FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Seda, G Sanchez-Ortuno, MM Welsh, CH Halbower, AC Edinger, JD AF Seda, Gilbert Sanchez-Ortuno, Maria M. Welsh, Carolyn H. Halbower, Ann C. Edinger, Jack D. TI Comparative Meta-Analysis of Prazosin and Imagery Rehearsal Therapy for Nightmare Frequency, Sleep Quality, and Posttraumatic Stress SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE posttraumatic stress disorder; nightmares; prazosin; imagery rehearsal therapy; cognitive behavior therapy; insomnia ID RANDOMIZED CONTROLLED-TRIAL; SEXUAL ASSAULT SURVIVORS; BEHAVIORAL TREATMENT; COMBAT VETERANS; CLINICAL-TRIAL; PTSD; DISORDER; TRAUMA; DISTURBANCES; SYMPTOMS AB Study Objective: In this meta-analysis, we compare the short-term efficacy of prazosin vs. IRT on nightmares, sleep quality, and posttraumatic stress symptoms (PTSS). Methods: Reference databases were searched for randomized controlled trials using IRT or prazosin for nightmares, sleep disturbance, and/or PTSS. Effect sizes were calculated by subtracting the mean posttest score in the control group from the mean posttest score in the treatment group, and dividing the result by the pooled standard deviation of both groups. Mixed effects models were performed to evaluate effects of treatment characteristics, as well as sample characteristics (veteran vs. civilian) on treatment efficacy. Results: Four studies used prazosin, 10 used IRT alone or in combination with another psychological treatment, and 1 included a group receiving prazosin and another group receiving IRT. Overall effect sizes of both treatments were of moderate magnitude for nightmare frequency, sleep quality, and PTSS (p < 0.01). Effect size was not significantly different with type of treatment (psychological vs. pharmacological) on nightmare frequency (p = 0.79), sleep quality (p = 0.65), or PTSS, (p = 0.52). IRT combined with CBT for insomnia showed more improvement in sleep quality compared to prazosin (p = 0.03), IRT alone (p = 0.03), or IRT combined with another psychological intervention, (p < 0.01). Conclusion: Although IRT interventions and prazosin yield comparable acute effects for the treatment of nightmares, adding CBT for insomnia to IRT seems to enhance treatment outcomes pertaining to sleep quality and PTSS. More randomized clinical trials with long-term follow-up are warranted. Commentary: A commentary on this article appears in this issue on page 9. C1 [Seda, Gilbert] Naval Med Ctr, Dept Pulm & Sleep Med, San Diego, CA USA. [Sanchez-Ortuno, Maria M.] Univ Murcia, Sch Nursing, Murcia, Spain. [Welsh, Carolyn H.] Univ Colorado, Dept Med, Div Pulm Sci & Crit Care Med, Denver, CO USA. [Halbower, Ann C.] Childrens Hosp Colorado, Dept Pulm Med, Denver, CO USA. [Halbower, Ann C.] Univ Colorado, Denver, CO 80202 USA. [Sanchez-Ortuno, Maria M.; Edinger, Jack D.] Natl Jewish Hlth, Dept Med, Denver, CO USA. [Welsh, Carolyn H.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Edinger, Jack D.] Duke Univ, Med Ctr, Durham, NC USA. RP Seda, G (reprint author), 8546 Chevy Chase Dr, La Mesa, CA 91941 USA. EM gilbert.seda@gmail.com FU Fundacion Seneca, Murcia, Spain FX This was not an industry supported study. The authors have indicated no financial conflicts of interest. Dr. Sanchez-Ortuno was supported by a research fellowship award from Fundacion Seneca, Murcia, Spain. The opinions expressed herein are those of the authors and do not necessarily reflect those of the Department of the Navy, Department of Defense, the U.S. Government, or any of its agencies. NR 51 TC 5 Z9 5 U1 4 U2 16 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 EI 1550-9397 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2015 VL 11 IS 1 BP 11 EP 22 DI 10.5664/jcsm.4354 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA CD5ZN UT WOS:000351167800004 PM 25325592 ER PT J AU Dzierzewski, JM Mitchell, M Rodriguez, JC Fung, CH Jouldjian, S Alessi, CA Martin, JL AF Dzierzewski, Joseph M. Mitchell, Michael Rodriguez, Juan Carlos Fung, Constance H. Jouldjian, Stella Alessi, Cathy A. Martin, Jennifer L. TI Patterns and Predictors of Sleep Quality Before, During, and After Hospitalization in Older Adults SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE sleep; hospitalization; aging; latent class analysis; clinical cutoffs ID POST-ACUTE REHABILITATION; LATENT CLASS ANALYSIS; ILLNESS RATING-SCALE; CLINICAL-OUTCOMES; POOR SLEEP; INDEX; PAIN; DEPRESSION; INSOMNIA; PEOPLE AB Study Objectives: The impact of hospitalization on sleep in late-life is underexplored. The current study examined patterns of sleep quality before, during, and following hospitalization, investigated predictors of sleep quality patterns, and examined predictors of classification discordance between two suggested clinical cutoffs used to demarcate poor/good sleep. Methods: This study included older adults (n = 163; mean age 79.7 +/- 6.9 years, 31% female) undergoing inpatient post-acute rehabilitation. Upon admission to inpatient postacute rehabilitation, patients completed the Pittsburgh Sleep Quality Index (PSQI) retrospectively regarding their sleep prior to hospitalization. They subsequently completed the PSQI at discharge, and 3 months, 6 months, 9 months, and 1 year post discharge. Patient demographic and clinical characteristics (pain, depression, cognition, comorbidity) were collected upon admission. Results: Using latent class analysis methods, older adults could be classified into (1) Consistently Good Sleepers and (2) Chronically Poor Sleepers based on patterns of self-reported sleep quality pre-illness, during, and up to 1 year following inpatient rehabilitation. This pattern was maintained regardless of the clinical cutoff employed (> 5 or > 8). Logistic regression analyses indicated that higher pain and depressive symptoms were consistently associated with an increased likelihood of being classified as a chronic poor sleeper. While there was substantial classifi cation discordance based on clinical cutoff employed, no significant predictors of this discordance emerged. Conclusions: Clinicians should exercise caution in assessing sleep quality in inpatient settings. Alterations in the cutoffs employed may result in discordant clinical classifi cations of older adults. Pain and depression warrant detailed considerations when working with older adults on inpatient units when poor sleep is a concern. C1 [Dzierzewski, Joseph M.; Rodriguez, Juan Carlos; Fung, Constance H.; Alessi, Cathy A.; Martin, Jennifer L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Dzierzewski, Joseph M.; Mitchell, Michael; Rodriguez, Juan Carlos; Fung, Constance H.; Jouldjian, Stella; Alessi, Cathy A.; Martin, Jennifer L.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Rodriguez, Juan Carlos] Pontificia Univ Catolica Chile, Sch Med, Santiago, Chile. RP Martin, JL (reprint author), VA GRECC 11E,16111 Plummer St, North Hills, CA 91343 USA. EM jennifer.martin@va.gov FU UCLA Claude Pepper Older Americans Independence Center by NIA [5P30AG028748, AG-10415]; NIH/NCATS UCLA CTSI [UL1TR000124]; NIA [K23 AG028452]; VA Health Services Research Development [IIR-01-053-1, IIR 04-321-2, AIA-03-047]; VA Advanced Geriatrics Fellowship Program; VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center; National Institute on Aging [K23AG045937] FX This work was performed at the University of California, Los Angeles and the VA Greater Los Angeles Healthcare System. This work was supported by UCLA Claude Pepper Older Americans Independence Center by NIA (5P30AG028748 & AG-10415), NIH/NCATS UCLA CTSI (UL1TR000124), NIA K23 AG028452, VA Health Services Research & Development IIR-01-053-1, IIR 04-321-2, and AIA-03-047, VA Advanced Geriatrics Fellowship Program, and VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center. CHF was supported by National Institute on Aging (K23AG045937). The content is solely the responsibility of the authors and not necessarily the responsibility of the funding agencies (VA or NIH). The authors have indicated no financial conflicts of interest. NR 40 TC 0 Z9 0 U1 2 U2 10 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 EI 1550-9397 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2015 VL 11 IS 1 BP 45 EP 51 DI 10.5664/jcsm.4362 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA CD5ZN UT WOS:000351167800008 PM 25325580 ER PT J AU Akhigbe, T Chin, AS Svircev, JN Hoenig, H Burns, SP Weaver, FM Bailey, L Carbone, L AF Akhigbe, Titilola Chin, Amy S. Svircev, Jelena N. Hoenig, Helen Burns, Stephen P. Weaver, Frances M. Bailey, Lauren Carbone, Laura TI A retrospective review of lower extremity fracture care in patients with spinal cord injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Lower extremity fractures; Spinal cord injury; Wheelchairs; Osteoporosis therapies ID ANKLE FRACTURES; OSTEOPOROTIC FRACTURES; HIP FRACTURE; RISK-FACTORS; WHEELCHAIR; WOMEN; PARAPLEGIA; COHORT AB Context/Objective: To identify circumstances surrounding incident lower extremity fractures (ILEFs) in patients with spinal cord injury (SCI) and to describe the impact of these fractures on service needs and provision of pharmacological therapies for osteoporosis. Design: Retrospective medical record review. Setting: Four Veterans Affairs Medical Centers in the USA. Participants: One hundred and forty patients with traumatic SCI who sustained an ILEF from 2002 to 2007. Outcome measures: Fracture circumstances and use of assistive devices were described using percentages, means, and standard deviations. Fisher's exact test was used to determine the relationship between fracture site, and patient age and duration of SCI. Differences in pharmacological provision of therapies for osteoporosis pre- and post-fracture were examined using exact McNemar's test. Results: One hundred and fifty-five ILEFs were identified in 140 patients. Tibia/fibula and femur fractures were the most common fractures. Fracture site was not related to patient's age or duration of SCI. Almost one-third of all fractures occurred during transfers to and from wheelchairs. Post-fracture, the provision of new or modified assistive devices, primarily wheelchairs, was frequent, occurring in 83% of patients in the year post-fracture. Few patients transferred residence to a nursing home following the fracture. There was a significant difference in the use of pharmacological therapies for osteoporosis in the first year post-fracture compared with the year prior to the fracture (P < 0.01), with significant differences in the volume of prescriptions for calcium supplements (P < 0.01) and bisphosphonates (P = 0.02). Overall, the amount of prescriptions for osteoporosis increased the year post-fracture (56%) from the year pre-fracture (39%); this increase was secondary to increases in prescriptions for calcium supplements (pre = 13%; post = 30%) and bisphosphonates (pre = 2%; post = 7%). Conclusions: We have identified that wheelchair and other transfer activities are a key area that could be a focus of fracture prevention in SCI. The need for new or modified assistive devices and/or wheelchair skills retraining post-fracture should be anticipated. Examination of whether treatments for osteoporosis following a fracture can prevent future osteoporotic fractures is warranted. C1 [Akhigbe, Titilola; Carbone, Laura] Dept Vet Affairs Med Ctr, Memphis, TN USA. [Akhigbe, Titilola; Carbone, Laura] Univ Tennessee, Ctr Hlth Sci, Dept Med, Memphis, TN 38163 USA. [Chin, Amy S.; Weaver, Frances M.; Bailey, Lauren] Edward J Hines Jr Vet Affairs Hosp, Hines, IL USA. [Svircev, Jelena N.; Burns, Stephen P.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Hoenig, Helen] Durham Vet Affairs Med Ctr, Durham, NC USA. [Weaver, Frances M.] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. RP Carbone, L (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Med, Div Rheumatol, 956 Court Ave,Room G326, Memphis, TN 38163 USA. EM lcarbone@uthsc.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development [IIR 08-033] FX This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development #IIR 08-033. NR 36 TC 5 Z9 5 U1 0 U2 1 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 EI 2045-7723 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD JAN PY 2015 VL 38 IS 1 BP 2 EP 9 DI 10.1179/2045772313Y.0000000156 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CD4RJ UT WOS:000351070900001 PM 24621029 ER PT J AU Bauman, WA La Fountaine, MF Cirnigliaro, CM Kirshblum, SC Spungen, AM AF Bauman, William A. La Fountaine, Michael F. Cirnigliaro, Christopher M. Kirshblum, Steven C. Spungen, Ann M. TI Lean tissue mass and energy expenditure are retained in hypogonadal men with spinal cord injury after discontinuation of testosterone replacement therapy SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Spinal cord injury; Lean tissue mass; Hypogonadism; Testosterone ID DENSITY LIPOPROTEIN CHOLESTEROL; ANDROGEN DEFICIENCY SYNDROMES; CLINICAL-PRACTICE GUIDELINE; BODY-COMPOSITION; CARDIOVASCULAR-DISEASE; MUSCLE STRENGTH; ADULT MEN; INDIVIDUALS; PLASMA; RISK AB Objective: To determine whether favorable changes to lean tissue mass (LTM), resting energy expenditure (REE), and testosterone (T) that occurred with 12 months of physiological testosterone replacement therapy (TRT) were retained 6 months after discontinuing treatment. Design: Prospective, open-label, controlled drug intervention trial. Setting: Metropolitan area hospitals. Subjects: Eugonadal (n = 11) and hypogonadal (n = 13) men with chronic spinal cord injury (SCI). Interventions: Hypogonadal subjects received a 5 or 10 mg transdermal T patch daily for 12 months, with adjustment of the dose to normalize the serum T concentration; TRT was discontinued after 12 months (TRT-12M) and subjects were followed for an additional 6 months and re-evaluated (Post-TRT). Total body dual energy X-ray absorptiometry and blood draws were performed at baseline (BL) prior to TRT, TRT-12M, and Post-TRT. Eugonadal subjects did not receive treatment and were evaluated at comparable time points. Results: There were no significant differences between groups prior to TRT at BL for any of the study endpoints. In the hypogonadal group, a significant increase in LTM was observed from BL to TRT-12M (50.2 +/- 7.4 vs. 52.9 +/- 6.8 kg, P < 0.01), which persisted Post-TRT compared to BL (52.2 +/- 7.8 kg, P < 0.05). The increase in REE from BL to TRT-12M (1283 +/- 246 vs. 1410 +/- 250 kcal/day) was also retained at Post-TRT (1393 +/- 220 kcal/day). These sustained improvements in LTM and REE after termination of anabolic hormonal therapy may be associated with persistent beneficial effects on health and physical function of hypogonadal men with chronic SCI. C1 [Bauman, William A.; La Fountaine, Michael F.; Cirnigliaro, Christopher M.; Spungen, Ann M.] James J Peters VA Med Ctr, VA RR&D Natl Ctr Excellence Med Consequences Spin, Bronx, NY 10468 USA. [Bauman, William A.; Spungen, Ann M.] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA. [Bauman, William A.; Spungen, Ann M.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Bauman, William A.; Spungen, Ann M.] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. [La Fountaine, Michael F.] Seton Hall Univ, Sch Hlth & Med Sci, Dept Phys Therapy, S Orange, NJ 07079 USA. [Kirshblum, Steven C.] Kessler Inst Rehabil, W Orange, NJ USA. [Kirshblum, Steven C.] Rutgers New Jersey Med Sch, Dept Phys Med & Rehabil, Newark, NJ USA. RP Bauman, WA (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM william.bauman@va.gov FU Veteran Affairs Rehabilitation Research and Development Service [B9212-C, B4162-C, B2468-C]; James J. Peters VA Medical Center FX Veteran Affairs Rehabilitation Research and Development Service (#B9212-C, #B4162-C, and #B2468-C) and the James J. Peters VA Medical Center. NR 41 TC 3 Z9 3 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1079-0268 EI 2045-7723 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD JAN PY 2015 VL 38 IS 1 BP 38 EP 47 DI 10.1179/2045772314Y.0000000206 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA CD4RJ UT WOS:000351070900005 PM 24968251 ER PT J AU Hausmann, LRM Myaskovsky, L Niyonkuru, C Oyster, ML Switzer, GE Burkitt, KH Fine, MJ Gao, SS Boninger, ML AF Hausmann, Leslie R. M. Myaskovsky, Larissa Niyonkuru, Christian Oyster, Michelle L. Switzer, Galen E. Burkitt, Kelly H. Fine, Michael J. Gao, Shasha Boninger, Michael L. TI Examining implicit bias of physicians who care for individuals with spinal cord injury: A pilot study and future directions SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Racism; Social discrimination; Spinal cord injuries; Wheelchair ID ASSOCIATION TEST; HEALTH-STATUS; MEDICAL-CARE; RACIAL/ETHNIC DISCRIMINATION; RACIAL-DISCRIMINATION; ETHNIC IDENTIFICATION; UNFAIR TREATMENT; NATIONAL LATINO; ASIAN-AMERICANS; ATTITUDES AB Context: Despite evidence that healthcare providers have implicit biases that can impact clinical interactions and decisions, implicit bias among physicians caring for individuals with spinal cord injury (SCI) has not been examined. Objective: Conduct a pilot study to examine implicit racial bias of SCI physicians and its association with functioning and wellbeing for individuals with SCI. Design: Combined data from cross-sectional surveys of individuals with SCI and their SCI physicians. Setting: Four national SCI Model Systems sites. Participants: Individuals with SCI (N = 162) and their SCI physicians (N = 14). Outcome measures: SCI physicians completed online surveys measuring implicit racial (pro-white/anti-black) bias. Individuals with SCI completed questionnaires assessing mobility, physical independence, occupational functioning, social integration, self-reported health, depression, and life satisfaction. We used multilevel regression analyses to examine the associations of physician bias and outcomes of individuals with SCI. Results: Physicians had a mean bias score of 0.62 (SD = 0.35), indicating a strong pro-white/anti-black bias. Greater physician bias was associated with disability among individuals with SCI in the domain of social integration (odds ratio = 4.80, 95% confidence interval (CI) = 1.44, 16.04), as well as higher depression (B = 3.24, 95% CI = 1.06, 5.41) and lower life satisfaction (B = -4.54, 95% CI= -8.79, -0.28). Conclusion: This pilot study indicates that SCI providers are susceptible to implicit racial bias and provides preliminary evidence that greater implicit racial bias of physicians is associated with poorer psychosocial health outcomes for individuals with SCI. It demonstrates the feasibility of studying implicit bias among SCI providers and provides guidance for future research on physician bias and patient outcomes. C1 [Hausmann, Leslie R. M.; Myaskovsky, Larissa; Switzer, Galen E.; Burkitt, Kelly H.; Fine, Michael J.; Gao, Shasha] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Hausmann, Leslie R. M.; Myaskovsky, Larissa; Switzer, Galen E.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Niyonkuru, Christian; Oyster, Michelle L.; Boninger, Michael L.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Oyster, Michelle L.; Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Ctr Excellence Wheelchairs & Associated Rehabil E, Pittsburgh, PA 15240 USA. RP Hausmann, LRM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Bldg 30,Univ Dr 151C, Pittsburgh, PA 15240 USA. EM leslie.hausmann@gmail.com OI Boninger, Michael/0000-0001-6966-919X FU Veterans Affairs Health Services Research and Development Career Development Program [RCD 06-287]; National Institute on Disability and Rehabilitation Research, Office of Special Education and Rehabilitation Services, U.S. Department of Education [H133N060019] FX This research was funded by the National Institute on Disability and Rehabilitation Research, Office of Special Education and Rehabilitation Services, U.S. Department of Education (grant no. H133N060019; PI: M.L.B.). Dr L.R.M.H.'s effort was supported by the Veterans Affairs Health Services Research and Development Career Development Program (RCD 06-287). NR 46 TC 10 Z9 10 U1 5 U2 8 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 EI 2045-7723 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD JAN PY 2015 VL 38 IS 1 BP 102 EP 110 DI 10.1179/2045772313Y.0000000184 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CD4RJ UT WOS:000351070900013 PM 24621034 ER PT J AU Reish, A Bastas, G Popescu, A Friedberger, M AF Reish, Andrew Bastas, Gerasimos Popescu, Adrian Friedberger, Marylouis TI Newly Diagnosed Lumbar Nerve Root Intradural Mass in the Setting of Chronic Lumbar Radicular Pain Refractory to Conservative Management SO PAIN PHYSICIAN LA English DT Article ID DISK DISEASE; SHEATH; TUMORS C1 [Reish, Andrew] Univ Michigan, Dept Phys Med & Rehabil, Ann Arbor, MI 48108 USA. [Bastas, Gerasimos] Vanderbilt Univ, Med Ctr, Dept Phys Med & Rehabil, Nashville, TN USA. [Popescu, Adrian] Univ Penn, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. [Friedberger, Marylouis] Vet Affairs Med Ctr, Pain Clin Philadelphia, Philadelphia, PA USA. RP Reish, A (reprint author), Univ Michigan, Dept Phys Med & Rehabil, 325 E Eisenhower Pkwy,Suite 100, Ann Arbor, MI 48108 USA. EM reisha@med.umich.edu NR 10 TC 0 Z9 0 U1 3 U2 4 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD JAN-FEB PY 2015 VL 18 IS 1 BP E79 EP E82 PG 4 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA CE0JF UT WOS:000351489600022 PM 25675075 ER PT J AU Cerulli, C Kothari, C Dichter, M Marcus, S Kim, TK Wiley, J Rhodes, KV AF Cerulli, Catherine Kothari, Catherine Dichter, Melissa Marcus, Steve Kim, Tae Kuen Wiley, Jim Rhodes, Karin V. TI Help-Seeking Patterns Among Women Experiencing Intimate Partner Violence: Do They Forgo the Criminal Justice System if Their Adjudication Wishes Are Not Met? SO VIOLENCE AND VICTIMS LA English DT Article DE domestic violence; prosecution; displacement; resources ID DOMESTIC VIOLENCE; PROCEDURAL JUSTICE; AFRICAN-AMERICAN; LEGAL; RISK; VICTIMS; CHRONICITY; PREVALENCE; DECISION; BARRIERS AB Following a criminal case disposition, an intimate partner violence (IPV) victim's willingness to seek future police and prosecutorial assistance may depend on her prior experiences within the system. This longitudinal study examines the relationship between IPV victims' future help-seeking based on past experiences. We hypothesized women would return to the criminal justice system if their adjudication wishes corresponded with prosecutors' actions. Contrary to the hypothesis, results suggest women return to the criminal system and other venues even if prosecutors' actions do not correspond to their earlier stated wishes. This has important policy implications given pro-prosecution protocols that encourage adjudication regardless of a woman's participation. C1 [Cerulli, Catherine] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Kothari, Catherine] Western Michigan Univ, Kalamazoo, MI 49008 USA. [Dichter, Melissa] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Marcus, Steve; Rhodes, Karin V.] Univ Penn, Philadelphia, PA 19104 USA. [Kim, Tae Kuen] Adelphi Univ, New York, NY USA. [Wiley, Jim] Univ Calif San Francisco, Inst Hlth Policy Studies & Family & Community Med, San Francisco, CA 94143 USA. RP Cerulli, C (reprint author), Univ Rochester, Med Ctr, Rochester, NY 14642 USA. EM Catherine_Cerulli@urmc.rochester.edu NR 42 TC 0 Z9 0 U1 7 U2 21 PU SPRINGER PUBLISHING CO PI NEW YORK PA 11 WEST 42ND STREET, NEW YORK, NY 10036 USA SN 0886-6708 EI 1945-7073 J9 VIOLENCE VICTIMS JI Violence Vict. PY 2015 VL 30 IS 1 BP 16 EP 31 DI 10.1891/0886-6708.VV-D-13-00064 PG 16 WC Criminology & Penology SC Criminology & Penology GA CE1VR UT WOS:000351601300002 PM 25774412 ER PT S AU Hu, W MacDonald, ML Elswick, DE Sweet, RA AF Hu, Wei MacDonald, Matthew L. Elswick, Daniel E. Sweet, Robert A. BE Geschwind, DH TI The glutamate hypothesis of schizophrenia: evidence from human brain tissue studies SO YEAR IN NEUROLOGY AND PSYCHIATRY SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE brain tissue; EAAT; glutamate receptors; glutamatergic neurons; schizophrenia ID MESSENGER-RNA EXPRESSION; MEDIAL TEMPORAL-LOBE; AMINO-ACID OXIDASE; ANTERIOR CINGULATE CORTEX; DENDRITIC SPINE DENSITY; DORSOLATERAL PREFRONTAL CORTEX; CORTICAL PYRAMIDAL NEURONS; PRIMARY AUDITORY-CORTEX; D-ASPARTATE RECEPTOR; NEUROLEPTIC-FREE SCHIZOPHRENICS AB A number of studies have indicated that antagonists of the N-methyl-d-aspartate subtypes of glutamate receptors can cause schizophrenia-like symptoms in healthy individuals and exacerbate symptoms in individuals with schizophrenia. These findings have led to the glutamate hypothesis of schizophrenia. Here we review the evidence for this hypothesis in postmortem studies of brain tissue from individuals affected by schizophrenia, summarizing studies of glutamate neuron morphology, of expression of glutamate receptors and transporters, and of the synthesizing and metabolizing enzymes for glutamate and its co-agonists. We found consistent evidence of morphological alterations of dendrites of glutamatergic neurons in the cerebral cortex of subjects with schizophrenia and of reduced levels of the axon bouton marker synaptophysin. There were no consistent alterations of mRNA expression of glutamate receptors, although there has been limited study of the corresponding proteins. Studies of the glutamate metabolic pathway have been limited, although there is some evidence that excitatory amino acid transporter-2, glutamine synthetase, and glutaminase have altered expression in schizophrenia. Future studies would benefit from additional direct examination of glutamatergic proteins. Further advances, such as selective testing of synaptic microdomains, cortical layers, and neuronal subtypes, may also be required to elucidate the nature of glutamate signaling impairments in schizophrenia. C1 [Hu, Wei; Elswick, Daniel E.] W Virginia Univ, Hlth Sci Ctr, Dept Behav Med & Psychiat, Morgantown, WV 26506 USA. [MacDonald, Matthew L.; Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA USA. RP Sweet, RA (reprint author), Biomed Sci Tower,Room W-1645,3811 OHara St, Pittsburgh, PA 15213 USA. EM sweetra@upmc.edu FU NIMH NIH HHS [MH 103204, MH 16804, MH 071533, P50 MH103204, R01 MH071533, R21 MH066231, T32 MH016804] NR 181 TC 21 Z9 21 U1 4 U2 27 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2015 VL 1338 BP 38 EP 57 DI 10.1111/nyas.12547 PG 20 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BC3ES UT WOS:000351581400004 PM 25315318 ER PT J AU Axon, RN Gebregziabher, M Craig, J Zhang, JW Mauldin, P Moran, WP AF Axon, R. Neal Gebregziabher, Mulugeta Craig, Janet Zhang, Jingwen Mauldin, Patrick Moran, William P. TI Frequency and Costs of Hospital Transfers for Ambulatory Care-Sensitive Conditions SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID NURSING-HOME RESIDENTS; LONG-TERM-CARE; RANDOMIZED CONTROLLED-TRIAL; PREVENTABLE HOSPITALIZATIONS; EARLY READMISSION; INPATIENT CARE; HEALTH-CARE; QUALITY; MEDICAID; ASSOCIATION AB Objectives Nursing home (NH) patients are frequently transferred to emergency departments (EDs) and/or hospitalized in situations in which transfer might have been avoided. This study describes the frequency of NH transfers for ambulatory care-sensitive conditions (ACSCs) and estimates associated expenditures. Study Design Retrospective cohort study of 62,379 NH patients with Medicare coverage receiving care in South Carolina between 2007 and 2009. Methods Subjects were analyzed to determine the frequency of acute ED or hospital care for conditions. Comparison is made to similar patients transferred for acute treatment of non-ACSCs. Generalized linear models were used to estimate the costs attributable to treating ACSCs. Results Over 3 years, 20,867 NH subjects were transferred from NHs to acute care facilities, and 85.3% of subjects had at least 1 episode of care for an ACSC. An average of 13,317 subjects per year were transferred for an average of 17,060 episodes of ED or hospital care per year between 2007 and 2009. More ACSC patients transferred to EDs were subsequently admitted to the hospital (50.4% vs 25%; P < .0001). In adjusted analyses, mean ED costs per episode of care ($401 vs $294; P < .0001) were higher, but mean hospitalization costs per episode of care were lower ($8356 vs $10,226; P < .0001) for ACSC patients compared with non-ACSC patients. Conclusions A significant proportion of Medicare NH patients are treated acutely for ACSCs, which are associated with higher healthcare utilization and costs. Better access to onsite evaluation might enable significant cost savings and reduce morbidity in this population. C1 [Axon, R. Neal] Ralph H Johnson VA Med Ctr, Hlth Equ & Rural Outreach Innovat Ctr, Charleston, NC USA. [Axon, R. Neal; Zhang, Jingwen; Mauldin, Patrick; Moran, William P.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta] Med Univ S Carolina, Dept Publ Hlth Serv, Charleston, SC 29425 USA. [Craig, Janet] Clemson Univ, Sch Nursing, Clemson, SC USA. [Craig, Janet] Hlth Sci South Carolina, Columbia, SC USA. RP Axon, RN (reprint author), Ralph H Johnson VAMC, 109 Bee St, Charleston, SC 29401 USA. EM axon@musc.edu OI Gebregziabher, Mulugeta/0000-0002-4826-481X FU South Carolina Clinical & Translational Research Institute; NIH [UL1 RR029882, UL1 TR000062] FX This project was supported by the South Carolina Clinical & Translational Research Institute, with an academic home at the Medical University of South Carolina, through NIH grant numbers UL1 RR029882 and UL1 TR000062. NR 38 TC 1 Z9 1 U1 0 U2 2 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JAN PY 2015 VL 21 IS 1 BP 51 EP 59 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CD3GC UT WOS:000350965300013 PM 25880150 ER PT J AU Rinne, ST Wong, ES Lemon, JM Perkins, M Bryson, CL Liu, CF AF Rinne, Seppo T. Wong, Edwin S. Lemon, Jaclyn M. Perkins, Mark Bryson, Christopher L. Liu, Chuan-Fen TI Survey Nonresponders Incurred Higher Medical Utilization and Lower Medication Adherence SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID HEALTH-CARE UTILIZATION; PATIENT SATISFACTION; DIABETES-MELLITUS; RISK-ADJUSTMENT; BIAS; POPULATION; VALIDATION; IMPACT; COHORT; ADULTS AB Objectives To compare healthcare costs, utilization, and medication adherence between diabetic responders and nonresponders to a patient satisfaction survey. Study Design We performed a retrospective cohort study of 40,766 patients with diabetes who had been randomly selected to receive the 2006 Veterans Affairs' Survey of Healthcare Experiences of Patients. Outcomes were measured during the following year. Methods We used multivariable models to compare healthcare costs (generalized linear models), utilization (negative binomial regression), and adherence to oral hypoglycemic medications (logistic regression) between survey responders and nonresponders. Results There were 26,051 patients (64%) who responded to the survey. Survey nonresponders incurred significantly higher healthcare costs (incremental effect, $792; 95% CI, $599-$986; P < .01). Nonresponders had a modest increase in primary care (incidence rate ratio [IRR], 1.06; 95% CI, 1.05-1.08; P < .01) and specialty care visits (IRR, 1.17; 95% CI, 1.12-1.22; P < .01), but more substantial increases in mental health visits (IRR, 1.74; 95% CI, 1.62-1.87; P < .01) and hospitalizations (IRR, 1.60; 95% CI, 1.46-1.75; P < .01). Medication adherence was significantly lower among survey nonresponders (odds ratio, 0.68; 95% CI, 0.65-0.74; P < .01). Conclusions Nonresponders to a patient satisfaction survey incurred higher healthcare costs and utilization, but had lower medication adherence. Understanding these characteristics helps to assess the impact of nonresponse bias on patient satisfaction surveys and identifies clinical practices to improve care delivery. C1 [Rinne, Seppo T.; Wong, Edwin S.; Lemon, Jaclyn M.; Perkins, Mark; Bryson, Christopher L.; Liu, Chuan-Fen] Dept Vet Affairs, VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Rinne, Seppo T.] Univ Washington, Div Pulm, Seattle, WA 98195 USA. [Rinne, Seppo T.] Univ Washington, Div Crit Care, Seattle, WA 98195 USA. [Rinne, Seppo T.; Bryson, Christopher L.] Univ Washington, Dept Med, Seattle, WA USA. [Bryson, Christopher L.] Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. [Liu, Chuan-Fen] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Rinne, ST (reprint author), 1100 Ol Way,Ste 1400, Seattle, WA 98104 USA. EM srinne@uw.edu FU US Department of Veterans Affairs, Office of Research and Development, Health Services Research Development FX This research is based upon work supported by the US Department of Veterans Affairs, Office of Research and Development, Health Services Research & 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 41 TC 0 Z9 0 U1 3 U2 4 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JAN PY 2015 VL 21 IS 1 BP E1 EP E8 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CD3GC UT WOS:000350965300001 PM 25880264 ER PT J AU Grindle, GG Wang, HW Jeannis, H Teodorski, E Cooper, RA AF Grindle, Garrett G. Wang, Hongwu Jeannis, Hervens Teodorski, Emily Cooper, Rory A. TI Design and User Evaluation of a Wheelchair Mounted Robotic Assisted Transfer Device SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID SITTING PIVOT TRANSFERS; SPINAL-CORD-INJURY; MANIPULATION APPLIANCE; PERSONAL MOBILITY; CARE FACILITIES; LIFTING DEVICES; KINEMATICS; SHOULDER; OVERHEAD; SYSTEM AB Purpose. The aim of this study is to describe the robotic assisted transfer device (RATD) and an initial focus group evaluation by end users. The purpose of the device is to aid in the transfers of people with disabilities to and from their electric powered wheelchair (EPW) onto other surfaces. The device can be used for both stand-pivot transfers and fully dependent transfers, where the person being transferred is in a sling and weight is fully on the robot. The RATD is fixed to an EPW to allow for its use in community settings. Method. A functional prototype of the RATD was designed and fabricated. The prototype was presented to a group of 16 end users and feedback on the device was obtained via a survey and group discussion. Results. Thirteen out of sixteen (83%) participants agreed that it was important to develop this type of technology. They also indicated that user, caregiver, and robotic controls were important features to be included in the device. Conclusions. Participants in this study suggested that they would be accepting the use of robotic technology for transfers and a majority did not feel that they would be embarrassed to use this technology. C1 [Grindle, Garrett G.; Wang, Hongwu; Jeannis, Hervens; Teodorski, Emily; Cooper, Rory A.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15232 USA. [Grindle, Garrett G.; Wang, Hongwu; Jeannis, Hervens; Teodorski, Emily; Cooper, Rory A.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15232 USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15232 USA. EM rcooper@pitt.edu RI Wang, Hongwu/J-6133-2013 OI Wang, Hongwu/0000-0002-6567-9144 FU National Science Foundation [EEC-540865, ERC-0540865]; Office of Research and Development; Rehabilitation Research & Development Service; Department of Veterans Affairs [B3142C]; Quality of Life Technology Engineering Research Center; VA Rehabilitation Research and Development Service [B6789C] FX This material is based upon work supported in part by the National Science Foundation Grant no. EEC-540865, Office of Research and Development, Rehabilitation Research & Development Service, Department of Veterans Affairs, Grant no. B3142C, Quality of Life Technology Engineering Research Center, National Science Foundation (ERC-0540865), and the VA Rehabilitation Research and Development Service (B6789C). The contents of this paper do not represent the views of the Department of Veterans Affairs or the United States Government. NR 26 TC 0 Z9 0 U1 2 U2 11 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2015 AR 198476 DI 10.1155/2015/198476 PG 9 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CD4ZX UT WOS:000351097200001 ER PT J AU Lin, AY Kotova, S Yanagawa, J Elbuluk, O Wang, G Kar, N Elashoff, D Grogan, T Cameron, RB Singh, A Chmielowski, B Federman, N Nelson, SD Lee, P Eilber, FC Lee, JM AF Lin, Anthony Y. Kotova, Svetlana Yanagawa, Jane Elbuluk, Osama Wang, Gerald Kar, Nivedita Elashoff, David Grogan, Tristan Cameron, Robert B. Singh, Arun Chmielowski, Bartosz Federman, Noah Nelson, Scott D. Lee, Percy Eilber, Fritz C. Lee, Jay M. TI Risk stratification of patients undergoing pulmonary metastasectomy for soft tissue and bone sarcomas SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID LONG-TERM SURVIVAL; HIGH-GRADE OSTEOSARCOMA; PROGNOSTIC-FACTORS; RESECTION; CHEMOTHERAPY; OUTCOMES; BENEFIT AB Objectives: Our objective was to identify risk factors associated with survival in patients who underwent pulmonary metastasectomy for soft tissue or bone sarcoma and to create a risk stratification model. Methods: A retrospective review of the prospectively maintained University of California Los Angeles Sarcoma Database was performed. Clinical, pathologic, and treatment variables were analyzed for overall survival and disease-free survival. Univariate and multivariate analyses were performed, and variables that were identified as significant were included to create a risk model. A total of 155 patients who underwent pulmonary metastasectomy for soft tissue sarcoma (n = 108 patients) or bone sarcoma (n = 47 patients) from 1994 to 2010 were identified. Results: Multivariate analysis identified 7 factors associated with poor overall survival: age more than 45 years, disease-free interval less than 1 year, thoracotomy, synchronous disease, location and type of sarcoma (soft tissue vs bone sarcoma), and performance of a lobectomy. The number of factors present was associated with poor overall survival, which varied widely from 64% in patients with 2 factors to 3% in those with 5 factors. Conclusions: We have identified prognostic variables associated with overall survival after lung metastasectomy. Our model may be used as a risk stratification model to guide treatment decisions on the basis of the number of risk factors present. Although prospective studies are warranted to determine the benefit of surgical intervention in all cohorts compared with other local therapies or medical therapy, given the attendant dismal prognosis in patients with 5 or more risk factors, the benefit of surgical resection in this group is questioned. C1 [Lin, Anthony Y.; Kotova, Svetlana; Yanagawa, Jane; Elbuluk, Osama; Cameron, Robert B.; Lee, Jay M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Div Thorac Surg, Los Angeles, CA 90095 USA. [Wang, Gerald] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. [Kar, Nivedita] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biostat, Los Angeles, CA 90095 USA. [Kar, Nivedita] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Elashoff, David; Grogan, Tristan] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Singh, Arun; Chmielowski, Bartosz] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Med Oncol, Los Angeles, CA 90095 USA. [Federman, Noah] Univ Calif Los Angeles, David Geffen Sch Med, Div Pediat Hematol & Med Oncol, Dept Pediat, Los Angeles, CA 90095 USA. [Nelson, Scott D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Lee, Percy] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiat Oncol, Los Angeles, CA 90095 USA. [Eilber, Fritz C.] Univ Calif Los Angeles, David Geffen Sch Med, Div Surg Oncol, Dept Surg, Los Angeles, CA 90095 USA. [Kotova, Svetlana; Cameron, Robert B.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Thorac Surg, Dept Surg, Los Angeles, CA USA. RP Lee, JM (reprint author), Univ Calif Los Angeles, Med Ctr, Div Thorac Surg, Box 957313,Room 64-128 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM jaymoonlee@mednet.ucla.edu OI Chmielowski, Bartosz/0000-0002-2374-3320 FU Jonsson Comprehensive Cancer Center Sarcoma Program FX Funded by the Jonsson Comprehensive Cancer Center Sarcoma Program. NR 20 TC 7 Z9 7 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JAN PY 2015 VL 149 IS 1 BP 85 EP 92 DI 10.1016/j.jtcvs.2014.09.039 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CC7LW UT WOS:000350550100030 PM 25312228 ER PT S AU Yang, XH Friedl, A AF Yang, Xinhai Friedl, Andreas BE Diakonova, M TI A Positive Feedback Loop Between Prolactin and STAT5 Promotes Angiogenesis SO RECENT ADVANCES IN PROLACTIN RESEARCH SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID BREAST-CANCER-CELLS; CAPILLARY ENDOTHELIAL-CELLS; GROWTH-HORMONE FAMILY; N-TERMINAL FRAGMENTS; CYCLIN D1 PROMOTER; SIGNAL-TRANSDUCTION; MESSENGER-RNA; 16-KDA PROLACTIN; JAK/STAT PATHWAY; SERINE PHOSPHORYLATION AB The signal transduction events that orchestrate cellular activities required for angiogenesis remain incompletely understood. We and others recently described that proangiogenic mediators such as fibroblast growth factors can activate members of the signal transducers and activators of transcription (STAT) family. STAT5 activation is necessary and sufficient to induce migration, invasion and tube formation of endothelial cells. STAT5 effects on endothelial cells require the secretion of the prolactin (PRL) family member proliferin-1 (PLF1) in mice and PRL in humans. In human endothelial cells, PRL activates the PRL receptor (PRLR) resulting in MAPK and STAT5 activation, thus closing a positive feedback loop. In vivo, endothelial cell-derived PRL is expected to combine with PRL of tumor cell and pituitary origin to raise the concentration of this polypeptide hormone in the tumor microenvironment. Thus, PRL may stimulate tumor angiogenesis via autocrine, paracrine, and endocrine pathways. The disruption of tumor angiogenesis by interfering with PRL signaling may offer an attractive target for therapeutic intervention. C1 [Yang, Xinhai; Friedl, Andreas] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53705 USA. [Friedl, Andreas] William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Dept Vet Affairs, Med Ctr, Madison, WI 53705 USA. [Friedl, Andreas] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. RP Friedl, A (reprint author), Univ Wisconsin, Dept Pathol & Lab Med, 6051 WIMR,MC-2275,1111 Highland Ave, Madison, WI 53705 USA. EM afriedl@wisc.edu FU NCI NIH HHS [P30 CA014520] NR 134 TC 4 Z9 4 U1 3 U2 10 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-3-319-12114-7; 978-3-319-12113-0 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2015 VL 846 BP 265 EP 280 DI 10.1007/978-3-319-12114-7_12 D2 10.1007/978-3-319-12114-7 PG 16 WC Biology; Medicine, Research & Experimental; Physiology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Physiology GA BC1TY UT WOS:000350422800013 PM 25472543 ER PT J AU Locatelli, SM Turcios, S LaVela, SL AF Locatelli, Sara M. Turcios, Stephanie LaVela, Sherri L. TI Optimizing the Patient-Centered Environment: Results of Guided Tours With Health Care Providers and Employees SO HERD-HEALTH ENVIRONMENTS RESEARCH & DESIGN JOURNAL LA English DT Article DE patient-centered care; design; architecture; patient and/or family; health care ID PARTICIPATORY ACTION RESEARCH; DESIGN; COMPLEMENTARY; INTERVENTION; EXPERIENCE; VETERANS; MEDICINE; STORIES; QUALITY; EXPLORE AB Objective: To examine providers' perspectives on the care environment and patient-centered care (PCC) through the eyes of the veteran patient, using guided tours qualitative methodology. Background: Environmental factors, such as attractiveness and function, have the potential to improve patients' experiences. Participatory qualitative methods allow researchers to explore the environment and facilitate discussion. Methods: Guided tours were conducted with 25 health care providers/employees at two Veterans Affairs (VA) health care facilities. In guided tours, participants lead the researcher through an environment, commenting on their surroundings, thoughts, and feelings. The researcher walks along with the participant, asking open-ended questions as needed to foster discussion and gain an understanding of the participant's view. Participants were asked to walk through the facility as though they were a veteran. Tours were audio recorded, with participant permission, and transcribed verbatim by research assistants. Three qualitative researchers were responsible for code-book development and coding transcripts and used data-driven coding approaches. Results: Participants discussed physical appearance of the environment and how that influences perceptions about care. Overall, participants highlighted the need to shed the "institutional'' appearance. Differences between VA and non-VA health care facilities were discussed, including availability of private rooms and staff to assist with navigating the facility. They reviewed resources in the facility, such as the information desk to assist patients and families. Finally, they offered suggestions for future improvements, including improvements to waiting areas and quiet areas for patients to relax and "get away'' from their rooms. Conclusions: Participants highlighted many small changes to the care environment that could enhance the patient experience. Additionally, they examined the environment from the patient's perspective, to identify elements that enhance, or detract from, the patient's care experience. C1 [Locatelli, Sara M.; LaVela, Sherri L.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Innovat Complex Chron Healthcare, Hines, IL 60141 USA. [Locatelli, Sara M.; Turcios, Stephanie; LaVela, Sherri L.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Evaluat Practices & Experiences Patient Ctr C, Hines, IL 60141 USA. [LaVela, Sherri L.] Northwestern Univ, Feinberg Sch Med, Ctr Healthcare Studies, Chicago, IL 60611 USA. RP Locatelli, SM (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Innovat Complex Chron Healthcare, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. EM sara.locatelli@va.gov FU Veterans Affairs (VA) Office of Patient-Centered Care & Cultural Transformation; VA Health Services Research & Development Quality Enhancement Research Initiative [PCE 13-002] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This article is based on an evaluation funded by the Veterans Affairs (VA) Office of Patient-Centered Care & Cultural Transformation and the VA Health Services Research & Development Quality Enhancement Research Initiative (PCE 13-002, PI: LaVela). NR 42 TC 3 Z9 3 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1937-5867 EI 2167-5112 J9 HERD-HEALTH ENV RES JI Herd-Health Env. Res. Des. J. PD JAN PY 2015 VL 8 IS 2 BP 18 EP 30 DI 10.1177/1937586714565610 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CC5QF UT WOS:000350414800004 PM 25816378 ER PT J AU Genther, DJ Betz, J Pratt, S Kritchevsky, SB Martin, KR Harris, TB Helzner, E Satterfield, S Xue, QL Yaffe, K Simonsick, EM Lin, FR AF Genther, Dane J. Betz, Joshua Pratt, Sheila Kritchevsky, Steven B. Martin, Kathryn R. Harris, Tamara B. Helzner, Elizabeth Satterfield, Suzanne Xue, Qian-Li Yaffe, Kristine Simonsick, Eleanor M. Lin, Frank R. CA Hlth ABC Study TI Association of Hearing Impairment and Mortality in Older Adults SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Epidemiology; Longevity; Outcomes; Public health; Successful aging ID BLUE-MOUNTAINS HEARING; HEALTH INTERVIEW SURVEY; UNITED-STATES; LONGITUDINAL ANALYSIS; GAIT SPEED; SURVIVAL; RISK; PREDICTORS; DISEASE; DEPRESSION AB Background. Hearing impairment (HI) is highly prevalent in older adults and is associated with social isolation, depression, and risk of dementia. Whether HI is associated with broader downstream outcomes is unclear. We undertook this study to determine whether audiometric HI is associated with mortality in older adults. Methods. Prospective observational data from 1,958 adults >= 70 years of age from the Health, Aging, and Body Composition Study were analyzed using Cox proportional hazards regression. Participants were followed for 8 years after audiometric examination. Mortality was adjudicated by obtaining death certificates. Hearing was defined as the pure-tone average of hearing thresholds in decibels re: hearing level (dB HL) at frequencies from 0.5 to 4 kHz. HI was defined as pure-tone average >25 dB HL in the better ear. Results. Of the 1,146 participants with HI, 492 (42.9%) died compared with 255 (31.4%) of the 812 with normal hearing (odds ratio = 1.64, 95% CI: 1.36-1.98). After adjustment for demographics and cardiovascular risk factors, HI was associated with a 20% increased mortality risk compared with normal hearing (hazard ratio = 1.20, 95% CI: 1.03-1.41). Confirmatory analyses treating HI as a continuous predictor yielded similar results, demonstrating a nonlinear increase in mortality risk with increasing HI (hazard ratio = 1.14, 95% CI: 1.00-1.29 per 10 dB of threshold elevation up to 35 dB HL). Conclusions. HI in older adults is associated with increased mortality, independent of demographics and cardiovascular risk factors. Further research is necessary to understand the basis of this association and whether these pathways might be amenable to hearing rehabilitation. C1 [Genther, Dane J.; Lin, Frank R.] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA. [Genther, Dane J.; Betz, Joshua; Xue, Qian-Li; Lin, Frank R.] Johns Hopkins Ctr Aging & Hlth, Baltimore, MD USA. [Betz, Joshua] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Pratt, Sheila] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. [Pratt, Sheila] Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. [Kritchevsky, Steven B.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27103 USA. [Kritchevsky, Steven B.] J Paul Sticht Ctr Aging, Winston Salem, NC USA. [Martin, Kathryn R.] Univ Aberdeen, Dept Epidemiol, Aberdeen AB9 1FX, Scotland. [Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Helzner, Elizabeth] Suny Downstate Med Ctr, Dept Epidemiol & Biostat, Brooklyn, NY 11203 USA. [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Xue, Qian-Li; Simonsick, Eleanor M.; Lin, Frank R.] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Dept Med, Baltimore, MD 21287 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 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. [Simonsick, Eleanor M.] NIA, Intramural Res Program, Bethesda, MD 20892 USA. [Lin, Frank R.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Lin, Frank R.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. RP Genther, DJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, 601 N Caroline St,JHOC 6210, Baltimore, MD 21287 USA. EM dgenthe2@jhmi.edu OI Genther, Dane/0000-0002-7925-012X; Betz, Joshua/0000-0003-4488-9799 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050, K24AG031155]; National Institute of Nursing Research (NINR) [R01-NR012459]; National Institutes of Health (NIH) [T32DC000027]; National Institute on Deafness and Other Communication Disorders (NIDCD) [K23DC011279]; Intramural Research Program of the National Institute on Aging; Triological Society; American College of Surgeons through the Clinician Scientist Award; Eleanor Schwartz Charitable Foundation FX This research was supported by National Institute on Aging (NIA) (N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106); NIA grant (R01-AG028050); and National Institute of Nursing Research (NINR) grant (R01-NR012459). This study was further supported in part by National Institutes of Health (NIH) grant (T32DC000027), NIA grant (K24AG031155), National Institute on Deafness and Other Communication Disorders (NIDCD) grant (K23DC011279), Intramural Research Program of the National Institute on Aging, Triological Society and American College of Surgeons through the Clinician Scientist Award, and Eleanor Schwartz Charitable Foundation. S.P. was supported with resources and the use of facilities at the VA Pittsburgh Healthcare System, Pittsburgh, PA; however, the contents do not represent the views of the Department of Veterans Affairs or the United States Government. The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation of the manuscript. NR 41 TC 14 Z9 15 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2015 VL 70 IS 1 BP 85 EP 90 DI 10.1093/gerona/glu094 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CC1RJ UT WOS:000350119900011 PM 25024235 ER PT J AU Zhao, W Wang, J Varghese, M Ho, L Mazzola, P Haroutunian, V Katsel, PL Gibson, GE Levine, S Dubner, L Pasinetti, GM AF Zhao, Wei Wang, Jun Varghese, Merina Ho, Lap Mazzola, Paolo Haroutunian, Vahram Katsel, Pavel L. Gibson, Gary E. Levine, Samara Dubner, Lauren Pasinetti, Giulio Maria TI Impaired mitochondrial energy metabolism as a novel risk factor for selective onset and progression of dementia in oldest-old subjects SO NEUROPSYCHIATRIC DISEASE AND TREATMENT LA English DT Article DE Alzheimer disease; energy metabolism; neuropathology; mitochondria; dementia ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; 6-PHOSPHOFRUCTO-1-KINASE ISOZYMES; OXIDATIVE STRESS; BRAIN; PATHOPHYSIOLOGY; NEUROPATHOLOGY; PREVALENCE; NITRATION; PROTEINS AB Recent evidence shows that Alzheimer disease (AD) dementia in the oldest-old subjects was associated with significantly less amyloid plaque and fibrillary tangle neuropathology than in the young-old population. In this study, using quantitative (q) PCR studies, we validated genome-wide microarray RNA studies previously conducted by our research group. We found selective downregulation of mitochondrial energy metabolism genes in the brains of oldest-old, but not young-old, AD dementia cases, despite a significant lack of classic AD neuropathology features. We report a significant decrease of genes associated with mitochondrial pyruvate metabolism, the tricarboxylic acid cycle (TCA), and glycolytic pathways. Moreover, significantly higher levels of nitrotyrosylated (3-NT)-proteins and 4-hydroxy-2-nonenal (HNE) adducts, which are indexes of cellular protein oxidation and lipid peroxidation, respectively, were detected in the brains of oldest-old subjects at high risk of developing AD, possibly suggesting compensatory mechanisms. These findings support the hypothesis that although oldest-old AD subjects, characterized by significantly lower AD neuropathology than young-old AD subjects, have brain mitochondrial metabolism impairment, which we hypothesize may selectively contribute to the development of dementia. Outcomes from this study provide novel insights into the molecular mechanisms underlying clinical dementia in young-old and oldest-old AD subjects and provide novel strategies for AD prevention and treatment in oldest-old dementia cases. C1 [Zhao, Wei; Wang, Jun; Varghese, Merina; Ho, Lap; Mazzola, Paolo; Levine, Samara; Dubner, Lauren; Pasinetti, Giulio Maria] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Zhao, Wei; Wang, Jun; Ho, Lap; Haroutunian, Vahram; Katsel, Pavel L.; Pasinetti, Giulio Maria] James J Peter VA Med Ctr, Geriatr Res Educ Clin Ctr, Bronx, NY USA. [Mazzola, Paolo] Univ Milano Bicocca, Dept Hlth Sci, Monza, Italy. [Haroutunian, Vahram; Katsel, Pavel L.; Pasinetti, Giulio Maria] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Haroutunian, Vahram] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Gibson, Gary E.] Weill Cornell Med Coll, Burke Med Res Inst, Dept Neurol & Neurosci, New York, NY USA. [Pasinetti, Giulio Maria] Icahn Sch Med Mt Sinai, Dept Geriatr, New York, NY 10029 USA. RP Pasinetti, GM (reprint author), Icahn Sch Med Mt Sinai, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu OI Mazzola, Paolo/0000-0002-0484-1136; Varghese, Merina/0000-0002-1517-3903 FU Career Scientist Award in the Research and Development unit FX This material is the result of work supported in part with resources and the use of facilities at the James J. Peters Veterans Affairs Medical Center, Bronx, NY. In addition, Dr. Pasinetti holds a Career Scientist Award in the Research and Development unit and is the Director of the Basic and Biomedical Research and Training Program, GRECC, James J. Peters Veterans Affairs Medical Center. We also acknowledge that the contents of this manuscript do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. NR 40 TC 7 Z9 7 U1 1 U2 3 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2021 J9 NEUROPSYCH DIS TREAT JI Neuropsychiatr. Dis. Treat. PY 2015 VL 11 BP 565 EP 574 DI 10.2147/NDT.S74898 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CC4SK UT WOS:000350343500001 PM 25784811 ER PT J AU Ford, JM Palzes, VA Roach, BJ Potkin, SG van Erp, TGM Turner, JA Mueller, BA Calhoun, VD Voyvodic, J Belger, A Bustillo, J Vaidya, JG Preda, A McEwen, SC Mathalon, DH AF Ford, Judith M. Palzes, Vanessa A. Roach, Brian J. Potkin, Steven G. van Erp, Theo G. M. Turner, Jessica A. Mueller, Bryon A. Calhoun, Vincent D. Voyvodic, Jim Belger, Aysenil Bustillo, Juan Vaidya, Jatin G. Preda, Adrian McEwen, Sarah C. Mathalon, Daniel H. CA Functional Imaging Biomed TI Visual Hallucinations Are Associated With Hyperconnectivity Between the Amygdala and Visual Cortex in People With a Diagnosis of Schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Article ID PARKINSONS-DISEASE PATIENTS; MULTI-FEATURE PARADIGM; AUDITORY HALLUCINATIONS; MISMATCH NEGATIVITY; CONSCIOUS PERCEPTION; BRAIN; FMRI; MEMORY; FRAMEWORK; SYSTEM AB While auditory verbal hallucinations (AH) are a cardinal symptom of schizophrenia, people with a diagnosis of schizophrenia (SZ) may also experience visual hallucinations (VH). In a retrospective analysis of a large sample of SZ and healthy controls (HC) studied as part of the functional magnetic resonance imaging (fMRI) Biomedical Informatics Research Network (FBIRN), we asked if SZ who endorsed experiencing VH during clinical interviews had greater connectivity between visual cortex and limbic structures than SZ who did not endorse experiencing VH. We analyzed resting state fMRI data from 162 SZ and 178 age- and gender-matched HC. SZ were sorted into groups according to clinical ratings on AH and VH: SZ with VH (VH-SZ; n = 45), SZ with AH but no VH (AH-SZ; n = 50), and SZ with neither AH nor VH (NoH-SZ; n = 67). Our primary analysis was seed based, extracting connectivity between visual cortex and the amygdala (because of its role in fear and negative emotion) and visual cortex and the hippocampus (because of its role in memory). Compared with the other groups, VH-SZ showed hyperconnectivity between the amygdala and visual cortex, specifically BA18, with no differences in connectivity among the other groups. In a voxel-wise, whole brain analysis comparing VH-SZ with AH-SZ, the amygdala was hyperconnected to left temporal pole and inferior frontal gyrus in VH-SZ, likely due to their more severe thought broadcasting. VH-SZ have hyperconnectivity between subcortical areas subserving emotion and cortical areas subserving higher order visual processing, providing biological support for distressing VH in schizophrenia. C1 [Ford, Judith M.; Palzes, Vanessa A.; Roach, Brian J.; Mathalon, Daniel H.] San Francisco VA Med Ctr, Psychiat Serv, San Francisco, CA 94121 USA. [Ford, Judith M.; Palzes, Vanessa A.; Roach, Brian J.; Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Potkin, Steven G.; van Erp, Theo G. M.; Preda, Adrian] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [Turner, Jessica A.; Calhoun, Vincent D.] Mind Res Network, Albuquerque, NM USA. [Turner, Jessica A.] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. [Turner, Jessica A.] Georgia State Univ, Dept Neurosci, Atlanta, GA 30303 USA. [Mueller, Bryon A.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Calhoun, Vincent D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Voyvodic, Jim; Belger, Aysenil] Duke Univ, Univ N Carolina, Brain Imaging & Anal Ctr, Durham, NC USA. [Belger, Aysenil] Univ N Carolina, Dept Psychiat, Durham, NC USA. [Bustillo, Juan] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [Vaidya, Jatin G.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [McEwen, Sarah C.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Functional Imaging Biomed] Funct Imaging Biomed Informat Res Network FBIRN, Sao Paulo, Brazil. RP Ford, JM (reprint author), San Francisco VA Med Ctr, Psychiat Serv 116D, 4150 Clement St, San Francisco, CA 94121 USA. EM Judith.Ford@ucsf.edu RI Preda, Adrian /K-8889-2013 OI Preda, Adrian /0000-0003-3373-2438; Roach, Brian/0000-0002-3264-1465; Potkin, Steven/0000-0003-1028-1013 FU Biomedical Informatics Research Network [U24RR021992] FX Biomedical Informatics Research Network (U24RR021992). NR 42 TC 20 Z9 20 U1 1 U2 23 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2015 VL 41 IS 1 BP 223 EP 232 DI 10.1093/schbul/sbu031 PG 10 WC Psychiatry SC Psychiatry GA CC0WA UT WOS:000350057900031 PM 24619536 ER PT J AU Lener, MS Wong, E Tang, CY Byne, W Goldstein, KE Blair, NJ Haznedar, MM New, AS Chemerinski, E Chu, KW Rimsky, LS Siever, LJ Koenigsberg, HW Hazlett, EA AF Lener, Marc S. Wong, Edmund Tang, Cheuk Y. Byne, William Goldstein, Kim E. Blair, Nicholas J. Haznedar, M. Mehmet New, Antonia S. Chemerinski, Eran Chu, King-Wai Rimsky, Liza S. Siever, Larry J. Koenigsberg, Harold W. Hazlett, Erin A. TI White Matter Abnormalities in Schizophrenia and Schizotypal Personality Disorder SO SCHIZOPHRENIA BULLETIN LA English DT Article DE DTI; MRI; schizotypal personality disorder; schizophrenia; psychosis; white matter; genu; cingulum; inferior longitudinal fasciculus ID DIFFUSION TENSOR TRACTOGRAPHY; INTERNAL CAPSULE; CORPUS-CALLOSUM; 1ST-EPISODE SCHIZOPHRENIA; UNCINATE FASCICULUS; RHESUS-MONKEY; ANTERIOR LIMB; IMAGING DTI; BRAIN; INTEGRITY AB Prior diffusion tensor imaging (DTI) studies examining schizotypal personality disorder (SPD) and schizophrenia, separately have shown that compared with healthy controls (HCs), patients show frontotemporal white matter (WM) abnormalities. This is the first DTI study to directly compare WM tract coherence with tractography and fractional anisotropy (FA) across the schizophrenia spectrum in a large sample of demographically matched HCs (n = 55), medication-naive SPD patients (n = 49), and unmedicated/never-medicated schizophrenia patients (n = 22) to determine whether (a) frontal-striatal-temporal WM tract abnormalities in schizophrenia are similar to, or distinct from those observed in SPD; and (b) WM tract abnormalities are associated with clinical symptom severity indicating a common underlying pathology across the spectrum. Compared with both the HC and SPD groups, schizophrenia patients showed WM abnormalities, as indexed by lower FA in the temporal lobe (inferior longitudinal fasciculus) and cingulum regions. SPD patients showed lower FA in the corpus callosum genu compared with the HC group, but this regional abnormality was more widespread in schizophrenia patients. Across the schizophrenia spectrum, greater WM disruptions were associated with greater symptom severity. Overall, frontal-striatal-temporal WM dysconnectivity is attenuated in SPD compared with schizophrenia patients and may mitigate the emergence of psychosis. C1 [Lener, Marc S.; Byne, William; Goldstein, Kim E.; Haznedar, M. Mehmet; New, Antonia S.; Chemerinski, Eran; Rimsky, Liza S.; Siever, Larry J.; Koenigsberg, Harold W.; Hazlett, Erin A.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Wong, Edmund; Tang, Cheuk Y.] Icahn Sch Med Mt Sinai, Translat & Mol Imaging Inst, Dept Radiol, New York, NY 10029 USA. [Byne, William; Blair, Nicholas J.; New, Antonia S.; Chu, King-Wai; Siever, Larry J.; Hazlett, Erin A.] James J Peters Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr MIRECC VISN 3, Bronx, NY USA. [Byne, William; Haznedar, M. Mehmet; Chemerinski, Eran; Siever, Larry J.; Koenigsberg, Harold W.] James J Peters Vet Affairs Med Ctr, Dept Outpatient Psychiat, Bronx, NY USA. [Blair, Nicholas J.; Chu, King-Wai; Hazlett, Erin A.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Hazlett, EA (reprint author), James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr, 130 West Kingsbridge Rd,Room 6A-44, Bronx, NY 10468 USA. EM erin.hazlett@mssm.edu FU National Institutes of Health; Veterans Administration [NIMH-R01-MH073911, VA MERIT-I01CX00026] FX National Institutes of Health and the Veterans Administration (NIMH-R01-MH073911 and VA MERIT-I01CX00026 to E.A.H.). Partial support for the schizophrenia sample was also provided (NIMH-R01-MH069947 to H.W.K.). NR 71 TC 13 Z9 13 U1 9 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2015 VL 41 IS 1 BP 300 EP 310 DI 10.1093/schbul/sbu093 PG 11 WC Psychiatry SC Psychiatry GA CC0WA UT WOS:000350057900038 PM 24962608 ER PT J AU Patel, BR AF Patel, Bina R. TI Caregivers of Veterans with "Invisible" Injuries: What We Know and Implications for Social Work Practice SO SOCIAL WORK LA English DT Article DE caregivers; Iraq; Afghanistan caregivers; military caregivers; Operation Iraqi Freedom and Operation Enduring Freedom caregivers; veteran caregivers ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN-INJURY; MENTAL-HEALTH; WAR VETERANS; MILITARY; FAMILIES; PARTNERS; SPOUSES; SUPPORT; BURDEN AB Today, as a result of the longest volunteer-fought conflict in U.S. history, there are many wounded coming home not only with posttraumatic stress disorder (PTSD), but also with traumatic brain injury (TBI), which together have been called the "signature" or "invisible" injuries of the Iraq and Afghanistan wars. Caregivers are an important part of their recovery, yet little is known about them, as previous research on caregivers mostly focused on geriatric populations. According to one estimate 275,000 to 1 million people are currently caring or have cared for loved ones who have returned from Iraq and Afghanistan. These caregivers are unique in that they are younger, some with children, and they are caring for a unique understudied population for longer periods of time. This article summarizes literature on caregivers of veterans who suffer from PTSD, TBI, or both; provides a theoretical framework; and discusses implications for social workers in assisting caregivers and their families. C1 US Dept Vet Affairs, Social Work, Gainesville, FL 32608 USA. RP Patel, BR (reprint author), US Dept Vet Affairs, Social Work, 1601 SW Archer Rd,Mail Code 116A-4, Gainesville, FL 32608 USA. EM beepat617@hotmail.com NR 52 TC 0 Z9 0 U1 3 U2 17 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0037-8046 EI 1545-6846 J9 SOC WORK JI Soc. Work PD JAN PY 2015 VL 60 IS 1 BP 9 EP 17 DI 10.1093/sw/swu043 PG 9 WC Social Work SC Social Work GA CC1PJ UT WOS:000350113200002 PM 25643571 ER PT J AU Mendez, MF Sabodash, V AF Mendez, Mario F. Sabodash, Valeriy TI Clinical Amyloid Imaging in Logopenic Progressive Aphasia SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE primary progressive aphasia (PPA); logopenic; Alzheimer disease; amyloid imaging; florbetapir ID ALZHEIMERS-DISEASE AB The introduction of florbetapir (Amyvid) positron emission tomography biomarkers could dramatically change how we clinically evaluate young patients who present with nonamnestic cognitive complaints for possible Alzheimer disease (AD). Logopenic progressive aphasia (LPA) may be the most common example of this type of clinical problem. In most, but not all, cases, LPA is an early-onset AD variant presenting with language changes that can be difficult to distinguish from other progressive aphasias. We clinically evaluated 3 patients with LPA, in comparison with age-matched and severity-matched patients with typical amnestic AD, using florbetapir amyloid neuroimaging. The fluorodeoxyglucose-positron emission tomography scans of LPA patients revealed focal hypometabolism in the left temporoparietal areas, and the florbetapir scans were diffusely positive for the presence of amyloid deposition. The florbetapir scans did not differ in distribution between patients with LPA and those with typical amnestic AD. Clinical amyloid imaging, although lacking localizing value, is a major advance in the assessment of early-onset and nonamnestic patients for the presence of beta-amyloid Alzheimer pathology. C1 [Mendez, Mario F.; Sabodash, Valeriy] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Mendez, Mario F.; Sabodash, Valeriy] VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit, Los Angeles, CA 90073 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@UCLA.edu FU National Institute on Aging [R01 AG034499] FX M.F.M. supported by National Institute on Aging R01 AG034499. NR 10 TC 2 Z9 2 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD JAN-MAR PY 2015 VL 29 IS 1 BP 94 EP 96 PG 3 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA CC1RG UT WOS:000350119500016 PM 23995816 ER PT J AU Singh, JA Noorbaloochi, S MacDonald, R Maxwell, LJ AF Singh, Jasvinder A. Noorbaloochi, Shahrzad MacDonald, Roderick Maxwell, Lara J. TI Chondroitin for osteoarthritis SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID SYMPTOMATIC KNEE OSTEOARTHRITIS; PLACEBO-CONTROLLED TRIAL; CLINICALLY SIGNIFICANT DIFFERENCE; ANALOG SCALE PAIN; DOUBLE-BLIND; GLUCOSAMINE HYDROCHLORIDE; MANGANESE ASCORBATE; HIP OSTEOARTHRITIS; OSTEO-ARTHRITIS; 6 SULFATE AB Background Osteoarthritis, a common joint disorder, is one of the leading causes of disability. Chondroitin has emerged as a new treatment. Previous meta-analyses have shown contradictory results on the efficacy of chondroitin. This, in addition to the publication of more trials, necessitates a systematic review. Objectives To evaluate the benefit and harm of oral chondroitin for treating osteoarthritis compared with placebo or a comparator oral medication including, but not limited to, nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics, opioids, and glucosamine or other "herbal" medications. Search methods We searched seven databases up to November 2013, including the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, CINAHL, EMBASE, Science Citation Index (Web of Science) and Current Controlled Trials. We searched the US Food andDrug Administration (FDA) and EuropeanMedicines Agency (EMEA) websites for adverse effects. Trial registers were not searched. Selection criteria All randomized or quasi-randomized clinical trials lasting longer than two weeks, studying adults with osteoarthritis in any joint, and comparing chondroitin with placebo, an active control such as NSAIDs, or other "herbal" supplements such as glucosamine. Data collection and analysis Two review authors independently performed all title assessments, data extractions, and risk of bias assessments. Main results Forty-three randomized controlled trials including 4,962 participants treated with chondroitin and 4,148 participants given placebo or another control were included. The majority of trials were in knee OA, with few in hip and hand OA. Trial duration varied from 1 month to 3 years. Participants treated with chondroitin achieved statistically significantly and clinically meaningful better pain scores (0-100) in studies less than 6 months than those given placebo with an absolute risk difference of 10% lower (95% confidence interval (CI), 15% to 6% lower; number needed to treat (NNT) = 5 (95% CI, 3 to 8; n = 8 trials) (level of evidence, low; risk of bias, high); but there was high heterogeneity between the trials (T-2 = 0.07; I-2 = 70%, which was not easily explained by differences in risk of bias or study sample size). In studies longer than 6 months, the absolute risk difference for pain was 9% lower (95% CI 18% lower to 0%); n = 6 trials; T-2 = 0.18; I-2 = 83%), again with low level of evidence. For the Western Ontario and McMaster Universities Osteoarthritis Index Minimal Clinically Important Improvement (WOMAC MCII Pain subscale) outcome, a reduction in knee pain by 20% was achieved by 53/100 in the chondroitin group versus 47/100 in the placebo group, an absolute risk difference of 6% (95% CI 1% to 11%), (RR 1.12, 95% CI 1.01 to 1.24; T-2 = 0.00; I-2 = 0%) (n = 2 trials, 1253 participants; level of evidence, high; risk of bias, low). Differences in Lequesne's index (composite of pain, function and disability) statistically significantly favoured chondroitin as compared with placebo in studies under six months, with an absolute risk difference of 8% lower (95% CI 12% to 5% lower; T-2 = 0.78; n = 7 trials) (level of evidence, moderate; risk of bias, unclear), also clinically meaningful. Loss of minimum joint space width in the chondroitin group was statistically significantly less than in the placebo group, with a relative risk difference of 4.7% less (95% CI 1.6% to 7.8% less; n = 2 trials) (level of evidence, high; risk of bias, low). Chondroitin was associated with statistically significantly lower odds of serious adverse events compared with placebo with Peto odds ratio of 0.40 (95% CI 0.19 to 0.82; n = 6 trials) (level of evidence, moderate). Chondroitin did not result in statistically significant numbers of adverse events or withdrawals due to adverse events compared with placebo or another drug. Adverse events were reported in a limited fashion, with some studies providing data and others not. Comparisons of chondroitin taken alone or in combination with glucosamine or another supplement showed a statistically significant reduction in pain (0-100) when compared with placebo or an active control, with an absolute risk difference of 10% lower (95% CI 14% to 5% lower); NNT = 4 (95% CI 3 to 6); T-2 = 0.33; I-2 = 91%; n = 17 trials) (level of evidence, low). For physical function, chondroitin in combination with glucosamine or another supplement showed no statistically significant difference from placebo or an active control, with an absolute risk difference of 1% lower (95% CI 6% lower to 3% higher with T-2 = 0.04; n = 5 trials) (level of evidence, moderate). Differences in Lequesne's index statistically significantly favoured chondroitin as compared with placebo, with an absolute risk difference of 8% lower (95% CI, 12% to 4% lower; T-2 = 0.12; n = 10 trials) (level of evidence, moderate). Chondroitin in combination with glucosamine did not result in statistically significant differences in the numbers of adverse events, withdrawals due to adverse events, or in the numbers of serious adverse events compared with placebo or with an active control. The beneficial effects of chondroitin in pain and Lequesne's index persisted when evidence was limited to studies with adequate blinding or studies that used appropriate intention to treat (ITT) analyses. These beneficial effects were uncertain when we limited data to studies with appropriate allocation concealment or a large study sample (>200) or to studies without pharmaceutical funding. Authors' conclusions A review of randomized trials of mostly low quality reveals that chondroitin (alone or in combination with glucosamine) was better than placebo in improving pain in participants with osteoarthritis in short-term studies. The benefit was small to moderate with an 8 point greater improvement in pain (range 0 to 100) and a 2 point greater improvement in Lequesne's index (range 0 to 24), both seeming clinically meaningful. These differences persisted in some sensitivity analyses and not others. Chondroitin had a lower risk of serious adverse events compared with control. More high-quality studies are needed to explore the role of chondroitin in the treatment of osteoarthritis. The combination of some efficacy and low risk associated with chondroitin may explain its popularity among patients as an over-the-counter supplement. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Dept Med, Birmingham, AL 35294 USA. [Noorbaloochi, Shahrzad] Minneapolis VA Med Ctr, Dept Med, Minneapolis, MN USA. [Noorbaloochi, Shahrzad] Univ Minnesota, Minneapolis, MN USA. [MacDonald, Roderick] VA Med Ctr, Minneapolis, MN USA. [Maxwell, Lara J.] Univ Ottawa, Inst Populat Hlth, Ctr Global Hlth, Ottawa, ON, Canada. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Dept Med, Fac Off Tower 805B,510 20th St South, Birmingham, AL 35294 USA. EM jasvinder.md@gmail.com FU University of Alabama at Birmingham, Birmingham, Alabama, USA; Birmingham VA Medical Center, Birmingham, Alabama, USA; Center for Chronic Disease Outcomes Research and Center for Epidemiological and Clinical Research, Minneapolis VA Medical Center, Minneapolis, Minnesota, USA; Cochrane Complementary Medicine Field Bursary, USA; Cochrane Complementary Medicine Field Bursary FX Internal sources; University of Alabama at Birmingham and the Birmingham VA Medical Center, Birmingham, Alabama, USA.; Center for Chronic Disease Outcomes Research and Center for Epidemiological and Clinical Research, Minneapolis VA Medical Center, Minneapolis, Minnesota, USA.; External sources; Cochrane Complementary Medicine Field Bursary, USA.; We received a $5,000 Cochrane Complementary Medicine Field Bursary to complete this review. This money was used to pay research associates to perform data abstraction and data quality assurance/quality improvement. NR 153 TC 4 Z9 4 U1 3 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2015 IS 1 AR CD005614 DI 10.1002/14651858.CD005614.pub2 PG 304 WC Medicine, General & Internal SC General & Internal Medicine GA CB5ST UT WOS:000349688600008 ER PT J AU Ruggiero, KJ Davidson, TM McCauley, J Gros, KS Welsh, K Price, M Resnick, HS Danielson, CK Soltis, K Galea, S Kilpatrick, DG Saunders, BE Nissenboim, J Muzzy, W Fleeman, A Amstadter, AB AF Ruggiero, Kenneth J. Davidson, Tatiana M. McCauley, Jenna Gros, Kirstin Stauffacher Welsh, Kyleen Price, Matthew Resnick, Heidi S. Danielson, Carla Kmett Soltis, Kathryn Galea, Sandro Kilpatrick, Dean G. Saunders, Benjamin E. Nissenboim, Josh Muzzy, Wendy Fleeman, Anna Amstadter, Ananda B. TI Bounce Back Now! Protocol of a population-based randomized controlled trial to examine the efficacy of a Web-based intervention with disaster-affected families SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Disaster mental health; Population-based research; Web intervention; Adolescents ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL TREATMENT; NEW-YORK-CITY; MENTAL-HEALTH; SUBSTANCE USE; HURRICANE KATRINA; RARE VARIANTS; YOUNG-PEOPLE; CHILDREN; ADOLESCENTS AB Disasters have far-reaching and potentially long-lasting effects on youth and families. Research has consistently shown a clear increase in the prevalence of several mental health disorders after disasters, including depression and posttraumatic stress disorder. Widely accessible evidence-based interventions are needed to address this unmet need for youth and families, who are underrepresented in disaster research. Rapid growth in Internet and Smartphone access, as well as several Web based evaluation studies with various adult populations has shown that Web-based interventions are likely to be feasible in this context and can improve clinical outcomes. Such interventions also are generally cost-effective, can be targeted or personalized, and can easily be integrated in a stepped care approach to screening and intervention delivery. This is a protocol paper that describes an innovative study design in which we evaluate a self-help Web-based resource, Bounce Back Now, with a population-based sample of disaster affected adolescents and families. The paper includes description and justification for sampling selection and procedures, selection of assessment measures and methods, design of the intervention, and statistical evaluation of critical outcomes. Unique features of this study design include the use of address-based sampling to recruit a population-based sample of disaster-affected adolescents and parents, telephone and Web-based assessments, and development and evaluation of a highly individualized Web intervention for adolescents. Challenges related to large-scale evaluation of technology-delivered interventions with high-risk samples in time-sensitive research are discussed, as well as implications for future research and practice. Published by Elsevier Inc. C1 [Ruggiero, Kenneth J.; Davidson, Tatiana M.; Soltis, Kathryn; Muzzy, Wendy] Med Univ S Carolina, Coll Nursing, Technol Applicat Ctr Healthful Lifestyles, Charleston, SC 29425 USA. [Ruggiero, Kenneth J.; Gros, Kirstin Stauffacher; Welsh, Kyleen; Muzzy, Wendy] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Davidson, Tatiana M.; Welsh, Kyleen; Resnick, Heidi S.; Danielson, Carla Kmett; Soltis, Kathryn; Kilpatrick, Dean G.; Saunders, Benjamin E.] MUSC, Dept Psychiat & Behav Sci, Natl Crime Victims Res & Treatment Ctr, Charleston, SC USA. [McCauley, Jenna] MUSC, Dept Psychiat & Behav Sci, Clin Neurosci Div, Charleston, SC USA. [Price, Matthew] Univ Vermont, Ctr Res Emot Stress & Technol, Burlington, VT USA. [Galea, Sandro] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Nissenboim, Josh] Fuzzco Inc, Charleston, SC USA. [Fleeman, Anna] Abt SRBI, New York, NY USA. [Amstadter, Ananda B.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat Psychol & Human & Mol Genet, Richmond, VA USA. RP Ruggiero, KJ (reprint author), Med Univ S Carolina, Coll Nursing, Technol Applicat Ctr Healthful Lifestyles, Charleston, SC 29425 USA. EM ruggierk@musc.edu RI Emchi, Karma/Q-1952-2016 FU National Institute of Mental Health (NIMH) [R01 MH081056]; NIMH [MH081056, T32 MH018869]; National Institute on Drug Abuse (NIDA) [R01 DA031285]; National Institute on Alcohol Abuse and Alcoholism (NIAAA) [P50 AA010761]; NIDA [K12 DA031794]; NIAAA [K02 AA023239]; [R21 MH086313] FX This research was supported by National Institute of Mental Health (NIMH) Grant R01 MH081056 (PI: KJ Ruggiero). This includes two supplements to NIMH Grant MH081056: an OppNet supplement awarded to Dr. Amstadter, and a Diversity supplement awarded to Dr. Davidson. Grant R21 MH086313 (PI: CK Danielson) also supported some elements of this work. The preparation of this manuscript was supported by National Institute on Drug Abuse (NIDA) Grant R01 DA031285 (PI: CK Danielson) and National Institute on Alcohol Abuse and Alcoholism (NIAAA) Grant P50 AA010761 (PI: Becker); NIDA Grant K12 DA031794 (PI: Brady; support to JM), NIMH Grant T32 MH018869 (PI: Kilpatrick; support to MP), and NIAAA K02 AA023239 (PI: Amstadter). All views and opinions expressed herein are those of the authors and do not necessarily reflect those of the funding agency or respective institutions. NR 85 TC 6 Z9 6 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2015 VL 40 BP 138 EP 149 DI 10.1016/j.cct.2014.11.018 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA CB6IZ UT WOS:000349732000016 PM 25478956 ER PT J AU Karlin, BE Trockel, M Brown, GK Gordienko, M Yesavage, J Taylor, CB AF Karlin, Bradley E. Trockel, Mickey Brown, Gregory K. Gordienko, Maria Yesavage, Jerome Taylor, C. Barr TI Comparison of the Effectiveness of Cognitive Behavioral Therapy for Depression among Older Versus Younger Veterans: Results of a National Evaluation SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article DE Cognitive behavioral therapy; Department of Veterans Affairs; Depression; Geriatrics; Older adultsVeterans ID LATE-LIFE DEPRESSION; WORKING ALLIANCE INVENTORY; COLLABORATIVE RESEARCH-PROGRAM; GERIATRIC MENTAL-HEALTH; QUALITY-OF-LIFE; PSYCHOMETRIC PROPERTIES; ELDERLY-PATIENTS; ADULTS; PSYCHOTHERAPY; CARE AB Objectives. The effectiveness of cognitive behavioral therapy for depression (CBT-D) among older adults in routine clinical settings has received limited attention. The current article examines and compares outcomes of older versus younger veterans receiving CBT-D nationally. Method. Patient outcomes were assessed using the Beck Depression Inventory-II and World Health Organization Quality of Life-BREF. Therapeutic alliance was assessed using the Working Alliance Inventory-Short Revised. Results. A total of 764 veterans aged 18-64 and 100 veterans aged 65+ received CBT-D; 68.0% of older and 68.3% of younger patients completed all sessions or finished early due to symptom relief, and mean depression scores declined from 27.0 (standard deviation [SD] = 10.7) to 16.2 (SD = 12.4) in the older group and from 29.1 (SD = 11.2) to 17.8 (SD = 13.5) in the younger group. Within-group effect sizes were d = 1.01 for both groups. Significant increases in quality of life and therapeutic alliance were observed for both groups. Discussion. CBT-D resulted in significant improvements in depression and quality of life among older patients. Outcomes and rate of attrition were equivalent to younger patients. Findings indicate that CBT-D is an effective and acceptable treatment for older veterans in real-world settings with often high levels of depression. C1 [Karlin, Bradley E.] US Dept Vet Affairs, Mental Hlth Serv, Cent Off, Washington, DC USA. [Karlin, Bradley E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Trockel, Mickey; Gordienko, Maria; Yesavage, Jerome; Taylor, C. Barr] Stanford Univ, Med Ctr, Dept Psychiat, Palo Alto, CA 94304 USA. [Trockel, Mickey; Gordienko, Maria; Yesavage, Jerome; Taylor, C. Barr] Vet Affairs Palo Alto Hlth Care Syst, VISN Mental Illness Res Educ & Clin Ctr 21, Palo Alto, CA 94304 USA. [Brown, Gregory K.] Philadelphia VA Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 4, Philadelphia, PA USA. [Brown, Gregory K.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Karlin, BE (reprint author), VA Cent Off, Mental Hlth Serv 10P4M, 810 Vermont Ave NW, Washington, DC 20420 USA. EM Bradley.Karlin2@va.gov FU Mental Health Services, U. S. Department of Veterans Affairs (VA) Central Office FX This project was supported by Mental Health Services, U. S. Department of Veterans Affairs (VA) Central Office. NR 71 TC 3 Z9 3 U1 1 U2 18 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5014 EI 1758-5368 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD JAN PY 2015 VL 70 IS 1 BP 3 EP 12 DI 10.1093/geronb/gbt096 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA CC0QA UT WOS:000350039400002 PM 24218096 ER PT J AU Phipps, C Gopal, AK Storer, BE Cassaday, RD Press, OW Till, BG Pagel, JM Palanca-Wessels, MC Philip, M Bensinger, WI Holmberg, LA Shustov, AR Green, DJ Chauncey, T Maloney, DG Libby, EN AF Phipps, Colin Gopal, Ajay K. Storer, Barry E. Cassaday, Ryan D. Press, Oliver W. Till, Brian G. Pagel, John M. Palanca-Wessels, Maria C. Philip, Mary Bensinger, William I. Holmberg, Leona A. Shustov, Andrei R. Green, Damian J. Chauncey, Thomas Maloney, David G. Libby, Edward N., III TI Autologous transplant for relapsed follicular lymphoma: impact of pre-transplant rituximab sensitivity SO LEUKEMIA & LYMPHOMA LA English DT Article DE Follicular lymphoma; autologous transplant; rituximab-refractory ID STEM-CELL TRANSPLANTATION; INTERNATIONAL PROGNOSTIC INDEX; NON-HODGKIN-LYMPHOMA; EVENT-FREE SURVIVAL; MARROW-TRANSPLANTATION; THERAPY; EXPRESSION; RESISTANCE; BENDAMUSTINE; CHEMOTHERAPY AB Patients with rituximab-refractory follicular lymphoma (FL) have limited options. Before the rituximab era, autologous stem cell transplant (ASCT) was shown to improve outcomes in chemotherapy-sensitive, relapsed FL, but the impact of rituximab-sensitivity on these results is unknown. We analyzed 194 consecutive relapsed patients with FL who underwent ASCT at out center and categorized them as rituximab-sensitive (RS, n = 35), rituximab-refractory (RR, n = 65) or no rituximab (NoR, n = 94) if transplanted before rituximab was used. Progression-free survival at 3 years was 85% in RS and 35% in RR patients (p = 0.0004). Only rituximab-sensitivity was significant on multivariate analysis with improved overall survival (OS) (hazard ratio [HR] 0.24, p = 0.01) and progression-free survival (PFS) (HR 0.35, p = 0.006) in RS patients and increased relapse in RR patients (HR 2.11, p = 0.01). Pre-transplant rituximab-sensitivity is a strong independent predictor of post-transplant outcomes in relapsed FL, although one-third of RR patients achieved a PFS of over 3 years with ASCT. C1 [Phipps, Colin; Gopal, Ajay K.; Storer, Barry E.; Cassaday, Ryan D.; Press, Oliver W.; Till, Brian G.; Pagel, John M.; Palanca-Wessels, Maria C.; Philip, Mary; Bensinger, William I.; Holmberg, Leona A.; Shustov, Andrei R.; Green, Damian J.; Chauncey, Thomas; Maloney, David G.; Libby, Edward N., III] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98104 USA. [Phipps, Colin] Singapore Gen Hosp, Dept Haematol, Singapore, Singapore. [Gopal, Ajay K.; Press, Oliver W.; Till, Brian G.; Pagel, John M.; Palanca-Wessels, Maria C.; Philip, Mary; Bensinger, William I.; Holmberg, Leona A.; Shustov, Andrei R.; Green, Damian J.; Chauncey, Thomas; Maloney, David G.; Libby, Edward N., III] Univ Washington, Sch Med, Seattle, WA USA. [Storer, Barry E.] Univ Washington, Sch Publ Hlth & Biostat, Seattle, WA USA. [Chauncey, Thomas] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Phipps, C (reprint author), Seattle Canc Care Alliance, 825 Eastlake Ave East, Seattle, WA 98109 USA. EM phipps_8@msn.com FU NIH [PO1CA44991]; Mary A. Wright Memorial Research Fund FX This study received funding from NIH PO1CA44991, the Mary A. Wright Memorial Research Fund and a donation from Frank and Betty Vandermeer. A.K.G. is a Scholar in Clinical Research of the Leukemia and Lymphoma Society. The authors also thank members of the research and clinical staff at the Seattle Cancer Care Alliance, and referring physicians for their contribution to the care of our patients. NR 23 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JAN PY 2015 VL 56 IS 1 BP 92 EP 96 DI 10.3109/10428194.2014.911866 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA CB5IR UT WOS:000349661200016 PM 24707941 ER PT B AU Walker, RH AF Walker, Ruth H. BE LeDoux, MS TI Genetics of Huntington Disease (HD), HD-Like Disorders, and Other Choreiform Disorders SO MOVEMENT DISORDERS: GENETICS AND MODELS, 2ND EDITION LA English DT Article; Book Chapter ID BENIGN HEREDITARY CHOREA; AGE-OF-ONSET; CAG REPEAT LENGTH; PAROXYSMAL KINESIGENIC DYSKINESIA; MCLEOD-SYNDROME; TRINUCLEOTIDE REPEAT; INFANTILE CONVULSIONS; CLINICAL PROGRESSION; HEMIPLEGIC MIGRAINE; JAPANESE FAMILY C1 [Walker, Ruth H.] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Walker, Ruth H.] Mt Sinai Sch Med, New York, NY USA. RP Walker, RH (reprint author), James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. NR 132 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-405516-2; 978-0-12-405195-9 PY 2015 BP 519 EP 532 DI 10.1016/B978-0-12-405195-9.00030-5 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BB9KO UT WOS:000348389700032 ER PT B AU Handforth, A AF Handforth, Adrian BE LeDoux, MS TI Use of the Harmaline and alpha 1 Knockout Models to Identify Molecular Targets for Essential Tremor SO MOVEMENT DISORDERS: GENETICS AND MODELS, 2ND EDITION LA English DT Article; Book Chapter ID INFERIOR OLIVARY NEURONS; DRUG-INDUCED TREMOR; OPEN-LABEL TRIAL; CEREBELLAR CLIMBING FIBERS; GABA(A) RECEPTOR SUBTYPES; CALCIUM-CHANNEL BLOCKERS; PLACEBO-CONTROLLED TRIAL; COMPLEX SPIKE ACTIVITY; RAT SENSORY NEURONS; OLIVOCEREBELLAR SYSTEM C1 Vet Affairs Greater Los Angeles Healthcare Syst, Neurol Serv, Los Angeles, CA 90073 USA. RP Handforth, A (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Neurol Serv, Los Angeles, CA 90073 USA. NR 150 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-405516-2; 978-0-12-405195-9 PY 2015 BP 615 EP 629 DI 10.1016/B978-0-12-405195-9.00037-8 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BB9KO UT WOS:000348389700039 ER PT J AU Jain, D Sheth, H Green, JA Bender, FH Weisbord, SD AF Jain, Deepika Sheth, Heena Green, Jamie A. Bender, Filitsa H. Weisbord, Steven D. TI Health Literacy in Patients on Maintenance Peritoneal Dialysis: Prevalence and Outcomes SO PERITONEAL DIALYSIS INTERNATIONAL LA English DT Article ID ASSOCIATIONS; HEMODIALYSIS; ADHERENCE; DISEASE C1 [Jain, Deepika; Sheth, Heena; Bender, Filitsa H.; Weisbord, Steven D.] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA 15260 USA. [Green, Jamie A.] Geisinger Med Ctr, Dept Nephrol, Danville, PA 17822 USA. [Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Jain, D (reprint author), Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA 15260 USA. EM 26.deepika@gmail.com NR 14 TC 3 Z9 3 U1 0 U2 6 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 0896-8608 J9 PERITON DIALYSIS INT JI Perit. Dial. Int. PD JAN-FEB PY 2015 VL 35 IS 1 DI 10.3747/pdi.2013.00211 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA CB9XM UT WOS:000349987600017 PM 25700462 ER PT J AU Shadel, WG Elliott, MN Haas, AC Haviland, AM Orr, N Farmer, MM Ma, S Weech-Maldonado, R Farley, DO Cleary, PD AF Shadel, William G. Elliott, Marc N. Haas, Ann C. Haviland, Amelia M. Orr, Nate Farmer, Melissa M. Ma, Sai Weech-Maldonado, Robert Farley, Donna O. Cleary, Paul D. TI Clinician advice to quit smoking among seniors SO PREVENTIVE MEDICINE LA English DT Article DE Physician/patient communication; Medicare; Patient education; Smoking cessation ID ALZHEIMER-DISEASE; TOBACCO MEASURES; HEALTH-CARE; CESSATION; SMOKERS; OLDER; RISK; INTERVENTIONS; US; DISPARITIES AB Objective. Little smoking research in the past 20 years includes persons 50 and older; herein we describe patterns of clinician cessation advice to US seniors, including variation by Medicare beneficiary characteristics. Method. In 2012-4, we analyzed 2010 Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey data from Medicare beneficiaries over age 64 (n=346,674). We estimated smoking rates and the proportion of smokers whose clinicians encouraged cessation. Results. 12% of male and 8% of female respondents aged 65 and older smoke. The rate decreases with age (14% of 65-69,3% of 85+) and education (12-15% with no high school degree, 5-6% with BA +). Rates are highest among American Indian/Alaskan Native (16%), multiracial (14%), and African-American (13%) seniors, and in the Southeast (14%). Only 51% of smokers say they receive cessation advice "always" or "usually" at doctor visits, with advice more often given to the young, those in low-smoking regions, Asians, and women. For all results cited p < 0.05. Conclusions. Smoking cessation advice to seniors is variable. Providers may focus on groups or areas in which smoking is less common or when they are most comfortable giving advice. More consistent interventions are needed, including cessation advice from clinicians. (C) 2014 Elsevier Inc. All rights reserved. C1 [Shadel, William G.; Haas, Ann C.; Haviland, Amelia M.; Farley, Donna O.] RAND Corp, Pittsburgh, PA 15213 USA. [Elliott, Marc N.; Orr, Nate] RAND Corp, Santa Monica, CA 90407 USA. [Haviland, Amelia M.] Carnegie Mellon Univ, H John Heinz Coll 3, Pittsburgh, PA 15213 USA. [Orr, Nate] Ctr Medicare & Medicaid Serv, Baltimore, MD 21244 USA. [Weech-Maldonado, Robert] Univ Alabama Birmingham, Dept Hlth Serv Adm, Birmingham, AL 35294 USA. [Farmer, Melissa M.] VA Greater Los Angeles Healthcare Syst, Vet Adm HSR&D Ctr Study Healthcare Innovat Implem, Sepulveda, CA 91343 USA. [Cleary, Paul D.] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA. RP Elliott, MN (reprint author), RAND Corp, 1776 Main St, Santa Monica, CA 90401 USA. EM shadel@rand.org; elliott@rand.org; ahaas@rand.org; haviland@cmu.edu; orr@rand.org; Melissa.Farmer@va.gov; sai.ma@cms.hhs.gov; rweech@uab.edu; farley@rand.org; paul.cleary@yale.edu FU CMS [HHSM-500-2005-00028I] FX This study was funded by CMS contract HHSM-500-2005-00028I to RAND. NR 48 TC 5 Z9 5 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD JAN PY 2015 VL 70 BP 83 EP 89 DI 10.1016/j.ypmed.2014.11.020 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA CB9GB UT WOS:000349938900016 PM 25482423 ER PT J AU Shamran, HA Kadhim, HS Hussain, AR Kareem, A Taub, DD Price, RL Nagarkatti, M Nagarkatti, PS Singh, UP AF Shamran, Haidar A. Kadhim, Haider S. Hussain, Aws R. Kareem, Abdulameer Taub, Dennis D. Price, Robert L. Nagarkatti, Mitzi Nagarkatti, Prakash S. Singh, Udai P. TI Detection of Human Cytomegalovirus in Different Histopathological Types of Glioma in Iraqi Patients SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID GROWTH-FACTOR RECEPTOR; HUMAN BRAIN-TUMORS; CELL-TO-CELL; GLYCOPROTEIN-B; GLIOBLASTOMA; EXPRESSION; INFECTION; FUSION; ASSOCIATION; THERAPY AB Human Cytomegalovirus (HCMV) is an endemic herpes virus that reemerges in cancer patients enhancing oncogenic potential. HCMV infection is associated with certain types of cancer morbidity such as glioblastomas. HCMV, like all other herpes viruses, has the ability to remain latent within the body of the host and can contribute in chronic inflammation. To determine the role of HCMV in glioma pathogenesis, paraffin-embedded blocks from glioma patients (n = 50) and from benign meningioma patients (n = 30) were obtained and evaluated by immunohistochemistry and polymerase chain reaction for the evidence of HCMV antigen expression and the presence of viral DNA. We detected HCMV antigen and DNA for IEI-72, pp65, and late antigen in 33/36, 28/36, and 26/36 in glioblastoma multiforme patients whereas 12/14, 10/14, and 9/14 in anaplastic astrocytoma patients, respectively. Furthermore, 84% of glioma patients were positive for immunoglobulin G (IgG) compared to 72.5% among control samples (P = 0.04). These data indicate the presence of the HCMV virus in a high percentage of glioma samples demonstrating distinct histopathological grades and support previous reports showing the presence of HCMV infection in glioma tissue. These studies demonstrate that detection of low-levels of latent viral infections may play an active role in glioma development and pathogenesis. C1 [Shamran, Haidar A.] Univ Al Nahrain, Sch Med, Med Res Unit, Baghdad 10066, Iraq. [Kadhim, Haider S.] Univ Al Nahrain, Sch Med, Dept Microbiol, Baghdad 10066, Iraq. [Hussain, Aws R.] Univ Al Qadisiya, Sch Med, Dept Pathol, Dewaniya 58011, Iraq. [Kareem, Abdulameer] Univ Al Qadisiya, Sch Nursing, Dept Med Sci, Dewaniya 58011, Iraq. [Taub, Dennis D.] US Dept Vet Affairs, Ctr Translat Studies, VA Med Ctr, Med Serv, Washington, DC 20422 USA. [Price, Robert L.] Univ S Carolina, Sch Med, Dept Cell Biol & Anat, Columbia, SC 29208 USA. [Nagarkatti, Mitzi; Nagarkatti, Prakash S.; Singh, Udai P.] Univ S Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC 29208 USA. RP Singh, UP (reprint author), Univ S Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC 29208 USA. EM udai.singh@uscmed.sc.edu OI Kadhim, Haider/0000-0003-4561-5669; Nagarkatti, Mitzi/0000-0002-5977-5615 NR 37 TC 0 Z9 0 U1 0 U2 2 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2015 AR 642652 DI 10.1155/2015/642652 PG 7 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CB5WN UT WOS:000349698700001 ER PT J AU Deutsch, MB Mendez, MF Teng, E AF Deutsch, Mariel B. Mendez, Mario F. Teng, Edmond TI Interactions between Traumatic Brain Injury and Frontotemporal Degeneration SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Brain injuries; Frontotemporal degeneration; Frontotemporal dementia; Frontotemporal lobar degeneration; Primary progressive aphasia; Neuropsychological features in subjects with dementia ID ENVIRONMENTAL RISK-FACTORS; MILD COGNITIVE IMPAIRMENT; DATA SET UDS; HEAD-INJURY; FUNCTIONAL-ACTIVITIES; CLINICAL PHENOTYPE; LOBAR DEGENERATION; ALZHEIMERS-DISEASE; SEMANTIC DEMENTIA; ENCEPHALOPATHY AB Background/Aims: Prior work in smaller cohorts suggests that traumatic brain injury (TBI) may be a risk factor for frontotemporal degeneration (FTD). We sought to confirm and extend these results using the National Alzheimer's Coordinating Center Uniform Data Set. Methods: We compared the TBI prevalence between FTD subjects and matched normal controls. Indices of cognitive, behavioral, functional, and global dementia severity were compared between FTD subjects with and without prior TBI. Results: Remote TBI with extended loss of consciousness (TBI-ext) was more common in individuals with FTD than in controls (OR: 1.67; 95% CI: 1.004-2.778). With TBI-ext, less functional and global impairment was seen in the behavioral variant of FTD, but more behavioral pathology was seen in the semantic variant. Conclusion: TBI may increase the FTD risk and influence clinical symptomatology and severity in FTD sub-types. (C) 2014 S. Karger AG, Basel C1 [Deutsch, Mariel B.; Mendez, Mario F.; Teng, Edmond] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol Sci, Los Angeles, CA 90095 USA. [Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Deutsch, Mariel B.; Mendez, Mario F.; Teng, Edmond] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Deutsch, MB (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Neurobehav Serv 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mdeutsch@mednet.ucla.edu OI Deutsch, Mariel/0000-0003-1228-8868 FU NIA [P50 AG16570, K08 AG34628, R01AG034499-05, U01 AG016976]; NIA (American Federation for Aging Research); NIA (John A. Hartford Foundation); NIA (Atlantic Philanthropies); NIA (Starr Foundation); Alzheimer's Disease Research Centers of California; Sidell-Kagan Foundation FX This study was supported by the NIA (P50 AG16570 and K08 AG34628 to E.T.; jointly sponsored by the NIA, the American Federation for Aging Research, the John A. Hartford Foundation, the Atlantic Philanthropies, the Starr Foundation, and an anonymous donor) and R01AG034499-05 (M. F. M., principle investigator), the Alzheimer's Disease Research Centers of California, and the Sidell-Kagan Foundation. The NACC database is funded by the NIA (U01 AG016976). NR 47 TC 3 Z9 3 U1 1 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 EI 1421-9824 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2015 VL 39 IS 3-4 BP 143 EP 153 DI 10.1159/000369787 PG 11 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA CB5UJ UT WOS:000349692800003 PM 25531628 ER PT J AU Teng, E Chow, N Hwang, KS Thompson, PM Gylys, KH Cole, GM Jack, CR Shaw, LM Trojanowski, JQ Soares, HD Weiner, MW Apostolova, LG AF Teng, Edmond Chow, Nicole Hwang, Kristy S. Thompson, Paul M. Gylys, Karen H. Cole, Gregory M. Jack, Clifford R., Jr. Shaw, Leslie M. Trojanowski, John Q. Soares, Holly D. Weiner, Michael W. Apostolova, Liana G. CA Alzheimer's Dis Neuroimaging Initi TI Low Plasma ApoE Levels Are Associated with Smaller Hippocampal Size in the Alzheimer's Disease Neuroimaging Initiative Cohort SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Alzheimer's disease; Mild cognitive impairment; Magnetic resonance imaging; Hippocampus; Biomarkers; ADNI; Apolipoprotein E ID MILD COGNITIVE IMPAIRMENT; APOLIPOPROTEIN-E; BRAIN; GENOTYPE; MRI; POLYMORPHISM; SEGMENTATION; BIOMARKERS; DEPOSITION; CLEARANCE AB Apolipoprotein E (APOE) genotype is the strongest known genetic risk factor for sporadic Alzheimer's disease (AD), but the utility of plasma ApoE levels for assessing the severity of underlying neurodegenerative changes remains uncertain. Here, we examined cross-sectional associations between plasma ApoE levels and volumetric magnetic resonance imaging indices of the hippocampus from 541 participants [57 with normal cognition (NC), 375 with mild cognitive impairment (MCI), and 109 with mild AD] who were enrolled in the Alzheimer's Disease Neuroimaging Initiative. Across the NC and MCI groups, lower plasma ApoE levels were significantly correlated with smaller hippocampal size, as measured by either hippocampal volume or hippocampal radial distance. These associations were driven primarily by findings from carriers of an APOE epsilon 4 allele and are consistent with prior reports that lower plasma ApoE levels correlate with greater global cortical Pittsburgh Compound B retention. In this high-risk group, plasma ApoE levels may represent a peripheral marker of underlying AD neuropathology in nondemented elderly individuals. (C) 2014 S. Karger AG, Basel C1 [Teng, Edmond; Chow, Nicole; Hwang, Kristy S.; Thompson, Paul M.; Cole, Gregory M.; Apostolova, Liana G.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Chow, Nicole; Hwang, Kristy S.; Thompson, Paul M.; Apostolova, Liana G.] Univ Calif Los Angeles, Lab Neuro Imaging, Imaging Genet Ctr, Los Angeles, CA USA. [Thompson, Paul M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Semel Inst, Los Angeles, CA 90095 USA. [Gylys, Karen H.] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. [Teng, Edmond; Cole, Gregory M.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Jack, Clifford R., Jr.] Mayo Clin, Dept Diagnost Radiol, Rochester, MN USA. [Shaw, Leslie M.; Trojanowski, John Q.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Soares, Holly D.] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Weiner, Michael W.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. RP Teng, E (reprint author), West Los Angeles Vet Affairs Healthcare Ctr, Neurobehav Serv 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM eteng@ucla.edu RI Jack, Clifford/F-2508-2010 OI Jack, Clifford/0000-0001-7916-622X FU ADNI; National Institute on Aging [U01 AG024904]; National Institute of Biomedical Imaging and Bioengineering; NIH [K01 AG030514, K08 AG34628, R01 MH097268, R01 AG040060, R01 AG040770, P50 AG16570]; Easton Consortium for Alzheimer's Drug Discovery and Biomarker Development FX Data collection and sharing for this project was funded by ADNI, which is supported by the National Institute on Aging (U01 AG024904), the National Institute of Biomedical Imaging and Bioengineering, and contributions from: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd./Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research and Development, LLC.; Johnson & Johnson Pharmaceutical Research and Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc., and Takeda Pharmaceutical Company. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (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 Southern California. This research was also supported by NIH grants (K01 AG030514, K08 AG34628, R01 MH097268, R01 AG040060, R01 AG040770, P50 AG16570, and P30 AG010129) and the Easton Consortium for Alzheimer's Drug Discovery and Biomarker Development. NR 51 TC 8 Z9 9 U1 2 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 EI 1421-9824 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2015 VL 39 IS 3-4 BP 154 EP 166 DI 10.1159/000368982 PG 13 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA CB5UJ UT WOS:000349692800004 PM 25547651 ER PT J AU Haley, KP Gaddy, JA AF Haley, Kathryn P. Gaddy, Jennifer A. TI Helicobacter pylori: Genomic Insight into the Host-Pathogen Interaction SO INTERNATIONAL JOURNAL OF GENOMICS LA English DT Review ID GASTRIC EPITHELIAL-CELLS; IV SECRETION SYSTEM; VACUOLATING TOXIN; IRON-DEFICIENCY; INFECTION; VACA; CANCER; EAST; CARCINOGENESIS; EXPRESSION AB The advent of genomic analyses has revolutionized the study of human health. Infectious disease research in particular has experienced an explosion of bacterial genomic, transcriptomic, and proteomic data complementing the phenotypic methods employed in traditional bacteriology. Together, these techniques have revealed novel virulence determinants in numerous pathogens and have provided information for potential chemotherapeutics. The bacterial pathogen, Helicobacter pylori, has been recognized as a class 1 carcinogen and contributes to chronic inflammation within the gastric niche. Genomic analyses have uncovered remarkable coevolution between the human host and H. pylori. Perturbation of this coevolution results in dysregulation of the host-pathogen interaction, leading to oncogenic effects. This review discusses the relationship of H. pylori with the human host and environment and the contribution of each of these factors to disease progression, with an emphasis on features that have been illuminated by genomic tools. C1 [Haley, Kathryn P.; Gaddy, Jennifer A.] Vanderbilt Univ, Dept Med, Sch Med, Nashville, TN 37232 USA. [Gaddy, Jennifer A.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA. RP Gaddy, JA (reprint author), Vanderbilt Univ, Dept Med, Sch Med, Nashville, TN 37232 USA. EM jennifer.a.gaddy@vanderbilt.edu FU Office of Medical Research, Department of Veterans Affairs [IK2BX001701]; NIH [P30DK058404]; National Center for Research Resources [UL1 RR024975-01]; National Center for Advancing Translational Sciences [2 UL1 TR000445-06] FX This work has been funded primarily by a Career Development Award IK2BX001701 (to Jennifer A. Gaddy) from the Office of Medical Research, Department of Veterans Affairs. Core Services including use of the Cell Imaging Shared Resource were performed through both Vanderbilt University Medical Center's Digestive Disease Research Center supported by NIH Grant P30DK058404 Core Scholarship and Vanderbilt Institute for Clinical and Translational Research Program supported by the National Center for Research Resources, Grant UL1 RR024975-01, and the National Center for Advancing Translational Sciences, Grant 2 UL1 TR000445-06. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 73 TC 7 Z9 7 U1 1 U2 13 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-436X EI 2314-4378 J9 INT J GENOMICS JI Int. J. Genomics PY 2015 AR 386905 DI 10.1155/2015/386905 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA CB6ZS UT WOS:000349776200001 ER PT J AU Claxton, A Baker, LD Hanson, A Trittschuh, EH Cholerton, B Morgan, A Callaghan, M Arbuckle, M Behl, C Craft, S AF Claxton, Amy Baker, Laura D. Hanson, Angela Trittschuh, Emily H. Cholerton, Brenna Morgan, Amy Callaghan, Maureen Arbuckle, Matthew Behl, Colin Craft, Suzanne TI Long-Acting Intranasal Insulin Detemir Improves Cognition for Adults with Mild Cognitive Impairment or Early-Stage Alzheimer's Disease Dementia SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; clinical trials; randomized; insulin; intranasal drug administration; mild cognitive impairment ID APOLIPOPROTEIN-E GENOTYPE; AMYLOID PRECURSOR PROTEIN; NPH INSULIN; BETA; BRAIN; MEMORY; RESISTANCE; GLUCOSE; THERAPY; ALBUMIN AB Previous trials have shown promising effects of intranasally administered insulin for adults with Alzheimer's disease dementia (AD) or amnestic mild cognitive impairment (MCI). These trials used regular insulin, which has a shorter half-life compared to long-lasting insulin analogues such as insulin detemir. The current trial examined whether intranasal insulin detemir improves cognition or daily functioning for adults with MCI or AD. Sixty adults diagnosed with MCI or mild to moderate AD received placebo (n = 20), 20 IU of insulin detemir (n = 21), or 40 IU of insulin detemir (n = 19) for 21 days, administered with a nasal drug delivery device. Results revealed a treatment effect for the memory composite for the 40 IU group compared with placebo (p < 0.05). This effect was moderated by APOE status (p < 0.05), reflecting improvement for APOE-epsilon 4 carriers (p < 0.02), and worsening for non-carriers (p < 0.02). Higher insulin resistance at baseline predicted greater improvement with the 40 IU dose (r = 0.54, p < 0.02). Significant treatment effects were also apparent for verbal working memory (p < 0.03) and visuospatial working memory (p < 0.04), reflecting improvement for subjects who received the high dose of intranasal insulin detemir. No significant differences were found for daily functioning or executive functioning. In conclusion, daily treatment with 40 IU insulin detemir modulated cognition for adults with AD or MCI, with APOE-related differences in treatment response for the primary memory composite. Future research is needed to examine the mechanistic basis of APOE-related treatment differences, and to further assess the efficacy and safety of intranasal insulin detemir. C1 [Claxton, Amy; Hanson, Angela; Trittschuh, Emily H.; Morgan, Amy; Callaghan, Maureen; Behl, Colin] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Claxton, Amy; Hanson, Angela; Trittschuh, Emily H.; Cholerton, Brenna; Morgan, Amy; Callaghan, Maureen; Behl, Colin] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Baker, Laura D.; Craft, Suzanne] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC 27157 USA. [Arbuckle, Matthew] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. RP Craft, S (reprint author), Wake Forest Sch Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM suzcraft@wakehealth.edu FU National Institute of Aging [P50 AG05136, T32 AG000258]; Department of Veterans Affairs FX Suzanne Craft and Amy Claxton had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. This research was supported by National Institute of Aging grants P50 AG05136 (to Dr. Craft) and T32 AG000258 (to Dr. Claxton), and the Department of Veterans Affairs. NR 48 TC 48 Z9 49 U1 6 U2 26 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2015 VL 44 IS 3 BP 897 EP 906 DI 10.3233/JAD-141791 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CB4RQ UT WOS:000349616000018 PM 25374101 ER PT J AU West, RK Ravona-Springer, R Heymann, A Schmeidler, J Leroith, D Koifman, K Guerrero-Berroa, E Preiss, R Hoffman, H Silverman, JM Beeri, MS AF West, Rebecca K. Ravona-Springer, Ramit Heymann, Anthony Schmeidler, James Leroith, Derek Koifman, Keren Guerrero-Berroa, Elizabeth Preiss, Rachel Hoffman, Hadas Silverman, Jeremy M. Beeri, Michal Schnaider TI Shorter Adult Height is Associated with Poorer Cognitive Performance in Elderly Men with Type II Diabetes SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Cognitive performance; height; risk factors; type 2 diabetes mellitus; vascular dementia ID CORONARY-HEART-DISEASE; ALZHEIMERS-DISEASE; BODY HEIGHT; RISK-FACTORS; LATE-LIFE; LEG LENGTH; DEMENTIA; CIRCUMFERENCE; EDUCATION; GROWTH AB We studied the relationship of adult body height with five cognitive outcomes (executive functioning, semantic categorization, attention/working memory, episodic memory, and an overall cognition measure) in 897 cognitively normal elderly with type 2 diabetes. Regression analyses controlling for sociodemographic, cardiovascular, and diabetes-related risk factors and depression demonstrated that in males, shorter stature was associated with poorer executive functioning (p = 0.001), attention/working memory (p = 0.007), and overall cognition (p = 0.016), but not with episodic memory (p = 0.715) or semantic categorization (p = 0.948). No relationship between height and cognition was found for females. In cognitively normal type 2 diabetes male subjects, shorter stature, a surrogate for early-life stress and poor nutrition, was associated with cognitive functions. C1 [West, Rebecca K.; Schmeidler, James; Guerrero-Berroa, Elizabeth; Silverman, Jeremy M.; Beeri, Michal Schnaider] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Ravona-Springer, Ramit; Koifman, Keren; Preiss, Rachel; Hoffman, Hadas; Beeri, Michal Schnaider] Sheba Med Ctr, Joseph Sagol Neurosci Ctr, Ramat Gan, Israel. [Silverman, Jeremy M.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Heymann, Anthony] Maccabi Healthcare Serv, Tel Aviv, Israel. [Leroith, Derek] Icahn Sch Med Mt Sinai, Dept Med, Div Med Endocrinol Diabet & Bone Dis, New York, NY 10029 USA. RP West, RK (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1230,One Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM rebecca.west@mssm.edu FU NIA [R01 AG034087, P50 AG05138]; Helen Bader Foundation; Leroy Schecter Foundation; Irma T. Hirschl Scholar award; American Federation for Aging Research (AFAR) Young Investigator award; Alzheimer's Association [NIRG-11-205083] FX This study was supported by NIA grants R01 AG034087 to Dr. Beeri and P50 AG05138 to Dr. Sano, the Helen Bader Foundation, the Leroy Schecter Foundation, and the Irma T. Hirschl Scholar award to Dr. Beeri, the American Federation for Aging Research (AFAR) Young Investigator award, and the Alzheimer's Association grant NIRG-11-205083 to Dr. Ravona-Springer. NR 40 TC 2 Z9 2 U1 1 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2015 VL 44 IS 3 BP 927 EP 935 DI 10.3233/JAD-142049 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CB4RQ UT WOS:000349616000021 PM 25374105 ER PT J AU Tsai, J El-Gabalawy, R Sledge, WH Southwick, SM Pietrzak, RH AF Tsai, J. El-Gabalawy, R. Sledge, W. H. Southwick, S. M. Pietrzak, R. H. TI Post-traumatic growth among veterans in the USA: results from the National Health and Resilience in Veterans Study SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Coping behavior; post-traumatic stress disorder; spirituality; veterans ID SOCIAL SUPPORT; STRESS SYMPTOMS; 5-FACTOR MODEL; PHYSICAL HEALTH; MENTAL-HEALTH; TRAUMA; DISORDER; PTSD; WAR; VALIDATION AB Background. There is increasing recognition that, in addition to negative psychological consequences of trauma such as post-traumatic stress disorder (PTSD), some individuals may develop post-traumatic growth (PTG) following such experiences. To date, however, data regarding the prevalence, correlates and functional significance of PTG in population-based samples are lacking. Method. Data were analysed from the National Health and Resilience in Veterans Study, a contemporary, nationally representative survey of 3157 US veterans. Veterans completed a survey containing measures of sociodemographic, military, health and psychosocial characteristics, and the Posttraumatic Growth Inventory-Short Form. Results. We found that 50.1% of all veterans and 72.0% of veterans who screened positive for PTSD reported at least 'moderate' PTG in relation to their worst traumatic event. An inverted U-shaped relationship was found to best explain the relationship between PTSD symptoms and PTG. Among veterans with PTSD, those with PTSD reported better mental functioning and general health than those without PTG. Experiencing a life-threatening illness or injury and re-experiencing symptoms were most strongly associated with PTG. In multivariable analysis, greater social connectedness, intrinsic religiosity and purpose in life were independently associated with greater PTG. Conclusions. PTG is prevalent among US veterans, particularly among those who screen positive for PTSD. These results suggest that there may be a 'positive legacy' of trauma that has functional significance for veterans. They further suggest that interventions geared toward helping trauma-exposed US veterans process their re-experiencing symptoms, and to develop greater social connections, sense of purpose and intrinsic religiosity may help promote PTG in this population. C1 [Tsai, J.] US Dept Vet Affairs, New England Mental Illness Res Educ & Clin Ctr, West Haven, CT USA. [Tsai, J.; Sledge, W. H.; Southwick, S. M.; Pietrzak, R. H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [El-Gabalawy, R.] Univ Manitoba, Dept Psychol, Winnipeg, MB R3T 2N2, Canada. [Southwick, S. M.; Pietrzak, R. H.] US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, Clin Neurosci Div, West Haven, CT USA. RP Tsai, J (reprint author), 950 Campbell Ave,151D, West Haven, CT 06516 USA. EM Jack.Tsai@yale.edu FU United States Department of Veterans Affairs National Center for Posttraumatic Stress Disorder; United States Department of Veterans Affairs, Office of Research and Development FX This work was supported in part by the United States Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, the United States Department of Veterans Affairs, Office of Research and Development, and a private donation. The views presented here are those of the authors alone and do not represent the position of any federal agency or of the United States Government. None of the authors reports any conflicts of interest with this work. NR 58 TC 16 Z9 16 U1 6 U2 31 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 EI 1469-8978 J9 PSYCHOL MED JI Psychol. Med. PD JAN PY 2015 VL 45 IS 1 BP 165 EP 179 DI 10.1017/S0033291714001202 PG 15 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CB4RY UT WOS:000349616800014 PM 25065450 ER PT J AU Shin, SS Grandhi, R Henchir, J Yan, HQ Badylak, SF Dixon, CE AF Shin, Samuel S. Grandhi, Ramesh Henchir, Jeremy Yan, Hong Q. Badylak, Stephen F. Dixon, C. Edward TI Neuroprotective effects of collagen matrix in rats after traumatic brain injury SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Article DE Collagen; matrix; traumatic brain injury; bioscaffold; neuroregeneration; neurorepair ID CONTROLLED CORTICAL IMPACT; NEURAL STEM-CELLS; SYSTEM EXTRACELLULAR-MATRIX; SPINAL-CORD; CEREBRAL-ISCHEMIA; PROGENITOR CELLS; DURAL GRAFT; SCAFFOLDS; GROWTH; TRANSPLANTATION AB Purpose: In previous studies, collagen based matrices have been implanted into the site of lesion in different models of brain injury. We hypothesized that semisynthetic collagen matrix can have neuroprotective function in the setting of traumatic brain injury. Methods: Rats were subjected to sham injury or controlled cortical impact. They either received extracellular matrix graft (DuraGen) over the injury site or did not receive any graft and underwent beam balance/beam walking test at post injury days 1-5 and Morris water maze at post injury days 14-18. Animals were sacrificed at day 18 for tissue analysis. Results: Collagen matrix implantation in injured rats did not affect motor function (beam balance test: p = 0.627, beam walking test: p = 0.921). However, injured group with collagen matrix had significantly better spatial memory acquisition (p < 0.05). There was a significant reduction in lesion volume, as well as neuronal loss in CA1 (p < 0.001) and CA3 (p < 0.05) regions of the hippocampus in injured group with collagen matrix (p < 0.05). Conclusions: Collagen matrix reduces contusional lesion volume, neuronal loss, and cognitive deficit after traumatic brain injury. Further studies are needed to demonstrate the mechanisms of neuroprotection by collagen matrix. C1 [Shin, Samuel S.; Henchir, Jeremy; Yan, Hong Q.; Dixon, C. Edward] Univ Pittsburgh, Brain Trauma Res Ctr, Pittsburgh, PA 15260 USA. [Shin, Samuel S.; Grandhi, Ramesh; Henchir, Jeremy; Yan, Hong Q.; Dixon, C. Edward] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA. [Shin, Samuel S.; Yan, Hong Q.; Dixon, C. Edward] Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA 15260 USA. [Badylak, Stephen F.] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA 15260 USA. [Dixon, C. Edward] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Dixon, CE (reprint author), Univ Pittsburgh, Dept Neurol Surg, 201 Hill Bldg,3434 Fifth Ave, Pittsburgh, PA 15260 USA. EM dixonec@upmc.edu OI Badylak, Stephen/0000-0003-3555-0689 FU NIH/NINDS; Pittsburgh Foundation Walter L. Copeland Fund FX This work was supported by NIH/NINDS and by the Pittsburgh Foundation Walter L. Copeland Fund. NR 34 TC 1 Z9 1 U1 0 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0922-6028 EI 1878-3627 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PY 2015 VL 33 IS 2 BP 95 EP 104 DI 10.3233/RNN-140430 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CB7UX UT WOS:000349835000001 PM 25624423 ER PT J AU Wiederhold, NP Najvar, LK Fothergill, AW McCarthy, DI Bocanegra, R Olivo, M Kirkpatrick, WR Everson, MP Duncanson, FP Patterson, TF AF Wiederhold, Nathan P. Najvar, Laura K. Fothergill, Annette W. McCarthy, Dora I. Bocanegra, Rosie Olivo, Marcos Kirkpatrick, William R. Everson, Michael P. Duncanson, Frederick P. Patterson, Thomas F. TI The Investigational Agent E1210 Is Effective in Treatment of Experimental Invasive Candidiasis Caused by Resistant Candida albicans SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID BROAD-SPECTRUM ANTIFUNGAL; IN-VITRO ACTIVITY; BROTH MICRODILUTION METHODS; SUSCEPTIBILITY; CLSI; MODELS; FAMILY; SPP. AB The in vitro and in vivo activity of the inositol acyltransferase inhibitor E1210 was evaluated against echinocandin-resistant Candida albicans. E1210 demonstrated potent in vitro activity, and in mice with invasive candidiasis caused by echinocandin-resistant C. albicans, oral doses of 10 and 40 mg E1210/kg of body weight twice daily significantly improved survival and reduced fungal burden compared to those of controls and mice treated with caspofungin (10 mg/kg/day). These results demonstrate the potential use of E1210 against resistant C. albicans infections. C1 [Wiederhold, Nathan P.; Najvar, Laura K.; Fothergill, Annette W.; McCarthy, Dora I.; Bocanegra, Rosie; Olivo, Marcos; Kirkpatrick, William R.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Najvar, Laura K.; Bocanegra, Rosie; Olivo, Marcos; Kirkpatrick, William R.; Patterson, Thomas F.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Everson, Michael P.; Duncanson, Frederick P.] Eisai Inc, Woodcliff Lake, NJ USA. RP Wiederhold, NP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. EM wiederholdn@uthscsa.edu OI Wiederhold, Nathan/0000-0002-2225-5122 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHS272201000018I, HHSN272201000038I, A03, A13]; Astellas; Dow; F2G; Merck; Merz; Viamet FX This project utilized preclinical services funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract no. HHS272201000018I and HHSN272201000038I, task orders A03 and A13, respectively.; N.P.W. has received research support from Astellas, Dow, F2G, Merck, Merz, and Viamet and has served on advisory boards for Merck, Astellas, Toyama, and Viamet. T.F.P. has received research grants to UT Health Science Center San Antonio from Astellas and Merck and has served as a consultant for Astellas, Merck, Toyama, Viamet, and Scynexis. M.P.E. and F.P.D. are salaried employees of Eisai Inc. All other authors have no conflicts. NR 18 TC 4 Z9 6 U1 2 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2015 VL 59 IS 1 BP 690 EP 692 DI 10.1128/AAC.03944-14 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA CA0LO UT WOS:000348609500089 PM 25331706 ER PT S AU Haake, DA Levett, PN AF Haake, David A. Levett, Paul N. BE Adler, B TI Leptospirosis in Humans SO LEPTOSPIRA AND LEPTOSPIROSIS SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID ACUTE-RENAL-FAILURE; LINKED-IMMUNOSORBENT-ASSAY; INTERROGANS SEROVAR ICTEROHAEMORRHAGIAE; LATEX AGGLUTINATION ASSAY; POLYMERASE-CHAIN-REACTION; QUANTITATIVE PCR ASSAY; TANDEM-REPEAT ANALYSIS; ACUTE FEBRILE ILLNESS; ACUTE KIDNEY INJURY; REAL-TIME PCR AB Leptospirosis is a widespread and potentially fatal zoonosis that is endemic in many tropical regions and causes large epidemics after heavy rainfall and flooding. Infection results from direct or indirect exposure to infected reservoir host animals that carry the pathogen in their renal tubules and shed pathogenic leptospires in their urine. Although many wild and domestic animals can serve as reservoir hosts, the brown rat (Rattus norvegicus) is the most important source of human infections. Individuals living in urban slum environments characterized by inadequate sanitation and poor housing are at high risk of rat exposure and leptospirosis. The global burden of leptospirosis is expected to rise with demographic shifts that favor increases in the number of urban poor in tropical regions subject to worsening storms and urban flooding due to climate change. Data emerging from prospective surveillance studies suggest that most human leptospiral infections in endemic areas are mild or asymptomatic. Development of more severe outcomes likely depends on three factors: epidemiological conditions, host susceptibility, and pathogen virulence (Fig. 1). Mortality increases with age, particularly in patients older than 60 years of age. High levels of bacteremia are associated with poor clinical outcomes and, based on animal model and in vitro studies, are related in part to poor recognition of leptospiral LPS by human TLR4. Patients with severe leptospirosis experience a cytokine storm characterized by high levels of IL-6, TNF-alpha, and IL-10. Patients with the HLA DQ6 allele are at higher risk of disease, suggesting a role for lymphocyte stimulation by a leptospiral superantigen. Leptospirosis typically presents as a nonspecific, acute febrile illness characterized by fever, myalgia, and headache and may be confused with other entities such as influenza and dengue fever. Newer diagnostic methods facilitate early diagnosis and antibiotic treatment. Patients progressing to multisystem organ failure have widespread hematogenous dissemination of pathogens. Nonoliguric (high output) renal dysfunction should be supported with fluids and electrolytes. When oliguric renal failure occurs, prompt initiation of dialysis can be life saving. Elevated bilirubin levels are due to hepatocellular damage and disruption of intercellular junctions between hepatocytes, resulting in leaking of bilirubin out of bile caniliculi. Hemorrhagic complications are common and are associated with coagulation abnormalities. Severe pulmonary hemorrhage syndrome due to extensive alveolar hemorrhage has a fatality rate of >50 %. Readers are referred to earlier, excellent summaries related to this subject (Adler and de la Pena-Moctezuma 2010; Bharti et al. 2003; Hartskeerl et al. 2011; Ko et al. 2009; Levett 2001; McBride et al. 2005). C1 [Haake, David A.] VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. [Levett, Paul N.] Saskatchewan Dis Control Lab, Regina, SK, Canada. RP Haake, DA (reprint author), VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. EM dhaake@ucla.edu; plevett@health.gov.sk.ca FU BLRD VA [I01 BX002003]; NIAID NIH HHS [R01 AI034431] NR 186 TC 27 Z9 30 U1 4 U2 33 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-662-45059-8; 978-3-662-45058-1 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2015 VL 387 BP 65 EP 97 DI 10.1007/978-3-662-45059-8_5 D2 10.1007/978-3-662-45059-8 PG 33 WC Immunology; Microbiology SC Immunology; Microbiology GA BC0EH UT WOS:000348986500006 PM 25388133 ER PT S AU Haake, DA Zuckert, WR AF Haake, David A. Zueckert, Wolfram R. BE Adler, B TI The Leptospiral Outer Membrane SO LEPTOSPIRA AND LEPTOSPIROSIS SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID INTERROGANS SEROVAR COPENHAGENI; SURFACE-EXPOSED LIPOPROTEIN; IMMUNOGLOBULIN-LIKE PROTEINS; PROXIMAL TUBULE CELLS; PATHOGENIC LEPTOSPIRA; ESCHERICHIA-COLI; BORRELIA-BURGDORFERI; EXTRACELLULAR-MATRIX; PROTECTIVE IMMUNITY; MOLECULAR-CLONING AB The outer membrane (OM) is the front line of leptospiral interactions with their environment and the mammalian host. Unlike most invasive spirochetes, pathogenic leptospires must be able to survive in both free-living and host-adapted states. As organisms move from one set of environmental conditions to another, the OM must cope with a series of conflicting challenges. For example, the OM must be porous enough to allow nutrient uptake, yet robust enough to defend the cell against noxious substances. In the host, the OM presents a surface decorated with adhesins and receptors for attaching to, and acquiring, desirable host molecules such as the complement regulator, Factor H. On the other hand, the OM must enable leptospires to evade detection by the host's immune system on their way from sites of invasion through the bloodstream to the protected niche of the proximal tubule. The picture that is emerging of the leptospiral OM is that, while it shares many of the characteristics of the OMs of spirochetes and Gram-negative bacteria, it is also unique and different in ways that make it of general interest to microbiologists. For example, unlike most other pathogenic spirochetes, the leptospiral OM is rich in lipopolysaccharide (LPS). Leptospiral LPS is similar to that of Gram-negative bacteria but has a number of unique structural features that may explain why it is not recognized by the LPS-specific Toll-like receptor 4 of humans. As in other spirochetes, lipoproteins are major components of the leptospiral OM, though their roles are poorly understood. The functions of transmembrane outer membrane proteins (OMPs) in many cases are better understood, thanks to homologies with their Gram-negative counterparts and the emergence of improved genetic techniques. This chapter will review recent discoveries involving the leptospiral OM and its role in leptospiral physiology and pathogenesis. C1 [Haake, David A.] VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. [Zueckert, Wolfram R.] Univ Kansas, Sch Med, Dept Microbiol Mol Genet & Immunol, Kansas City, KS 66160 USA. RP Haake, DA (reprint author), VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. EM dhaake@ucla.edu; wzueckert@kumc.edu FU BLRD VA [I01 BX002003]; NIAID NIH HHS [R01 AI034431]; NIGMS NIH HHS [P30 GM103326] NR 117 TC 3 Z9 4 U1 2 U2 9 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-662-45059-8; 978-3-662-45058-1 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2015 VL 387 BP 187 EP 221 DI 10.1007/978-3-662-45059-8_8 D2 10.1007/978-3-662-45059-8 PG 35 WC Immunology; Microbiology SC Immunology; Microbiology GA BC0EH UT WOS:000348986500009 PM 25388136 ER PT B AU Klein, E AF Klein, Eran BE VanRysewyk, SP Pontier, M TI Models of the Patient-Machine-Clinician Relationship in Closed-Loop Machine Neuromodulation SO MACHINE MEDICAL ETHICS SE Intelligent Systems Control and Automation Science and Engineering LA English DT Article; Book Chapter ID DEEP BRAIN-STIMULATION; SUBTHALAMIC NUCLEUS; PARKINSONS-DISEASE; PROFESSION AB Closed-loop neuromodulation represents an emerging area in clinical medicine. Neural devices capable of measuring brain function and using measurements to iteratively guide output, such as deep brain stimulation, will be a significant advance in neuromodulatory technology. The introduction of closed-loop devices, particularly "smart" machines, will require changes in clinical ethical practice. A model of the clinical relationship could be a useful tool for addressing ethical challenges arising in this new area. Traditional models of the clinical relationship, like Emanuel and Emanuel's "four models," are suited to current unidirectional forms of neuromodulation. An adequate model of the patient-machine-clinician relationship may need to move beyond traditional models. Thus, I explore three new models: the design model, the customer service model, and the quality monitoring model. The exploration of these models of the patient-machine-clinician relationship will benefit from keeping an Aristotelian ideal of friendship in mind. C1 [Klein, Eran] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Klein, Eran] Portland VA Med Ctr, Portland, OR USA. [Klein, Eran] Univ Washington, Dept Philosophy, Seattle, WA 98195 USA. [Klein, Eran] Univ Washington, Ctr Sensorimotor Neural Engn, Seattle, WA 98195 USA. RP Klein, E (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. EM kleine@ohsu.edu NR 36 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 978-3-319-08108-3; 978-3-319-08107-6 J9 INTEL SYST CONTR AUT PY 2015 VL 74 BP 273 EP 290 DI 10.1007/978-3-319-08108-3_17 D2 10.1007/978-3-319-08108-3 PG 18 WC Ethics; Robotics SC Social Sciences - Other Topics; Robotics GA BB8KL UT WOS:000346771800018 ER PT J AU Hiremath, SV Intille, SS Kelleher, A Cooper, RA Ding, D AF Hiremath, Shivayogi V. Intille, Stephen S. Kelleher, Annmarie Cooper, Rory A. Ding, Dan TI Detection of physical activities using a physical activity monitor system for wheelchair users SO MEDICAL ENGINEERING & PHYSICS LA English DT Article DE Spinal cord injury; Physical activity; Wheelchair users; Activity monitor system; Smartphones; Machine learning; Classification ID SPINAL-CORD-INJURY; ENERGY-EXPENDITURE; VALIDATION AB Availability of physical activity monitors for wheelchair users can potentially assist these individuals to track regular physical activity (PA), which in turn could lead to a healthier and more active lifestyle. Therefore, the aim of this study was to develop and validate algorithms for a physical activity monitoring system (PAMS) to detect wheelchair based activities. The PAMS consists of a gyroscope based wheel rotation monitor (G-WRM) and an accelerometer device (wocket) worn on the upper arm or on the wrist. A total of 45 persons with spinal cord injury took part in the study, which was performed in a structured university-based laboratory environment, a semi-structured environment at the National Veterans Wheelchair Games, and in the participants' home environments. Participants performed at least ten PAs, other than resting, taken from a list of PAs. The classification performance for the best classifiers on the testing dataset for PAMS-Arm (G-WRM and wocket on upper arm) and PAMS-Wrist (G-WRM and wocket on wrist) was 89.26% and 88.47%, respectively. The outcomes of this study indicate that multi-modal information from the PAMS can help detect various types of wheelchair-based activities in structured laboratory, semi-structured organizational, and unstructured home environments. (C) 2014 IPEM. Published by Elsevier Ltd. All rights reserved. C1 [Hiremath, Shivayogi V.; Kelleher, Annmarie; Cooper, Rory A.; Ding, Dan] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs, Pittsburgh, PA USA. [Kelleher, Annmarie; Cooper, Rory A.; Ding, Dan] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15206 USA. [Hiremath, Shivayogi V.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15206 USA. [Intille, Stephen S.] Northeastern Univ, Coll Comp & Informat Sci, Boston, MA 02115 USA. [Intille, Stephen S.] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA. [Cooper, Rory A.; Ding, Dan] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15206 USA. RP Ding, D (reprint author), Univ Pittsburgh, Dept Rehabil Sci & Technol, Human Engn Res Labs, VA Pittsburgh Healthcare Syst, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15206 USA. EM dad5@pitt.edu FU Department of Defense [W81XWH-10-1-0816]; National Institute on Disability and Rehabilitation Research, Department of Education [H133F110032]; Human Engineering Research Laboratories, VA Pittsburgh Healthcare System FX The work is supported by the Department of Defense (W81XWH-10-1-0816). SVH's work on this article was funded through the Switzer Research Fellowship (H133F110032) awarded by the National Institute on Disability and Rehabilitation Research, Department of Education. The work is also supported by the Human Engineering Research Laboratories, VA Pittsburgh Healthcare System. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. The authors thank their colleagues at the Human Engineering Research Laboratories, especially Alejandra Manoela Ojeda, Monsak Socharoentum, Natthasit Wongsirikul, and Matthew Hannan for their input and effort during development and data collection. NR 17 TC 5 Z9 5 U1 1 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1350-4533 EI 1873-4030 J9 MED ENG PHYS JI Med. Eng. Phys. PD JAN PY 2015 VL 37 IS 1 BP 68 EP 76 DI 10.1016/j.medengphy.2014.10.009 PG 9 WC Engineering, Biomedical SC Engineering GA CB4GB UT WOS:000349585100009 PM 25465284 ER PT J AU Nilsagard, Y Gunn, H Freeman, J Hoang, P Lord, S Mazumder, R Cameron, M AF Nilsagard, Y. Gunn, H. Freeman, J. Hoang, P. Lord, S. Mazumder, Rajarshi Cameron, Michelle TI Falls in people with MS-an individual data meta-analysis from studies from Australia, Sweden, United Kingdom and the United States SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article DE Accidental falls; multiple sclerosis; risk factors; cohort studies; meta-analysis ID DISABILITY STATUS SCALE; PREDICTING ACCIDENTAL FALLS; MULTIPLE-SCLEROSIS; RISK-FACTORS; OLDER-ADULTS; BALANCE; PREVENTION; IMBALANCE; STRENGTH; COHORT AB Background: Falls are common in people with multiple sclerosis (PwMS). Previous studies have generally included small samples and had varied methods. Objectives: The objectives of this paper are to compile fall rates across a broad range of ages and disease severity and to definitively assess the extent to which MS-associated and demographic factors influence fall rates. Methods: Individual data from studies in four countries that prospectively measured falls for three months were analyzed. We determined fall rates, prevalence of fallers (1 falls) and frequent fallers (2 falls), location and timing of falls, and fall-related demographic factors. Results: A total of 537 participants reported 1721 falls: 56% were fallers and 37% frequent fallers. Most falls occurred indoors (65%) between 6 a.m. and 6 p.m. (75%). Primary progressive MS was associated with significantly increased odds of being a faller (odds ratio (OR) 2.02; CI 1.08-3.78). Fall risk peaked at EDSS levels of 4.0 and 6.0 with significant ORs between 5.30 (2.23-12.64) and 5.10 (2.08-12.47). The fall rate was lower in women than men (relative risk (RR) 0.80; CI 0.67-0.94) and decreased with increasing age (RR 0.97 for each year, CI 0.95-0.98). Conclusion: PwMS are at high risk of falls and there are important associations between falls and MS-associated disability, gender and age. C1 [Nilsagard, Y.] Orebro Cty Council, Ctr Hlth Care Sci, Orebro, Sweden. [Nilsagard, Y.] Orebro Univ, Sch Hlth & Med Sci, SE-70113 Orebro, Sweden. [Gunn, H.; Freeman, J.] Univ Plymouth, Sch Hlth Profess, Plymouth PL4 8AA, Devon, England. [Hoang, P.; Lord, S.] Univ NSW, Neurosci Res Australia NeuRA, Sydney, NSW, Australia. [Mazumder, Rajarshi; Cameron, Michelle] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Cameron, Michelle] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. RP Nilsagard, Y (reprint author), Orebro Univ, Sch Hlth & Med Sci, Orebro Cty Council, Ctr Hlth Care Sci, POB 1324, SE-70113 Orebro, Sweden. EM ylva.nilsagard@orebroll.se RI Lord, Stephen/C-9612-2011 FU Research Committee in Orebro County Council; Biogen Idec; Norrbacka- Eugenia Foundation; VA, Rehabilitation Research & Development Service; Agency for Healthcare Research and Quality (AHRQ) [T32 HS017582]; Foundation of the Consortium of Multiple Sclerosis Centers; NHMRC; Multiple Sclerosis Research Australia; Physiotherapy Research Foundation, Chartered Society of Physiotherapy, UK FX SE: Ylva Nilsagard was supported by the Research Committee in Orebro County Council, Biogen Idec and the Norrbacka- Eugenia Foundation.; US: Michelle Cameron was supported by a Career Development Award from the VA, Rehabilitation Research & Development Service.; Rajarshi Mazumder was supported by the Oregon Multidisciplinary Training Program in Health Services Research, grant number T32 HS017582 from the Agency for Healthcare Research and Quality (AHRQ) and the 2012 Foundation of the Consortium of Multiple Sclerosis Centers.; AUS: Phu Hoang and Stephen Lord were supported by NHMRC Fellowships and a grant from Multiple Sclerosis Research Australia.; UK: Hillary Gunn and Jennifer Freeman were supported by a grant from the Physiotherapy Research Foundation, Chartered Society of Physiotherapy, UK. NR 35 TC 11 Z9 11 U1 2 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD JAN PY 2015 VL 21 IS 1 BP 92 EP 100 DI 10.1177/1352458514538884 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CB0AW UT WOS:000349288100014 PM 24948687 ER PT J AU Harris, AHS Bowe, T Del Re, AC Finlay, AK Oliva, E Myrick, HL Rubinsky, AD AF Harris, Alex H. S. Bowe, Thomas Del Re, Aaron C. Finlay, Andrea K. Oliva, Elizabeth Myrick, Hugh L. Rubinsky, Anna D. TI Extended Release Naltrexone for Alcohol Use Disorders: Quasi-Experimental Effects on Mortality and Subsequent Detoxification Episodes SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Use Disorders; Alcohol Dependence; Naltrexone; Medication-Assisted Treatment; Veterans Health Administration; Veterans ID DEPENDENCE; PHARMACOTHERAPY; BARRIERS; METAANALYSIS; REGRESSION; TRIAL; DEPOT AB BackgroundUtilization of extended release naltrexone (XRN) for alcohol use disorders (AUDs) in the U.S. Veterans Health Administration (VHA) has been limited, perhaps due to high cost, lack of established superiority over less expensive alternatives including oral naltrexone, and related formulary restrictions. Despite these barriers, pockets of higher utilization exist in VHA, allowing for the quasi-experimental examination of the effects of XRN on 1-year mortality and number of subsequent detoxification episodes among patients with high rates of psychiatric comorbidities and previous psychosocial and pharmacological addiction treatment. MethodsUsing propensity score-weighted mixed-effects logistic regression, 1-year mortality was compared between patients with AUDs who received XRN in fiscal year 2010 (n=387) and a random sample of patients with AUDs who did not receive XRN (n=3,759). Among the subgroup of patients who had at least 1 detoxification episode in the previous year, 1-year mortality and number of subsequent detoxification episodes were compared between those who did and did not receive XRN. ResultsOverall, 1-year mortality for the patients receiving XRN was significantly lower than for the comparison group who did not receive XRN (odds ratio [OR]=0.30; p<0.001). Among patients with a detoxification episode in the previous year, those receiving XRN had, on average, 0.80 fewer subsequent detoxification episodes (p<0.001) and significantly lower mortality (OR=0.78, p<0.001) in the postindex year. ConclusionsAmong patients with AUDs, those receiving XRN had lower 1-year mortality and fewer detoxifications compared to similar patients not receiving XRN. These results, although observational, support the use of XRN, especially among patients with high rates of psychiatric comorbidities and previous addiction treatment who are still struggling with AUDs and/or facing a period of vulnerability to relapse. C1 [Harris, Alex H. S.; Bowe, Thomas; Del Re, Aaron C.; Finlay, Andrea K.; Oliva, Elizabeth; Rubinsky, Anna D.] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, VA Subst Use Disorder Qual Enhancement Res Initia, Menlo Pk, CA 94025 USA. [Myrick, Hugh L.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Harris, AHS (reprint author), VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat MPD 152, 795 Willow Rd, Menlo Pk, CA 94025 USA. EM alexander.harris2@va.gov OI Del Re, Aaron/0000-0002-9571-7623 FU VA Substance Use Disorder Quality Enhancement Research Initiative Locally Initiated Project [LIP QLP 59-028] FX This work was supported by a VA Substance Use Disorder Quality Enhancement Research Initiative Locally Initiated Project (LIP QLP 59-028). The views expressed do not represent those of the U.S. Department of Veterans Affairs. NR 17 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JAN PY 2015 VL 39 IS 1 BP 79 EP 83 DI 10.1111/acer.12597 PG 5 WC Substance Abuse SC Substance Abuse GA CA2DM UT WOS:000348719100010 PM 25623408 ER PT J AU Worley, MJ Witkiewitz, K Brown, SA Kivlahan, DR Longabaugh, R AF Worley, Matthew J. Witkiewitz, Katie Brown, Sandra A. Kivlahan, Daniel R. Longabaugh, Richard TI Social Network Moderators of Naltrexone and Behavioral Treatment Effects on Heavy Drinking in the COMBINE Study SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Dependence; Naltrexone; Pharmacotherapy; Social Network; Moderators ID ALCOHOL-USE DISORDERS; COMBINED PHARMACOTHERAPIES; CONTROLLED-TRIAL; MISSING DATA; DEPENDENCE; OUTCOMES; SUPPORT; PHARMACOGENETICS; INTERVENTIONS; MEDICATIONS AB BackgroundOral naltrexone is an efficacious medication for treatment of alcohol dependence, but small effect sizes and variability in outcomes suggest the presence of person-level moderators of naltrexone response. Identification of contextual or psychosocial moderators may assist in guiding clinical recommendations. Given the established importance of social networks in drinking outcomes, as well as the potential effects of naltrexone in reducing cue reactivity which may be especially important among those with more heavy drinkers and more alcohol cues in their networks, we examined pretreatment social network variables as potential moderators of naltrexone treatment effects in the COMBINE study. MethodsThe sample included all COMBINE study participants in medication conditions with full data on the Important People Inventory (IPI) and covariates at intake (N=1,197). The intake IPI assessed whether participants had any frequent drinkers in their network and the average frequency of contact with these drinkers. The effects of treatment condition, pretreatment network variables, and their interactions on percent heavy drinking days were tested in hierarchical linear models, controlling for demographics and baseline clinical covariates. ResultsIn treatment conditions involving medical management and combined behavioral intervention (CBI), the effects of active naltrexone on heavy drinking were significantly greater for individuals with frequent drinkers in their network (z=-2.66, p<0.01) and greater frequency of contact with those drinkers (z=-3.19, p<0.01). These network variables did not moderate the effects of active naltrexone without CBI. ConclusionsWhen delivered in conjunction with behavioral interventions, naltrexone can be more potent for alcohol-dependent adults who have greater contact with frequent drinkers prior to treatment, which may indicate patterns of environmental exposure to alcohol. Contextual, social risk factors are a potential avenue to guide personalized treatment of alcohol dependence. C1 [Worley, Matthew J.] Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA 90024 USA. [Witkiewitz, Katie] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Brown, Sandra A.] Univ Calif San Diego, Off Res Affairs, La Jolla, CA 92093 USA. [Kivlahan, Daniel R.] VA Puget Sound Healthcare Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. [Longabaugh, Richard] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. RP Worley, MJ (reprint author), Univ Calif Los Angeles, 10880 Wilshire Blvd,Suite 1800, Los Angeles, CA 90024 USA. EM mworley@mednet.ucla.edu FU NIAAA NIH HHS [R01 AA022328]; NIDA NIH HHS [F31 DA030861] NR 50 TC 2 Z9 2 U1 3 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JAN PY 2015 VL 39 IS 1 BP 93 EP 100 DI 10.1111/acer.12605 PG 8 WC Substance Abuse SC Substance Abuse GA CA2DM UT WOS:000348719100012 PM 25623409 ER PT J AU Jahshan, C Wynn, JK Mathis, KI Green, MF AF Jahshan, Carol Wynn, Jonathan K. Mathis, Kristopher I. Green, Michael F. TI The neurophysiology of biological motion perception in schizophrenia SO BRAIN AND BEHAVIOR LA English DT Article DE Biological motion; electroencephalography; event-related potential; schizophrenia; visual perception ID EVENT-RELATED POTENTIALS; RECOGNITION; ATTENTION; COGNITION; SPECTRUM; FORM AB Introduction: The ability to recognize human biological motion is a fundamental aspect of social cognition that is impaired in people with schizophrenia. However, little is known about the neural substrates of impaired biological motion perception in schizophrenia. In the current study, we assessed event-related potentials (ERPs) to human and nonhuman movement in schizophrenia. Methods: Twenty-four subjects with schizophrenia and 18 healthy controls completed a biological motion task while their electroencephalography (EEG) was simultaneously recorded. Subjects watched clips of point-light animations containing 100%, 85%, or 70% biological motion, and were asked to decide whether the clip resembled human or nonhuman movement. Three ERPs were examined: P1, N1, and the late positive potential (LPP). Results: Behaviorally, schizophrenia subjects identified significantly fewer stimuli as human movement compared to healthy controls in the 100% and 85% conditions. At the neural level, P1 was reduced in the schizophrenia group but did not differ among conditions in either group. There were no group differences in N1 but both groups had the largest N1 in the 70% condition. There was a conditionxgroup interaction for the LPP: Healthy controls had a larger LPP to 100% versus 85% and 70% biological motion; there was no difference among conditions in schizophrenia subjects. Conclusions: Consistent with previous findings, schizophrenia subjects were impaired in their ability to recognize biological motion. The EEG results showed that biological motion did not influence the earliest stage of visual processing (P1). Although schizophrenia subjects showed the same pattern of N1 results relative to healthy controls, they were impaired at a later stage (LPP), reflecting a dysfunction in the identification of human form in biological versus nonbiological motion stimuli. C1 [Jahshan, Carol; Wynn, Jonathan K.; Mathis, Kristopher I.; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Jahshan, Carol; Wynn, Jonathan K.; Mathis, Kristopher I.; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. RP Jahshan, C (reprint author), VA Greater Los Angeles Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Bldg 210,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM carol.jahshan@ucla.edu RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU Department of Veterans Affairs Desert Pacific Mental Illness Research, Education and Clinical Center (MIRECC); National Institute of Mental Health [MH065707] FX Funding for this study was provided by grants from the Department of Veterans Affairs Desert Pacific Mental Illness Research, Education and Clinical Center (MIRECC), and the National Institute of Mental Health (MH065707 to MFG). The MIRECC and National Institutes of Health had no 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 authors thank C. Gibson, C. Tripp, K. Weiner, M. McGee, and A. Bender for their assistance with recruitment and testing. The authors also thank Jejoong Kim, Ph.D. for providing the biological motion task. NR 31 TC 0 Z9 0 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2162-3279 J9 BRAIN BEHAV JI Brain Behav. PD JAN PY 2015 VL 5 IS 1 AR e00303 DI 10.1002/brb3.303 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CA6OO UT WOS:000349034700008 ER PT J AU Beste, LA Ioannou, GN Yang, Y Chang, MF Ross, D Dominitz, JA AF Beste, Lauren A. Ioannou, George N. Yang, Yin Chang, Michael F. Ross, David Dominitz, Jason A. TI Improved Surveillance for Hepatocellular Carcinoma With a Primary Care-Oriented Clinical Reminder SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Liver Cancer; Screening; Veterans; Cirrhosis ID UNITED-STATES; HEPATITIS-C; LIVER-TRANSPLANTATION; PATIENT SURVIVAL; CIRRHOSIS; CANCER; RATES; STAGE; VETERANS; FUTURE AB BACKGROUND & AIMS: Surveillance of patients with cirrhosis for hepatocellular carcinoma (HCC) with liver ultrasound every 6 months has been linked to longer survival and greater use of definitive treatment. However, less than 20% of patients typically undergo routine surveillance. METHODS: We conducted a quasi-experimental study to assess whether a primary care-oriented, point-of-care clinical reminder improves HCC surveillance. Our study included patients with cirrhosis who made 1 or more primary care visits to 8 Veterans Affairs (VA) facilities over 18 months. Clinicians at 1 facility were sent a reminder to perform liver ultrasound assessments for patients with cirrhosis who had not received surveillance in the preceding 6 months. Outcomes included the proportion of patients receiving adequate HCC surveillance (defined as >2 instances of liver imaging >6 months apart) and HCC diagnosis and stage. Because it was a quality improvement project, this study did not require approval by an institutional review board under Federal law and VA policy. RESULTS: Baseline rates of adequate HCC surveillance were similar at all facilities (18.2% at the intervention site vs 16.1% elsewhere; P = .23). After the reminder was implemented, adequate surveillance at the intervention site (for 790 patients) increased by 51%, but was unchanged at the other facilities (for 2094 patients) (27.6% vs 17.5%; P < .001). Adequate surveillance occurred more often at the intervention site (adjusted odds ratio, 1.29; 95% confidence interval, 1.03-1.61; P = .02). A higher crude percentage of patients was diagnosed with HCC at the intervention site than elsewhere (3.2% vs 1.9%; P = .03). We detected no difference in tumor stage at diagnosis. CONCLUSIONS: In a VA population, a clinical reminder system increased HCC surveillance in patients with cirrhosis. C1 [Beste, Lauren A.] Vet Affairs Puget Sound Hlth Care Syst, Gen Internal Med, Seattle, WA USA. [Beste, Lauren A.; Yang, Yin; Dominitz, Jason A.