] 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. [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 Surg, 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, Beth Israel Deaconess Med Ctr, Sch Med, Div Infect Dis,Dept Med, Boston, MA 02215 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, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, 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 FU Infectious Diseases Society of America FX Support for these guidelines was provided by the Infectious Diseases Society of America. NR 358 TC 217 Z9 237 U1 9 U2 50 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 JUN 15 PY 2012 VL 54 IS 12 BP E132 EP U232 DI 10.1093/cid/cis346 PG 42 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 948YT UT WOS:000304541000005 PM 22619242 ER PT J AU Hall, DE Hanusa, BH Switzer, GE Fine, MJ Arnold, RM AF Hall, Daniel E. Hanusa, Barbara H. Switzer, Galen E. Fine, Michael J. Arnold, Robert M. TI The Impact of iMedConsent on Patient Decision-Making Regarding Cholecystectomy and Inguinal Herniorrhaphy SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE informed consent; decision-making; information preference; participation preference; ethics; trust; anxiety ID SURGICAL INFORMED-CONSENT; BONE-MARROW DONATION; SHORT-FORM; CLINICAL ANESTHESIA; SURGERY RESEARCH; PHYSICIAN SCALE; CANCER-PATIENTS; ANXIETY; INFORMATION; DONORS AB Background. The Veterans Affairs Healthcare System implemented a computer-based tool (iMedConsent) to improve the quality of informed consent in 2004. The impact of this tool on the process of informed consent remains unknown. Our aim was to determine the impact of iMedConsent on patient information preference, anxiety, trust in the surgeon, ambivalence about the surgical decision, and comprehension of procedure-specific risk, benefits, and alternatives. Materials and Methods. We prospectively enrolled a consecutive cohort of patients presenting to a general surgery clinic for possible cholecystectomy or inguinal herniorrhaphy from October 2009 to August 2010. We administered questionnaires before and after the clinic visit. Results. Seventy-five patients completed pre-visit questionnaires. After evaluation by the surgeon, 42 patients were offered surgery and documented their informed consent using iMedConsent, of whom 38 (90%) also completed a post-visit questionnaire. Among the participants who completed both pre- and post-visit questionnaires, participant comprehension of procedure-specific risks benefits and alternatives improved from 50% at baseline to 60% after the clinic visit (P < 0.001). No differences were noted in ambivalence, trust, or anxiety. After the clinic visit, significantly more patients expressed a preference for participating in decision making with their surgeon (98% versus 71%, P = 0.008). However, significantly fewer expressed a preference for knowing all possible details about their illness (25% to 83%, P <= 0.001). Conclusions. The informed consent process using iMedConsent improves patient comprehension of procedure-specific risks, benefits, and alternatives. It also increases patient preferences for participating more actively in the decision-making process. However, the process may provide more detail than patients want regarding their illness. Published by Elsevier Inc. C1 [Hall, Daniel E.; Hanusa, Barbara H.; Switzer, Galen E.; Fine, Michael J.] Healthcare Syst, VA Pittsburgh, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Hall, Daniel E.] Univ Pittsburgh, Dept Gen Surg, Pittsburgh, PA USA. [Switzer, Galen E.; Fine, Michael J.; Arnold, Robert M.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. RP Hall, DE (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr 151C-H, Pittsburgh, PA 15206 USA. EM hallde@upmc.edu RI Hall, Daniel/H-4843-2013 OI Hall, Daniel/0000-0001-6382-0522 FU VA HSRD [CDA 08-281]; VISN4 [XVA 72-057]; CHERP [LIP 72-043] FX The authors thank Drs. Aaron Fink and Alan Prochazka for their gracious advice regarding the design of this study. This research was funded by grants from VA HSR&D (CDA 08-281), VISN4 Competitive Pilot Project Fund (XVA 72-057), and the CHERP Pilot Project Program (LIP 72-043). NR 33 TC 3 Z9 3 U1 2 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 EI 1095-8673 J9 J SURG RES JI J. Surg. Res. PD JUN 15 PY 2012 VL 175 IS 2 BP 227 EP 233 DI 10.1016/j.jss.2011.04.056 PG 7 WC Surgery SC Surgery GA 939AB UT WOS:000303774400016 PM 21704336 ER PT J AU Hattler, B Messenger, JC Shroyer, AL Collins, JF Haugen, SJ Garcia, JA Baltz, JH Cleveland, JC Novitzky, D Grover, FL AF Hattler, Brack Messenger, John C. Shroyer, A. Laurie Collins, Joseph F. Haugen, Scott J. Garcia, Joel A. Baltz, Janet H. Cleveland, Joseph C., Jr. Novitzky, Dimitri Grover, Frederick L. CA Vet Affairs Randomized On Off TI Off-Pump Coronary Artery Bypass Surgery Is Associated With Worse Arterial and Saphenous Vein Graft Patency and Less Effective Revascularization Results From the Veterans Affairs Randomized On/Off Bypass (ROOBY) Trial SO CIRCULATION LA English DT Article DE coronary artery bypass; coronary artery bypass; off-pump ID TERM-FOLLOW-UP; ON-PUMP; LIFE OUTCOMES; HEART; MORTALITY; SURVIVAL; PRAGUE-4; FATE AB Background-The Department of Veterans Affairs Randomized On/Off Bypass (ROOBY) trial compared clinical and angiographic outcomes in off-pump versus on-pump coronary artery bypass graft (CABG) surgery to ascertain the relative efficacy of the 2 techniques. Methods and Results-From February 2002 to May 2007, the ROOBY trial randomized 2203 patients to off-pump versus on-pump CABG. Follow-up angiography was obtained in 685 off-pump (62%) and 685 on-pump (62%) patients. Angiograms were analyzed (blinded to treatment) for FitzGibbon classification (A=widely patent, B=flow limited, O=occluded) and effective revascularization. Effective revascularization was defined as follows: All 3 major coronary territories with significant disease were revascularized by a FitzGibbon A-quality graft to the major diseased artery, and there were no new postanastomotic lesions. Off-pump CABG resulted in lower FitzGibbon A patency rates than on-pump CABG for arterial conduits (85.8% versus 91.4%; P=0.003) and saphenous vein grafts (72.7% versus 80.4%; P<0.001). Fewer off-pump patients were effectively revascularized (50.1% versus 63.9% on-pump; P<0.001). Within each major coronary territory, effective revascularization was worse off pump than on pump (all P<0.001). The 1-year adverse cardiac event rate was 16.4% in patients with ineffective revascularization versus 5.9% in patients with effective revascularization (P<0.001). Conclusions-Off-pump CABG resulted in significantly lower FitzGibbon A patency for arterial and saphenous vein graft conduits and less effective revascularization than on-pump CABG. At 1 year, patients with less effective revascularization had higher adverse event rates. C1 [Hattler, Brack; Shroyer, A. Laurie; Baltz, Janet H.; Cleveland, Joseph C., Jr.; Grover, Frederick L.] Eastern Colorado Hlth Care Syst, Dept Vet Affairs, Denver, CO USA. [Hattler, Brack; Messenger, John C.; Garcia, Joel A.] Univ Colorado Hosp Denver, Dept Med, Aurora, CO USA. [Hattler, Brack; Messenger, John C.; Garcia, Joel A.; Cleveland, Joseph C., Jr.; Grover, Frederick L.] Hlth Sci Ctr, Aurora, CO USA. [Shroyer, A. Laurie] Northport Vet Affairs Med Ctr, Northport, NY USA. [Collins, Joseph F.] Vet Affairs Med Ctr, Cooperat Studies Program Coordinating Ctr, Perry Point, MD USA. [Haugen, Scott J.] Bellevue Med Ctr, Grp Hlth Cooperat, Bellevue, WA USA. [Cleveland, Joseph C., Jr.; Grover, Frederick L.] Univ Colorado Hosp Denver, Dept Surg, Aurora, CO USA. [Novitzky, Dimitri] James A Haley Vet Hosp, Tampa, FL 33612 USA. RP Hattler, B (reprint author), Denver VAMC, 1055 Clermont St,111B, Denver, CO 80220 USA. EM brack.hattler@va.gov RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 FU VA Office of Research and Development; VA Central Office, Office of Patient Care Services; Office of Research and Development at the Eastern Colorado Health Care System; Office of Denver VA Medical Center; Office of Northport VA Medical Center FX This work was supported by the Cooperative Studies Program of the VA Office of Research and Development and the VA Central Office, Office of Patient Care Services, and in part by the Offices of Research and Development at the Eastern Colorado Health Care System, Denver VA Medical Center, and the Northport VA Medical Center. NR 25 TC 74 Z9 79 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 12 PY 2012 VL 125 IS 23 BP 2827 EP 2835 DI 10.1161/CIRCULATIONAHA.111.069260 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 981NM UT WOS:000306975100022 PM 22592900 ER PT J AU Lustgarten, MS Bhattacharya, A Muller, FL Jang, YC Shimizu, T Shirasawa, T Richardson, A Van Remmen, H AF Lustgarten, Michael S. Bhattacharya, Arunabh Muller, Florian L. Jang, Youngmok C. Shimizu, Takahiko Shirasawa, Takuji Richardson, Arlan Van Remmen, Holly TI Complex I generated, mitochondrial matrix-directed superoxide is released from the mitochondria through voltage dependent anion channels SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Mitochondria; Superoxide; Voltage dependent anion channels ID BENZODIAZEPINE-RECEPTOR; SKELETAL-MUSCLE; OXIDATIVE STRESS; CELL-DEATH; MEMBRANES; PERMEABILITY; DISMUTASE; DIPHENYLENEIODONIUM; PROTEIN; CYTOSOL AB Mitochondrial complex I has previously been shown to release superoxide exclusively towards the mitochondrial matrix, whereas complex III releases superoxide to both the matrix and the cytosol. Superoxide produced at complex III has been shown to exit the mitochondria through voltage dependent anion channels (VDAC). To test whether complex I-derived, mitochondrial matrix-directed superoxide can be released to the cytosol, we measured superoxide generation in mitochondria isolated from wild type and from mice genetically altered to be deficient in MnSOD activity (TnIFastCreSod2(fl/fl)). Under experimental conditions that produce superoxide primarily by complex I (glutamate/malate plus rotenone, GM + R), MnSOD-deficient mitochondria release similar to 4-fold more superoxide than mitochondria isolated from wild type mice. Exogenous CuZnSOD completely abolished the EPR-derived GM + R signal in mitochondria isolated from both genotypes, evidence that confirms mitochondrial superoxide release. Addition of the VDAC inhibitor DIDS significantly reduced mitochondrial superoxide release (similar to 75%) in mitochondria from either genotype respiring on GM + R. Conversely, inhibition of potential inner membrane sites of superoxide exit, including the matrix face of the mitochondrial permeability transition pore and the inner membrane anion channel did not reduce mitochondrial superoxide release in the presence of GM + R in mitochondria isolated from either genotype. These data support the concept that complex I-derived mitochondrial superoxide release does indeed occur and that the majority of this release occurs through VDACs. (C) 2012 Elsevier Inc. All rights reserved. C1 [Lustgarten, Michael S.; Bhattacharya, Arunabh; Muller, Florian L.; Jang, Youngmok C.; Richardson, Arlan; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Bhattacharya, Arunabh; Muller, Florian L.; Jang, Youngmok C.; Richardson, Arlan; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Richardson, Arlan; Van Remmen, Holly] S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. [Shimizu, Takahiko] Chiba Univ, Grad Sch Med, Dept Adv Aging Med, Chiba, Japan. [Shirasawa, Takuji] Juntendo Univ, Grad Sch Med, Dept Aging Control Med, Tokyo, Japan. RP Van Remmen, H (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, 15355 Lambda Dr, San Antonio, TX 78229 USA. EM vanremmen@uthscsa.edu FU NIH [P01 AG020591]; NIA [5T3-AG021890-02] FX This work was funded by NIH Grant P01 AG020591 (to H.V.R.) and NIA Training Grant 5T3-AG021890-02. NR 30 TC 30 Z9 30 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 8 PY 2012 VL 422 IS 3 BP 515 EP 521 DI 10.1016/j.bbrc.2012.05.055 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 974NT UT WOS:000306443800027 PM 22613204 ER PT J AU Santa-Maria, I Varghese, M Ksiezak-Reding, H Dzhun, A Wang, J Pasinetti, GM AF Santa-Maria, Ismael Varghese, Merina Ksiezak-Reding, Hanna Dzhun, Anastasiya Wang, Jun Pasinetti, Giulio M. TI Paired Helical Filaments from Alzheimer Disease Brain Induce Intracellular Accumulation of Tau Protein in Aggresomes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROGRESSIVE SUPRANUCLEAR PALSY; SEED POLYPHENOLIC EXTRACT; NEURONAL CELLS; NEUROFIBRILLARY DEGENERATION; NEURODEGENERATIVE DISEASES; EXTRACELLULAR TAU; ALPHA-SYNUCLEIN; EXOSOMES; TAUOPATHY; MODEL AB Abnormal folding of tau protein leads to the generation of paired helical filaments (PHFs) and neurofibrillary tangles, a key neuropathological feature in Alzheimer disease and tauopathies. A specific anatomical pattern of pathological changes developing in the brain suggests that once tau pathology is initiated it propagates between neighboring neuronal cells, possibly spreading along the axonal network. We studied whether PHFs released from degenerating neurons could be taken up by surrounding cells and promote spreading of tau pathology. Neuronal and non-neuronal cells overexpressing green fluorescent protein-tagged tau (GFP-Tau) were treated with isolated fractions of human Alzheimer disease-derived PHFs for 24 h. We found that cells internalized PHFs through an endocytic mechanism and developed intracellular GFP-Tau aggregates with attributes of aggresomes. This was particularly evident by the perinuclear localization of aggregates and redistribution of the vimentin intermediate filament network and retrograde motor protein dynein. Furthermore, the content of Sarkosyl-insoluble tau, a measure of abnormal tau aggregation, increased 3-fold in PHF-treated cells. An exosome-related mechanism did not appear to be involved in the release of GFP-Tau from untreated cells. The evidence that cells can internalize PHFs, leading to formation of aggresome-like bodies, opens new therapeutic avenues to prevent propagation and spreading of tau pathology. C1 [Santa-Maria, Ismael; Varghese, Merina; Ksiezak-Reding, Hanna; Dzhun, Anastasiya; Wang, Jun; Pasinetti, Giulio M.] Mt Sinai Sch Med, Ctr Excellence Res Complementary & Alternat Med A, Ctr Excellence Novel Approaches Neurodiagnost & N, Brain Inst,Dept Neurol, New York, NY 10029 USA. [Varghese, Merina; Ksiezak-Reding, Hanna; Dzhun, Anastasiya; Pasinetti, Giulio M.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY 10468 USA. [Santa-Maria, Ismael] Queen Sofia Fdn, Ctr Invest Enfermedades Neurol Fdn, Alzheimer Dis Res Unit, Madrid 28031, Spain. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Ctr Excellence Res Complementary & Alternat Med A, Ctr Excellence Novel Approaches Neurodiagnost & N, Brain Inst,Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu OI Varghese, Merina/0000-0002-1517-3903 FU NCI, National Institutes of Health [5R24 CA095823-04, PO1 AT004511]; National Institutes of Health Shared Instrumentation [1 S10 RR0 9145-01]; Society for Progressive Supranuclear Palsy; Veterans Affairs merit review grant; National Science Foundation Major Research Instrumentation [DBI-9724504] FX Confocal laser scanning microscopy was performed at the James J. Peters Veteran Affairs Medical Center and conventional fluorescence microscopy was performed at the Mount Sinai School of Medicine Microscopy Shared Resource Facility supported with funding from NCI, National Institutes of Health Shared Resource Grant 5R24 CA095823-04, National Science Foundation Major Research Instrumentation Grant DBI-9724504, and National Institutes of Health Shared Instrumentation Grant 1 S10 RR0 9145-01. We thank Jesus Avila (Universidad Auto noma de Madrid, Madrid, Spain) for help with preparing GFP and GFP-Tau plasmids. We also thank Miguel Gama-Sosa (Mount Sinai School of Medicine, New York, NY) for lending his expertise in confocal microscopy.; This work was supported, in whole or in part, by National Institutes of Health Grant PO1 AT004511 (to G. M. P.). This work was also supported by the Society for Progressive Supranuclear Palsy and in part by Veterans Affairs merit review grant (to G. M. P.). Dr. Pasinetti has filed a patent application (pending) through Mount Sinai School of Medicine related to grape seed polyphenolic extract. In the event that the pending patent is licensed, Dr. Pasinetti would be entitled to a share of any proceeds Mount Sinai School of Medicine receives from the license. NR 67 TC 44 Z9 46 U1 0 U2 12 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 JUN 8 PY 2012 VL 287 IS 24 BP 20522 EP 20533 DI 10.1074/jbc.M111.323279 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 974FB UT WOS:000306414500073 PM 22496370 ER PT J AU Sonnenberg, GF Monticelli, LA Alenghat, T Fung, TC Hutnick, NA Kunisawa, J Shibata, N Grunberg, S Sinha, R Zahm, AM Tardif, MR Sathaliyawala, T Kubota, M Farber, DL Collman, RG Shaked, A Fouser, LA Weiner, DB Tessier, PA Friedman, JR Kiyono, H Bushman, FD Chang, KM Artis, D AF Sonnenberg, Gregory F. Monticelli, Laurel A. Alenghat, Theresa Fung, Thomas C. Hutnick, Natalie A. Kunisawa, Jun Shibata, Naoko Grunberg, Stephanie Sinha, Rohini Zahm, Adam M. Tardif, Melanie R. Sathaliyawala, Taheri Kubota, Masaru Farber, Donna L. Collman, Ronald G. Shaked, Abraham Fouser, Lynette A. Weiner, David B. Tessier, Philippe A. Friedman, Joshua R. Kiyono, Hiroshi Bushman, Frederic D. Chang, Kyong-Mi Artis, David TI Innate Lymphoid Cells Promote Anatomical Containment of Lymphoid-Resident Commensal Bacteria SO SCIENCE LA English DT Article ID ALCALIGENES-XYLOSOXIDANS; INTESTINAL BACTERIA; HOST-DEFENSE; MICROBIOTA; ACHROMOBACTER; INFLAMMATION; HOMEOSTASIS; IDENTIFICATION; IMMUNITY; SYSTEM AB The mammalian intestinal tract is colonized by trillions of beneficial commensal bacteria that are anatomically restricted to specific niches. However, the mechanisms that regulate anatomical containment remain unclear. Here, we show that interleukin-22 (IL-22)-producing innate lymphoid cells (ILCs) are present in intestinal tissues of healthy mammals. Depletion of ILCs resulted in peripheral dissemination of commensal bacteria and systemic inflammation, which was prevented by administration of IL-22. Disseminating bacteria were identified as Alcaligenes species originating from host lymphoid tissues. Alcaligenes was sufficient to promote systemic inflammation after ILC depletion in mice, and Alcaligenes-specific systemic immune responses were associated with Crohn's disease and progressive hepatitis C virus infection in patients. Collectively, these data indicate that ILCs regulate selective containment of lymphoid-resident bacteria to prevent systemic inflammation associated with chronic diseases. C1 [Sonnenberg, Gregory F.; Monticelli, Laurel A.; Alenghat, Theresa; Fung, Thomas C.; Grunberg, Stephanie; Sinha, Rohini; Bushman, Frederic D.; Artis, David] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. [Sonnenberg, Gregory F.; Monticelli, Laurel A.; Alenghat, Theresa; Fung, Thomas C.; Grunberg, Stephanie; Sinha, Rohini; Bushman, Frederic D.; Artis, David] Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA. [Hutnick, Natalie A.; Weiner, David B.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Kunisawa, Jun; Shibata, Naoko; Kiyono, Hiroshi] Univ Tokyo, Inst Med Sci, Div Mucosal Immunol, Tokyo 1088639, Japan. [Kunisawa, Jun; Shibata, Naoko; Kiyono, Hiroshi] Univ Tokyo, Grad Sch Frontier Sci, Dept Med Genome Sci, Chiba 2778562, Japan. [Zahm, Adam M.; Friedman, Joshua R.] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Dept Pediat,Div Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA. [Tardif, Melanie R.; Tessier, Philippe A.] Univ Laval, Fac Med, CHU Laval, Ctr Rech Infectiol, Quebec City, PQ G1K 7P4, Canada. [Sathaliyawala, Taheri; Kubota, Masaru; Farber, Donna L.] Columbia Univ, Med Ctr, Dept Surg, New York, NY 10032 USA. [Sathaliyawala, Taheri; Kubota, Masaru; Farber, Donna L.] Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10032 USA. [Collman, Ronald G.; Chang, Kyong-Mi] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Shaked, Abraham] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. [Fouser, Lynette A.] Pfizer Worldwide R&D, Inflammat & Immunol Res Unit, Biotherapeut Res & Dev, Cambridge, MA 02140 USA. [Kiyono, Hiroshi] Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Tokyo 1020075, Japan. [Chang, Kyong-Mi] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Artis, David] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA. RP Artis, D (reprint author), Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. EM dartis@mail.med.upenn.edu RI Weiner, David/H-8579-2014 OI Tessier, Philippe/0000-0001-7177-7763; Bushman, Frederic/0000-0003-4740-4056 FU NIH [AI061570, AI087990, AI074878, AI083480, AI095466, AI095608, T32-AI007532, T32-AI055428, T32-RR007063, K08-DK093784, AI47619, P30 AI 045008]; Burroughs Wellcome Fund Investigator in Pathogenesis of Infectious Disease Award; Philadelphia VA Medical Research and Merit Review; American Gastroenterological Association; Ministry of Education, Culture, Sports, Science and Technology of Japan; Program for Promotion of Basic and Applied Researches for Innovations in Bio-Oriented Industry; Matthew J. Ryan Veterinary Hospital Pathology Lab, the National Institute of Diabetes and Digestive and Kidney Disease Center for the Molecular Studies in Digestive and Liver Disease Molecular Pathology and Imaging Core [P30DK50306]; National Cancer Institute (NCI) Comprehensive Cancer Center [2-P30 CA016520] FX We thank members of the Artis laboratory for discussions and critical reading of the manuscript. We also thank S. Olland, R. Zollner, K. Lam, and A. Root at Pfizer for the preparation of IL-22 cytokine and antibodies. The research is supported by the NIH (grants AI061570, AI087990, AI074878, AI083480, AI095466, and AI095608 to D. A.; T32-AI007532 to G. F. S and L. A. M.; T32-AI055428 to G. F. S.; T32-RR007063 and K08-DK093784 to T. A.; and AI47619 to K.-M. C.); the NIH-funded Penn Center for AIDS Research (grant P30 AI 045008 to G. F. S. and D. A.); the Burroughs Wellcome Fund Investigator in Pathogenesis of Infectious Disease Award (to D. A.); the Philadelphia VA Medical Research and Merit Review and American Gastroenterological Association (to K.-M. C.); the Ministry of Education, Culture, Sports, Science and Technology of Japan (to J.K., N.S., and H. K); and the Program for Promotion of Basic and Applied Researches for Innovations in Bio-Oriented Industry (to J.K.). We also thank the Matthew J. Ryan Veterinary Hospital Pathology Lab, the National Institute of Diabetes and Digestive and Kidney Disease Center for the Molecular Studies in Digestive and Liver Disease Molecular Pathology and Imaging Core (grant P30DK50306), the Penn Microarray Facility, and the Abramson Cancer Center Flow Cytometry and Cell Sorting Resource Laboratory [partially supported by National Cancer Institute (NCI) Comprehensive Cancer Center Support grant # 2-P30 CA016520] for technical advice and support. Several human tissue samples were provided by the Cooperative Human Tissue Network, which is funded by the NCI. The data presented in the paper are tabulated in the main paper and in the supplementary materials. NR 29 TC 257 Z9 266 U1 1 U2 38 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 8 PY 2012 VL 336 IS 6086 BP 1321 EP 1325 DI 10.1126/science.1222551 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 953WV UT WOS:000304905300051 PM 22674331 ER PT J AU Bendlin, BB Carlsson, CM Johnson, SC Zetterberg, H Blennow, K Willette, AA Okonkwo, OC Sodhi, A Ries, ML Birdsill, AC Alexander, AL Rowley, HA Puglielli, L Asthana, S Sager, MA AF Bendlin, Barbara B. Carlsson, Cynthia M. Johnson, Sterling C. Zetterberg, Henrik Blennow, Kaj Willette, Auriel A. Okonkwo, Ozioma C. Sodhi, Aparna Ries, Michele L. Birdsill, Alex C. Alexander, Andrew L. Rowley, Howard A. Puglielli, Luigi Asthana, Sanjay Sager, Mark A. TI CSF T-Tau/A beta(42) Predicts White Matter Microstructure in Healthy Adults at Risk for Alzheimer's Disease SO PLOS ONE LA English DT Article ID MILD COGNITIVE IMPAIRMENT; CEREBROSPINAL-FLUID BIOMARKERS; VOXEL-BASED MORPHOMETRY; CORPUS-CALLOSUM ATROPHY; APOE EPSILON-4 ALLELE; BRAIN ATROPHY; IN-VIVO; NEUROFILAMENT PROTEIN; PHOSPHORYLATED-TAU; MYELIN BREAKDOWN AB Cerebrospinal fluid (CSF) biomarkers T-Tau and A beta(42) are linked with Alzheimer's disease (AD), yet little is known about the relationship between CSF biomarkers and structural brain alteration in healthy adults. In this study we examined the extent to which AD biomarkers measured in CSF predict brain microstructure indexed by diffusion tensor imaging (DTI) and volume indexed by T1-weighted imaging. Forty-three middle-aged adults with parental family history of AD received baseline lumbar puncture and MRI approximately 3.5 years later. Voxel-wise image analysis methods were used to test whether baseline CSF A beta(42), total tau (T-Tau), phosphorylated tau (P-Tau) and neurofilament light protein predicted brain microstructure as indexed by DTI and gray matter volume indexed by T1-weighted imaging. T-Tau and T-Tau/A beta(42) were widely correlated with indices of brain microstructure (mean, axial, and radial diffusivity), notably in white matter regions adjacent to gray matter structures affected in the earliest stages of AD. None of the CSF biomarkers were related to gray matter volume. Elevated P-Tau and P-Tau/A beta(42) levels were associated with lower recognition performance on the Rey Auditory Verbal Learning Test. Overall, the results suggest that CSF biomarkers are related to brain microstructure in healthy adults with elevated risk of developing AD. Furthermore, the results clearly suggest that early pathological changes in AD can be detected with DTI and occur not only in cortex, but also in white matter. C1 [Bendlin, Barbara B.; Carlsson, Cynthia M.; Johnson, Sterling C.; Willette, Auriel A.; Okonkwo, Ozioma C.; Sodhi, Aparna; Ries, Michele L.; Birdsill, Alex C.; Puglielli, Luigi; Asthana, Sanjay; Sager, Mark A.] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI USA. [Bendlin, Barbara B.; Carlsson, Cynthia M.; Johnson, Sterling C.; Willette, Auriel A.; Okonkwo, Ozioma C.; Sodhi, Aparna; Ries, Michele L.; Birdsill, Alex C.; Puglielli, Luigi; Asthana, Sanjay; Sager, Mark A.] Univ Wisconsin, Dept Med, Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA. [Zetterberg, Henrik; Blennow, Kaj] Univ Gothenburg, Sahlgrenska Acad, Dept Psychiat & Neurochem, Inst Neurosci & Physiol, Gothenburg, Sweden. [Alexander, Andrew L.] Univ Wisconsin, Dept Med Phys, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Alexander, Andrew L.] Univ Wisconsin, Dept Psychiat, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Alexander, Andrew L.] Waisman Lab Brain Imaging & Behav, Madison, WI USA. [Rowley, Howard A.] Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53706 USA. RP Bendlin, BB (reprint author), William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI USA. EM bbb@medicine.wisc.edu OI Bendlin, Barbara/0000-0002-0580-9875 FU National Institute on Aging [R01 AG027161, K23 AG026752, ADRC P50 AG033514]; University of Wisconsin Institute for Clinical and Translational Research; National Center for Research Resources/National Institutes of Health Clinical and Translational Science Award [1UL1RR025011]; program of the National Center for Research Resources, United States National Institutes of Health; Swedish Research Council; Pfizer Inc.; Innogenetics; Vastra Gotalandsregionen, Sweden; Swedish Brain Power Project; Swedish Council for Working Life and Social Research; Swedish Alzheimer Foundation; Stiftelsen for Gamla Tjanarinnor; King Gustaf V and Queen Victoria Foundation; Alzheimer's Association; Royal Swedish Academy of Sciences FX This project was supported in part by the National Institute on Aging (R01 AG027161 [MAS], K23 AG026752 [CMC]; ADRC P50 AG033514 [SA]), the University of Wisconsin Institute for Clinical and Translational Research, funded through a National Center for Research Resources/National Institutes of Health Clinical and Translational Science Award, 1UL1RR025011, a program of the National Center for Research Resources, United States National Institutes of Health, and the Swedish Research Council. The project was also facilitated by the facilities and resources at the Geriatric Research, Education, and Clinical Center (GRECC) of the William S. Middleton Memorial Veterans Hospital, Madison, WI. GRECC MS # 2011-19. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; Dr. Blennow has served on scientific advisory boards for Adlyfe Inc., Bayer Schering Pharma, Bristol-Myers Squibb, and Merz Pharmaceuticals GmbH; received a speaker honorarium from Pfizer Inc.; serves as a consultant for Wyeth, AstraZeneca, Bristol-Myers Squibb, and Eli Lilly and Company; and has received research support from Pfizer Inc., Innogenetics, the Swedish Research Council, Vastra Gotalandsregionen, Sweden, the Swedish Brain Power Project, the Swedish Council for Working Life and Social Research, the Swedish Alzheimer Foundation, Stiftelsen for Gamla Tjanarinnor, and the King Gustaf V and Queen Victoria Foundation. Dr. Zetterberg has served on a scientific advisory board for GlaxoSmithKline; serves as an Associate Editor for the Journal of Alzheimer's Disease; and receives research support from the Swedish Research Council, the Alzheimer's Association, and the Royal Swedish Academy of Sciences. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. NR 123 TC 24 Z9 24 U1 0 U2 13 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 JUN 6 PY 2012 VL 7 IS 6 AR e37720 DI 10.1371/journal.pone.0037720 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959WK UT WOS:000305348400018 PM 22701578 ER PT J AU Renquist, BJ Murphy, JG Larson, EA Olsen, D Klein, RF Ellacott, KLJ Cone, RD AF Renquist, Benjamin J. Murphy, Jonathan G. Larson, Emily A. Olsen, Dawn Klein, Robert F. Ellacott, Kate L. J. Cone, Roger D. TI Melanocortin-3 receptor regulates the normal fasting response SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE energy homeostasis; nonesterified fatty acid; corticotrophin-releasing hormone; hormone-sensitive lipase ID AGOUTI-RELATED PROTEIN; WHITE ADIPOSE-TISSUE; MONOCYTE CHEMOATTRACTANT PROTEIN-1; SYMPATHETIC NERVOUS-SYSTEM; PITUITARY-ADRENAL AXIS; INSULIN-RESISTANCE; BONE MASS; PROOPIOMELANOCORTIN PEPTIDES; FRAMESHIFT MUTATION; TRIGLYCERIDE LIPASE AB The melanocortin-3 receptor-deficient (MC3-R-/-) mouse exhibits mild obesity without hyperphagia or hypometabolism. MC3-R deletion is reported to increase adiposity, reduce lean mass and white adipose tissue inflammation, and increase sensitivity to salt-induced hypertension. We show here that the MC3-R-/- mouse exhibits defective fasting-induced white adipose tissue lipolysis, fasting-induced liver triglyceride accumulation, fasting-induced refeeding, and fasting-induced regulation of the adipostatic and hypothalamic-adrenal-pituitary axes. Close examination of the hypothalamic-pituitary-adrenal axis showed that MC3-R-/- mice exhibit elevated nadir corticosterone as well as a blunted fasting-induced activation of the axis. The previously described phenotypes of this animal and the reduced bone density reported here parallel those of Cushing syndrome. Thus, MC3-R is required for communicating nutritional status to both central and peripheral tissues involved in nutrient partitioning, and this defect explains much of the metabolic phenotype in the model. C1 [Renquist, Benjamin J.; Ellacott, Kate L. J.; Cone, Roger D.] Vanderbilt Univ Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Murphy, Jonathan G.] Univ Colorado Denver Sch Med, Dept Pharmacol, Aurora, CO 80045 USA. [Larson, Emily A.; Olsen, Dawn; Klein, Robert F.] Oregon Hlth & Sci Univ, Dept Med, Bone & Mineral Unit, Portland, OR 97201 USA. [Olsen, Dawn; Klein, Robert F.] Portland VA Med Ctr, Portland, OR 97201 USA. RP Cone, RD (reprint author), Vanderbilt Univ Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. EM roger.cone@vanderbilt.edu OI Ellacott, Kate/0000-0001-5261-7465 FU National Institutes of Health [DK078850]; VA Medical Research Service and National Institutes of Health [R01 AR44659] FX We thank Savannah Y. Williams and Katelijn Van Munster for technical assistance. This work was supported by National Institutes of Health Grant DK078850 (to R.D.C.), and by the VA Medical Research Service and National Institutes of Health Grant R01 AR44659 (to R.F.K.). NR 56 TC 27 Z9 27 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 5 PY 2012 VL 109 IS 23 BP E1489 EP E1498 DI 10.1073/pnas.1201994109 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 955BC UT WOS:000304991100008 PM 22573815 ER PT J AU Dey, N Das, F Ghosh-Choudhury, N Mandal, CC Parekh, DJ Block, K Kasinath, BS Abboud, HE Choudhury, GG AF Dey, Nirmalya Das, Falguni Ghosh-Choudhury, Nandini Mandal, Chandi Charan Parekh, Dipen J. Block, Karen Kasinath, Balakuntalam S. Abboud, Hanna E. Choudhury, Goutam Ghosh TI microRNA-21 Governs TORC1 Activation in Renal Cancer Cell Proliferation and Invasion SO PLOS ONE LA English DT Article ID TUMOR-SUPPRESSOR PTEN; GROWTH-FACTOR RECEPTOR; HIPPEL-LINDAU GENE; NF-KAPPA-B; KIDNEY CANCER; BREAST-CANCER; HIGH GLUCOSE; GLIOBLASTOMA CELLS; PROGNOSTIC-FACTORS; MAMMALIAN TARGET AB Metastatic renal cancer manifests multiple signatures of gene expression. Deviation in expression of mature miRNAs has been linked to human cancers. Importance of miR-21 in renal cell carcinomas is proposed from profiling studies using tumor tissue samples. However, the role of miR-21 function in causing renal cancer cell proliferation and invasion has not yet been shown. Using cultured renal carcinoma cells, we demonstrate enhanced expression of mature miR-21 along with pre-and pri-miR-21 by increased transcription compared to normal proximal tubular epithelial cells. Overexpression of miR-21 Sponge to quench endogenous miR-21 levels inhibited proliferation, migration and invasion of renal cancer cells. In the absence of mutation in the PTEN tumor suppressor gene, PTEN protein levels are frequently downregulated in renal cancer. We show that miR-21 targets PTEN mRNA 3'untranslated region to decrease PTEN protein expression and augments Akt phosphorylation in renal cancer cells. Downregulation of PTEN as well as overexpression of constitutively active Akt kinase prevented miR-21 Sponge-induced inhibition of renal cancer cell proliferation and migration. Moreover, we show that miR-21 Sponge inhibited the inactivating phosphorylation of the tumor suppressor protein tuberin and attenuated TORC1 activation. Finally, we demonstrate that expression of constitutively active TORC1 attenuated miR-21 Sponge-mediated suppression of proliferation and migration of renal cancer cells. Our results uncover a layer of post-transcriptional regulation of PTEN by transcriptional activation of miR-21 to force the canonical oncogenic Akt/TORC1 signaling conduit to drive renal cancer cell proliferation and invasion. C1 [Dey, Nirmalya; Das, Falguni; Block, Karen; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ghosh-Choudhury, Nandini; Block, Karen; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, Vet Adm Res, San Antonio, TX USA. [Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. [Ghosh-Choudhury, Nandini; Mandal, Chandi Charan] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Parekh, Dipen J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. RP Dey, N (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. EM choudhuryg@uthscsa.edu FU United States National Institutes of Health (NIH) [RO1 DK50190]; VA Research Service Merit Review; Juvenile Diabetes Research Foundation [1-2008-185]; VA Senior Research Career Scientist Award; VA Merit Review, NIH [RO1 AR 52425]; Cancer Therapy and Research Center, San Antonio, Texas; VA Research Service Career Scientist Award; Merit Review Awards; [NIH RO1 CA 131272]; [NIH RO1 DK 077295]; [NIH RO1 DK078971]; [NIH RC2A 036613] FX A United States National Institutes of Health (NIH) RO1 DK50190 grant to GGC supported this work. Part of this work was also supported by VA Research Service Merit Review grant to GGC. GGC is also supported by Juvenile Diabetes Research Foundation 1-2008-185 grants and is recipient of VA Senior Research Career Scientist Award. NGC is supported by VA Merit Review, NIH RO1 AR 52425 grants and Ronald P. Williams Orthopedic Oncology Developmental Research Award from Cancer Therapy and Research Center, San Antonio, Texas. KB, BSK and HEA are supported by grants, NIH RO1 CA 131272 (KB), NIH RO1 DK 077295 (BSK), NIH RO1 DK078971 (HEA), NIH RC2A 036613 (BSK) and VA Research Service Career Scientist Award (KB) and Merit Review Awards (KB, BSK and HEA). NR 118 TC 35 Z9 35 U1 2 U2 9 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 JUN 4 PY 2012 VL 7 IS 6 AR e37366 DI 10.1371/journal.pone.0037366 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UU UT WOS:000305341700013 PM 22685542 ER PT J AU Souza, P Hoover, E Gallun, F AF Souza, Pamela Hoover, Eric Gallun, Frederick TI Application of the Envelope Difference Index to Spectrally Sparse Speech SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE compression; consonant recognition; envelope; vocoding ID HEARING-IMPAIRED LISTENERS; PHONEME RECOGNITION; AMPLITUDE COMPRESSION; NOISE; INTELLIGIBILITY; INFORMATION; CHANNELS; QUALITY; CUES; MODULATION AB Purpose: Amplitude compression is a common hearing aid processing strategy that can improve speech audibility and loudness comfort but also has the potential to alter important cues carried by the speech envelope. In previous work, a measure of envelope change, the Envelope Difference Index (EDI; Fortune, Woodruff, & Preves, 1994), was moderately related to recognition of spectrally robust consonants. This follow-up study investigated the relationship between the EDI and recognition of spectrally sparse consonants. Method: Stimuli were vowel-consonant-vowel tokens processed to reduce spectral cues. Compression parameters were chosen to achieve a range of EDI values. Recognition was measured for 20 listeners with normal hearing. Results: Both overall recognition and perception of consonant features were reduced at higher EDI values. Similar effects were noted with noise-vocoded and sine-vocoded processing and regardless of whether periodicity cues were available. Conclusion: The data provide information about the acceptable limits of envelope distortion under constrained conditions. These limits can be used to consider the impact of envelope distortions in situations where other cues are available to varying extents. C1 [Souza, Pamela; Hoover, Eric] Northwestern Univ, Evanston, IL 60208 USA. [Gallun, Frederick] Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR USA. RP Souza, P (reprint author), Northwestern Univ, Evanston, IL 60208 USA. EM p-souza@northwestern.edu OI Gallun, Frederick/0000-0002-4145-2199 FU National Institutes of Health [R01 DC0060014]; Department of Veterans Affairs Rehabilitation Research and Development Service [C4963W]; National Center for Rehabilitative Auditory Research FX This work was supported by National Institutes of Health Grant R01 DC0060014 to Pamela Souza, by Department of Veterans Affairs Rehabilitation Research and Development Service Grant C4963W to Frederick Gallun, and by the National Center for Rehabilitative Auditory Research. We thank Steve Armstrong and the Gennum Corporation for providing the hearing aid simulation software; Stuart Rosen for sharing the FIX program and vocoding algorithms; and Ashley Arrington, Alexandra Dykhouse, Louisa Ha, and Marcee Wickline for assistance in data collection. NR 56 TC 4 Z9 4 U1 1 U2 5 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD JUN 1 PY 2012 VL 55 IS 3 BP 824 EP 837 DI 10.1044/1092-4388(2011/10-0301) PG 14 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 084FO UT WOS:000314523500013 PM 22232401 ER PT J AU Ford, JM Dierks, T Fisher, DJ Herrmann, CS Hubl, D Kindler, J Koenig, T Mathalon, DH Spencer, KM Strik, W van Lutterveld, R AF Ford, Judith M. Dierks, Thomas Fisher, Derek J. Herrmann, Christoph S. Hubl, Daniela Kindler, Jochen Koenig, Thomas Mathalon, Daniel H. Spencer, Kevin M. Strik, Werner van Lutterveld, Remko TI Neurophysiological Studies of Auditory Verbal Hallucinations SO SCHIZOPHRENIA BULLETIN LA English DT Article DE auditory hallucinations; EEG; MEG; ERPs ID MULTI-FEATURE PARADIGM; MISMATCH NEGATIVITY; SCHIZOPHRENIA; P300; ATTENTION; SYMPTOMS; CORTEX; SYNCHRONIZATION; METAANALYSIS; PERCEPTION AB We discuss 3 neurophysiological approaches to study auditory verbal hallucinations (AVH). First, we describe "state" (or symptom capture) studies where periods with and without hallucinations are compared "within" a patient. These studies take 2 forms: passive studies, where brain activity during these states is compared, and probe studies, where brain responses to sounds during these states are compared. EEG (electroencephalography) and MEG (magnetoencephalography) data point to frontal and temporal lobe activity, the latter resulting in competition with external sounds for auditory resources. Second, we discuss "trait" studies where EEG and MEG responses to sounds are recorded from patients who hallucinate and those who do not. They suggest a tendency to hallucinate is associated with competition for auditory processing resources. Third, we discuss studies addressing possible mechanisms of AVH, including spontaneous neural activity, abnormal self-monitoring, and dysfunctional interregional communication. While most studies show differences in EEG and MEG responses between patients and controls, far fewer show symptom relationships. We conclude that efforts to understand the pathophysiology of AVH using EEG and MEG have been hindered by poor anatomical resolution of the EEG and MEG measures, poor assessment of symptoms, poor understanding of the phenomenon, poor models of the phenomenon, decoupling of the symptoms from the neurophysiology due to medications and comorbidites, and the possibility that the schizophrenia diagnosis breeds truer than the symptoms it comprises. These problems are common to studies of other psychiatric symptoms and should be considered when attempting to understand the basic neural mechanisms responsible for them. C1 [Ford, Judith M.; Mathalon, Daniel H.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Psychiat Serv, Dept Psychiat, San Francisco, CA 94121 USA. [Dierks, Thomas; Hubl, Daniela; Kindler, Jochen; Koenig, Thomas; Strik, Werner] Univ Bern, Univ Hosp Psychiat, Bern, Switzerland. [Fisher, Derek J.] Mt St Vincent Univ, Dept Psychol, Halifax, NS B3M 2J6, Canada. [Fisher, Derek J.] Univ Ottawa, Neuroelectrophysiol Unit, Mental Hlth Res Inst, Ottawa, ON, Canada. [Herrmann, Christoph S.] Carl von Ossietzky Univ Oldenburg, Dept Expt Psychol, D-2900 Oldenburg, Germany. [Spencer, Kevin M.] Harvard Univ, Sch Med, Res Serv, Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Spencer, Kevin M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [van Lutterveld, Remko] Univ Med Ctr, Dept Psychiat, Utrecht, Netherlands. [van Lutterveld, Remko] Rudolf Magnus Inst Neurosci, Dept Psychiat, NL-3508 TA Utrecht, Netherlands. RP Ford, JM (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Psychiat Serv, Dept Psychiat, 116D,4150 Clement St, San Francisco, CA 94121 USA. EM judith.ford@ucsf.edu RI Dierks, Thomas/B-7092-2012; Koenig, Thomas/F-6454-2010; Fisher, Derek/H-2297-2013; Strik, Werner/N-7807-2013 OI Dierks, Thomas/0000-0002-4173-5308; Mathalon, Daniel/0000-0001-6090-4974; Koenig, Thomas/0000-0002-1472-4638; Fisher, Derek/0000-0003-2366-8225; Strik, Werner/0000-0001-7108-1993; Spencer, Kevin/0000-0002-5500-7627 FU National Institutes of Health [MH080187, MH076989, MH058262]; VA Merit Award; National Alliance for Research on Schizophrenia and Depression; Canadian Institutes of Health Research; Dutch Science Organization (Nederlandse Wetenschappelijke Organisatie) FX National Institutes of Health (MH080187 to K.M.S., MH076989 to D.H.M., and MH058262 to J.M.F.); VA Merit Award (K.M.S. and J.M.F.); National Alliance for Research on Schizophrenia and Depression (to D.H.M); Canadian Institutes of Health Research (to D.J.F.); Dutch Science Organization (Nederlandse Wetenschappelijke Organisatie) (to R.v.L.). NR 49 TC 26 Z9 27 U1 2 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JUN PY 2012 VL 38 IS 4 BP 715 EP 723 DI 10.1093/schbul/sbs009 PG 9 WC Psychiatry SC Psychiatry GA 979ZX UT WOS:000306864500012 PM 22368236 ER PT J AU Green, MF Bearden, CE Cannon, TD Fiske, AP Hellemann, GS Horan, WP Kee, K Kern, RS Lee, J Sergi, MJ Subotnik, KL Sugar, CA Ventura, J Yee, CM Nuechterlein, KH AF Green, Michael F. Bearden, Carrie E. Cannon, Tyrone D. Fiske, Alan P. Hellemann, Gerhard S. Horan, William P. Kee, Kimmy Kern, Robert S. Lee, Junghee Sergi, Mark J. Subotnik, Kenneth L. Sugar, Catherine A. Ventura, Joseph Yee, Cindy M. Nuechterlein, Keith H. TI Social Cognition in Schizophrenia, Part 1: Performance Across Phase of Illness SO SCHIZOPHRENIA BULLETIN LA English DT Article DE social cognition; illness phase; schizophrenia ID FACIAL AFFECT RECOGNITION; NEUROCOGNITIVE ENDOPHENOTYPES; EMOTIONAL INTELLIGENCE; PERCEPTION DEFICITS; FUNCTIONAL STATUS; PSYCHOSIS; MIND; SCHIZOTYPY; METAANALYSIS; RISK AB Social cognitive impairments are consistently reported in schizophrenia and are associated with functional outcome. We currently know very little about whether these impairments are stable over the course of illness. In the current study, 3 different aspects of social cognition were assessed (emotion processing, Theory of Mind [ToM], and social relationship perception) at 3 distinct developmental phases of illness: prodromal, first episode, and chronic. In this cross-sectional study, participants included 50 individuals with the prodromal risk syndrome for psychosis and 34 demographically comparable controls, 81 first-episode schizophrenia patients and 46 demographically comparable controls, and 53 chronic schizophrenia patients and 47 demographically comparable controls. Outcome measures included total and subtest scores on 3 specialized measures of social cognition: (1) emotion processing assessed with the Mayer-Salovey-Caruso Emotional Intelligence Test, (2) ToM assessed with The Awareness of Social Inference Test, and (3) social relationship perception assessed the Relationships Across Domains Test. Social cognitive performance was impaired across all domains of social cognition and in all clinical samples. Group differences in performance were comparable across phase of illness, with no evidence of progression or improvement. Age had no significant effect on performance for either the clinical or the comparison groups. The findings suggest that social cognition in these 3 domains fits a stable pattern that has outcome and treatment implications. An accompanying article prospectively examines the longitudinal stability of social cognition and prediction of functional outcome in the first-episode sample. C1 [Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Green, Michael F.; Horan, William P.; Kee, Kimmy; Kern, Robert S.; Lee, Junghee; Sergi, Mark J.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Bearden, Carrie E.; Cannon, Tyrone D.; Yee, Cindy M.; Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Fiske, Alan P.] Univ Calif Los Angeles, Dept Anthropol, Los Angeles, CA 90095 USA. [Kee, Kimmy] Calif State Univ, Dept Psychol, Camarillo, CA USA. [Sergi, Mark J.] Calif State Univ Northridge, Dept Psychol, Northridge, CA 91330 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA. RP Green, MF (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, 300 Med Plaza,Room 2263, Los Angeles, CA 90095 USA. EM mgreen@ucla.edu RI Lee, Junghee/C-5226-2014 OI Lee, Junghee/0000-0001-9567-8700 FU National Institute of Mental Health Center [P50 MH066286, MH037705, MH043292] FX National Institute of Mental Health Center grant (P50 MH066286 and MH037705 to K.H.N.; MH043292 to M.F.G.). NR 65 TC 134 Z9 139 U1 7 U2 44 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JUN PY 2012 VL 38 IS 4 BP 854 EP 864 DI 10.1093/schbul/sbq171 PG 11 WC Psychiatry SC Psychiatry GA 979ZX UT WOS:000306864500027 PM 21345917 ER PT J AU Horan, WP Green, MF DeGroot, M Fiske, A Hellemann, G Kee, K Kern, RS Lee, J Sergi, MJ Subotnik, KL Sugar, CA Ventura, J Nuechterlein, KH AF Horan, William P. Green, Michael F. DeGroot, Michael Fiske, Alan Hellemann, Gerhard Kee, Kimmy Kern, Robert S. Lee, Junghee Sergi, Mark J. Subotnik, Kenneth L. Sugar, Catherine A. Ventura, Joseph Nuechterlein, Keith H. TI Social Cognition in Schizophrenia, Part 2: 12-Month Stability and Prediction of Functional Outcome in First-Episode Patients SO SCHIZOPHRENIA BULLETIN LA English DT Article DE functional outcome; emotional processing; theory of mind; social perception; cross-lagged panel analyses; longitudinal prediction ID FACIAL AFFECT RECOGNITION; EMOTIONAL INTELLIGENCE; NEUROCOGNITIVE ENDOPHENOTYPES; PERCEPTION DEFICITS; 1ST EPISODE; MIND; SCHIZOTYPY; PSYCHOSIS; VULNERABILITY; REMISSION AB This study evaluated the longitudinal stability and functional correlates of social cognition during the early course of schizophrenia. Fifty-five first-episode schizophrenia patients completed baseline and 12-month follow-up assessments of 3 key domains of social cognition (emotional processing, theory of mind, and social/relationship perception), as well as clinical ratings of real-world functioning and symptoms. Scores on all 3 social cognitive tests demonstrated good longitudinal stability with test-retest correlations exceeding .70. Higher baseline and 12-month social cognition scores were both robustly associated with significantly better work functioning, independent living, and social functioning at the 12-month follow-up assessment. Furthermore, cross-lagged panel analyses were consistent with a causal model in which baseline social cognition drove later functional outcome in the domain of work, above and beyond the contribution of symptoms. Social cognitive impairments are relatively stable, functionally relevant features of early schizophrenia. These results extend findings from a companion study, which showed stable impairments across patients in prodromal, first-episode, and chronic phases of illness on the same measures. Social cognitive impairments may serve as useful vulnerability indicators and early clinical intervention targets. C1 [Horan, William P.] Univ Calif Los Angeles, Semel Inst, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Horan, William P.; Green, Michael F.; DeGroot, Michael; Kee, Kimmy; Kern, Robert S.; Lee, Junghee; Sergi, Mark J.; Subotnik, Kenneth L.; Sugar, Catherine A.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. [Fiske, Alan] Univ Calif Los Angeles, Dept Anthropol, Los Angeles, CA 90095 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA. [Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Kee, Kimmy] Calif State Univ, Dept Psychol, Channel Islands, CA USA. [Sergi, Mark J.] Calif State Univ Northridge, Dept Psychol, Northridge, CA 91330 USA. RP Horan, WP (reprint author), Univ Calif Los Angeles, Semel Inst, Dept Psychiat & Biobehav Sci, 300 Med Plaza,Room 2263, Los Angeles, CA 90095 USA. EM horan@ucla.edu RI Lee, Junghee/C-5226-2014 OI Lee, Junghee/0000-0001-9567-8700 FU National Institute of Mental Health Center [MH066286, MH037705, MH043292] FX National Institute of Mental Health Center grant P50 (MH066286, MH037705 to K.H.N., MH043292 to M.F.G.). NR 55 TC 90 Z9 95 U1 3 U2 24 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JUN PY 2012 VL 38 IS 4 BP 865 EP 872 DI 10.1093/schbul/sbr001 PG 8 WC Psychiatry SC Psychiatry GA 979ZX UT WOS:000306864500028 PM 21382881 ER PT J AU DuPriest, EA Kupfer, P Lin, B Sekiguchi, K Morgan, TK Saunders, KE Chatkupt, TT Denisenko, ON Purnell, JQ Bagby, SP AF DuPriest, E. A. Kupfer, P. Lin, B. Sekiguchi, K. Morgan, T. K. Saunders, K. E. Chatkupt, T. T. Denisenko, O. N. Purnell, J. Q. Bagby, S. P. TI Altered adipocyte structure and function in nutritionally programmed microswine offspring SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE LA English DT Article DE adipose tissue; catch-up growth; maternal protein restriction ID FOR-GESTATIONAL-AGE; PITUITARY-ADRENAL AXIS; LOW-BIRTH-WEIGHT; ADIPONECTIN GENE-EXPRESSION; PLASMA-CORTISOL CONCENTRATIONS; MATERNAL PROTEIN RESTRICTION; INSULIN-RESISTANCE SYNDROME; ADIPOSE-TISSUE; 11-BETA-HYDROXYSTEROID DEHYDROGENASE; VISCERAL ADIPOSITY AB Adipose tissue (AT) dysfunction links obesity of any cause with cardiometabolic disease, but whether early-life nutritional deficiency can program adipocyte dysfunction independently of obesity is untested. In 3-5-month-old juvenile microswine offspring exposed to isocaloric perinatal maternal protein restriction (MPR) and exhibiting accelerated prepubertal fat accrual without obesity, we assessed markers of acquired obesity: adiponectin and tumor necrosis factor (TNF)-alpha messenger ribonucleic acid (mRNA) levels and adipocyte size in intra-abdominal (ABD-AT) and subcutaneous (SC-AT) adipose tissues. Plasma cortisol, leptin and insulin levels were measured in fetal, neonatal and juvenile offspring. In juvenile low-protein offspring (LPO), adipocyte size in ABD-AT was reduced 22% (P = 0.011 v. controls), whereas adipocyte size in SC-AT was increased in female LPO (P = 0.05) and normal in male LPO; yet, adiponectin mRNA in LPO was low in both sexes and in both depots (P < 0.001). Plasma leptin (P = 0.004) and cortisol (P < 0.05) were reduced only in neonatal LPO during MPR. In juveniles, correlations between % body fat and adiponectin mRNA, TNF-alpha mRNA or plasma leptin were significant in normal-protein offspring (NPO) but absent in LPO. Plasma glucose in juvenile LPO was increased in males but decreased in females (interaction, P = 0.023); plasma insulin levels and insulin sensitivity were unaffected. Findings support nutritional programming of adipocyte size and gene expression and subtly altered glucose homeostasis. Reduced adiponectin mRNA and adipokine dysregulation in juvenile LPO following accelerated growth occurred independently of obesity, adipocyte hypertrophy or inflammatory markers; thus, perinatal MPR and/or growth acceleration can alter adipocyte structure and disturb adipokine homeostasis in metabolically adverse patterns predictive of enhanced disease risk. C1 [Bagby, S. P.] Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Dept Med, Portland, OR 97239 USA. [DuPriest, E. A.; Bagby, S. P.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [DuPriest, E. A.; Kupfer, P.; Lin, B.; Sekiguchi, K.; Bagby, S. P.] Portland VA Med Ctr, Res Serv, Portland, OR USA. [DuPriest, E. A.] Warner Pacific Coll, Dept Nat Sci & Hlth, Portland, OR USA. [Morgan, T. K.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA. [Saunders, K. E.; Chatkupt, T. T.] Oregon Hlth & Sci Univ, Dept Comparat Med, Portland, OR 97239 USA. [Denisenko, O. N.] Univ Washington, Dept Med, Seattle, WA USA. RP Bagby, SP (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Dept Med, 3303 SW Bond Ave,CH12R, Portland, OR 97239 USA. EM bagbys@ohsu.edu FU NIH/NICHD [1P01 HD34430, R01 HD042570]; Medical Research Foundation of Oregon; Eagles Foundation of Spokane, WA; American Heart Association Pacific Mountain Affiliate Predoctoral Fellowship Award [0415530Z]; Oregon Health & Science University Tartar Trust Fellowship FX Work was supported by NIH/NICHD 1P01 HD34430, R01 HD042570, Medical Research Foundation of Oregon, and the Eagles Foundation of Spokane, WA. EA DuPriest was supported by American Heart Association Pacific Mountain Affiliate Predoctoral Fellowship Award no. 0415530Z and by the Oregon Health & Science University Tartar Trust Fellowship. NR 69 TC 0 Z9 0 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 2040-1744 J9 J DEV ORIG HLTH DIS JI J. Dev. Orig. Health Dis. PD JUN PY 2012 VL 3 IS 3 BP 198 EP 209 DI 10.1017/S2040174412000232 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 984IL UT WOS:000307183200009 PM 25102010 ER PT J AU Puppin, C Passon, N Hershman, JM Filetti, S Bulotta, S Celano, M Russo, D Damante, G AF Puppin, Cinzia Passon, Nadia Hershman, Jerome M. Filetti, Sebastiano Bulotta, Stefania Celano, Marilena Russo, Diego Damante, Giuseppe TI Cooperative effects of SAHA and VPA on NIS gene expression and proliferation of thyroid cancer cells SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID HISTONE DEACETYLASE INHIBITORS; SODIUM-IODIDE SYMPORTER; SODIUM/IODIDE SYMPORTER; NA+/I-SYMPORTER; UPSTREAM ENHANCER; BREAST-CANCER; VALPROIC ACID; ACETYLATION; H3; IDENTIFICATION AB Histone deacetylase inhibitors (HDACi) have shown both anti-proliferative and redifferentiating effects in thyroid cancer cells. Also, they induce the expression of the sodium-iodide symporter gene (NIS (SLC5A5)), a crucial step for radioiodine treatment of thyroid malignancies. Here we investigated the effects of suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA) on BCPAP and FRO thyroid cancer cells, extending our analysis on the epigenetic mechanisms underlying the NIS gene expression stimulation. In both cell lines we found a cooperative effect of the two compounds on either cell viability and NIS gene expression, resulting in acquired/increased ability to uptake the radioiodine. Such effect was specific since it was not observed for expression of other genes or when SAHA was used in combination with trichostatin A. By using chromatin immunoprecipitation, we investigated epigenetic mechanisms underlying SAHA and VPA effects. Cooperation among the two HDACi occurred on H3 histone trimethylation at lysine 4 (H3K4me3) and not on histone acetylation. However, effects on H3K4me3 were detected only at the level of NIS Proximal Basal Promoter (NIS-PBP) in FRO cells and only at the level of NIS Upstream Enhancer (NIS-NUE) in BCPAP cells. Our data indicate that epigenetic changes are involved in the synergistic effects of VPA and SAHA on NIS gene expression and that the cellular context modifies effects of HDACi in terms of H3K4me3 target sequence. Investigation of cooperation among different HDACi may provide clues for better defining their mechanism of action in view of their use in thyroid cancer treatment. Journal of Molecular Endocrinology (2012) 48, 217-227 C1 [Puppin, Cinzia; Passon, Nadia; Damante, Giuseppe] Univ Udine, Dipartimento Sci Med & Biol, I-33100 Udine, Italy. [Hershman, Jerome M.] Vet Adm Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Filetti, Sebastiano] Univ Roma La Sapienza, Dipartimento Med Interna & Specialita Med, Rome, Italy. [Bulotta, Stefania; Celano, Marilena; Russo, Diego] Univ Catanzaro, Dipartimento Sci Farmacobiol, Catanzaro, Italy. [Damante, Giuseppe] Univ S Maria della Misericordia, Azienda Osped, Udine, Italy. RP Damante, G (reprint author), Univ Udine, Dipartimento Sci Med & Biol, Piazzale Kolbe 1, I-33100 Udine, Italy. EM giuseppe.damante@uniud.it FU Associazione Italiana per la Ricerca sul Cancro (AIRC) [IG 10296]; MIUR (PRIN) [20093WAPIK_003] FX This work was supported by grants to G D from Associazione Italiana per la Ricerca sul Cancro (AIRC) (grant number IG 10296) and MIUR (PRIN grant number 20093WAPIK_003). NR 51 TC 8 Z9 8 U1 0 U2 2 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD JUN PY 2012 VL 48 IS 3 BP 217 EP 227 DI 10.1530/JME-11-0063 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 985PI UT WOS:000307279100006 ER PT J AU Hosain, GMM Khan, MM Amiel, GE Lerner, SP Latini, DM Chen, GJ AF Hosain, G. M. Monawar Khan, Myrna M. Amiel, Gilad E. Lerner, Seth P. Latini, David M. Chen, G. John TI RACIAL/ETHNIC DIFFERENCES IN UPPER-TRACT UROTHELIAL CANCER SO ETHNICITY & DISEASE LA English DT Article DE Race/ethnicity; Urothelial Cancer; Difference; SEER Program ID UPPER URINARY-TRACT; BLADDER-CANCER; AFRICAN-AMERICAN; PROSTATE-CANCER; BREAST-CANCER; LYMPH-NODES; PELVIC LYMPHADENECTOMY; RACIAL DISPARITY; BLACK PATIENTS; WHITE PATIENTS AB Objectives: Information on clinical characteristics, pattern of initial treatment and survival in patient with upper-tract urothelial carcinomas (UTUC) is scarce. Our study examined the racial/ethnic differences in patients diagnosed with incident UTUC. Design: Observational study. The data analyses included: proportion and ANOVA for categorical and continuous variables, respectively; Kaplan-Meier method for calculating overall survival; and Cox-proportional hazards models for obtaining adjusted hazard-ratios. Setting: Regions of the Surveillance, Epidemiology and End Results (SEER). Patients or Participants: 16,702 incident UTUC patients identified from the SEER dataset 1988-2007 (14,192 White, 967 Hispanic, 718 African American and 825 Asian). Interventions: None. Main Outcome Measures: Race/ethnicity-specific distributions of demographics, tumor characteristics, patterns of initial treatment, and survival. Results: African American and Hispanic patients were diagnosed at a younger age than Whites and Asians (P=.001). Hispanics were more likely to be diagnosed with larger tumor size than Whites and Asians (P<.0001). Asians were more likely to be diagnosed with advanced stage and higher tumor grade. Cox-regression revealed that Whites and Asians were significantly less likely to die after UTUC diagnosis than African Americans (HR=.78, 95% CI=.67.91 and HR=.75, 95% C1.61.91, respectively; all P=<.01). Conclusions: Our study found that Asians had worse tumor characteristics at the initial presentation than the other groups in this study, but that their risk of dying was lower. Further research is needed to include a larger number of Asian patients to examine subgroup differences and to confirm the paradoxical finding of higher survival with poor clinical characteristics. (Ethn Dis. 2012;22[3]:295-301) C1 [Hosain, G. M. Monawar; Khan, Myrna M.; Chen, G. John] VA Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. [Khan, Myrna M.; Amiel, Gilad E.; Lerner, Seth P.; Latini, David M.; Chen, G. John] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. RP Hosain, GMM (reprint author), DeBakey Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM monawarhosain@gmail.com OI Latini, David/0000-0002-6161-4861 FU Houston VA HSR&D Center of Excellence [HFP90-020] FX This work was supported in part by 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). NR 37 TC 1 Z9 2 U1 1 U2 2 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD SUM PY 2012 VL 22 IS 3 BP 295 EP 301 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 978EP UT WOS:000306723700007 PM 22870572 ER PT J AU Sawers, A Hahn, ME AF Sawers, Andrew Hahn, Michael E. TI Regulation of whole-body frontal plane balance varies within a step during unperturbed walking SO GAIT & POSTURE LA English DT Article DE Balance; Gait; Variability; Motor control; Rehabilitation ID LATERAL MOTION; STABILIZATION AB This study sought to determine whether the need to actively control lateral balance is consistent within a step. Variability of the frontal plane COM-Ankle angle was calculated over 50 strides at discrete gait events for twenty-one healthy young adults to quantify active control of lateral balance within a step. Frontal plane COM-Ankle angle variability was found to vary significantly between all gait events, decreasing progressively within a step. This suggests that active control of lateral balance varies significantly within a step and that the greatest degree of active control occurs at heel-strike. The increased active control of lateral balance during heel-strike indicates a degree of preparation to ensure sufficient lateral balance control prior to more challenging events. These results provide insight into the mechanisms of lateral balance control and how to assess and treat locomotor balance control impairments. Published by Elsevier B.V. C1 [Sawers, Andrew; Hahn, Michael E.] Rehabil Res & Dev Ctr Excellence Limb Loss Preven, Dept Vet Affairs VA, VA Puget Sound, Seattle, WA 98108 USA. [Sawers, Andrew] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Hahn, Michael E.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. RP Hahn, ME (reprint author), Rehabil Res & Dev Ctr Excellence Limb Loss Preven, Dept Vet Affairs VA, VA Puget Sound, 1660 S Columbian Way, Seattle, WA 98108 USA. EM mehahn@u.washington.edu FU Center of Excellence grant from the Department of Veterans Affairs, Rehabilitation Research and Development [A4843C] FX This research was supported by a Center of Excellence grant (A4843C) from the Department of Veterans Affairs, Rehabilitation Research and Development. NR 16 TC 7 Z9 7 U1 1 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD JUN PY 2012 VL 36 IS 2 BP 322 EP 324 DI 10.1016/j.gaitpost.2012.03.003 PG 3 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 976YP UT WOS:000306623600030 PM 22465707 ER PT J AU Flint, LA Sudore, RL Widera, E AF Flint, Lynn A. Sudore, Rebecca L. Widera, Eric TI Assessing Financial Capacity Impairment in Older Adults SO GENERATIONS-JOURNAL OF THE AMERICAN SOCIETY ON AGING LA English DT Article ID COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; DEMENTIA; COMPETENCE; CAREGIVERS; ABILITIES C1 [Flint, Lynn A.; Sudore, Rebecca L.; Widera, Eric] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Flint, Lynn A.; Sudore, Rebecca L.; Widera, Eric] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. RP Flint, LA (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. EM lynn.flint@ucsf.edu; rebecca.sudore@ucsf.edu; eric.widera@ucsf.edu NR 17 TC 3 Z9 3 U1 0 U2 2 PU AMER SOC AGING PI SAN FRANCISCO PA 833 MARKET ST, STE 511, SAN FRANCISCO, CA 94103-1824 USA SN 0738-7806 J9 GENERATIONS JI Generations-J. Am. Soc. Aging PD SUM PY 2012 VL 36 IS 2 BP 59 EP 65 PG 7 WC Gerontology SC Geriatrics & Gerontology GA 970DL UT WOS:000306108200010 ER PT J AU Leykum, L Kumar, P Parchman, M McDaniel, RR Lanham, H Agar, M AF Leykum, Luci Kumar, Pradeep Parchman, Michael McDaniel, Reuben R. Lanham, Holly Agar, Michael TI Use of an Agent-Based Model to Understand Clinical Systems SO JASSS-THE JOURNAL OF ARTIFICIAL SOCIETIES AND SOCIAL SIMULATION LA English DT Article DE Healthcare Delivery; Sensemaking; Clinical Systems ID RANDOMIZED-TRIAL; PRIMARY-CARE; INTERVENTION; REMINDERS AB Health care improvement efforts often focus on changing the behavior of individuals while the interdependencies among individuals are overlooked. The application of complex adaptive systems approach to studying healthcare delivery changes the focus of improvement efforts from the individual to the relationships and interdependencies among individuals in the system. Sensemaking and improvising are social activities that take place in the context of relationships between individuals. We explore the impact of sensemaking and improvising on patient outcomes in healthcare settings. We conducted an in-depth observational study of relationships in inpatient general medicine teams. Data collection focused on examining associations between team relationship behaviors of sensemaking and improvising and patient outcomes. Data analysis revealed that these activities were positively associated with patient outcomes. Based on these observational data and findings, we developed an agent-based model to further explore and clarify the relationships between sensemaking and improvising on physician teams and patient outcomes. Specifically, we used the agent-based model to simulate the impact of variation in physicians' sensemaking and improvisation abilities on patient length of stay, the likelihood of a patient worsening or developing complications, the need for transfer to a higher level of care, and mortality. Our in-depth study indicates that systematic differences in patient outcomes are associated with differences in the capacity of physician teams to effectively make sense and improvise in the dynamic conditions inherent in healthcare systems. The results of our simulation demonstrate that an agent-based modeling approach is feasible and useful for exploring the impact of physician team behaviors on patient outcomes. This finding suggests the need for new tools and approaches to improve sensemaking and improvisation in physician care teams as strategies to improve patient outcomes. C1 [Leykum, Luci; Lanham, Holly] UTHSCSA, South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Kumar, Pradeep] Univ Texas, Austin, TX USA. [Parchman, Michael] Univ Texas Hlth Sci Ctr, San Antonio, TX USA. [McDaniel, Reuben R.] McCombs Sch Business, Austin, TX USA. [Agar, Michael] Ethknoworks, Santa Fe, NM USA. RP Leykum, L (reprint author), Univ Texas Hlth Sci Ctr, Sch Med, Off Dean 373L,7703 Floyd Curl Dr, San Antonio, TX 78209 USA. EM leykum@uthscsa.edu; pradeepkumar23@ymail.com; parchman@uthscsa.edu; reuben.mcdaniel@mccombs.utexas.edu; lanham@uthscsa.edu; magar@anth.umd.edu NR 25 TC 4 Z9 4 U1 1 U2 13 PU J A S S S PI GUILDFORD PA UNIV SURREY, DEPT SOCIOLOGY, GUILDFORD GU2 7XH, SURREY, ENGLAND SN 1460-7425 J9 JASSS-J ARTIF SOC S JI JASSS PD JUN PY 2012 VL 15 IS 3 AR 2 PG 25 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA 976FY UT WOS:000306567500008 ER PT J AU Zhao, J Wei, JX Mialki, R Zou, CB Mallampalli, RK Zhao, YT AF Zhao, Jing Wei, Jianxin Mialki, Rachel Zou, Chunbin Mallampalli, Rama K. Zhao, Yutong TI Extracellular Signal-regulated Kinase (ERK) Regulates Cortactin Ubiquitination and Degradation in Lung Epithelial Cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIGHT-CHAIN KINASE; F-BOX PROTEINS; KAPPA-B-ALPHA; ARP2/3 COMPLEX; TYROSINE PHOSPHORYLATION; ACTIN POLYMERIZATION; BETA-TRCP; BARRIER ENHANCEMENT; PROTEASOME PATHWAY; MIGRATION AB Cortactin, an actin-binding protein, is essential for cell growth and motility. We have shown that cortactin is regulated by reversible phosphorylation, but little is known regarding cortactin protein stability. Here, we show that lipopolysaccharide (LPS)-induced cortactin degradation is mediated by extracellular regulated signal kinase (ERK). LPS induces cortactin serine phosphorylation, ubiquitination, and degradation in mouse lung epithelia, an effect abrogated by ERK inhibition. Serine phosphorylation sites mutant, cortactin(S405A/S418A), enhances its protein stability. Cortactin is polyubiquitinated and degraded within the proteasome, whereas a cortactin(K79R) mutant exhibited proteolytic stability during cyclohexamide (CHX) or LPS treatment. The E3 ligase subunit beta-Trcp interacts with cortactin, and its overexpression reduced cortactin protein levels, an effect attenuated by ERK inhibition. Overexpression of beta-Trcp was sufficient to reduce the protective effects of exogenous cortactin on epithelial cell barrier integrity, an effect not observed after expression of a cortactin(K79R) mutant. These results provide evidence that LPS modulation of cortactin stability is coordinately regulated by stress kinases and the ubiquitin-proteasomal network. C1 [Zhao, Jing; Wei, Jianxin; Mialki, Rachel; Zou, Chunbin; Mallampalli, Rama K.; Zhao, Yutong] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. RP Zhao, J (reprint author), Univ Pittsburgh, Dept Med, 3459 5th Ave,MUH NW628, Pittsburgh, PA 15213 USA. EM zhaoj@upmc.edu RI Wei, Jianxin/P-5431-2016 FU National Institutes of Health [R01 HL091916, R01 HL096376, R01 HL097376, R01 HL098174]; United States Department of Veterans Affairs; American Heart Association Scientist Development [12SDG9050005]; United States Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development FX This work was supported, in whole or in part, by National Institutes of Health Grants R01 HL091916 (to Y. Z.), and R01 HL096376, R01 HL097376, and R01 HL098174 (to R. K. M.). This work was also supported by a Merit Review Award from the United States Department of Veterans Affairs and American Heart Association Scientist Development Grant 12SDG9050005 (to J. Z.). This material is based upon work supported, in part, by the United States Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. NR 52 TC 12 Z9 12 U1 2 U2 7 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 JUN 1 PY 2012 VL 287 IS 23 BP 19105 EP 19114 DI 10.1074/jbc.M112.339507 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 974EF UT WOS:000306411900021 PM 22514278 ER PT J AU Kearney, DJ Milton, ML Malte, CA McDermott, KA Martinez, M Simpson, TL AF Kearney, David J. Milton, Meredith L. Malte, Carol A. McDermott, Kelly A. Martinez, Michelle Simpson, Tracy L. TI Participation in mindfulness-based stress reduction is not associated with reductions in emotional eating or uncontrolled eating SO NUTRITION RESEARCH LA English DT Article DE Food intake; Posttraumatic stress disorders; Eating behavior; Meditation; Longitudinal studies; Veterans ID DIALECTICAL BEHAVIOR-THERAPY; FOOD-FREQUENCY QUESTIONNAIRE; TERM WEIGHT-LOSS; BODY-MASS INDEX; QUALITY-OF-LIFE; COGNITIVE THERAPY; WOMEN; OBESITY; PROGRAM; DISINHIBITION AB The adverse health effects and increasing prevalence of obesity in the United States make interventions for obesity a priority in health research. Diet-focused interventions generally do not result in lasting reductions in weight. Behavioral interventions that increase awareness of eating cues and satiety have been postulated to result in healthier eating habits. We hypothesized that participation in a program called mindfulness-based stress reduction (MBSR) would positively influence the eating behaviors and nutritional intake of participants through changes in emotional eating (EE), uncontrolled eating (UE), and type and quantity of food consumed. Forty-eight veterans at a large urban Veterans Administration medical center were assessed before MBSR, after MBSR, and 4 months later. For all participants (N = 48), MBSR participation was not associated with significant changes in EE or UE. In addition, there were no significant differences in the intake of energy, fat, sugar, fruit, or vegetables at either follow-up time point as compared with baseline.. Enhanced mindfulness skills and reduced depressive symptoms were seen over time with medium to large effect sizes. Changes in mindfulness skills were significantly and negatively correlated with changes in EE and UE over time. Overall, there was no evidence that participation in MBSR was associated with beneficial changes in eating through reductions in disinhibited eating or significant changes in dietary intake. Randomized studies are needed to further define the relationship between mindfulness program participation and eating behaviors. Published by Elsevier Inc. C1 [Kearney, David J.] Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. [Milton, Meredith L.] Bastyr Univ, Sch Nutr & Exercise Sci, Kenmore, WA USA. [Malte, Carol A.; Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, CESATE, Seattle, WA USA. [Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, MIRECC, Seattle, WA USA. [Simpson, Tracy L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Kearney, DJ (reprint author), Seattle VAMC 111GI, Seattle, WA 98108 USA. EM david.kearney@va.gov NR 52 TC 16 Z9 17 U1 6 U2 69 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD JUN PY 2012 VL 32 IS 6 BP 413 EP 420 DI 10.1016/j.nutres.2012.05.008 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 973XE UT WOS:000306392800004 PM 22749177 ER PT J AU Zhang, Y Nateras, OS Peng, Q Rosende, CA Duong, TQ AF Zhang, Yi Nateras, Oscar San Emeterio Peng, Qi Rosende, Carlos A. Duong, Timothy Q. TI Blood Flow MRI of the Human Retina/Choroid during Rest and Isometric Exercise SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID INTRAOCULAR-PRESSURE; OCULAR HEMODYNAMICS; PERFUSION; AUTOREGULATION; INVERSION; RELAXATION; EFFICIENCY; RETINA; RABBIT; WATER AB PURPOSE. To investigate blood flow (BF) in the human retina/choroid during rest and handgrip isometric exercise using magnetic resonance imaging (MRI). METHODS. Four healthy volunteers (25-36 years old) in multiple sessions (1-3) on different days. MRI studies were performed on a 3-Tesla scanner using a custom-made surface coil (7 x 5cm in diameter) at the spatial resolution of 0.5 x 0.8 x 6.0 mm. BF was measured using the pseudo-continuous arterial-spin-labeling technique with background suppression and turbo-spin-echo acquisition. During MRI, subjects rested for 1 minute followed by 1 minute of handgrip, repeating three times, while maintaining stable eye fixation on a target with cued eye blinks at the end of each data acquisition (every 4.6 seconds). RESULTS. Robust BF of the unanesthetized human retina/choroid was detected. Basal BF in the posterior retina/choroid was 149 +/- 48 mL/100 mL/min with a mean heart rate of 60 +/- 5 beats per minute, mean arterial pressure of 78 +/- 5 mm Hg, ocular perfusion pressure of 67 +/- 4 mm Hg at rest (mean +/- SD, n = 4 subjects). Handgrip significantly increased retina/choroid BF by 25% +/- 7%, heart rate by 19% +/- 8%, mean arterial pressure by 22% +/- 5% (measured at the middle of the handgrip task), and ocular perfusion pressure by 25% +/- 6% (averaged across the entire handgrip task) (P < 0.01), but did not change intraocular pressure, arterial oxygen saturation, end-tidal CO2, and respiration rate (P > 0.05). CONCLUSIONS. This study demonstrates a novel MRI application to image quantitative BF of the human retina/choroid during rest and isometric exercise. Retina/choroid BF increases during brief handgrip exercise, paralleling increases in mean arterial pressure. Handgrip exercise changes ocular perfusion pressure free of potential drug side effect and can be done in the MRI scanner. MRI offers quantitative BF with large field of view without depth limitation, potentially providing insights into retinal pathophysiology. (Invest Ophthalmol Vis Sci. 2012;53:4299-4305) DOI:10.1167/iovs.11-9384 C1 [Zhang, Yi; Nateras, Oscar San Emeterio; Peng, Qi; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Rosende, Carlos A.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Zhang, Yi; Peng, Qi; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008 FU Pilot grant via the Clinical Translational Science Award (CTSA) [UL1RR025767]; Translational Technology Resource grant via the Clinical Translational Science Award (CTSA) [UL1RR025767]; NIH/NEI [R01 EY014211, EY018855]; Department of Veterans Affairs FX Supported by a Pilot grant (TQD) and a Translational Technology Resource grant (QP) via the Clinical Translational Science Award (CTSA, Parent Grant UL1RR025767), NIH/NEI Grants R01 EY014211 and EY018855 (TQD), and a MERIT award from the Department of Veterans Affairs (TQD). NR 39 TC 15 Z9 15 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2012 VL 53 IS 7 BP 4299 EP 4305 DI 10.1167/iovs.11-9384 PG 7 WC Ophthalmology SC Ophthalmology GA 971CM UT WOS:000306181200121 PM 22661466 ER PT J AU Shores, MM Smith, NL Forsberg, CW Anawalt, BD Matsumoto, AM AF Shores, Molly M. Smith, Nicholas L. Forsberg, Christopher W. Anawalt, Bradley D. Matsumoto, Alvin M. TI Testosterone Treatment and Mortality in Men with Low Testosterone Levels SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LOW SERUM TESTOSTERONE; ANDROGEN DEFICIENCY SYNDROMES; CLINICAL-PRACTICE GUIDELINE; QUALITY-OF-LIFE; ELDERLY-MEN; VETERANS-AFFAIRS; HEART-FAILURE; DOUBLE-BLIND; OLDER MEN; RISK AB Context: Low testosterone levels in men have been associated with increased mortality. However, the influence of testosterone treatment on mortality in men with low testosterone levels is not known. Objective: The objective of the study was to examine the association between testosterone treatment and mortality in men with low testosterone levels. Design: This was an observational study of mortality in testosterone-treated compared with untreated men, assessed with time-varying, adjusted Cox proportional hazards regression models. Effect modification by age, diabetes, and coronary heart disease was tested a priori. Setting: The study was conducted with a clinical database that included seven Northwest Veterans Affairs medical centers. Patients: Patients included a cohort of 1031 male veterans, aged older than 40 yr, with low total testosterone [<= 250 ng/dl (8.7 nmol/liter)] and no history of prostate cancer, assessed between January 2001 and December 2002 and followed up through the end of 2005. Main Outcome Measure: Total mortality in testosterone-treated compared with untreated men was measured. Results: Testosterone treatment was initiated in 398 men (39%) during routine clinical care. The mortality in testosterone-treated men was 10.3% compared with 20.7% in untreated men (P<0.0001) with a mortality rate of 3.4 deaths per 100 person-years for testosterone-treated men and 5.7 deaths per 100 person-years in men not treated with testosterone. After multivariable adjustment including age, body mass index, testosterone level, medical morbidity, diabetes, and coronary heart disease, testosterone treatment was associated with decreased risk of death (hazard ratio 0.61; 95% confidence interval 0.42-0.88; P = 0.008). No significant effect modification was found by age, diabetes, or coronary heart disease. Conclusions: In an observational cohort of men with low testosterone levels, testosterone treatment was associated with decreased mortality compared with no testosterone treatment. These results should be interpreted cautiously because residual confounding may still be a source of bias. Large, randomized clinical trials are needed to better characterize the health effects of testosterone treatment in older men with low testosterone levels. (J Clin Endocrinol Metab 97: 2050-2058, 2012) C1 [Shores, Molly M.; Smith, Nicholas L.; Forsberg, Christopher W.; Matsumoto, Alvin M.] Vet Affairs VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Smith, Nicholas L.; Forsberg, Christopher W.] VA Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. [Matsumoto, Alvin M.] VA Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Shores, Molly M.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98105 USA. [Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98105 USA. [Anawalt, Bradley D.; Matsumoto, Alvin M.] Univ Washington, Dept Med, Seattle, WA 98105 USA. [Smith, Nicholas L.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA. RP Shores, MM (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-116PES, Seattle, WA 98108 USA. EM molly.shores@va.gov FU Abbott; GSK; BHR Pharmaceuticals; Department of Veterans Affairs, Office of Research and Development; Veterans Affairs Puget Sound Health Care System; Royalty Research Fund of the University of Washington FX This manuscript is based on work supported in part by the Department of Veterans Affairs, Office of Research and Development, and the Veterans Affairs Puget Sound Health Care System, and the Royalty Research Fund of the University of Washington. Analytic support was provided by the Cooperative Studies Seattle Epidemiologic Research and Information Center of the Veterans Affairs Office of Research and Development, Seattle, Washington. The content of this article does not necessarily represent the views of the Department of Veterans Affairs or the U. S. Government. We thank Daniel Kivlahan, Ph.D., who provided excellent consultation for the grant proposal for this study, and Margaret Moroz for technical support. M.M.S. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.; Disclosure Summary: A.M.M. received research support from Abbott, GSK, and BHR Pharmaceuticals and served on advisory boards for Abbott, Endo Pharmaceuticals, Ligand Pharmaceuticals, and Trimmel. All other authors have no disclosures to make. NR 35 TC 176 Z9 181 U1 0 U2 10 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 JUN PY 2012 VL 97 IS 6 BP 2050 EP 2058 DI 10.1210/jc.2011-2591 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 970AP UT WOS:000306100800058 PM 22496507 ER PT J AU Heckman, CJ Darlow, S Cohen-Filipic, J Kloss, JD Manne, SL Munshi, T Perlis, CS AF Heckman, Carolyn J. Darlow, Susan Cohen-Filipic, Jessye Kloss, Jacqueline D. Manne, Sharon L. Munshi, Teja Perlis, Clifford S. TI Psychosocial Correlates of Sunburn among Young Adult Women SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE sunburn; young adult women; psychosocial correlates; sunscreen; Health Beliefs Model; skin cancer prevention ID SUN PROTECTION PRACTICES; INDOOR TANNING BEHAVIORS; SKIN-CANCER; SUNSCREEN USE; MALIGNANT-MELANOMA; HEALTH BELIEFS; ATTITUDES; ADOLESCENTS; STUDENTS; NORMS AB Skin cancer is an increasingly common disease, particularly among young adult women. Sunburn early in life is a risk factor for skin cancer. Few studies have reported on psychosocial correlates of sunburn. The current study consisted of an online survey of undergraduate women from a university in the northeastern part of the USA. A logistic regression demonstrated that young women who reported a history of four or more sunburns were significantly more likely to report fair skin, higher perceived susceptibility to skin cancer, greater perceived benefits of tanning (e.g., appearance enhancement), lower perceived control over skin protection, and more frequent sunscreen use. Sunbathing was not associated with a greater number of sunburns. These results suggest that young women who sunburn more often possess other skin cancer risk factors, are aware of their susceptibility to skin cancer, and try to use sunscreen, but feel limited control over their skin protection behavior and are not less likely to sunbathe than others. Therefore, interventions are needed to assist high risk young women in asserting more control over their sun protection behavior and perhaps improve the effectiveness of the sunscreen or other skin protection methods they do employ. C1 [Heckman, Carolyn J.; Darlow, Susan; Munshi, Teja; Perlis, Clifford S.] Fox Chase Canc Ctr, Canc Prevent & Control Program, Philadelphia, PA 19111 USA. [Cohen-Filipic, Jessye] Portland VA Med Ctr, Portland, OR 97239 USA. [Kloss, Jacqueline D.] Drexel Univ, Dept Psychol, Philadelphia, PA 19104 USA. [Manne, Sharon L.] Canc Inst New Jersey, Canc Prevent & Control Program, New Brunswick, NJ 08901 USA. RP Heckman, CJ (reprint author), Fox Chase Canc Ctr, Canc Prevent & Control Program, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM Carolyn.Heckman@fccc.edu; susan.darlow@fccc.edu; jessyecohen@gmail.com; jdk29@drexel.edu; mannesl@umdnj.edu; teja.munshi@fccc.edu; clifford.perlis@fccc.edu FU Cancer Center Grant [R03CA1504202, P30CA006927] FX This work was funded by R03CA1504202 (CH) and P30CA006927 (Cancer Center Grant). The authors would like to thank Jeanne Pomenti, BS for her technical assistance in the preparation of this manuscript and Sara Filseth, BA for her assistance with data collection. NR 48 TC 8 Z9 8 U1 0 U2 11 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD JUN PY 2012 VL 9 IS 6 BP 2241 EP 2251 DI 10.3390/ijerph9062241 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 966AM UT WOS:000305808900016 PM 22829801 ER PT J AU Munhall, AC Wu, YN Belknap, JK Meshul, CK Johnson, SW AF Munhall, Adam C. Wu, Yan-Na Belknap, John K. Meshul, Charles K. Johnson, Steven W. TI NMDA alters rotenone toxicity in rat substantia nigra zona compacta and ventral tegmental area dopamine neurons SO NEUROTOXICOLOGY LA English DT Article DE Dendrite; Histology; N-methyl-D-aspartate; Rotenone; Substantia nigra; Ventral tegmental area ID PARKINSONS-DISEASE; NEUROTROPHIC FACTOR; COMPLEX-I; RECEPTOR CHANNELS; BRAIN SLICES; CELL-DEATH; NEUROPROTECTION; CURRENTS; DEGENERATION; STIMULATION AB Previous patch-clamp studies by our laboratory showed that acute exposure to the pesticide rotenone augments inward currents evoked by N-methyl-D-aspartate (NMDA) in substantia nigra zona compacta (SNC) dopamine neurons in slices of rat brain. The present experiments were done to search for histological evidence of increased neurotoxicity produced by combined rotenone and NMDA treatments. In horizontal slices of rat midbrain, we found that a 30 min superfusion with 100 nM rotenone caused significant injury to tyrosine hydroxylase (TH)-positive proximal dendrites in dorsal and ventral regions of the SNC and ventral tegmental area (VTA). Moreover, treatment with 100 mu M NMDA potentiated rotenone toxicity. In contrast, treatment with 30 mu M NMDA protected against rotenone-induced injury to dendrites in the ventral SNC and ventral VTA. Interestingly, treatment with 30 mu M NMDA-alone produced an apparent increase in proximal dendrite scores in ventral SNC and dorsal VTA. We conclude that NMDA has concentration-dependent actions on rotenone toxicity that differ according to regional subtype of dopamine neuron. Published by Elsevier Inc. C1 [Johnson, Steven W.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Neurol, Portland, OR 97239 USA. [Belknap, John K.; Meshul, Charles K.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. [Belknap, John K.; Meshul, Charles K.; Johnson, Steven W.] Vet Affairs Med Ctr, Portland, OR 97207 USA. RP Johnson, SW (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Neurol, R&D-61,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM johnsost@ohsu.edu FU Department of Veterans Affairs; American Parkinson's Disease Association; Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center FX This research was supported by Department of Veterans Affairs Merit Review grants (SWJ and CKM), a grant from the American Parkinson's Disease Association (SWJ), and by the Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center (SWJ). NR 37 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD JUN PY 2012 VL 33 IS 3 BP 429 EP 435 DI 10.1016/j.neuro.2012.04.006 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 951OO UT WOS:000304730100019 PM 22521663 ER PT J AU Marcus, SC Bridge, JA Olfson, M AF Marcus, Steven C. Bridge, Jeffrey A. Olfson, Mark TI Payment Source and Emergency Management of Deliberate Self-Harm SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID QUALITY-OF-CARE; SUICIDE ATTEMPTS; COMPLETED SUICIDE; MENTAL-HEALTH; FOLLOW-UP; COHORT; RISK; REPEAT; HOSPITALIZATION; PREVENTION AB Objectives. We investigated whether health insurance type (private vs Medicaid) influences the delivery of acute mental health care to patients with deliberate self-harm. Methods. Using National Medicaid Analytic Extract Files (2006) and Market-Scan Research Databases (2005-2007), we analyzed claims focusing on emergency episodes of deliberate self-harm of Medicaid- (n = 8228) and privately (n = 2352) insured adults. We analyzed emergency department mental health assessments and outpatient mental health visits in the 30 days following the emergency visit for discharged patients. Results. Medicaid-insured patients were more likely to be discharged (62.7%), and among discharged patients they were less likely to receive a mental health assessment in the emergency department (47.8%) and more likely to receive follow-up outpatient mental health care (52.9%) than were privately insured patients (46.9%, 57.3%, and 41.2%, respectively). Conclusions. Acute emergency management of deliberate self-harm is less intensive for Medicaid- than for privately insured patients, although discharged Medicaid-insured patients are more likely to receive follow-up care. Programmatic reforms are needed to improve access to emergency mental health services, especially in hospitals that serve substantial numbers of Medicaid-insured patients. (Am J Public Health. 2012;102:1145-1153. doi:10.2105/AJPH.2011.300598) C1 [Olfson, Mark] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Olfson, Mark] Columbia Univ, Dept Psychiat, New York, NY USA. [Marcus, Steven C.] Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. [Bridge, Jeffrey A.] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. [Bridge, Jeffrey A.] Ohio State Univ, Res Inst, Nationwide Childrens Hosp, Ctr Innovat Pediat Practice, Columbus, OH 43210 USA. RP Olfson, M (reprint author), New York State Psychiat Inst & Hosp, 1051 Riverside Dr, New York, NY 10032 USA. EM mo49@columbia.edu FU American Foundation for Suicide Prevention of Columbia University [2DIG-00005-1207-1208] FX The American Foundation for Suicide Prevention of Columbia University supported this study (grant no. 2DIG-00005-1207-1208). NR 49 TC 6 Z9 6 U1 2 U2 5 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 2012 VL 102 IS 6 BP 1145 EP 1153 DI 10.2105/AJPH.2011.300598 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 951LX UT WOS:000304723200020 PM 22515853 ER PT J AU Thase, ME Kennedy, SH Larsen, KG AF Thase, Michael E. Kennedy, Sidney H. Larsen, Klaus G. TI Can a 'true' effect be built on a 'wrong' model? reply SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Letter C1 [Thase, Michael E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Kennedy, Sidney H.] H Lundbeck & Co AS, Copenhagen, Denmark. [Larsen, Klaus G.] Univ Toronto, Toronto, ON, Canada. RP Thase, ME (reprint author), Univ Penn, Sch Med, Suite 689,3535 Market St, Philadelphia, PA 19104 USA. EM thase@mail.med.upenn.edu NR 1 TC 0 Z9 0 U1 0 U2 1 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD JUN PY 2012 VL 200 IS 6 BP 512 EP 513 DI 10.1192/bjp.200.6.512a PG 2 WC Psychiatry SC Psychiatry GA 959GK UT WOS:000305300700017 ER PT J AU Merrick, DT AF Merrick, Daniel T. TI GRP78, Intronic Polymorphisms, and Pharmacogenomics in Non-small Cell Lung Cancer SO CHEST LA English DT Editorial Material ID ENDOPLASMIC-RETICULUM C1 Denver Vet Affairs Med Ctr, Dept Pathol, Denver, CO 80220 USA. RP Merrick, DT (reprint author), Denver Vet Affairs Med Ctr, Dept Pathol, 113,1055 Clermont St, Denver, CO 80220 USA. EM Daniel.Merrick@va.gov FU NCI NIH HHS [P50-CA058187] NR 8 TC 4 Z9 4 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUN PY 2012 VL 141 IS 6 BP 1377 EP 1378 DI 10.1378/chest.11-2662 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 955RT UT WOS:000305039300004 PM 22670016 ER PT J AU Maguen, S Cohen, B Cohen, G Madden, E Bertenthal, D Seal, K AF Maguen, Shira Cohen, Beth Cohen, Greg Madden, Erin Bertenthal, Daniel Seal, Karen TI Gender Differences in Health Service Utilization Among Iraq and Afghanistan Veterans with Posttraumatic Stress Disorder SO JOURNAL OF WOMENS HEALTH LA English DT Article ID MENTAL-HEALTH; FEMALE VETERANS; MILITARY SERVICE; CARE SERVICES; VA; DIAGNOSES; WOMEN; PREVALENCE; SYMPTOMS; EXPOSURE AB Background: Little is known about gender differences in healthcare use among newly returning veterans with posttraumatic stress disorder (PTSD). We investigated gender differences in Veterans Affairs (VA) medical center health service use among Iraq and Afghanistan veterans with PTSD with and without comorbid depression and alcohol use disorders (AUD). Methods: Using VA administrative data, bivariate and multivariate statistics were used to examine gender differences in health service use among 159,705 Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans with PTSD seeking VA healthcare from October 7, 2001, to December 31, 2010. Results: Female veterans with PTSD were more likely to be black and single and to have higher mental health, primary care, and emergency care use compared to men with PTSD. Men were more likely to have higher mental health inpatient use compared to women. Women and men with comorbid PTSD and depression or comorbid PTSD and AUD were more likely to have higher use in all domains compared to their counterparts with PTSD without these comorbid disorders. Women with comorbid PTSD and depression were 12.5 times more likely to have a mental health inpatient hospitalization compared to their female counterparts without depression and twice as likely to have a mental health hospitalization compared to men with comorbid PTSD and depression. Conclusions: Women with PTSD had higher use than men in almost all areas, as did all veterans with comorbid PTSD and depression and comorbid PTSD and AUD, regardless of gender. Better understanding these health service use differences will allow for targeted evaluation and integrated treatment interventions in veterans with PTSD. C1 [Maguen, Shira; Cohen, Beth; Cohen, Greg; Madden, Erin; Bertenthal, Daniel; Seal, Karen] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Maguen, Shira; Cohen, Beth; Seal, Karen] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Bertenthal, Daniel] Mental Illness Res Educ & Clin Ctr, San Francisco, CA USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, 4150 Clement St 116-P, San Francisco, CA 94121 USA. EM shira.maguen@va.gov FU Department of Defense Concept Award [W81XWH-08-2-0077]; VA Health Services Research and Development Career Development Award [RCD 06-042] FX This research was supported by Department of Defense Concept Award Grant W81XWH-08-2-0077 and VA Health Services Research and Development Career Development Award RCD 06-042. NR 33 TC 22 Z9 22 U1 1 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD JUN PY 2012 VL 21 IS 6 BP 666 EP 673 DI 10.1089/jwh.2011.3113 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 962VK UT WOS:000305575100010 PM 22313026 ER PT J AU Dodge, HH Mattek, NC Austin, D Hayes, TL Kaye, JA AF Dodge, H. H. Mattek, N. C. Austin, D. Hayes, T. L. Kaye, J. A. TI In-home walking speeds and variability trajectories associated with mild cognitive impairment SO NEUROLOGY LA English DT Article ID ALZHEIMER-DISEASE; OLDER-ADULTS; GAIT; MOBILITY; ABNORMALITY; DYSFUNCTION; ATTENTION; DEMENTIA; DECLINE; MRI AB Objective: To determine whether unobtrusive long-term in-home assessment of walking speed and its variability can distinguish those with mild cognitive impairment (MCI) from those with intact cognition. Methods: Walking speed was assessed using passive infrared sensors fixed in series on the ceiling of the homes of elderly individuals participating in the Intelligent Systems for Assessing Aging Change (ISAAC) cohort study. Latent trajectory models were used to analyze weekly mean speed and walking speed variability (coefficient of variation [COV]). Results: ISAAC participants living alone included 54 participants with intact cognition, 31 participants with nonamnestic MCI (naMCI), and 8 participants with amnestic MCI at baseline, with a mean follow-up of 2.6 +/- 1.0 years. Trajectory models identified 3 distinct trajectories (fast, moderate, and slow) of mean weekly walking speed. Participants with naMCI were more likely to be in the slow speed group than in the fast (p = 0.01) or moderate (p = 0.04) speed groups. For COV, 4 distinct trajectories were identified: group 1, the highest baseline and increasing COV followed by a sharply declining COV; groups 2 and 3, relatively stable COV; and group 4, the lowest baseline and decreasing COV. Participants with naMCI were more likely to be members of either highest or lowest baseline COV groups (groups 1 or 4), possibly representing the trajectory of walking speed variability for early-and late-stage MCI, respectively. Conclusion: Walking speed and its daily variability may be an early marker of the development of MCI. These and other real-time measures of function may offer novel ways of detecting transition phases leading to dementia. Neurology (R) 2012; 78: 1946-1952 C1 [Dodge, H. H.; Mattek, N. C.; Austin, D.; Hayes, T. L.; Kaye, J. A.] Oregon Hlth & Sci Univ, Oregon Ctr Aging & Technol, Portland, OR 97201 USA. [Dodge, H. H.; Mattek, N. C.; Kaye, J. A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Hayes, T. L.] Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97201 USA. [Kaye, J. A.] Portland VA Med Ctr, Neurol Serv, Portland, OR USA. RP Dodge, HH (reprint author), Oregon Hlth & Sci Univ, Oregon Ctr Aging & Technol, Portland, OR 97201 USA. EM dodgeh@ohsu.edu OI Kaye, Jeffrey/0000-0002-9971-3478 FU National Institutes of Health [P30-AG024978, R01-AG024059, P30-AG008017, R01-AG033581]; Intel Corporation FX Supported by grants from the National Institutes of Health (P30-AG024978, R01-AG024059, P30-AG008017, and R01-AG033581) and the Intel Corporation. NR 40 TC 34 Z9 35 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 2012 VL 78 IS 24 BP 1946 EP 1952 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 958ZG UT WOS:000305278900013 PM 22689734 ER PT J AU Restrepo, MI Anzueto, A AF Restrepo, Marcos I. Anzueto, Antonio TI Global Trends in Community-Acquired Pneumonia Preface SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material C1 [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Pulm & Crit Care Med, S Texas Vet Hlth Care Syst Audie L Murphy Div, San Antonio, TX 78229 USA. [Restrepo, Marcos I.; Anzueto, Antonio] S Texas Vet Hlth Care Syst Audie Murphy VA Hosp, Vet Evidence Res Disseminat & Implementat Ctr VER, San Antonio, TX USA. RP Restrepo, MI (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Pulm & Crit Care Med, S Texas Vet Hlth Care Syst Audie L Murphy Div, 7400 Merton Minter Blvd 11C6, San Antonio, TX 78229 USA. EM restrepom@uthscsa.edu RI Restrepo, Marcos/H-4442-2014 FU NHLBI NIH HHS [K23 HL096054] NR 0 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 J9 SEMIN RESP CRIT CARE JI Semin. Respir. Crit. Care Med. PD JUN PY 2012 VL 33 IS 3 BP 211 EP 211 DI 10.1055/s-0032-1315646 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 963PK UT WOS:000305634500001 PM 22718206 ER PT J AU Steinman, MA Sudore, RL Peterson, CA Harlow, JB Fried, TR AF Steinman, Michael A. Sudore, Rebecca L. Peterson, Carolyn A. Harlow, John B. Fried, Terri R. TI Influence of Patient Age and Comorbid Burden on Clinician Attitudes Toward Heart Failure Guidelines SO AMERICAN JOURNAL OF GERIATRIC PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Gen Internal Med DE aged; clinical practice guidelines; comorbidity; geriatrics; physician attitudes ID QUALITY-OF-CARE; ELDERLY-PATIENTS; EFFECTIVE MANAGEMENT; BARRIERS; TRIAL; THERAPY; RISK; LIFE AB Background: Clinical practice guidelines have been criticized for insufficient attention to the unique needs of patients of advanced age and with multiple comorbid conditions. However, little empiric research is available to inform this topic. Methods: We conducted telephone interviews with staff physicians and nurse practitioners in 4 VA health care systems. Respondents were asked to rate the usefulness of national heart failure guidelines for patients of different ages and levels of comorbid burden on a 5-point scale and to comment on the reasons for their ratings. Results: Of 139 clinicians contacted, 65 (47%) completed the interview. Almost half (49%) were women, and 48 (74%) were general internists or family practitioners. On a 5-point scale assessing the usefulness of clinical practice guidelines for heart failure, the mean (SD) response ranged from 4.4 (0.7) for patients younger than 65 years with few comorbid conditions to 3.5 (1.2) for patients older than 80 years with multiple comorbid conditions (P < 0.001). The difference in perceived usefulness varied more by patient age than by degree of comorbidity (P = 0.02). Four major concepts underlay the perceived usefulness of guidelines across different patient types: (1) harm of treatment and complexity of the patient's clinical condition and pharmacologic needs, (2) expected benefits of treatment, (3) patient preferences and abilities, and (4) confidence in the validity of guideline recommendations. Conclusion: Clinicians perceive heart failure guidelines to be substantially less useful in patients of older age and with greater comorbid burden. Concerns about the clinical and pharmacologic complexity of these patients and the expected benefits of drug therapy were commonly invoked as reasons for this skepticism. (Am J Geriatr Pharmacother. 2012;10:211-218) Published by Elsevier HS Journals, Inc. C1 [Steinman, Michael A.; Sudore, Rebecca L.; Peterson, Carolyn A.; Harlow, John B.] San Francisco VA Med Ctr, Hlth Serv Res & Dev Res Enhancement Award Program, San Francisco, CA 94121 USA. [Steinman, Michael A.; Sudore, Rebecca L.; Peterson, Carolyn A.; Harlow, John B.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Harlow, John B.] Med Univ S Carolina, Sch Med, Charleston, SC 29425 USA. [Fried, Terri R.] Yale Univ, Sch Med, Div Geriatr, New Haven, CT USA. RP Steinman, MA (reprint author), San Francisco VA Med Ctr, Hlth Serv Res & Dev Res Enhancement Award Program, 4150 Clement St,Box 181G, San Francisco, CA 94121 USA. EM mike.steinman@ucsf.edu FU NIA NIH HHS [K23 AG030999, K24 AG028443] NR 31 TC 4 Z9 4 U1 0 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 1543-5946 J9 AM J GERIATR PHARMAC JI Am. J. Geriatr. Pharmacother. PD JUN PY 2012 VL 10 IS 3 BP 211 EP 218 DI 10.1016/j.amjopharm.2012.04.003 PG 8 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 962LE UT WOS:000305545800006 PM 22579695 ER PT J AU Reidelberger, R Haver, A Chelikani, PK Apenteng, B Perriotte-Olson, C Anders, K Steenson, S Blevins, JE AF Reidelberger, Roger Haver, Alvin Chelikani, Prasanth K. Apenteng, Bettye Perriotte-Olson, Curtis Anders, Krista Steenson, Sharalyn Blevins, James E. TI Effects of leptin replacement alone and with exendin-4 on food intake and weight regain in weight-reduced diet-induced obese rats SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE food restriction; hyperphagia; leptin sensitivity; glucagon-like peptide-1 receptor agonist ID INTERMITTENT INTRAPERITONEAL INFUSION; Y GASTRIC BYPASS; LOW-DOSE LEPTIN; BODY-WEIGHT; INTRAVENOUS-INFUSION; RODENT MODELS; GUT HORMONE; ADIPOSITY; AMYLIN; CHOLECYSTOKININ AB Weight loss in obese humans produces a relative leptin deficiency, which is postulated to activate potent orexigenic and energy conservation mechanisms to restrict weight loss and promote weight regain. Here we determined whether leptin replacement alone or with GLP-1 receptor agonist exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced diet-induced obese (DIO) rats. Forty percent restriction in daily intake of a high-fat diet in DIO rats for 4 wk reduced body weight by 12%, body fat by 29%, and plasma leptin by 67% and normalized leptin sensitivity. When food restriction ended, body weight, body fat, and plasma leptin increased rapidly. Daily administration of leptin [3-h intraperitoneal (ip) infusions (4 nmol.kg (-1).h (-1))] at onset and end of dark period for 3 wk did not attenuate hyperphagia and weight regain, nor did it affect mean daily meal sizes or meal numbers. Exendin-4 (50 pmol.kg (-1).h (-1)) infusions during the same intervals prevented postrestriction hyperphagia and weight regain by normalizing meal size. Coadministration of leptin and exendin-4 did not reduce body weight more than exendin-4 alone. Instead, leptin began to attenuate the inhibitory effects of exendin-4 on food intake, meal size, and weight regain by the end of the second week of administration. Plasma leptin in rats receiving leptin was sevenfold greater than in rats receiving vehicle and 17-fold greater than in rats receiving exendin-4. Together, these results do not support the hypothesis that leptin replacement alone or with exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced DIO rats. C1 [Reidelberger, Roger; Haver, Alvin; Perriotte-Olson, Curtis] Vet Affairs Nebraska Western Iowa Hlth Care Syst, Vet Affairs Res Serv, Omaha, NE USA. [Reidelberger, Roger; Haver, Alvin; Chelikani, Prasanth K.; Apenteng, Bettye; Anders, Krista; Steenson, Sharalyn] Creighton Univ, Dept Biomed Sci, Omaha, NE 68178 USA. [Blevins, James E.] Vet Affairs Puget Sound Hlth Care Syst, Vet Affairs Res Serv, Seattle, WA USA. [Blevins, James E.] Univ Washington, Sch Med, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Chelikani, Prasanth K.] Univ Calgary, Gastrointestinal Res Grp, Dept Prod Anim Hlth, Snyder Inst Chron Dis,Fac Vet Med, Calgary, AB, Canada. RP Reidelberger, R (reprint author), VA NWIHCS 151,4101 Woolworth Ave, Omaha, NE 68105 USA. EM rogerr@creighton.edu FU National Institutes of Health [R01-DK-70851, P20-RR-16469]; National Institutes of Health Diabetes Research Center [P30-DK-17047]; Department of Veterans Affairs; Veterans Health Administration; Office of Research and Development; Rehabilitation Research, and Development Service and Biomedical Laboratory Research and Development FX This work was performed at the Veterans Affairs Nebraska-Western Iowa Health Care System and Veterans Affairs Puget Sound Health Care System and was supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research, and Development Service and Biomedical Laboratory Research and Development. This research was also supported in part by the National Institutes of Health (R01-DK-70851 and P20-RR-16469) and the Cellular and Molecular Imaging Core of the National Institutes of Health Diabetes Research Center (P30-DK-17047). The contents of this article do not represent the views of the Department of Veterans Affairs or the US Government. NR 49 TC 9 Z9 9 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUN PY 2012 VL 302 IS 12 BP E1576 EP E1585 DI 10.1152/ajpendo.00058.2012 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 960XQ UT WOS:000305426900014 PM 22510712 ER PT J AU Velez, JCQ Ierardi, JL Bland, AM Morinelli, TA Arthur, JM Raymond, JR Janech, MG AF Velez, Juan Carlos Q. Ierardi, Jessalyn L. Bland, Alison M. Morinelli, Thomas A. Arthur, John M. Raymond, John R. Janech, Michael G. TI Enzymatic processing of angiotensin peptides by human glomerular endothelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE angiotensin-converting enzyme; prolylendopeptidase; endothelium ID CONVERTING-ENZYME; ASPARTYL AMINOPEPTIDASE; PERIPHERAL-TISSUES; ACE2 EXPRESSION; IGA NEPHROPATHY; CLEAVING ENZYME; HUMAN KIDNEY; SYSTEM; LOCALIZATION; METABOLISM AB Velez JC, Ierardi JL, Bland AM, Morinelli TA, Arthur JM, Raymond JR, Janech MG. Enzymatic processing of angiotensin peptides by human glomerular endothelial cells. Am J Physiol Renal Physiol 302: F1583-F1594, 2012. First published March 28, 2012; doi: 10.1152/ajprenal.00087.2012.-The intraglomerular renin-angiotensin system (RAS) is linked to the pathogenesis of progressive glomerular diseases. Glomerular podocytes and mesangial cells play distinct roles in the metabolism of angiotensin (ANG) peptides. However, our understanding of the RAS enzymatic capacity of glomerular endothelial cells (GEnCs) remains incomplete. We explored the mechanisms of endogenous cleavage of ANG substrates in cultured human GEnCs (hGEnCs) using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and isotope-labeled peptide quantification. Overall, hGEnCs metabolized ANG II at a significantly slower rate compared with podocytes, whereas the ANG I processing rate was comparable between glomerular cell types. ANG II was the most abundant fragment of ANG I, with lesser amount of ANG-(1-7) detected. Formation of ANG II from ANG I was largely abolished by an ANG-converting enzyme (ACE) inhibitor, whereas ANG-(1-7) formation was decreased by a prolylendopeptidase (PEP) inhibitor, but not by a neprilysin inhibitor. Cleavage of ANG II resulted in partial conversion to ANG-(1-7), a process that was attenuated by an ACE2 inhibitor, as well as by an inhibitor of PEP and prolylcarboxypeptidase. Further fragmentation of ANG-(1-7) to ANG-(1-5) was mediated by ACE. In addition, evidence of aminopeptidase N activity (APN) was demonstrated by detecting amelioration of conversion of ANG III to ANG IV by an APN inhibitor. While we failed to find expression or activity of aminopeptidase A, a modest activity attributable to aspartyl aminopeptidase was detected. Messenger RNA and gene expression of the implicated enzymes were confirmed. These results indicate that hGEnCs possess prominent ACE activity, but modest ANG II-metabolizing activity compared with that of podocytes. PEP, ACE2, prolylcarboxypeptidase, APN, and aspartyl aminopeptidase are also enzymes contained in hGEnCs that participate in membrane-bound ANG peptide cleavage. Injury to specific cell types within the glomeruli may alter the intrarenal RAS balance. C1 [Velez, Juan Carlos Q.; Ierardi, Jessalyn L.; Bland, Alison M.; Morinelli, Thomas A.; Arthur, John M.; Janech, Michael G.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Velez, Juan Carlos Q.; Arthur, John M.; Janech, Michael G.] Ralph H Johnson Vet Affairs Med Ctr, Med & Res Serv, Charleston, SC USA. [Raymond, John R.] Med Coll Wisconsin, Dept Med, Div Nephrol, Milwaukee, WI 53226 USA. RP Velez, JCQ (reprint author), 96 Jonathan Lucas St,Clinical Sci Bldg,Rm 826F, Charleston, SC 29425 USA. EM velezj@musc.edu RI Velez, Juan Carlos/N-3782-2016 OI Janech, Michael/0000-0002-3202-4811 FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [DK080944-04]; Dialysis Clinics, Inc.; Ralph H. Johnson Veterans Affairs Med. Ctr.; Veterans Affairs CDA-2 Career Development Award; Nephcure Foundation FX J.C.V. is supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, Grant DK080944-04, Dialysis Clinics, Inc., and the Ralph H. Johnson Veterans Affairs Med. Ctr. Research Enhancement Award Program. M.G.J. was supported by a Veterans Affairs CDA-2 Career Development Award and the Nephcure Foundation Young Investigator Award. NR 65 TC 18 Z9 19 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUN PY 2012 VL 302 IS 12 BP F1583 EP F1594 DI 10.1152/ajprenal.00087.2012 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 960XC UT WOS:000305425300009 PM 22461301 ER PT J AU Vickrey, BG Hirtz, D Waddy, S Cheng, EM Johnston, SC AF Vickrey, Barbara G. Hirtz, Deborah Waddy, Salina Cheng, Eric M. Johnston, S. Claiborne TI Comparative effectiveness and implementation research: Directions for Neurology SO ANNALS OF NEUROLOGY LA English DT Article ID HEALTH-SERVICES RESEARCH; MYOCARDIAL-INFARCTION; ETHNIC DISPARITIES; CONTROLLED-TRIAL; STROKE; OUTCOMES; WARFARIN; EPILEPSY; THERAPY; ASPIRIN AB There is an enormous unmet need for knowledge about how new insights from discovery and translational research can yield measurable, population-level improvements in health and reduction in mortality among those having or at risk for neurological disease. Once several, well-conducted randomized controlled trials establish the efficacy of a given therapy, implementation research can generate new knowledge about barriers to uptake of the therapy into widespread clinical care, and what strategies are effective in overcoming those barriers and in addressing health disparities. Comparative effectiveness research aims to elucidate the relative value (including clinical benefit, clinical harms, and/or costs) of alternative efficacious management approaches to a neurological disorder, generally through direct comparisons, and may include comparisons of methodologies for implementation. Congress has recently appropriated resources and established an institute to prioritize funding for such research. Neurologists and neuroscientists should understand the scope and objectives of comparative effectiveness and implementation research, their range of methodological approaches (formal literature syntheses, randomized trials, observational studies, modeling), and existing research resources (centers for literature synthesis, registries, practice networks) relevant to research for neurological conditions, to close the well-documented evidence-to-practice gap. Future directions include building this research resource capacity, producing scientists trained to conduct rigorous comparative effectiveness and implementation research, and embracing innovative strategies to set research priorities in these areas. Ann Neurol 2012;71:732742 C1 [Vickrey, Barbara G.; Cheng, Eric M.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. [Vickrey, Barbara G.; Cheng, Eric M.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Hirtz, Deborah; Waddy, Salina] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Johnston, S. Claiborne] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Vickrey, BG (reprint author), Univ Calif Los Angeles, Dept Neurol, Box 951769,C128 RNRC,710 Westwood Plaza, Los Angeles, CA 90095 USA. EM bvickrey@ucla.edu FU Genentech; Kansas City Area Life Sciences Institute; NINDS; Partners Neurology; University of Maryland FX B.G.V.: board membership, National Advisory Neurological Disorders and Stroke, National Multiple Sclerosis Society, Sports Concussion Institute; consultancy, EMD Serono, Research Triangle Institute, RAND, National Academy of Sciences; grants/grants pending, Genentech; speaking fees, Kansas City Area Life Sciences Institute, Partners Neurology, University of Maryland; travel expenses, French National Foundation on Alzheimer's Disease and Related Disorders. E.M.C.: grants/grants pending, NINDS. NR 59 TC 11 Z9 12 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 2012 VL 71 IS 6 BP 732 EP 742 DI 10.1002/ana.22672 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 961YU UT WOS:000305506300005 PM 22718542 ER PT J AU Merkow, RP Bilimoria, KY Chow, WB Merkow, JS Weyant, MJ Ko, CY Bentrem, DJ AF Merkow, Ryan P. Bilimoria, Karl Y. Chow, Warren B. Merkow, Justin S. Weyant, Michael J. Ko, Clifford Y. Bentrem, David J. TI Variation in Lymph Node Examination After Esophagectomy for Cancer in the United States SO ARCHIVES OF SURGERY LA English DT Article ID US-POPULATION DATABASE; LONG-TERM SURVIVAL; LYMPHADENECTOMY EXTENT; COLON-CANCER; PANCREATIC-CANCER; PREDICTS SURVIVAL; QUALITY MEASURE; GASTRIC-CANCER; STAGING SYSTEM; NUMBER AB Objectives: To evaluate the quality of lymph node examination after esophagectomy for cancer in the United States based on current treatment guidelines (>= 15 nodes) and to assess the association of patient, tumor, and hospital factors with the adequacy of lymph node examination. Design: Retrospective observational study from 1998 to 2007. Setting: National cancer database. Patients: Patients with stage I through III esophageal cancer undergoing esophagectomy and not treated with neoadjuvant chemoradiotherapy. Main Outcome Measure: Rate of adequate lymph node examination (>= 15 nodes). Results: A total of 13 995 patients were identified from 639 hospitals. Overall, 4014 patients (28.7%) had at least 15 lymph nodes examined, which increased from 23.5% to 34.4% during the study period. At the hospital level, only 45 centers (7.0%) examined a median of at least 15 lymph nodes. In the most recent period (2005-2007), at least 15 nodes were examined in 38.9% of patients at academic centers vs 28.0% at community hospitals and in 44.1% at high-volume centers vs 29.3% at low-volume centers. On multivariable analysis, hospital type, surgical volume status, and geographic location remained significant predictors of having at least 15 lymph nodes examined. Conclusions: Fewer than one-third of patients and fewer than 1 in 10 hospitals met the benchmark of examining at least 15 lymph nodes. Hospitals should perform internal process improvement activities to improve guideline adherence. C1 [Merkow, Ryan P.; Bilimoria, Karl Y.; Bentrem, David J.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. [Merkow, Ryan P.; Merkow, Justin S.; Weyant, Michael J.] Univ Colorado, Sch Med, Dept Surg, Aurora, CO USA. [Chow, Warren B.; Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Chow, Warren B.; Ko, Clifford Y.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Bentrem, DJ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Surg, 676 St Clair St,Ste 650, Chicago, IL 60611 USA. EM dbentrem@nmff.org NR 36 TC 10 Z9 10 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD JUN PY 2012 VL 147 IS 6 BP 505 EP 511 DI 10.1001/archsurg.2011.2215 PG 7 WC Surgery SC Surgery GA 960YD UT WOS:000305428500003 PM 22351873 ER PT J AU Antiel, RM Van Arendonk, KJ Reed, DA Terhune, KP Tarpley, JL Porterfield, JR Hall, DE Joyce, DL Wightman, SC Horvath, KD Heller, SF Farley, DR AF Antiel, Ryan M. Van Arendonk, Kyle J. Reed, Darcy A. Terhune, Kyla P. Tarpley, John L. Porterfield, John R. Hall, Daniel E. Joyce, David L. Wightman, Sean C. Horvath, Karen D. Heller, Stephanie F. Farley, David R. TI Surgical Training, Duty-Hour Restrictions, and Implications for Meeting the Accreditation Council for Graduate Medical Education Core Competencies Views of Surgical Interns Compared With Program Directors SO ARCHIVES OF SURGERY LA English DT Article ID INSTITUTE-OF-MEDICINE; HOURS ENHANCING SLEEP; OPERATIVE EXPERIENCE; GENERAL-SURGERY; SUPERVISION; SAFETY; RECOMMENDATIONS; ASSOCIATION; RESIDENTS; TRAINEES AB Objective: To describe the perspectives of surgical interns regarding the implications of the new Accreditation Council for Graduate Medical Education (ACGME) duty-hour regulations for their training. Design: We compared responses of interns and surgery program directors on a survey about the proposed ACGME mandates. Setting: Eleven general surgery residency programs. Participants: Two hundred fifteen interns who were administered the survey during the summer of 2011 and a previously surveyed national sample of 134 surgery program directors. Main Outcome Measures: Perceptions of the implications of the new duty-hour restrictions on various aspects of surgical training, including the 6 ACGME core competencies of graduate medical education, measured using 3-point scales (increase, no change, or decrease). Results: Of 215 eligible surgical interns, 179 (83.3%) completed the survey. Most interns believed that the new duty-hour regulations will decrease continuity with patients (80.3%), time spent operating (67.4%), and coordination of patient care (57.6%), while approximately half believed that the changes will decrease their acquisition of medical knowledge (48.0%), development of surgical skills (52.8%), and overall educational experience (51.1%). Most believed that the changes will improve or will not alter other aspects of training, and 61.5% believed that the new standards will decrease resident fatigue. Surgical interns were significantly less pessimistic than surgery program directors regarding the implications of the new duty-hour restrictions on all aspects of surgical training (P <.05 for all comparisons). Conclusions: Although less pessimistic than program directors, interns beginning their training under the new paradigm of duty-hour restrictions have significant concerns about the effect of these regulations on the quality of their training. C1 [Antiel, Ryan M.; Heller, Stephanie F.; Farley, David R.] Mayo Clin, Dept Surg, Rochester, MN 55905 USA. [Reed, Darcy A.] Mayo Clin, Dept Primary Care Internal Med, Rochester, MN 55905 USA. [Van Arendonk, Kyle J.] Johns Hopkins Univ, Dept Surg, Baltimore, MD USA. [Terhune, Kyla P.; Tarpley, John L.] Vanderbilt Univ, Nashville, TN USA. [Porterfield, John R.] Univ Alabama Birmingham, Birmingham, AL USA. [Hall, Daniel E.] Univ Pittsburgh, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Joyce, David L.] Stanford Univ, Stanford, CA 94305 USA. [Wightman, Sean C.] Univ Chicago, Chicago, IL 60637 USA. [Horvath, Karen D.] Univ Washington, Seattle, WA 98195 USA. RP Farley, DR (reprint author), Mayo Clin, Dept Surg, 200 1st St SW, Rochester, MN 55905 USA. EM farley.david@mayo.edu RI Hall, Daniel/H-4843-2013 OI Hall, Daniel/0000-0001-6382-0522 NR 24 TC 23 Z9 23 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0004-0010 EI 1538-3644 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD JUN PY 2012 VL 147 IS 6 BP 536 EP 541 PG 6 WC Surgery SC Surgery GA 960YD UT WOS:000305428500010 PM 22786539 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Reliability measures in managing GI bleeding SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID EPIDEMIOLOGY; DIAGNOSIS AB Background: Multiple procedures and devices are used in a complex interplay to diagnose and treat GI bleeding. Objective: To model how a large variety of diagnostic and therapeutic components interact in the successful management of GI bleeding. Design: The analysis uses the concept of reliability block diagrams from probability theory to model management outcome. Separate components of the management process are arranged in a serial or parallel fashion. If the outcome depends on the function of each component individually, such components are modeled to be arranged in series. If components complement each other and can mutually compensate for each of their failures, such components are arranged in a parallel fashion. Setting: General endoscopy practice. Patients: Patients with GI bleeding of unknown etiology. Interventions: All available endoscopic and radiographic means to diagnose and treat GI bleeding. Main Outcome Measurements: Process reliability in achieving hemostasis. Results: Serial arrangements tend to reduce process reliability, whereas parallel arrangements increase it. Whenever possible, serial components should be bridged and complemented by additional alternative (parallel) routes of operation. Parallel components with low individual reliability can still contribute to overall process reliability as long as they function independently of other pre-existing alternatives. Limitations: Probability of success associated with individual components is partly unknown. Conclusions: Modeling management of GI bleeding by a reliability block diagram provides a useful tool in assessing the impact of individual endoscopic techniques and administrative structures on the overall outcome. (Gastrointest Endosc 2012;75:1184-9.) C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR 97239 USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. NR 9 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUN PY 2012 VL 75 IS 6 BP 1184 EP 1189 DI 10.1016/j.gie.2012.01.047 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 961HA UT WOS:000305453700009 PM 22624809 ER PT J AU Gidwani, R Goetz, MB Kominski, G Asch, S Mattocks, K Samet, JH Justice, A Gandhi, N Needleman, J AF Gidwani, Risha Goetz, Matthew Bidwell Kominski, Gerald Asch, Steven Mattocks, Kristin Samet, Jeffrey H. Justice, Amy Gandhi, Neel Needleman, Jack TI A BUDGET IMPACT ANALYSIS OF RAPID HUMAN IMMUNODEFICIENCY VIRUS SCREENING IN VETERANS ADMINISTRATION EMERGENCY DEPARTMENTS SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE HIV; screening; budget impact; Rapid Testing; Emergency Department ID HEALTH-CARE SETTINGS; COST-EFFECTIVENESS; HIV-INFECTION; ANTIRETROVIRAL THERAPY; UNITED-STATES; OUTCOMES AB Background: Human immunodeficiency virus (HIV) screening is cost-effective and recommended in populations with low disease prevalence. However, because screening is not cost-saying, its financial feasibility must be understood. Study Objectives: We forecast the costs of two Emergency Department-based HIV testing programs in the Veterans Administration: 1) implementing a non-targeted screening program and providing treatment for all patients thusly identified (Rapid Testing); and 2) treating patients identified due to late-stage symptoms (Usual Care); to determine which program was the most financially feasible. Methods: Using a dynamic decision-analysis model, we estimated the financial impact of each program over a 7-year period. Costs were driven by patient disease-severity at diagnosis, measured by CD4+ category, and the proportion of patients in each disease-severity category. Cost per CD4+ category was modeled from chart review and database analysis of treatment-naive HIV-positive patients. Distributions of CD4+ counts differed in patients across the Rapid Testing and Usual Care arms. Results: A non-targeted Rapid Testing program was not significantly more costly than Usual Care. Although Rapid Testing had substantial screening costs, they were offset by lower inpatient expenses associated with earlier identification of disease. Assuming an HIV prevalence of 1% and 80% test acceptance, the cost of Rapid Testing was $1,418,088, vs. $1,320,338 for Usual Care (p = 0.5854). Results support implementation of non-targeted rapid HIV screening in integrated systems. Conclusions: This analysis adds a new component of support for HIV screening by demonstrating that rapid, non-targeted testing does not cost significantly more than a diagnostic testing approach. (C) 2012 Elsevier Inc. C1 [Gidwani, Risha; Goetz, Matthew Bidwell; Asch, Steven] VA Greater Los Angeles Healthcare Syst, QUERI HIV HEPATITIS C, Los Angeles, CA USA. [Gidwani, Risha; Kominski, Gerald; Needleman, Jack] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Goetz, Matthew Bidwell; Asch, Steven] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Mattocks, Kristin; Justice, Amy] W Haven VA Healthcare Syst, West Haven, CT USA. [Mattocks, Kristin; Justice, Amy] Yale Univ, Sch Med, New Haven, CT USA. [Samet, Jeffrey H.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Gandhi, Neel] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Gandhi, Neel] Montefiore Med Ctr, Bronx, NY 10467 USA. RP Gidwani, R (reprint author), VA Greater Los Angeles Healthcare Syst, QUERI HIV HEPATITIS C, Los Angeles, CA USA. EM rishagidwani@yahoo.com RI Needleman, Jack/I-5461-2013 OI Needleman, Jack/0000-0002-2875-0589; Samet, Jeffrey/0000-0002-0897-3400; Goetz, Matthew/0000-0003-4542-992X; Kominski, Gerald/0000-0001-5214-7133 FU VA Health Services Research & Development Service Rapid Response Project (RRP) [07-283] FX This work was funded by the VA Health Services Research & Development Service Rapid Response Project (RRP) 07-283. NR 18 TC 1 Z9 1 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JUN PY 2012 VL 42 IS 6 BP 719 EP 726 DI 10.1016/j.jemermed.2010.11.038 PG 8 WC Emergency Medicine SC Emergency Medicine GA 962ZX UT WOS:000305591000019 PM 21277144 ER PT J AU Nedjat-Haiem, FR Lorenz, KA Ell, K Hamilton, A Palinkas, L AF Nedjat-Haiem, Frances R. Lorenz, Karl A. Ell, Kathleen Hamilton, Alison Palinkas, Lawrence TI Experiences With Advanced Cancer Among Latinas in a Public Health Care System SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Sociocultural; advanced cancer; low-income Latinas; pain; coping; religious beliefs ID QUALITY-OF-LIFE; HISPANIC PATIENTS; LOW-INCOME; EXPLANATORY MODELS; PATIENT NAVIGATION; BREAST; DEPRESSION; WOMEN; END; COMMUNICATION AB Context. Cultural dimensions related to illness are triggered at significant times in an illness trajectory, such as at illness onset or when death approaches. These factors influence views on how illness is understood and managed, which is likely more difficult for minority populations. Although Latinos experience barriers to high-quality health care, late-stage cancer diagnoses, and poor health outcomes, little is known about their experiences with advanced, life-threatening cancers. Objectives. We examined Latinas' experiences with advanced, metastatic cancers to identify sociocultural beliefs that influenced their care. Methods. We interviewed 24 Latinas taking part in a randomized controlled trial focused on improving quality-of-life outcomes for co-occurring cancer and depression and explored their beliefs about the cause, course, and cure of cancer. This study used a phenomenological analytical approach to explore women's lived experiences of having advanced cancer. Results. Themes revealed issues about experiencing advanced cancer that included the following: initial reactions to cancer, disbelief about the lack of pain, economic impact, beliefs about the cause, coping with cancer, beliefs about the cure, and confusion about cancer severity. Sociocultural factors influence misunderstanding and confusion about cancer care but also can be a source of strength. Conclusion. Providers need to become culturally sensitive to the needs of underserved Latinas. Denial or ignorance of these issues can create other problems, such as gaps in patient-centered decision making from diagnosis through the end of life. J Pain Symptom Manage 2012; 43: 1013-1024. Published by Elsevier Inc. on behalf of U.S. Cancer Pain Relief Committee. C1 [Nedjat-Haiem, Frances R.; Lorenz, Karl A.; Hamilton, Alison] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Ell, Kathleen; Palinkas, Lawrence] Univ So Calif, Sch Social Work, Los Angeles, CA 90089 USA. [Hamilton, Alison] Univ Calif Los Angeles, Los Angeles, CA USA. RP Nedjat-Haiem, FR (reprint author), VA Greater Los Angeles Healthcare Syst, HSR&D Ctr Excellence, Off Acad Affiliat, VA Associated Hlth Postdoctoral Fellowship Progra, 11301 Wilshire Blvd,Code 111-G, Los Angeles, CA 90073 USA. EM nedjatha@gmail.com FU Office of Academic Affiliations, VA Associated Health Postdoctoral Fellowship Program, VA Greater Los Angeles, Healthcare System, HSR&D Center of Excellence; American Cancer Society Doctoral Training Grants in Oncology Social Work [DSW-06-220-01-SW]; National Cancer Institute [R01CA105269] FX This research was supported by the Office of Academic Affiliations, VA Associated Health Postdoctoral Fellowship Program, VA Greater Los Angeles, Healthcare System, HSR&D Center of Excellence, the American Cancer Society Doctoral Training Grants in Oncology Social Work DSW-06-220-01-SW (F.R. Nedjat-Haiem, Principal Investigator) and the National Cancer Institute grant R01CA105269 (K. Ell, Principal Investigator). The authors declare no conflicts of interest. NR 35 TC 6 Z9 6 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JUN PY 2012 VL 43 IS 6 BP 1013 EP 1024 DI 10.1016/j.jpainsymman.2011.06.018 PG 12 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 961HY UT WOS:000305456500004 PM 22575719 ER PT J AU Perez-Rodriguez, MM Hazlett, EA Rich, EL Ripoll, LH Weiner, DM Spence, N Goodman, M Koenigsberg, HW Siever, LJ New, AS AF Perez-Rodriguez, M. Mercedes Hazlett, Erin A. Rich, Erin L. Ripoll, Luis H. Weiner, Daniel M. Spence, Nicole Goodman, Marianne Koenigsberg, Harold W. Siever, Larry J. New, Antonia S. TI Striatal activity in borderline personality disorder with comorbid intermittent explosive disorder: Sex differences SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Borderline personality disorder; Intermittent explosive disorder; Striatum; Aggression; Positron emission tomography ID POSITRON-EMISSION-TOMOGRAPHY; BRAIN GLUCOSE-METABOLISM; EVENT-RELATED FMRI; ACTIVATED FDG-PET; DSM-IV CRITERIA; BASAL GANGLIA; GENDER-DIFFERENCES; ORBITOFRONTAL CORTEX; IMPULSIVE-AGGRESSION; NEURONAL-ACTIVITY AB Borderline Personality Disorder (BPD) is associated with behavioral and emotional dysregulation, particularly in social contexts; however, the underlying pathophysiology at the level of brain function is not well understood. Previous studies found abnormalities in frontal cortical and limbic areas suggestive of poor frontal regulation of downstream brain regions. However, the striatum, which is closely connected with the medial frontal cortices and plays an important role in motivated behaviors and processing of rewarding stimuli, has been understudied in BPD. Here we hypothesized that, in addition to frontal dysfunction, BPD patients may show abnormal striatal function. In this study, 38 BPD patients with intermittent explosive disorder (BPD-IED) and 36 healthy controls (HC) participated in the Point Subtraction Aggression Paradigm (PSAP), a computer game played with a fictitious other player. (18)Fluoro-deoxyglucose positron emission tomography (FOG-PET) measured relative glucose metabolism (rGMR) within caudate and putamen in response to aggression-provoking and non-provoking versions of the PSAP. Male BPD-IED patients had significantly lower striatal rGMR than all other groups during both conditions, although male and female BPD-IED patients did not differ in clinical or behavioral measures. These sex differences suggest differential involvement of frontal-striatal circuits in BPD-IED, and are discussed in relation to striatal involvement in affective learning and social decision-making. Published by Elsevier Ltd. C1 [Perez-Rodriguez, M. Mercedes; Hazlett, Erin A.; Ripoll, Luis H.; Goodman, Marianne; Koenigsberg, Harold W.; Siever, Larry J.; New, Antonia S.] James J Peters Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY 10468 USA. [Perez-Rodriguez, M. Mercedes; Hazlett, Erin A.; Rich, Erin L.; Ripoll, Luis H.; Weiner, Daniel M.; Spence, Nicole; Goodman, Marianne; Koenigsberg, Harold W.; Siever, Larry J.; New, Antonia S.] Mt Sinai Sch Med, Dept Psychiat, MIRECC, Bronx, NY 10468 USA. [Rich, Erin L.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. RP New, AS (reprint author), James J Peters Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM antonia.new@mssm.edu RI Perez Rodriguez, Maria/B-9410-2013 OI Perez Rodriguez, Maria/0000-0001-5137-1993 FU James J. Peters Veterans Affairs Medical Center; National Institutes of Health (NIH) [1-R01-MH067918-01, 1-R01-MH07911]; Mount Sinai General Clinical Research Center from the National Center for Research Resources at the NIH [5-M01 RR00071] FX This work was supported by the James J. Peters Veterans Affairs Medical Center and by a grant to ASN from the National Institutes of Health (NIH) (1-R01-MH067918-01) and to EAH (1-R01-MH07911) and by 5-M01 RR00071 for the Mount Sinai General Clinical Research Center from the National Center for Research Resources at the NIH. NR 97 TC 13 Z9 13 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD JUN PY 2012 VL 46 IS 6 BP 797 EP 804 DI 10.1016/j.jpsychires.2012.02.014 PG 8 WC Psychiatry SC Psychiatry GA 961UD UT WOS:000305494100016 PM 22464337 ER PT J AU Goodman, M AF Goodman, Marianne TI Complex PTSD is on the trauma spectrum: Comment on Resick et al. (2012) SO JOURNAL OF TRAUMATIC STRESS LA English DT Article AB Conceptualizing posttraumatic stress disorder (PTSD) along a spectrum with complex and simple features is integrative and models an approach taken by disciplines in medicine outside of psychiatry. This perspective is offered in the Resick et al. (2012) review. To best delineate the nature and permeability of the border between Complex PTSD and PTSD, an emphasis on clarifying underlying biological processes is needed to move beyond our current reliance on symptomatic description. C1 [Goodman, Marianne] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Goodman, Marianne] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. RP Goodman, M (reprint author), Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. EM marianne.goodman@va.gov NR 8 TC 8 Z9 8 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2012 VL 25 IS 3 BP 254 EP 255 DI 10.1002/jts.21695 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 962VV UT WOS:000305576500005 PM 22729976 ER PT J AU Lee, AH Weintraub, D AF Lee, Angela H. Weintraub, Daniel TI Psychosis in Parkinson's disease without dementia: Common and comorbid with other non-motor symptoms SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; psychosis; non-demented; cognitively intact ID DEPRESSIVE SYMPTOMATOLOGY IDS; SLEEP BEHAVIOR DISORDER; COGNITIVE IMPAIRMENT; DAYTIME SLEEPINESS; HALLUCINATIONS; INVENTORY; SCALE; INSTRUMENT; MORTALITY AB Psychosis in Parkinson's disease (PD) is common and associated with a range of negative outcomes. Dementia and psychosis are highly correlated in PD, but the frequency and correlates of psychosis in patients without cognitive impairment are not well understood. One hundred and ninety-one non-demented PD patients at two movement disorders centers participated in a study of neuropsychiatric complications in PD and completed a detailed neurological and neuropsychiatric assessment, including the rater-administered Parkinson Psychosis Rating Scale for hallucinations, delusions, and minor symptoms of psychosis (illusions and misidentification of persons). Psychotic symptoms were present in 21.5% of the sample. Visual hallucinations were most common (13.6%), followed by auditory hallucinations (6.8%), illusions or misidentification of people (7.3%), and paranoid ideation (4.7%). Visual hallucinations and illusions or misidentification of people were the most common comorbid symptoms (3.1%). Depression (P = 0.01) and rapid eye movement behavior disorder symptoms (P = 0.03) were associated with psychosis in a multivariable model. The odds of experiencing psychotic symptoms were approximately five times higher in patients with comorbid disorders of depression and sleep-wakefulness. Even in patients without global cognitive impairment, psychosis in PD is common and most highly correlated with other non-motor symptoms. Screening for psychosis should occur at all stages of PD as part of a broad non-motor assessment. In addition, these findings suggest a common neural substrate for disturbances of perception, mood, sleep-wakefulness, and incipient cognitive decline in PD. (c) 2012 Movement Disorder Society C1 [Weintraub, Daniel] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Parkinsons Dis Res Educ & Clin Ctr, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Weintraub, Daniel] Mental Illness Res Educ & Clin Ctr, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Weintraub, D (reprint author), 3615 Chestnut St,330, Philadelphia, PA 19104 USA. EM daniel.weintraub@uphs.upenn.edu FU National Institute of Mental Health [067894]; Mental Illness Research, Education, and Clinical Center at the Philadelphia Veterans Affairs Medical Center FX Funding agencies: This work was supported, in part, by grants from the National Institute of Mental Health (067894) and the Mental Illness Research, Education, and Clinical Center at the Philadelphia Veterans Affairs Medical Center. NR 42 TC 36 Z9 37 U1 2 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUN PY 2012 VL 27 IS 7 BP 858 EP 863 DI 10.1002/mds.25003 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 962XE UT WOS:000305581900011 PM 22674352 ER PT J AU Chattergoon, NN Louey, S Stork, P Giraud, GD Thornburg, KL AF Chattergoon, Natasha N. Louey, Samantha Stork, Philip Giraud, George D. Thornburg, Kent L. TI Mid-Gestation Ovine Cardiomyocytes Are Vulnerable to Mitotic Suppression by Thyroid Hormone SO REPRODUCTIVE SCIENCES LA English DT Article DE fetal heart; cardiomyocyte proliferation; thyroid hormone; p21; cyclin D1 ID FETAL SHEEP CARDIOMYOCYTES; SIGNAL-REGULATED KINASE; CELL-CYCLE ACTIVITY; CARDIAC MYOCYTES; NEONATAL-RAT; FETUS; PLACENTA; GROWTH; PROLIFERATION; HYPERTROPHY AB Circulating fetal 3,3',5-tri-iodo-L-thyronine (T-3) is maintained at very low levels until a dramatic prepartum surge. 3,3',5-Tri-iodo-L-thyronine inhibits serum-stimulated proliferation in near-term ovine cardiomyocytes, but it is not known whether midgestation myocytes are also inhibited. Because early cessation of cardiomyocyte mitosis would result in an underendowed heart, we hypothesized that 0.67 gestation (100 of 145 days gestation) ovine cardiomyocytes would be insensitive to suppressive growth effects of T-3. These younger cardiomyocytes were grown with T-3 in 10% serum-enriched media for 24 hours. Physiological (0.37, 0.75, and 1.5 nmol/L) concentrations of T-3 dramatically suppressed mitotic activity in cardiomyocytes (P < .001). 3,30,5-Tri-iodo-L-thyronine stimulated phosphorylation of extracellular signal-regulated kinase and AKT (also known as Protein Kinase B [PKB]) signaling pathways. Nevertheless, the protein content of the cell cycle suppressor, p21, increased 2-fold (P < .05), and promoter, cyclin D1, decreased by 50%. Contrary to our hypothesis, elevated levels of T-3 powerfully inhibit proliferation of midgestation fetal cardiomyocytes. Thus, midgestation maternal hyperthyroidism might lead to an underendowed fetal myocardium. C1 [Chattergoon, Natasha N.; Louey, Samantha; Stork, Philip; Giraud, George D.; Thornburg, Kent L.] Oregon Hlth & Sci Univ, Heart Res Ctr, Portland, OR 97239 USA. [Louey, Samantha; Giraud, George D.; Thornburg, Kent L.] Oregon Hlth & Sci Univ, Dept Med Cardiovasc Med, Portland, OR 97201 USA. [Stork, Philip] Oregon Hlth & Sci Univ, Vollum Inst Adv Biomed Res, Portland, OR 97201 USA. [Giraud, George D.; Thornburg, Kent L.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. [Giraud, George D.] Portland VA Med Ctr, Portland, OR USA. RP Thornburg, KL (reprint author), Oregon Hlth & Sci Univ, Heart Res Ctr, 3303 SW Bond Ave,CH15H, Portland, OR 97239 USA. EM thornbur@ohsu.edu FU NIH [NICHD P01 HD 34430, NINDS R37, NS045737, NHLBI R21 HL093617, R01 HL102763]; NHLBI [T32HL094294]; M. Lowell Edwards Endowment FX The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: supported by NIH grants NICHD P01 HD 34430, NINDS R37, NS045737, NHLBI R21 HL093617, and R01 HL102763; NNC was supported by NHLBI training grant T32HL094294 and KLT was supported by the M. Lowell Edwards Endowment. NR 44 TC 6 Z9 6 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD JUN PY 2012 VL 19 IS 6 BP 642 EP 649 DI 10.1177/1933719111432860 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 963NH UT WOS:000305627200010 PM 22421446 ER PT J AU Ringden, O Shrestha, S da Silva, GT Zhang, MJ Dispenzieri, A Remberger, M Kamble, R Freytes, CO Gale, RP Gibson, J Gupta, V Holmberg, L Lazarus, H McCarthy, P Meehan, K Schouten, H Milone, GA Lonial, S Hari, PN AF Ringden, O. Shrestha, S. da Silva, G. T. Zhang, M-J Dispenzieri, A. Remberger, M. Kamble, R. Freytes, C. O. Gale, R. P. Gibson, J. Gupta, V. Holmberg, L. Lazarus, H. McCarthy, P. Meehan, K. Schouten, H. Milone, G. A. Lonial, S. Hari, P. N. TI Effect of acute and chronic GVHD on relapse and survival after reduced-intensity conditioning allogeneic transplantation for myeloma SO BONE MARROW TRANSPLANTATION LA English DT Article DE graft-vs-host disease; reduced intensity; allogeneic; myeloma ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; DIAGNOSED MULTIPLE-MYELOMA; VERSUS-HOST DISEASE; CHRONIC GRAFT; CHRONIC LEUKEMIA; EUROPEAN GROUP; RECIPIENTS; TRIAL; CYCLOSPORINE AB We evaluated the effect of acute and chronic GVHD on relapse and survival after allogeneic hematopoietic SCT (HSCT) for multiple myeloma using non-myeloablative conditioning (NMA) and reduced-intensity conditioning (RIC). The outcomes of 177 HLA-identical sibling HSCT recipients between 1997 and 2005, following NMA (n = 98) or RIC (n = 79) were analyzed. In 105 patients, autografting was followed by planned NMA/RIC allogeneic transplantation. The impact of GVHD was assessed as a time-dependent covariate using Cox models. The incidence of acute GVHD (aGVHD; grades I-IV) was 42% (95% confidence interval (CI), 35-49%) and of chronic GVHD (cGVHD) at 5 years was 59% (95% CI, 49-69%), with 70% developing extensive cGVHD. In multivariate analysis, aGVHD (>= grade I) was associated with an increased risk of TRM (relative risk (RR) = 2.42, P = 0.016), whereas limited cGVHD significantly decreased the risk of myeloma relapse (RR = 0.35, P = 0.035) and was associated with superior EFS (RR = 0.40, P = 0.027). aGVHD had a detrimental effect on survival, especially in those receiving autologous followed by allogeneic HSCT (RR = 3.52, P = 0.001). The reduction in relapse risk associated with cGVHD is consistent with a beneficial graft-vs-myeloma effect, but this did not translate into a survival advantage. Bone Marrow Transplantation (2012) 47, 831-837; doi:10.1038/bmt.2011.192; published online 26 September 2011 C1 [Shrestha, S.; Zhang, M-J; Hari, P. N.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Ringden, O.; Remberger, M.] Karolinska Univ Hosp, Dept Clin Immunol, Stockholm, Sweden. [da Silva, G. T.] Univ Sao Paulo, Dept Stat, Sao Paulo, Brazil. [Dispenzieri, A.] Mayo Clin, Rochester, MN USA. [Kamble, R.] Baylor Coll Med, Dept Hematol & Oncol, Houston, TX 77030 USA. [Freytes, C. O.] S Texas Vet Hlth Care Syst, Dept Hematol, San Antonio, TX USA. [Gale, R. P.] Celgene Corp, Dept Hematol & Oncol, Summit, NJ USA. [Gibson, J.] Royal Prince Alfred Hosp, Dept Haematol, Inst Haematol, Camperdown, NSW 2050, Australia. [Gupta, V.] Princess Margaret Hosp, Dept Med, Toronto, ON M4X 1K9, Canada. [Holmberg, L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Lazarus, H.] Univ Hosp Case Med Ctr, Dept Med, Cleveland, OH USA. [McCarthy, P.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Meehan, K.] Dartmouth Hitchcock Med Ctr, Dept Med, Lebanon, NH 03766 USA. [Schouten, H.] Univ Hosp Maastricht, Dept Internal Med, Maastricht, Netherlands. [Milone, G. A.] Angelica Ocampo Fundaleu, Buenos Aires, DF, Argentina. [Lonial, S.] Emory Univ Hosp, Dept Med, Atlanta, GA 30322 USA. RP Hari, PN (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 9200 W Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA. EM phari@mcw.edu OI Dispenzieri, Angela/0000-0001-8780-9512; Hari, Parameswaran/0000-0002-8800-297X FU Public Health Service from the National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases; NHLBI [5U01HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS) [HHSH 234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; AABB; Aetna; American Society for Blood and Marrow Transplantation; Amgen, Inc.; Swedish Cancer Society; Children's Cancer Foundation; Swedish Research Council; Cancer Society in Stockholm; Karolinska Institutet 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; a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract HHSH 234200637015C 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 AABB; Aetna; American Society for Blood and Marrow Transplantation, Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US, Inc.; Baxter International, Inc.; Bayer HealthCare Pharmaceuticals; Be the Match Foundation; Biogen IDEC; BioMarin Pharmaceutical, Inc.; Biovitrum AB; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Buchanan Family Foundation; Canadian Blood and Marrow Transplant Group; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Centers for Disease Control and Prevention; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Cubist Pharmaceuticals; Cylex, Inc.; CytoTherm; DOR BioPharma, Inc.; Dynal Biotech (an Invitrogen Company); Eisai, Inc.; Enzon Pharmaceuticals, Inc.; European Group for Blood and Marrow Transplantation; Gamida Cell, Ltd.; GE Healthcare; Genentech, Inc.; Genzyme Corporation; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewery Co., Ltd.; The Leukemia and Lymphoma Society; Merck and Company; The Medical College of Wisconsin; MGI Pharma, Inc.; Michigan Community Blood Centers; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Nature Publishing Group; New York Blood Center; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Pall Life Sciences; Pfizer, Inc.; Saladax Biomedical, Inc.; Schering Corporation; Society for Healthcare Epidemiology of America; Soligenix, Inc.; StemCyte, Inc.; StemSoft Software, Inc.; Sysmex America, Inc.; THERAKOS, Inc.; Thermogenesis Corporation; Vidacare Corporation; Vion Pharmaceuticals, Inc.; ViraCor Laboratories; ViroPharma, Inc.; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense or any other agency of the US Government. Olle Ringden is supported by grants from the Swedish Cancer Society, the Children's Cancer Foundation, the Swedish Research Council, the Cancer Society in Stockholm, and Karolinska Institutet. NR 28 TC 14 Z9 14 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUN PY 2012 VL 47 IS 6 BP 831 EP 837 DI 10.1038/bmt.2011.192 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 958YF UT WOS:000305276200010 PM 21946381 ER PT J AU Barnes, DE Palmer, RM Kresevic, DM Fortinsky, RH Kowal, J Chren, MM Landefeld, CS AF Barnes, Deborah E. Palmer, Robert M. Kresevic, Denise M. Fortinsky, Richard H. Kowal, Jerome Chren, Mary-Margaret Landefeld, C. Seth TI Acute Care For Elders Units Produced Shorter Hospital Stays At Lower Cost While Maintaining Patients' Functional Status SO HEALTH AFFAIRS LA English DT Article ID COMPREHENSIVE GERIATRIC ASSESSMENT; RANDOMIZED CONTROLLED-TRIAL; OLDER PATIENTS; MEDICAL UNIT; METAANALYSIS; OUTCOMES; ADULTS; HOME; ACE; INTERVENTION AB Acute Care for Elders Units offer enhanced care for older adults in specially designed hospital units. The care is delivered by interdisciplinary teams, which can include geriatricians, advanced practice nurses, social workers, pharmacists, and physical therapists. In a randomized controlled trial of 1,632 elderly patients, length-of-stay was significantly shorter-6.7 days per patient versus 7.3 days per patient-among those receiving care in the Acute Care for Elders Unit compared to usual care. This difference produced lower total inpatient costs-$9,477 per patient versus $10,451 per patient-while maintaining patients' functional abilities and not increasing hospital readmission rates. The practices of Acute Care for Elders Units, and the principles they embody, can provide hospitals with effective strategies for lowering costs while preserving quality of care for hospitalized elders. C1 [Barnes, Deborah E.; Landefeld, C. Seth] Univ Calif San Francisco, Mt Zion Ctr Aging, San Francisco, CA 94143 USA. [Barnes, Deborah E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Palmer, Robert M.] Eastern Virginia Med Sch, Glennan Ctr Geriatr & Gerontol, Norfolk, VA 23501 USA. [Kresevic, Denise M.] Louis Stokes Vet Affairs Med Ctr, Cleveland, OH USA. [Fortinsky, Richard H.] Univ Connecticut, Sch Med, Farmington, CT USA. [Kowal, Jerome] Case Western Reserve Sch Med, Cleveland, OH USA. [Landefeld, C. Seth] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Barnes, DE (reprint author), Univ Calif San Francisco, Mt Zion Ctr Aging, San Francisco, CA 94143 USA. EM deborah.barnes@ucsf.edu FU National Institutes of Health [R01 AG029233, AG10418, K24 AR052667]; S.D. Bechtel Jr. Foundation FX Some results from this paper were presented to the Society of General Internal Medicine, Chicago, Illinois, April 23-25, 1998. Support for this study was provided by the National Institutes of Health (R01 AG029233 and AG10418, principal investigator C. Seth Landefeld; K24 AR052667, principal investigator Mary-Margaret Chren) and the S.D. Bechtel Jr. Foundation. The authors thank Laura Sands and Katharine Kirby for performing statistical analyses, Ken Covinsky for providing comments on the manuscript, and the clinical Acute Care for Elders teams that have provided care to the authors' patients. NR 32 TC 19 Z9 19 U1 1 U2 13 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JUN PY 2012 VL 31 IS 6 BP 1227 EP 1236 DI 10.1377/hlthaff.2012.0142 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 957AM UT WOS:000305130900010 PM 22665834 ER PT J AU Quigley, KS McAndrew, LM Almeida, L D'Andrea, EA Engel, CC Hamtil, H Ackerman, AJ AF Quigley, Karen S. McAndrew, Lisa M. Almeida, Liliana D'Andrea, Elizabeth A. Engel, Charles C. Hamtil, Heather Ackerman, Adam J. TI Prevalence of Environmental and Other Military Exposure Concerns in Operation Enduring Freedom and Operation Iraqi Freedom Veterans SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID GULF-WAR VETERANS; TRAUMATIC BRAIN-INJURY; UNEXPLAINED PHYSICAL SYMPTOMS; PRIMARY-CARE; HEALTH; SEEKING; STRESS; ASSOCIATION; POPULATION; COMMUNITY AB Objective: This study examined the prevalence of self-reported exposures in returning Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) veterans and the relationship of exposure reports to current physical symptoms. Methods: Using self-reports obtained immediately after return from deployment in a cohort of 760 enlisted Army reserve component military personnel, we assessed prevalence rates of environmental and other exposures and the association of these exposures to severity of physical symptoms. Results: Reporting of environmental exposures was relatively low in veterans of OEF/OIF, but reporting more environmental and other exposures, in particular screening positive for a traumatic brain injury, was related to greater physical symptom severity immediately after deployment. Conclusions: Non-treatment-seeking, enlisted Army reserve component personnel reported relatively few exposures immediately after return from deployment; however, more exposures was modestly associated with greater severity of physical symptoms when controlling for predeployment symptoms, gender, and other deployment-related exposures. C1 [Quigley, Karen S.] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Quigley, Karen S.] Edith Nourse Rogers Mem Vet Adm Hosp, Bedford, MA 01730 USA. [Quigley, Karen S.; McAndrew, Lisa M.; Almeida, Liliana; Hamtil, Heather; Ackerman, Adam J.] NJ WRIISC, Dept Vet Affairs New Jersey Healthcare Syst, E Orange, NJ USA. [Quigley, Karen S.; McAndrew, Lisa M.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Psychiat, Newark, NJ 07103 USA. [D'Andrea, Elizabeth A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Engel, Charles C.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Engel, Charles C.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Psychiat, Bethesda, MD 20814 USA. [Almeida, Liliana] Alliant Int Univ, CSPP, Los Angeles, CA USA. [Hamtil, Heather] Rutgers State Univ, Ctr Behav Hlth Serv & Criminal Justice Res, New Brunswick, NJ 08903 USA. RP Quigley, KS (reprint author), Northeastern Univ, Dept Psychol, 125 Nightingale Hall, Boston, MA 02115 USA. EM k.quigley@neu.edu RI Quigley, Karen/B-9003-2013 OI Quigley, Karen/0000-0001-8844-990X FU Department of Veterans Affairs [IIR 02-296]; NJ WRIISC; Jersey Healthcare System at Department of Veterans Affairs; Deployment Health Clinical Center, Walter Reed Army Medical Center FX This work was supported by a Department of Veterans Affairs, Health Services Research and Development grant (IIR 02-296) to Dr Quigley while she was employed. at the NJ WRIISC. Additional funds were provided by the NJ WRIISC and the Center for Healthcare Knowledge Management (NJ REAP; VA Health Services Research and Development) at the Department of Veterans Affairs Now Jersey Healthcare System, and by the Deployment Health Clinical Center, Walter Reed Army Medical Center. NR 40 TC 10 Z9 10 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JUN PY 2012 VL 54 IS 6 SI SI BP 659 EP 664 DI 10.1097/JOM.0b013e3182570506 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 957MA UT WOS:000305165900002 PM 22588478 ER PT J AU Friedlander, AH AF Friedlander, Arthur H. TI PROSTHETIC JOINT INFECTIONS SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Letter ID DENTAL PROCEDURES C1 Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Friedlander, AH (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JUN PY 2012 VL 143 IS 6 BP 552 EP + PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 957LF UT WOS:000305163800003 PM 22653926 ER PT J AU Spira, AP Covinsky, K Rebok, GW Punjabi, NM Stone, KL Hillier, TA Ensrud, KE Yaffe, K AF Spira, Adam P. Covinsky, Kenneth Rebok, George W. Punjabi, Naresh M. Stone, Katie L. Hillier, Teresa A. Ensrud, Kristine E. Yaffe, Kristine TI Poor Sleep Quality and Functional Decline in Older Women SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE sleep; actigraphy; function; IADLs; women ID OSTEOPOROTIC FRACTURES; CARDIOVASCULAR HEALTH; ELDERLY PERSONS; PERSISTENCE; ACTIVATION; ACTIGRAPHY; COMPLAINTS; COMMUNITY; ADULTS; MEN AB Objectives To determine whether objectively measured sleep quality predicts 5-year incident instrumental activity of daily living (IADL) impairment and decline in grip strength and gait speed in older women. Design Prospective cohort. Setting Participants' homes, Study of Osteoporotic Fractures sites. Participants Eight hundred seventeen women with a mean age of 82.4 at baseline. Measurements Participants completed 4.1 +/- 0.7 nights of wrist actigraphy at baseline and measures of IADL impairment, grip strength, and gait speed at baseline and 5-year follow-up. Results After 5years of follow-up, approximately 41% of participants had incident impairment in one or more IADLs. The quartile of women with the shortest total sleep time (TST) had 93% greater odds of incident IADL impairment than the longest sleepers (adjusted odds ratio (AOR)=1.93, 95% confidence interval (CI)=1.252.97). Similarly, the quartile of women with the lowest sleep efficiency (SE) had 65% greater odds of impairment than those with the highest (AOR=1.65, 95% CI=1.062.57). Women in the shortest TST quartile had twice the odds of declining grip strength as those with the longest TST (AOR=1.97, 95% CI=1.173.32). Finally, women in the quartiles with the most wake after sleep onset (WASO) and the lowest SE had approximately 90% greater odds of grip strength decline than those with the least WASO (AOR=1.90, 95% CI=1.113.24) and SE (AOR=1.92, 95% CI=1.123.29). Conclusion Findings indicate that shorter sleep duration, greater WASO, and lower SE are risk factors for functional or physical decline in older women. C1 [Spira, Adam P.; Rebok, George W.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Covinsky, Kenneth] Univ Calif San Francisco, Div Geriatr, Dept Med, San Francisco, CA USA. [Covinsky, Kenneth] San Francisco VA Med Ctr, San Francisco, CA USA. [Punjabi, Naresh M.] Johns Hopkins Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD USA. [Punjabi, Naresh M.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Stone, Katie L.] Calif Pacific Med Ctr Res Inst, San Francisco, CA USA. [Hillier, Teresa A.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Ensrud, Kristine E.] Minneapolis Vet Affairs Med Ctr, Dept Med, Minneapolis, MN USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Med, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 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. RP Spira, AP (reprint author), 624 N Broadway,Hampton House,Rm 794, Baltimore, MD 21205 USA. EM aspira@jhsph.edu FU National Institutes of Health (NIH) [R01 AR35582, R01 AR35583, R01 AR35584, R01 AG026720, R01 AG005407, R01 AG027574, R01 AG027576, R01 AG005394, 2R01-HL075078, 5R01-HL089467]; Alzheimer's Association [IIRG-08-88872]; National Institute on Aging [1K01AG033195, K24AG031155]; National Institute of Mental Health; National Institute of Diabetes and Digestive and Kidney Diseases; Department of Defense; Department of Veterans Affairs FX Supported by National Institutes of Health (NIH) Grants R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG026720, R01 AG005407, R01 AG027574, R01 AG027576, and R01 AG005394, and by and Alzheimer's Association award IIRG-08-88872. Dr. Spira is supported by a Mentored Research Scientist Development Award (1K01AG033195) from the National Institute on Aging. Dr. Yaffe is partially supported by a Midcareer Investigator Award in Patient-Oriented Research (K24AG031155) from the National Institute on Aging. Dr. Punjabi was supported by NIH grants 2R01-HL075078 and 5R01-HL089467. 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.; Adam Spira is supported by a grant from the National Institute on Aging (NIA); he received honoraria while serving as a clinical editor for the International Journal of Sleep and Wakefulnessu Primary Care, which receives pharmaceutical company support. Kenneth Covinsky is supported by grants from the NIA. Naresh Punjabi is supported by National Institutes of Health (NIH) grants 2R01-HL075078 and 5R01-HL089467, and has received grant support from Resmed for a multicenter clinical trial on the effects of positive airway pressure therapy for sleep apnea in type 2 diabetes mellitus. Katie Stone reports that NIH funding has been obtained for this work. Teresa Hillier received support from the NIA for this work. Kristine Ensrud received grant support from the NIH (and supporting agencies) as listed under Funding Sources. Kristine Yaffe has received grants from the NIA, National Institute of Mental Health, National Institute of Diabetes and Digestive and Kidney Diseases, Department of Defense, Department of Veterans Affairs, the Alzheimer's Association, and an anonymous donor. She has served on data safety monitoring boards for Pfizer and Medivation, and received honoraria from Novartis as an advisory board member. She is a member of the boards of the Beeson Program, the National Institute of Mental Health, and the National Heart, Lung, and Blood Institute. NR 25 TC 19 Z9 20 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUN PY 2012 VL 60 IS 6 BP 1092 EP 1098 DI 10.1111/j.1532-5415.2012.03968.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 957AW UT WOS:000305131900013 PM 22690985 ER PT J AU Williams, BA Goodwin, JS Baillargeon, J Ahalt, C Walter, LC AF Williams, Brie A. Goodwin, James S. Baillargeon, Jacques Ahalt, Cyrus Walter, Louise C. TI Addressing the Aging Crisis in US Criminal Justice Health Care SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE aging; health disparities; prisoner ID PRISON; INMATES; SYSTEM AB The U.S. criminal justice population is aging at a significantly more rapid rate than the overall U.S. population, with the population of older adults in prison having more than tripled since 1990. This increase is at the root of a prison healthcare crisis that is spilling into communities and public healthcare systems because nearly 95% of prisoners are eventually released. The graying prison population is also straining state and local budgets. In prison, older prisoners cost approximately three times as much as younger prisoners to incarcerate, largely because of healthcare costs. In the community, older former prisoners present the least risk of recidivism yet are vulnerable to serious and costly social and medical challenges such as housing instability, poor employability, multiple chronic health conditions, and health-related mortality; however older current and former prisoners are largely ignored in the current geriatrics evidence base. Knowledge about the health, functional, and cognitive status of older prisoners is limited, with even less known about risk factors for long-term poor health outcomes during and after incarceration. This article provides an overview of aging in the criminal justice system. It then describes how geriatric models of care could be adapted to address the mounting older prisoner healthcare crisis and identifies areas where additional research is needed to explore prison-specific models of care for older adults. C1 [Williams, Brie A.; Ahalt, Cyrus; Walter, Louise C.] Univ Calif San Francisco, Div Geriatr, Dept Med, San Francisco, CA 94118 USA. [Williams, Brie A.; Walter, Louise C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Goodwin, James S.] Univ Texas Med Branch, Dept Internal Med, Div Geriatr Med, Galveston, TX USA. [Baillargeon, Jacques] Univ Texas Med Branch, Dept Prevent Med & Community Hlth, Galveston, TX USA. RP Williams, BA (reprint author), Univ Calif San Francisco, Div Geriatr, Dept Med, 3333 Calif St,Suite 380, San Francisco, CA 94118 USA. EM brie.williams@ucsf.edu FU National Institute of Aging [K23AG033102]; Jacob & Valeria Langeloth Foundation; University of California at San Francisco; National Cancer Institute [R01 CA134425] FX Dr. Williams is supported by the National Institute of Aging (K23AG033102), The Jacob & Valeria Langeloth Foundation, and the University of California at San Francisco Program for the Aging Century. Dr. Walter is supported by National Cancer Institute Contract R01 CA134425. Drs. Williams and Walter are employees of the Department of Veterans Affairs (VA). The opinions expressed in this manuscript may not represent those of the VA. NR 30 TC 28 Z9 28 U1 1 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUN PY 2012 VL 60 IS 6 BP 1150 EP 1156 DI 10.1111/j.1532-5415.2012.03962.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 957AW UT WOS:000305131900023 PM 22642489 ER PT J AU Kirkpatrick, WR Wiederhold, NP Najvar, LK Bocanegra, RA Patterson, TF AF Kirkpatrick, W. R. Wiederhold, N. P. Najvar, L. K. Bocanegra, R. A. Patterson, T. F. TI Comparison of disseminated and pulmonary models of invasive Aspergillosis for the detection of surrogate markers of infection SO MYCOSES LA English DT Meeting Abstract C1 [Kirkpatrick, W. R.; Wiederhold, N. P.; Najvar, L. K.; Bocanegra, R. A.; Patterson, T. F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Kirkpatrick, W. R.; Najvar, L. K.; Bocanegra, R. A.; Patterson, T. F.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Wiederhold, N. P.] Univ Texas Austin, Austin, TX 78712 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 0933-7407 J9 MYCOSES JI Mycoses PD JUN PY 2012 VL 55 SU 4 SI SI BP 283 EP 283 PG 1 WC Dermatology; Mycology SC Dermatology; Mycology GA 956DK UT WOS:000305069801228 ER PT J AU Johansen, KL Finkelstein, FO Revicki, DA Evans, C Wan, SW Gitlin, M Agodoa, IL AF Johansen, Kirsten L. Finkelstein, Fredric O. Revicki, Dennis A. Evans, Christopher Wan, Shaowei Gitlin, Matthew Agodoa, Irene L. TI Systematic review of the impact of erythropoiesis-stimulating agents on fatigue in dialysis patients SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Review DE anemia; dialysis; ESA; fatigue; hemoglobin ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; QUALITY-OF-LIFE; CHRONIC KIDNEY-DISEASE; HEMODIALYSIS-PATIENTS; EPOETIN-ALPHA; RECEIVING HEMODIALYSIS; DARBEPOETIN ALPHA; HEALTH-STATUS; ANEMIA; TRIAL AB Background. One of the cardinal symptoms of anemia in chronic kidney disease (CKD) patients is fatigue. Recently, results from Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) raised questions about the role of erythropoiesis-stimulating agents (ESAs) in improving fatigue and the appropriate hemoglobin (Hb) target in anemic patients with CKD. These discussions should be considered with all available evidence to determine the level of benefits and risks associated with ESA therapy on fatigue among both early-stage CKD patients and end-stage renal disease patients on dialysis. Methods. The study was a systematic review of the literature on fatigue in adults on maintenance dialysis therapy. The requirement for inclusion in the review was the measurement of fatigue before and after ESA treatment. Outcomes that were assessed were fatigue as measured by the Kidney Disease Questionnaire, the 36-item Short-Form general health survey, the Nottingham Health Profile, the Profile of Mood States or the Functional Assessment of Chronic Illness Therapy-Fatigue scale. Several different measures of fatigue were used in the studies. Results. Fifteen articles met the criteria for inclusion, including 10 distinct studies and one extension study. There was one placebo-controlled randomized clinical trial (RCT) and one extension, five single-arm, three high versus low, one intravenous versus subcutaneous and one switch from epoetin alfa to darbepoetin alfa. The only placebo-controlled RCT found a 22-26% improvement in fatigue. Single-arm cohort studies demonstrated a reduction in fatigue after a substantial increase in Hb. Studies with a baseline Hb <10 g/dL and partial correction to a minimum Hb >= 10 g/dL showed an average improvement in fatigue of 34.6%. Studies with a baseline Hb >= 11 g/dL and full correction to a minimum Hb >= 12 g/dL showed an average improvement in fatigue of 5.5%, while studies with no change in Hb (either placebo or control group) showed a decline of 0.7% in fatigue outcomes. Conclusion. Partial correction of anemia with ESA results in improvement of fatigue among patients on dialysis, most strikingly in those patients with baseline Hb levels <10 g/dL. C1 [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA. [Finkelstein, Fredric O.] Yale Univ, Hosp St Raphael, New Haven, CT USA. [Revicki, Dennis A.] United BioSource Corp, Bethesda, MD USA. [Evans, Christopher] Mapi Values, Boston, MA USA. [Wan, Shaowei; Gitlin, Matthew; Agodoa, Irene L.] Amgen Inc, Thousand Oaks, CA 91320 USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA. EM Kirsten.Johansen@ucsf.edu FU Amgen FX K.L.J. and F.O.F. have received research support from Amgen; D.A.R. and C.E. have received consulting fees and research support from Amgen; S.W., M.G. and I.L.A. are employees of Amgen. This study was funded by Amgen and conceived by employees of Amgen. NR 34 TC 18 Z9 18 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD JUN PY 2012 VL 27 IS 6 BP 2418 EP 2425 DI 10.1093/ndt/gfr697 PG 8 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 952YK UT WOS:000304832100045 PM 22187314 ER PT J AU Hsueh, MT Eastman, K McFarland, LV Raugi, GJ Reiber, GE AF Hsueh, Martha T. Eastman, Kristin McFarland, Lynne V. Raugi, Gregory J. Reiber, Gayle E. TI Teledermatology Patient Satisfaction in the Pacific Northwest SO TELEMEDICINE AND E-HEALTH LA English DT Article DE teledermatology; patient satisfaction; store-and-forward; Veterans Affairs ID RANDOMIZED CONTROLLED-TRIAL; FORWARD TELEDERMATOLOGY; CONSULT SYSTEM; TELEMEDICINE; DERMATOLOGY AB Background: The aim of this quality improvement project is to assess patient satisfaction with a store-and-forward teledermatology project and to identify factors associated with patient satisfaction and dissatisfaction. Subjects and Methods: Veterans receiving care in rural clinics in the Pacific Northwest were surveyed using a 5-point Likert scale about satisfaction with face-to-face care for a skin complaint prior to any teledermatology exposure. One year later, veterans in the same rural clinics were surveyed about satisfaction with teledermatology care using a more comprehensive survey. Ninety-six patients completed the face-to-face satisfaction survey questions, and 501 completed the teledermatology satisfaction survey. Results: Most (78%) of surveyed patients were highly satisfied or satisfied with face-to-face dermatology care. After 1 year of teledermatology, 77% of patients were highly satisfied or satisfied with teledermatology care. The mean patient satisfaction score for teledermatology was equivalent to face-to-face care (4.1 +/- 1.2 and 4.3 +/- 1.0, p= 0.4). Factors associated with teledermatology patient satisfaction included short wait times for initial consultation, a perception that the initial wait time was not too long, a perception that the skin condition was properly treated, and the belief that adequate follow-up was received. Factors associated with teledermatology patient dissatisfaction included perceptions that the skin condition was not properly treated and that inadequate follow-up was received. Conclusions: Teledermatology was widely accepted by the majority of patients receiving care at rural clinics. Patient satisfaction with care received through teledermatology was equivalent to that with face-to-face dermatology. C1 [Eastman, Kristin; McFarland, Lynne V.; Raugi, Gregory J.; Reiber, Gayle E.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Hsueh, Martha T.; Eastman, Kristin] Univ Washington, Sch Med, Seattle, WA USA. [Eastman, Kristin; Reiber, Gayle E.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Rehabil Res & Dev, Seattle, WA 98101 USA. [Raugi, Gregory J.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Primary Med Serv, Dermatol Sect, Seattle, WA 98101 USA. [Raugi, Gregory J.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Specialty Med Serv, Dermatol Sect, Seattle, WA 98101 USA. RP McFarland, LV (reprint author), VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev, Metropolitan Pk W,1100 Olive Way,1400, Seattle, WA 98101 USA. EM lynne.mcfarland@va.gov FU Veterans Health Administration Office of Rural Health, U.S. Department of Veterans Affairs; Veterans Health Administration Health Services Research & Development, U.S. Department of Veterans Affairs FX We are indebted to Jeff Rodenbaugh for database programming. G.E.R. is the recipient of a Veterans Affairs Senior Career Scientist award. Funding for the VISN 20 Rural Teledermatology Project came from the Veterans Health Administration Office of Rural Health, U.S. Department of Veterans Affairs. This project was supported by the Veterans Health Administration Health Services Research & Development, U.S. Department of Veterans Affairs. NR 12 TC 18 Z9 18 U1 1 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED E-HEALTH JI Telemed. e-Health PD JUN PY 2012 VL 18 IS 5 BP 377 EP 381 DI 10.1089/tmj.2011.0181 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 956OA UT WOS:000305097800009 PM 22489931 ER PT J AU Gubner, NR McKinnon, CS Cunningham, CL Phillips, TJ AF Gubner, N. R. McKinnon, C. S. Cunningham, C. L. Phillips, T. J. TI VARENICLINE DOES NOT ATTENUATE THE EXPRESSION OF ETHANOL-INDUCED CPP OR THE DEVELOPMENT OF ETHANOL-INDUCED SENSITIZATION IN DBA/2J MICE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 [Gubner, N. R.; McKinnon, C. S.; Cunningham, C. L.; Phillips, T. J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland Alcohol Res Ctr, Portland VA Med Ctr, Portland, OR 97239 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 19A EP 19A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806000034 ER PT J AU Kincaid, CL Rasmussen, DD AF Kincaid, C. L. Rasmussen, D. D. TI PRAZOSIN, AN alpha 1-ADRENERGIC RECEPTOR ANTAGONIST, DECREASES VOLUNTARY ALCOHOL INTAKE BY WISTAR RATS IN THE INTERMITTENT ACCESS TO ALCOHOL (IAA) MODEL SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 Univ Washington, VISN Mental Illness Res 20, Educ & Clin Ctr MIRECC, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat, Seattle, WA 98108 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 22A EP 22A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806000046 ER PT J AU Fryer, SL Shanbhag, H Watson, TD Krystal, JH Mathalon, DH AF Fryer, S. L. Shanbhag, H. Watson, T. D. Krystal, J. H. Mathalon, D. H. TI FMRI REVEALS DIFFERENTIAL LIMBIC RESPONSE TO ALCOHOL CUE DISTRACTORS ACROSS STAGES OF ALCOHOL DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94122 USA. San Francisco VA Med Ctr, San Francisco, CA 92121 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 46A EP 46A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806000141 ER PT J AU Kincaid, CL Rasmussen, DD AF Kincaid, C. L. Rasmussen, D. D. TI SOURCE (VENDOR) OF WISTAR RATS IS AN IMPORTANT VARIABLE IN THE INTERMITTENT ACCESS TO ALCOHOL (IAA) MODEL OF INCREASED VOLUNTARY ALCOHOL DRINKING SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 Univ Washington, VISN Mental Illness Res Educ & Clin Ctr MIRECC 20, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat, Seattle, WA 98108 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 108A EP 108A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806000390 ER PT J AU Rasmussen, DD Kincaid, CL AF Rasmussen, D. D. Kincaid, C. L. TI ACOUSTIC STARTLE AMPLITUDE PREDICTS VOLUNTARY ALCOHOL INTAKE DURING SUBSEQUENT INTERMITTENT ACCESS TO ALCOHOL (IAA) SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 Univ Washington, VA Puget Sound Hlth Care Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 20, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat, Seattle, WA 98108 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 111A EP 111A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806000401 ER PT J AU Rasmussen, DD Kincaid, CL Froehlich, JC AF Rasmussen, D. D. Kincaid, C. L. Froehlich, J. C. TI PRAZOSIN, AN alpha 1-ADRENERGIC RECEPTOR ANTAGONIST, BLOCKS THE EFFECT OF STRESS ON ANXIETY BEHAVIOR DURING SUBSEQUENT ALCOHOL WITHDRAWAL SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 Univ Washington, VA Puget Sound Hlth Care Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 20, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat, Seattle, WA 98108 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 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 JUN PY 2012 VL 36 SU 1 SI SI BP 112A EP 112A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806001004 ER PT J AU Lapham, GT Rubinsky, AD Williams, EC Maynard, C Heagerty, P Kivlahan, DR Au, DH Bradley, KA AF Lapham, G. T. Rubinsky, A. D. Williams, E. C. Maynard, C. Heagerty, P. Kivlahan, D. R. Au, D. H. Bradley, K. A. TI FACTORS ASSOCIATED WITH REPEATED NEGATIVE ALCOHOL SCREENS: IS ANNUAL ALCOHOL SCREENING UNNECESSARY FOR SOME VA PATIENTS? SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 US Dept Vet Affairs, Seattle, WA 98101 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98104 USA. Grp Hlth Res Inst, Seattle, WA 98101 USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 155A EP 155A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806001169 ER PT J AU Grossbard, JR Hawkins, EJ Lapham, GT Williams, EC Rubinsky, AD Chavez, LJ Bradley, KA AF Grossbard, J. R. Hawkins, E. J. Lapham, G. T. Williams, E. C. Rubinsky, A. D. Chavez, L. J. Bradley, K. A. TI RATES OF ALCOHOL MISUSE AND FOLLOW-UP CARE AMONG OEF/OIF VETERANS IN VA: ASSOCIATIONS WITH SUBSTANCE USE DISORDERS AND PTSD SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 VA Puget Sound, Dept Vet Affairs, Hlth Serv Res & Dev, Seattle, WA 98101 USA. SUD QuERI, Seattle, WA 98101 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 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 JUN PY 2012 VL 36 SU 1 SI SI BP 160A EP 160A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806001191 ER PT J AU Batki, SL Lasher, BA Heinz, AJ Herbst, E Metzler, T Prathikanti, S Waldrop, A Neylan, TC Tarasovsky, G AF Batki, S. L. Lasher, B. A. Heinz, A. J. Herbst, E. Metzler, T. Prathikanti, S. Waldrop, A. Neylan, T. C. Tarasovsky, G. TI RISK-TAKING, IMPULSIVITY, MEMORY & EXECUTIVE FUNCTIONING AS OUTCOME PREDICTORS IN A TRIAL OF TOPIRAMATE FOR ALCOHOL DEPENDENCE IN VETERANS WITH PTSD SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 UCSF, Dept Psychiat, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA 94121 USA. NR 0 TC 1 Z9 1 U1 1 U2 5 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 JUN PY 2012 VL 36 SU 1 SI SI BP 226A EP 226A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806002055 ER PT J AU Heinz, AJ Waldrop, A Lasher, BA Herbst, E Prathikanti, S Neylan, TC Metzler, T Petrakis, I Tarasovsky, G Batki, SL AF Heinz, A. J. Waldrop, A. Lasher, B. A. Herbst, E. Prathikanti, S. Neylan, T. C. Metzler, T. Petrakis, I. Tarasovsky, G. Batki, S. L. TI COGNITIVE FUNCTIONING, IMPULSIVITY AND RISK-TAKING: RELATIONSHIPS WITH MEASURES OF CLINICAL SYMPTOMOLOGY IN VETERANS WITH PTSD AND AUD SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 UCSF, Dept Psychiat, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA 94121 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 226A EP 226A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806002054 ER PT J AU Raskind, MA Simpson, T AF Raskind, M. A. Simpson, T. TI EFFECTS OF PRAZOSIN ON DRINKING PARAMETERS IN ALCOHOL DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 [Raskind, M. A.; Simpson, T.] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Tacoma, WA 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 247A EP 247A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806002140 ER PT J AU Raskind, M Simpson, T AF Raskind, M. Simpson, T. TI EFFECTS OF PRAZOSIN ON DRINKING PARAMETERS IN ALCOHOL DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98108 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 JUN PY 2012 VL 36 SU 1 SI SI BP 318A EP 318A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806002424 ER PT J AU Rasmussen, DD Froehlich, JC AF Rasmussen, D. D. Froehlich, J. C. TI PRECLINICAL PRAZOSIN STUDIES: DEPENDENCE OF APPROPRIATE DOSE ON DRINKING HISTORY, AND BENEFIT OF COMBINING PRAZOSIN plus PROPRANOLOL TO DECREASE RELAPSE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98108 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 318A EP 318A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806002422 ER PT J AU Durazzo, TC Mon, A Pennington, D Abe, C Meyerhoff, DJ AF Durazzo, T. C. Mon, A. Pennington, D. Abe, C. Meyerhoff, D. J. TI CHRONIC CIGARETTE SMOKING IN ALCOHOL USE DISORDERS: ASSOCIATIONS WITH NEUROBIOLOGICAL ABNORMALITIES IN THE BRAIN REWARD/EXECUTIVE OVERSIGHT SYSTEM SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 349A EP 349A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806002546 ER PT J AU Schacht, JP Anton, RF Randall, PK Li, X Henderson, S Myrick, H AF Schacht, J. P. Anton, R. F. Randall, P. K. Li, X. Henderson, S. Myrick, H. TI INTERACTING EFFECTS OF NALTREXONE AND OPRM1 AND DAT VARIATION ON THE NEURAL RESPONSE TO ALCOHOL CUES SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 [Schacht, J. P.; Anton, R. F.; Randall, P. K.; Li, X.; Henderson, S.; Myrick, H.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Myrick, H.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 366A EP 366A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806002616 ER PT J AU Hua, P Feng, WG Rezonzew, G Chumley, P Jaimes, EA AF Hua, Ping Feng, Wenguang Rezonzew, Gabriel Chumley, Phillip Jaimes, Edgar A. TI The transcription factor ETS-1 regulates angiotensin II-stimulated fibronectin production in mesangial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE chronic kidney disease; renin-angiotensin system ID NF-KAPPA-B; RECEPTOR TRANSACTIVATION; EXTRACELLULAR-MATRIX; PROTEIN-SYNTHESIS; POINTED DOMAIN; EXPRESSION; BINDING; GROWTH; GENE; PHOSPHORYLATION AB Hua P, Feng W, Rezonzew G, Chumley P, Jaimes EA. The transcription factor ETS-1 regulates angiotensin II-stimulated fibronectin production in mesangial cells. Am J Physiol Renal Physiol 302: F1418-F1429, 2012. First published February 22, 2012; doi:10.1152/ajprenal.00477.2011.-Angiotensin II (ANG II) produced as result of activation of the renin-angiotensin system (RAS) plays a critical role in the pathogenesis of chronic kidney disease via its hemodynamic effects on the renal microcirculation as well as by its nonhemodynamic actions including the production of extracellular matrix proteins such as fibronectin, a multifunctional extracellular matrix protein that plays a major role in cell adhesion and migration as well as in the development of glomerulosclerosis. ETS-1 is an important transcription factor essential for normal kidney development and glomerular integrity. We previously showed that ANG II increases ETS-1 expression and is required for fibronectin production in mesangial cells. In these studies, we determined that ANG II induces phosphorylation of ETS-1 via activation of the type 1 ANG II receptor and that Erk1/2 and Akt/PKB phosphorylation are required for these effects. In addition, we characterized the role of ETS-1 on the transcriptional activation of fibronectin production in mesangial cells. We determined that ETS-1 directly activates the fibronectin promoter and by utilizing gel shift assays and chromatin immunoprecipitation assays identified two different ETS-1 binding sites that promote the transcriptional activation of fibronectin in response to ANG II. In addition, we identified the essential role of CREB and its coactivator p300 on the transcriptional activation of fibronectin by ETS-1. These studies unveil novel mechanisms involved in RAS-induced production of the extracellular matrix protein fibronectin in mesangial cells and establish the role of the transcription factor ETS-1 as a direct mediator of these effects. C1 [Hua, Ping; Feng, Wenguang; Rezonzew, Gabriel; Chumley, Phillip; Jaimes, Edgar A.] Univ Alabama Birmingham, Div Nephrol, Birmingham, AL 35294 USA. [Jaimes, Edgar A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Jaimes, EA (reprint author), Univ Alabama Birmingham, Div Nephrol, 1530 3rd Ave S,ZRB 637, Birmingham, AL 35294 USA. EM ejaimes@uab.edu FU Veterans Affairs Administration; O'Brien Kidney Center at the University of Alabama at Birmingham FX These studies were funded by a Merit Review Award of the Veterans Affairs Administration (to E. A. Jaimes). We also thank the support of the O'Brien Kidney Center at the University of Alabama at Birmingham. NR 49 TC 12 Z9 12 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUN PY 2012 VL 302 IS 11 BP F1418 EP F1429 DI 10.1152/ajprenal.00477.2011 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 952SN UT WOS:000304812700008 PM 22357921 ER PT J AU Weisbord, SD AF Weisbord, Steven D. TI Female Sexual Dysfunction in ESRD: An Underappreciated Epidemic? SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID QUALITY-OF-LIFE; CHRONIC KIDNEY-DISEASE; HEMODIALYSIS-PATIENTS; ERECTILE DYSFUNCTION; DIALYSIS; WOMEN; PREVALENCE; SYMPTOMS; INDEX; MEN C1 [Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Renal Sect, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Med Specialty Serv Line, 7E Room 120,111F U, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu NR 17 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUN PY 2012 VL 7 IS 6 BP 881 EP 883 DI 10.2215/CJN.03870412 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 954VE UT WOS:000304975100003 PM 22580787 ER PT J AU Kang, EW Pike, F Ramer, S Abdel-Kader, K Myaskovsky, L Dew, MA Unruh, M AF Kang, Ea Wha Pike, Francis Ramer, Sarah Abdel-Kader, Khaled Myaskovsky, Larissa Dew, Mary Anianda Unruh, Mark TI The Association of Mental Health over Time with Cardiac Outcomes in HEMO Study Patients SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID QUALITY-OF-LIFE; STAGE RENAL-DISEASE; HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS; MAINTENANCE HEMODIALYSIS; PRACTICE PATTERNS; UNITED-STATES; MORTALITY; DEPRESSION; SF-36 AB Background and objectives Poor mental health over time is significantly associated with cardiovascular morbidity and mortality in the general population, which is the leading cause of death in dialysis patients. Most studies of dialysis patients, however, have investigated the relationship between baseline mental health measurements and all-cause mortality and not mental health measured longitudinally throughout a study and cause-specific mortality. Design, setting, participants, & measurements This study examined the association of changes in mental health over time with all-cause and cause-specific deaths and cardiac hospitalizations in the Hemodialysis study patients. Mental health was assessed at baseline and annually during the study with short form 36 mental health index scores. Poorer mental health was defined by a mental health index score <= 60. Results Patients with poorer mental health at baseline were more likely to have less than a high school education and be unmarried, have significantly higher index of coexistent disease scores, and report taking beta-blockers and sleep medications. Low mental health scores over time were independently associated with a decrease in survival time from all-cause mortality by -0.06 (-0.10, -0.03; P<0.001), and they also significantly hastened time to first cardiac hospitalization by -0.08 (-0.13, -0.02; P=0.01) and composite of first cardiac hospitalization or cardiac death by -0.04 (-0.07, -0.02; P<0.001). Conclusions This study found an independent association between poor mental health over time and all-cause mortality, cardiac hospitalization, and the composite of cardiac death or cardiac hospitalization in hemodialysis patients. The results underscore the importance of attention to mental health related to cardiac complications and even death in dialysis patients. Clin J Am Soc Nephrol 7: 957-964, 2012. doi: 10.2215/CJN.06730711 C1 [Unruh, Mark] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Med Ctr, Pittsburgh, PA 15213 USA. [Kang, Ea Wha] Natl Hlth Insurance Corp, Dept Med, Ilsan Hosp, Goyangshi, Gyeonggi Do, South Korea. [Myaskovsky, Larissa] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Myaskovsky, Larissa] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Dew, Mary Anianda] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15213 USA. RP Unruh, M (reprint author), Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Med Ctr, 200 Lothrop St,PUH C-1111, Pittsburgh, PA 15213 USA. EM unruh@pitt.edu OI Abdel-Kader, Khaled/0000-0002-6412-8498 FU NIDDK NIH HHS [K23 DK090304] NR 46 TC 8 Z9 9 U1 0 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUN PY 2012 VL 7 IS 6 BP 957 EP 964 DI 10.2215/CJN.06730711 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 954VE UT WOS:000304975100013 PM 22490873 ER PT J AU O'Connor, CM Mentz, RJ Cotter, G Metra, M Cleland, JG Davison, BA Givertz, MM Mansoor, GA Ponikowski, P Teerlink, JR Voors, AA Fiuzat, M Wojdyla, D Chiswell, K Massie, BM AF O'Connor, Christopher M. Mentz, Robert J. Cotter, Gad Metra, Marco Cleland, John G. Davison, Beth A. Givertz, Michael M. Mansoor, George A. Ponikowski, Piotr Teerlink, John R. Voors, Adriaan A. Fiuzat, Mona Wojdyla, Daniel Chiswell, Karen Massie, Barry M. TI The PROTECT in-hospital risk model: 7-day outcome in patients hospitalized with acute heart failure and renal dysfunction SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Heart failure; Risk model; Risk score; Worsening heart failure ID INITIATE LIFESAVING TREATMENT; NATIONAL REGISTRY ADHERE; ORGANIZED PROGRAM; OPTIMIZE-HF; MORTALITY; SURVIVAL; PREDICTORS; IMPACT; SCORE; ASSOCIATION AB In patients with acute heart failure (AHF), early worsening heart failure (WHF) predicts a significant proportion of post-discharge readmissions and mortality. We aimed to identify the predictors of 7-day heart failure events or death in patients hospitalized with AHF. A predictive model and risk score for the short-term primary composite endpoint of 7-day death, HF rehospitalization, or WHF was created using variables collected within 24 h of admission from patients with complete data (n 2015) enrolled in the PROTECT trial of AHF patients. The 7-day composite was experienced by 294 patients (14.6), with a mortality rate of 1.8 (n 37), HF rehospitalization rate of 0.5 (n 9), and WHF rate of 13.1 (n 264). In multivariable analyses, the strongest predictor of short-term morbidity and mortality was higher blood urea nitrogen (BUN) concentration. Additional independent predictors of a worse outcome were lower serum albumin, cholesterol, and systolic blood pressure, as well as higher heart rate and respiratory rate. Model coefficients were converted to an additive risk score for predicting the 7-day composite endpoint with a total point range of 0100. The risk score allowed discrimination of a wide spectrum of risk (4.8 risk with score 35, to 28.7 risk with score 55). Using the PROTECT 7-day risk model and score, the main determinants of an adverse outcome for AHF patients included impaired metabolic status, neurohormonal activation, and reduced cardiac performance, gauged by BUN, serum albumin and cholesterol levels, systolic blood pressure, heart rate, and respiratory rate. C1 [O'Connor, Christopher M.] Duke Univ, Med Ctr, Div Cardiol, Duke Clin Res Inst, Durham, NC 27710 USA. [Cotter, Gad; Davison, Beth A.] Momentum Res Inc, Durham, NC USA. [Metra, Marco] Univ Brescia, Pzza Spedali Civili, Brescia, Italy. [Cleland, John G.] Univ Hull, Kingston Upon Hull, Yorks, England. [Givertz, Michael M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mansoor, George A.] Merck Res Labs, Rahway, NJ USA. [Ponikowski, Piotr] Kardiol Klin, Wroclaw, Poland. [Teerlink, John R.; Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Teerlink, John R.; Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. RP O'Connor, CM (reprint author), Duke Univ, Med Ctr, Div Cardiol, Duke Clin Res Inst, Box 3356, Durham, NC 27710 USA. EM christophe.oconnor@dm.duke.edu RI Ponikowski, Piotr/O-6454-2015 OI Ponikowski, Piotr/0000-0002-3391-7064; Davison, Beth/0000-0003-2374-6449; Cleland, John/0000-0002-1471-7016; Metra, Marco/0000-0001-6691-8568 FU NovaCardia, a subsidiary of Merck; Merck; Abbott; Amgen; Biogen Idec; Corthera; Cytokinetics; Johnson and Johnson; Scios; Novartis; Relypsa; Solvay; NovaCardia FX The PROTECT trial was supported by NovaCardia, a subsidiary of Merck.; C.M.O. is a consultant to Merck which purchased the rights to rolofylline from NovaCardia, sponsors of the PROTECT study, after completion of the PROTECT pilot study. G. C. and B. A. D are employees of Momentum Research Inc., which was contracted to perform work on the project by Merck & Co, Inc. M. M. has received honoraria and reimbursements from NovaCardia and from Merck. J.G.C. was on the Steering Committee for the study, served on the Advisory Board for MSD, and received payments for both. M. M. G. has received institutional research support and served on a scientific Advisory Board for Merck. G. A. M. is an employee of Merck. P. P. has received honoraria from Merck. J.R.T. has received research funds and consulting fees from Merck for the conduct of this study and has also received research funds and consulting fees from Abbott, Amgen, Biogen Idec, Corthera, Cytokinetics, Johnson and Johnson, Scios, Novartis, Relypsa, and Solvay for research in related areas. A. A. V. has received speakers and consultancy fees from Merck. B. M. M. has received consulting fees from NovaCardia and from Merck. The remaining authors report no relevant conflicts of interest. NR 34 TC 44 Z9 44 U1 0 U2 2 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 JUN PY 2012 VL 14 IS 6 BP 605 EP 612 DI 10.1093/eurjhf/hfs029 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 948VH UT WOS:000304530400008 PM 22535795 ER PT J AU Mounzer, R Langmead, CJ Wu, BU Evans, AC Bishehsari, F Muddana, V Singh, VK Slivka, A Whitcomb, DC Yadav, D Banks, PA Papachristou, GI AF Mounzer, Rawad Langmead, Christopher J. Wu, Bechien U. Evans, Anna C. Bishehsari, Faraz Muddana, Venkata Singh, Vikesh K. Slivka, Adam Whitcomb, David C. Yadav, Dhiraj Banks, Peter A. Papachristou, Georgios I. TI Comparison of Existing Clinical Scoring Systems to Predict Persistent Organ Failure in Patients With Acute Pancreatitis SO GASTROENTEROLOGY LA English DT Article DE Marker; Organ Failure; Predictors; Pancreas ID INFLAMMATORY RESPONSE; CLASSIFICATION-SYSTEM; APACHE-II; SEVERITY; MORTALITY; MARKER; DYSFUNCTION; NECROSIS; INDEX; RISK AB BACKGROUND & AIMS: It is important to identify patients with acute pancreatitis who are at risk for developing persistent organ failure early in the course of disease. Several scoring systems have been developed to predict which patients are most likely to develop persistent organ failure. We head-to-head compared the accuracy of these systems in predicting persistent organ failure, developed rules that combined these scores to optimize predictive accuracy, and validated our findings in an independent cohort. METHODS: Clinical data from 2 prospective cohorts were used for training (n = 256) and validation (n = 397). Persistent organ failure was defined as cardiovascular, pulmonary, and/or renal failure that lasted for 48 hours or more. Nine clinical scores were calculated when patients were admitted and 48 hours later. We developed 12 predictive rules that combined these scores, in order of increasing complexity. RESULTS: Existing scoring systems showed modest accuracy (areas under the curve at admission of 0.62-0.84 in the training cohort and 0.57-0.74 in the validation cohort). The Glasgow score was the best classifier at admission in both cohorts. Serum levels of creatinine and blood urea nitrogen provided similar levels of discrimination in each set of patients. Our 12 predictive rules increased accuracy to 0.92 in the training cohort and 0.84 in the validation cohort. CONCLUSIONS: The existing scoring systems seem to have reached their maximal efficacy in predicting persistent organ failure in acute pancreatitis. Sophisticated combinations of predictive rules are more accurate but cumbersome to use, and therefore of limited clinical use. Our ability to predict the severity of acute pancreatitis cannot be expected to improve unless we develop new approaches. C1 [Mounzer, Rawad; Evans, Anna C.; Bishehsari, Faraz; Muddana, Venkata; Slivka, Adam; Whitcomb, David C.; Yadav, Dhiraj; Papachristou, Georgios I.] Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. [Langmead, Christopher J.] Carnegie Mellon Univ, Dept Comp Sci, Pittsburgh, PA 15213 USA. [Wu, Bechien U.; Singh, Vikesh K.; Banks, Peter A.] Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA. [Papachristou, Georgios I.] Vet Affairs Pittsburgh Hlth Syst, Div Gastroenterol & Hepatol, Pittsburgh, PA USA. RP Papachristou, GI (reprint author), Presbyterian Univ Hosp, Div Gastroenterol Hepatol & Nutr, M2,C Wing,200 Lothrop St, Pittsburgh, PA 15213 USA. EM papachri@pitt.edu FU Doris Duke Clinical Research Fellowship FX Anna Evans was supported by a Doris Duke Clinical Research Fellowship. NR 40 TC 83 Z9 91 U1 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2012 VL 142 IS 7 BP 1476 EP 1482 DI 10.1053/j.gastro.2012.03.005 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 952GF UT WOS:000304778700026 PM 22425589 ER PT J AU Lieberman, D AF Lieberman, David TI Presentation of the Julius M. Friedenwald Medal to Emmet B. Keeffe, MD SO GASTROENTEROLOGY LA English DT Biographical-Item C1 [Lieberman, David] Oregon Hlth & Sci Univ, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. [Lieberman, David] Portland VA Med Ctr, Portland, OR USA. RP Lieberman, D (reprint author), Oregon Hlth & Sci Univ, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2012 VL 142 IS 7 BP 1610 EP 1612 DI 10.1053/j.gastro.2012.04.041 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 952GF UT WOS:000304778700038 PM 22542834 ER PT J AU Bernhardt, BA Zayac, C Trerotola, SO Asch, DA Pyeritz, RE AF Bernhardt, Barbara A. Zayac, Cara Trerotola, Scott O. Asch, David A. Pyeritz, Reed E. TI Cost savings through molecular diagnosis for hereditary hemorrhagic telangiectasia SO GENETICS IN MEDICINE LA English DT Article DE cost-effectiveness; economic analysis; genetic screening; genetic testing; hereditary hemorrhagic telangiectasia ID PULMONARY ARTERIOVENOUS-MALFORMATIONS; COLORECTAL-CANCER; LYNCH SYNDROME; HEALTH-CARE; STRATEGIES; MUTATIONS; MEDICINE; OUTCOMES; IMPACT; TESTS AB Purpose: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder of vascular development resulting in direct connections between the arterial and venous systems, bypassing capillaries. Symptoms and signs can appear throughout life and marked intrafamilial variability confounds diagnosis based purely on clinical criteria. We set out to determine the impact of genetic testing on the cost of screening for HHT in at-risk relatives. Methods: We performed economic modeling of idealized pedigrees following two scenarios: repeated clinical screening until an HHT diagnosis could be either affirmed or excluded, and mutation testing in the proband, followed by genetic testing of at-risk relatives and clinical monitoring of only those relatives who test positive for the familial mutation. Results: Based on actual reimbursement data from our region's largest health insurer, the molecular diagnostic model saved over $22,000 for a family with four relatives at risk for the initial diagnostic work-up. For a cohort of 100 probands, the total savings for the molecular diagnostic model over a reasonable period of follow-up was greater than $9 million. Conclusion: In this idealized setting in which all probands and at-risk relatives accepted molecular testing, the economic advantages of genetic screening over repeated clinical screening are substantial. C1 [Bernhardt, Barbara A.; Zayac, Cara; Pyeritz, Reed E.] Univ Penn, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA. [Bernhardt, Barbara A.; Zayac, Cara; Asch, David A.; Pyeritz, Reed E.] Univ Penn, Raymond & Ruth Perelman Sch Med, Ctr Integrat Genet Healthcare Technol, Philadelphia, PA 19104 USA. [Bernhardt, Barbara A.; Asch, David A.; Pyeritz, Reed E.] Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. [Trerotola, Scott O.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Asch, David A.; Pyeritz, Reed E.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Pyeritz, Reed E.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Pyeritz, Reed E.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. RP Pyeritz, RE (reprint author), Univ Penn, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA. EM reed.pyeritz@uphs.upenn.edu OI Asch, David/0000-0002-7970-286X FU National Human Genome Research Institute [P50HG004487] FX We thank Joseph Monkoski for helpful information. This work was supported by National Human Genome Research Institute grant P50HG004487. The preparation of this manuscript occurred while R. E. P. was in residence at the Brocher Foundation, Hermance, Switzerland. NR 34 TC 5 Z9 5 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD JUN PY 2012 VL 14 IS 6 BP 604 EP 610 DI 10.1038/gim.2011.56 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 955GL UT WOS:000305005000005 PM 22281938 ER PT J AU Bates, ML Fulmer, BR Farrell, ET Drezdon, A Pegelow, DF Conhaim, RL Eldridge, MW AF Bates, Melissa L. Fulmer, Brendan R. Farrell, Emily T. Drezdon, Alyssa Pegelow, David F. Conhaim, Robert L. Eldridge, Marlowe W. TI Hypoxia recruits intrapulmonary arteriovenous pathways in intact rats but not isolated rat lungs SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE arteriovenous anastamoses; hypoxia; intrapulmonary shunts; lung; microspheres ID PULMONARY GAS-EXCHANGE; HEALTHY HUMANS; VASCULAR PRESSURES; BLOOD VOLUME; EXERCISE; EPINEPHRINE; STROKE; TRANSPULMONARY; DISTENSIBILITY; PERFUSION AB Bates ML, Fulmer BR, Farrell ET, Drezdon A, Pegelow DF, Conhaim RL, Eldridge MW. Hypoxia recruits intrapulmonary arteriovenous pathways in intact rats but not isolated rat lungs. J Appl Physiol 112: 1915-1920, 2012. First published March 15, 2012; doi:10.1152/japplphysiol.00985.2011.-Intrapulmonary arteriovenous anastomoses (IPAVS) directly connect the arterial and venous circulations in the lung, bypassing the capillary network. Here, we used solid, latex microspheres and isolated rat lung and intact, spontaneously breathing rat models to test the hypothesis that IPAVS are recruited by alveolar hypoxia. We found that hypoxia recruits IPAVS in the intact rat, but not the isolated lung. IPAVS are at least 70 mu m in the rat and, interestingly, appear to be recruited when the mixed venous PO2 falls below 22 mmHg. These data provide evidence that large-diameter, direct arteriovenous connections exist in the lung and are recruitable by hypoxia in the intact animal. C1 [Bates, Melissa L.] Univ Wisconsin, Clin Sci Ctr H6 551, Sch Med & Publ Hlth, Dept Pediat, Madison, WI 53792 USA. [Bates, Melissa L.; Fulmer, Brendan R.; Farrell, Emily T.; Drezdon, Alyssa; Pegelow, David F.; Eldridge, Marlowe W.] Univ Wisconsin, Sch Med & Publ Hlth, John Rankin Lab Pulm Med, Madison, WI 53792 USA. [Eldridge, Marlowe W.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biomed Engn, Madison, WI 53792 USA. [Eldridge, Marlowe W.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Kinesiol, Madison, WI 53792 USA. [Conhaim, Robert L.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI 53792 USA. [Conhaim, Robert L.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Bates, ML (reprint author), Univ Wisconsin, Clin Sci Ctr H6 551, Sch Med & Publ Hlth, Dept Pediat, 600 Highland Ave, Madison, WI 53792 USA. EM mlbates@pediatrics.wisc.edu FU National Institutes of Health [5R01-HL-086897, 5T32-HL-007654]; American Heart Association FX This work was supported by grants from the National Institutes of Health (5R01-HL-086897 and 5T32-HL-007654) and a postdoctoral fellowship from the American Heart Association. NR 32 TC 16 Z9 16 U1 0 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUN PY 2012 VL 112 IS 11 BP 1915 EP 1920 DI 10.1152/japplphysiol.00985.2011 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 952RS UT WOS:000304810500014 PM 22422800 ER PT J AU Bent, S Bertoglio, K Ashwood, P Nemeth, E Hendren, RL AF Bent, Stephen Bertoglio, Kiah Ashwood, Paul Nemeth, Edward Hendren, Robert L. TI Brief Report: Hyperbaric Oxygen Therapy (HBOT) in Children with Autism Spectrum Disorder: A Clinical Trial SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Clinical trial; Alternative therapy ID OXIDATIVE STRESS; MULTICENTER; BRAIN AB We sought to determine whether HBOT leads to parental reported behavioral changes and alterations in cytokines in children with ASD. Ten children completed 80 sessions of HBOT and all improved by 2 points on the clinician-rated CGI-I scale (much improved) as well as several parent-completed measures of behavior. The lack of a control group limits the ability to determine if improvements were related to HBOT. Enrolled children did not exhibit abnormal cytokine levels at baseline and no significant changes in mean cytokine levels were observed. Although this study was limited by the small sample size and by the variable nature of cytokines, we found no evidence that HBOT affects cytokine levels or that cytokine levels were associated with behavioral changes. C1 [Bent, Stephen] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Bent, Stephen; Hendren, Robert L.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Bent, Stephen] Univ Calif San Francisco, Dept Med, Osher Ctr Integrat Med, San Francisco, CA USA. [Bent, Stephen] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Bertoglio, Kiah] Univ Calif Irvine, Sch Med, Irvine, CA 92717 USA. [Ashwood, Paul] Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. [Nemeth, Edward] CHERISH Fdn, Sacramento, CA USA. RP Bent, S (reprint author), San Francisco VA Med Ctr, 111-A1,4150 Clement St, San Francisco, CA 94121 USA. EM Stephen.Bent@ucsf.edu FU Autism Speaks [AS2311]; NCRR NIH HHS [UL1 RR024131] NR 17 TC 9 Z9 11 U1 1 U2 13 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD JUN PY 2012 VL 42 IS 6 BP 1127 EP 1132 DI 10.1007/s10803-011-1337-3 PG 6 WC Psychology, Developmental SC Psychology GA 949YA UT WOS:000304613000025 PM 21818676 ER PT J AU Goodlin, SJ AF Goodlin, Sarah J. TI Hospice Care Following Heart Failure Admission: What Next? SO JOURNAL OF CARDIAC FAILURE LA English DT Editorial Material ID PALLIATIVE CARE; COMMUNICATION C1 [Goodlin, Sarah J.] Portland VA Med Ctr, Portland, OR USA. [Goodlin, Sarah J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Goodlin, Sarah J.] Patient Ctr Educ & Res, Salt Lake City, UT USA. RP Goodlin, SJ (reprint author), P3 Med Portland VAMC, POB 1034, Portland, OR 97207 USA. EM sgoodlin@patient-centered.org NR 13 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD JUN PY 2012 VL 18 IS 6 BP 478 EP 479 DI 10.1016/j.cardfail.2012.03.004 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 957MF UT WOS:000305166400006 PM 22633305 ER PT J AU Yamaleyeva, LM Lindsey, SH Varagic, J Zhang, LL Gallagher, PE Chen, AF Chappell, MC AF Yamaleyeva, Liliya M. Lindsey, Sarah H. Varagic, Jasmina Zhang, Li Li Gallagher, Patricia E. Chen, Alex F. Chappell, Mark C. TI Amelioration of Renal Injury and Oxidative Stress by the nNOS Inhibitor L-VNIO in the Salt-sensitive mRen2. Lewis Congenic Rat SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE albuminuria; renal inflammation; renal cortex; tetrahy-drobiopterin; 8-hydroxy-deoxyguanosine ID NITRIC-OXIDE SYNTHASE; BLOOD-PRESSURE; SEX-DIFFERENCES; ANGIOTENSIN-II; HYPERTENSION; KIDNEY; EXPRESSION; MECHANISM; DYSFUNCTION; ESTROGEN AB Salt sensitivity is a key risk factor for cardiovascular disease and renal injury. Alterations in renal nitric oxide may contribute to salt-dependent increases in blood pressure and tissue damage. Therefore, we assessed the expression of nitric oxide synthase (NOS) isoforms in the kidney and the effects of nNOS inhibition on renal injury, inflammation, and oxidative stress in the female mRen2.Lewis rat (mRen), a model of salt-sensitive hypertension. We find that a high-salt diet (4% sodium) significantly reduced endothelial NOS mRNA (2.6-fold) and protein (1.5-fold) but increased nNOS mRNA (2.4-fold) and protein (1.9-fold) in the renal cortex of these animals. Immunostaining for nNOS also seemed higher in macula densa and cortical tubules of the rats fed a high-salt diet. Circulating nitrate and nitrite levels were reduced, including the tissue levels of the NOS cofactor tetrahydrobiopterin. Cortical markers of oxidative stress (4HNE, 8-OH-deoxyguanosine) and fibrosis were increased; however, mRNA levels of the NAD(P) H oxidase components NOX4, p22phox, and p47phox were reduced. Chronic treatment with the nNOS inhibitor N-5-(1-Imino-3-butenyl)-L-ornithine did not influence systolic blood pressure after 4 weeks but significantly attenuated albuminuria, renal fibrosis, inflammation, and indices of oxidative stress. We conclude that an increase in nNOS expression in conjunction with reduced levels of cortical tetrahydrobiopterin may stimulate oxidative stress and renal injury in the salt-sensitive female mRen2.Lewis rat. C1 [Yamaleyeva, Liliya M.; Lindsey, Sarah H.; Varagic, Jasmina; Gallagher, Patricia E.; Chappell, Mark C.] Wake Forest Univ, Bowman Gray Sch Med, Hypertens & Vasc Res Ctr, Winston Salem, NC USA. [Zhang, Li Li; Chen, Alex F.] Univ Pittsburgh, Sch Med, Dept Surg, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Yamaleyeva, LM (reprint author), Wake Forest Sch Med, Hypertens & Vasc Res Ctr, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM lyamaley@wake-health.edu FU National Heart Lung and Blood Institute, NIH [HL-56973, HL-51952]; NIH [HL-103974]; American Heart Association Mid-Atlantic Affiliate [AHA-151521, AHA-2300114, AHA-525586U]; National Institute of General Medical Science, NIH [R01GM077352]; American Diabetes Association [7-08-RA-23] FX Supported by grants from the National Heart Lung and Blood Institute, NIH, to M.C. Chappell (HL-56973, HL-51952); NIH to S.H. Lindsey (HL-103974); the American Heart Association Mid-Atlantic Affiliate to M.C. Chappell (AHA-151521), J. Varagic (AHA-2300114), and to L.M. Yamaleyeva (AHA-525586U); the National Institute of General Medical Science, NIH (R01GM077352), and the American Diabetes Association (7-08-RA-23) to A.F. Chen. NR 39 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD JUN PY 2012 VL 59 IS 6 BP 529 EP 538 DI 10.1097/FJC.0b013e31824dd15b PG 10 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 956IF UT WOS:000305082600006 PM 22370956 ER PT J AU Fujimoto, WY Boyko, EJ Hayashi, T Kahn, SE Leonetti, DL McNeely, MJ Shuman, WP AF Fujimoto, Wilfred Y. Boyko, Edward J. Hayashi, Tomoshige Kahn, Steven E. Leonetti, Donna L. McNeely, Marguerite J. Shuman, William P. TI Risk factors for type 2 diabetes: Lessons learned from Japanese Americans in Seattle SO JOURNAL OF DIABETES INVESTIGATION LA English DT Review DE Japanese Americans; Lifestyle; Obesity ID IMPAIRED GLUCOSE-TOLERANCE; BETA-CELL FUNCTION; CORONARY-HEART-DISEASE; BODY-FAT DISTRIBUTION; FASTING PLASMA-GLUCOSE; EARLY INSULIN-RESPONSE; 5-YEAR FOLLOW-UP; VISCERAL ADIPOSITY; ORAL GLUCOSE; COMPUTED-TOMOGRAPHY AB Migrant Japanese populations in both the USA and Brazil have for a long time shown a higher prevalence of type 2 diabetes than native Japanese, suggesting an interaction of lifestyle and genetic predisposition in the etiology of type 2 diabetes. The overall objective of the Seattle Japanese American Community Diabetes Study was to learn more about the etiology and pathogenesis of type 2 diabetes in Japanese Americans. This metabolically based epidemiological study included extensive assessments of insulin sensitivity, insulin response, and adiposity with the latter including measurements of body fat distribution by both anthropometry and computed tomography. Because of this, the importance of visceral adiposity as a risk factor for abnormal glucose tolerance, hypertension, coronary heart disease and the metabolic syndrome was shown. In conjunction with an examination of diet and physical activity patterns, the result was a clearer understanding of the etiology and pathogenesis of type 2 diabetes in Japanese Americans. We propose that a lifestyle that fosters increased weight gain, especially in the visceral adipose depot, promotes the development of insulin resistance, which in turn exposes an underlying reduced beta-cell reserve in susceptible individuals, resulting in glucose intolerance and, eventually in many, the development of diabetes. We have shown that it might be possible to delay or prevent the development of diabetes through dietary and exercise interventions in individuals identified as having impaired glucose tolerance. The lessons learned from studying migrant Japanese in Seattle might in many ways be applicable to other populations of Asian origin. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00195.x, 2012) C1 [Fujimoto, Wilfred Y.; Boyko, Edward J.; Kahn, Steven E.; McNeely, Marguerite J.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Leonetti, Donna L.] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. [Shuman, William P.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Boyko, Edward J.; Hayashi, Tomoshige] Epidemiol Res & Informat Ctr, Seattle, WA USA. [Boyko, Edward J.; Kahn, Steven E.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Hayashi, Tomoshige] Osaka City Univ, Dept Prevent Med & Environm Hlth, Grad Sch Med, Osaka 558, Japan. RP Fujimoto, WY (reprint author), Univ Washington, Dept Med, Seattle, WA 98195 USA. EM wilfuji@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002; Boyko, Edward/0000-0002-3695-192X FU Kroc Foundation; American Diabetes Association; National Institutes of Health [DK-02654, DK-02860, DK-31170, DK-48152, DK-50703, DK-55460, HL-07028, HL-49293]; United States Department of Veterans Affairs; Japan Society for the Promotion of Science; Uehara Memorial Foundation; Nakatomi Foundation; Japanese Ministry of Education, Science, Sports, and Culture FX This work was supported by grants from the Kroc Foundation and American Diabetes Association; National Institutes of Health Grants DK-02654, DK-02860, DK-31170, DK-48152, DK-50703, DK-55460, HL-07028 and HL-49293; and facilities and services provided by the Diabetes and Endocrinology Research Center (DK-17047), Clinical Nutrition Research Unit (DK-35816), and the General Clinical Research Center (RR-00037) at the University of Washington. EJB and SEK were also supported by the United States Department of Veterans Affairs. WYF was also supported by a grant from the Japan Society for the Promotion of Science as a Visiting Researcher at the University of Tokyo, and gratefully acknowledges the support and assistance provided by Dr Kinori Kosaka, Dr Yasuo Akanuma and Dr Yasunori Kanazawa at the University of Tokyo and Dr Nobusada Kuzuya at the Asahi Institute in Tokyo. TH was supported by grants from the Uehara Memorial Foundation, the Nakatomi Foundation, and the Japanese Ministry of Education, Science, Sports, and Culture as a Visiting Scholar at the University of Washington. All of the authors have contributed significantly to the collection and analysis of data, have reviewed and edited the manuscript, and have agreed to its content and submission for publication, and none have any financial relationships or support that might pose a conflict of interest. We thank the many skilled staff members at the University of Washington, especially Pamela Asberry, Jane Shofer, Christine Tsunehara, Pamela Yang and the staff of the General Clinical Research Center for their assistance, and also acknowledge the collaboration of many colleagues whose contributions are documented by their co-authorship of the many papers that have resulted from this research. Last but not least, we are particularly grateful for the unswerving support and cooperation of the King County Japanese American community and our Community Advisory Board, without which we would not have been able to carry out this study. NR 91 TC 18 Z9 18 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2040-1116 J9 J DIABETES INVEST JI J. Diabetes Investig. PD JUN PY 2012 VL 3 IS 3 BP 212 EP 224 DI 10.1111/j.2040-1124.2012.00195.x PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 953KG UT WOS:000304865500003 PM 22798980 ER PT J AU Carnes, M Devine, PG Isaac, C Manwell, LB Ford, CE Byars-Winston, A Fine, E Sheridan, J AF Carnes, Molly Devine, Patricia G. Isaac, Carol Manwell, Linda Baier Ford, Cecelia E. Byars-Winston, Angela Fine, Eve Sheridan, Jennifer TI Promoting Institutional Change Through Bias Literacy SO JOURNAL OF DIVERSITY IN HIGHER EDUCATION LA English DT Article DE gender bias; faculty; STEM; intervention studies; prejudice; academic medical centers ID SELF-REGULATION; TRANSTHEORETICAL MODEL; PREJUDICE-REDUCTION; INTERGROUP CONTACT; PERSPECTIVE-TAKING; QUEEN BEE; WOMEN; DISCRIMINATION; STEREOTYPES; COMMITMENT AB The National Science Foundation and others conclude that institutional transformation is required to ensure equal opportunities for the participation and advancement of men and women in academic science, technology, engineering, mathematics, and medicine (STEMM). Such transformation requires changing the habitual attitudes and behaviors of faculty. Approaching implicit bias as a remediable habit, we present the theoretical basis and conceptual model underpinning an educational intervention to promote bias literacy among university faculty as a step toward institutional transformation regarding gender equity. We describe the development and implementation of a Bias Literacy Workshop in detail so others can replicate or adapt it to their setting. Of the 220 (167 faculty and 53 nonfaculty) attendees from the initial 17 departments/divisions offered this workshop, all 180 who completed a written evaluation found the workshop at least "somewhat useful" and 74% found it "very useful." Over 68% indicated increased knowledge of the workshop material. Of the 186 participants who wrote a commitment to engage in new activities to promote gender equity, 87% incorporated specific workshop content. Twenty-four participants were interviewed 4-6 months after attending the workshop; 75% of these not only demonstrated increased bias awareness, but described plans to change-or had actually changed-behaviors because of the workshop. Based on our sample of faculty from a Midwestern university, we conclude that at least one third of STEMM faculty who are invited will attend a 2.5-hr Bias Literacy Workshop, that nearly all will find it useful, and that most will complete a written commitment to promoting gender equity. These findings suggest that this educational intervention May effectively promote institutional change regarding gender equity. C1 [Carnes, Molly; Isaac, Carol; Manwell, Linda Baier; Byars-Winston, Angela] Univ Wisconsin, Ctr Womens Hlth Res, Madison, WI 53715 USA. [Byars-Winston, Angela] Univ Wisconsin, Dept Med, Div Gen Internal Med, Madison, WI 53715 USA. [Carnes, Molly] Univ Wisconsin, Dept Psychiat, Madison, WI 53715 USA. [Carnes, Molly] Univ Wisconsin, Dept Ind & Syst Engn, Madison, WI 53715 USA. [Carnes, Molly; Manwell, Linda Baier; Fine, Eve; Sheridan, Jennifer] Univ Wisconsin, WISELI, Madison, WI 53715 USA. [Carnes, Molly] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Devine, Patricia G.] Univ Wisconsin, Dept Psychol, Madison, WI 53715 USA. [Ford, Cecelia E.] Univ Wisconsin, Dept English, Madison, WI 53715 USA. RP Carnes, M (reprint author), Univ Wisconsin, Ctr Womens Hlth Res, 700 Regent St,Suite 301, Madison, WI 53715 USA. EM mlcarnes@wisc.edu FU NIGMS NIH HHS [R01 GM088477] NR 76 TC 21 Z9 21 U1 5 U2 38 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1938-8926 J9 J DIVERS HIGH EDUC JI J. Divers. High. Educ. PD JUN PY 2012 VL 5 IS 2 BP 63 EP 77 DI 10.1037/a0028128 PG 15 WC Education & Educational Research; Psychology, Educational; Psychology, Social SC Education & Educational Research; Psychology GA 950ZM UT WOS:000304690400001 PM 22822416 ER PT J AU Masri, KR Shaver, TS Shahouri, SH Wang, S Anderson, JD Busch, RE Michaud, K Mikuls, TR Caplan, L Wolfe, F AF Masri, Karim R. Shaver, Timothy S. Shahouri, Shadi H. Wang, Shirley Anderson, James D. Busch, Ruth E. Michaud, Kaleb Mikuls, Ted R. Caplan, Liron Wolfe, Frederick TI Validity and Reliability Problems with Patient Global as a Component of the ACR/EULAR Remission Criteria as Used in Clinical Practice SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE RHEUMATOID ARTHRITIS; REMISSION; RELIABILITY ID ARTHRITIS DISEASE-ACTIVITY; HEALTH-ASSESSMENT QUESTIONNAIRE; RHEUMATOID-ARTHRITIS; AMERICAN-COLLEGE; ACTIVITY INDEX; IMPORTANT DIFFERENCE; OSTEOARTHRITIS; FIBROMYALGIA; DETERMINANTS; FATIGUE AB Objective. To investigate what factors influence patient global health assessment (PtGlobal), and how those factors and the reliability of PtGlobal affect the rate, reliability, and validity of recently published American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) rheumatoid arthritis (RA) remission criteria when used in clinical practice. Methods. We examined consecutive patients with RA in clinical practice and identified 77 who met ACR/EULAR joint criteria for remission (<= 1 swollen joint and <= 1 tender joint). We evaluated factors associated with a PtGlobal > 1, because a PtGlobal <= 1 defined ACR/EULAR remission in this group of patients who had already met ACR/EULAR joint criteria. Results. Of the 77 patients examined, only 17 (22.1%) had PtGlobal <= 1 and thus fully satisfied ACR/EULAR criteria. A large proportion of patients not in remission by ACR/EULAR criteria had high PtGlobal related to noninflammatory issues, including low back pain, fatigue, and functional limitations, and a number of patients clustered in the range of PtGlobal > 1 and <= 2. However, the minimal detectable difference for PtGlobal was 2.3. In addition, compared with a PtGlobal severity score, a PtGlobal activity score was 3.3% less likely to be abnormal (> 1). Conclusion. Noninflammatory factors contribute to the level of PtGlobal and result in the exclusion of many patients who would otherwise be in "true" remission according to the ACR/EULAR definition. Reliability problems associated with PtGlobal can also result in misclassification, and may explain the observation of low longterm remission rates in RA. As currently constituted, the use of the ACR/EULAR remission criteria in clinical practice appears to be problematic. (First Release May 15 2012; J Rheumatol 2012;39:1139-45; doi:10.3899/jrheum.111543) C1 [Wolfe, Frederick] Univ Kansas, Natl Data Bank Rheumat Dis, Sch Med, Wichita, KS 67214 USA. [Shaver, Timothy S.; Shahouri, Shadi H.; Wang, Shirley; Anderson, James D.] Univ Kansas, Arthrit & Rheumatol Clin Kansas, Sch Med, Wichita, KS 67214 USA. [Busch, Ruth E.] Wichita State Univ, Arthrit & Rheumatol Clin Kansas, Wichita, KS 67260 USA. [Michaud, Kaleb] Univ Nebraska Med Ctr, Natl Data Bank Rheumat Dis, Omaha, NE USA. [Mikuls, Ted R.] Omaha VA Med Ctr, Omaha, NE USA. [Mikuls, Ted R.] Univ Nebraska, Omaha, NE 68182 USA. [Caplan, Liron] Denver VA Med Ctr, Denver, CO USA. [Caplan, Liron] Univ Colorado, Denver, CO 80202 USA. US Natl Data Bank Rheumat Dis, Wichita, KS USA. RP Wolfe, F (reprint author), Univ Kansas, Natl Data Bank Rheumat Dis, Sch Med, 1035 N Emporia,Suite 288, Wichita, KS 67214 USA. EM fwolfe@arthritis-research.org FU VA HSRD CDA [07-221] FX Dr. Caplan is supported by VA HSR&D CDA 07-221. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the US Department of Veterans Affairs or the US government. NR 33 TC 28 Z9 28 U1 0 U2 4 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUN PY 2012 VL 39 IS 6 BP 1139 EP 1145 DI 10.3899/jrheum.111543 PG 7 WC Rheumatology SC Rheumatology GA 953SP UT WOS:000304893800008 PM 22589262 ER PT J AU Yeh, CK Harris, SE Mohan, S Horn, D Fajardo, R Chun, YHP Jorgensen, J MacDougall, M Abboud-Werner, S AF Yeh, Chih-Ko Harris, Stephen E. Mohan, Sumathy Horn, Diane Fajardo, Roberto Chun, Yong-Hee Patricia Jorgensen, James MacDougall, Mary Abboud-Werner, Sherry TI Hyperglycemia and xerostomia are key determinants of tooth decay in type 1 diabetic mice SO LABORATORY INVESTIGATION LA English DT Article DE diabetes; enamel; hyperglycemia; pulpitis; saliva ID RAT PAROTID-GLAND; SALIVARY-GLAND; SECRETORY AMELOBLASTS; PROTEIN EXPRESSION; DENTINAL TUBULES; ORAL-HEALTH; MOUSE MODEL; IN-VITRO; STREPTOZOTOCIN; MELLITUS AB Insulin-dependent type 1 diabetes mellitus (DM) and oral diseases are closely interrelated. Poor metabolic control in diabetics is associated with a high risk of gingivitis, periodontitis and tooth loss. Salivary flow declines in diabetics and patients suffer from xerostomia. Reduced saliva predisposes to enamel hypomineralization and caries formation; however, the mechanisms that initiate and lead to progression of tooth decay and periodontitis in type 1 DM have not been explored. To address this issue, we analyzed tooth morphology in Akita -/- mice that harbor a point mutation in the Ins2 insulin gene, which leads to progressive hyperglycemia. Mandibles from Akita -/- and wild-type littermates were analyzed by microCT, scanning EM and histology; teeth were examined for amelogenin (Amel) and ameloblastin (Ambn) expression. Mice were injected with pilocarpine to assess saliva production. As hyperglycemia may alter pulp repair, the effect of high glucose levels on the proliferation/differentiation of cultured MD10-F2 pulp cells was also analyzed. Results showed that Akita -/- mice at 6 weeks of age showed chalky white incisors that correlated with marked hyperglycemia and impaired saliva production. MicroCT of Akita -/- teeth revealed excessive enamel wearing and hypomineralization; immunostaining for Amel and Ambn was decreased. A striking feature was invasion of dentinal tubules with Streptococcus mitis and microabcesses that originated in the coronal pulp and progressed to pulp necrosis and periapical periodontitis. High levels of glucose also inhibited MD10-F2 cell proliferation and differentiation. Our findings provide the first evidence that hyperglycemia in combination with reduced saliva in a model of type1 DM leads to decreased enamel mineralization/matrix proteins and predisposes to excessive wearing and decay. Importantly, hyperglycemia adversely affects enamel matrix proteins and pulp repair. Early detection and treatment of hyperglycemia and hyposalivation may provide a useful strategy for preventing the dental complications of diabetes and promoting oral health in this population. Laboratory Investigation (2012) 92, 868-882; doi:10.1038/labinvest.2012.60; published online 26 March 2012 C1 [Yeh, Chih-Ko] Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, San Antonio, TX 78229 USA. [Yeh, Chih-Ko; Abboud-Werner, Sherry] S Texas Vet Healthcare Syst, Geriatr Res Educ & Clin Ctr GRECC & Pathol, San Antonio, TX 78229 USA. [Harris, Stephen E.; Chun, Yong-Hee Patricia] Univ Texas Hlth Sci Ctr San Antonio, Dept Periodont, San Antonio, TX 78229 USA. [Mohan, Sumathy; Horn, Diane; Jorgensen, James; Abboud-Werner, Sherry] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Fajardo, Roberto] Univ Texas Hlth Sci Ctr San Antonio, Dept Orthoped, San Antonio, TX 78229 USA. [MacDougall, Mary] Univ Alabama Birmingham, Inst Oral Hlth Res, Birmingham, AL USA. RP Abboud-Werner, S (reprint author), S Texas Vet Healthcare Syst, GRECC, Dept Pathol, San Antonio, TX 78229 USA. EM abboudwerner@uthscsa.edu FU National Institutes of Health, NIDCR [DE015857, DE0211084] FX We thank the micro-CT Core Facility at UTHSCSA for their assistance in analyzing dental tissues and Drs Alan Lin and Yi Zhou (Comprehensive Dentistry, UTHSCSA) for assisting with saliva/salivary gland collection. We also thank Chris Edwards and the Microscopy and Image-analysis Laboratory at the University of Michigan School of Medicine for scanning electron microscopic studies. This work has been supported, in part, by funding from the National Institutes of Health, NIDCR (DE015857, SAW) and (DE0211084, C-KY). NR 59 TC 12 Z9 13 U1 1 U2 12 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 JUN PY 2012 VL 92 IS 6 BP 868 EP 882 DI 10.1038/labinvest.2012.60 PG 15 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 951OT UT WOS:000304730600006 PM 22449801 ER PT J AU McLay, RN Graap, K Spira, J Perlman, K Johnston, S Rothbaum, BO Difede, J Deal, W Oliver, D Baird, A Bordnick, PS Spitalnick, J Pyne, JM Rizzo, A AF McLay, Robert N. Graap, Kenneth Spira, James Perlman, Karen Johnston, Scott Rothbaum, Barbara O. Difede, JoAnn Deal, William Oliver, David Baird, Alicia Bordnick, Patrick S. Spitalnick, Josh Pyne, Jeffrey M. Rizzo, Albert TI Development and Testing of Virtual Reality Exposure Therapy for Post-Traumatic Stress Disorder in Active Duty Service Members Who Served in Iraq and Afghanistan SO MILITARY MEDICINE LA English DT Article ID PSYCHOMETRIC PROPERTIES; ANXIETY DISORDERS; PTSD; TRIAL; FEAR; METAANALYSIS; VALIDATION; CLINICIAN; SYMPTOMS AB This study was an open-label, single-group, treatment-development project aimed at developing and testing a method for applying virtual reality exposure therapy (VRET) to active duty service members diagnosed with combat post-traumatic stress disorder (PTSD). Forty-two service members with PTSD were enrolled, and 20 participants completed treatment. The PTSD Checklist-Military version, Patient Health Questionnaire-9 for depression, and the Beck Anxiety Inventory were used as outcome measures. Of those who completed post-treatment assessment, 75% had experienced at least a 50% reduction in PTSD symptoms and no longer met DSM-IV criteria for PTSD at post treatment. Average PSTD scores decreased by 50.4%, depression scores by 46.6%, and anxiety scores by 36%. Intention-to-treat analyses showed that statistically significant improvements in PTSD, depression, and anxiety occurred over the course of treatment and were maintained at follow up. There were no adverse events associated with VRET treatment. This study provides preliminary support for the use of VRET in combat-related PTSD. Further study will be needed to determine the wider utility of the method and to determine if it offers advantages over other established PTSD treatment modalities. C1 [McLay, Robert N.; Deal, William; Oliver, David; Baird, Alicia] USN, San Diego Med Ctr, San Diego, CA 92134 USA. [Graap, Kenneth] CNS Response Inc, Aliso Viejo, CA 92656 USA. [Spira, James] US Dept Vet Affairs, Natl Ctr PTSD, Pacific Isl Div Vet Hlth Adm, Honolulu, HI 96819 USA. [Johnston, Scott] USN, Ctr Combat & Operat Stress Control, San Diego, CA 92134 USA. [Rothbaum, Barbara O.] Emory Univ, Trauma & Anxiety Recovery Program, Dept Psychiat, Sch Med, Atlanta, GA 30306 USA. [Difede, JoAnn] Weill Cornell Med Coll, Dept Psychiat, New York, NY 10021 USA. [Bordnick, Patrick S.] Univ Houston, Grad Coll Social Work, Child & Family Ctr Innovat Res, Houston, TX 77204 USA. [Spitalnick, Josh] Virtually Better Corp, Decatur, GA USA. [Pyne, Jeffrey M.] Centra, Arkansas Vet Healthcare Syst, Ctr Mental Hlth Outcomes Res, Little Rock, AR 72205 USA. [Rizzo, Albert] Univ So Calif, Inst Creat Technol, Marina Del Rey, CA 90292 USA. RP McLay, RN (reprint author), USN, San Diego Med Ctr, 34800 Bob Wilson Dr, San Diego, CA 92134 USA. FU Office of Naval Research [DOD-N0384] FX This study was funded by a grant from the Office of Naval Research, grant number DOD-N0384. NR 29 TC 12 Z9 13 U1 12 U2 37 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD JUN PY 2012 VL 177 IS 6 BP 635 EP 642 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 955QP UT WOS:000305036300004 PM 22730837 ER PT J AU Leung, FW AF Leung, Felix W. TI COLONOSCOPY Reducing faecal incontinence following colonoscopy SO NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY LA English DT Editorial Material AB Faecal incontinence can occur in patients who have undergone a colonoscopy. The incidence of postexamination faecal incontinence in a large Norwegian cohort has now been reported, and the risk of faecal incontinence found to be reduced if CO2 is used instead of air to insufflate the colon. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Gastroenterol Sect, Sepulveda Ambulatory Care Ctr, N Hill, CA 91343 USA. RP Leung, FW (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Gastroenterol Sect, Sepulveda Ambulatory Care Ctr, 111G,16111 Plummer St, N Hill, CA 91343 USA. EM felix.leung@va.gov NR 10 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5045 J9 NAT REV GASTRO HEPAT JI Nat. Rev. Gastroenterol. Hepatol. PD JUN PY 2012 VL 9 IS 6 BP 308 EP 309 DI 10.1038/nrgastro.2012.93 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 955JZ UT WOS:000305016200003 PM 22585133 ER PT J AU Harel, NY Tseng, BY AF Harel, Noam Y. Tseng, Benjamin Y. TI Cerebral perfusion in acute stroke prognostication Go with the flow, or know with the quo? SO NEUROLOGY LA English DT Editorial Material ID PREDICTION C1 [Harel, Noam Y.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Harel, Noam Y.] James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, New York, NY USA. [Tseng, Benjamin Y.] Univ Texas SW Med Ctr Dallas, Dept Internal Med Cardiol, Dallas, TX 75390 USA. [Tseng, Benjamin Y.] Texas Hlth Presbyterian Hosp, Inst Exercise & Environm Med, Dallas, TX USA. RP Harel, NY (reprint author), Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. EM noam.harel@mssm.edu NR 10 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 2012 VL 78 IS 23 BP 1811 EP 1812 DI 10.1212/WNL.0b013e318258f867 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 953XC UT WOS:000304906100005 PM 22573632 ER PT J AU Myaskovsky, L Doebler, DA Posluszny, DM Dew, MA Unruh, M Crowley-Matoka, M Switzer, GE Dabbs, AD Chang, CCH DiMartini, AF Shapiro, R Tan, HK AF Myaskovsky, Larissa Doebler, Donna Almario Posluszny, Donna M. Dew, Mary Amanda Unruh, Mark Crowley-Matoka, Megan Switzer, Galen E. Dabbs, Annette DeVito Chang, Chung-Chou H. DiMartini, Andrea F. Shapiro, Ron Tan, Henkie TI Rates and correlates of health maintenance behaviors after living kidney donation SO PROGRESS IN TRANSPLANTATION LA English DT Article ID QUALITY-OF-LIFE; TERM-FOLLOW-UP; DONOR NEPHRECTOMY; TRANSPLANTATION; OUTCOMES; CONSEQUENCES; DISEASE; IMPACT AB Context and Objective-Donating a kidney may provide an opportunity for donors to reevaluate their health maintenance behaviors (eg, regular exercise, smoking cessation, medical checkups). Although the effect of donation on donors' health, quality of life, and financial outcomes has received growing attention, no studies have examined whether donation is related to changes in health maintenance behaviors. The study aims were to (I) describe and compare kidney donors' health maintenance behaviors before and after donation, and (2) determine the correlates of health maintenance behaviors after donation. Design, Setting, Participants and Measures-We conducted a telephone-interview study with 85 randomly selected laparoscopic kidney donors in a major US transplant center to assess health behaviors before and after donation, postdonation characteristics (eg, quality of life, postsurgical pain), and demographics. Results-Sample demographics included a median age of 48 years; 55% were female, 82% were white, 71% were married, and 52% were college graduates. Few health behaviors changed significantly from before to after donation. Only the rate of medical checkups increased after donation (P<.001). Logistic regression was used to examine the association of demographics and postdonation characteristics with postdonation health maintenance behaviors, after adjusting for predonation behavior. Older age, higher income, less postsurgical pain, and better physical functioning were associated with more exercise after donation. Longer time since donation was associated with a higher prevalence of obesity. Conclusions-These results may help identify donors who are at greater risk for poor health maintenance behaviors after donation and suggest areas of health behavior that should be the focus of education sessions before donation. (Progress in Transplantation. 2012;22:147-154) (C) 2012 NATCO, The Organization for Transplant Professionals doi: http://dx.doi.org/10.7182/pit2012287 C1 [Myaskovsky, Larissa] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Myaskovsky, Larissa; Doebler, Donna Almario; Posluszny, Donna M.; Dew, Mary Amanda; Unruh, Mark; Switzer, Galen E.; Dabbs, Annette DeVito; Chang, Chung-Chou H.; DiMartini, Andrea F.; Shapiro, Ron; Tan, Henkie] Univ Pittsburgh, Pittsburgh, PA USA. [Crowley-Matoka, Megan] Northwestern Univ, Evanston, IL USA. RP Myaskovsky, L (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr,151C-H, Pittsburgh, PA 15206 USA. EM larissa.myaskovsky@va.gov FU UPMC Starzl Transplant Institute [XNV 72-069]; VA Health Services Research and Development Division [IIR 06-220] FX Funding for this project was provided by grant XNV 72-069 from the UPMC Starzl Transplant Institute and grant IIR 06-220 from the VA Health Services Research and Development Division. NR 41 TC 5 Z9 5 U1 0 U2 1 PU INNOVISION COMMUNICATIONS PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1526-9248 J9 PROG TRANSPLANT JI Prog. Transplant. PD JUN PY 2012 VL 22 IS 2 BP 147 EP 154 DI 10.7182/pit2012287 PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 956NA UT WOS:000305095200006 PM 22878071 ER PT J AU Carmody, TP Delucchi, K Simon, JA Duncan, CL Solkowitz, SN Huggins, J Lee, SK Hall, SM AF Carmody, Timothy P. Delucchi, Kevin Simon, Joel A. Duncan, Carol L. Solkowitz, Sharon N. Huggins, Joy Lee, Sharon K. Hall, Sharon M. TI Expectancies Regarding the Interaction Between Smoking and Substance Use in Alcohol-Dependent Smokers in Early Recovery SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article DE smoking cessation; tobacco use; nicotine dependence; alcohol dependence; expectancies ID ADDICTION SEVERITY INDEX; FAGERSTROM TOLERANCE QUESTIONNAIRE; NICOTINE DEPENDENCE; ABUSE TREATMENT; CESSATION INTERVENTIONS; ABSTINENCE; DISORDERS; TOBACCO; METAANALYSIS; INDIVIDUALS AB The purpose of this study was to investigate expectancies regarding the interaction between cigarette smoking and use of alcohol among alcohol-dependent smokers in early recovery, using the Nicotine and Other Substances Interaction Expectancies Questionnaire (NOSIE). Participants were 162 veterans, 97% male, with a mean age of 50 years, enrolled in a clinical trial aimed at determining the efficacy of an intensive smoking cessation intervention versus usual care. At baseline, participants were assessed on measures of smoking behavior, abstinence thoughts about alcohol and tobacco use, symptoms of depression, and smoking-substance use interaction expectancies. In addition, biologically verified abstinence from tobacco and alcohol was assessed at 26 weeks. Participants reported that they expected smoking to have less of an impact on substance use than substance use has on smoking (p < .001). Severity of depressive symptoms was significantly associated with the expectancy that smoking provides a way of coping with the urge to use other substances (p < .01). The expectation that smoking increases substance urges/use was predictive of prospectively measured and biologically verified abstinence from smoking at 26 weeks (p < .03). The results add to our knowledge of smoking-substance use interaction expectancies among alcohol-dependent smokers in early recovery and will inform the development of more effective counseling interventions for concurrent alcohol and tobacco use disorders. C1 [Carmody, Timothy P.; Simon, Joel A.; Duncan, Carol L.; Solkowitz, Sharon N.; Huggins, Joy; Lee, Sharon K.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [Delucchi, Kevin; Hall, Sharon M.] Univ Calif San Francisco, Treatment Res Ctr, Dept Psychiat, San Francisco, CA 94143 USA. RP Carmody, TP (reprint author), Vet Affairs Med Ctr, Mental Hlth Serv 116B, 4150 Clement St, San Francisco, CA 94121 USA. EM timothy.carmody@va.gov FU NIDA NIH HHS [P50 DA009253, P50 DA009253-09, P50 DA09253] NR 36 TC 8 Z9 8 U1 2 U2 5 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD JUN PY 2012 VL 26 IS 2 BP 358 EP 363 DI 10.1037/a0024424 PG 6 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 956NX UT WOS:000305097500021 PM 21707127 ER PT J AU Atwood, CW AF Atwood, Charles W., Jr. TI "The Times They Are A Changin:" Home Diagnosis of Sleep Apnea Has Arrived Commentary on Rosen et al. A multisite randomized trial of portable sleep studies and positive airway pressure autotitration versus laboratory-based polysomnography for the diagnosis and treatment of obstructive sleep apnea: The HomePAP Study. SLEEP 2012;35:757-767 SO SLEEP LA English DT Editorial Material ID OUTCOMES C1 [Atwood, Charles W., Jr.] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Med Ctr, UPMC Sleep Med Ctr, Pittsburgh, PA 15213 USA. [Atwood, Charles W., Jr.] VA Pittsburgh Healthcare Syst, Pulm Sect, Pittsburgh, PA USA. [Atwood, Charles W., Jr.] VA Pittsburgh Healthcare Syst, Sleep Disorders Program, Pittsburgh, PA USA. RP Atwood, CW (reprint author), Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Med Ctr, UPMC Sleep Med Ctr, 3459 5th Ave,NW628 MUH, Pittsburgh, PA 15213 USA. EM atwoodcw@upmc.edu NR 8 TC 2 Z9 2 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD JUN 1 PY 2012 VL 35 IS 6 BP 735 EP 736 DI 10.5665/sleep.1848 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 952CM UT WOS:000304767300003 PM 22654184 ER PT J AU Biering-Sorensen, F Krassioukov, A Alexander, MS Donovan, W Karlsson, AK Mueller, G Perkash, I Sheel, AW Wecht, J Schilero, GJ AF Biering-Sorensen, F. Krassioukov, A. Alexander, M. S. Donovan, W. Karlsson, A-K Mueller, G. Perkash, I. Sheel, A. William Wecht, J. Schilero, G. J. TI International Spinal Cord Injury Pulmonary Function Basic Data Set SO SPINAL CORD LA English DT Article DE spinal cord injury; international data set; pulmonary function; pneumonia; sleep apnea; ventilator ID FORCED VITAL CAPACITY; MORTALITY; SLEEP; DEATH; FEV1; FVC AB Objectives: To develop the International Spinal Cord Injury (SCI) Pulmonary Function Basic Data Set within the framework of the International SCI Data Sets in order to facilitate consistent collection and reporting of basic bronchopulmonary findings in the SCI population. Setting: International. Methods: The SCI Pulmonary Function Data Set was developed by an international working group. The initial data set document was revised on the basis of suggestions from members of the Executive Committee of the International SCI Standards and Data Sets, the International Spinal Cord Society (ISCoS) Executive and Scientific Committees, American Spinal Injury Association (ASIA) Board, other interested organizations and societies and individual reviewers. In addition, the data set was posted for 2 months on ISCoS and ASIA websites for comments. Results: The final International SCI Pulmonary Function Data Set contains questions on the pulmonary conditions diagnosed before spinal cord lesion, if available, to be obtained only once; smoking history; pulmonary complications and conditions after the spinal cord lesion, which may be collected at any time. These data include information on pneumonia, asthma, chronic obstructive pulmonary disease and sleep apnea. Current utilization of ventilator assistance including mechanical ventilation, diaphragmatic pacing, phrenic nerve stimulation and Bi-level positive airway pressure can be reported, as well as results from pulmonary function testing includes: forced vital capacity, forced expiratory volume in one second and peak expiratory flow. The complete instructions for data collection and the data sheet itself are freely available on the website of ISCoS (http://www.iscos.org.uk). Spinal Cord (2012) 50, 418-421; doi:10.1038/sc.2011.183; published online 24 January 2012 C1 [Biering-Sorensen, F.] Rigshosp, Clin Spinal Cord Injuries, Ctr Neurosci, DK-2100 Copenhagen, Denmark. [Biering-Sorensen, F.] Univ Copenhagen, DK-2100 Copenhagen O, Denmark. [Krassioukov, A.; Sheel, A. William] Univ British Columbia, ICORD, Vancouver, BC V5Z 1M9, Canada. [Krassioukov, A.; Sheel, A. William] Vancouver Coastal Hlth, Vancouver, BC, Canada. [Alexander, M. S.] Renown Rehabil Hosp, Reno, NV USA. [Donovan, W.] Univ Texas Hlth Sci Ctr, Baylor Coll Med, Houston, TX USA. [Karlsson, A-K] Sahlgrens Univ Hosp, Gothenburg, Sweden. [Mueller, G.] Swiss Parapleg Ctr, Clin Trial Unit, Nottwil, Switzerland. [Perkash, I.] Stanford Univ, Palo Alto, CA 94304 USA. [Perkash, I.] Vet Adm Palo Alto, Palo Alto, CA USA. [Wecht, J.; Schilero, G. J.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Wecht, J.; Schilero, G. J.] Mt Sinai Sch Med, New York, NY USA. RP Biering-Sorensen, F (reprint author), RIGSHOSP TH2091, Clin Spinal Cord Injuries, Ctr Neurosci, 9 Blegdamsvej, DK-2100 Copenhagen O, Denmark. EM finbs@rh.dk FU Coloplast A/S, Denmark FX Coloplast A/S, Denmark has supported the work with this Data Set with an unconditional grant. We are thankful for comments and suggestions received from Lawrence Vogel, Susan Charlifue, Gordana Savic and Michael DeVivo. NR 15 TC 10 Z9 10 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD JUN PY 2012 VL 50 IS 6 BP 418 EP 421 DI 10.1038/sc.2011.183 PG 4 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 951LC UT WOS:000304721100005 PM 22270192 ER PT J AU Cervera, R Bakaeen, FG Cornwell, LD Wang, XL Coselli, JS LeMaire, SA Chu, D AF Cervera, Roberto Bakaeen, Faisal G. Cornwell, Lorraine D. Wang, Xing Li Coselli, Joseph S. LeMaire, Scott A. Chu, Danny TI Impact of Functional Status on Survival After Coronary Artery Bypass Grafting in a Veteran Population SO ANNALS OF THORACIC SURGERY LA English DT Article ID AORTIC-VALVE-REPLACEMENT; HIGH-RISK PATIENTS; CARDIAC-SURGERY; LATE MORTALITY; FRAILTY; OLDER; OUTCOMES; AGE; DISEASE; INDEX AB Background. Although functional impairment has been shown to be an adverse outcome of frailty, little is known of its effect on patients after cardiac operations. We aimed to assess the effect of limited functional status on long-term survival after coronary artery bypass grafting (CABG). Methods. We reviewed prospectively gathered data from 1,503 consecutive patients who underwent isolated CABG between 1997 and 2009. We compared the outcomes of 318 patients with limited functional status and 1,185 patients without any functional impairment. The mean follow-up period was 65 months (range, 1 to 157 months). We assessed the relationship between functional status impairment and long-term survival by Cox regression analysis adjusted for confounding factors. Results. Functionally impaired patients were slightly older (63 +/- 9 vs 62 +/- 8 years, p = 0.05) and had more risk factors for adverse outcomes than patients who were functionally unimpaired. After adjustment for potential confounding variables by multivariate logistic regression analysis, preoperative limited functional status was not an independent predictor (odds ratio [95% confidence interval]) of 30-day mortality (1.4 [0.3 to 5.8], p = 0.67) or major adverse cardiac events (1.3 [0.5 to 3.3], p = 0.71), nor was it predictive of reduced long-term survival (10-year hazard ratio 1.0 [0.7 to 1.4], p = 0.85). Conclusions. Limited functional status was not an independent risk factor for early postoperative complications or death. Long-term survival in patients whose functional status was impaired before they underwent CABG was similar to that of patients who were functionally independent. C1 [Chu, Danny] Baylor Coll Med, Texas Heart Inst, Michael E DeBakey Vet Affairs Med Ctr, Div Cardiothorac Surg, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX 77030 USA. St Lukes Episcopal Hosp, Texas Heart Inst, Div Cardiovasc Surg, Houston, TX USA. RP Chu, D (reprint author), Baylor Coll Med, Texas Heart Inst, Michael E DeBakey Vet Affairs Med Ctr, Div Cardiothorac Surg, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA. EM dchu@bcm.edu NR 21 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUN PY 2012 VL 93 IS 6 BP 1950 EP 1955 DI 10.1016/j.athoracsur.2012.02.071 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 947VG UT WOS:000304460000038 PM 22560262 ER PT J AU Carrick, R Ge, L Lee, LC Zhang, ZH Mishra, R Axel, L Guccione, JM Grossi, EA Ratcliffe, MB AF Carrick, Richard Ge, Liang Lee, Lik Chuan Zhang, Zhihong Mishra, Rakesh Axel, Leon Guccione, Julius M. Grossi, Eugene A. Ratcliffe, Mark B. TI Patient-Specific Finite Element-Based Analysis of Ventricular Myofiber Stress After Coapsys: Importance of Residual Stress SO ANNALS OF THORACIC SURGERY LA English DT Article ID ISCHEMIC MITRAL REGURGITATION; VOLUME REDUCTION SURGERY; DILATED CARDIOMYOPATHY; PAPILLARY-MUSCLE; REPAIR TECHNIQUE; ANNULOPLASTY; VALVE; MODEL AB Background. We sought to determine regional myofiber stress after Coapsys device (Myocor, Inc, Maple Grove, MN) implantation using a finite element model of the left ventricle (LV). Chronic ischemic mitral regurgitation is caused by LV remodeling after posterolateral myocardial infarction. The Coapsys device consists of a single trans-LV chord placed below the mitral valve such that when tensioned it alters LV shape and decreases chronic ischemic mitral regurgitation. Methods. Finite element models of the LV were based on magnetic resonance images obtained before (preoperatively) and after (postoperatively) coronary artery bypass grafting with Coapsys implantation in a single patient. To determine the effect of Coapsys and LV before stress, virtual Coapsys was performed on the preoperative model. Diastolic and systolic material variables in the preoperative, postoperative, and virtual Coapsys models were adjusted so that model LV volume agreed with magnetic resonance imaging data. Chronic ischemic mitral regurgitation was abolished in the postoperative models. In each case, myofiber stress and pump function were calculated. Results. Both postoperative and virtual Coapsys models shifted end-systolic and end-diastolic pressure-volume relationships to the left. As a consequence and because chronic ischemic mitral regurgitation was reduced after Coapsys, pump function was unchanged. Coapsys decreased myofiber stress at end-diastole and end-systole in both the remote and infarct regions of the myocardium. However, knowledge of Coapsys and LV prestress was necessary for accurate calculation of LV myofiber stress, especially in the remote zone. Conclusions. Coapsys decreases myofiber stress at end-diastole and end-systole. The improvement in myofiber stress may contribute to the long-term effect of Coapsys on LV remodeling. C1 Univ Vermont, Coll Med, Burlington, VT USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. NYU, Dept Cardiothorac Surg, New York, NY USA. NYU, Dept Radiol, New York, NY 10016 USA. New York Harbor Vet Affairs Med Ctr, New York, NY USA. RP Ratcliffe, MB (reprint author), San Francisco VA Med Ctr, Surg Serv 112, 4150 Clement St, San Francisco, CA 94121 USA. EM mark.ratclifte@va.gov OI GROSSI, eugene/0000-0002-2066-7035; Axel, Leon/0000-0003-0608-4690 FU NIH [R01-HL084431, R01-HL077921, R01-HL086400]; University of Vermont FX This study was supported by NIH grants R01-HL084431 (M.B.R.), R01-HL077921 (J.M.G.), and R01-HL086400 (J.M.G.). RC. was supported by a Summer Research Fellowship from the University of Vermont. This support is gratefully acknowledged. NR 30 TC 14 Z9 14 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUN PY 2012 VL 93 IS 6 BP 1964 EP 1971 DI 10.1016/j.athoracsur.2012.03.001 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 947VG UT WOS:000304460000040 PM 22560323 ER PT J AU Jernigan, MG Press, EG Nguyen, MH Clancy, CJ Shields, RK AF Jernigan, Meredith G. Press, Ellen G. Nguyen, M. Hong Clancy, Cornelius J. Shields, Ryan K. TI The Combination of Doripenem and Colistin Is Bactericidal and Synergistic against Colistin-Resistant, Carbapenemase-Producing Klebsiella pneumoniae SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID RISK-FACTORS; INFECTION; OUTCOMES; PHARMACOKINETICS; ACQUISITION; PREDICTORS; MORTALITY; IMPACT AB We tested two-drug combinations of doripenem, colistin, gentamicin, and doxycycline against 12 carbapenemase-producing Klebsiella pneumoniae (KPC) isolates by time-kill. The combination of doripenem and colistin reduced the starting inocula by 2 logs for each isolate (range, 2.02 to 6.01 log(10)) and was bactericidal and synergistic against 75 and 50%, respectively. Among colistin- and pan-drug-resistant isolates, synergy was identified in 60 and 67%, respectively. All other combinations were inferior. We are currently evaluating the combination of doripenem and colistin as a frontline therapy for KPC infection. C1 [Press, Ellen G.; Nguyen, M. Hong; Clancy, Cornelius J.; Shields, Ryan K.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Jernigan, Meredith G.] Univ Pittsburgh, Dept Pharm & Therapeut, Pittsburgh, PA USA. [Clancy, Cornelius J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Clancy, CJ (reprint author), Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. EM cjc76@pitt.edu FU National Center for Research Resources [KL2 RR024154] FX The project described was supported by award number KL2 RR024154 from the National Center for Research Resources to R.K.S. NR 24 TC 37 Z9 44 U1 0 U2 2 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 JUN PY 2012 VL 56 IS 6 BP 3395 EP 3398 DI 10.1128/AAC.06364-11 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 947LZ UT WOS:000304432800082 PM 22430958 ER PT J AU Roemer, FW Kwoh, CK Hannon, MJ Green, SM Jakicic, JM Boudreau, R Crema, MD Moore, CE Guermazi, A AF Roemer, Frank W. Kwoh, C. Kent Hannon, Michael J. Green, Stephanie M. Jakicic, John M. Boudreau, Robert Crema, Michel D. Moore, Carolyn E. Guermazi, Ali TI Risk factors for magnetic resonance imaging-detected patellofemoral and tibiofemoral cartilage loss during a six-month period: The Joints On Glucosamine study SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYMPTOMATIC KNEE OSTEOARTHRITIS; RADIOGRAPHIC OSTEOARTHRITIS; DISEASE PROGRESSION; MULTICENTER OSTEOARTHRITIS; MENISCAL EXTRUSION; NATURAL-HISTORY; ASSOCIATION; FRAMINGHAM; SYNOVITIS; VOLUME AB Objective To assess several baseline risk factors that may predict patellofemoral and tibiofemoral cartilage loss during a 6-month period. Methods For 177 subjects with chronic knee pain, 3T magnetic resonance imaging (MRI) of both knees was performed at baseline and followup. Knees were semiquantitatively assessed, evaluating cartilage morphology, subchondral bone marrow lesions, meniscal morphology/extrusion, synovitis, and effusion. Age, sex, and body mass index (BMI), bone marrow lesions, meniscal damage/extrusion, synovitis, effusion, and prevalent cartilage damage in the same subregion were evaluated as possible risk factors for cartilage loss. Logistic regression models were applied to predict cartilage loss. Models were adjusted for age, sex, treatment, and BMI. Results Seventy-nine subregions (1.6%) showed incident or worsening cartilage damage at followup. None of the demographic risk factors was predictive of future cartilage loss. Predictors of patellofemoral cartilage loss were effusion, with an adjusted odds ratio (OR) of 3.5 (95% confidence interval [95% CI] 1.39.4), and prevalent cartilage damage in the same subregion with an adjusted OR of 4.3 (95% CI 1.314.1). Risk factors for tibiofemoral cartilage loss were baseline meniscal extrusion (adjusted OR 3.6 [95% CI 1.310.1]), prevalent bone marrow lesions (adjusted OR 4.7 [95% CI 1.119.5]), and prevalent cartilage damage (adjusted OR 15.3 [95% CI 4.947.4]). Conclusion Cartilage loss over 6 months is rare, but may be detected semiquantitatively by 3T MRI and is most commonly observed in knees with Kellgren/Lawrence grade 3. Predictors of patellofemoral cartilage loss were effusion and prevalent cartilage damage in the same subregion. Predictors of tibiofemoral cartilage loss were prevalent cartilage damage, bone marrow lesions, and meniscal extrusion. C1 [Roemer, Frank W.] Boston Univ, Med Ctr, Dept Radiol, Quantitat Imaging Ctr, Boston, MA 02118 USA. [Roemer, Frank W.] Klinikum Augsburg, Augsburg, Germany. [Kwoh, C. Kent; Hannon, Michael J.; Green, Stephanie M.; Jakicic, John M.; Boudreau, Robert] Univ Pittsburgh, Pittsburgh, PA USA. [Kwoh, C. Kent] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Crema, Michel D.] Inst Diagnost Imaging, Ribeirao Preto, Brazil. [Crema, Michel D.] Univ Sao Paulo, BR-14049 Ribeirao Preto, Brazil. [Moore, Carolyn E.] Texas Womans Univ, Houston, TX USA. RP Roemer, FW (reprint author), Boston Univ, Med Ctr, Dept Radiol, Quantitat Imaging Ctr, FGH Bldg,3rd Floor,820 Harrison Ave, Boston, MA 02118 USA. EM froemer@bu.edu OI Boudreau, Robert/0000-0003-0162-5187 FU Beverage Institute for Health & Wellness, the Coca Cola Company; Multidisciplinary Clinical Research Center for Musculoskeletal and Skin Diseases at the University of Pittsburgh (NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases) [P60]; Beverage Institute for Health Wellness; Jenny Craig; Alere Wellbeing; Facet Solutions; Genzyme; Stryker; Merck Serono; AstraZeneca; General Electric Healthcare FX The Joints On Glucosamine study is funded by a grant from the Beverage Institute for Health & Wellness, the Coca Cola Company. The statistical analysis was partially supported by the Multidisciplinary Clinical Research Center for Musculoskeletal and Skin Diseases at the University of Pittsburgh (NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases P60 grant).; Drs. Roemer and Guermazi own stock or stock options in Boston Imaging Core Lab; Dr. Roemer is vice president and Dr. Guermazi is president of Boston Imaging Core Lab. Dr. Kwoh has received a research grant from the Beverage Institute for Health & Wellness. Dr. Jakicic has received consulting fees, speaking fees, and/or honoraria from Jenny Craig and Alere Wellbeing (less than $10,000 each). Dr. Crema owns stock or stock options in Boston Imaging Core Lab. Dr. Guermazi has received consulting fees, speaking fees, and/or honoraria from Facet Solutions, Genzyme, and Stryker (less than $10,000 each) and from Merck Serono and AstraZeneca (more than $10,000 each) and has received a research grant from General Electric Healthcare. NR 51 TC 29 Z9 29 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD JUN PY 2012 VL 64 IS 6 BP 1888 EP 1898 DI 10.1002/art.34353 PG 11 WC Rheumatology SC Rheumatology GA 948SE UT WOS:000304522100022 PM 22213129 ER PT J AU De Costa, AMA Schuyler, CA Walker, DD Young, MRI AF De Costa, Anna-Maria A. Schuyler, Corinne A. Walker, David D. Young, M. Rita I. TI Characterization of the evolution of immune phenotype during the development and progression of squamous cell carcinoma of the head and neck SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE HNSCC; Premalignant; Immunoediting; Th1/Tc1 cells; Th17 cells ID T-CELLS; PD-1 EXPRESSION; TH17 CELLS; CANCER; MODEL; DYSFUNCTION; MICE; INFLAMMATION; LYMPHOCYTES; INTERFERON AB While studies have indicated that squamous cell carcinoma of the head and neck (HNSCC) is associated with immune suppression, these studies did not analyze the immune response at the dysplastic stage. The present study utilized a mouse model of 4-nitroquinoline 1-oxide-induced oral carcinogenesis to examine the alterations in immune phenotype at the premalignant and malignant stages of HNSCC. Cervical lymph nodes of HNSCC-bearing mice were found to contain a greater number of cells, including a greater number of conventional (Tconv) and regulatory (Treg) T cells, compared to cervical lymph nodes of control and premalignant lesion-bearing mice, though the Tconv cells appear to be less proliferative and the Treg cells appear to be less suppressive at the HNSCC stage. Premalignant lesion-bearing mouse lymph nodes consist of a greater percentage of Tconv cells expressing markers for activation, memory, and exhaustion compared to both control and HNSCC-bearing mice. Also, lymph nodes' cells from both premalignant lesion-bearing and HNSCC-bearing mice include increased levels of Th1, Tc1, and Th17 cells, with no differences in levels of Th2 cells, compared to control mice. The data show that while there is the expected increase in immunosuppressive Tregs in lymph nodes when HNSCC is present, there is also an unexpected increase in immune populations usually associated with a beneficial antitumor response, including Tconv cells and Th1 and Tc1 cells. In addition, the results demonstrate that the premalignant stage of HNSCC development is associated with a robust immune response involving an increase in inflammatory Th1, Tc1, and Th17 cells. C1 [De Costa, Anna-Maria A.; Schuyler, Corinne A.; Young, M. Rita I.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv 151, Charleston, SC 29401 USA. [De Costa, Anna-Maria A.; Walker, David D.; Young, M. Rita I.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29401 USA. [De Costa, Anna-Maria A.; Young, M. Rita I.] Med Univ S Carolina, Dept Med, Charleston, SC 29401 USA. RP Young, MRI (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Res Serv 151, Charleston, SC 29401 USA. EM rita.young@va.gov FU Medical Research Service of the Department of Veterans Affairs; National Institutes of Health [RO1 CA128837, RO1 DE018268] FX This work was supported by the Medical Research Service of the Department of Veterans Affairs and by grants RO1 CA128837 and RO1 DE018268 from the National Institutes of Health to MRIY. NR 37 TC 15 Z9 15 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD JUN PY 2012 VL 61 IS 6 BP 927 EP 939 DI 10.1007/s00262-011-1154-8 PG 13 WC Oncology; Immunology SC Oncology; Immunology GA 950AU UT WOS:000304621900017 PM 22116344 ER PT J AU Carrithers, MD AF Carrithers, Michael D. TI Current Immunotherapy of Multiple Sclerosis and Future Challenges: Relevance of Immune-Mediated Repair SO CURRENT PHARMACEUTICAL BIOTECHNOLOGY LA English DT Review DE Brain; demyelination; immune surveillance; innate immunity; interferon; lymphocyte; natalizumab ID PLACEBO-CONTROLLED TRIAL; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; CENTRAL-NERVOUS-SYSTEM; CONTROLLED PHASE IIB; DOUBLE-BLIND; T-CELLS; GLATIRAMER ACETATE; INTERFERON-BETA; IN-VITRO; INTRAMUSCULAR INTERFERON AB Multiple sclerosis is the most common chronic inflammatory disease of the central nervous system and can cause severe neurological disability. Current immune therapy with beta-interferons, glatiramer acetate, immune suppressives, or selective adhesion molecule inhibitors can reduce the frequency and severity of acute attacks in a majority of patients but have little effect on the progressive phase of the disease. Patients who require aggressive immune therapy are also at risk for the development of potentially fatal opportunistic infections. Here current and emerging immune therapy options are discussed, and immune-mediated strategies to preserve normal immune surveillance and mediate tissue repair are proposed. C1 [Carrithers, Michael D.] Univ Wisconsin, Dept Neurol, Madison, WI 53706 USA. [Carrithers, Michael D.] William S Middleton Mem Vet Adm Med Ctr, Neurol Serv, Madison, WI USA. RP Carrithers, MD (reprint author), Univ Wisconsin, Dept Neurol, 1300 Univ Ave, Madison, WI 53706 USA. EM carrithers@neurology.wisc.edu NR 96 TC 3 Z9 3 U1 1 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2010 J9 CURR PHARM BIOTECHNO JI Curr. Pharm. Biotechnol. PD JUN PY 2012 VL 13 IS 8 BP 1409 EP 1417 PG 9 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 949SQ UT WOS:000304596600005 PM 22339217 ER PT J AU Lee, W Nelson, R Akmal, Y Mailey, B McKenzie, S Artinyan, A Ashing-Giwa, KT Chen, YJ Garcia-Aguilar, J Kim, J AF Lee, Wendy Nelson, Rebecca Akmal, Yasir Mailey, Brian McKenzie, Shaun Artinyan, Avo Ashing-Giwa, Kimlin Tam Chen, Yi-Jen Garcia-Aguilar, Julio Kim, Joseph TI Racial and ethnic disparities in outcomes with radiation therapy for rectal adenocarcinoma SO INTERNATIONAL JOURNAL OF COLORECTAL DISEASE LA English DT Article DE Rectal cancer; Radiation; Neoadjuvant; Disparities ID PATHOLOGICAL COMPLETE RESPONSE; COLORECTAL-CANCER TREATMENTS; PREOPERATIVE CHEMORADIATION; SOCIOECONOMIC-STATUS; PREDICTIVE FACTORS; ADJUVANT THERAPY; SURVIVAL; CHEMORADIOTHERAPY; RADIOTHERAPY; CAPECITABINE AB Race/ethnicity may modify cancer outcomes and manifest as survival disparities for patients with rectal cancer. Our objective was to determine whether disparate rectal cancer outcomes result from variable efficacy of radiation therapy for major racial/ethnic groups. The Los Angeles County Cancer Surveillance Program (CSP) identified patients with rectal adenocarcinoma between the years 1988 and 2006. Patients who underwent curative-intent surgery were grouped by race/ethnicity and by receipt (yes vs. no) and timing (neoadjuvant vs. adjuvant) of radiation therapy. The impact of receipt and timing of radiation therapy on overall survival was then assessed. Of 4,961 patients in CSP, 2,229 (45%) received radiation therapy. Overall, there was no difference in survival among patients according to receipt of radiation therapy. We then examined the radiation cohort, wherein 919 (41%) and 1,310 (59%) patients received neoadjuvant or adjuvant radiation, respectively. Overall, patients who received neoadjuvant compared to adjuvant radiation had improved survival (median survival (MS), 9.4 vs. 6.8 years, respectively; p < 0.001). Among those patients who received neoadjuvant radiation, whites, Hispanics, and Asians had significantly longer survival than blacks (MS, 10.4, 10.4, and 10.4 vs. 4.4 years, respectively; p = 0.003). On multivariate analysis, race/ethnicity was an independent predictor of survival (p = 0.001). To our knowledge, this is the first study examining the efficacy of radiation therapy for racial/ethnic groups with rectal cancer. Disparate outcomes were observed for the administration of radiation therapy for select racial/ethnic groups. The reasons for these disparities in outcomes should be investigated to better optimize radiation therapy for patients with rectal cancer. C1 [Lee, Wendy; Akmal, Yasir; Mailey, Brian; Garcia-Aguilar, Julio; Kim, Joseph] City Hope Comprehens Canc Ctr, Dept Surg, Duarte, CA 91010 USA. [Nelson, Rebecca] City Hope Comprehens Canc Ctr, Dept Biostat, Duarte, CA 91010 USA. [McKenzie, Shaun] Univ Kentucky, Sch Med, Dept Surg, Lexington, KY 40536 USA. [Ashing-Giwa, Kimlin Tam] City Hope Comprehens Canc Ctr, Dept Populat Sci, Duarte, CA 91010 USA. [Chen, Yi-Jen] City Hope Comprehens Canc Ctr, Dept Radiat Oncol, Duarte, CA 91010 USA. [Artinyan, Avo] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. [Artinyan, Avo] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Res Ctr Excellence, Houston, TX 77030 USA. [Artinyan, Avo] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston Hlth Serv, Houston, TX 77030 USA. RP Kim, J (reprint author), City Hope Comprehens Canc Ctr, Dept Surg, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM jokim@coh.org RI Nelson, Rebecca/C-4438-2014 NR 32 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0179-1958 J9 INT J COLORECTAL DIS JI Int. J. Colorectal Dis. PD JUN PY 2012 VL 27 IS 6 BP 737 EP 749 DI 10.1007/s00384-011-1378-2 PG 13 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 947VQ UT WOS:000304461400007 PM 22159751 ER PT J AU So, C Kirby, KA Mehta, K Hoffman, RM Powell, AA Freedland, SJ Sirovich, B Yano, EM Walter, LC AF So, Cynthia Kirby, Katharine A. Mehta, Kala Hoffman, Richard M. Powell, Adam A. Freedland, Stephen J. Sirovich, Brenda Yano, Elizabeth M. Walter, Louise C. TI Medical Center Characteristics Associated with PSA Screening in Elderly Veterans with Limited Life Expectancy SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE PSA screening; regional variation; elderly; life expectancy ID PRIMARY-CARE PHYSICIANS; ANTIGEN TEST USE; PROSTATE-CANCER; COLORECTAL-CANCER; UNITED-STATES; DECISION-MAKING; MEN; OLDER; DETERMINANTS; COMORBIDITY AB Although guidelines recommend against prostate-specific antigen (PSA) screening in elderly men with limited life expectancy, screening is common. We sought to identify medical center characteristics associated with screening in this population. We conducted a prospective study of 622,262 screen-eligible men aged 70+ seen at 104 VA medical centers in 2003. Primary outcome was the percentage of men at each center who received PSA screening in 2003, based on VA data and Medicare claims. Men were stratified into life expectancy groups ranging from favorable (age 70-79 with Charlson score = 0) to limited (age 85+ with Charlson score a parts per thousand yen1 or age 70+ with Charlson score a parts per thousand yen4). Medical center characteristics were obtained from the 1999-2000 VA Survey of Primary Care Practices and publicly available VA data sources. Among 123,223 (20%) men with limited life expectancy, 45% received PSA screening in 2003. Across 104 VAs, the PSA screening rate among men with limited life expectancy ranged from 25-79% (median 43%). Higher screening was associated with the following center characteristics: no academic affiliation (50% vs. 43%, adjusted RR = 1.14, 95% CI 1.04-1.25), a ratio of midlevel providers to physicians a parts per thousand yen3:4 (55% vs. 45%, adjusted RR = 1.20, 95% CI 1.09-1.32) and location in the South (49% vs. 39% in the West, adjusted RR = 1.25, 95% CI 1.12-1.40). Use of incentives and high scores on performance measures were not independently associated with screening. Within centers, the percentages of men screened with limited and favorable life expectancies were highly correlated (r = 0.90). Substantial practice variation exists for PSA screening in older men with limited life expectancy across VAs. The high center-specific correlation of screening among men with limited and favorable life expectancies indicates that PSA screening is poorly targeted according to life expectancy. C1 [So, Cynthia] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Kirby, Katharine A.; Mehta, Kala; Walter, Louise C.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. [Hoffman, Richard M.] New Mexico VA Hlth Care Syst, Albuquerque, NM USA. [Hoffman, Richard M.] Univ New Mexico, Dept Med, Albuquerque, NM 87131 USA. [Powell, Adam A.] Minneapolis VA Hlth Care Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Powell, Adam A.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Freedland, Stephen J.] Duke Univ, Durham VA Med Ctr, Durham, NC USA. [Freedland, Stephen J.] Duke Univ, Duke Prostate Ctr, Durham, NC USA. [Sirovich, Brenda] White River Junct VA, Windsor, VT USA. [Yano, Elizabeth M.] UCLA Sch Publ Hlth, VA Greater Los Angeles Hlth Syst, VA HSR&D Ctr Study Healthcare Provider Behav, Los Angeles, CA USA. [Yano, Elizabeth M.] UCLA Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. RP Walter, LC (reprint author), VA Med Ctr 181G, 4150 Clement St, San Francisco, CA 94121 USA. EM Louise.Walter@ucsf.edu FU National Cancer Institute at the National Institutes of Health [R01 CA134425]; American Federation for Aging Research; National Institute on Aging [K-01AG025444]; New Mexico VA Health Care System; White River Junction VA; VA HSRD [05-195] FX This work was supported by the National Cancer Institute at the National Institutes of Health (grant number R01 CA134425) to [LW, RH, AP, and SF]; the Medical Student Training in Aging Research Program at the American Federation for Aging Research to [CS]; the National Institute on Aging (grant number K-01AG025444) to [KM]; the New Mexico VA Health Care System to [RH]; the White River Junction VA to [BS]; and the VA HSR&D Research Career Development Award (Project #05-195) to [EY]. NR 46 TC 8 Z9 8 U1 0 U2 1 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 JUN PY 2012 VL 27 IS 6 BP 653 EP 660 DI 10.1007/s11606-011-1945-9 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 947BZ UT WOS:000304402900009 PM 22180196 ER PT J AU Pandhi, N DeVoe, JE Schumacher, JR Bartels, C Thorpe, CT Thorpe, JM Smith, MA AF Pandhi, Nancy DeVoe, Jennifer E. Schumacher, Jessica R. Bartels, Christie Thorpe, Carolyn T. Thorpe, Joshua M. Smith, Maureen A. TI Number of First-Contact Access Components Required to Improve Preventive Service Receipt in Primary Care Homes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE patient-centered medical home; preventive medicine; access to care; continuity of care; primary care; health care utilization; aging ID INFLUENZA VACCINATION; SCREENING MAMMOGRAPHY; METAANALYSIS; MORTALITY; ADULTS; CONTINUITY; COMMUNITY; DEATHS; US AB A fundamental aim of primary care redesign and the patient-centered medical home is improving access to care. Patients who report having a usual site of care and usual provider are more likely to receive preventive services, but less is known about the influence of specific components of first-contact access (e.g., availability of appointments, advice by telephone) on preventive services receipt. To examine the relationship between number of first-contact access components and receipt of recommended preventive services. Secondary survey data analysis. Five thousand five hundred and seven insured adults who had continuity with a usual primary care physician and participated in the 2003-2006 round of the Wisconsin Longitudinal Survey. Using multivariable logistic regression, we calculated adjusted risk ratios, adjusted predicted probabilities and 95% confidence intervals for each preventive service. Experiencing more first-contact access components was significantly associated with a higher rate of receiving cholesterol tests, flu shots and prostate exams but not mammography. There was variation in the number of components needed (between two and seven) to achieve a significant difference. Having an increasing number of first-access components in a primary care office may improve preventive services receipt, and more components may be required for those services requiring greater provider contact (e.g., prostate exam) versus those that require less (e.g., mammography). In primary care redesign, the largest gains in preventive services receipt likely will come with redesign of multiple components simultaneously. While our study is a necessary step towards broadly understanding the relationship between first-contact access and preventive service receipt, other important questions remain. Certain components may drive greater improvements in the receipt of different services, and the effect of some of these components may depend on individual patient characteristics. Further research is critical for understanding redesign strategies that may optimize preventive service delivery. C1 [Pandhi, Nancy; Smith, Maureen A.] Univ Wisconsin Madison, Dept Family Med, Madison, WI USA. [Pandhi, Nancy; Smith, Maureen A.] Univ Wisconsin Madison, Dept Populat Hlth Sci, Madison, WI USA. [DeVoe, Jennifer E.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97201 USA. [Schumacher, Jessica R.] Univ Florida Gainesville, Dept Hlth Serv Res Management & Policy, Gainesville, FL USA. [Bartels, Christie] Univ Wisconsin, Dept Med, Rheumatol Sect, Sch Med & Publ Hlth, Madison, WI USA. [Thorpe, Carolyn T.; Thorpe, Joshua M.] Vet Affairs Pittsburgh Healthcare Syst, Hlth Serv Res & Dev, Pittsburgh, PA USA. [Thorpe, Carolyn T.; Thorpe, Joshua M.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Pandhi, Nancy; Schumacher, Jessica R.; Bartels, Christie; Thorpe, Carolyn T.; Thorpe, Joshua M.; Smith, Maureen A.] Univ Wisconsin, Hlth Innovat Program, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. [Smith, Maureen A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth Madison, Madison, WI 53706 USA. RP Pandhi, N (reprint author), 800 Univ Bay Dr,Box 9445, Madison, WI 53705 USA. EM nancy.pandhi@fammed.wisc.edu RI Thorpe, Joshua/C-1188-2013 FU University of Wisconsin Institute for Clinical and Translational Research (UW ICTR); NIH [1 UL1 RR025011]; National Institute on Aging [l K08 AG029527, R01 AG09775, R01 AG033285]; Agency for Healthcare Research and Quality (AHRQ) [K08 HS16181]; University of Wisconsin Carbone Cancer Center (UWCCC) from the National Cancer Institute [P30 CA014520]; Vilas Estate Trust; National Science Foundation; Spencer Foundation; Graduate School of the University of Wisconsin-Madison; UW School of Medicine and Public Health FX This project was supported by the Health Innovation Program and the Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research (UW ICTR) funded through an NIH Clinical and Translational Science Award (CTSA), grant number 1 UL1 RR025011. In addition, Nancy Pandhi is supported by a National Institute on Aging Mentored Clinical Scientist Research Career Development Award, grant number l K08 AG029527. Dr. DeVoe's time on this project was supported by grant number K08 HS16181 from the Agency for Healthcare Research and Quality (AHRQ). This project was also supported by the University of Wisconsin Carbone Cancer Center (UWCCC) Support Grant from the National Cancer Institute, grant number P30 CA014520. Additional support was provided by the UW School of Medicine and Public Health from the Wisconsin Partnership Program. This research uses data from the Wisconsin Longitudinal Study of the University of Wisconsin-Madison. Since 1991, the WLS has been supported principally by the National Institute on Aging (R01 AG09775, R01 AG033285), with additional support from the Vilas Estate Trust, the National Science Foundation, the Spencer Foundation, and the Graduate School of the University of Wisconsin-Madison. A public use file of data from the Wisconsin Longitudinal Study is available from the Wisconsin Longitudinal Study, University of Wisconsin-Madison, 1180 Observatory Drive, Madison, Wisconsin, 53706 and at http://www.ssc.wisc.edu/wlsresearch/data/. The view 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 37 TC 5 Z9 5 U1 1 U2 8 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 JUN PY 2012 VL 27 IS 6 BP 677 EP 684 DI 10.1007/s11606-011-1955-7 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 947BZ UT WOS:000304402900012 PM 22215269 ER PT J AU Chen, B Covinsky, KE Cenzer, IS Adler, N Williams, BA AF Chen, Bonnie Covinsky, Kenneth E. Cenzer, Irena Stijacic Adler, Nancy Williams, Brie A. TI Subjective Social Status and Functional Decline in Older Adults SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE health disparities; functional decline; geriatrics; socioeconomic status; determinants of health ID SELF-RATED HEALTH; SOCIOECONOMIC-STATUS; UNITED-STATES; WHITEHALL-II; LIFE-COURSE; MORTALITY; INEQUALITIES; AMERICANS; POSITION; OUTCOMES AB It is unknown whether subjective assessment of social status predicts health outcomes in older adults. To describe the relationship between subjective social status and functional decline in older adults. Longitudinal cohort study. The Health and Retirement Study, a nationally representative survey of community-dwelling older adults (2004-2008). Two thousand five hundred and twenty-three community-dwelling older adults. Self-report of social status (SSS), categorized into three groups, reported by participants who marked a 10-rung ladder to represent where they stand in society. Four-year functional decline (new difficulty in any of five activities of daily living, mobility decline and/or death) Mean age was 64; 46% were male, 85% were white. At baseline, lower SSS was associated with being younger, unmarried, of nonwhite race/ethnicity, higher rates of chronic medical conditions and ADL impairment (P < 0.01). Over 4 years, 50% in the lowest SSS group declined in function, compared to the middle and highest groups (28% and 26%), P-trend < 0.001. Those in the lowest rungs of SSS were at increased risk of 4-year functional decline (unadjusted RR = 1.91, CI 1.-9-2.46). The relationship between a subjective belief that one is worse off than others and functional decline persisted after serial adjustment for demographics, objective SES measures, and baseline health and functional status (RR 1.36, CI 1.08-1.73). In older adults, the belief that one is in the lowest rungs of social status is a measure of socioeconomic distress and of significant risk for functional decline. These findings suggest that self-report of low subjective social status may give clinicians additional information about which older adults are at high risk for future functional decline. C1 [Covinsky, Kenneth E.; Cenzer, Irena Stijacic; Williams, Brie A.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94143 USA. [Covinsky, Kenneth E.; Williams, Brie A.] Hlth Serv Res & Dev Res Enhancement Award Program, San Francisco VA Med Ctr, San Francisco, CA USA. [Adler, Nancy] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Adler, Nancy] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Adler, Nancy] Univ Calif San Francisco, Ctr Hlth & Commun, San Francisco, CA 94143 USA. RP Williams, BA (reprint author), Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94143 USA. EM brie.williams@ucsf.edu FU Brookdale Leadership in Aging Fellowship; National Institute on Aging [K23AG033102, R01 AG028481, K24 AG029812]; UCSF Hartford Foundation Center of Excellence; Program for the Aging Century; MacArthur Foundation Research Network on Socioeconomic Status and Health; Veterans Affairs Medical Center, San Francisco, California FX Dr. Williams was funded by the Brookdale Leadership in Aging Fellowship, the National Institute on Aging (K23AG033102), the UCSF Hartford Foundation Center of Excellence Physician-Scholar Award and the Program for the Aging Century. Dr. Covinsky was supported by the National Institute on Aging (R01 AG028481and K24 AG029812). The R01 was administered by the Northern California Institute for Research and Education, and with resources of the San Francisco Veterans Affairs Medical Center. Dr. Adler received support from the MacArthur Foundation Research Network on Socioeconomic Status and Health. These funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. This work was supported with resources of the Veterans Affairs Medical Center, San Francisco, California. Drs. Williams and Covinsky are employees of the Department of Veterans Affairs. The opinions expressed in this manuscript may not represent those of the VA. NR 40 TC 17 Z9 17 U1 1 U2 12 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 JUN PY 2012 VL 27 IS 6 BP 693 EP 699 DI 10.1007/s11606-011-1963-7 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 947BZ UT WOS:000304402900014 PM 22215272 ER PT J AU Dinh, TA Alperin, P Walter, LC Smith, R AF Dinh, Tuan A. Alperin, Peter Walter, Louise C. Smith, Robert TI Impact of Comorbidity on Colorectal Cancer Screening Cost-Effectiveness Study in Diabetic Populations SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE colorectal cancer screening; cost-effectiveness analysis; health care modeling; comorbidity; optimal screening cessation; individualized guidelines ID SERVICES TASK-FORCE; FECAL OCCULT BLOOD; ADJUSTED LIFE-YEAR; UNITED-STATES; PHYSICAL-ACTIVITY; AMERICAN-COLLEGE; WOMENS HEALTH; EQ-5D INDEX; RISK; COLONOSCOPY AB Although comorbidity has been shown to affect the benefits and risks of colorectal cancer (CRC) screening, it has not been accounted for in prior cost-effectiveness analyses of CRC screening. To evaluate the impact of diagnosis of diabetes mellitus, a highly prevalent comorbidity in U.S. adults aged 50 and older, on health and economic outcomes of CRC screening. Cost-effectiveness analysis using an integrated modeling framework. Derived from basic and epidemiologic studies, clinical trials, cancer registries, and a colonoscopy database. U.S. 50-year-old population. Lifetime. Costs are based on Medicare reimbursement rates. Colonoscopy screening at ten-year intervals, beginning at age 50, and discontinued after age 50, 60, 70, 80 or death. Health outcomes and cost effectiveness. Diabetes diagnosis significantly affects cost-effectiveness of CRC screening. For the same CRC screening strategy, a person without diabetes at age 50 gained on average 0.07-0.13 life years more than a person diagnosed with diabetes at age 50 or younger. For a population of 1,000 patients diagnosed with diabetes at baseline, increasing stop age from 70 years to 80 years increased quality-adjusted life years (QALYs) gained by 0.3, with an incremental cost-effectiveness ratio of $206,671/QALY. The corresponding figures for 1,000 patients without diabetes are 2.3 QALYs and $46,957/QALY. Cost-effectiveness results are sensitive to cost of colonoscopy and adherence to colonoscopy screening. Results depend on accuracy of model assumptions. Benefits of CRC screening differ substantially for patients with and without diabetes. Screening for CRC in patients diagnosed with diabetes at age 50 or younger is not cost-effective beyond age 70. Screening recommendations should be individualized based on the presence of comorbidities. C1 [Dinh, Tuan A.; Alperin, Peter] Archimedes Inc, San Francisco, CA 94105 USA. [Walter, Louise C.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. [Walter, Louise C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Smith, Robert] Amer Canc Soc, Canc Control Dept, Atlanta, GA 30329 USA. RP Dinh, TA (reprint author), Archimedes Inc, 201 Mission St,29th Floor, San Francisco, CA 94105 USA. EM tuan.dinh@archimedesmodel.com FU National Cancer Institute [1R01CA134425] FX The authors declare no conflict of interest. This study was carried out by Archimedes in collaboration with Drs. Smith and Walter. Dr. Walter is supported by a grant 1R01CA134425 from the National Cancer Institute. NR 68 TC 6 Z9 6 U1 0 U2 4 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 JUN PY 2012 VL 27 IS 6 BP 730 EP 738 DI 10.1007/s11606-011-1972-6 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 947BZ UT WOS:000304402900018 PM 22237663 ER PT J AU Vick, A Kraemer, RR Morris, JL Willett, LL Centor, RM Estrada, CA Rodriguez, JM AF Vick, Amanda Kraemer, Ryan R. Morris, Jason L. Willett, Lisa L. Centor, Robert M. Estrada, Carlos A. Rodriguez, J. Martin TI A 60-Year-Old Woman with Chorea and Weight Loss SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE diagnostic reasoning; clinical problem solving; dual process theory; illness scripts; chorea; paraneoplastic syndrome ID STRATEGIES; MODEL C1 [Vick, Amanda; Kraemer, Ryan R.; Morris, Jason L.; Willett, Lisa L.; Centor, Robert M.; Estrada, Carlos A.; Rodriguez, J. Martin] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Kraemer, Ryan R.; Morris, Jason L.; Centor, Robert M.; Estrada, Carlos A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Estrada, Carlos A.] Vet Affairs Natl Qual Scholars Program, Birmingham, AL USA. RP Rodriguez, JM (reprint author), Univ Alabama Birmingham, THT 229 1530 3rd Ave S, Birmingham, AL 35294 USA. EM mrodri2@uab.edu NR 11 TC 4 Z9 4 U1 0 U2 1 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 JUN PY 2012 VL 27 IS 6 BP 747 EP 751 DI 10.1007/s11606-011-1928-x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 947BZ UT WOS:000304402900021 PM 22143453 ER PT J AU Zorick, T Lee, B Mandelkern, MA Fong, T Robertson, C Ghahremani, DG Brown, AK Sumerel, B London, ED AF Zorick, T. Lee, B. Mandelkern, M. A. Fong, T. Robertson, C. Ghahremani, D. G. Brown, A. K. Sumerel, B. London, E. D. TI Low striatal dopamine receptor availability linked to caloric intake during abstinence from chronic methamphetamine abuse SO MOLECULAR PSYCHIATRY LA English DT Letter ID FOOD C1 [Zorick, T.; Lee, B.; Fong, T.; Ghahremani, D. G.; Brown, A. K.; Sumerel, B.; London, E. D.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Zorick, T.] Greater Los Angeles Vet Adm Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. [Mandelkern, M. A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. [Robertson, C.; London, E. D.] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA. [London, E. D.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. RP Zorick, T (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. EM elondon@mednet.ucla.edu FU NCRR NIH HHS [M01 RR000865, MO1 RR00865]; NIDA NIH HHS [P20 DA022539, R01 DA020726, R01 DA015179] NR 9 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JUN PY 2012 VL 17 IS 6 BP 569 EP 571 DI 10.1038/mp.2011.137 PG 4 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 947TU UT WOS:000304454700002 PM 22024765 ER PT J AU Prohaska, R Sibon, OCM Rudnicki, DD Danek, A Hayflick, SJ Verhaag, EM Vonk, JJ Margolis, RL Walker, RH AF Prohaska, Rainer Sibon, Ody C. M. Rudnicki, Dobrila D. Danek, Adrian Hayflick, Susan J. Verhaag, Esther M. Vonk, Jan J. Margolis, Russell L. Walker, Ruth H. TI Brain, blood, and iron: Perspectives on the roles of erythrocytes and iron in neurodegeneration SO NEUROBIOLOGY OF DISEASE LA English DT Review DE Neuroacanthocytosis; Neurodegeneration; Iron; NBIA ID KINASE-ASSOCIATED NEURODEGENERATION; INFANTILE NEUROAXONAL DYSTROPHY; INDEPENDENT PHOSPHOLIPASE A(2); HALLERVORDEN-SPATZ-SYNDROME; DISEASE-LIKE 2; DOMINANT CHOREA-ACANTHOCYTOSIS; LIGHT-POLYPEPTIDE GENE; KELL-NULL PHENOTYPE; MCLEOD-SYNDROME; HUNTINGTONS-DISEASE AB The terms "neuroacanthocytosis" (NA) and "neurodegeneration with brain iron accumulation" (NBIA) both refer to groups of genetically heterogeneous disorders, classified together due to similarities of their phenotypic or pathological findings. Even collectively, the disorders that comprise these sets are exceedingly rare and challenging to study. The NBIA disorders are defined by their appearance on brain magnetic resonance imaging, with iron deposition in the basal ganglia. Clinical features vary, but most include a movement disorder. New causative genes are being rapidly identified; however, the mechanisms by which mutations cause iron accumulation and neurodegeneration are not well understood. NA syndromes are also characterized by a progressive movement disorder, accompanied by cognitive and psychiatric features, resulting from mutations in a number of genes whose roles are also basically unknown. An overlapping feature of the two groups, NBIA and NA, is the occurrence of acanthocytes, spiky red cells with a poorly-understood membrane dysfunction. In this review we summarise recent developments in this field, specifically insights into cellular mechanisms and from animal models. Cell membrane research may shed light upon the significance of the erythrocyte abnormality, and upon possible connections between the two sets of disorders. Shared pathophysiologic mechanisms may lead to progress in the understanding of other types of neurodegeneration. Published by Elsevier Inc. C1 [Walker, Ruth H.] James P Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY 10468 USA. [Walker, Ruth H.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Prohaska, Rainer] Med Univ Vienna, Max F Perutz Labs, Vienna, Austria. [Sibon, Ody C. M.; Verhaag, Esther M.; Vonk, Jan J.] Univ Groningen, Sect Radiat & Stress Cell Biol, Dept Cell Biol, Univ Med Ctr Groningen, Groningen, Netherlands. [Rudnicki, Dobrila D.; Margolis, Russell L.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Div Neurobiol,Lab Genet Neurobiol, Baltimore, MD 21205 USA. [Danek, Adrian] Univ Munich, Neurol Klin & Poliklin, Munich, Germany. [Hayflick, Susan J.] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. [Hayflick, Susan J.] Oregon Hlth & Sci Univ, Dept Pediat & Neurol, Portland, OR 97201 USA. [Margolis, Russell L.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Margolis, Russell L.] Johns Hopkins Univ, Sch Med, Program Cellular & Mol Med, Baltimore, MD USA. RP Walker, RH (reprint author), James P Peters Vet Affairs Med Ctr, Dept Neurol 127, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM ruth.walker@mssm.edu RI Danek, Adrian/G-7339-2011 OI Danek, Adrian/0000-0001-8857-5383 FU National Institute of Neurological Diseases and Stroke; Office of Rare Diseases Research; National Institute of Child Health and Human Development [1R13NS067922-01]; Movement Disorder Society; Advocacy for Neuroacanthocytosis Patients (UK); Associazione Italiana Sindromi Neurodegenerative da Accumulo di Ferro (AISNAF) (Italy); NBIA Disorders Association (USA); Hoffnungsbaum e.V. (Germany); GlaxoSmithKline; European Multidisciplinary Initiative on Neuroacanthocytosis (EMINA) [01GM1003]; RP (FWF) [I 438-B13]; OCMS (ZonMW) [113301162] FX This article reflects presentations and discussion at a meeting entitled "Brain, Blood and Iron: Joint International Symposium on Neuroacanthocytosis and Neurodegeneration with Brain Iron Accumulation" which was held in Bethesda, MD, USA on Oct 1-2 2010. This meeting was supported by the National Institute of Neurological Diseases and Stroke; the Office of Rare Diseases Research, and the National Institute of Child Health and Human Development [1R13NS067922-01], and also by the Movement Disorder Society, Advocacy for Neuroacanthocytosis Patients (UK), Associazione Italiana Sindromi Neurodegenerative da Accumulo di Ferro (AISNAF) (Italy), NBIA Disorders Association (USA), Hoffnungsbaum e.V. (Germany) and GlaxoSmithKline. Funding by an ERA-Net E-Rare project, "European Multidisciplinary Initiative on Neuroacanthocytosis (EMINA)", is gratefully acknowledged by AD (BMBF/DLR grant 01GM1003), RP (FWF grant I 438-B13), and OCMS (ZonMW grant 113301162). NR 228 TC 22 Z9 23 U1 1 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 EI 1095-953X J9 NEUROBIOL DIS JI Neurobiol. Dis. PD JUN PY 2012 VL 46 IS 3 BP 607 EP 624 DI 10.1016/j.nbd.2012.03.006 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 950DK UT WOS:000304629300011 PM 22426390 ER PT J AU Madan, A Archambeau, OG Milsom, VA Goldman, RL Borckardt, JJ Grubaugh, AL Tuerk, PW Frueh, BC AF Madan, Alok Archambeau, Olga G. Milsom, Vanessa A. Goldman, Rachel L. Borckardt, Jeffery J. Grubaugh, Anouk L. Tuerk, Peter W. Frueh, B. Christopher TI More Than Black and White: Differences in Predictors of Obesity Among Native Hawaiian/Pacific Islanders and European Americans SO OBESITY LA English DT Article ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; DSM-IV; PACIFIC ISLANDERS; YOUNG-ADULTS; RISK-FACTORS; WEIGHT; HAWAIIANS; DISORDER; MINI AB Although Native Hawaiians and Pacific Islanders exhibit the highest rates of obesity and associated chronic diseases of any racial/ethnic group, they remain vastly underrepresented in health research. In a cross-sectional survey of college students (N = 402) we examined BMI and health outcomes in an ethno-racially diverse rural sample of Native Hawaiian/Pacific Islanders (25.1%), Asian Americans (39.8%), and European Americans (35.1%). Measures assessed BMI, health status, health behaviors, frequency of exercise, and symptoms of psychiatric disorders (i.e., depression, anxiety, posttraumatic stress, and substance abuse and dependence). Regression analyses revealed that an overall model of five predictors (gender, race, regular exercise, difficulty sleeping, and anxiety) was significantly associated with obesity (P < 0.001) and correctly classified 84.2% of cases. A 30.7% of Native Hawaiians/Pacific Islanders were obese as compared with 9.2% of European Americans and 10.6% of Asian Americans. These findings suggest that Native Hawaiian/Pacific Islanders are at high risk for obesity and associated medical comorbidities, but that regular physical activity may ameliorate this risk. Further, these results support the consideration of Native Hawaiians/Pacific Islanders as a distinct racial/ethnic subgroup separate from other Asian populations. C1 [Madan, Alok; Goldman, Rachel L.; Borckardt, Jeffery J.; Grubaugh, Anouk L.; Tuerk, Peter W.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Archambeau, Olga G.; Frueh, B. Christopher] Univ Hawaii, Dept Psychol, Hilo, HI 96720 USA. [Milsom, Vanessa A.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Grubaugh, Anouk L.; Tuerk, Peter W.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Frueh, B. Christopher] Menninger Clin, Houston, TX USA. RP Madan, A (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave, Charleston, SC 29425 USA. EM madana@musc.edu OI Goldman, Rachel/0000-0001-6147-3934 FU National Institute of Mental Health [MH074468]; McNair Foundation FX This work was partially supported by the grant MH074468 from the National Institute of Mental Health, and from the McNair Foundation. Elements of the current work were included in O.G.A.'s master's thesis. NR 18 TC 5 Z9 5 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 J9 OBESITY JI Obesity PD JUN PY 2012 VL 20 IS 6 BP 1325 EP 1328 DI 10.1038/oby.2012.15 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 948QO UT WOS:000304517900034 PM 22286530 ER PT J AU Maples, NJ Copeland, LA Zeber, JE Li, XY Moore, TA Dassori, A Velligan, DI Miller, AL AF Maples, Natalie J. Copeland, Laurel Anne Zeber, John E. Li, Xueying Moore, Troy A. Dassori, Albana Velligan, Dawn Irene Miller, Alexander L. TI Can Medication Management Coordinators Help Improve Continuity of Care After Psychiatric Hospitalization? SO PSYCHIATRIC SERVICES LA English DT Article ID ALGORITHM PROJECT; MENTAL-ILLNESS; RISK-FACTORS; SCHIZOPHRENIA; REHOSPITALIZATION; PATIENT; IMPLEMENTATION; INDIVIDUALS; STRATEGIES; DISORDER AB Objective: This demonstration project examined whether medication management coordinators enhanced continuity of care from inpatient facilities to an outpatient public mental health clinic. Methods: From 2004 to 2008, patients (N=325) hospitalized with schizophrenia or schizoaffeetive or bipolar disorder enrolled in a medication management program before discharge or at their first clinic appointment. Medication management coordinators supplemented existing clinic practices by identifying recently hospitalized patients, providing inpatient and outpatient prescribing clinicians with patients' complete medication history, meeting with patients for six months postdischarge to assess clinical status and provide medication education, and advocating guideline-concordant prescribing. Recently discharged patients (N=345) assigned to a different outpatient clinic within the same agency served as the comparison group. Intent-to-treat, repeated-measures analyses for mixed models compared the groups' number of hospital admissions, hospital days, and medication appointments kept and use of nurse or case manager contact hours and emergency or crisis services during the 12 months before enrollment, the six-month intervention, and the six-month follow-up period. Results: After discharge, individuals enrolled in medication management were more likely than comparison patients to attend outpatient appointments, and they had more medication visits and nurse or case manager treatment hours than the comparison group. Use of hospital and crisis or emergency services by all patients decreased. Almost one-third of patients never attended an outpatient appointment after hospital discharge. Conclusions: Although this program succeeded in improving continuity of care, additional interventions may be required to reduce rehospitalization and crisis care. (Psychiatric Services 63:554-560, 2012; doi: 10.1176/appi.ps.201100264) C1 [Maples, Natalie J.; Li, Xueying; Moore, Troy A.; Velligan, Dawn Irene; Miller, Alexander L.] UT Hlth Sci Ctr San Antonio, Div Schizophrenia & Related Disorders, Dept Psychiat, San Antonio, TX 78229 USA. [Copeland, Laurel Anne; Zeber, John E.] Scott & White Healthcare, Ctr Appl Hlth Res, Temple, TX USA. [Copeland, Laurel Anne; Zeber, John E.] Cent Texas Vet Hlth Care Syst, Temple, TX USA. [Dassori, Albana] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Maples, NJ (reprint author), UT Hlth Sci Ctr San Antonio, Div Schizophrenia & Related Disorders, Dept Psychiat, 7703 Floyd Curl Dr,MS 7797, San Antonio, TX 78229 USA. EM maplesn@uthscsa.edu OI Copeland, Laurel/0000-0002-9478-0209 FU AstraZeneca; U.S. Veterans Health Administration; UT Health Science Center San Antonio; Scott & White Healthcare; GlaxoSmithKline; Pfizer FX This demonstration project was funded by AstraZeneca through a grant to the National Center for Behavioral Health Care Solutions, a 501(c)3 organization affiliated with the Center for Health Care Services. Additional support was provided by the U.S. Veterans Health Administration, the UT Health Science Center San Antonio, and Scott & White Healthcare. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the U.S. Department of Veterans Affairs or the U.S. government.; Dr. Zeber received a research grant in 2011-2012 from GlaxoSmithKline as principal investigator for one site of a multisite study unrelated to this article. Dr. Velligan is a consultant for or on the advisory boards of Ortho-McNeil Janssen Pharmaceuticals, Teva Pharmaceuticals, AstraZeneca Pharmaceuticals, Roche Genentech, Abbott Pharmaceuticals, Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Bristol-Myers Squibb, Amgen, and Merck and Shire Pharmaceuticals. Dr. Miller is a member of the data monitoring committee for Otsuka and was on the advisory board of Myriad RBM in 2010. He has received investigator-initiated grant funding from Pfizer. The other authors report no competing interests. NR 25 TC 4 Z9 4 U1 0 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JUN PY 2012 VL 63 IS 6 BP 554 EP 560 DI 10.1176/appi.ps.201100264 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 949IE UT WOS:000304569100007 PM 22476107 ER PT J AU Gellis, LA AF Gellis, Les A. TI An Investigation of a Cognitive Refocusing Technique To Improve Sleep SO PSYCHOTHERAPY LA English DT Article DE insomnia; cognitive therapy; behavior therapy; sleep ID CHRONIC INSOMNIA; VALIDATION; THOUGHTS; INDEX AB Developing techniques designed to minimize arousing cognitions during the evening may be important to help improve the treatment of insomnia. This investigation assessed an intervention that focused exclusively on enhancing cognitive refocusing at sleep onset to change the content and style of presleep cognitions in order to improve sleep. Individuals with primary insomnia (N = 10; 90% male, mean age = 49.2, SD = 12.6) attended four weekly individual meetings. Sleep quality (the Pittsburgh Sleep Quality Index), insomnia severity (the Insomnia Severity Index), sleep parameters based on one week of sleep diaries, and arousing thought content, were compared at baseline, posttreatment, and at a 1-month follow-up. Adherence was high, and participants showed good ability to engage in the procedure. Significant improvements in sleep quality, insomnia severity, sleep onset latency, total sleep time, and arousing thought content were revealed. Large effect sizes were observed on the majority of sleep variables at follow-up. Preliminary results were encouraging regarding a technique that targets the refocusing of thoughts during the evening in order to improve sleep. Further study regarding the efficacy of this procedure is warranted. C1 [Gellis, Les A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Gellis, LA (reprint author), Syracuse Univ, Dept Psychol, 430 Huntington Hall, Syracuse, NY 13244 USA. EM lesgellis@gmail.com NR 24 TC 3 Z9 3 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC, DIV PSYCHOTHERAPY PI CORAL GABLES PA 1390 SOUTH DIXIE HIGHWAY, STE 2222, CORAL GABLES, FL 33146-2946 USA SN 0033-3204 J9 PSYCHOTHERAPY JI Psychotherapy PD JUN PY 2012 VL 49 IS 2 BP 251 EP 257 DI 10.1037/a0025746 PG 7 WC Psychology, Clinical SC Psychology GA 951TH UT WOS:000304742400018 PM 22309052 ER PT J AU Rosenbaum, JT Ku, J Ali, A Choi, D Suhler, EB AF Rosenbaum, James T. Ku, Jennifer Ali, Amro Choi, Dongseok Suhler, Eric B. TI Patients with Retinal Vasculitis Rarely Suffer from Systemic Vasculitis SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Review DE retinal vasculitis; vasculitis; Behcet's; granulomatosis with polyangiitis; polyarteritis nodosa ID POLYARTERITIS-NODOSA; WEGENERS GRANULOMATOSIS; OCULAR MANIFESTATIONS; DISEASE; COMPLICATIONS; UVEITIS AB Objectives: Systemic vasculitis is often mistakenly assumed to be a common cause of retinal vasculitis. We sought to determine the relationship between retinal vasculitis and systemic vasculitis. Methods: A selected review was performed on 1390 charts of patients attending the uveitis clinic at the Oregon Health and Science University between 1985 and 2010. Included in the review were all patients with diagnoses commonly associated with retinal vasculitis and all patients who were diagnosed with a systemic vasculitis. Retinal vasculitis was identified by perivascular exudates, intraretinal hemorrhage, or cotton wool spots as seen on clinical examination or by vascular occlusion or leakage as identified by fluorescein angiogram. Results: Two hundred seven or 14.9% of patients with uveitis had retinal vasculitis as a component of the intraocular inflammation. Thirty-five patients had retinal vasculitis that was primary, ie, not associated with a systemic disease, and the dominant manifestation of the uveitis. Fourteen of the patients with retinal vasculitis had Behcet's disease. Only 11 of the 1390 patients with uveitis had a systemic vasculitis. Of these 11, four had retinal vasculitis including 1 secondary to a cytomegalovirus retinitis. Thus, systemic vasculitis was directly responsible for 1.4% or 3 of 207 cases of retinal vasculitis. Nonvasculitic systemic diseases such as sarcoidosis (n = 13), syndromes confined to the eye such as pars planitis (n = 36), and intraocular infections (n = 29) were far more common causes of retinal vasculitis. Conclusions: Retinal vasculitis is a relatively common feature of uveitis. Patients with retinal vasculitis, however, rarely suffer from 1 of the classical systemic vasculitides. (C) 2012 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 41:859-865 C1 [Rosenbaum, James T.; Ali, Amro; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97239 USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Ku, Jennifer; Choi, Dongseok] Oregon Hlth & Sci Univ, Dept Publ Hlth, Portland, OR 97239 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. RP Rosenbaum, JT (reprint author), Oregon Hlth & Sci Univ, Dept Ophthalmol, 3181 SW Sam Jackson Pk Rd,L467Ad, Portland, OR 97239 USA. EM rosenbaj@ohsu.edu FU Research to Prevent Blindness; William C. Kuzell Foundation; Stan and Madelle Rosenfeld Family Trust; William and Mary Bauman Foundation FX This work was supported by Research to Prevent Blindness, the William C. Kuzell Foundation, the Stan and Madelle Rosenfeld Family Trust, and the William and Mary Bauman Foundation. NR 24 TC 11 Z9 11 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0049-0172 J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD JUN PY 2012 VL 41 IS 6 BP 859 EP 865 DI 10.1016/j.semarthrit.2011.10.006 PG 7 WC Rheumatology SC Rheumatology GA 950XL UT WOS:000304685100012 PM 22177107 ER PT J AU Weycker, D Malin, J Barron, R Edelsberg, J Kartashov, A Oster, G AF Weycker, Derek Malin, Jennifer Barron, Rich Edelsberg, John Kartashov, Alex Oster, Gerry TI Comparative Effectiveness of Filgrastim, Pegfilgrastim, and Sargramostim as Prophylaxis Against Hospitalization for Neutropenic Complications in Patients With Cancer Receiving Chemotherapy SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE filgrastim; pegfilgrastim; sargramostim; febrile neutropenia; outcomes ID COLONY-STIMULATING FACTOR; SINGLE-ADMINISTRATION PEGFILGRASTIM; BREAST-CANCER; MYELOSUPPRESSIVE CHEMOTHERAPY; FEBRILE NEUTROPENIA; DOSE-INTENSITY; DOUBLE-BLIND; PHASE-III; RHUGM-CSF; MULTICENTER AB Background: Comparative effectiveness of filgrastim, pegfilgrastim, and sargramostim in preventing hospitalization for febrile neutropenia (FN) during myelosuppressive chemotherapy has not been well characterized and is an important clinical question in oncology. Methods: This study used a retrospective cohort design and US healthcare claims data. Source population included patients with solid tumors receiving filgrastim, pegfilgrastim, or sargramostim during their first observed course of chemotherapy between July 2001 and June 2007. For each patient, every unique chemotherapy cycle during the course was identified, along with each cycle in which filgrastim, pegfilgrastim, or sargramostim was administered by the fifth day of the cycle (ie, as prophylaxis). Risks of hospitalization for neutropenic complications (broad definition: admission with a diagnosis of neutropenia, fever, or infection; narrow definition: admission with a diagnosis of neutropenia) and for any reason were examined on a cycle-specific basis during all the cycles in which colony-stimulating factor prophylaxis was administered. Unadjusted and adjusted odds ratios (ORs) for hospitalization were estimated. Results: Risk (unadjusted) of hospitalization for neutropenic complications (narrow definition) was 2.1% for filgrastim prophylaxis (n = 8286), 1.1% for pegfilgrastim prophylaxis (n = 67,247), and 2.5% for sargramostim prophylaxis (n = 1736). Corresponding risks of hospitalization based on the broad definition were 4.0%, 2.6%, and 5.1%. Risks of all-cause hospitalization were 7.9%, 5.3%, and 9.6%, respectively. Adjusted odds of hospitalization were significantly higher for filgrastim [OR (range across the 3 alternative measures of hospitalization): 1.58-1.79; P<0.001] and sargramostim (OR: 1.89-2.68; P<0.001) versus pegfilgrastim. Conclusions: Risk of hospitalization for neutropenic complications during cancer chemotherapy is lower with pegfilgrastim prophylaxis than with filgrastim or sargramostim prophylaxis. C1 [Weycker, Derek; Edelsberg, John; Kartashov, Alex; Oster, Gerry] PAI, Four Davis Court, Brookline, MA 02445 USA. [Malin, Jennifer] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Barron, Rich] Amgen Inc, Global Hlth Econ, Thousand Oaks, CA 91320 USA. RP Weycker, D (reprint author), PAI, Four Davis Court, Brookline, MA 02445 USA. EM dweycker@pai2.com FU Amgen Inc FX Funding for this research was provided by Amgen Inc, to Policy Analysis Inc (PAI). NR 28 TC 19 Z9 19 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD JUN PY 2012 VL 35 IS 3 BP 267 EP 274 DI 10.1097/COC.0b013e31820dc075 PG 8 WC Oncology SC Oncology GA 946QF UT WOS:000304367400012 PM 21378538 ER PT J AU Alessi, CA Vitiello, MV AF Alessi, Cathy A. Vitiello, Michael V. TI Sleep Disturbance Among Older Adults in Long-Term Care: A Significant Problem in an Important Clinical Setting SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Editorial Material ID HOMES C1 [Alessi, Cathy A.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Geriatr Res Educ & Clin, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Vitiello, Michael V.] Univ Washington, Seattle, WA 98195 USA. RP Alessi, CA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Geriatr Res Educ & Clin, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. EM cathy.alessi@va.gov OI Vitiello, Michael/0000-0002-9776-0473 NR 12 TC 1 Z9 1 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUN PY 2012 VL 20 IS 6 BP 457 EP 459 DI 10.1097/JGP.0b013e31825688e4 PG 3 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 945FC UT WOS:000304257200001 PM 22517060 ER PT J AU Martin, JL Jouldjian, S Mitchell, MN Josephson, KR Alessi, CA AF Martin, Jennifer L. Jouldjian, Stella Mitchell, Michael N. Josephson, Karen R. Alessi, Cathy A. TI A Longitudinal Study of Poor Sleep After Inpatient Post-Acute Rehabilitation: The Role of Depression and Pre-Illness Sleep Quality SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Aging; depression; rehabilitation; sleep ID HIP FRACTURE; RATING-SCALE; OLDER-ADULTS; RECOVERY; MORTALITY; SYMPTOMS AB Objectives: To explore the unique impact of poor sleep and symptoms of depression on sleep quality for up to 1 year after inpatient post-acute rehabilitation among older adults. Design: Prospective longitudinal cohort study. Setting: Two inpatient post-acute rehabilitation facilities. Participants: A total of 245 individuals older than 65 years (mean age = 80 years, 38% women). Interventions: None. Measurements: Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) during the post-acute care stay twice to evaluate pre-illness sleep quality and sleep quality during the post-acute care stay, and again at 3-, 6-, 9-, and 12-month follow-up. Demographics, symptoms of depression, cognitive functioning, and comorbidities were also assessed. Results: Across time points, sleep was significantly disturbed for many individuals. Nested regression models predicting PSQI total score at 3, 6, 9, and 12 months showed that variables entered in Block 1 (age, gender, cognitive functioning, and comorbidities) were significant predictors of poor sleep at 6-month follow-up but not at 3-, 9-, or 12-month follow-up. Depression (Block 2) and pre-illness PSQI total score (Block 3) were significant predictors of PSQI total score at all follow-up time points. PSQI total score during post-acute care (Block 4) explained a significant proportion of variance only at the 3-month follow-up. Conclusions: This study confirms that chronic poor sleep is common among older adults during postacute rehabilitation and resolution of sleep disturbance after acute health events may be a lengthy process. Our findings expand understanding of the role of depressive symptoms and preexisting sleep complaints in predicting poor sleep over time among these vulnerable older adults. (Am J Geriatr Psychiatry 2012; 20:477-484) C1 [Martin, Jennifer L.; Alessi, Cathy A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Martin, Jennifer L.; Jouldjian, Stella; Mitchell, Michael N.; Josephson, Karen R.; Alessi, Cathy A.] VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. RP Martin, JL (reprint author), VA GRECC 11E, 16111 Plummer St, North Hills, CA 91343 USA. EM jennifer.martin@va.gov FU NIA [K23 AG028452]; UCLA Claude Pepper Older Americans Independence Center [AG-10415]; VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center; VA Health Services Research Development [IIR-01-053-1, IIR 04-321-2, AIA-03-047] FX This study was supported by NIA K23 AG028452; UCLA Claude Pepper Older Americans Independence Center (AG-10415), VA Health Services Research & Development IIR-01-053-1, IIR 04-321-2, and AIA-03-047; and VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center. NR 24 TC 2 Z9 3 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUN PY 2012 VL 20 IS 6 BP 477 EP 484 DI 10.1097/JGP.0b013e31824877c1 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 945FC UT WOS:000304257200004 PM 22617164 ER PT J AU Fung, CH Martin, JL Chung, C Fiorentino, L Mitchell, M Josephson, KR Jouldjian, S Alessi, C AF Fung, Constance H. Martin, Jennifer L. Chung, Carol Fiorentino, Lavinia Mitchell, Michael Josephson, Karen R. Jouldjian, Stella Alessi, Cathy TI Sleep Disturbance Among Older Adults in Assisted Living Facilities SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Assisted living facilities; long-term care; sleep ID NURSING-HOME RESIDENTS; ALZHEIMERS-DISEASE; DEPRESSION; QUALITY; SYMPTOMS; INSOMNIA; QUESTIONNAIRE; COMORBIDITY; COMPLAINTS; DIAGNOSIS AB Objectives: To evaluate whether objectively and subjectively measured sleep disturbances persist among older adults in assisted living facilities (ALFs) and to identify predictors of sleep disturbance in this setting. Design: Prospective, observational cohort study. Setting and Participants: A total of 121 residents, age >= 65 years, in 18 ALFs in the Los Angeles area. Measurements: Objective (actigraphy) and subjective (Pittsburgh Sleep Quality Index) sleep measures were collected at baseline and 3- and 6-month follow-up. Predictors of baseline sleep disturbance tested in bivariate analyses and multiple regression models included demographics, Mini-Mental State Examination score, number of comorbidities, nighttime sedating medication use, functional status (activities of daily living; instrumental activities of daily living), restless legs syndrome, and sleep apnea risk. Results: Objective and subjective sleep measures were similar at baseline and 3- and 6-month follow-up (objective nighttime total sleep [hours] 6.3, 6.5, and 6.4; objective nighttime percent sleep 77.2, 77.7, and 78.3; and Pittsburgh Sleep Quality Index total score 8.0, 7.8, and 7.7, respectively). The mean baseline nighttime percent sleep decreased by 2% for each additional unit increase in baseline comorbid conditions (measured as the number of conditions), and increased by 4.5% for each additional unit increase in baseline activities of daily living (measured as the number of activities of daily living), in a multiple regression model. Conclusions: In this study, we found that objectively and subjectively measured sleep disturbances are persistent among ALF residents and are related to a greater number of comorbidities and poorer functional status at baseline. Interventions are needed to improve sleep in this setting. (Am J Geriatr Psychiatry 2012; 20:485-493) C1 [Fung, Constance H.; Martin, Jennifer L.; Josephson, Karen R.; Jouldjian, Stella; Alessi, Cathy] Vet Adm Greater Los Angeles Healthcare Syst, GRECC, North Hills, CA 91343 USA. [Martin, Jennifer L.; Chung, Carol; Mitchell, Michael; Alessi, Cathy] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Fiorentino, Lavinia] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Fung, CH (reprint author), VA Greater Los Angeles Healthcare Syst, GRECC 11E, 16111 Plummer St, North Hills, CA 91343 USA. EM Connie.Fung@va.gov FU VA Advanced Geriatrics Fellowship Program; NIH NIA [K23 AG028452]; NIMH [T32 MH 019925-11]; UCLA Academic Senate Council on Research; VA Greater Los Angeles Healthcare System, Geriatric Research, Education and Clinical Center; VA Health Services Research and Development [IIR 04-321-2]; UCLA Cousins Center for Psychoneuroimmunology; Sepracor Inc., Marlborough, MA FX This study was supported by the VA Advanced Geriatrics Fellowship Program; NIH NIA K23 AG028452, NIMH T32 MH 019925-11; UCLA Academic Senate Council on Research; VA Greater Los Angeles Healthcare System, Geriatric Research, Education and Clinical Center; VA Health Services Research and Development (IIR 04-321-2); and UCLA Cousins Center for Psychoneuroimmunology. Additional financial support was provided by Sepracor Inc., Marlborough, MA. The authors thank the study project coordinators, Terry Vandenberg, MA, and Rebecca Saia, the research staff, the staff at the participating facilities, and the ALF residents. NR 39 TC 8 Z9 8 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUN PY 2012 VL 20 IS 6 BP 485 EP 493 DI 10.1097/JGP.0b013e318252e3e0 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 945FC UT WOS:000304257200005 PM 22531104 ER PT J AU Strakowski, SM Adler, CM Almeida, J Altshuler, LL Blumberg, HP Chang, KKD DelBello, MP Frangou, S McIntosh, A Phillips, ML Sussman, JE Townsend, JD AF Strakowski, Stephen M. Adler, Caleb M. Almeida, Jorge Altshuler, Lori L. Blumberg, Hilary P. Chang, Kiki D. DelBello, Melissa P. Frangou, Sophia McIntosh, Andrew Phillips, Mary L. Sussman, Jessika E. Townsend, Jennifer D. TI The functional neuroanatomy of bipolar disorder: a consensus model SO BIPOLAR DISORDERS LA English DT Article DE amygdala; bipolar disorder; connectivity; functional magnetic resonance imaging (fMRI); neuroimaging; prefrontal cortex ID VENTRAL PREFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX; WHITE-MATTER INTEGRITY; FACIAL EXPRESSIONS; AMYGDALA; ABNORMALITIES; FMRI; ADOLESCENTS; ACTIVATION; DEPRESSION AB Strakowski SM, Adler CM, Almeida J, Altshuler LL, Blumberg HP, Chang KD, DelBello MP, Frangou S, McIntosh A, Phillips ML, Sussman JE, Townsend JD. The functional neuroanatomy of bipolar disorder: a consensus model. ?Bipolar Disord 2012: 14: 313325. (c) 2012 The Authors. Journal compilation (c) 2012 John Wiley & Sons A/S. Objectives: Functional neuroimaging methods have proliferated in recent years, such that functional magnetic resonance imaging, in particular, is now widely used to study bipolar disorder. However, discrepant findings are common. A workgroup was organized by the Department of Psychiatry, University of Cincinnati (Cincinnati, OH, USA) to develop a consensus functional neuroanatomic model of bipolar I disorder based upon the participants work as well as that of others. Methods: Representatives from several leading bipolar disorder neuroimaging groups were organized to present an overview of their areas of expertise as well as focused reviews of existing data. The workgroup then developed a consensus model of the functional neuroanatomy of bipolar disorder based upon these data. Results: Among the participants, a general consensus emerged that bipolar I disorder arises from abnormalities in the structure and function of key emotional control networks in the human brain. Namely, disruption in early development (e.g., white matter connectivity and prefrontal pruning) within brain networks that modulate emotional behavior leads to decreased connectivity among ventral prefrontal networks and limbic brain regions, especially the amygdala. This developmental failure to establish healthy ventral prefrontallimbic modulation underlies the onset of mania and ultimately, with progressive changes throughout these networks over time and with affective episodes, a bipolar course of illness. Conclusions: This model provides a potential substrate to guide future investigations and areas needing additional focus are identified. C1 [Strakowski, Stephen M.; Adler, Caleb M.; DelBello, Melissa P.] Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, Cincinnati, OH 45267 USA. [Almeida, Jorge; Phillips, Mary L.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Altshuler, Lori L.; Townsend, Jennifer D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Altshuler, Lori L.] VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. [Blumberg, Hilary P.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Chang, Kiki D.] Stanford Univ, Pediat Bipolar Disorders Res Program, Div Child & Adolescent Psychiat, Dept Psychiat & Behav Sci,Sch Med, Stanford, CA 94305 USA. [Frangou, Sophia] Kings Coll London, Sect Neurobiol Psychosis, Dept Psychosis Studies, Inst Psychiat, London WC2R 2LS, England. [McIntosh, Andrew; Sussman, Jessika E.] Univ Edinburgh, Div Psychiat, Sch Mol & Clin Med, Edinburgh, Midlothian, Scotland. [Phillips, Mary L.] Cardiff Univ Sch Med, Dept Psychol Med, Cardiff, S Glam, Wales. RP Strakowski, SM (reprint author), Univ Cincinnati, Coll Med, Dept Psychiat, 260 Stetson Suite 3200, Cincinnati, OH 45267 USA. EM stephen.strakowski@uc.edu RI McIntosh, Andrew/B-9379-2008; Frangou, Sophia/A-2672-2013; Almeida, Jorge/O-5185-2014 OI McIntosh, Andrew/0000-0002-0198-4588; Almeida, Jorge/0000-0002-1213-1986 FU NIH [P50 MH077138, R01 MH076971, R01 MH088371, 2R01MH070902, 1RC1MH088366, R01MH069747, 5R21MH075944, 1K24MH001848, 1R01MH084955, R01 MH077047, R01 MH080973, R01 MH078043] FX This workgroup was supported in part by the Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH, USA. This manuscript was supported in part by NIH grants P50 MH077138 (SMS); R01 MH076971 and R01 MH088371 (MLP); 2R01MH070902, 1RC1MH088366, and R01MH069747 (HPB); 5R21MH075944, 1K24MH001848, and 1R01MH084955 (LLA); R01 MH077047 (KDC); R01 MH080973 (MPD); and R01 MH078043 (CMA). NR 72 TC 147 Z9 151 U1 5 U2 31 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2012 VL 14 IS 4 BP 313 EP 325 DI 10.1111/j.1399-5618.2012.01022.x PG 13 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 947PE UT WOS:000304441200001 PM 22631617 ER PT J AU Townsend, J Altshuler, LL AF Townsend, Jennifer Altshuler, Lori L. TI Emotion processing and regulation in bipolar disorder: a review SO BIPOLAR DISORDERS LA English DT Review DE amygdala; bipolar disorder; emotion processing; emotion regulation; functional neuroimaging; vlPFC ID INCREASED AMYGDALA ACTIVATION; FACIAL AFFECT RECOGNITION; MEDIAL PREFRONTAL CORTEX; FUNCTIONAL CONNECTIVITY; NEGATIVE EMOTION; MOOD DISORDERS; RHESUS-MONKEY; VOLUNTARY SUPPRESSION; ORBITOFRONTAL CORTEX; COGNITIVE CONTROL AB Townsend J, Altshuler LL. Emotion processing and regulation in bipolar disorder: a review. ?Bipolar Disord 2012: 14: 326339. (c) 2012 The Authors. Journal compilation (c) 2012 John Wiley & Sons A/S. Objectives: Bipolar disorder (BP) is characterized by a dysfunction of mood, alternating between states of mania/hypomania and depression. Thus, the primary abnormality appears to be an inability to regulate emotion, the result of which is emotional extremes. The purpose of this paper is to review the current functional magnetic resonance imaging (fMRI) literature on adult patients with BP using emotion processing or regulation paradigms. Methods: A search was conducted on PubMed using the keywords: bipolar disorder, fMRI, mania, bipolar depression, bipolar euthymia, emotion, and amygdala. Only those studies that were conducted in adult patients using an emotion activation task were included in the final review. Results: Using tasks that assess neural functioning during emotion processing and emotion regulation, many fMRI studies have examined BP subjects during mania and euthymia. Fewer fMRI studies have been conducted during depression, and fewer still have included the same subjects in multiple mood states. Despite these limitations, these studies have demonstrated specific abnormalities in frontallimbic regions. Using a variety of paradigms, investigators have specifically evaluated the amygdala (a structure within the limbic system known to be critical for emotion) and the prefrontal cortex (PFC) (a region known to have a regulatory function over the limbic system). Conclusions: These investigations reveal that amygdala activation varies as a function of mood state, while the PFC remains persistently hypoactivated across mood states. Emotional dysregulation and lability in mania and depression may reflect disruption of a frontallimbic functional neuroanatomical network. C1 [Townsend, Jennifer; Altshuler, Lori L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Townsend, Jennifer; Altshuler, Lori L.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Altshuler, Lori L.] VA 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, 300 UCLA Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu FU Forest Laboratories; Sepracor; Eli Lilly Co. FX LLA has received past funding from Forest Laboratories (advisory board honoraria, March 2008), Sepracor (advisory board honoraria, January 2010), and Eli Lilly & Co. (consultant, September 2010). JT does not have any commercial associations that might pose a conflict of interest in connection with this manuscript. NR 117 TC 91 Z9 93 U1 9 U2 64 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2012 VL 14 IS 4 BP 326 EP 339 DI 10.1111/j.1399-5618.2012.01021.x PG 14 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 947PE UT WOS:000304441200002 PM 22631618 ER PT J AU Townsend, JD Bookheimer, SY Foland-Ross, LC Moody, TD Eisenberger, NI Fischer, JS Cohen, MS Sugar, CA Altshuler, LL AF Townsend, Jennifer D. Bookheimer, Susan Y. Foland-Ross, Lara C. Moody, Teena D. Eisenberger, Naomi I. Fischer, Jeffrey S. Cohen, Mark S. Sugar, Catherine A. Altshuler, Lori L. TI Deficits in inferior frontal cortex activation in euthymic bipolar disorder patients during a response inhibition task SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; fMRI; orbitofrontal cortex; response inhibition; striatum ID MEDIAL PREFRONTAL CORTEX; BRAIN ACTIVATION; I DISORDER; FMRI; MANIA; ABNORMALITIES; MONKEYS; INTERFERENCE; IMPULSIVITY; DYSFUNCTION AB Townsend JD, Bookheimer SY, Foland-Ross LC, Moody TD, Eisenberger NI, Fischer JS, Cohen MS, Sugar CA, Altshuler LL. Deficits in inferior frontal cortex activation in euthymic bipolar disorder patients during a response inhibition task. ?Bipolar Disord 2012: 14: 442450. (c) 2012 The Authors. Journal compilation (c) 2012 John Wiley & Sons A/S. Objectives: The inferior frontal corticalstriatal network plays an integral role in response inhibition in normal populations. While inferior frontal cortex (IFC) impairment has been reported in mania, this study explored whether this dysfunction persists in euthymia. Methods: Functional magnetic resonance imaging (fMRI) activation was evaluated in 32 euthymic patients with bipolar I disorder and 30 healthy subjects while performing the Go/NoGo response inhibition task. Behavioral data were collected to evaluate accuracy and response time. Within-group and between-group comparisons of activation were conducted using whole-brain analyses to probe significant group differences in neural function. Results: Both groups activated bilateral IFC. However, between-group comparisons showed a significantly reduced activation in this brain region in euthymic patients with bipolar disorder compared to healthy subjects. Other frontal and basal ganglia regions involved in response inhibition were additionally significantly reduced in bipolar disorder patients, in both the medicated and the unmedicated subgroups. No areas of greater activation were observed in bipolar disorder patients versus healthy subjects. Conclusions: Bipolar disorder patients, even during euthymia, have a persistent reduction in activation of brain regions involved in response inhibition, suggesting that reduced activation in the orbitofrontal cortex and striatum is not solely related to the state of mania. These findings may represent underlying trait abnormalities in bipolar disorder. C1 [Townsend, Jennifer D.; Bookheimer, Susan Y.; Moody, Teena D.; Fischer, Jeffrey S.; Cohen, Mark S.; Altshuler, Lori L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Foland-Ross, Lara C.] Univ Calif Los Angeles, David Geffen Sch Med, Lab NeuroImaging, Dept Neurol, Los Angeles, CA 90095 USA. [Foland-Ross, Lara C.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. [Moody, Teena D.; Sugar, Catherine A.; Altshuler, Lori L.] Univ Calif Los Angeles, Sch Publ Hlth, Jane & Terry Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Eisenberger, Naomi I.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Psychol, 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.] VA Greater Los Angeles Healthcare Syst, Dept Psychiat, W Los Angeles Healthcare Ctr, Los Angeles, CA USA. RP Altshuler, LL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, 300 UCLA Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu RI Cohen, Mark/C-6610-2011 OI Cohen, Mark/0000-0001-6731-4053 FU Stanley Medical Research Institute; National Alliance for Research on Schizophrenia and Depression; National Institute of Mental Health [K24 MH001848, R21 MH075944, 5F31MH078556]; National Center for Research Resources [RR12169, RR13642, RR00865]; Forest Laboratories; Sepracor; Eli Lilly Co. FX This work was supported by The Stanley Medical Research Institute, the National Alliance for Research on Schizophrenia and Depression, the National Institute of Mental Health (K24 MH001848, R21 MH075944 and 5F31MH078556), and the National Center for Research Resources (RR12169, RR13642 and RR00865). The authors also wish to thank the Brain Mapping Medical Research Organization, the Brain Mapping Support Foundation, the Pierson-Lovelace Foundation, The Ahmanson Foundation, the William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation, the Tamkin Foundation, the Jennifer Jones-Simon Foundation, the Capital Group Companies Charitable Foundation, the Robson Family, and the Northstar Fund for generous support.; LLA has received past funding from Forest Laboratories (advisory board honoraria, March 2008), Sepracor (advisory board honoraria, January 2010), and Eli Lilly & Co. (consultant, September 2010). JDT, SYB, LCF-R, TDM, NIE, JSF, MSC, and CAS do not have any commercial associations that might pose a conflict of interest in connection with this manuscript. NR 38 TC 28 Z9 28 U1 3 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2012 VL 14 IS 4 BP 442 EP 450 DI 10.1111/j.1399-5618.2012.01020.x PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 947PE UT WOS:000304441200008 PM 22631623 ER PT J AU Glynn, SM AF Glynn, Shirley M. TI Family Interventions in Schizophrenia: Promise and Pitfalls over 30 Years SO CURRENT PSYCHIATRY REPORTS LA English DT Article DE Schizophrenia; Family treatment; Psychosocial interventions; Family therapy; Family interventions; Psychosis; Evidence-based practice; Relatives ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIOR THERAPY; SUBSTANCE USE DISORDERS; SERIOUS MENTAL-ILLNESS; TREATMENT RECOMMENDATIONS; RELATIVES; PROGRAM; EDUCATION; RECOVERY; OUTCOMES AB The stress of living with unpredictable, disturbing schizophrenic symptoms can erode interpersonal relationships. Stressful family interactions are associated with poorer prognosis. Several investigators have developed educational or more intensive skills-based family programs to increase illness knowledge and improve prognosis in schizophrenia. An extensive body of research supports the benefits of participating in family-based treatments for schizophrenia, especially those of longer duration and emphasizing skill development, in reducing relapse rates. In spite of the data, these programs are underimplemented and underutilized. Barriers to their use likely arise from patients, relatives, and mental health professionals. Newer programs, which include novel engagement strategies, target subpopulations with poor prognoses, or use innovative technologies, may make these programs more accessible to a wider range of families. Engaging individuals with schizophrenia and their loved ones in a collaborative effort to design new, more consumer-driven family interventions is warranted. C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst W Los Ange, Semel Inst, Los Angeles, CA 90073 USA. RP Glynn, SM (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst W Los Ange, Semel Inst, B151j,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM sglynn@ucla.edu NR 49 TC 7 Z9 7 U1 6 U2 31 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3812 J9 CURR PSYCHIAT REP JI Curr. Psychiatry Rep. PD JUN PY 2012 VL 14 IS 3 BP 237 EP 243 DI 10.1007/s11920-012-0265-z PG 7 WC Psychiatry SC Psychiatry GA 940AL UT WOS:000303862300011 PM 22437626 ER PT J AU Zuleger, CL Albertini, MR AF Zuleger, Cindy L. Albertini, Mark R. TI OMIP-008: Measurement of Th1 and Th2 cytokine polyfunctionality of human T cells SO CYTOMETRY PART A LA English DT Article DE immunophenotype; T cells; intracellular cytokine staining; melanoma C1 [Albertini, Mark R.] William S Middleton Mem Vet Adm Med Ctr, Med Serv, Madison, WI 53705 USA. [Zuleger, Cindy L.; Albertini, Mark R.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. [Zuleger, Cindy L.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Dermatol, Madison, WI USA. [Albertini, Mark R.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. RP Albertini, MR (reprint author), William S Middleton Mem Vet Adm Med Ctr, Med Serv, Room B-5057,2500 Overlook Terrace, Madison, WI 53705 USA. EM mralbert@wisc.edu FU National Cancer Institute [P30 CA014520]; Office of Research and Development, Biomedical Laboratory Research and Development Service, Department of Veterans Affairs; Gretchen and Andrew Dawes Melanoma Research Fund; Ann's Hope Foundation; Steve Leuthold Family; U.S. PHS [T32AR055893]; Tim Eagle Memorial FX Grant sponsor: National Cancer Institute; Grant number: P30 CA014520; Grant sponsors: Office of Research and Development, Biomedical Laboratory Research and Development Service, Department of Veterans Affairs; Gretchen and Andrew Dawes Melanoma Research Fund; Ann's Hope Foundation; Jay Van Sloan Memorial from the Steve Leuthold Family; Tim Eagle Memorial. Grant sponsor: CLZ was supported by a postdoctoral fellowship by U.S. PHS; Grant number: T32AR055893. NR 5 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD JUN PY 2012 VL 81A IS 6 BP 450 EP 452 DI 10.1002/cyto.a.22035 PG 3 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 945FO UT WOS:000304258400005 PM 22431369 ER PT J AU Lopes-Virella, MF Baker, NL Hunt, KJ Lyons, TJ Jenkins, AJ Virella, G AF Lopes-Virella, Maria F. Baker, Nathaniel L. Hunt, Kelly J. Lyons, Timothy J. Jenkins, Alicia J. Virella, Gabriel CA DCCT EDIC Study Grp TI High Concentrations of AGE-LDL and Oxidized LDL in Circulating Immune Complexes Are Associated With Progression of Retinopathy in Type 1 Diabetes SO DIABETES CARE LA English DT Article ID INTIMA-MEDIA THICKNESS; COMPLICATIONS TRIAL; ADVANCED GLYCATION; HUMAN MACROPHAGES; MELLITUS; EPIDEMIOLOGY; LIPOPROTEIN; PRODUCTS; CELLS; INFLAMMATION AB OBJECTIVE-To determine whether immunocomplexes (ICs) containing advanced glycation end product (AGE)-LDL (AGE-LDL) and oxidized LDL (oxLDL) contribute to the development of retinopathy over a 16-year period in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS-Levels of AGE-LDL and oxLDL in ICs were measured in 517 patients of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort. Retinopathy was assessed by stereoscopic fundus photography. Cox proportional hazards models were used to assess the effect of AGE-LDL-ICs and oxLDL-ICs on retinopathy progression. RESULTS-In unadjusted models, higher baseline levels of AGE-LDL-ICs and oxLDL-ICs significantly predicted progression of diabetic retinopathy outcomes. After adjustment by study-design variables (treatment group, retinopathy cohort, duration of type 1 diabetes, and baseline albumin excretion rate [AER], hemoglobin A(1c) (HbA(1c)), and Early Treatment Diabetic Retinopathy Study [ETDRS] score), one SD increase in IC levels was associated with 47% (hazard ratio [HR] 1.47 [95% CI 1.19-1.81]; AGE-LDL-IC) and 45% (1.45 [1.17-1.80]; oxLDL-IC) increased risk of developing proliferative diabetic retinopathy (PDR) and 37% (1.37 [1.12-1.66]; to both ICs) increased risk of progressing to severe nonproliferative retinopathy. Analyses were stratified by retinopathy cohort because results differed between primary and secondary cohorts. For AGE-LDL-ICs, FIR for progression to PDR was 2.38 (95% CI 1.30-4.34) in the primary cohort and attenuated in the secondary cohort (1.29 [1.03-1.62]). Similar results were observed for oxLDL-ICs. CONCLUSIONS-Increased levels of AGE-LDL and oxLDL in ICs are associated with increased risk for progression to advanced retinopathy in patients with type 1 diabetes, indicating that the antibody response to modified LDL plays a significant role in retinopathy progression. C1 [Lopes-Virella, Maria F.; Baker, Nathaniel L.; Hunt, Kelly J.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Lopes-Virella, Maria F.; Hunt, Kelly J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Lyons, Timothy J.; Jenkins, Alicia J.] Univ Oklahoma, Hlth Sci Ctr, Harold Hamm Oklahoma Diabet Ctr, Oklahoma City, OK USA. [Lyons, Timothy J.; Jenkins, Alicia J.] Univ Oklahoma, Hlth Sci Ctr, Sect Endocrinol & Diabet, Oklahoma City, OK USA. [Virella, Gabriel] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Lopes-Virella, MF (reprint author), Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. EM virellam@musc.edu FU National Institutes of Health(NIH)/National Heart, Lung, and Blood Institute [P01-HL-55782]; NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01-DK-081352, R01-DK-088778]; Juvenile Diabetes Research Foundation [2006-49]; Research Service of the Ralph H. Johnson VA Medical Center; Division of Diabetes, Endocrinology, and Metabolic Diseases (NIDDK) of the NIH; National Center for Research Resources; Genentech Inc.; NIDDK FX This work was supported by a Program Project funded by the National Institutes of Health(NIH)/National Heart, Lung, and Blood Institute (P01-HL-55782), R01 grants funded by NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R01-DK-081352 and R01-DK-088778), and by a Juvenile Diabetes Research Foundation grant (2006-49). This work was also supported by the Research Service of the Ralph H. Johnson VA Medical Center. The DCCT/EDIC was sponsored through research contracts from the Division of Diabetes, Endocrinology, and Metabolic Diseases (NIDDK) of the NIH. Additional support was provided by the National Center for Research Resources through the General Clinical Research Centers program and by Genentech Inc., through a Cooperative Research and Development Agreement with the NIDDK. No other potential conflicts of interest relevant to this article were reported. NR 41 TC 20 Z9 21 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2012 VL 35 IS 6 BP 1333 EP 1340 DI 10.2337/dc11-2040 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 950DY UT WOS:000304631000023 PM 22511260 ER PT J AU de Boer, IH Katz, R Chonchol, MB Fried, LF Ix, JH Kestenbaum, B Mukamal, KJ Peralta, CA Siscovick, DS AF de Boer, Ian H. Katz, Ronit Chonchol, Michel B. Fried, Linda F. Ix, Joachim H. Kestenbaum, Bryan Mukamal, Kenneth J. Peralta, Carmen A. Siscovick, David S. TI Insulin Resistance, Cystatin C, and Mortality Among Older Adults SO DIABETES CARE LA English DT Article ID HOMEOSTASIS MODEL ASSESSMENT; INCIDENT CARDIOVASCULAR-DISEASE; CHRONIC KIDNEY-DISEASE; METABOLIC SYNDROME; SERUM CREATININE; HEART-DISEASE; RISK; POPULATION; HYPERINSULINEMIA; INDIVIDUALS AB OBJECTIVE-Insulin resistance is a risk factor for cardiovascular and noncardiovascular diseases. Impaired kidney function is linked with insulin resistance and may affect relationships of insulin resistance with health outcomes. RESEARCH DESIGN AND METHODS-We performed a cohort study of 3,138 Cardiovascular Health Study participants (age >= 65years) without diabetes. Insulin sensitivity index (ISI) was calculated from fasting and 2-h postload insulin and glucose concentrations. Associations of ISI and fasting insulin concentration with all-cause mortality were tested using Cox proportional hazards models, adjusting for demographic variables, prevalent cardiovascular disease, lifestyle variables, waist circumference, and LDL cholesterol. Subsequent models were additionally adjusted for or stratified by glomerular filtration rate estimated using serum cystatin C (eGFR). RESULTS-A total of 1,810 participants died during the 14.7-year median follow-up. Compared with the highest quartile of ISI, the lowest quartile (most insulin resistant) was associated with 21% (95% CI 6-41) and 11% (-3 to 29) higher risks of death without and with adjustment for eGFR, respectively. Compared with the lowest quartile of fasting insulin concentration, the highest quartile was associated with 22% (4-43) and 4% (-12 to 22) higher risks of death without and with adjustment for eGFR, respectively. Similar attenuation by eGFR was observed when blood pressure, triglycerides, HDL cholesterol, and C-reactive protein were included in models. CONCLUSIONS-Insulin resistance measured as ISI or fasting insulin concentration is associated with increased risk of death among older adults, adjusting for conventional confounding characteristics. Impaired kidney function may mediate or confound this relationship. Diabetes Care 35:1355-1360,2012 C1 [de Boer, Ian H.; Katz, Ronit; Kestenbaum, Bryan; Siscovick, David S.] Univ Washington, Seattle, WA 98195 USA. [Chonchol, Michel B.] Univ Colorado, Denver, CO 80202 USA. [Fried, Linda F.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Ix, Joachim H.] Univ Calif San Diego, San Diego, CA 92103 USA. [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Peralta, Carmen A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP de Boer, IH (reprint author), Univ Washington, Seattle, WA 98195 USA. EM deboer@u.washington.edu FU National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, U01-HL-080295]; National Institutes of Health [R01-AG-027002, R01-DK-087726]; National Institute of Neurologic Disorders and Stroke FX The research reported in this article was supported by Contracts N0I-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, and N01-HC-45133 and Grant U01-HL-080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurologic Disorders and Stroke. Additional support came from National Institutes of Health Grants R01-AG-027002 and R01-DK-087726. A full list of principal CHS investigators and 10. institutions can be found at hup://www.chs-nhIbi. org/pi.htm. NR 36 TC 13 Z9 13 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 JUN PY 2012 VL 35 IS 6 BP 1355 EP 1360 DI 10.2337/dcl1-1657 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 950DY UT WOS:000304631000026 PM 22432118 ER PT J AU Houser, CR Zhang, NH Peng, ZC Huang, CS Cetina, Y AF Houser, Carolyn R. Zhang, Nianhui Peng, Zechun Huang, Christine S. Cetina, Yliana TI Neuroanatomical clues to altered neuronal activity in epilepsy: From ultrastructure to signaling pathways of dentate granule cells SO EPILEPSIA LA English DT Article DE Electron microscopy; Extracellular signal-regulated kinase; Fos; Mossy fiber sprouting; Seizure; Temporal lobe epilepsy ID TEMPORAL-LOBE EPILEPSY; REGULATED KINASE ACTIVATION; MOSSY FIBER SYNAPSES; PILOCARPINE-INDUCED SEIZURES; KAPPA-OPIOID RECEPTORS; LONG-TERM POTENTIATION; ACID-TREATED RATS; SYNAPTIC REORGANIZATION; HIPPOCAMPAL-FORMATION; FASCIA-DENTATA AB The dynamic aspects of epilepsy, in which seizures occur sporadically and are interspersed with periods of relatively normal brain function, present special challenges for neuroanatomical studies. Although numerous morphologic changes can be identified during the chronic period, the relationship of many of these changes to seizure generation and propagation remains unclear. Mossy fiber sprouting is an example of a frequently observed morphologic change for which a functional role in epilepsy continues to be debated. This review focuses on neuroanatomically identified changes that would support high levels of activity in reorganized mossy fibers and potentially associated granule cell activation. Early ultrastructural studies of reorganized mossy fiber terminals in human temporal lobe epilepsy tissue have identified morphologic substrates for highly efficacious excitatory connections among granule cells. If similar connections in animal models contribute to seizure activity, activation of granule cells would be expected. Increased labeling with two activity-related markers, Fos and phosphorylated extracellular signalregulated kinase, has suggested increased activity of dentate granule cells at the time of spontaneous seizures in a mouse model of epilepsy. However, neuroanatomical support for a direct link between activation of reorganized mossy fiber terminals and increased granule cell activity remains elusive. As novel activity-related markers are developed, it may yet be possible to demonstrate such functional links and allow mapping of seizure activity throughout the brain. Relating patterns of neuronal activity during seizures to the underlying morphologic changes could provide important new insights into the basic mechanisms of epilepsy and seizure generation. C1 [Houser, Carolyn R.; Zhang, Nianhui; Peng, Zechun; Huang, Christine S.; Cetina, Yliana] Univ Calif Los Angeles, Dept Neurobiol, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Houser, Carolyn R.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. [Houser, Carolyn R.] Vet Adm Greater Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. RP Houser, CR (reprint author), Univ Calif Los Angeles, Dept Neurobiol, David Geffen Sch Med, CHS 73-235,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM houser@mednet.ucla.edu FU Veterans Affairs Medical Research Funds; National Institutes of Health [NS046524, NS051311] FX This work was supported by Veterans Affairs Medical Research Funds (C.R.H.) and the National Institutes of Health grants NS046524 and NS051311 (C.R.H.). We are grateful to Drs. J.R. Rich, P.S. Dwan, B.E. Swartz, G.O. Walsh, and A.V. Delgado-Escueta, and to their patients, for invaluable contributions to our early studies of human temporal lobe epilepsy tissue. This review is contributed as a tribute to H. Jurgen Wenzel in recognition of his careful, detailed morphologic studies, which have been linked consistently to function, and his great interest in mossy fibers of the dentate gyrus, from their early development (Wenzel et al., 1981) to their functionally associated transporters (Wenzel et al., 1997), and to their reorganization in epilepsy (Wenzel et al., 2000). NR 73 TC 15 Z9 15 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUN PY 2012 VL 53 SU 1 SI SI BP 67 EP 77 DI 10.1111/j.1528-1167.2012.03477.x PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 945FH UT WOS:000304257700010 PM 22612811 ER PT J AU Kim, H Miller, LM Byl, N Abrams, GM Rosen, J AF Kim, Hyunchul Miller, Levi Makaio Byl, Nancy Abrams, Gary M. Rosen, Jacob TI Redundancy Resolution of the Human Arm and an Upper Limb Exoskeleton SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Exoskeleton; inverse kinematic; redundancy; swivel angle ID POWERED EXOSKELETON; INVERSE KINEMATICS; COMPLEX MOVEMENTS; MICROSTIMULATION; CONFIGURATION; CORTEX AB The human arm has 7 degrees of freedom (DOF) while only 6 DOF are required to position the wrist and orient the palm. Thus, the inverse kinematics of an human arm has a nonunique solution. Resolving this redundancy becomes critical as the human interacts with a wearable robot and the inverse kinematics solution of these two coupled systems must be identical to guarantee an seamless integration. The redundancy of the arm can be formulated by defining the swivel angle, the rotation angle of the plane defined by the upper and lower arm around a virtual axis that connects the shoulder and wrist joints. Analyzing reaching tasks recorded with a motion capture system indicates that the swivel angle is selected such that when the elbow joint is flexed, the palm points to the head. Based on these experimental results, a new criterion is formed to resolve the human arm redundancy. This criterion was implemented into the control algorithm of an upper limb 7-DOF wearable robot. Experimental results indicate that by using the proposed redundancy resolution criterion, the error between the predicted and the actual swivel angle adopted by the motor control system is less then 5 degrees. C1 [Kim, Hyunchul] Univ Calif Santa Cruz, Dept Elect Engn, Santa Cruz, CA 95064 USA. [Kim, Hyunchul] Optodynamics Inc, Songnam 463870, South Korea. [Miller, Levi Makaio] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. [Miller, Levi Makaio] Carbon Design Grp, Seattle, WA 98105 USA. [Byl, Nancy] Univ Calif San Francisco, Dept Phys Therapy & Rehabil Sci, Sch Med, San Francisco, CA 94158 USA. [Abrams, Gary M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Abrams, Gary M.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Rosen, Jacob] Univ Calif Santa Cruz, Dept Comp Engn, Santa Cruz, CA 95064 USA. [Rosen, Jacob] Univ Calif Santa Cruz, Bion Lab, Santa Cruz, CA 95064 USA. RP Kim, H (reprint author), Atromax Inc, Santa Clara, CA USA. EM hyunchul78@gmail.com; makaio@uw.edu; BylN@ptrehab.ucsf.edu; Gary.Abrams@ucsf.edu; rosen@ucsc.edu NR 26 TC 27 Z9 27 U1 2 U2 33 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD JUN PY 2012 VL 59 IS 6 BP 1770 EP 1779 DI 10.1109/TBME.2012.2194489 PG 10 WC Engineering, Biomedical SC Engineering GA 944ZQ UT WOS:000304242700029 PM 22510944 ER PT J AU Lambert, A Picardeau, M Haake, DA Sermswan, RW Srikram, A Adler, B Murray, GA AF Lambert, Ambroise Picardeau, Mathieu Haake, David A. Sermswan, Rasana W. Srikram, Amporn Adler, Ben Murray, Gerald A. TI FlaA Proteins in Leptospira interrogans Are Essential for Motility and Virulence but Are Not Required for Formation of the Flagellum Sheath SO INFECTION AND IMMUNITY LA English DT Article ID BORRELIA-BURGDORFERI; PERIPLASMIC FLAGELLA; INACTIVATION; MUTAGENESIS; GENE; INVOLVEMENT; CHEMOTAXIS; TRANSPOSON; MUTANT AB Spirochetes have periplasmic flagella composed of a core surrounded by a sheath. The pathogen Leptospira interrogans has four flaB (proposed core subunit) and two flaA (proposed sheath subunit) genes. The flaA genes are organized in a locus with flaA2 immediately upstream of flaA1. In this study, flaA1 and flaA2 mutants were constructed by transposon mutagenesis. Both mutants still produced periplasmic flagella. The flaA 1 mutant did not produce FlaA1 but continued to produce FlaA2 and retained normal morphology and virulence in a hamster model of infection but had reduced motility. The flaA2 mutant did not produce either the FlaA1 or the FlaA2 protein. Cells of the flaA2 mutant lacked the distinctive hook-shaped ends associated with L. interrogans and lacked translational motility in liquid and semisolid media. These observations were confirmed with a second, independent flaA2 mutant. The flaA2 mutant failed to cause disease in animal models of acute infection. Despite lacking FlaA proteins, the flagella of the flaA2 mutant were of the same thickness as wild-type flagella, as measured by electron microscopy, and exhibited a normal flagellum sheath, indicating that FlaA proteins are not essential for the synthesis of the flagellum sheath, as observed for other spirochetes. This study shows that FlaA subunits contribute to leptospiral translational motility, cellular shape, and virulence. C1 [Adler, Ben; Murray, Gerald A.] Monash Univ, Dept Microbiol, Australian Res Council Ctr Excellence Struct & Fu, Clayton, Vic 3168, Australia. [Sermswan, Rasana W.; Srikram, Amporn] Khon Kaen Univ, Melioidosis Res Ctr, Khon Kaen, Thailand. [Sermswan, Rasana W.] Khon Kaen Univ, Dept Biochem, Khon Kaen, Thailand. [Haake, David A.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Lambert, Ambroise] Univ Paris Diderot, Paris, France. [Lambert, Ambroise; Picardeau, Mathieu] Inst Pasteur, Unite Biol Spirochetes, Paris, France. RP Adler, B (reprint author), Monash Univ, Dept Microbiol, Australian Res Council Ctr Excellence Struct & Fu, Clayton, Vic 3168, Australia. EM ben.adler@monash.edu FU Australian Research Council; National Health and Medical Research Council; Institut Pasteur; French Ministry of Research [ANR-08-MIE-018]; University Paris Diderot; VA Medical Research funds; Public Health Service from the National Institute of Allergy and Infectious Diseases [AI-034431] FX This work was supported by the Australian Research Council, the National Health and Medical Research Council, the Institut Pasteur, the French Ministry of Research (ANR-08-MIE-018), the doctoral program of the University Paris Diderot, VA Medical Research funds, and Public Health Service grant AI-034431 from the National Institute of Allergy and Infectious Diseases. NR 33 TC 44 Z9 44 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 2012 VL 80 IS 6 BP 2019 EP 2025 DI 10.1128/IAI.00131-12 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 946WH UT WOS:000304387700008 PM 22451522 ER PT J AU Mukherjee, A Larson, EA Carlos, AS Belknap, JK Rotwein, P Klein, RF AF Mukherjee, Aditi Larson, Emily A. Carlos, Amy S. Belknap, John K. Rotwein, Peter Klein, Robert F. TI Congenic mice provide in vivo evidence for a genetic locus that modulates intrinsic transforming growth factor beta 1-mediated signaling and bone acquisition SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE HEREDITY; GENETICS; TRANSFORMING GROWTH FACTOR; BONE STRENGTH; OSTEOPOROSIS ID QUANTITATIVE TRAIT LOCI; INHIBITS OSTEOBLAST DIFFERENTIATION; TGF-BETA ACTIVATION; MINERAL DENSITY; MECHANICAL-PROPERTIES; PARATHYROID-HORMONE; COMPLEX TRAITS; OSTEOPOROSIS; MOUSE; IDENTIFICATION AB Osteoporosis, the most common skeletal disorder, is characterized by low bone mineral density (BMD) and an increased risk of fragility fractures. BMD is the best clinical predictor of future osteoporotic fracture risk, but is a complex trait controlled by multiple environmental and genetic determinants with individually modest effects. Quantitative trait locus (QTL) mapping is a powerful method for identifying chromosomal regions encompassing genes involved in shaping complex phenotypes, such as BMD. Here we have applied QTL analysis to male and female genetically-heterogeneous F2 mice derived from a cross between C57BL/6 and DBA/2 strains, and have identified 11 loci contributing to femoral BMD. Further analysis of a QTL on mouse chromosome 7 following the generation of reciprocal congenic strains has allowed us to determine that the high BMD trait, which tracks with the DBA/2 chromosome and exerts equivalent effects on male and female mice, is manifested by enhanced osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro and by increased growth of metatarsal bones in short-term primary culture. An insertion/deletion DNA polymorphism in Ltbp4 exon 12 that causes the in-frame removal of 12 codons in the DBA/2-derived gene maps within 0.6?Mb of the marker most tightly linked to the QTL. LTBP4, one of four paralogous mouse proteins that modify the bioavailability of the transforming growth factor beta (TGF-beta) family of growth factors, is expressed in differentiating MSC-derived osteoblasts and in long bones, and reduced responsiveness to TGF-beta 1 is observed in MSCs of mice homozygous for the DBA/2 chromosome 7. Taken together, our results identify a potential genetic and biochemical relationship between decreased TGF-beta 1mediated signaling and enhanced femoral BMD that may be regulated by a variant LTBP4 molecule. (C) 2012 American Society for Bone and Mineral Research. C1 [Larson, Emily A.; Carlos, Amy S.; Klein, Robert F.] Oregon Hlth & Sci Univ, Bone & Mineral Res Unit, Dept Med, Portland, OR 97201 USA. [Mukherjee, Aditi; Rotwein, Peter] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA. [Belknap, John K.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Belknap, John K.; Klein, Robert F.] Portland VA Med Ctr, Portland, OR USA. RP Klein, RF (reprint author), Oregon Hlth & Sci Univ, Bone & Mineral Res Unit CR113, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. EM kleinro@ohsu.edu FU National Institutes of Health [R01 DK42748, P50 AA10760, R01 AR44659]; VA Medical Research Service FX These studies were supported in part by National Institutes of Health grants R01 DK42748 (to PR), P50 AA10760 (to JKB), R01 AR44659 (to RFK), and the VA Medical Research Service (to RFK). We thank Dr. Lynn Sakai for polyclonal antibodies to LTBP4. NR 59 TC 8 Z9 8 U1 0 U2 3 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 JUN PY 2012 VL 27 IS 6 BP 1345 EP 1356 DI 10.1002/jbmr.1590 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 943QY UT WOS:000304141500012 PM 22407846 ER PT J AU Heckman, CJ Cohen-Filipic, J AF Heckman, Carolyn J. Cohen-Filipic, Jessye TI Brief Report: Ultraviolet Radiation Exposure, Considering Acculturation Among Hispanics (Project URECAH) SO JOURNAL OF CANCER EDUCATION LA English DT Article DE Hispanics; Skin cancer; Prevention; Acculturation ID SUN PROTECTION PRACTICES; BEHAVIORS AB Very few studies have examined acculturation of Hispanics as it relates to skin cancer prevention attitudes and behaviors. This pilot study used the Abbreviated Acculturation Rating Scale for Mexican Americans-II to classify 14-25-year-old Hispanics as traditional, bicultural, or acculturated. More acculturated individuals reported significantly higher perceived benefits of ultraviolet radiation exposure and lower worry about skin damage than traditional individuals. Bicultural individuals reported using sunscreen significantly more often than acculturated individuals. These preliminary data suggest that more acculturated Hispanic young adults may demonstrate riskier skin cancer-related attitudes and behaviors than others. C1 [Heckman, Carolyn J.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Cohen-Filipic, Jessye] Portland VA Med Ctr, Portland, OR 97239 USA. RP Heckman, CJ (reprint author), Fox Chase Canc Ctr, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM Carolyn.Heckman@fccc.edu; JessyeCohen@gmail.com FU NCI NIH HHS [K07 CA108685, K07 CA108685-05] NR 15 TC 7 Z9 7 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD JUN PY 2012 VL 27 IS 2 BP 342 EP 346 DI 10.1007/s13187-011-0308-x PG 5 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 943SC UT WOS:000304144500021 PM 22228464 ER PT J AU Ghosh, PM Shu, ZJ Zhu, B Lu, ZD Ikeno, YJ Barnes, JL Yeh, CK Zhang, BX Katz, MS Kamat, A AF Ghosh, Paramita M. Shu, Zhen-Ju Zhu, Bing Lu, Zhongding Ikeno, Yuji Barnes, Jeffrey L. Yeh, Chih-Ko Zhang, Bin-Xian Katz, Michael S. Kamat, Amrita TI Role of beta-adrenergic receptors in regulation of hepatic fat accumulation during aging SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID ISOLATED RAT HEPATOCYTES; LIVER-DISEASE; MYOCARDIAL-INFARCTION; METABOLIC SYNDROME; ADENYLATE-CYCLASE; FISCHER-344 RATS; ADIPOSE-TISSUE; AGE; EXPRESSION; ADRENOCEPTOR AB Excessive fat accumulation in liver (hepatic steatosis) predisposes to hepatic functional and structural impairment and overall metabolic risk. Previous studies noted an association between hepatic steatosis and age in humans and rodents. However, the mechanisms leading to age-associated hepatic fat accumulation remain unknown. Earlier work from our group showed that beta-adrenergic receptor (beta-AR) levels and beta-AR-stimulated adenylyl cyclase activity increase in rat liver during aging. Herewe investigated whether age-associated increases in beta-AR signaling play a role in augmenting hepatic lipid accumulation. We demonstrate an increase in hepatic lipid content during senescence and a significant correlation between hepatic fat content and stimulation of adenylyl cyclase activity by the beta-AR agonist isoproterenol in rat liver. Isoproterenol administration to young and old rodents in vivo increased hepatic lipid accumulation. Furthermore, in vitro overexpression of b1-and b2-AR subtypes in hepatocytes from young rodents increased cellular lipid content, whereas inhibition of beta-ARs by receptor subtype-specific inhibitors reduced lipid levels in hepatocytes from senescent animals. Isoproterenol-induced hepatic lipid accumulation in vivo was prevented by the beta-AR nonselective blocker propranolol, suggesting a novel therapeutic effect of this class of drugs in hepatic steatosis. Acipimox, which inhibits adipose tissue lipolysis, did not alter isoproterenolmediated hepatic fat accumulation; thus beta-AR responsive hepatic lipid accumulation does not appear to be related primarily to altered lipolysis. These findings suggest that augmented hepatic beta-AR signaling during aging may increase lipid accumulation in liver and advocate a possible role for beta-adrenergic blockers in preventing or retarding the development of hepatic steatosis. Journal of Endocrinology (2012) 213, 251-261 C1 [Ghosh, Paramita M.; Yeh, Chih-Ko; Zhang, Bin-Xian; Katz, Michael S.; Kamat, Amrita] S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr 182, San Antonio, TX 78229 USA. [Shu, Zhen-Ju; Barnes, Jeffrey L.; Zhang, Bin-Xian; Katz, Michael S.; Kamat, Amrita] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Zhu, Bing; Lu, Zhongding; Yeh, Chih-Ko; Katz, Michael S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, San Antonio, TX 78229 USA. [Ikeno, Yuji] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Ikeno, Yuji; Yeh, Chih-Ko; Kamat, Amrita] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. RP Kamat, A (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr 182, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM kamat@uthscsa.edu FU Department of Veterans Affairs VISN 17; American Heart Association; Kronos Longevity Research Institute FX Grant sponsor: Department of Veterans Affairs VISN 17 award to A K; grant sponsor: American Heart Association grant in aid to A K; and grant sponsor: Kronos Longevity Research Institute award to M S K. NR 53 TC 16 Z9 16 U1 1 U2 5 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD JUN PY 2012 VL 213 IS 3 BP 251 EP 261 DI 10.1530/JOE-11-0406 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 946PZ UT WOS:000304366600006 PM 22457517 ER PT J AU Danczyk, RC Mitchell, EL Burk, C Singh, S Liem, TK Landry, GJ Petersen, BD Moneta, GL AF Danczyk, Rachel C. Mitchell, Erica L. Burk, Chad Singh, Sarguni Liem, Timothy K. Landry, Gregory J. Petersen, Bryan D. Moneta, Gregory L. TI Comparing patient outcomes between multiple ipsilateral iliac artery stents and isolated iliac artery stents SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Western-Vascular-Society CY SEP 17-20, 2011 CL Kauai, HI SP Western Vasc Soc ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; AORTOILIAC OCCLUSIVE DISEASE; CONSENSUS-CLASS-C; ENDOVASCULAR TREATMENT; PREDICTORS; LESIONS; MULTICENTER; EXPERIENCE; ISCHEMIA; THERAPY AB Objective: Endovascular stents are accepted therapy for iliac artery stenoses and occlusions. Surgery is the recommended therapy for patients with severe iliac artery disease, including those with the combination of ipsilateral common iliac artery (CIA) and external iliac artery (EIA) stenoses/occlusions. This study compared patient outcomes, including late open conversion rates, for combined ipsilateral CIA and EIA stenting vs CIA or EIA stents alone. Methods: Between 1998 and 2010, 588 patients underwent iliac artery stenting at two institutions. Patient comorbidities and outcomes were retrospectively reviewed, and analyses were performed using multivariate regression and Kaplan-Meier methods. Results: There were 436 extremities with CIA stents, 195 with EIA stents, and 157 with CIA and EIA stents. The groups did not differ significantly in demographics, comorbidities, or treatment indications. During follow-up, 183 patients died, 95 underwent an endovascular reintervention, and 48 required late open conversion. For patients in the CIA or EIA stent group, the mean +/- standard error survival was 5.3 +/- 0.3 years, secondary endovascular intervention-free survival was 7.4 +/- 0.6 years, late open conversion-free survival was 9.8 +/- 0.4 years, and amputation-free survival was 7.6 +/- 0.4 years. In the CIA and EIA stent group, survival was 6.1 +/- 0.6 years, secondary endovascular intervention-free survival was 7.2 +/- 0.6 years, late open conversion-free survival was 9.0 +/- 1.1 years, and amputation-free survival was 8.4 +/- 0.5 years. Survival, reintervention-free survival, late open conversion-free survival, and amputation-free survival were all similar between patient groups (all P > .05). CIA and EIA stenting in combination was not a predictor of death, reintervention, late open conversion, or amputation. Conclusions: Outcomes are similar for patients with CIA or EIA stents and for those with combined ipsilateral CIA and EIA stents. Late open conversions for iliac artery stent failure are uncommon and not influenced by the location or extent of prior iliac artery stent placement. Endovascular therapy for aortoiliac disease should be extended to consider selected patients with ipsilateral CIA and EIA stenoses/occlusions. (J Vasc Surg 2012; 55: 1637-46.) C1 [Danczyk, Rachel C.; Mitchell, Erica L.; Burk, Chad; Singh, Sarguni; Liem, Timothy K.; Landry, Gregory J.; Moneta, Gregory L.] Oregon Hlth & Sci Univ, Div Vasc Surg, Portland, OR 97239 USA. [Petersen, Bryan D.] Oregon Hlth & Sci Univ, Dotter Inst, Portland, OR 97239 USA. [Petersen, Bryan D.] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. RP Mitchell, EL (reprint author), Oregon Hlth & Sci Univ, Div Vasc Surg, OP11, Portland, OR 97239 USA. EM mitcheer@ohsu.edu NR 21 TC 3 Z9 4 U1 0 U2 0 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 JUN PY 2012 VL 55 IS 6 BP 1637 EP U411 DI 10.1016/j.jvs.2011.12.048 PG 16 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 944MF UT WOS:000304206000014 PM 22360919 ER PT J AU Cook, DB Stegner, AJ Nagelkirk, PR Meyer, JD Togo, F Natelson, BH AF Cook, Dane B. Stegner, Aaron J. Nagelkirk, Paul R. Meyer, Jacob D. Togo, Fumiharu Natelson, Benjamin H. TI Responses to Exercise Differ for Chronic Fatigue Syndrome Patients with Fibromyalgia SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE PAIN; FATIGUE; IMPEDANCE CARDIOGRAPHY; STROKE VOLUME; RPE ID PHYSIOLOGICAL-RESPONSES; CARDIOVASCULAR-RESPONSE; RESISTANCE EXERCISE; WOMEN; ILLNESS; MUSCLE; PAIN; SYMPTOMS; CAPACITY AB COOK, D. B., A. J. STEGNER, P. R. NAGELKIRK, J. D. MEYER, F. TOGO, and B. H. NATELSON. Responses to Exercise Differ for Chronic Fatigue Syndrome Patients with Fibromyalgia. Med. Sci. Sports Exerc., Vol. 44, No. 6, pp. 1186-1193, 2012. Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are chronic multisymptom illnesses with substantial clinical and diagnostic overlap. We have previously shown that, when controlling for aerobic fitness and accounting for comorbid FM, CFS patients do not exhibit abnormal cardiorespiratory responses during maximal aerobic exercise compared with healthy controls, despite differences in pain and exertion. Purpose: The purpose of the present study was to examine cardiac and perceptual responses to steady-state submaximal exercise in CFS patients and healthy controls. Methods: Twenty-one CFS patients (13 CFS with comorbid FM (CFS + FM)) and 14 controls completed 20 min of submaximal cycling exercise. Impedance cardiography was used to determine cardiac responses during exercise. Systolic blood pressure (SBP), RPE, and leg muscle pain were also measured. Data were analyzed using a doubly multivariate, repeated-measures MANOVA to model the exercise response. Results: There was a significant multivariate time-by-group interaction (P < 0.05). The CFS + FM group exhibited an exercise response characterized by higher stroke index, ventilatory equivalents for oxygen and carbon dioxide and RPE, lower SBP, and similar HR responses compared to controls. Conclusions: The present results extend on our previous work with maximal exercise and show that CFS and CFS + FM differ in their responses to steady-state exercise. These results highlight the importance of accounting for comorbid conditions when conducting CFS research, particularly when examining psychophysiological responses to exercise. C1 [Cook, Dane B.; Stegner, Aaron J.; Meyer, Jacob D.] Univ Wisconsin Madison, Dept Kinesiol, Madison, WI 53706 USA. [Cook, Dane B.; Stegner, Aaron J.] William S Middleton Mem Vet Adm Med Ctr, Res Serv, Madison, WI USA. [Nagelkirk, Paul R.] Ball State Univ, Sch Phys Educ Sport & Exercise Sci, Muncie, IN 47306 USA. [Togo, Fumiharu] Univ Tokyo, Grad Sch Educ, Tokyo, Japan. [Natelson, Benjamin H.] Beth Israel Deaconess Med Ctr, Pain & Fatigue Study Ctr, New York, NY 10003 USA. RP Cook, DB (reprint author), Univ Wisconsin Madison, Dept Kinesiol, 2000 Observ Dr, Madison, WI 53706 USA. EM dcook@education.wisc.edu FU National Institutes of Health [AI-32247] FX This research was supported by the National Institutes of Health grant AI-32247. NR 40 TC 11 Z9 11 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JUN PY 2012 VL 44 IS 6 BP 1186 EP 1193 DI 10.1249/MSS.0b013e3182417b9a PG 8 WC Sport Sciences SC Sport Sciences GA 944TQ UT WOS:000304227100027 PM 22157881 ER PT J AU Taylor, JJ Borckardt, JJ George, MS AF Taylor, Joseph J. Borckardt, Jeffrey J. George, Mark S. TI Endogenous opioids mediate left dorsolateral prefrontal cortex rTMS-induced analgesia SO PAIN LA English DT Article DE Pain modulation; Endogenous opioids; rTMS; Analgesia; Prefrontal cortex ID TRANSCRANIAL MAGNETIC STIMULATION; ROSTRAL VENTROMEDIAL MEDULLA; ANTERIOR CINGULATE CORTEX; PERIAQUEDUCTAL GRAY; HEALTHY-VOLUNTEERS; PLACEBO ANALGESIA; BRAIN-STEM; CORTICAL PROJECTIONS; PAIN THRESHOLDS; MOOD DISORDERS AB The concurrent rise of undertreated pain and opiate abuse poses a unique challenge to physicians and researchers alike. A focal, noninvasive form of brain stimulation called repetitive transcranial magnetic stimulation (rTMS) has been shown to produce acute and chronic analgesic effects when applied to dorsolateral prefrontal cortex (DLPFC), but the anatomical and pharmacological mechanisms by which prefrontal rTMS induces analgesia remain unclear. Data suggest that DLPFC mediates top-down analgesia via gain modulation of the supraspinal opioidergic circuit. This potential pathway might explain how prefrontal rTMS reduces pain. The purpose of this sham-controlled, double-blind, crossover study was to determine whether left DLPFC rTMS-induced analgesia was sensitive to l-opioid blockade. Twenty-four healthy volunteers were randomized to receive real or sham TMS after either intravenous saline or naloxone pretreatment. Acute hot and cold pain via quantitative sensory testing and hot allodynia via block testing on capsaicin-treated skin were assessed at baseline and at 0, 20, and 40 minutes after TMS treatment. When compared to sham, real rTMS reduced hot pain and hot allodynia. Naloxone pretreatment significantly reduced the analgesic effects of real rTMS. These results demonstrate that left DLPFC rTMS-induced analgesia requires opioid activity and suggest that rTMS drives endogenous opioidergic pain relief in the human brain. Further studies with chronic dosing regimens of drugs that block or augment the actions of opiates are needed to determine whether TMS can augment opiates in chronic or postoperative pain management. (C) 2012 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved. C1 [Taylor, Joseph J.] Med Univ S Carolina, Inst Psychiat, Brain Stimulat Lab, Dept Psychiat, Charleston, SC 29414 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Taylor, JJ (reprint author), Med Univ S Carolina, Inst Psychiat, Brain Stimulat Lab, Dept Psychiat, 67 President St,Room 504 N, Charleston, SC 29414 USA. EM taylorjj@musc.edu FU NIDA NIH HHS [F30 DA033748] NR 72 TC 32 Z9 32 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUN PY 2012 VL 153 IS 6 BP 1219 EP 1225 DI 10.1016/j.pain.2012.02.030 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 945BZ UT WOS:000304249100017 PM 22444187 ER PT J AU Yagi, M Murray, J Strand, K Blystone, S Interlandi, G Suda, Y Sobel, M AF Yagi, Mayumi Murray, Jacqueline Strand, Kurt Blystone, Scott Interlandi, Gianluca Suda, Yasuo Sobel, Michael TI Heparin modulates the conformation and signaling of platelet integrin alpha IIb beta 3 SO THROMBOSIS RESEARCH LA English DT Article DE Heparin; Integrin alpha IIb beta 3 (platelet glycoprotein IIbIIIa); Platelet activation; Src kinase; Surface plasmon resonance; Tyrosine phosphorylation ID PERCUTANEOUS CORONARY INTERVENTION; MOLECULAR-WEIGHT HEPARIN; UNFRACTIONATED-HEPARIN; TYROSINE PHOSPHORYLATION; BINDING DOMAIN; LIGAND-BINDING; ACTIVATION; AGGREGATION; ADHESION; IIIA AB Introduction: The glycosaminoglycan heparin has been shown to bind to platelet integrin alpha IIb beta 3 and induce platelet activation and aggregation, although the relationship between binding and activation is unclear. We analyzed the interaction of heparin and alpha IIb beta 3 in detail, to obtain a better understanding of the mechanism by which heparin acts on platelets. Methods: We assessed conformational changes in alpha IIb beta 3 by flow cytometry of platelets exposed to unfractionated heparin. In human platelets and K562 cells engineered to express alpha IIb beta 3, we assayed the effect of heparin on key steps in integrin signaling: phosphorylation of the beta 3 chain cytoplasmic tail, and activation of src kinase. We measured the heparin binding affinity of purified alpha IIb beta 3, and of recombinant fragments of alpha IIb and beta 3, by surface plasmon resonance. Results and conclusions: Heparin binding results in conformational changes in alpha IIb beta 3, similar to those observed upon ligand binding. Heparin binding alone is not sufficient to induce tyrosine phosphorylation of the integrin beta 3 cytoplasmic domain, but the presence of heparin increased both beta 3 phosphorylation and src kinase activation in response to ligand binding. Specific recombinant fragments derived from alpha IIb bound heparin, while recombinant beta 3 did not bind. This pattern of heparin binding, compared to the crystal structure of alpha IIb beta 3, suggests that heparin-binding sites are located in clusters of basic amino acids in the headpiece and/or leg domains of alpha IIb. Binding of heparin to these clusters may stabilize the transition of alpha IIb beta 3 to an open conformation with enhanced affinity for ligand, facilitating outside-in signaling and platelet activation. Published by Elsevier Ltd. C1 [Yagi, Mayumi; Murray, Jacqueline; Strand, Kurt; Sobel, Michael] VA Puget Sound Hlth Care Syst, Res & Dev, Seattle, WA 98108 USA. [Murray, Jacqueline; Sobel, Michael] Univ Washington, Dept Surg, Div Vasc Surg, Seattle, WA 98195 USA. [Blystone, Scott] SUNY Upstate Med Univ, Dept Cell & Dev Biol, Syracuse, NY USA. [Interlandi, Gianluca] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. [Suda, Yasuo] Kagoshima Univ, Dept Nanostruct & Adv Mat, Grad Sch Sci & Engn, Kagoshima 890, Japan. RP Yagi, M (reprint author), VA Puget Sound Hlth Care Syst, Res & Dev 151, Seattle Div, 1660 S Columbian Way, Seattle, WA 98108 USA. EM myagi@uw.edu FU National Institutes of Health [HL39903]; Department of Veterans Affairs FX This work was supported by grants from the National Institutes of Health (HL39903) and the Department of Veterans Affairs to MS. NR 38 TC 6 Z9 6 U1 1 U2 6 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 JUN PY 2012 VL 129 IS 6 BP 743 EP 749 DI 10.1016/j.thromres.2011.11.054 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 945HG UT WOS:000304263100013 PM 22197178 ER PT J AU Aspinall, SL Smith, KJ Good, CB Zhao, X Stone, RA Tonnu-Mihara, IQ Cunningham, FE AF Aspinall, S. L. Smith, K. J. Good, C. B. Zhao, X. Stone, R. A. Tonnu-Mihara, I. Q. Cunningham, F. E. TI INCREMENTAL COST-EFFECTIVENESS OF PHARMACIST-MANAGED ERYTHROPOIESIS-STIMULATING AGENTS CLINICS FOR NON-DIALYSIS CHRONIC KIDNEY DISEASE PATIENTS SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Aspinall, S. L.; Good, C. B.; Cunningham, F. E.] VA Ctr Medicat Safety, Hines, IL USA. [Smith, K. J.; Stone, R. A.] Univ Pittsburgh, Pittsburgh, PA USA. [Zhao, X.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Tonnu-Mihara, I. Q.] VA Long Beach Healthcare Syst, Long Beach, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD JUN PY 2012 VL 15 IS 4 BP A155 EP A156 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 947XP UT WOS:000304468200806 ER PT J AU Forrest, G Larson, K Crompton, M Patel, H Boening, AJ AF Forrest, G. Larson, K. Crompton, M. Patel, H. Boening, A. J. TI HEALTH OUTCOMES WITH DAPTOMYCIN (DAP) IN THE TREATMENT OF METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS BACTEREMIA (MRSA-B) WITH VANCOMYCIN (VAN) MINIMUM INHIBITORY CONCENTRATION (MIC)=2 mu G/Ml SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Forrest, G.] OHSU, Portland, OR USA. [Forrest, G.] Portland VA Med Ctr, Portland, OR USA. [Larson, K.; Crompton, M.; Patel, H.; Boening, A. J.] Cubist Pharmaceut Inc, Lexington, MA USA. 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 1098-3015 J9 VALUE HEALTH JI Value Health PD JUN PY 2012 VL 15 IS 4 BP A237 EP A237 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 947XP UT WOS:000304468201425 ER PT J AU Sansgiry, S Naik, AD Brown, AC Latini, DM AF Sansgiry, S. Naik, A. D. Brown, A. C. Latini, D. M. TI VARIATION IN ATTACHMENT STYLE AND HEALTH OUTCOMES OF DIABETES PATIENTS SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Sansgiry, S.; Naik, A. D.] Baylor Coll Med, VA HSR&D Ctr Excellence, Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Latini, D. M.] San Francisco VA Med Ctr, Baylor Coll Med, Scott Dept Urol, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD JUN PY 2012 VL 15 IS 4 BP A184 EP A185 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 947XP UT WOS:000304468201151 ER PT J AU Spiegel, B Poysophon, P Snyder, B Agarwal, N Yen, L Hodgkins, P Cohen, E Vu, M Kurzbard, N Atia, M Sheen, V Kaneshiro, M Fuller, G Bolus, R AF Spiegel, B. Poysophon, P. Snyder, B. Agarwal, N. Yen, L. Hodgkins, P. Cohen, E. Vu, M. Kurzbard, N. Atia, M. Sheen, V Kaneshiro, M. Fuller, G. Bolus, R. TI RESOURCE UTILIZATION AND COSTS ASSOCIATED WITH DIVERTICULITIS INPATIENT ADMISSIONS: AN ANALYSIS OF THE ECONOMIC BURDEN OF DIVERTICULITIS SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Spiegel, B.; Poysophon, P.; Snyder, B.; Agarwal, N.; Cohen, E.; Vu, M.; Kurzbard, N.; Atia, M.; Sheen, V; Kaneshiro, M.; Fuller, G.; Bolus, R.] Univ Calif Los Angeles, Cedars Sinai Med Ctr, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90048 USA. [Yen, L.; Hodgkins, P.] Shire Dev LLC, Wayne, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD JUN PY 2012 VL 15 IS 4 BP A139 EP A139 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 947XP UT WOS:000304468200722 ER PT J AU Lanternier, F Sun, HY Ribaud, P Singh, N Kontoyiannis, DP Lortholary, O AF Lanternier, Fanny Sun, Hsin-Yun Ribaud, Patricia Singh, Nina Kontoyiannis, Dimitrios P. Lortholary, Olivier TI Mucormycosis in Organ and Stem Cell Transplant Recipients SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INVASIVE FUNGAL-INFECTIONS; LIPOSOMAL AMPHOTERICIN-B; SURVEILLANCE NETWORK TRANSNET; MOLD INFECTIONS; HEMATOLOGIC MALIGNANCY; ANTIFUNGAL THERAPY; MURINE ZYGOMYCOSIS; RHIZOPUS-ORYZAE; IRON OVERLOAD; RISK-FACTORS AB Mucormycosis is a devastating invasive fungal disease whose incidence has increased during the past decade. Mucormycosis now represents a major threat in transplant recipients, accounting for 2% and 8% of invasive fungal infections in recent cohorts of solid-organ and allogeneic stem-cell transplant recipients, respectively. Mucormycosis most often occurs late, >3 months after transplantation, although cases occurring early have been observed, especially among liver transplant recipients and in cases of graft-transmitted infection. Recent guidelines have emphasized the direct examination of the involved fluid or tissue and culture from a sterile site as the most appropriate diagnostic strategy and the use of lipid formulations of amphotericin B and major surgery when feasible as the most appropriate first-line therapeutic strategy for mucormycosis in organ and stem cell transplant recipients. C1 [Lanternier, Fanny; Lortholary, Olivier] Univ Paris 05, Hop Necker Enfants Malad, Ctr Infect Necker Pasteur, F-75105 Paris, France. [Lanternier, Fanny; Lortholary, Olivier] IHU Imagine, Paris, France. [Lanternier, Fanny; Lortholary, Olivier] Ctr Natl Reference Mycol & Antifong, Inst Pasteur, Paris, France. [Lortholary, Olivier] CNRS, URA 3012, Paris, France. [Sun, Hsin-Yun; Singh, Nina] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Sun, Hsin-Yun; Singh, Nina] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Sun, Hsin-Yun] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Sun, Hsin-Yun] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan. [Ribaud, Patricia] Univ Paris 07, UFR Denis Diderot, F-75221 Paris 05, France. [Ribaud, Patricia] Hop St Louis, Assistance Publ Hop Paris, Serv Hematol Greffe Moelle, Paris, France. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Dept Infect Dis, Houston, TX 77030 USA. RP Lortholary, O (reprint author), Univ Paris 05, Hop Necker Enfants Malad, Ctr Infect Necker Pasteur, 149 Rue Sevres, F-75105 Paris, France. EM olivier.lortholary@nck.aphp.fr OI SUN, HSIN-YUN/0000-0003-0074-7721 NR 62 TC 37 Z9 39 U1 0 U2 3 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 JUN 1 PY 2012 VL 54 IS 11 BP 1629 EP 1636 DI 10.1093/cid/cis195 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 942MO UT WOS:000304048400020 PM 22431807 ER PT J AU Musher, DM Stager, C AF Musher, Daniel M. Stager, Charles TI Diagnosis of Clostridium difficile Infection SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 [Musher, Daniel M.] Baylor Coll Med, Houston, TX 77030 USA. [Stager, Charles] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Lab Serv Care Line, Infect Dis Sect, Houston, TX 77030 USA. [Musher, Daniel M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Stager, Charles] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. RP Musher, DM (reprint author), Baylor Coll Med, Houston, TX 77030 USA. EM dmusher@bcm.edu NR 4 TC 6 Z9 6 U1 0 U2 0 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 JUN 1 PY 2012 VL 54 IS 11 BP 1675 EP 1675 DI 10.1093/cid/cis259 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 942MO UT WOS:000304048400027 PM 22503848 ER PT J AU Borrero, S Mor, MK Zhao, XH McNeil, M Ibrahim, S Hayes, P AF Borrero, Sonya Mor, Maria K. Zhao, Xinhua McNeil, Melissa Ibrahim, Said Hayes, Patricia TI Contraceptive care in the VA health care system SO CONTRACEPTION LA English DT Article DE VA; Women's health; Contraception; Race/ethnicity ID OF-VETERANS-AFFAIRS; INTRAUTERINE-DEVICE; WOMEN VETERANS; DELIVERY; AVAILABILITY; ORGANIZATION; PHYSICIANS; INNOVATION; KNOWLEDGE; ATTITUDES AB Background: Little is known about contraceptive care within the Veterans Affairs (VA) health care system. This study was conducted to assess the prevalence of documented contraception by race/ethnicity within the VA and to examine the association between receiving primary care in women's health clinics (WHCs) and having a documented contraceptive method. Study Design: We examined national VA administrative and pharmacy data for 103,950 female veterans aged 18-45 years who made at least one primary care clinic visit in 2008. Multivariable regression models were used to examine the associations between race/ethnicity and receipt of care in a WHC with having a method of contraception while controlling for confounders. Results: Only 22% of women veterans had a documented method of contraception during 2008. After adjusting for potential confounders, Hispanic and African-American women were significantly less likely to have a method compared to whites [odds ratio (OR): 0.82; 95% confidence interval (CI): 0.76-0.88 and OR: 0.85; 95% CI: 0.81-0.89, respectively]. Women who went to WHCs were significantly more likely to have a method of contraception compared to women who went to traditional primary care clinics (OR: 2.05; 95% CI: 1.97-2.14). Conclusions: Overall contraceptive prevalence in the VA is low, but receiving care in a WHC is associated with a significantly higher likelihood of having a contraceptive method. Published by Elsevier Inc. C1 [Borrero, Sonya; Mor, Maria K.; Zhao, Xinhua] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Borrero, Sonya; McNeil, Melissa] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Ibrahim, Said] Philadelphia Vet Adm, Med Ctr, Philadelphia, PA 19104 USA. [Ibrahim, Said] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Hayes, Patricia] US Dept Vet Affairs, Women Vet Hlth Strateg Hlth Care Grp, Off Publ Hlth & Environm Hazards, Washington, DC 20420 USA. RP Borrero, S (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr,151C-H, Pittsburgh, PA 15206 USA. EM borrerosp@upmc.edu FU Department of Veterans Affairs, Veteran Health Administration, Office of Research and Development, VISN 4 CHERP FX This study was supported by the Department of Veterans Affairs, Veteran Health Administration, Office of Research and Development, VISN 4 CHERP Pilot Project Award (PI: Sonya Borrero). Dr. Borrero had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The contents of this manuscript do not represent the views of the Department of Veterans Affairs or the United States Government. The abstract of this manuscript was presented at The Society of General Internal Medicine annual meeting in Phoenix, AZ, in May 2011. NR 20 TC 11 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0010-7824 J9 CONTRACEPTION JI Contraception PD JUN PY 2012 VL 85 IS 6 BP 580 EP 588 DI 10.1016/j.contraception.2011.10.010 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 944FP UT WOS:000304185000009 PM 22176794 ER PT J AU Cecere, LM Slatore, CG Uman, JE Evans, LE Udris, EM Bryson, CL Au, DH AF Cecere, Laura M. Slatore, Christopher G. Uman, Jane E. Evans, Laura E. Udris, Edmunds M. Bryson, Chris L. Au, David H. TI Adherence to Long-Acting Inhaled Therapies among Patients with Chronic Obstructive Pulmonary Disease (COPD) SO COPD-JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Article DE Medication adherence; Pulmonary diseases; Chronic disease; Pharmacoepidemiology ID CLINICAL-TRIAL; MEDICATION NONADHERENCE; ASTHMATIC-PATIENTS; CORTICOSTEROIDS; MANAGEMENT; BELIEFS; PERSISTENCE; VALIDATION; CHILDREN; UNDERUSE AB Background: Long-acting inhaled medications are an important component of the treatment of patients with chronic obstructive pulmonary disease (COPD), yet few studies have examined the determinants of medication adherence among this patient population. Objective: We sought to identify factors associated with adherence to long-acting beta-agonists (LABA) and inhaled corticosteroids (ICS) among patients with COPD. Methods: We performed secondary analysis of baseline data collected in a randomized trial of 376 Veterans with spirometrically confirmed COPD. We used electronic pharmacy records to assess adherence, defined as a medication possession ratio of >= 0.80. We investigated the following exposures: patient characteristics, disease severity, medication regimen complexity, health behaviors, confidence in self-management, and perceptions of provider skill. We performed multivariable logistic regression, clustered by provider, to estimate associations. Results: Of the 167 patients prescribed LABA, 54% (n = 90) were adherent to therapy while only 40% (n = 74) of 184 the patients prescribed ICS were adherent. Higher adherence to LABA and ICS was associated with patient perception of their provider as being an "expert" in diagnosing and managing lung disease [For LABA: OR = 21.70 (95% CI 6.79, 69.37); For ICS OR = 7.93 (95% CI 1.71, 36.67)]. Factors associated with adherence to LABA, but not ICS, included: age, education, race, COPD severity, smoking status, and confidence in self-management. Conclusions: Adherence to long-acting inhaled medications among patients with COPD is poor, and determinants of adherence likely differ by medication class. Patient perception of clinician expertise in lung disease was the factor most highly associated with adherence to long-acting therapies. C1 [Cecere, Laura M.; Uman, Jane E.; Udris, Edmunds M.; Bryson, Chris L.; Au, David H.] Dept Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Cecere, Laura M.; Au, David H.] Univ Washington, Dept Med, Div Pulm & Crit Care Med, Seattle, WA USA. [Slatore, Christopher G.] Dept Vet Affairs Med Ctr, Portland, OR USA. [Slatore, Christopher G.] Oregon Hlth & Sci Univ, Dept Med, Div Pulm & Crit Care Med, Portland, OR 97201 USA. [Evans, Laura E.] NYU, Med Ctr, Div Pulm & Crit Care Med, Dept Med, New York, NY 10016 USA. RP Cecere, LM (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM lcecere@u.washington.edu OI Slatore, Christopher/0000-0003-0958-8122 FU VA Advanced Fellowship Program in Health Services Research and Development [TPM 61-037]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development [IIR 02-292]; Portland VA Medical Center, Portland, OR; Firland Foundation FX This material is based upon work supported by a VA Advanced Fellowship Program in Health Services Research and Development [TPM 61-037] and a Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development grant [IIR 02-292]. Dr. Slatore is supported by a Veterans Affairs HSR&D Career Development Award and resources from the Portland VA Medical Center, Portland, OR. Additional support also comes from the Firland Foundation. 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. Some of the results of this work were presented in abstract form at the American Thoracic Society International Conference, in Denver, Colorado on May 15, 2011. NR 35 TC 23 Z9 23 U1 1 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1541-2555 J9 COPD JI COPD-J. Chronic Obstr. Pulm. Dis. PD JUN PY 2012 VL 9 IS 3 BP 251 EP 258 DI 10.3109/15412555.2011.650241 PG 8 WC Respiratory System SC Respiratory System GA 942ZM UT WOS:000304090200008 PM 22497533 ER PT J AU Sosenko, JM Skyler, JS Herold, KC Palmer, JP AF Sosenko, Jay M. Skyler, Jay S. Herold, Kevan C. Palmer, Jerry P. CA Type 1 Diabet TrialNet Study Grp Diabet Prevention Trial-Type 1 TI The Metabolic Progression to Type 1 Diabetes as Indicated by Serial Oral Glucose Tolerance Testing in the Diabetes Prevention Trial-Type 1 SO DIABETES LA English DT Article ID BETA-CELL FUNCTION; INSULIN-RESISTANCE; C-PEPTIDE; CLINICAL-MANIFESTATIONS; NATURAL-HISTORY; RISK SCORE; MELLITUS; ONSET; SECRETION; RELATIVES C1 [Sosenko, Jay M.; Skyler, Jay S.] Univ Miami, Miller Sch Med, Div Endocrinol, Miami, FL 33136 USA. [Herold, Kevan C.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Palmer, Jerry P.] Univ Washington, VA Puget Sound Hlth Care Syst, Div Endocrinol Metab & Nutr, Seattle, WA 98195 USA. RP Sosenko, JM (reprint author), Univ Miami, Miller Sch Med, Div Endocrinol, Miami, FL 33136 USA. EM jsosenko@med.miami.edu RI Skyler, Jay/F-4211-2016 OI Gallagher, Mary/0000-0002-5844-2309 FU Type 1 Diabetes TrialNet Study Group; National Institutes of Health (NTH) through the National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01 DK-061010, U01 DK-061016, U01 DK-061034, U01 DK-061036, U01 DK-061040, U01 DK-061041, U01 DK-061042, U01 DK-061055, U01 DK-061058, U01 DK-084565, U01 DK-085453, U01 DK-085461, U01 DK-085463, U01 DK-085466, U01 DK-085499, U01 DK-085505, U01 DK-085509, HHSN267200800019C]; National Center for Research Resources [UL1 RR-024131, UL1 RR-024139, UL1 RR-024153, UL1 RR-024975, UL1 RR-024982, UL1 RR-025744, UL1 RR-025761, UL1 RR-025780, UL1 RR-029890, UL1 RR-031986]; General Clinical Research Center [M01 RR-00400]; Juvenile Diabetes Research Foundation International (JDRF); ADA FX The sponsor of the study was the Type 1 Diabetes TrialNet Study Group. Type 1 Diabetes TrialNet Study Group is a clinical trials network funded by the National Institutes of Health (NTH) through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, through the cooperative agreements U01 DK-061010, U01 DK-061016, U01 DK-061034, U01 DK-061036, U01 DK-061040, U01 DK-061041, U01 DK-061042, U01 DK-061055, U01 DK-061058, U01 DK-084565, U01 DK-085453, U01 DK-085461, U01 DK-085463, U01 DK-085466, U01 DK-085499, U01 DK-085505, and U01 DK-085509, and a contract HHSN267200800019C; the National Center for Research Resources, through Clinical Translational Science Awards UL1 RR-024131, UL1 RR-024139, UL1 RR-024153, UL1 RR-024975, UL1 RR-024982, UL1 RR-025744, UL1 RR-025761, UL1 RR-025780, UL1 RR-029890, and UL1 RR-031986, and General Clinical Research Center Award M01 RR-00400; the Juvenile Diabetes Research Foundation International (JDRF); and the ADA. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, JDRF, or ADA. NR 50 TC 19 Z9 20 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2012 VL 61 IS 6 BP 1331 EP 1337 DI 10.2337/db11-1660 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 948FX UT WOS:000304490100004 PM 22618768 ER PT J AU Rapuano, BE Lee, JJE MacDonald, DE AF Rapuano, Bruce E. Lee, Jani J. E. MacDonald, Daniel E. TI Titanium alloy surface oxide modulates the conformation of adsorbed fibronectin to enhance its binding to alpha(5)beta(1) integrins in osteoblasts SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article DE conformation; fibronectin; integrins; osteoblast; titanium alloy ID HUMAN PLASMA FIBRONECTIN; ATOMIC-FORCE MICROSCOPY; AMINO-ACID-SEQUENCE; CELL-ADHESION; CHEMICAL-MODIFICATION; BONE SIALOPROTEIN; SYNERGY SITE; NET CHARGE; IN-VITRO; ATTACHMENT AB Rapuano BE, Lee JJE, MacDonald DE. Titanium alloy surface oxide modulates the conformation of adsorbed fibronectin to enhance its binding to a5 beta 1 integrins in osteoblasts. ?Eur J Oral Sci 2012; 120: 185194. (C) 2012 Eur J Oral Sci Our laboratory has previously demonstrated that heat (600 degrees C) or radiofrequency plasma glow discharge (RFGD) pretreatment of a titanium alloy (Ti6Al4V) increased the net negative charge of the alloy's surface oxide and the attachment of osteoblastic cells to adsorbed fibronectin. The purpose of the current study was to investigate the biological mechanism by which these surface pretreatments enhance the capacity of fibronectin to stimulate osteoblastic cell attachment. Each pretreatment was found to increase the binding (measured by ELISA) of a monoclonal anti-fibronectin Ig to the central integrin-binding domain of adsorbed fibronectin, and to increase the antibody's inhibition of osteogenic cell attachment (measured by hexosaminidase assay). Pretreatments also increased the binding (measured by ELISA) of anti-integrin IgGs to the a5 and beta 1 integrin subunits that became attached to fibronectin during cell incubation. These findings suggest that negatively charged surface oxides of Ti6Al4V cause conformational changes in fibronectin that increase the availability of its integrin-binding domain to a5 beta 1 integrins. C1 [Rapuano, Bruce E.; Lee, Jani J. E.; MacDonald, Daniel E.] Cornell Univ, Weill Med Coll, Hosp Special Surg, New York, NY 10021 USA. [MacDonald, Daniel E.] James J Peters VA Med Ctr, Bronx, NY USA. [MacDonald, Daniel E.] Columbia Univ, Langmuir Ctr Colloids & Interfaces, New York, NY USA. RP MacDonald, DE (reprint author), Cornell Univ, Weill Med Coll, Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA. EM dem14@columbia.edu FU NIH [RO1 DE017695]; National Center for Research Resources, NIH [C06- RR12538-01] FX The project described was supported by Grant Number NIH RO1 DE017695 (awarded to D.E.M.). This material is also the result of work supported with resources and the use of facilities at the James J. Peters VA Medical Center, Bronx, New York. This investigation was also conducted at the HSS research facility constructed with support of Grant C06- RR12538-01 from the National Center for Research Resources, NIH. We would like to acknowledge Dr Stephen Doty and Tony Labisserie for their help with scanning electron microscopy. Special thanks go to Tiffany Leung, Ryan Jeong, and Kyle Hackshaw for their technical assistance. NR 51 TC 14 Z9 15 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD JUN PY 2012 VL 120 IS 3 BP 185 EP 194 DI 10.1111/j.1600-0722.2012.954_e.x PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 944HC UT WOS:000304188900002 PM 22607334 ER PT J AU Thompson, GR Wiederhold, NP Najvar, LK Bocanegra, R Kirkpatrick, WR Graybill, JR Patterson, TF AF Thompson, George R., III Wiederhold, Nathan P. Najvar, Laura K. Bocanegra, Rosie Kirkpatrick, William R. Graybill, John R. Patterson, Thomas F. TI A murine model of Cryptococcus gattii meningoencephalitis SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE cryptococcal meningoencephalitis; C; gattii; Cryptococcus neoformans; posaconazole; fluconazole ID NEOFORMANS; MENINGITIS; OUTBREAK; FLUCONAZOLE; FLUCYTOSINE; GENOTYPE; VARIETY AB Meningoencephalitis caused by Cryptococcus gattii is associated with significant morbidity and the need for aggressive therapy, and often necessitates neurosurgical intervention. We adapted a previously described murine model of cryptococcal meningoencephalitis due to Cryptococcus neoformans to that caused by C. gattii. Mice were inoculated intracranially with either C. gattii (genotype VGIIa) or C. neoformans. In virulence studies, different C. gattii infecting inocula were compared with a fixed inoculum of C. neoformans, and differences were assessed by survival, brain tissue fungal burden, serum antigen titres and histopathological changes within brain tissue. For treatment, fluconazole or posaconazole (10 mg/kg orally twice daily) was initiated 24 h post-inoculation. C. gattii was more virulent than C. neoformans, as evident by shorter median survival, earlier histopathological changes and higher serum antigen titres. However, no differences in fungal burden or dissemination to other organs were observed among the various groups. In treatment studies, both fluconazole and posaconazole improved the median survival of mice infected with either species. However, neither regimen improved the percentage of animals surviving to the predetermined study endpoint. These results demonstrate the virulence of C. gattii meningoencephalitis and the potential of this model for the assessment of new treatment strategies. C1 [Thompson, George R., III] Univ Calif Davis, Div Infect Dis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. [Thompson, George R., III] Univ Calif Davis, Div Infect Dis, Dept Internal Med, Davis, CA 95616 USA. [Wiederhold, Nathan P.; Najvar, Laura K.; Bocanegra, Rosie; Kirkpatrick, William R.; Graybill, John R.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, Dept Internal Med, San Antonio, TX 78229 USA. [Wiederhold, Nathan P.