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Ioannou, George N.; Dominitz, Jason A.] Vet Affairs Puget Sound Hlth Care Syst, Gastroenterol Sect, Seattle, WA USA. [Beste, Lauren A.] Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. [Ioannou, George N.; Dominitz, Jason A.] Univ Washington, Div Gastroenterol, Seattle, WA 98195 USA. [Chang, Michael F.] Portland VA Med Ctr, Dept Gastroenterol & Hepatol, Portland, OR USA. [Chang, Michael F.] Oregon Hlth & Sci Univ, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. [Ross, David] Dept Vet Affairs, Off Clin Publ Hlth, HIV Hepatitis & Publ Hlth Pathogens Program C, Washington, DC USA. [Ross, David] George Washington Univ, Div Infect Dis, Washington, DC USA. RP Beste, LA (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, 1660 S Columbian Way, Seattle, WA 98018 USA. EM lauren.beste@va.gov OI Dominitz, Jason/0000-0002-8070-7086 FU Veterans Affairs Puget Sound Health Care System; Veterans Affairs National Hepatitis C Resource Centers program, through the Office of HIV, Hepatitis C, and Public Health Pathogens FX This material is the result of work supported by resources from the Veterans Affairs Puget Sound Health Care System and the Portland Veterans Affairs Medical Center. Funding also was provided by the Veterans Affairs National Hepatitis C Resource Centers program, through the Office of HIV, Hepatitis C, and Public Health Pathogens. 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. NR 32 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JAN PY 2015 VL 13 IS 1 BP 172 EP 179 DI 10.1016/j.cgh.2014.04.033 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ2BW UT WOS:000348040500030 PM 24813175 ER PT J AU Ghany, MG Perrillo, R Li, RS Belle, SH Janssen, HLA Terrault, NA Shuhart, MC Lau, DTY Kim, WR Fried, MW Sterling, RK Di Bisceglie, AM Han, SHB Ganova-Raeva, LM Chang, KM Lok, ASF AF Ghany, Marc G. Perrillo, Robert Li, Ruosha Belle, Steven H. Janssen, Harry L. A. Terrault, Norah A. Shuhart, Margaret C. Lau, Daryl T-Y. Kim, W. Ray Fried, Michael W. Sterling, Richard K. Di Bisceglie, Adrian M. Han, Steven-Huy B. Ganova-Raeva, Lilia Milkova Chang, Kyong-Mi Lok, Anna Suk-Fong CA Hepatitis B Res Network TI Characteristics of Adults in the Hepatitis B Research Network in North America Reflect Their Country of Origin and Hepatitis B Virus Genotype SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE HBeAg; Chronic Hepatitis B Virus Infection; USA; ALT ID UNITED-STATES; HBV INFECTION; EPIDEMIOLOGY; PREVALENCE; WORLDWIDE; DISEASE; BURDEN; HEALTH AB BACKGROUND & AIMS: Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma worldwide; populations that migrate to the United States and Canada might be affected disproportionately. The Hepatitis B Research Network (HBRN) is a cooperative network of investigators from the United States and Canada, created to facilitate clinical, therapeutic, and translational research in adults and children with hepatitis B. We describe the structure of the network and baseline characteristics of adults with hepatitis B enrolled in the network. METHODS: The HBRN collected data on the clinical characteristics of 1625 adults with chronic HBV infection who are not receiving antiviral therapy from 21 clinical centers in North America. RESULTS: Half of the subjects in the HBRN are men, and the median age is 42 years; 72% are Asian, 15% are black, and 11% are white; with 82% born outside of North America. The most common HBV genotype was B (39%); 74% of subjects were negative for the hepatitis B e antigen. The median serum level of HBV DNA when the study began was 3.6 log(10) IU/mL; 68% of male subjects and 67% of female subjects had alanine aminotransferase levels higher than the normal range. CONCLUSIONS: The HBRN cohort is used to address important clinical and therapeutic questions for North Americans infected with chronic HBV and to guide health policies on HBV prevention and management in North America. C1 [Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Perrillo, Robert] Baylor Univ, Med Ctr, Hepatol Div, Dallas, TX USA. [Li, Ruosha; Belle, Steven H.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Janssen, Harry L. A.] Toronto Western Hosp, Div Gastroenterol, Univ Hlth Network, Toronto, ON M5T 2S8, Canada. [Janssen, Harry L. A.] Toronto Gen Hosp, Div Gastroenterol, Univ Hlth Network, Toronto, ON, Canada. [Terrault, Norah A.] Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA. [Shuhart, Margaret C.] Univ Washington, Harborview Med Ctr, Viral Hepatitis & Liver Clin, Seattle, WA 98104 USA. [Lau, Daryl T-Y.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gastroenterol, Boston, MA 02215 USA. [Kim, W. Ray] Stanford Univ, Sch Med, Div Gastroenterol, Palo Alto, CA 94304 USA. [Fried, Michael W.] Univ N Carolina, Ctr Liver, Sect Hepatol, Chapel Hill, NC USA. [Sterling, Richard K.] Virginia Commonwealth Univ Hlth Syst, Sect Hepatol, Richmond, VA USA. [Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Dept Internal Med, St Louis, MO USA. [Han, Steven-Huy B.] Univ Calif Los Angeles, David Geffen Sch Med, Pfleger Liver Inst Clin, Los Angeles, CA 90095 USA. [Ganova-Raeva, Lilia Milkova] Ctr Dis Control & Prevent, Div Viral Hepatitis, Mol Epidemiol & Bioinformat Sequencing Lab, Atlanta, GA USA. [Chang, Kyong-Mi] Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Penn Ctr Viral Hepatitis, Philadelphia, PA 19104 USA. [Lok, Anna Suk-Fong] Univ Michigan, Div Gastroenterol & Hepatol, Ann Arbor, MI 48109 USA. RP Ghany, MG (reprint author), NIDDK, Liver Dis Branch, NIH, Bdg 10,Room 9B-16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. EM marcg@intra.niddk.nih.gov OI Cloonan, Yona/0000-0003-3893-3693; Wahed, Abdus/0000-0001-6911-7221; Barritt, Alfred/0000-0002-4200-3256 FU National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK082872, DK082864, DK082874, U01 DK082944, DK082943, DK082919, DK 082843, DK082867, DK082923, DK082871, DK082927, DK082866, DK082863, A-DK-3002-001]; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Immunology Center (National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases, Center of Molecular Studies in Digestive and Liver Diseases) [P30DK50306]; Immunology Center (National Institutes of Health Public Health Service Research) [M01RR00040]; National Center for Advancing Translational Sciences, National Institutes of Health [UL1TR000058]; Clinical and Translational Science Awards [UL1TR000004, UL1TR001111, UL1RR024986]; Gilead Sciences, Inc; Roche Molecular Systems through National Institute of Diabetes and Digestive and Kidney Diseases FX The Hepatitis B Research Network was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases to the following investigators: U01 DK082872 (W.L.), DK082864 (S.B.), DK082874 (H.J.), U01 DK082944 (N.T.), DK082943 (R.C.), DK082919 (D.T.-Y.L.), DK 082843 (L.R.R.), DK082867 (M.W.F.), DK082923 (R.K.S.), DK082871 (A.D.B.), DK082927 (S.-H.B.H.), DK082866 (K.-M.C.), and DK082863 (A.S.-F.L.); an interagency agreement with the National Institute of Diabetes and Digestive and Kidney Diseases: A-DK-3002-001 (L.M.G.-R.); and support from the intramural program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (M.G.G.). Additional funding for this study was provided by the Immunology Center (National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases, Center of Molecular Studies in Digestive and Liver Diseases: P30DK50306; and a National Institutes of Health Public Health Service Research grant: M01RR00040 to K.-M.C.), by the National Center for Advancing Translational Sciences, National Institutes of Health (UL1TR000058 to R.K.S.); and Clinical and Translational Science Awards grants: UL1TR000004 (N.A.T.), UL1TR001111 (M.W.F.), and UL1RR024986 (A.S.-F.L.). Additional support was provided by Gilead Sciences, Inc, and Roche Molecular Systems via a Cooperative Research And Development Agreement through the National Institute of Diabetes and Digestive and Kidney Diseases. NR 15 TC 13 Z9 13 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JAN PY 2015 VL 13 IS 1 BP 183 EP 192 DI 10.1016/j.cgh.2014.06.028 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ2BW UT WOS:000348040500032 PM 25010003 ER PT J AU Thames, AD Panos, SE Arentoft, A Byrd, DA Hinkin, CH Arbid, N AF Thames, April D. Panos, Stella E. Arentoft, Alyssa Byrd, Desiree A. Hinkin, Charles H. Arbid, Natalie TI Mild Test Anxiety Influences Neurocognitive Performance Among African Americans and European Americans: Identifying Interfering and Facilitating Sources SO CULTURAL DIVERSITY & ETHNIC MINORITY PSYCHOLOGY LA English DT Article DE anxiety; assessment; cognition; ethnicity; performance ID OBSESSIVE-COMPULSIVE DISORDER; STEREOTYPE THREAT; NEUROPSYCHOLOGICAL PERFORMANCE; WORKING-MEMORY; ACADEMIC-PERFORMANCE; SELF-REPORT; RACE; CORTISOL; ABILITY; CORTICOSTEROIDS AB The current study examined ethnic/racial differences in test-related anxiety and its relationship to neurocognitive performance in a community sample of African American (n = 40) and European American (n = 36) adults. The authors hypothesized the following: (a) Test-anxiety related to negative performance evaluation would be associated with lower neurocognitive performance, whereas anxiety unrelated to negative evaluation would be associated with higher neurocognitive performance. (b) African American participants would report higher levels of anxiety about negative performance evaluation than European Americans. (c) European Americans would report higher levels of anxiety unrelated to negative performance evaluation. The first two hypotheses were supported: Ethnic/racial differences in test-taking anxiety emerged such that African Americans reported significantly higher levels of negative performance evaluation, which was associated with lower cognitive performance. The third hypothesis was not supported: African Americans and European Americans reported similar levels of test-anxiety unrelated to negative evaluation. C1 [Thames, April D.; Panos, Stella E.; Arentoft, Alyssa; Hinkin, Charles H.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Panos, Stella E.; Arentoft, Alyssa; Hinkin, Charles H.; Arbid, Natalie] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Byrd, Desiree A.] Mt Sinai Sch Med, Dept Neurol & Psychiat, New York, NY USA. RP Thames, AD (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza C8-226, Los Angeles, CA 90095 USA. EM athames@mednet.ucla.edu OI Arentoft, Alyssa/0000-0002-4235-4638 FU National Academy of Neuropsychology, Clinical Research Grants; National Institutes of Health/National Institute of Mental Health Career Development Award [K23 MH095661] FX This work was supported by the National Academy of Neuropsychology, Clinical Research Grants (Principal Investigator: April D. Thames) and National Institutes of Health/National Institute of Mental Health Career Development Award K23 MH095661 (Principal Investigator: April D. Thames). NR 61 TC 4 Z9 4 U1 8 U2 15 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1099-9809 EI 1939-0106 J9 CULT DIVERS ETHN MIN JI Cult. Divers. Ethn. Minor. Psychol. PD JAN PY 2015 VL 21 IS 1 BP 105 EP 113 DI 10.1037/a0037530 PG 9 WC Ethnic Studies; Psychology, Social SC Ethnic Studies; Psychology GA AZ6YH UT WOS:000348364300011 PM 25111554 ER PT J AU Damodarasamy, M Vernon, RB Chan, CK Plymate, SR Wight, TN Reed, MJ AF Damodarasamy, Mamatha Vernon, Robert B. Chan, Christina K. Plymate, Stephen R. Wight, Thomas N. Reed, May J. TI Hyaluronan in aged collagen matrix increases prostate epithelial cell proliferation SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE Aging; Benign prostatic hypertrophy; Collagen gel; 3-Dimensional; Extracellular matrix; In vitro ID TUMOR PROGRESSION; I COLLAGEN; CANCER; EXPRESSION; GROWTH; MICROENVIRONMENT; ANGIOGENESIS; MIGRATION; DENSITY; GLYCOSAMINOGLYCANS AB The extracellular matrix (ECM) of the prostate, which is comprised primarily of collagen, becomes increasingly disorganized with age, a property that may influence the development of hyperplasia and cancer. Collageous ECM extracted from the tails of aged mice exhibits many characteristics of collagen in aged tissues, including the prostate. When polymerized into a 3-dimensional (3D) gel, these collagen extracts can serve as models for the study of specific cell-ECM interactions. In the present study, we examined the behaviors of human prostatic epithelial cell lines representing normal prostate epithelial cells (PEC), benign prostatic hyperplasia (BPH-1), and adenocarcinoma (LNCaP) cultured in contact with 3D gels made from collagen extracts of young and aged mice. We found that proliferation of PEC, BPH-1, and LNCaP cells were all increased by culture on aged collagen gels relative to young collagen gels. In examining age-associated differences in the composition of the collagen extracts, we found that aged and young collagen had a similar amount of several collagen-associated ECM components, but aged collagen had a much greater content of the glycosaminoglycan hyaluronan (HA) than young collagen. The addition of HA (of similar size and concentration to that found in aged collagen extracts) to cells placed in young collagen elicited significantly increased proliferation in BPH-1 cells, but not in PEC or LNCaP cells, relative to controls not exposed to HA. Of note, histochemical analyses of human prostatic tissues showed significantly higher expression of HA in BPH and prostate cancer stroma relative to stroma of normal prostate. Collectively, these results suggest that changes in ECM involving increased levels of HA contribute to the growth of prostatic epithelium with aging. C1 [Damodarasamy, Mamatha; Plymate, Stephen R.; Reed, May J.] Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA. [Vernon, Robert B.; Chan, Christina K.; Wight, Thomas N.] Benaroya Res Inst Virginia Mason, Matrix Biol Program, Seattle, WA 98101 USA. [Plymate, Stephen R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Reed, MJ (reprint author), Univ Washington, Harborview Med Ctr, Dept Med, 325 9th Ave,Box 359625, Seattle, WA 98104 USA. EM mjr@uw.edu FU NIA/NIH [R21 AG033391]; NIBIB/NIH [R01 EB012558] FX R21 AG033391 NIA/NIH (M.J.R.); R01 EB012558, NIBIB/NIH (R.B.V./T.N.W) NR 51 TC 3 Z9 3 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 EI 1543-706X J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD JAN PY 2015 VL 51 IS 1 BP 50 EP 58 DI 10.1007/s11626-014-9800-z PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA CA6AF UT WOS:000348989700008 PM 25124870 ER PT J AU Harper, DC Selleck, CS Eagerton, G Froelich, K AF Harper, Doreen C. Selleck, Cynthia S. Eagerton, Gregory Froelich, Kimberly TI PARTNERSHIP TO IMPROVE QUALITY CARE FOR VETERANS: THE VA NURSING ACADEMY SO JOURNAL OF PROFESSIONAL NURSING LA English DT Article DE Veterans; Partnerships; Nursing education; VA Nursing Academy AB More than 22 million living veterans reside in the United States. In fact, understanding military culture and the experiences of these veterans is important to their ongoing health care and the unique challenges faced by many. The Veterans Affairs (VA) Nursing Academy began in 2007 to fund pilot partnerships between schools of nursing and local VA health care facilities to better serve our veteran population. Fifteen academic/service partnerships were selected for funding between 2007 and 2009 with the goals of expanding faculty and professional development, increasing nursing student enrollment, providing opportunities for educational and practice innovations, and increasing the recruitment and retention of VA nurses. This article details critical components of the partnership developed between the Birmingham VA Medical Center and the University of Alabama at Birmingham School of Nursing, a VA Nursing Academy partnership funded in the 2009 cohort. Site-specific goals of the partnership are described along with a discussion of the framework used to develop the Birmingham VA Nursing Academy, which includes relationship building, engagement, governance, evaluation of outcomes, and sustainability. The logic model developed for the partnership is included, and the interim outputs and outcomes of this practice academic partnership are detailed, a number of which can be replicated by VAs and schools of nursing across the country. (C) 2015 Elsevier Inc. All rights reserved. C1 [Harper, Doreen C.; Selleck, Cynthia S.] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL 35294 USA. [Eagerton, Gregory] Durham VA Med Ctr, Durham, NC 27705 USA. [Eagerton, Gregory] Birmingharn VA Med Ctr, Birmingham, AL 35233 USA. [Froelich, Kimberly] Birmingham VA Med Ctr, Patient Care Serv Outpatient & Staff Dev, Birmingham, AL 35294 USA. RP Selleck, CS (reprint author), Univ Alabama Birmingham, Sch Nursing, 1720 2nd Ave South, Birmingham, AL 35294 USA. EM cselleck@uab.edu NR 4 TC 5 Z9 5 U1 0 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 8755-7223 EI 1532-8481 J9 J PROF NURS JI J. Prof. Nurs. PD JAN-FEB PY 2015 VL 31 IS 1 BP 57 EP 63 DI 10.1016/j.profnurs.2014.06.004 PG 7 WC Nursing SC Nursing GA CA1RR UT WOS:000348689800009 PM 25601246 ER PT J AU Gabayan, GZ Sarkisian, CA Liang, LJ Sun, BC AF Gabayan, Gelareh Z. Sarkisian, Catherine A. Liang, Li-Jung Sun, Benjamin C. TI Predictors of Admission After Emergency Department Discharge in Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE emergency department; Medicare; outcomes ID PUBLIC HOSPITAL EMERGENCY; ADVERSE HEALTH OUTCOMES; DEATH AFTER-DISCHARGE; ELDERLY-PATIENTS; UNSCHEDULED RETURNS; MEDICAL ADVICE; RISK-FACTORS; CARE; ACCIDENT; VISITS AB ObjectivesTo identify predictors of hospital inpatient admission of older Medicare beneficiaries after discharge from the emergency department (ED). DesignRetrospective cohort study. SettingNonfederal California hospitals (n=284). ParticipantsVisits of Medicare beneficiaries aged 65 and older discharged from California EDs in 2007 (n=505,315). MeasurementsUsing the California Office of Statewide Health Planning and Development files, predictors ofhospital inpatient admission within 7days of ED discharge in older adults (65) with Medicare were evaluated. ResultsHospital inpatient admissions within 7days of ED discharge occurred in 23,340 (4.6%) visits and were associated with older age (70-74: adjusted odds ratio (AOR)=1.12, 95% confidence interval (CI)=1.07-1.17; 75-79: AOR=1.18, 95% CI=1.13-1.23; 80: AOR= 1.4, 95% CI=1.35-1.46), skilled nursing facility use (AOR=1.82, 95% CI=1.72-1.94), leaving the ED against medical advice (AOR=1.82, 95% CI=1.67-1.98), and the following diagnoses with the highest odds of admission: end-stage renal disease (AOR=3.83, 95% CI=2.42-6.08), chronic renal disease (AOR=3.19, 95% CI=2.26-4.49), and congestive heart failure (AOR= 3.01, 95% CI=2.59-3.50). ConclusionFive percent of older Medicare beneficiaries have a hospital inpatient admission after discharge from the ED. Chronic conditions such as renal disease and heart failure were associated with the greatest odds of admission. C1 [Gabayan, Gelareh Z.; Sarkisian, Catherine A.; Liang, Li-Jung] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Gabayan, Gelareh Z.; Sarkisian, Catherine A.] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Med, Portland, OR USA. [Sun, Benjamin C.] Oregon Hlth & Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. RP Gabayan, GZ (reprint author), Dept Med, 11301 Wilshire Blvd,Bldg 500,111-G, Los Angeles, CA 90073 USA. EM Gelareh@gabayan.com FU Emergency Medicine Foundation; Agency for Healthcare Research and Quality [R03 HS18098]; University of California at Los Angeles Older American Independence Center National Institutes of Health (NIH); National Institute on Aging (NIA) pilot grant; NIH, National Center for Research Resources; National Center for Advancing Translational Sciences; University of California at Los Angeles Clinical and Translational Science Institute [KL2TR000122] FX This research was supported by the Emergency Medicine Foundation (Sun), the Agency for Healthcare Research and Quality (Sun R03 HS18098), and the University of California at Los Angeles Older American Independence Center National Institutes of Health (NIH), National Institute on Aging (NIA) pilot grant. Dr. Gabayan receives support from the NIH, National Center for Research Resources, National Center for Advancing Translational Sciences, University of California at Los Angeles Clinical and Translational Science Institute (Grant KL2TR000122). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the NIA. NR 32 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2015 VL 63 IS 1 BP 39 EP 45 DI 10.1111/jgs.13185 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AZ7BW UT WOS:000348374200005 PM 25537073 ER PT J AU Ganz, DA Kim, SB Zingmond, DS Ramirez, KD Roth, CP Jennings, LA Mori, T Keeler, EB Wenger, NS Reuben, DB AF Ganz, David A. Kim, Sung-Bou Zingmond, David S. Ramirez, Karina D. Roth, Carol P. Jennings, Lee A. Mori, Takahiro Keeler, Emmett B. Wenger, Neil S. Reuben, David B. TI Effect of a Falls Quality Improvement Program on Serious Fall-Related Injuries SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE quality improvement; practice redesign; ACOVE; falls; fall-related injuries ID OLDER-ADULTS; CONTROLLED-TRIAL; PREVENTION; RISK; FRACTURES; CARE; DISSEMINATION; INTERVENTION; PEOPLE AB ObjectivesTo determine whether a program that improves the quality of care for falls reduces the number of episodes of care for serious fall-related injuries. DesignNonrandomized controlled trial. SettingFour community-based primary care practices. ParticipantsIndividuals aged 75 and older who screened positive for fall risk. InterventionA multicomponent quality improvement program (Assessing Care of Vulnerable Elders Practice Redesign for Improved Medical Care for Elders) involving face-to-face clinician education about falls and decision support to prompt primary care providers to implement appropriate care, including referral to appropriate community resources, in response to individuals screening positive for fall risk. MeasurementsEpisodes of care for selected fall-related injuries, based on healthcare claims. ResultsOf 1,791 individuals with data available for analysis, 1,187 were in the intervention group, and 604 were in the control group. Mean age was 83, and more than two-thirds of the sample were women. After adjusting for potential confounders, there were no statistically significant differences between intervention and control groups in episodes of care for fall-related injuries during the 12-month (incidence rate ratio (IRR) 1.27, 95% confidence interval (CI)=0.93-1.73) or 24-month (IRR 1.18, 95% CI=0.93-1.49) period after initiation of the intervention. ConclusionDespite improving the care of falls, this quality improvement initiative did not result in a change in the number of episodes of care for serious fall-related injuries. Future work in community-based settings should test higher-intensity interventions to reduce fall-related injuries. C1 [Ganz, David A.; Ramirez, Karina D.; Jennings, Lee A.; Mori, Takahiro; Reuben, David B.] Univ Calif Los Angeles, David Geffen Sch Med, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA 90095 USA. [Ganz, David A.; Mori, Takahiro] Vet Affairs Los Greater Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Ganz, David A.; Roth, Carol P.; Keeler, Emmett B.; Wenger, Neil S.] RAND Hlth, Santa Monica, CA USA. [Kim, Sung-Bou] Pardee RAND Grad Sch, Santa Monica, CA USA. [Zingmond, David S.; Wenger, Neil S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. RP Ganz, DA (reprint author), VA Greater Los Angeles Healthcare Syst 11G, 11301 Wilshire Blvd,Bldg 220,Room 313, Los Angeles, CA 90073 USA. EM dganz@mednet.ucla.edu FU National Institute on Aging (NIA) [R01AG036776]; UCLA Claude Pepper Older Americans Independence Center - NIA [5P30AG028748]; National Institutes of Health; National Center for Advancing Translational Science UCLA Clinical and Translational Science Institute Grant [UL1TR000124] FX This project was supported by Grant R01AG036776 from the National Institute on Aging (NIA). Dr. Jennings was supported by the UCLA Claude Pepper Older Americans Independence Center funded by the NIA (5P30AG028748) and National Institutes of Health. National Center for Advancing Translational Science UCLA Clinical and Translational Science Institute Grant UL1TR000124. NR 24 TC 3 Z9 3 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2015 VL 63 IS 1 BP 63 EP 70 DI 10.1111/jgs.13154 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AZ7BW UT WOS:000348374200008 PM 25597558 ER PT J AU Aspinall, SL Zhao, XH Semla, TP Cunningham, FE Paquin, AM Pugh, MJ Schmader, KE Stone, RA Hanlon, JT AF Aspinall, Sherrie L. Zhao, Xinhua Semla, Todd P. Cunningham, Francesca E. Paquin, Allison M. Pugh, Mary Jo Schmader, Kenneth E. Stone, Roslyn A. Hanlon, Joseph T. CA Vet Affairs Community Living Ctr TI Epidemiology of Drug-Disease Interactions in Older Veteran Nursing Home Residents SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE drug-disease interactions; Beers criteria; nursing homes ID INAPPROPRIATE MEDICATION USE; PHARMACOLOGICAL MANAGEMENT; BEERS CRITERIA; RISK; CARE; PEOPLE; ADULTS; FALLS; DEMENTIA; HOSPITALIZATIONS AB ObjectivesTo describe the prevalence of and factors associated with drug-disease interactions (DDIs) in older nursing home residents according to the American Geriatrics Society 2012 Beers Criteria. DesignCross-sectional. SettingFifteen Veterans Affairs Community Living Centers. ParticipantsIndividuals aged 65 and older with a diagnosis of dementia or cognitive impairment, a history of falls or hip fracture, heart failure (HF), a history of peptic ulcer disease (PUD), or Stage IV or V chronic kidney disease (CKD). MeasurementsMedications that could exacerbate the above conditions (DDIs). ResultsThree hundred sixty-one of 696 (51.9%) eligible residents had one or more DDIs. None involved residents with a history of PUD, one involved a resident with CKD, and four occurred in residents with HF. Of 540 residents with dementia or cognitive impairment, 50.7% took a drug that could exacerbate these conditions; the most commonly involved medications were antipsychotics (35.4%) and benzodiazepines (14.4%). Of 267 with a history of falls or hip fracture, 67.8% received an interacting medication, with selective serotonin reuptake inhibitors (33.1%), antipsychotics (30.7%), and anticonvulsants (25.1%) being most commonly involved. Using separate multivariable logistic regression models, factors associated with DDIs in dementia or cognitive impairment and falls or fractures included age 85 and older (adjusted odds ratio (aOR)=0.38, 95% confidence interval (CI)=0.24-0.60 and aOR=0.48, 95% CI=0.24-0.96, respectively), taking five to eight medications (aOR=2.06, 95% CI=1.02-4.16 and aOR=4.76, 95% CI=1.68-13.5, respectively), taking nine or more medications (aOR=1.99, 95% CI=1.03-3.85 and aOR=3.68, 95% CI=1.41-9.61, respectively), and being a long-stay resident (aOR=1.80, 95% CI=1.04-3.12 and aOR=2.35, 95% CI=1.12-4.91, respectively). ConclusionDDIs were common in older nursing home residents with dementia or cognitive impairment or a history of falls or fractures. C1 [Aspinall, Sherrie L.; Semla, Todd P.; Cunningham, Francesca E.] Vet Affairs Pharm Benefits Management Serv, Hines, IL USA. [Aspinall, Sherrie L.; Zhao, Xinhua; Stone, Roslyn A.; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Aspinall, Sherrie L.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. [Semla, Todd P.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA. [Semla, Todd P.] Northwestern Univ, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Paquin, Allison M.] Vet Affairs Boston Healthcare Syst, Dept Pharm, Boston, MA USA. [Pugh, Mary Jo] South Texas Vet Hlth Care Syst, Res, San Antonio, TX USA. [Pugh, Mary Jo] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Schmader, Kenneth E.] Durham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA. [Schmader, Kenneth E.] Duke Univ, Med Ctr, Div Geriatr, Durham, NC USA. [Stone, Roslyn A.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr, Pittsburgh, PA 15213 USA. RP Aspinall, SL (reprint author), VA Pittsburgh Healthcare Syst, VA Ctr Hlth Equity Res & Promot, Univ Dr 151C,Bldg 30, Pittsburgh, PA 15240 USA. EM sherrie.aspinall@va.gov FU National Institute on Aging [R01-AG 027017, P30-AG024827, K07-AG033174, R01 AG037451]; Agency for Healthcare Research and Quality Grant [R01 HS018721]; ASHP Grant FX Dr. Hanlon was supported by National Institute on Aging Grants R01-AG 027017, P30-AG024827, K07-AG033174, and R01 AG037451 and Agency for Healthcare Research and Quality Grant R01 HS018721.; Dr. Semla has author or editor royalties from LexiComp, Inc. and honoraria from Omnicare, Inc. for serving on its Pharmacy and Therapeutics Committee. His spouse is an employee of AbbVie and owns stock in Hospira, Abbott, and Abbvie through her employment benefits. Dr. Paquin has an ASHP Grant for Award in Excellence in Medication-Use Safety to support dissemination of a postdischarge telephone program focused on helping older adults with cognitive difficulties transition from hospital to home. NR 38 TC 2 Z9 2 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2015 VL 63 IS 1 BP 77 EP 84 DI 10.1111/jgs.13197 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AZ7BW UT WOS:000348374200010 PM 25537124 ER PT J AU Lo-Ciganic, WH Perera, S Gray, SL Boudreau, RM Zgibor, JC Strotmeyer, ES Donohue, JM Bunker, CH Newman, AB Simonsick, EM Bauer, DC Satterfield, S Caserotti, P Harris, T Shorr, RI Hanlon, JT AF Lo-Ciganic, Wei-Hsuan Perera, Subashan Gray, Shelly L. Boudreau, Robert M. Zgibor, Janice C. Strotmeyer, Elsa S. Donohue, Julie M. Bunker, Clareann H. Newman, Anne B. Simonsick, Eleanor M. Bauer, Douglas C. Satterfield, Suzanne Caserotti, Paolo Harris, Tamara Shorr, Ronald I. Hanlon, Joseph T. CA Hlth Aging Body Composition Study TI Statin Use and Decline in Gait Speed in Community-Dwelling Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hydroxymethylglutaryl-CoA reductase inhibitors; statins; gait speed; physical function; aged ID PERIPHERAL ARTERIAL-DISEASE; COA REDUCTASE INHIBITORS; PHYSICAL PERFORMANCE; HEALTH; ATORVASTATIN; CHOLESTEROL; PREDICTOR; SYMPTOMS; THERAPY; PEOPLE AB ObjectivesTo examine the association between statin use and objectively assessed decline in gait speed in community-dwelling older adults. DesignLongitudinal cohort study. SettingHealth, Aging and Body Composition (Health ABC) Study. ParticipantsTwo thousand five participants aged 70-79 at baseline with medication and gait speed data at 1998-99, 1999-2000, 2001-02, and 2002-03. MeasurementsThe independent variables were any statin use and their standardized daily doses (low, moderate, high) and lipophilicity. The primary outcome measure was decline in gait speed of 0.1m/s or more in the following year of statin use. Multivariable generalized estimating equations were used, adjusting for demographic characteristics, health-related behaviors, health status, and access to health care. ResultsStatin use increased from 16.2% in 1998-99 to 25.6% in 2002-03. The overall proportions of those with decline in gait speed of 0.1m/s or more increased from 22.2% in 1998 to 23.9% in 2003. Statin use was not associated with decline in gait speed of 0.1m/s or more (adjusted odds ratio (AOR)=0.90, 95% confidence interval (CI)=0.77-1.06). Similar nonsignificant trends were also seen with the use of hydrophilic or lipophilic statins. Users of low-dose statins were found to have a 22% lower risk of decline in gait speed than nonusers (AOR=0.78, 95% CI=0.61-0.99), which was mainly driven by the results from 1999-2000 follow-up. ConclusionThese results suggest that statin use did not increase decline in gait speed in community-dwelling older adults. C1 [Lo-Ciganic, Wei-Hsuan; Hanlon, Joseph T.] Univ Pittsburgh, Ctr Pharmaceut Policy & Prescribing, Hlth Policy Inst, Pittsburgh, PA 15261 USA. [Perera, Subashan; Newman, Anne B.; Hanlon, Joseph T.] Univ Pittsburgh, Div Geriatr, Dept Med, Sch Med, Pittsburgh, PA 15261 USA. [Gray, Shelly L.] Univ Washington, Sch Pharm, Seattle, WA 98195 USA. [Boudreau, Robert M.; Zgibor, Janice C.; Strotmeyer, Elsa S.; Bunker, Clareann H.; Newman, Anne B.; Hanlon, Joseph T.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Donohue, Julie M.] Univ Pittsburgh, Dept Hlth Policy & Management, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Simonsick, Eleanor M.; Harris, Tamara] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Bauer, Douglas C.] Univ Calif San Francisco, Sch Med, Div Gen Med, San Francisco, CA USA. [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Caserotti, Paolo] Univ Southern Denmark, Inst Sports Sci & Clin Biomech, Odense, Denmark. [Shorr, Ronald I.] North Florida South Georgia Vet Hlth Syst, Geriatr Res Educ & Clin Ctr, Gainesville, FL USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res, Pittsburgh, PA USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Lo-Ciganic, WH (reprint author), Univ Pittsburgh, Ctr Pharmaceut Policy & Prescribing, 130 DeSoto St,A636, Pittsburgh, PA 15261 USA. EM wel32@pitt.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150; Strotmeyer, Elsa/0000-0002-4093-6036; Boudreau, Robert/0000-0003-0162-5187; Donohue, Julie/0000-0003-2418-6017 FU National Institute on Aging [R01-AG 027017, P30-AG024827, T32-AG021885, K07-AG033174, R01-AG034056, R01-AG028050, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Institute of Nursing Research grants [R01-NR010135, R01-NR012459]; Agency for Healthcare Research and Quality grants [R01-HS017695, R01-HS018721]; Intramural Research Program of the National Institutes of Health, National Institute on Aging FX This work was supported by National Institute on Aging grants and contracts (R01-AG 027017, P30-AG024827, T32-AG021885, K07-AG033174, R01-AG034056, R01-AG028050, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106), National Institute of Nursing Research grants (R01-NR010135, R01-NR012459), Agency for Healthcare Research and Quality grants (R01-HS017695, R01-HS018721), and the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 30 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2015 VL 63 IS 1 BP 124 EP 129 DI 10.1111/jgs.13134 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AZ7BW UT WOS:000348374200017 PM 25537649 ER PT J AU Ventura, MM Brittain, K Pruskowski, J Hogan, D Walker, T AF Ventura, MaryAnne M. Brittain, Kevin Pruskowski, Jennifer Hogan, Diana Walker, Tiffany TI DEVELOPMENT OF AN AGE-DEPENDENT ANTIBIOGRAM IN A VETERANS AFFAIRS COMMUNITY SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter C1 [Ventura, MaryAnne M.; Brittain, Kevin; Pruskowski, Jennifer; Hogan, Diana; Walker, Tiffany] William Jennings Bryan Dorn Vet Affairs Med Ctr, Columbia, SC 29209 USA. [Pruskowski, Jennifer] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Ventura, MM (reprint author), William Jennings Bryan Dorn Vet Affairs Med Ctr, Columbia, SC 29209 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2015 VL 63 IS 1 BP 186 EP 188 DI 10.1111/jgs.13224 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AZ7BW UT WOS:000348374200034 PM 25597575 ER PT J AU Dickey, MW Warren, T AF Dickey, Michael Walsh Warren, Tessa TI The influence of event-related knowledge on verb-argument processing in aphasia SO NEUROPSYCHOLOGIA LA English DT Article DE Language comprehension; Conceptual semantics; Aphasia; Sentence processing ID MINI-MENTAL STATE; LANGUAGE COMPREHENSION; EYE-MOVEMENTS; SENTENCE COMPREHENSION; SELECTIONAL RESTRICTION; SEMANTIC IMPAIRMENT; WORLD KNOWLEDGE; CORTEX; PLAUSIBILITY; INTEGRATION AB Event-related conceptual knowledge outside the language system rapidly affects verb-argument processing in unimpaired adults (McRae and Matsuki, 2009). Some have argued that verb-argument processing is in fact reducible to the activation of such event-related knowledge. However, data favoring this conclusion have come primarily from college-aged healthy adults, for whom both linguistic and conceptual semantic processing is fast and automatic. This study examined the influence of event-related knowledge on verb-argument processing among adults with aphasia (n=8) and older unimpaired controls (n=60), in two self-paced reading studies. Participants read sentences containing a plausible verb-argument combination (Mary used a knife to chop the large carrots before dinner), a combination that violated event-related world knowledge (Mary used some bleach to clean the large carrots before dinner), or a combination that violated the verb's selectional restrictions (Mary used a pump to inflate the large carrots before dinner). The participants with aphasia naturally split into two groups: Group 1 (n=4) had conceptual-semantic impairments (evidenced by poor performance on tasks like Pyramids & Palm Trees) but reasonably intact language processing (higher Western Aphasia Battery Aphasia Quotients), while Group 2 (n=4) had intact conceptual semantics but poorer language processing. Older unimpaired controls and aphasic Group 1 showed rapid on-line disruption for sentences with selectional-restriction violations (SRVs) and event-related knowledge violations, and also showed SRV-specific penalties in sentence-final acceptability judgments (Experiment 1) and comprehension questions (Experiment 2). In contrast, Group 2 showed very few reliable differences across conditions in either on-line or off-line measures. This difference between aphasic groups suggests that verb-related information and event-related knowledge may be dissociated in aphasia. Furthermore, it suggests that intact language processing is more critical for successful verb-argument integration than intact access to event-related world knowledge. This pattern is unexpected if verb-argument processing is reducible to activation of event-related conceptual knowledge. Published by Elsevier Ltd. C1 [Dickey, Michael Walsh] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Dickey, Michael Walsh; Warren, Tessa] Univ Pittsburgh, Learning Res & Dev Ctr, Pittsburgh, PA 15213 USA. RP Dickey, MW (reprint author), Dept Commun Sci & Disorders, 4032 Forbes Tower, Pittsburgh, PA 15260 USA. EM mdickey@pitt.edu OI Dickey, Michael Walsh/0000-0002-9068-3313 FU National Institutes of Health [R01DC011520]; University of Pittsburgh [UL1TR000005] FX This research was supported by the National Institutes of Health through Grant number R01DC011520 to the authors and by Grant number UL1TR000005 to the Clinical and Translational Science Institute of the University of Pittsburgh. It is the result of work supported with resources and the use of facilities at the VA Pittsburgh Healthcare System. Thanks are due to Minas Abovyan, Amanda Fryd, Emily Kosenske, Molly Lane, Evelyn Milburn, Hannah Rosenberg, Hyunsoo Yoo, and Lidia Zacharczuk for help running participants, to Alice Proverbio and Federica Riva for sharing their picture stimuli from Proverbio and Riva (2009), and to audiences at the 2012 and 2013 CUNY Sentence Processing Conference and the 2013 Academy of Aphasia meeting for comments and suggestions. Special thanks are due to the adults with aphasia who participated in these studies. A preliminary version of this work was published as Warren and Dickey (2013). NR 62 TC 3 Z9 3 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 EI 1873-3514 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD JAN PY 2015 VL 67 BP 63 EP 81 DI 10.1016/j.neuropsychologia.2014.12.003 PG 19 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA CA4NH UT WOS:000348880800007 PM 25484306 ER PT J AU Williams, BA Ibinson, JW Mangione, MP Scanlan, RL Cohen, PZ AF Williams, Brian A. Ibinson, James W. Mangione, Michael P. Scanlan, Rick L. Cohen, Peter Z. TI Clinical Benchmarks Regarding Multimodal Peripheral Nerve Blocks for Postoperative Analgesia: Observations Regarding Combined Perineural Midazolam-Clonidine-Buprenorphine-Dexamethasone SO PAIN MEDICINE LA English DT Editorial Material ID OUTPATIENT KNEE SURGERY; CARE-UNIT BYPASS; SAME-DAY DISCHARGE; LOCAL-ANESTHETICS; ARTHROPLASTY; FALLS; ADJUVANTS; PAIN; TIME C1 [Williams, Brian A.; Ibinson, James W.; Mangione, Michael P.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15261 USA. [Cohen, Peter Z.] Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, Pittsburgh, PA 15261 USA. [Williams, Brian A.; Ibinson, James W.] Vet Affairs Pittsburgh Healthcare Syst, Dept Anesthesiol, Pittsburgh, PA USA. [Williams, Brian A.; Ibinson, James W.; Mangione, Michael P.; Scanlan, Rick L.; Cohen, Peter Z.] Vet Affairs Pittsburgh Healthcare Syst, Surg Serv Line, Pittsburgh, PA USA. [Williams, Brian A.; Ibinson, James W.; Mangione, Michael P.; Scanlan, Rick L.; Cohen, Peter Z.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Williams, BA (reprint author), Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15261 USA. OI Ibinson, James/0000-0002-5525-5225 NR 20 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD JAN PY 2015 VL 16 IS 1 BP 1 EP 6 DI 10.1111/pme.12599 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA CA2IN UT WOS:000348732200001 PM 25351887 ER PT J AU Williams, BA Ibinson, JW Mangione, MP Modrak, RT Tonarelli, EJ Rakesh, H Kmatz, AM Cohen, PZ AF Williams, Brian A. Ibinson, James W. Mangione, Michael P. Modrak, Robert T. Tonarelli, Elizabeth J. Rakesh, Hulimangala Kmatz, Alissa M. Cohen, Peter Z. TI Research Priorities Regarding Multimodal Peripheral Nerve Blocks for Postoperative Analgesia and Anesthesia Based on Hospital Quality Data Extracted from Over 1,300 Cases (2011-2014) SO PAIN MEDICINE LA English DT Editorial Material ID LOCAL-ANESTHETICS; PAIN; PREDICTORS C1 [Williams, Brian A.; Ibinson, James W.; Mangione, Michael P.; Cohen, Peter Z.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Williams, Brian A.; Ibinson, James W.; Mangione, Michael P.; Rakesh, Hulimangala] Vet Affairs Pittsburgh Healthcare Syst, Anesthesia Serv, Pittsburgh, PA USA. [Modrak, Robert T.; Cohen, Peter Z.] Vet Affairs Pittsburgh Healthcare Syst, Orthopaed Surg Serv, Pittsburgh, PA USA. [Tonarelli, Elizabeth J.; Kmatz, Alissa M.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Williams, BA (reprint author), Univ Pittsburgh, Pittsburgh, PA 15260 USA. OI Ibinson, James/0000-0002-5525-5225 NR 13 TC 7 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD JAN PY 2015 VL 16 IS 1 BP 7 EP 12 DI 10.1111/pme.12609 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA CA2IN UT WOS:000348732200002 PM 25377071 ER PT J AU Oliva, EM Midboe, AM Lewis, ET Henderson, PT Dalton, AL Im, JJ Seal, K Paik, MC Trafton, JA AF Oliva, Elizabeth M. Midboe, Amanda M. Lewis, Eleanor T. Henderson, Patricia T. Dalton, Aaron L. Im, Jinwoo J. Seal, Karen Paik, Meenah C. Trafton, Jodie A. TI Sex Differences in Chronic Pain Management Practices for Patients Receiving Opioids from the Veterans Health Administration SO PAIN MEDICINE LA English DT Article DE Pain Management; Opioids; Sex; Veterans ID PRIMARY-CARE; MUSCULOSKELETAL PAIN; IRAQI FREEDOM; GENDER; WOMEN; PREVALENCE; ORGANIZATION; COMORBIDITY; POPULATION; PATTERNS AB BackgroundWomen experience chronic pain and use pain-related health care at higher rates than men. It is not known whether the pain-related health care female veterans receive is consistent with clinical practice guideline recommendations or whether receipt of this care differs between men and women. ObjectiveThe aim of this study was to identify whether sex differences in chronic pain management care exist for patients served by the Veterans Health Administration (VHA). DesignData on patient demographics, diagnostic criteria, and health care utilization were extracted from VHA administrative databases for fiscal year 2010 (FY10). PatientsPatients in this study included all VHA patients (excluding metastatic cancer patients) who received more than 90 days of a short-acting opioid medication or a long-acting opioid medication prescription in FY10 study. MeasuresMultilevel logistic regressions were conducted to identify sex differences in receipt of guideline-recommended chronic pain management. ResultsA total of 480,809 patients met inclusion criteria. Female patients were more likely to receive most measures of guideline-recommended care for chronic pain including mental health assessments, psychotherapy, rehabilitation therapy, and pharmacy reconciliation. However, women were more likely to receive concurrent sedative prescriptions, which is inconsistent with guideline recommendations. Most of the observed sex differences persisted after controlling for key demographic and diagnostic differences. ConclusionsFindings suggest that female VHA patients are more likely to receive an array of pain management practices than male patients, including both contraindicated and recommended polypharmacy. Quality improvement efforts to address underutilization of mental health and rehabilitative services for pain by male patients and polypharmacy in female patients should be considered. C1 [Oliva, Elizabeth M.; Midboe, Amanda M.; Lewis, Eleanor T.; Henderson, Patricia T.; Dalton, Aaron L.; Paik, Meenah C.; Trafton, Jodie A.] Ctr Innovat Implementat, Dept Vet Affairs, Menlo Pk, CA USA. [Seal, Karen] San Francisco VA Med Ctr, Integrated Care Clin, San Francisco, CA USA. [Seal, Karen] San Francisco VA Med Ctr, Med Practice Pain Clin, San Francisco, CA USA. [Trafton, Jodie A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Trafton, Jodie A.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Im, Jinwoo J.] Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA. [Seal, Karen] Samsung Econ Res Inst, Ind & Strategy Dept, Seoul, South Korea. RP Oliva, EM (reprint author), VA Ctr Innovat Implementat, 795Willow Rd 152, Menlo Pk, CA 94025 USA. EM Elizabeth.Oliva@va.gov FU Department of Veterans' Affairs (VA) Health Services Research and Development program (HSRD); Quality Enhancement Research Initiative (QUERI) [RRP 10-106, RRP 12-445]; VA Office of Mental Health FX This project was funded by grants awarded by the Department of Veterans' Affairs (VA) Health Services Research and Development program (HSR&D) and Quality Enhancement Research Initiative (QUERI) to Dr. Trafton-RRP 10-106 entitled "Assessment of Gaps in Chronic Opioid Therapy Guideline Adherence"-and Dr. Lewis-RRP 12-445 entitled "Adherence to Practice Recommendations for Veterans with SUDs Receiving Opioids." Additional funding was provided by the VA Office of Mental Health Operations to the Program Evaluation and Resource Center (PERC). The authors gratefully acknowledge Dr. Robert Kerns, Dr. William Becker, Dr. Francine Goodman, Dr. Jack Rosenberg, and Dr. Rollin (Mac) Gallagher for their role in creating the CPG adherence metrics. We gratefully acknowledge the sacrifices of the men and women who have served in the United States military. NR 20 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD JAN PY 2015 VL 16 IS 1 BP 112 EP 118 DI 10.1111/pme.12501 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CA2IN UT WOS:000348732200018 PM 25039721 ER PT J AU Williams, BA Butt, MT Zeller, JR Coffee, S Pippi, MA AF Williams, Brian A. Butt, Mark T. Zeller, Jillynne R. Coffee, Samantha Pippi, Michael A. TI Multimodal Perineural Analgesia with Combined Bupivacaine-Clonidine-Buprenorphine-Dexamethasone: Safe In Vivo and Chemically Compatible in Solution SO PAIN MEDICINE LA English DT Article DE Bupivacaine; Clonidine; Buprenorphine; Dexamethasone; Midazolam; Nerve Block ID BRACHIAL-PLEXUS BLOCKADE; PERIPHERAL-NERVE BLOCKS; LOCAL-ANESTHETICS; NEUROTOXICITY; ROPIVACAINE; ADJUVANTS; PROLONGS; MEPIVACAINE; LIDOCAINE; TRIALS AB ObjectivesThe use of adjuvants in regional anesthesia has increased. However, there are knowledge gaps pertaining to 1) in vivo local tissue effects of these adjuvants; and 2) chemical compatibility and solubility of these drugs in solution with each other and with local anesthetics. This study addresses these gaps in knowledge. DesignIn vivo rat safety/toxicopathology study and analytical chemistry study. SettingCollaborating Good Laboratory Practice laboratories under the direction of the university-based principal investigator. MethodsSingle-injection formulations of clonidine, buprenorphine, and dexamethasone were combined with either bupivacaine or midazolam, and were administered to groups of rats. Post-injection behavior was monitored to assess changes related to the block. A continuous infusion of bupivacaine, clonidine, and dexamethasone was administered to another group of rats, and behavioral effects were recorded. After 15 days, rats were sacrificed and their nerves/dorsal root ganglia were examined by the pathologist. Samples of combined drug solutions were processed at an analytical chemistry laboratory for compatibility, solubility, and stability. ResultsEach of the single-injection formulations produced reversible sensory and/or motor block. None of the study drugs caused damage to any of the nerve segments or related tissue. The text describes the concentrations at which compatibility and solubility of the combined drug solutions were achieved. ConclusionsFour-drug single-injection formulations are described that 1) had compatible and stable concentrations in solution; and 2) produced reversible nerve block without causing long-term motor or sensory deficits or damage to sciatic nerves/dorsal root ganglia. C1 [Williams, Brian A.] Vet Affairs Pittsburgh Healthcare Syst, Dept Anesthesiol, Pittsburgh, PA USA. [Williams, Brian A.; Pippi, Michael A.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA 15261 USA. [Butt, Mark T.] TPS, Frederick, MD USA. [Zeller, Jillynne R.] NBR, Spring Lake, MI USA. [Coffee, Samantha] WIL Res Labs, Ashland, OH USA. RP Williams, BA (reprint author), Univ Pittsburgh, Sch Med, Dept Anesthesiol, 200 Lothrop St,A-1305 Scaife Hall, Pittsburgh, PA 15261 USA. EM williamsba@anes.upmc.edu FU VA Pittsburgh Health System FX The methodology was designed in detailed consultation with the participating GLP facilities (animal surgery and behavioral experiments, along with animal sacrifice and tissue harvest/preservation at Northern Biomedical Research [NBR], Inc., Spring Lake, Michigan, United States; Randall Reed, BA, SRS, laboratory director; and Tox Path Specialists [TPS], LLC, Frederick, Maryland, United States; co-author Mark T. Butt, DVM, DAVCP, study pathologist and company president). The contents of this manuscript do not reflect the views of the Department of Veterans Affairs or the United States Government. VA Pittsburgh Health System is acknowledged for support of lead author BAW. This manuscript/study was underwritten by the Department of Defense (OR090012 to author BAW) Peer Reviewed Orthopaedic Research Program (PRORP), Translational Research Partnership Award (TRPA), of the Office of the Congressionally Directed Medical Research Programs (CDMRP). NR 20 TC 8 Z9 8 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD JAN PY 2015 VL 16 IS 1 BP 186 EP 198 DI 10.1111/pme.12592 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA CA2IN UT WOS:000348732200026 PM 25339320 ER PT J AU Brown, TM AF Brown, Thomas M. TI Neuropsychiatric Scurvy SO PSYCHOSOMATICS LA English DT Review ID ACETYL-L-CARNITINE; VITAMIN-C-DEFICIENCY; ASCORBIC ACID DEFICIENCY; PARKINSONS-DISEASE; CATALYTIC METALS; BRAIN; STRIATUM; OXYGEN; PREVALENCE; DOPAMINE AB Background: Scurvy is a disease with well-known peripheral symptoms, such as bleeding and pain. Method: The clinical and historical evidence for a distinct form of scurvy affecting the central nervous system, called neuropsychiatric scurvy, is reviewed. Pathophysiologic factors are described, as well as its diagnosis and management. C1 Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78229 USA. RP Brown, TM (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, 7400 Merton Minton Blvd, San Antonio, TX 78229 USA. EM thomas.brown5@va.gov NR 61 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2015 VL 56 IS 1 BP 12 EP 20 PG 9 WC Psychiatry; Psychology SC Psychiatry; Psychology GA AZ9CY UT WOS:000348510300002 PM 25619670 ER PT J AU Badejo, OA Chang, CC So-Armah, KA Tracy, RP Baker, JV Rimland, D Butt, AA Gordon, AJ Rinaldo, CR Kraemer, K Samet, JH Tindle, HA Goetz, MB Rodriguez-Barradas, MC Bedimo, R Gibert, CL Leaf, DA Kuller, LH Deeks, SG Justice, AC Freiberg, MS AF Badejo, Oluwatosin A. Chang, Chung-Chou So-Armah, Kaku A. Tracy, Russell P. Baker, Jason V. Rimland, David Butt, Adeel A. Gordon, Adam J. Rinaldo, Charles R., Jr. Kraemer, Kevin Samet, Jeffrey H. Tindle, Hilary A. Goetz, Matthew B. Rodriguez-Barradas, Maria C. Bedimo, Roger Gibert, Cynthia L. Leaf, David A. Kuller, Lewis H. Deeks, Steven G. Justice, Amy C. Freiberg, Matthew S. TI CD8(+) T-Cells Count in Acute Myocardial Infarction in HIV Disease in a Predominantly Male Cohort SO Biomed Research International LA English DT Article ID INFECTED WOMEN; RISK; ACTIVATION; SYSTEM; RATES AB Human Immunodeficiency Virus-(HIV-) infected persons have a higher risk for acute myocardial infarction (AMI) than HIVuninfected persons. Earlier studies suggest that HIV viral load, CD4 + T-cell count, and antiretroviral therapy are associated with cardiovascular disease (CVD) risk. Whether CD8 + T-cell count is associated with CVD risk is not clear. We investigated the association between CD8 + T-cell count and incident AMI in a cohort of 73,398 people (of which 97.3% were men) enrolled in the U. S. Veterans Aging Cohort Study-Virtual Cohort (VACS-VC). Compared to uninfected people, HIV-infected people with high baselineCD8 + T-cell counts (> 1065 cells/ mm 3) had increasedAMI risk (adjustedHR = 1.82,.. < 0.001, 95% CI: 1.46 to 2.28). There was evidence that the effect of CD8 + T-cell tertiles on AMI risk differed by CD4 + T-cell level: compared to uninfected people, HIVinfected people with CD4 + T-cell counts = 200 cells/ mm 3 had increased AMI risk with high CD8 + T-cell count, while those with CD4 + T-cell counts < 200 cells/ mm 3 had increased AMI risk with low CD8 + T-cell count. CD8 + T-cell counts may add additional AMI risk stratification information beyond that provided by CD4 + T-cell counts alone. C1 [Badejo, Oluwatosin A.; Chang, Chung-Chou; Gordon, Adam J.; Kraemer, Kevin] Univ Pittsburgh, UPMC, Div Gen Internal Med, Montefiore Hosp, Pittsburgh, PA 15213 USA. [Chang, Chung-Chou] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [So-Armah, Kaku A.] Yale Univ, Sch Med, New Haven, CT 06510 USA. [Tracy, Russell P.] Univ Vermont, Burlington, VT 05446 USA. [Baker, Jason V.] Univ Minnesota, Hennepin Cty Med Ctr, Dept Med, Minneapolis, MN 55415 USA. [Rimland, David] Emory Univ, Sch Med, VA Med Ctr, Atlanta, GA 30033 USA. [Butt, Adeel A.] Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA 15213 USA. [Butt, Adeel A.; Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Butt, Adeel A.] Hamad Med Corp, Doha, Qatar. [Rinaldo, Charles R., Jr.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA. [Rinaldo, Charles R., Jr.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA. [Samet, Jeffrey H.] Boston Univ, Sch Med, Clin Addict Res & Educ Unit, Boston, MA 02118 USA. [Samet, Jeffrey H.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. [Tindle, Hilary A.] Vanderbilt Univ, Med Ctr, Dept Gen Internal Med & Publ Hlth, Nashville, TN 37203 USA. [Goetz, Matthew B.; Leaf, David A.] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. [Goetz, Matthew B.; Leaf, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Infect Dis Sect, Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Bedimo, Roger] VA North Texas Healthcare Syst, Dallas, TX 75216 USA. [Bedimo, Roger] Univ Texas SW Med Ctr Dallas, Div Infect Dis, Dallas, TX 75390 USA. [Gibert, Cynthia L.] Washington DC VA Med Ctr, Washington, DC 20422 USA. [Gibert, Cynthia L.] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Kuller, Lewis H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Deeks, Steven G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Justice, Amy C.] Yale Univ, Sch Med, West Haven Vet Adm Med Ctr, Vet Affairs Connecticut Hlth Care Syst, New Haven, CT 06516 USA. [Freiberg, Matthew S.] Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Nashville, TN 37203 USA. RP Freiberg, MS (reprint author), Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, 2525 West End,Suite 300-A, Nashville, TN 37203 USA. EM matthew.s.freiberg@vanderbilt.edu OI Butt, Adeel/0000-0002-1118-1826; Goetz, Matthew/0000-0003-4542-992X; Justice, Amy/0000-0003-0139-5502 NR 12 TC 0 Z9 0 U1 1 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2015 AR 246870 DI 10.1155/2015/246870 PG 5 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CA7DU UT WOS:000349078600001 ER PT J AU Nislow, C Lee, AY Allen, PL Giaever, G Smith, A Gebbia, M Stodieck, LS Hammond, JS Birdsall, HH Hammond, TG AF Nislow, Corey Lee, Anna Y. Allen, Patricia L. Giaever, Guri Smith, Andrew Gebbia, Marinella Stodieck, Louis S. Hammond, Jeffrey S. Birdsall, Holly H. Hammond, Timothy G. TI Genes Required for Survival in Microgravity Revealed by Genome-Wide Yeast Deletion Collections Cultured during Spaceflight SO Biomed Research International LA English DT Article ID SACCHAROMYCES-CEREVISIAE; DNA-DAMAGE; SMALL MOLECULES; APOPTOSIS; ORGANISM; CELLS; MITOXANTRONE; PATHWAY AB Spaceflight is a unique environment with profound effects on biological systems including tissue redistribution and musculoskeletal stresses. However, the more subtle biological effects of spaceflight on cells and organisms are difficult to measure in a systematic, unbiased manner. Here we test the utility of the molecularly barcoded yeast deletion collection to provide a quantitative assessment of the effects of microgravity on a model organism. We developed robust hardware to screen, in parallel, the complete collection of similar to 4800 homozygous and similar to 5900 heterozygous (including similar to 1100 single-copy deletions of essential genes) yeast deletion strains, each carrying unique DNA that acts as strain identifiers. We compared strain fitness for the homozygous and heterozygous yeast deletion collections grown in spaceflight and ground, as well as plus and minus hyperosmolar sodium chloride, providing a second additive stressor. The genome-wide sensitivity profiles obtained from these treatments were then queried for their similarity to a compendium of drugs whose effects on the yeast collection have been previously reported. We found that the effects of spaceflight have high concordance with the effects of DNA-damaging agents and changes in redox state, suggesting mechanisms by which spaceflight may negatively affect cell fitness. C1 [Nislow, Corey; Giaever, Guri] Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC V6T 1Z3, Canada. [Lee, Anna Y.; Smith, Andrew; Gebbia, Marinella] Univ Toronto, Donnelly CCBR, Toronto, ON M5S 3E1, Canada. [Allen, Patricia L.; Hammond, Timothy G.] Durham VA Med Ctr, Res & Dev Serv, Durham, NC 27705 USA. [Stodieck, Louis S.] Univ Colorado, Bioserve Space Technol, Boulder, CO 80309 USA. [Hammond, Jeffrey S.] Inst Med Res, Durham, NC 27705 USA. [Birdsall, Holly H.; Hammond, Timothy G.] US Dept Vet Affairs, Off Res & Dev, Washington, DC 20420 USA. [Birdsall, Holly H.] Baylor Coll Med, Dept Otorhinolaryngol, Houston, TX 77030 USA. [Birdsall, Holly H.] Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. [Birdsall, Holly H.] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. [Hammond, Timothy G.] Duke Univ, Sch Med, Dept Internal Med, Div Nephrol, Durham, NC 27705 USA. [Hammond, Timothy G.] George Washington Univ, Sch Med, Dept Internal Med, Nephrol Sect, Washington, DC 20052 USA. RP Hammond, TG (reprint author), Durham VA Med Ctr, Res & Dev Serv, Durham, NC 27705 USA. EM grumpy70115@yahoo.com OI Nislow, Corey/0000-0002-4016-8874 FU NASA [NNX10AP01G] FX These studies were supported by NASA Grant no. NNX10AP01G. The authors thank NASA for spaceflight access under the auspices of the International Space Station National Lab Pathfinder program. This material is the result of work supported with resources and the use of facilities at the Durhan Veterans Affairs Medical Center and the Office of Research and Development, Department of Veterans Affairs, Veterans Health Administration. Sequencing was performed, in part at UBCSeq, Vancouver. Contents do not represent the views of the Department of Veterans Affairs or the United States of America. NR 33 TC 0 Z9 0 U1 0 U2 5 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2015 AR 976458 DI 10.1155/2015/976458 PG 10 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CA3DL UT WOS:000348786200001 ER PT J AU Ravona-Springer, R Haratz, S Tanne, D Schmeidler, J Efrati, S Rosendorff, C Beeri, MS Silverman, JM AF Ravona-Springer, Ramit Haratz, Salo Tanne, David Schmeidler, James Efrati, Shai Rosendorff, Clive Beeri, Michal Schnaider Silverman, Jeremy M. TI Arterial Wall Function is Associated with Cognitive Performance Primarily in Elderly with Type 2 Diabetes SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Arterial wall function; cognitive function; large artery elasticity index; total vascular impedance; type 2 diabetes ID PULSE-WAVE VELOCITY; MINI-MENTAL-STATE; ALZHEIMER-DISEASE; CEREBROVASCULAR REACTIVITY; CAROTID ATHEROSCLEROSIS; ENDOTHELIAL FUNCTION; FASTING GLUCOSE; OLDEST-OLD; STIFFNESS; DEMENTIA AB Regression analyses compared 41 type 2 diabetes (T2D) and 131 non-T2D cognitively normal elderly males on the associations of arterial wall function measures [large artery elasticity index (LAEI), small artery elasticity index (SAEI), systemic vascular resistance (SVR), and total vascular impedance (TVI)] with cognitive performance (memory, language, and executive functions), controlling for socio-demographic and cardiovascular factors. Higher LAEI and lower TVI were significantly associated with better executive functions performance in T2D but not in non-T2D subjects. Lower TVI was more associated with better language performance in T2D. Results suggest that arterial wall function is associated with cognition in T2D. C1 [Ravona-Springer, Ramit] Sheba Med Ctr, Memory Clin, IL-52621 Ramat Gan, Israel. [Ravona-Springer, Ramit; Haratz, Salo; Tanne, David; Efrati, Shai] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Haratz, Salo; Tanne, David] Sheba Med Ctr, Dept Neurol, Stroke Unit, IL-52621 Ramat Gan, Israel. [Schmeidler, James; Beeri, Michal Schnaider; Silverman, Jeremy M.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Efrati, Shai] Assaf Harofeh Med Ctr, Inst Hyperbar Med, IL-70300 Zerifin, Israel. [Efrati, Shai] Assaf Harofeh Med Ctr, Res & Dev Unit, IL-70300 Zerifin, Israel. [Efrati, Shai] Tel Aviv Univ, Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel. [Rosendorff, Clive; Silverman, Jeremy M.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Rosendorff, Clive] Mt Sinai Sch Med, Dept Med Cardiol, New York, NY USA. [Beeri, Michal Schnaider] Sheba Med Ctr, Josef Sagol Neurosci Ctr, IL-52621 Ramat Gan, Israel. RP Ravona-Springer, R (reprint author), Sheba Med Ctr, IL-52621 Ramat Gan, Israel. EM ramit.ravona@sheba.health.gov.il RI Tanne, David/F-2560-2010 OI Tanne, David/0000-0002-6699-2220 FU American Federation for Aging Research (AFAR) [NIRG-11-205083]; NIA [R01 AG034087, NIA-AG02219]; Helen Bader Foundation; Leroy Schecter Foundation; National Institute of Aging [P01-AG02219]; United States Department of Veterans Affairs FX This study was supported by the American Federation for Aging Research (AFAR), Young investigator award 2011 and NIRG-11-205083 Alzheimer's Association, 2012 to Dr. Ravona-Springer, NIA grant R01 AG034087 to Dr. Beeri, NIA-AG02219 (VH), the Helen Bader Foundation and the Irma T. Hirschl Scholar Award as well as the Leroy Schecter Foundation Award to Dr. Beeri, National Institute of Aging grant P01-AG02219 (to Mary Sano), a Merit Award to Dr. Silverman from the United States Department of Veterans Affairs. NR 46 TC 0 Z9 0 U1 1 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2015 VL 44 IS 2 BP 687 EP 693 DI 10.3233/JAD-141197 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AZ6WC UT WOS:000348357600029 PM 25352451 ER PT J AU Wells, TS Seelig, AD Ryan, MAK Jones, JM Hooper, TI Jacobson, IG Boyko, EJ AF Wells, Timothy S. Seelig, Amber D. Ryan, Margaret A. K. Jones, Jason M. Hooper, Tomoko I. Jacobson, Isabel G. Boyko, Edward J. TI Hearing loss associated with US military combat deployment SO NOISE & HEALTH LA English DT Article DE Combat disorders; hearing loss; military personnel ID TRAUMATIC BRAIN-INJURY; MILLENNIUM COHORT; SERVICE MEMBERS; NATIONAL-HEALTH; IMPULSE NOISE; ADULTS; PERSONNEL; RISK; POPULATION; IMPAIRMENT AB The objective of this study was to define the risk of hearing loss among US military members in relation to their deployment experiences. Data were drawn from the Millennium Cohort Study. Self-reported data and objective military service data were used to assess exposures and outcomes. Among all 48,540 participants, 7.5% self-reported new-onset hearing loss. Self-reported hearing loss showed moderate to substantial agreement (k = 0.57-0.69) with objective audiometric measures. New-onset hearing loss was associated with combat deployment (adjusted odds ratio [AOR] = 1.63, 95% confidence interval [CI] = 1.49-1.77), as well as male sex and older age. Among deployers, new-onset hearing loss was also associated with proximity to improvised explosive devices (AOR = 2.10, 95% CI = 1.62-2.73) and with experiencing a combat-related head injury (AOR = 6.88, 95% CI = 3.77-12.54). These findings have implications for health care and disability planning, as well as for prevention programs. C1 [Wells, Timothy S.] Adv Analyt Optum, Ann Arbor, MI USA. [Wells, Timothy S.] Adv Analyt Optum, San Diego, CA USA. [Seelig, Amber D.; Jacobson, Isabel G.] Naval Hlth Res Ctr, San Diego, CA USA. [Ryan, Margaret A. K.; Jones, Jason M.] Naval Hosp Camp Pendleton, San Diego, CA USA. [Hooper, Tomoko I.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [Seelig, Amber D.; Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. [Boyko, Edward J.] Univ Washington, Dept Med, Seattle, WA USA. RP Wells, TS (reprint author), 1839 Waverly Rd, Holt, MI USA. EM tmlbwells@wowway.com OI Boyko, Edward/0000-0002-3695-192X NR 48 TC 2 Z9 2 U1 3 U2 7 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 1463-1741 EI 1998-4030 J9 NOISE HEALTH JI Noise Health PD JAN-FEB PY 2015 VL 17 IS 74 BP 34 EP 42 PG 9 WC Audiology & Speech-Language Pathology; Public, Environmental & Occupational Health SC Audiology & Speech-Language Pathology; Public, Environmental & Occupational Health GA AZ7EH UT WOS:000348381200005 PM 25599756 ER PT J AU Katiyar, SK AF Katiyar, Santosh K. TI Proanthocyanidins from Grape Seeds Inhibit UV-Radiation-Induced Immune Suppression in Mice: Detection and Analysis of Molecular and Cellular Targets SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Review ID ULTRAVIOLET-INDUCED CARCINOGENESIS; CD8(+) T-CELLS; SKIN-CANCER; CONTACT HYPERSENSITIVITY; DENDRITIC CELLS; INDUCED IMMUNOSUPPRESSION; TRANSPLANT RECIPIENTS; PYRIMIDINE DIMERS; IRRADIATED MICE; RISK-FACTOR AB Ultraviolet (UV)-radiation-induced immunosuppression has been linked with the risk of skin carcinogenesis. Approximately, 2million new cases of skin cancers, including melanoma and nonmelanoma, diagnosed each year in the USA and therefore have a tremendous bad impact on public health. Dietary phytochemicals are promising options for the development of effective strategy for the prevention of photodamaging effects of UV radiation including the risk of skin cancer. Grape seed proanthocyanidins (GSPs) are such phytochemicals. Dietary administration of GSPs with AIN76A control diet significantly inhibits UV-induced skin tumor development as well as suppression of immune system. UV-induced suppression of immune system is commonly determined using contact hypersensitivity (CHS) model which is a prototype of T-cell-mediated immune response. We present evidence that inhibition of UV-induced suppression of immune system by GSPs is mediated through: (i) the alterations in immunoregulatory cytokines, interleukin (IL)-10 and IL-12, (ii) DNA repair, (iii) stimulation of effector T cells and (iv) DNA repair-dependent functional activation of dendritic cells in mouse model. These information have important implications for the use of GSPs as a dietary supplement in chemoprevention of UV-induced immunosuppression as well as photocarcinogenesis. C1 [Katiyar, Santosh K.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama Birmingham, Nutr Obes Res Ctr, Birmingham, AL USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU National Cancer Institute/NCCAM/NIH [CA140197, CA140832]; Veterans Administration Merit Review Award FX The work reported from Dr. Katiyar's laboratory was supported by the funds from National Cancer Institute/NCCAM/NIH (CA140197, CA140832) and Veterans Administration Merit Review Award (S.K.K.). The content of this article does not necessarily reflect the views or policies of the funding agencies. NR 55 TC 1 Z9 1 U1 5 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0031-8655 EI 1751-1097 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JAN-FEB PY 2015 VL 91 IS 1 BP 156 EP 162 DI 10.1111/php.12330 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AZ8CN UT WOS:000348442600019 PM 25112437 ER PT J AU Nasti, TH Timares, L AF Nasti, Tahseen H. Timares, Laura TI MC1R, Eumelanin and Pheomelanin: Their Role in Determining the Susceptibility to Skin Cancer SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Review ID MELANOCYTE-STIMULATING HORMONE; MOUSE EPIDERMAL MELANOCYTES; T-CELL-ACTIVATION; NF-KAPPA-B; HUMAN MELANOCORTIN-1 RECEPTOR; FIBROBLAST-GROWTH-FACTOR; ALPHA-MSH; RED HAIR; TRANSCRIPTION FACTOR; 1,25-DIHYDROXYVITAMIN D-3 AB Skin pigmentation is due to the accumulation of two types of melanin granules in the keratinocytes. Besides being the most potent blocker of ultraviolet radiation, the role of melanin in photoprotection is complex. This is because one type of melanin called eumelanin is UV absorbent, whereas the other, pheomelanin, is photounstable and may even promote carcinogenesis. Skin hyperpigmentation may be caused by stress or exposure to sunlight, which stimulates the release of -melanocyte stimulating hormone (-MSH) from damaged keratinocytes. Melanocortin 1 receptor (MC1R) is a key signaling molecule on melanocytes that responds to -MSH by inducing expression of enzymes responsible for eumelanin synthesis. Persons with red hair have mutations in the MC1R causing its inactivation; this leads to a paucity of eumelanin production and makes red-heads more susceptible to skin cancer. Apart from its effects on melanin production, the -MSH/MC1R signaling is also a potent anti-inflammatory pathway and has been shown to promote antimelanoma immunity. This review will focus on the role of MC1R in terms of its regulation of melanogenesis and influence on the immune system with respect to skin cancer susceptibility. C1 [Nasti, Tahseen H.; Timares, Laura] Univ Alabama Birmingham, Dept Dermatol, Sch Med, Birmingham, AL 35294 USA. [Timares, Laura] Univ Alabama Birmingham, Skin Dis Res Ctr, Sch Med, Birmingham, AL USA. [Timares, Laura] Birmingham VA Med Ctr, Birmingham, AL USA. RP Timares, L (reprint author), Univ Alabama Birmingham, Dept Dermatol, Sch Med, Birmingham, AL 35294 USA. EM timares@uab.edu FU VA Merit Award from NIAMS; UAB Skin Diseases Research Center award from NIAMS FX The authors extend their thanks to Dr. Craig Elmets for his constant support and intellectual guidance for our research-most recently on the regulation of melanoma initiation and progression by immune factors. It was he who pointed out that the increased susceptibility to melanoma development in C3H mouse strains mimics one of the most important risk factors for humans, specifically blond and red hair color-which was the inspiration for this review article. This work was supported by funding from a VA Merit Award and The UAB Skin Diseases Research Center award from NIAMS. NR 133 TC 8 Z9 9 U1 4 U2 27 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0031-8655 EI 1751-1097 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JAN-FEB PY 2015 VL 91 IS 1 BP 188 EP 200 DI 10.1111/php.12335 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AZ8CN UT WOS:000348442600022 PM 25155575 ER PT J AU Li, H Prasad, R Katiyar, SK Yusuf, N Elmets, CA Xu, H AF Li, Hui Prasad, Ram Katiyar, Santosh K. Yusuf, Nabiha Elmets, Craig A. Xu, Hui TI Interleukin-17 Mediated Inflammatory Responses Are Required for Ultraviolet Radiation-Induced Immune Suppression SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID CONTACT HYPERSENSITIVITY RESPONSES; POLYMORPHIC LIGHT ERUPTION; CD8(+) T-CELLS; INDUCED IMMUNOSUPPRESSION; LANGERHANS CELLS; UV-RADIATION; SKIN-CANCER; IN-VIVO; SYSTEMIC IMMUNOSUPPRESSION; TUMOR-DEVELOPMENT AB Ultraviolet radiation (UVR) induces immunosuppression and is a major factor for development of skin cancer. Numerous efforts have been made to determine mechanisms for UVR-induced immunosuppression and to develop strategies for prevention and treatment of UVR-induced cancers. In the current study, we use IL-17 receptor (IL-17R) deficient mice to examine whether IL-17 mediated responses have a role in UVB (290-320)-induced immunosuppression of contact hypersensitivity responses. Results demonstrate that IL-17 mediated responses are required for UVB-induced immunosuppression of contact hypersensitivity responses. The systemic immune suppression and development of regulatory T cells are inhibited in UVB-treated IL-17R deficient mice compared to wild-type animals. The deficiency in IL-17R inhibits the infiltration and development of a tolerogenic myeloid cell population in UVB-treated skin, which expresses CD11b and Gr-1 and produces reactive oxygen species. We speculate that the development of the tolerogenic myeloid cells is dependent on IL-17-induced chemokines and inflammatory mediators in UVB-treated skin. The inhibition of the tolerogenic myeloid cells may be attributed to the suppression of regulatory T cells in UVR-treated IL-17R(-/-) mice. The findings may be exploited to new strategies for prevention and treatment of UVR-induced skin diseases and cancers. C1 [Li, Hui; Prasad, Ram; Katiyar, Santosh K.; Yusuf, Nabiha; Elmets, Craig A.; Xu, Hui] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.; Yusuf, Nabiha; Elmets, Craig A.; Xu, Hui] Univ Alabama Birmingham, Skin Dis Res Ctr, Birmingham, AL USA. [Katiyar, Santosh K.; Yusuf, Nabiha; Elmets, Craig A.; Xu, Hui] Birmingham VA Med Ctr, Birmingham, AL USA. RP Xu, H (reprint author), Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. EM xuhui@uabmc.edu FU VA Merit Review [18-103-02]; [R01CA140197]; [P30 AR050948]; [P30 CA013148] FX This study was supported by R01CA140197, P30 AR050948, P30 CA013148, and by VA Merit Review18-103-02. NR 68 TC 3 Z9 3 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0031-8655 EI 1751-1097 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JAN-FEB PY 2015 VL 91 IS 1 BP 235 EP 241 DI 10.1111/php.12351 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AZ8CN UT WOS:000348442600027 PM 25250896 ER PT J AU Lovejoy, T Heckman, T Sikkema, K Hansen, N Kochman, A AF Lovejoy, Travis I. Heckman, Timothy G. Sikkema, Kathleen J. Hansen, Nathan B. Kochman, Arlene TI Changes in Sexual Behavior of HIV-Infected Older Adults Enrolled in a Clinical Trial of Standalone Group Psychotherapies Targeting Depression SO AIDS AND BEHAVIOR LA English DT Article DE HIV/AIDS; Aging; Depression; Clinical trial; Unprotected sex ID RANDOMIZED CONTROLLED-TRIAL; IMPROVEMENT GROUP INTERVENTION; SECONDARY PREVENTION; RISK BEHAVIORS; MEN; HIV/AIDS; AGE AB By 2015, one-half of all HIV-positive persons in the U.S. will be 50-plus years of age, and as many as 30 % of older adults living with HIV/AIDS continue to engage in unprotected sexual intercourse. Contemporary positive prevention models often include mental health treatment as a key component of HIV prevention interventions. This secondary data analysis characterized longitudinal patterns of sexual behavior in HIV-positive older adults enrolled in a randomized controlled trial of group mental health interventions and assessed the efficacy of psychosocial treatments that targeted depression to reduce sexual risk behavior. Participants were 295 HIV-positive adults a parts per thousand yen50 years of age experiencing mild to severe depressive symptoms, randomized to one of three study conditions: a 12-session coping improvement group intervention, a 12-session interpersonal support group intervention, or individual therapy upon request. Approximately one-fifth of participants reported one or more occasions of unprotected anal or vaginal intercourse with HIV-negative sexual partners or persons of unknown HIV serostatus over the study period. Changes in sexual behavior did not vary by intervention condition, indicating that standalone treatments that target and reduce depression may be insufficient to reduce sexual risk behavior in depressed HIV-positive older adults. C1 [Lovejoy, Travis I.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Lovejoy, Travis I.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR 97239 USA. [Heckman, Timothy G.; Hansen, Nathan B.] Univ Georgia, Coll Publ Hlth, Athens, GA 30602 USA. [Sikkema, Kathleen J.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA. RP Lovejoy, T (reprint author), Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM travis.lovejoy@va.gov RI Hansen, Nathan/F-2074-2016 FU NIMH NIH HHS [R01 MH067566, R01 MH067568, R01-MH067568] NR 29 TC 3 Z9 3 U1 1 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD JAN PY 2015 VL 19 IS 1 BP 1 EP 8 DI 10.1007/s10461-014-0746-7 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA AZ6OT UT WOS:000348339500001 PM 24668254 ER PT J AU Rinker, JR Salter, AR Walker, H Amara, A Meador, W Cutter, GR AF Rinker, John R., II Salter, Amber R. Walker, Harrison Amara, Amy Meador, William Cutter, Gary R. TI Prevalence and characteristics of tremor in the NARCOMS multiple sclerosis registry: a cross-sectional survey SO BMJ OPEN LA English DT Article ID ADULT MOVEMENT-DISORDER; POPULATION; DISABILITY; VALIDATION; COMMON AB Objectives: (1) To describe the prevalence and severity of tremor in patients with multiple sclerosis (MS) registered within a large North American MS registry; (2) to provide detailed descriptions on the characteristics and severity of tremor in a subset of registrants and (3) to compare several measures of tremor severity for strength of agreement. Setting: The North American Research Committee on MS (NARCOMS) registry. Participants: Registrants of NARCOMS reporting mild or greater tremor severity. Outcome measures: We determined the cross-sectional prevalence of tremor in the NARCOMS registry over three semiannual updates between fall 2010 and fall 2011. A subset of registrants (n=552) completed a supplemental survey providing detailed descriptions of their tremor. Outcomes included descriptive characteristics of their tremors and correlations between outcome measures to determine the strength of agreement in assessing tremor severity. Results: The estimated prevalence of tremor in NARCOMS ranged from 45% to 46.8%, with severe tremor affecting 5.5-5.9% of respondents. In the subset completing the supplemental survey, mild tremor severity was associated with younger age of MS diagnosis and tremor onset than those with moderate or severe tremor. However, tremor severity did not differ by duration of disease or tremor. Respondents provided descriptions of tremor symptoms on the Clinical Ataxia Rating Scale, which had a moderate to good (rho=0.595) correlation with the Tremor Related Activities of Daily Living (TRADL) scale. Objectively scored Archimedes' spirals had a weaker (rho=0.358) correlation with the TRADL. Rates of unemployment, disability and symptomatic medication use increased with tremor severity, but were high even among those with mild tremor. Conclusions: Tremor is common among NARCOMS registrants and severely disabling for some. Both ADL-based and symptom-descriptive measures of tremor severity can be used to stratify patients. C1 [Rinker, John R., II; Walker, Harrison; Amara, Amy; Meador, William] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Rinker, John R., II] Birmingham VA Med Ctr, Birmingham, AL USA. [Salter, Amber R.; Cutter, Gary R.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA. RP Rinker, JR (reprint author), Univ Alabama Birmingham, Dept Neurol, UAB Stn, Birmingham, AL 35294 USA. EM rinkerj@uab.edu OI Amara, Amy/0000-0003-0762-9656 FU Biogen Idec [US-TYS-11-10238]; National Institutes of Health/National Institutes of Neurological Disorders and Stroke; [K23NS067053]; [K23NS080912] FX This study was funded by an Investigator Initiated Grant/Trial Award from Biogen Idec (US-TYS-11-10238). HW and AA receive grant support from the National Institutes of Health/National Institutes of Neurological Disorders and Stroke. HW is supported by K23NS067053 and AA is supported by K23NS080912. NR 18 TC 3 Z9 3 U1 1 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2015 VL 5 IS 1 AR e006714 DI 10.1136/bmjopen-2014-006714 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AZ4DH UT WOS:000348171800041 PM 25573524 ER PT J AU Robinson, ES Feng, R Okawa, J Werth, VP AF Robinson, E. S. Feng, R. Okawa, J. Werth, V. P. TI Improvement in the cutaneous disease activity of patients with dermatomyositis is associated with a better quality of life SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID RHEUMATOID-ARTHRITIS; LUPUS-ERYTHEMATOSUS; SEVERITY INDEX; SKIN-DISEASE; VALIDITY; SMOKING; RESPONSIVENESS; RELIABILITY; INSTRUMENT; IMPACT AB BackgroundCutaneous dermatomyositis (DM) disease activity is associated with decreased quality of life. ObjectivesTo assess if an improvement in quality of life, as measured by the Skindex-29 and patient-reported itch and pain on a 10-point visual analogue scale (VAS), correlated with an improvement in cutaneous DM disease activity. MethodsPatients with a completed cutaneous DM disease area and severity index [Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)] at two visits separated by at least 2months were classified into responder (n=15) and nonresponder (n=30) groups according to the point change in the CDASI activity scores between visits. Responders had at least a four-point improvement in CDASI activity, indicating clinically relevant improvement. ResultsThe change from baseline to the follow-up visit of the Skindex-29 subscale scores for the responders vs. the nonresponders were significantly different for emotions (P<001), functioning (P<001) and symptoms (P<001). The change in VAS score between responders and nonresponders was also significant for itch (P=001) and pain (P=004). There was no significant difference between the groups in terms of disease subtype, sex, race, age, treatment for DM, smoking history or a history of malignancy within 5years of a diagnosis of DM. ConclusionsThis is the first study to demonstrate that the quality of life of patients with DM improved as their cutaneous disease activity decreased. C1 [Robinson, E. S.; Okawa, J.; Werth, V. P.] Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Robinson, E. S.; Okawa, J.; Werth, V. P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Feng, R.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU NIAMS NIH HHS [K24-AR 02207, K24 AR002207, R21 AR066286] NR 16 TC 4 Z9 5 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JAN PY 2015 VL 172 IS 1 BP 169 EP 174 DI 10.1111/bjd.13167 PG 6 WC Dermatology SC Dermatology GA AY7FK UT WOS:000347726500026 PM 24909747 ER PT J AU Drye, BD Drye, EE AF Drye, Barbara D. Drye, Elizabeth E. TI Older Patients With Cardiac Devices The Need for Better Patient-Doctor Conversations SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Editorial Material DE communication; defibrilators, implantable; informed consent; patient care planning; patient preference C1 San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. RP Drye, EE (reprint author), Yale Univ, Sch Med, 1 Church St,Suite 200, New Haven, CT 06510 USA. EM Elizabeth.Drye@Yale.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2015 VL 8 IS 1 BP 112 EP 113 DI 10.1161/CIRCOUTCOMES.114.000916 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AZ3RT UT WOS:000348145100017 PM 25604558 ER PT J AU Jones, LG Sin, MK Hage, FG Kheirbek, RE Morgan, CJ Zile, MR Wu, WC Deedwania, P Fonarow, GC Aronow, WS Prabhu, SD Fletcher, RD Ahmed, A Allman, RM AF Jones, Linda G. Sin, Mo-Kyung Hage, Fadi G. Kheirbek, Raya E. Morgan, Charity J. Zile, Michael R. Wu, Wen-Chih Deedwania, Prakash Fonarow, Gregg C. Aronow, Wilbert S. Prabhu, Sumanth D. Fletcher, Ross D. Ahmed, Ali Allman, Richard M. TI Characteristics and Outcomes of Patients With Advanced Chronic Systolic Heart Failure Receiving Care at the Veterans Affairs Versus Other Hospitals Insights From the Beta-blocker Evaluation of Survival Trial (BEST) SO CIRCULATION-HEART FAILURE LA English DT Article DE hospitals; outcomes; systolic heart failure; veterans ID VENTRICULAR EJECTION FRACTION; VASODILATOR THERAPY; ATRIAL-FIBRILLATION; INCREASED MORTALITY; NATURAL-HISTORY; HEALTH; RACE; ASSOCIATION; AMIODARONE; BUCINDOLOL AB Background-Characteristics and outcomes of patients with heart failure and reduced ejection fraction receiving care at Veterans Affairs (VA) versus non-VA hospitals have not been previously reported. Methods and Results-In the randomized controlled Beta-blocker Evaluation of Survival Trial (BEST; 1995-1999), of the 2707 (bucindolol=1353; placebo=1354) patients with heart failure and left ventricular ejection fraction <= 35%, 918 received care at VA hospitals, of which 98% (n=898) were male. Of the 1789 receiving care at non-VA hospitals, 68% (n=1216) were male. Our analyses were restricted to these 2114 male patients. VA patients were older with higher symptom and comorbidity burdens. There was no significant between-group difference in unadjusted primary end point of 2-year all-cause mortality (35% VA versus 32% non-VA; hazard ratio associated with VA hospitals, 1.09; 95% confidence interval, 0.94-1.26), which remained unchanged after adjustment for age and race (hazard ratio, 1.00; 95% confidence interval, 0.86-1.16) or multivariable adjustment, including cardiovascular morbidities (hazard ratio, 0.94; 95% confidence interval, 0.80-1.10). There was no between-group difference in cause-specific mortalities or hospitalizations. Chronic kidney disease, pulmonary edema, left ventricular ejection fraction <20%, and peripheral arterial disease were significant predictors of mortality for both groups. African America race, New York Heart Association class IV symptoms, atrial fibrillation, and right ventricular ejection fraction <20% were associated with higher mortality among non-VA hospital patients only; however, these differences from VA patients were not significant. Conclusions-Patients with heart failure and reduced ejection fraction receiving care at VA hospitals were older and sicker; yet their risk of mortality and hospitalization was similar to younger and healthier patients receiving care at non-VA hospitals. C1 [Jones, Linda G.; Hage, Fadi G.; Prabhu, Sumanth D.] Vet Affairs Med Ctr, Dept Med, Birmingham, AL USA. [Jones, Linda G.; Hage, Fadi G.; Prabhu, Sumanth D.] Univ Alabama Birmingham, Dept Med, Birmingham, AL USA. [Morgan, Charity J.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL USA. [Sin, Mo-Kyung] Seattle Univ, Coll Nursing, Dept Adult Hlth, Seattle, WA 98122 USA. [Kheirbek, Raya E.; Fletcher, Ross D.; Ahmed, Ali] Vet Affairs Med Ctr, Off Chief Staff, Washington, DC USA. [Zile, Michael R.] Ralph H Johnson Vet Affairs Med Ctr, Dept Med, Charleston, SC USA. [Zile, Michael R.] Med Univ S Carolina, Dept Med, Charleston, SC USA. [Wu, Wen-Chih] Vet Affairs Med Ctr, Dept Med, Providence, RI USA. [Wu, Wen-Chih] Brown Univ, Dept Med, Providence, RI 02912 USA. [Deedwania, Prakash] Univ Calif San Francisco, Dept Med, Fresno, CA USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Aronow, Wilbert S.] New York Med Coll, Dept Med, Valhalla, NY 10595 USA. [Allman, Richard M.] Dept Vet Affairs, Geriatr Serv, Washington, DC USA. [Allman, Richard M.] Dept Vet Affairs, Extended Care Serv, Washington, DC USA. RP Ahmed, A (reprint author), Washington DC VA Med Ctr, 50 Irving St NW, Washington, DC 20422 USA. EM aliahmedmdmph@gmail.com OI Hage, Fadi/0000-0002-1397-4942 FU National Heart, Lung, and Blood Institute (NHLBI), Bethesda, Maryland [R01-HL085561, R01-HL097047]; University of Alabama at Birmingham Comprehensive Cardiovascular Center, Birmingham, Alabama FX Dr Ahmed was in part supported by grants (R01-HL085561 and R01-HL097047) from the National Heart, Lung, and Blood Institute (NHLBI), Bethesda, Maryland, and an intramural support from the University of Alabama at Birmingham Comprehensive Cardiovascular Center, Birmingham, Alabama. NR 35 TC 3 Z9 3 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JAN PY 2015 VL 8 IS 1 BP 17 EP 24 DI 10.1161/CIRCHEARTFAILURE.114.001300 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AZ3RX UT WOS:000348145400004 PM 25480782 ER PT J AU Jotwani, V Scherzer, R Abraham, A Estrella, MM Bennett, M Cohen, MH Nowicki, M Sharma, A Young, M Tien, PC Ix, JH Sarnak, MJ Parikh, CR Shlipak, MG AF Jotwani, Vasantha Scherzer, Rebecca Abraham, Alison Estrella, Michelle M. Bennett, Michael Cohen, Mardge H. Nowicki, Marek Sharma, Anjali Young, Mary Tien, Phyllis C. Ix, Joachim H. Sarnak, Mark J. Parikh, Chirag R. Shlipak, Michael G. TI Association of Urine alpha 1-Microglobulin with Kidney Function Decline and Mortality in HIV-Infected Women SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE HIV nephropathy; CKD; proximal tubule ID SERUM CYSTATIN-C; IMMUNODEFICIENCY-VIRUS-INFECTION; ACUTE TUBULAR-NECROSIS; STAGE RENAL-DISEASE; ANTIRETROVIRAL THERAPY; INTERAGENCY HIV; PROXIMAL TUBULE; ESTIMATING GFR; TENOFOVIR; INJURY AB Background and objectivesDespite advances in therapy, HIV-infected individuals remain at higher risk for kidney dysfunction than uninfected individuals. It was hypothesized that urine levels of 1-microglobulin, a biomarker of proximal tubular dysfunction, would predict kidney function decline and mortality risk in HIV-infected and uninfected women.Design, setting, participants, & measurementsIn the Women's Interagency HIV Study, urine 1-microglobulin and creatinine concentrations were measured in 903 HIV-infected and 287 uninfected women using stored urine from 1999 to 2000, when prevalence of tenofovir use was <1%. Participants were categorized into three categories by level of 1-microglobulin-to-creatinine ratio, and associations with kidney decline and all-cause mortality over 8 years were evaluated.ResultsUrine 1-microglobulin was detectable in 60% of HIV-infected and 40% of uninfected women (P<0.001). Among HIV-infected women, there were 177 (22%), 61 (7%), and 128 (14%) patients with incident CKD, with 10% annual eGFR decline, and who died, respectively. Compared with HIV-infected women in the lowest 1-microglobulin category, HIV-infected women in the highest 1-microglobulin category had a 2.1-fold risk of incident CKD (95% confidence interval, 1.3 to 3.4), 2.7-fold risk of 10% annual eGFR decline (95% confidence interval, 1.2 to 5.9), and 1.6-fold mortality risk (95% confidence interval, 1.0 to 2.6) in models adjusting for kidney risk factors, baseline eGFR, and albuminuria. Among uninfected women, the highest 1-microglobulin category was associated with 3% (relative risk, 2.2; 95% confidence interval, 1.4 to 3.5) and 5% (relative risk, 2.2; 95% confidence interval, 1.1 to 4.3) annual eGFR decline relative to the lowest 1-microglobulin category.ConclusionsProximal tubular dysfunction, indicated by urine 1-microglobulin, was independently associated with kidney function decline in HIV-infected and uninfected women and mortality risk among HIV-infected women. C1 San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. RP Shlipak, MG (reprint author), San Francisco VA Med Ctr, Dept Med, 4150 Clement Street, San Francisco, CA 94121 USA. EM Michael.Shlipak@ucsf.edu FU National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Cancer Institute; National Institute on Drug Abuse; National Institute on Mental Health; National Institute of Dental and Craniofacial Research; National Institute on Alcohol Abuse and Alcoholism; National Institute on Deafness and Other Communication Disorders; National Institutes of Health (NIH) Office of Research on Women's Health; [1 R01 AG034853-01A2]; [1K23-DK-081317]; [U01-AI-103401]; [U01-AI-103408]; [U01-AI-035004]; [U01-AI-031834]; [U01-AI-034993]; [U01-AI-034994]; [U01-AI-103397]; [U01-AI-103390]; [U01-AI-034989]; [U01-AI-042590]; [U01-HD-032632]; [UL1-TR000004]; [UL1-TR000454] FX The WIHS Kidney Aging Study is funded by Grant 1 R01 AG034853-01A2 (Principal Investigator: M.G.S.), which was administered by the Northern California Institute for Research and Education with resources of the Veterans Affairs Medical Center (San Francisco, California). M.M.E. is supported by Grant 1K23-DK-081317. Data in this manuscript were collected by the Women's Interagency HIV Study (WIHS). WIHS (Principal Investigators): UAB-MS WIHS (Michael Saag, Mirjam-Colette Kempf, and Deborah Konkle-Parker), Grant U01-AI-103401; Atlanta WIHS (Ighovwerha Ofotokun and Gina Wingood), Grant U01-AI-103408; Bronx WIHS (Kathryn Anastos), Grant U01-AI-035004; Brooklyn WIHS (Howard Minkoff and Deborah Gustafson), Grant U01-AI-031834; Chicago WIHS (M.H.C.), Grant U01-AI-034993; Metropolitan Washington WIHS (M.Y.), Grant U01-AI-034994; Miami WIHS (Margaret Fischl and Lisa Metsch), Grant U01-AI-103397; UNC WIHS (Adaora Adimora), Grant U01-AI-103390; Connie Wofsy Women's HIV Study, northern California (Ruth Greenblatt, Bradley Aouizerat, and Phyllis Tien), Grant U01-AI-034989; WIHS Data Management and Analysis Center (Stephen Gange and Elizabeth Golub), Grant U01-AI-042590; and Southern California WIHS (Alexandra Levine and M.N.), Grant U01-HD-032632 (WIHS I to WIHS IV). The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases, with additional cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Mental Health. Targeted supplemental funding for specific projects is also provided by the National Institute of Dental and Craniofacial Research, the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Deafness and Other Communication Disorders, and the National Institutes of Health (NIH) Office of Research on Women's Health. WIHS data collection is also supported by Grants UL1-TR000004 (to UCSF CTSA) and UL1-TR000454 (to Atlanta CTSA). NR 41 TC 9 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 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JAN PY 2015 VL 10 IS 1 BP 63 EP 73 DI 10.2215/CJN.03220314 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA AY7BS UT WOS:000347716900011 PM 25370597 ER PT J AU Alge, JL Arthur, JM AF Alge, Joseph L. Arthur, John M. TI Biomarkers of AKI: A Review of Mechanistic Relevance and Potential Therapeutic Implications SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review DE acute renal failure; pathophysiology of renal disease and progression; renin-angiotensin system ID ACUTE KIDNEY INJURY; ACID-BINDING PROTEIN; ACUTE-RENAL-FAILURE; GELATINASE-ASSOCIATED LIPOCALIN; ISCHEMIA-REPERFUSION INJURY; EARLY URINARY BIOMARKER; ADULT CARDIAC-SURGERY; INTENSIVE-CARE-UNIT; CHAIN FATTY-ACID; GROWTH-FACTOR-I AB AKI is a common clinical condition associated with a number of adverse outcomes. More timely diagnosis would allow for earlier intervention and could improve patient outcomes. The goal of early identification of AKI has been the primary impetus for AKI biomarker research, and has led to the discovery of numerous novel biomarkers. However, in addition to facilitating more timely intervention, AKI biomarkers can provide valuable insight into the molecular mechanisms of this complex and heterogeneous disease. Furthermore, AKI biomarkers could also function as molecular phenotyping tools that could be used to direct clinical intervention. This review highlights the major studies that have characterized the diagnostic and prognostic predictive power of these biomarkers. The mechanistic relevance of neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, IL-18, liver-type fatty acid-binding protein, angiotensinogen, tissue inhibitor of metalloproteinase-2, and IGF-binding protein 7 to the pathogenesis and pathobiology of AKI is discussed, putting these biomarkers in the context of the progressive phases of AKI. A biomarker-integrated model of AKI is proposed, which summarizes the current state of knowledge regarding the roles of these biomarkers and the molecular and cellular biology of AKI. C1 [Alge, Joseph L.; Arthur, John M.] Med Univ S Carolina, Div Nephrol, Charleston, SC 29425 USA. [Arthur, John M.] Ralph H Johnson Vet Affairs Med Ctr, Med Serv, Charleston, SC USA. RP Arthur, JM (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 96 Jonathan Lucas Street,MSC 629, Charleston, SC 29425 USA. EM arthurj@musc.edu OI Alge, Joseph/0000-0002-2491-1066 FU Department of Veterans Affairs; National Institutes of Health [R01-DK080234] FX This manuscript was supported by the Department of Veterans Affairs and National Institutes of Health Grant R01-DK080234. NR 86 TC 38 Z9 40 U1 1 U2 16 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JAN PY 2015 VL 10 IS 1 BP 147 EP 155 DI 10.2215/CJN.12191213 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA AY7BS UT WOS:000347716900020 PM 25092601 ER PT J AU Metra, M Mentz, RJ Chiswell, K Bloomfield, DM Cleland, JGF Cotter, G Davison, BA Dittrich, HC Fiuzat, M Givertz, MM Lazzarini, V Mansoor, GA Massie, BM Ponikowski, P Teerlink, JR Voors, AA O'Connor, CM AF Metra, Marco Mentz, Robert J. Chiswell, Karen Bloomfield, Daniel M. Cleland, John G. F. Cotter, Gad Davison, Beth A. Dittrich, Howard C. Fiuzat, Mona Givertz, Michael M. Lazzarini, Valentina Mansoor, George A. Massie, Barry M. Ponikowski, Piotr Teerlink, John R. Voors, Adriaan A. O'Connor, Christopher M. TI Acute heart failure in elderly patients: worse outcomes and differential utility of standard prognostic variables. Insights from the PROTECT trial SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Age; Elderly; Acute heart failure; Blood pressure ID CLINICAL CHARACTERISTICS; EJECTION FRACTION; PULSE PRESSURE; TASK-FORCE; RISK; ASSOCIATION; AGE; ROLOFYLLINE; PREVALENCE; ANTAGONIST AB AimsPrevious heart failure (HF) trials suggested that age influences patient characteristics and outcome; however, under-representation of elderly patients has limited characterization of this cohort. Whether standard prognostic variables have differential utility in various age groups is unclear. Methods and resultsThe PROTECT trial investigated 2033 patients (median age 72 years) with acute HF randomized to rolofylline or placebo. Patients were divided into five groups based on the quintiles of age: 59, 60-68, 69-74, 75-79, and 80years. Baseline characteristics, medications, and outcomes (30-day death or cardiovascular/renal hospitalization, and death at 30 and 180 days) were explored. The prognostic utility of baseline characteristics for outcomes was investigated in the different groups and in those aged <80years vs. 80years. With increasing age, patients were more likely to be women with hypertension, AF, and higher EF. Increased age was associated with increased risk of 30- and 180-day outcomes, which persisted after multivariable adjustment (hazard ratio for 180-day death=1.17; 95% confidence interval 1.11-1.24 for each 5-year increase). The prognostic utility of baseline characteristics such as previous HF hospitalization and serum sodium, systolic blood pressure, and NYHA class was attenuated in the elderly for the endpoint of 180-day mortality. An increase in albumin was associated with a greater reduction in risk in patients aged 80years vs. <80years. ConclusionsIn a large trial of acute HF, there were differences in baseline characteristics and outcomes amongst patients of different ages. Standard prognostic variables exhibit different utility in elderly patients. C1 [Metra, Marco; Lazzarini, Valentina] Univ Brescia, Dept Med & Surg Specialties, Brescia, Italy. [Mentz, Robert J.; Fiuzat, Mona; O'Connor, Christopher M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Div Cardiovasc Med, Durham, NC USA. [Chiswell, Karen] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Bloomfield, Daniel M.; Mansoor, George A.] Merck Res Labs, Rahway, NJ USA. [Cleland, John G. F.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Royal Brompton Hosp, Kingston Upon Hull, Yorks, England. [Cleland, John G. F.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Harefield Hosp, Kingston Upon Hull, Yorks, England. [Cleland, John G. F.] Univ Hull, Dept Cardiol, Castle Hill Hosp, Kingston Upon Hull, Yorks, England. [Cotter, Gad; Davison, Beth A.] Momentum Res Inc, Durham, NC USA. [Dittrich, Howard C.] Univ Iowa, Carver Coll Med Cardiovasc Res Ctr, Iowa City, IA USA. [Givertz, Michael M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Massie, Barry M.; Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Massie, Barry M.; Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Ponikowski, Piotr] Med Univ, Mil Hosp, Wroclaw, Poland. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. RP Metra, M (reprint author), Spedali Civil Brescia, Piazza Spedali Civili 1, I-25123 Brescia, Italy. EM metramarco@libero.it RI Ponikowski, Piotr/O-6454-2015 OI Ponikowski, Piotr/0000-0002-3391-7064; Cleland, John/0000-0002-1471-7016; Metra, Marco/0000-0001-6691-8568 FU National Institute of General Medical Sciences [5-T32GM086330] FX R.J.M. is supported by grant no. 5-T32GM086330 from the National Institute of General Medical Sciences. NR 23 TC 15 Z9 15 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD JAN PY 2015 VL 17 IS 1 BP 109 EP 118 DI 10.1002/ejhf.207 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AZ2IU UT WOS:000348058300014 PM 25431336 ER PT J AU Littman, AJ Damschroder, LJ Verchinina, L Lai, ZS Kim, HM Hoerster, KD Klingaman, EA Goldberg, RW Owen, RR Goodrich, DE AF Littman, Alyson J. Damschroder, Laura J. Verchinina, Lilia Lai, Zongshan Kim, Hyungjin Myra Hoerster, Katherine D. Klingaman, Elizabeth A. Goldberg, Richard W. Owen, Richard R. Goodrich, David E. TI National evaluation of obesity screening and treatment among veterans with and without mental health disorders SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Obesity; Weight management; Veterans; Serious mental illness; Depressive disorder ID WEIGHT-MANAGEMENT PROGRAM; LIFE-STYLE INTERVENTION; UNITED-STATES; CARDIOVASCULAR RISK; METABOLIC SYNDROME; ANXIETY DISORDERS; CONTROLLED-TRIAL; PRIMARY-CARE; ILLNESS; ADULTS AB Objective: The objective was to determine whether obesity screening and weight management program participation and outcomes are equitable for individuals with serious mental illness (SMI) and depressive disorder (DD) compared to those without SMI/DD in Veterans Health Administration (VHA), the largest integrated US health system, which requires obesity screening and offers weight management to all in need. Methods: We used chart-reviewed, clinical and administrative VHA data from fiscal years 2010-2012 to estimate obesity screening and participation in the VHA's weight management program (MOVE!) across groups. Six-and 12-month weight changes in MOVE! participants were estimated using linear mixed models adjusted for confounders. Results: Compared to individuals without SMI/DD, individuals with SMI or DD were less frequently screened for obesity (94%-94.7% vs. 95.7%) but had greater participation in MOVE! (10.1%-10.4% vs. 7.4%). MOVE! participants with SMI or DD lost approximately 1 lb less at 6 months. At 12 months, average weight loss for individuals with SMI or neither SMI/DD was comparable (-3.5 and -3.3 lb, respectively), but individuals with DD lost less weight (mean=-2.7 lb). Conclusions: Disparities in obesity screening and treatment outcomes across mental health diagnosis groups were modest. However, participation in MOVE! was low for every group, which limits population impact. Published by Elsevier Inc. C1 [Littman, Alyson J.] VA Puget Sound Healthcare Syst, Seattle Div Epidemiol Res & Informat Ctr ERIC, Seattle, WA 98108 USA. [Littman, Alyson J.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Damschroder, Laura J.; Verchinina, Lilia; Lai, Zongshan; Kim, Hyungjin Myra; Goodrich, David E.] VA Ann Arbor Healthcare Syst, CCMR, Ann Arbor, MI 48105 USA. [Lai, Zongshan; Goodrich, David E.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI 48109 USA. [Kim, Hyungjin Myra] Univ Michigan, Ctr Stat Consultat & Res, Ann Arbor, MI 48109 USA. [Hoerster, Katherine D.] VA Puget Sound Healthcare Syst, Seattle Div Mental Hlth Serv, Seattle, WA 98108 USA. [Hoerster, Katherine D.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Klingaman, Elizabeth A.; Goldberg, Richard W.] VA Capitol Hlth Care Network, Mental Illness Res Educ & Clin Ctr, Baltimore, MD USA. [Owen, Richard R.] Cent Arkansas Vet Healthcare Syst, Ctr Mental Healthcare & Outcomes Res, Little Rock, AR USA. [Owen, Richard R.] Univ Arkansas Med Sci, Coll Med, Dept Psychiat, Little Rock, AR 72205 USA. [Klingaman, Elizabeth A.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. RP Littman, AJ (reprint author), VA Puget Sound Healthcare Syst, Seattle Epidemiol Res & Informat Ctr ERIC, 1660 South Columbia Way,S-152-E, Seattle, WA 98108 USA. EM Alyson.littman@va.gov; Laura.damschroder@va.gov; Lilia.verchinina@va.gov; Zongshan.Lai@va.gov; Myrakim@umich.edu; Katherine.hoerster@va.gov; Elizabeth.klingaman@va.gov; Richard.goldberg@va.gov; Richard.Owen2@va.gov; David.goodrich2@va.gov OI Damschroder, Laura/0000-0002-3657-8459; Goodrich, David/0000-0003-3232-2189 FU VHA Center for Health Promotion & Disease Prevention (NCP); VA Health Services Research and Development Quality Enhancement Research Initiative (QUERI) [QLP 55-017]; Rehabilitation R&D Career Development Award [6982] FX This study was funded by was initiated at the request of the VHA Center for Health Promotion & Disease Prevention (NCP). Funding was provided by VA Health Services Research and Development Quality Enhancement Research Initiative (QUERI) programs for Diabetes and Mental Health research as a locally initiated project (QLP 55-017). Dr. Littman's time was supported by a Rehabilitation R&D Career Development Award (#6982). The authors would like to acknowledge the support of Dr. Amy M. Kilbourne, Dr. Kenneth J. Jones, Dr. Caroline R. Richardson and Ms. Trang Lance in this work. The views expressed in this article are those of the authors and do not necessarily represent the views of the Veterans Administration. NR 59 TC 11 Z9 11 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JAN-FEB PY 2015 VL 37 IS 1 BP 7 EP 13 DI 10.1016/j.genhosppsych.2014.11.005 PG 7 WC Psychiatry SC Psychiatry GA AZ2CQ UT WOS:000348042700005 PM 25500194 ER PT J AU Iyer, SP Young, AS AF Iyer, Sharat P. Young, Alexander S. TI Health screening, counseling, and hypertension control for people with serious mental illness at primary care visits SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Primary care; Serious mental illness; Health screening; Health counseling; Hypertension ID MEDICAL-CARE; SCHIZOPHRENIA; MORTALITY; COHORT; OUTPATIENTS; DISORDERS; BARRIERS; RECEIPT; STATE AB Objective: This study sought to determine if primary care visits for people with serious mental illness (SMI) demonstrate different rates of basic physical health services compared to others, and to determine factors associated with differing rates of these measures in people with SMI. Method: The study used 2005-2010 visit-level primary care data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. The provision of health counseling, receipt of any diagnostic or screening test, measurement of blood pressure or weight and evidence of hypertension control were assessed, adjusting for identified patient, provider and visit-level factors. Results: After adjustment for covariates, we found no significant differences between visits for people with SMI and those without for any outcome. Probability of blood pressure measurement and diagnostic or screening testing significantly increased over time. Conclusion: The lack of significant differences found here might be due to adjustment for covariates, a focus only on primary care visits, the use of visit-level data or evolution over time. Mortality differences for people with SMI may be attributable to those not receiving primary care, self-management of disease or subsets of the population requiring targeted interventions. Published by Elsevier Inc. C1 [Iyer, Sharat P.] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN3, Bronx, NY 10468 USA. [Iyer, Sharat P.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Young, Alexander S.] West Los Angeles VA Med Ctr, Desert Pacific Mental Illness Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Young, Alexander S.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Iyer, SP (reprint author), VA Med Ctr MIRECC OOMH, 130 W Kingsbridge Rd,Room 6A-44, Bronx, NY 10468 USA. EM sharu.p@mssm.edu; ayoung@ucla.edu RI Young, Alexander/A-1523-2009 OI Young, Alexander/0000-0002-9367-9213 FU Robert Wood Johnson Foundation Clinical Scholars program; US Department of Veterans Affairs FX This material is the result of work supported with resources and the use of facilities at the James J. Peters VA Medical Center, Bronx, NY, and the West Los Angeles VA Medical Center, Los Angeles, CA. Additional support was provided by the Mount Sinai Conduits Institutes for Translational Sciences. Assistance for this article was provided by Kenneth Wells, M.D., M.P.H., and Lisa Dixon, M.D., M.P.H., who reviewed the manuscript and contributed to the discussion, and Alan Weinberg, M.S., who contributed to the analytic plan. Funding for Dr. Parameswaran was provided by the Robert Wood Johnson Foundation Clinical Scholars program and the US Department of Veterans Affairs. 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 24 TC 0 Z9 0 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JAN-FEB PY 2015 VL 37 IS 1 BP 60 EP 66 DI 10.1016/j.genhosppsych.2014.10.003 PG 7 WC Psychiatry SC Psychiatry GA AZ2CQ UT WOS:000348042700014 PM 25480463 ER PT J AU Scheuner, MT Peredo, J Benkendorf, J Bowdish, B Feldman, G Fleisher, L Mulvihill, JJ Watson, M Herman, GE Evans, J AF Scheuner, Maren T. Peredo, Jane Benkendorf, Judith Bowdish, Bruce Feldman, Gerald Fleisher, Lynn Mulvihill, John J. Watson, Michael Herman, Gail E. Evans, James TI Reporting genomic secondary findings: ACMG members weigh in SO GENETICS IN MEDICINE LA English DT Article DE incidental findings; informed consent; next-generation sequencing; return of results; secondary findings ID INCIDENTAL FINDINGS; GENETICS PROFESSIONALS; CLINICAL GENOME; RETURN; EXOME; PERSPECTIVES; VIEWS AB Purpose: The aim of this study was to survey American College of Medical Genetics and Genomics members about secondary findings from clinical genome-scale sequencing. Methods: A Web-based survey was mailed to 1,687 members of the American College of Medical Genetics and Genomics. Exploratory factor analysis identified underlying factors assessed by survey items. Linear regression assessed associations between factor scores and respondent characteristics. Results: The response rate was 29%. Four factors explained 51% of the survey variance: best practices, patient preferences, guidance, and informed consent. Most agreed with "best practice" items describing seeking and reporting of secondary findings as consistent with medical standards, having sufficient evidence, and, for adults, the benefits generally outweighing potential harms. There was lack of agreement regarding benefits versus harms for children and impact on health-care resources. The majority agreed that patient preferences should be considered, including ability to opt out, and that informed consent was feasible and critical. Characteristics significantly associated with factor scores included country of residence, sequencing experience, and years in practice. Conclusion: The American College of Medical Genetics and Genomics should update a list of genes to be assessed when clinical genome-scale sequencing is performed. Informed consent is necessary, and reporting of secondary findings should be optional. Research on implementation of secondary findings reporting is needed. C1 [Scheuner, Maren T.; Peredo, Jane] VA Greater Los Angeles Healthcare Syst, Dept Med, Div Med Genet, Los Angeles, CA 90073 USA. [Scheuner, Maren T.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Benkendorf, Judith; Bowdish, Bruce; Watson, Michael] Amer Coll Med Genet & Genom, Bethesda, MD USA. [Feldman, Gerald] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. [Feldman, Gerald] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. [Feldman, Gerald] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. [Fleisher, Lynn] Sidley & Austin, Chicago, IL USA. [Mulvihill, John J.] Univ Oklahoma, Dept Pediat, Oklahoma City, OK USA. [Herman, Gail E.] Ohio State Univ, Nationwide Childrens Res Inst, Columbus, OH 43210 USA. [Herman, Gail E.] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. [Evans, James] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Evans, James] Univ N Carolina, Dept Med, Chapel Hill, NC USA. RP Scheuner, MT (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, Div Med Genet, Los Angeles, CA 90073 USA. EM maren.scheuner@va.gov NR 19 TC 9 Z9 9 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD JAN PY 2015 VL 17 IS 1 BP 27 EP 35 DI 10.1038/gim.2014.165 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA AY7MT UT WOS:000347744900005 PM 25394173 ER PT J AU Sayegh, AI Washington, MC Johnson, RE Johnson-Rouse, T Freeman, C Harrison, A Lucas, J Shelby, M Fisher, B Willis, W Reeve, JJ AF Sayegh, Ayman I. Washington, Martha C. Johnson, Ruth E. Johnson-Rouse, Tanisha Freeman, Corren Harrison, Anna Lucas, Jennifer Shelby, Mandy Fisher, Brittley Willis, William Reeve, Joseph J., Jr. TI Celiac and the cranial mesenteric arteries supply gastrointestinal sites that regulate meal size and intermeal interval length via cholecystokinin-58 in male rats SO HORMONES AND BEHAVIOR LA English DT Article DE Cholecystokinin-58; Meal size; Intermeal interval; Celiac artery; Cranial mesenteric artery ID DORSAL VAGAL COMPLEX; REDUCE FOOD-INTAKE; MYENTERIC PLEXUS; INTESTINAL-MUCOSA; CCK1 RECEPTOR; CCK-58; SATIETY; SECRETION; TRACT; IMMUNOREACTIVITY AB The site(s) of action that control meal size and intermeal interval (IMI) length by cholecystokinin-58 (CCK-58), the only detectable endocrine form of CCK in the rat, are not known. To test the hypothesis that the gastrointestinal tract may contain such sites, we infused low doses of CCK-58 (0.01, 0.05, 0.15 and 0.25 nmol/kg) into the celiac artery (CA, supplying stomach and upper duodenum), the cranial mesenteric artery (CMA, supplying small and most of the large intestines), the femoral artery (FA, control) and the portal vein (PV, draining the gastrointestinal tract) prior to the onset of the dark cycle in freely fed male rats. We measured the first meal size (chow), second meal size, IMI and satiety ratio (SR, IMI/meal size). We found that (1) all doses of CCK-58 given in the CA and the highest dose given in the CMA reduced the first meal size, (2) all doses of CCK-58 given in the CA reduced the second meal size, (3) a CCK-58 dose of 0.15 nmol/kg given in the CA and 0.15 and 0.25 nmol/kg given in the CMA prolonged the IMI, (4) CCK-58.(0.05, 0.15, 0.25 nmol/kg) given in the CA and 0.25 nmol/kg given in the CMA increased the SR, and (5) CCK-58 given in the FA and PV had no effect on the meal size or intermeal interval. These results support our hypothesis that the gastrointestinal tract contains sites of action that regulate meal size and IMI length via CCK-58. The stomach and upper duodenum may contain sites regulating meal size, whereas the small intestine and part of the large intestine may contain sites regulating the IMI. Published by Elsevier Inc. C1 [Sayegh, Ayman I.; Washington, Martha C.; Johnson, Ruth E.; Johnson-Rouse, Tanisha; Freeman, Corren; Harrison, Anna; Lucas, Jennifer; Shelby, Mandy; Fisher, Brittley; Willis, William; Reeve, Joseph J., Jr.] Tuskegee Univ, Coll Vet Med, Dept Biomed Sci, Gastroenterol Lab, Tuskegee, AL 36088 USA. [Reeve, Joseph J., Jr.] Vet Adm Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Los Angeles, CA USA. [Reeve, Joseph J., Jr.] Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA USA. RP Sayegh, AI (reprint author), Tuskegee Univ, Coll Vet Med, Dept Biomed Sci, Gastroenterol Lab, Tuskegee, AL 36088 USA. EM sayeghai@mytu.tuskegee.edu FU NIH [5R01DK083449]; [1SC1DK094972-01A1] FX The research was supported by grant 1SC1DK094972-01A1 (AS) and NIH grant 5R01DK083449 (J.R.R, Jr.) NR 40 TC 8 Z9 8 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0018-506X EI 1095-6867 J9 HORM BEHAV JI Horm. Behav. PD JAN PY 2015 VL 67 BP 48 EP 53 DI 10.1016/j.yhbeh.2014.11.011 PG 6 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA AZ5GX UT WOS:000348249300006 PM 25479193 ER PT J AU Phipps, JE Vela, D Hoyt, T Halaney, DL Mancuso, JJ Buja, LM Asmis, R Milner, TE Feldman, MD AF Phipps, Jennifer E. Vela, Deborah Hoyt, Taylor Halaney, David L. Mancuso, J. Jacob Buja, L. Maximilian Asmis, Reto Milner, Thomas E. Feldman, Marc D. TI Macrophages and Intravascular OCT Bright Spots A Quantitative Study SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE intravascular optical; coherence tomography; macrophages; quantitative analysis bright spots ID OPTICAL COHERENCE TOMOGRAPHY; CORONARY PLAQUE CHARACTERISTICS; VULNERABLE PLAQUE; ATHEROSCLEROSIS; INFLAMMATION AB OBJECTIVES This study hypothesized that bright spots in intravascular optical coherence tomography (IVOCT) images may originate by colocalization of plaque materials of differing indexes of refraction. To quantitatively identify bright spots, we developed an algorithm that accounts for factors including tissue depth, distance from light source, and signal-to-noise ratio. We used this algorithm to perform a bright spot analysis of IVOCT images and compared these results with histological examination of matching tissue sections. BACKGROUND Bright spots are thought to represent macrophages in IVOCT images, and studies of alternative etiologies have not been reported. METHODS Fresh human coronary arteries (n = 14 from 10 hearts) were imaged with IVOCT in a mock catheterization Laboratory and then processed for histological analysis. The quantitative bright spot algorithm was applied to all images. RESULTS Results are reported for 1,599 IVOCT images co-registered with histology. Macrophages alone were responsible for only 23% of the bright spot-positive regions, although they were present in 57% of bright spot-positive regions (as determined by histology). Additional etiologies for bright spots included cellular fibrous tissue (8%), interfaces between calcium and fibrous tissue (10%), calcium and Lipids (5%), and fibrous cap and Lipid pool (3%). Additionally, we showed that Large pools of macrophages in CD68(+) histology sections corresponded to dark regions in comparative IVOCT images; this is due to the fact that a pool of lipid-rich macrophages will have the same index of refraction as a pool of Lipid and thus will not cause bright spots. CONCLUSIONS Bright spots in IVOCT images were correlated with a variety of plaque components that cause sharp changes in the index of refraction. Algorithms that incorporate these correlations may be developed to improve the identification of some types of vulnerable plaque and allow standardization of IVOCT image interpretation. (C) 2015 by the American College of Cardiology Foundation. C1 [Phipps, Jennifer E.; Hoyt, Taylor; Halaney, David L.; Mancuso, J. Jacob; Asmis, Reto; Feldman, Marc D.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Vela, Deborah; Buja, L. Maximilian] Texas Heart Inst, Houston, TX 77025 USA. [Halaney, David L.; Feldman, Marc D.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. [Milner, Thomas E.] Univ Texas Austin, Austin, TX 78712 USA. RP Feldman, MD (reprint author), Univ Texas Hlth Sci Ctr San Antonio, 7703 Floyd Curl Dr,MSC 7872, San Antonio, TX 78229 USA. EM feldmanm@uthscsa.edu OI Buja, Louis Maximilian/0000-0001-8386-7029; Halaney, David/0000-0003-4437-0516 FU Veterans Health Administration merit grant [I01 BX000397]; Clayton Foundation; Janey and Dolph Briscoe Division of Cardiology at the University of Texas Health Science Center [NIH T32 HL007446]; American Heart Association [13POST17080074]; Biomedical Engineering Advancement fund at the University of Texas at Austin FX This study was funded by the Veterans Health Administration merit grant I01 BX000397, Clayton Foundation, Janey and Dolph Briscoe Division of Cardiology at the University of Texas Health Science Center (NIH T32 HL007446), American Heart Association (13POST17080074), and the Biomedical Engineering Advancement fund at the University of Texas at Austin. The intravascular optical coherence tomography system used in this study was provided by Volcano Corporation. All authors have reported that they have no relationships relevant to the contents of this paper to disdose. NR 27 TC 24 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD JAN PY 2015 VL 8 IS 1 BP 63 EP 72 DI 10.1016/j.jcmg.2014.07.027 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AZ4GZ UT WOS:000348181000011 PM 25499133 ER PT J AU Ju, MH Ko, CY Hall, BL Bosk, CL Bilimoria, KY Wick, EC AF Ju, Mila H. Ko, Clifford Y. Hall, Bruce L. Bosk, Charles L. Bilimoria, Karl Y. Wick, Elizabeth C. TI A Comparison of 2 Surgical Site Infection Monitoring Systems SO JAMA SURGERY LA English DT Article ID CARE-ASSOCIATED INFECTIONS; ADMINISTRATIVE DATA; RISK ADJUSTMENT; NATIONAL-HEALTH; SAFETY NETWORK; SURVEILLANCE; HOSPITALS; COSTS; STATE AB IMPORTANCE Surgical site infection (SSI) has emerged as the leading publicly reported surgical outcome and is tied to payment determinations. Many hospitals monitor SSIs using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP), in addition to mandatory participation (for most states) in the Centers for Disease Control and Prevention's National Healthcare Safety Network (NHSN), which has resulted in duplication of effort and incongruent data. OBJECTIVE To identify discrepancies in the implementation of the NHSN and the ACS NSQIP at hospitals that may be affecting the respective SSI rates. DESIGN, SETTING, AND PARTICIPANTS A pilot sample of hospitals that participate in both the NHSN and the ACS NSQIP. INTERVENTIONS For each hospital, observed rates and risk-adjusted observed to expected ratios for year 2012 colon SSIs were collected from both programs. The implementation methods of both programs were identified, including telephone interviews with infection preventionists who collect data for the NHSN at each hospital. MAIN OUTCOMES AND MEASURES Collection methods and colon SSI rates for the NHSN at each hospital were compared with those of the ACS NSQIP. RESULTS Of 16 hospitals, 11 were teaching hospitals with at least 500 beds. The mean observed colon SSI rates were dissimilar between the 2 programs, 5.7%(range, 2.0%-14.5%) for the NHSN vs 13.5%(range, 4.6%-26.7%) for the ACS NSQIP. The mean difference between the NHSN and the ACS NSQIP was 8.3%(range, 1.6%-18.8%), with the ACS NSQIP rate always higher. The correlation between the observed to expected ratios for the 2 programs was nonsignificant (Pearson product moment correlation, rho = 0.4465; P =.08). The NHSN collection methods were dissimilar among interviewed hospitals. An SSI managed as an outpatient case would usually be missed under the current NHSN practices. CONCLUSIONS AND RELEVANCE Colon SSI rates from the NHSN and the ACS NSQIP cannot be used interchangeably to evaluate hospital performance and determine reimbursement. Hospitals should not use the ACS NSQIP colon SSI rates for the NHSN reports because that would likely result in the hospital being an outlier for performance. It is imperative to reconcile SSI monitoring, develop consistent definitions, and establish one reliable method. The current state hinders hospital improvement efforts by adding unnecessary confusion to the already complex arena of perioperative improvement. C1 [Ju, Mila H.; Ko, Clifford Y.; Hall, Bruce L.; Bilimoria, Karl Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Ju, Mila H.; Bilimoria, Karl Y.] Northwestern Univ, NW Mem Hosp, Feinberg Sch Med, Surg Outcomes & Qual Improvement Ctr,Dept Surg, Chicago, IL 60611 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Ko, Clifford Y.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Hall, Bruce L.] Washington Univ, Dept Surg, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Olin Business Sch, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Ctr Hlth Policy, St Louis, MO USA. [Hall, Bruce L.] St Louis Vet Affairs Med Ctr, St Louis, MO USA. [Hall, Bruce L.] BJC HealthCare, St Louis, MO USA. [Bosk, Charles L.] Univ Penn, Leonard Davis Inst Hlth Econ, Dept Sociol, Philadelphia, PA 19104 USA. [Bosk, Charles L.] Univ Penn, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. [Wick, Elizabeth C.] Johns Hopkins Univ, Dept Surg, Baltimore, MD 21287 USA. RP Wick, EC (reprint author), Johns Hopkins Univ, Dept Surg, 600 N Wolfe St,Blalock Room 658, Baltimore, MD 21287 USA. EM ewick1@jhmi.edu FU National Institutes of Health [5T32HL094293]; American College of Surgeons Clinical Scholars in Residence program FX Dr Ju reported receiving a stipend that is partially supported by grant 5T32HL094293 from the National Institutes of Health and the American College of Surgeons Clinical Scholars in Residence program. Dr Hall reported being a paid consultant for the American College of Surgeons. No other disclosures were reported. NR 23 TC 16 Z9 16 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD JAN PY 2015 VL 150 IS 1 BP 51 EP 57 DI 10.1001/jamasurg.2014.2891 PG 7 WC Surgery SC Surgery GA AZ5AO UT WOS:000348232900011 PM 25426765 ER PT J AU Rajab, HA Baker, NL Hunt, KJ Klein, R Cleary, PA Lachin, J Virella, G Lopes-Virella, MF AF Rajab, Hussein A. Baker, Nathaniel L. Hunt, Kelly J. Klein, Richard Cleary, Patricia A. Lachin, John Virella, Gabriel Lopes-Virella, Maria F. CA DCCT EDIC Grp Investigators TI The predictive role of markers of Inflammation and endothelial dysfunction on the course of diabetic retinopathy in type 1 diabetes SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE Type I diabetes; Diabetes complications; Retinopathy; Biomarkers; E-selectin; Plasminogen activator inhibitor type 1 ID INTERVAL-CENSORED DATA; COMPLICATIONS TRIAL; ADHESION MOLECULE-1; RETINAL LEUKOSTASIS; INSULIN-RESISTANCE; PROGRESSION; COAGULATION; MELLITUS; COHORT; RISK AB Aims: This study was undertaken to determine whether levels of inflammation and endothelial dysfunction biomarkers in serum samples collected at baseline in the Diabetes Control and Complications Trial (DCCT) cohort could predict the development of retinopathy. Methods: Levels of clotting/fibrinolysis, inflammation and endothelial dysfunction biomarkers were measured in 1391 subjects with type I diabetes to determine whether their levels predicted increased risk to develop or accelerate progression of retinopathy during 16 years of follow-up. Results: Using regression models adjusted for DCCf treatment group, duration of diabetes, baseline retinopathy scores, HbA1c and albumin excretion rate, the baseline levels of sE-selectin and PAI-1 (active) were significantly associated with increased risk of a 3-step progression in retinopathy score in the primary prevention cohort (PPC). After adjusting for additional covariates ACE/ARE and statin therapy), this association persisted. Levels of active and total PAI-1 in the same group were also significantly associated, after similar adjustments, with the time to progress to severe non-proliferative retinopathy during the followup period (54 and 29%, respectively of increased risk). No associations were observed in the secondary intervention cohort for any of the outcomes. Conclusions: High levels of sE-selectin and PAI-1 are associated with the development of retinopathy in patients with uncomplicated type I diabetes. Published by Elsevier Inc. C1 [Rajab, Hussein A.; Klein, Richard; Lopes-Virella, Maria F.] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. [Baker, Nathaniel L.; Hunt, Kelly J.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Klein, Richard; Lopes-Virella, Maria F.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Cleary, Patricia A.; Lachin, John] George Washington Univ, Ctr Biostat, Washington, DC USA. [Virella, Gabriel] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Lopes-Virella, MF (reprint author), 114 Doughty St, Charleston, SC 29425 USA. EM virellam@musc.edu OI Lachin, John/0000-0001-9838-2841 FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01-DK-081352]; Research Service of the Ralph H. Johnson Department of the Veterans Affairs Medical Center; Division of Diabetes, Endocrinology and Metabolic Diseases (NIDDK) of the National Institutes of Health; National Center for Research Resources; Genentech Inc.; NIDDK FX This work was supported by the grant R01-DK-081352 (M.F. L-V) funded by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and by the Research Service of the Ralph H. Johnson Department of the Veterans Affairs Medical Center. The DCCT/EDIC was sponsored through research contracts from the Division of Diabetes, Endocrinology and Metabolic Diseases (NIDDK) of the National Institutes of Health.; 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. NR 37 TC 5 Z9 5 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 EI 1873-460X J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD JAN-FEB PY 2015 VL 29 IS 1 BP 108 EP 114 DI 10.1016/j.jdiacomp.2014.08.004 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AZ5EY UT WOS:000348244400022 PM 25441222 ER PT J AU Cerulli, C Trabold, N Kothari, CL Dichter, ME Raimondi, C Lucas, J Cobus, A Rhodes, KV AF Cerulli, Catherine Trabold, Nicole Kothari, Catherine L. Dichter, Melissa E. Raimondi, Christina Lucas, Janine Cobus, Alex Rhodes, Karin V. TI In Our Voice: Survivors' Recommendations for Change SO JOURNAL OF FAMILY VIOLENCE LA English DT Article DE Intimate partner violence; Reform court procedures; Socio-ecological model ID INTIMATE PARTNER VIOLENCE; COORDINATED COMMUNITY RESPONSES; DOMESTIC VIOLENCE; PROTECTION ORDERS; HEALTH-CARE; INTERVENTION; ARREST; BATTERERS; SERVICES; ASSAULT AB Seven focus groups with a diverse group of intimate partner violence (IPV) survivors (n = 39) explored how to improve survivor satisfaction, empowerment, and safety related to their court-based experiences. These occurred in three jurisdictions which all supported community coordinated responses to IPV. This paper contributes to the literature by asking survivors about existing service gaps and how helping professionals might enhance court operations. Analysis was conducted using a framework approach based on the socio-ecological model. Findings suggest four areas worthy of improvement: Logistics, Emotional Enhancements, Society's Perception of IPV, and Court Procedures. The recommendations for change are neither expensive nor complicated; rather, modest changes may result in greater victim satisfaction with the courts. C1 [Cerulli, Catherine; Raimondi, Christina] Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA. [Trabold, Nicole] Univ Rochester, Med Ctr, Sch Nursing, Rochester, NY 14642 USA. [Kothari, Catherine L.] Michigan State Univ, Kalamazoo Ctr Med Studies, E Lansing, MI 48824 USA. [Dichter, Melissa E.] Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA. [Lucas, Janine] Alternat Battered Women Inc, Rochester, NY USA. [Rhodes, Karin V.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. RP Cerulli, C (reprint author), Univ Rochester, Med Ctr, Dept Psychiat, 300 Crittenden Blvd, Rochester, NY 14642 USA. EM Catherine_Cerulli@URMC.Rochester.edu NR 41 TC 1 Z9 1 U1 3 U2 12 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 EI 1573-2851 J9 J FAM VIOLENCE JI J. Fam. Violence PD JAN PY 2015 VL 30 IS 1 BP 75 EP 83 DI 10.1007/s10896-014-9657-7 PG 9 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA AZ2GC UT WOS:000348051500007 ER PT J AU Gutierrez, JC Terwiesch, C Pelak, M Pettit, AR Marcus, SC AF Gutierrez, Jennifer C. Terwiesch, Christian Pelak, Mary Pettit, Amy R. Marcus, Steven C. TI Characterizing Primary Care Visit Activities at Veterans Health Administration Clinics SO JOURNAL OF HEALTHCARE MANAGEMENT LA English DT Article ID PATIENT-CARE; OFFICE VISITS; TIME; PHYSICIANS; US AB Medical home models seek to increase efficiency and maximize the use of resources by ensuring that all care team members work at the top of their licenses. We sought to break down primary care office visits into measurable activities to better understand how primary care providers (PCPs) currently spend visit time and to provide insight into potential opportunities for revision or redistribution of healthcare tasks. We videotaped 27 PCPs during office visits with 121 patients at four Veterans Health Administration medical centers. Based on patterns emerging from the data, we identified a taxonomy of 12 provider activity categories that enabled us to quantify the frequency and duration of activities occurring during routine primary care visits. We conducted descriptive and multivariate analyses to examine associations between visit characteristics and provider and clinic characteristics. We found that PCPs spent the greatest percentage of their visit time discussing existing conditions (20%), discussing new conditions (18%), record keeping (13%), and examining patients (13%). Providers spent the smallest percentage of time on preventive care and coordination of care. Mean visit length was 22.9 minutes (range 7.9-58.0 minutes). Site-level ratings of medical home implementation were not associated with differences in how visit time was spent. These data provide a window into how PCPs are spending face-to-face time with patients. The methodology and taxonomy presented here may prove useful for future quality improvement and research endeavors, particularly those focused on opportunities to increase nonappointment care and to ensure that team members work at the top of their skill level. C1 [Gutierrez, Jennifer C.] Philadelphia Vet Affairs Med Ctr, CEPACT, Philadelphia, PA 19104 USA. [Terwiesch, Christian] Univ Penn, CEPACT, Philadelphia, PA 19104 USA. [Terwiesch, Christian] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Terwiesch, Christian] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Gutierrez, JC (reprint author), Philadelphia Vet Affairs Med Ctr, CEPACT, Philadelphia, PA 19104 USA. EM jennifer.gutierrez@va.gov NR 23 TC 2 Z9 2 U1 2 U2 3 PU AMER COLL HEALTHCARE EXEC HEALTH ADMINISTRATION PRESS PI CHICAGO PA ONE NORTH FRANKLIN ST SUITE 1700, CHICAGO, IL 60606 USA SN 1096-9012 EI 1944-7396 J9 J HEALTHC MANAG JI J. Healthc. Manag. PD JAN-FEB PY 2015 VL 60 IS 1 BP 30 EP 42 PG 13 WC Health Policy & Services SC Health Care Sciences & Services GA AZ5KM UT WOS:000348260000007 PM 26529991 ER PT J AU Pomposelli, T Hart, J Elliott, B Robison, J Brothers, T AF Pomposelli, Thomas Hart, Joseph Elliott, Bruce Robison, Jacob Brothers, Thomas TI Estimation of Mortality Risk for Vascular Operations by Trainees vs Attending Surgeons SO JOURNAL OF SURGICAL EDUCATION LA English DT Article DE vascular; surgery; education; mortality; training ID QUALITY IMPROVEMENT PROGRAM; SURGICAL QUALITY; POSTOPERATIVE MORBIDITY; ADJUSTMENT; RESIDENTS; FACULTY AB OBJECTIVE: The development of the ability to estimate patient mortality preoperatively in surgical trainees has not been well studied. DESIGN: Prospective comparative study in which the expected perioperative mortality risk and the maximum tolerable mortality at which operation would still be offered were estimated by the operating surgeons immediately before planned vascular procedures. SETTING: University vascular surgery teaching service. PARTICIPANTS: Predicted and maximum allowable mortality risks were compared between trainees and attending surgeons, with the mortality calculated using the Veterans Administration Surgical Quality Improvement Program (VASQIP) as a reference. RESULTS: Surveys were performed before 379 procedures over a 10-month period. The median expected mortality risk predicted by trainees (2%; interquartile range [IQR]: 1%-5%) was higher than the risk predicted by attending surgeons (1%; IQR: 0.8%-3%) (p < 0.01). The median expected mortality risk calculated by VASQIP (0.8%; IQR: 0.4%-1.7%) was less than that estimated by trainees by a median of 0.3% (IQR: 0.2%-3.2%) or and that by attending surgeons by 0.3% (IQR: 0.2-1.3%) (p < 0.01). The median maximum tolerable mortality risk predicted by trainees (10%; IQR: 5%-27.5%) was equal to the risk predicted by attending surgeons (10%; IQR: 5%-17.5%). The perioperative mortality calculated by VASQIP exceeded the maximum tolerable mortality offered by trainees or attending surgeons in 1% of cases each. Discrepancies between expected mortality and maximum tolerable mortality for trainees and attending surgeons were greater for younger (postgraduate year 1 or 2) trainees (0.8%; IQR: 0-3.0%) than for more senior (postgraduate year 4 or 5) trainees (0.4%; IQR: 0.1%-2.0%). CONCLUSION: Surgeons in training overestimated the perioperative mortality risk of operations and were willing to tolerate a greater mortality risk compared with attending surgeons. Both trainee and attending surgeons tended to overestimate the perioperative mortality risk compared with that calculated by VASQIP. (C) 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved. C1 [Pomposelli, Thomas; Hart, Joseph; Elliott, Bruce; Robison, Jacob; Brothers, Thomas] Med Univ S Carolina, Div Vasc Surg, Charleston, SC 29425 USA. [Brothers, Thomas] Ralph H Johnson VA Med Ctr, Dept Vet Affairs, Charleston, SC USA. RP Brothers, T (reprint author), 25 Courtenay Dr,Suite 7018, Charleston, SC 29425 USA. EM brothete@musc.edu NR 16 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 1931-7204 EI 1878-7452 J9 J SURG EDUC JI J. Surg. Educ. PD JAN-FEB PY 2015 VL 72 IS 1 BP 68 EP 72 DI 10.1016/j.jsurg.2014.07.007 PG 5 WC Education, Scientific Disciplines; Surgery SC Education & Educational Research; Surgery GA AZ5GS UT WOS:000348248900011 PM 25498880 ER PT J AU Kopacz, MS McCarten, JM Vance, CG Connery, AL AF Kopacz, Marek S. McCarten, Janet M. Vance, C. Garland Connery, April L. TI A Preliminary Study for Exploring Different Sources of Guilt in a Sample of Veterans Who Sought Chaplaincy Services SO MILITARY PSYCHOLOGY LA English DT Article DE suicide; veterans; guilt ID POSTTRAUMATIC-STRESS-DISORDER; SUICIDAL IDEATION; COMBAT VETERANS; MOOD DISORDERS; RISK-FACTORS; SHAME; PREVALENCE; CARE; EXPOSURE; PLANS AB Limited research has suggested that experiencing guilt may contribute to the risk of suicidal behavior in some veteran populations. Using data collected by chaplains, this study compared the frequency with which 94 veterans with a history of suicide ideation experienced guilt relative to 670 veterans without a history of ideation. We then compared main sources of guilt reported by ideators and nonideators. Ideators reported experiencing guilt significantly more often than nonideators. No differences were noted for the source of guilt among those who reported frequently experiencing this emotion. Ideators with an infrequent experience of guilt significantly more often named life and the military as the main source of this emotion. Clinicians should be mindful of the need to appropriately assess for and address guilt among veterans at increased risk of suicide. A variety of sources, not limited only to military experiences, may contribute to a veteran's sense of guilt. C1 [Kopacz, Marek S.; McCarten, Janet M.] US Dept Vet Affairs, VISN Ctr Excellence Suicide Prevent 2, Canandaigua, NY 14424 USA. [Vance, C. Garland] US Dept Vet Affairs, Charles George VA Med Ctr, Asheville, NC USA. [Connery, April L.] US Dept Vet Affairs, Canandaigua VA Med Ctr, Canandaigua, NY 14424 USA. RP Kopacz, MS (reprint author), US Dept Vet Affairs, VISN Ctr Excellence Suicide Prevent 2, 400 Ft Hill Ave, Canandaigua, NY 14424 USA. EM marek.kopacz@va.gov NR 39 TC 3 Z9 3 U1 1 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0899-5605 EI 1532-7876 J9 MIL PSYCHOL JI Milit. Psychol. PD JAN PY 2015 VL 27 IS 1 BP 1 EP 8 DI 10.1037/mil0000061 PG 8 WC Psychology, Multidisciplinary SC Psychology GA AZ0DX UT WOS:000347917500001 ER PT J AU Schoenleber, M Sippel, LM Jakupcak, M Tull, MT AF Schoenleber, Michelle Sippel, Lauren M. Jakupcak, Matthew Tull, Matthew T. TI Role of Trait Shame in the Association Between Posttraumatic Stress and Aggression Among Men With a History of Interpersonal Trauma SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE posttraumatic stress; shame; guilt; aggression; interpersonal violence ID INTIMATE PARTNER VIOLENCE; COGNITIVE-PROCESSING THERAPY; EXPERIENTIAL AVOIDANCE; MILITARY VETERANS; DISORDER SYMPTOMS; PSYCHOMETRIC PROPERTIES; GUILT; PTSD; PERPETRATION; VICTIMS AB Given the theoretical and empirical associations among posttraumatic stress, shame, and interpersonal aggression, this study examined whether trait shame accounts for the associations between posttraumatic stress and aggressive behavior in a sample of 103 men with a history of interpersonal trauma. Results indicated that trait shame accounted for the associations of posttraumatic stress with the variety of both physically and psychologically aggressive behavior, as well as with the frequency of physical aggression. This study also examined trait guilt, given its conceptual relationship to both shame and posttraumatic stress; unlike trait shame, trait guilt did not account for the association between posttraumatic stress and the variety of physically aggressive acts. Additionally, although trait guilt reduced the association between posttraumatic stress and the frequency of physical aggression, the indirect path including guilt was nonsignificant. Taken together, the present study supports existing theories suggesting that shame, but not guilt, may contribute to aggressive behavior, especially among individuals with histories of traumatic exposure. C1 [Schoenleber, Michelle; Sippel, Lauren M.; Tull, Matthew T.] Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Jackson, MS 39216 USA. [Jakupcak, Matthew] VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. [Jakupcak, Matthew] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Schoenleber, M (reprint author), Univ Mississippi, Med Ctr, Div Psychol, Dept Psychiat & Human Behav, 2500 N State St, Jackson, MS 39216 USA. EM mschoenleber@umc.edu NR 61 TC 3 Z9 3 U1 7 U2 16 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD JAN PY 2015 VL 7 IS 1 BP 43 EP 49 DI 10.1037/a0037434 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AZ3BA UT WOS:000348101500007 PM 25793592 ER PT J AU Hoerster, KD Jakupcak, M Stephenson, KR Fickel, JJ Simons, CE Hedeen, A Dwight-Johnson, M Whealin, JM Chaney, E Felker, BL AF Hoerster, Katherine D. Jakupcak, Matthew Stephenson, Kyle R. Fickel, Jacqueline J. Simons, Carol E. Hedeen, Ashley Dwight-Johnson, Megan Whealin, Julia M. Chaney, Edmund Felker, Bradford L. TI A Pilot Trial of Telephone-Based Collaborative Care Management for PTSD Among Iraq/Afghanistan War Veterans SO TELEMEDICINE AND E-HEALTH LA English DT Article DE primary care mental health; posttraumatic stress disorder; veterans; collaborative care ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH DIAGNOSES; RANDOMIZED CONTROLLED-TRIAL; AFGHANISTAN VETERANS; ANXIETY DISORDERS; DEPRESSION; SERVICES; IRAQ; PSYCHOTHERAPY; SYMPTOMS AB Background: Collaborative care and care management are cornerstones of Primary Care-Mental Health Integration (PC-MHI) and have been shown to reduce depressive symptoms. Historically, the standard of Veterans Affairs (VA) collaborative care was referring patients with posttraumatic stress disorder (PTSD) to specialty care. Although referral to evidence-based specialty care is ideal, many veterans with PTSD do not receive such care. To address this issue and reduce barriers to care, VA currently recommends veterans with PTSD be offered treatment within PC-MHI as an alternative. The current project outlines a pilot implementation of an established telephone-based collaborative care model-Translating Initiatives for Depression into Effective Solutions (TIDES)-adapted for Iraq/Afghanistan War veterans with PTSD symptoms (TIDES/PTSD) seen in a postdeployment primary care clinic. Materials and Methods: Structured medical record extraction and qualitative data collection procedures were used to evaluate acceptability, feasibility, and outcomes. Results: Most participants (n=17) were male (94.1%) and white (70.6%). Average age was 31.2 (standard deviation=6.4) years. TIDES/PTSD was successfully implemented within PC-MHI and was acceptable to patients and staff. Additionally, the total number of care manager calls was positively correlated with number of psychiatry visits (r=0.63, p<0.05) and amount of reduction in PTSD symptoms (r=0.66, p<0.05). Overall, participants in the pilot reported a significant reduction in PTSD symptoms over the course of the treatment (t=2.87, p=0.01). Conclusions: TIDES can be successfully adapted and implemented for use among Iraq/Afghanistan veterans with PTSD. Further work is needed to test the effectiveness and implementation of this model in other sites and among veterans of other eras. C1 [Hoerster, Katherine D.; Jakupcak, Matthew; Stephenson, Kyle R.; Felker, Bradford L.] VA Puget Sound Healthcare Syst, Seattle Div, Mental Hlth Serv, Seattle, WA 98108 USA. [Hoerster, Katherine D.; Jakupcak, Matthew; Chaney, Edmund; Felker, Bradford L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Stephenson, Kyle R.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. [Fickel, Jacqueline J.; Dwight-Johnson, Megan] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Simons, Carol E.; Hedeen, Ashley; Chaney, Edmund] VA Puget Sound Healthcare Syst, Seattle Div, Res & Dev Serv, Seattle, WA USA. [Whealin, Julia M.] Natl Ctr PTSD, Pacific Isl Div, Honolulu, HI USA. [Whealin, Julia M.] Natl Ctr PTSD, VA Pacific Isl Healthcare Syst, Honolulu, HI USA. [Whealin, Julia M.] Univ Hawaii, Sch Med, Dept Psychiat, Honolulu, HI 96822 USA. RP Hoerster, KD (reprint author), VA Puget Sound Healthcare Syst, Seattle Div, Mental Hlth Serv, 1660 South Columbian Way S-116, Seattle, WA 98108 USA. EM Katherine.Hoerster@va.gov FU Office of Research and Development, U.S. Department of Veterans Affairs [SHP08-184] FX This material is based on work supported by the Office of Research and Development, U.S. Department of Veterans Affairs (grant SHP08-184). NR 29 TC 2 Z9 2 U1 2 U2 7 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 EI 1556-3669 J9 TELEMED E-HEALTH JI Telemed. e-Health PD JAN 1 PY 2015 VL 21 IS 1 BP 42 EP 47 DI 10.1089/tmj.2013.0337 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AZ6BI UT WOS:000348302800007 PM 25405394 ER PT J AU Shah, AA Seiffert-Sinha, K Sirois, D Werth, VP Rengarajan, B Zrnchik, W Attwood, K Sinha, AA AF Shah, Amit Aakash Seiffert-Sinha, Kristina Sirois, David Werth, Victoria P. Rengarajan, Badri Zrnchik, William Attwood, Kristopher Sinha, Animesh A. TI Development of a Disease Registry for Autoimmune Bullous Diseases: Initial Analysis of the Pemphigus Vulgaris Subset SO ACTA DERMATO-VENEREOLOGICA LA English DT Article DE autoimmune bullous disease; disease registry; epidemiology; pemphigus vulgaris ID GENDER-DIFFERENCES; EPIDEMIOLOGY; POPULATION; RISK AB Pemphigus vulgaris (PV) is a rare, potentially life threatening, autoimmune blistering skin disease. The International Pemphigus and Pemphigoid Foundation (IPPF) has recently developed a disease registry with the aim to enhance our understanding of autoimmune bulbous diseases with the long-term goal of acquiring information to improve patient care. Patients were recruited to the IPPF disease registry through direct mail, e-mail, advertisements, and articles in the IPPF-quarterly, -website, -Facebook webpage, and IPPF Peer Health Coaches to complete a 38-question survey. We present here the initial analysis of detailed clinical information collected on 393 PV patients. We report previously unrecognized gender differences in terms of lesion location, autoimmune comorbidity, and delay in diagnosis. The IPPF disease registry serves as a useful resource and guide for future clinical investigation. C1 [Shah, Amit Aakash; Seiffert-Sinha, Kristina; Sinha, Animesh A.] SUNY Buffalo, Dept Dermatol, Buffalo, NY 14203 USA. [Sirois, David] NYU, Coll Dent, Dept Oral Med, New York, NY USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Werth, Victoria P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Rengarajan, Badri] Archimedes Inc, San Francisco, CA USA. [Zrnchik, William] Int Pemphigus & Pemphigoid Fdn, Sacramento, CA USA. [Attwood, Kristopher] Roswell Pk Canc Inst, Dept Biostat & Bioinformat, Buffalo, NY 14263 USA. RP Sinha, AA (reprint author), SUNY Buffalo, Dept Dermatol, Clin & Translat Res Ctr, Room 6078,875 Ellicott St, Buffalo, NY 14203 USA. EM aasinha@buffalo.edu NR 31 TC 2 Z9 2 U1 0 U2 0 PU ACTA DERMATO-VENEREOLOGICA PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 0001-5555 EI 1651-2057 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PY 2015 VL 95 IS 1 BP 86 EP 90 DI 10.2340/00015555-1854 PG 5 WC Dermatology SC Dermatology GA AY7TR UT WOS:000347762200017 PM 24691863 ER PT J AU Zaky, A Zeliadt, SB Treggiari, MM AF Zaky, A. Zeliadt, S. B. Treggiari, M. M. TI Patient-level interventions to prevent the acquisition of resistant Gram-negative bacteria in critically ill patients: a systematic review SO ANAESTHESIA AND INTENSIVE CARE LA English DT Review DE decontamination; Gram-negative bacterial infections; infection control; intensive care units ID INTENSIVE-CARE-UNIT; VENTILATOR-ASSOCIATED PNEUMONIA; PLACEBO-CONTROLLED TRIAL; SEVERE ACUTE-PANCREATITIS; DIGESTIVE-TRACT; DOUBLE-BLIND; SELECTIVE DECONTAMINATION; ANTIMICROBIAL RESISTANCE; PROBIOTIC PROPHYLAXIS; DISEASES SOCIETY AB The rising incidence of multidrug-resistant Gram-negative bacterial (MDR-GNB) infections acquired in intensive care units has prompted a variety of patient-level infection control efforts. However, it is not known whether these measures are effective in reducing colonisation and infection. The purpose of this systematic review was to assess the efficacy of patient-level interventions for the prevention of colonisation with MDR-GNB and whether these interventions are associated with a reduction in the rate of infection due to MDR-GNB in the intensive care unit. Searches were conducted on Pub Med, Cochrane, EMBASE and World of Science databases to identify comparative interventional studies on patient-level interventions implemented in the intensive care unit. Literature published in English, Spanish or French from January 1, 2000, until April 30, 2013, was searched. A total of 631 reports were found and we included and analysed 13 comparative studies that reported outcomes for an intervention compared with a control group. There were ten randomised and three observational interventional trials evaluating seven interventions. Overall, there was a reduction in colonisation (odds ratio [OR] 0.75; 95% confidence interval [CI] 0.66 to 0.85) and infection (OR 0.66; 95% CI 0.59 to 0.75) with MDR-GNB. This trend persisted after restricting pooled analysis to randomised controlled trials (pooled OR 0.66; 95% CI 0.57 to 0.76 and pooled OR 0.62; 95% Cl 0.54 to 0.72, respectively). We identified a significant reduction in MDR-GNB colonisation and infection through the use of patient-level interventions. This effect was mostly accounted for by selective digestive decontamination. However, given the limitations of the analysed trials, adequately powered controlled studies are needed to further explore the effects of patient-level interventions on colonisation and infection with MDR-GNB. C1 [Zaky, A.; Zeliadt, S. B.] Univ Washington, Dept Hlth Serv, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Treggiari, M. M.] Univ Washington, Dept Epidemiol, Dept Anaesthesiol, Seattle, WA 98195 USA. RP Zaky, A (reprint author), Univ Washington, Dept Hlth Serv, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. EM azaky@uab.edu NR 37 TC 0 Z9 0 U1 0 U2 1 PU AUSTRALIAN SOC ANAESTHETISTS PI EDGECLIFF PA P O BOX 600, EDGECLIFF, NSW 2027, AUSTRALIA SN 0310-057X EI 1448-0271 J9 ANAESTH INTENS CARE JI Anaesth. Intensive Care PD JAN PY 2015 VL 43 IS 1 BP 23 EP 33 PG 11 WC Anesthesiology; Critical Care Medicine SC Anesthesiology; General & Internal Medicine GA AY7TZ UT WOS:000347762900005 PM 25579286 ER PT J AU Smith, KM Eyal, E Weintraub, D AF Smith, Kara M. Eyal, Eli Weintraub, Daniel CA ADAGIO Investigators TI Combined Rasagiline and Antidepressant Use in Parkinson Disease in the ADAGIO Study Effects on Nonmotor Symptoms and Tolerability SO JAMA NEUROLOGY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; MAJOR DEPRESSIVE DISORDER; DELAYED-START TRIAL; DOUBLE-BLIND; PRAMIPEXOLE; SCALE; AUGMENTATION; METAANALYSIS; SELEGILINE; INHIBITOR AB IMPORTANCE Depression, cognitive impairment, and other nonmotor symptoms (NMSs) are common early in Parkinson disease (PD) and may be in part due to disease-related dopamine deficiency. Many patients with PD are treated with antidepressants for NMSs, and the effect of the combination of PD medications that enhance dopamine neurotransmission and antidepressants on NMSs has not been studied. We report the effects of the addition of a monoamine oxidase B inhibitor, rasagiline, to antidepressant treatment in PD. OBJECTIVE To evaluate the effect of rasagiline on depression, cognition, and other PD NMSs in patients taking an antidepressant in the Attenuation of Disease Progression With Azilect Given Once Daily (ADAGIO) study. DESIGN, SETTING, AND PARTICIPANTS The ADAGIO study was a double-blind, placebo-controlled, delayed-start trial of rasagiline in de novo PD. In this exploratory post hoc analysis, we analyzed patients taking an antidepressant during the 36-week phase 1 period, in which patients were randomized to rasagiline (1 or 2mg/d) or placebo. MAIN OUTCOMES AND MEASURES We evaluated the change in NMSs in patients taking an antidepressant and rasagiline compared with those taking placebo. The NMSs were assessed by Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Nonmotor Experiences of Daily Living, the original Unified Parkinson's Disease Rating Scale, and the Parkinson Fatigue Scale. RESULTS A total of 191 of the 1174 patients (16.3%) were treated with antidepressants during phase 1 and provided efficacy data. Depression and cognition scores revealed significantly less worsening in the rasagiline group compared with the placebo group (differences in Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale item-adjusted means [SEs], -0.19 [0.10], P = .048, and -0.20 [0.05], P < .001, respectively). Parkinson Fatigue Scale (mean [SE] difference, -0.42 [0.09], P < .001) and daytime sleepiness (mean [SE] difference, -0.24 [0.09], P = .006) scores also revealed significantly less worsening in the rasagiline group compared with placebo. There was a nonsignificant trend toward less worsening in apathy and no significant between-group differences in anxiety or sleep. The effect on depression remained significant after controlling for improvement in motor symptoms (mean [SE] difference, -0.23 [0.09], P = .009). There were no serious adverse events in the combined rasagiline-antidepressant group suggestive of serotonin syndrome. CONCLUSIONS AND RELEVANCE The combination of rasagiline and antidepressants in patients with de novo PD is associated with reduced worsening of a range of NMSs in preliminary analyses. Adverse effects appear uncommon with this combination. These findings suggest a role for dopamine-enhancing therapies in NMSs in early PD and encourage further study and confirmation. C1 [Smith, Kara M.; Weintraub, Daniel] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19107 USA. [Eyal, Eli] Teva Pharmaceut Ind, Petah Tiqwa, Israel. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19107 USA. [Weintraub, Daniel] Philadelphia VA Med Ctr, Dept Vet Affairs, Philadelphia, PA USA. RP Smith, KM (reprint author), Univ Penn, Dept Neurol, Perelman Sch Med, 330 S Ninth St, Philadelphia, PA 19107 USA. EM kara.smith@uphs.upenn.edu RI Deuschl, Gunther/A-7986-2010 OI Schnitzler, Alfons/0000-0002-6414-7939; Calopa, Matilde/0000-0002-6943-3707 FU Teva Pharmaceuticals FX The ADAGIO study was funded by Teva Pharmaceuticals. NR 40 TC 20 Z9 22 U1 3 U2 18 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD JAN PY 2015 VL 72 IS 1 BP 88 EP 95 DI 10.1001/jamaneurol.2014.2472 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AY8PI UT WOS:000347815300014 PM 25420207 ER PT J AU Collins, S Storrow, AB Albert, NM Butler, J Ezekowitz, J Felker, GM Fermann, GJ Fonarow, GC Givertz, MM Hiestand, B Hollander, JE Fonarow, GC Givertz, MM Hiestand, B Hollander, JE Lanfear, DE Levy, PD Pang, PS Peacock, WF Sawyer, DB Teerlink, JR Lenihan, DJ AF Collins, Sean Storrow, Alan B. Albert, Nancy M. Butler, Javed Ezekowitz, Justin Felker, G. Michael Fermann, Gregory J. Fonarow, Gregg C. Givertz, Michael M. Hiestand, Brian Hollander, Judd E. Fonarow, Gregg C. Givertz, Michael M. Hiestand, Brian Hollander, Judd E. Lanfear, David E. Levy, Phillip D. Pang, Peter S. Peacock, W. Frank Sawyer, Douglas B. Teerlink, John R. Lenihan, Daniel J. CA SAEM HFSA Acute Heart Failure TI Early Management of Patients With Acute Heart Failure: State of the Art and Future Directions. A Consensus Document From the Society for Academic Emergency Medicine/Heart Failure Society of America Acute Heart Failure Working Group SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Acute heart failure; emergency medicine; early management ID BRAIN NATRIURETIC PEPTIDE; RANDOMIZED CONTROLLED-TRIAL; IN-HOSPITAL MORTALITY; PULMONARY ARTERIAL-HYPERTENSION; RIGHT-VENTRICULAR DYSFUNCTION; PRESERVED SYSTOLIC FUNCTION; NATIONAL REGISTRY ADHERE; BEDSIDE ULTRASOUND INBU; END-DIASTOLIC PRESSURE; INTENSIVE-CARE-UNIT AB Heart failure (HF) afflicts nearly 6 million Americans, resulting in one million emergency department (ED) visits and over one million annual hospital discharges. An aging population and improved survival from cardiovascular diseases is expected to further increase I-IF prevalence. Emergency providers play a significant role in the management of patients with acute heart failure (AHF). It is crucial that emergency physicians and other providers involved in early management understand the latest developments in diagnostic testing, therapeutics and alternatives to hospitalization. Further, clinical trials must be conducted in the ED in order to improve the evidence base and drive optimal initial therapy for ARE Should ongoing and future studies suggest early phenotype-driven therapy improves in-hospital and post-discharge outcomes, ED treatment decisions will need to evolve accordingly. The potential impact of future studies which incorporate risk-stratification into ED disposition decisions cannot be underestimated. Predictive instruments that identify a cohort of patients safe for ED discharge, while simultaneously addressing barriers to successful outpatient management, have the potential to significantly impact quality of life and resource expenditures. C1 [Collins, Sean] Nashville Vet Affairs Med Ctr, Nashville, TN USA. [Collins, Sean; Storrow, Alan B.; Sawyer, Douglas B.; Lenihan, Daniel J.] Vanderbilt Univ, Nashville, TN 37232 USA. [Albert, Nancy M.] Cleveland Clin, Cleveland, OH 44106 USA. [Butler, Javed] Emory Univ, Atlanta, GA 30322 USA. [Ezekowitz, Justin] Univ Alberta, Edmonton, AB, Canada. [Felker, G. Michael] Duke Univ, Durham, NC USA. [Fermann, Gregory J.] Univ Cincinnati, Cincinnati, OH USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. [Givertz, Michael M.] Harvard Univ, Sch Med, Boston, MA USA. [Hiestand, Brian] Wake Forest Univ, Winston Salem, NC 27109 USA. [Hollander, Judd E.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Lanfear, David E.] Henry Ford Hosp, Detroit, MI 48202 USA. [Levy, Phillip D.] Wayne State Univ, Detroit, MI USA. [Pang, Peter S.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Peacock, W. Frank] Baylor Coll Med, Houston, TX 77030 USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Collins, S (reprint author), Vanderbilt Univ, Dept Emergency Med, 1313 21st Ave South, Nashville, TN 37232 USA. EM sean.collins@vanderbilt.edu RI Ezekowitz, Justin/C-4579-2013 OI Ezekowitz, Justin/0000-0002-2724-4086; Hollander, Judd/0000-0002-1318-2785 FU National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) [K23HL085387]; Medtronic; Cardiorentis; Abbott Point-of-Care; Novartis; Medicines Company; Astellas; Intersection Medical; Radiometer; Abbott Diagnostics; Centers for Medicaid and Medicare Services (CMS); NIH/NHLBI [K12HL1090]; National Center for Advancing Translational Sciences [UL1TR000445]; Roche Diagnostics; NIH [RO10HL105448, U-10HL110312]; European Union; Health Resources and Services Administration; Amgen; Trevena; Portola; Siemens; Insys; Mayday Fund Pfizer; NHLBI; Sanofi Aventis; Dyax; Novartis Pharmaceuticals; Trevena, Inc.; Mespere; BG Medicine; NIH/NIMHD [5 R01 MD005849-04]; Abbott; Alere; Banyan; Roche; Acorda Therapeutics; Cardio3 Bioscience; Cytokinetics; Sorbent Therapeutics; St Jude FX Sean Collins: research support: National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) (K23HL085387), Medtronic, Cardiorentis, Abbott Point-of-Care, Novartis, The Medicines Company, Astellas, Intersection Medical, Radiometer; consultant: Trevena, Novartis, Otsuka, Radiometer, The Medicines Company, Medtronic, Brahms, Insys, Intersection Medical, Cardioxyl. Alan B. Storrow: current or recent grant support: Abbott Diagnostics, Centers for Medicaid and Medicare Services (CMS), NIH/NHLBI (K12HL1090), National Center for, Advancing Translational Sciences (UL1TR000445), Roche Diagnostics; current consultant: Roche Diagnostics, Novartis Pharmaceuticals Corp USA, Alere Diagnostics, Trevena, Beckman Coulter. Nancy Albert: none. Javed Butler: research support: NIH, European Union, Health Resources and Services Administration; consultant: Amgen, Bayer, BG Medicine, Cardiocell, Celladon, Gambro, GE Healthcare, Medtronic, Novartis, Ono Pharma, Takeda, Trevena, Zensun. Justin A. Ezekowitz: conflicts available online at www.vigour.ualberta.ca. G. Michael Felker: consultant: Novartis, Amgen, Trevena, Roche Diagnostics, Singulex, Sorbent Therapeutics, BMS; research funding NIH (RO10HL105448, U-10HL110312), Novartis, Amgen, Roche Diagnostics. Gregory J. Fermann: research support: Novartis, Cardiorentis, Trevena, Portola, Radiometer, Medtronic, Siemens, Insys, The Mayday Fund Pfizer; advisory board: Intersection Medical, Janssen, Insys, The Medicines Company. Gregg C. Fonarow: consultant: Medtronic, Novartis, Johnson and Johnson. Michael M. Givertz: scientific advisory board: Merck, Janssen, Cardioxyl; grant support: NHLBI. Brian Hiestand: consultant: Motive Medical Intelligence, Insight PD, Intersection Medical; advisory board: Janssen Pharmaceuticals; research funding: The Medicines Company, Sanofi Aventis, Dyax, Radiometer, Cardiorentis, Novartis. Judd Hollander: Consultant: Novartis. David Lanfear: consultant: Bayer, Otsuka, Covis, Biocontrol, Janssen. Phillip D. Levy: consultant: Novartis Pharmaceuticals, Trevena, Intersection Medical, The Medicines Company, Ostuka, Janssen, Astellas, Astrazeneca, Beckman Coulter, research support: Novartis Pharmaceuticals; Cardiorentis, Trevena, Inc., Intersection Medical, Mespere, BG Medicine, NIH/NIMHD (5 R01 MD005849-04). Peter S. Pang: consultant: Janssen, Medtronic, Novartis, Trevena, Springleaftx, BG Medicine, Cornerstone Therapeutics; research support Abbott, Alere, NIH. W. Frank Peacock: research support: Abbott, Alere, Banyan, Cardiorentis, Portola, Roche, The Medicines Company; consultant: BG Medicine, Beckman, Boehringer-Ingelheim, Instrument Labs, The Medicines Company; consultant: Alere, Cardiorentis, Janssen; ownership interests: Comprehensive Research Associates, Emergencies in Medicine. Douglas B. Sawyer: grant support and consultant: Acorda Therapeutics. John R. Teerlink: consulting fees and research grants: Amgen, Cardio3 Bioscience, Cytokinetics, Novartis, Sorbent Therapeutics, St Jude, Trevena. Daniel J. Lenihan: none. NR 163 TC 17 Z9 17 U1 1 U2 9 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD JAN PY 2015 VL 21 IS 1 BP 27 EP 43 DI 10.1016/j.cardfail.2014.07.003 PG 17 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AY9KR UT WOS:000347869300006 PM 25042620 ER PT J AU Pugh, MJV Orman, JA Jaramillo, CA Salinsky, MC Eapen, BC Towne, AR Amuan, ME Roman, G McNamee, SD Kent, TA McMillan, KK Hamid, H Grafman, JH AF Pugh, Mary Jo V. Orman, Jean A. Jaramillo, Carlos A. Salinsky, Martin C. Eapen, Blessen C. Towne, Alan R. Amuan, Megan E. Roman, Gustavo McNamee, Shane D. Kent, Thomas A. McMillan, Katharine K. Hamid, Hamada Grafman, Jordan H. TI The Prevalence of Epilepsy and Association With Traumatic Brain Injury in Veterans of the Afghanistan and Iraq Wars SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE epidemiology; epilepsy; traumatic brain injury; Veterans ID ONSET UNPROVOKED SEIZURES; PENETRATING HEAD-INJURY; POSTTRAUMATIC EPILEPSY; BIDIRECTIONAL RELATION; ADMINISTRATIVE DATA; ANTIEPILEPTIC DRUG; CHRONIC PAIN; DISORDERS; COMORBIDITY; HYPERTENSION AB Objective: To examine the association of epilepsy with traumatic brain injury (TBI) in Afghanistan and Iraq (Operation Enduring Freedom [OEF]/Operation Iraqi Freedom [OIF]) Veterans. Design: Cross-sectional observational study. Participants: A total 256 284 OEF/OIF Veterans who received inpatient and outpatient care in the Veterans Health Administration in fiscal years 2009-2010. Main Outcome Measures: We used algorithms developed for use with International Classification of Diseases, Ninth Revision, Clinical Modification, codes to identify epilepsy, TBI (penetrating TBI [pTBI]/other TBI), and other risk factors for epilepsy (eg, stroke). TBI and other risk factors were identified prior to the index date (first date of seizure or October 1, 2009) for primary analyses. Results: Epilepsy prevalence was 10.6 per 1000 (N = 2719) in fiscal year 2010; age-adjusted prevalence was 6.1. Of 37 718 individuals with a diagnosis of TBI, 29 297 Veterans had a diagnosis of TBI prior to the index date. Statistically significant associations were found between epilepsy and prior TBI diagnosis (pTBI: adjusted odds ratio = 18.77 [95% confidence interval, 9.21-38.23]; other TBI: adjusted odds ratio = 1.64 [1.43-1.89]). Conclusions: Among OEF/OIF Veterans, epilepsy was associated with previous TBI diagnosis, with pTBI having the strongest association. Because war-related epilepsy in Vietnam War Veterans with TBI continued 35 years postwar, a detailed, prospective study is needed to understand the relationship between epilepsy and TBI severity in OEF/OIF Veterans. C1 [Pugh, Mary Jo V.; McMillan, Katharine K.] South Texas Vet Hlth Care Syst VERDICT, San Antonio, TX USA. [Pugh, Mary Jo V.; Orman, Jean A.; McMillan, Katharine K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Pugh, Mary Jo V.] Texas A&M Univ, Dept Med, Sch Med, College Stn, TX 77843 USA. [Orman, Jean A.] US Army Inst Surg Res, Houston, TX USA. [Orman, Jean A.] Univ Texas San Antonio, Sch Publ Hlth, San Antonio, TX USA. [Jaramillo, Carlos A.; Eapen, Blessen C.] UT Hlth Sci Ctr San Antonio, Dept Rehabil Med, Polytrauma Rehabil Ctr South Texas Vet Hlth Care, San Antonio, TX USA. [Salinsky, Martin C.] Portland VA Med Ctr, Portland, OR USA. [Salinsky, Martin C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Towne, Alan R.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Towne, Alan R.] McGuire Vet Adm Hosp, Epilepsy Ctr Excellence, Richmond, VA USA. [Amuan, Megan E.] Edith Nourse Rogers Mem Hosp, CHQOER, Bedford, MA USA. [Roman, Gustavo] Methodist Neurol Inst, Nantz Natl Alzheimer Ctr, Houston, TX USA. [McNamee, Shane D.] Hunter Holmes McGuire Vet Adm Hosp, Phys Med & Rehabil Serv, Richmond, VA USA. [Kent, Thomas A.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Kent, Thomas A.] Baylor Coll Med, Houston, TX 77030 USA. [Hamid, Hamada] West Haven VA Med Ctr, West Haven, CT USA. [Grafman, Jordan H.] Rehabil Inst Chicago, Chicago, IL 60611 USA. RP Pugh, MJV (reprint author), South Texas Vet Hlth Care Syst ALMD, 7400 Merton Minter Blvd 11C6, San Antonio, TX 78229 USA. EM pughm@uthscsa.edu OI Kent, Thomas/0000-0002-9877-7584; Grafman, Jordan H./0000-0001-8645-4457 FU VA Health Services Research and Development [DHI 09-237] FX The study was funded by VA Health Services Research and Development (DHI 09-237). Administrative, technical, or material support was provided by Kathleen Franklin, South Texas Veterans Healthcare System. Data analysis was conducted by Ms Amuan. NR 51 TC 8 Z9 8 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JAN-FEB PY 2015 VL 30 IS 1 BP 29 EP 37 DI 10.1097/HTR.0000000000000045 PG 9 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AY8BW UT WOS:000347780400012 PM 24695268 ER PT J AU Kearns, WD Fozard, JL Schonfeld, L Scott, S Marshall, K AF Kearns, William D. Fozard, James L. Schonfeld, Lawrence Scott, Steven Marshall, Katharine TI Elevated Movement Path Tortuosity in Voluntary Outdoor Ambulation in Community-Dwelling Veterans With a History of Traumatic Brain Injury SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE global positioning systems; (GPS); movement path tortuosity; outdoor ambulation; traumatic brain injury; veterans ID REHABILITATION; IMPAIRMENT; GAIT; VARIABILITY; PATTERNS; OUTCOMES; PROFILE; WALKING AB Objective: In comparison to veterans without a history of traumatic brain injury (TBI), we hypothesized that veterans with past TBI would have slower walking speed and more path tortuosity, TBI symptoms, problems with spatial orientation, and poorer executive function. Setting: Community nonclinical. Participants: Seventeen males (mean age of 37.2 years) reporting prior TBI and 20 non-TBI (mean age of 42.9 years). The number of years separating date of discharge and testing was 10.8 and 15.4 for the TBI and non-TBI groups, respectively. Design: Small 2 groups without random assignment. Main Measures: Brief Traumatic Brain Injury Screen, Trail Making Test-B, Clock Drawing Test, walking speed, and distance and path tortuosity in 30 minutes of voluntary outdoor walking wearing a small Global Positioning Systems recorder. Results: Those with TBI reported 4 Brief Traumatic Brain Injury Screen symptoms versus 0.4 for controls (F = 49.1; df = 1,35; P < .001) but did not differ on Trail Making Test-B or the Clock Drawing Test. Veterans with TBI walked shorter distances, 2.33 km versus 2.84 km (F = 4.8; df = 1,35; P < .05), and had greater path tortuosity (fractal D of 1.22 vs 1.15; F = 3.5; df = 1,35; P < .05) but did not differ on travel speed or time spent walking. Conclusions: Traumatic brain injury has persistent symptomatic effects and significantly affects ambulation and spatial orientation years after the event. These findings corroborate and extend observations linking cognitive impairment and ambulation. C1 [Kearns, William D.; Marshall, Katharine] Univ S Florida, Dept Rehabil & Mental Hlth Counseling, Tampa, FL 33612 USA. [Fozard, James L.] Univ S Florida, Sch Aging Studies, Tampa, FL 33612 USA. [Schonfeld, Lawrence] Univ S Florida, Florida Mental Hlth Inst, Tampa, FL 33612 USA. [Scott, Steven] James A Haley Vet Adm Hosp, Phys Med & Rehabil Serv, US Dept Vet Affairs, Tampa, FL USA. RP Kearns, WD (reprint author), Univ S Florida, Coll Behav & Community Sci, Dept Rehabil & Mental Hlth Counseling, 13301 B Downs Blvd,MHC1601 Tampa, Tampa, FL 33612 USA. EM Kearns@usf.edu RI Kearns, William/F-9810-2015 OI Kearns, William/0000-0002-0241-814X FU US Department of Defense [W81XWH-11-1-0634] FX This research was supported by the US Department of Defense under award number W81XWH-11-1-0634 to Dr Paul Sanberg "Battlefield-Related Injury Translational Research, Post-Traumatic Disease, and Disability Veterans Re-Integration." The authors also acknowledge Mr Charles Dion for his assistance with the statistical analysis. NR 28 TC 4 Z9 4 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JAN-FEB PY 2015 VL 30 IS 1 BP E8 EP E14 DI 10.1097/HTR.0000000000000021 PG 7 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AY8BW UT WOS:000347780400002 PM 24590148 ER PT J AU Salinsky, M Storzbach, D Goy, E Evrard, C AF Salinsky, Martin Storzbach, Daniel Goy, Elizabeth Evrard, Collette TI Traumatic Brain Injury and Psychogenic Seizures in Veterans SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE epilepsy; psychogenic seizures; PTSD; TBI; Veterans ID POSTTRAUMATIC-STRESS-DISORDER; NONEPILEPTIC SEIZURES; VIDEO-EEG; EPILEPSY; HEALTH; IRAQ; COMORBIDITY; SYMPTOMS; SEQUELAE; OUTCOMES AB Objective: To evaluate a proposed seizure etiology of traumatic brain injury (TBI) as a risk factor for psychogenic nonepileptic seizures (PNESs), the effect of reported TBI severity on the diagnosis of PNES versus epileptic seizures (ESs), and the potential moderating role of posttraumatic stress disorder (PTSD). Participants, Setting: Veterans with a diagnosis of PNES or ES during epilepsy monitoring at a Veterans Affairs Medical Center. Design: Retrospective review of seizure type, proposed seizure etiology, TBI severity, and PTSD. Main Outcomes: Both PNES and ES groups were compared for TBI history and severity, and prior diagnosis of PTSD. Results: Traumatic brain injury was the proposed seizure etiology for 57% of 67 PNES patients versus 35% of 54 ES patients (P < .05). It was mild in 87% of PNES patients and 37% of ES patients (P < .001). Posttraumatic stress disorder increased the likelihood of diagnosing PNES versus ES in Veterans with mild TBI as the proposed seizure etiology. Conclusions: Veterans with PNES commonly cite a TBI as the cause for seizures. Mild TBI was strongly associated with PNES versus ES. Posttraumatic stress disorder may moderate the development of PNES in Veterans with a history of mild TBI. Clinicians caring for Veterans with seizures may use these results in selecting patients for early diagnostic evaluation. C1 [Salinsky, Martin; Storzbach, Daniel; Goy, Elizabeth; Evrard, Collette] Portland VA Med Ctr, Portland, OR USA. [Salinsky, Martin] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Salinsky, M (reprint author), Portland VAMC Epilepsy Ctr, 3710 SWUS Vet Hosp Rd P3ECOE, Portland, OR 97239 USA. EM Salinsky@ohsu.edu NR 38 TC 5 Z9 5 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JAN-FEB PY 2015 VL 30 IS 1 BP E65 EP E70 DI 10.1097/HTR.0000000000000057 PG 6 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AY8BW UT WOS:000347780400008 PM 24901325 ER PT J AU Kasckow, J Yeager, DE Magruder, K AF Kasckow, John Yeager, Derik E. Magruder, Kathryn TI Levels of Symptom Severity and Functioning in Four Different Definitions of Subthreshold Posttraumatic Stress Disorder in Primary Care Veterans SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Posttraumatic stress disorder; subthreshold; functioning; posttraumatic checklist score ID NATIONAL EPIDEMIOLOGIC SURVEY; SF-36 HEALTH SURVEY; IQOLA PROJECT; PTSD SYMPTOMS; WAVE 2; FULL; COMORBIDITY; PREVALENCE; PREDICTORS; VICTIMS AB Four definitions of subthreshold posttraumatic stress disorder (PTSD) were compared in 815 veterans seen in Veterans Affairs Medical Center primary care clinics. We compared PTSD Checklist (PCL) scores and Short Form 36 (SF-36) scores between participants meeting criteria for one of the subthreshold PTSD definitions (based on Schnurr, Marshall, Blanchard, or Stein) to those with and without PTSD. Using regression, thosemeeting subthreshold criteria by any of the four definitions had lower mental and physical health functioning and higher PCL scores relative to those without PTSD; they also had higher mental health functioning and lower PCL scores relative to those with PTSD. With SF-36 physical functioning scores, only those meeting the Stein definition differed from the group with PTSD. Thus, these definitions appear to distinguish individuals who are qualitatively different from individuals with no PTSD or with PTSD and are nearly equivalent in their ability to discriminate individuals. C1 [Kasckow, John] Vet Affairs Pittsburgh Hlth Care Syst, Pittsburgh, PA 15420 USA. [Kasckow, John] Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA. [Yeager, Derik E.; Magruder, Kathryn] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Yeager, Derik E.; Magruder, Kathryn] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. RP Kasckow, J (reprint author), Vet Affairs Pittsburgh Hlth Care Syst, Univ Dr C, Pittsburgh, PA 15420 USA. EM kasckowjw@upmc.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development [VCR 99-010-2] FX This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development: VCR 99-010-2. NR 29 TC 3 Z9 3 U1 4 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JAN PY 2015 VL 203 IS 1 BP 43 EP 47 DI 10.1097/NMD.0000000000000233 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AY5TM UT WOS:000347634600009 PM 25503958 ER PT J AU Tache, Y Million, M AF Tache, Yvette Million, Mulugeta TI Role of Corticotropin-releasing Factor Signaling in Stress-related Alterations of Colonic Motility and Hyperalgesia SO JOURNAL OF NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE Colonic motility; Corticotropin-releasing factor; Irritable bowel syndrome; Stress; Visceral pain ID IRRITABLE-BOWEL-SYNDROME; BRAIN-GUT AXIS; FACTOR CRF FAMILY; INDUCED VISCERAL HYPERALGESIA; RECEPTOR-MEDIATED MECHANISMS; WATER-AVOIDANCE STRESS; ENTERIC NERVOUS-SYSTEM; MUCOSAL BARRIER FUNCTION; LOCUS-COERULEUS NEURONS; HORMONE TYPE-1 RECEPTOR AB The corticotropin-releasing factor (CRF) signaling systems encompass CRF and the structurally related peptide urocortin (Ucn) 1, 2, and 3 along with 2 G-protein coupled receptors, CRF1 and CRF2. CRF binds with high and moderate affinity to CRF1 and CRF2 receptors, respectively while Ucn1 is a high-affinity agonist at both receptors, and Ucn2 and Ucn3 are selective CRF2 agonists. The CRF systems are expressed in both the brain and the colon at the gene and protein levels. Experimental studies established that the activation of CRF1 pathway in the brain or the colon recaptures cardinal features of diarrhea predominant irritable bowel syndrome (IBS) (stimulation of colonic motility, activation of mast cells and serotonin, defecation/watery diarrhea, and visceral hyperalgesia). Conversely, selective CRF1 antagonists or CRF1/CRF2 antagonists, abolished or reduced exogenous CRF and stress-induced stimulation of colonic motility, defecation, diarrhea and colonic mast cell activation and visceral hyperalgesia to colorectal distention. By contrast, the CRF2 signaling in the colon dampened the CRF1 mediated stimulation of colonic motor function and visceral hyperalgesia. These data provide a conceptual framework that sustained activation of the CRF1 system at central and/or peripheral sites may be one of the underlying basis of IBS-diarrhea symptoms. While targeting these mechanisms by CRF1 antagonists provided a relevant novel therapeutic venue, so far these promising preclinical data have not translated into therapeutic use of CRF1 antagonists. Whether the existing or newly developed CRF1 antagonists will progress to therapeutic benefits for stress-sensitive diseases including IBS for a subset of patients is still a work in progress. C1 Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Ctr Neurobiol Stress, Div Digest Dis, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Neurovisceral Sci & Womens Hlth, CURE Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU NIHDDK [R01 DK-33061, R01 DK-57236, R01 DK-078676, DK-41301, P50 AR-049550]; VA Merit and Senior Scientist Awards FX This work was supported by the NIHDDK grants R01 DK-33061 (YT), R01 DK-57236 (YT), R01 DK-078676 (MM), DK-41301 (Animal Models Core, YT, MM), P50 AR-049550 (YT, MM), and VA Merit and Senior Scientist Awards (YT). NR 210 TC 19 Z9 20 U1 1 U2 15 PU KOREAN SOC NEUROGASTROENTEROLOGY & MOTILITY PI GANGNAM-GU PA RM 305, LOTTE GOLD ROSE VILL II, 31 SEOLLEUNG-RO 86-GIL, GANGNAM-GU, SEOUL 135-839, SOUTH KOREA SN 2093-0879 EI 2093-0887 J9 J NEUROGASTROENTEROL JI J. Neurogastroenterol. Motil. PD JAN PY 2015 VL 21 IS 1 BP 8 EP 24 DI 10.5056/jnm14162 PG 17 WC Gastroenterology & Hepatology; Clinical Neurology SC Gastroenterology & Hepatology; Neurosciences & Neurology GA AY7JI UT WOS:000347736300003 PM 25611064 ER PT J AU Lam, DL McNeeley, MF Bhargava, P AF Lam, Diana L. McNeeley, Michael F. Bhargava, Puneet TI Lessons From the Happiest Place on Earth SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Lam, Diana L.; McNeeley, Michael F.] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. [Bhargava, Puneet] Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Diagnost Imaging Serv, Seattle, WA USA. [Bhargava, Puneet] Univ Washington, Seattle, WA 98108 USA. RP Lam, DL (reprint author), Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. EM bhargp@uw.edu OI Bhargava, Puneet/0000-0002-3849-9666 NR 13 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JAN PY 2015 VL 12 IS 1 BP 6 EP 8 DI 10.1016/j.jacr.2014.02.014 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AY7NT UT WOS:000347747400004 PM 24713503 ER PT J AU Pivtoraiko, VN Abrahamson, EE Leurgans, SE DeKosky, ST Mufson, EJ Ikonomovic, MD AF Pivtoraiko, Violetta N. Abrahamson, Eric E. Leurgans, Sue E. DeKosky, Steven T. Mufson, Elliott J. Ikonomovic, Milos D. TI Cortical pyroglutamate amyloid-beta levels and cognitive decline in Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Article DE Pyroglutamate-modified A beta; Amyloid-beta; Alzheimer's disease; Posterior cingulate cortex; MCI; Episodic memory ID EPISODIC MEMORY RETRIEVAL; PROTEIN A-BETA; OLDER PERSONS; NEUROPATHOLOGIC ASSESSMENT; SENILE PLAQUES; ASSOCIATION GUIDELINES; SYNAPTIC PLASTICITY; NATIONAL INSTITUTE; GLUTAMINYL CYCLASE; PRECURSOR PROTEIN AB Posterior cingulate cortex (PCC) accumulates amyloid-beta (A beta) early in Alzheimer's disease (AD). The relative concentrations of full-length Ab and truncated, pyroglutamate-modified A beta (NpE3) forms, and their correlations to cognitive dysfunction in AD, are unknown. We quantified A beta NpE3-42, A beta NpE3-40, A beta 1-42, and A beta 1-40 concentrations in soluble (nonfibrillar) and insoluble (fibrillar) pools in PCC from subjects with an antemortem clinical diagnosis of no cognitive impairment, mild cognitive impairment, or mild-moderate AD. In clinical AD, increased PCC concentrations of Ab were observed for all A beta forms in the insoluble pool but only for A beta 1-42 in the soluble pool. Lower Mini-Mental State Exam and episodic memory scores correlated most strongly with higher concentrations of soluble and insoluble A beta 1-42. Greater neuropathology severity by Consortium to Establish a Registry for Alzheimer's Disease and National Institute on Aging-Reagan pathologic criteria was associated with higher concentrations of all measured Ab forms, except soluble A beta NpE3-40. Low concentrations of soluble pyroglutamate A beta across clinical groups likely reflect its rapid sequestration into plaques, thus, the conversion to fibrillar A beta may be a therapeutic target. Published by Elsevier Inc. C1 [Pivtoraiko, Violetta N.; Abrahamson, Eric E.; Ikonomovic, Milos D.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Abrahamson, Eric E.; Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Leurgans, Sue E.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [DeKosky, Steven T.] Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA. [Mufson, Elliott J.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. RP Ikonomovic, MD (reprint author), Univ Pittsburgh, Dept Neurol, 200 Lothrop St,BSTWR S 521, Pittsburgh, PA 15213 USA. EM ikonomovicmd@upmc.edu FU National Institute on Aging, National Institutes of Health [PO1AG014449, PO1AG025204, RO1AG043375, P30AG10161] FX This study was supported by grants PO1AG014449, PO1AG025204, RO1AG043375 and P30AG10161 from the National Institute on Aging, National Institutes of Health. The authors are indebted to the Catholic nuns, priests, and lay brothers who participated in the Rush Religious Orders Study. They are grateful to Dr Ana W. Capuano (Rush University Medical Center) for assistance with statistical analyses and to Mr. William Paljug for expert technical assistance. NR 58 TC 6 Z9 6 U1 2 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JAN PY 2015 VL 36 IS 1 BP 12 EP 19 DI 10.1016/j.neurobiolaging.2014.06.021 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AY2HD UT WOS:000347408600003 PM 25048160 ER PT J AU Swanson, GP Jones, WE Ha, CS Jenkins, CA Kumar, AP Basler, J AF Swanson, Gregory P. Jones, William E., III Ha, Chul S. Jenkins, Carol A. Kumar, Addanki Pratap Basler, Joseph TI Tolerance of Phellodendron amurense Bark Extract (Nexrutine (R)) in Patients with Human Prostate Cancer SO PHYTOTHERAPY RESEARCH LA English DT Article DE Nexrutine (R); Phellodendron amurense extract; prostate cancer; prostatectomy; radiation therapy; combined modality ID ANDROGEN-DEPRIVATION THERAPY; DEFINITIVE RADIOTHERAPY; ADJUVANT; INHIBITION; CARCINOMA; RISK; MEN AB Phellodendron amurense bark extract (Nexrutine (R)) has shown a favorable effect on prostate cancer in vivo and in vitro. We evaluated its tolerance in patients undergoing surgery or radiation for prostate cancer. Patients received Nexrutine (R) orally (500mg tid) either 1 to 2 months preoperatively or 1 to 2months prior to and with radiation therapy. Common Terminology Criteria for Adverse Events were used to measure tolerance. In total, 21 patients (9 surgery and 12 radiation) underwent treatment. During the Nexrutine (R) alone component, there were two transient grade 3 toxicities (hypokalemia and urinary incontinence). There was no grade 4 toxicity. For the combined Nexrutine (R) and radiation component, no additional patients suffered a grade 3 toxicity. All the toxicities were transient. By the end of the neoadjuvant treatment, 81% of the patients had a decline in prostate-specific antigen. This is the first report of patients with prostate cancer being treated with P. amurense bark extract, and it was very well tolerated. Toxicities were minimal and self-limited. This compound can be safely used in further evaluation of a treatment effect on cancer. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Swanson, Gregory P.; Jones, William E., III; Ha, Chul S.; Jenkins, Carol A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiat Oncol, San Antonio, TX 78229 USA. [Kumar, Addanki Pratap; Basler, Joseph] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Kumar, Addanki Pratap] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Kumar, Addanki Pratap] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Swanson, Gregory P.; Jones, William E., III; Kumar, Addanki Pratap; Basler, Joseph] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Swanson, GP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Radiat Oncol, 7979 Wurzbach Rd, San Antonio, TX 78229 USA. EM swansong@uthscsa.edu FU CTRC P30 Cancer Center Support Grant from the National Cancer Institute [CA054174]; VA-Merit Award [BX 000766]; National Center for Research Resources; National Center for Advancing Translational Sciences, National Institutes of Health [1UL TR001120] FX CTRC Clinical Trial Fund: CTRC P30 Cancer Center Support Grant from the National Cancer Institute (CA054174) and VA-Merit Award BX 000766 (APK).; The project described was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant 1UL TR001120. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 13 TC 5 Z9 5 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0951-418X EI 1099-1573 J9 PHYTOTHER RES JI Phytother. Res. PD JAN PY 2015 VL 29 IS 1 BP 40 EP 42 DI 10.1002/ptr.5221 PG 3 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AZ2JP UT WOS:000348060300006 PM 25205619 ER PT J AU Molina, Y Ceballos, RM Dolan, ED Albano, D McGregor, BA AF Molina, Yamile Ceballos, Rachel M. Dolan, Emily D. Albano, Denise McGregor, Bonnie A. TI Perceived breast cancer risk and breast cancer worry among women with a family history of breast cancer: a new perspective on coping as a mediator SO PSYCHO-ONCOLOGY LA English DT Article DE coping; distress; family history; breast cancer; risk perception C1 [Molina, Yamile; Ceballos, Rachel M.; Albano, Denise; McGregor, Bonnie A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Molina, Yamile; Ceballos, Rachel M.; Albano, Denise; McGregor, Bonnie A.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Molina, Yamile] Univ Illinois, Sch Publ Hlth, Chicago, IL USA. [Dolan, Emily D.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP McGregor, BA (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N MP900,POB 19024, Seattle, WA 98109 USA. EM bmcgrego@fhcrc.org FU National Cancer Institute [K07CA107085, P50CA148143, R25CA92408, K01CA154938-01A1] FX Data collection was supported by the National Cancer Institute (K07CA107085, P50CA148143, R25CA92408, K01CA154938-01A1). The content does not necessarily represent the official views of the National Cancer Institute/National Institutes of Health. NR 10 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JAN PY 2015 VL 24 IS 1 BP 113 EP 116 DI 10.1002/pon.3587 PG 4 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA AY9TY UT WOS:000347894500015 PM 24986795 ER PT J AU Scott, JC Matt, GE Wrocklage, KM Crnich, C Jordan, J Southwick, SM Krystal, JH Schweinsburg, BC AF Scott, J. Cobb Matt, Georg E. Wrocklage, Kristen M. Crnich, Cassandra Jordan, Jessica Southwick, Steven M. Krystal, John H. Schweinsburg, Brian C. TI A Quantitative Meta-Analysis of Neurocognitive Functioning in Posttraumatic Stress Disorder SO PSYCHOLOGICAL BULLETIN LA English DT Article DE posttraumatic stress disorder; neuropsychology; meta-analysis; memory; attention ID TRAUMATIC BRAIN-INJURY; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; CONFIRMATORY FACTOR-ANALYSIS; TEST-RETEST RELIABILITY; MAJOR DEPRESSIVE DISORDER; VERBAL-LEARNING TEST; CARD SORTING TEST; DEFICIT HYPERACTIVITY DISORDER; NEAR-INFRARED SPECTROSCOPY; CHILDHOOD SEXUAL-ABUSE AB Posttraumatic stress disorder (PTSD) is associated with regional alterations in brain structure and function that are hypothesized to contribute to symptoms and cognitive deficits associated with the disorder. We present here the first systematic meta-analysis of neurocognitive outcomes associated with PTSD to examine a broad range of cognitive domains and describe the profile of cognitive deficits, as well as modifying clinical factors and study characteristics. This report is based on data from 60 studies totaling 4,108 participants, including 1,779 with PTSD, 1,446 trauma-exposed comparison participants, and 895 healthy comparison participants without trauma exposure. Effect-size estimates were calculated using a mixed-effects meta-analysis for 9 cognitive domains: attention/working memory, executive functions, verbal learning, verbal memory, visual learning, visual memory, language, speed of information processing, and visuospatial abilities. Analyses revealed significant neurocognitive effects associated with PTSD, although these ranged widely in magnitude, with the largest effect sizes in verbal learning (d = -.62), speed of information processing (d = -.59), attention/working memory (d = -.50), and verbal memory (d = -.46). Effect-size estimates were significantly larger in treatment-seeking than community samples and in studies that did not exclude participants with attention-deficit/hyperactivity disorder, and effect sizes were affected by between-group IQ discrepancies and the gender composition of the PTSD groups. Our findings indicate that consideration of neuropsychological functioning in attention, verbal memory, and speed of information processing may have important implications for the effective clinical management of persons with PTSD. Results are further discussed in the context of cognitive models of PTSD and the limitations of this literature. C1 [Scott, J. Cobb] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN4, Philadelphia, PA 19104 USA. [Scott, J. Cobb] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Matt, Georg E.] San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA. [Wrocklage, Kristen M.; Crnich, Cassandra; Jordan, Jessica; Southwick, Steven M.; Krystal, John H.; Schweinsburg, Brian C.] VA Connecticut Healthcare Syst, Natl Ctr PTSD, West Haven, CT USA. [Southwick, Steven M.; Krystal, John H.; Schweinsburg, Brian C.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. [Krystal, John H.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06520 USA. [Krystal, John H.] Yale New Haven Med Ctr, Psychiat Serv, New Haven, CT 06504 USA. RP Scott, JC (reprint author), Philadelphia VA Med Ctr, MIRECC 116,3900 Woodland Ave, Philadelphia, PA 19104 USA. EM scott1@upenn.edu FU Department of Veterans Affairs Career Development Awards [1IK2CX000772, MH070345]; Clinical Neurosciences Division of the National Center for Posttraumatic Stress Disorder; VA National Center for PTSD; National Institute on Alcohol Abuse and Alcoholism [P50 AA012870]; National Center for Advancing Translational Sciences via Yale Center for Clinical Investigation [UL1 RR024139] FX This work was supported by Department of Veterans Affairs Career Development Awards 1IK2CX000772 to J. Cobb Scott and MH070345 to Steven M. Southwick and by the Clinical Neurosciences Division of the National Center for Posttraumatic Stress Disorder. John H. Krystal's participation was supported by the VA National Center for PTSD, the National Institute on Alcohol Abuse and Alcoholism (P50 AA012870), and the National Center for Advancing Translational Sciences via its support for the Yale Center for Clinical Investigation (UL1 RR024139). We thank Henry Kranzler for his helpful feedback on the manuscript and Blake Buss for his assistance in data entry. J. Cobb Scott presented initial results of this meta-analysis at the February 2014 meeting of the International Neuropsychological Society in Seattle, Washington. 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. NR 356 TC 33 Z9 34 U1 22 U2 77 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0033-2909 EI 1939-1455 J9 PSYCHOL BULL JI Psychol. Bull. PD JAN PY 2015 VL 141 IS 1 BP 105 EP 140 DI 10.1037/a0038039 PG 36 WC Psychology; Psychology, Multidisciplinary SC Psychology GA AY6SX UT WOS:000347696900005 PM 25365762 ER PT J AU O'Donovan, A Chao, LL Paulson, J Samuelson, KW Shigenaga, JK Grunfeld, C Weiner, MW Neylan, TC AF O'Donovan, Aoife Chao, Linda L. Paulson, Jennifer Samuelson, Kristin W. Shigenaga, Judy K. Grunfeld, Cart Weiner, Mike W. Neylan, Thomas C. TI Altered inflammatory activity associated with reduced hippocampal volume and more severe posttraumatic stress symptoms in Gulf War veterans SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Hippocampus; Inflammation; Posttraumatic stress disorder; Structural magnetic resonance imaging; Trauma; Veterans ID C-REACTIVE PROTEIN; MAJOR DEPRESSIVE DISORDER; DECLARATIVE MEMORY; CHRONIC NEURODEGENERATION; ELEVATED INFLAMMATION; PSYCHOLOGICAL STRESS; CHILDHOOD TRAUMA; BRAIN; PTSD; INTERLEUKIN-6 AB Background: Inflammation may reduce hippocampal volume by blocking neurogenesis and promoting neurodegeneration. Posttraumatic stress disorder (PTSD) has been linked with both elevated inflammation and reduced hippocampal volume. However, few studies have examined associations between inflammatory markers and hippocampal volume, and none have examined these associations in the context of PTSD. Methods: We measured levels of the inflammatory markers interleukin-6 (IL-6) and soluble receptor II for tumor necrosis factor (sTNF-RII) as well as hippocampal volume in 246 Gulf War veterans with and without current and past PTSD as assessed with the Clinician Administered PTSD Scale (CAPS). Enzyme-linked immunosorbent assays were used to measure inflammatory markers, and 1.5 Testa magnetic resonance imaging (MRI) and Freesurfer version 4.5 were used to quantify hippocampal volume. Hierarchical linear regression and analysis of covariance models were used to examine if hippocampal volume and PTSD status would be associated with elevated levels of IL-6 and sTNF-RII. Results: Increased sTNF-RII, but not IL-6, was significantly associated with reduced hippocampal volume (beta = -0.14, p = 0.01). The relationship between sTNF-RII and hippocampal volume was independent of potential confounds and covariates, including PTSD status. Although we observed no PTSD diagnosis-related differences in either IL-6 or sTNF-RII, higher PTSD severity was associated with significantly increased sTNF-RII (beta = 0.24, p = 0.04) and reduced IL-6 levels (beta = 0.24, p = 0.04). Conclusions: Our results indicate that specific inflammatory proteins may be associated with brain structure and function as indexed by hippocampal volume and PTSD symptoms. (C) 2014 Published by Elsevier Ltd. C1 [O'Donovan, Aoife; Chao, Linda L.; Paulson, Jennifer; Shigenaga, Judy K.; Grunfeld, Cart; Weiner, Mike W.; Neylan, Thomas C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [O'Donovan, Aoife; Chao, Linda L.; Paulson, Jennifer; Samuelson, Kristin W.; Shigenaga, Judy K.; Grunfeld, Cart; Weiner, Mike W.; Neylan, Thomas C.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [O'Donovan, Aoife; Chao, Linda L.; Paulson, Jennifer; Samuelson, Kristin W.; Shigenaga, Judy K.; Grunfeld, Cart; Weiner, Mike W.; Neylan, Thomas C.] Northern Calif Inst Res & Educ, San Francisco, CA USA. [Paulson, Jennifer; Samuelson, Kristin W.] Alliant Int Univ, Calif Sch Profess Psychol, Alhambra, CA 91803 USA. RP O'Donovan, A (reprint author), San Francisco VA Med Ctr, 4150 Clement St,116-C1, San Francisco, CA 94121 USA. EM Aoife.ODonovan@ucsf.edu FU Lightfighter Foundation; US Army Military Operational Medicine Research Program, Department of Defense [W81XWH-11-2-0189]; Mental Illness Research and Education Clinical Center (MIRECC) of the U.S. Veterans Health Administration; National Institute on Aging [K24 AG031155]; National Center for Advancing Translational Sciences Career Development Award [KL2 TR000143]; Society in Science-Branco Weiss Fellowship FX This study was generously supported by grants from the Lightfighter Foundation, the US Army Military Operational Medicine Research Program, Department of Defense W81XWH-11-2-0189 entitled, "Investigation of Links Between PTSD and Dementia," awarded to the Northern California Institute for Research and the Mental Illness Research and Education Clinical Center (MIRECC) of the U.S. Veterans Health Administration and the National Institute on Aging (K24 AG031155) as well as by a National Center for Advancing Translational Sciences Career Development Award (KL2 TR000143) and a Society in Science-Branco Weiss Fellowship (to AOD). Resources and the use of facilities were provided by the Veterans Administration Medical Center, San Francisco, California. This manuscript's contents are solely the responsibility of the authors and do not necessarily represent the official views of any of the funding bodies. The authors thank Jennifer Hlavin, Mark Pacult, Natasha Sukerkar, and Kevin Kim for assistance with this study and manuscript. NR 65 TC 13 Z9 13 U1 6 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN PY 2015 VL 51 BP 557 EP 566 DI 10.1016/j.psyneuen.2014.11.010 PG 10 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA AY5BI UT WOS:000347588000051 PM 25465168 ER PT J AU Bierer, LM Ivanov, I Carpenter, DM Wong, EW Golier, JA Tang, CY Yehuda, R AF Bierer, Linda M. Ivanov, Iliyan Carpenter, David M. Wong, Edmund W. Golier, Julia A. Tang, Cheuk Y. Yehuda, Rachel TI White matter abnormalities in Gulf War veterans with posttraumatic stress disorder: A pilot study SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE PTSD; DTI; Diffusion tensor imaging; White matter; Gulf War veterans; Connectivity; Cingulum bundle ID MEDIAL PREFRONTAL CORTEX; SCRIPT-DRIVEN IMAGERY; DIFFUSION TENSOR; ANTERIOR CINGULATE; ACTION-POTENTIALS; NEURAL-NETWORKS; BLOOD-FLOW; PTSD; INTEGRITY; AMYGDALA AB Background: Gulf War veterans were exposed to environmental toxins not present in other combat theaters resulting in a unique biological signature that only partially resembles that seen in other combat veterans with PTSD. Thus it is important to determine if brain abnormalities seen in non-Gulf War veterans with PTSD are also present in Gulf War veterans. In this pilot study, diffusion tensor imaging (DTI) tractography was used to assess the ultra-structural integrity of fronto-limbic white matter connections in Gulf War veterans with and without PTSD. The effects of chronic multisymptom illness on DTI measures was also evaluated. Methods: Subjects were 20 previously studied Gulf War veterans on whom MRIs had been obtained. Mean diffusivity (MD) and fractional anisotropy (FA) were determined for left and right cingulum bundle by DTI tractography and compared in separate analyses for 12 veterans with, and 8 without PTSD. The effect of chronic multisymptom illness and it's interaction with PTSD, were similarly investigated using multivariate ACOVA. Partial correlations were used to test the associations of both DTI indices with PTSD severity and plasma cortisol, controlling for whole brain volume. Results: Significantly lower MD was demonstrated in the right cingulum bundle among Gulf War veterans with PTSD. There were no significant differences in MD or FA in the left cingulum bundle. The presence of chronic multisymptom illness significantly attenuated the PTSD associated decrement in right cingulum MD. Clinician and self-rated PTSD symptom severity scores were significantly associated with reduced MD and increased FA in the right cingulum. Similar associations were observed for 8am plasma cortisol in a subset of participants. Conclusions: The preliminary findings indicate increased structural integrity supporting enhanced connectivity - between right amygdala and anterior cingulate cortex in PTSD. This effect was strongest among Gulf War veterans without chronic multisymptom illness. The association of both MD and FA in the right cingulum with PTSD severity, and with heightened glucocorticoid responsivity, suggests that these DTI findings are a reflection of current PTSD illness expression. Although based on a small sample, these microstructural observations are consistent with a functional model suggesting increased amygdala responsivity in association with anterior cingulate modulation in PTSD. (C) 2014 Published by Elsevier Ltd. C1 [Bierer, Linda M.; Ivanov, Iliyan; Golier, Julia A.; Yehuda, Rachel] Icahn Sch Med Mt Sinai, Dept Psychiat, Traumat Stress Studies Div, New York, NY 10029 USA. [Bierer, Linda M.; Ivanov, Iliyan; Golier, Julia A.; Yehuda, Rachel] James J Peters VA Med Ctr, Traumat Stress Studies Div, Bronx, NY 10468 USA. [Carpenter, David M.; Wong, Edmund W.; Tang, Cheuk Y.] Icahn Sch Med Mt Sinai, Dept Radiol, New York, NY 10029 USA. RP Bierer, LM (reprint author), James J Peters VAMC, OOMH, 116-A,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM Linda.Bierer@va.gov FU VA MERIT entitled "Glucocorticoid Responsivity in Gulf War Veterans"; National Center for Research Resources, National Institutes of Health [5 MO1 RR00071] FX This work was supported principally by a VA MERIT entitled "Glucocorticoid Responsivity in Gulf War Veterans." In addition, partial support was obtained through a grant (5 MO1 RR00071) to the Mount Sinai General Clinical Research Center from the National Center for Research Resources, National Institutes of Health. NR 71 TC 2 Z9 3 U1 4 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN PY 2015 VL 51 BP 567 EP 576 DI 10.1016/j.psyneuen.2014.11.007 PG 10 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA AY5BI UT WOS:000347588000052 PM 25465169 ER PT J AU Neumeister, A Seidel, J Ragen, BJ Pietrzak, RH AF Neumeister, Alexander Seidel, Jordan Ragen, Benjamin J. Pietrzak, Robert H. TI Translational evidence for a role of endocannabinoids in the etiology and treatment of posttraumatic stress disorder SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE PTSD; Endocannabinoids; 5-Factor PTSD model; Anxious arousal; Treatment ID VENLAFAXINE EXTENDED-RELEASE; CHRONIC UNPREDICTABLE STRESS; RANDOMIZED CONTROLLED-TRIAL; NATIONAL COMORBIDITY SURVEY; QUALITY-OF-LIFE; GENDER-DIFFERENCES; CANNABINOID RECEPTORS; HIPPOCAMPAL CB1; 5-FACTOR MODEL; PTSD SYMPTOMS AB Introduction: Posttraumatic stress disorder (PTSD) is a prevalent, chronic, and disabling anxiety disorder that may develop following exposure to a traumatic event. Despite the public health significance of PTSD, relatively little is known about the etiology or pathophysiology of this disorder, and pharmacotherapy development to date has been largely opportunistic instead of mechanism-based. Recently, an accumulating body of evidence has implicated the endocannabinoid system in the etiology of PTSD, and targets within this system are believed to be suitable for treatment development. Methods: Herein, we describe evidence from translational studies arguing for the relevance of the endocannabinoid system in the etiology of PTSD. We also show mechanisms relevant for treatment development. Results: There is convincing evidence from multiple studies for reduced endocannabinoid availability in PTSD. Brain imaging studies show molecular adaptations with elevated cannabinoid type 1 (CB1) receptor availability in PTSD which is linked to abnormal threat processing and anxious arousal symptoms. Conclusion: Of particular relevance is evidence showing reduced levels of the endocannabinoid anandamide and compensatory increase of CB1 receptor availability in PTSD, and an association between increased CB1 receptor availability in the amygdala and abnormal threat processing, as well as increased severity of hyperarousal, but not dysphoric symptomatology, in trauma survivors. Given that hyperarousal symptoms are the key drivers of more disabling aspects of PTSD such as emotional numbing or suicidality, novel, mechanism-based pharmacotherapies that target this particular symptom cluster in patients with PTSD may have utility in mitigating the chronicity and morbidity of the disorder. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Neumeister, Alexander; Seidel, Jordan; Ragen, Benjamin J.] NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA. [Neumeister, Alexander] NYU, Sch Med, Dept Radiol, New York, NY 10016 USA. [Pietrzak, Robert H.] VA Connecticut Healthcare Syst, US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, Clin Neurosci Div, West Haven, CT USA. [Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RP Neumeister, A (reprint author), NYU, Sch Med, Mol Imaging Program Anxiety & Mood Disorders, One Pk Ave,8th Floor,Room 225, New York, NY 10016 USA. EM alexander.neumeister@nyumc.org FU National Institutes of Health (NIH) [R21MH096105, R21MH085627, RO1MH096876, R01MH102566]; Office of the Assistant Secretary of Defense for Health Affairs [W81XWH-14-1-0084]; Pfizer, Inc.; Lilly, Inc. FX This project was supported by the National Institutes of Health (NIH) through the following awards: R21MH096105, R21MH085627, RO1MH096876 and R01MH102566; the Office of the Assistant Secretary of Defense for Health Affairs under Award No. W81XWH-14-1-0084. The Clinical Neurosciences Division of the United States Department of Veterans Affairs National Center for Posttraumatic Stress Disorder. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense, the NIH or VA.; Dr. Neumeister has received consulting fees from Pfizer, Inc. This activity is unrelated to the present publication. Dr. Neumeister has received grant support from Lilly, Inc. which is unrelated to the present publication. Dr. Pietrzak is a scientific consultant to Cogstate, Ltd. and this activity is unrelated to the present report. NR 84 TC 15 Z9 15 U1 4 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN PY 2015 VL 51 BP 577 EP 584 DI 10.1016/j.psyneuen.2014.10.012 PG 8 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA AY5BI UT WOS:000347588000053 PM 25456347 ER PT J AU Yehuda, R Bierer, LM Pratchett, LC Lehrner, A Koch, EC Van Manen, JA Flory, JD Makotkine, I Hildebrandt, T AF Yehuda, Rachel Bierer, Linda M. Pratchett, Laura C. Lehrner, Amy Koch, Erin C. Van Manen, Jaklyn A. Flory, Janine D. Makotkine, Iouri Hildebrandt, Tom TI Cortisol augmentation of a psychological treatment for warfighters with posttraumatic stress disorder: Randomized trial showing improved treatment retention and outcome SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE PTSD; Prolonged exposure; Hydrocortisone; Pharmacological augmentation strategies; Psychotherapy; Glucocorticoid receptor; Veterans; Treatment outcome ID PROLONGED EXPOSURE THERAPY; BASOLATERAL AMYGDALA; CONDITIONED FEAR; GLUCOCORTICOID ENHANCEMENT; NORADRENERGIC ACTIVATION; MEMORY; RATS; PTSD; EXTINCTION; RETRIEVAL AB Background: Prolonged exposure (PE) therapy for post-traumatic stress disorder (PTSD) in military veterans has established efficacy, but is ineffective for a substantial number of patients. PE is also associated with high dropout rates. We hypothesized that hydrocortisone augmentation would enhance symptom improvement and reduce drop-out rates by diminishing the distressing effects of traumatic memories retrieved during imaginal exposure. We also hypothesized that in responders, hydrocortisone augmentation would be more effective in reversing glucocorticoid indices associated with PTSD than placebo augmentation. Method: Twenty-four veterans were randomized to receive either 30 mg oral hydrocortisone or placebo prior to PE sessions 3-10 in a double-blind protocol. Glucocorticoid receptor sensitivity was assessed in cultured peripheral blood mononuclear cells (PBMC) using the in vitro lysozyme inhibition test and was determined before and after treatment. Intent-to-treat analysis was performed using latent growth curve modeling of treatment effects on change in PTSD severity over time. Veterans who no longer met diagnostic criteria for PTSD at post-treatment were designated as responders. Results: Veterans randomized to hydrocortisone or placebo augmentation did not differ significantly in clinical severity or glucocorticoid sensitivity at pre-treatment. Hydrocortisone augmentation was associated with greater reduction in total PTSD symptoms compared to placebo, a finding that was explained by significantly greater patient retention in the hydrocortisone augmentation condition. A significant treatment condition by responder status interaction for glucocorticoid sensitivity indicated that responders to hydrocortisone augmentation had the highest pre-treatment glucocorticoid sensitivity (lowest lysozyme IC50-DEX) that diminished over the course of treatment. There was a significant association between decline in glucocorticoid responsiveness and improvement in PTSD symptoms among hydrocortisone recipients. Conclusions: The results of this pilot study suggest that hydrocortisone augmentation of PE may result in greater retention in treatment and thereby promote PTSD symptom improvement. Further, the results suggest that particularly elevated glucocorticoid responsiveness at pre-treatment may identify veterans likely to respond to PE combined with an intervention that targets glucocorticoid sensitivity. Confirmation of these findings will suggest that pharmacologic interventions that target PTSD-associated glucocorticoid dysregulation may be particularly helpful in promoting a positive clinical response to PTSD psychotherapy. Published by Elsevier Ltd. C1 [Yehuda, Rachel; Bierer, Linda M.; Pratchett, Laura C.; Lehrner, Amy; Koch, Erin C.; Van Manen, Jaklyn A.; Flory, Janine D.; Makotkine, Iouri] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Yehuda, Rachel; Bierer, Linda M.; Pratchett, Laura C.; Lehrner, Amy; Flory, Janine D.; Makotkine, Iouri; Hildebrandt, Tom] Icahn Sch Med Mt Sinai, Dept Psychiat, Traumat Stress Studies Div, New York, NY 10029 USA. RP Yehuda, R (reprint author), James J Peters VA Med Ctr, OOMH, 116-A,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM Rachel.yehuda@va.gov OI Hildebrandt, Thomas/0000-0001-7054-9590 FU Lightfighters Trust Foundation [LFT2009-02-1]; Department of Defense (DOD) [W81XWH-10-2-0072] FX This work was supported by a grant from the Lightfighters Trust Foundation (LFT2009-02-1) entitled, 'Cortisol augmentation of a psychological treatment in warfighters with PTSD.'; Additional support received from a grant from the Department of Defense (DOD W81XWH-10-2-0072) entitled, 'Improving PTSD outcomes in OIF/OEF returnees: A randomized clinical trial of hydrocortisone augmentation of prolonged exposure therapy.' NR 48 TC 23 Z9 23 U1 3 U2 24 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN PY 2015 VL 51 BP 589 EP 597 DI 10.1016/j.psyneuen.2014.08.004 PG 9 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA AY5BI UT WOS:000347588000055 PM 25212409 ER PT J AU Waye, C Wong, M Lee, S AF Waye, Courtney Wong, Mark Lee, Shuko TI Implementation of a CIWA-Ar Alcohol Withdrawal Protocol in a Veterans Hospital SO SOUTHERN MEDICAL JOURNAL LA English DT Article DE alcohol-withdrawal syndrome; alcohol detoxification; Clinical Institute Withdrawal Assessment for Alcohol Scale; fixed-dose benzodiazepine; revised; symptom-triggered benzodiazepine ID SCALE; MANAGEMENT AB Objectives The South Texas Veterans Health Care System (STVHCS) implemented a Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar)-based alcohol-withdrawal protocol in June 2013. The aim of this study was to determine the efficacy and safety of the new protocol. The primary objective was the evaluation of whether implementation of the CIWA-Ar alcohol-withdrawal protocol decreased the average length of hospital stay for patients admitted with alcohol withdrawal syndrome (AWS) as compared with treatment before the introduction of the protocol. Secondary endpoints evaluated benzodiazepine (BZD)-prescribing practices, use of adjunctive medications for AWS, and safety outcomes. Methods We reviewed 748 admissions with documented AWS or alcohol-related diagnoses during the study periods of July 2012 to December 2012 (preprotocol) and July 2013 to December 2013 (postprotocol). Patients in the preprotocol group needed to have a scheduled dose of a BZD in the electronic medical record, and those assigned to the postprotocol group needed to have at least one documented CIWA-Ar note in their electronic medical record. Exclusion criteria included prior conditions that interfered with accurate treatment of alcohol withdrawal. Results There were no statistical differences in baseline characteristics between groups. No difference was found in the primary endpoint of length of stay when comparing hospitalizations pre- and postprotocol implementation (3.84 2.31 days vs 3.82 +/- 2.7 days; P = 0.667). There was no statistical significance in total cumulative dose of BZD, daily dose of BZD, or duration of BZD use when compared pre- and postprotocol. No safety events requiring further intervention occurred. Conclusions Implementation of a CIWA-Ar protocol at our institution did not result in a decreased duration of hospital stay; however, a decline in prescribing fixed-schedule BZDs was documented. C1 South Texas Vet Hlth Care Syst, Serv Pharm, San Antonio, TX 78229 USA. Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ Res Ctr, San Antonio, TX 78229 USA. Univ Texas Austin, Pharmacotherapy Div, Coll Pharm, Austin, TX 78712 USA. South Texas Vet Hlth Care Syst, Res & Dev, San Antonio, TX 78229 USA. RP Waye, C (reprint author), South Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd 119, San Antonio, TX 78229 USA. EM courtney.waye@va.gov NR 16 TC 1 Z9 1 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0038-4348 EI 1541-8243 J9 SOUTH MED J JI South.Med.J. PD JAN PY 2015 VL 108 IS 1 BP 23 EP 28 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA AZ0QJ UT WOS:000347949500006 PM 25580753 ER PT J AU Collins, SP Storrow, AB Levy, PD Albert, N Butler, J Ezekowitz, JA Felker, GM Fermann, GJ Fonarow, GC Givertz, MM Hiestand, B Hollander, JE Lanfear, DE Pang, PS Peacock, WF Sawyer, DB Teerlink, JR Lenihan, DJ AF Collins, Sean P. Storrow, Alan B. Levy, Phillip D. Albert, Nancy Butler, Javed Ezekowitz, Justin A. Felker, G. Michael Fermann, Gregory J. Fonarow, Gregg C. Givertz, Michael M. Hiestand, Brian Hollander, Judd E. Lanfear, David E. Pang, Peter S. Peacock, W. Frank Sawyer, Douglas B. Teerlink, John R. Lenihan, Daniel J. TI Early Management of Patients With Acute Heart Failure: State of the Art and Future Directions-A Consensus Document from the SAEM/HFSA Acute Heart Failure Working Group SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID BRAIN NATRIURETIC PEPTIDE; RANDOMIZED CONTROLLED-TRIAL; IN-HOSPITAL MORTALITY; PULMONARY ARTERIAL-HYPERTENSION; EMERGENCY-DEPARTMENT PATIENTS; RIGHT-VENTRICULAR DYSFUNCTION; PRESERVED SYSTOLIC FUNCTION; NATIONAL REGISTRY ADHERE; END-DIASTOLIC PRESSURE; RISK STRATIFICATION AB Heart failure (HF) afflicts nearly 6 million Americans, resulting in 1million emergency department (ED) visits and over 1million annual hospital discharges. The majority of inpatient admissions originate in the ED; thus, it is crucial that emergency physicians and other providers involved in early management understand the latest developments in diagnostic testing, therapeutics, and alternatives to hospitalization. This article discusses contemporary ED management as well as the necessary next steps for ED-based acute HF research. C1 [Collins, Sean P.; Storrow, Alan B.; Sawyer, Douglas B.] Vanderbilt Univ, Nashville Vet Affairs Med Ctr, Dept Emergency Med, Nashville, TN 37235 USA. [Levy, Phillip D.] Wayne State Univ, Dept Emergency Med, Detroit, MI USA. [Fermann, Gregory J.] Univ Cincinnati, Dept Emergency Med, Cincinnati, OH USA. [Givertz, Michael M.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA. [Hiestand, Brian] Wake Forest Univ, Dept Emergency Med, Winston Salem, NC 27109 USA. [Hollander, Judd E.] Thomas Jefferson Univ, Dept Emergency Med, Philadelphia, PA 19107 USA. [Pang, Peter S.] Northwestern Univ, Dept Emergency Med, Chicago, IL 60611 USA. [Peacock, W. Frank] Baylor Univ, Dept Emergency Med, Houston, TX 77030 USA. [Albert, Nancy] Cleveland Clin, Div Cardiol, Cleveland, OH 44106 USA. [Butler, Javed] Emory Univ, Div Cardiol, Atlanta, GA 30322 USA. [Ezekowitz, Justin A.] Univ Alberta, Div Cardiol, Edmonton, AB, Canada. [Felker, G. Michael] Duke Univ, Div Cardiol, Durham, NC USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Div Cardiol, Los Angeles, CA USA. [Lanfear, David E.] Wayne State Univ, Div Cardiol, Detroit, MI USA. [Teerlink, John R.] Univ Calif San Francisco, Div Cardiol, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. [Lenihan, Daniel J.] Vanderbilt Univ, Div Cardiol, Nashville Vet Affairs Med Ctr, Nashville, TN 37232 USA. RP Collins, SP (reprint author), Vanderbilt Univ, Nashville Vet Affairs Med Ctr, Dept Emergency Med, 221 Kirkland Hall, Nashville, TN 37235 USA. EM sean.collins@vanderbilt.edu RI Ezekowitz, Justin/C-4579-2013 OI Ezekowitz, Justin/0000-0002-2724-4086; Hollander, Judd/0000-0002-1318-2785 FU NIH/NHLBI [K12HL1090]; Medtronic; Cardiorentis; Abbott Point-of-Care; Novartis; Medicines Company; Astellas; Intersection Medical; Radiometer; Abbott Diagnostics; Centers for Medicaid and Medicare Services (CMS); National Center for Advancing Translational Sciences [UL1TR000445]; Roche Diagnostics; National Institutes of Health; European Union; Health Resources Service Administration; NIH; Amgen; Trevena; Portola; Siemens; Mayday Foundation; Pfizer; NHLBI; Sanofi Aventis; Dyax; Insys; Novartis Pharmaceuticals; Cardiorentis Inc.; Trevena Inc.; Mespere; BG Medicine; NIH/NIMHD [5 R01 MD005849-04]; Alere; Abbott; Acorda Therapeutics Inc.; Cardio3 Bioscience; Cytokinetics; Sorbent Therapeutics; St. Jude FX SC-Research support from NIH/NHLBI, Medtronic, Cardiorentis, Abbott Point-of-Care, Novartis, The Medicines Company, Astellas, Intersection Medical, and Radiometer; consultant for Trevena, Novartis, Otsuka, Radiometer, The Medicines Company, Medtronic, BRAHMS, Insys, Intersection Medical, and Cardioxyl.; ABS-Current or recent grant support from Abbott Diagnostics, Centers for Medicaid and Medicare Services (CMS), NIH/NHLBI (K12HL1090), UL1TR000445 National Center for Advancing Translational Sciences, and Roche Diagnostics; current consultant for Roche Diagnostics, Novartis Pharmaceuticals Corp., Alere Diagnostics, Trevena, and Beckman Coulter.; JB-Research support from the National Institutes of Health, European Union, and Health Resources Service Administration; consultant for Amgen, Bayer, BG Medicine, Cardiocell, Celladon, Gambro, GE Healthcare, Medtronic, Novartis, Ono Pharma, Takeda, Trevena, and Zensun.; GMF-Consultant for Novartis, Amgen, Trevena, Roche Diagnostics, Singulex, Sorbent Therapeutics, and BMS; research funding from NIH, Novartis, Amgen, and Roche Diagnostics.; GJF-Research support from Novartis, Cardiorentis, Trevena, Portola, Radiometer, Medtronic, Siemens, Insys, The Mayday Foundation, and Pfizer; advisory board for Intersection Medical, Janssen, Insys, and The Medicines Company.; MMG-Scientific advisory board for Merck, Janssen, and Cardioxyl; grant support from NHLBI.; BH-Consulting relationship with Motive Medical Intelligence, Insight PD, and Intersection Medical Inc.; advisory board for Janssen Pharmaceuticals; research funding from The Medicines Company, Sanofi Aventis, Dyax, Radiometer, Cardiorentis, and Novartis.; PDL-Consultant for Novartis Pharmaceuticals, Trevena Inc., Intersection Medical, The Medicines Company, Ostuka, Janssen, Astellas, AstraZeneca, Beckman Coulter; research grant/support from Novartis Pharmaceuticals, Cardiorentis Inc., Trevena Inc., Intersection Medical, Mespere, and BG Medicine; support from NIH/NIMHD 5 R01 MD005849-04.; PSP-Consultant for Janssen, Medtronic, Novartis, Trevena, SpringLeafTx, BG Medicine, and Cornerstone Therapeutics; research support from Abbott, Alere, and NIH.; DBS-Grant support and consultant for Acorda Therapeutics Inc.; JT-Consulting fees/research grants from Amgen, Cardio3 Bioscience, Cytokinetics, Novartis, Sorbent Therapeutics, St. Jude, and Trevena. NR 162 TC 7 Z9 7 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JAN PY 2015 VL 22 IS 1 BP 94 EP 112 DI 10.1111/acem.12538 PG 19 WC Emergency Medicine SC Emergency Medicine GA AY2WW UT WOS:000347447900013 PM 25423908 ER PT J AU Bromley, E Mikesell, L Armstrong, NP Young, AS AF Bromley, Elizabeth Mikesell, Lisa Armstrong, Nikki Panasci Young, Alexander S. TI "You Might Lose Him Through the Cracks": Clinicians' Views on Discharge from Assertive Community Treatment SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Article DE Assertive Community Treatment; Serious mental illness; Community mental health; Therapeutic alliance ID INTENSIVE CASE-MANAGEMENT; MENTAL-HEALTH-SERVICES; TREATMENT TEAMS; CRITICAL INGREDIENTS; TREATMENT PROGRAM; RANDOMIZED-TRIAL; ACT; ADHERENCE; RECOVERY; ILLNESS AB Assertive Community Treatment (ACT) teams are increasingly interested in improving access to ACT through discharge of improved clients to less intensive mental health care services. We report results from a process evaluation of three teams in the VA's ACT program, Mental Health Intensive Case Management (MHICM), that began to implement discharge. MHICM clinicians (n = 15) describe significant barriers to discharge. Clinicians support the concept of discharge but raise concerns about clients' future stability, clients' feelings about discharge, and other aspects of the discharge process. We propose strategies that can be used to support clinicians and clients in discharge decision-making. C1 [Bromley, Elizabeth; Young, Alexander S.] Greater Los Angeles Dept Vet Affairs Healthcare C, Desert Pacific VA Mental Illness Res,Educ & Clin, Los Angeles, CA USA. [Bromley, Elizabeth; Young, Alexander S.