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Patterson, Thomas F.] S Texas Vet Hlth Care Syst, Div Infect Dis, Dept Internal Med, San Antonio, TX USA. RP Thompson, GR (reprint author), Univ Calif Davis, Div Infect Dis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. EM grthompson@ucdavis.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 J. R. G. and T. F. P.; G. R. T. has received research support from Pfizer. N. P. W. has received research support from Pfizer, Schering-Plough, Merck, Basilea and Astellas. J. R. G. has received research support from Pfizer, Merck and Astellas, and has been paid to act as a consultant for Merck. T. F. P. has received research grants from Astellas, Basilea, Merck and Pfizer (to the University of Texas Health Science Center at San Antonio), and has been paid to act as a consultant for Astellas, Basilea, Merck, Pfizer and Toyoma. All other authors: none to declare. NR 19 TC 13 Z9 13 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JUN PY 2012 VL 67 IS 6 BP 1432 EP 1438 DI 10.1093/jac/dks060 PG 7 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 942RJ UT WOS:000304064400020 PM 22378683 ER PT J AU Huttner, B Jones, M Rubin, MA Madaras-Kelly, K Nielson, C Goetz, MB Neuhauser, MM Samore, MH AF Huttner, Benedikt Jones, Makoto Rubin, Michael A. Madaras-Kelly, Karl Nielson, Christopher Goetz, Matthew Bidwell Neuhauser, Melinda M. Samore, Matthew H. TI Double trouble: how big a problem is redundant anaerobic antibiotic coverage in Veterans Affairs medical centres? SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE antibiotic stewardship; anaerobes; metronidazole; inappropriate antibiotic use ID METRONIDAZOLE; THERAPY AB Objectives: To assess the prevalence of, and the variation in, avoidable use of metronidazole in the Veterans Affairs (VA) healthcare system Methods: Barcode Medication Administration (BCMA) data were retrospectively assessed for all patients hospitalized between January 2006 and December 2010 in acute-care wards of all VA medical centres (VAMCs) with complete BCMA data and at least 10 acute-care non-intensive care unit (ICU) beds. Potentially avoidable metronidazole days of therapy (DOT) were defined as the administration of metronidazole with anotheranti-anaerobic antibiotic on the same day for at least two consecutive days during the same hospitalization. Metronidazole was not considered redundant in combination with another anti-anaerobic agent within 28 days after a positive test for Clostridium difficile and during hospitalizations associated with discharge diagnosis codes for cholecystitis or cholangitis. Results: A total of 128 VAMCs satisfied the inclusion criteria. Over the study period there were a total of 782821 DOT of metronidazole (57.4 DOT per 1000 patient-days), of which 183267 (23.4%) fulfilled the criteria for avoidable metronidazole DOT. The percentage of avoidable metronidazole DOT remained stable over the study period (22.8% in 2006 and 22.9% in 2010) despite a decrease in overall metronidazole use. There was wide variation in the percentage of avoidable metronidazole DOT among facilities (2010: median 20.3%, IQR 15.3%-29.4%). Piperacillin/tazobactam was the most commonly administered drug on avoidable metronidazole DOT (56.8%). Conclusions: Potentially avoidable use of metronidazole affected about a quarter of all days when metronidazole was given. The combination of metronidazole with piperacillin/tazobactam was particularly common and represents a possible target for antibiotic stewardship interventions. C1 [Huttner, Benedikt; Jones, Makoto; Rubin, Michael A.; Samore, Matthew H.] VA Salt Lake City Hlth Care Syst, IDEAS Ctr, Salt Lake City, UT 84148 USA. [Huttner, Benedikt; Jones, Makoto; Rubin, Michael A.; Samore, Matthew H.] Univ Utah, Div Epidemiol, Salt Lake City, UT 84132 USA. [Madaras-Kelly, Karl] Boise VA Med Ctr, Boise, ID 83702 USA. [Madaras-Kelly, Karl] Idaho State Univ, Coll Pharm, Meridian, ID 83713 USA. [Nielson, Christopher] VA Sierra Nevada Hlth Care Syst, Reno, NV 89502 USA. [Goetz, Matthew Bidwell] VA Greater LA Healthcare Syst, Los Angeles, CA 90073 USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Neuhauser, Melinda M.] Dept Vet Affairs Pharm Benefit Management Serv, Hines, IL USA. RP Huttner, B (reprint author), VA Salt Lake City Hlth Care Syst, IDEAS Ctr, 500 Foothill Dr, Salt Lake City, UT 84148 USA. EM huttner.benedikt@gmail.com RI Huttner, Benedikt/M-5616-2014 OI Huttner, Benedikt/0000-0002-1749-9464; Goetz, Matthew/0000-0003-4542-992X FU George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT, USA [CDA 10-030-02]; Geneva University Hospitals, Switzerland FX This material is the result of work supported with resources and the use of facilities at the George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT, USA, a career development award (to M. J., CDA 10-030-02) and a fellowship grant from Geneva University Hospitals, Switzerland (to B. H.). NR 10 TC 10 Z9 11 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JUN PY 2012 VL 67 IS 6 BP 1537 EP 1539 DI 10.1093/jac/dks074 PG 3 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 942RJ UT WOS:000304064400037 PM 22398652 ER PT J AU Chirinos, JA AF Chirinos, Julio A. TI Arterial Stiffness: Basic Concepts and Measurement Techniques SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Article DE Arterial stiffness; Compliance; Distensibility; Pulse wave velocity; Elastic modulus ID PRESSURE WAVE-FORMS; ALL-CAUSE MORTALITY; CAROTID-ARTERY; CARDIOVASCULAR-DISEASE; AORTIC STIFFNESS; IN-VIVO; NONINVASIVE EVALUATION; HYPERTENSIVE PATIENTS; CLINICAL-APPLICATIONS; HEALTHY-INDIVIDUALS AB Arterial stiffness is highly relevant to cardiovascular disease. Arterial stiffness is central to the pathogenesis of isolated systolic hypertension and directly impacts left ventricular afterload, pressure pulsatility in the arterial tree, and its penetration into the microvasculature of target organs such as the brain and kidney. Arterial stiffness is affected by various risk factors and biologic processes. Measurements of arterial stiffness may therefore not only provide information about prevalent processes, but also valuable information regarding the cumulative history of risk factor exposure. Available studies consistently demonstrate that large artery stiffness, measured via carotid-femoral pulse wave velocity, independently predicts the risk of incident cardiovascular events in clinical and community-based cohorts. Understanding the basic principles and definitions related to arterial stiffness is therefore desirable for cardiovascular clinicians and researchers. This introductory paper reviews basic physical principles and definitions regarding arterial stiffness and the most important non-invasive methods for its quantification in vivo. C1 Univ Penn, Perelman Sch Med, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Chirinos, JA (reprint author), Univ Penn, Perelman Sch Med, Philadelphia VA Med Ctr, Rm 8B111,Univ & Woodland Av, Philadelphia, PA 19104 USA. EM julio.chirinos@uphs.upenn.edu NR 56 TC 39 Z9 39 U1 1 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1937-5387 J9 J CARDIOVASC TRANSL JI J. Cardiovasc. Transl. Res. PD JUN PY 2012 VL 5 IS 3 SI SI BP 243 EP 255 DI 10.1007/s12265-012-9359-6 PG 13 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA 943HK UT WOS:000304111300001 PM 22447229 ER PT J AU Fiorentino, L Saxbe, D Alessi, CA Woods, DL Martin, JL AF Fiorentino, Lavinia Saxbe, Darby Alessi, Cathy A. Woods, Diana Lynn Martin, Jennifer L. TI Diurnal Cortisol and Functional Outcomes in Post-Acute Rehabilitation Patients SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Cortisol; Older adults; Rehabilitation; Inpatient; Functional Status ID PITUITARY-ADRENAL AXIS; NURSING-HOME RESIDENTS; UNDER-THE-CURVE; OLDER-PEOPLE; YOUNG-ADULTS; DEMENTIA; DECLINE; DISEASE; CARDIA; CLOCK AB Background. Cortisol is a stress-related hormone with a robust circadian rhythm where levels typically peak in the morning hours and decline across the day. Although acute cortisol increases resulting from stressors are adaptive, chronic elevated cortisol levels are associated with poor functioning. Studies have shown age-related changes in cortisol levels. The present study investigated the relationship between salivary diurnal cortisol and functional outcomes among older adults undergoing inpatient post-acute rehabilitation. Methods. Thirty-two older adults (mean age 78 years; 84% men) in a Veterans Administration inpatient post-acute rehabilitation unit were studied. Functional outcomes were assessed with the motor component of the Functional Independence Measure (mFIM; where mFIM change = discharge - admission score). Saliva samples were collected on 1 day at wake time, 45 minutes later, 11:30 am, 2 pm, 4:30 pm, and bedtime. We analyzed the relationship between cortisol measures and functional outcomes, demographics, and health measures. Results. The analyses consistently showed that greater functional improvement (mFIM change) from admission to discharge was associated with lower comorbidity scores and higher cortisol levels at 2 pm, 4: 30 pm, and bedtime. A morning cortisol rise was also associated with greater mFIM change. Conclusions. Measurement of cortisol in saliva may be a useful biological marker for identification of patients who are "at risk" of lower benefits from inpatient rehabilitation services and who may require additional assistance or intervention during their post-acute care stay. C1 [Alessi, Cathy A.; Martin, Jennifer L.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, North Hills, CA 91343 USA. [Fiorentino, Lavinia] Univ Calif San Diego, Sch Med, Dept Psychiat, San Diego, CA 92103 USA. [Saxbe, Darby] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. [Alessi, Cathy A.; Martin, Jennifer L.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Woods, Diana Lynn] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. RP Martin, JL (reprint author), VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr 11E, 16111 Plummer St,Bldg 25,Room B136, North Hills, CA 91343 USA. EM jennifer.martin@va.gov FU National Institute of Mental Health [T32 MH019934, MH080002, T32 MH019925-11]; National Institute on Aging at the National Institutes of Health [K23 AG028452]; Veterans Administration Health Services Research & Development Service [IIR 01-053-1, IIR 04-321-2, AIA 03-047]; Veterans Affairs Greater Los Angeles Healthcare System, Geriatric Research, Education and Clinical Center FX This work was supported by the National Institute of Mental Health [T32 MH019934 (Jeste), MH080002 (Jeste), and T32 MH019925-11 (Irwin)] and the National Institute on Aging [K23 AG028452 (J.L.M.)] at the National Institutes of Health; Veterans Administration Health Services Research & Development Service (IIR 01-053-1, C. A. A.; IIR 04-321-2, C. A. V.; and AIA 03-047 J.L.M.); and the Veterans Affairs Greater Los Angeles Healthcare System, Geriatric Research, Education and Clinical Center. NR 22 TC 2 Z9 2 U1 1 U2 5 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 JUN PY 2012 VL 67 IS 6 BP 677 EP 682 DI 10.1093/gerona/glr230 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 942OM UT WOS:000304054700013 PM 22219521 ER PT J AU D'Souza, DC Fridberg, DJ Skosnik, PD Williams, A Roach, B Singh, N Carbuto, M Elander, J Schnakenberg, A Pittman, B Sewell, RA Ranganathan, M Mathalon, D AF D'Souza, Deepak Cyril Fridberg, Daniel J. Skosnik, Patrick D. Williams, Ashley Roach, Brian Singh, Nagendra Carbuto, Michelle Elander, Jacqueline Schnakenberg, Ashley Pittman, Brian Sewell, R. Andrew Ranganathan, Mohini Mathalon, Daniel TI Dose-Related Modulation of Event-Related Potentials to Novel and Target Stimuli by Intravenous Delta(9)-THC in Humans SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Delta(9)-THC; cannabinoids; cannabis; P300; perception; psychosis ID CANNABINOID CB1 RECEPTOR; SELECTIVE ATTENTION; METABOTROPIC GLUTAMATE; MEDIATED INHIBITION; MARIJUANA SMOKING; EVOKED-POTENTIALS; NOVELTY DETECTION; AUDITORY-STIMULI; FREQUENT USERS; HUMAN BRAIN AB Cannabinoids induce a host of perceptual alterations and cognitive deficits in humans. However, the neural correlates of these deficits have remained elusive. The current study examined the acute, dose-related effects of delta-9-tetrahydrocannabinol (Delta(9)-THC) on psychophysiological indices of information processing in humans. Healthy subjects (n = 26) completed three test days during which they received intravenous Delta(9)-THC (placebo, 0.015 and 0.03 mg/kg) in a within-subject, double-blind, randomized, cross-over, and counterbalanced design. Psychophysiological data (electroencephalography) were collected before and after drug administration while subjects engaged in an event-related potential (ERP) task known to be a valid index of attention and cognition (a three-stimulus auditory 'oddball' P300 task). Delta(9)-THC dose-dependently reduced the amplitude of both the target P300b and the novelty P300a. Delta(9)-THC did not have any effect on the latency of either the P300a or P300b, or on early sensory-evoked ERP components preceding the P300 (the N100). Concomitantly, Delta(9)-THC induced psychotomimetic effects, perceptual alterations, and subjective 'high' in a dose-dependent manner. Delta(9)-THC -induced reductions in P3b amplitude correlated with Delta(9)-THC-induced perceptual alterations. Lastly, exploratory analyses examining cannabis use status showed that whereas recent cannabis users had blunted behavioral effects to Delta(9)-THC, there were no dose-related effects of Delta(9)-THC on P300a/b amplitude between cannabis-free and recent cannabis users. Overall, these data suggest that at doses that produce behavioral and subjective effects consistent with the known properties of cannabis, Delta(9)-THC reduced P300a and P300b amplitudes without altering the latency of these ERPs. Cannabinoid agonists may therefore disrupt cortical processes responsible for context updating and the automatic orientation of attention, while leaving processing speed and earlier sensory ERP components intact. Collectively, the findings suggest that CB1R systems modulate top-down and bottom-up processing. Neuropsychopharmacology (2012) 37, 1632-1646; doi:10.1038/npp.2012.8; published online 15 February 2012 C1 [D'Souza, Deepak Cyril; Skosnik, Patrick D.; Williams, Ashley; Singh, Nagendra; Carbuto, Michelle; Elander, Jacqueline; Schnakenberg, Ashley; Pittman, Brian; Sewell, R. Andrew; Ranganathan, Mohini] Connecticut Mental Hlth Ctr, Abraham Ribicoff Res Facil, New Haven, CT 06519 USA. [D'Souza, Deepak Cyril; Skosnik, Patrick D.; Williams, Ashley; Singh, Nagendra; Carbuto, Michelle; Elander, Jacqueline; Schnakenberg, Ashley; Pittman, Brian; Sewell, R. Andrew; Ranganathan, Mohini; Mathalon, Daniel] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Roach, Brian; Mathalon, Daniel] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Roach, Brian; Mathalon, Daniel] San Francisco VA Med Ctr, Mental Hlth Serv Line, San Francisco, CA USA. [D'Souza, Deepak Cyril; Fridberg, Daniel J.; Skosnik, Patrick D.; Williams, Ashley; Singh, Nagendra; Carbuto, Michelle; Elander, Jacqueline; Schnakenberg, Ashley; Sewell, R. Andrew; Ranganathan, Mohini] VA Connecticut Healthcare Syst, Psychiat Serv, West Haven, CT 06516 USA. RP D'Souza, DC (reprint author), VA Connecticut Healthcare Syst, Psychiat Serv, 116A,950 Campbell Ave, West Haven, CT 06516 USA. EM deepak.dsouza@yale.edu OI Mathalon, Daniel/0000-0001-6090-4974 FU Department of Veterans Affairs; National Institute of Mental Health; National Institute of Drug Abuse [R21 DA020750]; National Institute of Alcoholism and Alcohol Abuse (NIAAA); Yale Center for Clinical Investigation (YCCI); NARSAD; AstraZeneca, Inc; Pfizer, Inc.; Abbott Laboratories; Eli Lilly; Organon; Pfizer; Sanofi; Astra Zeneca FX We acknowledge support from the (1) Department of Veterans Affairs, (2) National Institute of Mental Health, (3) National Institute of Drug Abuse, (4) National Institute of Alcoholism and Alcohol Abuse (NIAAA), and (5) the Yale Center for Clinical Investigation (YCCI). This research project was funded in part by grants from NIDA (R21 DA020750 to DCD) and a NARSAD Young Investigator Award to PDS. We also thank Angelina Genovese, RNC, MBA; Michelle San Pedro, RN; Elizabeth O'Donnell, RN; Brenda Breault, RN, BSN; Sonah Yoo, RPh; Rachel Galvan, RPh; and Willie Ford of the Neurobiological Studies Unit at the VA Connecticut Healthcare System, West Haven Campus for their central contributions to the success of this project.; Daniel Fridberg, Patrick Skosnik, Ashley Williams, Brian Roach, Nagendra Singh, Michelle Carbuto, Jacqueline Elander, Ashley Schnakenberg, Brian Pittman, and Andrew Sewell report no financial relationships with commercial interests. Dr Mathalon reports research funding from AstraZeneca, Inc, consulting fees from Pfizer, Inc., and that his name is included under a provisional patent titled 'A non-invasive biomarker of human cortical plasticity and cognition', USPTO serial number 61/140 833. Mohini Ranganathan has in the past 3 years or currently receives research grant support administered through Yale University School of Medicine from Eli Lilly. Deepak Cyril D'Souza has in the past 3 years or currently receives research grant support administered through Yale University School of Medicine from Astra Zeneca, Abbott Laboratories, Eli Lilly, Organon, Pfizer, and Sanofi; he is a consultant for Bristol Meyers Squibb. NR 93 TC 35 Z9 36 U1 3 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUN PY 2012 VL 37 IS 7 BP 1632 EP 1646 DI 10.1038/npp.2012.8 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 942LO UT WOS:000304045700008 PM 22334121 ER PT J AU Lotfipour, S Mandelkern, M Alvarez-Estrada, M Brody, AL AF Lotfipour, Shahrdad Mandelkern, Mark Alvarez-Estrada, Miguel Brody, Arthur L. TI A Single Administration of Low-Dose Varenicline Saturates alpha 4 beta 2* Nicotinic Acetylcholine Receptors in the Human Brain SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE cigarettes; nicotinic receptors; addiction; varenicline; withdrawal; thalamus ID PARTIAL AGONIST VARENICLINE; GENETICALLY-MODIFIED MICE; IN-VIVO; WITHDRAWAL SYMPTOMS; TOBACCO WITHDRAWAL; BINDING-PROPERTIES; SMOKING-CESSATION; PRENATAL-EXPOSURE; MATERNAL-SMOKING; DRUG-USE AB The primary objective of this project was to determine the alpha 4 beta 2* nicotinic acetylcholine receptor (nAChR) occupancy in human brain of a single low dose of varenicline (0.5 mg), and to explore the relationship between receptor occupancy by varenicline and tobacco withdrawal symptoms (*denoting other putative nAChR subunits). Otherwise healthy smokers (n = 9) underwent two positron emission tomography (PET) sessions with the selective alpha 4 beta 2* radioligand 2-FA. For the PET sessions, participants received either a low dose of varenicline (0.5 mg) or matching placebo pill (double-blind, random order) before imaging. For both sessions, participants received bolus plus continuous infusions of 2-FA, were scanned for 1 h after allowing the radiotracer to reach a steady state, smoked to satiety, and were scanned for 2 more hours. We estimated the fractional receptor occupancy by a single dose of varenicline (0.5 mg) and the corresponding varenicline dissociation constant (K-V), along with the effect of low-dose varenicline, pill placebo, and smoking-to-satiety on withdrawal rating scales. The data are compatible with 100% occupancy of alpha 4 beta 2* nAChRs by a single dose of varenicline, with a 90% lower confidence limit of 89% occupancy for the thalamus and brainstem. The corresponding 90% upper limit on effective K-V with respect to plasma varenicline was 0.49 nM. Smoking to satiety, but not low-dose varenicline, significantly reduced withdrawal symptoms. Our findings demonstrate that low-dose varenicline results in saturation of alpha 4 beta 2* nAChRs in the thalamus and brainstem without reducing withdrawal symptoms. Neuropsychopharmacology (2012) 37, 1738-1748; doi:10.1038/npp.2012.20; published online 7 March 2012 C1 [Lotfipour, Shahrdad] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, MacDonald Res Labs, Los Angeles, CA 90095 USA. [Lotfipour, Shahrdad; Brody, Arthur L.] Univ Calif Los Angeles, Hatos Ctr Neuropharmacol, Semel Inst, Los Angeles, CA 90095 USA. [Lotfipour, Shahrdad; Mandelkern, Mark; Alvarez-Estrada, Miguel; Brody, Arthur L.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Mandelkern, Mark] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Lotfipour, S (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, MacDonald Res Labs, 675 Charles E Young Dr S, Los Angeles, CA 90095 USA. EM shahrdad@ucla.edu RI Lotfipour, Shahrdad/K-8335-2014 OI Lotfipour, Shahrdad/0000-0002-2425-1096 FU Pfizer Pharmaceutical Corporation [WS653344]; NIMH [MH17140]; NIDA [R01 DA20872]; Richard Metzner Chair in Clinical Neuropharmacology FX We thank Karen Ta, Jaime La Charite, Betram Nweke, Stuart Mirell, Van Cayetano, Chien Nguyen, Judah Farahi, Andrew Leuchter, Hans Rollema, Maziar Maghsoodnia, Alison Curtin, Ron Waldorf, Diep Seversen, and Josephine Ribe for their assistance on the study. This work was funded by Pfizer Pharmaceutical Corporation (Grant number: WS653344) (SL) and, in part, by T-32 NIMH post-doctoral fellowship (MH17140) (SL), NIDA (R01 DA20872) (ALB), and the Richard Metzner Chair in Clinical Neuropharmacology (ALB). NR 52 TC 13 Z9 13 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUN PY 2012 VL 37 IS 7 BP 1738 EP 1748 DI 10.1038/npp.2012.20 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 942LO UT WOS:000304045700018 PM 22395733 ER PT J AU Zinzow, HM Resnick, HS McCauley, JL Amstadter, AB Ruggiero, KJ Kilpatrick, DG AF Zinzow, Heidi M. Resnick, Heidi S. McCauley, Jenna L. Amstadter, Ananda B. Ruggiero, Kenneth J. Kilpatrick, Dean G. TI Prevalence and risk of psychiatric disorders as a function of variant rape histories: results from a national survey of women SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article DE Rape; Sexual assault; Posttraumatic stress disorder; Depression; Alcohol abuse; Drug abuse; Comorbidity ID POSTTRAUMATIC-STRESS-DISORDER; SEXUAL ASSAULT; INCAPACITATED RAPE; MENTAL-HEALTH; SUBSTANCE USE; ALCOHOL; SAMPLE; COMMUNITY; VIOLENCE; COMORBIDITY AB Rape is an established risk factor for mental health disorders, such as posttraumatic stress disorder (PTSD), major depressive episodes (MDE), and substance use disorders. The majority of studies have not differentiated substance-involved rape or examined comorbid diagnoses among victims. Therefore, the aim of the present study was to estimate the prevalence of common trauma-related psychiatric disorders (and their comorbidity) in a national sample of women, with an emphasis on distinguishing between rape tactics. A secondary objective was to estimate the risk for psychiatric disorders among victims of variant rape tactics, in comparison to non-victims. A nationally representative population-based sample of 3,001 non-institutionalized, civilian, English or Spanish speaking women (aged 18-86 years) participated in a structured telephone interview assessing rape history and DSM-IV criteria for PTSD, MDE, alcohol abuse (AA), and drug abuse (DA). Descriptive statistics and multivariate logistic regression analyses were employed. Women with rape histories involving both substance facilitation and forcible tactics reported the highest current prevalence of PTSD (36%), MDE (36%), and AA (20%). Multivariate models demonstrated that this victim group was also at highest risk for psychiatric disorders, after controlling for demographics and childhood and multiple victimization history. Women with substance-facilitated rapes reported higher prevalence of substance abuse in comparison to women with forcible rape histories. Comorbidity between PTSD and other psychiatric disorders was higher among rape victims in comparison to non-rape victims. Researchers and clinicians should assess substance-facilitated rape tactics and attend to comorbidity among rape victims. Empirically supported treatments are needed to address the complex presentations observed among women with variant rape histories. C1 [Zinzow, Heidi M.] Clemson Univ, Dept Psychol, Clemson, SC 29634 USA. [Resnick, Heidi S.; McCauley, Jenna L.; Amstadter, Ananda B.; Ruggiero, Kenneth J.; Kilpatrick, Dean G.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Natl Crime Victims Res & Treatment Ctr, Charleston, SC 29425 USA. [Ruggiero, Kenneth J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Zinzow, HM (reprint author), Clemson Univ, Dept Psychol, 418 Brackett Hall, Clemson, SC 29634 USA. EM hzinzow@clemson.edu FU National Institute of Justice [2005-WG-BX-0006]; NIDA [1R01DA023099-01A2] FX The research design and data collection were supported by National Institute of Justice Grant #2005-WG-BX-0006 (principal investigator: Dean G. Kilpatrick). Support for manuscript preparation was provided by NIDA 1R01DA023099-01A2 (principal investigator: Heidi Resnick). Views expressed in this article do not necessarily represent those of the agencies supporting this research. NR 27 TC 19 Z9 19 U1 7 U2 23 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0933-7954 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD JUN PY 2012 VL 47 IS 6 BP 893 EP 902 DI 10.1007/s00127-011-0397-1 PG 10 WC Psychiatry SC Psychiatry GA 944AT UT WOS:000304171300006 PM 21603967 ER PT J AU Singh, JA Wells, GA Christensen, R Tanjong, E MacDonald, J Tugwell, P Buchbinder, R AF Singh, J. A. Wells, G. A. Christensen, R. Tanjong, E. MacDonald, J. Tugwell, P. Buchbinder, R. CA Biol Safety Study Grp TI ADVERSE EFFECTS OF BIOLOGICS: A NETWORK META-ANALYSIS AND COCHRANE OVERVIEW SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract C1 [Singh, J. A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, J. A.] Univ Alabama Birmingham, Birmingham, AL USA. [Wells, G. A.] McMaster Univ, Ottawa, ON, Canada. [Christensen, R.] Univ Denmark, Copenhagen, Denmark. [Tanjong, E.; Tugwell, P.] Univ Ottawa, Montreal, PQ, Canada. [MacDonald, J.] Univ Washington, Seattle, WA 98195 USA. [Buchbinder, R.] Monash Univ, Monash, Australia. NR 0 TC 0 Z9 0 U1 2 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2012 VL 71 SU 3 BP 628 EP 628 PG 1 WC Rheumatology SC Rheumatology GA V31QQ UT WOS:000208898503315 ER PT J AU Bikle, DD AF Bikle, Daniel D. TI Vitamin D and Bone SO CURRENT OSTEOPOROSIS REPORTS LA English DT Article DE Vitamin D; Vitamin D receptor; CYP27B1; 25hydroxyvitamin; 1,25 dihydroxyvitamin D; 24,25 dihydroxyvitamin D; Bone; Chondrocytes; Osteoblasts; Osteoclasts AB All cells comprising the skeleton-chondrocytes, osteoblasts, and osteoclasts-contain both the vitamin D receptor and the enzyme CYP27B1 required for producing the active metabolite of vitamin D, 1,25 dihydroxyvitamin D. Direct effects of 25 hydroxyvitamin D and 1,25 dihydroxyvitamin D on these bone cells have been demonstrated. However, the major skeletal manifestations of vitamin D deficiency or mutations in the vitamin D receptor and CYP27B1, namely rickets and osteomalacia, can be corrected by increasing the intestinal absorption of calcium and phosphate, indicating the importance of indirect effects. On the other hand, these dietary manipulations do not reverse defects in osteoblast or osteoclast function that lead to osteopenic bone. This review discusses the relative importance of the direct versus indirect actions of vitamin D on bone, and provides guidelines for the clinical use of vitamin D to prevent/treat bone loss and fractures. C1 [Bikle, Daniel D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Bikle, DD (reprint author), San Francisco VA Med Ctr, 4150 Clement St 111N, San Francisco, CA 94121 USA. EM Daniel.bikle@ucsf.edu FU National Institutes of Health [RO1 DK054793, AR055924, AR050023] FX D.D. Bikle: has received grant support from the National Institutes of Health (RO1 DK054793, AR055924, and AR050023); and receives loyalties from Lange textbook chapter. NR 86 TC 37 Z9 39 U1 0 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA EI 1544-2241 J9 CURR OSTEOPOROS REP JI Curr. Osteoporos. Rep. PD JUN PY 2012 VL 10 IS 2 BP 151 EP 159 DI 10.1007/s11914-012-0098-z PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V35YS UT WOS:000209181600007 PM 22544628 ER PT J AU Rapuano, BE Hackshaw, K MacDonald, DE AF Rapuano, Bruce E. Hackshaw, Kyle MacDonald, Daniel E. TI Heat or radiofrequency plasma glow discharge treatment of a titanium alloy stimulates osteoblast gene expression in the MC3T3 osteoprogenitor cell line SO JOURNAL OF PERIODONTAL AND IMPLANT SCIENCE LA English DT Article DE Cell differentiation; Dental implants; Fibronectins; Integrin alpha5beta1; Osteoblasts AB Purpose: The purpose of this study was to determine whether increasing the Ti6Al4V surface oxide negative charge through heat (600 degrees C) or radiofrequency plasma glow discharge (RFGD) pretreatment, with or without a subsequent coating with fibronectin, stimulated osteoblast gene marker expression in the MC3T3 osteoprogenitor cell line. Methods: Quantitative real-time polymerase chain reaction was used to measure changes over time in the mRNA levels for osteoblast gene markers, including alkaline phosphatase, bone sialoprotein, collagen type I (alpha 1), osteocalcin, osteopontin and parathyroid hormone-related peptide (PTH-rP), and the osteoblast precursor genes Runx2 and osterix. Results: Osteoprogenitors began to differentiate earlier on disks that were pretreated with heat or RFGD. The pretreatments increased gene marker expression in the absence of a fibronectin coating. However, pretreatments increased osteoblast gene expression for fibronectin-coated disks more than uncoated disks, suggesting a surface oxide-mediated specific enhancement of fibronectin's bioactivity. Heat pretreatment had greater effects on the mRNA expression of genes for PTH-rP, alkaline phosphatase and osteocalcin while RFGD pretreatment had greater effects on osteopontin and bone sialoprotein gene expression. Conclusions: The results suggest that heat and RFGD pretreatments of the Ti6Al4V surface oxide stimulated osteoblast differentiation through an enhancement of (a) coated fibronectin's bioactivity and (b) the bioactivities of other serum or matrix proteins. The quantitative differences in the effects of the two pretreatments on osteoblast gene marker expression may have arisen from the unique physico-chemical characteristics of each resultant oxide surface. Therefore, engineering the Ti6Al4V surface oxide to become more negatively charged can be used to accelerate osteoblast differentiation through fibronectin-dependent and independent mechanisms. C1 [Rapuano, Bruce E.; Hackshaw, Kyle; MacDonald, Daniel E.] Cornell Univ, Hosp Special Surg, Weill Med Coll, New York, NY 10021 USA. [MacDonald, Daniel E.] James J Peters VA Med Ctr, Bronx, NY USA. [MacDonald, Daniel E.] Columbia Univ, Langmuir Ctr Colloids & Interfaces, New York, NY 10027 USA. RP MacDonald, DE (reprint author), Columbia Univ, Langmuir Ctr Colloids & Interfaces, 911 SW Mudd Bldg,500 West 120th St, New York, NY 10027 USA. EM dem14@columbia.edu FU National Center for Research Resources, NIH [C06-RR12538-01]; [NIH RO1 DE017695] FX The project described was supported by Grant Number NIH RO1 DE017695 (Awarded to DEM). This material is also the result of work supported with resources and the use of facilities at the James J. Peters VA Medical Center, Bronx, New York. This investigation was also conducted at the HSS research facility constructed with support of Grant C06-RR12538-01 from the National Center for Research Resources, NIH. We would like to acknowledge Dr. Xiaoyu Hu for technical advice with the qRT-PCR analyses. Special thanks goes to Paul Lee, Carrie Guan, and Jani Jae Eun Lee for the preparation and treatment of titanium alloy disks. NR 38 TC 6 Z9 6 U1 3 U2 6 PU KOREAN ACAD PERIODONTOLOGY PI SEOUL PA OFFICIAL B-D 2212, 163 SINMUNRO 1-GA, JONGNO-GU, SEOUL, 110-990, SOUTH KOREA SN 2093-2278 EI 2093-2286 J9 J PERIODONTAL IMPLAN JI J. Periodontal Implant Sci. PD JUN PY 2012 VL 42 IS 3 BP 95 EP 104 DI 10.5051/jpis.2012.42.3.95 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA V34HG UT WOS:000209076900006 PM 22803011 ER PT J AU Allen, NE Javdani, S Lehrner, AL Walden, AL AF Allen, Nicole E. Javdani, Shabnam Lehrner, Amy L. Walden, Angela L. TI "Changing the Text": Modeling Council Capacity to Produce Institutionalized Change SO AMERICAN JOURNAL OF COMMUNITY PSYCHOLOGY LA English DT Article DE Councils; Institutionalized change; Coordinating councils; Coalitions; Domestic violence; Intimate partner violence; Interagency coordination ID VIOLENCE COORDINATING COUNCILS; COMMUNITY-HEALTH COALITIONS; SUBSTANCE-ABUSE PREVENTION; GOVERNANCE PROCESSES; PARTICIPATION; EMPOWERMENT; PARTNERSHIPS; OUTCOMES; IMPLEMENTATION; PERSPECTIVE AB Collaboration is a ubiquitous approach to change, but is notoriously difficult and not definitively linked to desirable outcomes. Not surprisingly, the collaboration literature is replete with numerous facilitators and barriers to collaborative efforts. The current study aimed to develop a parsimonious model of factors influencing the success of collaborative efforts both internal and external to the council, including, (a) features of the council environment, (b) intermediate outcomes including the empowerment of members in the council context and the degree to which councils have generated social capital and (c) the extent to which collaborative efforts are occurring in a community context supportive of their aims. In particular, this study examines whether these factors affect the extent to which councils are positioned to achieve institutionalized change, or changes "in the text" that govern front line providers' (e.g., police, advocates) practices in the community response to intimate partner violence. Results suggest that perceived member empowerment, generation of social capital, and supportive community context are the most important predictors of the extent to which councils foster shifts in institutionalized change. Features of the council environment are only indirectly related to the degree to which institutionalized change is ultimately fostered as mediated by the generation of social capital. This suggests that the ability of members to act as change agents and the extent to which those in power support council efforts figure more prominently to facilitate or constrain council efforts than council functioning itself. C1 [Allen, Nicole E.; Javdani, Shabnam; Walden, Angela L.] Univ Illinois, Dept Psychol, Champaign, IL 61820 USA. [Lehrner, Amy L.] James J Peters VA Med Ctr, Traumat Stress Studies Div, Bronx, NY USA. RP Allen, NE (reprint author), Univ Illinois, Dept Psychol, 603 E Daniel St, Champaign, IL 61820 USA. EM allenne@illinois.edu OI Javdani, Shabnam/0000-0003-3949-1970 NR 50 TC 13 Z9 13 U1 2 U2 11 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0562 J9 AM J COMMUN PSYCHOL JI Am. J. Community Psychol. PD JUN PY 2012 VL 49 IS 3-4 BP 317 EP 331 DI 10.1007/s10464-011-9460-z PG 15 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Social Work SC Public, Environmental & Occupational Health; Psychology; Social Work GA 939HR UT WOS:000303800600002 PM 21842302 ER PT J AU Gunduz-Bruce, H Reinhart, RMG Roach, BJ Gueorguieva, R Oliver, S D'Souza, DC Ford, JM Krystal, JH Mathalon, DH AF Gunduz-Bruce, Handan Reinhart, Robert M. G. Roach, Brian J. Gueorguieva, Ralitza Oliver, Stephen D'Souza, Deepak C. Ford, Judith M. Krystal, John H. Mathalon, Daniel H. TI Glutamatergic Modulation of Auditory Information Processing in the Human Brain SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Glutamate; ketamine; MMN; N-acetylcysteine; NMDA; P300 ID MISMATCH NEGATIVITY MMN; HUMAN SELECTIVE ATTENTION; N-ACETYL-CYSTEINE; HEALTHY-VOLUNTEERS; P300 AMPLITUDE; GLUTATHIONE PRECURSOR; MENSTRUAL-CYCLE; SYSTEM X(C)(-); IN-VIVO; SCHIZOPHRENIA AB Background: Auditory mismatch negativity (MMN) and P300 event-related potentials (ERPs) are reduced in schizophrenia patients and healthy volunteers administered the N-methyl-D-aspartate glutamate receptor antagonist, ketamine. In rodents, N-acetylcysteine (NAC), a stimulator of the cystine-glutamate exchanger, attenuates the cognitive and behavioral effects of N-methyl-D-aspartate receptor antagonists. On the basis of these findings, we tested whether NAC would reduce ketamine effects on behavior, MMN, and P300 in healthy humans. Methods: This randomized, double-blind, placebo-controlled study consisted of 2 test days during which subjects (n = 16) were administered oral NAC (3000 mg in divided doses) or matching placebo 165 min before the infusion of saline and then ketamine (as a bolus of .23 mg/kg over 1 min followed by .58 mg/kg for 30 min, and then .29 mg/kg for 40 min) in a fixed order. Behavioral and ERP data including auditory MMN and P300 were collected during each test day. Results: Ketamine produced psychotic-like positive symptoms, reductions in working memory and sustained attention performance, and amplitude reductions for the frequency- and intensity-deviant MMNs and P300. NAC pretreatment did not reduce the behavioral or ERP effects of ketamine. In addition, NAC reduced frequency-deviant MMN amplitude and increased target and novelty P3 amplitudes. The decrements in frequency-deviant MMN amplitude produced by ketamine and NAC were not additive. Conclusions: NAC did not attenuate the effects of ketamine in humans, in contrast to previous studies in animals. NAC merits further investigation as a cognitive enhancing agent due to its ability to increase the P300 amplitude. C1 [Gunduz-Bruce, Handan; D'Souza, Deepak C.; Krystal, John H.] VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. [Gunduz-Bruce, Handan; Gueorguieva, Ralitza; Oliver, Stephen; D'Souza, Deepak C.; Ford, Judith M.; Krystal, John H.; Mathalon, Daniel H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Reinhart, Robert M. G.] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. [Ford, Judith M.; Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Ford, Judith M.; Mathalon, Daniel H.] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. RP Gunduz-Bruce, H (reprint author), VA Connecticut Healthcare Syst, 116-A,950 Campbell Ave, West Haven, CT 06516 USA. EM handan.gunduz-bruce@yale.edu OI Roach, Brian/0000-0002-3264-1465; Mathalon, Daniel/0000-0001-6090-4974; Gueorguieva, Ralitza/0000-0003-0944-5973 FU National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD); National Institute on Alcohol Abuse and Alcoholism [K05 AA 14906, 2P50 AA 012870]; US Department of Veterans Affairs Alcohol Research Center, National Center Post Traumatic Stress Disorder, Clinical Neurosciences Division, West Haven, Connecticut; VA Schizophrenia Biological Research Center; National Institute of Mental Health [MH40052, MH 58262, MH067967]; Astra Zeneca; Abbott Laboratories; Eli Lilly; Organon; Pfizer; Sanofi; Department of Veterans Affairs; Janssen Research Foundation; [R01 MH076989] FX This study was supported by a National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD) Hammerschlag Young Investigator Award to Dr. Gunduz-Bruce. Part of the data was previously presented as a poster at the 2007 annual meeting of the American College of Neuropsychopharmacology. We are thankful to the Biostudies Laboratory Nursing Staff; Angelina M. Genovese, RNC, MBA; Elizabeth O'Donnell, RN; Michelle Sanpedro, RN; and Brenda Breault, RN, BSN, for their outstanding nursing; and Sonah Perry, R.Ph., for excellent Research Pharmacy support. We also thank all the research participants. This study was also partly supported by funding from the National Institute on Alcohol Abuse and Alcoholism, K05 AA 14906, National Institute on Alcohol Abuse and Alcoholism, 2P50 AA 012870, US Department of Veterans Affairs Alcohol Research Center, National Center Post Traumatic Stress Disorder, Clinical Neurosciences Division, West Haven, Connecticut, to JHK; R01 MH076989 to DHM; VA Schizophrenia Biological Research Center, and grants from the National Institute of Mental Health (MH40052, MH 58262, MH067967) and NARSAD to JMF.; Drs. Gunduz-Bruce, Gueorguieva, Ford, and Mathalon and Mr. Reinhart, Mr. Roach, and Mr. Oliver report no biomedical financial interests or potential conflict of interests. Dr. D'Souza reports research grant support from Astra Zeneca, Abbott Laboratories, Eli Lilly, Organon, Pfizer, and Sanofi. Dr. Krystal reports serving as consultant for the following companies (the Individual Consultant Agreements listed are <$10,000/year): Aisling Capital, LLC, AstraZeneca Pharmaceuticals, Brintnall and Nicolini, Easton Associates, Gilead Sciences, GlaxoSmith-Kline, Janssen Pharmaceuticals, Lundbeck Research USA, Medivation, Merz Pharmaceuticals, MK Medical Communications, F. Hoffmann-La Roche, SK Holdings, Takeda Industries, and Teva Pharmaceutical Industries. Dr. Krystal also serves for the Scientific Advisory Board of Abbott Laboratories, Bristol-Myers Squibb, Eisai, Eli Lilly, Forest Laboratories, Lohocla Research Corporation, Mnemosyne Pharmaceuticals, Naurex, Pfizer Pharmaceuticals, and Shire Pharmaceuticals. Dr. Krystal holds Exercisable Warrant Options that include Tetragenex Pharmaceuticals (value <$150), and he serves as Board of Directors for the Coalition for Translational Research in Alcohol and Substance Use Disorders. Dr. Krystal is a President Elect for American College of Neuropsychopharmacology and receives research support from Department of Veterans Affairs and Janssen Research Foundation (provided drug and some study support to the Department of Veterans Affairs). Dr. Krystal receives >$10,000 as the Editor of Biological Psychiatry. Patents and Inventions for Dr. Krystal include: 1) Seibyl JP, Krystal JH, Charney DS. Dopamine and noradrenergic reuptake inhibitors in treatment of schizophrenia. Patent #:5,447,948. September 5, 1995; 2) co-inventor with Dr. Gerard Sanacora on a filed patent application by Yale University related to targeting the glutamatergic system for the treatment of neuropsychiatric disorders (PCTWO06108055A1); and 3) Intranasal Administration of Ketamine to Treat Depression (pending). NR 75 TC 28 Z9 29 U1 2 U2 12 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 JUN 1 PY 2012 VL 71 IS 11 BP 969 EP 977 DI 10.1016/j.biopsych.2011.09.031 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 939MH UT WOS:000303814800009 PM 22036036 ER PT J AU Yomogida, K Chou, Y Pang, J Baravati, B Maniaci, BJ Wu, S Zhu, Y Chu, CQ AF Yomogida, Kentaro Chou, Yuan Pang, Jonathan Baravati, Bobby Maniaci, Brian J. Wu, Shili Zhu, Yong Chu, Cong-Qiu TI Streptavidin suppresses T cell activation and inhibits IL-2 production and CD25 expression SO CYTOKINE LA English DT Article DE Streptavidin; Biotin; T Cell activation; Interleukin 2; Interleukin 2 receptor ID JURKAT CELLS; PRETARGETED RADIOIMMUNOTHERAPY; RENAL-TRANSPLANTATION; CHAIN IMMUNOTOXIN; BIOTIN DEFICIENCY; BINDING-PROTEIN; FUSION PROTEIN; REJECTION; DIFFERENTIATION; BIOTINYLATION AB Streptavidin is widely used as a detection tool in biology research because of its high affinity and specificity binding to biotin. Biotin-streptavidin system has also been explored for detection of infection and tumor in clinical medicine. Here, we show immunosuppressive property of streptavidin on T cell activation and proliferation. Upon CD3 and CD28 stimulation, CD4(+) T cells produce interleukin 2 (IL-2) and express IL-2 receptor alpha chain (CD25). Addition of streptavidin in T cell culture suppressed IL-2 synthesis and CD25 expression with no cytotoxicity. The immunosuppressive effect of streptavidin was reversed by excessive biotin. Conjugated to a single chain anti-CD7 variable fragment (scFvCD7), streptavidin was directly delivered to T cells and showed substantially more profound suppressive effect on T cell activation. These results suggest that streptavidin could potentially be used as a novel immunomodulator. Published by Elsevier Ltd. C1 [Yomogida, Kentaro; Chou, Yuan; Chu, Cong-Qiu] Oregon Hlth & Sci Univ, Div Arthrit & Rheumat Dis, Portland, OR USA. [Yomogida, Kentaro; Chou, Yuan; Chu, Cong-Qiu] Portland VA Med Ctr, Portland, OR USA. [Pang, Jonathan; Baravati, Bobby; Maniaci, Brian J.; Wu, Shili; Zhu, Yong] VivoScript Inc, Costa Mesa, CA USA. RP Chu, CQ (reprint author), 3181 SW Sam Jackson Pk Rd 0P09, Portland, OR 97239 USA. EM chuc@ohsu.edu FU NIH [AR055254]; Portland VA Medical Center FX This work was supported by a Grant from NIH to C.Q.C. (AR055254) and Portland VA Medical Center. NR 46 TC 4 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD JUN PY 2012 VL 58 IS 3 BP 431 EP 436 DI 10.1016/j.cyto.2012.02.007 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 941FA UT WOS:000303947900018 PM 22410319 ER PT J AU Walker, DD Reeves, TD de Costa, AM Schuyler, C Young, MRI AF Walker, David D. Reeves, Travis D. de Costa, Anna-Maria Schuyler, Corinne Young, M. Rita I. TI Immunological modulation by 1 alpha,25-dihydroxyvitamin D-3 in patients with squamous cell carcinoma of the head and neck SO CYTOKINE LA English DT Article DE Cytokines; Head and neck cancer; HNSCC; Vitamin D ID ENDOTHELIAL GROWTH-FACTOR; CANCER-PATIENTS; PERIPHERAL-BLOOD; CD34(+) CELLS; DENDRITIC CELLS; VITAMIN-D; IMMUNITY; DIFFERENTIATION; CARCINOGENESIS; IMMUNOTHERAPY AB Prior studies showing that treatment of head and neck squamous cell carcinoma (HNSCC) patients with 1 alpha,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] stimulated intratumoral immune infiltration were extended to analysis of cytokine profiles in the periphery and in oral tissues. Most prominent was the disparity between cytokine levels in plasma and in either pathologically normal oral tissue or HNSCC tissue from patients that were untreated or treated with 1,25(OH)(2)D-3. Levels of IL-6 and IL-10, but not IL-2, IFN-gamma or TNF-alpha, tended to be increased in the plasma of HNSCC patients and 1,25(OH)(2)D-3 further increased plasma levels of all of these cytokines. While these cytokines tended to be increased in HNSCC tissue, 1,25(OH)(2)D-3 resulted in variable cytokine responses that showed a general tendency toward further increased levels. Levels of IL-8 and VEGF were increased in plasma and tissue of untreated HNSCC patients, and were further increased in plasma, but not in tissues, of patients treated with 1,25(OH)(2)D-3. Levels of IL-1 alpha and IL-1 beta were similar in plasma of controls and HNSCC patients, but were increased in HNSCC tissues. In contrast to that seen in plasma where 1,25(OH)(2)D-3 increased levels of IL-1 alpha and IL-1 beta, this was not seen in tissue following 1,25(OH)(2)D-3 treatment. These results show a discordant relationship between systemic and intratumoral cytokine profiles and suggest a tendency of 1,25(OH)(2)D(3)to increase a multitude of cytokines within tumor tissue. Published by Elsevier Ltd. C1 [Walker, David D.; Reeves, Travis D.; Young, M. Rita I.] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC 29401 USA. [de Costa, Anna-Maria] Med Univ S Carolina, Dept Otolaryngol, Charleston, SC USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC USA. [Young, M. Rita I.] Med Univ S Carolina, Dept Med, Charleston, SC USA. RP Young, MRI (reprint author), Ralph H Johnson VA Med Ctr, Res Serv, 109 Bee St, Charleston, SC 29401 USA. EM david.walker4@gmail.com; reevestd@musc.edu; clarkann@musc.edu; schuylec@musc.edu; rita.young@va.gov FU Biomedical Laboratory and Clinical Sciences of the Department of Veterans Affairs; National Institute of Health [I01-CX000100, R01-CA128837, R01-DE018268] FX This work has been supported by awards from the Biomedical Laboratory and Clinical Sciences Programs of the Department of Veterans Affairs and by grants from the National Institute of Health (MRIY, I01-CX000100, R01-CA128837 and R01-DE018268). NR 28 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD JUN PY 2012 VL 58 IS 3 BP 448 EP 454 DI 10.1016/j.cyto.2012.03.002 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 941FA UT WOS:000303947900020 PM 22450225 ER PT J AU Rose, DE Tisnado, DM Tao, ML Malin, JL Adams, JL Ganz, PA Kahn, KL AF Rose, Danielle E. Tisnado, Diana M. Tao, May L. Malin, Jennifer L. Adams, John L. Ganz, Patricia A. Kahn, Katherine L. TI Prevalence, Predictors, and Patient Outcomes Associated with Physician Co-management: Findings from the Los Angeles Women's Health Study SO HEALTH SERVICES RESEARCH LA English DT Article DE Quality of care; physician practice style; physician co-management; patient ratings of care; breast cancer care; provider network restrictions ID PRIMARY-CARE PHYSICIANS; BREAST-CANCER SURVIVORS; QUALITY-OF-CARE; FINANCIAL INCENTIVES; SPECIALTY-CARE; SYSTEM; SATISFACTION; GENERALIST; INTERFACE; PATTERNS AB Background Physician co-management, representing joint participation in the planning, decision-making, and delivery of care, is often cited in association with coordination of care. Yet little is known about how physicians manage tasks and how their management style impacts patient outcomes. Objectives To describe physician practice style using breast cancer as a model. We characterize correlates and predictors of physician practice style for 10 clinical tasks, and then test for associations between physician practice style and patient ratings of care. Methods We queried 347 breast cancer physicians identified by a population-based cohort of women with incident breast cancer regarding care using a clinical vignette about a hypothetical 65-year-old diabetic woman with incident breast cancer. To test the association between physician practice style and patient outcomes, we linked medical oncologists responses to patient ratings of care (physician n = 111; patient n = 411). Results After adjusting for physician and practice setting characteristics, physician practice style varied by physician specialty, practice setting, financial incentives, and barriers to referrals. Patients with medical oncologists who co-managed tasks had higher patient ratings of care. Conclusion Physician practice style for breast cancer is influenced by provider and practice setting characteristics, and it is an important predictor of patient ratings. We identify physician and practice setting factors associated with physician practice style and found associations between physician co-management and patient outcomes (e.g., patient ratings of care). C1 [Rose, Danielle E.] VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, Sepulveda, CA 91343 USA. [Tisnado, Diana M.; Kahn, Katherine L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Tao, May L.] Ctr Radiat Therapy Beverly Hills, Beverly Hills, CA USA. [Adams, John L.] RAND Corp, Santa Monica, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Publ Hlth, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA. RP Rose, DE (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, 16111 Plummer St 152, Sepulveda, CA 91343 USA. EM droseash@gmail.com FU California Breast Cancer Research program [7PB-0126S]; National Cancer Institute; Agency for Health Care Research and Quality [1-R01-CA81338-01A1]; University of California, Los Angeles; Resource Centers for Minority Aging Research Center for Health Improvement of Minority Elderly (RCMAR/CHIME) under NIH/NIA [P30-AG021684]; UCLA; National Cancer Institute [R25 CA087949] FX This research was funded by the California Breast Cancer Research program grant 7PB-0126S and the National Cancer Institute and the Agency for Health Care Research and Quality grant 1-R01-CA81338-01A1. Dr. Tisnado received support from the University of California, Los Angeles, Resource Centers for Minority Aging Research Center for Health Improvement of Minority Elderly (RCMAR/CHIME) under NIH/NIA Grant P30-AG021684, and the content does not necessarily represent the official views of the NIA or the NIH. Dr. Rose received support from the UCLA Cancer Education and Career Development Program, National Cancer Institute grant R25 CA087949. We thank the two anonymous referees for suggestions that significantly strengthened the analyses. We acknowledge Diane Fitzpatrick and Ann Zisser for their data collection efforts (under supervision); Fang Ashlee Hu for programming and data management, and Judith Magee for administrative support. 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 47 TC 4 Z9 4 U1 2 U2 5 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 JUN PY 2012 VL 47 IS 3 BP 1091 EP 1116 DI 10.1111/j.1475-6773.2011.01359.x PN 1 PG 26 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 939HN UT WOS:000303800200012 PM 22171977 ER PT J AU Chung, M Newberry, SJ Ansari, MT Yu, WW Wu, H Lee, J Suttorp, M Gaylor, JM Motala, A Moher, D Balk, EM Shekelle, PG AF Chung, Mei Newberry, Sydne J. Ansari, Mohammed T. Yu, Winifred W. Wu, Helen Lee, Jounghee Suttorp, Marika Gaylor, James M. Motala, Aneesa Moher, David Balk, Ethan M. Shekelle, Paul G. TI Two methods provide similar signals for the need to update systematic reviews SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Review DE Evidence-based methodology; Systematic reviews; Comparative effectiveness reviews; Omega-3 fatty acids; Cardiovascular disease risk factors; Cancer; Cognitive function ID OMEGA-3-FATTY-ACIDS; GUIDELINES AB Objective: Apply and compare two methods that identify signals for the need to update systematic reviews, using three Evidence-based Practice Center reports on omega-3 fatty acids as test cases. Study Design and Setting: We applied the RAND method, which uses domain (subject matter) expert guidance, and a modified Ottawa method, which uses quantitative and qualitative signals. For both methods, we conducted focused electronic literature searches of recent studies using the key terms from the original reports. We assessed the agreement between the methods and qualitatively assessed the merits of each system. Results: Agreement between the two methods was "substantial" or better (kappa > 0.62) in three of the four systematic reviews. Overall agreement between the methods was "substantial" (kappa = 0.64, 95% confidence interval [Cl] 0.45-0.83). Conclusion: The RAND and modified Ottawa methods appear to provide similar signals for the possible need to update systematic reviews in this pilot study. Future evaluation with a broader range of clinical topics and eventual comparisons between signals to update reports and the results of full evidence review updates will be needed. We propose a hybrid approach combining the best features of both methods, which should allow efficient review and assessment of the need to update. (C) 2012 Elsevier Inc. All rights reserved. C1 [Chung, Mei; Yu, Winifred W.; Lee, Jounghee; Gaylor, James M.; Balk, Ethan M.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Tufts Evidence Based Practice Ctr, Boston, MA 02111 USA. [Newberry, Sydne J.; Wu, Helen; Suttorp, Marika; Motala, Aneesa; Shekelle, Paul G.] So Calif Evidence Based Practice Ctr, RAND Hlth, Santa Monica, CA USA. [Shekelle, Paul G.] W Los Angeles VA Med Ctr, Los Angeles, CA USA. [Ansari, Mohammed T.; Moher, David] Univ Ottawa, Evidence Based Practice Ctr, Ottawa Methods Ctr, Clin Epidemiol Program,Ottawa Hosp Res Inst, Ottawa, ON, Canada. RP Chung, M (reprint author), Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Tufts Evidence Based Practice Ctr, Box 63,800 Washington St, Boston, MA 02111 USA. EM mchung1@tuftsmedicalcenter.org OI , /0000-0002-6834-7583; Wu, Helen/0000-0001-7775-5282; Moher , David /0000-0003-2434-4206 FU NHLBI NIH HHS [T32 HL069772] NR 16 TC 14 Z9 14 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JUN PY 2012 VL 65 IS 6 BP 660 EP 668 DI 10.1016/j.jclinepi.2011.12.004 PG 9 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 940PA UT WOS:000303904300011 PM 22464414 ER PT J AU Kopp, RP Stroup, SP Schroeck, FR Freedland, SJ Millard, F Terris, MK Aronson, WJ Presti, JC Amling, CL Kane, CJ AF Kopp, Ryan P. Stroup, Sean P. Schroeck, Florian R. Freedland, Stephen J. Millard, Frederick Terris, Martha K. Aronson, William J. Presti, Joseph C., Jr. Amling, Christopher L. Kane, Christopher J. TI Are Repeat Prostate Biopsies Safe? A Cohort Analysis From the SEARCH Database SO JOURNAL OF UROLOGY LA English DT Article DE biopsy; prostatic neoplasms; prostatectomy; recurrence; diagnosis ID INTRAEPITHELIAL NEOPLASIA; NEEDLE BIOPSIES; HIGH-GRADE; CANCER; PROPHYLAXIS; INFECTION; TRENDS; MEN AB Purpose: Patients question whether multiple biopsy sessions cause worse prostate cancer outcomes. Therefore, we investigated whether there is an association between the number of prior biopsy sessions and biochemical recurrence after radical prostatectomy. Materials and Methods: Men in the SEARCH (Shared Equal Access Regional Cancer Hospital) database who underwent radical prostatectomy between 1988 and 2010 after a known number of prior biopsies were included in the analysis. Number of biopsy sessions (range 1 to 8) was examined as a continuous and categorical (1, 2 and 3 to 8) variable. Biochemical recurrence was defined as a prostate specific antigen greater than 0.2 ng/ml, 2 values at 0.2 ng/ml or secondary treatment for an increased prostate specific antigen. The association between number of prior biopsy sessions and biochemical recurrence was analyzed using the Cox proportional hazards model. Kaplan-Meier estimates of freedom from biochemical recurrence were compared among the groups. Results: Of the 2,739 men in the SEARCH database who met the inclusion criteria 2,251 (82%) had only 1 biopsy, 365(13%) had 2 biopsies and 123 (5%) had 3 or more biopsies. More biopsy sessions were associated with higher prostate specific antigen (p < 0.001), greater prostate weight (p < 0.001), lower biopsy Gleason sum (p = 0.01) and more organ confined (pT2) disease (p = 0.017). The Cox proportional hazards model demonstrated no association between number of biopsy sessions as a continuous or categorical variable and biochemical recurrence. Kaplan-Meier estimates of freedom from biochemical recurrence were similar across biopsy groups (log rank p = 0.211). Conclusions: Multiple biopsy sessions are not associated with an increased risk of biochemical recurrence in men undergoing radical prostatectomy. Multiple biopsy sessions appear to select for a low risk cohort. C1 [Kopp, Ryan P.; Stroup, Sean P.; Kane, Christopher J.] Univ Calif San Diego, Div Urol, San Diego, CA 92103 USA. [Stroup, Sean P.; Millard, Frederick; Kane, Christopher J.] Moores UCSD Canc Ctr, Sect Urol Oncol, La Jolla, CA USA. [Stroup, Sean P.; Kane, Christopher J.] Vet Affairs San Diego Med Ctr, Urol Sect, La Jolla, CA USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Aronson, William J.] Vet Affairs Greater Los Angeles Healthcare Syst, Urol Sect, Los Angeles, CA USA. [Presti, Joseph C., Jr.] Stanford Univ, Sch Med, Dept Urol, Palo Alto, CA 94304 USA. [Presti, Joseph C., Jr.] Vet Affairs Med Ctr, Urol Sect, Palo Alto, CA 94304 USA. [Schroeck, Florian R.; Freedland, Stephen J.] Duke Univ, Sch Med, Dept Surg, Div Urol Surg, Durham, NC USA. [Freedland, Stephen J.] Duke Univ, Sch Med, Dept Pathol, Durham, NC 27706 USA. [Freedland, Stephen J.] Duke Univ, Sch Med, Duke Prostate Ctr, Durham, NC USA. [Freedland, Stephen J.] Vet Affairs Med Ctr, Urol Sect, Durham, NC USA. [Terris, Martha K.] Vet Affairs Med Ctr, Urol Sect, Augusta, GA USA. [Terris, Martha K.] Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. [Amling, Christopher L.] Oregon Hlth & Sci Univ, Div Urol, Portland, OR 97201 USA. RP Kane, CJ (reprint author), Univ Calif San Diego, Div Urol, 200 W Arbor Dr,8897, San Diego, CA 92103 USA. EM ckane@ucsd.edu OI Terris, Martha/0000-0002-3843-7270; Schroeck, Florian/0000-0002-1860-2611 FU Department of Veterans Affairs; Department of Defense; Prostate Cancer Research Program; NIH [R01CA100938, P50 CA92131-01A1]; Georgia Cancer Coalition; American Urological Association Foundation FX Supported by the Department of Veterans Affairs, the Department of Defense, Prostate Cancer Research Program (SJF), NIH R01CA100938 (WJA), NIH Specialized Programs of Research Excellence Grant P50 CA92131-01A1 (WJA), Georgia Cancer Coalition (MKT) and the American Urological Association Foundation/Astellas Rising Star in Urology Award (SJF). Views and opinions of and endorsements by the author(s) do not reflect those of the U.S. Army, U.S. Navy or the Department of Defense. NR 18 TC 5 Z9 5 U1 0 U2 1 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 JUN PY 2012 VL 187 IS 6 BP 2056 EP 2060 DI 10.1016/j.juro.2012.01.083 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 939OK UT WOS:000303821300033 PM 22498218 ER PT J AU Hung, WW Ross, JS Boockvar, KS Siu, AL AF Hung, William W. Ross, Joseph S. Boockvar, Kenneth S. Siu, Albert L. TI Association of Chronic Diseases and Impairments With Disability in Older Adults A Decade of Change? SO MEDICAL CARE LA English DT Article DE chronic disease; impairment; disability; prevalence trends ID VISUAL FUNCTION QUESTIONNAIRE; LATE-LIFE DISABILITY; COGNITIVE IMPAIRMENT; FUNCTIONAL DISABILITY; DIABETES-MELLITUS; WOMENS HEALTH; UNITED-STATES; POPULATION; RETIREMENT; TRENDS AB Background: Little is known about how the relationship between chronic disease, impairment, and disability has changed over time among older adults. Objective: To examine how the associations of chronic disease and impairment with specific disability have changed over time. Research Design: Repeated cross-sectional analysis, followed by examining the collated sample using time interaction variables, of 3 recent waves of the Health and Retirement Study. Subjects: The subjects included 10,390, 10,621 and 10,557 community-dwelling adults aged 65 years and above in 1998, 2004, and 2008. Measurements: Survey-based history of chronic diseases including hypertension, heart disease, heart failure, stroke, diabetes, cancer, chronic lung disease, and arthritis; impairments, including cognition, vision, and hearing; and disability, including mobility, complex activities of daily living (ADL), and self-care ADL. Results: Over time, the relationship of chronic diseases and impairments with disability was largely unchanged; however, the association between hypertension and complex ADL disability weakened from 1998 to 2004 and 2008 [odds ratio (OR) = 1.24; 99% confidence interval (CI), 1.06-1.46; OR = 1.07; 99% CI, 0.90-1.27; OR = 1.00; 99% CI, 0.83-1.19, respectively], as it did for hypertension and self-care disability (OR = 1.32; 99% CI, 1.13-1.54; OR= 0.97; 99% CI, 0.82-1.14; OR = 0.99; 99% CI, 0.83-1.17). The association between diabetes and self-care disability strengthened from 1998 to 2004 and 2008 (OR = 1.21; 99% CI, 1.01-1.46; OR = 1.37; 99% CI, 1.15-1.64; OR = 1.52; 99% CI, 1.29-1.79), as it also did for lung disease and self-care disability (OR = 1.64; 99% CI, 1.33-2.03; OR = 1.63; 99% CI, 1.32-2.01; OR = 2.11; 99% CI, 1.73-2.57). Conclusions: Although relationships between diseases, impairments, and disability were largely unchanged, disability became less associated with hypertension and more with diabetes and lung disease. C1 [Hung, William W.; Boockvar, Kenneth S.; Siu, Albert L.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Hung, William W.; Boockvar, Kenneth S.; Siu, Albert L.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Ross, Joseph S.] Yale Univ, Sch Med, Dept Med, Gen Internal Med Sect, New Haven, CT 06510 USA. [Ross, Joseph S.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. [Boockvar, Kenneth S.] Jewish Home Lifecare, New York, NY USA. [Hung, William W.; Boockvar, Kenneth S.; Siu, Albert L.] James J Peters VA Hlth Serv Res & Dev Res Enhance, Bronx, NY USA. RP Hung, WW (reprint author), Mt Sinai Sch Med, Dept Geriatr & Palliat Med, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM william.hung@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU John A Hartford Foundation Center of Excellence; New York Academy of Medicine; National Institute on Aging [K08 AG032886, U01AG009740]; American Federation of Aging Research; Greenwall Foundation FX W.W.H. is a John A Hartford Foundation Center of Excellence Scholar and a New York Academy of Medicine Hoar Fellow. J.S.R. is currently supported by the National Institute on Aging (K08 AG032886) and by the American Federation of Aging Research through the Paul B. Beeson Career Development Award Program. K. S. B. is supported by the Greenwall Foundation. The Health and Retirement Study is sponsored by the National Institute on Aging (grant number U01AG009740) and conducted by the Institute for Social Research at the University of Michigan. NR 35 TC 20 Z9 22 U1 2 U2 7 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 JUN PY 2012 VL 50 IS 6 BP 501 EP 507 DI 10.1097/MLR.0b013e318245a0e0 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 941ST UT WOS:000303985900006 PM 22584885 ER PT J AU Okunseri, C Okunseri, E Thorpe, JM Xiang, Q Szabo, A AF Okunseri, Christopher Okunseri, Elaye Thorpe, Joshua M. Xiang, Qun Szabo, Aniko TI Medications Prescribed in Emergency Departments for Nontraumatic Dental Condition Visits in the United States SO MEDICAL CARE LA English DT Article DE dental care; dental service utilization; emergency service; medications ID ETHNIC DISPARITIES; CARE; ANALGESIA; PAIN; MANAGEMENT; PATIENT AB Background: Prior research has documented factors associated with nontraumatic dental condition (NTDC) visits to emergency departments (EDs), but little is known about the care received by patients in EDs for NTDC visits. Objective: We examined national trends in prescription of analgesics and antibiotics in EDs for NTDC visits in the United States. Research Design: We analyzed data from the National Hospital Ambulatory Medical Care survey from 1997 to 2007. We used a multivariable logistic regression model to examine factors associated with receiving analgesics and antibiotics for NTDC visits in EDs. Results: Overall 74% received at least 1 analgesic, 56% received at least 1 antibiotic, and 13% received no medication at all during NTDC visits to EDs. The prescription of medications at EDs for NTDC visits steadily increased over time for analgesics (odds ratio = 1.11/y, P < 0.0001) and antibiotics (odds ratio = 1.06/y,P < 0.0001). In the multivariable analysis, self-pay patients had significantly higher adjusted odds of receiving antibiotics, whereas those with nondental reasons for visits and children (0-4 y) had significantly lower adjusted odds of receiving a prescription for antibiotics in EDs for NTDC visits. Children (0-4 y), adults (53-72 y), and older adults (73 y and older) had lower adjusted odds (P < 0.001) of receiving analgesics. Conclusions: Nationally, analgesic and antibiotic prescriptions for NTDC visits to EDs have increased substantially over time. Selfpay patients had significantly higher odds of being prescribed antibiotics. Adults over 53 years and especially those 73 years and older had significantly lower odds of receiving analgesics in EDs for NTDC visits. C1 [Okunseri, Christopher; Okunseri, Elaye] Marquette Univ, Dept Clin Serv, Sch Dent, Milwaukee, WI 53201 USA. [Thorpe, Joshua M.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Thorpe, Joshua M.] Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Xiang, Qun; Szabo, Aniko] Med Coll Wisconsin, Div Biostat, Inst Hlth & Soc, Milwaukee, WI 53226 USA. RP Okunseri, C (reprint author), Marquette Univ, Dept Clin Serv, Sch Dent, Room 356,POB 1881, Milwaukee, WI 53201 USA. EM christopher.okunseri@mu.edu RI Szabo, Aniko/F-9656-2012; Thorpe, Joshua/C-1188-2013 FU National Institute of Health [1R15DE021196-01] FX Supported by the National Institute of Health Grant #1R15DE021196-01. The authors declare no conflict of interest. NR 25 TC 19 Z9 19 U1 0 U2 1 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 JUN PY 2012 VL 50 IS 6 BP 508 EP 512 DI 10.1097/MLR.0b013e318245a575 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 941ST UT WOS:000303985900007 PM 22584886 ER PT J AU Genta, RM Sonnenberg, A AF Genta, R. M. Sonnenberg, A. TI Non-Helicobacter pylori gastritis is common among paediatric patients with inflammatory bowel disease SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID FOCALLY ENHANCED GASTRITIS; CROHNS-DISEASE; ULCERATIVE-COLITIS; PEPTIC-ULCER; INFECTION; MORTALITY; BIOPSIES; DUODENUM AB Background Helicobacter-negative gastritis and duodenitis occur more often in patients with inflammatory bowel disease (IBD) than in non-IBD controls. Preliminary evidence suggests that they are particularly common among children. Aim To study the age-specific occurrence of gastritis and duodenitis among paediatric IBD patients. Methods From a computerised database of surgical pathology reports, we selected 344 IBD patients and 4241 non-IBD controls between the age 0 and 21 years, who underwent colonoscopy and oesophago-gastro-duodenoscopy with biopsy results from both procedures. Results Helicobacter-negative chronic active gastritis was found in 2% of controls and 20% of IBD patients (Crohn's disease (CD) 26%, ulcerative colitis (UC) 13%). Duodenitis was found in 2% of controls and 17% of IBD patients (Crohn's disease 28%, UC 8%). Similar prevalence rates were observed in male and female patients. The most striking age-specific patterns were seen in Crohn's disease, with chronic active gastritis being highest in the 59 years age-group and declining in all subsequent age-groups. The age-specific rise and fall of duodenitis appeared more protracted, reaching a peak at age 1014 years and then gradually declining. Conclusions Helicobacter-negative gastritis and duodenitis occur significantly more often in paediatric IBD patients than in non-IBD controls, as well as in adult IBD patients. Such upper gastrointestinal inflammation appears to be particularly common in patients with Crohn's disease. C1 [Genta, R. M.] Miraca Life Sci, Irving, TX USA. [Genta, R. M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Genta, R. M.] Dallas VA Med Ctr, Dallas, TX USA. [Sonnenberg, A.] Portland VA Med Ctr, Portland, OR USA. [Sonnenberg, A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr P3 GI, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu FU Takeda Pharmaceuticals FX Declaration of personal interests: Robert M. Genta is employed by Miraca Life Sciences, Irving, TX, USA. Amnon Sonnenberg is supported by a grant from Takeda Pharmaceuticals. NR 22 TC 12 Z9 13 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD JUN PY 2012 VL 35 IS 11 BP 1310 EP 1316 DI 10.1111/j.1365-2036.2012.05090.x PG 7 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 934IF UT WOS:000303437000007 PM 22486730 ER PT J AU Stephens, CE Newcomer, R Blegen, M Miller, B Harrington, C AF Stephens, Caroline E. Newcomer, Robert Blegen, Mary Miller, Bruce Harrington, Charlene TI Emergency Department Use by Nursing Home Residents: Effect of Severity of Cognitive Impairment SO GERONTOLOGIST LA English DT Article DE cognitive impairment; nursing home; emergency department; hospitalization; ambulatory care-sensitive condition ID MINIMUM DATA SET; FACILITY RESIDENTS; TRANSITIONAL CARE; ADVANCED DEMENTIA; AMBULATORY-CARE; OLDER-PEOPLE; HOSPITALIZATION; HEALTH; DECISIONS; MDS AB To examine the 1-year prevalence and risk of emergency department (ED) use and ambulatory care-sensitive (ACS) ED use by nursing home (NH) residents with different levels of severity of cognitive impairment (CI). We used multinomial logistic regression to estimate the effect of CI severity on the odds of any ED visit and any ACS ED visit in a 2006 national random sample of NH residents, controlling for predisposing, enabling, and need characteristics. Of 132,753 NH residents, 62% had at least one ED visit and approximately 24% had at least one ACS ED visit in 2006. The probability of any ED visit or any ACS ED visit varied with the severity of resident CI. Residents with mild CI had up to15% higher odds of any ED or any ACS ED visit and those with more moderate CI had 9% higher odds of an ACS ED visit compared with those without CI. The probability of any ED visit was negatively associated with advanced dementia (adjusted odds ratio = 0.60; 95% CI = 0.55-0.65). Earlier identification of persons with mild CI may facilitate patient, family, and staff education, as well as advanced care planning to reduce ACS ED visits. Both ACS ED use and hospitalizations, adjusted for case mix, should be used as quality indicators to help ensure greater accountability for high-quality NH care and more appropriate utilization of ED resources. C1 [Stephens, Caroline E.; Newcomer, Robert; Harrington, Charlene] Univ Calif San Francisco, Dept Social & Behav Sci, San Francisco, CA 94143 USA. [Stephens, Caroline E.] San Francisco VA Med Ctr, Div Geriatr Palliat & Extended Care, San Francisco, CA USA. [Blegen, Mary] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Miller, Bruce] Univ Calif San Francisco, Dept Community Hlth Syst, San Francisco, CA 94143 USA. RP Stephens, CE (reprint author), Univ Calif San Francisco, Dept Social & Behav Sci, 3333 Calif St,Suite 455, San Francisco, CA 94143 USA. EM caroline.stephens@ucsf.edu NR 42 TC 11 Z9 11 U1 1 U2 8 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 JUN PY 2012 VL 52 IS 3 BP 383 EP 393 DI 10.1093/geront/gnr109 PG 11 WC Gerontology SC Geriatrics & Gerontology GA 936OM UT WOS:000303599900009 PM 22056961 ER PT J AU Menschikowski, M Hagelgans, A Fuessel, S Mareninova, OA Neumeister, V Wirth, MP Siegert, G AF Menschikowski, Mario Hagelgans, Albert Fuessel, Susanne Mareninova, Olga A. Neumeister, Volker Wirth, Manfred P. Siegert, Gabriele TI Serum Levels of Secreted Group IIA Phospholipase A(2) in Benign Prostatic Hyperplasia and Prostate Cancer: A Biomarker for Inflammation or Neoplasia? SO INFLAMMATION LA English DT Article DE prostate cancer; benign prostatic hyperplasia; secreted phospholipase A(2); C-reactive protein; inflammation ID C-REACTIVE PROTEIN; PROGNOSTIC MARKER; EXPRESSION; DISEASES; RISK; ANTIGEN; INTERLEUKIN-6; ASSOCIATION; INCIDENT; ENZYMES AB Secreted group IIA phospholipase A(2) (sPLA(2)-IIA) is markedly up-regulated in human prostate cancer (PCa) specimens and in some PCa-derived cell lines, indicating an important role of this enzyme in tumourigenesis. In this study, we measured levels of sPLA(2)-IIA, C-reactive protein (CRP), and prostate-specific antigen (PSA) in serum samples obtained from patients with benign prostatic hyperplasia (BPH) and with PCa of different stages. We found that serum levels of sPLA(2)-IIA and CRP in BPH and PCa patients were significantly elevated compared to those of healthy individuals, but the concentrations of these inflammatory biomarkers did not differ between patients with BPH or PCa. Furthermore, serum levels of sPLA(2)-IIA correlated with concentrations of CRP, but not with PSA, Gleason grade or tumour stage. In conclusion, these findings suggest that cancer-related changes are not exclusive factors contributing to elevated serum sPLA(2)-IIA levels and emphasize the utility of sPLA(2)-IIA as a circulating marker of inflammation in patients with BPH and PCa. C1 [Menschikowski, Mario; Hagelgans, Albert; Neumeister, Volker; Siegert, Gabriele] Tech Univ Dresden, Med Fac Carl Gustav Carus, Inst Clin Chem & Lab Med, D-01307 Dresden, Germany. [Fuessel, Susanne; Wirth, Manfred P.] Tech Univ Dresden, Med Fac Carl Gustav Carus, Dept Urol, D-01307 Dresden, Germany. [Mareninova, Olga A.] Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Menschikowski, M (reprint author), Tech Univ Dresden, Med Fac Carl Gustav Carus, Inst Clin Chem & Lab Med, Fetscherstr 74, D-01307 Dresden, Germany. EM Mario.Menschikowski@uniklinikum-dresden.de NR 40 TC 9 Z9 9 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0360-3997 EI 1573-2576 J9 INFLAMMATION JI Inflammation PD JUN PY 2012 VL 35 IS 3 BP 1113 EP 1118 DI 10.1007/s10753-011-9418-1 PG 6 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 933SI UT WOS:000303382400041 PM 22189868 ER PT J AU So, K Ganguly, K Jimenez, J Gastpar, MC Carmena, JM AF So, Kelvin Ganguly, Karunesh Jimenez, Jessica Gastpar, Michael C. Carmena, Jose M. TI Redundant information encoding in primary motor cortex during natural and prosthetic motor control SO JOURNAL OF COMPUTATIONAL NEUROSCIENCE LA English DT Article DE Mutual information; Neural ensemble; Motor control; Brain-machine interface; Electrophysiology; Primary motor cortex ID CORTICAL-NEURONS; POPULATION CODES; MOVEMENT DIRECTION; ARM MOVEMENTS; DISCHARGE; SYNERGY; REORGANIZATION; INDEPENDENCE; INTERFACE AB Redundant encoding of information facilitates reliable distributed information processing. To explore this hypothesis in the motor system, we applied concepts from information theory to quantify the redundancy of movement-related information encoded in the macaque primary motor cortex (M1) during natural and neuroprosthetic control. Two macaque monkeys were trained to perform a delay center-out reaching task controlling a computer cursor under natural arm movement (manual control, 'MC'), and using a brain-machine interface (BMI) via volitional control of neural ensemble activity (brain control, 'BC'). During MC, we found neurons in contralateral M1 to contain higher and more redundant information about target direction than ipsilateral M1 neurons, consistent with the laterality of movement control. During BC, we found that the M1 neurons directly incorporated into the BMI ('direct' neurons) contained the highest and most redundant target information compared to neurons that were not incorporated into the BMI ('indirect' neurons). This effect was even more significant when comparing to M1 neurons of the opposite hemisphere. Interestingly, when we retrained the BMI to use ipsilateral M1 activity, we found that these neurons were more redundant and contained higher information than contralateral M1 neurons, even though ensembles from this hemisphere were previously less redundant during natural arm movement. These results indicate that ensembles most associated to movement contain highest redundancy and information encoding, which suggests a role for redundancy in proficient natural and prosthetic motor control. C1 [So, Kelvin; Jimenez, Jessica; Gastpar, Michael C.; Carmena, Jose M.] Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA. [Ganguly, Karunesh] San Francisco VA Med Ctr, San Francisco, CA USA. [Ganguly, Karunesh] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Gastpar, Michael C.] Ecole Polytech Fed Lausanne, Sch Comp & Commun Sci, EPFL, Lausanne, Switzerland. [Carmena, Jose M.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. [Carmena, Jose M.] Univ Calif Berkeley, UCB UCSF Joint Grad Grp Bioengn, Berkeley, CA 94720 USA. [Carmena, Jose M.] Univ Calif Berkeley, Program Cognit Sci, Berkeley, CA 94720 USA. RP Carmena, JM (reprint author), Univ Calif Berkeley, Dept Elect Engn & Comp Sci, 754 Sutardja Dai Hall, Berkeley, CA 94720 USA. EM carmena@eecs.berkeley.edu FU National Science Foundation CDI; Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development; American Heart Association/American Stroke Association FX The research reported here was supported by the National Science Foundation CDI Type-I grant to M.C.G. and J.M.C., and the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development, and the American Heart Association/American Stroke Association to K.G. NR 26 TC 4 Z9 4 U1 1 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5313 J9 J COMPUT NEUROSCI JI J. Comput. Neurosci. PD JUN PY 2012 VL 32 IS 3 BP 555 EP 561 DI 10.1007/s10827-011-0369-1 PG 7 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA 936KO UT WOS:000303589500011 PM 22042443 ER PT J AU Garrido, MM Allison, KC Bergeron, MJ Dowd, B AF Garrido, Melissa M. Allison, Kirk C. Bergeron, Mark J. Dowd, Bryan TI Hospital Religious Affiliation and Outcomes for High-Risk Infants SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE infant mortality; hospital ownership; religious affiliation ID BIRTH-WEIGHT INFANTS; OF-LIFE; EMERGENCY CONTRACEPTION; MORTALITY-RATES; INTENSIVE-CARE; NEONATAL CARE; UNITED-STATES; SERVICES; END; PROVISION AB The effect of hospital organizational affiliation on perinatal outcomes is unknown. Using the 2004 American Hospital Association Annual Survey and Healthcare Cost and Utilization Project State Inpatient Databases, the authors examined relationships among organizational affiliation, equipment and service availability and provision, and in-hospital mortality for 5,133 infants across five states born with very low and extremely low birth weight and congenital anomalies. In adjusted bivariate probit selection models, the authors found that government hospitals had significantly higher mortality rates than not-for-profit nonreligious hospitals. Mortality differences among other types of affiliation (Catholic, not-for-profit religious, not-for-profit nonreligious, and for-profit) were not statistically significant. This is encouraging as health care reform efforts call for providers at facilities with different institutional values to coordinate care across facilities. Although there are anecdotes of facility religious affiliation being related to health care decisions, the authors did not find evidence of these relationships in their data. C1 [Garrido, Melissa M.] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Garrido, Melissa M.] Mt Sinai Sch Med, New York, NY USA. [Allison, Kirk C.; Dowd, Bryan] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN 55455 USA. [Bergeron, Mark J.] Univ Minnesota, Sch Med, St Paul, MN 55108 USA. RP Garrido, MM (reprint author), James J Peters VA Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM melissa.garrido@mssm.edu OI Garrido, Melissa/0000-0002-8986-3536 FU Wessner Foundation; MacLaurinCSF FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This grant was supported in part by funding to Dr. Dowd from the Wessner Foundation and MacLaurinCSF. NR 52 TC 1 Z9 1 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 J9 MED CARE RES REV JI Med. Care Res. Rev. PD JUN PY 2012 VL 69 IS 3 BP 316 EP 338 DI 10.1177/1077558711432156 PG 23 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 933YB UT WOS:000303401900004 PM 22203647 ER PT J AU Kahn, JM Werner, RM Carson, SS Iwashyna, TJ AF Kahn, Jeremy M. Werner, Rachel M. Carson, Shannon S. Iwashyna, Theodore J. TI Variation in Long-Term Acute Care Hospital Use After Intensive Care SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE mechanical ventilation; intensive care; long-term acute care; post-acute care utilization; practice variation ID PROLONGED MECHANICAL VENTILATION; MEDICARE; OUTCOMES; ILLNESS; TRIAL; UNITS AB Long-term acute care hospitals (LTACs) are an increasingly common discharge destination for patients recovering from intensive care. In this article the authors use U.S. Medicare claims data to examine regional- and hospital-level variation in LTAC utilization after intensive care to determine factors associated with their use. Using hierarchical regression models to control for patient characteristics, this study found wide variation in LTAC utilization across hospitals, even controlling for LTAC access within a region. Several hospital characteristics were independently associated with increasing LTAC utilization, including increasing hospital size, for-profit ownership, academic teaching status, and colocation of the LTAC within an acute care hospital. These findings highlight the need for research into LTAC admission criteria and the incentives driving variation in LTAC utilization across hospitals. C1 [Kahn, Jeremy M.] Univ Pittsburgh, Dept Crit Med, Sch Med, Pittsburgh, PA 15261 USA. [Kahn, Jeremy M.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Werner, Rachel M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Carson, Shannon S.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Iwashyna, Theodore J.] Univ Michigan, Sch Med, Ann Arbor, MI USA. RP Kahn, JM (reprint author), Univ Pittsburgh, Dept Crit Med, Sch Med, Scaife Hall,Room 602-B,3550 Terrace St, Pittsburgh, PA 15261 USA. EM kahnjm@upmc.edu OI Iwashyna, Theodore/0000-0002-4226-9310 FU United States National Institutes of Health [R01HL096651] FX This work was funded by the United States National Institutes of Health (R01HL096651). NR 20 TC 17 Z9 18 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 J9 MED CARE RES REV JI Med. Care Res. Rev. PD JUN PY 2012 VL 69 IS 3 BP 339 EP 350 DI 10.1177/1077558711432889 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 933YB UT WOS:000303401900005 PM 22311957 ER PT J AU Bartzokis, G AF Bartzokis, George TI Neuroglialpharmacology: Myelination as a shared mechanism of action of psychotropic treatments SO NEUROPHARMACOLOGY LA English DT Review DE White matter; Oligodendrocyte; Intracortical myelin; Medication; MRI; NG2 cells; Neuregulin; ErbB; DISC1; IGF1; Reelin; Cdk; MAPK; mTOR; Leptin ID GROWTH-FACTOR-I; CENTRAL-NERVOUS-SYSTEM; GLYCOGEN-SYNTHASE KINASE-3; WHITE-MATTER ABNORMALITIES; ACTIVATED PROTEIN-KINASE; NICOTINIC ACETYLCHOLINE-RECEPTOR; OLIGODENDROCYTE PROGENITOR CELLS; DORSOLATERAL PREFRONTAL CORTEX; SEIZURES INDUCE PROLIFERATION; NG2-EXPRESSING GLIAL-CELLS AB Current psychiatric diagnostic schema segregate symptom clusters into discrete entities, however, large proportions of patients suffer from comorbid conditions that fit neither diagnostic nor therapeutic schema. Similarly, psychotropic treatments ranging from lithium and antipsychotics to serotonin reuptake inhibitors (SSRIs) and acetylcholinesterase inhibitors have been shown to be efficacious in a wide spectrum of psychiatric disorders ranging from autism, schizophrenia (SZ), depression, and bipolar disorder (BD) to Alzheimer's disease (AD). This apparent lack of specificity suggests that psychiatric symptoms as well as treatments may share aspects of pathophysiology and mechanisms of action that defy current symptom-based diagnostic and neuron-based therapeutic schema. A myelin-centered model of human brain function can help integrate these incongruities and provide novel insights into disease etiologies and treatment mechanisms. Available data are integrated herein to suggest that widely used psychotropic treatments ranging from antipsychotics and antidepressants to lithium and electroconvulsive therapy share complex signaling pathways such as Akt and glycogen synthase kinase-3 (GSK3) that affect myelination, its plasticity, and repair. These signaling pathways respond to neurotransmitters, neurotrophins, hormones, and nutrition, underlie intricate neuroglial communications, and may substantially contribute to the mechanisms of action and wide spectra of efficacy of current therapeutics by promoting myelination. Imaging and genetic technologies make it possible to safely and non-invasively test these hypotheses directly in humans and can help guide clinical trial efforts designed to correct myelination abnormalities. Such efforts may provide insights into novel avenues for treatment and prevention of some of the most prevalent and devastating human diseases. Published by Elsevier Ltd. C1 [Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA. [Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Div Brain Mapping, Lab Neuroimaging,Dept Neurol, Los Angeles, CA 90095 USA. [Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. [Bartzokis, George] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90073 USA. RP Bartzokis, G (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, 300 UCLA Med Plaza,Suite 2200, Los Angeles, CA 90095 USA. EM gbar@ucla.edu RI Bartzokis, George/K-2409-2013 FU Pfizer; Janssen; Novartis; NIH [MH066029, AG027342]; Research and Psychiatry Services of the Department of Veterans Affairs; RCS Foundation FX George Bartzokis has consulted for and received research funding from Pfizer, Janssen, and Novartis, and consulted for Bristol-Myers Squibb Company.; This work was supported in part by NIH grants (MH066029; AG027342), Research and Psychiatry Services of the Department of Veterans Affairs, and the RCS Foundation. The author thanks Lori L Altshuler, M.D., and Keith H. Nuechterlein, Ph.D. for reading the manuscript and providing helpful suggestions. NR 271 TC 47 Z9 48 U1 2 U2 23 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JUN PY 2012 VL 62 IS 7 BP 2137 EP 2153 DI 10.1016/j.neuropharm.2012.01.015 PG 17 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 931MG UT WOS:000303223400001 PM 22306524 ER PT J AU Shabani, S Dobbs, LK Ford, MM Mark, GP Finn, DA Phillips, TJ AF Shabani, Shkelzen Dobbs, Lauren K. Ford, Matthew M. Mark, Gregory P. Finn, Deborah A. Phillips, Tamara J. TI A genetic animal model of differential sensitivity to methamphetamine reinforcement SO NEUROPHARMACOLOGY LA English DT Article DE Methamphetamine; Addiction; Oral self-administration; Reinforcement; Appetitive; Aversive ID RECOMBINANT INBRED MICE; C57BL/6J MICE; D-AMPHETAMINE; BEHAVIORAL SENSITIZATION; ETHANOL SEEKING; NATURAL REWARDS; DRUG; RATS; ALCOHOL; COCAINE AB Sensitivity to reinforcement from methamphetamine (MA) likely influences risk for MA addiction, and genetic differences are one source of individual variation. Generation of two sets of selectively bred mouse lines for high and low MA drinking has shown that genetic factors influence MA intake, and pronounced differences in sensitivity to rewarding and aversive effects of MA play a significant role. Further validation of these lines as a unique genetic model relevant to MA addiction was obtained using operant methods to study MA reinforcement High and low MA drinking line mice were used to test the hypotheses that: 1) oral and intracerebroventricular (ICV) MA serve as behavioral reinforcers, and 2) MA exhibits greater reinforcing efficacy in high than low MA drinking mice. Operant responses resulted in access to an MA or non-MA drinking tube or intracranial delivery of MA. Behavioral activation consequent to orally consumed MA was determined. MA available for consumption maintained higher levels of reinforced instrumental responding in high than low MA drinking line mice, and MA intake in the oral operant procedure was greater in high than low MA drinking line mice. Behavioral activation was associated with amount of MA consumed during operant sessions. High line mice delivered more MA via ICV infusion than did low line mice across a range of doses. Thus, genetic risk factors play a critical role in the reinforcing efficacy of MA and the oral self-administration procedure is suitable for delineating genetic contributions to MA reinforcement. Published by Elsevier Ltd. C1 [Shabani, Shkelzen; Dobbs, Lauren K.; Ford, Matthew M.; Mark, Gregory P.; Finn, Deborah A.; Phillips, Tamara J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. [Shabani, Shkelzen; Dobbs, Lauren K.; Ford, Matthew M.; Mark, Gregory P.; Finn, Deborah A.; Phillips, Tamara J.] Oregon Hlth & Sci Univ, Methamphetamine Abuse Res Ctr, Portland, OR 97239 USA. [Finn, Deborah A.; Phillips, Tamara J.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Phillips, TJ (reprint author), Portland VA Med Ctr VAMC, R&D 32,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM shabanis@scripps.edu; dobbsl@ohsu.edu; fordma@ohsu.edu; markg@ohsu.edu; finnd@ohsu.edu; phillipt@ohsu.edu OI Ford, Matthew/0000-0002-1204-1980 FU Department of Veterans Affairs; NIDA [T32 DA07262]; NIDA Center [P50 DA018165]; NIAAA [K01 AA016849] FX We thank Andrew Fredericks and Becca Rieger for their help collecting oral operant self-administration data. We also thank Tammie Painter, Marcia Ramaker and Nathan Klett for their help with ICV data collection. This work was supported by the Department of Veterans Affairs, NIDA T32 DA07262, and NIDA Center grant P50 DA018165. In addition, NIAAA K01 AA016849 provided some salary support. The oral operant self-administration and locomotor activity studies were in part supported with resources and the use of facilities at the Portland VA Medical Center. NR 54 TC 14 Z9 15 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JUN PY 2012 VL 62 IS 7 BP 2169 EP 2177 DI 10.1016/j.neuropharm.2012.01.002 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 931MG UT WOS:000303223400003 PM 22280875 ER PT J AU Forman, EM Chapman, JE Herbert, JD Goetter, EM Yuen, EK Moitra, E AF Forman, Evan M. Chapman, Jason E. Herbert, James D. Goetter, Elizabeth M. Yuen, Erica K. Moitra, Ethan TI Using Session-by-Session Measurement to Compare Mechanisms of Action for Acceptance and Commitment Therapy and Cognitive Therapy SO BEHAVIOR THERAPY LA English DT Article DE ACT; CBT; psychotherapy mechanisms; mediation ID BEHAVIORAL TREATMENT; CONFIDENCE-LIMITS; CONTROLLED TRIAL; DEPRESSION; ANXIETY; MEDIATION; PREVENT; RELAPSE; QUESTIONNAIRE; RELIABILITY AB Debate continues about the extent to which postulated mechanisms of action of cognitive behavior therapies (CBT), including standard CBT (i.e., Beckian cognitive therapy [CT]) and acceptance and commitment therapy (ACT) are supported by mediational analyses. Moreover, the distinctiveness of CT and ACT has been called into question. One contributor to ongoing uncertainty in this arena is the lack of time-varying process data. In this study, 174 patients presenting to a university clinic with anxiety or depression who had been randomly assigned to receive either ACT or CT completed an assessment of theorized mediators and outcomes before each session. Hierarchical linear modeling of session-by-session data revealed that increased utilization of cognitive and affective change strategies relative to utilization of psychological acceptance strategies mediated outcome for CT, whereas for ACT the mediation effect was in the opposite direction. Decreases in self-reported dysfunctional thinking, cognitive "defusion" (the ability to see one's thoughts as mental events rather than necessarily as representations of reality), and willingness to engage in behavioral activity despite unpleasant thoughts or emotions were equivalent mediators across treatments. These results have potential implications for the theoretical arguments behind, and distinctiveness of, CT and ACT. C1 [Forman, Evan M.] Drexel Univ, Dept Psychol, Philadelphia, PA 19102 USA. [Yuen, Erica K.] Med Univ S Carolina, Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. [Moitra, Ethan] Brown Univ, Providence, RI 02912 USA. RP Forman, EM (reprint author), Drexel Univ, Dept Psychol, 245 N 15th St,MS 626, Philadelphia, PA 19102 USA. EM evan.forman@drexel.edu RI Forman, Evan/I-1042-2012 NR 61 TC 36 Z9 36 U1 6 U2 43 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD JUN PY 2012 VL 43 IS 2 BP 341 EP 354 PG 14 WC Psychology, Clinical SC Psychology GA 920GZ UT WOS:000302393600010 PM 22440070 ER PT J AU Seyedali, M Czerniecki, JM Morgenroth, DC Hahn, ME AF Seyedali, Mahyo Czerniecki, Joseph M. Morgenroth, David C. Hahn, Michael E. TI Co-contraction patterns of trans-tibial amputee ankle and knee musculature during gait SO JOURNAL OF NEUROENGINEERING AND REHABILITATION LA English DT Article DE Electromyography; Myoelectric control; Trans-tibial amputees; Activation patterns; Muscle amplitude ID MUSCLE-ACTIVITY; WALKING SPEEDS; EMG PROFILES; CHILDREN; PROSTHESIS; LOCOMOTION; INDEX; JOINT AB Background: Myoelectric control of upper extremity powered prostheses has been used clinically for many years, however this approach has not been fully developed for lower extremity prosthetic devices. With the advent of powered lower extremity prosthetic components, the potential role of myoelectric control systems is of increasing importance. An understanding of muscle activation patterns and their relationship to functional ambulation is a vital step in the future development of myoelectric control. Unusual knee muscle co-contractions have been reported in both limbs of trans-tibial amputees. It is currently unknown what differences exist in co-contraction between trans-tibial amputees and controls. This study compares the activation and co-contraction patterns of the ankle and knee musculature of trans-tibial amputees (intact and residual limbs), and able-bodied control subjects during three speeds of gait. It was hypothesized that residual limbs would have greater ankle muscle co-contraction than intact and able-bodied control limbs and that knee muscle co-contraction would be different among all limbs. Lastly it was hypothesized that the extent of muscle co-contraction would increase with walking speed. Methods: Nine unilateral traumatic trans-tibial amputees and five matched controls participated. Surface electromyography recorded activation from the Tibialis Anterior, Medial Gastrocnemius, Vastus Lateralis and Biceps Femoris of the residual, intact and control limbs. A series of filters were applied to the signal to obtain a linear envelope of the activation patterns. A co-contraction area (ratio of the integrated agonist and antagonist activity) was calculated during specific phases of gait. Results: Co-contraction of the ankle muscles was greater in the residual limb than in the intact and control limbs during all phases of gait. Knee muscle co-contraction was greater in the residual limb than in the control limb during all phases of gait. Conclusion: Co-contractions may represent a limb stiffening strategy to enhance stability during phases of initial foot-contact and single limb support. These strategies may be functionally necessary for amputee gait; however, the presence of co-contractions could confound future development of myoelectric controls and should thus be accounted for. C1 [Seyedali, Mahyo; Czerniecki, Joseph M.; Morgenroth, David C.; Hahn, Michael E.] VA Puget Sound, Dept Vet Affairs VA, Rehabil Res & Dev Ctr Excellence Limb Loss Preven, Seattle, WA 98108 USA. [Seyedali, Mahyo; Hahn, Michael E.] Univ Washington, Dept Mech Engn, Seattle, WA 98105 USA. [Czerniecki, Joseph M.; Morgenroth, David C.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Hahn, ME (reprint author), VA Puget Sound, Dept Vet Affairs VA, Rehabil Res & Dev Ctr Excellence Limb Loss Preven, 1660 S Columbian Way, Seattle, WA 98108 USA. EM mhahn@uoregon.edu OI Morgenroth, David/0000-0002-0226-7775 FU Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service; Department of Defense [W81XWH-09-2-0142] FX This research was supported by the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service. Additionally, this research was funded by a Department of Defense grant (W81XWH-09-2-0142). We gratefully acknowledge the supporting efforts of Janice Pecoraro and Elise Wright. NR 35 TC 5 Z9 5 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-0003 J9 J NEUROENG REHABIL JI J. NeuroEng. Rehabil. PD MAY 28 PY 2012 VL 9 AR 29 DI 10.1186/1743-0003-9-29 PG 9 WC Engineering, Biomedical; Neurosciences; Rehabilitation SC Engineering; Neurosciences & Neurology; Rehabilitation GA 026IJ UT WOS:000310268300001 PM 22640660 ER PT J AU Grady, D Katz, MH Berkowitz, SA AF Grady, Deborah Katz, Mitchell H. Berkowitz, Seth A. TI A Role for Opioids in Chronic Pain Management reply SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter C1 [Grady, Deborah] Univ Calif San Francisco, Dept Med, San Francisco VA Med Ctr, San Francisco, CA 94115 USA. [Katz, Mitchell H.] Los Angeles Cty Dept Hlth Serv, Los Angeles, CA USA. RP Grady, D (reprint author), Univ Calif San Francisco, Dept Med, San Francisco VA Med Ctr, 1635 Divisadero St,Ste 600, San Francisco, CA 94115 USA. EM Deborah.Grady@ucsf.edu NR 2 TC 0 Z9 0 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 28 PY 2012 VL 172 IS 10 BP 824 EP 825 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 948FK UT WOS:000304488800019 ER PT J AU Gabbita, SP Srivastava, MK Eslami, P Johnson, MF Kobritz, NK Tweedie, D Greig, NH Zemlan, FP Sharma, SP Harris-White, ME AF Gabbita, S. Prasad Srivastava, Minu K. Eslami, Pirooz Johnson, Ming F. Kobritz, Naomi K. Tweedie, David Greig, Nigel H. Zemlan, Frank P. Sharma, Sherven P. Harris-White, Marni E. TI Early intervention with a small molecule inhibitor for tumor necrosis factor-alpha prevents cognitive deficits in a triple transgenic mouse model of Alzheimer's disease SO JOURNAL OF NEUROINFLAMMATION LA English DT Article DE Alzheimer's disease; memory; neuroinflammation; thalidomide; thiothalidomide; tumor necrosis factor-alpha ID CENTRAL-NERVOUS-SYSTEM; BETA-AMYLOID STIMULATION; MARROW-DERIVED CELLS; BLOOD-BRAIN-BARRIER; TNF-ALPHA; NEURODEGENERATIVE DISEASES; PERISPINAL ETANERCEPT; SYNAPTIC PLASTICITY; HEMATOPOIETIC-CELLS; THERAPEUTIC TARGET AB Background: Chronic neuroinflammation is an important component of Alzheimer's disease and could contribute to neuronal dysfunction, injury and loss that lead to disease progression. Multiple clinical studies implicate tumor necrosis factor-alpha as an inflammatory mediator of neurodegeneration in patients with Alzheimer's because of elevated levels of this cytokine in the cerebrospinal fluid, hippocampus and cortex. Current Alzheimer's disease interventions are symptomatic treatments with limited efficacy that do not address etiology. Thus, a critical need exists for novel treatments directed towards modifying the pathophysiology and progression. Methods: To investigate the effect of early immune modulation on neuroinflammation and cognitive outcome, we treated triple transgenic Alzheimer's disease mice (harboring PS1(M146V), APP(Swe), and tau(P301L) transgenes) with the small molecule tumor necrosis factor-alpha inhibitors, 3,6'-dithiothalidomide and thalidomide, beginning at four months of age. At this young age, mice do not exhibit plaque or tau pathology but do show mild intraneuronal amyloid beta protein staining and a robust increase in tumor necrosis factor-alpha. After 10 weeks of treatment, cognitive performance was assessed using radial arm maze and neuroinflammation was assessed using biochemical, stereological and flow cytometric endpoints. Results: 3,6'-dithiothalidomide reduced tumor necrosis factor-alpha mRNA and protein levels in the brain and improved working memory performance and the ratio of resting to reactive microglia in the hippocampus of triple transgenic mice. In comparison to non-transgenic controls, triple transgenic Alzheimer's disease mice had increased total numbers of infiltrating peripheral monomyelocytic/granulocytic leukocytes with enhanced intracytoplasmic tumor necrosis factor-alpha, which was reduced after treatment with 3,6'-dithiothalidomide. Conclusions: These results suggest that modulation of tumor necrosis factor-alpha with small molecule inhibitors is safe and effective with potential for the long-term prevention and treatment of Alzheimer's disease. C1 [Srivastava, Minu K.; Eslami, Pirooz; Johnson, Ming F.; Kobritz, Naomi K.; Sharma, Sherven P.; Harris-White, Marni E.] Univ Calif Los Angeles, Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Srivastava, Minu K.; Eslami, Pirooz; Johnson, Ming F.; Kobritz, Naomi K.; Sharma, Sherven P.; Harris-White, Marni E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. [Gabbita, S. Prasad; Zemlan, Frank P.] P2D Biosci, Cincinnati, OH 45242 USA. [Tweedie, David; Greig, Nigel H.] NIA, NIH, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Harris-White, ME (reprint author), Univ Calif Los Angeles, Vet Adm Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd 151, Los Angeles, CA 90073 USA. EM marni@ucla.edu FU Veterans Administration; Michael J. Fox Foundation; Alzheimer's Drug Discovery Foundation; Intramural Research Program of NIA, NIH FX The authors would like to thank Dr. Russell Brown at Eastern Tennessee State University for assistance with the design and analysis of the Radial Arm Maze experiments, Dr. Louis Hersh at the University of Kentucky for providing breeding pairs of 3 x Tg mice and Dr. Kenneth Hensley at the University of Toledo for assistance with data interpretation and critical scientific review of the manuscript. This work was supported by Veterans Administration Merit Funding (MEHW and SPS), Michael J. Fox Foundation (SPG), Alzheimer's Drug Discovery Foundation (MEHW and SPG) and the Intramural Research Program of NIA, NIH (DT and NHG). NR 81 TC 26 Z9 27 U1 2 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD MAY 25 PY 2012 VL 9 AR 99 DI 10.1186/1742-2094-9-99 PG 16 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 976PV UT WOS:000306597700001 PM 22632257 ER PT J AU Mathalon, DH Ford, JM AF Mathalon, Daniel H. Ford, Judith M. TI Neurobiology of schizophrenia: search for the elusive correlation with symptoms SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE schizophrenia; positive symptoms; negative symptoms; neurobiology; correlation; reliability; validity; rating scales ID TRANSCRANIAL MAGNETIC STIMULATION; PSYCHIATRIC RATING-SCALE; HEALTHY-VOLUNTEERS; WORKING-MEMORY; KETAMINE; DYSFUNCTION; NEGATIVITY; ANTAGONIST; PSYCHOSIS; DEFICITS AB In the last half-century, human neuro science methods provided a way to study schizophrenia in vivo, and established that it is associated with subtle abnormalities in brain structure and function. However, efforts to understand the neurobiological bases of the clinical symptoms that the diagnosis is based on have been largely unsuccessful. In this paper, we provide an overview of the conceptual and methodological obstacles that undermine efforts to link the severity of specific symptoms to specific neurobiological measures. These obstacles include small samples, questionable reliability and validity of measurements, medication confounds, failure to distinguish state and trait effects, correlation-causation ambiguity, and the absence of compelling animal models of specific symptoms to test mechanistic hypotheses derived from brain-symptom correlations. We conclude with recommendations to promote progress in establishing brain-symptom relationships. C1 [Mathalon, Daniel H.; Ford, Judith M.] San Francisco VA Med Ctr, Psychiat Serv, San Francisco, CA 94121 USA. [Mathalon, Daniel H.; Ford, Judith M.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Mathalon, DH (reprint author), San Francisco VA Med Ctr, Psychiat Serv 116D, 4150 Clement St, San Francisco, CA 94121 USA. EM daniel.mathalon@ucsf.edu OI Mathalon, Daniel/0000-0001-6090-4974 FU CSRD VA [I01 CX000497]; NIMH NIH HHS [R01 MH076989] NR 43 TC 16 Z9 16 U1 2 U2 14 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD MAY 25 PY 2012 VL 6 AR 136 DI 10.3389/fnhum.2012.00136 PG 6 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 953HT UT WOS:000304858500001 PM 22654745 ER PT J AU Mantegazza, AR Guttentag, SH El-Benna, J Sasai, M Iwasaki, A Shen, H Laufer, TM Marks, MS AF Mantegazza, Adriana R. Guttentag, Susan H. El-Benna, Jamel Sasai, Miwa Iwasaki, Akiko Shen, Hao Laufer, Terri M. Marks, Michael S. TI Adaptor Protein-3 in Dendritic Cells Facilitates Phagosomal Toll-like Receptor Signaling and Antigen Presentation to CD4(+) T Cells SO IMMUNITY LA English DT Article ID HERMANSKY-PUDLAK-SYNDROME; MHC CLASS-II; AP-3 ADAPTER; CROSS-PRESENTATION; BETA-3A SUBUNIT; SORTING SIGNALS; IMMUNE-RESPONSE; SYNDROME TYPE-2; TRAFFICKING; MUTATIONS AB Effective major histocompatibility complex-II (MHC-II) antigen presentation from phagocytosed particles requires phagosome-intrinsic Toll-like receptor (TLR) signaling, but the molecular mechanisms underlying TLR delivery to phagosomes and how signaling regulates antigen presentation are incompletely understood. We show a requirement in dendritic cells (DCs) for adaptor protein-3 (AP-3) in efficient TLR recruitment to phagosomes and MHC-II presentation of antigens internalized by phagocytosis but not receptor-mediated endocytosis. DCs from AP-3-deficient pearl mice elicited impaired CD4(+) T cell activation and Th1 effector cell function to particulate antigen in vitro and to recombinant Listeria monocytogenes infection in vivo. Whereas phagolysosome maturation and peptide:MHC-II complex assembly proceeded normally in pearl DCs, peptide:MHC-II export to the cell surface was impeded. This correlated with reduced TLR4 recruitment and proinflammatory signaling from phagosomes by particulate TLR ligands. We propose that AP-3-dependent TLR delivery from endosomes to phagosomes and subsequent signaling mobilize peptide:MHC-II export from intracellular stores. C1 [Mantegazza, Adriana R.; Marks, Michael S.] Univ Penn, Perelman Sch Med, Dept Pathol, Philadelphia, PA 19104 USA. [Mantegazza, Adriana R.; Marks, Michael S.] Univ Penn, Perelman Sch Med, Dept Lab Med, Philadelphia, PA 19104 USA. [Mantegazza, Adriana R.; Marks, Michael S.] Univ Penn, Perelman Sch Med, Dept Physiol, Philadelphia, PA 19104 USA. [Shen, Hao] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. [Laufer, Terri M.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Guttentag, Susan H.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [El-Benna, Jamel] Univ Paris 07, INSERM, U773, Fac Med, F-75018 Paris, France. [Sasai, Miwa; Iwasaki, Akiko] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA. [Laufer, Terri M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Marks, MS (reprint author), Univ Penn, Perelman Sch Med, Dept Pathol, Philadelphia, PA 19104 USA. EM marksm@mail.med.upenn.edu RI Guttentag, Susan/D-8705-2013 OI Guttentag, Susan/0000-0003-4420-5879; Marks, Michael/0000-0001-7435-7262 FU National Institutes of Health [R01 EY015625, R21 AI092398, R21 AI079724, R01 AI081884, R01 AI064705]; University Research Foundation from the University of Pennsylvania; HPS Network; United States Veterans Administration FX We thank R. Steinman, M. Pepper Pew, M. Jenkins, A. Rudensky, J. Liboon, S. Chatterjee, A. Fisher, S. Ross, S. Akira, P. Oliver, L. Eisenlohr, M. Chou, and C. Lopez for generous gifts of reagents; A. Stout, P. Zhang, S. Leach, A. Sitaram, and C. Lopez Haber for technical assistance; and the Amigorena laboratory for experimental protocols. This work was supported by National Institutes of Health grants R01 EY015625 (to M.S.M.), R21 AI092398 (to A.R.M. and M.S.M.), R21 AI079724 (to H.S.), and R01 AI081884 and R01 AI064705 (to A.I); a University Research Foundation grant from the University of Pennsylvania (to M.S.M.); Donna and Richard Appel and the HPS Network (to S.H.G.); and a research grant from the United States Veterans Administration (to T.M.L.). NR 57 TC 25 Z9 26 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY 25 PY 2012 VL 36 IS 5 BP 782 EP 794 DI 10.1016/j.immuni.2012.02.018 PG 13 WC Immunology SC Immunology GA 954VL UT WOS:000304976000012 PM 22560444 ER PT J AU Loewenstein, G Asch, DA Friedman, JY Melichar, LA Volpp, KG AF Loewenstein, George Asch, David A. Friedman, Joelle Y. Melichar, Lori A. Volpp, Kevin G. TI Can behavioural economics make us healthier? SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID FINANCIAL INCENTIVES; ASYMMETRIC PATERNALISM; MEDICATION ADHERENCE; RANDOMIZED-TRIAL; COPAYMENTS; VETERANS; INCREASE; SMOKING; IMPACT AB Behavioural economics is becoming increasingly popular as a way to improve public health. George Loewenstein and colleagues point out some of the pitfalls and warn that it cannot be used as a substitute for conventional policies to tackle fundamental problems C1 [Loewenstein, George] Carnegie Mellon Univ, Dept Social & Decis Sci, Pittsburgh, PA 15213 USA. [Loewenstein, George; Asch, David A.; Friedman, Joelle Y.; Volpp, Kevin G.] Univ Penn, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Asch, David A.; Volpp, Kevin G.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Asch, David A.; Volpp, Kevin G.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Asch, David A.; Volpp, Kevin G.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Melichar, Lori A.] Robert Wood Johnson Fdn, Princeton, NJ 08540 USA. RP Loewenstein, G (reprint author), Carnegie Mellon Univ, Dept Social & Decis Sci, 208 Porter Hall,5000 Forbes Ave, Pittsburgh, PA 15213 USA. EM GL20@andrew.cmu.edu OI Asch, David/0000-0002-7970-286X NR 31 TC 17 Z9 17 U1 3 U2 28 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BRIT MED J JI Br. Med. J. PD MAY 23 PY 2012 VL 344 AR e3482 DI 10.1136/bmj.e3482 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 949QT UT WOS:000304591500011 PM 22623635 ER PT J AU Volpp, KG Loewenstein, G Asch, DA AF Volpp, Kevin G. Loewenstein, George Asch, David A. TI Assessing Value in Health Care Programs SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID DISEASE C1 [Volpp, Kevin G.; Asch, David A.] Univ Penn Sch, Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Loewenstein, George; Asch, David A.] Univ Penn, Penn CMU Roybal Ctr Behav Econ & Hlth P30, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Loewenstein, George; Asch, David A.] Univ Penn, Leonard Davis Inst Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Asch, David A.] Univ Penn, Dept Med, Sch Med, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Asch, David A.] Univ Penn, Dept Hlth Care Management, Wharton Sch Decis Sci, Philadelphia, PA 19104 USA. [Loewenstein, George] Carnegie Mellon Univ, Dept Social & Decis Sci, Pittsburgh, PA 15213 USA. RP Volpp, KG (reprint author), Univ Penn Sch, Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, 1120 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM volpp70@wharton.upenn.edu OI Asch, David/0000-0002-7970-286X FU NIA NIH HHS [P30 AG034546] NR 9 TC 7 Z9 7 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 23 PY 2012 VL 307 IS 20 BP 2153 EP 2154 DI 10.1001/jama.2012.3619 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 945YX UT WOS:000304315200021 PM 22618919 ER PT J AU Hung, WW Egol, KA Zuckerman, JD Siu, AL AF Hung, William W. Egol, Kenneth A. Zuckerman, Joseph D. Siu, Albert L. TI Hip Fracture Management Tailoring Care for the Older Patient SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RANDOMIZED-CONTROLLED-TRIAL; QUALITY-OF-LIFE; FEMORAL-NECK; ELDERLY-PATIENTS; RISK-FACTORS; BIPOLAR HEMIARTHROPLASTY; FUNCTIONAL RECOVERY; HOSPITAL DISCHARGE; HOME EXERCISE; VITAMIN-D AB Hip fracture is a potentially devastating condition for older adults. Hip fracture leads to pain and immobilization with complications ranging from delirium to functional loss and death. Although a mainstay of treatment is orthopedic repair, a multidisciplinary comanagement approach, including medical specialists and rehabilitation, may maximize patient recovery. Using the case of Mr W, an older man who sustained a fall and hip fracture, we present evidence-based components of care both in the hospital and outpatient settings. Preoperatively, clinicians should correct medical abnormalities and consider the appropriateness, timing, and type of surgical repair in the context of the patient's life expectancy and goals of care. Perioperative care should include prophylaxis with antibiotics, chemoprophylaxis for venous thromboembolism, and correction of major clinical abnormalities prior to surgery. Pain control, delirium, and pressure ulcer prevention are important inpatient care elements. Multidisciplinary models incorporating these care elements can decrease complications during inpatient stay. Rehabilitation strategies should be tailored to patient needs; early mobilization followed by rehabilitation exercises in institutional, home, and group settings should be considered to maximize restoration of locomotive abilities. Attention to care transitions is necessary and treatment for osteoporosis should be considered. The road to recovery for hip fracture patients is long and most patients may not regain their prefracture functional status. Understanding and anticipating issues that may arise in the older patient with hip fracture, while delivering evidence-based care components, is necessary to maximize patient recovery. C1 [Hung, William W.; Siu, Albert L.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Hung, William W.; Siu, Albert L.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Hung, William W.; Siu, Albert L.] James J Peters Vet Affairs Med Ctr, Dev Res Enhancement Award Program, Bronx, NY USA. [Hung, William W.; Siu, Albert L.] James J Peters Vet Affairs Med Ctr, Hlth Serv Res, Bronx, NY USA. [Egol, Kenneth A.; Zuckerman, Joseph D.] NYU, Hosp Joint Dis, Dept Orthopaed Surg, New York, NY USA. RP Hung, WW (reprint author), Mt Sinai Sch Med, Dept Geriatr & Palliat Med, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM william.hung@mssm.edu FU Exactech; Orthopaedic Research & Education Foundation; Orthopaedic Trauma Association; New York Academy of Medicine; Claude D. Pepper Older Americans Independence Center at Mount Sinai School of Medicine [P30-AG028741]; SCAN Foundation FX All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Egol reports receipt of consultancy fees and royalties from Exactech; grants or pending grants from the Orthopaedic Research & Education Foundation and the Orthopaedic Trauma Association; and holding stock/stock options with Johnson & Johnson. The other authors report no disclosures.; Dr Hung is currently supported by the New York Academy of Medicine Hoar Fellowship. This article was supported in part by the Claude D. Pepper Older Americans Independence Center at Mount Sinai School of Medicine (P30-AG028741). The Care of the Aging Patient series is made possible by funding from The SCAN Foundation. NR 86 TC 53 Z9 58 U1 4 U2 22 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 23 PY 2012 VL 307 IS 20 BP 2185 EP 2194 DI 10.1001/jama.2012.4842 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 945YX UT WOS:000304315200028 PM 22618926 ER PT J AU Tseng, ZH Secemsky, EA Dowdy, D Vittinghoff, E Moyers, B Wong, JK Havlir, DV Hsue, PY AF Tseng, Zian H. Secemsky, Eric A. Dowdy, David Vittinghoff, Eric Moyers, Brian Wong, Joseph K. Havlir, Diane V. Hsue, Priscilla Y. TI Sudden Cardiac Death in Patients With Human Immunodeficiency Virus Infection SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE AIDS; arrhythmia; death; sudden ID LEFT-VENTRICULAR DYSFUNCTION; CONGESTIVE-HEART-FAILURE; MYOCARDIAL-INFARCTION; ANTIRETROVIRAL THERAPY; HIV; MORTALITY; POPULATION; COMMUNITY; DISEASE; COHORT AB Objectives The aim of this study was to determine the incidence and clinical characteristics of sudden cardiac death (SCD) in patients with human immunodeficiency virus (HIV) infection. Background As the HIV-infected population ages, cardiovascular disease prevalence and mortality are increasing, but the incidence and features of SCD have not yet been described. Methods The records of 2,860 consecutive patients in a public HIV clinic in San Francisco between April 2000 and August 2009 were examined. Identification of deaths, causes of death, and clinical characteristics were obtained by search of the National Death Index and/or clinic records. SCDs were determined using published retrospective criteria: 1) the International Classification of Diseases-10th Revision, code for all cardiac causes of death; and (2) circumstances of death meeting World Health Organization criteria. Results Of 230 deaths over a median of 3.7 years of follow-up, 30 (13%) met SCD criteria, 131 (57%) were due to acquired immune deficiency syndrome (AIDS), 25 (11%) were due to other (natural) diseases, and 44 (19%) were due to overdoses, suicides, or unknown causes. SCDs accounted for 86% of all cardiac deaths (30 of 35). The mean SCD rate was 2.6 per 1,000 person-years (95% confidence interval: 1.8 to 3.8), 4.5-fold higher than expected. SCDs occurred in older patients than did AIDS deaths (mean 49.0 vs. 44.9 years, p = 0.02). Compared with AIDS and natural deaths combined, SCDs had a higher prevalence of prior myocardial infarction (17% vs. 1%, p < 0.0005), cardiomyopathy (23% vs. 3%, p < 0.0005), heart failure (30% vs. 9%, p = 0.004), and arrhythmias (20% vs. 3%, p = 0.003). Conclusions SCDs account for most cardiac and many non-AIDS natural deaths in HIV-infected patients. Further investigation is needed to ascertain underlying mechanisms, which may include inflammation, antiretroviral therapy interruption, and concomitant medications. (J Am Coll Cardiol 2012;59:1891-6) (C) 2012 by the American College of Cardiology Foundation C1 [Tseng, Zian H.; Moyers, Brian] Univ Calif San Francisco, Cardiac Electrophysiol Sect, Div Cardiol, San Francisco, CA 94143 USA. [Secemsky, Eric A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Dowdy, David] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Vittinghoff, Eric] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Wong, Joseph K.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Havlir, Diane V.] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA 94143 USA. [Hsue, Priscilla Y.] Univ Calif San Francisco, San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94143 USA. RP Tseng, ZH (reprint author), Univ Calif San Francisco, Cardiac Electrophysiol Sect, Div Cardiol, 500 Parnassus Ave,MU-433,Box 1354, San Francisco, CA 94143 USA. EM zhtseng@medicine.ucsf.edu FU National Heart, Lung, and Blood Institute [5R01 HL102090, 5R01 HL095130, 5R01 HL091526]; Veterans Affairs Merit Review grant [R01 NS501132]; National Institutes of Health [K24 AI51982] FX This work was supported by grants 5R01 HL102090 (Dr. Tseng), 5R01 HL095130 (Dr. Hsue), and 5R01 HL091526 (Dr. Hsue) from the National Heart, Lung, and Blood Institute; Veterans Affairs Merit Review grant R01 NS501132 (Dr. Wong); and grant K24 AI51982 (Dr. Havlir) from the National Institutes of Health. Dr. Tseng has also received minor honorarium from Biotronik. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 27 TC 72 Z9 73 U1 0 U2 3 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 MAY 22 PY 2012 VL 59 IS 21 BP 1891 EP 1896 DI 10.1016/j.jacc.2012.02.024 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 942PF UT WOS:000304057200008 PM 22595409 ER PT J AU Song, YH Tai, JHY Bartsch, SM Zimmerman, RK Muder, RR Lee, BY AF Song, Yeohan Tai, Julie H. Y. Bartsch, Sarah M. Zimmerman, Richard K. Muder, Robert R. Lee, Bruce Y. TI The potential economic value of a Staphylococcus aureus vaccine among hemodialysis patients SO VACCINE LA English DT Article DE Staphylococcus aureus; Vaccine; Economics; Hemodialysis; Cost-effectiveness ID COST-EFFECTIVENESS ANALYSIS; LONG-TERM HEMODIALYSIS; METHICILLIN-RESISTANT; CLINICAL-OUTCOMES; CONJUGATE VACCINE; RISK-FACTORS; BACTEREMIA; MANAGEMENT; INFECTION; DIALYSIS AB Staphylococcus aureus infections are a substantial problem for hemodialysis patients. Several vaccine candidates are currently under development, with hemodialysis patients being one possible target population. To determine the potential economic value of an S. aureus vaccine among hemodialysis patients, we developed a Markov decision analytic computer simulation model. When S. aureus colonization prevalence was 1%, the incremental cost-effectiveness ratio (ICER) of vaccination was <=$25,217/quality-adjusted life year (QALY). Vaccination became more cost-effective as colonization prevalence, vaccine efficacy, or vaccine protection duration increased or vaccine cost decreased. Even at 10% colonization prevalence, a 25% efficacious vaccine costing $100 prevented 29 infections, 21 infection-related hospitalizations, and 9 inpatient deaths per 1000 vaccinated HD patients. Our results suggest that an S. aureus vaccine would be cost-effective (i.e., ICERs <= $50,000/QALY) among hemodialysis patients over a wide range of S. aureus prevalence, vaccine costs and efficacies, and vaccine protection durations and delineate potential target parameters for such a vaccine. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Lee, Bruce Y.] Univ Pittsburgh, Publ Hlth Computat & Operat Res Grp, Publ Hlth Computat & Operat Res PHICOR, Pittsburgh, PA 15213 USA. [Song, Yeohan; Tai, Julie H. Y.; Bartsch, Sarah M.; Lee, Bruce Y.] Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA 15260 USA. [Song, Yeohan; Tai, Julie H. Y.; Bartsch, Sarah M.; Lee, Bruce Y.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Zimmerman, Richard K.] Univ Pittsburgh, Sch Med, Dept Family Med, Pittsburgh, PA 15261 USA. [Muder, Robert R.] VA Pittsburgh Healthcare Syst, Div Infect Dis, Pittsburgh, PA 15240 USA. RP Lee, BY (reprint author), Univ Pittsburgh, Publ Hlth Computat & Operat Res Grp, Publ Hlth Computat & Operat Res PHICOR, 200 Meyran Ave,Suite 200, Pittsburgh, PA 15213 USA. EM ysongmd@umich.edu; juliehy@pitt.edu; smm168@pitt.edu; zimmrk@upmc.edu; robert.muder@va.gov; BYL1@pitt.edu OI Zimmerman, Richard/0000-0001-5941-6092 FU National Institute of General Medical Sciences Models of Infectious Disease Agent Study (MIDAS) [5U54GM088491-02]; Pennsylvania Department of Health (DOH) [4100047864] FX This work was supported by the National Institute of General Medical Sciences Models of Infectious Disease Agent Study (MIDAS) grant 5U54GM088491-02 and the Pennsylvania Department of Health (DOH) grant 4100047864. The funders 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. NR 78 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 21 PY 2012 VL 30 IS 24 BP 3675 EP 3682 DI 10.1016/j.vaccine.2012.03.031 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 951SY UT WOS:000304741500024 PM 22464963 ER PT J AU Abbas, KS Li, A Rivero, G Mitsiades, N Yellapragada, S AF Abbas, Kanza S. Li, Ang Rivero, Gustavo Mitsiades, Nicholas Yellapragada, Sarvari TI Survival outcome of veterans with myelodysplastic syndrome (MDS) treated with statins. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Baylor Coll Med, Houston, TX 77030 USA. Baylor Coll Med, Dan L Duncan Canc Ctr, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e17018 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801859 ER PT J AU Corless, CL Neff, T Heinrich, MC Beadling, C AF Corless, Christopher L. Neff, Tanaya Heinrich, Michael C. Beadling, Carol TI Combining semiconductor-based sequencing with amplicon-based cancer gene panels: A rapid next-gen approach to clinical cancer genotyping. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Oregon Hlth & Sci Univ, Knight Diagnost Labs, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 10591 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803550 ER PT J AU D'Ambrosio, L Brusa, F D'Ascenzo, F Cavallero, E Biondi-Zoccai, G Boccone, P Bironzo, P Levin, GN Eckel, RH Milani, RV Sagalowsky, AI Gasparini, M Grignani, G Gaita, F Ciuffreda, L Aglietta, M AF D'Ambrosio, Lorenzo Brusa, Federica D'Ascenzo, Fabrizio Cavallero, Erica Biondi-Zoccai, Giuseppe Boccone, Paola Bironzo, Paolo Levin, Glenn N. Eckel, Robert H. Milani, Richard V. Sagalowsky, Arthur I. Gasparini, Mauro Grignani, Giovanni Gaita, Fiorenzo Ciuffreda, Libero Aglietta, Massimo TI Risk of adverse cardiovascular events (CVE) and incident diabetes mellitus (DM) in patients (pts) with prostate cancer (PC) treated with androgen deprivation therapy (ADT): A meta-analysis of adjusted observational results SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Inst Canc Res & Treatment, Candiolo, Italy. Ctr Oncol & Ematol Subalpino, Turin, Italy. Univ Turin, Div Cardiol, Turin, Italy. Univ Modena & Reggio Emilia, Div Cardiol, Modena, Italy. Baylor Coll Med, Cardiac Care Unit, Houston, TX 77030 USA. Michael E DeBakey Med Ctr, Houston, TX USA. Univ Colorado, Aurora, CO USA. Ochsner Med Ctr, Div Cardiol, New Orleans, LA USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Politecn Torino, Dept Math, I-10128 Turin, Italy. Univ Turin, Div Cardiol, Corso Dogliotti, Italy. AOU S Giovanni Battista Molinette, Div Oncol, Turin, Italy. RI Milani, Richard/A-6045-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e15192 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802859 ER PT J AU Desai, P Braun, E Dehghan-Paz, I Gattuso, P Canar, J Cobleigh, MA AF Desai, Palak Braun, Eduardo Dehghan-Paz, Irene Gattuso, Paolo Canar, Jeff Cobleigh, Melody A. TI Synchronous bilateral breast cancer (SBBC): Concordance of receptor status between right and left breast SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Rush Univ, Med Ctr, Chicago, IL 60612 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Rush Univ, Natl Surg Adjuvant Breast & Bowel Project, Med Ctr, Chicago, IL 60612 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 572 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800078 ER PT J AU Gartrell, BA Hahn, NM Hutson, TE Sonpavde, G Hauke, RJ Starodub, A Small, AC Tsao, CK Galsky, MD AF Gartrell, Benjamin Adam Hahn, Noah M. Hutson, Thomas E. Sonpavde, Guru Hauke, Ralph J. Starodub, Alexander Small, Alexander C. Tsao, Che-Kai Galsky, Matt D. TI Phase II trial of gemcitabine and cisplatin plus ipilimumab as first-line treatment for metastatic urothelial carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY USA. Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Texas Oncol Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. Texas Oncol, Houston, TX USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Sect Med Oncol, Dept Med, Houston, TX 77030 USA. Nebraska Canc Specialists, Omaha, NE USA. Goshen Ctr Canc Care, Goshen, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS4676 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803064 ER PT J AU Goldkorn, A Ely, B Quinn, DI Tangen, CM Tai, YC Twardowski, P Van Veldhuizen, PJ Agarwal, N Anthony, M Monk, CJP Garzotto, M Mack, PC Lara, P Higano, CS Hussain, M Vogelzang, NJ Cote, RJ Thompson, IM AF Goldkorn, Amir Ely, Benjamin Quinn, David I. Tangen, Catherine M. Tai, Yu-Chong Twardowski, Przemyslaw Van Veldhuizen, Peter J. Agarwal, Neeraj Anthony, Michael Monk, Carducci J. P. Garzotto, Mark Mack, Philip C. Lara, Primo Higano, Celestia S. Hussain, Maha Vogelzang, Nicholas J. Cote, Richard J. Thompson, Ian Murchie CA Southwest Oncology Grp TI Results of telomerase activity measurements from live circulating tumor cells captured on a slot microfilter in a phase III SWOG-coordinated prostate cancer trial (S0421) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. SWOG Stat Ctr, Seattle, WA USA. CALTECH, Pasadena, CA 91125 USA. City Hope Natl Med Ctr, Duarte, CA USA. Univ Kansas, Ctr Canc, Westwood, KS USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Ohio State Univ, Columbus, OH 43210 USA. Portland VA Med Ctr, Portland, OR USA. Univ Calif Davis, Davis, CA 95616 USA. Univ Washington, Seattle Canc Care Alliance, Puget Sound Oncol Consortium, Seattle, WA 98195 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Comprehens Canc Ctr Nevada, Las Vegas, NV USA. Univ Miami, Miller Sch Med, Miami, FL 33136 USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4663 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803108 ER PT J AU Hahn, NM Daneshmand, S Posadas, EM Koch, MO Bihrle, R Foster, R Masterson, TA Cheng, L Liu, ZY Breen, T Fleming, MT Lance, R Ryan, CW Corless, CL Galsky, MD Alva, AS Mitchell, C Shen, SS Lerner, SP Sonpavde, G AF Hahn, Noah M. Daneshmand, Siamak Posadas, Edwin M. Koch, Michael O. Bihrle, Richard Foster, Richard Masterson, Timothy A. Cheng, Liang Liu, Ziyue Breen, Timothy Fleming, Mark T. Lance, Ray Ryan, Christopher W. Corless, Christopher L. Galsky, Matt D. Alva, Ajjai Shivaram Mitchell, Carmen Shen, Steven S. Lerner, Seth P. Sonpavde, Guru TI A phase II trial of neoadjuvant dasatinib (Neo-D) in muscle-invasive urothelial carcinoma of the bladder (miUCB): Hoosier Oncology Group GU07-122 trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. Indiana Univ, Med Ctr, Indianapolis, IN USA. Indiana Univ, Indianapolis, IN 46204 USA. Indiana Univ, Med Ctr, Dept Pathol & Lab Med, Indianapolis, IN USA. Indiana Univ, Div Biostat, Indianapolis, IN 46204 USA. Hoosier Oncol Grp, Indianapolis, IN USA. US Oncol Res, The Woodlands, TX USA. Virginia Oncol Associates, Hampton, VA USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Knight Diagnost Labs, Portland, OR 97201 USA. Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. Univ Michigan, Ann Arbor, MI 48109 USA. Baylor Coll Med, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. Texas Oncol, Houston, TX USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Sect Med Oncol, Houston, TX 77030 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4586 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802889 ER PT J AU Kim, B He, R Antonio, ALM Asch, SM Malin, J AF Kim, Benjamin He, Ren Antonio, Anna Liza M. Asch, Steven M. Malin, Jennifer TI Comparative effectiveness of erlotinib versus no treatment for advanced non-small cell lung cancer patients in the Veterans Administration. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 UCSF Sch Med, San Francisco, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. VA Palo Alto Hlth Care Syst, Menlo Pk, CA USA. Univ Calif Los Angeles, Greater Los Angeles Vet Adm Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6105 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803168 ER PT J AU Lerner, SP Sternberg, CN Younes, M Calabro, F Cerbone, L Chandrashekar, A Mitchell, C Shen, SS Sonpavde, G AF Lerner, Seth P. Sternberg, Cora N. Younes, Mamoun Calabro, Fabio Cerbone, Linda Chandrashekar, A. Mitchell, Carmen Shen, Steven S. Sonpavde, Guru TI Phase II trial of tamoxifen for progressive advanced urothelial carcinoma following prior chemotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Baylor Coll Med, Houston, TX 77030 USA. San Camillo & Forlanini Hosp, Rome, Italy. Univ Texas Hlth Sci Ctr, Houston, TX USA. San Camillo Forlanini Hosp, Rome, Italy. Methodist Hosp, Houston, TX 77030 USA. Texas Oncol, Houston, TX USA. Baylor Coll Med, Dept Med, Sect Med Oncol, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e15003 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803021 ER PT J AU Levitt, JM Chan, KS Jian, WG Lerner, SP Sonpavde, G AF Levitt, Jonathan M. Chan, Keith S. Jian, Weiguo Lerner, Seth P. Sonpavde, Guru TI The preclinical activity of lenalidomide in urothelial carcinoma (UC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Baylor Coll Med, Houston, TX 77030 USA. Texas Oncol, Houston, TX USA. Baylor Coll Med, Dept Med, Sect Med Oncol, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e15002 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803112 ER PT J AU Musuuza, JS Sherman, ME Knudsen, KJ Sweeney, H Tyler, CV Koroukian, SM AF Musuuza, Jackson S. Sherman, Marion E. Knudsen, Kraig J. Sweeney, HelenAnne Tyler, Carl V. Koroukian, Siran M. TI Analyzing excess mortality from cancer among individuals with mental illness. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ Wisconsin, Dept Populat Hlth Sci, Sch Med & Publ Hlth, Madison, WI USA. US Dept Vet Affairs, Joint Ambulatory Care Ctr, Pensacola, FL USA. Ohio Dept Mental Hlth, Columbus, OH USA. Cleveland Clin Hosp, Fairview Hosp, Cleveland, OH USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 1598 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801312 ER PT J AU Quinn, DI Tangen, CM Hussain, M Lara, P Goldkorn, A Garzotto, M Mack, PC Carducci, MA Monk, JP Twardowski, P Van Veldhuizen, PJ Agarwal, N Higano, CS Vogelzang, NJ Thompson, IM AF Quinn, David I. Tangen, Catherine M. Hussain, Maha Lara, Primo Goldkorn, Amir Garzotto, Mark Mack, Philip C. Carducci, Michael Anthony Monk, J. P. Twardowski, Przemyslaw Van Veldhuizen, Peter J. Agarwal, Neeraj Higano, Celestia S. Vogelzang, Nicholas J. Thompson, Ian Murchie TI SWOG S0421: Phase III study of docetaxel (D) and atrasentan (A) versus docetaxel and placebo (P) for men with advanced castrate resistant prostate cancer (CRPC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. SWOG Stat Ctr, Seattle, WA USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Univ Calif Davis, Sacramento, CA 95817 USA. Portland VA Med Ctr, Portland, OR USA. Johns Hopkins Univ, Baltimore ECOG, Baltimore, MD USA. Ohio State Univ, CALGB, Columbus, OH 43210 USA. City Hope Natl Med Ctr, Duarte, CA USA. Univ Kansas, Ctr Canc, Westwood, KS USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Univ Washington, Seattle Canc Care Alliance, Puget Sound Oncol Consortium, Seattle, WA 98195 USA. Comprehens Canc Ctr NV, US Oncol Res, Las Vegas, NV USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4511 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803074 ER PT J AU Small, AC Tsao, CK Moshier, EL Gartrell, BA Wisnivesky, JP Godbold, JH Smith, CB Sonpavde, G Oh, WK Galsky, MD AF Small, Alexander C. Tsao, Che-Kai Moshier, Erin L. Gartrell, Benjamin Adam Wisnivesky, Juan P. Godbold, James H. Smith, Cardinale B. Sonpavde, Guru Oh, William K. Galsky, Matt D. TI Prevalence and characteristics of patients with stage IV solid tumors who receive no anticancer therapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY USA. Mt Sinai Sch Med, Div Gen Internal Med, New York, NY USA. Mt Sinai Sch Med, Div Pulm & Crit Care Med, New York, NY USA. Texas Oncol, Houston, TX USA. Baylor Coll Med, Dept Med, Sect Med Oncol, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6065 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802050 ER PT J AU Sonpavde, G Amiel, G Margulis, V Link, RE Lerner, SP Raj, G Mayer, WA Palapattu, GS Lotan, Y Sagalowsky, AI Higgins, LC Tello, SA Pavia-Jimenez, A VonMerveldt, D Brugarolas, J AF Sonpavde, Guru Amiel, Gilad Margulis, Vitaly Link, Richard E. Lerner, Seth P. Raj, Ganesh Mayer, Wesley A. Palapattu, Ganesh S. Lotan, Yair Sagalowsky, Arthur I. Higgins, Linda C. Tello, Sebrina A. Pavia-Jimenez, Andrea VonMerveldt, Dendra Brugarolas, James TI Neoadjuvant therapy preceding cytoreductive nephrectomy to develop individualized first-line therapy with everolimus for advanced renal cell carcinoma (RCC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Texas Oncol, Houston, TX USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Sect Med Oncol, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Methodist Hosp, Houston, TX 77030 USA. Weill Cornell Med Coll, Houston, TX USA. Univ Texas Southwestern, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS4678 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802866 ER PT J AU Tsao, CK Small, AC Kates, M Gartrell, BA Wisnivesky, JP Sonpavde, G Palese, M Hall, S Oh, WK Galsky, MD AF Tsao, Che-Kai Small, Alexander C. Kates, Max Gartrell, Benjamin Adam Wisnivesky, Juan P. Sonpavde, Guru Palese, Michael Hall, Simon Oh, William K. Galsky, Matt D. TI Trends in the use of cytoreductive nephrectomy for metastatic renal cell carcinoma in the VEGFR tyrosine kinase inhibitor era SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY USA. Mt Sinai Sch Med, Div Gen Internal Med, New York, NY USA. Mt Sinai Sch Med, Div Pulm & Crit Care Med, New York, NY USA. Texas Oncol, Houston, TX USA. Baylor Coll Med, Dept Med, Sect Med Oncol, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Mt Sinai Sch Med, Dept Urol, New York, NY USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4623 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802603 ER PT J AU Vogelzang, NJ Ely, B Fink, LM Goldkorn, A Tangen, CM Twardowski, P Van Veldhuizen, PJ Agarwal, N Carducci, MA Monk, JP Datar, RH Garzotto, M Mack, PC Lara, P Higano, CS Hussain, M Quinn, DI Cote, RJ Thompson, IM AF Vogelzang, Nicholas J. Ely, Benjamin Fink, Louis M. Goldkorn, Amir Tangen, Catherine M. Twardowski, Przemyslaw Van Veldhuizen, Peter J. Agarwal, Neeraj Carducci, Michael Anthony Monk, J. P. Datar, Ram H. Garzotto, Mark Mack, Philip C. Lara, Primo Higano, Celestia S. Hussain, Maha Quinn, David I. Cote, Richard J. Thompson, Ian Murchie TI Circulating tumor cell counts (CTC) as prognostic of overall survival (OS) in SWOG S0421-docetaxel with or without atrasentan for metastatic castration resistant prostate cancer (mCRPC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) C1 Comprehens Canc Ctr Nevada, Las Vegas, NV USA. US Oncol Res, Las Vegas, NV USA. SWOG Stat Ctr, Seattle, WA USA. Nevada Canc Inst, Las Vegas, NV USA. Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. City Hope Natl Med Ctr, Duarte, CA USA. Univ Kansas, Ctr Canc, Westwood, KS USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Johns Hopkins Univ, Baltimore ECOG, Baltimore, MD USA. Ohio State Univ, CALGB, Columbus, OH 43210 USA. Univ Miami, Miller Sch Med, Miami, FL 33136 USA. Portland VA Med Ctr, Portland, OR USA. Univ Calif Davis, Sacramento, CA 95817 USA. Univ Washington, Seattle Canc Care Alliance, Puget Sound Oncol Consortium, Seattle, WA 98195 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 10503 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800014 ER PT J AU Jim, B Ghanta, M Qipo, A Fan, Y Chuang, PY Cohen, HW Abadi, M Thomas, DB He, JC AF Jim, Belinda Ghanta, Mythili Qipo, Andi Fan, Ying Chuang, Peter Y. Cohen, Hillel W. Abadi, Maria Thomas, David B. He, John Cijiang TI Dysregulated Nephrin in Diabetic Nephropathy of Type 2 Diabetes: A Cross Sectional Study SO PLOS ONE LA English DT Article ID SLIT-DIAPHRAGM PROTEIN; GLOMERULAR PROTEIN; NEPHROTIC SYNDROME; PODOCYTE NUMBER; KIDNEY-DISEASE; EXPRESSION; RAT; MICROALBUMINURIA; INHIBITION; EXCRETION AB Background: Podocyte specific proteins are dysregulated in diabetic nephropathy, though the extent of their expression loss is not identical and may be subject to different regulatory factors. Quantifying the degree of loss may help identify the most useful protein to use as an early biomarker of diabetic nephropathy. Methodology/Principal Findings: Protein expression of synaptopodin, podocin and nephrin were quantified in 15 Type 2 diabetic renal biopsies and 12 control patients. We found statistically significant downregulation of synaptopodin (P < 0.0001), podocin (P = 0.0002), and nephrin (P < 0.0001) in kidney biopsies of diabetic nephropathy as compared with controls. Urinary nephrin levels (nephrinuria) were then measured in 66 patients with Type 2 diabetes and 10 healthy controls by an enzyme-linked immunosorbent assay (Exocell, Philadelphia, PA). When divided into groups according to normo-, micro-, and macroalbuminuria, nephrinuria was found to be present in 100% of diabetic patients with micro-and macroalbuminuria, as well as 54% of patients with normoalbuminuria. Nephrinuria also correlated significantly with albuminuria (rho = 0.89, P < 0.001), systolic blood pressure (rho = 0.32, p = 0.007), and correlated negatively with serum albumin (rho = 20.48, P < 0.0001) and eGFR (rho = 20.33, p = 0.005). Conclusions/Significance: These data suggest that key podocyte-specific protein expressions are significantly and differentially downregulated in diabetic nephropathy. The finding that nephrinuria is observed in a majority of these normoalbuminuric patients demonstrates that it may precede microalbuminuria. If further research confirms nephrinuria to be a biomarker of pre-clinical diabetic nephropathy, it would shed light on podocyte metabolism in disease, and raise the possibility of new and earlier therapeutic targets. C1 [Jim, Belinda; Ghanta, Mythili; Qipo, Andi] Albert Einstein Coll Med, Jacobi Med Ctr, Dept Med, Div Nephrol, Bronx, NY 10467 USA. [Fan, Ying] Shanghai Jiao Tong Univ, Dept Nephrol, Affiliated Peoples Hosp 6, Shanghai 200030, Peoples R China. [Chuang, Peter Y.; He, John Cijiang] Mt Sinai Sch Med, Div Nephrol, Dept Med, New York, NY USA. [Cohen, Hillel W.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Abadi, Maria] Albert Einstein Coll Med, Dept Pathol, Jacobi Med Ctr, Bronx, NY 10467 USA. [Thomas, David B.] Nephrocor, Uniondale, NY USA. [He, John Cijiang] James J Peters VA Med Ctr, Dept Med Bronx, Div Nephrol, New York, NY USA. RP Jim, B (reprint author), Albert Einstein Coll Med, Jacobi Med Ctr, Dept Med, Div Nephrol, Bronx, NY 10467 USA. EM bun.jim@nbhn.net OI Cohen, Hillel/0000-0002-4524-0898 FU VA Merit Award; NIH [1R01 DK078897]; National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [UL1 RR025750, KL2 RR025749, TL1 RR025748]; NIH roadmap for Medical Research FX Dr. JC He is funded by the VA Merit Award and NIH 1R01 DK078897. This publication was supported in part by the Clinical Translational Science Award (CTSA) Grant UL1 RR025750, KL2 RR025749 and TL1 RR025748 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessary represent the official view of the NCRR or NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 41 Z9 50 U1 0 U2 11 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 MAY 17 PY 2012 VL 7 IS 5 AR e36041 DI 10.1371/journal.pone.0036041 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UQ UT WOS:000305341200005 PM 22615747 ER PT J AU Homma, S Thompson, JLP Pullicino, PM Levin, B Freudenberger, RS Teerlink, JR Ammon, SE Graham, S Sacco, RL Mann, DL Mohr, JP Massie, BM Labovitz, AJ Anker, SD Lok, DJ Ponikowski, P Estol, CJ Lip, GYH Di Tullio, MR Sanford, AR Mejia, V Gabriel, AP del Valle, ML Buchsbaum, R AF Homma, Shunichi Thompson, John L. P. Pullicino, Patrick M. Levin, Bruce Freudenberger, Ronald S. Teerlink, John R. Ammon, Susan E. Graham, Susan Sacco, Ralph L. Mann, Douglas L. Mohr, J. P. Massie, Barry M. Labovitz, Arthur J. Anker, Stefan D. Lok, Dirk J. Ponikowski, Piotr Estol, Conrado J. Lip, Gregory Y. H. Di Tullio, Marco R. Sanford, Alexandra R. Mejia, Vilma Gabriel, Andre P. del Valle, Mirna L. Buchsbaum, Richard CA WARCEF Investigators TI Warfarin and Aspirin in Patients with Heart Failure and Sinus Rhythm SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ATRIAL-FIBRILLATION; VENTRICULAR DYSFUNCTION; ANTITHROMBOTIC THERAPY; MYOCARDIAL-INFARCTION; RANDOMIZED-TRIAL; DOUBLE-BLIND; ANTICOAGULATION; STROKE; PREVENTION; ENALAPRIL AB BACKGROUND It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm. METHODS We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [+/- SD], 3.5 +/- 1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. RESULTS The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P=0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P=0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P=0.82). CONCLUSIONS Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized. C1 [Homma, Shunichi; Thompson, John L. P.; Levin, Bruce; Mohr, J. P.; Di Tullio, Marco R.; Sanford, Alexandra R.; Mejia, Vilma; Gabriel, Andre P.; del Valle, Mirna L.; Buchsbaum, Richard] Columbia Univ, Med Ctr, New York, NY 10032 USA. [Pullicino, Patrick M.] Univ Kent, Canterbury, Kent, England. [Lip, Gregory Y. H.] Univ Birmingham, Ctr Cardiovasc Sci, Birmingham, W Midlands, England. [Freudenberger, Ronald S.] Lehigh Valley Hosp, Allentown, PA USA. [Teerlink, John R.; Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.; Ammon, Susan E.; Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Graham, Susan] SUNY Buffalo, Buffalo, NY 14260 USA. [Sacco, Ralph L.] Univ Miami, Miami, FL USA. [Mann, Douglas L.] Washington Univ, St Louis, MO 63130 USA. [Labovitz, Arthur J.] Univ S Florida, Tampa, FL USA. [Anker, Stefan D.] Charite, D-13353 Berlin, Germany. [Anker, Stefan D.] IRCCS San Raffaele, Ctr Clin & Basic Res, Rome, Italy. [Lok, Dirk J.] Hosp Deventer, Deventer, Netherlands. [Ponikowski, Piotr] Mil Hosp, Wroclaw, Poland. [Estol, Conrado J.] Ctr Neurol Tratamiento & Rehabil, Buenos Aires, DF, Argentina. RP Homma, S (reprint author), Columbia Univ, Med Ctr, PH 3-342,622 W 168th St, New York, NY 10032 USA. RI Ponikowski, Piotr/O-6454-2015 OI Ponikowski, Piotr/0000-0002-3391-7064; Mann, Douglas /0000-0002-2516-0145; Kohsaka, Shun/0000-0003-3779-2972 FU National Institute of Neurological Disorders and Stroke [U01-NS-043975, U01-NS-039143]; St. Jude Medical; Boehringer Ingelheim; United Healthcare; Amgen; Cytokinetics; Novartis; NovaCardia/Merck; American College of Cardiology; Bosch Healthcare; GlaxoSmithKline; Helsinn; LoneStar Heart; Professional Dietetics; PsiOxus; Relypsa; SHL Telemedicine; Thermo Fisher; Vifor Pharma; Bayer; Coridea; Corthera; Johnson Johnson; Pfizer; Respicardia; Abbott; Merck Serono; Sanofi-Aventis; Servier; Astellas; AstraZeneca; Biotronik; Bristol-Myers Squibb; Merck; Portola; National Institute of Neurological Disorders and Stroke; WARCEF [NCT00041938] FX Funded by the National Institute of Neurological Disorders and Stroke; WARCEF ClinicalTrials.gov number, NCT00041938.; Supported by grants (U01-NS-043975 [to Dr. Homma] and U01-NS-039143 [to Dr. Thompson]) from the National Institute of Neurological Disorders and Stroke.; Dr. Homma reports receiving payment from AGA Medical (now St. Jude Medical) for his work as a member of a data and safety monitoring board and consulting fees from Boehringer Ingelheim; Dr. Levin, receiving consulting fees from United Healthcare; Dr. Teerlink, receiving consulting fees from Amgen and grant support from Amgen, Cytokinetics, and Novartis on behalf of himself and from NovaCardia/Merck on behalf of himself and his institution; Dr. Graham, owning stock in March Pharmaceuticals, Medtronic, and Pfizer; Dr. Labovitz, receiving grant support from Boehringer Ingelheim on behalf of his institution, lecture fees from Boehringer Ingelheim, and fees for the development of educational presentations from the American College of Cardiology; Dr. Anker, receiving consulting fees from Amgen, Bosch Healthcare, GlaxoSmithKline, Helsinn, LoneStar Heart, Novartis, Professional Dietetics, PsiOxus, Relypsa, SHL Telemedicine, and Thermo Fisher, grant support from Vifor Pharma, and lecture fees from Novartis, holding patents with Brahms AG and Charite Berlin, and receiving royalties from Imperial College; Dr. Ponikowski, receiving consulting fees from Bayer, Boehringer Ingelheim, Coridea, Corthera, Johnson & Johnson, Pfizer, Respicardia, and Vifor Pharma, grant support from Vifor Pharma on behalf of himself and his institution, and lecture fees from Abbott, Boehringer Ingelheim, Merck Serono, Pfizer, Respicardia, Sanofi-Aventis, Servier, and Vifor Pharma; and Dr. Lip, receiving consulting fees from Astellas, AstraZeneca, Bayer, Biotronik, Boehringer Inhelheim, Bristol-Myers Squibb, Pfizer, Merck, Portola, and Sanofi-Aventis, speakers bureau fees from Bayer, Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, and Sanofi-Aventis, and payment for the development of educational presentations from Bayer, Boehringer Ingelheim, and Merck. No other potential conflict of interest relevant to this article was reported. NR 28 TC 171 Z9 175 U1 0 U2 28 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 MAY 17 PY 2012 VL 366 IS 20 BP 1859 EP 1869 DI 10.1056/NEJMoa1202299 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 942WU UT WOS:000304083000005 PM 22551105 ER PT J AU Gandy, S DeKosky, ST AF Gandy, Sam DeKosky, Steven T. TI APOE epsilon 4 Status and Traumatic Brain Injury on the Gridiron or the Battlefield SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Editorial Material ID ENCEPHALOPATHY; FOOTBALL C1 [DeKosky, Steven T.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Gandy, Sam] Ctr Cognit Hlth, New York, NY 10029 USA. [Gandy, Sam] NFL Neurol Program, New York, NY 10029 USA. [Gandy, Sam] Alzheimers Dis Res Ctr, New York, NY 10029 USA. [Gandy, Sam] Mt Sinai Sch Med, New York, NY 10029 USA. [Gandy, Sam] James J Peters VA Med Ctr, New York, NY 10029 USA. RP Gandy, S (reprint author), Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. EM samuel.gandy@mssm.edu; dekosky@virginia.edu FU NIA NIH HHS [P50 AG005138]; RRD VA [I01 RX000684] NR 5 TC 7 Z9 7 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD MAY 16 PY 2012 VL 4 IS 134 AR 134ed4 DI 10.1126/scitranslmed.3004274 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 943KY UT WOS:000304121500001 PM 22593171 ER PT J AU Kelley, KW McBane, S Thomas, T Karr, S AF Kelley, Kristi W. McBane, Sarah Thomas, Tyan Karr, Samantha TI Serving as a preceptor to pharmacy students: Tips on maintaining the desire to inspire SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material C1 [Kelley, Kristi W.] Auburn Univ, Harrison Sch Pharm, Auburn, AL 36849 USA. [Kelley, Kristi W.] Baptist Hlth Syst Inc, Continu Clin, Trinity Med Ctr, Birmingham, AL 35213 USA. [McBane, Sarah] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Thomas, Tyan] Univ Sci Philadelphia, Philadelphia Coll Pharm, Philadelphia, PA USA. [Thomas, Tyan] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Karr, Samantha] Midwestern Univ, Coll Pharm Glendale, Glendale, AZ USA. RP Kelley, KW (reprint author), Auburn Univ, Harrison Sch Pharm, Auburn, AL 36849 USA. EM watsokm@auburn.edu NR 3 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD MAY 15 PY 2012 VL 69 IS 10 BP 826 EP + DI 10.2146/ajhp110292 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 073VC UT WOS:000313770200005 PM 22555078 ER PT J AU Childs, L Alexander, E Duong, MT AF Childs, Lindsey Alexander, Earnest Minh-Tri Duong TI Risk evaluation and mitigation strategies: Assessment of a medical center's policies and procedures SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE Administration; Compliance; Computers; Education; Food and Drug Administration (US); Hospitals; Quality assurance; Risk management; Storage; Toxicity AB Purpose. The results of a hospital's initiative to evaluate and improve compliance with federally mandated risk evaluation and mitigation strategies (REMS) are presented. Summary. Food and Drug Administration approved REMS plans are required for more than 145 drugs, but clear guidance on strategies for achieving REMS compliance is lacking. As a first step toward determining the extent of REMS compliance at a large medical center, a systematic assessment was conducted to ascertain existing policies and procedures for the use of drugs subject to REMS requirements applicable in the inpatient setting. About 123 drugs with such "inpatient-applicable" REMS requirements were identified; of those, 10 had been ordered by hospital providers during a specified 18-month time frame and were included in the assessment of policies and procedures. The assessment revealed that the hospital lacked a formal REMS policy and had no REMS-compliant procedures in place for 7 evaluated drugs (ambrisentan, buprenorphine naloxone, darbepoetin alfa, epoetin alfa, oxycodone controlled-release tablets, prasugrel, and pregabalin). Pursuant to the compliance assessment, new procedures to help ensure the safe use of those 7 drugs were developed, and REMS-focused educational programs, order-entry system enhancements, and drug storage modifications were implemented. Conclusion. Quality-improvement initiatives including staff education, incorporation of REMS requirements into existing policy, development of an electronic resource, and creation of a separate storage section for drugs subject to REMS were implemented at a large academic medical center to help ensure compliance with inpatient-applicable REMS requirements. C1 [Childs, Lindsey] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Childs, Lindsey; Alexander, Earnest; Minh-Tri Duong] Tampa Gen Hosp, Serv Pharm, Tampa, FL 33606 USA. [Alexander, Earnest] Tampa Gen Hosp, Clin Pharm Serv, Tampa, FL 33606 USA. [Minh-Tri Duong] Tampa Gen Hosp, Residency Programs, Tampa, FL 33606 USA. RP Childs, L (reprint author), S Texas Vet Hlth Care Syst, 7400 Merton Minter St, San Antonio, TX 78229 USA. EM lmchilds000410@gmail.com NR 6 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD MAY 15 PY 2012 VL 69 IS 10 BP 885 EP 889 DI 10.2146/ajhp110356 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 073VC UT WOS:000313770200012 PM 22555085 ER PT J AU Schiros, CG Dell'Italia, LJ Gladden, JD Clark, D Aban, I Gupta, H Lloyd, SG McGiffin, DC Perry, G Denney, TS Ahmed, MI AF Schiros, Chun G. Dell'Italia, Louis J. Gladden, James D. Clark, Donald, III Aban, Inmaculada Gupta, Himanshu Lloyd, Steven G. McGiffin, David C. Perry, Gilbert Denney, Thomas S., Jr. Ahmed, Mustafa I. TI Magnetic Resonance Imaging With 3-Dimensional Analysis of Left Ventricular Remodeling in Isolated Mitral Regurgitation Implications Beyond Dimensions SO CIRCULATION LA English DT Article DE magnetic resonance imaging; surgery; ventricular dysfunction left; ventricular remodeling ID VALVE-REPLACEMENT; PERFORMANCE; SURGERY; ECHOCARDIOGRAPHY; RECONSTRUCTION; DETERMINANTS; DYSFUNCTION; PREDICTION; GEOMETRY; SURVIVAL AB Background-Although surgery is indicated in patients with mitral regurgitation (MR) when left ventricular (LV) end-systolic (LVES) dimension is >40 mm, LV ejection fraction may decrease after mitral valve surgery. We hypothesize that significant LV remodeling before surgery is not reflected by standard echocardiographic parameters measured at the base of the heart. Methods and Results-Ninety-four patients (age, 54 +/- 11 years; 38% female) with degenerative isolated MR underwent cine magnetic resonance imaging with tissue tagging and 3-dimensional analysis. In 51 control subjects (age, 44 +/- 14 years; 53% female), the relation between LVES volume (LVESV) and LVES dimension was quadratic, whereas in 94 MR patients, this relation was cubic, indicating a greater increase in LVESV per LVES dimension among MR patients. Moreover, magnetic resonance imaging LVESV from summated serial short-axis slices was significantly greater than LVESV assessed with the Bullet formula in MR patients, attributed to a more spherical remodeling distal to the tips of the papillary muscles (P<0.001). Thirty-five patients underwent mitral valve repair per current guideline recommendations. LV ejection fraction decreased from 61 +/- 7% to 54 +/- 8% (P<0.0001) and maximum shortening decreased significantly below normal at 1 year postoperatively (P<0.0001). Despite normalization of LV stroke volume and LV end-diastolic volume/mass ratio, there was a persistent significant increase in distal LVES 3-dimensional radius/wall thickness ratio and LVESV index after surgery. Conclusions-Despite apparently preserved LVES dimension, MR patients demonstrate significant spherical mid to apical LVES remodeling that contributes to higher LVESV than predicted by standard geometry-based calculations. Decreased LV strain after surgery suggests that a volumetric analysis of LV remodeling and function may be preferred to evaluate disease progression in isolated MR. C1 [Schiros, Chun G.; Denney, Thomas S., Jr.] Auburn Univ, Dept Elect & Comp Engn, Samuel Ginn Coll Engn, Auburn, AL 36849 USA. [Dell'Italia, Louis J.; Gupta, Himanshu; Lloyd, Steven G.; Perry, Gilbert] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Dell'Italia, Louis J.; Gladden, James D.; Clark, Donald, III; Gupta, Himanshu; Lloyd, Steven G.; McGiffin, David C.; Ahmed, Mustafa I.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Aban, Inmaculada] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA. RP Ahmed, MI (reprint author), Univ Alabama Birmingham, Dept Med, UAB Ctr Heart Failure Res, Div Cardiol, 434 BMR2,901 19th St S, Birmingham, AL 35294 USA. EM mahmed@uab.edu FU National Institutes of Health Specialized Center of Clinically Oriented Research in Cardiac Dysfunction [P50-HL077100] FX This work was supported by National Institutes of Health Specialized Center of Clinically Oriented Research in Cardiac Dysfunction P50-HL077100. NR 36 TC 24 Z9 25 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 15 PY 2012 VL 125 IS 19 BP 2334 EP + DI 10.1161/CIRCULATIONAHA.111.073239 PG 13 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 981YQ UT WOS:000307009202013 PM 22496130 ER PT J AU Esterberg, M Compton, M AF Esterberg, Michelle Compton, Michael TI Family history of psychosis negatively impacts age at onset, negative symptoms, and duration of untreated illness and psychosis in first-episode psychosis patients SO PSYCHIATRY RESEARCH LA English DT Article DE Age at onset; Duration of untreated psychosis (DUP); Family history; First-episode psychosis; Schizophrenia ID SCHIZOPHRENIA SPECTRUM DISORDERS; GENDER-DIFFERENCES; SPORADIC SCHIZOPHRENIA; SEX-DIFFERENCES; EPISODE; RISK; PSYCHOPATHOLOGY; DETERMINANTS; TRANSMISSION; FAMILIALITY AB Family history (FH) of psychosis has been a focus of investigations attempting to explain the heterogeneity in schizophrenia. Previous studies have demonstrated that FH is associated with earlier age at onset, severity of positive and negative symptoms, and the duration of untreated illness (DUI). The current study examined the impact of FH on the clinical presentation and help-seeking behaviors of a well-characterized, first-episode sample. The present study utilized the Symptom Onset in Schizophrenia (SOS) Inventory, the Positive and Negative Syndrome Scale (PANSS), and structured interviews on FH to examine these relationships in a large (n = 152) sample of predominantly African American patients. Results showed that patients with a first-degree FH of psychosis had a younger age at onset of both the prodrome and psychosis, but did not differ in duration of prodromal period. Furthermore, FH and sex interacted to influence severity of negative, but not positive symptoms. Finally, FH interacted with sex to influence both the DUI and DUP in that only males with FH had longer DUI and DUP. The findings have implications for understanding the impact of specific family-related mechanisms on both clinical and help-seeking factors, as well as for informing future family-based intervention efforts. Published by Elsevier Ireland Ltd. C1 [Esterberg, Michelle] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Mental Hlth Serv, Seattle, WA 98108 USA. [Compton, Michael] George Washington Univ, Sch Med & Hlth Sci, Dept Psychiat & Behav Sci, Washington, DC 20037 USA. RP Esterberg, M (reprint author), VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Mental Hlth Serv, Mail Stop S-116,1660 S Columbian Way, Seattle, WA 98108 USA. EM michelle.esterberg@va.gov; mcompton@mfa.gwu.edu FU National Institute of Mental Health [K23 MH067589, R01 MH081011] FX This work was supported by grants K23 MH067589 and R01 MH081011 from the National Institute of Mental Health to the second author (MTC). NR 61 TC 16 Z9 16 U1 3 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAY 15 PY 2012 VL 197 IS 1-2 BP 23 EP 28 DI 10.1016/j.psychres.2012.03.001 PG 6 WC Psychiatry SC Psychiatry GA 975WE UT WOS:000306541400005 PM 22503358 ER PT J AU Huang, G Wang, D Khan, UI Zeb, I Manson, JE Miller, V Hodis, HN Budoff, MJ Merriam, GR Harman, MS Brinton, EA Cedars, MI Su, YL Lobo, RA Naftolin, F Santoro, N Taylor, HS Wildman, RP AF Huang, Gary Wang, Dan Khan, Unab I. Zeb, Irfan Manson, Joann E. Miller, Virginia Hodis, Howard N. Budoff, Matthew J. Merriam, George R. Harman, Mitchell S. Brinton, Eliot A. Cedars, Marcelle I. Su, Yali Lobo, Rogerio A. Naftolin, Frederick Santoro, Nanette Taylor, Hugh S. Wildman, Rachel P. TI Associations between retinol-binding protein 4 and cardiometabolic risk factors and subclinical atherosclerosis in recently postmenopausal women: cross-sectional analyses from the KEEPS study SO CARDIOVASCULAR DIABETOLOGY LA English DT Article DE Retinol-binding protein 4; Subclinical atherosclerosis; Risk factors; Women ID CORONARY-ARTERY CALCIUM; INTIMA-MEDIA THICKNESS; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME; SERUM RETINOL-BINDING-PROTEIN-4; GLUCOSE-TOLERANCE; NONOBESE SUBJECTS; OBESITY; OVERWEIGHT AB Background: The published literature regarding the relationships between retinol-binding protein 4 (RBP4) and cardiometabolic risk factors and subclinical atherosclerosis is conflicting, likely due, in part, to limitations of frequently used RBP4 assays. Prior large studies have not utilized the gold-standard western blot analysis of RBP4 levels. Methods: Full-length serum RBP4 levels were measured by western blot in 709 postmenopausal women screened for the Kronos Early Estrogen Prevention Study. Cross-sectional analyses related RBP4 levels to cardiometabolic risk factors, carotid artery intima-media thickness (CIMT), and coronary artery calcification (CAC). Results: The mean age of women was 52.9 (+/- 2.6) years, and the median RBP4 level was 49.0 (interquartile range 36.9-61.5) mu g/mL. Higher RBP4 levels were weakly associated with higher triglycerides (age, race, and smoking-adjusted partial Spearman correlation coefficient = 0.10; P = 0.01), but were unrelated to blood pressure, cholesterol, C-reactive protein, glucose, insulin, and CIMT levels (all partial Spearman correlation coefficients <= 0.06, P > 0.05). Results suggested a curvilinear association between RBP4 levels and CAC, with women in the bottom and upper quartiles of RBP4 having higher odds of CAC (odds ratio [95% confidence interval] 2.10 [1.07-4.09], 2.00 [1.02-3.92], 1.64 [0.82-3.27] for the 1st, 3rd, and 4th RBP4 quartiles vs. the 2nd quartile). However, a squared RBP4 term in regression modeling was non-significant (P = 0.10). Conclusions: In these healthy, recently postmenopausal women, higher RBP4 levels were weakly associated with elevations in triglycerides and with CAC, but not with other risk factors or CIMT. These data using the gold standard of RBP4 methodology only weakly support the possibility that perturbations in RBP4 homeostasis may be an additional risk factor for subclinical coronary atherosclerosis. C1 [Huang, Gary; Wang, Dan; Wildman, Rachel P.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Wildman, Rachel P.] Albert Einstein Coll Med, Bronx, NY 10461 USA. [Khan, Unab I.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. [Zeb, Irfan; Budoff, Matthew J.] Harbor UCLA, Los Angeles Biomed Res Inst, Div Cardiol, Torrance, CA USA. [Manson, Joann E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Miller, Virginia] Mayo Clin, Dept Surg, Rochester, MN USA. [Miller, Virginia] Mayo Clin, Dept Physiol & Biomed Engn, Rochester, MN USA. [Hodis, Howard N.] Univ So Calif, Keck Sch Med, Atherosclerosis Res Unit, Los Angeles, CA 90033 USA. [Merriam, George R.] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Merriam, George R.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Harman, Mitchell S.] Kronos Longev Res Inst, Phoenix, AZ USA. [Brinton, Eliot A.] Univ Utah, Sch Med, Dept Cardiovasc Genet, Salt Lake City, UT USA. [Cedars, Marcelle I.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA. [Su, Yali] SliverCreek Technol, Gilbert, AZ USA. [Lobo, Rogerio A.] Columbia Univ, Coll Med, Dept Obstet & Gynecol, New York, NY USA. [Naftolin, Frederick] NYU, Dept Obstet & Gynecol, Sch Med, New York, NY 10016 USA. [Santoro, Nanette] Univ Colorado Denver, Sch Med, Dept Obstet & Gynecol & Womens Hlth, Aurora, CO USA. [Taylor, Hugh S.] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, New Haven, CT USA. RP Wildman, RP (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. EM Rachel.wildman@einstein.yu.edu FU Aurora Foundation; National Institutes of Health (NIH) [HL90639, 1 UL1 RR024150, Mayo CTSA 1 UL1 RR024150]; Mayo Foundation [CTSA UL1 RR024139]; National Center for Research Resources (NCRR) [UL1 RR024131]; NIH [HL094581] FX KEEPS is funded by grants from the Aurora Foundation to the Kronos Longevity Research Institute, National Institutes of Health (NIH) HL90639 to VMM, 1 UL1 RR024150, Mayo CTSA 1 UL1 RR024150, the Mayo Foundation, CTSA UL1 RR024139 and UL1 RR024131 from the National Center for Research Resources (NCRR), a component of at NIH and NIH Roadmap for Medical Research. The manuscript's contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Information on NCRR is available at http://www.ncrr.nih.gov. Study medications were supplied in part by Bayer Health Care and by Abbott Pharmaceuticals. RBP4, insulin, and CRP assays were funded by NIH grant HL094581 to Dr. Wildman. NR 40 TC 10 Z9 11 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2840 J9 CARDIOVASC DIABETOL JI Cardiovasc. Diabetol. PD MAY 15 PY 2012 VL 11 AR 52 DI 10.1186/1475-2840-11-52 PG 8 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism SC Cardiovascular System & Cardiology; Endocrinology & Metabolism GA 973MA UT WOS:000306363000001 PM 22587616 ER PT J AU Alef, MJ Tzeng, E Zuckerbraun, BS AF Alef, Matthew J. Tzeng, Edith Zuckerbraun, Brian S. TI Nitric oxide and nitrite-based therapeutic opportunities in intimal hyperplasia SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Review DE Xanthine oxidoreductase; Nitric oxide; Arginase; Nitrate; Vascular injury ID SMOOTH-MUSCLE-CELLS; MEDIATED GENE-TRANSFER; PERIPHERAL ARTERIAL-DISEASE; CYCLIC GUANOSINE-MONOPHOSPHATE; INHIBITS NEOINTIMAL FORMATION; L-ARGININE SUPPLEMENTATION; VIVO ISCHEMIA-REPERFUSION; REVERSED VEIN GRAFTS; RAT CAROTID ARTERIES; IN-STENT RESTENOSIS AB Vascular intimal hyperplasia (IH) limits the long term efficacy of current surgical and percutaneous therapies for atherosclerotic disease. There are extensive changes in gene expression and cell signaling in response to vascular therapies, including changes in nitric oxide (NO) signaling. NO is well recognized for its vasoregulatory properties and has been investigated as a therapeutic treatment for its vasoprotective abilities. The circulating molecules nitrite (NO2-) and nitrate (NO3-), once thought to be stable products of NO metabolism, are now recognized as important circulating reservoirs of NO and represent a complementary source of NO in contrast to the classic L-arginine-NO-synthase pathway. Here we review the background of IH, its relationship with the NO and nitrite/nitrate pathways, and current and future therapeutic opportunities for these molecules. Published by Elsevier Inc. C1 [Alef, Matthew J.; Tzeng, Edith; Zuckerbraun, Brian S.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Tzeng, Edith; Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Zuckerbraun, BS (reprint author), F1200 PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM zuckerbraunbs@upmc.edu FU BLRD VA [I01 BX000635] NR 163 TC 9 Z9 9 U1 1 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 EI 1089-8611 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD MAY 15 PY 2012 VL 26 IS 4 SI SI BP 285 EP 294 DI 10.1016/j.niox.2012.03.014 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 958UJ UT WOS:000305265900013 PM 22504069 ER PT J AU Banks, WA AF Banks, William A. TI Drug delivery to the brain in Alzheimer's disease: Consideration of the blood-brain barrier SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE Blood-brain barrier; Alzheimer's disease; Drug delivery; Cerebrospinal fluid; Biologicals; Peptides; Regulatory proteins; Transport; Transmembrane diffusion; P-glycoprotein ID AMYLOID-BETA-PEPTIDE; CENTRAL-NERVOUS-SYSTEM; AGED SAMP8 MICE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MICROVASCULAR ENDOTHELIAL-CELLS; ACTIVATING POLYPEPTIDE PACAP; SENESCENCE-ACCELERATED MICE; P-GLYCOPROTEIN EXPRESSION; GLUCAGON-LIKE PEPTIDES; NECROSIS-FACTOR-ALPHA AB The successful treatment of Alzheimer's disease (AD) will require drugs that can negotiate the blood brain barrier (BBB). However, the BBB is not simply a physical barrier, but a complex interface that is in intimate communication with the rest of the central nervous system (CNS) and influenced by peripheral tissues. This review examines three aspects of the BBB in AD. First, it considers how the BBB may be contributing to the onset and progression of AD. In this regard, the BBB itself is a therapeutic target in the treatment of AD. Second, it examines how the BBB restricts drugs that might otherwise be useful in the treatment of AD and examines strategies being developed to deliver drugs to the CNS for the treatment of AD. Third, it considers how drug penetration across the AD BBB may differ from the BBB of normal aging. In this case, those differences can complicate the treatment of CNS diseases such as depression, delirium, psychoses, and pain control in the AD population. Published by Elsevier B.V. C1 [Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Banks, William A.] Univ Washington, Sch Med, Dept Internal Med, Div Gerontol & Geriatr Med, Seattle, WA USA. RP Banks, WA (reprint author), Bldg 1,Rm 810A,1660 S Columbian Way, Seattle, WA 98108 USA. EM wabanks1@uw.edu FU VA Merit Review; [RO1 AG029839] FX This works was supported by VA Merit Review and RO1 AG029839. NR 195 TC 39 Z9 40 U1 8 U2 69 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD MAY 15 PY 2012 VL 64 IS 7 BP 629 EP 639 DI 10.1016/j.addr.2011.12.005 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 943OA UT WOS:000304132500006 PM 22202501 ER PT J AU Wheeler, C Nabors, LB Barnum, S Yang, XH Hu, XZ Schoeb, TR Chen, DQ Ardelt, AA King, PH AF Wheeler, Crystal Nabors, L. Burt Barnum, Scott Yang, Xiuhua Hu, Xianzhen Schoeb, Trenton R. Chen, Dongquan Ardelt, Agnieszka A. King, Peter H. TI Sex hormone-dependent attenuation of EAE in a transgenic mouse with astrocytic expression of the RNA regulator HuR SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE RNA binding protein; Posttranscriptional gene regulation; RNA stability; AU-rich element; Estrogen ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS; MEDIATED TRANSLATION; STABILITY; PROTEINS; ESTROGEN; REGION; MICE AB In experimental autoimmune encephalomyelitis (EAE) and other neurodegenerative diseases, astrocytes play an important role in promoting or attenuating the inflammatory response through induction of different cytokines and growth factors. HuR plays a major role in regulating many of these factors by modulating RNA stability and translational efficiency. Here, we engineered transgenic mice to express HuR in astrocytes using the human glial fibrillary acidic protein promoter and found that female transgenic mice had significantly less clinical disability and histopathological changes in the spinal cord. Ovariectomy prior to EAE induction abrogated the protective effect. Our findings support a role for the astrocyte and posttranscriptional regulation in hormonally-mediated attenuation of EAE. Published by Elsevier B.V. C1 [Wheeler, Crystal; Nabors, L. Burt] Univ Alabama Birmingham, Dept Neurobiol, Birmingham, AL 35294 USA. [Nabors, L. Burt; Yang, Xiuhua; King, Peter H.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Barnum, Scott; Hu, Xianzhen] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. [Schoeb, Trenton R.; King, Peter H.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA. [Chen, Dongquan] Univ Alabama Birmingham, Dept Prevent Med, Birmingham, AL 35294 USA. [Ardelt, Agnieszka A.] Univ Chicago, Dept Neurol, Med Ctr, Chicago, IL 60637 USA. [King, Peter H.] Univ Alabama Birmingham, Dept Physiol & Biophys, Birmingham, AL 35294 USA. [King, Peter H.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. RP King, PH (reprint author), Sparks Ctr, Suite 260,1720-7th Ave S, Birmingham, AL 35233 USA. EM pking@uab.edu FU VA Merit Review; NIH [R01 NS064133, R01 CA112397, R01 NS46032]; UAB Transgenic and Microarray Facilities [P30 CA013148-39]; UAB Neuroscience Blueprint Core [NS57098] FX This work was supported by a VA Merit Review, and NIH R01 NS064133 (PHK), R01 CA112397 (LBN), R01 NS46032 (SRB), the UAB Transgenic and Microarray Facilities (P30 CA013148-39), and the UAB Neuroscience Blueprint Core (NS57098). Histology services were provided by the UAB Comparative Pathology Laboratory. NR 19 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD MAY 15 PY 2012 VL 246 IS 1-2 BP 34 EP 37 DI 10.1016/j.jneuroim.2012.02.014 PG 4 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 942FA UT WOS:000304026900005 PM 22445740 ER PT J AU Sigel, K Wisnivesky, J Gordon, K Dubrow, R Justice, A Brown, ST Goulet, J Butt, AA Crystal, S Rimland, D Rodriguez-Barradas, M Gibert, C Park, LS Crothers, K AF Sigel, Keith Wisnivesky, Juan Gordon, Kirsha Dubrow, Robert Justice, Amy Brown, Sheldon T. Goulet, Joseph Butt, Adeel A. Crystal, Stephen Rimland, David Rodriguez-Barradas, Maria Gibert, Cynthia Park, Lesley S. Crothers, Kristina TI HIV as an independent risk factor for incident lung cancer SO AIDS LA English DT Article DE HIV; immunosuppression; incidence; lung cancer; non-AIDS-defining malignancy; smoking ID ACTIVE ANTIRETROVIRAL THERAPY; WOMENS INTERAGENCY HIV; INJECTION-DRUG USERS; DEFINING MALIGNANCIES; CIGARETTE-SMOKING; INFECTED PATIENTS; UNITED-STATES; AIDS; IMMUNODEFICIENCY; MORTALITY AB Background: It is unclear whether the elevated rate of lung cancer among HIV-infected persons is due to biological effects of HIV, surveillance bias, or excess smoking. We compared the incidence of lung cancer between HIV-infected and demographically similar HIV-uninfected patients, accounting for smoking and stage of lung cancer at diagnosis. Design: Data from the Veterans Aging Cohort Study Virtual Cohort were linked to data from the Veterans Affairs Central Cancer Registry, resulting in an analytic cohort of 37 294 HIV-infected patients and 75 750 uninfected patients. Methods: We calculated incidence rates of pathologically confirmed lung cancer by dividing numbers of cases by numbers of person-years at risk. We used Poisson regression to determine incidence rate ratios (IRRs), adjusting for age, sex, race/ethnicity, smoking prevalence, previous bacterial pneumonia, and chronic obstructive pulmonary disease. Results: The incidence rate of lung cancer in HIV-infected patients was 204 cases per 100 000 person-years [95% confidence interval (CI) 167-249] and among uninfected patients was 119 cases per 100 000 person-years (95% CI 110-129). The IRR of lung cancer associated with HIV infection remained significant after multivariable adjustment (IRR 1.7; 95% CI 1.5-1.9). Lung cancer stage at presentation did not differ between HIV-infected and uninfected patients. Conclusion: In our cohort of demographically similar HIV-infected and uninfected patients, HIV infection was an independent risk factor for lung cancer after controlling for potential confounders including smoking. The similar stage distribution between the two groups indicated that surveillance bias was an unlikely explanation for this finding. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Sigel, Keith; Wisnivesky, Juan; Brown, Sheldon T.] Mt Sinai Sch Med, New York, NY USA. [Gordon, Kirsha; Dubrow, Robert; Justice, Amy; Goulet, Joseph] Yale Univ, Sch Med, Vet Affairs VA Connecticut Healthcare Syst, New Haven, CT USA. [Gordon, Kirsha; Dubrow, Robert; Justice, Amy; Goulet, Joseph] Yale Univ, Sch Publ Hlth, Vet Affairs VA Connecticut Healthcare Syst, New Haven, CT USA. [Brown, Sheldon T.] James J Peters Vet Affairs VA Med Ctr, Bronx, NY USA. [Butt, Adeel A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Butt, Adeel A.] Sheikh Khalifa Med City, Abu Dhabi, U Arab Emirates. [Crystal, Stephen] Rutgers State Univ, New Brunswick, NJ 08903 USA. [Rimland, David] Emory Univ, Sch Med, Atlanta Vet Affairs VA Med Ctr, Decatur, GA 30033 USA. [Rodriguez-Barradas, Maria] Michael E DeBakey Vet Affairs VA Med Ctr, Houston, TX USA. [Rodriguez-Barradas, Maria] Baylor Coll Med, Houston, TX 77030 USA. [Gibert, Cynthia] George Washington Univ, Sch Med, Washington DC Vet Affairs Med Ctr, Washington, DC USA. [Crothers, Kristina] Univ Washington, Dept Internal Med, Div Pulm & Crit Care Med, Sch Med, Seattle, WA USA. RP Sigel, K (reprint author), 17 E 102nd St,6th Floor, New York, NY 10029 USA. EM keith.sigel@mssm.edu OI Goulet, Joseph/0000-0002-0842-804X; Sigel, Keith/0000-0002-4051-4861; Crothers, Kristina/0000-0001-9702-0371 FU National Center for Research Resources [KL2RR029885]; National Institute on Alcohol and Alcohol Abuse [3U01 AA 13566]; National Institute of Aging [K23 AG00826]; Robert Wood Johnson Generalist Faculty Scholar Award; National Institute on Aging, National Institute of Mental Health; Veterans Health Administration; Veterans Health Administration Office of Research and Development and Public Health Strategic Healthcare Group; National Heart, Lung, and Blood Institute [NIH/NHLBI R01 HL090342]; Novartis Pharmaceuticals; GlaxoSmithKline FX This study was supported by the National Center for Research Resources (KL2RR029885 to K. S.), National Institute on Alcohol and Alcohol Abuse (3U01 AA 13566), National Institute of Aging (K23 AG00826), Robert Wood Johnson Generalist Faculty Scholar Award, an interagency agreement between National Institute on Aging, National Institute of Mental Health and the Veterans Health Administration, and the Veterans Health Administration Office of Research and Development and Public Health Strategic Healthcare Group (to A.C.J.), and National Heart, Lung, and Blood Institute (NIH/NHLBI R01 HL090342 to K. C.).; J.P.W. reports receiving lecture honorarium from Novartis Pharmaceuticals, and a research grant from GlaxoSmithKline. NR 34 TC 77 Z9 77 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 15 PY 2012 VL 26 IS 8 BP 1017 EP 1025 DI 10.1097/QAD.0b013e328352d1ad PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 937JY UT WOS:000303656000013 PM 22382152 ER PT J AU Fan, VS Gaziano, JM Lew, R Bourbeau, J Adams, SG Leatherman, S Thwin, SS Huang, GD Robbins, R Sriram, PS Sharafkhaneh, A Mador, MJ Sarosi, G Panos, RJ Rastogi, P Wagner, TH Mazzuca, SA Shannon, C Colling, C Liang, MH Stoller, JK Fiore, L Niewoehner, DE AF Fan, Vincent S. Gaziano, J. Michael Lew, Robert Bourbeau, Jean Adams, Sandra G. Leatherman, Sarah Thwin, Soe Soe Huang, Grant D. Robbins, Richard Sriram, Peruvemba S. Sharafkhaneh, Amir Mador, M. Jeffery Sarosi, George Panos, Ralph J. Rastogi, Padmashri Wagner, Todd H. Mazzuca, Steven A. Shannon, Colleen Colling, Cindy Liang, Matthew H. Stoller, James K. Fiore, Louis Niewoehner, Dennis E. TI A Comprehensive Care Management Program to Prevent Chronic Obstructive Pulmonary Disease Hospitalizations A Randomized, Controlled Trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID SELF-MANAGEMENT; ACUTE EXACERBATIONS; ACTION PLAN; COPD; HEALTH; METAANALYSIS; MORTALITY; DIAGNOSIS; EDUCATION; RECOVERY AB Background: Improving a patient's ability to self-monitor and manage changes in chronic obstructive pulmonary disease (COPD) symptoms may improve outcomes. Objective: To determine the efficacy of a comprehensive care management program (CCMP) in reducing the risk for COPD hospitalization. Design: A randomized, controlled trial comparing CCMP with guideline-based usual care. (ClinicalTrials.gov registration number: NCT00395083) Setting: 20 Veterans Affairs hospital-based outpatient clinics. Participants: Patients hospitalized for COPD in the past year. Intervention: The CCMP included COPD education during 4 individual sessions and 1 group session, an action plan for identification and treatment of exacerbations, and scheduled proactive telephone calls for case management. Patients in both the intervention and usual care groups received a COPD informational booklet; their primary care providers received a copy of COPD guidelines and were advised to manage their patients according to these guidelines. Patients were randomly assigned, stratifying by site based on random, permuted blocks of variable size. Measurements: The primary outcome was time to first COPD hospitalization. Staff blinded to study group performed telephone-based assessment of COPD exacerbations and hospitalizations, and all hospitalizations were blindly adjudicated. Secondary outcomes included non-COPD health care use, all-cause mortality, health-related quality of life, patient satisfaction, disease knowledge, and self-efficacy. Results: Of the eligible patients, 209 were randomly assigned to the intervention group and 217 to the usual care group. Citing serious safety concerns, the data monitoring committee terminated the intervention before the trial's planned completion after 426 (44%) of the planned total of 960 patients were enrolled. Mean follow-up was 250 days. When the study was stopped, the 1-year cumulative incidence of COPD-related hospitalization was 27% in the intervention group and 24% in the usual care group (hazard ratio, 1.13 [95% CI, 0.70 to 1.80]; P = 0.62). There were 28 deaths from all causes in the intervention group versus 10 in the usual care group (hazard ratio, 3.00 [CI, 1.46 to 6.17]; P = 0.003). Cause could be assigned in 27 (71%) deaths. Deaths due to COPD accounted for the largest difference: 10 in the intervention group versus 3 in the usual care group (hazard ratio, 3.60 [CI, 0.99 to 13.08]; P = 0.053). Limitations: Available data could not fully explain the excess mortality in the intervention group. Ability to assess the quality of the educational sessions provided by the case managers was limited. Conclusion: A CCMP in patients with severe COPD had not decreased COPD-related hospitalizations when the trial was stopped prematurely. The CCMP was associated with unanticipated excess mortality, results that differ markedly from similar previous trials. A data monitoring committee should be considered in the design of clinical trials involving behavioral interventions. C1 [Fan, Vincent S.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98108 USA. Vet Affairs Boston Healthcare Syst, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Montreal Chest Inst, Montreal, PQ, Canada. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Dept Vet Affairs Cooperat Studies Program, Washington, DC USA. Phoenix Vet Affairs Med Ctr, Phoenix, AZ USA. N Florida S Georgia Vet Hlth Syst, Gainesville, FL USA. Michael E DeBakey VA Med Ctr, Houston, TX USA. Vet Affairs Western New York Healthcare Syst, Buffalo, NY USA. Cincinnati Vet Affairs Med Ctr, Cincinnati, OH USA. Dallas Vet Affairs Med Ctr, Dallas, TX USA. Vet Affairs Palo Alto Healthcare Syst, Menlo Pk, CA USA. Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA. Indiana Univ Sch Med, Indianapolis, IN USA. Vet Affairs Cooperat Studies Program Clin Res Pha, Albuquerque, NM USA. Minneapolis Vet Affairs Healthcare Syst, Minneapolis, MN USA. Cleveland Clin, Cleveland, OH 44106 USA. RP Fan, VS (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, 1600 S Columbian Way, Seattle, WA 98108 USA. EM vincent.fan@va.gov OI Sriram, P.S/0000-0002-6103-3573 FU Veterans Affairs Cooperative Study Program; Veterans Affairs Office of Research and Development [560] FX Veterans Affairs Cooperative Study Program.; By the Cooperative Studies Program (CSP #560), Veterans Affairs Office of Research and Development. NR 43 TC 133 Z9 133 U1 4 U2 24 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 15 PY 2012 VL 156 IS 10 BP 673 EP U46 DI 10.7326/0003-4819-156-10-201205150-00003 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA 944IQ UT WOS:000304193400013 PM 22586006 ER PT J AU Hayden, SJ Albert, TJ Watkins, TR Swenson, ER AF Hayden, Shailaja J. Albert, Tyler J. Watkins, Timothy R. Swenson, Erik R. TI Anemia in Critical Illness Insights into Etiology, Consequences, and Management SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE anemia; red blood cell; transfusion; erythropoietin; critical illness ID BLOOD-CELL TRANSFUSION; RANDOMIZED CONTROLLED-TRIAL; ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; RECOMBINANT-HUMAN-ERYTHROPOIETIN; ACUTE MYOCARDIAL-INFARCTION; SEVERE ISOVOLEMIC ANEMIA; PLACEBO-CONTROLLED TRIAL; CHRONIC KIDNEY-DISEASE; INTENSIVE-CARE UNITS AB Anemia is common in the intensive care unit, and may be associated with adverse consequences. However, current options for correcting anemia are not without problems and presently lack convincing efficacy for improving survival in critically ill patients. In this article we review normal red blood cell physiology; etiologies of anemia in the intensive care unit; its association with adverse outcomes; and the risks, benefits, and efficacy of various management strategies, including blood transfusion, erythropoietin, blood substitutes, iron therapy, and minimization of diagnostic phlebotomy. C1 [Hayden, Shailaja J.; Albert, Tyler J.; Watkins, Timothy R.; Swenson, Erik R.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Watkins, Timothy R.] Puget Sound Blood Ctr, Res Inst, Seattle, WA 98104 USA. [Albert, Tyler J.; Swenson, Erik R.] Vet Affairs Puget Sound Hlth Care Syst, Med Serv, Seattle, WA USA. RP Swenson, ER (reprint author), VA Puget Sound Hlth Care Syst, Box S-111-PULM,1660 S Columbian Way, Seattle, WA 98108 USA. EM eswenson@u.washington.edu FU National Institutes of Health, National Institute of General Medical Sciences [K23GM086729]; Department of Veterans Affairs FX Supported by a grant from the National Institutes of Health, National Institute of General Medical Sciences (K23GM086729; T.R.W.); supported by a Merit Review grant from the Department of Veterans Affairs (E.R.S.). No source of support was used in the creation of this manuscript. None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript. NR 117 TC 33 Z9 34 U1 0 U2 7 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAY 15 PY 2012 VL 185 IS 10 BP 1049 EP 1057 DI 10.1164/rccm.201110-1915CI PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 936WJ UT WOS:000303620400008 PM 22281832 ER PT J AU Sandoval, KE Farr, SA Banks, WA Crider, AM Morley, JE Witt, KA AF Sandoval, Karin E. Farr, Susan A. Banks, William A. Crider, Albert M. Morley, John E. Witt, Ken A. TI Somatostatin receptor subtype-4 agonist NNC 26-9100 decreases extracellular and intracellular A beta(1-42) trimers SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE NNC 26-9100; Somatostatin receptor subtype-4; Neprilysin; Amyloid-beta oligomers ID AMYLOID PRECURSOR PROTEIN; A-BETA LEVELS; ALZHEIMERS-DISEASE; SAMP8 MICE; SYNAPTIC PLASTICITY; OBJECT RECOGNITION; COGNITIVE DEFICITS; PLAQUE-FORMATION; TRANSGENIC MICE; MEMORY AB Soluble amyloid beta-protein (A beta) oligomers are primary mediators of synaptic dysfunction associated with the progression of Alzheimer's disease. Such A beta oligomers exist dependent on their rates of aggregation and metabolism. Use of selective somatostatin receptor-subtype agonists have been identified as a potential means to mitigate A beta accumulation in the brain, via regulation of the enzyme neprilysin. Herein, we first evaluated the impact of the somatostatin receptor subtype-4 agonist 1-[3-[N-(5-Bromopyridin-2-yl)-N-(3,4-dichlorobenzyl)amino]propyl]-3-[3-(1H-imidazol-4-yl)propyl]thiourea (NNC 26-9100) on learning and memory in 12-month SAMP8 mice (i.c.v. injection). NNC 26-9100 (0.2 mu g-dose) was shown to enhance both learning (T-maze) and memory (object recognition) compared to vehicle controls. Cortical and hippocampal tissues were evaluated subsequent to NNC 26-9100 (0.2 mu g) or vehicle administration for changes in neprilysin activity, along with protein expression of amyloid-precursor protein (APP), neprilysin, and A beta(1-42) oligomers within respective cellular fractions (extracellular, intracellular and membrane). NNC 26-9100 increased neprilysin activity in cortical tissue, with an associated protein expression increase in the extracellular fraction and decreased in the intracellular fraction. A decrease in intracellular APP expression was found with treatment in both cortical and hippocampal tissues. NNC 26-9100 also significantly decreased expression of A beta(1-42) trimers within both the extracellular and intracellular cortical fractions. No expression changes were found in membrane fractions for any protein. These finding suggest the potential use of selective SSTR4 agonists to mitigate toxic oligomeric forms of A beta(1-42) in critical regions of the brain identified with learning and memory decline. (C) 2012 Elsevier B.V. All rights reserved. C1 [Sandoval, Karin E.; Crider, Albert M.; Witt, Ken A.] So Illinois Univ, Sch Pharm, Dept Pharmaceut Sci, Edwardsville, IL 62026 USA. [Farr, Susan A.; Morley, John E.] Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, St Louis, MO USA. [Farr, Susan A.; Morley, John E.] St Louis Univ, Sch Med, Div Geriatr, Dept Internal Med, St Louis, MO 63103 USA. [Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. [Banks, William A.] Univ Washington, Sch Med, Dept Internal Med, Div Gerontol & Geriatr Med, Seattle, WA USA. RP Witt, KA (reprint author), So Illinois Univ, Sch Pharm, Dept Pharmaceut Sci, Campus Box 2000, Edwardsville, IL 62026 USA. EM kwitt@siue.edu FU Alzheimer's Drug Discovery Foundation [261105.01]; VA Merit Review; National Institutes of Health National Institute on Aging [R21AG029318] FX This work was supported by the Alzheimer's Drug Discovery Foundation (Grant: 261105.01), VA Merit Review, and the National Institutes of Health National Institute on Aging (Grant: R21AG029318). NR 42 TC 6 Z9 8 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD MAY 15 PY 2012 VL 683 IS 1-3 BP 116 EP 124 DI 10.1016/j.ejphar.2012.03.020 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 934HY UT WOS:000303436200015 PM 22449380 ER PT J AU Xu, GG McMahan, CA Hildreth, K Garcia, RA Herbert, DC Walter, CA AF Xu, Guogang McMahan, C. Alex Hildreth, Kim Garcia, Rebecca A. Herbert, Damon C. Walter, Christi A. TI Ionizing radiation-induced mutant frequencies increase transiently in male germ cells of older mice SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Ionizing radiation; Age; Mutagenesis; Spermatogenic cells; lacI mouse ID MOUSE MUTATION ASSAY; PARENTAL AGE; PATERNAL-AGE; SPERMATOGENIC CELLS; HETEROZYGOUS MICE; TRANSGENIC MICE; EXCISION-REPAIR; APERT-SYNDROME; TIME COURSES; RISK AB Spontaneous mutant frequency in the male germline increases with age, thereby increasing the risk of siring offspring with genetic disorders. In the present study we investigated the effect of age on ionizing radiation-induced male germline mutagenesis. lad transgenic mice were treated with ionizing radiation at 4-, 15- and 26-month-old, and mutant frequencies were determined for pachytene spermatocytes and round spermatids at 15 days or 49 days after ionizing radiation treatment. Cells collected 15 days after treatment were derivatives of irradiated differentiating spermatogenic cells while cells collected 49 days later were derivatives of spermatogonial stem cells. The results showed that (1) spontaneous mutant frequency increased in spermatogenic cells recovered from nonirradiated old mice (26-months-old), particularly in the round spermatids; (2) mutant frequencies were significantly increased in round spermatids obtained from middle-aged mice (15-months-old) and old age mice (26-months-old) at 15 and 49 days after irradiation compared to the sham-treated old mice; and (3) pachytene spermatocytes obtained from 15- or 26-month-old mice displayed a significantly increased mutant frequency at 15 days post irradiation. This study indicates that age modulates the mutagenic response to ionizing radiation in the male germline. Published by Elsevier B.V. C1 [Xu, Guogang; Hildreth, Kim; Garcia, Rebecca A.; Herbert, Damon C.; Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 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, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Walter, Christi A.] Audie Murphy Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Walter, CA (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. EM walter@uthscsa.edu FU NIH [AG24364, AG21163] FX This work was supported by NIH grants AG24364 and AG21163 to Dr. C.A. Walter. The contents are solely the responsibility of the authors, and do not necessarily represent the official views of the NIH or VHCS. NR 41 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD MAY 15 PY 2012 VL 744 IS 2 BP 135 EP 139 DI 10.1016/j.mrgentox.2012.01.003 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 932NO UT WOS:000303298000003 PM 22314132 ER PT J AU Khanna, A Bush, AL Swint, JM Peskin, MF Street, RL Naik, AD AF Khanna, Abhinav Bush, Amber L. Swint, J. Michael Peskin, Melissa Fleschler Street, Richard L., Jr. Naik, Aanand D. TI Hemoglobin A(1c) improvements and better diabetes-specific quality of life among participants completing diabetes self-management programs: A nested cohort study SO HEALTH AND QUALITY OF LIFE OUTCOMES LA English DT Article DE Diabetes-specific quality of life; Diabetes; Quality of life; Diabetes-39; Self-management; Hemoglobin A(1c) ID REPORTED HEALTH; CANCER-PATIENTS; OUTCOMES; SURVIVAL; PEOPLE; SCALE; CARE; CHEMOTHERAPY; COMORBIDITY; VALIDATION AB Background: Numerous primary care innovations emphasize patient-centered processes of care. Within the context of these innovations, greater understanding is needed of the relationship between improvements in clinical endpoints and patient-centered outcomes. To address this gap, we evaluated the association between glycosylated hemoglobin (HbA(1c)) and diabetes-specific quality of life among patients completing diabetes self-management programs. Methods: We conducted a retrospective cohort study nested within a randomized comparative effectiveness trial of diabetes self-management interventions in 75 diabetic patients. Multiple linear regression models were developed to examine the relationship between change in HbA(1c) from baseline to one-year follow-up and Diabetes-39 (a diabetes-specific quality of life measure) at one year. Results: HbA(1c) levels improved for the overall cohort from baseline to one-year follow-up (t (74) = 3.09, p =.0029). One-year follow up HbA(1c) was correlated with worse overall quality of life (r = 0.33, p = 0.004). Improvements in HbA(1c) from baseline to one-year follow-up were associated with greater D-39 diabetes control (beta = 0.23, p = .04) and D-39 sexual functioning (beta = 0.25, p = .03) quality of life subscales. Conclusions: Improvements in HbA(1c) among participants completing a diabetes self-management program were associated with better diabetes-specific quality of life. Innovations in primary care that engage patients in self-management and improve clinical biomarkers, such as HbA(1c), may also be associated with better quality of life, a key outcome from the patient perspective. C1 [Khanna, Abhinav; Bush, Amber L.; Street, Richard L., Jr.; Naik, Aanand D.] Baylor Coll Med, Houston, TX 77030 USA. [Bush, Amber L.; Street, Richard L., Jr.; Naik, Aanand D.] Michael E DeBakey VA Med Ctr 152, Houston Hlth Serv Res & Dev, Ctr Excellence, Houston, TX 77030 USA. [Swint, J. Michael; Peskin, Melissa Fleschler] Univ Texas Houston, Sch Publ Hlth, Houston, TX 77030 USA. [Street, Richard L., Jr.] Texas A&M Univ, Dept Commun, College Stn, TX 77843 USA. RP Naik, AD (reprint author), Baylor Coll Med, 1 Baylor Plaza, Houston, TX 77030 USA. EM anaik@bcm.edu FU Agency for Healthcare Research and Quality, Centers for Research and Education on Therapeutics [U18HS016093]; Clinical Scientist Development Award from the Doris Duke Charitable Foundation; National Institute of Aging [K23AG027144]; Houston Health Services Research and Development Center of Excellence at the Michael E. DeBakey Veterans Affairs Medical Center [HFP90-020] FX The EPIC study was supported by a grant from the Agency for Healthcare Research and Quality, Centers for Research and Education on Therapeutics (U18HS016093; principalinvestigator, Dr Suarez-Almazor). Additional support for the EPIC Study was provided by a Clinical Scientist Development Award from the Doris Duke Charitable Foundation (principal investigator, Dr Naik). Dr Naik received additional support from the National Institute of Aging (K23AG027144) and the Houston Health Services Research and Development Center of Excellence (HFP90-020) at the Michael E. DeBakey Veterans Affairs Medical Center. NR 44 TC 12 Z9 13 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1477-7525 J9 HEALTH QUAL LIFE OUT JI Health Qual. Life Outcomes PD MAY 14 PY 2012 VL 10 AR 48 DI 10.1186/1477-7525-10-48 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 986YZ UT WOS:000307384900001 PM 22583609 ER PT J AU Slatore, CG Cecere, LM LeTourneau, JL O'Neil, ME Duckart, JP Wiener, RS Farjah, F Cooke, CR AF Slatore, Christopher G. Cecere, Laura M. LeTourneau, Jennifer L. O'Neil, Maya E. Duckart, Jonathan P. Wiener, Renda Soylemez Farjah, Farhood Cooke, Colin R. TI Intensive Care Unit Outcomes Among Patients With Lung Cancer in the Surveillance, Epidemiology, and End Results-Medicare Registry SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CODE STATUS; LIFE; TRENDS; STATES; AGGRESSIVENESS; ADMISSION; MULTICENTER; POPULATION; MORTALITY; CARCINOMA AB Purpose Lung cancer is the leading cause of cancer-related mortality. Intensive care unit (ICU) use among patients with cancer is increasing, but data regarding ICU outcomes for patients with lung cancer are limited. Patients and Methods We used the Surveillance, Epidemiology, and End Results (SEER) -Medicare registry (1992 to 2007) to conduct a retrospective cohort study of patients with lung cancer who were admitted to an ICU for reasons other than surgical resection of their tumor. We used logistic and Cox regression to evaluate associations of patient characteristics and hospital mortality and 6-month mortality, respectively. We calculated adjusted associations for mechanical ventilation receipt with hospital and 6-month mortality. Results Of the 49,373 patients with lung cancer admitted to an ICU for reasons other than surgical resection, 76% of patients survived the hospitalization, and 35% of patients were alive 6 months after discharge. Receipt of mechanical ventilation was associated with increased hospital mortality (adjusted odds ratio, 6.95; 95% CI, 6.89 to 7.01; P < .001), and only 15% of these patients were alive 6 months after discharge. Of all ICU patients with lung cancer, the percentage of patients who survived 6 months from discharge was 36% for patients diagnosed in 1992 and 32% for patients diagnosed in 2005, whereas it was 16% and 11% for patients who received mechanical ventilation, respectively. Conclusion Most patients with lung cancer enrolled in Medicare who are admitted to an ICU die within 6 months of admission. To improve patient-centered care, these results should guide shared decision making between patients with lung cancer and their clinicians before an ICU admission. C1 [Slatore, Christopher G.; LeTourneau, Jennifer L.; O'Neil, Maya E.; Duckart, Jonathan P.] Portland Vet Affairs VA Med Ctr, Portland, Dorset, England. [Slatore, Christopher G.; LeTourneau, Jennifer L.; O'Neil, Maya E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Cecere, Laura M.] Univ Washington, Sch Med, Seattle, WA USA. [Cecere, Laura M.