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, Ctr Hlth Serv & Soc, Los Angeles, CA 90024 USA. [Bromley, Elizabeth] UCLA Ctr Hlth Serv & Soc, West Los Angeles VA Healthcare Ctr, Los Angeles, CA 90024 USA. [Mikesell, Lisa] Rutgers State Univ, Sch Commun & Informat, New Brunswick, NJ 08903 USA. [Armstrong, Nikki Panasci] San Francisco VA Med Ctr, San Francisco, CA USA. RP Bromley, E (reprint author), UCLA Ctr Hlth Serv & Soc, West Los Angeles VA Healthcare Ctr, 10920 Wilshire Blvd,Suite 300, Los Angeles, CA 90024 USA. EM ebromley@mednet.ucla.edu; mikesell.lisa@gmail.com; nikki@hawaii.edu; ayoung@mednet.ucla.edu NR 46 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-587X EI 1573-3289 J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD JAN PY 2015 VL 42 IS 1 BP 99 EP 110 DI 10.1007/s10488-014-0547-3 PG 12 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AY2EK UT WOS:000347401200011 PM 24692027 ER PT J AU Rasmussen, DD Kincaid, CL AF Rasmussen, Dennis D. Kincaid, Carrie L. TI Acoustic Startle in Alcohol-Na < ve Male Rats Predicts Subsequent Voluntary Alcohol Intake and Alcohol Preference SO ALCOHOL AND ALCOHOLISM LA English DT Article ID FEAR-POTENTIATED STARTLE; PREFERRING P RATS; ANXIETY DISORDERS; RECEPTOR ANTAGONIST; WISTAR RATS; ETHANOL; MODULATION; DRINKING; CONSUMPTION; WITHDRAWAL AB Aims: Acoustic startle response in rats is used to model sensorimotor reactivity. The aim of the study was to determine whether acoustic startle response in alcohol-na < ve rats predicts subsequent increased voluntary alcohol drinking or alcohol preference. Methods: Startle responses to 90, 95 and 100 decibel (dB) white noise stimuli presented in counterbalanced semi-randomized order were tested in alcohol-na < ve young adult male Wistar rats before voluntary alcohol intake was established with an intermittent alcohol access (IAA) model. Results: Startle amplitude in response to 95 or 100 dB stimuli was positively correlated with subsequent alcohol intake and alcohol preference following 3 months of IAA. Rats with high (median split) pre-IAA startle amplitude in response to 95 or 100 dB stimuli developed increased alcohol intake as well as increased alcohol preference following 3 months of IAA, relative to rats with low pre-IAA startle amplitude. Conclusion: Startle response to moderate acoustic stimuli can be a predictive index of vulnerability to developing increased alcohol drinking. C1 VA Puget Sound Hlth Care Syst, VISN Mental Illness Res Educ & Clin Ctr 20, Seattle, WA 98195 USA. Univ Washington, Seattle, WA 98195 USA. RP Rasmussen, DD (reprint author), VA Med Ctr, 116 MIRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM drasmuss@u.washington.edu FU US Army Medical Research Acquisition Activity CDMRP [W81XWH-13-1-0126]; National Institutes of Health [AA10567] FX This work was supported in part by resources from the VA Puget Sound Health Care System, Seattle, Washington; US Army Medical Research Acquisition Activity CDMRP (contract number W81XWH-13-1-0126); and National Institutes of Health (grant number AA10567). NR 32 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 EI 1464-3502 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD JAN-FEB PY 2015 VL 50 IS 1 BP 56 EP 61 DI 10.1093/alcalc/agu065 PG 6 WC Substance Abuse SC Substance Abuse GA AY2JL UT WOS:000347415400009 PM 25305255 ER PT J AU Kumar, PS Medina-Lezama, J Morey-Vargas, O Zamani, P Bolanos-Salazar, JF Chirinos, DA Haines, P Khan, ZA Coacalla-Guerra, JC Davalos-Robles, ME Llerena-Dongo, GR Zapata-Ponze, M Chirinos, JA AF Kumar, Prithvi Shiva Medina-Lezama, Josefina Morey-Vargas, Oscar Zamani, Payman Bolanos-Salazar, Juan F. Chirinos, Diana A. Haines, Philip Khan, Zubair A. Coacalla-Guerra, Johanna C. Davalos-Robles, Maria E. Llerena-Dongo, Gladys R. Zapata-Ponze, Mardelangel Chirinos, Julio A. CA PREVENCION Investigators TI Prospective Risk Factors for Increased Central Augmentation Index in Men and Women SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE augmentation index; blood pressure; hypertension; prospective; gender differences; wave reflections ID ARTERIAL WAVE REFLECTIONS; PERUVIAN ANDEAN HISPANICS; CENTRAL PULSE PRESSURE; CARDIOVASCULAR RISK; LONGITUDINAL OBSERVATIONS; ENDOTHELIAL FUNCTION; METABOLIC SYNDROME; AORTIC IMPEDANCE; REFERENCE VALUES; AGE DEPENDENCY AB BACKGROUND Arterial wave reflections are important determinants of central pressure pulsatility and left ventricular afterload. The augmentation index (AIx) is the most widely used surrogate of arterial wave reflections. Despite multiple cross-sectional studies assessing the correlates of AIx, little prospective data exist regarding changes in AIx over time. We aimed to assess the predictors of changes in AIx over time in adults from the general population. METHODS We performed radial arterial tonometry assessments a median of 3.18 +/- 0.4 years apart on 143 nondiabetic adult participants in the population-based PREVENCION study. Central AIx was obtained using the generalized transfer function of the Sphygmocor device. RESULTS Predictors of the change in AIx over time were investigated. Among men (n = 67), the change in AIx was predicted by abdominal obesity (standardized beta for waist circumference = 0.34; P = 0.002), impaired fasting glucose (standardized beta = 0.24; P = 0.009), and the change in heart rate (standardized beta = -0.78; P < 0.001). Among women (n = 76), the change in AIx was predicted by non-high-density lipoprotein cholesterol (standardized beta = 0.33; P = 0.001), C-reactive protein levels (standardized beta = 0.24; P = 0.02), change in mean arterial pressure (standardized beta = 0.33; P = 0.001), and change in heart rate (standardized beta = -0.52; P < 0.001). CONCLUSIONS Metabolic and inflammatory factors predicted changes in AIx over time, with important sex differences. Metabolic factors, such as abdominal obesity and impaired fasting glucose, predicted changes in AIx in men, whereas C-reactive protein and non-high-density lipoprotein cholesterol levels predicted changes in women. Our findings highlight the impact of sex on arterial properties and may guide the design of interventions to favorably impact changes in late systolic pressure augmentation. C1 [Kumar, Prithvi Shiva; Zamani, Payman; Bolanos-Salazar, Juan F.; Haines, Philip; Khan, Zubair A.; Chirinos, Julio A.] Philadelphia VA Med Ctr, Div Cardiol, Philadelphia, PA 19104 USA. [Kumar, Prithvi Shiva; Zamani, Payman; Bolanos-Salazar, Juan F.; Haines, Philip; Khan, Zubair A.; Chirinos, Julio A.] Univ Penn, Philadelphia, PA 19104 USA. [Medina-Lezama, Josefina; Coacalla-Guerra, Johanna C.; Davalos-Robles, Maria E.; Llerena-Dongo, Gladys R.; Zapata-Ponze, Mardelangel] Santa Maria Catholic Univ, Dept Med, Arequipa, Peru. [Morey-Vargas, Oscar] Mayo Clin, Dept Med, Rochester, MN USA. [Chirinos, Diana A.] Univ Miami, Dept Psychol, Miami, FL USA. RP Kumar, PS (reprint author), Philadelphia VA Med Ctr, Div Cardiol, Philadelphia, PA 19104 USA. EM prithvisk@gmail.com OI Khan, Zubair/0000-0002-0451-9155 FU FOCUS Junior Faculty Investigator Award; Edna G. Kynett Memorial Foundation; Santa Maria Research Institute (Arequipa, Peru); [5-T32-HL007843-17]; [UL1RR024134] FX This work was supported through a FOCUS Junior Faculty Investigator Award for Research in Women's Cardiovascular Health supported by the Edna G. Kynett Memorial Foundation and the Santa Maria Research Institute (Arequipa, Peru). Payman Zamani received research and salary support from 5-T32-HL007843-17 and UL1RR024134. The abstract of this work was presented at the American College of Cardiology Scientific Annual Meeting 2013. NR 37 TC 2 Z9 2 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0895-7061 EI 1941-7225 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JAN PY 2015 VL 28 IS 1 BP 121 EP 126 DI 10.1093/ajh/hpu093 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AY2JI UT WOS:000347415100016 ER PT J AU Kohno, M Ghahremani, DG Morales, AM Robertson, CL Ishibashi, K Morgan, AT Mandelkern, MA London, ED AF Kohno, Milky Ghahremani, Dara G. Morales, Angelica M. Robertson, Chelsea L. Ishibashi, Kenji Morgan, Andrew T. Mandelkern, Mark A. London, Edythe D. TI Risk-Taking Behavior: Dopamine D2/D3 Receptors, Feedback, and Frontolimbic Activity SO CEREBRAL CORTEX LA English DT Article DE decision-making; dopamine receptors; fMRI; pet; risk-taking; striatum ID NUCLEUS-ACCUMBENS DOPAMINE; EXCITATORY AMINO-ACIDS; REFERENCE TISSUE MODEL; DECISION-MAKING; PREFRONTAL CORTEX; SUBCORTICAL CIRCUITS; COGNITIVE CONTROL; WORKING-MEMORY; FRONTAL-CORTEX; HUMAN BRAIN AB Decision-making involves frontolimbic and dopaminergic brain regions, but how prior choice outcomes, dopamine neurotransmission, and frontostriatal activity are integrated to affect choices is unclear. We tested 60 healthy volunteers using the Balloon Analogue Risk Task (BART) during functional magnetic resonance imaging. In the BART, participants can pump virtual balloons to increase potential monetary reward or cash out to receive accumulated reward; each pump presents greater risk and potential reward (represented by the pump number). In a separate session, we measured striatal D2/D3 dopamine receptor binding potential (BPND) with positron emission tomography in 13 of the participants. Losses were followed by fewer risky choices than wins; and during risk-taking after loss, amygdala and hippocampal activation exhibited greater modulation by pump number than after a cash-out event. Striatal D2/D3 BPND was positively related to the modulation of ventral striatal activation when participants decided to cash out and negatively to the number of pumps in the subsequent trial; but negatively related to the modulation of prefrontal cortical activation by pump number when participants took risk, and to overall earnings. These findings provide in vivo evidence for a potential mechanism by which dopaminergic neurotransmission may modulate risk-taking behavior through an interactive system of frontal and striatal activity. C1 [Kohno, Milky; Ghahremani, Dara G.; Morales, Angelica M.; Ishibashi, Kenji; Morgan, Andrew T.; London, Edythe D.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Kohno, Milky; Morales, Angelica M.; London, Edythe D.] Univ Calif Los Angeles, Neurosci Interdept Program, Los Angeles, CA 90024 USA. [Robertson, Chelsea L.; London, Edythe D.] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA. [London, Edythe D.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. [London, Edythe D.] Univ Calif Los Angeles, Semel Inst, Los Angeles, CA 90024 USA. [Robertson, Chelsea L.; Ishibashi, Kenji; Morgan, Andrew T.; Mandelkern, Mark A.; London, Edythe D.] Univ Calif Irvine, Vet Adm Greater Los Angeles Healthcare Syst, Irvine, CA USA. [Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP London, ED (reprint author), Univ Calif Los Angeles, Semel Inst, 740 Westwood Plaza,C8-831, Los Angeles, CA 90024 USA. EM elondon@mednet.ucla.edu RI Morales, Angelica/P-4108-2015 OI Morgan, Andrew/0000-0001-6017-2179 FU NIH [P20 DA022539, R01 DA020726, F31 DA033120-02, F31 DA0331-17]; Philip Morris USA; [T32 DA 024635] FX The research described here was funded in part by NIH grants P20 DA022539 and R01 DA020726, a grant from Philip Morris USA, and endowments from the Thomas P. and Katherine K. Pike Chair in Addiction Studies, and the Marjorie M. Greene Trust. M. K., A. M. M., and C.L.R. were supported by training grant T32 DA 024635. M. K. and A. M. M. were also supported by NIH grants F31 DA033120-02 and F31 DA0331-17, respectively. None of the sponsors were involved with the design, collection, analysis or interpretation of data, writing the manuscript, or the decision to submit the manuscript for publications. NR 63 TC 21 Z9 21 U1 2 U2 13 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD JAN PY 2015 VL 25 IS 1 BP 236 EP 245 DI 10.1093/cercor/bht218 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AY2KA UT WOS:000347417600022 PM 23966584 ER PT J AU Dewan, NA Nieto, FJ Somers, VK AF Dewan, Naresh A. Nieto, F. Javier Somers, Virend K. TI Intermittent Hypoxemia and OSA Implications for Comorbidities SO CHEST LA English DT Editorial Material ID OBSTRUCTIVE SLEEP-APNEA; POSITIVE AIRWAY PRESSURE; SYMPATHETIC-NERVE RESPONSES; HYPOXIA-INDUCIBLE FACTORS; LONG-TERM EFFICACY; BLOOD-PRESSURE; MOUSE MODEL; NEUROCOGNITIVE FUNCTION; CARDIOVASCULAR-DISEASE; ATRIAL-FIBRILLATION AB OSA is a common chronic disorder that is associated with significant morbidity and mortality including cardiovascular, metabolic, and neurocognitive disease and increased cancer-related deaths. OSA is characterized by recurrent episodes of apneas and hypopneas associated with repetitive episodes of intermittent hypoxemia, intrathoracic pressure changes, and arousals. Intermittent hypoxemia (IH) is now being recognized as a potential major factor contributing to the pathogenesis of OSA-related comorbidities. OSA-related high-frequency IH is characterized by cycles of hypoxemia with reoxygenation that is distinctly different than sustained low-frequency hypoxia and contributes to ischemia-reperfusion injury. Data from both animal and human studies support mechanistic links between IH and its adverse impact at the tissue level. IH promotes oxidative stress by increased production of reactive oxygen species and angiogenesis, increased sympathetic activation with BP elevation, and systemic and vascular inflammation with endothelial dysfunction that contributes to diverse multiorgan chronic morbidity and mortality affecting cardiovascular disease, metabolic dysfunction, cognitive decline, and progression of cancer. Data from observational studies in large population groups also support the role for hypoxia in the pathogenesis of OSA comorbidity. Treatment with CPAP to reverse OSA-related symptoms and comorbidities has been shown to provide variable benefit in some but not all patient groups. Early treatment with CPAP makes intuitive sense to promote maximal functional recovery and minimize residual injury. More studies are needed to determine the interacting effects of IH and obesity, differential effects of both short-term and long-term hypoxemia, and the effect of CPAP treatment. C1 [Dewan, Naresh A.] Creighton Univ, Dept Med, Div Pulm Crit Care & Sleep Med, Omaha, NE 68178 USA. US Dept Vet Affairs, Omaha VA Med Ctr, Pulm Sect, Omaha, NE USA. Univ Wisconsin, Sch Med & Publ Hlth, Board Regents Univ Wisconsin Syst, Madison, WI USA. Mayo Clin, Mayo Fdn Med Educ & Res, Coll Med, Sleep & Cardiovasc Clin Res Unit, Rochester, MN USA. RP Dewan, NA (reprint author), Creighton Univ, Dept Med, Div Pulm Crit Care & Sleep Med, Omaha, NE 68178 USA. FU National Institutes of Health (NIH) [R01HL062252-11]; University of Wisconsin; NIH [HL-65176] FX Dr Nieto's contributions were supported in part by the National Institutes of Health (NIH) [Grant R01HL062252-11] and by the University of Wisconsin Helfaer Endowed Chair of Public Health. Dr Somers' contribution to this work was supported by the NIH [Grant HL-65176]. NR 86 TC 47 Z9 54 U1 2 U2 28 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2015 VL 147 IS 1 BP 266 EP 274 DI 10.1378/chest.14-0500 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AY3AH UT WOS:000347456500047 PM 25560865 ER PT J AU Wang, J Vodovotz, Y Fan, LY Li, YH Liu, Z Namas, R Barclay, D Zamora, R Billiar, TR Wilson, MA Fan, J Jiang, Y AF Wang, Juan Vodovotz, Yoram Fan, Liyan Li, Yuehua Liu, Zheng Namas, Rami Barclay, Derek Zamora, Ruben Billiar, Timothy R. Wilson, Mark A. Fan, Jie Jiang, Yong TI Injury-induced MRP8/MRP14 stimulates IP-10/CXCL10 in monocytes/macrophages SO FASEB JOURNAL LA English DT Article DE IFN regulatory factor 3; myeloid-related protein; Toll-like receptor 4 ID NF-KAPPA-B; INDUCIBLE PROTEIN-10 PRODUCTION; DOUBLE-STRANDED-RNA; TOLL-LIKE RECEPTORS; REGULATORY T-CELLS; IFN-GAMMA; ENDOTHELIAL-CELLS; TNF-ALPHA; CPG OLIGODEOXYNUCLEOTIDES; NEUTROPHIL MIGRATION AB Trauma/hemorrhagic shock is associated with morbidity and mortality due to dysregulated inflammation, which is driven in part by monocytes/macrophages stimulated by injury-induced release of damage-associated molecular pattern (DAMP) molecules. MRP8/MRP14 is an endogenous DAMP involved in various inflammatory diseases, though its mechanism of action is unclear. Circulating MRP8/MRP14 levels in human blunt trauma nonsurvivors were significantly lower than those of survivors (P < 0.001). Human monocytic THP-1 cells stimulated with MRP8/MRP14 expressed the chemokine IFN-gamma inducible protein 10 (IP-10)/CXCL10. Circulating IP-10 levels in human blunt trauma patients were correlated positively with MRP8/MRP14 levels (r = 0.396, P < 0.001), and were significantly lower in trauma nonsurvivors than in survivors (P < 0.001). We therefore sought to determine the mechanisms by which MRP8/MRP14 stimulates IP-10 in monocytes/macrophages, and found that induction of IP-10 by MRP8/MRP14 required Toll-like receptor 4 and TRIF but not MyD88. Full induction of IP-10 by MRP8/MRP14 required synergy between the transcription factors NF-kappa B and IFN regulatory factor 3 (IRF3). The receptor for IP-10 is CXCR3, and MRP8/MRP14-induced chemotaxis of CXCR3(+) cells was dependent on the production of IP-10 in monocytes/macrophages. Furthermore, in vivo study with a mouse trauma/hemorrhagic shock model showed that administration of neutralizing antibody against MRP8 prevented activation of NF-kB and IRF3 as well as IP-10 production. Thus, the current study identified a novel signaling mechanism that controls IP-10 expression in monocytes/macrophages by MRP8/MRP14, which may play an important role in injury-induced inflammation. C1 [Wang, Juan; Liu, Zheng; Fan, Jie; Jiang, Yong] Southern Med Univ, State Key Lab Organ Failure Res, Key Lab Transcript & Prote, Minist Educ China,Key Lab Prote Guangdong Prov, Guangzhou 510515, Guangdong, Peoples R China. [Wang, Juan; Vodovotz, Yoram; Li, Yuehua; Namas, Rami; Barclay, Derek; Zamora, Ruben; Billiar, Timothy R.; Wilson, Mark A.; Fan, Jie] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Wilson, Mark A.; Fan, Jie] Vet Affairs Pittsburgh Healthcare Syst, Res & Dev, Pittsburgh, PA USA. [Fan, Liyan] Univ Pittsburgh, Sch Arts & Sci, Pittsburgh, PA USA. [Vodovotz, Yoram; Billiar, Timothy R.; Fan, Jie] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA USA. RP Jiang, Y (reprint author), Southern Med Univ, Dept Pathophysiol, Guangzhou 510515, Guangdong, Peoples R China. EM jif7@pitt.edu; jiang48231@163.com OI Namas, Rami/0000-0002-8582-5321 FU BLRD VA [I01 BX002729]; NHLBI NIH HHS [R01 HL079669, R01-HL-079669]; NIGMS NIH HHS [P50 GM053789, P50-GM-53789] NR 60 TC 11 Z9 12 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD JAN PY 2015 VL 29 IS 1 BP 250 EP 262 DI 10.1096/fj.14-255992 PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AY1UX UT WOS:000347378600024 PM 25342131 ER PT J AU Markland, A Wang, L Jelovsek, JE Brubaker, L Tuteja, A Weidner, AC LoSavio, A Corton, M Meikle, S Richter, HE AF Markland, Alayne Wang, Lu Jelovsek, J. Eric Brubaker, Linda Tuteja, Ashook Weidner, Alison C. LoSavio, Andelka Corton, Marlene Meikle, Susan Richter, Holly E. TI Symptom Improvement in Women After Fecal Incontinence Treatments: A Multicenter Cohort Study of the Pelvic Floor Disorders Network SO FEMALE PELVIC MEDICINE AND RECONSTRUCTIVE SURGERY LA English DT Article DE fecal incontinence; cohort study; surgical treatment; nonsurgical treatment; quality of life ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; BIOFEEDBACK; QUESTIONNAIRE; EPIDEMIOLOGY; POPULATION; OUTCOMES; PATIENT; ADULTS AB Objectives: The study aims were to characterize women with fecal incontinence (FI) and measure changes in FI severity and quality of life 3 and 12 months after treatment. Methods: This study is a secondary analysis of a multicenter study measuring adaptive behaviors among women with FI. Women included had a primary complaint of at least monthly FI over 3 consecutive months and planned FI treatment. Demographic and medical history data were obtained at baseline. Data were collected at baseline, 3 months, and 12 months after clinically selected, nonstandardized treatment. Validated questionnaires were as follows: Fecal Incontinence Severity Index, Modified Manchester Health Questionnaire, Pelvic Floor Disorders Inventory's Colorectal and Anal Distress Inventory, Pelvic Floor Impact Questionnaire's Colorectal and Anal Impact Questionnaire, and Medical Outcomes Study Short Form. Questionnaire score changes from baseline were compared using paired t tests at 3 and 12 months after treatment. Results: Of the 133 women enrolled, 90 women had treatment data at 3 months and 77 at 12 months. Nonsurgical therapies were the most common (78%) with anal sphincter repair in 22%. Fecal Incontinence Severity Index scores and Modified Manchester Health Questionnaire scores significantly improved 3 months after nonsurgical and surgical treatments (-8.8 +/- 12.0 and -12.6 +/- 19.2, respectively, P < 0.001), as did Colorectal-Anal Distress Inventory and Colorectal-Anal Impact Questionnaire scores (-52.7 +/- 70.0 and -60.6 +/- 70.0, respectively, P < 0.001) and Medical Outcomes Study Short Form mental health scores (4.2 +/- 9.4, P = 0.001). Improvement persisted 12 months posttreatment. Conclusions: In women seeking care for FI, symptom severity and condition-specific quality of life significantly improve within the first 3 months after FI treatment and are maintained up to 12 months. C1 [Markland, Alayne] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Wang, Lu] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Jelovsek, J. Eric] Cleveland Clin, Dept Obstet Gynecol, Cleveland, OH 44106 USA. [Jelovsek, J. Eric] Cleveland Clin, Womens Hlth Inst, Cleveland, OH 44106 USA. [Brubaker, Linda] Loyola Univ Chicago, Stritch Sch Med, Dept Obstet & Gynecol, Chicago, IL USA. [Tuteja, Ashook] Univ Utah, Salt Lake City Vet Affairs Med Ctr, Dept Med, Salt Lake City, UT USA. [Weidner, Alison C.] Duke Univ, Dept Obstet & Gynecol, Durham, NC USA. [LoSavio, Andelka] Loyola Univ Chicago, Stritch Sch Med, Dept Med, Chicago, IL USA. [Corton, Marlene] Univ Texas Southwestern, Dept Obstet & Gynecol, Dallas, TX USA. [Meikle, Susan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Richter, Holly E.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL USA. RP Markland, A (reprint author), Birmingham Vet Affairs Med Ctr, Dept Med, Div Gerontol Geriatr & Palliat Care, GRECC 11-G,Room 8220,700 South 19th St, Birmingham, AL 35233 USA. EM amarkland@uabmc.edu OI Markland, Alayne/0000-0002-6567-6744 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health Office of Research on Women's Health [U01 HD41249, U10 HD41250, U10 HD41261, U10 HD41267, U10 HD54136, U10 HD54214, U10 HD54215, U10 HD54241] FX Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women's Health (U01 HD41249, U10 HD41250, U10 HD41261, U10 HD41267, U10 HD54136, U10 HD54214, U10 HD54215, and U10 HD54241). NR 29 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2151-8378 EI 2154-4212 J9 FEMALE PELVIC MED RE JI Female Pelvic Med. Reconstr. Surg. PD JAN-FEB PY 2015 VL 21 IS 1 BP 46 EP 52 DI 10.1097/SPV.0000000000000099 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AY3DN UT WOS:000347464800015 PM 25185613 ER PT J AU Gellad, WF Zhao, XH Thorpe, CT Mor, MK Good, CB Fine, MJ AF Gellad, Walid F. Zhao, Xinhua Thorpe, Carolyn T. Mor, Maria K. Good, Chester B. Fine, Michael J. TI Dual Use of Department of Veterans Affairs and Medicare Benefits and Use of Test Strips in Veterans With Type 2 Diabetes Mellitus SO JAMA INTERNAL MEDICINE LA English DT Article ID HEALTH-CARE-SYSTEM; BLOOD-GLUCOSE; PATIENT DATA; INSULIN; QUALITY; VA; METAANALYSIS; ENROLLEES; OUTCOMES; ACCESS AB IMPORTANCE Self-monitoring of blood glucose is a costly component of care for diabetes mellitus, with unclear benefits for patients not taking insulin. Veterans with dual Department of Veterans Affairs (VA) and Medicare benefits have access to test strips through both systems, raising the potential for overuse. OBJECTIVES To examine the patterns of test strip receipt among older veterans with diabetes and determine whether receipt of strips from dual health care systems is associated with overuse. DESIGN, SETTING, AND PARTICIPANTS We performed a cross-sectional, retrospective cohort study using national VA administrative data linked to Medicare Parts A, B, and D claims for fiscal years 2008 and 2009. A total of 363 996 community-dwelling veterans 65 years or older with diabetes who used the VA health care system and received test strips in fiscal year 2009 were included in the study. EXPOSURES Receipt of test strips from the VA only, Medicare only, or both the VA and Medicare; covariates included sociodemographics, comorbidity, diabetes complications, and hemoglobin A(1c) level. MAIN OUTCOMES AND MEASURES Quantity of test strips dispensed and overuse of test strips, defined as more than 1 strip per day (>365 strips per year) among those taking no diabetes medications, oral diabetes medications alone, or long-acting insulin without short-acting insulin or more than 4 strips per day (>1460 strips per year) among those taking short-acting insulin. RESULTS Overall, 260 688 older veterans (71.6%) with diabetes received strips from the VA only, 82 826 (22.8%) from Medicare only, and 20 482 (5.6%) from the VA and Medicare. Veterans receiving strips from both the VA and Medicare received more strips (median, 600; interquartile range [IQR], 350-1000) than the Medicare only (median, 400; IQR, 200-700) and VA only (median, 200; IQR, 100-500) groups (P<.001) and had substantially greater odds of overuse than the VA only group (55.4% vs 15.8%) (adjusted odds ratio [OR], 16.3; 95% CI, 14.6-18.1 for no medications; 55.3% vs 6.0%; OR, 19.8; 95% CI, 18.9-20.8 for oral medications; 87.4% vs 65.5%; OR, 3.69; 95% CI, 3.30-4.14 for long-acting insulin; and 32.8% vs 13.5%; OR, 3.24; 95% CI, 3.05-3.45 for short-acting insulin). Patterns were similar when using more conservative thresholds of overuse. CONCLUSIONS AND RELEVANCE Veterans who receive glucose test strips through both the VA and Medicare use more strips and are more likely to potentially overuse strips. These results illustrate the profound importance of understanding dual VA and Medicare coverage and are emblematic of waste and inefficiency. C1 [Gellad, Walid F.; Zhao, Xinhua; Thorpe, Carolyn T.; Mor, Maria K.; Good, Chester B.; Fine, Michael J.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. [Gellad, Walid F.; Good, Chester B.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Med, Pittsburgh, PA 15213 USA. [Thorpe, Carolyn T.; Good, Chester B.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Mor, Maria K.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Good, Chester B.] US Dept Vet Affairs, Pharm Benefits Management Serv, Hines, IL USA. RP Gellad, WF (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Univ Dr,Mail Code 151C, Pittsburgh, PA 15240 USA. EM walid.gellad@va.gov FU Veterans Affairs Health Services Research & Development Service [CDA 09-207]; Veterans Affairs Center for Health Equity Research and Promotion FX This study was supported by grant CDA 09-207 from the Veterans Affairs Health Services Research & Development Service and from pilot funding from the Veterans Affairs Center for Health Equity Research and Promotion (Dr Gellad). NR 45 TC 6 Z9 6 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN PY 2015 VL 175 IS 1 BP 26 EP 34 DI 10.1001/jamainternmed.2014.5405 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AY1BM UT WOS:000347328500011 PM 25383920 ER PT J AU Okulicz, JF Le, TD Agan, BK Camargo, JF Landrum, ML Wright, E Dolan, MJ Ganesan, A Ferguson, TM Smith, DM Richman, DD Little, SJ Clark, RA He, WJ Ahuja, SK AF Okulicz, Jason F. Le, Tuan D. Agan, Brian K. Camargo, Jose F. Landrum, Michael L. Wright, Edwina Dolan, Matthew J. Ganesan, Anuradha Ferguson, Tomas M. Smith, Davey M. Richman, Douglas D. Little, Susan J. Clark, Robert A. He, Weijing Ahuja, Sunil K. TI Influence of the Timing of Antiretroviral Therapy on the Potential for Normalization of Immune Status in Human Immunodeficiency Virus 1-Infected Individuals SO JAMA INTERNAL MEDICINE LA English DT Article ID HIV-INFECTED PATIENTS; T-CELL COUNTS; CLINICAL-OUTCOMES; CD4 COUNT; AIDS; RESTORATION; RESERVOIRS; INITIATION; RECOVERY; HAART AB IMPORTANCE In individuals with human immunodeficiency virus 1 (HIV-1) infection who are receiving antiretroviral therapy (ART), factors that promote full immune recovery are not well characterized. OBJECTIVE To investigate the influence of the timing of ART relative to HIV-1 infection on normalization of CD4(+) T-cell counts, AIDS risk, and immune function. DESIGN, SETTING, AND PARTICIPANTS Participants in the observational US Military HIV Natural History Study with documented estimated dates of seroconversion (EDS) who achieved virologic suppression with ART were evaluated. Markers indicative of immune activation, dysfunction, and responsiveness were determined. Responses to hepatitis B virus (HBV) vaccine, an indicator of in vivo immune function, were also assessed. The timing of ART was indexed to the EDS and/or entry into the cohort. The CD4(+) counts in HIV-1-uninfected populations were surveyed. MAIN OUTCOMES AND MEASURES Normalization of CD4(+) counts to 900 cells/mu L or higher, AIDS development, HBV vaccine response, as well as T-cell activation, dysfunction, and responsiveness. RESULTS The median CD4(+) count in HIV-1-uninfected populations was approximately 900 cells/mu L. Among 1119 HIV-1-infected participants, CD4(+) normalization was achieved in 38.4% vs 28.3% of those initiating ART within 12 months vs after 12 months from the EDS (P=.001). Incrementally higher CD4(+) recovery (<500, 500-899, and >= 900 cells/mu L) was associated with stepwise decreases in AIDS risk and reversion of markers of immune activation, dysfunction, and responsiveness to levels approximating those found in HIV-1-uninfected persons. Participants with CD4(+) counts of 500 cells/mu L or higher at study entry (adjusted odds ratio [aOR], 2.00; 95% CI, 1.51-2.64; P<.001) or ART initiation (aOR, 4.08; 95% CI, 3.14-5.30; P<.001) had significantly increased CD4(+) normalization rates compared with other participants. However, even among individuals with a CD4(+) count of 500 cells/mu L or higher at both study entry and before ART, the odds of CD4(+) normalization were 80% lower in those initiating ART after 12 months from the EDS and study entry (aOR, 0.20; 95% CI, 0.07-0.53; P=001). Initiation of ART within 12 months of EDS vs later was associated with a significantly lower risk of AIDS (7.8% vs 15.3%; P=.002), reduced T-cell activation (percent CD4(+) HLA-DR+ effector memory T cells, 12.0% vs 15.6%; P=.03), and increased responsiveness to HBV vaccine (67.9% vs 50.9%; P=.07). CONCLUSIONS AND RELEVANCE Deferral of ART beyond 12 months of the EDS diminishes the likelihood of restoring immunologic health in HIV-1-infected individuals. C1 [Okulicz, Jason F.; Agan, Brian K.; Landrum, Michael L.; Ganesan, Anuradha; Ferguson, Tomas M.] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD 20814 USA. [Okulicz, Jason F.] San Antonio Mil Med Ctr, Infect Dis Serv, Ft Sam Houston, TX USA. [Le, Tuan D.; Camargo, Jose F.; Clark, Robert A.; He, Weijing; Ahuja, Sunil K.] South Texas Vet Hlth Care Syst, Vet Affairs VA Res Ctr AIDS & HIV Infect 1, San Antonio, TX 78229 USA. [Le, Tuan D.; Camargo, Jose F.; Clark, Robert A.; He, Weijing; Ahuja, Sunil K.] South Texas Vet Hlth Care Syst, Vet Affairs Ctr Personalized Med, San Antonio, TX 78229 USA. [Le, Tuan D.; Camargo, Jose F.; Clark, Robert A.; He, Weijing; Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Agan, Brian K.] Henry M Jackson Fdn Adv Mil Med Inc, Bethesda, MD USA. [Landrum, Michael L.] Brooke Army Med Ctr, Infect Dis Serv, Ft Sam Houston, TX 78234 USA. [Wright, Edwina] Alfred Hosp, Dept Infect Dis, Melbourne, Vic, Australia. [Wright, Edwina] Burnet Inst, Melbourne, Vic, Australia. [Wright, Edwina] Monash Univ, Dept Infect Dis, Melbourne, Vic 3004, Australia. [Dolan, Matthew J.] Mil Med Inc, Henry M Jackson Fdn Adv, Lackland AFB, TX USA. [Ganesan, Anuradha] Walter Reed Natl Mil Med Ctr, Infect Dis Serv, Bethesda, MD USA. [Ferguson, Tomas M.] Tripler Army Med Ctr, Infect Dis Serv, Honolulu, HI 96859 USA. [Smith, Davey M.; Richman, Douglas D.; Little, Susan J.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Smith, Davey M.; Richman, Douglas D.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. [Richman, Douglas D.] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. RP Ahuja, SK (reprint author), South Texas Vet Hlth Care Syst, Vet Affairs VA Res Ctr AIDS & HIV Infect 1, 7400 Merton Minter Blvd,Room W200, San Antonio, TX 78229 USA. EM ahujas@uthscsa.edu OI Agan, Brian/0000-0002-5114-1669 FU Veterans Affairs (VA) Research Center [IP1 CX000875-01A1]; National Institutes of Health (NIH) [R37AI046326]; Doris Duke Distinguished Clinical Scientist Award; VA MERIT award; Elizabeth Glaser Pediatric AIDS Foundation; Burroughs Wellcome Clinical Scientist Award; Max and Minnie Tomerlin Voelcker Fund; NIH [UL1TR001120, DA034978, AI43638, AI69432, MH62512, AI74621, MH097520, AI077304, AI007384, AI080193, AI106039, AI096113]; VA Career Development Award-2; National Health and Medical Research Council of Australia; Infectious Disease Clinical Research Program (IDCRP); Uniformed Services University of the Health Sciences [IDCRP-000-03]; National Institute of Allergy and Infectious Diseases; International AIDS Vaccine Initiative [DMS0714991] FX The work was supported by the Veterans Affairs (VA) Research Center for AIDS and HIV Infection and VA Center for Personalized Medicine grant IP1 CX000875-01A1, National Institutes of Health (NIH) MERIT grant R37AI046326, and the Doris Duke Distinguished Clinical Scientist Award to Dr Ahuja. Dr Ahuja is also supported by a VA MERIT award, the Elizabeth Glaser Pediatric AIDS Foundation, the Burroughs Wellcome Clinical Scientist Award in Translational Research and the Senior Scholar Award from the Max and Minnie Tomerlin Voelcker Fund. This work was also supported by NIH grant UL1TR001120 (Clinical and Translational Science Award). Dr Le was supported by a VA Career Development Award-2. DrWright was supported by an Early Career Fellowship from the National Health and Medical Research Council of Australia. Support for this work was also provided in part by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense program executed through the Uniformed Services University of the Health Sciences (IDCRP-000-03). This project has been funded in part with federal funds from the National Institute of Allergy and Infectious Diseases, NIH, under Inter-Agency Agreement Y1-AI-5072. Drs Smith, Richman, and Little were supported by NIH grants DA034978, AI43638, AI69432, MH62512, AI74621, MH097520, AI077304, AI007384, AI080193, AI106039, and AI096113 and the International AIDS Vaccine Initiative grant DMS0714991. NR 34 TC 24 Z9 24 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN PY 2015 VL 175 IS 1 BP 88 EP 99 DI 10.1001/jamainternmed.2014.4010 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA AY1BM UT WOS:000347328500019 PM 25419650 ER PT J AU Hamilton, AB Chinman, M Cohen, AN Oberman, RS Young, AS AF Hamilton, Alison B. Chinman, Matthew Cohen, Amy N. Oberman, Rebecca Shoai Young, Alexander S. TI Implementation of Consumer Providers into Mental Health Intensive Case Management Teams SO JOURNAL OF BEHAVIORAL HEALTH SERVICES & RESEARCH LA English DT Article ID PEER SUPPORT; CONCEPTUAL-FRAMEWORK; STRATEGIES; PROGRAMS; FACILITATION; EXPERIENCES; AGENCIES; SERVICES; STAFF; VA AB In mental health care, consumer providers (CPs) are individuals with serious mental illness (SMI) who draw upon their lived experiences while providing services to others with SMI. Implementation of CPs has proven to be challenging in a variety of settings. The PEER project (Peers Enhancing Recovery) involved rolling out CPs using an implementation science model and evaluating implementation and impact in mental health treatment settings (three intervention, three control). In qualitative interviews, facilitators and challenges to implementation were described by the CPs, their team members, clients, and study researchers. Site preparation, external facilitation, and positive, reinforcing experiences with CPs facilitated implementation. Role definitions and deficiencies in CPs' technical knowledge posed challenges to implementation. Sustainability was not realized due to insufficient resources. However, implementation was positive overall, characterized by diffusion of innovation concepts of high relative advantage, strong trialability, compatibility with prevailing norms, compelling observability, and relatively low complexity. By preparing and working systematically with intervention sites to incorporate new services, implementation was strengthened and challenges were minimized. C1 [Hamilton, Alison B.; Cohen, Amy N.; Oberman, Rebecca Shoai; Young, Alexander S.] VA Greater Los Angeles Healthcare Syst, VA Desert Pacific MIRECC, Los Angeles, CA 90073 USA. [Chinman, Matthew] VA Pittsburgh Healthcare Syst, VISN MIRECC 4, Pittsburgh, PA USA. RP Hamilton, AB (reprint author), VA Greater Los Angeles Healthcare Syst, VA Desert Pacific MIRECC, 11301 Wilshire Blvd 210A, Los Angeles, CA 90073 USA. EM alisonh@ucla.edu; chinman@rand.org; amy.cohen@va.gov; rebecca.oberman@va.gov; ayoung@ucla.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [IIR 06-227]; Mental Illness Research, Education, and Clinical Center of VISN 4; Mental Illness Research, Education, and Clinical Center of VISN 22; National Institute of Mental Health [R25 MH080916-01A2]; VA HSRD QUERI FX The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (IIR 06-227). Support was also provided by the Mental Illness Research, Education, and Clinical Centers of VISN 4 and VISN 22. At the time of the study, Dr. Hamilton was an investigator with the Implementation Research Institute (IRI), at the George Warren Brown School of Social Work, Washington University, St. Louis, through an award from the National Institute of Mental Health (R25 MH080916-01A2) and VA HSR&D QUERI. NR 20 TC 5 Z9 5 U1 2 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1094-3412 EI 1556-3308 J9 J BEHAV HEALTH SER R JI J. Behav. Health Serv. Res. PD JAN PY 2015 VL 42 IS 1 BP 100 EP 108 DI 10.1007/s11414-013-9365-8 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AY2KW UT WOS:000347420100010 PM 24091610 ER PT J AU Chinman, M Oberman, RS Hanusa, BH Cohen, AN Salyers, MP Twamley, EW Young, AS AF Chinman, Matthew Oberman, Rebecca S. Hanusa, Barbara H. Cohen, Amy N. Salyers, Michelle P. Twamley, Elizabeth W. Young, Alexander S. TI A Cluster Randomized Trial of Adding Peer Specialists to Intensive Case Management Teams in the Veterans Health Administration SO JOURNAL OF BEHAVIORAL HEALTH SERVICES & RESEARCH LA English DT Article ID ASSERTIVE COMMUNITY TREATMENT; PATIENT ACTIVATION MEASURE; SERIOUS MENTAL-ILLNESS; CONSUMER-PROVIDERS; SELF-MANAGEMENT; CLIENT OUTCOMES; RECOVERY; PROGRAM; SERVICES; SUPPORT AB Use of peer specialists (PSs)-individuals with serious mental illness who use their experiences to help others with serious mental illness-is increasing. However, their impact on patient outcomes has not been demonstrated definitively. This cluster randomized, controlled trial within the Veterans Health Administration compared patients served by three intensive case management teams that each deployed two PSs for 1 year, to the patients of three similar teams without PSs (Usual Care). All patients (PS group = 149, Usual Care = 133) had substantial psychiatric inpatient histories and a primary Axis 1 psychiatric disorder. Before and after the year PSs worked, patients were surveyed on their recovery, quality of life, activation (health self-management efficacy), interpersonal relations, and symptoms. Patients in the PS group improved significantly more (z = 2.00, df = 1, p = 0.05) than those receiving Usual Care on activation. There were no other significant differences. PSs helped patients become more active in treatment, which can promote recovery. C1 [Chinman, Matthew] VA Pittsburgh Healthcare, VISN 4, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. [Chinman, Matthew] RAND Corp, VA Healthcare Syst, Pittsburgh, PA 15206 USA. [Oberman, Rebecca S.] West Los Angeles VA Healthcare Syst, VA Desert Pacific Mental Illness Res Educ & Clin, MIRECC, Los Angeles, CA 90073 USA. [Hanusa, Barbara H.] VA Pittsburgh Healthcare, Ctr Hlth Equ Res & Promot CHERP, Pittsburgh, PA 15206 USA. [Hanusa, Barbara H.] VA Pittsburgh Healthcare, MIRECC, Pittsburgh, PA 15206 USA. [Cohen, Amy N.] VA Desert Pacific Mental Illness Res Educ & Clin, Hlth Serv Unit, Los Angeles, CA USA. [Cohen, Amy N.] Univ Calif Los Angeles, MIRECC, West Los Angeles VA Healthcare Syst, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. [Salyers, Michelle P.] Indiana Univ Purdue Univ, IUPUI Sch Sci LD, Dept Psychol, Indianapolis, IN 46202 USA. [Twamley, Elizabeth W.] VA San Diego Healthcare Syst, Ctr Excellence, Neuropsychol Unit, San Diego, CA USA. [Twamley, Elizabeth W.] Univ Calif San Diego, San Diego, CA 92103 USA. RP Chinman, M (reprint author), VA Pittsburgh Healthcare, VISN 4, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. EM matthew_chinman@rand.org; Rebecca.Shoai@va.gov; barbara.hanusa@va.gov; Amy.cohen@va.gov; mpsalyer@iupui.edu; etwamley@ucsd.edu; Ayoung@ucla.edu RI Young, Alexander/A-1523-2009 OI Young, Alexander/0000-0002-9367-9213 FU Department of Veterans' Affairs Health Services Research and Development, PEers Enhancing Recovery (PEER) [IIR 06-227] FX Financial support for the paper was provided by a grant from the Department of Veterans' Affairs Health Services Research and Development, PEers Enhancing Recovery (PEER, IIR 06-227). All authors do not have any conflict of interests to report. The contents do not represent the views of the Department of Veterans Affairs or the US Government. Dr. Chinman 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. NR 71 TC 12 Z9 12 U1 3 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1094-3412 EI 1556-3308 J9 J BEHAV HEALTH SER R JI J. Behav. Health Serv. Res. PD JAN PY 2015 VL 42 IS 1 BP 109 EP 121 DI 10.1007/s11414-013-9343-1 PG 13 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AY2KW UT WOS:000347420100011 PM 23657754 ER PT J AU Chinman, M Oberman, RS Hanusa, BH Cohen, AN Salyers, MP Twamley, EW Young, AS AF Chinman, Matthew Oberman, Rebecca S. Hanusa, Barbara H. Cohen, Amy N. Salyers, Michelle P. Twamley, Elizabeth W. Young, Alexander S. TI A Cluster Randomized Trial of Adding Peer Specialists to Intensive Case Management Teams in the Veterans Health Administration (vol 42, pg 109, 2015) SO JOURNAL OF BEHAVIORAL HEALTH SERVICES & RESEARCH LA English DT Correction C1 [Chinman, Matthew] VA Pittsburgh Healthcare, Mental Illness Res Educ & Clin Ctr, VISN 4, Pittsburgh, PA 15240 USA. [Chinman, Matthew] RAND Corp, VA Healthcare Syst, Pittsburgh, PA 15206 USA. RP Chinman, M (reprint author), VA Pittsburgh Healthcare, Mental Illness Res Educ & Clin Ctr, VISN 4, Pittsburgh, PA 15240 USA. EM matthew_chinman@rand.org NR 1 TC 0 Z9 0 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1094-3412 EI 1556-3308 J9 J BEHAV HEALTH SER R JI J. Behav. Health Serv. Res. PD JAN PY 2015 VL 42 IS 1 BP 122 EP 122 DI 10.1007/s11414-013-9377-4 PG 1 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AY2KW UT WOS:000347420100012 PM 24217992 ER PT J AU Lynch, CP Gebregziabher, M Axon, RN Hunt, KE Payne, E Egede, LE AF Lynch, Cheryl P. Gebregziabher, Mulugeta Axon, R. Neal Hunt, Kelly E. Payne, Elizabeth Egede, Leonard E. TI Geographic and Racial/Ethnic Variations in Patterns of Multimorbidity Burden in Patients with Type 2 Diabetes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE multimorbidity; racial/ethnic; rural residence; pattern; veterans ID MEDICATION NONADHERENCE; GENERAL-PRACTICE; HEALTH-STATUS; VETERANS; PREVALENCE; CARE; MANAGEMENT; MORTALITY; DISEASES; PROGRAM AB Multimorbidity presents a significant public health challenge, but regional, rural/urban, and racial/ethnic differences in patterns of multimorbidity in diabetes are poorly understood. To describe patterns of multimorbidity in medical and mental health by regional, rural/urban, and racial/ethnic variation in patients with type 2 diabetes mellitus. Retrospective cohort study from 2002 through 2006 A national cohort of 892,223 veterans with diabetes Multimorbidity was the main outcome defined as: the measure of multimorbidity and two categorical outcomes, with pattern of medical and mental health comorbidities combined and separately. Among patients, 52% had 2+ comorbidities, 33% had a single comorbidity, and 14% had no comorbidity; 13.9% had both medical and mental health comorbidities, 70.3% had medical only, and 1.5% had mental health only. The odds of having 3+ comorbidities were nearly fourfold greater in patients 75 years and older relative to patients younger than 50 years (OR=3.95 [95% CI: 3.84, 4.06]). Compared to non-Hispanic whites, the odds of 3+ comorbidities among non-Hispanic blacks were 1.67 times greater (95% CI: 1.63, 1.71). Hispanics were more likely to have a mental health comorbidity alone (OR=1.20 [95% CI: 1.13, 1.28]) than non-Hispanic whites. For patients living in rural areas, the odds were higher of having 3+ comorbidities (OR=1.21 [95% CI: 1.19, 1.23]) and of having both medical and mental health comorbidities (OR=1.15 [95% CI: 1.13, 1.17]) compared to urban dwellers. Among individuals with diabetes, traditionally disadvantaged groups, including non-Hispanic blacks and rural patients, appear to bear the greatest burden and risk of multimorbidity. Significantly greater odds with increasing number of comorbidities were seen by race/ethnicity, rural residence, and geographic region. C1 [Lynch, Cheryl P.; Gebregziabher, Mulugeta; Axon, R. Neal; Hunt, Kelly E.; Payne, Elizabeth; Egede, Leonard E.] Ralph H Johnson Dept Vet Affairs Med Ctr, Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC USA. [Lynch, Cheryl P.; Axon, R. Neal; Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta; Hunt, Kelly E.; Payne, Elizabeth] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Div Gen Internal Med, Ctr Hlth Dispar Res, 135 Rutledge Ave,MSC 593, Charleston, SC 29425 USA. EM egedel@musc.edu OI Gebregziabher, Mulugeta/0000-0002-4826-481X FU NIDDK NIH HHS [K24 DK093699] NR 38 TC 6 Z9 6 U1 3 U2 15 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 JAN PY 2015 VL 30 IS 1 BP 25 EP 32 DI 10.1007/s11606-014-2990-y PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AY2JG UT WOS:000347414800007 PM 25127728 ER PT J AU Adepoju, O AF Adepoju, Omolola TI Capsule Commentary on Lynch et al., Geographic and Racial/Ethnic Variations in Patterns of Multimorbidity Burden in Patients with Type 2 Diabetes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 [Adepoju, Omolola] United Hlth Grp, Accountable Care Program, Sugar Land, TX USA. [Adepoju, Omolola] United Hlth Grp, Hlth Homes Program, Sugar Land, TX USA. RP Adepoju, O (reprint author), Baylor Coll Med, Sect Hlth Serv Res Vet Affairs Hlth Serv Res & De, Michael E DeBakey Vet Affairs Med Ctr, Ctr Innovat Qual Effectiveness & Safety, Houston, TX 77030 USA. EM omololaelizabeth.adepoju@va.gov NR 5 TC 1 Z9 1 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 JAN PY 2015 VL 30 IS 1 BP 93 EP 93 DI 10.1007/s11606-014-3005-8 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AY2JG UT WOS:000347414800017 PM 25361684 ER PT J AU Spiegel, BMR Reid, MW Bolus, R Whitman, CB Talley, J Dea, S Shahedi, K Karsan, H Teal, C Melmed, GY Cohen, E Fuller, G Yen, L Hodgkins, P Erder, MH AF Spiegel, Brennan M. R. Reid, Mark W. Bolus, Roger Whitman, Cynthia B. Talley, Jennifer Dea, Stanley Shahedi, Kamyar Karsan, Hetal Teal, Chassidy Melmed, Gil Y. Cohen, Erica Fuller, Garth Yen, Linnette Hodgkins, Paul Erder, M. Haim TI Development and validation of a disease-targeted quality of life instrument for chronic diverticular disease: the DV-QOL SO QUALITY OF LIFE RESEARCH LA English DT Article DE Patient-reported outcomes; Health-related quality of life; Diverticulosis; Diverticulitis ID IRRITABLE-BOWEL-SYNDROME; INFORMATION-SYSTEM PROMIS; UNITED-STATES; SIGMOID DIVERTICULITIS; PRACTICE PARAMETERS; COLON; DIAGNOSIS; FRAMEWORK; SYMPTOMS; PATTERNS AB Colonic diverticular disease is typically conceived as acute diverticulitis attacks surrounded by periods of clinical silence. However, evolving data indicate that many patients have persistent symptoms and diminished health-related quality of life (HRQOL) long after acute attacks. We developed a disease-targeted HRQOL measure for symptomatic uncomplicated diverticular disease (SUDD)-the diverticulitis quality of life (DV-QOL) instrument. We conducted a systematic literature review to craft a conceptual model of SUDD HRQOL. This was complemented by three focus groups including 45 SUDD patients. We developed items based on our literature search, focus groups, and cognitive debriefings. We administered the items to SUDD patients with persistent symptoms following a confirmed diverticulitis event. We created scales based on factor analysis and evaluated the scales for reliability and validity. Concept elicitation revealed a range of illness experiences attributed to SUDD. Coding of 20,490 transcribed words yielded a 52-code network with four primary, condition-related concepts: (1) physical symptoms (e.g., bloating); (2) behaviors (e.g., restrictions); (3) cognitions and concerns (e.g., fear); and (4) impact and consequences (e.g., absenteeism, anxiety). Based on patient language, we developed the 17-item DV-QOL instrument. In a cross-sectional validation sample of 197 patients, DV-QOL discriminated between patients with recent versus distant diverticulitis events and correlated highly with Short Form 36 and hospital anxiety and depression scores. Patients with SUDD attribute a wide range of negative psychological, social, and physical symptoms to their condition, both during and after acute attacks; DV-QOL captures these symptoms in a valid, reliable manner. C1 [Spiegel, Brennan M. R.; Reid, Mark W.; Talley, Jennifer; Cohen, Erica] VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol, Los Angeles, CA 90073 USA. [Spiegel, Brennan M. R.; Bolus, Roger] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Spiegel, Brennan M. R.; Fuller, Garth] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Spiegel, Brennan M. R.; Reid, Mark W.; Bolus, Roger; Whitman, Cynthia B.; Talley, Jennifer; Fuller, Garth] CS CORE, Los Angeles, CA USA. [Dea, Stanley; Shahedi, Kamyar] UCLA Olive View Med Ctr, Dept Gastroenterol, Los Angeles, CA USA. [Karsan, Hetal; Teal, Chassidy] Atlanta Gastroenterol Associates, Atlanta, GA USA. [Melmed, Gil Y.; Cohen, Erica] Cedars Sinai Med Ctr, Dept Gastroenterol, Los Angeles, CA 90048 USA. [Yen, Linnette; Hodgkins, Paul; Erder, M. Haim] Shire Dev LLC, Wayne, PA USA. RP Spiegel, BMR (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol, 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu FU Shire Development LLC; Amgen Pharmaceuticals; Ironwood Pharmaceuticals; Theravance Pharmaceuticals; Pfizer; Linnette Yen FX Brennan Spiegel has received research support from Amgen Pharmaceuticals, Ironwood Pharmaceuticals, Shire Development LLC, and Theravance Pharmaceuticals. Gil Melmed has consulted for Abbvie, Jannsen, Given Imaging, Celgene, and Luitpold. He has received research support from Pfizer, and been on the speaker's bureau for Abbott. Linnette Yen, deceased, was an employee of Shire and held stock/options in Shire. Paul Hodgkins and M. Haim Erder are Shire employees and own stock in the company. This study is supported by a research grant from Shire Development LLC. NR 43 TC 5 Z9 5 U1 0 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 EI 1573-2649 J9 QUAL LIFE RES JI Qual. Life Res. PD JAN PY 2015 VL 24 IS 1 BP 163 EP 179 DI 10.1007/s11136-014-0753-1 PG 17 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AY0OO UT WOS:000347296200016 PM 25059533 ER PT J AU Latif, R Ali, MR Ma, RS David, M Morshed, SA Ohlmeyer, M Felsenfeld, DP Lau, Z Mezei, M Davies, TF AF Latif, Rauf Ali, M. Rejwan Ma, Risheng David, Martine Morshed, Syed A. Ohlmeyer, Michael Felsenfeld, Dan P. Lau, Zerlina Mezei, Mihaly Davies, Terry F. TI New Small Molecule Agonists to the Thyrotropin Receptor SO THYROID LA English DT Article ID STIMULATING HORMONE-RECEPTOR; THROUGHPUT SCREENING ASSAYS; PROTEIN-COUPLED RECEPTOR; TSH RECEPTOR; SIGNAL-TRANSDUCTION; THYROID-FUNCTION; GRAVES-DISEASE; HINGE REGION; CRYSTAL-STRUCTURE; LIGAND-BINDING AB Background: Novel small molecular ligands (SMLs) to the thyrotropin receptor (TSHR) have potential as improved molecular probes and as therapeutic agents for the treatment of thyroid dysfunction and thyroid cancer. Methods: To identify novel SMLs to the TSHR, we developed a transcription-based luciferase-cAMP high-throughput screening system and we screened 48,224 compounds from a 100K library in duplicate. Results: We obtained 62 hits using the cut-off criteria of the mean +/- three standard deviations above the baseline. Twenty molecules with the greatest activity were rescreened against the parent CHO-luciferase cell for nonspecific activation, and we selected two molecules (MS437 and MS438) with the highest potency for further study. These lead molecules demonstrated no detectible cross-reactivity with homologous receptors when tested against luteinizing hormone (LH)/human chorionic gonadotropin receptor and follicle stimulating hormone receptor-expressing cells. Molecule MS437 had a TSHR-stimulating potency with an EC50 of 13x10(-8) M, and molecule MS438 had an EC50 of 5.3x10(-8) M. The ability of these small molecule agonists to bind to the transmembrane domain of the receptor and initiate signal transduction was suggested by their activation of a chimeric receptor consisting of an LHR ectodomain and a TSHR transmembrane. Molecular modeling demonstrated that these molecules bound to residues S505 and E506 for MS438 and T501 for MS437 in the intrahelical region of transmembrane helix 3. We also examined the G protein activating ability of these molecules using CHO cells co-expressing TSHRs transfected with luciferase reporter vectors in order to measure G(s alpha), G(beta gamma), G(alpha q), and G(alpha 12) activation quantitatively. The MS437 and MS438 molecules showed potent activation of G(s alpha), G(alpha q), and G(alpha 12) similar to TSH, but neither the small molecule agonists nor TSH showed activation of the G(beta gamma) pathway. The small molecules MS437 and MS438 also showed upregulation of thyroglobulin (Tg), sodium iodine symporter (NIS), and TSHR gene expression. Conclusions: Pharmacokinetic analysis of MS437 and MS438 indicated their pharmacotherapeutic potential, and their intraperitoneal administration to normal female mice resulted in significantly increased serum thyroxine levels, which could be maintained by repeated treatments. These molecules can therefore serve as lead molecules for further development of powerful TSH agonists. C1 [Latif, Rauf; Ali, M. Rejwan; Ma, Risheng; David, Martine; Morshed, Syed A.; Davies, Terry F.] Icahn Sch Med Mt Sinai, Dept Med, Thyroid Res Unit, New York, NY 10029 USA. [Latif, Rauf; Ali, M. Rejwan; Ma, Risheng; David, Martine; Morshed, Syed A.; Davies, Terry F.] James J Peters VAMC, New York, NY 10468 USA. [Ohlmeyer, Michael; Mezei, Mihaly] Icahn Sch Med Mt Sinai, Dept Struct & Chem Biol, New York, NY 10029 USA. [Felsenfeld, Dan P.; Lau, Zerlina] Icahn Sch Med Mt Sinai, Expt Therapeut Inst, Integrated Screening Core, New York, NY 10029 USA. RP Latif, R (reprint author), James J Peters VAMC, Room 2F-30,130 West Kingsbridge Rd, New York, NY 10468 USA. EM rauf.latif@mssm.edu FU NIH [DK069713, DK052464]; VA Merit Award program FX This work was supported in part by NIH grants DK069713, DK052464, and the VA Merit Award program (to T.F.D.). NR 58 TC 7 Z9 8 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD JAN 1 PY 2015 VL 25 IS 1 BP 51 EP 62 DI 10.1089/thy.2014.0119 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AY4GP UT WOS:000347536600007 PM 25333622 ER PT J AU Sun, R Celli, A Crumrine, D Hupe, M Adame, LC Pennypacker, SD Park, K Uchida, Y Feingold, KR Elias, PM Ilic, D Mauro, TM AF Sun, Richard Celli, Anna Crumrine, Debra Hupe, Melanie Adame, Lillian C. Pennypacker, Sally D. Park, Kyungho Uchida, Yoshikazu Feingold, Kenneth R. Elias, Peter M. Ilic, Dusko Mauro, Theodora M. TI Lowered Humidity Produces Human Epidermal Equivalents with Enhanced Barrier Properties SO TISSUE ENGINEERING PART C-METHODS LA English DT Article ID RECONSTRUCTED HUMAN EPIDERMIS; HUMAN SKIN EQUIVALENTS; AIR-LIQUID INTERFACE; STRATUM-CORNEUM; PERMEABILITY BARRIER; HUMAN KERATINOCYTES; IN-VITRO; CALCIUM GRADIENT; ANTIMICROBIAL PEPTIDE; TIGHT JUNCTIONS AB Multilayered human keratinocyte cultures increasingly are used to model human epidermis. Until now, studies utilizing human epidermal equivalents (HEEs) have been limited because previous preparations do not establish a normal epidermal permeability barrier. In this report, we show that reducing environmental humidity to 50% relative humidity yields HEEs that closely match human postnatal epidermis and have enhanced repair of the permeability barrier. These cultures display low transepidermal water loss and possess a calcium and pH gradient that resembles those seen in human epidermis. These cultures upregulate glucosylceramide synthase and make normal-appearing lipid lamellar bilayers. The epidermal permeability barrier of these cultures can be perturbed, using the identical tools previously described for human skin, and recover in the same time course seen during in vivo barrier recovery. These cultures will be useful for basic and applied studies on epidermal barrier function. C1 [Sun, Richard; Celli, Anna; Crumrine, Debra; Hupe, Melanie; Adame, Lillian C.; Pennypacker, Sally D.; Park, Kyungho; Uchida, Yoshikazu; Elias, Peter M.; Mauro, Theodora M.] San Francisco Vet Adm Med Ctr, Dept Dermatol, San Francisco, CA 94158 USA. [Celli, Anna; Crumrine, Debra; Hupe, Melanie; Pennypacker, Sally D.; Uchida, Yoshikazu; Elias, Peter M.; Mauro, Theodora M.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Feingold, Kenneth R.] San Francisco Vet Adm Med Ctr, Metab Unit, San Francisco, CA 94158 USA. [Ilic, Dusko] Kings Coll London, Womens Hlth Acad Ctr, Div Womens Hlth, Stem Cell Lab,Assisted Concept Unit, London WC2R 2LS, England. RP Mauro, TM (reprint author), San Francisco Vet Adm Med Ctr, Dept Dermatol, 1700 Owens,Rm 338, San Francisco, CA 94158 USA. EM maurot@derm.ucsf.edu FU NIH [R21 ARO61583, R01 AR051930, AR062025]; Research Service, Department of Veterans Affairs FX The authors gratefully acknowledge the superb editorial assistance of Ms. Joan Wakefield, Ms. Jerelyn Magnusson, and Dr. Mathias Sulk. This work was supported by NIH grants R21 ARO61583 and R01 AR051930 (T.M.M.) and AR062025 (Y.U.) and the Research Service, Department of Veterans Affairs. NR 53 TC 8 Z9 9 U1 0 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3384 EI 1937-3392 J9 TISSUE ENG PART C-ME JI Tissue Eng. Part C-Methods PD JAN 1 PY 2015 VL 21 IS 1 BP 15 EP 22 DI 10.1089/ten.tec.2014.0065 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA AY4HI UT WOS:000347538400002 PM 24803151 ER PT J AU Virani, SS Woodard, LD Ramsey, DJ Urech, TH Akeroyd, JM Shah, T Deswal, A Bozkurt, B Ballantyne, CM Petersen, LA AF Virani, Salim S. Woodard, LeChauncy D. Ramsey, David J. Urech, Tracy H. Akeroyd, Julia M. Shah, Tina Deswal, Anita Bozkurt, Biykem Ballantyne, Christie M. Petersen, Laura A. TI Gender Disparities in Evidence-Based Statin Therapy in Patients With Cardiovascular Disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID DENSITY-LIPOPROTEIN; PRIMARY PREVENTION; CHOLESTEROL LEVELS; CONTROLLED-TRIAL; GOAL ATTAINMENT; DIABETES CARE; SIMVASTATIN; WOMEN; ATORVASTATIN; METAANALYSIS AB Studies have shown gender disparities in cholesterol care in patients with cardiovascular disease (CVD), with women less likely than men to have low-density lipoprotein cholesterol levels <100 mg/dl. Whether this is related to a lower evidence-based statin or high-intensity statin use is not known. We used a national cohort of 972,532 patients with CVD (coronary heart disease, peripheral artery disease, and ischemic stroke) receiving care in 130 Veterans Health Administration facilities from October 1, 2010, to September 30, 2011, to identify the proportion of male and female patients with CVD receiving any statin and high-intensity statin. Women with CVD (n = 13,371) were less likely than men to receive statins (57.6% vs 64.8%, p <0.0001) or high-intensity statins (21.1% vs 23.6%, p <0.0001). Mean low-density lipoprotein cholesterol levels (99 vs 85 mg/dl) were higher in women compared with men (p <0.0001). In adjusted models, female gender was independently associated with a lower likelihood of receiving statins (odds ratio 0.68, 95% confidence interval 0.66 to 0.71) or high-intensity statins (odds ratio 0.76, 95% confidence interval 0.73 to 0.80). The median facility-level rate of statin and high-intensity statin use among female patients (57.3% [interquartile range = 8.93%] for statin, 20% [interquartile range = 7.7%] for high-intensity statin use) showed significant variation. In conclusion, women with CVD are less likely to receive evidence-based statin and high-intensity statins compared with men, although, their use remains low in both genders. There is a significant facility-level variation in evidence-based statin or high-intensity statin use in female patients with CVD. With the "statin dose-based approach" proposed by the recent cholesterol guidelines, these results highlight areas for quality improvement. Published by Elsevier Inc. C1 [Virani, Salim S.; Woodard, LeChauncy D.; Ramsey, David J.; Urech, Tracy H.; Akeroyd, Julia M.; Petersen, Laura A.] Hlth Serv Res & Dev Ctr Innovat, Michael E DeBakey Vet Affairs Med Ctr, Hlth Policy Qual & Informat Program, Houston, TX 77030 USA. [Virani, Salim S.; Shah, Tina; Deswal, Anita; Bozkurt, Biykem] Michael E DeBakey VA Med Ctr, Cardiol Sect, Houston, TX USA. [Virani, Salim S.; Shah, Tina; Deswal, Anita; Bozkurt, Biykem; Ballantyne, Christie M.] Baylor Coll Med, Dept Med, Cardiol Sect, Houston, TX 77030 USA. [Virani, Salim S.; Ballantyne, Christie M.] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX USA. RP Virani, SS (reprint author), Hlth Serv Res & Dev Ctr Innovat, Michael E DeBakey Vet Affairs Med Ctr, Hlth Policy Qual & Informat Program, Houston, TX 77030 USA. EM virani@bcm.edu OI Virani, Salim/0000-0001-9541-6954 FU Houston Veterans Affairs Health Services Research and Development Center for Innovations grant [HFP 90-020] FX This work was also supported by the Houston Veterans Affairs Health Services Research and Development Center for Innovations grant (grant HFP 90-020). 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 19 TC 24 Z9 25 U1 0 U2 9 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 2015 VL 115 IS 1 BP 21 EP 26 DI 10.1016/j.amjcard.2014.09.041 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AY0HP UT WOS:000347278300004 PM 25456865 ER PT J AU Oates, JC AF Oates, Jim C. TI Endothelial Dysfunction in Injury and Inflammation SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Editorial Material C1 [Oates, Jim C.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Oates, Jim C.] Ralph H Johnson VA Med Ctr, Med Serv, Rheumatol Sect, Charleston, SC USA. [Oates, Jim C.] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA. RP Oates, JC (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, 96 Jonathan Lucas St,Suite 816,MSC 637, Charleston, SC 29425 USA. EM oatesjc@musc.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD JAN PY 2015 VL 349 IS 1 BP 2 EP 2 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AX7CS UT WOS:000347075200003 PM 25535885 ER PT J AU Baker, JF Long, J Ibrahim, S Leonard, MB Katz, P AF Baker, Joshua F. Long, Jin Ibrahim, Said Leonard, Mary B. Katz, Patricia TI Are Men at Greater Risk of Lean Mass Deficits in Rheumatoid Arthritis? SO ARTHRITIS CARE & RESEARCH LA English DT Article ID BODY-COMPOSITION; PHYSICAL-ACTIVITY; SEX-DIFFERENCES; DISEASE CHARACTERISTICS; REFERENCE VALUES; NECROSIS-FACTOR; SARCOPENIA; CACHEXIA; ASSOCIATION; OBESITY AB Objective. We aimed to determine if there were sex differences in lean body mass (LBM) in patients with rheumatoid arthritis (RA) when compared with sex-and race-specific National Health and Nutrition Examination Survey (NHANES) reference data, and to investigate the impact of sex differences in risk factors for LBM deficits. Methods. Dual x-ray absorptiometry measures of whole body LBM and appendicular LBM (arms and legs, appendicular lean mass [ALM]) were obtained on a total of 190 subjects from 2 independent cohorts (141 from San Francisco [SF], 49 from Philadelphia [PA]), expressed as indices adjusted for height (LBM index and ALM index, kg/m(2)), and converted to sex-and race-specific Z scores relative to age and based on NHANES data. Sarcopenia was defined using 4 different sex-specific definitions. Multivariable linear and logistic regression analyses adjusted for disease activity, disease duration, physical activity, anti-cyclic citrullinated peptide seropositivity, fat mass index, and glucocorticoid use. Results. While there were significant differences between the 2 cohorts, ALM index Z scores were significantly lower in men compared to women in both (SF: -1.43 versus -0.43, P < 0.0001; PA: -0.83 versus -0.06, P = 0.03). Observed sex differences were significant after adjustment in multivariable analyses within both cohorts. Odds of sarcopenia were 3 to 8 times greater in men in the SF cohort. Men in the PA cohort also had a higher, but nonsignificant, risk of sarcopenia. Conclusion. RA is associated with significant LBM deficits, with greater deficits observed in men. Future study may help elucidate the mechanisms driving greater deficits among men. C1 [Baker, Joshua F.; Ibrahim, Said] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Long, Jin; Leonard, Mary B.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Leonard, Mary B.] Univ Penn, Philadelphia, PA 19104 USA. [Katz, Patricia] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Katz, P (reprint author), Univ Calif San Francisco, 3333 Calif St,Suite 270, San Francisco, CA 94143 USA. EM patti.katz@ucsf.edu FU NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases [P60-AR-053308]; NIH/National Center for Research Resources [UL1-RR-024131]; Rosalind Russell Medical Research Center for Arthritis; University of Pennsylvania Clinical and Translational Research Center [UL1-RR-024134]; Veterans Affairs Clinical Science Research and Development Career Development Award [IK2 CX000955]; K24 Award from the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases [K24-AR-055259, K24-DK-076808] FX Research at University of California, San Francisco was supported by the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant P60-AR-053308), the NIH/National Center for Research Resources (grant UL1-RR-024131), and by the Rosalind Russell Medical Research Center for Arthritis. Research at University of Pennsylvania was supported by the University of Pennsylvania Clinical and Translational Research Center (UL1-RR-024134). Dr. Baker's work was supported by a Veterans Affairs Clinical Science Research and Development Career Development Award (IK2 CX000955). Drs. Ibrahim and Leonard's work was supported by a K24 Award (grants K24-AR-055259 and K24-DK-076808, respectively) from the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases. NR 42 TC 6 Z9 6 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD JAN PY 2015 VL 67 IS 1 BP 112 EP 119 DI 10.1002/acr.22396 PG 8 WC Rheumatology SC Rheumatology GA AX4QS UT WOS:000346917200016 PM 25048740 ER PT J AU Wecksler, AT Hwang, SH Liu, JY Wettersten, HI Morisseau, C Wu, J Weiss, RH Hammock, BD AF Wecksler, Aaron T. Hwang, Sung Hee Liu, Jun-Yan Wettersten, Hiromi I. Morisseau, Christophe Wu, Jian Weiss, Robert H. Hammock, Bruce D. TI Biological evaluation of a novel sorafenib analogue, t-CUPM SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Sorafenib analogue; Hepatoma cells; Kinase selectivity profile; Pharmacokinetics; Caspase-independent cell death; NCI-60 cell lines ID SOLUBLE EPOXIDE HYDROLASE; ADVANCED HEPATOCELLULAR-CARCINOMA; APOPTOSIS-INDUCING FACTOR; CELL-DEATH; MULTIKINASE INHIBITOR; EPOXYEICOSATRIENOIC ACIDS; RAF/MEK/ERK PATHWAY; GROWTH-FACTOR; CANCER-CELLS; ANGIOGENESIS AB Sorafenib (Nexavar(A (R))) is currently the only FDA-approved small molecule targeted therapy for advanced hepatocellular carcinoma. The use of structural analogues and derivatives of sorafenib has enabled the elucidation of critical targets and mechanism(s) of cell death for human cancer lines. We previously performed a structure-activity relationship study on a series of sorafenib analogues designed to investigate the inhibition overlap between the major targets of sorafenib Raf-1 kinase and VEGFR-2, and an enzyme shown to be a potent off-target of sorafenib, soluble epoxide hydrolase. In the current work, we present the biological data on our lead sorafenib analogue, t-CUPM, demonstrating that this analogue retains cytotoxicity similar to sorafenib in various human cancer cell lines and strongly inhibits growth in the NCI-60 cell line panel. Co-treatment with the pan-caspase inhibitor, Z-VAD-FMK, failed to rescue the cell viability responses of both sorafenib and t-CUPM, and immunofluorescence microscopy shows similar mitochondrial depolarization and apoptosis-inducing factor release for both compounds. These data suggest that both compounds induce a similar mechanism of caspase-independent apoptosis in hepatoma cells. In addition, t-CUPM displays anti-proliferative effects comparable to sorafenib as seen by a halt in G0/G1 in cell cycle progression. The structural difference between sorafenib and t-CUPM significantly reduces inhibitory spectrum of kinases by this analogue, and pharmacokinetic characterization demonstrates a 20-fold better oral bioavailability of t-CUPM than sorafenib in mice. Thus, t-CUPM may have the potential to reduce the adverse events observed from the multikinase inhibitory properties and the large dosing regimens of sorafenib. C1 [Wecksler, Aaron T.; Hwang, Sung Hee; Liu, Jun-Yan; Morisseau, Christophe; Hammock, Bruce D.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Wecksler, Aaron T.; Hwang, Sung Hee; Liu, Jun-Yan; Morisseau, Christophe; Wu, Jian; Weiss, Robert H.; Hammock, Bruce D.] Univ Calif Davis, Ctr Comprehens Canc, Sacramento, CA 95817 USA. [Wettersten, Hiromi I.; Weiss, Robert H.] Univ Calif Davis, Davis Med Ctr, Dept Internal Med, Div Nephrol, Sacramento, CA 95817 USA. [Wu, Jian] Univ Calif Davis, Davis Med Ctr, Dept Internal Med, Div Gastroenterol & Hepatol, Sacramento, CA 95817 USA. [Weiss, Robert H.] US Dept Vet Affairs, Med Ctr, Sacramento, CA 95655 USA. RP Hammock, BD (reprint author), Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. EM bdhammock@ucdavis.edu OI Wu, Jian/0000-0001-9933-7364 FU NIEHS [ES02710, P42 ES04699]; NIHLB [HL059699]; NIH [5UO1CA86402, 1R01CA135401-01A1, 1R01DK082690-01A1]; Medical Service of the US Department of Veterans' Affairs; National Institutes of Health [T32CA108459] FX We thank Dr. Michael Praddy of the MCB Imaging Facility for help with collecting and analyzing our immunohistochemical data on the Olympus FV100 laser point scanning microscope. Special thanks to Carol Oxford and the UCD Flow Cytometry Shared Resource facility for help with collecting and analyzing cell cycle data. This work was supported in part by NIEHS Grant ES02710, NIEHS Superfund Grant P42 ES04699, and NIHLB Grant HL059699 (all to B.D.H.). This work was also supported by NIH Grants 5UO1CA86402 (Early Detection Research Network), 1R01CA135401-01A1, and 1R01DK082690-01A1 (all to R.H.W.), and the Medical Service of the US Department of Veterans' Affairs (R.H.W.). A.T.W. was support by Award No. T32CA108459 from the National Institutes of Health. B.D.H. is a George and Judy Marcus senior fellow of the American Asthma Foundation. NR 39 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JAN PY 2015 VL 75 IS 1 BP 161 EP 171 DI 10.1007/s00280-014-2626-2 PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA AX8IL UT WOS:000347153200017 PM 25413440 ER PT J AU Mattis, AN Song, GS Hitchner, K Kim, RY Lee, AY Sharma, AD Malato, Y McManus, MT Esau, CC Koller, E Koliwad, S Lim, LP Maher, JJ Raffai, RL Willenbring, H AF Mattis, Aras N. Song, Guisheng Hitchner, Kelly Kim, Roy Y. Lee, Andrew Y. Sharma, Amar D. Malato, Yann McManus, Michael T. Esau, Christine C. Koller, Erich Koliwad, Suneil Lim, Lee P. Maher, Jacquelyn J. Raffai, Robert L. Willenbring, Holger TI A Screen in Mice Uncovers Repression of Lipoprotein Lipase by MicroRNA-29a as a Mechanism for Lipid Distribution Away From the Liver SO HEPATOLOGY LA English DT Article ID FATTY LIVER; IN-VIVO; METABOLIC-DISORDERS; MOUSE-LIVER; EXPRESSION; HOMEOSTASIS; GENES; DISEASE; ATHEROSCLEROSIS; STEATOHEPATITIS AB Identification of microRNAs (miRNAs) that regulate lipid metabolism is important to advance the understanding and treatment of some of the most common human diseases. In the liver, a few key miRNAs have been reported that regulate lipid metabolism, but since many genes contribute to hepatic lipid metabolism, we hypothesized that other such miRNAs exist. To identify genes repressed by miRNAs in mature hepatocytes in vivo, we injected adult mice carrying floxed Dicer1 alleles with an adenoassociated viral vector expressing Cre recombinase specifically in hepatocytes. By inactivating Dicer in adult quiescent hepatocytes we avoided the hepatocyte injury and regeneration observed in previous mouse models of global miRNA deficiency in hepatocytes. Next, we combined gene and miRNA expression profiling to identify candidate gene/miRNA interactions involved in hepatic lipid metabolism and validated their function in vivo using antisense oligonucleotides. A candidate gene that emerged from our screen was lipoprotein lipase (Lpl), which encodes an enzyme that facilitates cellular uptake of lipids from the circulation. Unlike in energy-dependent cells like myocytes, LPL is normally repressed in adult hepatocytes. We identified miR-29a as the miRNA responsible for repressing LPL in hepatocytes, and found that decreasing hepatic miR-29a levels causes lipids to accumulate in mouse livers. Conclusion: Our screen suggests several new miRNAs are regulators of hepatic lipid metabolism. We show that one of these, miR-29a, contributes to physiological lipid distribution away from the liver and protects hepatocytes from steatosis. Our results, together with miR-29a's known antifibrotic effect, suggest miR-29a is a therapeutic target in fatty liver disease. (Hepatology 2015;61:141-152) C1 [Mattis, Aras N.; Song, Guisheng; Hitchner, Kelly; Lee, Andrew Y.; Sharma, Amar D.; Malato, Yann; Lim, Lee P.; Willenbring, Holger] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA. [Mattis, Aras N.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Mattis, Aras N.; Koliwad, Suneil; Maher, Jacquelyn J.; Willenbring, Holger] Univ Calif San Francisco, Ctr Liver, San Francisco, CA 94143 USA. [Kim, Roy Y.; Raffai, Robert L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Malato, Yann; Willenbring, Holger] Univ Calif San Francisco, Dept Surg, Div Transplantat, San Francisco, CA 94143 USA. [McManus, Michael T.