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Wiener, Renda Soylemez] Edith Nourse Rogers Mem VA Hosp, Bedford, England. [Wiener, Renda Soylemez] Boston Univ, Sch Med, Boston, MA 02118 USA. [Farjah, Farhood] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Cooke, Colin R.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Slatore, CG (reprint author), 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM christopher.slatore@va.gov OI Wiener, Renda/0000-0001-7712-2135; Slatore, Christopher/0000-0003-0958-8122; Cooke, Colin/0000-0001-9713-5371 FU University of Washington Division of Pulmonary and Critical Care Medicine; Veterans Affairs (VA) Health Services [10-025, TPM 61-037]; National Cancer Institute [K07 CA 138772]; Robert Wood Johnson Foundation FX Supported by a University of Washington Division of Pulmonary and Critical Care Medicine Endowment Grant (C. G. S), a Veterans Affairs (VA) Health Services Research and Development Career Development Award (Grant No. 10-025, C. G. S.), a VA Health Services Research and Development Fellowship (Grant. No. TPM 61-037; L. M. C.), a career development award from the National Cancer Institute (K07 CA 138772; R. S. W.), and the Robert Wood Johnson Foundation Clinical Scholars Program (C.R.C). NR 39 TC 28 Z9 29 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 10 PY 2012 VL 30 IS 14 BP 1686 EP 1691 DI 10.1200/JCO.2011.40.0846 PG 6 WC Oncology SC Oncology GA 940TA UT WOS:000303914800022 PM 22473159 ER PT J AU Hempel, S Newberry, SJ Maher, AR Wang, Z Miles, JNV Shanman, R Johnsen, B Shekelle, PG AF Hempel, Susanne Newberry, Sydne J. Maher, Alicia R. Wang, Zhen Miles, Jeremy N. V. Shanman, Roberta Johnsen, Breanne Shekelle, Paul G. TI Probiotics for the Prevention and Treatment of Antibiotic-Associated Diarrhea A Systematic Review and Meta-analysis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID HELICOBACTER-PYLORI ERADICATION; PLACEBO-CONTROLLED TRIAL; LACTOBACILLUS-ACIDOPHILUS CL1285; CLOSTRIDIUM-DIFFICILE DIARRHEA; SACCHAROMYCES-BOULARDII; DOUBLE-BLIND; TRIPLE THERAPY; CLINICAL-TRIAL; BIFIDOBACTERIUM-LACTIS; CONTAINING YOGURT AB Context Probiotics are live microorganisms intended to confer a health benefit when consumed. One condition for which probiotics have been advocated is the diarrhea that is a common adverse effect of antibiotic use. Objective To evaluate the evidence for probiotic use in the prevention and treatment of antibiotic-associated diarrhea (AAD). Data Sources Twelve electronic databases were searched (DARE, Cochrane Library of Systematic Reviews, CENTRAL, PubMed, EMBASE, CINAHL, AMED, MANTIS, TOXLINE, ToxFILE, NTIS, and AGRICOLA) and references of included studies and reviews were screened from database inception to February 2012, without language restriction. Study Selection Two independent reviewers identified parallel randomized controlled trials (RCTs) of probiotics (Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and/or Bacillus) for the prevention or treatment of AAD. Data Extraction Two independent reviewers extracted the data and assessed trial quality. Results A total of 82 RCTs met inclusion criteria. The majority used Lactobacillus-based interventions alone or in combination with other genera; strains were poorly documented. The pooled relative risk in a DerSimonian-Laird random-effects meta-analysis of 63 RCTs, which included 11 811 participants, indicated a statistically significant association of probiotic administration with reduction in AAD (relative risk, 0.58; 95% CI, 0.50 to 0.68; P<.001; I-2, 54%; [risk difference, -0.07; 95% CI, -0.10 to -0.05], [number needed to treat, 13; 95% CI, 10.3 to 19.1]) in trials reporting on the number of patients with AAD. This result was relatively insensitive to numerous subgroup analyses. However, there exists significant heterogeneity in pooled results and the evidence is insufficient to determine whether this association varies systematically by population, antibiotic characteristic, or probiotic preparation. Conclusions The pooled evidence suggests that probiotics are associated with a reduction in AAD. More research is needed to determine which probiotics are associated with the greatest efficacy and for which patients receiving which specific antibiotics. JAMA. 2012;307(18):1959-1969 www.jama.com C1 [Hempel, Susanne; Newberry, Sydne J.; Shanman, Roberta; Johnsen, Breanne; Shekelle, Paul G.] RAND Hlth, So Calif Evidence Based Practice Ctr, Santa Monica, CA 90401 USA. [Maher, Alicia R.; Wang, Zhen; Miles, Jeremy N. V.] RAND Corp, Santa Monica, CA USA. [Shekelle, Paul G.] W Los Angeles VA Med Ctr, Los Angeles, CA USA. [Maher, Alicia R.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Hempel, S (reprint author), RAND Hlth, So Calif Evidence Based Practice Ctr, 1776 Main St, Santa Monica, CA 90401 USA. EM susanne_hempel@rand.org RI Wang, Zhen/D-5991-2013 OI Wang, Zhen/0000-0002-9368-6149 FU HHSA [290-2007-10062-I]; National Institutes of Health (NIH) Office of Dietary Supplements; NIH National Center for Complementary and Alternative Medicine; US Food and Drug Administration (USFDA) Center for Food Safety and Applied Nutrition; Department of Veterans Affairs; RAND Corporation FX The RAND Corporation internally funded this review, building on the literature database established for contract HHSA 290-2007-10062-I, an evidence report on the safety of probiotics commissioned by the Agency for Healthcare Research and Quality and funded jointly by the National Institutes of Health (NIH) Office of Dietary Supplements, the NIH National Center for Complementary and Alternative Medicine, and the US Food and Drug Administration (USFDA) Center for Food Safety and Applied Nutrition. Dr Shekelle reports support from the Department of Veterans Affairs. NR 96 TC 206 Z9 236 U1 9 U2 104 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 9 PY 2012 VL 307 IS 18 BP 1959 EP 1969 DI 10.1001/jama.2012.3507 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 938OD UT WOS:000303741900030 PM 22570464 ER PT J AU Chao, LL Lenoci, M Neylan, TC AF Chao, Linda L. Lenoci, Maryann Neylan, Thomas C. TI Effects of post-traumatic stress disorder on occipital lobe function and structure SO NEUROREPORT LA English DT Article DE functional magnetic resonance imaging; lateral occipital complex; occipital cortex; post-traumatic stress disorder ID SCRIPT-DRIVEN IMAGERY; POSITRON-EMISSION-TOMOGRAPHY; CHILDHOOD SEXUAL-ABUSE; SYMPTOM PROVOCATION; PTSD; CORTEX; RESPONSES; AMYGDALA AB Although there is evidence for strong connectivity between the amygdala and the visual cortex and some evidence for reduced occipital lobe gray matter volume in patients with post-traumatic stress disorder (PTSD), few studies have directly examined the effects of PTSD on occipital function. The current study used functional and structural MRI to examine occipital cortex function and structure in male combat veterans with and without PTSD. Left occipital gray matter volume was reduced in PTSD patients relative to the controls and correlated negatively with the severity of PTSD symptoms. Functional activity in the lateral occipital complex to aversive and nonaversive pictures presented in novel and repeated presentations was not altered by PTSD. These findings suggest that PTSD adversely affects occipital lobe volume but not the reactivity of the lateral occipital complex to generally aversive, trauma nonspecific stimuli. NeuroReport 23:412-419 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Chao, Linda L.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. [Chao, Linda L.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Chao, Linda L.; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Lenoci, Maryann; Neylan, Thomas C.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA 94121 USA. RP Chao, LL (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, 4150 Clement St,114M, San Francisco, CA 94121 USA. EM linda.chao@ucsf.edu FU Department of Defense [W81XWH-05-2-0094]; Mental Illness Research and Education Clinical Center of the US Veterans Health Administration; Veterans Administration Medical Center, San Francisco, California FX This work was supported by a grant from the Department of Defense (W81XWH-05-2-0094) to Linda L. Chao. The authors thank Dr Charles Marmar for helpful discussions about the study design, Jacqueline Thao Mai for technical assistance, and the research participants. This work was also supported by the Mental Illness Research and Education Clinical Center of the US Veterans Health Administration and the resources and facilities at the Veterans Administration Medical Center, San Francisco, California. NR 25 TC 18 Z9 18 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAY 9 PY 2012 VL 23 IS 7 BP 412 EP 419 DI 10.1097/WNR.0b013e328352025e PG 8 WC Neurosciences SC Neurosciences & Neurology GA 927ZF UT WOS:000302948500002 PM 22453299 ER PT J AU Hegarty, CE Foland-Ross, LC Narr, KL Townsend, JD Bookheimer, SY Thompson, PM Altshuler, LL AF Hegarty, Catherine E. Foland-Ross, Lara C. Narr, Katherine L. Townsend, Jennifer D. Bookheimer, Susan Y. Thompson, Paul M. Altshuler, Lori L. TI Anterior cingulate activation relates to local cortical thickness SO NEUROREPORT LA English DT Article DE anterior cingulate cortex; cortical thickness; functional magnetic resonance imaging; response inhibition ID RESPONSE-INHIBITION; BRAIN; SCHIZOPHRENIA; CHILDREN; CORTEX; ROBUST; MODEL; FMRI AB Few studies have examined the relationship between local anatomic thickness of the cortex and the activation signals arising from it. Using structural and functional MRI, we examined whether a relationship exists between cortical thickness and brain activation. Twenty-eight participants were asked to perform the Go/NoGo response inhibition task known to activate the anterior cingulate and the prefrontal cortex. Structural data of the same regions were simultaneously collected. We hypothesized that cortical thickness in these brain regions would positively correlate with brain activation. Data from the structural MRI were aligned with those of functional MRI activation. There was a positive linear correlation between cortical thickness and activation during response inhibition in the right anterior cingulate cortex (Brodmann's Area 24). No significant thickness-activation correlations were found in the prefrontal cortex. Correlations between cortical thickness and activation may occur only in certain brain regions. NeuroReport 23:420-424 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Foland-Ross, Lara C.] Stanford Univ, Dept Psychol, Mood & Anxiety Disorders Lab, Stanford, CA 94305 USA. [Altshuler, Lori L.] VA Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, Dept Psychiat, Los Angeles, CA USA. RP Altshuler, LL (reprint author), UCLA Neuropsychiat Inst & Hosp, 300 Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu OI Hegarty, Catherine/0000-0003-4976-774X FU National Institute of Mental Health [5R21 MH075944, K24 MH001848, R01 MH084955, 5F31MH078556]; Abbott Laboratories; Forest Laboratories FX For their financial support of this study, the authors gratefully acknowledge the National Institute of Mental Health [5R21 MH075944 (LA), K24 MH001848 (LA), R01 MH084955 (LA), and 5F31MH078556 (LF)].; Dr Altshuler has received past (and potential future) funding from Abbott Laboratories (research support and consulting honoraria); Forest Laboratories (consulting and speakers bureau honoraria); GlaxoSmithKline (speakers bureau honoraria); and no past, but potential future honoraria from Astra-Zeneca (speakers bureau) and Merck and Co. (consulting). Drs Bookheimer, Foland-Ross, Narr and Thompson, Hegarty, and Townsend report no financial relationships with commercial interests. NR 23 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAY 9 PY 2012 VL 23 IS 7 BP 420 EP 424 DI 10.1097/WNR.0b013e3283525a95 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 927ZF UT WOS:000302948500003 PM 22440976 ER PT J AU Stephen, TL Wilson, BS Laufer, TM AF Stephen, Tom Li Wilson, Bridget S. Laufer, Terri M. TI Subcellular distribution of Lck during CD4 T-cell maturation in the thymic medulla regulates the T-cell activation threshold SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autoreactivity; thymic selection; T cell receptor signaling ID PROTEIN-TYROSINE-PHOSPHATASE; SRC-FAMILY KINASES; CLASS-II MHC; ANTIGEN RECEPTOR; POSITIVE SELECTION; THYMOCYTE SENSITIVITY; ELECTRON-MICROSCOPY; CENTRAL TOLERANCE; EXPRESSION; SIGNALS AB Mature peripheral T cells respond to foreign but not to self-antigens. During development in the thymus, deletion of high-affinity self-reactive immature thymocytes contributes to tolerance of mature T cells. However, double-positive thymocytes are positively selected to survive if they respond to self-peptide-MHC complexes; thus, there must be mechanisms to prevent overt reactivity to those same complexes in the periphery. "Developmental tuning" is the active process through which T-cell receptor (TCR)-associated signaling pathways of single-positive (SP) thymocytes are attenuated to respond appropriately to self-peptide-MHC complexes in the periphery. We previously showed that MHC class II expression in the thymic medulla was necessary to tune CD4(+) SP (CD4 SP) thymocytes. CD4 SP thymocytes from mice lacking medullary MHC class II expression had inappropriately enhanced proximal TCR signaling to low-affinity self-ligands that was associated with altered cellular distribution of the tyrosine kinase Lck. Now, we report that activation of both tuned and untuned CD4 SP thymocytes is Lck-dependent. Untuned CD4 SP cells contain a pool of Lck with increased basal phosphorylation that is not associated with the CD4 coreceptor. Phosphorylation of this pool of Lck decreases with tuning. Immunogold transmission electron microscopy of membrane sheets permitted direct visualization of Lck. In the absence of tuning, a significant proportion of Lck and the TCR subunit CD3 zeta are expressed on the same protein island; this close association of Lck and the TCR probably explains the enhanced activation of untuned CD4 SP cells. Thus, changes in membrane topography during thymic maturation determine the set point for TCR responsiveness. C1 [Stephen, Tom Li; Laufer, Terri M.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Wilson, Bridget S.] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. [Wilson, Bridget S.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. [Laufer, Terri M.] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA 19104 USA. RP Laufer, TM (reprint author), Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. EM tlaufer@mail.med.upenn.edu FU National Institutes of Health [R01 AI068819]; Arthritis Foundation FX We thank Mary Ann Raymond-Stintz at the University of New Mexico for assistance with plasma membrane sheet preparations and TEM analysis. This work was supported by National Institutes of Health Grant R01 AI068819 (to T. M. L.) and an Arthritis Foundation postdoctoral fellowship (to T. L. S.). NR 53 TC 7 Z9 7 U1 0 U2 7 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 MAY 8 PY 2012 VL 109 IS 19 BP 7415 EP 7420 DI 10.1073/pnas.1119272109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 942ZQ UT WOS:000304090600061 PM 22529380 ER PT J AU Li, YH Siegel, DL Scholler, N Kaplan, DE AF Li, Yonghai Siegel, Donald L. Scholler, Nathalie Kaplan, David E. TI Validation of glypican-3-specific scFv isolated from paired display/secretory yeast display library SO BMC BIOTECHNOLOGY LA English DT Article ID HUMAN HEPATOCELLULAR-CARCINOMA; PHASE-II; IN-VITRO; MARKER; EXPRESSION; ANTIBODY; CELLS; GENERATION; PROTEIN; GROWTH AB Background: Glypican-3 (GPC3) is a heparan-sulfate proteoglycan frequently expressed on the cell membrane of malignant hepatocytes in hepatocellular carcinoma. The capacity for screening potential antibodies in vitro using human hepatocellular lines is critical to ensure binding to this highly post-translationally modified glycophosphatidylinositiol linked protein. We hypothesized that we could utilize a recently described paired display/secretory yeast library to isolate human-derived scFv against glypican-3 for potential diagnostic and/or therapeutic application. Results: Using two different biotinylated antigen targets, a synthesized 29mer fragment GPC3(550-558) and a truncated GPC3(368-548) fused with glutathione S-transferase (GST) we enriched the yeast display library to greater than 30% target-specific yeast with both positive selection and depletion of streptavidin-and GST-specific clones. After cloning of scFv cDNA from the enriched sub-library, scFv specificity was validated by ELISA for binding to recombinant protein from prokaryotic and eukaryotic sources and ultimately naturally presented human protein on the cell membrane of human hepatocellular cell lines. Specificity was confirmed using non-expressing cell lines and shRNA knockdown. Ultimately, five unique scFv with affinity EC50 ranging from 5.0-110.9nM were identified. Conclusions: Using a paired display/secretory yeast library, five novel and unique scFvs for potential humoral or chimeric therapeutic development in human hepatocellular carcinoma were isolated and characterized. C1 [Kaplan, David E.] Philadelphia VA Med Ctr, Med & Res Serv, Philadelphia, PA 19104 USA. [Li, Yonghai; Kaplan, David E.] Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. [Siegel, Donald L.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Scholler, Nathalie] Univ Penn, Dept Obstet & Gynecol, Ctr Res Reprod & Womens Hlth, Penn Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA. RP Kaplan, DE (reprint author), Philadelphia VA Med Ctr, Med & Res Serv, Philadelphia, PA 19104 USA. EM dakaplan@mail.med.upenn.edu RI Scholler, Nathalie/O-9003-2014 OI Kaplan, David E./0000-0002-3839-336X FU McCabe Family Research Foundation [R21 CA149908]; Veterans Health Administration; University of Pennsylvania FX This work was supported by R21 CA149908 (DEK), McCabe Family Research Foundation, and Research Career Development Award from the Veterans Health Administration (DEK), academic development funds from the University of Pennsylvania (DEK). The authors would like to thank Aizhi Zhao for his technical assistance. The content of this article does not reflect the views of the VA or of the US Government. NR 32 TC 3 Z9 4 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6750 J9 BMC BIOTECHNOL JI BMC Biotechnol. PD MAY 7 PY 2012 VL 12 AR 23 DI 10.1186/1472-6750-12-23 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 992EH UT WOS:000307757900001 PM 22564378 ER PT J AU Nunez, AL Jhala, NC Carroll, AJ Mikhail, FM Reddy, VVB Xian, RR Jhala, DN AF Nunez, Amberly L. Jhala, Nirag C. Carroll, Andrew J. Mikhail, Fady M. Reddy, Vishnu V. B. Xian, Rena R. Jhala, Darshana N. TI Endoscopic ultrasound and endobronchial ultrasound-guided fine-needle aspiration of deep-seated lymphadenopathy: Analysis of 1338 cases SO CYTOJOURNAL LA English DT Article DE Endoscopic ultrasound; endobronchial ulatrsound; fine-needle aspiration; mediastinum; flow cytometry; fluorescence in situ hybridization; lymph node; lymphoma ID B-CELL LYMPHOMA; FLOW-CYTOMETRY; CENTER EXPERIENCE; RECURRENT LYMPHOMA; DIAGNOSIS; BIOPSY; SUBCLASSIFICATION; CYTOMORPHOLOGY; CLASSIFICATION; ACCURATE AB Background: We retrospectively studied 1338 samples of lymph nodes obtained by endoscopic and endobronchial ultrasound-guided fine needle aspiration biopsy (EUS and EBUS-FNAB) with an objective of characterizing the utility of this diagnostic modality in the assessment of deep-seated lymphadenopathy. The secondary aims were to establish the utility in the diagnosis of lymphoma and to determine the number of passes required to obtain adequate cellularity for flow cytometric analysis. Materials and Methods: On-site assessment was performed by a cytopathologist using Diff-Quik (American Scientific Products, McGraw Park, IL) stain. In addition, Papanicolaou and immunohistochemical stains were performed and additional samples were sent for flow cytometric analyses (n = 145). The final cytologic diagnosis was correlated with surgical pathology diagnosis and/or clinical follow-up. In select cases, fluorescence in situ hybridization analysis with specific probes was performed on Diff-Quik smears. Results: Both morphology as well as ancillary studies (flow cytometry or immunohistochemical stain and/or fluorescence in situ hybridization) show that EUS and EBUS-FNA are effective techniques to detect and stage intrathoracic and intra-abdominal tumors. Operating characteristics show that these are highly sensitive (89) and specific (100) techniques for the diagnosis of lymphoma. At least two passes provided an average of 5.66 million cells (range, 0.12-62.32 million) for lymphoma cases. Conclusions: EUS and EBUS-FNA are powerful modalities to stage malignancies and at least two passes can provide adequate cells for flow cytometric analysis. We also demonstrate that fluorescence in situ hybridization analysis can be performed on Diff-Quik-stained and mounted smears. C1 [Nunez, Amberly L.; Reddy, Vishnu V. B.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Carroll, Andrew J.; Mikhail, Fady M.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA. [Jhala, Nirag C.; Xian, Rena R.; Jhala, Darshana N.] Univ Penn, Philadelphia, PA 19104 USA. [Jhala, Nirag C.; Reddy, Vishnu V. B.; Xian, Rena R.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Nunez, AL (reprint author), Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. EM alinda@uab.edu; nirag.jhala@uphs.upenn.edu; acarroll@uab.edu; fmikhail@uab.edu; vreddy@uab.edu; rena.xian@uphs.upenn.edu; darshana.jhala@uphs.upenn.edu OI Reddy, Vishnu/0000-0001-5474-3289 NR 28 TC 11 Z9 11 U1 0 U2 2 PU MEDKNOW PUBLICATIONS PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 0974-5963 J9 CYTOJOURNAL JI CytoJournal PD MAY 5 PY 2012 VL 9 AR 14 DI 10.4103/1742-6413.95845 PG 10 WC Pathology SC Pathology GA 976CF UT WOS:000306557400002 PM 22615712 ER PT J AU Zhang, ZL Wu, XM Duan, J Hinrichs, D Wegmann, K Zhang, GL Hall, M Rosenbaum, JT AF Zhang, Zili Wu, Xiumei Duan, Jie Hinrichs, David Wegmann, Keith Zhang, Gary L. Hall, Mark Rosenbaum, James T. TI Low Dose Rapamycin Exacerbates Autoimmune Experimental Uveitis SO PLOS ONE LA English DT Article ID INDUCED CELL-DEATH; OF-THE-LITERATURE; MAMMALIAN TARGET; T-CELLS; METABOLIC-REGULATION; CYCLOSPORINE-A; MTOR; SIROLIMUS; MICE; ACTIVATION AB Background: Rapamycin, a potent immune modulator, is used to treat transplant rejection and some autoimmune diseases. Uveitis is a potentially severe inflammatory eye disease, and 2 clinical trials of treating uveitis with rapamycin are under way. Unexpectedly, recent research has demonstrated that low dose rapamycin enhances the memory T cell population and function. However, it is unclear how low dose rapamycin influences the immune response in the setting of uveitis. Design and Methods: B10.RIII mice were immunized to induce experimental autoimmune uveitis (EAU). Ocular inflammation of control and rapamycin-treated mice was compared based on histological change. ELISPOT and T cell proliferation assays were performed to assess splenocyte response to ocular antigen. In addition, we examined the effect of rapamycin on activation-induced cell death (AICD) using the MitoCapture assay and Annexin V staining. Results: Administration of low dose rapamycin exacerbated EAU, whereas treating mice with high dose rapamycin attenuated ocular inflammation. The progression of EAU by low dose rapamycin coincided with the increased frequency of antigen-reactive lymphocytes. Lastly, fewer rapamycin-treated T cells underwent AICD, which might contribute to exaggerated ocular inflammation and the uveitogenic immune response. Conclusion: These data reveal a paradoxical role for rapamycin in uveitis in a dose-dependent manner. This study has a potentially important clinical implication as rapamycin might cause unwanted consequences dependent on dosing and pharmacokinetics. Thus, more research is needed to further define the mechanism by which low dose rapamycin augments the immune response. C1 [Zhang, Zili; Wu, Xiumei; Duan, Jie; Zhang, Gary L.; Hall, Mark] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97201 USA. [Hinrichs, David; Wegmann, Keith] Portland VA Med Ctr, Portland, OR USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. RP Zhang, ZL (reprint author), Oregon Hlth & Sci Univ, Dept Pediat, 3181 Sw Sam Jackson Pk Rd, Portland, OR 97201 USA. EM zhangzi@ohsu.edu; rosenbaj@ohsu.edu FU National Institutes of Health [EY016788, EY013093, EY006484]; Stan and Madelle Rosenfeld Family Trust; William and Mary Bauman Foundation; Research to Prevent Blindness; William C. Kuzell Foundation FX This work was supported by National Institutes of Health Grants EY016788 (ZZ), EY013093 (JTR), and EY006484 (JTR). Funds from the Stan and Madelle Rosenfeld Family Trust, the William and Mary Bauman Foundation, Research to Prevent Blindness and William C. Kuzell Foundation also supported this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 14 Z9 15 U1 1 U2 3 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 MAY 4 PY 2012 VL 7 IS 5 AR e36589 DI 10.1371/journal.pone.0036589 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959WV UT WOS:000305349800085 PM 22574188 ER PT J AU Xu, GS Liu, K Anderson, J Patrene, K Lentzsch, S Roodman, GD Ouyang, HJ AF Xu, Guoshuang Liu, Kai Anderson, Judy Patrene, Kenneth Lentzsch, Suzanne Roodman, G. David Ouyang, Hongjiao TI Expression of XBP1s in bone marrow stromal cells is critical for myeloma cell growth and osteoclast formation SO BLOOD LA English DT Article ID UNFOLDED PROTEIN RESPONSE; TRANSCRIPTION FACTOR XBP-1; MULTIPLE-MYELOMA; DIFFERENTIATION; MICROENVIRONMENT; DISEASE; STRESS; IDENTIFICATION; PATHOGENESIS; IRE1-ALPHA AB BM stromal cells (BMSCs) are key players in the microenvironmental support of multiple myeloma (MM) cell growth and bone destruction. A spliced form of the X-boxbinding protein-1 (XBP1s), a major proximal effector of unfolded protein response signaling, is highly expressed in MM cells and plays an indispensable role in MM pathogenesis. In the present study, we found that XBP1s is induced in the BMSCs of the MM microenvironment. XBP1s overexpression in healthy human BMSCs enhanced gene and/or protein expression of VCAM-1, IL-6, and receptor activator of NF-kappa B ligand (RANKL), enhancing BMSC support of MM cell growth and osteoclast formation in vitro and in vivo. Conversely, deficiency of XBP1 in healthy donor BMSCs displayed a range of effects on BMSCs that were opposite to those cells with overexpression of XBP1s. Knock-down of XBP1 in MM patient BM-SCs greatly compromised their increased VCAM-1 protein expression and IL-6 and RANKL secretion in response to TNF alpha and reversed their enhanced support of MM-cell growth and osteoclast formation. Our results demonstrate that XBP1s is a pathogenic factor underlying BMSC support of MM cell growth and osteoclast formation and therefore represents a therapeutic target for MM bone disease. (Blood. 2012;119(18):4205-4214) C1 [Xu, Guoshuang; Liu, Kai; Anderson, Judy; Patrene, Kenneth; Lentzsch, Suzanne; Roodman, G. David; Ouyang, Hongjiao] Univ Pittsburgh, Sch Med, Dept Med, Div Hematol & Oncol, Pittsburgh, PA USA. [Xu, Guoshuang] Fourth Mil Med Univ PLA, Xijing Hosp, Dept Nephrol, Xian, Peoples R China. [Lentzsch, Suzanne] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Roodman, G. David] VA Med Ctr, Pittsburgh, PA USA. [Ouyang, Hongjiao] Univ Pittsburgh, Sch Dent Med, Dept Comprehens Care Restorat Dent & Endodont, Pittsburgh, PA USA. RP Ouyang, HJ (reprint author), VA Pittsburgh Healthcare Syst, R&D 151-U,2W-143 Univ Dr C, Pittsburgh, PA 15240 USA. EM hoo1@pitt.edu FU Multiple Myeloma Research Foundation; National Institutes of Health/National Institute of Dental and Craniofacial Research [DE017439]; VA Merit Review FX This work was supported by the Multiple Myeloma Research Foundation (to H.O.), a National Institutes of Health/National Institute of Dental and Craniofacial Research grant (DE017439 to H.O.), and by a Multiple Myeloma Research Foundation and VA Merit Review Grant (to G.D.R). NR 34 TC 24 Z9 25 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 3 PY 2012 VL 119 IS 18 BP 4205 EP 4214 DI 10.1182/blood-2011-05-353300 PG 10 WC Hematology SC Hematology GA 959BL UT WOS:000305284600017 PM 22427205 ER PT J AU Singh, JA AF Singh, Jasvinder A. TI Stem cells and other innovative intra-articular therapies for osteoarthritis: what does the future hold? SO BMC MEDICINE LA English DT Editorial Material DE osteoarthritis; intra-articular; novel; treatment; gene therapy; stem cell ID CRUCIATE LIGAMENT TRANSECTION; FIBROBLAST GROWTH FACTOR-18; RANDOMIZED CONTROLLED-TRIAL; PLATELET-RICH PLASMA; BOTULINUM-TOXIN-A; QUALITY-OF-LIFE; KNEE OSTEOARTHRITIS; ARTICULAR-CARTILAGE; IN-VIVO; OARSI RECOMMENDATIONS AB Osteoarthritis (OA), the most common type of arthritis in the world, is associated with suffering due to pain, productivity loss, decreased mobility and quality of life. Systemic therapies available for OA are mostly symptom modifying and have potential gastrointestinal, renal, hepatic, and cardiac side effects. BMC Musculoskeletal Disorders recently published a study showing evidence of reparative effects demonstrated by homing of intra-articularly injected autologous bone marrow stem cells in damaged cartilage in an animal model of OA, along with clinical and radiographic benefit. This finding adds to the growing literature showing the potential benefit of intra-articular (IA) bone marrow stem cells. Other emerging potential IA therapies include IL-1 receptor antagonists, conditioned autologous serum, botulinum toxin, and bone morphogenetic protein-7. For each of these therapies, trial data in humans have been published, but more studies are needed to establish that they are safe and effective. Several additional promising new OA treatments are on the horizon, but challenges remain to finding safe and effective local and systemic therapies for OA. Please see related article: http://www.biomedcentral.com/1471-2474/12/259 C1 [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 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 Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Birmingham VA Med Ctr, Med Serv, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 NR 59 TC 5 Z9 5 U1 0 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7015 J9 BMC MED JI BMC Med. PD MAY 2 PY 2012 VL 10 AR 44 DI 10.1186/1741-7015-10-44 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 951HV UT WOS:000304712400001 PM 22551396 ER PT J AU Pletcher, MJ Kertesz, SG AF Pletcher, Mark J. Kertesz, Stefan G. TI Long-term Marijuana Use and Pulmonary Function Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID RECRUITMENT; CARDIA C1 [Pletcher, Mark J.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Kertesz, Stefan G.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Pletcher, MJ (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. EM mpletcher@epi.ucsf.edu NR 2 TC 0 Z9 0 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 2 PY 2012 VL 307 IS 17 BP 1796 EP 1797 DI 10.1001/jama.2012.3607 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 933TV UT WOS:000303386800011 ER PT J AU Pae, CU Bodkin, JA Portland, KB Thase, ME Patkar, AA AF Pae, Chi-Un Bodkin, J. Alexander Portland, Kimberly Blanchard Thase, Michael E. Patkar, Ashwin A. TI Safety of Selegiline Transdermal System in Clinical Practice: Analysis of Adverse Events From Postmarketing Exposures SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID MAJOR DEPRESSIVE DISORDER; MONOAMINE-OXIDASE INHIBITORS; DOUBLE-BLIND; PARALLEL-GROUP; DRUG SAFETY; TRIAL; SURVEILLANCE; PRODUCT; FDA AB Objective: The objective of this analysis is to present the safety profile of selegiline transdermal system (STS) in clinical practice after US Food and Drug Administration approval by analyzing reported postmarketing adverse events (AEs). Method: Deidentified data were obtained on AEs, regardless of causality, as collected and compiled in the pharmaceutical company's adverse event collection systems/databases after the launch of STS in the United States. All reports of hypertensive crisis, suicide attempts, and STS overdoses were carefully examined to independently determine relation of the AE to STS. Results: From April 2006 to October 2010, a total of 3,155 AEs in 1,516 patients were reported (5.2% of the total exposures; N = 29,141), regardless of causality. The most frequently reported categories of AEs were general disorders (no. of AEs = 1,037, 3.6%) and central nervous system (CNS) disorders (no. of AEs = 574, 2.0%). A total of 266 reports (0.9%) were classified as serious AEs; CNS disorders (no. of AEs = 71, 26.7%) and cardiac and vascular disorders (no. of AEs = 44, 16.5%) were most common. There were 13 self-reports of possible hypertensive events or hypertension, although objective clinical data were not submitted in any of these cases. Thirteen drug-drug interactions (0.04%) were reported, and 5 were classified as serious. Conclusions: The most commonly reported AEs were application site reactions and insomnia. Very few patients reported a hypertensive event, and there were no objectively confirmed reports of hypertensive crisis with food at any STS dose. Therapeutic doses of STS appear to have a safety profile in clinical practice that is consistent with that observed in clinical trials. However, given the relatively modest exposure numbers, continued safety monitoring is recommended. J Clin Psychiatry 2012;73(5):661-668 (c) Copyright 2012 Physicians Postgraduate Press, Inc. C1 [Pae, Chi-Un; Patkar, Ashwin A.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27705 USA. [Pae, Chi-Un] Catholic Univ Korea, Coll Med, Seoul, South Korea. [Bodkin, J. Alexander] McLean Hosp, Clin Psychopharmacol Res Program, Belmont, MA 02178 USA. [Portland, Kimberly Blanchard] Mylan Specialty LP, Basking Ridge, NJ USA. [Thase, Michael E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Patkar, AA (reprint author), Duke Univ, Med Ctr, Dept Psychiat, 2218 Elder St,Suite B-2, Durham, NC 27705 USA. EM pae@catholic.ac.kr; ashwin.patkar@duke.edu FU GlaxoSmithKline Korea; GlaxoSmithKline; AstraZeneca Korea; Janssen Pharmaceuticals Korea; Eli Lilly Korea; KHIDI; Otsuka Korea; Wyeth Korea; Ministry of Health and Welfare; Korea Research Foundation; Korean Institute of Science and Technology Evaluation and Planning; Pfizer; Shire; Merck; Bristol Myers Squibb; Otsuka; CeNeRx; Eli Lilly; National Institute of Mental Health; Agency for Healthcare Research and Quality; Sepracor; National Institutes of Health (National Institute on Drug Abuse/National Institute on Alcohol Abuse and Alcoholism); Duke Endowment; AstraZeneca; Forest; Cephalon; Janssen; Jazz; McNeil; Organon; Orphan; Lundbeck; Titan; Sunovion; Mylan Specialty LP, Basking Ridge, New Jersey FX Dr Pae has received research grants from GlaxoSmithKline Korea, GlaxoSmithKline, AstraZeneca Korea, Janssen Pharmaceuticals Korea, Eli Lilly Korea, KHIDI, Otsuka Korea, Wyeth Korea, Ministry of Health and Welfare, Korea Research Foundation, and Korean Institute of Science and Technology Evaluation and Planning; has received honoraria from and is on the speakers bureaus of GlaxoSmithKline Korea, Pfizer Korea, Lundbeck Korea, Sandoz Korea, AstraZeneca Korea, Jeil Pharmaceuticals, Eisai Korea, Janssen Korea, Eli Lilly Korea, and Otsuka Korea; and has stock holdings in Dongwha Pharmaceuticals. Dr Bodkin has received grant/research support from Pfizer, Shire, Merck, Bristol Myers Squibb, Otsuka, and CeNeRx; has been on the speakers bureau of Bristol-Myers Squibb; and has been a consultant to Bristol-Myers Squibb, Alkermes, and Mylan. Dr Portland is an employee of Mylan. Dr Thase has provided scientific consultation to AstraZeneca, Bristol-Myers Squibb, Mylan, Eli Lilly, Forest, Gerson Lehman Group, GlaxoSmithKline, Guidepoint Global, H. Lundbeck A/S, MedAvante, Merck, Neuronetics, Novartis, Otsuka, Ortho-McNeil, PamLab, Pfizer (formerly Wyeth-Ayerst Laboratories), Schering-Plough (formerly Organon), Shire US, Supernus, Takeda (Lundbeck), and Transcept; has been on the speakers bureaus of AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck, and Pfizer (formerly Wyeth-Ayerst Laboratories); receives grant funding from Eli Lilly, GlaxoSmithKline, National Institute of Mental Health, Agency for Healthcare Research and Quality, and Sepracor; has equity holdings in MedAvante; and receives royalty income from American Psychiatric Foundation, Guilford Publications, Herald House, Oxford University Press, and W W Norton & Co. His wife is employed as the Group Scientific Director for Embryon-formerly Advogent. Dr Patkar has received research support from National Institutes of Health (National Institute on Drug Abuse/National Institute on Alcohol Abuse and Alcoholism), Duke Endowment, AstraZeneca, Forest, Cephalon, Janssen, Jazz, McNeil, Organon, Orphan, Merck, Lundbeck, Pfizer, Titan, Shire, and Sunovion; has been a consultant to/advisory board member for Forest, Gilead, Mylan, Titan, and Reckitt Benckiser; and has been on the speakers bureaus of Alkermes, Bristol-Myers Squibb, Mylan, Pfizer, and Sunovion.; Sponsored by Mylan Specialty LP, Basking Ridge, New Jersey. NR 25 TC 17 Z9 18 U1 1 U2 5 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 MAY PY 2012 VL 73 IS 5 BP 661 EP 668 DI 10.4088/JCP.12m07648 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 090SI UT WOS:000314999900009 PM 22697192 ER PT J AU Steinman, MA Lee, SJ Peterson, CA Fung, KZ Goldstein, MK AF Steinman, Michael A. Lee, Sei J. Peterson, Carolyn A. Fung, Kathy Z. Goldstein, Mary K. TI A Clinically Guided Approach for Improving Performance Measurement for Hypertension SO MEDICAL CARE LA English DT Article DE quality of health care; quality indicators; health care; hypertension; physician's prescribing practices ID QUALITY-OF-CARE; ELECTRONIC HEALTH RECORDS; CORONARY-ARTERY-DISEASE; TREATMENT INTENSIFICATION; BLOOD-PRESSURE; MEDICATION; GUIDELINES; ADHERENCE; OUTCOMES; PAY AB Background: Performance measures often fail to account for legitimate reasons why patients do not achieve recommended treatment targets. Methods: We tested a novel performance measurement system for blood pressure (BP) control that was designed to mimic clinical reasoning. This clinically guided approach focuses on (1) exempting patients for whom tight BP control may not be appropriate or feasible and (2) assessing BP over time. Trained abstractors conducted structured chart reviews of 201 adults with hypertension in 2 VA health care systems. Results were compared with traditional methods of performance measurement. Results: Among 201 veterans, 183 (91%) were male, and the mean age was 71 +/- 11 years. Using the clinically guided approach, 61 patients (30%) were exempted from performance measurement. The most common reasons for exemption were inadequate opportunity to manage BP (35 patients, 17%) and the use of 4 or more anti-hypertensive medications (19 patients, 9%). Among patients eligible for performance measurement, there was little agreement on the presence of controlled versus uncontrolled BP when comparing the most recent BP (the traditional approach) with an integrated assessment of BP control (kappa 0.14). After accounting for clinically guided exemptions and methods of BP assessment, only 15 of 72 patients (21%) whose last BP was >= 140/90 mm Hg were classified as problematic by the clinically guided approach. Conclusions: Many patients have legitimate reasons for not achieving tight BP control, and the methods used for BP assessment have marked effects on whether a patient is classified as having adequate or inadequate BP control. C1 [Steinman, Michael A.; Lee, Sei J.; Peterson, Carolyn A.; Fung, Kathy Z.] San Francisco VA Med Ctr, Hlth Serv Res & Dev Res Enhancement Award Program, San Francisco, CA 94121 USA. [Steinman, Michael A.; Lee, Sei J.; Peterson, Carolyn A.; Fung, Kathy Z.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Goldstein, Mary K.] VA Palo Alto Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Palo Alto, CA USA. [Goldstein, Mary K.] Stanford Univ, Sch Med, Dept Med, Palo Alto, CA 94304 USA. RP Steinman, MA (reprint author), San Francisco VA Med Ctr, Hlth Serv Res & Dev Res Enhancement Award Program, 4150 Clement St,Box 181G, San Francisco, CA 94121 USA. EM mike.steinman@ucsf.edu FU Department of Veterans Affairs (VA) Health Services Research & Development Service [CDTA 01-013, IAF 06-080-02, CPI 99-275, IMV 04-062]; National Institutes on Aging; American Federation for Aging Research [K23 AG030999]; San Francisco Veterans Affairs Medical Center Health Services Research and Development Research Enhancement Award Program; NIH/NCRR/OD UCSF-CTSI [KL2 RR024130] FX Supported by the Department of Veterans Affairs (VA) Health Services Research & Development Service (CDTA 01-013 and related to IAF 06-080-02, CPI 99-275, and IMV 04-062) and by the National Institutes on Aging and the American Federation for Aging Research (K23 AG030999), and further supported with resources of the San Francisco Veterans Affairs Medical Center Health Services Research and Development Research Enhancement Award Program. Dr Lee was supported by NIH/NCRR/OD UCSF-CTSI Grant number KL2 RR024130. NR 30 TC 0 Z9 0 U1 1 U2 5 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 MAY PY 2012 VL 50 IS 5 BP 399 EP 405 DI 10.1097/MLR.0b013e318245a147 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 083IH UT WOS:000314456400007 PM 22627680 ER PT J AU Karr, S Kelley, KW McBane, S Thomas, T AF Karr, Samantha Kelley, Kristi W. McBane, Sarah Thomas, Tyan TI Overcoming practice site challenges in clinical faculty positions SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material ID PHARMACY; PRACTITIONERS C1 [Karr, Samantha] Midwestern Univ, Coll Pharm Glendale, Glendale, AZ 85308 USA. [Kelley, Kristi W.] Auburn Univ, Harrison Sch Pharm, Auburn, AL 36849 USA. [Kelley, Kristi W.] Baptist Hlth Syst Inc, Trinity Med Ctr, Continu Clin, Birmingham, AL USA. [McBane, Sarah] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Thomas, Tyan] Univ Sci Philadelphia, Philadelphia Coll Pharm, Philadelphia, PA USA. [Thomas, Tyan] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Karr, S (reprint author), Midwestern Univ, Coll Pharm Glendale, 19555 N 59th Ave, Glendale, AZ 85308 USA. EM skarrx@midwestern.edu NR 13 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD MAY 1 PY 2012 VL 69 IS 9 BP 738 EP + DI 10.2146/ajhp110289 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 073VA UT WOS:000313770000005 PM 22517019 ER PT J AU Kamboh, MI Demirci, FY Wang, X Minster, RL Carrasquillo, MM Pankratz, VS Younkin, SG Saykin, AJ Jun, G Baldwin, C Logue, MW Buros, J Farrer, L Pericak-Vance, MA Haines, JL Sweet, RA Ganguli, M Feingold, E DeKosky, ST Lopez, OL Barmada, MM AF Kamboh, M. I. Demirci, F. Y. Wang, X. Minster, R. L. Carrasquillo, M. M. Pankratz, V. S. Younkin, S. G. Saykin, A. J. Jun, G. Baldwin, C. Logue, M. W. Buros, J. Farrer, L. Pericak-Vance, M. A. Haines, J. L. Sweet, R. A. Ganguli, M. Feingold, E. DeKosky, S. T. Lopez, O. L. Barmada, M. M. CA Alzheimers Dis Neuroimaging Initia TI Genome-wide association study of Alzheimer's disease SO TRANSLATIONAL PSYCHIATRY LA English DT Article DE Alzheimer's disease; genome-wide association study; meta-analysis; PPP1R3B; PTK2B; single-nucleotide polymorphisms ID IDENTIFIES VARIANTS; COMMON VARIANTS; APOE; SUSCEPTIBILITY; POPULATION; RISK; LOCI; CLU; POLYMORPHISM; PROGRESS AB In addition to apolipoprotein E (APOE), recent large genome-wide association studies (GWASs) have identified nine other genes/loci (CR1, BIN1, CLU, PICALM, MS4A4/MS4A6E, CD2AP, CD33, EPHA1 and ABCA7) for late-onset Alzheimer's disease (LOAD). However, the genetic effect attributable to known loci is about 50%, indicating that additional risk genes for LOAD remain to be identified. In this study, we have used a new GWAS data set from the University of Pittsburgh (1291 cases and 938 controls) to examine in detail the recently implicated nine new regions with Alzheimer's disease (AD) risk, and also performed a meta-analysis utilizing the top 1% GWAS single-nucleotide polymorphisms (SNPs) with P < 0.01 along with four independent data sets (2727 cases and 3336 controls) for these SNPs in an effort to identify new AD loci. The new GWAS data were generated on the Illumina Omni1-Quad chip and imputed at similar to 2.5 million markers. As expected, several markers in the APOE regions showed genome-wide significant associations in the Pittsburg sample. While we observed nominal significant associations (P < 0.05) either within or adjacent to five genes (PICALM, BIN1, ABCA7, MS4A4/MS4A6E and EPHA1), significant signals were observed 69-180 kb outside of the remaining four genes (CD33, CLU, CD2AP and CR1). Meta-analysis on the top 1% SNPs revealed a suggestive novel association in the PPP1R3B gene (top SNP rs3848140 with P = 3.05E-07). The association of this SNP with AD risk was consistent in all five samples with a meta-analysis odds ratio of 2.43. This is a potential candidate gene for AD as this is expressed in the brain and is involved in lipid metabolism. These findings need to be confirmed in additional samples. Translational Psychiatry (2012) 2, e117; doi:10.1038/tp.2012.45; published online 15 May 2012 C1 [Kamboh, M. I.; Demirci, F. Y.; Wang, X.; Minster, R. L.; Feingold, E.; Barmada, M. M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [Kamboh, M. I.; Lopez, O. L.] Univ Pittsburgh, Alzheimers Dis Res Ctr, Pittsburgh, PA 15261 USA. [Kamboh, M. I.; Sweet, R. A.; Ganguli, M.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. [Carrasquillo, M. M.; Pankratz, V. S.; Younkin, S. G.] Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA. [Saykin, A. J.] Indiana Univ Sch Med, Dept Radiol & Imaging Sci, Indianapolis, IN USA. [Saykin, A. J.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN USA. [Jun, G.; Baldwin, C.; Logue, M. W.; Buros, J.; Farrer, L.] Boston Univ, Sch Med & Publ Hlth, Dept Med, Genet Program, Boston, MA 02215 USA. [Jun, G.; Logue, M. W.; Farrer, L.] Boston Univ, Sch Med & Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Jun, G.; Farrer, L.] Boston Univ, Sch Med & Publ Hlth, Dept Opthalmol, Boston, MA 02215 USA. [Baldwin, C.] Boston Univ, Sch Med & Publ Hlth, Ctr Human Genet, Boston, MA 02215 USA. [Farrer, L.] Boston Univ, Sch Med & Publ Hlth, Dept Neurol, Boston, MA 02215 USA. [Farrer, L.] Boston Univ, Sch Med & Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Pericak-Vance, M. A.] Univ Miami, John P Hussman Inst Human Genom, Miami, FL USA. [Haines, J. L.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Sweet, R. A.; Lopez, O. L.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Sweet, R. A.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. [DeKosky, S. T.] Univ Virginia, Sch Med, Off Dean, Charlottesville, VA 22908 USA. [DeKosky, S. T.] Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA. RP Kamboh, MI (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. EM kamboh@pitt.edu RI Haines, Jonathan/C-3374-2012; Saykin, Andrew/A-1318-2007; MORAN, CATHERINE/C-9539-2015 OI Saykin, Andrew/0000-0002-1376-8532; Logue, Mark/0000-0001-9347-7892; Farrer, Lindsay/0000-0001-5533-4225; Buros, Jacqueline/0000-0001-9588-4889; Demirci, F. Yesim/0000-0001-6907-9843; Kamboh, M. Ilyas/0000-0002-3453-1438; Barmada, M Michael/0000-0002-3604-6460; Feingold, Eleanor/0000-0003-2898-6484 FU National Institute on Aging [AG030653, AG005133, AG027224, AG07562, AG023651, AG18023]; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant) [U01 AG024904, RC2 AG036535]; National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; NIH [P30 AG010129, K01 AG030514]; Dana Foundation; NIA National Cell Repository for Alzheimer's Disease (NCRAD) [U24 AG021886]; [R01 AG19771]; [P30 AG10133] FX This study was supported by the National Institute on Aging grants AG030653 (MIK), AG005133 (ADRC), AG027224 (RAS), AG07562 and AG023651 (MG) and AG18023 (SGY). We thank Drs Peter Gregersen and Annette Lee of the Feinstein Institute of Medical Research where the genotyping of the discovery sample was performed. We acknowledge Drs Neill R Graff-Radford, Dennis W Dickson and Ronald C Petersen for their key contribution in collecting the Mayo replication sample. One of the replication data sets was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904; RC2 AG036535). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences; AstraZeneca; Bayer HealthCare; BioClinica; Biogen Idec; Bristol-Myers Squibb Company; Eisai; Elan Pharmaceuticals; Eli Lilly and Company; F Hoffmann-La Roche and its affiliated company Genentech; GE Healthcare; Innogenetics, N.V.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace; Merck & Co.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer; Servier; Synarc; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514 and the Dana Foundation. Some sample collection was supported by the NIA National Cell Repository for Alzheimer's Disease (NCRAD; U24 AG021886) and additional support for data analysis was provided by R01 AG19771 and P30 AG10133.. We thank the following people for their contributions to the ADNI genotyping project: Tatiana Foroud, Kelley Faber, Li Shen, Steven G Potkin, Matthew J Huentelman, David W Craig, Sungeun Kim, Kwangsik Nho and Bryan M DeChairo. NR 30 TC 72 Z9 73 U1 8 U2 25 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD MAY PY 2012 VL 2 AR e117 DI 10.1038/tp.2012.45 PG 7 WC Psychiatry SC Psychiatry GA 062CC UT WOS:000312895700010 PM 22832961 ER PT J AU Rice, TR Sher, L AF Rice, Timothy R. Sher, Leo TI Suicidal behavior in war veterans SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Review DE OEF/OIF; Operation Enduring Freedom/Operation Iraqi Freedom; post-traumatic mood disorder; suicidal behavior; suicidal ideation; suicide; suicide risk factors; traumatic brain injury; veteran ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN-INJURY; RANDOMIZED CONTROLLED-TRIAL; NATIONAL COMORBIDITY SURVEY; VIETNAM THEATER VETERANS; MENTAL-HEALTH PROBLEMS; PERSIAN-GULF-WAR; TERM-FOLLOW-UP; US-AIR-FORCE; RISK-FACTORS AB Expert Rev. Neurother. 12(5), 611-624 (2012) Military veterans represent a unique, heterogeneous population with suicide prevalence rates, risk factors and preventative management needs that differ from those of the rest of community. Veterans worldwide receive high proportions of their healthcare from community providers, and sensitivity to these distinct needs is required for optimized care. An overview of the recent prevalence-study literature, with a focus upon statistical design, is presented in order to provide a critical orientation within this field with high levels of popular media attention. Attention to psychiatric comorbidity, subthreshold symptomology, select signature disorders of contemporary conflicts (namely, post-traumatic stress disorder and traumatic brain injury), and veteran life narratives before, within and beyond military service will guide our review of risk factor assessment and management strategies. This critical review of the literature provides an overview of this active field of neuropsychiatric research with a select focus upon these topics of special interest. C1 [Rice, Timothy R.; Sher, Leo] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Rice, Timothy R.; Sher, Leo] James J Peters Vet Adm Med Ctr, Bronx, NY 10468 USA. RP Rice, TR (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1425 Madison Ave,Box 1230, New York, NY 10029 USA. EM timothy.rice@mssm.edu NR 164 TC 7 Z9 7 U1 14 U2 27 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD MAY PY 2012 VL 12 IS 5 BP 611 EP 624 DI 10.1586/ERN.12.31 PG 14 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 056FP UT WOS:000312474100018 PM 22550989 ER PT J AU Thliveris, AT Clipson, L Sommer, LL Schoenike, BA Hasenstein, JR Schlamp, CL Alexander, CM Newton, MA Dove, WF Amos-Landgraf, JM AF Thliveris, Andrew T. Clipson, Linda Sommer, Lacy L. Schoenike, Barry A. Hasenstein, Jason R. Schlamp, Cassandra L. Alexander, Caroline M. Newton, Michael A. Dove, William F. Amos-Landgraf, James M. TI Regulated Expression of Chromobox Homolog 5 Revealed in Tumors of Apc(Min/+) ROSA11 Gene Trap Mice SO G3-GENES GENOMES GENETICS LA English DT Article DE WNT signaling; cancer progenitor; lacZ reporter; Cre drivers ID UCSC GENOME BROWSER; SEQUENCE DATABASE; STEM-CELLS; MOUSE; HETEROCHROMATIN; TRANSCRIPTS; HP1; EUKARYOTES; NEOPLASIA; ADENOMAS AB The gene-trap lacZ reporter insertion, ROSA11, in the Cbx5 mouse gene illuminates the regulatory complexity of this locus in Apc(Min/+) mice. The insertion site of the beta-Geo gene-trap element lies in the 24-kb intron proximal to the coding region of Cbx5. Transcript analysis indicates that two promoters for Cbx5 flank this insertion site. Heterozygotes for the insertion express lacZ widely in fetal tissues but show limited expression in adult tissues. In the intestine, strong expression is limited to proliferative zones of crypts and tumors. Homozygotes for ROSA11, found at a lower than Mendelian frequency, express reduced levels of the coding region transcript in normal tissues, using a downstream promoter. Analysis via real-time polymerase chain reaction indicates that the upstream promoter is the dominant promoter in normal epithelium and tumors. Bioinformatic analysis of the Cbx5 locus indicates that WNT and its target transcription factor MYC can establish a feedback loop that may play a role in regulating the self-renewal of the normal intestinal epithelium and its tumors. C1 [Clipson, Linda; Hasenstein, Jason R.; Alexander, Caroline M.; Dove, William F.; Amos-Landgraf, James M.] Univ Wisconsin, McArdle Lab Canc Res, Dept Oncol, Madison, WI 53706 USA. [Thliveris, Andrew T.; Sommer, Lacy L.; Schlamp, Cassandra L.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA. [Schoenike, Barry A.] Univ Wisconsin, Dept Neurosci, Madison, WI 53706 USA. [Newton, Michael A.] Univ Wisconsin, Dept Stat, Madison, WI 53706 USA. [Newton, Michael A.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA. [Dove, William F.] Univ Wisconsin, Genet Lab, Madison, WI 53706 USA. [Thliveris, Andrew T.] William S Middleton Mem Vet Adm Med Ctr, Surg Serv, Madison, WI 53705 USA. RP Dove, WF (reprint author), Univ Wisconsin, McArdle Lab Canc Res, Dept Oncol, 1400 Univ Ave, Madison, WI 53706 USA. EM dove@oncology.wisc.edu RI Amos-Landgraf, James/K-9288-2013 OI Amos-Landgraf, James/0000-0003-2535-7746 FU National Cancer Institute [R37 CA63677, U01 CA84227]; Helmerich Chair from the Retina Research Foundation FX We thank Phil Soriano for his generous gift of the R11 strain; Karen Gould for the initial discovery of the R11 intestinal expression pattern; Alexandra Shedlovsky for making the congenic strain; Ryan Burch and Dawn Albrecht for assistance with experiments; and Jane Weeks, Harlene Edwards, and other members of the Histotechology Facility for expert support. This study was supported by National Cancer Institute grants R37 CA63677 and U01 CA84227 to WFD and the Helmerich Chair from the Retina Research Foundation to A.T.T. This is publication 3649 from the Laboratory of Genetics, University of Wisconsin-Madison. NR 41 TC 3 Z9 3 U1 0 U2 3 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 2160-1836 J9 G3-GENES GENOM GENET JI G3-Genes Genomes Genet. PD MAY 1 PY 2012 VL 2 IS 5 BP 569 EP 578 DI 10.1534/g3.112.002436 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 055YH UT WOS:000312453500006 PM 22670227 ER PT J AU Emmons, RR Cirnigliaro, CM Jensen, AM Kirshblum, SC Bauman, WA AF Emmons, Racine R. Cirnigliaro, Christopher M. Jensen, A. Marley Kirshblum, Steven C. Bauman, William A. TI Association of Apolipoprotein B with Postprandial Lipemic Responses in Persons with Chronic Spinal Cord Injury SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Emmons, Racine R.] William Paterson Univ, Wayne, NJ USA. [Cirnigliaro, Christopher M.; Jensen, A. Marley; Bauman, William A.] James J Peters VA Med Ctr, Bronx, NY USA. [Kirshblum, Steven C.] Kessler Inst Rehabil, W Orange, NJ 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 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2012 VL 44 SU 2 BP 261 EP 261 PG 1 WC Sport Sciences SC Sport Sciences GA 027OT UT WOS:000310363301381 ER PT J AU Hula, WD Fergadiotis, G Martin, N AF Hula, William D. Fergadiotis, Gerasimos Martin, Nadine TI Model Choice and Sample Size in Item Response Theory Analysis of Aphasia Tests SO AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Article DE aphasia; psychometrics; assessment ID CONFIRMATORY FACTOR-ANALYSIS; RASCH MODEL; MONTE-CARLO; ABILITY; REHABILITATION; VALIDITY; OUTCOMES; CURVES; LIKERT AB Purpose: The purpose of this study was to identify the most appropriate item response theory (IRT) measurement model for aphasia tests requiring 2-choice responses and to determine whether small samples are adequate for estimating such models. Method: Pyramids and Palm Trees (Howard & Patterson, 1992) test data that had been collected from individuals with aphasia were analyzed, and the resulting item and person estimates were used to develop simulated test data for 3 sample size conditions. The simulated data were analyzed using a standard 1-parameter logistic (1-PL) model and 3 models that accounted for the influence of guessing: augmented 1-PL and 2-PL models and a 3-PL model. The model estimates obtained from the simulated data were compared to their known true values. Results: With small and medium sample sizes, an augmented 1-PL model was the most accurate at recovering the known item and person parameters; however, no model performed well at any sample size. Follow-up simulations confirmed that the large influence of guessing and the extreme easiness of the items contributed substantially to the poor estimation of item difficulty and person ability. Conclusion: Incorporating the assumption of guessing into IRT models improves parameter estimation accuracy, even for small samples. However, caution should be exercised in interpreting scores obtained from easy 2-choice tests, regardless of whether IRT modeling or percentage correct scoring is used. C1 [Hula, William D.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Hula, William D.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Fergadiotis, Gerasimos] Arizona State Univ, Tempe, AZ USA. [Martin, Nadine] Temple Univ, Philadelphia, PA 19122 USA. RP Hula, WD (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. EM william.hula@va.gov FU Veterans Affairs Rehabilitation Research & Development Career Development Award [C7476W]; VA Pittsburgh Healthcare System Geriatric Research Education and Clinical Center; National Institutes of Health (National Institute on Deafness and Other Communication Disorders) [DC01924-15] FX This research was supported by Veterans Affairs Rehabilitation Research & Development Career Development Award C7476W, the VA Pittsburgh Healthcare System Geriatric Research Education and Clinical Center, and Grant DC01924-15 from the National Institutes of Health (National Institute on Deafness and Other Communication Disorders) to Temple University (PI N. Martin). The authors also gratefully acknowledge the support and assistance of Heather Harris Wright and Michelene Kalinyak-Fliszar. The contents of this paper do not represent the views of the Department of Veterans Affairs or the U.S. Government. NR 52 TC 1 Z9 1 U1 0 U2 5 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1058-0360 J9 AM J SPEECH-LANG PAT JI Am. J. Speech-Lang. Pathol. PD MAY 1 PY 2012 VL 21 IS 2 BP S38 EP S50 DI 10.1044/1058-0360(2011/11-0090) PG 13 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 019SZ UT WOS:000309760900003 PM 22230175 ER PT J AU Vigen, R Shetterly, S Magid, DJ O'Connor, PJ Margolis, KL Schmittdiel, J Ho, PM AF Vigen, Rebecca Shetterly, Susan Magid, David J. O'Connor, Patrick J. Margolis, Karen L. Schmittdiel, Julie Ho, P. Michael TI A Comparison Between Antihypertensive Medication Adherence and Treatment Intensification as Potential Clinical Performance Measures SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE hypertension; performance measures; medication adherence; treatment intensification; quality of care ID BLOOD-PRESSURE CONTROL; CORONARY-ARTERY-DISEASE; ASSOCIATION TASK-FORCE; COLLEGE-OF-CARDIOLOGY; AMERICAN-COLLEGE; DIABETES-MELLITUS; HYPERTENSION; CARE; QUALITY; THERAPY AB Background-Medication adherence and treatment intensification have been advocated as performance measures to assess the quality of care provided. Whereas previous studies have shown that adherence and treatment intensification (TI) of antihypertensive medications is associated with blood pressure (BP) control at the patient level, less is known about whether adherence and TI is associated with BP control at the clinic level. Methods and Results-We included 162 879 patients among 89 clinics in the Cardiovascular Research Network Hypertension Registry with incident hypertension who were started on antihypertensive medications. Adherence was measured by the proportion of days covered (PDC). TI was defined by the standard based method with scores ranging between -1 to 1 and categorized as: -1 indicated no TI occurred when BP was elevated; 0 indicated TI occurred when BP was elevated; and 1 indicated that TI was made at all visits, even when BP was not elevated. Logistic regression models assessed the association between adherence and TI with blood pressure control (BP <= 140/90 at the clinic visit closest to 12 months after study entry) at the patient and clinic levels. Mean adherence was 0.77 +/- 0.28 (PDC +/- SD) at the patient level and 0.78 +/- 0.05 at the clinic level. Mean TI was 0.026 +/- 0.23 at the patient level and 0.01 +/- 0.04 at the clinic level. At the patient level, for each 0.25 increase in adherence and TI, the odds (OR) of achieving blood pressure control increased by 28% and 55%, respectively [OR for adherence, 1.28 (1.26-1.29), and for TI, 1.55 (1.53-1.57)]. At the clinic level, each 0.04 increment increase in treatment intensification was associated with a 25% increased odds of achieving blood pressure control (OR, 1.24; 95% CI, 1.21-1.27). In contrast, there was an inverse association between increasing adherence and BP control (OR, 0.93; 95% confidence interval, 0.90-0.95). Conclusions-Patient adherence to antihypertensive medications is not associated with BP control at the clinic level and may not be suitable as a performance measure. TI is associated with BP control, but its use as a performance measure may be constrained by challenges in measuring it and by concerns about unintended consequences of aggressive hypertension treatment in some subgroups of patients. (Circ Cardiovasc Qual Outcomes. 2012; 5: 276-282.) C1 [Vigen, Rebecca; Ho, P. Michael] Univ Colorado, Denver, CO 80202 USA. [Shetterly, Susan; Magid, David J.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [O'Connor, Patrick J.; Margolis, Karen L.] HealthPartners Res Fdn, Minneapolis, MN USA. [Schmittdiel, Julie] Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. [Ho, P. Michael] Denver VA Med Ctr, Denver, CO USA. RP Vigen, R (reprint author), Denver VAMC, Cardiol Sect 111B, 1055 Clermont St, Denver, CO 80220 USA. EM Rebecca.vigen@ucdenver.edu FU Cardiovascular Outcomes Research Fellowship through a Department of Veterans Affairs Graduate Medical Education Enhancement Grant; Berman Center [HHSN268201100027C]; Assessing Accuracy of Blood Pressure Measurement in HealthPartners Usual Clinical Care [A12-046]; [HL 089471]; [HL 093345]; [DK 079861]; [HL 102144]; [NIH/R01HL093345-01]; [KPNC/U19 HL091179]; [NHLBI/1R01HL089451-01A1]; [NHLBI/R01 HL090965-01]; [NHLBI/N01-WH-3-2101]; [NIA/U01AG029824]; [NHLBI/1R01HL102144-01] FX Dr Vigen was supported by a Cardiovascular Outcomes Research Fellowship through a Department of Veterans Affairs Graduate Medical Education Enhancement Grant.; Dr O'Connor was supported by Research Grants HL 089471, HL 093345, DK 079861, and HL 102144. Dr Margolis was supported by Research Grants NIH/R01HL093345-01; Berman Center/HHSN268201100027C; KPNC/U19 HL091179; NHLBI/1R01HL089451-01A1; NHLBI/R01 HL090965-01; NHLBI/N01-WH-3-2101; NIA/U01AG029824; NHLBI/1R01HL102144-01; A12-046 Assessing Accuracy of Blood Pressure Measurement in HealthPartners Usual Clinical Care. NR 16 TC 7 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2012 VL 5 IS 3 BP 276 EP 282 DI 10.1161/CIRCOUTCOMES.112.965665 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 002NO UT WOS:000308539100009 PM 22576846 ER PT J AU Hou, JG Wu, LJ Moore, S Ward, C York, M Atassi, F Fincher, L Nelson, N Sarwar, A Lai, EC AF Hou, Jyhgong Gabriel Wu, Laura J. Moore, Suzanne Ward, Constance York, Michele Atassi, Farah Fincher, Linda Nelson, Naomi Sarwar, Aliya Lai, Eugene C. TI Assessment of appropriate medication administration for hospitalized patients with Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease; Hospitalization; Medication administration; Medication schedule ID EXCESS LENGTH; COMPLICATIONS; ADMISSIONS; MANAGEMENT; FREQUENCY; ADHERENCE; EVENTS; STAY; CARE AB Background: For Parkinson's disease (PD) patients, adherence to a regular PD medication schedule is important in achieving optimal symptom control. There are few published studies quantifying PD medication administrations in hospitalized PD patients. Methods: Hospitalization records for 100 veterans with idiopathic PD and admitted to our center were reviewed to determine the on time rate and contraindicated medication doses. A barcode based computerized medication administration system within the electronic medical record provided information of the exact time the medication was given to a patient. Results: Eighty-nine idiopathic PD patients met study inclusion criteria. Among them, 87 were on levodopa monotherapy or in combination with other PD medications. Two patients were on dopamine agonists only. A total of 3873 doses of PD medications were prescribed during hospitalization. Among 675 incorrect medication administrations, 322 doses were omitted, 300 doses late by >= 30 min, and 53 doses given early by >= 30 min. Contraindicated medications were prescribed for 19 patients. The correct administration percentage was lower during the first 2 days post-admission compared to subsequent days (mean 74.6% vs. 82.8%) and higher for patients who had neurological consultations (mean 85.5% vs. 76.5%). Correct administration rates were better for patient-based medication schedules (85.6%) than with hospital-based schedules (77.5%), but did not achieve statistical significance. Conclusion: Adherence to regular PD medication dosing schedules during hospitalization is problematic, but improves with specialist consultation. Staff involved in the admission process for PD patients should work to safeguard against disruption of the prescribed home dosing schedule. Published by Elsevier Ltd. C1 [Hou, Jyhgong Gabriel; Wu, Laura J.; Moore, Suzanne; Ward, Constance; York, Michele; Atassi, Farah; Fincher, Linda; Nelson, Naomi; Sarwar, Aliya] Baylor Coll Med, Dept Neurol, Parkinsons Dis Res Educ & Clin Ctr, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Wu, Laura J.] SUNY Stony Brook, Dept Neurol, Med Ctr, Stony Brook, NY 11794 USA. [Atassi, Farah; Lai, Eugene C.] Methodist Neurol Inst, Dept Neurol, Houston, TX 77030 USA. RP Hou, JG (reprint author), Baylor Coll Med, Dept Neurol, Parkinsons Dis Res Educ & Clin Ctr, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. EM jhou@bcm.edu FU Department of Veterans Affairs FX This study is sponsored by the Department of Veterans Affairs. NR 29 TC 14 Z9 14 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD MAY PY 2012 VL 18 IS 4 BP 377 EP 381 DI 10.1016/j.parkreldis.2011.12.007 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 991CK UT WOS:000307678900014 PM 22236581 ER PT J AU Kaczorowski, DJ Scott, MJ Pibris, JP Afrazi, A Nakao, A Edmonds, RD Kim, S Kwak, JH Liu, YJ Fan, J Billiar, TR AF Kaczorowski, David J. Scott, Melanie J. Pibris, John P. Afrazi, Amin Nakao, Atsunori Edmonds, Rebecca D. Kim, Sodam Kwak, Joon H. Liu, Yujian Fan, Jie Billiar, Timothy R. TI Mammalian DNA Is an Endogenous Danger Signal That Stimulates Local Synthesis and Release of Complement Factor B SO MOLECULAR MEDICINE LA English DT Article ID ISCHEMIA-REPERFUSION INJURY; PLASMACYTOID DENDRITIC CELLS; COLLAGEN-INDUCED ARTHRITIS; INNATE IMMUNE-RESPONSES; TOLL-LIKE RECEPTOR-4; ACUTE-RENAL-FAILURE; TNF-ALPHA; INFLAMMATORY RESPONSES; ENDOTHELIAL-CELLS; CYTOPLASMIC DNA AB Complement factor B plays a critical role in ischemic tissue injury and autoimmunity. Factor B is dynamically synthesized and released by cells outside of the liver, but the molecules that trigger local factor B synthesis and release during endogenous tissue injury nave not been identified. We determined that factor B is upregulated early after cold ischemia-eperfusion in mice, using a heterotopic heart transplant model. These data suggested upregulation of factor B by damage-associated molecular patterns (DAMPs), but multiple common DAMPs did not induce factor B in RAW264.7 mouse macrophages. However, exogenous DNA induced factor B mRNA and protein expression in RAW cells in vitro, as well as in peritoneal and alveolar macrophages in vivo. To determine the cellular mechanisms involved in DNA-induced factor B upregulation we then investigated the role of multiple known DNA receptors or binding partners. We stimulated peritoneal macrophages from wild-type (WT), toll-like receptor 9 (TLR9)-deficient, receptor for advanced glycation end products (RAGE)(-/-) and myeloid differentiation factor 88 (MyD88)(-/-) mice, or mouse macrophages deficient in high-mobility group box proteins (HMGBs). DNA-dependent activator of interferon-regulatory factors (DAI) or absent in melanoma 2 (AIM2), with DNA in the presence or absence of lipofection reagent. Reverse transcription-polymerase chain reaction, Western blotting and immunocytochemical analysis were employed for analysis. Synthesis of factor B was independent of TLR9, RAGE, DAI and AIM2, but was dependent on HMGBs, MyD88, p38 and NF-kappa B. Our data therefore show that mammalian DNA is an endogenous molecule that stimulates factor B synthesis and release from macrophages via HMGBs, MyD88, p38 and NF-kappa B signaling. This activation of the immune system likely contributes to damage following sterile injury such as hemorrhagic shock and ischemia-reperfusion. Online address: http://www.molmed.org doi: 10.2119/molmed.2012.00011 C1 [Scott, Melanie J.; Pibris, John P.; Afrazi, Amin; Nakao, Atsunori; Edmonds, Rebecca D.; Kim, Sodam; Kwak, Joon H.; Billiar, Timothy R.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. [Kaczorowski, David J.] Univ Penn, Div Cardiovasc Surg, Philadelphia, PA 19104 USA. [Liu, Yujian; Fan, Jie] Vet Affairs Pittsburgh Healthcare Syst, Surg Res, Pittsburgh, PA USA. RP Billiar, TR (reprint author), Univ Pittsburgh, Med Ctr, Dept Surg, Presbyterian Univ Hosp, F1281,200 Lothrop St, Pittsburgh, PA 15213 USA. EM billiartr@upmc.edu FU National Institutes of Health [P50-GM-53789]; American College of Surgeons Resident Research Scholarships FX This work was supported by National Institutes of Health grant P50-GM-53789 (TR Billiar). DJ Kaczorowski and RD Edmonds are each recipients of American College of Surgeons Resident Research Scholarships. We thank M Bo, H Liao and D Reiser for technical assistance. NR 52 TC 10 Z9 10 U1 0 U2 2 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD MAY PY 2012 VL 18 IS 5 BP 851 EP 860 DI 10.2119/molmed.2012.00011 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 983TY UT WOS:000307142800014 PM 22526919 ER PT J AU Chitsaz, S Gundiah, N Blackshear, C Tegegn, N Yan, KS Azadani, AN Hope, M Tseng, EE AF Chitsaz, Sam Gundiah, Namrata Blackshear, Charlie Tegegn, Nebiyu Yan, Kimberly S. Azadani, Ali N. Hope, Michael Tseng, Elaine E. TI Correlation of Calcification on Excised Aortic Valves by Micro-Computed Tomography with Severity of Aortic Stenosis SO JOURNAL OF HEART VALVE DISEASE LA English DT Article ID ELECTRON-BEAM TOMOGRAPHY; MULTIDETECTOR ROW CT; CALCIUM; ECHOCARDIOGRAPHY; QUANTIFICATION; MARKER; AREA AB Background and aim of the study: The quantification of incidentally found aortic valve calcification on computed tomography (CT) is not performed routinely, as data relating to the accuracy of aortic valve calcium for estimating the severity of aortic stenosis (AS) is neither consistent nor validated. As aortic valve calcium quantification by CT is confounded by wall and coronary ostial calcification, as well as motion artifact, the ex-vivo micro-computed tomography (micro-CT) of stenotic aortic valves allows a precise measurement of the amounts of calcium present. The study aim, using excised aortic valves from patients with confirmed AS, was to determine if the amount of calcium on micro-CT correlated with the severity of AS. Methods: Each of 35 aortic valves that had been excised from patients during surgical valve replacement were examined using micro-CT imaging. The amount of calcium present was determined by absolute and proportional values of calcium volume in the specimen. Subsequently, the correlation between calcium volume and preoperative mean aortic valve gradient (MAVG), peak transaortic velocity (V-max), and aortic valve area (AVA) on echocardiography, was evaluated. Results: The mean calcium volume across all valves was 603.2 +/- 398.5 mm(3), and the mean ratio of calcium volume to total valve volume was 0.36 +/- 0.16. The mean aortic valve gradient correlated positively with both calcium volume and ratio (r = 0.72, p <0.001). V-max also correlated positively with the calcium volume and ratio (r = 0.69 and 0.76 respectively; p <0.001). A logarithmic curvilinear model proved to be the best fit to the correlation. A calcium volume of 480 mm(3) showed sensitivity and specificity of 0.76 and 0.83, respectively, for a diagnosis of severe AS, while a calcium ratio of 0.37 yielded sensitivity and specificity of 0.82 and 0.94, respectively. Conclusion: A radiological estimation of calcium amount by volume, and its proportion to the total valve volume, were shown to serve as good predictive parameters for severe AS. An estimation of the calcium volume may serve as a complementary measure for determining the severity of AS when aortic valve calcification is identified on CT imaging. The Journal of Heart Valve Disease 2012;21:320-327 C1 [Chitsaz, Sam; Gundiah, Namrata; Blackshear, Charlie; Tegegn, Nebiyu; Yan, Kimberly S.; Azadani, Ali N.; Tseng, Elaine E.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Chitsaz, Sam; Gundiah, Namrata; Blackshear, Charlie; Tegegn, Nebiyu; Yan, Kimberly S.; Azadani, Ali N.; Tseng, Elaine E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Gundiah, Namrata] Indian Inst Sci, Dept Mech Engn, Bangalore 560012, Karnataka, India. [Hope, Michael] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. RP Tseng, EE (reprint author), UCSF Med Ctr, 500 Parnassus Ave,Suite W405,Box 0118, San Francisco, CA 94143 USA. EM elaine.tseng@ucsfmedctr.org RI Chitsaz, Sam/C-4586-2008 NR 21 TC 4 Z9 4 U1 1 U2 4 PU I C R PUBLISHERS PI NORTHWOOD PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD HA6 2ET, ENGLAND SN 0966-8519 J9 J HEART VALVE DIS JI J. Heart Valve Dis. PD MAY PY 2012 VL 21 IS 3 BP 320 EP 327 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 977OY UT WOS:000306675500008 PM 22808832 ER PT J AU Littman, AJ Boyko, EJ McDonell, MB Fihn, SD AF Littman, Alyson J. Boyko, Edward J. McDonell, Mary B. Fihn, Stephan D. TI Evaluation of a Weight Management Program for Veterans SO PREVENTING CHRONIC DISEASE LA English DT Article ID OBESITY; INTERVENTIONS; PREVALENCE; FACILITIES; ADULTS AB Introduction To improve the health of overweight and obese veterans, the Department of Veterans Affairs (VA) developed the MOVE! Weight Management Program for Veterans. The aim of this evaluation was to assess its reach and effectiveness. Methods We extracted data on program involvement, demographics, medical conditions, and outcomes from VA administrative databases in 4 Western states. Eligibility criteria for MOVE! were being younger than 7 0 years and having a body mass index (BMI, in kg/m(2)) of at least 30.0, or 25.0 to 29.9 with an obesity-related condition. To evaluate reach, we estimated the percentage of eligible veterans who participated in the program and their representativeness. To evaluate effectiveness, we estimated changes in weight and BMI using multivariable linear regression. Results Less than 5% of eligible veterans participated, of whom half had only a single encounter. Likelihood of participation was greater in women, those with a higher BMI, and those with more primary care visits, sleep apnea, or a mental health condition. Likelihood of participation was lower among those who were younger than 5 5 (vs 55-64), widowed, current smokers, and residing farther from the medical center (>= 3 0 vs <30 miles). At 6- and 12-month follow-up, participants lost an average of 1.3 lb (95% confidence interval [CI], -2.6 to -0.02 lb) and 0.9 lb (95% CI, -2.0 to 0.1 lb) more than nonparticipants, after covariate adjustment. More intensive treatment (>= 6 encounters) was associated with greater weight loss at 12 months (-3.7 lb; 95% CI, -5.1 to -2.3 lb). Conclusion Few eligible patients participated in the program during the study period, and overall estimates of effectiveness were low. C1 [Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [McDonell, Mary B.] Off Analyt & Business Intelligence, VHA Off Informat & Analyt, Seattle, WA USA. [Boyko, Edward J.; Fihn, Stephan D.] Univ Washington, Dept Med, Seattle, WA USA. [Littman, Alyson J.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Littman, AJ (reprint author), VA Puget Sound Hlth Care Syst 152E, Seattle Epidemiol Res & Informat Ctr, 1100 Ol Way,Ste 1400, Seattle, WA 98101 USA. EM alyson@u.washington.edu FU Quality Enhancement Research Initiative [RRP-07-279]; Cooperative Studies Program; VA Puget Sound Health Care System, Department of Veterans Affairs; VA Rehabilitation Research and Development Career Development Award [6982] FX This study was supported in part by the Quality Enhancement Research Initiative (RRP-07-279), the Cooperative Studies Program, and VA Puget Sound Health Care System, Department of Veterans Affairs. Dr Littman was supported by a VA Rehabilitation Research and Development Career Development Award (#6982). Dr Leila Kahwati provided valuable feedback on program components, study analysis, and interpretation. NR 19 TC 7 Z9 8 U1 0 U2 3 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD MAY PY 2012 VL 9 AR 110267 DI 10.5888/pcd9.110267 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 977HU UT WOS:000306648100007 ER PT J AU Morgenroth, DC Gellhorn, AC Suri, P AF Morgenroth, David C. Gellhorn, Alfred C. Suri, Pradeep TI Osteoarthritis in the Disabled Population: A Mechanical Perspective SO PM&R LA English DT Article ID COMPARTMENT KNEE OSTEOARTHRITIS; TRANS-TIBIAL AMPUTATION; BONE-MINERAL DENSITY; TO-STEP TRANSITIONS; REACTION FORCE DATA; SPINAL-CORD-INJURY; LOW-BACK-PAIN; HUMAN WALKING; PROSTHETIC FEET; AMPUTEE GAIT AB Primary disabling conditions, such as amputation, not only limit mobility, but also predispose individuals to secondary musculoskeletal impairments, such as osteoarthritis (OA) of the intact limb joints, that can result in additive disability. Altered gait biomechanics that cause increased loading of the intact limb have been suggested as a cause of the increased prevalence of intact limb knee and hip osteoarthritis in this population. Optimizing socket fit and prosthetic alignment, as well as developing and prescribing prosthetic feet with improved push-off characteristics, can lead to reduced asymmetric loading of the intact limb and therefore are potential strategies to prevent and treat osteoarthritis in the amputee population. Research on disabled populations associated with altered biomechanics offers an opportunity to focus on the mechanical risk factors associated with this condition. Continued research into the causes of secondary disability and the development of preventive strategies are critical to enable optimal rehabilitation practices to maximize function and quality of life in patients with disabilities. PM R 2012;4:S20-S27 C1 [Morgenroth, David C.] Vet Affairs Puget Sound Healthcare Syst, RR&D Res Ctr, Seattle, WA USA. [Morgenroth, David C.; Gellhorn, Alfred C.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Suri, Pradeep] Vet Affairs Boston Healthcare Syst, Div Phys Med & Rehabil, Boston, MA USA. [Suri, Pradeep] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Suri, Pradeep] Spaulding Rehabil Hosp, Boston, MA USA. [Suri, Pradeep] New England Baptist Hosp, Boston, MA USA. RP Morgenroth, DC (reprint author), RCS 117,1660 S Columbian Way, Seattle, WA 98108 USA. EM dmorgen@uw.edu FU NIH [K12 HD001097] FX 8B, NIH (grant #K12 HD001097) NR 94 TC 32 Z9 34 U1 4 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD MAY PY 2012 VL 4 IS 5 SU 1 BP S20 EP S27 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 966YJ UT WOS:000305873000004 PM 22632698 ER PT J AU Mutluoglu, M Uzun, G Turhan, V Gorenek, L Ay, H Lipsky, BA AF Mutluoglu, Mesut Uzun, Gunalp Turhan, Vedat Gorenek, Levent Ay, Hakan Lipsky, Benjamin A. TI How reliable are cultures of specimens from superficial swabs compared with those of deep tissue in patients with diabetic foot ulcers? SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE Diabetic foot ulcer; Swab culture; Tissue biopsy; Wound microbiology ID RESISTANT STAPHYLOCOCCUS-AUREUS; INFECTION; MICROBIOLOGY; MANAGEMENT; CONSENSUS; ISCHEMIA; DISEASE; WOUNDS; BURDEN; BIOPSY AB Purpose: To assess the reliability of cultures of superficial swabs (SS) by comparing them with cultures of concomitantly obtained deep tissue (DT) specimens in patients with diabetic foot ulcers. Methods: We reviewed clinical and microbiological data from patients with diabetes who presented during a two-year period to our hyperbaric medicine center with a foot ulcer. We identified patients who had at least one concomitantly collected SS and DT pair of specimens sent for culture. Results: A total of 89 culture pairs were available from 54 eligible patients, 33 (61.1%) of whom were hospitalized. Wounds were infected in 47 (87.0%) of the patients and 28 (51.9%) patients had received antibiotic therapy within the previous month. Overall, 65(73%) of the SS and DT pairs had identical culture results, but in 11(16.9%) cases the cultures were sterile; thus, only 54 (69.2%) of the 78 culture-positive pairs had identical results. Compared with DT, SS cultures yielded >= 1 extra organism in 10 (11.2%) cases, missed at least one organism in 8 (9.0%), and were completely different in 6 (6.7%). When compared to DT culture results, SS cultures had a positive predictive value of 84.4%, negative predictive value of 44.0%, and overall accuracy of 73.0%. Conclusions: In patients with diabetic foot ulcers, results of specimens for culture taken by SS did not correlate well with those obtained by DT. This suggests that SS specimens may be less reliable for guiding antimicrobial therapy than DT specimens. (c) 2012 Elsevier Inc. All rights reserved. C1 [Mutluoglu, Mesut; Uzun, Gunalp; Ay, Hakan] GATA Haydarpasa Teaching Hosp, Dept Underwater & Hyperbar Med, TR-34668 Istanbul, Turkey. [Turhan, Vedat; Gorenek, Levent] GATA Haydarpasa Teaching Hosp, Dept Infect Dis & Clin Microbiol, TR-34668 Istanbul, Turkey. [Lipsky, Benjamin A.] Univ Washington, Primary Care Clin, VA Puget Sound, Seattle, WA 98108 USA. RP Mutluoglu, M (reprint author), Haydarpasa Teaching Hosp, Gulhane Mil Med Acad, Dept Underwater & Hyperbar Med, TR-34668 Istanbul, Turkey. EM drmutluoglu@gmail.com; balipsky@uw.edu RI mutluoglu, mesut/B-4451-2009 OI Lipsky, Benjamin A./0000-0001-9886-5114; Mutluoglu, Mesut/0000-0002-1112-5779; Uzun, Gunalp/0000-0002-8717-6230 NR 25 TC 14 Z9 15 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD MAY-JUN PY 2012 VL 26 IS 3 BP 225 EP 229 DI 10.1016/j.jdiacomp.2012.03.015 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 960BH UT WOS:000305362500013 PM 22520404 ER PT J AU Narayanavari, SA Sritharan, M Haake, DA Matsunaga, J AF Narayanavari, Suneel A. Sritharan, Manjula Haake, David A. Matsunaga, James TI Multiple leptospiral sphingomyelinases (or are there?) SO MICROBIOLOGY-SGM LA English DT Review ID BACILLUS-CEREUS SPHINGOMYELINASE; INTERROGANS SEROVAR HARDJO; STAPHYLOCOCCUS-AUREUS; BETA-TOXIN; NEUTRAL SPHINGOMYELINASE; BINDING PROTEIN; HEMOLYSIN; LAI; EXPRESSION; MATRIX AB Culture supernatants of leptospiral pathogens have long been known to haemolyse erythrocytes. This property is due, at least in part, to sphingomyelinase activity. Indeed, genome sequencing reveals that pathogenic Leptospira species are richly endowed with sphingomyelinase homologues: five genes have been annotated to encode sphingomyelinases in Leptospira interrogans. Such redundancy suggests that this class of genes is likely to benefit leptospiral pathogens in their interactions with the mammalian host. Surprisingly, sequence comparison with bacterial sphingomyelinases for which the crystal structures are known reveals that only one of the leptospiral homologues has the active site amino acid residues required for enzymic activity. Based on studies of other bacterial toxins, we propose that leptospiral sphingomyelinase homologues, irrespective of their catalytic activity, may possess additional molecular functions that benefit the spirochaete. Potential secretion pathways and roles in pathogenesis are discussed, including nutrient acquisition, dissemination, haemorrhage and immune evasion. Although leptospiral sphingomyelinase-like proteins are best known for their cytolytic properties, we believe that a better understanding of their biological role requires the examination of their sublytic properties as well. C1 [Narayanavari, Suneel A.; Sritharan, Manjula] Univ Hyderabad, Dept Anim Sci, Hyderabad 500134, Andhra Pradesh, India. [Haake, David A.] VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. [Haake, David A.; Matsunaga, James] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Haake, David A.] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. [Haake, David A.] Univ Calif Los Angeles, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA USA. [Matsunaga, James] VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. RP Narayanavari, SA (reprint author), Univ Hyderabad, Dept Anim Sci, Hyderabad 500134, Andhra Pradesh, India. EM leptolysin@gmail.com FU Public Health Service National Institute of Allergy and Infectious Diseases [AI-034431]; VA Medical Research Funds; United States India Educational Foundation (USIEF) FX S. A. N. would like to acknowledge the United States India Educational Foundation (USIEF) for financial support in the form of Fulbright Nehru Doctoral and Professional Research Fellowship. This study was supported by Public Health Service National Institute of Allergy and Infectious Diseases grant AI-034431 (to D. A. H.) and VA Medical Research Funds (to J. M. and D. A. H.). We thank Ben Adler (Monash University) for providing the sphingomyelinase sequences of Lept. interrogans serovars Manilae and Pomona. NR 60 TC 9 Z9 10 U1 0 U2 3 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD MAY PY 2012 VL 158 BP 1137 EP 1146 DI 10.1099/mic.0.057737-0 PN 5 PG 10 WC Microbiology SC Microbiology GA 960GL UT WOS:000305375900001 PM 22422753 ER PT J AU Furmaga, H Carreno, FR Frazer, A AF Furmaga, Havan Carreno, Flavia Regina Frazer, Alan TI Vagal Nerve Stimulation Rapidly Activates Brain-Derived Neurotrophic Factor Receptor TrkB in Rat Brain SO PLOS ONE LA English DT Article ID TREATMENT-RESISTANT DEPRESSION; HIPPOCAMPAL-NEURONS; GROWTH-FACTOR; SIGNAL-TRANSDUCTION; TYROSINE KINASE; FACTOR BDNF; SEROTONIN TRANSPORTER; ANTIDEPRESSANT ACTION; TRUNCATED RECEPTORS; GENE-EXPRESSION AB Background: Vagal nerve stimulation (VNS) has been approved for treatment-resistant depression. Many antidepressants increase expression of brain-derived neurotrophic factor (BDNF) in brain or activate, via phosphorylation, its receptor, TrkB. There have been no studies yet of whether VNS would also cause phosphorylation of TrkB. Methods: Western blot analysis was used to evaluate the phosphorylation status of TrkB in the hippocampus of rats administered VNS either acutely or chronically. Acute effects of VNS were compared with those caused by fluoxetine or desipramine (DMI) whereas its chronic effects were compared with those of sertraline or DMI. Results: All treatments, given either acutely or chronically, significantly elevated phosphorylation of tyrosines 705 and 816 on TrkB in the hippocampus. However, only VNS increased the phosphorylation of tyrosine 515, with both acute and chronic administration causing this effect. Pretreatment with K252a, a nonspecific tyrosine kinase inhibitor, blocked the phosphorylation caused by acute VNS at all three tyrosines. Downstream effectors of Y515, namely Akt and ERK, were also phosphorylated after acute treatment with VNS, whereas DMI did not cause this effect. Conclusion: VNS rapidly activates TrkB phosphorylation and this effect persists over time. VNS-induced phosphorylation of tyrosine 515 is distinct from the effect of standard antidepressant drugs. C1 [Furmaga, Havan; Carreno, Flavia Regina; Frazer, Alan] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Frazer, Alan] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Furmaga, H (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. EM frazer@uthscsa.edu FU National Institute of Mental Health grant [R01 MH082933]; Cyberonics, Inc. FX This work was supported by National Institute of Mental Health grant R01 MH082933 (Alan Frazer). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; Drs. Furmaga and Carreno have no competing interests to declare. Previously, Dr. Frazer received financial compensation as a consultant for Cyberonics, Inc. and had also obtained grant support from them for a preclinical study. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. NR 66 TC 28 Z9 29 U1 3 U2 14 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 MAY 1 PY 2012 VL 7 IS 5 AR e34844 DI 10.1371/journal.pone.0034844 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UN UT WOS:000305340700007 PM 22563458 ER PT J AU Palyo, SA Schopmeyer, KA McQuaid, JR AF Palyo, Sarah A. Schopmeyer, Kathryn A. McQuaid, John R. TI Tele-Pain Management: Use of Videoconferencing Technology in the Delivery of an Integrated Cognitive-Behavioral and Physical Therapy Group Intervention SO PSYCHOLOGICAL SERVICES LA English DT Article DE chronic pain; pain management; telehealth; depression AB Chronic pain has been recognized as a highly prevalent problem, and interdisciplinary treatments have been shown to be effective in the treatment of chronic pain. An integrated cognitive behavioral and physical therapy group protocol has been developed and then implemented at remote sites using videoconferencing technology to provide pain management for veterans. The treatment model is summarized and recommendations are made for addressing challenges in implementing this type of treatment via videoconferencing. C1 [Palyo, Sarah A.; McQuaid, John R.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA 94121 USA. [Palyo, Sarah A.; McQuaid, John R.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Schopmeyer, Kathryn A.] San Francisco VA Med Ctr, Neurol & Rehabil Serv, San Francisco, CA 94121 USA. RP Palyo, SA (reprint author), San Francisco VA Med Ctr, Mental Hlth Serv, 4150 Clement St,116B, San Francisco, CA 94121 USA. EM sarah.palyo@va.gov NR 0 TC 4 Z9 4 U1 0 U2 1 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 MAY PY 2012 VL 9 IS 2 SI SI BP 200 EP 202 DI 10.1037/a0025987 PG 3 WC Psychology, Clinical SC Psychology GA 957WO UT WOS:000305198000008 PM 22662734 ER PT J AU Barnwell, SVS Juretic, MA Hoerster, KD Van de Plasch, R AF Barnwell, Sara V. Smucker Juretic, Meghan A. Hoerster, Katherine D. Van de Plasch, Richard TI VA Puget Sound Telemental Health Service to Rural Veterans: A Growing Program SO PSYCHOLOGICAL SERVICES LA English DT Article DE telemental health; telepsychology; telehealth; veteran AB The VA Puget Sound Health Care System Telemental Health program connects veterans with psychologists, psychiatrists, and social workers via live clinical video teleconferencing. Providers deliver care to veterans in rural Veteran Affairs medical centers, community-based outpatient clinics and residences, and thus, increase access to specialty mental health care for rural and medically underserved veteran communities. C1 [Van de Plasch, Richard] Dept Vet Affairs Med Ctr, VISN Pacific NW Mental Illness Res Educ & Clin Ct, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. [Barnwell, Sara V. Smucker; Hoerster, Katherine D.; Van de Plasch, Richard] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Barnwell, SVS (reprint author), VA Puget Sound Hlth Care Syst, S-116-MHC,1660 S Columbian Way, Seattle, WA 98108 USA. EM ssmucker@post.harvard.edu NR 0 TC 7 Z9 7 U1 2 U2 3 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 MAY PY 2012 VL 9 IS 2 SI SI BP 209 EP 211 DI 10.1037/a0025999 PG 3 WC Psychology, Clinical SC Psychology GA 957WO UT WOS:000305198000011 PM 22662737 ER PT J AU Hayden, LJ Glynn, SM Hahn, TJ Randall, F Randolph, E AF Hayden, Lisa J. Glynn, Shirley M. Hahn, Theodore J. Randall, Frychettya Randolph, Eugenia TI The Use of Internet Technology for Psychoeducation and Support With Dementia Caregivers SO PSYCHOLOGICAL SERVICES LA English DT Article DE internet technology; Alzheimer's disease; dementia; caregiver support; randomized trial AB A large randomized trial evaluated the benefits of online education, support, and self-care promotion for caregivers of persons with dementia. Anecdotal reports from participants indicated enjoyment of the materials, convenient access from home, and support from professionals and other caregivers. A substantial number of screened caregivers experienced obstacles of access, cost, and time regarding use of technology. Telephone options are being explored, and future caregiving generations are expected to have increased exposure and willingness to use computer technology, such as the program described here. C1 [Hayden, Lisa J.; Randolph, Eugenia] VA Greater Los Angeles Healthcare Syst W Los Angl, Res Serv, Los Angeles, CA 90073 USA. [Glynn, Shirley M.; Randall, Frychettya] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Hahn, Theodore J.] VA Greater Los Angeles Healthcare Syst W Los Angl, Geriatr Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Hahn, Theodore J.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Hayden, LJ (reprint author), VA Greater Los Angeles Healthcare Syst W Los Angl, Res Serv, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM lisa.hayden@va.gov RI LOPES, LAIS/F-7380-2012 NR 1 TC 9 Z9 10 U1 5 U2 23 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 MAY PY 2012 VL 9 IS 2 SI SI BP 215 EP 218 DI 10.1037/a0027056 PG 4 WC Psychology, Clinical SC Psychology GA 957WO UT WOS:000305198000013 PM 22662739 ER PT J AU Wong, MH Chapin, OC Johnson, MD AF Wong, Mandi H. Chapin, Olivia C. Johnson, Meshell D. TI LPS-Stimulated Cytokine Production in Type I Cells Is Modulated by the Renin-Angiotensin System SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE cytokines; alveolar Type I cells; angiotensin Type 1 receptor; angiotensin-converting enzyme 2; lipopolysaccharide ID ALVEOLAR EPITHELIAL-CELLS; INDUCED LUNG INJURY; CONVERTING ENZYME-INHIBITOR; NECROSIS-FACTOR-ALPHA; PRIMARY CULTURE; AT(1) RECEPTOR; CXC CHEMOKINES; TNF-ALPHA; RAT MODEL; LIPOPOLYSACCHARIDE AB The alveolar epithelium serves as a barrier to the entry of potential respiratory pathogens. Alveolar Type II (TII) cells have immunomodulatory functions, but whether Type I (TI) cells, which comprise approximately 95% of the alveolar epithelium, also play a role in immunity is unknown. Because the renin-angiotensin system (RAS) is emerging as an important mediator of inflammation, and angiotensin-converting enzyme 2 (ACE2), an element of the RAS, has been implicated in lung injury, we hypothesize that TI cells canproduce cytokines in response to LPS stimulation, and that this inflammation can be modulated by the RAS. Alveolar TI cells were isolated from adult Sprague-Dawley rat lungs that had been injured with an intratracheal instillation of LPS. PCR was performed to determine whether TI cells expressed transcripts for TNF-alpha, IL-6, or IL-1 beta at baseline and after lung injury. Immunocytochemical and protein analysis detected angiotensin II (Ang II) and ACE2, as well as angiotensin Type 1 receptor (AT1R) and Type 2 receptor (AT2R), in TI cells. To separate cell-specific responses, primary TI cells were isolated, cultured, and exposed to LPS, Ang II, or specific inhibitors of AT1R or AT2R. Cytokine production was assayed by ELISA. LPS stimulated the production of all cytokines, whereas ACE2 and losartan, an AT1R inhibitor, blocked elements of the LPS-induced cytokine response. Primary TI cells produce cytokines when treated with LPS, contain important components of the RAS, and can modulate LPS-induced cytokine production via the RAS, suggesting a role for TI cells in the innate immune response of 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. [Chapin, Olivia C.; Johnson, Meshell D.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Johnson, MD (reprint author), San Francisco VA Med Ctr, 4150 Clement St,111-D, San Francisco, CA 94121 USA. EM meshell.johnson@ucsf.edu FU Department of Veterans Affairs; Northern California Institute for Research and Education; National Institutes of Health [HL088025] FX This work was supported by grants from the Department of Veterans Affairs and the Northern California Institute for Research and Education, and by grant HL088025 from the National Institutes of Health (M.D.J). NR 44 TC 11 Z9 13 U1 0 U2 7 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAY PY 2012 VL 46 IS 5 BP 641 EP 650 DI 10.1165/rcmb.2011-0289OC PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 956CX UT WOS:000305068500011 PM 22205632 ER PT J AU Shacka, JJ AF Shacka, John J. TI Mouse models of neuronal ceroid lipofuscinoses: Useful pre-clinical tools to delineate disease pathophysiology and validate therapeutics SO BRAIN RESEARCH BULLETIN LA English DT Review DE NCL; Lysosome; Autophagy; Cathepsin D; Apoptosis; Therapeutic ID PALMITOYL-PROTEIN THIOESTERASE-1; LYSOSOMAL STORAGE DISEASE; TRIPEPTIDYL-PEPTIDASE-I; CATHEPSIN-D DEFICIENCY; DEGENERATION MND MOUSE; CENTRAL-NERVOUS-SYSTEM; ENZYME-REPLACEMENT THERAPY; JUVENILE BATTEN-DISEASE; CELL-DEATH PATHWAYS; LATE INFANTILE NCL AB The neuronal ceroid lipofuscinoses (NCL, also known as Batten disease) is a devastating neurodegenerative diseases caused by mutations in either soluble enzymes or membrane-associated structural proteins that result in lysosome dysfunction. Different forms of NCL were defined initially by age of onset, affected population and/or type of storage material but collectively represent the most prevalent pediatric hereditary neurovisceral storage disorder. Specific gene mutations are now known for each subclass of NCL in humans that now largely define the disease: cathepsin D (CTSD) for congenital (CLN10 form); palmitoyl protein thioesterase 1 (PPT1) for infantile (CLN1 form); tripeptidyl peptidase 1 (TPP1) for classic late infantile (CLN2 form); variant late infantile-CLN5, CLN6 or CLN8 for variant late infantile forms; and CLN3 for juvenile (CLN3 form). Several mouse models of NCL have been developed, or in some cases exist sporadically, that exhibit mutations producing a progressive neurodegenerative phenotype similar to that observed in human NCL The study of these mouse models of NCL has dramatically advanced our knowledge of NCL pathophysiology and in some cases has helped delineate the function of proteins mutated in human NCL In addition, NCL mutant mice have been tested for several different therapeutic approaches and as such they have become important pre-clinical models for validating treatment options. In this review we will assess the current state of mouse models of NCL with regards to their unique pathophysiology and how these mice have helped investigators achieve a better understanding of human NCL disease and therapy. This article is part of a Special Issue entitled 'Mose Models'. Published by Elsevier Inc. C1 [Shacka, John J.] Univ Alabama Birmingham, Dept Pathol, Div Neuropathol, Birmingham, AL 35294 USA. [Shacka, John J.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Shacka, JJ (reprint author), Univ Alabama Birmingham, Dept Pathol, Div Neuropathol, Birmingham, AL 35294 USA. EM shacka@uab.edu RI di Ronza, Alberto/H-7674-2016 OI di Ronza, Alberto/0000-0002-9813-5143 FU VA Merit Review Award [1 I01 BX000957-01] FX I wish to thank Rhonda Carr and Barry Bailey for expert technical assistance, and to Kathryn Davidson for expert technical support in preparation of this manuscript. I wish to also thank the UAB Neuroscience Molecular Detection Core (P30 NS47466; Kevin Roth, MD, PhD, Director; Terry Lewis, Technical Director) for their help in preparation of this manuscript. Dr. Shacka is supported by a VA Merit Review Award (1 I01 BX000957-01). NR 171 TC 23 Z9 23 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD MAY 1 PY 2012 VL 88 IS 1 SI SI BP 43 EP 57 DI 10.1016/j.brainresbull.2012.03.003 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 950EB UT WOS:000304631300005 PM 22502604 ER PT J AU Piette, EW Werth, VP AF Piette, Evan W. Werth, Victoria P. TI Dapsone in the Management of Autoimmune Bullous Diseases SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Article DE Dapsone; Autoimmune bullous disease; Review ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; DERMATITIS-HERPETIFORMIS; ACQUISITA; PEMPHIGUS; DIAGNOSIS; ERUPTION; COLCHICINE; DERMATOSIS; THERAPY; WOMAN AB Dapsone is used in the treatment of autoimmune bullous diseases (AIBD), a group of disorders resulting from autoimmunity directed against basement membrane and/or intercellular adhesion molecules on cutaneous and mucosal surfaces. This review summarizes the limited published data evaluating dapsone as a therapy for AIBD. C1 [Piette, Evan W.; Werth, Victoria P.] Perelman Ctr Adv Med, Dept Dermatol, Philadelphia, PA 19104 USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Div Dermatol, Philadelphia, PA 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 National Institutes of Health [NIH K24-AR 02207] FX Funding: National Institutes of Health, including NIH K24-AR 02207 (V.P.W.). NR 41 TC 9 Z9 9 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD MAY PY 2012 VL 32 IS 2 BP 317 EP + DI 10.1016/j.iac.2012.04.011 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 955RP UT WOS:000305038900013 PM 22560144 ER PT J AU Drager, KK du Sac, P AF Drager, Kristin K. du Sac, Prairie TI IMPROVING PATIENT OUTCOMES WITH COMPRESSION-ONLY CPR: WILL BYSTANDER CPR RATES IMPROVE? SO JOURNAL OF EMERGENCY NURSING LA English DT Article ID HOSPITAL CARDIAC-ARREST; CARDIOPULMONARY-RESUSCITATION; CHEST COMPRESSION; SURVIVAL C1 [Drager, Kristin K.] William S Middleton Mem Vet Adm Med Ctr, Emergency Dept, Madison, WI USA. [Drager, Kristin K.] William S Middleton Mem Vet Adm Med Ctr, ACLS, Madison, WI USA. [Drager, Kristin K.] St Xavier Univ, Clin Nurse Leader Program, Chicago, IL USA. RP Drager, KK (reprint author), William S Middleton Mem Vet Adm Med Ctr, Emergency Dept, Madison, WI USA. EM Kristin.Drager@va.gov NR 10 TC 2 Z9 2 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-1767 J9 J EMERG NURS JI J. Emerg. Nurs. PD MAY PY 2012 VL 38 IS 3 BP 234 EP 238 DI 10.1016/j.jen.2011.02.008 PG 5 WC Emergency Medicine; Nursing SC Emergency Medicine; Nursing GA 953FN UT WOS:000304852400009 PM 21514650 ER PT J AU Pena, A Estrada, CA Soniat, D Taylor, B Burton, M AF Pena, Adolfo Estrada, Carlos A. Soniat, Debbie Taylor, Benjamin Burton, Michael TI Nominal group technique: A brainstorming tool for identifying areas to improve pain management in hospitalized patients SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID PRODUCTIVITY LOSS; CARE AB BACKGROUND: Pain management in hospitalized patients remains a priority area for improvement; effective strategies for consensus development are needed to prioritize interventions. OBJECTIVE: To identify challenges, barriers, and perspectives of healthcare providers in managing pain among hospitalized patients. DESIGN: Qualitative and quantitative group consensus using a brainstorming technique for quality improvementthe nominal group technique (NGT). SETTING: One medical, 1 medical-surgical, and 1 surgical hospital unit at a large academic medical center. PARTICIPANTS: Nurses, resident physicians, patient care technicians, and unit clerks. MEASUREMENTS: Responses and ranking to the NGT question: What causes uncontrolled pain in your unit? RESULTS: Twenty-seven health workers generated a total of 94 ideas. The ideas perceived contributing to a suboptimal pain control were grouped as system factors (timeliness, n = 18 ideas; communication, n = 11; pain assessment, n = 8), human factors (knowledge and experience, n = 16; provider bias, n = 8; patient factors, n = 19), and interface of system and human factors (standardization, n = 14). Knowledge, timeliness, provider bias, and patient factors were the top ranked themes. CONCLUSIONS: Knowledge and timeliness are considered main priorities to improve pain control. NGT is an efficient tool for identifying general and context-specific priority areas for quality improvement; teams of healthcare providers should consider using NGT to address their own challenges and barriers. Journal of Hospital Medicine 2012; (c) 2011 Society of Hospital Medicine C1 [Estrada, Carlos A.] Univ Alabama Birmingham, Birmingham Vet Affair Med Ctr, Vet Affair Natl Qual Scholars Program, Birmingham, AL 35294 USA. [Pena, Adolfo] St Joseph Hosp, Sect Hosp Med, London, KY USA. [Estrada, Carlos A.; Soniat, Debbie; Taylor, Benjamin] Univ Alabama Birmingham, Div Gen Internal Med, Birmingham, AL USA. [Estrada, Carlos A.; Soniat, Debbie; Taylor, Benjamin] Univ Hosp, Birmingham, AL USA. [Burton, Michael] Univ Texas SW Med Ctr Dallas, Div Gen Internal Med, Dallas, TX 75390 USA. RP Estrada, CA (reprint author), Univ Alabama Birmingham, Birmingham Vet Affair Med Ctr, Vet Affair Natl Qual Scholars Program, FOT 732,510 20th St S, Birmingham, AL 35294 USA. EM cestrada@uab.edu FU Veterans Affairs National Quality Scholars Program FX Drs. Pena, Burton, and Estrada were supported by the Veterans Affairs National Quality Scholars Program. The opinions expressed in this article are those of the authors alone and do not reflect the views of the Department of Veterans Affairs. NR 24 TC 11 Z9 11 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD MAY-JUN PY 2012 VL 7 IS 5 BP 416 EP 420 DI 10.1002/jhm.1900 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 953LA UT WOS:000304867600010 PM 22190453 ER PT J AU Dell'Italia, LJ AF Dell'Italia, Louis J. TI Anatomy and Physiology of the Right Ventricle SO CARDIOLOGY CLINICS LA English DT Article DE Right ventricle; Anatomy; Physiology ID CANINE RIGHT VENTRICLE; PRESSURE-VOLUME RELATIONSHIP; PULMONARY ARTERIAL SYSTEM; TIME-VARYING ELASTANCE; MYOCARDIAL BLOOD-FLOW; RIGHT ATRIAL PRESSURE; PULSE WAVE VELOCITY; OPEN-CHEST DOGS; OXYGEN-METABOLISM; POSTEXTRASYSTOLIC POTENTIATION AB Under normal baseline conditions the unique anatomy, myocardial ultrastructure, and coronary physiology of the right ventricle (RV) reflect a high-volume low-pressure pump. Early work described the RV as a passive conduit with minimal pumping capability. It is now appreciated that through a mechanism of ventricular interdependence, RV systolic function and diastolic load are extremely important in the prognosis and treatment of congestive heart failure, cardiac transplantation, pulmonary hypertension, congenital heart disease, and left ventricle assist devices. Magnetic resonance imaging with three-dimensional analysis has shown the complex geometry of the RV and the interaction of both ventricles within the pericardium. C1 Birmingham VA Med Ctr, Div Cardiovasc Dis, Birmingham, AL 35294 USA. RP Dell'Italia, LJ (reprint author), Birmingham VA Med Ctr, Div Cardiovasc Dis, Birmingham, AL 35294 USA. EM loudell@uab.edu NR 135 TC 24 Z9 27 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8651 J9 CARDIOL CLIN JI Cardiol. Clin. PD MAY PY 2012 VL 30 IS 2 BP 167 EP + DI 10.1016/j.cc1.2012.03.009 PG 22 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 949JN UT WOS:000304572600004 PM 22548810 ER PT J AU Marcum, ZA Gellad, WF AF Marcum, Zachary A. Gellad, Walid F. TI Medication Adherence to Multidrug Regimens SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Medication; Adherence; Polypharmacy; Elderly; Geriatric ID PRIMARY-CARE PATIENTS; OLDER-ADULTS; PREDICTIVE-VALIDITY; ELDERLY-PATIENTS; BLOOD-PRESSURE; POLYPHARMACY; HEALTH; NONADHERENCE; PERSISTENCE; COST AB Polypharmacy and medication adherence present a unique challenge for the older adult, their caregiver(s), and the health care team. There appears to be an association in the literature between polypharmacy and poorer medication adherence in older adults. However, the heterogeneity of how adherence is defined in the literature limits the certainty of this conclusion. Nonetheless, improving medication adherence to maximize the therapeutic benefit of pharmacotherapy remains a cornerstone of geriatric care. We discuss strategies for limiting polypharmacy and improving adherence and suggest ideas for future research focused on identifying and translating safe and effective interventions to improve adherence into routine clinical practice. C1 [Gellad, Walid F.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15206 USA. [Marcum, Zachary A.] Univ Pittsburgh, Sch Med, Dept Med Geriatr, Pittsburgh, PA 15213 USA. [Gellad, Walid F.] Univ Pittsburgh, Sch Med, Dept Med Gen Med, Pittsburgh, PA 15213 USA. [Gellad, Walid F.] RAND Hlth, Pittsburgh, PA 15213 USA. RP Gellad, WF (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM Walid.gellad@va.gov FU National Institute on Aging [P30AG024827]; VA Career Development Award [09-207] FX Dr Marcum is supported by a National Institute on Aging grant (P30AG024827), and Dr Gellad is supported by a VA Career Development Award (09-207). NR 44 TC 26 Z9 28 U1 1 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 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD MAY PY 2012 VL 28 IS 2 BP 287 EP + DI 10.1016/j.cger.2012.01.008 PG 15 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 949JJ UT WOS:000304572200010 PM 22500544 ER PT J AU Barnett, B Ciocca, M Goenka, R Barnett, L Wu, JM Laufer, T Burkhardt, J Cancro, M Reiner, S AF Barnett, Burton Ciocca, Maria Goenka, Radhika Barnett, Lisa Wu, Junmin Laufer, Terri Burkhardt, Janis Cancro, Michael Reiner, Steven TI Asymmetric division of germinal center B cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Barnett, Burton; Ciocca, Maria; Barnett, Lisa; Wu, Junmin; Laufer, Terri; Burkhardt, Janis; Reiner, Steven] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Barnett, Burton; Ciocca, Maria; Wu, Junmin; Reiner, Steven] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Goenka, Radhika; Cancro, Michael] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Barnett, Burton; Ciocca, Maria; Barnett, Lisa; Wu, Junmin; Laufer, Terri; Burkhardt, Janis] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Laufer, Terri] Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Burkhardt, Janis] Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Reiner, Steven] Columbia Univ Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10032 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700669 ER PT J AU Ding, YN Hsu, HC Druey, K Wu, Q Li, J Yang, PA Zajac, A Mountz, J AF Ding, Yanna Hsu, Hui-Chen Druey, Kirk Wu, Qi Li, Jun Yang, PingAr Zajac, Allan Mountz, John TI IL-17-induced Rgs16 expression is essential for follicular T helper cell localization in the germinal centers of autoimmune BXD2 mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Ding, Yanna; Hsu, Hui-Chen; Wu, Qi; Li, Jun; Yang, PingAr; Zajac, Allan; Mountz, John] Univ Alabama Birmingham, Birmingham, AL USA. [Druey, Kirk] NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. [Mountz, John] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701305 ER PT J AU Li, H Hsu, HC Li, J Yang, PA Wu, Q Cua, D Oukka, M Mountz, J AF Li, Hao Hsu, Hui-Chen Li, Jun Yang, PingAr Wu, Qi Cua, Daniel Oukka, Mohamed Mountz, John TI IL-23 induces IRF5 and polarizes inflammatory M1 macrophages to promote inflammation in a mouse model of arthritis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Li, Hao; Hsu, Hui-Chen; Li, Jun; Yang, PingAr; Wu, Qi; Mountz, John] Univ Alabama Birmingham, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Mountz, John] Birmingham VA Med Ctr, Birmingham, AL USA. [Cua, Daniel] Merck Res Labs, Merck Res Lab, Palo Alto, CA USA. [Oukka, Mohamed] Univ Washington, Seattle Childrens Res Inst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659702083 ER PT J AU Li, H Hsu, HC Li, J Yang, P Wu, Q Cua, D Oukka, M Mountz, J AF Li, Hao Hsu, Hui-Chen Li, Jun Yang, PingAr Wu, Qi Cua, Daniel Oukka, Mohamed Mountz, John TI IL-23 inhibits autoimmunity by facilitating clearance of apoptotic bodies in the marginal zone SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Li, Hao; Hsu, Hui-Chen; Li, Jun; Yang, PingAr; Wu, Qi; Mountz, John] Univ Alabama Birmingham, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Mountz, John] Birmingham VA Med Ctr, Birmingham, AL USA. [Cua, Daniel] Merck Res Lab, Palo Alto, CA USA. [Oukka, Mohamed] Univ Washington, Seattle Childrens Res Inst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659702062 ER PT J AU Li, J Hsu, HC Yang, PA Wu, Q Li, H Spalding, D Chatham, W Kimberly, R Bridges, S Mountz, J AF Li, Jun Hsu, Hui-Chen Yang, PingAr Wu, Qi Li, Hao Spalding, David Chatham, W. Kimberly, Robert Bridges, S. Mountz, John TI Death Receptor 5 (DR5) marks the highly pathogenic interacting GM-CSF+ T helper cells and IL-23(+) macrophages rendering it as an attractive therapeutic target of autoimmunity SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Li, Jun; Hsu, Hui-Chen; Yang, PingAr; Wu, Qi; Li, Hao; Spalding, David; Chatham, W.; Kimberly, Robert; Bridges, S.; Mountz, John] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Hsu, Hui-Chen; Yang, PingAr; Mountz, John] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700272 ER PT J AU Mountz, J Wang, J New, J Yang, P Wu, Q Druey, K Hsu, HC AF Mountz, John Wang, John New, James Yang, PingAr Wu, Qi Druey, Kirk Hsu, Hui-Chen TI IL-17-induced Regulator of G-protein Signaling orchestrates germinal center kinetics in the onset of autoimmunity in BXD2 mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Mountz, John; Wang, John; New, James; Yang, PingAr; Wu, Qi; Hsu, Hui-Chen] Univ Alabama Birmingham, Birmingham, AL USA. [Mountz, John] Birmingham VA Med Ctr, Birmingham, AL USA. [Druey, Kirk] NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701457 ER PT J AU Paintlia, M Paintlia, A Singh, A Singh, I AF Paintlia, Manjeet Paintlia, Ajaib Singh, Avtar Singh, Inderjit TI Endogenous S-Nitrosothiol Induced hypertrophic Astrogliosis has potential to maintain CNS homeostasis under pathological Conditions SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Paintlia, Manjeet; Paintlia, Ajaib; Singh, Avtar; Singh, Inderjit] MUSC, Charleston, SC USA. [Singh, Avtar] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700556 ER PT J AU Zhang, X Suzuki, E Karam, E Williams, S Gikeson, G AF Zhang, Xian Suzuki, Eiji Karam, Eva Williams, Sarah Gikeson, Gary TI Fli-1 transcription factor directly regulates expression of inflammatory chemokine MCP-1 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Zhang, Xian; Suzuki, Eiji; Karam, Eva; Williams, Sarah; Gikeson, Gary] Med Univ S Carolina, Charleston, SC 29425 USA. [Zhang, Xian; Gikeson, Gary] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700113 ER PT J AU Li, X Priest, RA Woodward, WJ Siddiqui, F Beer, TM Garzotto, MG Rooney, WD Springer, CS AF Li, Xin Priest, Ryan A. Woodward, William J. Siddiqui, Faisal Beer, Tomasz M. Garzotto, Mark G. Rooney, William D. Springer, Charles S., Jr. TI Cell membrane water exchange effects in prostate DCE-MRI SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Dynamic-Contrast-Enhanced; Water exchange; Contrast reagent; Prostate cancer ID CONTRAST-ENHANCED-MRI; CR BOLUS-TRACKING; SHUTTER-SPEED; IN-VIVO; CANCER; BENIGN; DIFFERENTIATION; TISSUES; MUSCLE; NMR AB Prostate Dynamic-Contrast-Enhanced (DCE) MRI often exhibits fast and extensive global contrast reagent (CR) extravasation - measured by K-trans, a pharmacokinetic parameter proportional to its rate. This implies that the CR concentration [CR] is high in the extracellular, extravascular space (EES) during a large portion of the DCE-MRI study. Since CR is detected indirectly, through water proton signal change, the effects of equilibrium transcytolemmal water exchange may be significant in the data and thus should be admitted in DCE-MRI pharmacokinetic modeling. The implications for parameter values were investigated through simulations, and analyses of actual prostate data, with different models. Model parameter correlation and precision were also explored. A near-optimal version of the exchange-sensitized model was found. Our results indicate that Delta K-trans (the K-trans difference returned by this version and a model assuming exchange to be effectively infinitely fast) may be a very useful biomarker for discriminating malignant from benign prostate tissue. Using an exchange-sensitized model, we find that the mean intracellular water lifetime (tau(i)) - an exchange measure - can be meaningfully mapped for the prostate. Our results show prostate glandular zone differences in tau(i) values. (C) 2012 Elsevier Inc. All rights reserved. C1 [Li, Xin; Woodward, William J.; Rooney, William D.; Springer, Charles S., Jr.] Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, WM Keck Fdn High Field MRI Lab, Portland, OR 97239 USA. [Priest, Ryan A.; Siddiqui, Faisal] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97239 USA. [Priest, Ryan A.; Siddiqui, Faisal] Oregon Hlth & Sci Univ, Dept Radiol, Portland, OR 97239 USA. [Beer, Tomasz M.] Oregon Hlth & Sci Univ, Dept Hematol Oncol, Portland, OR 97239 USA. [Garzotto, Mark G.] Oregon Hlth & Sci Univ, Dept Urol, Portland, OR 97239 USA. [Beer, Tomasz M.; Springer, Charles S., Jr.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. [Garzotto, Mark G.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Li, X (reprint author), Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, WM Keck Fdn High Field MRI Lab, Mail Code L452, Portland, OR 97239 USA. EM lxin@ohsu.edu OI Springer, Charles/0000-0002-5966-2135 FU Medical Research Foundation of Oregon; NIH [R01-EB00422, R01-NS40801, UL1RR024140-04S1] FX Grant Support: Medical Research Foundation of Oregon (XL), NIH: R01-EB00422 (CSS), R01-NS40801 (CSS,WDR), computational support provided by an administrative supplement NIH UL1RR024140-04S1, and RSNA Research and Education Foundation: Research Medical Student Grant #RMS0801 (FS). We thank Dr. Charles Thomas for continued support and encouragement. NR 32 TC 10 Z9 10 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD MAY PY 2012 VL 218 BP 77 EP 85 DI 10.1016/j.jmr.2012.03.019 PG 9 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 948GK UT WOS:000304491400012 PM 22578558 ER PT J AU Gennatas, ED Cholfin, JA Zhou, J Crawford, RK Sasaki, DA Karydas, A Boxer, AL Bonasera, SJ Rankin, KP Gorno-Tempini, ML Rosen, HJ Kramer, JH Weiner, M Miller, BL Seeley, WW AF Gennatas, E. D. Cholfin, J. A. Zhou, J. Crawford, R. K. Sasaki, D. A. Karydas, A. Boxer, A. L. Bonasera, S. J. Rankin, K. P. Gorno-Tempini, M. L. Rosen, H. J. Kramer, J. H. Weiner, M. Miller, B. L. Seeley, W. W. TI COMT Val(158)Met genotype influences neurodegeneration within dopamine-innervated brain structures SO NEUROLOGY LA English DT Article ID FRONTOTEMPORAL LOBAR DEGENERATION; ALZHEIMERS-DISEASE; MESSENGER-RNA; DEMENTIA; SCHIZOPHRENIA; ATROPHY; POLYMORPHISM; PATTERNS; RISK AB Objective: We sought to determine whether the Val(158)Met polymorphism in the catechol-O-methyltransferase (COMT) gene influences neurodegeneration within dopamine-innervated brain regions. Methods: A total of 252 subjects, including healthy controls and patients with Alzheimer disease, behavioral variant frontotemporal dementia, and semantic dementia, underwent COMT genotyping and structural MRI. Results: Whole-brain voxel-wise regression analyses revealed that COMT Val(158)Met Val allele dosage, known to produce a dose-dependent decrease in synaptic dopamine (DA) availability, correlated with decreased gray matter in the region of the ventral tegmental area (VTA), ventromedial prefrontal cortex, bilateral dorsal midinsula, left dorsolateral prefrontal cortex, and right ventral striatum. Unexpectedly, patients carrying a Met allele showed greater VTA volumes than age-matched controls. Gray matter intensities within COMT-related brain regions correlated with cognitive and behavioral deficits. Conclusions: The results are consistent with the hypothesis that increased synaptic DA catabolism promotes neurodegeneration within DA-innervated brain regions. Neurology (R) 2012;78:1663-1669 C1 [Gennatas, E. D.; Cholfin, J. A.; Zhou, J.; Crawford, R. K.; Sasaki, D. A.; Karydas, A.; Boxer, A. L.; Rankin, K. P.; Gorno-Tempini, M. L.; Rosen, H. J.; Kramer, J. H.; Miller, B. L.; Seeley, W. W.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94122 USA. [Bonasera, S. J.] Univ Nebraska Med Ctr, Dept Internal Med, Div Geriatr, Omaha, NE USA. [Weiner, M.] San Francisco Vet Adm Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. RP Seeley, WW (reprint author), Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94122 USA. EM wseeley@memory.ucsf.edu RI Gorno-Tempini, Maria Luisa/E-7203-2012 OI Bonasera, Stephen/0000-0001-6808-2821 FU National Institute of Aging [AG19724, AG1657303]; Larry L. Hillblom Foundation [2005/2T]; National Institute of Mental Health (NIMH) [K08 MH065938]; Stephen D. Bechtel Foundation FX Supported by grants from the National Institute of Aging (AG19724 and AG1657303 to B. L. M.), the Larry L. Hillblom Foundation (grant 2005/2T to W. W. S.), National Institute of Mental Health (NIMH grant K08 MH065938 to S.J.B.), and the Stephen D. Bechtel Foundation to S.J.B. NR 25 TC 13 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 2012 VL 78 IS 21 BP 1663 EP 1669 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 948UB UT WOS:000304527000011 PM 22573634 ER PT J AU Okonkwo, OC Xu, G Dowling, NM Bendlin, BB LaRue, A Hermann, BP Koscik, R Jonaitis, E Rowley, HA Carlsson, CM Asthana, S Sager, MA Johnson, SC AF Okonkwo, O. C. Xu, G. Dowling, N. M. Bendlin, B. B. LaRue, A. Hermann, B. P. Koscik, R. Jonaitis, E. Rowley, H. A. Carlsson, C. M. Asthana, S. Sager, M. A. Johnson, S. C. TI Family history of Alzheimer disease predicts hippocampal atrophy in healthy middle-aged adults SO NEUROLOGY LA English DT Article ID NORMAL INDIVIDUALS; MATERNAL HISTORY; TEMPORAL-LOBE; APOLIPOPROTEIN-E; GRAY-MATTER; BASE-LINE; VOLUME; CHILDREN; STATISTICS; TRIALS AB Objective: To evaluate the longitudinal influence of family history (FH) of Alzheimer disease (AD) and apolipoprotein E epsilon 4 allele (APOE4) on brain atrophy and cognitive decline over 4 years among asymptomatic middle-aged individuals. Methods: Participants were cognitively healthy adults with (FH+) (n = 60) and without (FH-) (n = 48) a FH of AD (mean age at baseline 54 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention. They underwent APOE genotyping, cognitive testing, and an MRI scan at baseline and 4 years later. A covariate-adjusted voxel-based analysis interrogated gray matter (GM) modulated probability maps at the 4-year follow-up visit as a function of FH and APOE4. We also examined the influence of parent of origin on GM atrophy. Parallel analyses investigated the effects of FH and APOE4 on cognitive decline. Results: Neither FH nor APOE4 had an effect on regional GM or cognition at baseline. Longitudinally, a FH x APOE4 interaction was found in the right posterior hippocampus, which was driven by a significant difference between the FH+ and FH- subjects who were APOE4-. In addition, a significant FH main effect was observed in the left posterior hippocampus. No significant APOE4 main effects were detected. Persons with a maternal history of AD were just as likely as those with a paternal history of AD to experience posterior hippocampal atrophy. There was no longitudinal decline in cognition within the cohort. Conclusion: Over a 4-year interval, asymptomatic middle-aged adults with FH of AD exhibit significant atrophy in the posterior hippocampi in the absence of measurable cognitive changes. This result provides further evidence that detectable disease-related neuroanatomic changes do occur early in the AD pathologic cascade. Neurology (R) 2012;78:1769-1776 C1 [Okonkwo, O. C.; Xu, G.; Bendlin, B. B.; Carlsson, C. M.; Asthana, S.; Johnson, S. C.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Okonkwo, O. C.; Xu, G.; Dowling, N. M.; Bendlin, B. B.; LaRue, A.; Hermann, B. P.; Koscik, R.; Jonaitis, E.; Rowley, H. A.; Carlsson, C. M.; Asthana, S.; Sager, M. A.; Johnson, S. C.] Univ Wisconsin, Sch Med, Alzheimers Dis Res Ctr, Madison, WI 53706 USA. [Okonkwo, O. C.; Xu, G.; Dowling, N. M.; Bendlin, B. B.; LaRue, A.; Hermann, B. P.; Koscik, R.; Jonaitis, E.; Rowley, H. A.; Carlsson, C. M.; Asthana, S.; Sager, M. A.; Johnson, S. C.] Univ Wisconsin, Sch Med, Wisconsin Alzheimers Inst, Madison, WI 53706 USA. [Dowling, N. M.] Univ Wisconsin, Sch Med, Dept Biostat & Med Informat, Madison, WI 53706 USA. RP Johnson, SC (reprint author), William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. EM scj@medicine.wisc.edu OI Bendlin, Barbara/0000-0002-0580-9875 FU NIA [AG021155, AG027161, P50-AG033514]; Veterans Administration [I01CX000165]; Clinical and Translational Science Award [UL1-RR025011]; Helen Bader Foundation; Northwestern Mutual Foundation; Extendicare Foundation; Clinical Center of the William S. Middleton Memorial Veterans Hospital, Madison, WI. FX Supported by NIA grants AG021155 (S.C.J.), AG027161 (M.A.S.), and P50-AG033514 (S.A.); by Veterans Administration Merit Review grant I01CX000165 (S.C.J.); and by a Clinical and Translational Science Award (UL1-RR025011) to the University of Wisconsin, Madison. Portions of this research were supported by the Helen Bader Foundation, Northwestern Mutual Foundation, Extendicare Foundation, and the Veterans Administration including facilities and resources at the Geriatric Research Education and Clinical Center of the William S. Middleton Memorial Veterans Hospital, Madison, WI. NR 39 TC 16 Z9 16 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 2012 VL 78 IS 22 BP 1769 EP 1776 DI 10.1212/WNL.0b013e3182583047 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 948UZ UT WOS:000304529600017 PM 22592366 ER PT J AU Khaled, S Gupta, KB Kucik, DF AF Khaled, Saman Gupta, Kiran B. Kucik, Dennis F. TI Ionizing Radiation Increases Adhesiveness of Human Aortic Endothelial Cells via a Chemokine-Dependent Mechanism SO RADIATION RESEARCH LA English DT Article ID ATOMIC-BOMB SURVIVORS; ADHESION MOLECULES; LEUKOCYTE ADHESION; AVIDITY REGULATION; P-SELECTIN; ATHEROSCLEROSIS; INFLAMMATION; MICE; DISEASE; EXPRESSION AB Exposure to radiation from a variety of sources is associated with increased risk of heart disease and stroke. Since radiation also induces inflammation, a possible mechanism is a change in the adhesiveness of vascular endothelial cells, triggering pro-atherogenic accumulation of leukocytes. To investigate this mechanism at the cellular level, the effect of X rays on adhesiveness of cultured human aortic endothelial cells (HAECs) was determined. HAECs were grown as monolayers and exposed to 0 to 30 Gy X rays, followed by measurement of adhesiveness under physiological shear stress using a flow chamber adhesion assay. Twenty-four hours after irradiation, HAEC adhesiveness was increased, with a peak effect at 15 Gy. Radiation had no significant effect on surface expression of the endothelial adhesion molecules ICAM-1 and VCAM-1. Antibody blockade of the leukocyte integrin receptors for ICAM-1 and VCAM-1, however, abolished the radiation-induced adhesiveness. Since these leukocyte integrins can be activated by chemokines presented on the endothelial cell surface, the effect of pertussis toxin (PTX), an inhibitor of chemokine-mediated integrin activation, was tested. PTX specifically inhibited radiation-induced adhesiveness, with no significant effect on nonirradiated cells. Therefore, radiation induces increased adhesiveness of aortic endothelial cells through chemokine-dependent signaling from endothelial cells to leukocytes, even in the absence of increased expression of the adhesion molecules involved. (C) 2012 by Radiation Research Society C1 [Khaled, Saman; Gupta, Kiran B.; Kucik, Dennis F.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Kucik, Dennis F.] Univ Alabama Birmingham, Dept Biomed Engn, Birmingham, AL 35294 USA. [Kucik, Dennis F.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Kucik, DF (reprint author), Univ Alabama Birmingham, Dept Pathol, 640A Kaul Bldg,720 S 20th St, Birmingham, AL 35294 USA. EM Kucik@uab.edu FU National Space Biomedical Research Institute through NASA [NCC 9-58] FX This work was supported by the National Space Biomedical Research Institute through NASA NCC 9-58. NR 37 TC 16 Z9 18 U1 0 U2 6 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD MAY PY 2012 VL 177 IS 5 BP 594 EP 601 DI 10.1667/RR2557.1 PG 8 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 948JD UT WOS:000304498600008 PM 22087741 ER PT J AU Braunstein, I Klein, R Okawa, J Werth, VP AF Braunstein, I. Klein, R. Okawa, J. Werth, V. P. TI The interferon-regulated gene signature is elevated in subacute cutaneous lupus erythematosus and discoid lupus erythematosus and correlates with the cutaneous lupus area and severity index score SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID DISEASE-ACTIVITY; EXPRESSION; RECRUITMENT; ASSOCIATION; LESIONS; CELLS AB Background There is increased expression of type I interferon (IFN)-regulated proteins in the blood and target tissues of patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). Patients with SLE have increased IFN-regulated gene expression pointing towards a possible underlying genetic defect. Objectives To determine expression levels of five type I IFN-regulated genes that are highly expressed in SLE in the peripheral blood of patients with CLE and to correlate the expression levels with cutaneous disease activity. Methods Peripheral blood was obtained from 10 healthy controls and 30 patients with CLE, including eight with concomitant SLE. Total RNA was extracted and reverse transcribed into complementary DNA. Gene expression levels were measured by real-time polymerase chain reaction. Gene expression was normalized to GAPDH, standardized to healthy controls and then summed to calculate an IFN score for each patient. Disease activity was assessed with the Cutaneous Lupus Area and Severity Index (CLASI). Results Patients with subacute CLE (SCLE) and discoid lupus erythematosus (DLE) had elevated IFN scores compared with healthy controls regardless of concomitant SLE (P < 0 01 with SLE and P < 0 05 without SLE). There was no difference between patients with tumid lupus erythematosus (TLE) and healthy controls. The IFN score correlated with CLASI scores (Spearman's rho = 0 55, P = 0 0017). Conclusions Patients with SCLE and DLE have an IFN signature, as seen in SLE. The level of gene expression correlates with cutaneous disease activity. These findings support a shared pathogenesis between SLE and some subtypes of CLE. C1 [Werth, V. P.] Philadelphia Vet Affairs Med Ctr, Dermatol Sect, Philadelphia, PA 19104 USA. Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Philadelphia Vet Affairs Med Ctr, Dermatol Sect, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; National Institutes of Health (NIH) [K24-AR 02207] FX The study was supported by a Merit Review Grant from the Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development and by the National Institutes of Health (NIH K24-AR 02207) to V.P.W. NR 13 TC 23 Z9 23 U1 0 U2 1 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 MAY PY 2012 VL 166 IS 5 BP 971 EP 975 DI 10.1111/j.1365-2133.2012.10825.x PG 5 WC Dermatology SC Dermatology GA 950PQ UT WOS:000304661600012 PM 22242767 ER PT J AU Osborn, CY Egede, LE AF Osborn, Chandra Y. Egede, Leonard E. TI The relationship between depressive symptoms and medication nonadherence in type 2 diabetes: the role of social support SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; CORONARY-HEART-DISEASE; GLYCEMIC CONTROL; RANDOMIZED-TRIAL; CARE MANAGEMENT; DOUBLE-BLIND; ADHERENCE; METAANALYSIS; MEDIATION; ASSOCIATION AB Objective: Medication adherence promotion interventions are needed that target modifiable behavioral factors contributing to the link between depressive symptoms and poor adherence to diabetes self-care behaviors. In an effort to identify what factors contribute to this link, we examined the role of social support as a mediator of the relationship between depressive symptoms and medication nonadherence. Method: We recruited 139 subjects with type 2 diabetes. Using an indirect effect test with bias-corrected (BC) bootstrapping, we tested whether depressive symptoms had an indirect effect on medication nonadherence through a lack of social support. Results: More depressive symptoms were associated with medication nonadherence (total effect=.06, P<.001), more depressive symptoms were associated with less social support (direct effect of the predictor on the mediator=.96, P=.02), and less social support was associated with medication nonadherence (direct effect of the mediator on the outcome=-.01, P<.01). While the relationship between more depressive symptoms and medication nonadherence persisted with social support in the predicted pathway, the degree of this relationship was partially explained by a relationship between more depressive symptoms and less social support (indirect effect=.01, 95% BC bootstrapped confidence interval of .0005 to .0325). Conclusion: Providing social support to patients with diabetes who have symptoms of depression may ameliorate some of the deleterious effects of depressive symptoms on medication nonadherence, but social support alone is not enough. (C) 2012 Elsevier Inc. All rights reserved. C1 Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Osborn, Chandra Y.] Vanderbilt Univ, Dept Med, Sch Med, Nashville, TN 37232 USA. [Osborn, Chandra Y.] Vanderbilt Univ, Dept Biomed Informat, Sch Med, Nashville, TN 37232 USA. [Osborn, Chandra Y.] Vanderbilt Univ, Vanderbilt Diabet Res & Training Ctr, Sch Med, Nashville, TN 37232 USA. [Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC 29401 USA. [Egede, Leonard E.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. EM egedel@musc.edu FU National Institutes of Health (NIH) [NIDDK K01 DK087894]; NTH [NIDDK K24 DK093699] FX Dr. Osborn is supported by a National Institutes of Health (NIH) Career Development Award (NIDDK K01 DK087894). Dr. Egede is supported by an NTH Career Development Award (NIDDK K24 DK093699). NR 41 TC 22 Z9 24 U1 3 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD MAY-JUN PY 2012 VL 34 IS 3 BP 249 EP 253 DI 10.1016/j.genhosppsych.2012.01.015 PG 5 WC Psychiatry SC Psychiatry GA 944XR UT WOS:000304237600006 PM 22401705 ER PT J AU Sher, L AF Sher, Leo TI Bipolar Psychopharmacotherapy: Caring for the Patient SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 [Sher, Leo] Mt Sinai Sch Med, New York, NY USA. [Sher, Leo] James J Peters Vet Adm Med Ctr, New York, NY USA. RP Sher, L (reprint author), Mt Sinai Sch Med, New York, NY USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD MAY PY 2012 VL 200 IS 5 BP 454 EP 454 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 946ET UT WOS:000304335000014 ER PT J AU Lipsky, BA Kuss, M Edmonds, M Reyzelman, A Sigal, F AF Lipsky, Benjamin A. Kuss, Michael Edmonds, Michael Reyzelman, Alexander Sigal, Felix TI Topical Application of a Gentamicin-Collagen Sponge Combined with Systemic Antibiotic Therapy for the Treatment of Diabetic Foot Infections of Moderate Severity A Randomized, Controlled, Multicenter Clinical Trial SO JOURNAL OF THE AMERICAN PODIATRIC MEDICAL ASSOCIATION LA English DT Article ID IN-VITRO ACTIVITY; RESISTANT STAPHYLOCOCCUS-AUREUS; CALCIUM-SULFATE PELLETS; ANTIMICROBIAL AGENTS; FLUOROQUINOLONES; MANAGEMENT; SYNERGY AB Background: The aim of this pilot study was to determine the safety and potential benefit of adding a topical gentamicin-collagen sponge to standard of care (systemic antibiotic therapy plus standard diabetic wound management) for treating diabetic foot infections of moderate severity. Methods: We randomized 56 patients with moderately infected diabetic foot ulcers in a 2:1 ratio to receive standard of care plus the gentamicin-collagen sponge (treatment group, n=38) or standard of care only (control group, n = 18) for up to 28 days of treatment. Investigators performed clinical, microbiological, and safety assessments at regularly scheduled intervals and collected pharmacokinetic samples from patients treated with the gentamicin-collagen sponge. Test of cure was clinically assessed 14 days after all antibiotic therapy was stopped. Results: On treatment day 7, we noted clinical cure in no treatment patients and three control patients (P=.017). However, for evaluable patients at the test-of-cure visit, the treatment group had a significantly higher proportion of patients with clinical cure than did the control group (22 of 22 [100.0%] versus 7 of 10 [70.0%]; P=.024). Patients in the treatment group also had a higher rate of eradication of baseline pathogens at all visits (P <=.038) and a reduced time to pathogen eradication (P<.001). Safety data were similar for both groups. Conclusions: Topical application of the gentamicin-collagen sponge seems safe and may improve clinical and microbiological outcomes of diabetic foot infections of moderate severity when combined with standard of care. These pilot data suggest that a larger trial of this treatment is warranted. (J Am Podiatr Med Assoc 102(3): 223-232, 2012) C1 [Lipsky, Benjamin A.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Sch Med, Seattle, WA 98116 USA. [Kuss, Michael] Premier Res Grp Ltd, Austin, TX USA. [Edmonds, Michael] Kings Coll Hosp London, London, England. [Reyzelman, Alexander] Clin Res Ctr, Castro Valley, CA USA. [Sigal, Felix] Pacific Clin Ctr, Los Angeles, CA USA. RP Lipsky, BA (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Sch Med, S-111-PCC,1660 S Columbian Way, Seattle, WA 98116 USA. EM balipsky@uw.edu OI Lipsky, Benjamin A./0000-0001-9886-5114 FU Innocoll Technologies Ltd. FX This study was funded in whole by Innocoll Technologies Ltd. NR 21 TC 16 Z9 19 U1 0 U2 7 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 MAY-JUN PY 2012 VL 102 IS 3 BP 223 EP 232 PG 10 WC Orthopedics SC Orthopedics GA 945OW UT WOS:000304286900007 PM 22659765 ER PT J AU Derose, SF Gabayan, GZ Chiu, VY Sun, BC AF Derose, Stephen F. Gabayan, Gelareh Z. Chiu, Vicki Y. Sun, Benjamin C. TI Patterns and Preexisting Risk Factors of 30-Day Mortality After a Primary Discharge Diagnosis of Syncope or Near Syncope SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID EMERGENCY ROOM PATIENTS; SHORT-TERM; PROSPECTIVE VALIDATION; EXTERNAL VALIDATION; SERIOUS OUTCOMES; PREDICT PATIENTS; FOLLOW-UP; RULE; STRATIFICATION; POPULATION AB Objectives: The risk of short-term mortality after an emergency department (ED) visit for syncope is poorly understood, resulting in prognostic uncertainty and frequent hospital admission. The authors determined patterns and risk factors for short-term mortality after a diagnosis of syncope or near syncope to aid in medical decision-making. Methods: A retrospective cohort study was performed of adult members of Kaiser Permanente Southern California seen at 11 EDs from 2002 to 2006 with a primary discharge diagnosis of syncope or near syncope (International Classification of Diseases, Ninth Revision [ICD-9] 780.2). The outcome was 30-day mortality. Proportional hazards time-to-event regression models were used to identify risk factors. Results: There were 22,189 participants with 23,951 ED visits, resulting in 307 deaths by 30 days. A relatively lower risk of death was reached within 2 weeks for ages 18 to 59 years, but not until 3 months or more for ages 60 and older. Preexisting comorbidities associated with increased mortality included heart failure (hazard ratio [HR] = 14.3 in ages 18 to 59 years, HR = 3.09 in ages 60 to 79 years, HR = 2.34 in ages 80 years plus; all p < 0.001), diabetes (HR = 1.49, p = 0.002), seizure (HR = 1.65, p = 0.016), and dementia (HR = 1.41, p = 0.034). If the index visit followed one or more visits for syncope in the previous 30 days, it was associated with increased mortality (HR = 1.86, p = 0.024). Absolute risk of death at 30 days was under 0.2% in those under 60 years without heart failure and more than 2.5% across all ages in those with heart failure. Conclusions: The low risk of death after an ED visit for syncope or near syncope in patients younger than 60 years old without heart failure may be helpful when deciding who to admit for inpatient evaluation. The presence of one or more comorbidities that predict death and a prior visit for syncope should be considered in clinical decisions and risk stratification tools for patients with syncope. Close clinical follow-up seems advisable in patients 60 years and older due to a prolonged risk of death. ACADEMIC EMERGENCY MEDICINE 2012; 19: 488-496 (C) 2012 by the Society for Academic Emergency Medicine C1 [Derose, Stephen F.; Chiu, Vicki Y.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA. [Gabayan, Gelareh Z.; Sun, Benjamin C.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Gabayan, Gelareh Z.; Sun, Benjamin C.] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Med, Los Angeles, CA USA. RP Derose, SF (reprint author), Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA. EM stephen.f.derose@kp.org FU American Geriatrics Society [20051687]; University of California, Los Angeles, National Institutes of Aging [AG 02-004]; UCLA Older Americans Independence Center, NIH/NIA [P30-AG028748]; Greater Los Angeles Veteran's Affairs Health Services Research and Development Fellowship FX This research was supported by grants from American Geriatrics Society Dennis Jahnigen Career Development Award (20051687, BCS) and University of California, Los Angeles, National Institutes of Aging K12 Mentored Clinical Scientist Development Program in Geriatrics (AG 02-004, BCS). Dr. Sun received support from the UCLA Older Americans Independence Center, NIH/NIA Grant P30-AG028748, and the content does not necessarily represent the official views of the National Institute on Aging or the National Institutes of Health.; We thank the Greater Los Angeles Veteran's Affairs Health Services Research and Development Fellowship for their support of Dr. Gabayan. We thank Robert Weiss, UCLA School of Public Health Professor of Biostatistics, for his helpful manuscript review. NR 47 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAY PY 2012 VL 19 IS 5 BP 488 EP 496 DI 10.1111/j.1553-2712.2012.01336.x PG 9 WC Emergency Medicine SC Emergency Medicine GA 943OI UT WOS:000304133300002 PM 22594351 ER PT J AU Craft, S AF Craft, Suzanne TI Insulin and Alzheimer Disease reply SO ARCHIVES OF NEUROLOGY LA English DT Letter C1 [Craft, Suzanne] Univ Washington, Sch Med, Vet Affairs Puget Sound Healthcare Syst, Seattle, WA 98108 USA. RP Craft, S (reprint author), Univ Washington, Sch Med S GRECC 182, Vet Affairs Puget Sound Healthcare Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM scraft@uw.edu NR 4 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 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 2012 VL 69 IS 5 BP 671 EP 671 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 941ZO UT WOS:000304009100022 ER PT J AU Sher, L AF Sher, Leo TI Educating health care professionals about suicide prevention SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Letter C1 [Sher, Leo] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Sher, Leo] James J Peters Vet Adm Med Ctr, New York, NY USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Leo.Sher@mssm.edu NR 5 TC 0 Z9 0 U1 1 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD MAY PY 2012 VL 46 IS 5 BP 481 EP 482 DI 10.1177/0004867411434722 PG 2 WC Psychiatry SC Psychiatry GA 944EI UT WOS:000304181700015 PM 22535300 ER PT J AU Yoo, SE Chen, LJ Na, R Liu, YH Rios, C Van Remmen, H Richardson, A Ran, QT AF Yoo, Si-Eun Chen, Liuji Na, Ren Liu, Yuhong Rios, Carmen Van Remmen, Holly Richardson, Arlan Ran, Qitao TI Gpx4 ablation in adult mice results in a lethal phenotype accompanied by neuronal loss in brain SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Gpx4; Knockout mice; Lipid peroxidation; Mitochondria; Neurodegeneration; Apoptosis; Oxidative stress ID HYDROPEROXIDE GLUTATHIONE-PEROXIDASE; OXIDATIVE STRESS; ALZHEIMERS-DISEASE; CYTOCHROME-C; SUPEROXIDE-PRODUCTION; LIPID-PEROXIDATION; INDUCED APOPTOSIS; CELL-DEATH; MOUSE; GLUTATHIONE-PEROXIDASE-4 AB Glutathione peroxidase 4 (Gpx4) is an antioxidant defense enzyme important in reducing hydroperoxides in membrane lipids and lipoproteins. Gpx4 is essential for survival of embryos and neonatal mice; however, whether Gpx4 is required for adult animals remains unclear. In this study, we generated a floxed Gpx4 mouse (Gpx4(f/f)) in which exons 2-4 of Gpx4 gene are flanked by loxP sites. We then cross-bred the Gpx4(f/f) mice with a tamoxifen (tam)-inducible Cre transgenic mouse (R26CreER mice) to obtain mice in which the Gpx4 gene could be ablated by tam administration (Gpx4(f/f)/Cre mice). After treatment with tam, adult Gpx4(f/f)/Cre mice (6-9 months of age) showed a significant reduction of Gpx4 levels (a 75-85% decrease) in tissues such as brain, liver, lung, and kidney. Tam-treated Gpx4(f/f)/Cre mice lost body weight and died within 2 weeks, indicating that Gpx4 is essential for survival of adult animals. Tam-treated Gpx4(f/f)/Cre mice exhibited increased mitochondrial damage, as evidenced by the elevated 4-hydroxylnonenal (4-HNE) level, decreased activities of electron transport chain complexes I and IV, and reduced ATP production in liver. Tam treatment also significantly elevated apoptosis in Gpx4(f/f)/Cre mice. Moreover, tam-treated Gpx4(f/f)/Cre mice showed neuronal loss in the hippocampus region and had increased astrogliosis. These data indicate that Gpx4 is essential for mitochondria integrity and survival of neurons in adult animals. Published by Elsevier Inc. C1 [Yoo, Si-Eun; Chen, Liuji; Na, Ren; Liu, Yuhong; Rios, Carmen; Van Remmen, Holly; Richardson, Arlan; Ran, Qitao] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Yoo, Si-Eun] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Chen, Liuji; Rios, Carmen; Van Remmen, Holly; Richardson, Arlan; Ran, Qitao] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Van Remmen, Holly; Richardson, Arlan; Ran, Qitao] S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX 78229 USA. RP Ran, QT (reprint author), 15355 Lambda Dr, San Antonio, TX 78245 USA. EM ran@uthscsa.edu FU NIH [P01 AG19316, P01AG020591]; San Antonio Nathan Shock Aging Center [1P30-AG13319]; Department of Veteran Affairs FX This work was supported by NIH Grants P01 AG19316 and P01AG020591, the San Antonio Nathan Shock Aging Center (1P30-AG13319), and a Merit Review grant (Q.R.) from the Department of Veteran Affairs. NR 34 TC 18 Z9 18 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAY 1 PY 2012 VL 52 IS 9 BP 1820 EP 1827 DI 10.1016/j.freeradbiomed.2012.02.043 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 944DB UT WOS:000304177500034 PM 22401858 ER PT J AU Condray, R Siegle, GJ Keshavan, MS Steinhauer, SR AF Condray, Ruth Siegle, Greg J. Keshavan, Matcheri S. Steinhauer, Stuart R. TI Effects of word frequency on semantic memory in schizophrenia: Electrophysiological evidence for a deficit in linguistic access (vol 75, pg 141, 2010) SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Correction C1 [Condray, Ruth] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Sch Med, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. RP Condray, R (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Sch Med, 3811 OHara St, Pittsburgh, PA 15213 USA. EM condrayr@upmc.com NR 1 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD MAY PY 2012 VL 84 IS 2 BP 226 EP 231 DI 10.1016/j.ijpsycho.2011.05.011 PG 6 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 941JW UT WOS:000303960500016 ER PT J AU Perez, VB Ford, JM Roach, BJ Woods, SW McGlashan, TH Srihari, VH Loewy, RL Vinogradov, S Mathalon, DH AF Perez, Veronica B. Ford, Judith M. Roach, Brian J. Woods, Scott W. McGlashan, Thomas H. Srihari, Vinod H. Loewy, Rachel L. Vinogradov, Sophia Mathalon, Daniel H. TI Error Monitoring Dysfunction Across the Illness Course of Schizophrenia SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE schizophrenia; prodrome; at-risk; error-related negativity; performance monitoring ID ANTERIOR CINGULATE CORTEX; CROSSMODAL DIVIDED ATTENTION; MEDIAL FRONTAL-CORTEX; CHOICE REACTION TASKS; LATE ERP COMPONENTS; EVENT-RELATED FMRI; BRAIN ACTIVITY; INTERRATER RELIABILITY; PREDICTIVE-VALIDITY; PRODROMAL SYNDROMES AB Response monitoring abnormalities have been reported in chronic schizophrenia patients, but it is unknown whether they predate the onset of psychosis, are present in early stages of illness, or are late-developing abnormalities associated with illness progression. Response-synchronized event-related potentials (ERP) recorded during a picture-word matching task yielded error-related negativity (ERN), correct-response negativity (CRN), and error positivity (Pe) from 84 schizophrenia patients (SZ), 48 clinical high risk patients (CHR), and their age-matched healthy controls (HC; n = 110 and 88, respectively). A sub-sample of 35 early illness schizophrenia patients (ESZ) was compared to 93 age-matched HC and the CHR patients (after statistically removing the effects of normal aging). Relative to HC, 1) SZ, ESZ, and CHR had smaller ERNs, and 2) SZ and ESZ had larger CRNs and smaller Pes. Within the SZ, longer illness duration was associated with larger CRNs but was unrelated to ERN or Pe. CHR and ESZ did not differ on ERN or CRN, although Pe was smaller in ESZ than CHR. These results indicate that while ERN, CRN, and Pe abnormalities are present early in the illness, only the ERN abnormality is evident prior to psychosis onset, and only the CRN abnormality appears to worsen progressively over the illness course. Brain regions subserving response monitoring may be compromised early in the illness and possibly during its clinical prodrome. C1 [Perez, Veronica B.; Ford, Judith M.; Roach, Brian J.; Loewy, Rachel L.; Vinogradov, Sophia; Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Perez, Veronica B.; Ford, Judith M.; Roach, Brian J.; Vinogradov, Sophia; Mathalon, Daniel H.] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. [Woods, Scott W.; McGlashan, Thomas H.; Srihari, Vinod H.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. RP Mathalon, DH (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. EM daniel.mathalon@ucsf.edu OI Roach, Brian/0000-0002-3264-1465; Mathalon, Daniel/0000-0001-6090-4974; Srihari, Vinod/0000-0003-1556-2332 FU NIMH NIH HHS [K02 MH067967, R01 MH058262, R01 MH076989, RC1 MH088971, T32 MH089920, T32 MH089920-01] NR 98 TC 21 Z9 21 U1 3 U2 14 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD MAY PY 2012 VL 121 IS 2 BP 372 EP 387 DI 10.1037/a0025487 PG 16 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 943NQ UT WOS:000304131400008 PM 22060947 ER PT J AU Bergman, BC Howard, D Schauer, IE Maahs, DM Snell-Bergeon, JK Eckel, RH Perreault, L Rewers, M AF Bergman, Bryan C. Howard, David Schauer, Irene E. Maahs, David M. Snell-Bergeon, Janet K. Eckel, Robert H. Perreault, Leigh Rewers, Marian TI Features of Hepatic and Skeletal Muscle Insulin Resistance Unique to Type 1 Diabetes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORONARY-ARTERY CALCIFICATION; GLUCOSE-METABOLISM; CARDIOVASCULAR-DISEASE; MELLITUS; COMPLICATIONS; MECHANISMS; DISPOSAL; DEFECT; WOMEN; LIVER AB Context: Type 1 diabetes is known to be a state of insulin resistance; however, the tissues involved in whole-body insulin resistance are less well known. It is unclear whether insulin resistance is due to glucose toxicity in the post-Diabetes Control and Complications Trial era of tighter glucose control. Objective: We performed this study to determine muscle and liver insulin sensitivity individuals with type 1 diabetes after overnight insulin infusion to lower fasting glucose concentration. Design, Patients, and Methods: Fifty subjects [25 controls without and 25 individuals with type 1 diabetes (diabetes duration 22.9 +/- 1.7 yr, without known end organ damage] were frequency matched on age and body mass index by group and studied. After 3 d of dietary control and overnight insulin infusion to normalize glucose, we performed a three-stage hyperinsulinemic/euglycemic clamp infusing insulin at 4, 8, and 40 mU/m(2).min. Glucose metabolism was quantified using an infusion of [6,6-H-2(2)] glucose. Hepatic insulin sensitivity was measured using the insulin IC50 for glucose rate of appearance (Ra), whereas muscle insulin sensitivity was measured using the glucose rate of disappearance during the highest insulin dose. Results: Throughout the study, glucose Ra was significantly greater in individuals compared with those without type 1 diabetes. The concentration of insulin required for 50% suppression of glucose Ra was 2-fold higher in subjects with type 1 diabetes. Glucose rate of disappearance was significantly lower in individuals with type 1 diabetes during the 8-and 40-mU/m(2).min stages. Conclusion: Insulin resistance in liver and skeletal muscle was a significant feature in type 1 diabetes. Nevertheless, the etiology of insulin resistance was not explained by body mass index, percentage fat, plasma lipids, visceral fat, and physical activity and was also not fully explained by hyperglycemia. (J Clin Endocrinol Metab 97: 1663-1672, 2012) C1 [Bergman, Bryan C.; Howard, David; Schauer, Irene E.; Eckel, Robert H.; Perreault, Leigh] Univ Colorado, Div Endocrinol Metab & Diabet, Dept Med, Aurora, CO 80045 USA. [Snell-Bergeon, Janet K.; Rewers, Marian] Univ Colorado, Sch Med, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80045 USA. [Schauer, Irene E.] Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. RP Bergman, BC (reprint author), Univ Colorado, Div Endocrinol Metab & Diabet, Dept Med, Anschutz Med Campus,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's 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 (Denver, CO); National Institutes of Health Diabetes Endocrinology Research Center [P30 DK57516]; National Institute for Diabetes and Digestive and Kidney Diseases [K01 DK066219, K23 DK075360]; American Diabetes Association [1-10-JF-50] FX This work was supported by the National Institutes of Health's National Heart, Lung, and Blood Institute Grants R01 HL-61753 and R01 HL-079611, and 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 (Denver, CO). Support was also provided by the National Institutes of Health Diabetes Endocrinology Research Center Clinical Investigation Core Grant P30 DK57516; National Institute for Diabetes and Digestive and Kidney Diseases Grants K01 DK066219 (to B.C.B.) and K23 DK075360 (to D.M.M.); and the American Diabetes Association Junior Faculty Award 1-10-JF-50 (to J.K.S.-B.). NR 42 TC 29 Z9 29 U1 0 U2 4 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 MAY PY 2012 VL 97 IS 5 BP 1663 EP 1672 DI 10.1210/jc.2011-3172 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 940TL UT WOS:000303915900059 PM 22362823 ER PT J AU Burney, BO Hayes, TG Smiechowska, J Cardwell, G Papusha, V Bhargava, P Konda, B Auchus, RJ Garcia, JM AF Burney, Basil O. Hayes, Teresa G. Smiechowska, Joanna Cardwell, Gina Papusha, Victor Bhargava, Peeyush Konda, Bhavana Auchus, Richard J. Garcia, Jose M. TI Low Testosterone Levels and Increased Inflammatory Markers in Patients with Cancer and Relationship with Cachexia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LOW SERUM TESTOSTERONE; ERECTILE DYSFUNCTION; HYPOGONADAL MEN; GRIP STRENGTH; OLDER MEN; SURVIVORS; ANOREXIA; MASS; INTERLEUKIN-6; ASSOCIATIONS AB Context: Male cancer patients suffer from fatigue, sexual dysfunction, and decreased functional performance and muscle mass. These symptoms are seen in men with hypogonadism and/or inflammatory conditions. However, the relative contribution of testosterone and inflammation to symptom burden in cancer has not been well-established. Objective: The aim of this study was to measure testosterone levels in male cancer patients and determine the relationship between testosterone, inflammation, and symptom burden. Design/Setting: This cross-sectional study enrolled patients from a tertiary-care center. Subjects/Outcome Measures: Subjects included males with cancer-cachexia (CC; n = 45) and cancer without cachexia (CNC; n = 50), as well as noncancer controls (CO; n = 45). Total testosterone (TT), bioavailable testosterone, C-reactive protein (CRP), and IL-6 were measured in plasma. Functional performance was assessed by the ECOG (Eastern Cooperative Oncology Group) and KPS (Karnofsky Performance Scales), and sexual function was assessed by the IIEF (International Index of Erectile Function). Results: Low testosterone levels were seen in more than 70% of CC cases. TT was lower in CC compared to CNC(P < 0.05). Also, CC had lower bioavailable testosterone, grip strength, IIEF scores, appendicular lean body mass, and fat mass and higher IL-6 and CRP compared to controls (P <= 0.05). ECOG and KPS were lower in CC and CNC compared to controls (P <= 0.05). On multiple regression analysis, TT, albumin, and CRP predicted symptoms differentially in cancer patients. Conclusions: CC patients have higher inflammation and lower testosterone, grip strength, functional status, erectile function, fat mass, and appendicular lean body mass. Inflammation, TT, and albumin are associated with heavier symptom burden in this population. Interventional trials are needed to determine whether testosterone replacement and/or antiinflammatory agents benefit cancer patients. (J Clin Endocrinol Metab 97: E700-E709, 2012) C1 [Garcia, Jose M.] Baylor Coll Med, Div Endocrinol Diabet & Metab, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Hayes, Teresa G.] Michael E DeBakey VA Med Ctr, Div Hematol & Oncol, Houston, TX 77030 USA. [Smiechowska, Joanna] Michael E DeBakey VA Med Ctr, Div Geriatr, Houston, TX 77030 USA. [Konda, Bhavana] Univ Miami, Miller Sch Med, Dept Med, Atlantis, FL 33136 USA. [Auchus, Richard J.] Univ Michigan, Div Metab Endocrinol & Diabet, Dept Internal Med, Ann Arbor, MI 48109 USA. [Smiechowska, Joanna; Garcia, Jose M.] Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA. [Bhargava, Peeyush] Michael E DeBakey VA Med Ctr, Dept Radiol, Houston, TX 77030 USA. RP Garcia, JM (reprint author), Baylor Coll Med, Div Endocrinol Diabet & Metab, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd,Bldg 109,Room 210, Houston, TX 77030 USA. EM jgarcia1@bcm.edu FU Abbott; MERIT from the Department of Veterans Affairs [I01-BX000507]; Clinical Scientist Award in Translational Research from the Burroughs-Welcome Fund [1005954] FX This work was supported by an unrestricted grant from Abbott and a MERIT grant from the Department of Veterans Affairs (to J.M.G.; I01-BX000507). R.J.A. is supported by a Clinical Scientist Award in Translational Research (no. 1005954) from the Burroughs-Welcome Fund. NR 47 TC 23 Z9 25 U1 1 U2 2 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 MAY PY 2012 VL 97 IS 5 BP E700 EP E709 DI 10.1210/jc.2011-2387 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 940TL UT WOS:000303915900001 PM 22419719 ER PT J AU Wang, S Wong, ML Hamilton, N Ben Davoren, J Jahan, TM Walter, LC AF Wang, Sunny Wong, Melisa L. Hamilton, Nathan Ben Davoren, J. Jahan, Thierry M. Walter, Louise C. TI Impact of Age and Comorbidity on Non-Small-Cell Lung Cancer Treatment in Older Veterans SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COMBINED-MODALITY THERAPY; HEALTH-CARE UTILIZATION; QUALITY-OF-LIFE; ELDERLY-PATIENTS; PHASE-III; MEDICARE BENEFICIARIES; CHEMOTHERAPY REGIMENS; VINORELBINE; CISPLATIN; ONCOLOGY AB Purpose Because comorbidity affects cancer treatment outcomes, guidelines recommend considering comorbidity when making treatment decisions in older patients with lung cancer. Yet, it is unclear whether treatment is targeted to healthier older adults who might reasonably benefit. Patients and Methods Receipt of first-line guideline-recommended treatment was assessed for 20,511 veterans age >= 65 years with non-small-cell lung cancer (NSCLC) in the Veterans Affairs (VA) Central Cancer Registry from 2003 to 2008. Patients were stratified by age (65 to 74, 75 to 84, >= 85 years), Charlson comorbidity index score (0, 1 to 3, >= 4), and American Joint Committee on Cancer stage (I to II, IIIA to IIIB, IIIB with malignant effusion to IV). Comorbidity and patient characteristics were obtained from VA claims and registry data. Multivariate analysis identified predictors of receipt of guideline-recommended treatment. Results In all, 51% of patients with local, 35% with regional, and 27% with metastatic disease received guideline-recommended treatment. Treatment rates decreased more with advancing age than with worsening comorbidity for all stages, such that older patients with no comorbidity had lower rates than younger patients with severe comorbidity. For example, 50% of patients with local disease age 75 to 84 years with no comorbidity received surgery compared with 57% of patients age 65 to 74 years with severe comorbidity (P < .001). In multivariate analysis, age and histology remained strong negative predictors of treatment for all stages, whereas comorbidity and nonclinical factors had a minor effect. Conclusion Advancing age is a much stronger negative predictor of treatment receipt among older veterans with NSCLC than comorbidity. Individualized decisions that go beyond age and include comorbidity are needed to better target NSCLC treatments to older patients who may reasonably benefit. C1 [Wang, Sunny; Hamilton, Nathan; Ben Davoren, J.; Walter, Louise C.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Wang, Sunny; Jahan, Thierry M.] Univ Calif San Francisco, Thorac Oncol Program, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. RP Wang, S (reprint author), San Francisco VA Med Ctr, 4150 Clement St,111H1, San Francisco, CA 94121 USA. EM sunny.wang@ucsf.edu FU San Francisco Veterans Affairs (VA) Medical Center; University of California at San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center; Division of Hematology/Oncology, Department of Medicine at USCF; USCF Pathways Funding Agency; Philip R. Lee Program; Department of General Internal Medicine, UCSF; San Francisco VA Medical Center; National Cancer Institute, National Institutes of Health [R01 CA134425]; Eli Lilly; Genentech/OSI Pharmaceuticals; ImClone Systems; Morphotek; Pfizer FX Supported by the San Francisco Veterans Affairs (VA) Medical Center (S. W.); the Thoracic Oncology Program, University of California at San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, and the Division of Hematology/Oncology, Department of Medicine at USCF (S. W. and T.M.J.); the USCF Pathways Funding Agency, the Philip R. Lee Program, and the Department of General Internal Medicine, UCSF (M. L. W.); San Francisco VA Medical Center (J.B.D.); and by Grant No. R01 CA134425 from the National Cancer Institute, National Institutes of Health, and the San Francisco VA Medical Center (L. C. W.).; Sunny Wang, Eli Lilly, Genentech/OSI Pharmaceuticals, ImClone Systems, Morphotek, Pfizer; Thierry M. Jahan, Eli Lilly, Genentech/OSI Pharmaceuticals, ImClone Systems, Morphotek, Pfizer NR 61 TC 53 Z9 55 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2012 VL 30 IS 13 BP 1447 EP 1455 DI 10.1200/JCO.2011.39.5269 PG 9 WC Oncology SC Oncology GA 939ZJ UT WOS:000303859400013 PM 22454424 ER PT J AU Shen, KZ Johnson, SW AF Shen, Ke-Zhong Johnson, Steven W. TI Regulation of polysynaptic subthalamonigral transmission by D2, D3 and D4 dopamine receptors in rat brain slices SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID NIGRA PARS RETICULATA; SUBSTANTIA-NIGRA; NUCLEUS NEURONS; PARKINSONS-DISEASE; GLOBUS-PALLIDUS; BASAL GANGLIA; IN-VITRO; CEREBRAL-CORTEX; MESSENGER-RNA; LOCALIZATION AB Dopamine depletion in experimental models of Parkinson's disease promotes burst firing of neurons in the subthalamic nucleus (STN) and substantia nigra zona reticulata (SNR). A synaptically generated form of burst firing has been shown to arise from complex excitatory postsynaptic currents (EPSCs) that are evoked in SNR neurons by STN stimulation. The present experiments were designed to characterize actions of dopamine on complex EPSCs in slices of rat brain. Using patch pipettes to record whole-cell currents under voltage clamp, dopamine (30 mu M) caused a reversible 64% reduction in complex EPSC charge. This effect was partially mimicked by D2, D3 and D4 receptor agonists, and the action of dopamine could be nearly completely blocked by the combined effects of the D2/3 antagonist sulpiride and the D4 antagonist L-745,870. Local application of dopamine to the STN caused a larger inhibition of the complex EPSC (55% reduction) than did dopamine application to the SNR (15% reduction). Simple, monophasic EPSCs, which were evoked in SNR neurons by stimulating the SNR close to the recording pipette, were inhibited to a smaller extent compared to complex EPSCs. Bursts of action potentials evoked in SNR neurons by STN stimulation were inhibited by dopamine to a greater extent than was spontaneous firing. These results show that dopamine D2-like receptors inhibit complex EPSCs and burst discharges in the SNR by acting within the STN to suppress transmission in the subthalamonigral pathway. Dopamine receptor-mediated inhibition of polysynaptic connections in the STN might be beneficial in the treatment of Parkinson's disease. C1 [Shen, Ke-Zhong; Johnson, Steven W.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Johnson, Steven W.] Portland VA Med Ctr, Portland, OR 97207 USA. RP Johnson, SW (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. EM johnsost@ohsu.edu FU United States Public Health Service [NS38715, NS060662]; Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center FX This work was supported by United States Public Health Service grants NS38715 and NS060662, and by the Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center. NR 38 TC 3 Z9 3 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD MAY PY 2012 VL 590 IS 10 BP 2273 EP 2284 DI 10.1113/jphysiol.2011.225672 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 942ZK UT WOS:000304090000014 PM 22371474 ER PT J AU Xu, HP Covinsky, KE Stallard, E Thomas, J Sands, LP AF Xu, Huiping Covinsky, Kenneth E. Stallard, Eric Thomas, Joseph, III Sands, Laura P. TI Insufficient Help for Activity of Daily Living Disabilities and Risk of All-Cause Hospitalization SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE activities of daily living; disability; hospitalization; insufficient help ID UNMET NEED; OLDER-ADULTS; PERSONAL ASSISTANCE; ELDERLY-PATIENTS; CARE; SERVICES; HOME; CONSEQUENCES; VALIDATION; CAREGIVERS AB OBJECTIVES To determine whether insufficient help for activity of daily living (ADL) disability, a potentially modifiable condition, significantly increases disabled older adults risk of future hospital admissions. DESIGN Prospective study. SETTING Community-living participants with ADL disabilities in the 1994, 1999, and 2004 National Long-Term Care Survey (NLTCS). PARTICIPANTS Medicare recipients with one or more ADL disabilities completed 5,884 surveys. MEASUREMENTS Times to hospital admission in the year after the NLTCS community survey were obtained from linked Medicare claims. Insufficient ADL help for each ADL limitation was determined from a series of questions common to the three NLTCS community surveys. RESULTS Insufficient help for one or more ADL limitations was reported in 22% of surveys. Respondents to 3,629 surveys did not experience a hospital admission in the year after the survey. Of the remaining 2,255 surveys, one admission occurred for 382 surveys, two admissions for 525 surveys, three admissions for 193 surveys, and four or more admissions for 155 surveys. Participants reporting insufficient help were 14% (hazard ratio = 1.14, 95% confidence interval = 1.011.28) more likely to experience one or more hospitalizations than those who did not report insufficient help after controlling for demographic characteristics, comorbidities, prior hospitalizations, and level of ADL disability. CONCLUSION Self-reports of insufficient help provide prognostic information beyond what typical health assessments can capture. Greater recognition and referral for insufficient help for ADL disability may result in lower rates of hospitalization in a population that is at high risk of hospitalization. J Am Geriatr Soc 60:927-933, 2012. C1 [Sands, Laura P.] Purdue Univ, Sch Nursing, W Lafayette, IN 47907 USA. [Xu, Huiping] Indiana Univ, Sch Med, Indianapolis, IN USA. [Covinsky, Kenneth E.] Univ Calif San Francisco, Div Geriatr, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Stallard, Eric] Duke Univ, Ctr Populat Hlth & Aging, Durham, NC USA. [Thomas, Joseph, III] Purdue Univ, Ctr Aging & Life Course, Ctr Hlth Outcomes Res & Policy, Regenstrief Ctr Healthcare Engn,Coll Pharm, W Lafayette, IN 47907 USA. RP Sands, LP (reprint author), Purdue Univ, Sch Nursing, 502 N Univ St, W Lafayette, IN 47907 USA. EM lsands@purdue.edu RI Sands, Laura/E-8919-2015 OI Sands, Laura/0000-0003-2446-4486 FU National Institutes of Health [R01AG034160] FX This research was supported by Grant R01AG034160 from the National Institutes of Health to Dr. Sands. Drs. Xu, Covinsky, Thomas, and Sands and Prof. Stallard do not have any financial interest or personal conflicts with the methodologies discussed in this manuscript. NR 31 TC 10 Z9 11 U1 1 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2012 VL 60 IS 5 BP 927 EP 933 DI 10.1111/j.1532-5415.2012.03926.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 942HE UT WOS:000304033900016 PM 22587855 ER PT J AU Finlayson, E Zhao, SJ Boscardin, WJ Fries, BE Landefeld, CS Dudley, RA AF Finlayson, Emily Zhao, Shoujun Boscardin, W. John Fries, Brant E. Landefeld, C. Seth Dudley, R. Adams TI Functional Status After Colon Cancer Surgery in Elderly Nursing Home Residents SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE functional decline; nursing home residents; surgery ID CARE; COMORBIDITY; ADULTS; MDS AB OBJECTIVES To determine functional status and mortality rates after colon cancer surgery in older nursing home residents. DESIGN Retrospective cohort study. SETTING Nursing homes in the United States. PARTICIPANTS Six thousand eight hundred twenty-two nursing home residents aged 65 and older who underwent surgery for colon cancer in the United States between 1999 and 2005. MEASUREMENTS Changes in functional status were assessed before and after surgery using the Minimum Data Set Activity of Daily Living (MDS-ADL) summary scale, a 28-point scale in which score increases as functional dependence increases. Regression techniques were used to identify patient characteristics associated with mortality and functional decline 1 year after surgery. RESULTS On average, residents who underwent colectomy had a 3.9-point worsening in MDS-ADL score at 1 year. One year after surgery, rates of mortality and sustained functional decline were 53% and 24%, respectively. In multivariate analysis, older age (=80 vs 6569, adjusted relative risk (ARR) = 1.53, 95% confidence interval (CI) = 1.152.04, P < .001), readmission after surgical hospitalization (ARR = 1.15, 95% CI = 1.031.29, P = .02), surgical complications (ARR = 1.11, 95% CI = 1.021.21, P = .01), and functional decline before surgery (ARR = 1.21, 95% CI = 1.111.32, P < .001) were associated with functional decline at 1 year. CONCLUSION Mortality and sustained functional decline are common after colon cancer surgery in nursing home residents. Initiatives aimed at improving surgical outcomes are needed in this vulnerable population. J Am Geriatr Soc 60:967-973, 2012. C1 [Finlayson, Emily; Dudley, R. Adams] Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94118 USA. [Finlayson, Emily; Zhao, Shoujun] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Boscardin, W. John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Boscardin, W. John; Landefeld, C. Seth] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Boscardin, W. John; Landefeld, C. Seth] San Francisco VA Med Ctr, San Francisco, CA USA. [Fries, Brant E.] Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA. [Fries, Brant E.] Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Dudley, R. Adams] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Finlayson, E (reprint author), Philip R Lee Inst Hlth Policy Studies, 3333 Calif St, San Francisco, CA 94118 USA. EM emily.finlayson@ucsfmedctr.org FU National Institute on Aging [K08AG028965] FX Dr. Finlayson was supported by a National Institute on Aging/Paul B. Beeson Clinical Scientist Development Award in Aging (K08AG028965). NR 19 TC 28 Z9 28 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2012 VL 60 IS 5 BP 967 EP 973 DI 10.1111/j.1532-5415.2012.03915.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 942HE UT WOS:000304033900023 PM 22428583 ER PT J AU Cannuscio, CC Alley, DE Pagan, JA Soldo, B Krasny, S Shardell, M Asch, DA Lipman, TH AF Cannuscio, Carolyn C. Alley, Dawn E. Pagan, Jose A. Soldo, Beth Krasny, Sarah Shardell, Michelle Asch, David A. Lipman, Terri H. TI Housing strain, mortgage foreclosure, and health SO NURSING OUTLOOK LA English DT Article DE Housing security; Housing strain; Material resources; Housing policy; Economic strain; Health disparities AB Background: Foreclosure rates have risen rapidly since 2005, reaching historically high levels. The purpose of this study was to examine the health implications of the current housing crisis. Methods: We conducted a cross-sectional online consumer panel survey including residents of California, Arizona, Nevada, and Florida (n = 798) to determine the feasibility of contacting distressed homeowners via the Internet and to assess mental and physical health among respondents across the spectrum from those having no housing strain to those in loan default or home foreclosure. Results: Homeowners in default or foreclosure exhibited poorer mental health and more physical symptoms than renters, homeowners with moderate strain, and homeowners with no strainofollowing a gradient that was consistent across multiple health indicators. Conclusions: Internet panel sampling was an efficient method of contacting distressed homeowners. Record-high foreclosure rates may have broad implications for nursing and public health. Homeowners in default or foreclosure represent an identifiable high-risk group that may benefit from coordinated, affordable health and social services. Cite this article: Cannuscio, C. C., Alley, D. E., Pagan, J. A., Soldo, B., Krasny, S., Shardell, M., Asch, D. A., & Lipman, T. H. (2012, JUNE). Housing strain, mortgage foreclosure, and health. Nursing Outlook, 60(3), 134-142. doi:10.1016/j.outlook.2011.08.004. C1 [Lipman, Terri H.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Lipman, Terri H.] Univ Penn, Ctr Publ Hlth Initiat, Philadelphia, PA 19104 USA. [Cannuscio, Carolyn C.; Shardell, Michelle; Asch, David A.] Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Cannuscio, Carolyn C.; Shardell, Michelle] Univ Penn, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Alley, Dawn E.] Univ Maryland, Sch Med, Dept Epidemiol Publ Hlth, Baltimore, MD 21201 USA. [Pagan, Jose A.] Univ N Texas Hlth Sci Ctr, Dept Hlth Management & Policy, Ft Worth, TX USA. [Soldo, Beth] Univ Penn, Populat Aging Res Ctr, Ctr Populat Studies, Philadelphia, PA 19104 USA. [Krasny, Sarah] Univ Penn, Huntsman Program Int Studies & Business, Sch Arts & Sci, Philadelphia, PA 19104 USA. [Krasny, Sarah] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Lipman, TH (reprint author), Univ Penn, Sch Nursing, Room 224,Fagin Hall,418 Curie Blvd, Philadelphia, PA 19104 USA. EM lipman@nursing.upenn.edu OI Asch, David/0000-0002-7970-286X FU Robert Wood Johnson Foundation Health Society; University of Pennsylvania Center for Public Health Initiatives; Office of Practice and Community Affairs, University of Pennsylvania School of Nursing; Department of Veterans Affairs, Office of Health Services Research and Development, Center for Health Equity Research and Promotion FX We gratefully acknowledge the support provided by Jeannette Schroeder, as well as funding support from the Robert Wood Johnson Foundation Health & Society Scholars Program, University of Pennsylvania Center for Public Health Initiatives, and the Office of Practice and Community Affairs, University of Pennsylvania School of Nursing, Investment for the Future Funds. Drs. Asch and Cannusio are supported by the Department of Veterans Affairs, Office of Health Services Research and Development, Center for Health Equity Research and Promotion. The contents of this article do not represent the views of the Department of Veteran Affairs or the United States government. NR 0 TC 22 Z9 23 U1 1 U2 31 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD MAY-JUN PY 2012 VL 60 IS 3 BP 134 EP 142 DI 10.1016/j.outlook.2011.08.004 PG 9 WC Nursing SC Nursing GA 944DK UT WOS:000304178400006 PM 22000689 ER PT J AU Chen, BB Glasser, JR Coon, TA Mallampalli, RK AF Chen, B. B. Glasser, J. R. Coon, T. A. Mallampalli, R. K. TI F-box protein FBXL2 exerts human lung tumor suppressor-like activity by ubiquitin-mediated degradation of cyclin D3 resulting in cell cycle arrest SO ONCOGENE LA English DT Article DE ubiquitin; camodulin; lung ID CTP-PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE; D1 DEGRADATION; CALCIUM-CONCENTRATION; REGULATORY ENZYME; CALMODULIN; CANCER; PHOSPHORYLATION; EXPRESSION; KINASE; IDENTIFICATION AB Dysregulated behavior of cell cycle proteins and their control by ubiquitin E3 ligases is an emerging theme in human lung cancer. Here, we identified and characterized the activity of a novel F-box protein, termed FBXL2, belonging to the SCF (Skip-Cullin1-F-box protein) E3 ligase family. Ectopically expressed FBXL2 triggered G2/M-phase arrest, induced chromosomal anomalies and increased apoptosis of transformed lung epithelia by mediating polyubiquitination and degradation of the mitotic regulator, cyclin D3. Unlike other F-box proteins that target phosphodegrons within substrates, FBXL2 uniquely recognizes a canonical calmodulin (CaM)-binding motif within cyclin D3 to facilitate its polyubiquitination. CaM bound and protected cyclin D3 from FBXL2 by direct intermolecular competition with the F-box protein for access within this motif. The chemotherapeutic agent vinorelbine increased apoptosis of human lung carcinoma cells by inducing FBXL2 expression and cyclin D3 degradation, an effect accentuated by CaM knockdown. Depletion of endogenous FBXL2 stabilized cyclin D3 levels, accelerated cancer cell growth and increased cell viability after vinorelbine treatment. Last, ectopic expression of FBXL2 significantly inhibited the growth and migration of tumorogenic cells and tumor formation in athymic nude mice. These observations implicate SCFFBXL2 as an indispensible regulator of mitosis that serves as a tumor suppressor. Oncogene (2012) 31, 2566-2579; doi:10.1038/onc.2011.432; published online 24 October 2011 C1 [Mallampalli, R. K.] Univ Pittsburgh, Dept Med, Div Pulm Allergy & Crit Care Med, UPMC Montefiore,Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15213 USA. [Mallampalli, R. K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. [Mallampalli, R. K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA USA. RP Mallampalli, RK (reprint author), Univ Pittsburgh, Dept Med, Div Pulm Allergy & Crit Care Med, UPMC Montefiore,Acute Lung Injury Ctr Excellence, NW 628, Pittsburgh, PA 15213 USA. EM mallampallirk@upmc.edu FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; US Department of Veterans Affairs; National Institutes of Health [HL096376, HL097376, HL098174] FX We thank AF Stewart for critical review of the manuscript and helpful suggestions. This material is based upon work supported, in part, by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. This work was supported by a Merit Review Award from the US Department of Veterans Affairs and National Institutes of Health R01 grants HL096376, HL097376 and HL098174 (to RKM). The contents presented do not represent the views of the Department of Veterans Affairs or the United States Government. NR 56 TC 31 Z9 33 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY PY 2012 VL 31 IS 20 BP 2566 EP 2579 DI 10.1038/onc.2011.432 PG 14 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 944ID UT WOS:000304191800007 PM 22020328 ER PT J AU Messamore, E AF Messamore, Erik TI Niacin subsensitivity is associated with functional impairment in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Niacin; Schizophrenia; Niacin; Laser Doppler flowmetry; Psychiatric status rating scales ID SKIN-FLUSH RESPONSE; CATALEPTIC BEHAVIOR; NICOTINIC-ACID; FATTY-ACIDS; CYCLOOXYGENASE INHIBITORS; POSSIBLE INVOLVEMENT; HEALTHY CONTROLS; ABSENT RESPONSE; EARLY PSYCHOSIS; CHALLENGE TEST AB Objective: Sensitivity to the skin flush effect of niacin is reduced in a portion of patients with schizophrenia. Though this peripheral physiological abnormality has been widely replicated, its relevance to neuropsychiatric manifestations of the illness has been unclear. The goal of this study was to determine if the niacin response abnormality in schizophrenia is associated with functional impairment. Methods: Following psychiatric assessment, a Global Assessment of Functioning (GAF) score was assigned to each of 40 volunteers with schizophrenia. For each subject, the blood flow responses to several concentrations of topical methylnicotinate were recorded. Blood flow was measured objectively, using laser Doppler flowmetry. From the dose-response data, EC50 values were derived. GAF scores were assigned without knowledge of the participants' niacin response data. Results: There was a significant negative correlation between GAF scores and EC50 values for methylnicotinate (Pearson r=-0.42; p=0.007). Conclusions: Reduced niacin sensitivity is associated with greater functional impairment among patients with schizophrenia. These findings raise the possibility that a subset of schizophrenia patients possesses a biochemical abnormality that reduces niacin sensitivity in the skin and contributes to functional impairment from the disease. Published by Elsevier B.V. C1 [Messamore, Erik] Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR USA. [Messamore, Erik] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. RP Messamore, E (reprint author), Portland VA Med Ctr, Div Mental Hlth, P35C,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Erik.Messamore@va.gov FU NIMH [R03 MH070434]; VA Career Development Award FX Funding for this study was provided by NIMH grant R03 MH070434 and by a VA Career Development Award (to the author). Neither the NIMH nor VA funding sources had any 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. The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government. NR 47 TC 7 Z9 7 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2012 VL 137 IS 1-3 BP 180 EP 184 DI 10.1016/j.schres.2012.03.001 PG 5 WC Psychiatry SC Psychiatry GA 941AI UT WOS:000303933800029 PM 22445461 ER PT J AU Smith, MJ Horan, WP Karpouzian, TM Abram, SV Cobia, DJ Csernansky, JG AF Smith, Matthew J. Horan, William P. Karpouzian, Tatiana M. Abram, Samantha V. Cobia, Derin J. Csernansky, John G. TI Self-reported empathy deficits are uniquely associated with poor functioning in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Social cognition; Community functioning; Functional capacity ID SOCIAL COGNITION; NEUROCOGNITIVE DEFICITS; MIND; NEUROSCIENCE; DISORDER; OPPORTUNITIES; METAANALYSIS; WORKSHOP; RECOVERY; CNTRICS AB Background: Social cognitive deficits have been proposed to be among the causes of poor functional outcome in schizophrenia. Empathy, or sharing and understanding the unique emotions and experiences of other people, is one of the key elements of social cognition, and prior studies suggest that empathic processes are impaired in schizophrenia. The current study examined whether impairments in self-reported empathy were associated with poor functioning, above and beyond the influences of neurocognitive deficits and psychopathology. Methods: Individuals with schizophrenia (n=46) and healthy controls (n=37) completed the Interpersonal Reactivity Index (IRI), a measure of emotional and cognitive empathy. Participants also completed a neuropsychological test battery, clinical ratings of psychopathology, and functional outcome measures assessing both functional capacity and community functioning. After testing for between-group differences, we assessed the relationships between self-reported empathy and the measures of functioning, neurocognition, and psychopathology. Regression analyses examined whether empathic variables predicted functional outcomes. Results: Individuals with schizophrenia reported lower IRI scores for perspective-taking and empathic concern, and higher IRI scores for personal distress than controls. Among individuals with schizophrenia, lower perspective-taking, greater disorganized symptoms, and deficits in working memory and episodic memory were correlated with poorer functional capacity and community functioning. Lower scores for perspective-taking explained significant incremental variance in both functional capacity (Delta R-2=.09, p <.05) and community functioning (Delta R-2=.152, p <.01) after accounting for relevant neurocognitive and psychopathological variables. Conclusions: Impaired perspective-taking, a component of cognitive empathy, is associated with poor functioning even after taking into account the influences of neurocognitive deficits and psychopathology. These findings support further efforts to clarify the underlying causes of empathic disturbances and suggest that treatments for these disturbances may help functional recovery in schizophrenia. (C) 2012 Elsevier B.V. All rights reserved. C1 [Smith, Matthew J.; Karpouzian, Tatiana M.; Abram, Samantha V.; Cobia, Derin J.; Csernansky, John G.] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Horan, William P.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Horan, William P.] VISN22 MIRECC, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Smith, MJ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, 446 E Ontario St,Suite 1000, Chicago, IL 60611 USA. EM matthewsmith@northwestern.edu OI Smith, Matthew/0000-0002-0079-1477; Cobia, Derin/0000-0003-2339-958X FU Department of Psychiatry and Behavioral Sciences at Northwestern University Feinberg School of Medicine; Northwestern University Schizophrenia Research Group FX Sources of Support: Support for the preparation of this paper was provided by the Department of Psychiatry and Behavioral Sciences at Northwestern University Feinberg School of Medicine and the Northwestern University Schizophrenia Research Group. NR 62 TC 38 Z9 40 U1 3 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2012 VL 137 IS 1-3 BP 196 EP 202 DI 10.1016/j.schres.2012.01.012 PG 7 WC Psychiatry SC Psychiatry GA 941AI UT WOS:000303933800032 PM 22321668 ER PT J AU Irani, F Seligman, S Kamath, V Kohler, C Gur, RC AF Irani, Farzin Seligman, Sarah Kamath, Vidyulata Kohler, Christian Gur, Ruben C. TI A meta-analysis of emotion perception and functional outcomes in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Emotion perception; Social cognition; Schizophrenia; Functional outcome; Quality of life; Meta-analysis ID FACIAL-AFFECT RECOGNITION; SOCIAL COGNITION; TRAINING-PROGRAM; FLAT AFFECT; OTHER-RACE; REMEDIATION; DEFICITS; NEUROCOGNITION; EXPRESSIONS; COMPETENCE AB Introduction: Emotion perception (EP) is impaired in schizophrenia, is stable across clinical state, resistant to antipsychotic treatment and linked to symptom severity. Given its pervasive nature, there is a need to quantitatively examine whether this dysfunction impacts functional outcomes. We used a meta-analytic strategy to combine results from several studies and examine synthesized effect sizes. Methods: A Meta-analysis of Observational Studies in Epidemiology standard was used to extract data following a PubMed and PsychInfo search. Studies reporting correlations between measures of EP and functional outcomes in schizophrenia spectrum disorders were selected. The impact of potential methodological (task type), demographic (sex, age, race, education, marital status) and clinical (age of onset, duration of illness, setting, symptoms, anti-psychotic medication) moderators on effect sizes were examined. Results: Twenty-five studies met inclusion criteria and included 1306 patients who were 37 years old, with 12 years of education, 64% male and 63% Caucasian. There was a significant relationship between EP and functional outcomes in individuals with schizophrenia or schizoaffective disorder, with effect sizes in the medium range. Medium to large range positive correlations were observed between emotion identification and functional outcome domains involving social problem solving, social skills and community functioning. Significant moderators included task type (emotion identification tasks), sex (% male in sample), race (% Caucasian in sample) and clinical symptoms (negative and positive). Conclusions: Emotion identification deficits are associated with functional impairments in schizophrenia and moderated by sex, race and symptoms. This has implications for treatment efforts to improve outcomes. (C) 2012 Elsevier B.V. All rights reserved. C1 [Irani, Farzin; Seligman, Sarah; Kamath, Vidyulata; Kohler, Christian; Gur, Ruben C.] Univ Penn, Sch Med, Neuropsychiat Sect, Dept Psychiat, Philadelphia, PA 19104 USA. [Gur, Ruben C.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Irani, Farzin] Immaculata Univ, Dept Grad Psychol, Immaculata, PA USA. RP Irani, F (reprint author), Univ Penn, Sch Med, Neuropsychiat Sect, Dept Psychiat, 10th Floor,Gates Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. EM firani@upenn.edu OI Rycroft, Sarah/0000-0002-9041-0825 FU NIMH [T32MH019112] FX FI is supported by a training grant from NIMH (T32MH019112); the NIMH had no further role in the 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 70 TC 47 Z9 50 U1 0 U2 23 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2012 VL 137 IS 1-3 BP 203 EP 211 DI 10.1016/j.schres.2012.01.023 PG 9 WC Psychiatry SC Psychiatry GA 941AI UT WOS:000303933800033 PM 22341200 ER PT J AU Spiegel, BMR AF Spiegel, Brennan M. R. TI Treatment Center Characteristics Associated with Better Outcomes: A Role for the Medical Director? SO SEMINARS IN DIALYSIS LA English DT Article ID DIALYSIS; MORTALITY; HEMODIALYSIS; ADEQUACY; PROGRAM; QUALITY C1 Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. RP Spiegel, BMR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu NR 12 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD MAY-JUN PY 2012 VL 25 IS 3 BP 296 EP 298 DI 10.1111/j.1525-139X.2012.01077.x PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 944HP UT WOS:000304190200011 PM 22607212 ER PT J AU Yee, HS Chang, MF Pocha, C Lim, J Ross, D Morgan, TR Monto, A AF Yee, Helen S. Chang, Michael F. Pocha, Christine Lim, Joseph Ross, David Morgan, Timothy R. Monto, Alexander TI Update on the Management and Treatment of Hepatitis C Virus Infection: Recommendations from the Department of Veterans Affairs Hepatitis C Resource Center Program and the National Hepatitis C Program Office SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID SUSTAINED VIROLOGICAL RESPONSE; TREATMENT-NAIVE PATIENTS; GENOTYPE 1 INFECTION; CHRONIC HCV INFECTION; PEGINTERFERON ALPHA-2A; PLUS RIBAVIRIN; LIVER FIBROSIS; RANDOMIZED-TRIAL; TRANSIENT ELASTOGRAPHY; PEGYLATED INTERFERON AB Chronic hepatitis C virus (HCV) infection affects approximately 1.3% of the United States population and 4% of veterans who use Department of Veterans Affairs medical services. Chronic HCV is the primary cause of cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease requiring liver transplantation in the United States. Management of chronic HCV is aimed at halting disease progression, preventing cirrhosis decompensation, reducing the risk of HCC, and treating extrahepatic complications of the infection. As part of a comprehensive HCV management strategy, peginterferon alfa and ribavirin, along with the addition of a hepatitis C protease inhibitor therapy for many genotype 1-infected patients, are the current standard of care. Antiviral therapy should be provided to those individuals who are clinically stable, have moderate liver disease or compensated cirrhosis, and are motivated to pursue therapy. Many patients have comorbid medical and psychiatric conditions, which may affect their adherence to antiviral therapy or worsen while on antiviral therapy. To optimally manage hepatitis C and associated comorbidities, patients benefit from multidisciplinary teams that can provide HCV-specific care and treatment. Sustained virologic response is associated with "cure" of chronic HCV, and results in improved liver disease outcomes and prolonged survival. C1 [Yee, Helen S.; Chang, Michael F.; Pocha, Christine; Lim, Joseph; Monto, Alexander] US Dept Vet Affairs, Hepatitis Resource Ctr Program C, Washington, DC USA. [Yee, Helen S.; Monto, Alexander] US Dept Vet Affairs, Med Ctr, San Francisco, CA USA. [Chang, Michael F.] US Dept Vet Affairs, Med Ctr, Portland, OR USA. [Pocha, Christine] US Dept Vet Affairs, Med Ctr, Minneapolis, MN USA. [Lim, Joseph] US Dept Vet Affairs, Med Ctr, West Haven, CT USA. [Ross, David] Vet Hlth Adm, Off Publ Hlth Clin Publ Hlth, Washington, DC USA. [Morgan, Timothy R.] US Dept Vet Affairs, Med Ctr, Long Beach, CA USA. RP Monto, A (reprint author), 4150 Clement St,111B, San Francisco, CA 94121 USA. EM Alexander.monto@va.gov NR 93 TC 59 Z9 63 U1 1 U2 7 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 MAY PY 2012 VL 107 IS 5 BP 669 EP 689 DI 10.1038/ajg.2012.48 PG 21 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 937SU UT WOS:000303679700005 PM 22525303 ER PT J AU McFarland, LV AF McFarland, Lynne V. TI The Role of Compassion in the Practice of Evidence-Based Medicine SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material ID DIFFICILE-ASSOCIATED DISEASE AB Patients with diseases having a high failure rate with standard treatments typically enroll in randomized clinical trials of new investigational treatments. Not all potential therapies are amenable to these types of designs and thus may be offered compassionately; however, claims of efficacy are thus viewed with caution. In a paper in this issue, 43 patients with recurrent Clostridium difficile infections were treated with fecal microbiota transplants using a compassionate use protocol. By using standardized healthy donor stool preparations and following standardized protocols, the 92% response rate can be viewed with more confidence than other case series reports. C1 [McFarland, Lynne V.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Dept Vet Affairs, Seattle, WA 98101 USA. [McFarland, Lynne V.] Univ Washington, Dept Med Chem, Seattle, WA 98195 USA. RP McFarland, LV (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Dept Vet Affairs, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM lynne.mcfarland@va.gov NR 10 TC 0 Z9 0 U1 0 U2 3 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 MAY PY 2012 VL 107 IS 5 BP 768 EP 769 DI 10.1038/ajg.2011.489 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 937SU UT WOS:000303679700016 PM 22552243 ER PT J AU Boardman, CR Sonnenberg, A AF Boardman, Charles R. Sonnenberg, Amnon TI A Watched Pot Can Boil: Interval Cancer in Tightly Surveyed Barrett's Esophagus SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter ID ADENOCARCINOMA; SURVEILLANCE; PREVALENCE C1 [Boardman, Charles R.; Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR 97239 USA. [Boardman, Charles R.; Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 9 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 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2012 VL 107 IS 5 BP 793 EP 794 DI 10.1038/ajg.2012.27 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 937SU UT WOS:000303679700024 PM 22552249 ER PT J AU Behr, S Weinstein, S Aslam, R Jung, A Sebro, R Yee, J AF Behr, S. Weinstein, S. Aslam, R. Jung, A. Sebro, R. Yee, J. TI Can CT Performed for Nonspecific Abdominal Pain Reliably Exclude Acute Cholecystitis? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Behr, S.; Weinstein, S.; Aslam, R.; Jung, A.; Sebro, R.; Yee, J.] Univ Calif San Francisco, San Francisco Med Ctr, San Francisco, CA 94143 USA. [Weinstein, S.; Aslam, R.; Jung, A.; Yee, J.] San Francisco VA Med Ctr, San Francisco, CA USA. EM stefage00@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2012 VL 198 IS 5 SU S PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400468 ER PT J AU Lalwani, N Bhargava, P Moshiri, M Lee, J Wang, C Bastawrous, S Vaidya, S Dighe, M AF Lalwani, N. Bhargava, P. Moshiri, M. Lee, J. Wang, C. Bastawrous, S. Vaidya, S. Dighe, M. TI Abdominal Oncologic Emergencies: Imaging Appearances and Therapeutic Options SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Lalwani, N.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Bhargava, P.; Moshiri, M.; Lee, J.; Wang, C.; Bastawrous, S.; Vaidya, S.; Dighe, M.] Univ Washington, Shoreline, WA USA. [Bhargava, P.; Bastawrous, S.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. EM bhargp@uw.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400465 ER PT J AU Lalwani, N Bhargava, P Dighe, M Shanbhogue, A Nagar, A AF Lalwani, N. Bhargava, P. Dighe, M. Shanbhogue, A. Nagar, A. TI Primary and Secondary Sclerosing Cholangitis: Current Update and Role of Imaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Lalwani, N.; Shanbhogue, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Bhargava, P.; Dighe, M.] Univ Washington, Seattle, WA 98195 USA. [Bhargava, P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Nagar, A.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. EM neerajlalwani@hotmail.com NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400367 ER PT J AU Rosenthal, P Massoglia, D Lundy, K Gebregziabher, M Gilbert, G AF Rosenthal, P. Massoglia, D. Lundy, K. Gebregziabher, M. Gilbert, G. TI Under Our Noses: A Reformulation of Our Understanding of Incidental Paranasal Sinusitis and Its Application in Interpreting Routine Sinus Imaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Rosenthal, P.; Massoglia, D.; Lundy, K.; Gebregziabher, M.; Gilbert, G.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. EM peter.rosenthal@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400604 ER PT J AU Sebro, R Aparici, CM Pampaloni, MH AF Sebro, R. Aparici, Mari C. Pampaloni, Hernandez M. TI Comparison Between True Whole-Body and Limited Whole-Body FDG PET/CT Studies in Oncology Patients SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Sebro, R.; Aparici, Mari C.; Pampaloni, Hernandez M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Aparici, Mari C.] San Francisco VA Med Ctr, San Francisco, CA USA. EM ronnie.sebro@radiology.ucsf.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400684 ER PT J AU Weinstein, S Osei-Bonsu, S Sajewicz, A Yee, J AF Weinstein, S. Osei-Bonsu, S. Sajewicz, A. Yee, J. TI MDCT of the Postoperative Colon: Normal Findings and Common Complications SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Weinstein, S.; Yee, J.] Univ Calif San Francisco, San Francisco Med Ctr, San Francisco, CA 94143 USA. [Weinstein, S.; Yee, J.] San Francisco VA Med Ctr, San Francisco, CA USA. [Osei-Bonsu, S.] Chicago Med Sch, N Chicago, IL USA. [Sajewicz, A.] Redwood Reg Med Grp, Santa Rosa, CA USA. EM stefage00@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400466 ER EF