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. [McManus, Michael T.; Koliwad, Suneil] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. [Esau, Christine C.] Regulus Therapeut, San Diego, CA USA. [Koller, Erich] ISIS Pharmaceut, Carlsbad, CA 92008 USA. [Koliwad, Suneil] Univ Calif San Francisco, Dept Med, Div Endocrinol, San Francisco, CA 94143 USA. [Maher, Jacquelyn J.] Univ Calif San Francisco, Div Gastroenterol, Dept Med, San Francisco, CA 94143 USA. [Raffai, Robert L.] Univ Calif San Francisco, Div Vasc Surg, Dept Surg, San Francisco, CA 94143 USA. RP Willenbring, H (reprint author), Univ Calif San Francisco, 35 Med Ctr Way,Campus Box 0665, San Francisco, CA 94143 USA. EM willenbringh@stemcell.ucsf.edu RI Mattis, Aras/C-5558-2014 FU BLRD VA [I01 BX000532]; NHLBI NIH HHS [R01 HL089871]; NIDDK NIH HHS [DK063720, K08 DK098270, L30 DK089949, P30 DK026743, P30 DK063720, P30 DK26743, R01 DK068450]; NIGMS NIH HHS [R01 GM080783] NR 49 TC 13 Z9 13 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD JAN PY 2015 VL 61 IS 1 BP 141 EP 152 DI 10.1002/hep.27379 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AX6AF UT WOS:000347005100021 PM 25131933 ER PT J AU Maximos, M Bril, F Sanchez, PP Lomonaco, R Orsak, B Biernacki, D Suman, A Weber, M Cusi, K AF Maximos, Maryann Bril, Fernando Sanchez, Paola Portillo Lomonaco, Romina Orsak, Beverly Biernacki, Diane Suman, Amitabh Weber, Michelle Cusi, Kenneth TI The Role of Liver Fat and Insulin Resistance as Determinants of Plasma Aminotransferase Elevation in Nonalcoholic Fatty Liver Disease SO HEPATOLOGY LA English DT Article ID ALANINE-AMINOTRANSFERASE; CLINICAL-IMPLICATIONS; OBESE-PATIENTS; STEATOHEPATITIS; PREVALENCE; NAFLD; LIPOTOXICITY; METABOLISM; ETHNICITY; BIOPSIES AB Plasma aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) are usually increased in patients with nonalcoholic fatty liver disease (NAFLD). However, the factors behind their elevation remain unclear. The aim of this study was to assess the role of insulin resistance (IR) and liver triglyceride content in relation to histology in patients with NAFLD/nonalcoholic steatohepatitis (NASH) with normal or elevated ALT levels. To this end, we enrolled 440 patients, divided into three groups: no NAFLD (n=60); NAFLD with normal ALT (n=165); and NAFLD with elevated ALT (n=215). We measured: (1) liver fat by proton magnetic resonance spectroscopy (H-1-MRS); (2) severity of liver disease by biopsy (n=293); and (3) insulin sensitivity in liver, muscle, and adipose tissue by a euglycemic hyperinsulinemic clamp with 3-H-3-glucose. Patients with NAFLD and elevated ALT, even when well matched for body mass index to those with normal ALT, had worse adipose tissue insulin resistance (ATIR; P<0.0001), higher liver triglyceride content (P<0.0001), and lower plasma adiponectin (P<0.05), but no differences in hepatic insulin resistance. Similar results were found when only patients with NASH were compared: both ATIR (P<0.0001) and liver triglyceride content by H-1-MRS (P<0.0001) were worse in NASH with elevated ALT. Consistent with the H-1-MRS data, steatosis on liver biopsy was also significantly increased in patients with NASH and elevated ALT levels (P<0.0001). However, and most important, there were no differences in inflammation (P=0.62), ballooning (P=0.13), or fibrosis (P=0.12). Conclusion: In patients with NAFLD or NASH, ATIR (but not HIR) and liver triglyceride content are major factors in the elevation of plasma aminotransferase levels. Patients with normal versus elevated ALT had similar severity of NASH, suggesting that plasma aminotransferase levels are misleading parameters for guiding clinical management. (Hepatology 2015;61:153-160) C1 [Maximos, Maryann] Univ Florida, Div Pediat Gastroenterol Hepatol & Nutr, Gainesville, FL 32610 USA. [Maximos, Maryann; Bril, Fernando; Sanchez, Paola Portillo; Lomonaco, Romina; Biernacki, Diane; Suman, Amitabh; Weber, Michelle; Cusi, Kenneth] South Georgia Vet Hlth Syst, Malcom Randall VA Hosp North Florida, Gainesville, FL USA. [Bril, Fernando; Sanchez, Paola Portillo; Lomonaco, Romina; Biernacki, Diane; Cusi, Kenneth] Univ Florida, Div Endocrinol Diabet & Metab, Gainesville, FL 32610 USA. [Orsak, Beverly; Cusi, Kenneth] Univ Texas Hlth Sci Ctr San Antonio, Div Diabet, San Antonio, TX 78229 USA. [Orsak, Beverly; Cusi, Kenneth] Audie L Murphy Vet Adm Med Ctr, San Antonio, TX USA. RP Cusi, K (reprint author), Univ Florida, Div Endocrinol Diabet & Metab, 1600 Southwest Archer Rd,Room H-2, Gainesville, FL 32610 USA. EM Kenneth.Cusi@medicine.ufl.edu NR 26 TC 31 Z9 31 U1 1 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD JAN PY 2015 VL 61 IS 1 BP 153 EP 160 DI 10.1002/hep.27395 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AX6AF UT WOS:000347005100022 PM 25145475 ER PT J AU Johansen, KL Painter, P Delgado, C Doyle, J AF Johansen, Kirsten L. Painter, Patricia Delgado, Cynthia Doyle, Julie TI Characterization of Physical Activity and Sitting Time Among Patients on Hemodialysis Using a New Physical Activity Instrument SO JOURNAL OF RENAL NUTRITION LA English DT Article ID MORTALITY; ASSOCIATION; FRAILTY; COHORT; METAANALYSIS; SURVIVAL; DIALYSIS; DISEASE AB Objectives: Physical activity questionnaires usually focus on moderate to vigorous activities and may not accurately capture physical activity or variation in levels of activity among extremely inactive groups like dialysis patients. Design: Cross-sectional study. Setting: Three dialysis facilities in the San Francisco Bay Area. Subjects: Sixty-eight prevalent hemodialysis patients. Intervention: We administered a new physical activity questionnaire designed to capture activity in the lower end of the range, the Low Physical Activity Questionnaire (LoPAQ). Main Outcome Measure: Outcome measures were correlation with a validated physical activity questionnaire, the Minnesota Leisure Time Activity (LTA) questionnaire and with self-reported physical function (physical function score of the SF-36) and physical performance (gait speed, chair stand, balance, and short physical performance battery). We also determined whether patients who were frail or reported limitations in activities of daily living were less active on the LoPAQ. Results: Sixty-eight participants (mean age 59 +/- 14 years, 59% men) completed the study. Patients were inactive according to the LoPAQ, with a median (interquartile range) of 517 (204-1190) kcal/week of physical activity. Although activity from the LTA was lower than on the LoPAQ (411 [61-902] kcal/week), the difference was not statistically significant (P = .20), and results from the 2 instruments were strongly correlated (rho = 0.62, P < .001). In addition, higher physical activity measured by the LoPAQ was correlated with better self-reported functioning (rho = 0.64, P < .001), better performance on gait speed (rho = 0.32, P = .02), balance (rho = 0.45, P < .001), and chair rising (rho = -0.32, P = .03) tests and with higher short physical performance battery total score (rho = 0.51, P < .001). Frail patients and patients with activities of daily living limitations were less active than those who were not frail or limited. Conclusions: The LoPAQ performed similarly to the Minnesota LTA questionnaire in our cohort despite being shorter and easier to administer. (C) 2015 by the National Kidney Foundation, Inc. All rights reserved. C1 [Johansen, Kirsten L.; Delgado, Cynthia] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Johansen, Kirsten L.; Delgado, Cynthia] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Johansen, Kirsten L.; Doyle, Julie] Univ Calif San Francisco, US Renal Data Syst Nutr Special Studies Ctr, San Francisco, CA 94143 USA. [Painter, Patricia] Univ Utah, Dept Phys Therapy, Salt Lake City, UT USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, 111J,4150 Clement St, San Francisco, CA 94121 USA. EM kirsten.johansen@ucsf.edu FU National Institutes of Health [N01-DK-0005, K24 DK 085153] FX This work was supported by the National Institutes of Health (Contract N01-DK-0005 to K.L.J. and by K24 DK 085153 to K.L.J.). The interpretation and reporting of the data presented here are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US government. NR 26 TC 4 Z9 4 U1 4 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 1051-2276 EI 1532-8503 J9 J RENAL NUTR JI J. Renal Nutr. PD JAN PY 2015 VL 25 IS 1 BP 25 EP 30 DI 10.1053/j.jrn.2014.06.012 PG 6 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA AX4ON UT WOS:000346911700006 PM 25213326 ER PT J AU Koo, KH Nguyen, HV Andrasik, MP George, WH AF Koo, Kelly H. Nguyen, Hong V. Andrasik, Michele P. George, William H. TI The Cultural Context of Nondisclosure of Alcohol-Involved Acquaintance Rape Among Asian American College Women: A Qualitative Study SO JOURNAL OF SEX RESEARCH LA English DT Article ID SOCIAL SUPPORT; UNITED-STATES; HELP-SEEKING; STUDENTS; VICTIMS; SELF; ATTITUDES; SEXUALITY; IMMIGRANT; SEVERITY AB With high college enrollment and increasing alcohol use, Asian American (AA) college women may be at particular risk for experiencing alcohol-involved acquaintance rape. Although AA women have expressed the weakest intentions to report rape when compared to other ethnic groups, cultural factors influencing these intentions remain unexamined. Guided by grounded theory, 17 self-identified AA college women were interviewed about how the average AA college woman would respond to an alcohol-involved acquaintance rape. Despite awareness of benefits of disclosing rape, participants emphasized that nondisclosure would be the normative response. Three themes emerged from participants: institutional, sociocultural, and psychological contexts of nondisclosure. At an institutional level, nondisclosure referenced mental health and police services, which included Asian stereotypes and mistrust of police. Within a sociocultural context, rape nondisclosure focused on negative consequences on relationships with parents and, to a lesser extent, on friendships. Emotional avoidance and not labeling an acquaintance rape as rape were psychological strategies for rape nondisclosure. Participant's conceptualizations of mental and physical health concerns, specifically post-rape concerns, were framed within sociocultural/macrostructural contexts and may not match that of the more individualistic U.S. mainstream conceptualizations of health. Culturally sensitive rape education may be more effective in increasing rape prevention and support. C1 [Koo, Kelly H.; Nguyen, Hong V.; George, William H.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Andrasik, Michele P.] Univ Washington, Dept Psychiat, Fred Hutchinson Canc Res Ctr, HIV Vaccine Trials Network, Seattle, WA 98195 USA. RP Koo, KH (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM Kelly.Koo@va.gov FU NIAAA NIH HHS [1R01AA016281-01A2, 1F31AA018237-01A1] NR 47 TC 4 Z9 4 U1 2 U2 22 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0022-4499 EI 1559-8519 J9 J SEX RES JI J. Sex Res. PD JAN PY 2015 VL 52 IS 1 BP 55 EP 68 DI 10.1080/00224499.2013.826168 PG 14 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA AX0OL UT WOS:000346651500005 PM 24215167 ER PT J AU El-Hage, N Rodriguez, M Dever, SM Masvekar, RR Gewirtz, DA Shacka, JJ AF El-Hage, Nazira Rodriguez, Myosotys Dever, Seth M. Masvekar, Ruturaj R. Gewirtz, David A. Shacka, John J. TI HIV-1 and Morphine Regulation of Autophagy in Microglia: Limited Interactions in the Context of HIV-1 Infection and Opioid Abuse SO JOURNAL OF VIROLOGY LA English DT Article ID BECLIN 1-INDEPENDENT AUTOPHAGY; CELL-DEATH; T-CELLS; NEURONAL AUTOPHAGY; VIRUS TYPE-1; MECHANISM; GP120; TAT; MACROPHAGES; DEMENTIA AB Microglia are the predominant resident central nervous system (CNS) cell type productively infected by HIV-1, and play a key role in the progression of HIV-associated dementia (HAD). Moreover, neural dysfunction and progression to HAD are accelerated in opiate drug abusers. In the present study, we examined the role of the autophagy pathway in the neuropathogenesis of HIV-1 using primary human microglial cells and determined whether opiates converge at this point. Infection of microglia with the HIV-1(SF162) macrophage-tropic strain resulted in increased Beclin1 expression, accompanied by an increase of LC3 protein levels and accumulation of LC3 reporter RFP+ CFP+ (yellow) puncta, suggesting that HIV-1 infection triggers autophagosome formation without promoting protein degradation by the lysosome. Conversely, coexposure with HIV-1 and morphine significantly decreased virus-induced Beclin1 expression and autophagosome formation. Exploration of the possible mechanism(s) used by morphine to disrupt the autophagic process unveiled a significant increase in intracellular pH, which coincided with a reduction in the formation of acidic vesicular organelles and in autophagolysosome formation. Small interfering RNA targeting BECN1, a gene critical for autophagosome formation, significantly reduced viral replication and the virus-induced inflammatory responses. Conversely, morphine-enhanced viral replication and inflammatory responses were not affected by gene silencing with siBeclin1, suggesting that the interactive effect of morphine in HIV-1 pathogenesis is mediated through a Beclin1-independent mechanism. These novel findings may have important implications on the connections between autophagy and HIV-1 pathogenesis mediated by microglial cells in opioid-abusing individuals. IMPORTANCE About 50% of individuals infected with HIV-1 will develop some sort of neurocognitive impairment that cannot be prevented nor eradicated by antiretroviral therapy. The neuropathogenesis is mostly due to inflammatory responses by infected microglia, the resident immune cells of the brain. Cognitive disorders may also be associated with drugs of abuse. In fact, opioid drug users have an increased risk of developing neurocognitive disorders with increased progression to dementia. Although the mechanism(s) by which opioids exacerbate the neuropathogenesis of HIV-1 are not entirely known, it is well accepted that glia are critical to opiate responses. This study gives us new insight into possible autophagic mechanism(s) in microglia that control HIV-1 replication and virus-induced inflammation in the context of opioid abuse and should greatly improve our knowledge in the pathogenesis of HIV-1 resulting from substance abuse to provide a better understanding for the design of candidate antiviral therapies targeting drug-abusing individuals. C1 [El-Hage, Nazira; Dever, Seth M.; Gewirtz, David A.] Virginia Commonwealth Univ, Dept Pharmacol Toxicol, Richmond, VA 23284 USA. [Masvekar, Ruturaj R.] Virginia Commonwealth Univ, Dept Anat Neurobiol, Richmond, VA USA. [Rodriguez, Myosotys] Univ Cent Caribe, Dept Microbiol Immunol, Bayamon, PR USA. [Shacka, John J.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Shacka, John J.] Birmingham VA Med Ctr, Birmingham, AL USA. RP El-Hage, N (reprint author), Virginia Commonwealth Univ, Dept Pharmacol Toxicol, Med Coll Virginia Campus, Richmond, VA 23284 USA. EM nelhage@fiu.edu FU National Institutes of Health (NIH) [R01 DA036154, R03 DA026744, F32 DA033898]; NIH National Cancer Institute Cancer Center [P30 CA016059] FX This study was funded by National Institutes of Health (NIH) grants R01 DA036154 and R03 DA026744 (N.E.H.) and F32 DA033898 (S.M.D.). blow cytometry was supported, in part, by NIH National Cancer Institute Cancer Center support grant P30 CA016059. NR 74 TC 12 Z9 13 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JAN PY 2015 VL 89 IS 2 BP 1024 EP 1035 DI 10.1128/JVI02022-14 PG 12 WC Virology SC Virology GA AX8SN UT WOS:000347178900012 PM 25355898 ER PT J AU Garcia, JM Boccia, RV Graham, CD Yan, Y Duus, EM Allen, S Friend, J AF Garcia, Jose M. Boccia, Ralph V. Graham, Charles D. Yan, Ying Duus, Elizabeth Manning Allen, Suzan Friend, John TI Anamorelin for patients with cancer cachexia: an integrated analysis of two phase 2, randomised, placebo-controlled, double-blind trials SO LANCET ONCOLOGY LA English DT Article ID GROWTH-HORMONE SECRETAGOGUE; GHRELIN RECEPTOR AGONIST; HEALTHY-VOLUNTEERS; BODY-COMPOSITION; TUMOR-GROWTH; STRENGTH; ANOREXIA; MODEL; MASS; INTERLEUKIN-6 AB Background Cancer anorexia-cachexia syndrome is associated with increased morbidity and mortality. Anamorelin is an oral ghrelin-receptor agonist with appetite-enhancing and anabolic activity. We assessed the effects of anamorelin on body composition, strength, quality of life, biochemical markers, and safety in patients with cancer anorexia-cachexia. Methods Data were pooled, a priori, from two completed phase 2, multicentre, placebo-controlled, double-blind trials in patients with advanced or incurable cancer and weight loss of 5% or more. Patients were stratified by weight loss severity (5-15%, >15%) and randomly allocated (1: 1) with a computer-generated randomisation schedule to anamorelin hydrochloride 50 mg or placebo once-daily for 12 weeks. Primary outcome was lean body mass by dual-energy x-ray absorptiometry over the 12 week treatment period in eligible patients who had at least one dose of study drug and post-treatment efficacy assessment. We assessed safety in all patients who received at least one dose of study drug. The trials are registered with ClinicalTrials.gov, numbers NCT00219817 and NCT00267358. Findings Between June 29, 2005, and Oct 26, 2006, we enrolled 44 patients in the anamorelin group and 38 patients in the placebo group. 74 patients were eligible for the efficacy analyses. Over 12 weeks, lean body mass increased in 38 patients in the anamorelin group by a least-squares mean of 1.89 kg (95% CI 0.84 to 2.95) compared with a decrease of a least-squares mean of -0.20 kg (-1.23 to 0.83) for 36 patients in the placebo group (difference 2.09 kg [0.94-3.25]; p=0.0006). 42 (95%) of 44 patients treated with anamorelin and 33 (87%) of 38 patients treated with placebo had adverse events. The most common grade 3-4 adverse events (treatment-related or not) in the anamorelin group were fatigue, asthenia, atrial fibrillation, and dyspnoea (two [5%] each); in the placebo group, such events were pneumonia (three [8%]) and anaemia, thrombocytopenia, abdominal pain, anxiety, and dyspnoea (two [5%] each). Interpretation Anamorelin treatment for 12 weeks had a favourable clinical response profile in patients with cancer anorexia-cachexia syndrome. These findings support further investigation in this setting. C1 [Garcia, Jose M.] Michael E DeBakey VA Med Ctr, Ctr Translat Res Inflammatory Dis, Div Endocrinol Diabet & Metab, Houston, TX 77030 USA. [Boccia, Ralph V.] Georgetown Univ, Ctr Canc & Blood Disorders, Bethesda, MD USA. [Graham, Charles D.] Charleston Canc Ctr, Charleston, SC USA. [Yan, Ying; Duus, Elizabeth Manning; Allen, Suzan; Friend, John] Helsinn Therapeut, Bridgewater, NJ USA. RP Garcia, JM (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Div Endocrinol Diabet & Metab, 2002 Holcombe Blvd,Bldg 109,Room 210, Houston, TX 77030 USA. EM jgarcia1@bcm.edu FU Helsinn Therapeutics (US), Helsinn Healthcare SA FX Helsinn Therapeutics (US), Helsinn Healthcare SA. NR 36 TC 50 Z9 53 U1 3 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD JAN PY 2015 VL 16 IS 1 BP 108 EP 116 DI 10.1016/S1470-2045(14)71154-4 PG 9 WC Oncology SC Oncology GA AX4OZ UT WOS:000346912800050 PM 25524795 ER PT J AU Samuel, CA Zaslavsky, AM Landrum, MB Lorenz, K Keating, NL AF Samuel, Cleo A. Zaslavsky, Alan M. Landrum, Mary Beth Lorenz, Karl Keating, Nancy L. TI Developing and Evaluating Composite Measures of Cancer Care Quality SO MEDICAL CARE LA English DT Article DE cancer care; quality measurement; composites ID PROSTATE-CANCER; OF-CARE; MULTIPLE COMPARISONS; AMBULATORY-CARE; PERFORMANCE; RADIOTHERAPY; INDICATORS; CASTRATION; CARCINOMA; VETERANS AB Background:Composite measures are useful for distilling quality data into summary scores; yet, there has been limited use of composite measures for cancer care.Objective:Compare multiple approaches for generating cancer care composite measures and evaluate how well composite measures summarize dimensions of cancer care and predict survival.Study Design:We computed hospital-level rates for 13 colorectal, lung, and prostate cancer process measures in 59 Veterans Affairs hospitals. We computed 4 empirical-factor (based on an exploratory factor analysis), 3 cancer-specific (colorectal, lung, prostate care), and 3 care modality-specific (diagnosis/evaluation, surgical, nonsurgical treatments) composite measures. We assessed correlations among all composite measures and estimated all-cause survival for colon, rectal, non-small cell lung, and small cell lung cancers as a function of composite scores, adjusting for patient characteristics.Results:Four factors emerged from the factor analysis: nonsurgical treatment, surgical treatment, colorectal early diagnosis, and prostate treatment. We observed strong correlations (r) among composite measures comprised of similar process measures (r=0.58-1.00, P<0.0001), but not among composite measures reflecting different care dimensions. Composite measures were rarely associated with survival.Conclusions:The empirical-factor domains grouped measures variously by cancer type and care modality. The evidence did not support any single approach for generating cancer care composite measures. Weak associations across different care domains suggest that low-quality and high-quality cancer care delivery may coexist within Veterans Affairs hospitals. C1 [Samuel, Cleo A.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC USA. [Zaslavsky, Alan M.; Landrum, Mary Beth; Keating, Nancy L.] Harvard Univ, Dept Hlth Care Policy, Sch Med, Boston, MA 02115 USA. [Lorenz, Karl] Vet Adm Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Los Angeles, CA USA. [Lorenz, Karl] Vet Adm Greater Los Angeles Healthcare Syst, Div Palliat Care, Los Angeles, CA USA. [Lorenz, Karl] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. RP Keating, NL (reprint author), Harvard Univ, Dept Hlth Care Policy, Sch Med, 180 Longwood Ave, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu FU Department of Veterans Affairs through the Office of Policy and Planning as part of an evaluation of oncology care; Ruth L. Kirschstein National Research Service Award; Harvard University Graduate Prize Fellowship FX Supported by the Department of Veterans Affairs through the Office of Policy and Planning as part of an evaluation of oncology care. C.A.S.'s effort was supported by the Ruth L. Kirschstein National Research Service Award and the Harvard University Graduate Prize Fellowship. NR 40 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD JAN PY 2015 VL 53 IS 1 BP 54 EP 64 DI 10.1097/MLR.0000000000000257 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AX0OE UT WOS:000346650700010 PM 25373407 ER PT J AU Aldridge, MD Canavan, M Cherlin, E Bradley, EH AF Aldridge, Melissa D. Canavan, Maureen Cherlin, Emily Bradley, Elizabeth H. TI Has Hospice Use Changed? 2000-2010 Utilization Patterns SO MEDICAL CARE LA English DT Article DE hospice; Medicare hospice benefit; health services research ID ENROLLMENT; CARE; CAREGIVERS; MEDICARE; DEPRESSION; LENGTH AB Background:Hospice use has increased substantially during the past decade by an increasingly diverse patient population; however, little is known about patterns of hospice use and how these patterns have changed during the past decade.Objective:To characterize Medicare hospice users in 2000 and 2010 and estimate the prevalence of (1) very short (1 wk) hospice enrollment; (2) very long (>6 mo) hospice enrollment; and (3) hospice disenrollment and how these utilization patterns have varied over time and by patient and hospice characteristics.Research Design:Cross-sectional analysis of Medicare hospice claims data from 2000 and 2010.Subjects:All US Medicare Hospice Benefit enrollees in 2000 (N=529,573) and 2010 (N=1,150,194).Results:As of 2010, more than half (53.4%) of all Medicare decedents who used hospice had either very short (1 wk, 32.4%) or very long (>6 mo, 13.9%) hospice enrollment or disenrolled from hospice before death (10.6%). This represents an increase of 4.9 percentage points from 2000. In multivariable analysis, patients with noncancer diagnoses, the fastest growing group of hospice users, were approximately twice as likely as those with cancer to have very short or long enrollment periods and to disenroll from hospice.Conclusion:The substantial proportion of hospice users with very short or long enrollment, or enrollments that end before death, underscores the potential for interventions to improve the timing and appropriateness of hospice referral so that the full benefits of hospice are received by patients and families. C1 [Aldridge, Melissa D.] Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Aldridge, Melissa D.] James J Peters VA Med Ctr, Bronx, NY USA. [Canavan, Maureen; Cherlin, Emily; Bradley, Elizabeth H.] Yale Univ, Sch Publ Hlth, Dept Hlth Policy & Management, New Haven, CT USA. RP Aldridge, MD (reprint author), Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, One Gustave L Levy Pl,POB 1070, New York, NY 10029 USA. EM melissa.aldridge@mssm.edu FU National Institute of Nursing Research [5R01NR013499]; John D. Thompson Foundation FX Supported by the National Institute of Nursing Research 5R01NR013499 (M.D.A.); and the John D. Thompson Foundation (E.H.B.). NR 27 TC 14 Z9 14 U1 7 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD JAN PY 2015 VL 53 IS 1 BP 95 EP 101 DI 10.1097/MLR.0000000000000256 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AX0OE UT WOS:000346650700015 PM 25373406 ER PT J AU Tache, Y AF Tache, Y. TI Corticotrophin-releasing factor 1 activation in the central amygdale and visceral hyperalgesia SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Review DE central amygdala; CRF; CRF1; antagonists; noradrenaline; stress; visceral hyperalgesia ID IRRITABLE-BOWEL-SYNDROME; FACTOR-I RECEPTORS; STRESS-RELATED ALTERATIONS; CENTRAL NUCLEUS; COLONIC HYPERSENSITIVITY; COLORECTAL DISTENSION; FACTOR CRF; PSYCHOLOGICAL STRESS; MEDIATED MECHANISMS; RECTAL DISTENSION AB Corticotropin-releasing factor (CRF)-CRF1 receptor in the brain plays a key role in stress-related alterations of behavior including anxiety/depression, and autonomic and visceral functions. In particular, CRF1 signaling mediates hypersensitivity to colorectal distension (CRD) in various models (early life adverse events, repeated psychological stress, chronic high anxiety, postcolonic inflammation, or repeated nociceptive CRD). So far, knowledge of brain sites involved is limited. A recent article demonstrates in rats that CRF microinjected into the central amygdala (CeA) induces a hyperalgesic response to CRD and enhances the noradrenaline and dopamine levels at this site. The visceral and noradrenaline, unlike dopamine, responses were blocked by a CRF1 antagonist injected into the CeA. Here, we review the emerging role that CRF-CRF1 signaling plays in the CeA to induce visceral hypersensitivity. In the somatic pain field, CRF in the CeA was shown to induce pain sensitization. This is mediated by the activation of postsynaptic CRF1 receptors and protein kinase A signaling that increases N-methyl-d-aspartate receptor neurotransmission. In addition, the activation of tetraethylamonium-sensitive ion channels such as Kv3 accelerates repolarization and firing rate. Whether facilitation of pain transmission underlies CRF action in the CeA-induced visceral hypersensitivity will need to be delineated. CRF1 signaling in the CeA is also an important component of the neuronal circuitry inducing anxiety-like behavior and positioned at the interphase of the reciprocal relationship between pain and affective state. The hyperactivity of this system may represent the neuroanatomical and biochemical substrate contributing to the coexpression of hypersensitivity to CRD and mood disorders in subsets of irritable bowel syndrome patients. This review describes the role of CRF-CRF1 receptor signaling in experimental models of visceral hyperalgesia with a focus on brain sites and mechanisms of action in the central amygdala. C1 [Tache, Y.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress & Womens Hlth, Los Angeles, CA 90095 USA. [Tache, Y.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. [Tache, Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU Veterans Administration Research Career Scientist Award; [NIHDDK-41303]; [NIHDDK-57238] FX Supported by NIHDDK-41303 (Animal core), NIHDDK-57238, and Veterans Administration Research Career Scientist Award. NR 64 TC 6 Z9 6 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 EI 1365-2982 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD JAN PY 2015 VL 27 IS 1 BP 1 EP 6 DI 10.1111/nmo.12495 PG 6 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA AX8NX UT WOS:000347167100001 PM 25557223 ER PT J AU Walker, RJ Gebregziabher, M Martin-Harris, B Egede, LE AF Walker, Rebekah J. Gebregziabher, Mulugeta Martin-Harris, Bonnie Egede, Leonard E. TI Understanding the influence of psychological and socioeconomic factors on diabetes self-care using structured equation modeling SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Diabetes; Self-care; Psychosocial factors; Social determinants; Socioeconomic ID OF-THE-LITERATURE; PSYCHOMETRIC PROPERTIES; DEPRESSION; DISTRESS; VALIDITY; HEALTH; SCALE; METAANALYSIS; PERSPECTIVES; INSTRUMENT AB Objective: To develop and test latent variables of the social determinants of health that influence diabetes self-care. Methods: 615 adults with type 2 diabetes were recruited from two adult primary care clinics in the southeastern United States. Confirmatory factor analyses (CFA) identified the latent factors underlying socioeconomic determinants, psychosocial determinants, and self-care (diet, exercise, foot care, glucose testing, and medication adherence). Structured equation modeling (SEM) investigated the relationship between determinants and self-care. Results: Latent variables were created for diabetes self-care, psychological distress, self-efficacy, social support and social status. The initial model (chi2(254) = 388.04, p < 0.001, RMSEA = 0.03, CFI = 0.98) showed that lower psychological distress (r = -0.13, p = 0.019), higher social support (r = 0.15, p = 0.008), and higher self-efficacy (r = 0.47, p < 0.001) were significantly related to diabetes self-care. Social status was not significantly related to self-care (r = 0.003, p = 0.952). In the trimmed model (chi2(189) = 211.40, p = 0.126, RMSEA = 0.01, CFI = 0.99) lower psychological distress (r = -0.13, p = 0.016), higher social support (r = 0.15, p = 0.007), and higher self-efficacy (r = 0.47, p <0.001) remained significantly related to diabetes self-care. Conclusion: Based on theoretical relationships, three latent factors that measure social determinants of health (psychological distress, social support and self-efficacy) are strongly associated with diabetes self-care. Practice implications: This suggests that social determinants should be taken into account when developing patient self-care goals. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Walker, Rebekah J.; Gebregziabher, Mulugeta; Egede, Leonard E.] HEROIC, Charleston VA HSR&D COIN, Ralph H Johnson VAMC, Charleston, SC USA. [Walker, Rebekah J.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Walker, Rebekah J.; Martin-Harris, Bonnie] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta] Med Univ S Carolina, Dept Med, Div Publ Hlth Sci, Charleston, SC 29425 USA. [Martin-Harris, Bonnie] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Egede, Leonard E.] Med Univ S Carolina, Dept Med, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu OI Gebregziabher, Mulugeta/0000-0002-4826-481X FU National Institute of Diabetes and Digestive and Kidney Disease [K24DK093699-01] FX This study was supported by Grant K24DK093699-01 from The National Institute of Diabetes and Digestive and Kidney Disease (PI: Leonard Egede). NR 47 TC 8 Z9 8 U1 1 U2 16 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD JAN PY 2015 VL 98 IS 1 BP 34 EP 40 DI 10.1016/j.pec.2014.10.002 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA AX5FO UT WOS:000346952400004 PM 25455793 ER PT J AU Fu, SS Roth, C Battaglia, CT Nelson, DB Farmer, MM Do, T Goldstein, MG Widome, R Hagedorn, H Zillich, AJ AF Fu, Steven S. Roth, Craig Battaglia, Catherine T. Nelson, David B. Farmer, Melissa M. Do, Tam Goldstein, Michael G. Widome, Rachel Hagedorn, Hildi Zillich, Alan J. TI Training primary care clinicians in motivational interviewing: A comparison of two models SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Motivational interviewing; Tobacco cessation; Primary care; Provider training ID TOBACCO CESSATION; RANDOMIZED-TRIAL; UNITED-STATES; COMPETENCE; STUDENTS; SMOKING; ADULTS; SCORES AB Objectives: To evaluate implementing two training models for motivational interviewing (MI) to address tobacco use with primary care clinicians. Methods: Clinicians were randomized to moderate or high intensity. Both training modalities included a single 1/2 day workshop facilitated by MI expert trainers. The high intensity (HI) training provided six booster sessions including telephone interactions with simulated patients and peer coaching by MI champions over 3 months. To assess performance of clinicians to deliver MI, an objective structured clinical evaluation (OSCE) was conducted before and 12 weeks after the workshop training. Results: Thirty-four clinicians were enrolled; 18 were randomly assigned to HI. Compared to the moderate intensity group, the HI group scored significantly higher during the OSCE for three of six global Motivational Interviewing Treatment Integrity scale scores. There was also significant improvement for three of the four measures of MI counseling knowledge, skills and confidence. Conclusions: Using champions and telephone interactions with simulated patients as enhancement strategies for MI training programs is feasible in the primary care setting and results in greater gains in MI proficiency. Practice implications: Results confirm and expand evidence for use of booster sessions to improve the proficiency of MI training programs for primary care clinicians. Published by Elsevier Ireland Ltd. C1 [Fu, Steven S.; Roth, Craig; Nelson, David B.; Do, Tam; Widome, Rachel; Hagedorn, Hildi] Minneapolis VA Healthcare Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN 55417 USA. [Fu, Steven S.; Roth, Craig; Nelson, David B.; Do, Tam; Widome, Rachel; Hagedorn, Hildi] Minneapolis VA Healthcare Syst, Gen Internal Med Sect, Minneapolis, MN 55417 USA. [Battaglia, Catherine T.] VA Eastern Colorado Hlth Care Syst, Denver Seattle Ctr Veteran Ctr & Value Driven Car, Denver, CO USA. [Battaglia, Catherine T.] Univ Colorado, Colorado Sch Publ Hlth, Denver, CO 80202 USA. [Farmer, Melissa M.] VA Greater Angeles Hlth Care Syst, Ctr Study Healthcare Innovat Implementat & Policy, Los Angeles, CA USA. [Goldstein, Michael G.] VHA Natl Ctr Hlth Promot & Dis, Durham, NH USA. [Zillich, Alan J.] Roudebush VA Med Ctr, Ctr Hlth Informat & Commun, Indianapolis, IN USA. [Zillich, Alan J.] Purdue Univ, Coll Pharm, W Lafayette, IN 47907 USA. RP Fu, SS (reprint author), Minneapolis VA Healthcare Syst, Ctr Chron Dis Outcomes Res, One Vet Dr 152, Minneapolis, MN 55417 USA. EM Steven.Fu@va.gov FU VA Health Services Research & Development (HSR&D) Rapid Response Project [11-019]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development and Health Services Research and Development; VA HSR&D Research Career Development Award [RCD 06-304-1, 09-012] FX This study was funded by the VA Health Services Research & Development (HSR&D) Rapid Response Project 11-019. The Center for Chronic Disease Outcomes Research is supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development and Health Services Research and Development. Dr. Zillich was supported by VA HSR&D Research Career Development Award (RCD 06-304-1). Dr. Widome was supported by a VA HSR&D Career Development Award #09-012. VA HSR&D had no role in the study design, data collection, analysis or interpretation, writing of the manuscript, and in the decision to submit the paper for publication. NR 27 TC 6 Z9 6 U1 1 U2 15 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD JAN PY 2015 VL 98 IS 1 BP 61 EP 68 DI 10.1016/j.pec.2014.10.007 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA AX5FO UT WOS:000346952400008 PM 25455795 ER PT J AU McMullen, CK Safford, MM Bosworth, HB Phansalkar, S Leong, A Fagan, MB Trontell, A Rumptz, M Vandermeer, ML Brinkman, WB Burkholder, R Frank, L Hommel, K Mathews, R Hornbrook, MC Seid, M Fordis, M Lambertt, B McElwee, N Singh, JA AF McMullen, Carmit K. Safford, Monika M. Bosworth, Hayden B. Phansalkar, Shobha Leong, Amye Fagan, Maureen B. Trontell, Anne Rumptz, Maureen Vandermeer, Meredith L. Brinkman, William B. Burkholder, Rebecca Frank, Lori Hommel, Kevin Mathews, Robin Hornbrook, Mark C. Seid, Michael Fordis, Michael Lambertt, Bruce McElwee, Newell Singh, Jasvinder A. CA CERTs PCMM Workshop Working Grp TI Patient-centered priorities for improving medication management and adherence SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Patient-centered research; Adherence; Chronic disease; Medication management; Stakeholder engagement ID OF-THE-LITERATURE; CARE; METAANALYSIS; INTERVENTIONS; STATEMENT; OUTCOMES; COST; RISK AB Objective: The Centers for Education and Research on Therapeutics convened a workshop to examine the scientific evidence on medication adherence interventions from the patient-centered perspective and to explore the potential of patient-centered medication management to improve chronic disease treatment. Methods: Patients, providers, researchers, and other stakeholders (N = 28) identified and prioritized ideas for future research and practice. We analyzed stakeholder voting on priorities and reviewed themes in workshop discussions. Results: Ten priority areas emerged. Three areas were highly rated by all stakeholder groups: creating tools and systems to facilitate and evaluate patient-centered medication management plans; developing training on patient-centered prescribing for providers; and increasing patients' knowledge about medication management. However, priorities differed across stakeholder groups. Notably, patients prioritized using peer support to improve medication management while researchers did not. Conclusion: Engaging multiple stakeholders in setting a patient-centered research agenda and broadening the scope of adherence interventions to include other aspects of medication management resulted in priorities outside the traditional scope of adherence research. Practice Implications: Workshop participants recognized the potential benefits of patient-centered medication management but also identified many challenges to implementation that require additional research and innovation. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [McMullen, Carmit K.; Rumptz, Maureen; Vandermeer, Meredith L.; Hornbrook, Mark C.] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR 97227 USA. [Safford, Monika M.; Singh, Jasvinder A.] Univ Alabama Birmingham, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. [Bosworth, Hayden B.; Mathews, Robin] Duke Univ, Durham, NC USA. [Phansalkar, Shobha] Partners Healthcare Syst Inc, Wellesley, MA USA. [Phansalkar, Shobha] Brigham & Womens Hosp, Boston, MA 02115 USA. [Phansalkar, Shobha; Fagan, Maureen B.] Harvard Univ, Sch Med, Boston, MA USA. [Leong, Amye] Healthy Motivat, Santa Barbara, CA USA. [Fagan, Maureen B.] Brigham & Womens Hosp, Ctr Patients & Families, Boston, MA 02115 USA. [Trontell, Anne] Agcy Hlth Care Res & Qual, Rockville, MD USA. [Brinkman, William B.; Hommel, Kevin; Seid, Michael] Cincinnati Childrens Hosp & Med Ctr, Cincinnati, OH USA. [Burkholder, Rebecca] Natl Consumers League, Washington, DC USA. [Frank, Lori] Patient Ctr Outcomes Res Inst, Washington, DC USA. [Fordis, Michael] Baylor Coll Med, Houston, TX 77030 USA. [Lambertt, Bruce] Northwestern Univ, Ctr Commun & Hlth, Chicago, IL 60611 USA. [McElwee, Newell] Merck & Co Inc, New York, NY USA. [Singh, Jasvinder A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP McMullen, CK (reprint author), Kaiser Permanente Northwest, Ctr Hlth Res, 3800N Interstate Ave, Portland, OR 97227 USA. EM Carmit.McMullen@kpchr.org FU Agency for Healthcare Research and Quality [U19HS021107] FX This project was supported by grant number U19HS021107 from the Agency for Healthcare Research and Quality. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality. We extend special acknowledgments to the late Jessie Gruman, who, as president and founder of the Center for Advancing Health provided a strong, articulate voice at the workshop. Her contributions as a patient representative brought focus and urgency to the issue of patient-centered medication management; she will be missed. NR 38 TC 5 Z9 5 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD JAN PY 2015 VL 98 IS 1 BP 102 EP 110 DI 10.1016/j.pec.2014.09.015 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA AX5FO UT WOS:000346952400014 PM 25448313 ER PT J AU Nguyen, KL Khan, SN Moriarty, JM Mohajer, K Renella, P Satou, G Ayad, I Patel, S Boechat, MI Finn, JP AF Nguyen, Kim-Lien Khan, Sarah N. Moriarty, John M. Mohajer, Kiyarash Renella, Pierangelo Satou, Gary Ayad, Ihab Patel, Swati Boechat, M. Ines Finn, J. Paul TI High-field MR imaging in pediatric congenital heart disease: Initial results SO PEDIATRIC RADIOLOGY LA English DT Article DE Magnetic resonance imaging; Magnetic resonance angiography; 3.0 Tesla; Congenital heart disease; Cardiovascular; Neonate; Children ID TO-NOISE RATIO; CARDIOVASCULAR MAGNETIC-RESONANCE; STATE FREE PRECESSION; CLINICAL-APPLICATIONS; TECHNICAL CONSIDERATIONS; SPATIAL-RESOLUTION; HIGH AGREEMENT; 3.0 TESLA; ANGIOGRAPHY; CHILDREN AB Comprehensive assessment of pediatric congenital heart disease (CHD) at any field strength mandates evaluation of both vascular and dynamic cardiac anatomy for which diagnostic quality contrast-enhanced magnetic resonance angiography (CEMRA) and cardiac cine are crucial. To determine whether high-resolution (HR) CEMRA and steady-state free precession (SSFP) cine can be performed reliably at 3.0 T in children with CHD and to compare the image quality to similar techniques performed at 1.5 T. Twenty-eight patients with a median age of 5 months and average weight 9.0 +/- 7.8 kg with suspected or known CHD were evaluated at 3.0 T. SSFP cine (n = 86 series) and HR-CEMRA (n = 414 named vascular segments) were performed and images were scored for image quality and artifacts. The findings were compared to those of 28 patients with CHD of similar weight who were evaluated at 1.5 T. Overall image quality on HR-CEMRA was rated as excellent or good in 96% (397/414) of vascular segments at 3.0 T (k = 0.49) and in 94% (349/371) of vascular segments at 1.5 T (k = 0.36). Overall image quality of SSFP was rated excellent or good in 91% (78/86) of cine series at 3.0 T (k = 0.55) and in 81% (87/108) at 1.5 T (k = 0.47). Off-resonance artifact was common at both field strengths, varied over the cardiac cycle and was more prevalent at 3.0 T. At 3.0 T, off-resonance dark band artifact on SSFP cine was absent in 3% (3/86), mild in 69% (59/86), moderate in 27% (23/86) and severe in 1% (1/86) of images; at 1.5 T, dark band artifact was absent in 16% (17/108), mild in 69% (75/108), moderate in 12% (13/108) and severe in 3% (3/108) of cine images. The signal-to-noise ratio and contrast-to-noise ratio of both SSFP cine and HR-CEMRA images were significantly higher at 3.0 T than at 1.5 T (P < 0.001). Signal-to-noise ratio and contrast-to-noise ratio of high-resolution contrast-enhanced magnetic resonance angiography and SSFP cine were higher at 3.0 T than at 1.5 T. Artifacts on SSFP cine were cardiac phase specific and more prevalent at 3.0 T such that frequency-tuning was required in one-third of exams. In neonates, high spatial resolution CEMRA was highly reliable in defining extracardiac vascular anatomy. C1 [Nguyen, Kim-Lien] Univ Calif Los Angeles, David Geffen Sch Med, Div Cardiol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Khan, Sarah N.; Moriarty, John M.; Mohajer, Kiyarash; Renella, Pierangelo; Boechat, M. Ines; Finn, J. Paul] Univ Calif Los Angeles, Dept Radiol Sci, Los Angeles, CA 90095 USA. [Satou, Gary] Univ Calif Los Angeles, David Geffen Sch Med, Div Pediat Cardiol, Los Angeles, CA 90095 USA. [Ayad, Ihab; Patel, Swati] Univ Calif Los Angeles, David Geffen Sch Med, Dept Anesthesia, Los Angeles, CA 90095 USA. RP Finn, JP (reprint author), Univ Calif Los Angeles, Dept Radiol Sci, Peter V Ueberroth Bldg,Ste 3371,10945 Le Conte, Los Angeles, CA 90095 USA. EM pfinn@mednet.ucla.edu OI Nguyen, Kim-Lien/0000-0002-8854-2976 NR 42 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD JAN PY 2015 VL 45 IS 1 BP 42 EP 54 DI 10.1007/s00247-014-3093-y PG 13 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA AX8NB UT WOS:000347165000009 PM 25086500 ER PT J AU Belanger, AY Cameron, MH Michlovitz, SL Bellew, JW Freeman, L AF Belanger, Alain Yvan Cameron, Michelle H. Michlovitz, Susan L. Bellew, James W. Freeman, Lynn TI The American Physical Therapy Association's top five Choosing Wisely recommendations SO PHYSICAL THERAPY LA English DT Letter C1 [Belanger, Alain Yvan] Univ Laval, Fac Med, Rehabil Dept, Quebec City, PQ G1K 7P4, Canada. [Cameron, Michelle H.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Cameron, Michelle H.] Portland VA Med Ctr, Portland, OR USA. [Michlovitz, Susan L.] Cayuga Hand Therapy & PT, Ithaca, NY USA. [Michlovitz, Susan L.] Cayuga Hand Therapy & PT, Indianapolis, IN 46227 USA. [Bellew, James W.] Univ Indianapolis, Indianapolis, IN 46227 USA. RP Belanger, AY (reprint author), Univ Laval, Fac Med, Rehabil Dept, Quebec City, PQ G1K 7P4, Canada. EM alainybelanger@gmail.com NR 5 TC 3 Z9 3 U1 0 U2 1 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 EI 1538-6724 J9 PHYS THER JI Phys. Ther. PD JAN PY 2015 VL 95 IS 1 BP 142 EP 143 DI 10.2522/ptj.2015.95.1.142 PG 2 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA AX8FU UT WOS:000347146400014 PM 25554705 ER PT J AU Carbonaro, TM Eshleman, AJ Forster, MJ Cheng, KJ Rice, KC Gatch, MB AF Carbonaro, Theresa M. Eshleman, Amy J. Forster, Michael J. Cheng, Kejun Rice, Kenner C. Gatch, Michael B. TI The role of 5-HT2A, 5-HT2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice SO PSYCHOPHARMACOLOGY LA English DT Article DE N,N-diisopropyltryptamine; N,N-dimethyltryptamine; Hallucinogens; Drug discrimination; 5-HT2A; 5-HT2C; mGluR2; Rat ID DISCRIMINATIVE STIMULUS; DOSE-RESPONSE; DRUG DISCRIMINATION; BINDING; HUMANS; LSD; LOCALIZATION; AGONISTS AB Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens. The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT). Drug discrimination, head twitch, and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084), and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT. MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT's effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT > DMT) which were blocked by MDL1000907. DiPT was a low-potency full agonist at 5-HT2CR in vitro. The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree. C1 [Carbonaro, Theresa M.; Forster, Michael J.; Gatch, Michael B.] Univ North Texas Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX 76107 USA. [Eshleman, Amy J.] Portland VA Med Ctr, Res Serv, Portland, OR USA. [Eshleman, Amy J.] Oregon Hlth & Sci Univ, Dept Psychiat & Behav Neurosci, Portland, OR 97201 USA. [Cheng, Kejun; Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA. [Cheng, Kejun; Rice, Kenner C.] NIAAA, Bethesda, MD 20892 USA. RP Gatch, MB (reprint author), Univ North Texas Hlth Sci Ctr, Dept Pharmacol & Neurosci, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA. EM michael.gatch@unthsc.edu FU Addiction Treatment Discovery Program of the National Institute on Drug Abuse [NIH N01DA-7-8872]; National Institute on Drug Abuse; National Institute on Alcohol Abuse and Alcoholism; [T32 AG020494] FX Funding was provided by the Addiction Treatment Discovery Program of the National Institute on Drug Abuse (NIH N01DA-7-8872) and by T32 AG020494. A portion of this work was supported by the Intramural Research Programs of the National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism. There are no conflicts of interest. NR 33 TC 9 Z9 9 U1 1 U2 24 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2015 VL 232 IS 1 BP 275 EP 284 DI 10.1007/s00213-014-3658-3 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AX8NI UT WOS:000347165700023 PM 24985890 ER PT J AU Fung, SJ Chase, MH AF Fung, Simon J. Chase, Michael H. TI Postsynaptic Inhibition of Hypoglossal Motoneurons Produces Atonia of the Genioglossal Muscle During Rapid Eye Movement Sleep SO SLEEP LA English DT Article DE atonia; hypoglossal; IPSP; motoneuron; OSA; postsynaptic inhibition; REM sleep ID ACTIVE SLEEP; MOTO-NEURONS; REM-SLEEP; RESPIRATORY MOTONEURONS; INTRACELLULAR ANALYSIS; NERVE-STIMULATION; XII-MOTONEURONS; SPINAL-CORD; CAT; RAT AB Study Objectives: Hypoglossal motoneurons were recorded intracellularly to determine whether postsynaptic inhibition or disfacilitation was responsible for atonia of the lingual muscles during rapid eye movement (REM) sleep. Design: Intracellular records were obtained of the action potentials and subthreshold membrane potential activity of antidromically identified hypoglossal motoneurons in cats during wakefulness, nonrapid eye movement (NREM) sleep, and REM sleep. A cuff electrode was placed around the hypoglossal nerve to antidromically activate hypoglossal motoneurons. The state-dependent changes in membrane potential, spontaneous discharge, postsynaptic potentials, and rheobase of hypoglossal motoneurons were determined. Analyses and Results: During quiet wakefulness and NREM sleep, hypoglossal motoneurons exhibited spontaneous repetitive discharge. In the transition from NREM sleep to REM sleep, repetitive discharge ceased and the membrane potential began to hyperpolarize; maximal hyperpolarization (10.5 mV) persisted throughout REM sleep. During REM sleep there was a significant increase in rheobase, which was accompanied by barrages of large-amplitude inhibitory postsynaptic potentials (IPSPs), which were reversed following the intracellular injection of chloride ions. The latter result indicates that they were mediated by glycine; IPSPs were not present during wakefulness or NREM sleep. Conclusions: We conclude that hypoglossal motoneurons are postsynaptically inhibited during naturally occurring REM sleep; no evidence of disfacilitation was observed. The data also indicate that glycine receptor-mediated postsynaptic inhibition of hypoglossal motoneurons is crucial in promoting atonia of the lingual muscles during REM sleep. C1 [Fung, Simon J.; Chase, Michael H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Fung, Simon J.; Chase, Michael H.] WebSci Int, Los Angeles, CA 90024 USA. [Chase, Michael H.] Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. RP Fung, SJ (reprint author), WebSci Int, 1251 Westwood Blvd, Los Angeles, CA 90024 USA. EM sfung@websciences.org FU [101BX00819]; [TGS-109219]; [1R01HL116845] FX This was not an industry supported study. This study was supported by grants 101BX00819, TGS-109219 and 1R01HL116845. The authors have indicated no financial conflicts of interest. NR 60 TC 5 Z9 5 U1 0 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD JAN 1 PY 2015 VL 38 IS 1 BP 139 EP 146 DI 10.5665/sleep.4340 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AX8OT UT WOS:000347169300016 PM 25325470 ER PT J AU Dugan, J Griffiths, E Snow, P Rosenzweig, H Lee, E Brown, B Carr, DW Rose, C Rosenbaum, J Davey, MP AF Dugan, Jae Griffiths, Eric Snow, Paige Rosenzweig, Holly Lee, Ellen Brown, Brieanna Carr, Daniel W. Rose, Carlos Rosenbaum, James Davey, Michael P. TI Blau Syndrome-Associated Nod2 Mutation Alters Expression of Full-Length NOD2 and Limits Responses to Muramyl Dipeptide in Knock-in Mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; EARLY-ONSET SARCOIDOSIS; CROHNS-DISEASE; SIGNALING PATHWAYS; CARD15 MUTATIONS; MURINE MODEL; ACTIVATION; PROTEINS; SUSCEPTIBILITY; PEPTIDOGLYCAN AB The biochemical mechanism by which mutations in nucleotide-binding oligomerization domain containing 2 (NOD2) cause Blau syndrome is unknown. Several studies have examined the effect of mutations associated with Blau syndrome in vitro, but none has looked at the implication of the mutations in vivo. To test the hypothesis that mutated NOD2 causes alterations in signaling pathways downstream of NOD2, we created a Nod2 knock-in mouse carrying the most common mutation seen in Blau syndrome, R314Q (corresponding to R334Q in humans). The endogenous regulatory elements of mouse Nod2 were unaltered. R314Q mice showed reduced cytokine production in response to i.p. and intravitreal muramyl dipeptide (MDP). Macrophages from R314Q mice showed reduced NF-kappa B and IL-6 responses, blunted phosphorylation of MAPKs, and deficient ubiquitination of receptorinteracting protein 2 in response to MDP. R314Q mice expressed a truncated 80-kDa form of NOD2 that was most likely generated by a posttranslational event because there was no evidence for a stop codon or alternative splicing event. Human macrophages from two patients with Blau syndrome also showed a reduction of both cytokine production and phosphorylation of p38 in response to MDP, indicating that both R314Q mice and cells from patients with Blau syndrome show reduced responses to MDP. These data indicate that the R314Q mutation when studied with the Nod2 endogenous regulatory elements left intact is associated with marked structural and biochemical changes that are significantly different from those observed from studies of the mutation using overexpression, transient transfection systems. C1 [Dugan, Jae; Griffiths, Eric; Snow, Paige; Rosenzweig, Holly; Carr, Daniel W.; Davey, Michael P.] Portland VA Med Ctr, Portland, OR 97239 USA. [Dugan, Jae; Carr, Daniel W.; Rosenbaum, James; Davey, Michael P.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Rosenzweig, Holly; Lee, Ellen; Brown, Brieanna; Rosenbaum, James] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97239 USA. [Rosenzweig, Holly; Davey, Michael P.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. [Rose, Carlos] DuPont Hosp Children, Div Rheumatol, Wilmington, DE 19803 USA. [Rosenbaum, James] Legacy Devers Eye Inst, Portland, OR 97210 USA. RP Davey, MP (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM michael.davey@va.gov OI Snow, Paige/0000-0001-9836-7705 FU Department of Veterans Affairs Biomedical Laboratory Research and Development Service [5 IK2 BX001295, 5 I01 BX000229]; National Institutes of Health [5-T32-AI07472] FX This work was supported by Career Development (5 IK2 BX001295) and Merit Review (5 I01 BX000229) Awards from the Department of Veterans Affairs Biomedical Laboratory Research and Development Service as well as National Institutes of Health Training Grant 5-T32-AI07472. NR 52 TC 2 Z9 2 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2015 VL 194 IS 1 BP 349 EP 357 DI 10.4049/jimmunol.1402330 PG 9 WC Immunology SC Immunology GA AX1IH UT WOS:000346700500037 PM 25429073 ER PT J AU Nosova, EV Conte, MS Grenon, SM AF Nosova, Emily V. Conte, Michael S. Grenon, S. Marlene TI Advancing beyond the "heart-healthy diet" for peripheral arterial disease SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; POLYUNSATURATED FATTY-ACIDS; CARDIOVASCULAR-DISEASE; ENDOTHELIAL FUNCTION; RISK-FACTORS; VITAMIN-D; BLOOD-PRESSURE; UNITED-STATES; FOLIC-ACID; OMEGA-3-FATTY-ACID SUPPLEMENTATION AB Objective: Peripheral arterial disease (PAD) is a burdensome cardiovascular condition that results from chronic inflammatory insults to the arterial vasculature. Key risk factors include age, gender, type 2 diabetes mellitus, hypertension, hypercholesterolemia, hyperhomocysteinemia, smoking, lack of physical fitness, and poor diet, the latter three being modifiable in the development and progression of PAD. A growing body of evidence indicates that imbalanced nutrient intake may contribute to the development and progression of PAD. The purpose of this review is to summarize current knowledge about nutritional patterns among patients with PAD and to ascertain whether certain health-promoting foods and nutrients could benefit patients with this condition. Methods: We conducted a comprehensive literature review to examine primary source evidence for or against the nutrients that are commonly associated with PAD and their potential utility as therapies. Results: We summarized nine categories of nutrients, as well as four diets endorsed by the American Heart Association that may be prescribed to patients with or at risk for PAD. The nutrients reviewed included omega-3 polyunsaturated fatty acids (n-3 PUFAs), folate and B-series vitamins, and antioxidants. The diet plans described include the Dietary Approaches to Stop Hypertension (DASH) diet, Mediterranean diet, low-fat diet, low carbohydrate diet, Dr Dean Ornish's Spectrum Diet and Dr Andrew Weil's Anti-Inflammatory Diet. Conclusions: PAD is a chronic inflammatory condition that is associated with longstanding poor nutrition habits. We advocate for an intensified use of diet in PAD therapy, and we specifically recommend following eating patterns that are rich in nutrients with anti-inflammatory and antioxidant properties. C1 [Nosova, Emily V.; Conte, Michael S.; Grenon, S. Marlene] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Nosova, Emily V.; Grenon, S. Marlene] Univ Calif San Francisco, VIPERx Lab, San Francisco, CA 94143 USA. [Conte, Michael S.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Grenon, S. Marlene] San Francisco VA Med Ctr, Dept Surg, San Francisco, CA 94121 USA. RP Grenon, SM (reprint author), San Francisco VA Med Ctr, Mail Code 112G,4150 Clement St, San Francisco, CA 94121 USA. EM marlene.grenon@ucsfmedctr.org FU NHLBI NIH HHS [K23 HL122446] NR 86 TC 0 Z9 0 U1 4 U2 20 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 JAN PY 2015 VL 61 IS 1 BP 265 EP 274 DI 10.1016/j.jvs.2014.10.022 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA AX0JB UT WOS:000346637600043 PM 25534981 ER PT J AU Wani, WY Boyer-Guittaut, M Dodson, M Chatham, J Darley-Usmar, V Zhang, JH AF Wani, Willayat Yousuf Boyer-Guittaut, Michael Dodson, Matthew Chatham, John Darley-Usmar, Victor Zhang, Jianhua TI Regulation of autophagy by protein post-translational modification SO LABORATORY INVESTIGATION LA English DT Review ID PARKIN-MEDIATED MITOPHAGY; O-GLCNAC MODIFICATION; E3 UBIQUITIN LIGASE; LINKED N-ACETYLGLUCOSAMINE; TRANSCRIPTION FACTOR NRF2; BECLIN 1; SELECTIVE AUTOPHAGY; CROSS-TALK; MITOCHONDRIAL DEPOLARIZATION; DAMAGED MITOCHONDRIA AB Autophagy is a lysosome-mediated intracellular protein degradation process that involves about 38 autophagy-related genes as well as key signaling pathways that sense cellular metabolic and redox status, and has an important role in quality control of macromolecules and organelles. As with other major cellular pathways, autophagy proteins are subjected to regulatory post-translational modification. Phosphorylation is so far the most intensively studied post-translational modification in the autophagy process, followed by ubiquitination and acetylation. An interesting and new area is also now emerging, which appears to complement these more traditional mechanisms, and includes O-GlcNAcylation and redox regulation at thiol residues. Identification of the full spectrum of post-translational modifications of autophagy proteins, and determination of their impact on autophagy will be crucial for a better understanding of autophagy regulation, its deficits in diseases, and how to exploit this process for disease therapies. C1 [Wani, Willayat Yousuf; Dodson, Matthew; Chatham, John; Darley-Usmar, Victor; Zhang, Jianhua] Univ Alabama Birmingham, Ctr Free Radical Biol, Birmingham, AL 35294 USA. [Wani, Willayat Yousuf; Dodson, Matthew; Chatham, John; Darley-Usmar, Victor; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Boyer-Guittaut, Michael] Univ Franche Comte, Lab Biochim, EA3922, SFR IBCT FED4234, F-25030 Besancon, France. [Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL USA. RP Zhang, JH (reprint author), Univ Alabama Birmingham, Dept Pathol, Biomed Res Bldg 2,901 19th St South, Birmingham, AL 35294 USA. EM zhanja@uab.edu OI Zhang, Jianhua/0000-0002-2128-9574 FU [HL101192]; [HL-110366]; [NIHR01-NS064090] FX This work was supported by HL101192, HL-110366 (JC), and NIHR01-NS064090 (JZ). NR 129 TC 23 Z9 24 U1 1 U2 40 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2015 VL 95 IS 1 BP 14 EP 25 DI 10.1038/labinvest.2014.131 PG 12 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA AX5QA UT WOS:000346980700002 PM 25365205 ER PT J AU Farrell, MJ Shin, JI Smith, LJ Mauck, RL AF Farrell, M. J. Shin, J. I. Smith, L. J. Mauck, R. L. TI Functional consequences of glucose and oxygen deprivation on engineered mesenchymal stem cell-based cartilage constructs SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE Mesenchymal stem cells; Chondrogenesis; Three-dimensional culture; Mechanical properties; Glucose; Hypoxia ID BONE-MARROW; CHONDROGENIC DIFFERENTIATION; MECHANICAL-PROPERTIES; OSTEOGENIC DIFFERENTIATION; CLONAL HETEROGENEITY; ARTICULAR-CARTILAGE; STROMAL CELLS; AGAROSE GELS; HYPOXIA; CULTURE AB Objective: Tissue engineering approaches for cartilage repair have focused on the use of mesenchymal stem cells (MSCs). For clinical success, MSCs must survive and produce extracellular matrix in the physiological context of the synovial joint, where low nutrient conditions engendered by avascularity, nutrient utilization, and waste production prevail. This study sought to delineate the role of microenvironmental stressors on MSC viability and functional capacity in three dimensional (3D) culture. Design: We evaluated the impact of glucose and oxygen deprivation on the functional maturation of 3D MSC-laden agarose constructs. Since MSC isolation procedures result in a heterogeneous cell population, we also utilized micro-pellet culture to investigate whether clonal subpopulations respond to these microenvironmental stressors in a distinct fashion. Results: MSC health and the functional maturation of 3D constructs were compromised by both glucose and oxygen deprivation. Importantly, glucose deprivation severely limited viability, and so compromised the functional maturation of 3D constructs to the greatest extent. The observation that not all cells died suggested there exists heterogeneity in the response of MSC populations to metabolic stressors. Population heterogeneity was confirmed through a series of studies utilizing clonally derived subpopulations, with a spectrum of matrix production and cell survival observed under conditions of metabolic stress. Conclusions: Our findings show that glucose deprivation has a significant impact on functional maturation, and that some MSC subpopulations are more resilient to metabolic challenge than others. These findings suggest that pre-selection of subpopulations that are resilient to metabolic challenge may improve in vivo outcomes. (C) 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 [Farrell, M. J.; Shin, J. I.; Smith, L. J.; Mauck, R. L.] Univ Penn, McKay Orthopaed Res Lab, Dept Orthopaed Surg, Perelman Sch Med, Philadelphia, PA 19104 USA. [Farrell, M. J.; Mauck, R. L.] Univ Penn, Dept Bioengn, Sch Engn & Appl Sci, Philadelphia, PA 19104 USA. [Farrell, M. J.; Smith, L. J.; Mauck, R. L.] Philadelphia VA Med Ctr, Translat Musculoskeletal Res Ctr, Dept Vet Affairs, Philadelphia, PA 19104 USA. [Smith, L. J.] Univ Penn, Dept Neurosurg, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Mauck, RL (reprint author), Univ Penn, McKay Orthopaed Res Lab, 424 Stemmler Hall,36th St & Hamilton Walk, Philadelphia, PA 19104 USA. EM lemauck@mail.med.upenn.edu FU National Institutes of Health [R01 EB008722]; Department of Veterans' Affairs [I01 RX000700] FX This work was supported by the National Institutes of Health (R01 EB008722) and the Department of Veterans' Affairs (I01 RX000700). The authors would like to thank Joseph Chiaro and Deborah Gorth for technical assistance with hypoxic culture. The authors have no conflicts of interest to report that relate to this work. NR 50 TC 7 Z9 7 U1 0 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD JAN PY 2015 VL 23 IS 1 BP 134 EP 142 DI 10.1016/j.joca.2014.09.012 PG 9 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA AX0OA UT WOS:000346650300018 PM 25241241 ER PT J AU Deng, L Huang, L Sun, Y Heath, JM Wu, H Chen, YB AF Deng, Liang Huang, Lu Sun, Yong Heath, Jack M. Wu, Hui Chen, Yabing TI Inhibition of FOXO1/3 Promotes Vascular Calcification SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE AKT; FOXO1/3; PTEN; Runx2; ubiquitination; vascular calcification ID SMOOTH-MUSCLE-CELLS; TUMOR-SUPPRESSOR GENE; OSTEOBLAST DIFFERENTIATION; TRANSCRIPTION FACTORS; NEOINTIMA FORMATION; PROSTATE-CANCER; PTEN; RUNX2; INACTIVATION; AKT AB Objective-Vascular calcification is a characteristic feature of atherosclerosis, diabetes mellitus, and end-stage renal disease. We have demonstrated that activation of protein kinase B (AKT) upregulates runt-related transcription factor 2 (Runx2), a key osteogenic transcription factor that is crucial for calcification of vascular smooth muscle cells (VSMC). Using mice with SMC-specific deletion of phosphatase and tensin homolog (PTEN), a major negative regulator of AKT, the present studies uncovered a novel molecular mechanism underlying PTEN/AKT/FOXO (forkhead box O)-mediated Runx2 upregulation and VSMC calcification. Approach and Results-SMC-specific PTEN deletion mice were generated by crossing PTEN floxed mice with SM22 alpha-Cre transgenic mice. The PTEN deletion resulted in sustained activation of AKT that upregulated Runx2 and promoted VSMC calcification in vitro and arterial calcification ex vivo. Runx2 knockdown did not affect proliferation but blocked calcification of the PTEN-deficient VSMC, suggesting that PTEN deletion promotes Runx2-depedent VSMC calcification that is independent of proliferation. At the molecular level, PTEN deficiency increased the amount of Runx2 post-transcriptionally by inhibiting Runx2 ubiquitination. AKT activation increased phosphorylation of FOXO1/3 that led to nuclear exclusion of FOXO1/3. FOXO1/3 knockdown in VSMC phenocopied the PTEN deficiency, demonstrating a novel function of FOXO1/3, as a downstream signaling of PTEN/AKT, in regulating Runx2 ubiquitination and VSMC calcification. Using heterozygous SMC-specific PTEN-deficient mice and atherogenic ApoE(-/-) mice, we further demonstrated AKT activation, FOXO phosphorylation, and Runx2 ubiquitination in vascular calcification in vivo. Conclusions-Our studies have determined a new causative effect of SMC-specific PTEN deficiency on vascular calcification and demonstrated that FOXO1/3 plays a crucial role in PTEN/AKT-modulated Runx2 ubiquitination and VSMC calcification. C1 [Deng, Liang; Huang, Lu; Sun, Yong; Heath, Jack M.; Chen, Yabing] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL USA. [Wu, Hui] Univ Alabama Birmingham, Dept Pediat Dent, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Chen, Yabing] Univ Alabama Birmingham, Dept Res Serv, Birmingham, AL USA. RP Chen, YB (reprint author), 1825 Univ Blvd,630 Shelby Biomed Res Bldg, Birmingham, AL 35294 USA. EM ybchen@uab.edu FU National Institutes of Health [HL092215, DK100847]; Veterans Administration [BX000369, BX001591]; American Heart Association [12PRE11840009] FX This work was supported in part by grants from the National Institutes of Health HL092215 and DK100847 and Veterans Administration BX000369 and BX001591 (project 2) to Y. Chen. J.M. Heath was supported by American Heart Association Grant 12PRE11840009. NR 49 TC 14 Z9 14 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JAN PY 2015 VL 35 IS 1 BP 175 EP 183 DI 10.1161/ATVBAHA.114.304786 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AW9EU UT WOS:000346561100025 PM 25378413 ER PT J AU Badr, H Smith, CB Goldstein, NE Gomez, JE Redd, WH AF Badr, Hoda Smith, Cardinale B. Goldstein, Nathan E. Gomez, Jorge E. Redd, William H. TI Dyadic Psychosocial Intervention for Advanced Lung Cancer Patients and Their Family Caregivers: Results of a Randomized Pilot Trial SO CANCER LA English DT Article DE caregivers; couples; lung cancer; palliative care; psychological distress; psychosocial intervention; supportive care ID OF-LIFE CARE; PALLIATIVE CARE; INFORMAL CAREGIVERS; DISTRESS; END; METAANALYSIS; BEREAVEMENT; GUIDELINES; MANAGEMENT; SYSTEM AB BACKGROUNDAdvanced lung cancer (LC) patients and their families have reported low self-efficacy for self-care/caregiving and high rates of distress, yet few programs exist to address their supportive care needs during treatment. This pilot study examined the feasibility, acceptability, and preliminary efficacy of a 6-session, telephone-based dyadic psychosocial intervention that was developed for advanced LC patients and their caregivers. The program was grounded in self-determination theory (SDT), which emphasizes the importance of competence (self-efficacy), autonomy (sense of choice/volition), and relatedness (sense of belonging/connection) for psychological functioning. The primary outcomes were patient and caregiver psychological functioning (depression/anxiety) and caregiver burden. The secondary outcomes were the SDT constructs of competence, autonomy, and relatedness. METHODSThirty-nine advanced LC patients who were within 1 month of treatment initiation (baseline) and their caregivers (51% spouses/partners) completed surveys and were randomized to the intervention or usual medical care. Eight weeks after baseline, they completed follow-up surveys. RESULTSSolid recruitment (60%) and low attrition rates demonstrated feasibility. Strong program evaluations (mean, 8.6/10) and homework completion rates (88%) supported acceptability. Participants receiving the intervention evidenced significant improvements (P<.0001) in depression, anxiety, and caregiver burden in comparison with usual medical care. Large effect sizes (d1.2) favoring the intervention were also found for patient and caregiver competence and relatedness and for caregiver autonomous motivation for providing care. CONCLUSIONThese findings support intervention feasibility, acceptability, and preliminary efficacy. By empowering families with the skills to coordinate care and meet the challenges of LC together, this intervention holds great promise for improving palliative/supportive care services in cancer. Cancer 2015;121:150-158. (c) 2014 American Cancer Society. Advanced lung cancer patients and their caregivers who receive an intervention show significant improvements in depression, anxiety, and caregiver burden in comparison with those receiving usual medical care. Large effect sizes (d>1.2) are also shown for patient and caregiver competence and relatedness and caregiver autonomous motivation for providing care. C1 [Badr, Hoda; Redd, William H.] Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 USA. [Smith, Cardinale B.] Icahn Sch Med Mt Sinai, Dept Med, Div Hematol & Med Oncol, New York, NY 10029 USA. [Smith, Cardinale B.; Goldstein, Nathan E.; Gomez, Jorge E.] Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Goldstein, Nathan E.] James J Peters VA Med Ctr, Geriatr Res Educ & Clin Care Unit, Bronx, NY USA. RP Badr, H (reprint author), Icahn Sch Med Mt Sinai, Dept Oncol Sci, One Gustave L Levy Pl,Box 1130, New York, NY 10029 USA. EM hoda.badr@mssm.edu FU [P30 AG028741] FX This work was supported by a pilot grant awarded to Hoda Badr under P30 AG028741 (Albert Siu, MD, principal investigator). NR 34 TC 17 Z9 18 U1 6 U2 28 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JAN 1 PY 2015 VL 121 IS 1 BP 150 EP 158 DI 10.1002/cncr.29009 PG 9 WC Oncology SC Oncology GA AW8CF UT WOS:000346487500022 PM 25209975 ER PT J AU Bjornstad, P Cree-Green, M Baumgartner, A Maahs, DM Cherney, DZ Pyle, L Regensteiner, JG Reusch, JE Nadeau, KJ AF Bjornstad, Petter Cree-Green, Melanie Baumgartner, Amy Maahs, David M. Cherney, David Z. Pyle, Laura Regensteiner, Judith G. Reusch, Jane E. Nadeau, Kristen J. TI Renal Function Is Associated With Peak Exercise Capacity in Adolescents With Type 1 Diabetes SO DIABETES CARE LA English DT Article ID CORONARY-ARTERY CALCIFICATION; GLOMERULAR-FILTRATION-RATE; EXCHANGE CLINIC REGISTRY; ALL-CAUSE MORTALITY; CARDIOVASCULAR-DISEASE; GENERAL-POPULATION; ENDOTHELIAL FUNCTION; INSULIN SENSITIVITY; RISK-FACTORS; HYPERFILTRATION AB OBJECTIVE Diabetic nephropathy and cardiovascular disease are strongly related in adults with type 1 diabetes, yet little is known about this relationship in adolescents prior to the onset of detectable clinical disease. We hypothesized that cardiopulmonary fitness would be directly associated with albumin-to-creatinine ratio (ACR) and inversely related to estimated glomerular filtration rate (eGFR) in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS Sixty-nine adolescents with type 1 diabetes and 13 nondiabetic control subjects of similar pubertal stage and BMI had insulin sensitivity (glucose infusion rate [GIR]), measured by hyperinsulinemic-euglycemic clamp, and lean body mass, measured by DEXA. Cardiopulmonary fitness was measured by cycle ergometry to obtain peak volume of oxygen (VO(2)peak), and renal function was measured by eGFR using the Bouvet equation (measuring creatinine and cystatin C levels) and ACR. RESULTS Adolescents (15.5 +/- 2.2 years of age) with type 1 diabetes (6.3 +/- 3.8 years diabetes duration) had reduced VO(2)peak (31.5 +/- 6.3 vs. 36.2 +/- 7.9 mL/kg . min, P = 0.046) and VO(2)peak/lean kg (43.7 +/- 7.0 vs. 51.068.6 mL/lean kg . min, P = 0.007) compared with nondiabetic control subjects. eGFR was inversely associated with VO(2)peak and VO(2)peak/lean kg after adjusting for sex, Tanner stage, GIR, HbA(1c\) level, systolic blood pressure, and LDL cholesterol level (beta +/- SE, VO(2)peak: 20.19 +/- 0.07, P = 0.02; VO(2)peak/lean kg: -0.19 +/- 0.09, P = 0.048). Moreover, participants in the highest tertile for eGFR had significantly lower sex-and Tanner-adjusted VO(2)peak and VO(2)peak/lean kg compared with participants in the lowest tertile. CONCLUSIONS Adolescents with type 1 diabetes had reduced exercise capacity, which was strongly associated with renal health, independent of insulin sensitivity. Future studies should examine the underlying interrelated pathophysiology in order to identify probable targets for treatment to reduce cardiovascular and renal complications. C1 [Bjornstad, Petter; Pyle, Laura] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO 80045 USA. [Cree-Green, Melanie; Baumgartner, Amy; Maahs, David M.; Nadeau, Kristen J.] Univ Colorado, Sch Med, Dept Pediat, Div Pediat Endocrinol, Aurora, CO USA. [Cree-Green, Melanie; Regensteiner, Judith G.; Reusch, Jane E.; Nadeau, Kristen J.] Univ Colorado, Sch Med, Ctr Womens Hlth Res, Aurora, CO USA. [Maahs, David M.] Univ Colorado, Sch Med, Barbara Davis Ctr Diabet, Aurora, CO USA. [Cherney, David Z.] Univ Toronto, Toronto Gen Hosp, Dept Med, Div Nephrol, Toronto, ON M5G 1L7, Canada. [Regensteiner, Judith G.] Univ Colorado, Sch Med, Dept Med, Div Internal Med, Aurora, CO USA. [Regensteiner, Judith G.] Univ Colorado, Sch Med, Div Cardiol, Aurora, CO USA. [Reusch, Jane E.] Denver VA Med Ctr, Dept Med, Div Internal Med, Denver, CO USA. RP Bjornstad, P (reprint author), Univ Colorado, Sch Med, Dept Pediat, Aurora, CO 80045 USA. EM petter.bjornstad@childrenscolorado.org OI Bjornstad, Petter/0000-0002-5160-2947 FU National Center for Research Resources [K23-RR-020038-01]; National Institutes of Health (NIH) [K12-5K12-HD-057022-04]; American Diabetes Association [7-11-CD-08, 1-11-JF-23]; JDRF [11-2010-343]; NIH-Department of Health and Human Services [R56-DK-088971]; NIH-National Center for Advancing Translational Sciences-Colorado Clinical and Translational Sciences Institute [UL1-TR-000154]; Center for Women's Health Research; U.S. Department of Veterans Affairs Merit Review Award FX Support for this study was provided by National Center for Research Resources grant K23-RR-020038-01, National Institutes of Health (NIH)-Building Interdisciplinary Research Careers in Women's Health grant K12-5K12-HD-057022-04, American Diabetes Association grants 7-11-CD-08 and 1-11-JF-23, JDRF Award 11-2010-343, NIH-Department of Health and Human Services grant R56-DK-088971, NIH-National Center for Advancing Translational Sciences-Colorado Clinical and Translational Sciences Institute grant UL1-TR-000154, the Center for Women's Health Research, and a U.S. Department of Veterans Affairs Merit Review Award. NR 40 TC 1 Z9 3 U1 0 U2 5 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 JAN PY 2015 VL 38 IS 1 BP 126 EP 131 DI 10.2337/dc14-1742 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX2GT UT WOS:000346762300024 PM 25414156 ER PT J AU Fung, CH Igodan, U Alessi, C Martin, JL Dzierzewski, JM Josephson, K Kramer, BJ AF Fung, Constance H. Igodan, Uyi Alessi, Cathy Martin, Jennifer L. Dzierzewski, Joseph M. Josephson, Karen Kramer, B. Josea TI Human factors/usability barriers to home medical devices among individuals with disabling conditions: In-depth interviews with positive airway pressure device users SO DISABILITY AND HEALTH JOURNAL LA English DT Article DE Sleep apnea syndromes; Continuous positive airway pressure; Disabled persons; Equipment design ID SLEEP-APNEA SYNDROME; OLDER-ADULTS; EQUIPMENT AB Background: Evidence suggests that medical equipment often fails to accommodate the needs of individuals with disabling conditions. Few studies have focused on the accessibility of home medical devices such as positive airway pressure (PAP), which is a type of home medical equipment prescribed for long-term therapy. Objective: The purpose of this study was to explore in detail the types of difficulties experienced by patients with physical/sensory impairments who use PAP devices, as an initial step in designing a questionnaire to survey users about this topic. Methods: In this descriptive study, in-depth interviews were conducted with 19 participants (9 patients with physical/sensory impairment and 10 health care providers). Interviews were coded and analyzed for major topics. Results: Participants detailed the numerous ways in which current PAP devices fail to meet the needs of individuals with physical/sensory impairments (e.g., tremor, poor depth perception, paresis), by requiring patients to perform manually difficult tasks, such as inserting PAP parts through small apertures, attaching parts using a twisting motion, and lifting arms overhead to apply PAP headgear. These demands contributed to patients' frustration with and reduced usage of the home medical device. Conclusions: Our findings suggest that home medical devices such as PAP may not be currently designed to meet the needs of some users with physical/sensory impairments. Additional studies are needed to measure the prevalence and impact of impairment-related barriers on PAP adherence for this common medical equipment. Published by Elsevier Inc. C1 [Fung, Constance H.; Alessi, Cathy; Martin, Jennifer L.; Dzierzewski, Joseph M.; Kramer, B. Josea] Univ Calif Los Angeles, David Geffen Sch Med, North Hills, CA 91343 USA. [Fung, Constance H.; Igodan, Uyi; Alessi, Cathy; Martin, Jennifer L.; Dzierzewski, Joseph M.; Josephson, Karen; Kramer, B. Josea] VA Greater Los Angeles Healthcare Syst, Dept Vet Affairs, North Hills, CA 91343 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 American Sleep Medicine Foundation; Department of Veterans Affairs; Veterans Administration Greater Los Angeles Geriatric Research, Education and Clinical Center; American Federation for Aging Research; John A. Hartford Foundation FX Special thanks to Stella Jouldjian, MSW, MPH, for her data management support. This work was supported by the American Sleep Medicine Foundation Physician Scientist Training Award (to CHF), the Department of Veterans Affairs Advanced Geriatrics Fellowship Program (to CHF, JMD), Veterans Administration Greater Los Angeles Geriatric Research, Education and Clinical Center, American Federation for Aging Research (to CHF), the John A. Hartford Foundation (to CHF). NR 20 TC 3 Z9 3 U1 4 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-6574 EI 1876-7583 J9 DISABIL HEALTH J JI Disabil. Health J. PD JAN PY 2015 VL 8 IS 1 BP 86 EP 92 DI 10.1016/j.dhjo.2014.06.002 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health; Rehabilitation SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Rehabilitation GA AW2YZ UT WOS:000346153800012 PM 25126995 ER PT J AU Chen, P Torralba, M Tan, J Embree, M Zengler, K Starkel, P van Pijkeren, JP DePew, J Loomba, R Ho, SB Bajaj, JS Mutlu, EA Keshavarzian, A Tsukamoto, H Nelson, KE Fouts, DE Schnabl, B AF Chen, Peng Torralba, Manolito Tan, Justin Embree, Mallory Zengler, Karsten Starkel, Peter van Pijkeren, Jan-Peter DePew, Jessica Loomba, Rohit Ho, Samuel B. Bajaj, Jasmohan S. Mutlu, Ece A. Keshavarzian, Ali Tsukamoto, Hidekazu Nelson, Karen E. Fouts, Derrick E. Schnabl, Bernd TI Supplementation of Saturated Long-Chain Fatty Acids Maintains Intestinal Eubiosis and Reduces Ethanol-induced Liver Injury in Mice SO GASTROENTEROLOGY LA English DT Article DE Metagenomics; Metabolomics; Microbiome; Microbiota ID LACTOBACILLUS-RHAMNOSUS GG; PARACELLULAR PERMEABILITY; ALCOHOLIC STEATOHEPATITIS; POSSIBLE MECHANISM; RAT MODEL; DISEASE; GUT; INFLAMMATION; ENDOTOXEMIA; MICROBIOME AB BACKGROUND & AIMS: Alcoholic liver disease is a leading cause of mortality. Chronic alcohol consumption is accompanied by intestinal dysbiosis, and development of alcoholic liver disease requires gut-derived bacterial products. However, little is known about how alterations to the microbiome contribute to pathogenesis of alcoholic liver disease. METHODS: We used the Tsukamoto-French mouse model, which involves continuous intragastric feeding of isocaloric diet or alcohol for 3 weeks. Bacterial DNA from the cecum was extracted for deep metagenomic sequencing. Targeted metabolomics assessed concentrations of saturated fatty acids in cecal contents. To maintain intestinal metabolic homeostasis, diets of ethanol-fed and control mice were supplemented with saturated long-chain fatty acids (LCFA). Bacterial genes involved in fatty acid biosynthesis, amounts of lactobacilli, and saturated LCFA were measured in fecal samples of nonalcoholic individuals and patients with active alcohol abuse. RESULTS: Analyses of intestinal contents from mice revealed alcohol-associated changes to the intestinal metagenome and metabolome, characterized by reduced synthesis of saturated LCFA. Maintaining intestinal levels of saturated fatty acids in mice resulted in eubiosis, stabilized the intestinal gut barrier, and reduced ethanol-induced liver injury. Saturated LCFA are metabolized by commensal Lactobacillus and promote their growth. Proportions of bacterial genes involved in fatty acid biosynthesis were lower in feces from patients with active alcohol abuse than controls. Total levels of LCFA correlated with those of lactobacilli in fecal samples from patients with active alcohol abuse but not in controls. CONCLUSIONS: In humans and mice, alcohol causes intestinal dysbiosis, reducing the capacity of the microbiome to synthesize saturated LCFA and the proportion of Lactobacillus species. Dietary approaches to restore levels of saturated fatty acids in the intestine might reduce ethanolinduced liver injury in patients with alcoholic liver disease. C1 [Chen, Peng; Loomba, Rohit; Ho, Samuel B.; Schnabl, Bernd] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Torralba, Manolito; DePew, Jessica; Nelson, Karen E.; Fouts, Derrick E.] J Craig Venter Inst, Rockville, MD USA. [Tan, Justin; Embree, Mallory; Zengler, Karsten] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Starkel, Peter] Catholic Univ Louvain, St Luc Univ Hosp, B-1200 Brussels, Belgium. [van Pijkeren, Jan-Peter] Univ Wisconsin, Dept Food Sci, Madison, WI 53706 USA. [Ho, Samuel B.] VA San Diego Healthcare Syst, Dept Med, San Diego, CA USA. [Bajaj, Jasmohan S.] Virginia Commonwealth Univ, Div Gastroenterol Hepatol & Nutr, Richmond, VA USA. [Bajaj, Jasmohan S.] McGuire VA Med Ctr, Richmond, VA USA. [Mutlu, Ece A.; Keshavarzian, Ali] Rush Univ, Med Ctr, Dept Med, Chicago, IL 60612 USA. [Tsukamoto, Hidekazu] Univ So Calif, Greater Los Angeles VA Healthcare Syst, Southern Calif Res Ctr Alcohol Liver & Pancreat D, Dept Pathol,Keck Sch Med, Los Angeles, CA 90033 USA. RP Schnabl, B (reprint author), Univ Calif San Diego, Dept Med, MC0063,9500 Gilman Dr, La Jolla, CA 92093 USA. EM beschnabl@ucsd.edu OI Zengler, Karsten/0000-0002-8062-3296 FU National Institutes of Health (NIH) [K08 DK081830, R01 AA020703, U01 AA021856]; ABMRF/The Foundation for Alcohol Research; American Gastroenterological Association Foundation-Sucampo-ASP Designated Research Award in Geriatric Gastroenterology; T. Franklin Williams Scholarship Award; Atlantic Philanthropies, Inc; John A. Hartford Foundation; Association of Specialty Professors; NIH [R01AA020216, RC2AA019405, R01 AA020203, DK097153]; National Institute on Alcohol Abuse and Alcoholism [P50AA011999]; [K23-DK090303] FX This study was supported in part by National Institutes of Health (NIH) grants K08 DK081830, R01 AA020703, U01 AA021856 and by ABMRF/The Foundation for Alcohol Research (to Bernd Schnabl). Rohit Loomba is supported in part by the American Gastroenterological Association Foundation-Sucampo-ASP Designated Research Award in Geriatric Gastroenterology, a T. Franklin Williams Scholarship Award, Atlantic Philanthropies, Inc, the John A. Hartford Foundation, the Association of Specialty Professors, and grant K23-DK090303. Ali Keshavarzian received support from NIH grants R01AA020216 and RC2AA019405. Jasmohan S. Bajaj is supported by NIH grant R01 AA020203. Animal studies at the Animal Core facility, Southern California Research Center for Alcoholic Liver and Pancreatic Diseases and Cirrhosis, University of Southern California were funded by the National Institute on Alcohol Abuse and Alcoholism (P50AA011999). This work utilized Core Services supported by grant DK097153 of NIH to the University of Michigan. NR 57 TC 39 Z9 42 U1 8 U2 52 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2015 VL 148 IS 1 BP 203 EP U345 DI 10.1053/j.gastro.2014.09.014 PG 28 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AW9LT UT WOS:000346579500033 PM 25239591 ER PT J AU Sung, JJY Ng, SC Chan, FKL Chiu, HM Kim, HS Matsuda, T Ng, SSM Lau, JYW Zheng, S Adler, S Reddy, N Yeoh, KG Tsoi, KKF Ching, JYL Kuipers, EJ Rabeneck, L Young, GP Steele, RJ Lieberman, D Goh, KL AF Sung, J. J. Y. Ng, S. C. Chan, F. K. L. Chiu, H. M. Kim, H. S. Matsuda, T. Ng, S. S. M. Lau, J. Y. W. Zheng, S. Adler, S. Reddy, N. Yeoh, K. G. Tsoi, K. K. F. Ching, J. Y. L. Kuipers, E. J. Rabeneck, L. Young, G. P. Steele, R. J. Lieberman, D. Goh, K. L. TI An updated Asia Pacific Consensus Recommendations on colorectal cancer screening SO GUT LA English DT Article ID OCCULT BLOOD-TEST; RANDOMIZED-CONTROLLED-TRIAL; ADENOMA DETECTION RATE; SOCIETY-TASK-FORCE; FECAL IMMUNOCHEMICAL TEST; AVERAGE-RISK CHINESE; BODY-MASS INDEX; CT-COLONOGRAPHY; ADVANCED NEOPLASIA; FAMILY-HISTORY AB Objective Since the publication of the first Asia Pacific Consensus on Colorectal Cancer (CRC) in 2008, there are substantial advancements in the science and experience of implementing CRC screening. The Asia Pacific Working Group aimed to provide an updated set of consensus recommendations. Design Members from 14 Asian regions gathered to seek consensus using other national and international guidelines, and recent relevant literature published from 2008 to 2013. A modified Delphi process was adopted to develop the statements. Results Age range for CRC screening is defined as 5075 years. Advancing age, male, family history of CRC, smoking and obesity are confirmed risk factors for CRC and advanced neoplasia. A risk-stratified scoring system is recommended for selecting high-risk patients for colonoscopy. Quantitative faecal immunochemical test (FIT) instead of guaiac-based faecal occult blood test (gFOBT) is preferred for average-risk subjects. Ancillary methods in colonoscopy, with the exception of chromoendoscopy, have not proven to be superior to high-definition white light endoscopy in identifying adenoma. Quality of colonoscopy should be upheld and quality assurance programme should be in place to audit every aspects of CRC screening. Serrated adenoma is recognised as a risk for interval cancer. There is no consensus on the recruitment of trained endoscopy nurses for CRC screening. Conclusions Based on recent data on CRC screening, an updated list of recommendations on CRC screening is prepared. These consensus statements will further enhance the implementation of CRC screening in the Asia Pacific region. C1 [Sung, J. J. Y.; Ng, S. C.; Chan, F. K. L.] Chinese Univ Hong Kong, Inst Digest Dis, Shatin, Hong Kong, Peoples R China. [Ng, S. C.; Chan, F. K. L.; Ching, J. Y. L.] Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China. [Chiu, H. M.] Natl Taiwan Univ, Coll Med, Dept Internal Med, Taipei, Taiwan. [Kim, H. S.] Yonsei Univ, Wonju Coll Med, Dept Internal Med, Wonju, South Korea. [Matsuda, T.] Natl Canc Ctr, Endoscopy Div, Tokyo, Japan. [Ng, S. S. M.; Lau, J. Y. W.] Chinese Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China. [Zheng, S.] Zhejiang Univ, Canc Inst, Hanggzhou, Zhejiang, Peoples R China. [Adler, S.] Bikur Holim Hosp, Div Gastroenterol, Jerusalem, Israel. [Reddy, N.] Asian Healthcare Fdn, Asian Inst Gastroenterol, Hyderabad, Andhra Pradesh, India. [Yeoh, K. G.] Natl Univ Singapore, Asian Healthcare Fdn, Dept Med, Singapore 117548, Singapore. [Tsoi, K. K. F.] Chinese Univ Hong Kong, Sch Publ Hlth & Primary Care, Hong Kong, Hong Kong, Peoples R China. [Kuipers, E. J.] Erasmus Univ, Med Ctr, Dept Med & Therapeut, Rotterdam, Netherlands. [Rabeneck, L.] Univ Toronto, Inst Clin Evaluat Sci, Toronto, ON M5S 1A1, Canada. [Young, G. P.] Flinders Med Ctr, Dept Gastroenterol, Adelaide, SA, Australia. [Steele, R. J.] Univ Dundee, Dept Surg & Mol Oncol, Dundee, Scotland. [Lieberman, D.] Portland VA Med Ctr, Portland, OR USA. [Goh, K. L.] Univ Malaya, Dept Gastroenterol & Hepatol, Kuala Lumpur, Malaysia. RP Sung, JJY (reprint author), Chinese Univ Hong Kong, Inst Digest Dis, Shatin, Hong Kong, Peoples R China. EM jjysung@cuhk.edu.hk RI Goh, Khean-Lee/B-6404-2009; Ng, Siew Chien/N-4733-2015; Chan, Francis K. L./F-4851-2010 OI Ng, Siew Chien/0000-0002-6850-4454; Chan, Francis K. L./0000-0001-7388-2436; CHIU, HAN-MO/0000-0003-2786-8056 FU Olympus Medical System Corporation; Given Imaging FX An unrestricted education grant was received from Olympus Medical System Corporation and Given Imaging. In order to avoid conflict of interest, industrial partners were not allowed to provide input for the statements, add references in the literature search, participate in the discussion and vote in the consensus conference. None of the sponsors contributed towards the development of the consensus statements or in their voting. NR 123 TC 62 Z9 66 U1 4 U2 19 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD JAN PY 2015 VL 64 IS 1 BP 121 EP 132 DI 10.1136/gutjnl-2013-306503 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AW3EE UT WOS:000346167700017 PM 24647008 ER PT J AU Wu, BU Pandol, SJ Liu, ILA AF Wu, Bechien U. Pandol, Stephen J. Liu, In-Lu Amy TI Simvastatin is associated with reduced risk of acute pancreatitis: findings from a regional integrated healthcare system SO GUT LA English DT Article ID STATINS; THERAPY AB Objective To characterise the relationship between simvastatin and risk of acute pancreatitis (AP). Design We conducted a retrospective cohort study (2006-2012) on data from an integrated healthcare system in southern California. Exposure to simvastatin was calculated from time of initial dispensation until 60 days following prescription termination. AP cases were defined by ICD-9 CM 577.0 and serum lipase >= 3 times normal. Patients were censored at death, last follow-up, and onset of AP or end-of-study. Incidence rate of pancreatitis among simvastatin users was compared with the adult reference population. Robust Poisson regression was used to generate risk ratio (RR) estimates for simvastatin use adjusted for age, gender, race/ethnicity, gallstone-related disorders, hypertriglyceridaemia, smoking and alcohol dependence. Analysis was repeated for atorvastatin. Results Among 3 967 859 adult patients (median duration of follow-up of 3.4 years), 6399 developed an initial episode of AP. A total of 707 236 patients received simvastatin during the study period. Patients that received simvastatin were more likely to have gallstone-related disorders, alcohol dependence or hypertriglyceridaemia compared with the reference population. Nevertheless, risk of AP was significantly reduced with simvastatin use, crude incidence rate ratio 0.626 (95% CL 0.588, 0.668), p<0.0001. In multivariate analysis, simvastatin was independently associated with reduced risk of pancreatitis, adjusted RR 0.29 (95% CL 0.27, 0.31) after adjusting for age, gender, race/ethnicity, gallstone disorders, alcohol dependence, smoking and hypertriglyceridaemia. Similar results were noted with atorvastatin, adjusted RR 0.33 (0.29, 0.38). Conclusions Use of simvastatin was independently associated with reduced risk of AP in this integrated healthcare setting. Similar findings for atorvastatin suggest a possible class effect. C1 [Wu, Bechien U.] W Los Angeles Vet Affairs Med Ctr, Kaiser Permanente, So Calif Permanente Med Grp, Div Gastroenterol,Ctr Pancreat Care, Los Angeles, CA 90027 USA. [Pandol, Stephen J.] Cedars Sinai Med Ctr, Program Basic & Translat Pancreat Res, Los Angeles, CA 90048 USA. [Liu, In-Lu Amy] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA. RP Wu, BU (reprint author), W Los Angeles Vet Affairs Med Ctr, Kaiser Permanente, Div Gastroenterol, Ctr Pancreat Care, 1526 North Edgemont Ave, Los Angeles, CA 90027 USA. EM Bechien.u.wu@kp.org FU BLRD VA [I01 BX001484]; NCI NIH HHS [P01 CA163200]; NIAAA NIH HHS [P50 AA011999]; NIDDK NIH HHS [P01 DK098108] NR 16 TC 7 Z9 9 U1 1 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD JAN PY 2015 VL 64 IS 1 BP 133 EP 138 DI 10.1136/gutjnl-2013-306564 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AW3EE UT WOS:000346167700018 PM 24742713 ER PT J AU Kwok, VPY Wang, TF Chen, SP Yakpo, K Zhu, LL Fox, PT Tan, LH AF Kwok, Veronica P. Y. Wang, Tianfu Chen, Siping Yakpo, Kofi Zhu, Linlin Fox, Peter T. Tan, Li Hai TI Neural Signatures of Lexical Tone Reading SO HUMAN BRAIN MAPPING LA English DT Article DE functional magnetic resonance imaging; language; pitch; prosody; temporal cortex; activation likelihood estimation ID HUMAN AUDITORY-CORTEX; CROSS-LINGUISTIC PET; LANGUAGE EXPERIENCE; SPEECH-PERCEPTION; BRAIN-DAMAGE; PITCH; CHINESE; CONNECTIVITY; ACTIVATION; PATTERNS AB Research on how lexical tone is neuroanatomically represented in the human brain is central to our understanding of cortical regions subserving language. Past studies have exclusively focused on tone perception of the spoken language, and little is known as to the lexical tone processing in reading visual words and its associated brain mechanisms. In this study, we performed two experiments to identify neural substrates in Chinese tone reading. First, we used a tone judgment paradigm to investigate tone processing of visually presented Chinese characters. We found that, relative to baseline, tone perception of printed Chinese characters were mediated by strong brain activation in bilateral frontal regions, left inferior parietal lobule, left posterior middle/medial temporal gyrus, left inferior temporal region, bilateral visual systems, and cerebellum. Surprisingly, no activation was found in superior temporal regions, brain sites well known for speech tone processing. In activation likelihood estimation (ALE) meta-analysis to combine results of relevant published studies, we attempted to elucidate whether the left temporal cortex activities identified in Experiment one is consistent with those found in previous studies of auditory lexical tone perception. ALE results showed that only the left superior temporal gyrus and putamen were critical in auditory lexical tone processing. These findings suggest that activation in the superior temporal cortex associated with lexical tone perception is modality-dependent. Hum Brain Mapp, 36:304-312, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Kwok, Veronica P. Y.; Fox, Peter T.] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China. [Kwok, Veronica P. Y.; Yakpo, Kofi] Univ Hong Kong, Dept Linguist, Hong Kong, Hong Kong, Peoples R China. [Wang, Tianfu; Chen, Siping; Tan, Li Hai] Shenzhen Univ, Sch Med, Dept Biomed Engn, Shenzhen 518060, Peoples R China. [Wang, Tianfu; Chen, Siping; Tan, Li Hai] Guangdong Key Lab Biomed Informat Detect & Ultras, Shenzhen 518060, Peoples R China. [Zhu, Linlin] Beijing Inst Technol, Sch Comp Sci, Beijing 100081, Peoples R China. [Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Tan, LH (reprint author), Shenzhen Univ, Sch Med, Dept Biomed Engn, Neuroimaging Unit, Shenzhen 518060, Peoples R China. EM lihaitan@gmail.com FU National Strategic Basic Research Program ("973" Program) of the Ministry of Science and Technology of China [2012CB720701]; National Natural Science Foundation of China [61372006] FX Contract grant sponsor: National Strategic Basic Research Program ("973" Program) of the Ministry of Science and Technology of China; Contract grant number: 2012CB720701; Contract grant sponsor: National Natural Science Foundation of China; Contract grant number: 61372006. NR 41 TC 3 Z9 4 U1 4 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JAN PY 2015 VL 36 IS 1 BP 304 EP 312 DI 10.1002/hbm.22629 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AW3ML UT WOS:000346190800021 PM 25196948 ER PT J AU Zamani, P Bluemke, DA Jacobs, DR Duprez, DA Kronmal, R Lilly, SM Ferrari, VA Townsend, RR Lima, JA Budoff, M Segers, P Hannan, P Chirinos, JA AF Zamani, Payman Bluemke, David A. Jacobs, David R., Jr. Duprez, Daniel A. Kronmal, Richard Lilly, Scott M. Ferrari, Victor A. Townsend, Raymond R. Lima, Joao A. Budoff, Matthew Segers, Patrick Hannan, Peter Chirinos, Julio A. TI Resistive and Pulsatile Arterial Load as Predictors of Left Ventricular Mass and Geometry The Multi-Ethnic Study of Atherosclerosis SO HYPERTENSION LA English DT Article DE hypertrophy, left ventricular; vascular resistance; ventricular remodeling ID PRESERVED EJECTION FRACTION; PRESSURE WAVE-FORM; CARDIOVASCULAR RISK-FACTORS; SEX-DIFFERENCES; HEART-FAILURE; DIASTOLIC FUNCTION; NONINVASIVE EVALUATION; UPPER-LIMB; BODY-SIZE; REFLECTION AB Arterial load is composed of resistive and various pulsatile components, but their relative contributions to left ventricular (LV) remodeling in the general population are unknown. We studied 4145 participants enrolled in the Multi-Ethnic Study of Atherosclerosis, who underwent cardiac MRI and radial arterial tonometry. We computed systemic vascular resistance (SVR=mean arterial pressure/cardiac output) and indices of pulsatile load including total arterial compliance (TAC, approximated as stroke volume/central pulse pressure), forward wave amplitude (P-f), and reflected wave amplitude (P-b). TAC and SVR were adjusted for body surface area to allow for appropriate sex comparisons. We performed allometric adjustment of LV mass for body size and sex and computed standardized regression coefficients (beta) for each measure of arterial load. In multivariable regression models that adjusted for multiple confounders, SVR (beta=0.08; P<0.001), TAC (beta=0.44; P<0.001), P-b (beta=0.73; P<0.001), and P-f (beta=-0.23; P=0.001) were significant independent predictors of LV mass. Conversely, TAC (beta=-0.43; P<0.001), SVR (beta=0.22; P<0.001), and P-f (beta=-0.18; P=0.004) were independently associated with the LV wall/LV cavity volume ratio. Women demonstrated greater pulsatile load than men, as evidenced by a lower indexed TAC (0.89 versus 1.04 mL/mm Hg per square meter; P<0.0001), whereas men demonstrated a higher indexed SVR (34.0 versus 32.8 Wood Unitsxm2; P<0.0001). In conclusion, various components of arterial load differentially associate with LV hypertrophy and concentric remodeling. Women demonstrated greater pulsatile load than men. For both LV mass and the LV wall/LV cavity volume ratio, the loading sequence (ie, early load versus late load) is an important determinant of LV response to arterial load. C1 [Zamani, Payman; Ferrari, Victor A.; Chirinos, Julio A.] Hosp Univ Penn, Div Cardiovasc Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Zamani, Payman; Ferrari, Victor A.; Chirinos, Julio A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. [Bluemke, David A.] Johns Hopkins Univ, Sch Med, Dept Med Radiol, Baltimore, MD USA. [Jacobs, David R., Jr.; Hannan, Peter] Univ Minnesota, Sch Med, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Duprez, Daniel A.] Univ Minnesota, Sch Med, Div Cardiol, Minneapolis, MN 55455 USA. [Kronmal, Richard] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Lilly, Scott M.] Ohio State Univ, Heart & Vasc Ctr, Div Cardiovasc Med, Columbus, OH 43210 USA. [Townsend, Raymond R.] Univ Penn, Perelman Sch Med, Div Nephrol & Hypertens, Philadelphia, PA 19104 USA. [Lima, Joao A.] Johns Hopkins Univ Hosp, Div Cardiol, Baltimore, MD 21287 USA. [Budoff, Matthew] Las Angeles Biomed Res Inst, Torrance, CA USA. [Segers, Patrick] Univ Ghent, Minds Med IT, IBiTech, B-9000 Ghent, Belgium. RP Zamani, P (reprint author), Hosp Univ Penn, Div Cardiovasc Med, 3400 Spruce St,8 Gates, Philadelphia, PA 19104 USA. EM pzamani@upenn.edu RI Lilly, Scott/K-3620-2013 OI Lilly, Scott/0000-0002-2597-6806; Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169]; National Center for Research Resources [UL1-TR-000040, UL1-RR-025005, RR-024156]; National Institutes of Aging [1R21AG043802-01, R01 HL098382]; Institute for Translational Medicine and Therapeutics of the University of Pennsylvania from the National Center for Research Resources [5UL1TR000003-09]; [5-T32-HL007843-17] FX This research was supported by contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the National Heart, Lung, and Blood Institute, grants UL1-TR-000040, UL1-RR-025005, and RR-024156 from National Center for Research Resources, and National Institutes of Aging grant 1R21AG043802-01 (Dr Chirinos), and R01 HL098382 (Dr Jacobs). Dr Zamani is supported, in part, by the Institute for Translational Medicine and Therapeutics of the University of Pennsylvania (grant number: 5UL1TR000003-09 from the National Center for Research Resources) and by 5-T32-HL007843-17. NR 47 TC 12 Z9 12 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD JAN PY 2015 VL 65 IS 1 BP 85 EP + DI 10.1161/HYPERTENSIONAHA.114.04333 PG 12 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW4KA UT WOS:000346248800020 PM 25287396 ER PT J AU Lin, F Roiland, R Chen, DG Qiu, C AF Lin, Feng Roiland, Rachel Chen, Ding-Geng (Din) Qiu, Christina TI Linking cognition and frailty in middle and old age: metabolic syndrome matters SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE frailty; executive function; episodic memory; metabolic syndrome ID INSULIN-RESISTANCE; ASSOCIATION; ADULTS; PHENOTYPE; QUALITY; PROGRAM; DECLINE; HEALTH AB ObjectivesThis study examined whether metabolic syndrome (MetS) would moderate the association of cognition with frailty in middle and old age. MethodsA cross-sectional design was used. Six hundred and ninety participants (age50years) from an on-going national survey were included in the study. Confirmatory factor analysis was applied to determine latent variables of executive function (EF), episodic memory (EM), and MetS based on relevant measurements. Frailty was defined using a modified form of Fried's criteria. ResultsApplying structural equation modeling, having MetS significantly increased the likelihood of being frail. Better performance on EM tasks, but not EF, was significantly associated with lower likelihood of MetS. Worse performance on EF, but not EM, significantly increased the likelihood of being frail. There was a significant interacting effect between MetS and EF, but not EM, on frailty. Further contrast analysis indicated that having MetS strengthened the negative association between EF and frailty. ConclusionMetabolic syndrome moderates the relationship between EF and frailty. A prospecitve study is needed to validate such relationships before developing interventions targeting the prevention or treatment of EF and frailty in individuals with MetS. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Lin, Feng; Chen, Ding-Geng (Din); Qiu, Christina] Univ Rochester, Sch Nursing, Rochester, NY 14642 USA. [Lin, Feng] Univ Rochester, Sch Med & Dent, Dept Psychiat, Rochester, NY 14642 USA. [Roiland, Rachel] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Chen, Ding-Geng (Din)] Univ Rochester, Sch Med & Dent, Dept Biostat & Computat Sci, Rochester, NY USA. RP Lin, F (reprint author), Univ Rochester, Sch Nursing, Rochester, NY 14642 USA. EM vankee_lin@urmc.rochester.edu FU National Institute on Aging [P01-AG020166]; University of Rochester CTSA award from the National Center for Advancing Translational Sciences of the National Institutes of Health [KL2 TR000095] FX MIDUS II was supported by from the National Institute on Aging (P01-AG020166).; The manuscript development was supported by the University of Rochester CTSA award number KL2 TR000095 from the National Center for Advancing Translational Sciences of the National Institutes of Health to F. Lin. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 32 TC 6 Z9 6 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-6230 EI 1099-1166 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD JAN PY 2015 VL 30 IS 1 BP 64 EP 71 DI 10.1002/gps.4115 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AW4WM UT WOS:000346278300007 PM 24733716 ER PT J AU Li, XD Pezeshkpour, G Phan, RT AF Li, Xiaodong Pezeshkpour, G. Phan, Ryan T. TI KRAS mutation status impacts diagnosis and treatment decision in a patient with two colon tumours: a case report SO JOURNAL OF CLINICAL PATHOLOGY LA English DT Article ID METASTATIC COLORECTAL-CANCER; RAS MUTATIONS; HETEROGENEITY AB KRAS mutation status predicts response to anti-EGFR therapy in colorectal cancer patients. Here we report an interesting case of discordant KRAS mutation status in a patient with two separate tumour foci. Tumour A in sigmoid colon invaded through muscularis propria into the subserosal fat with metastatic disease in regional lymph nodes (pT3N2b). Tumour B in ascending colon had a relatively lower stage and no metastasis (pT2N0). Both tumours showed similar morphology, immunohistochemical staining and microsatellite instability pattern. KRAS mutation, however, was detected only in tumour A. These findings indicate distinct clonal nature of these two tumours. The discordance of KRAS mutation status also suggests that a combination of anti-epidermal growth factor receptor and chemotherapy is likely the best treatment option for this patient. This case exemplifies a notion that comprehensive pathological work-up comprising molecular testing is critical to guide the diagnosis and treatment decisions for colorectal cancer patients with multiple tumours. C1 [Li, Xiaodong; Pezeshkpour, G.; Phan, Ryan T.] Univ So Calif, Keck Sch Med, USC LAC Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90033 USA. [Pezeshkpour, G.; Phan, Ryan T.] VA Greater Los Angles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA 90073 USA. RP Phan, RT (reprint author), VA Greater Los Angles Healthcare Syst, Dept Pathol & Lab Med, 11301 Wilshire Blvd,Bldg 500,Room 1255, Los Angeles, CA 90073 USA. EM Ryan.Phan@va.gov NR 15 TC 3 Z9 3 U1 0 U2 7 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0021-9746 EI 1472-4146 J9 J CLIN PATHOL JI J. Clin. Pathol. PD JAN PY 2015 VL 68 IS 1 BP 83 EP 85 DI 10.1136/jclinpath-2014-202591 PG 3 WC Pathology SC Pathology GA AW5ZU UT WOS:000346350200016 PM 25313410 ER PT J AU Noble, P Chan, G Young, M Weisbart, R Hansen, JE AF Noble, P. Chan, G. Young, M. Weisbart, R. Hansen, J. E. TI AN OPTIMIZED LUPUS AUTOANTIBODY FRAGMENT FOR TARGETED THERAPY OF DNA REPAIR-DEFICIENT MALIGNANCIES SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 [Noble, P.; Young, M.; Hansen, J. E.] Yale Univ, Sch Med, New Haven, CT USA. [Chan, G.; Weisbart, R.] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2015 VL 63 IS 1 MA 101 BP 117 EP 117 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AW9TQ UT WOS:000346600700117 ER PT J AU Boyd, M Bream, HJ Banks, W AF Boyd, M. Bream, H. J. Banks, W. TI BLOOD BRAIN BARRIER DISRUPTION AFTER MILD TRAUMATIC BRAIN INJURY IN A CLOSED SKULL MODEL SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 [Boyd, M.; Bream, H. J.; Banks, W.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Boyd, M.; Bream, H. J.; Banks, W.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2015 VL 63 IS 1 MA 121 BP 122 EP 123 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AW9TQ UT WOS:000346600700137 ER PT J AU Bream, HJ Boyd, M Banks, W AF Bream, H. J. Boyd, M. Banks, W. TI DEVELOPMENT OF A CLOSED SKULL MODEL FOR MILD REPETITIVE TRAUMATIC BRAIN INJURY SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 [Bream, H. J.; Boyd, M.; Banks, W.] Univ Washington, Seattle, WA 98195 USA. [Bream, H. J.; Boyd, M.; Banks, W.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2015 VL 63 IS 1 MA 122 BP 123 EP 123 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AW9TQ UT WOS:000346600700138 ER PT J AU Szkudlinska, MA von Frankenberg, AD Utzschneider, K AF Szkudlinska, M. A. von Frankenberg, A. D. Utzschneider, K. TI THE ANTIOXIDANT N-ACETYLCYSTEINE DOES NOT IMPROVE GLUCOSE TOLERANCE OR beta-CELL FUNCTION IN TYPE 2 DIABETES SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 [Szkudlinska, M. A.; von Frankenberg, A. D.; Utzschneider, K.] Univ Washington, Seattle, WA 98195 USA. [Utzschneider, K.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2015 VL 63 IS 1 MA 188 BP 142 EP 142 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AW9TQ UT WOS:000346600700201 ER PT J AU Zhang, J Lin, A Jimenez, E Paholpak, P Teng, E Mendez, M AF Zhang, J. Lin, A. Jimenez, E. Paholpak, P. Teng, E. Mendez, M. TI PREVALENCE OF TRAUMATIC BRAIN INJURY IN EARLY VERSUS LATE-ONSET ALZHEIMER'S DISEASE SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 [Zhang, J.; Jimenez, E.; Paholpak, P.; Teng, E.; Mendez, M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Lin, A.; Jimenez, E.; Paholpak, P.; Teng, E.; Mendez, M.] VA Greater Healthcare Syst, Neurobehav Unit, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2015 VL 63 IS 1 MA 312 BP 180 EP 180 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AW9TQ UT WOS:000346600700325 ER PT J AU Ziemke, MK Malkoski, S AF Ziemke, M. K. Malkoski, S. TI FEASABLITY OF A RETROSPECTIVE ANALYSIS DETERMINING IF REDUCED SMAD4 EXPRESSION PREDICTS RESPONSIVENESS TO DNA TOPOISMOERASE INHIBITORS IN LUNG CANCER SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 [Ziemke, M. K.; Malkoski, S.] Univ Colorado, Sch Med, Aurora, CO USA. [Ziemke, M. K.; Malkoski, S.] Denver Vet Affairs Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2015 VL 63 IS 1 MA 388 BP 202 EP 202 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AW9TQ UT WOS:000346600700397 ER PT J AU Zhou, YX Yu, F Duong, TQ AF Zhou, Yongxia Yu, Fang Duong, Timothy Q. CA Alzheimer's Dis Neuroimaging Initi TI White Matter Lesion Load Is Associated With Resting State Functional MRI Activity and Amyloid PET but not FDG in Mild Cognitive Impairment and Early Alzheimer's Disease Patients SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE white matter lesion; amyloid; resting state-fMRI; Alzheimer disease; fractional amplitude at low frequency fluctuation; default mode network ID BRAIN; INDIVIDUALS; MULTICENTER; DEPOSITION; DECLINE; PATTERN; MEMORY AB PurposeTo quantify and investigate the interactions between multimodal MRI/positron emission tomography (PET) imaging metrics in elderly patients with early Alzheimer's disease (AD), mild cognitive impairment (MCI) and healthy controls. Materials and MethodsThirteen early AD, 17 MCI patients, and 14 age-matched healthy aging controls from the Alzheimer's Disease Neuroimaging Initiative database were selected based on availability of data. Default mode network (DMN) functional connectivity and fractional amplitude of low frequency fluctuation (fALFF) were obtained for resting state functional MRI (RS-fMRI). White matter lesion load (WMLL) was quantified from MRI T2-weighted FLAIR images. Amyloid deposition with PET [F-18]-Florbetapir tracer and metabolism of glucose by means of [F-18]-fluoro-2-deoxyglucose (FDG) images were quantified using ratio of standard uptake values (rSUV). ResultsWhole-brain WMLL and amyloid deposition were significantly higher (P<0.005) in MCI and AD patients compared with controls. RS-fMRI results showed significantly reduced (corrected P<0.05) DMN connectivity and altered fALFF activity in both MCI and AD groups. FDG uptake results showed hypometabolism in AD and MCI patients compared with controls. Correlations (P<0.05) were found between WMLL and amyloid load, FDG uptake and amyloid load, as well as between amyloid load (rSUV) and fALFF. ConclusionOur quantitative results of four MRI and PET imaging metrics (fALFF/DMN, WMLL, amyloid, and FDG rSUV values) agree with published values. Significant correlations between MRI metrics, including WMLL/functional activity and PET amyloid load suggest the potential of MRI and PET-based biomarkers for early detection of AD.J. Magn. Reson. Imaging 2013. (c) 2013 Wiley Periodicals, Inc. J. Magn. Reson. Imaging 2015;41:102-109. (c) 2013 Wiley Periodicals, Inc. C1 [Zhou, Yongxia] NYU, Sch Med, Radiol Ctr Biomed Imaging, New York, NY 10016 USA. [Zhou, Yongxia] Univ Penn, Philadelphia, PA 19104 USA. [Yu, Fang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Ophthalmol, San Antonio, TX 78229 USA. [Yu, Fang; Duong, Timothy Q.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. RP Zhou, YX (reprint author), NYU, Sch Med, Dept Radiol, Ctr Biomed Imaging, 660 First Ave,4th Floor, New York, NY 10016 USA. EM yongxia.zhou@yahoo.com OI Zhou, Yongxia (Sharon)/0000-0002-4931-2318 FU National Institutes of Health [U01 AG024904, P30 AG010129, K01 AG030514] FX Contract grant sponsor: National Institutes of Health; Contract grant numbers: U01 AG024904, P30 AG010129, K01 AG030514. NR 39 TC 11 Z9 12 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 EI 1522-2586 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JAN PY 2015 VL 41 IS 1 BP 102 EP 109 DI 10.1002/jmri.24550 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AW7EP UT WOS:000346427800011 PM 24382798 ER PT J AU Tang, GL Weitz, K AF Tang, Gale L. Weitz, Kevin TI Impaired arteriogenesis in syndecan-1(-/-) mice SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Arteriogenesis; Syndecan-1; Mouse hindlimb ischemia; Angiogenesis ID FIBROBLAST-GROWTH-FACTOR; ANGIOGENESIS; ISCHEMIA; HINDLIMB; INHIBITOR; MODEL; MACROPHAGES; EXPRESSION; MONOCYTES; SYNSTATIN AB Background: Collateral artery development (arteriogenesis) is an important compensatory response to arterial occlusion caused by atherosclerosis. The heparan sulfate proteoglycan syndecan-1 (sdc1) has previously been shown to affect the response to arterial injury but has yet been studied in arteriogenesis. We tested the hypothesis that sdc1 knockout (sdc1(-/-)) mice would revascularize more poorly than wild type (wt) mice, and then used bone marrow transplantation experiments to determine whether sdc1' s effect on arteriogenesis was due to its presence in the local tissue environment or in bone marrow derived cells. Materials and methods: Hindlimb ischemia was induced by femoral artery ligation in wt and sdc1(-/-) female mice as well as in wt and sdc1(-/-) female mice transplanted with wt bone marrow or in wt mice transplanted with sdc1(-/-) bone marrow. Blood flow recovery was assessed by laser Doppler perfusion imaging. Arteriogenesis was assessed by measuring the diameter of the dominant collateral pathway after pressure perfusion fixation and intra-aortic contrast injection at 28 d. Immunohistochemistry was used to assess angiogenesis and peri-collateral macrophage infiltration at 7 d, postoperatively. Results: Sdc1(-/-) mice had impaired blood flow recovery in response to hindlimb ischemia. This impaired recovery was not secondary to a defect in capillary angiogenesis nor was it due to decreased peri-collateral macrophage infiltration. Wt bone marrow did not rescue the impaired recovery of sdc1(-/-) mice. Conclusions: Sdc1 affects arteriogenesis in response to hindlimb ischemia and is required in the local tissue environment for normal arteriogenesis. Published by Elsevier Inc. C1 [Tang, Gale L.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Tang, Gale L.; Weitz, Kevin] Univ Washington, Dept Surg, Div Vasc Surg, Seattle, WA 98108 USA. RP Tang, GL (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Surg Serv 112,1660 South Columbian Way, Seattle, WA 98108 USA. EM gtang@uw.edu NR 28 TC 1 Z9 1 U1 0 U2 2 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 JAN PY 2015 VL 193 IS 1 BP 22 EP 27 DI 10.1016/j.jss.2014.08.002 PG 6 WC Surgery SC Surgery GA AW4HH UT WOS:000346241300004 PM 25194470 ER PT J AU Murrell, DF Marinovic, B Caux, F Prost, C Ahmed, R Wozniak, K Amagai, M Bauer, J Beissert, S Borradori, L Culton, D Fairley, JA Fivenson, D Jonkman, MF Marinkovich, MP Woodley, D Zone, J Aoki, V Bernard, P Bruckner-Tuderman, L Cianchini, G Venning, V Diaz, L Eming, R Grando, SA Hall, RP Hashimoto, T Herrero-Gonzalez, JE Hertl, M Joly, P Karpati, S Kim, J Kim, SC Korman, NJ Kowalewski, C Lee, SE Rubenstein, DR Sprecher, E Yancey, K Zambruno, G Zillikens, D Doan, S Daniel, BS Werth, VP AF Murrell, Dedee F. Marinovic, Branka Caux, Frederic Prost, Catherine Ahmed, Razzaque Wozniak, Katarzyna Amagai, Masayuki Bauer, Johann Beissert, Stefan Borradori, Luca Culton, Donna Fairley, Janet A. Fivenson, David Jonkman, Marcel F. Marinkovich, M. Peter Woodley, David Zone, John Aoki, Valeria Bernard, Philippe Bruckner-Tuderman, Leena Cianchini, Giuseppe Venning, Vanessa Diaz, Luis Eming, Rudiger Grando, Sergei A. Hall, Russell P. Hashimoto, Takashi Herrero-Gonzalez, Josep E. Hertl, Michael Joly, Pascal Karpati, Sarolta Kim, Jaehwan Kim, Soo Chan Korman, Neil J. Kowalewski, Cezary Lee, Sang Eun Rubenstein, David R. Sprecher, Eli Yancey, Kim Zambruno, Giovanna Zillikens, Detlef Doan, Serge Daniel, Benjamin S. Werth, Victoria P. TI Definitions and outcome measures for mucous membrane pemphigoid: Recommendations of an international panel of experts SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Review DE consensus; definitions; mucous membrane pemphigoid; outcome measures; severity score ID CONSENSUS; DISEASE AB Mucous membrane pemphigoid encompasses a group of autoimmune bullous diseases with a similar phenotype characterized by subepithelial blisters, erosions, and scarring of mucous membranes, skin, or both. Although knowledge about autoimmune bullous disease is increasing, there is often a lack of clear definitions of disease, outcome measures, and therapeutic end points. With clearer definitions and outcome measures, it is possible to directly compare the results and data from various studies using meta-analyses. This consensus statement provides accurate and reproducible definitions for disease extent, activity, outcome measures, end points, and therapeutic response for mucous membrane pemphigoid and proposes a disease extent score, the Mucous Membrane Pemphigoid Disease Area Index. C1 [Murrell, Dedee F.; Kim, Jaehwan; Daniel, Benjamin S.] Univ New S Wales, St George Hosp, Dept Dermatol, Sydney, NSW 2317, Australia. [Marinovic, Branka] Univ Zagreb, Dept Dermatol & Venereol, Hosp Ctr & Sch Med, Zagreb 41000, Croatia. [Caux, Frederic] Univ Paris 13, Dept Dermatol, Avicenne Hosp, Bobigny, France. [Prost, Catherine] Univ Paris 13, Dept Dermatol, Dept Histol, Reference Ctr Autoimmune Bullous Dis,Avicenne Hos, Bobigny, France. [Ahmed, Razzaque] Ctr Blistering Dis, Boston, MA USA. [Wozniak, Katarzyna; Kowalewski, Cezary] Med Univ Warsaw, Dept Dermatol & Immunodermatol, Warsaw, Poland. [Amagai, Masayuki] Keio Univ, Sch Med, Dept Dermatol, Tokyo, Japan. [Bauer, Johann] Paracelsus Med Univ Salzburg, Div Mol Dermatol, Dept Dermatol, Salzburg, Austria. [Beissert, Stefan] Univ Dresden, Dept Dermatol, Dresden, Germany. [Borradori, Luca] Univ Hosp Bern, Dept Dermatol, Bern, Switzerland. [Culton, Donna; Diaz, Luis; Rubenstein, David R.] Univ N Carolina, Dept Dermatol, Chapel Hill, NC 27515 USA. [Fairley, Janet A.] Univ Iowa, Dept Dermatol, Iowa City, IA 52242 USA. [Fairley, Janet A.] Dept Vet Affairs Med Ctr, Palo Alto, CA USA. [Fivenson, David] St Joseph Mercy Hlth Syst, Dept Dermatol, Ann Arbor, MI USA. [Jonkman, Marcel F.] Univ Groningen, Univ Med Ctr Groningen, NL-9700 AB Groningen, Netherlands. [Marinkovich, M. Peter] Stanford Univ, Dept Dermatol, Sch Med, Stanford, CA 94305 USA. [Marinkovich, M. Peter] Dept Vet Affairs Palo Alto Healthcare Syst, Ctr Clin Sci Res, Palo Alto, CA USA. [Marinkovich, M. Peter] Dept Vet Affairs Palo Alto Healthcare Syst, Div Dermatol, Palo Alto, CA USA. [Woodley, David] Univ So Calif, Keck Sch Med, Dept Dermatol, Los Angeles, CA 90033 USA. [Zone, John] Univ Utah, Dept Dermatol, Sch Med, Salt Lake City, UT 84112 USA. [Aoki, Valeria] Univ Sao Paulo, Dept Dermatol, BR-05508 Sao Paulo, Brazil. [Bernard, Philippe] Univ Champagne Ardenne, Reims Univ Hosp, Dept Dermatol, Reims, France. [Bruckner-Tuderman, Leena] Univ Freiburg, Med Ctr, Dept Dermatol, Freiburg, Germany. [Cianchini, Giuseppe; Zambruno, Giovanna] IRCCS, Ist Dermopat Immacolata, Dept Immunodermatol, Rome, Italy. [Cianchini, Giuseppe] IRCCS, Ist Dermopat Immacolata, Lab Mol & Cell Biol, Rome, Italy. [Venning, Vanessa] Churchill Hosp, Dept Dermatol, Oxford OX3 7LJ, England. [Eming, Rudiger] Univ Marburg, Dept Dermatol & Allergol, Univ Hosp, D-35032 Marburg, Germany. [Grando, Sergei A.] Univ Calif Irvine, Dept Dermatol, Irvine, CA 92717 USA. [Grando, Sergei A.] Univ Calif Irvine, Dept Biol Chem, Ctr Canc, Irvine, CA 92717 USA. [Grando, Sergei A.] Univ Calif Irvine, Inst Immunol, Res Inst, Irvine, CA 92717 USA. [Hall, Russell P.] Duke Med Ctr, Div Dermatol, Durham, NC USA. [Hashimoto, Takashi] Kurume Univ, Sch Med, Kurume, Fukuoka, Japan. [Herrero-Gonzalez, Josep E.] Inst Hosp Mar Invest Med, Hosp del Mar, Dept Dermatol, Barcelona, Spain. [Hertl, Michael] Univ Hosp, Dept Dermatol, Marburg, Germany. [Joly, Pascal] Rouen Univ Hosp, INSERM U905, INSERM, Dermatol Clin, Rouen, France. [Joly, Pascal] Univ Rouen, Dept Dermatol, Rouen Univ Hosp, F-76821 Mont St Aignan, France. [Karpati, Sarolta] Semmelweis Univ, Dept Dermatol Venereol & Dermatooncol, H-1085 Budapest, Hungary. [Kim, Jaehwan] Rockefeller Univ, Invest Dermatol Lab, New York, NY 10021 USA. [Kim, Soo Chan] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Dermatol, Seoul, South Korea. [Kim, Soo Chan] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Cutaneous Biol Res Inst, Seoul, South Korea. [Korman, Neil J.] Univ Hosp Case Med Ctr, Dept Dermatol, Cleveland, OH USA. [Korman, Neil J.] Univ Hosp Case Med Ctr, Murdough Family Ctr Psoriasis, Cleveland, OH USA. [Lee, Sang Eun] CHA Univ, Dept Dermatol, CHA Bundang Med Ctr, Songnam, South Korea. [Sprecher, Eli] Tel Aviv Sourasky Med Ctr, Dept Dermatol, Tel Aviv, Israel. [Yancey, Kim] Univ Texas Southwestern Med Ctr, Dept Dermatol, Dallas, TX USA. [Zillikens, Detlef] Univ Lubeck, Dept Dermatol, Lubeck, Germany. [Doan, Serge] Hop Bichat Claude Bernard, Dept Ophthalmol, Paris, France. [Doan, Serge] Fdn Adolphe De Rothschild, Paris, France. [Werth, Victoria P.] Univ Penn, Philadelphia Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Werth, Victoria P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. RP Murrell, DF (reprint author), Univ New S Wales, St George Hosp, Dept Dermatol, Gray St,N8W, Sydney, NSW 2317, Australia. EM d.murrell@unsw.edu.au RI Amagai, Masayuki/K-5325-2013; Zillikens, Detlef/C-8572-2011; Aoki, Valeria/H-1415-2012 OI Amagai, Masayuki/0000-0003-3314-7052; Marinovic, Branka/0000-0001-8441-5016; Hashimoto, Takashi/0000-0002-0144-3255 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 International Pemphigus and Pemphigoid Foundation generously supported hiring rooms at the Annual Meetings of the American Academy of Dermatology and European Academy of Dermatology and Venereology as well as audiovisual equipment and open access. The Korean World Congress Committee and the Society for Investigative Dermatology provided meeting rooms. This material is based on work supported by 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 Dr Werth. NR 9 TC 14 Z9 14 U1 3 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2015 VL 72 IS 1 BP 168 EP 174 DI 10.1016/j.jaad.2014.08.024 PG 7 WC Dermatology SC Dermatology GA AW6UU UT WOS:000346404500046 PM 25443626 ER PT J AU Chen, BJ Zhou, XH Chan, G AF Chen, Baojiang Zhou, Xiao-Hua Chan, Gary TI Pseudoempirical-likelihood-based method using calibration for longitudinal data with dropout SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE Calibration; Dropout; Empirical likelihood; Longitudinal data ID GENERALIZED ESTIMATING EQUATIONS; IN-COVARIABLES MODELS; EMPIRICAL-LIKELIHOOD; REGRESSION-MODELS; LINEAR-MODELS; AUXILIARY INFORMATION; VALIDATION DATA; RESPONSE DATA; INFERENCE AB In observational studies, interest mainly lies in estimation of the population level relationship between the explanatory variables and dependent variables, and the estimation is often undertaken by using a sample of longitudinal data. In some situations, the longitudinal data sample features biases and loss of estimation efficiency due to non-random dropout. However, inclusion of population level information can increase estimation efficiency. We propose an empirical-likelihood-based method to incorporate population level information in a longitudinal study with dropout. The population level information is incorporated via constraints on functions of the parameters, and non-random dropout bias is corrected by using a weighted generalized estimating equations method. We provide a three-step estimation procedure that makes computation easier. Some commonly used methods are compared in simulation studies, which demonstrate that our proposed method can correct the non-random dropout bias and increase the estimation efficiency, especially for small sample sizes or when the missing proportion is high. In some situations, the improvement in efficiency is substantial. Finally, we apply the method to an Alzheimer's disease study. C1 [Chen, Baojiang] Univ Nebraska Med Ctr, Omaha, NE 68198 USA. [Zhou, Xiao-Hua; Chan, Gary] Univ Washington, Seattle, WA 98195 USA. [Zhou, Xiao-Hua] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Chen, BJ (reprint author), Univ Nebraska Med Ctr, Dept Biostat, Omaha, NE 68198 USA. EM baojiang.chen@unmc.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Research Career Scientist award [RCS 05-196]; National Institute on Aging [U01AG016976] FX The authors thank the Joint Editor, Associate Editor and two referees for their constructive comments and suggestions. Dr Xiao-Hua Zhou is at present a Core Investigator and Biostatistics Unit Director at the Northwest Health Services Research and Development Center of Excellence, Department of Veterans Affairs Medical Center, Seattle. Dr Zhou was supported in part by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Research Career Scientist award RCS 05-196. Both Dr Zhou and Dr Chen were supported in part by National Institute on Aging grant U01AG016976. This paper presents the findings and conclusions of the authors. It does not necessarily represent those of the Veterans Affairs Health Services Research and Development Service. NR 27 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0035-9254 EI 1467-9876 J9 J R STAT SOC C-APPL JI J. R. Stat. Soc. Ser. C-Appl. Stat. PD JAN PY 2015 VL 64 IS 1 BP 157 EP 174 DI 10.1111/rssc.12063 PG 18 WC Statistics & Probability SC Mathematics GA AW8FO UT WOS:000346496700007 PM 25587200 ER PT J AU Orbai, AM Truedsson, L Sturfelt, G Nived, O Fang, H Alarcon, GS Gordon, C Merrill, JT Fortin, PR Bruce, IN Isenberg, DA Wallace, DJ Ramsey-Goldman, R Bae, SC Hanly, JG Sanchez-Guerrero, J Clarke, AE Aranow, CB Manzi, S Urowitz, MB Gladman, DD Kalunian, KC Costner, MI Werth, VP Zoma, A Bernatsky, S Ruiz-Irastorza, G Khamashta, MA Jacobsen, S Buyon, JP Maddison, P Dooley, MA Van Vollenhoven, RF Ginzler, E Stoll, T Peschken, C Jorizzo, JL Callen, JP Lim, SS Fessler, BJ Inanc, M Kamen, DL Rahman, A Steinsson, K Franks, AG Sigler, L Hameed, S Pham, N Brey, R Weisman, MH McGwin, G Magder, LS Petri, M AF Orbai, A-M Truedsson, L. Sturfelt, G. Nived, O. Fang, H. Alarcon, G. S. Gordon, C. Merrill, J. T. Fortin, P. R. Bruce, I. N. Isenberg, D. A. Wallace, D. J. Ramsey-Goldman, R. Bae, S-C Hanly, J. G. Sanchez-Guerrero, J. Clarke, A. E. Aranow, C. B. Manzi, S. Urowitz, M. B. Gladman, D. D. Kalunian, K. C. Costner, M. I. Werth, V. P. Zoma, A. Bernatsky, S. Ruiz-Irastorza, G. Khamashta, M. A. Jacobsen, S. Buyon, J. P. Maddison, P. Dooley, M. A. Van Vollenhoven, R. F. Ginzler, E. Stoll, T. Peschken, C. Jorizzo, J. L. Callen, J. P. Lim, S. S. Fessler, B. J. Inanc, M. Kamen, D. L. Rahman, A. Steinsson, K. Franks, A. G., Jr. Sigler, L. Hameed, S. Pham, N. Brey, R. Weisman, M. H. McGwin, G., Jr. Magder, L. S. Petri, M. TI Anti-C1q antibodies in systemic lupus erythematosus SO LUPUS LA English DT Article DE Anti-dsDNA antibodies; renal lupus; systemic lupus erythematosus ID RENAL-DISEASE ACTIVITY; COLLAGEN-LIKE REGION; AUTOIMMUNE-DISEASES; PREDICTIVE-VALUE; IMMUNE DEPOSITS; C1Q DEFICIENCY; NEPHRITIS; AUTOANTIBODIES; COMPLEMENT; SERA AB Objective Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. Methods Information and blood samples were obtained in a cross-sectional study from patients with SLE (n=308) and other rheumatologic diseases (n=389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. Results Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR=2.7, 95% CI: 1.8-4, p<0.001). Anti-C1q was associated with proteinuria (OR=3.0, 95% CI: 1.7-5.1, p<0.001), red cell casts (OR=2.6, 95% CI: 1.2-5.4, p=0.015), anti-dsDNA (OR=3.4, 95% CI: 1.9-6.1, p<0.001) and anti-Smith (OR=2.8, 95% CI: 1.5-5.0, p=0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR=2.3, 95% CI: 1.3-4.2, p<0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR=14.9, 95% CI: 5.8-38.4, p<0.01). Conclusions Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis. C1 [Orbai, A-M; Fang, H.; Sigler, L.; Hameed, S.; Pham, N.; Petri, M.] Johns Hopkins Univ, Sch Med, Div Rheumatol, Baltimore, MD 21218 USA. [Truedsson, L.] Lund Univ, Dept Lab Med, Sect Microbiol Immunol & Glycobiol, Lund, Sweden. [Sturfelt, G.; Nived, O.] Skane Univ Hosp, Dept Rheumatol, Lund, Sweden. [Alarcon, G. S.; Fessler, B. J.; McGwin, G., Jr.] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Gordon, C.] Univ Birmingham, Rheumatol Res Grp, Sch Immun & Infect, Coll Med & Dent Sci, Birmingham, W Midlands, England. [Merrill, J. T.] Oklahoma Med Res Fdn, Dept Clin Pharmacol, Oklahoma City, OK 73104 USA. [Fortin, P. R.] Univ Laval, Dept Med, Ctr Hosp Univ CHU Quebec Axe Malad Infect & Immun, Div Rheumatol,CRCHU Quebec, Quebec City, PQ G1K 7P4, Canada. [Bruce, I. N.] Univ Manchester, Manchester Acad Hlth Sci Ctr, Arthrit Res UK Ctr Epidemiol, Ctr Musculoskeletal Res,Inst Inflammat & Repair, Manchester, Lancs, England. [Bruce, I. N.; Rahman, A.] Cent Manchester Univ Hosp NHS Fdn Trust, NIHR Manchester Musculoskeletal Biomed Res Unit, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Isenberg, D. A.] Ctr Rheumatol, Div Med Res, London, England. [Wallace, D. J.] Univ Calif Los Angeles, David Geffen Sch Med, Cedars Sinai Med Ctr, Los Angeles, CA 90095 USA. [Ramsey-Goldman, R.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Bae, S-C] Hanyang Univ Hosp Rheumat Dis, Dept Rheumatol, Seoul, South Korea. [Hanly, J. G.] Capital Hlth, Dept Med, Div Rheumatol, Halifax, NS, Canada. [Hanly, J. G.] Capital Hlth, Dept Pathol, Div Rheumatol, Halifax, NS, Canada. [Hanly, J. G.] Dalhousie Univ, Halifax, NS, Canada. [Sanchez-Guerrero, J.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Sanchez-Guerrero, J.] Univ Hlth Network, Toronto, ON, Canada. [Clarke, A. E.; Bernatsky, S.] McGill Univ, Ctr Hlth, Div Clin Epidemiol, Montreal, PQ, Canada. [Clarke, A. E.; Bernatsky, S.] McGill Univ, Ctr Hlth, Div Rheumatol, Montreal, PQ, Canada. [Aranow, C. B.] Feinstein Inst Med Res, Manhasset, NY USA. [Manzi, S.] Allegheny Gen Hosp, Allegheny Singer Res Inst, Div Rheumatol, Dept Med, Pittsburgh, PA 15212 USA. [Urowitz, M. B.; Gladman, D. D.] Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. [Kalunian, K. C.] UCSD Sch Med, Div Rheumatol Allergy & Immunol, La Jolla, CA USA. [Costner, M. I.] North Dallas Dermatol Associates, Dallas, TX USA. [Werth, V. P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Werth, V. P.] Univ Penn, Philadelphia, PA 19104 USA. [Zoma, A.] Lanarkshire Ctr Rheumatol, E Kilbride, Lanark, Scotland. [Zoma, A.] Hairmyres Hosp, E Kilbride, Lanark, Scotland. [Ruiz-Irastorza, G.] Univ Basque Country, Hosp Univ Cruces, Autoimmune Dis Res Unit, Baracaldo, Spain. [Khamashta, M. A.] Rayne Inst, London, England. [Khamashta, M. A.] St Thomas Hosp London, London, England. [Jacobsen, S.] Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark. [Buyon, J. P.; Franks, A. G., Jr.] NYU, New York, NY USA. [Maddison, P.] Ysbyty Gwynedd, Bangor, Gwynedd, Wales. [Dooley, M. A.] Univ N Carolina, Chapel Hill, NC USA. [Van Vollenhoven, R. F.] Karolinska Univ Hosp, Stockholm, Sweden. [Ginzler, E.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Stoll, T.] Kantonsspital Schaffhausen, Schaffhausen, Switzerland. [Peschken, C.] Univ Manitoba Winnipeg, Winnipeg, MB, Canada. [Jorizzo, J. L.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Callen, J. P.] Univ Louisville, Louisville, KY 40292 USA. [Lim, S. S.] Emory Univ, Atlanta, GA 30322 USA. [Inanc, M.] Istanbul Univ, Istanbul Fac Med, Dept Internal Med, Div Rheumatol, Istanbul, Turkey. [Kamen, D. L.] Med Univ S Carolina, Charleston, SC 29425 USA. [Steinsson, K.] Landspitali Univ Hosp, Reykjavik, Iceland. [Brey, R.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Weisman, M. H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Magder, L. S.] Univ Maryland, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. RP Petri, M (reprint author), Johns Hopkins Univ, Sch Med, Div Rheumatol, 1830 E Monument St,Suite 7500, Baltimore, MD 21218 USA. EM MPetri@jhmi.edu RI Ruiz-Irastorza, Guillermo/P-7058-2014 OI Ruiz-Irastorza, Guillermo/0000-0001-7788-1043; Peschken, Christine/0000-0002-4269-5213; Isenberg, David/0000-0001-9514-2455; Franks, Andrew/0000-0001-5427-6369 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Lupus Foundation of America; Human Genome Sciences; National Institutes of Health (NIH) [T32 AR048522]; Greta and Johan Kock's Foundation; King Gustaf V's 80th Birthday Foundation; Swedish Rheumatism Association; Lupus UK; Canada Research Chair on Systemic Autoimmune Rheumatic Diseases; National Institute for Health Research University College London Hospitals Biomedical Research Centre; Korea Healthcare Technology R & D Project, Ministry for Health and Welfare, Republic of Korea [A120404]; Arthritis Research UK; Manchester Academic Health Science Centre; NIHR Manchester Musculoskeletal Biomedical Research Unit; NIHR Manchester Wellcome Trust Clinical Research Facility; Manchester Biomedical Research Centre FX This work was supported in the form of grants or industrial support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and Lupus Foundation of America, and an unrestricted research grant from Human Genome Sciences.; Dr Ana-Maria Orbai is supported by National Institutes of Health (NIH) grant T32 AR048522.; Dr Gunnar Sturfelt and Dr Lennart Truedsson are supported by grants from the Greta and Johan Kock's Foundation, King Gustaf V's 80th Birthday Foundation and the Swedish Rheumatism Association.; Dr Caroline Gordon is supported by Lupus UK.; Dr Paul R. Fortin is supported by a Canada Research Chair on Systemic Autoimmune Rheumatic Diseases.; Dr David A. Isenberg and Dr Anisur Rahman are supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre.; Dr Sang-Cheol Bae is supported by the Korea Healthcare Technology R & D Project, Ministry for Health and Welfare, Republic of Korea (A120404).; Professor I. Bruce is a National Institute for Health Research (NIHR) Senior Investigator and is supported by Arthritis Research UK, The Manchester Academic Health Science Centre, the NIHR Manchester Musculoskeletal Biomedical Research Unit, The NIHR Manchester Wellcome Trust Clinical Research Facility and the Manchester Biomedical Research Centre. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. NR 33 TC 23 Z9 23 U1 0 U2 14 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0961-2033 EI 1477-0962 J9 LUPUS JI Lupus PD JAN PY 2015 VL 24 IS 1 BP 42 EP 49 DI 10.1177/0961203314547791 PG 8 WC Rheumatology SC Rheumatology GA AW3HR UT WOS:000346177700006 PM 25124676 ER PT J AU Regensteiner, JG Bauer, TA Huebschmann, AG Herlache, L Weinberger, HD Wolfel, EE Reusch, JEB AF Regensteiner, Judith G. Bauer, Timothy A. Huebschmann, Amy G. Herlache, Leah Weinberger, Howard D. Wolfel, Eugene E. Reusch, Jane E. B. TI Sex Differences in the Effects of Type 2 Diabetes on Exercise Performance SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE OXYGEN CONSUMPTION; OXYGEN UPTAKE KINETICS; FUNCTIONAL IMPAIRMENT; CARDIOVASCULAR ID SOCIETY-OF-ECHOCARDIOGRAPHY; OXYGEN-UPTAKE; DOPPLER-ECHOCARDIOGRAPHY; CARDIOVASCULAR-DISEASE; FILLING PRESSURES; VASCULAR-DISEASE; RISK-FACTORS; MELLITUS; WOMEN; MEN AB Purpose People with uncomplicated type 2 diabetes (T2D) have impaired peak exercise performance compared with that of their nondiabetic counterparts. This impairment may represent the earliest indication of cardiovascular (CV) abnormalities in T2D. Women with T2D are known to have worse CV outcomes than those in men with T2D. We hypothesized that women with diabetes have a greater exercise impairment than that in men with diabetes compared with that in their nondiabetic counterparts. Methods We studied 15 women (premenopausal) and 14 men with T2D as well as their nondiabetic counterparts (22 women and 13 men). Exercise testing was performed. Additional outcomes included measurements of insulin sensitivity, endothelial function, blood flow, and resting cardiac function. Results Men and women with T2D but not controls had impaired insulin sensitivity. Women with T2D had a lower peak oxygen consumption (VO2peak) compared with that of nondiabetic women (24%, P < 0.05) than men with diabetes compared with that in nondiabetic men (16%, P < 0.05) (P value between groups < 0.05). The time constants (phase 2) of the VO2 kinetic response tended to be slower in men and women with T2D than those in nondiabetic controls (P = 0.08). There were no differences in resting ventricular function by Doppler echocardiography techniques between groups. Women with T2D had significantly lower flow-mediated dilation and blood flow responses to hyperemia than those in nondiabetic women (both P < 0.05), whereas men with T2D had lower flow-mediated dilation but not lower blood flow than those in nondiabetic men. Conclusions Although both men and women with uncomplicated T2D had a lower VO2peak, the abnormality in women with T2D compared with that in nondiabetic women was greater than that seen in men. Because VO2peak has a strong inverse correlation with mortality, sex disparities observed in exercise capacity among people with T2D suggest a possible rationale for the increased CV morbidity and mortality observed in women compared with those observed in men with uncomplicated T2D. C1 [Regensteiner, Judith G.; Bauer, Timothy A.; Huebschmann, Amy G.; Herlache, Leah] Univ Colorado, Div Internal Med, Sch Med, Dept Med, Aurora, CO USA. [Regensteiner, Judith G.; Weinberger, Howard D.; Wolfel, Eugene E.] Univ Colorado, Div Cardiol, Sch Med, Dept Med, Aurora, CO USA. [Regensteiner, Judith G.; Huebschmann, Amy G.; Reusch, Jane E. B.] Univ Colorado, Ctr Womens Hlth Res, Sch Med, Dept Med, Aurora, CO USA. [Reusch, Jane E. B.] Univ Colorado, Div Endocrinol, Sch Med, Aurora, CO USA. [Weinberger, Howard D.] Natl Jewish Hlth, Div Cardiol, Dept Med, Denver, CO USA. [Reusch, Jane E. B.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Regensteiner, JG (reprint author), Univ Colorado, Ctr Womens Hlth Res, Sch Med, Mail Stop B180,Bldg AO1,12631 East 17th Ave, Aurora, CO 80045 USA. EM judy.regensteiner@ucdenver.edu FU American Diabetes Association; National Institutes of Health/National Center for Research Resources Colorado CTSI [UL1 RR025780] FX This research was funded by a clinical research grant from the American Diabetes Association. The research was also supported by the National Institutes of Health/National Center for Research Resources Colorado CTSI grant number UL1 RR025780. The electrodes for the study were provided by Vermed. NR 42 TC 6 Z9 6 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JAN PY 2015 VL 47 IS 1 BP 58 EP 65 DI 10.1249/MSS.0000000000000371 PG 8 WC Sport Sciences SC Sport Sciences GA AW6BP UT WOS:000346354800009 PM 24811327 ER PT J AU Roche, AM Richard, AL Rahkola, JT Janoff, EN Weiser, JN AF Roche, A. M. Richard, A. L. Rahkola, J. T. Janoff, E. N. Weiser, J. N. TI Antibody blocks acquisition of bacterial colonization through agglutination SO MUCOSAL IMMUNOLOGY LA English DT Article ID INFLUENZAE TYPE-B; INVASIVE PNEUMOCOCCAL DISEASE; STREPTOCOCCUS-PNEUMONIAE; CONJUGATE VACCINES; POLYSACCHARIDE; IMMUNOGLOBULIN; PROTECTION; INFECTION; IMMUNIZATION; PROTEINS AB Invasive infection often begins with asymptomatic colonization of mucosal surfaces. A murine model of bacterial colonization with Streptococcus pneumoniae was used to study the mechanism for mucosal protection by immunoglobulin. In previously colonized immune mice, bacteria were rapidly sequestered within large aggregates in the nasal lumen. To further examine the role of bacterial agglutination in protection by specific antibodies, mice were passively immunized with immunoglobulinG(IgG) purified from antipneumococcal sera or pneumococcal type-specific monoclonal human IgA (hIgA1 or hIgA2). Systemically delivered IgG accessed the mucosal surface and blocked acquisition of colonization and transmission between littermates. Optimal protection by IgG was independent of Fc fragment and complement and, therefore, did not involve an opsonophagocytic mechanism. Enzymatic digestion or reduction of IgG before administration showed that protection required divalent binding that maintained its agglutinating effect. Divalent hIgA1 is cleaved by the pneumococcal member of a family of bacterial proteases that generate monovalent Faba fragments. Thus, passive immunization with hIgA1 blocked colonization by an IgA1-protease-deficient mutant (agglutinated) but not the protease-producing wild-type parent (not agglutinated), whereas protease-resistant hIgA2 agglutinated and blocked colonization by both. Our findings highlight the importance of agglutinating antibodies in mucosal defense and reveal how successful pathogens evade this effect. C1 [Roche, A. M.; Richard, A. L.; Weiser, J. N.] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. [Rahkola, J. T.; Janoff, E. N.] Univ Colorado Denver, Div Infect Dis, Mucosal & Vaccine Res Program Colorado MAVRC, Aurora, CO USA. [Rahkola, J. T.; Janoff, E. N.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Weiser, JN (reprint author), Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. EM weiser@mail.med.upenn.edu FU US Public Health Service [AI38446, AI05168, AI092468, AI108479]; Robert Austrian Research Award in Pneumococcal Vaccinology; NIH/NIDDK Center for Molecular Studies in Digestive and Liver Diseases [P30-DK050306]; Molecular Pathology and Imaging core facilities; Mucosal and Vaccine Research Program Colorado (MAVRC) FX We thank Jan Erikson from The Wistar Institute for providing X31 Influenza virus. This work was supported by the US Public Health Service, grant number AI38446 and AI05168 (J.N.W.), AI092468 and AI108479 (E.N.J), and the Robert Austrian Research Award in Pneumococcal Vaccinology (A.M.R). Additional support was provided by the NIH/NIDDK Center for Molecular Studies in Digestive and Liver Diseases (P30-DK050306) and its Molecular Pathology and Imaging core facilities, and the Mucosal and Vaccine Research Program Colorado (MAVRC). NR 35 TC 18 Z9 18 U1 4 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 EI 1935-3456 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD JAN PY 2015 VL 8 IS 1 BP 176 EP 185 DI 10.1038/mi.2014.55 PG 10 WC Immunology SC Immunology GA AW5TB UT WOS:000346335600016 PM 24962092 ER PT J AU Malik, R Irodenko, V Zimmermann, L Green, A Layzer, R AF Malik, Rabia Irodenko, Viktoriya Zimmermann, Lara Green, Ari Layzer, Robert TI FOCAL AMYOTROPHY IN MULTIPLE SCLEROSIS SO MUSCLE & NERVE LA English DT Article DE amyotrophy; axonal; demyelination; multiple sclerosis; spinal cord ID CONGENITAL MUSCULAR-DYSTROPHY; CHOLINE KINASE BETA; MUTATIONS; MITOCHONDRIA; MYOPATHIES AB Introduction: The assumption that multiple sclerosis (MS) is purely a white matter disease has been challenged in recent years by observations of axonal damage and neuronal loss in gray matter of the cortex, subcortex, and spinal cord. Methods: We report the case of a 71-year-old man with primary progressive MS and longstanding right arm weakness who presented with intermittent right arm pain. Results: Neurological examination showed atrophy, weakness, and hyporeflexia, and electromyography (EMG) showed acute and chronic partial denervation in multiple segments of the right arm. Magnetic resonance imaging (MRI) demonstrated asymmetric volume loss and increased T2 signal in the right anterior spinal cord from C3 to C7, with no evidence of nerve root compression. Conclusions: Lower motor neuron involvement of his right arm was caused by MS with involvement of either the anterior horn cells or the intraspinal motor nerve roots. C1 [Malik, Rabia; Irodenko, Viktoriya; Zimmermann, Lara; Green, Ari; Layzer, Robert] Univ Calif San Francisco, Dept Neurol, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. RP Malik, R (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco VA Med Ctr, 505 Parnassus Ave,Box 0114,M-798, San Francisco, CA 94143 USA. EM rabia.mk@gmail.com NR 12 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X EI 1097-4598 J9 MUSCLE NERVE JI Muscle Nerve PD JAN PY 2015 VL 51 IS 1 BP 137 EP 143 DI 10.1002/mus.24439 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AW5UY UT WOS:000346340300021 PM 25186124 ER PT J AU Suri, P Hunter, DJ Boyko, EJ Rainville, J Guermazi, A Katz, JN AF Suri, Pradeep Hunter, David J. Boyko, Edward J. Rainville, James Guermazi, Ali Katz, Jeffrey N. TI Physical activity and associations with computed tomography-detected lumbar zygapophyseal joint osteoarthritis SO SPINE JOURNAL LA English DT Article DE Facet; Lumbar; Arthritis; Rehabilitation; Computed tomography; Exercise ID MALE MONOZYGOTIC TWINS; 5-YEAR FOLLOW-UP; DISC DEGENERATION; CARDIOVASCULAR-DISEASE; CORONARY-ARTERY; FACET JOINTS; BACK-PAIN; PROGRESSION; SPINE; DETERMINANTS AB BACKGROUND CONTEXT: There are no previous epidemiologic studies examining associations between physical activity and imaging-detected lumbar zygapophyseal joint osteoarthritis (ZJO) in a community-based sample. PURPOSE: To determine whether physical activity is associated with prevalent lumbar ZJO on computed tomography (CT). STUDY DESIGN/SETTING: A community-based cross-sectional study. PATIENT SAMPLE: Four hundred twenty-four older adults from the Framingham Heart Study. OUTCOME MEASURES: Participants received standardized CT assessments of lumbar ZJO at the L2-S1 levels. Severe lumbar ZJO was defined according to the presence and/or degree of joint space narrowing, osteophytosis, articular process hypertrophy, articular erosions, subchondral cysts, and intra-articular vacuum phenomenon. This definition of lumbar ZJO was based entirely on CT imaging findings and did not include any clinical criteria such as low back pain. METHODS: Physical activity was measured using the Physical Activity Index, which estimate hours per day typically spent in these activity categories: sleeping, sitting, slight activity, moderate activity, and heavy activity. Participants reported on usual frequency of walking, running, swimming, and weightlifting. We used multivariable logistic regression to examine associations between self-reported activity and severe lumbar ZJO, while adjusting for key covariates including age, sex, height, and weight. RESULTS: In multivariable analyses, ordinal categories of heavy physical activity duration per day were significantly associated with severe lumbar ZJO (p for trend = .04), with the greatest risk observed for the category 3 or more hours per day, odds ratio 2.13 (95% confidence interval [CI] 0.97-4.67). When heavy activity was modeled as a continuous independent variable, each hour was independently associated with 1.19 times the odds of severe lumbar ZJO (95% CI 1.03-1.38, p = .02). Less vigorous types of physical activity and the type of exercise were not associated with severe lumbar ZJO. Older age, lesser height, and greater weight were independently and significantly associated with severe lumbar ZJO. In multivariable models predicting lumbar ZJO, neither model discrimination nor reclassification improved with the addition of physical activity variables, compared with a multivariable model including age, sex, height, and weight. CONCLUSIONS: Our findings demonstrate a statistically significant cross-sectional association between heavy physical activity and CT-detected severe lumbar ZJO. However, the additional discriminatory capability of heavy physical activity above and beyond that contributed by other factors was negligible. Published by Elsevier Inc. C1 [Suri, Pradeep; Boyko, Edward J.] VA Puget Sound Healthcare Syst, Seattle, WA 98108 USA. [Suri, Pradeep] Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98103 USA. [Hunter, David J.] Univ Sydney, Royal N Shore Hosp, Clin Adm 7C, Dept Rheumatol,Kolling Inst, St Leonards, NSW 2065, Australia. [Boyko, Edward J.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98103 USA. [Rainville, James] New England Baptist Hosp, Boston, MA 02120 USA. [Guermazi, Ali] Boston Univ, Sch Med, Dept Radiol, Boston, MA 02215 USA. [Katz, Jeffrey N.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy,Dept Med, Boston, MA 02446 USA. [Katz, Jeffrey N.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02446 USA. RP Suri, P (reprint author), VA Puget Sound Healthcare Syst, 1660 S Columbian Way,RCS 117, Seattle, WA 98108 USA. EM pradeep.suriyaarachchi@va.gov OI Boyko, Edward/0000-0002-3695-192X FU Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health; Boston University School of Medicine; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; Rehabilitation Medicine Scientist Training Program; National Institutes of Health [K12 HD 01097]; New England Baptist Hospital Research Funding Award; Elizabeth Stent Fund; National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases [P60 AR 47782]; Australian Research Council Future Fellowship; VA Puget Sound FX From the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. The National Heart, Lung, and Blood Institute's Framingham Heart Study contract (No. N01-HC-25195) supported the recruitment, enrollment, and examination of the Offspring and Third-Generation Cohorts and the computed tomography scans. Dr PS and this research were funded by the Rehabilitation Medicine Scientist Training Program and the National Institutes of Health (K12 HD 01097), with supplemental funding from the New England Baptist Hospital Research Funding Award and the Elizabeth Stent Fund. VA Puget Sound provided support for Dr PS's participation in this research. Dr JNK was funded in part by National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases P60 AR 47782. Dr DJH was funded by an Australian Research Council Future Fellowship. VA Puget Sound provided support for Dr EJB's participation in this research. There were no study-specific conflict of interest-associated biases. NR 31 TC 1 Z9 1 U1 3 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 EI 1878-1632 J9 SPINE J JI Spine Journal PD JAN PY 2015 VL 15 IS 1 BP 42 EP 49 DI 10.1016/j.spinee.2014.06.022 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA AW6OP UT WOS:000346389000008 PM 25011094 ER PT J AU Ray, LA Courtney, KE Ghahremani, DG Miotto, K Brody, A London, ED AF Ray, Lara A. Courtney, Kelly E. Ghahremani, Dara G. Miotto, Karen Brody, Arthur London, Edythe D. TI Varenicline, naltrexone, and their combination for heavy-drinking smokers: preliminary neuroimaging findings SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE Craving; fMRI; heavy drinker; naltrexone; smoker; varenicline ID RECEPTOR PARTIAL AGONIST; RANDOMIZED CONTROLLED-TRIAL; NICOTINE REPLACEMENT THERAPY; SMOKING-CESSATION TREATMENT; SUSTAINED-RELEASE BUPROPION; WEIGHT-GAIN; ALCOHOL DEPENDENCE; CUE REACTIVITY; BRAIN ACTIVITY; EFFICACY AB Rationale: Heavy drinking smokers constitute a sizeable and hard-to-treat subgroup of smokers, for whom tailored smoking cessation therapies are not yet available. Objective: The present study used a double-blind, randomized, 2 x 2 medication design, testing varenicline alone (VAR; 1 mg twice daily), naltrexone alone (NTX; 25mg once daily), varenicline plus naltrexone, and placebo for effects on neural activation to cigarette cues in a sample (n = 40) of heavy drinking daily smokers (>= 10 cigarettes/day). Methods: All participants were tested after a 10-12-day titration period designed to reach steady state on the target medication. Participants underwent functional neuroimaging (fMRI) for examination of brain responses to visual smoking-related (vs. neutral) cues. Results: Region of interest (ROI) analyses of brain responses to Cigarette vs. Neutral Cues indicated that the combination of VAR + NTX was associated with reduced activation of the bilateral anterior cingulate cortex as compared to placebo and to NTX alone. Exploratory whole-brain analyses also indicated significant differences in brain activation during cigarette cues in the active medications versus placebo condition. All medications suppressed left nucleus accumbens activation relative to placebo, suggesting the possibility that both medications, either alone or in combination, reduce neural signals associated with appetitive behavior. Conclusions: Although preliminary, these neuroimaging findings indicate that clinical studies of the combination of VAR + NTX for heavy drinkers trying to quit smoking may be warranted. C1 [Ray, Lara A.; Courtney, Kelly E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Ray, Lara A.; Ghahremani, Dara G.; Miotto, Karen; Brody, Arthur; London, Edythe D.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Brody, Arthur] Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [London, Edythe D.] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. RP Ray, LA (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall,Box 951563, Los Angeles, CA 90095 USA. EM lararay@psych.ucla.edu RI Courtney, Kelly/L-6041-2016 OI Courtney, Kelly/0000-0002-9280-2435 FU California Tobacco Related Disease Research Program (TRDRP) [18KT-0020]; National Institute on Drug Abuse [DA030898]; UCLA Clinical and Translational Science Institute (CTSI) [UL1RR033176, UL1TR000124]; UCLA Training Program in Translational Neuroscience of Drug Abuse [T32 DA024635]; GSK FX This research was supported grants from the California Tobacco Related Disease Research Program (TRDRP 18KT-0020) and from the National Institute on Drug Abuse (DA030898) to LAR. Support for this study was also provided by a grant from the UCLA Clinical and Translational Science Institute (CTSI), grants UL1RR033176 and UL1TR000124. KEC was supported by the UCLA Training Program in Translational Neuroscience of Drug Abuse (T32 DA024635). LAR is a paid consultant for GSK. NR 64 TC 6 Z9 6 U1 0 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0095-2990 EI 1097-9891 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PD JAN PY 2015 VL 41 IS 1 BP 35 EP 44 DI 10.3109/00952990.2014.927881 PG 10 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA AW1TQ UT WOS:000346073600005 PM 24949564 ER PT J AU Toto, PE Skidmore, ER Terhorst, L Rosen, J Weiner, DK AF Toto, Pamela E. Skidmore, Elizabeth R. Terhorst, Lauren Rosen, Jules Weiner, Debra K. TI Goal Attainment Scaling (GAS) in geriatric primary care: A feasibility study SO ARCHIVES OF GERONTOLOGY AND GERIATRICS LA English DT Article DE GAS; Older adults; Primary care; Chronic conditions; Patient-centered care ID MONTREAL COGNITIVE ASSESSMENT; RANDOMIZED CONTROLLED-TRIAL; DECISION-MAKING; OLDER-ADULTS; CLINICAL UTILITY; OUTCOME MEASURE; MANAGEMENT; PARTICIPATE; PREFERENCES; PREVALENCE AB Objective: Evaluate the feasibility of generating patient-centered goals using GAS with older adults who have multiple chronic conditions, recruited through primary care. Method: Adults age 65+ (N = 27) were recruited from a geriatric primary care center. Participants were asked to identify 2-4 activity-based goals and set attainment levels using GAS. At 8 weeks, participants were asked to rate current level of their goal performance. Physician surveys were used to evaluate if goals were realistic and feasible, and patient surveys were implemented to evaluate satisfaction. GAS T-scores were used to quantify change in goal achievement. Results: Ninety-three percent (n = 25) of participants were able to establish a minimum of two goals using GAS. 100% of participants were able to rate goal performance at follow-up. Physician survey results identified 100% of goals realistic and 93% achievable and 100% of participants were either neutral or satisfied with the process. Significant improvement was reported in GAS change scores (t(24) = 6.54, p < 0.001). Conclusion: Findings support the feasibility of GAS for older adults with multiple chronic conditions in geriatric primary care as a strategy to facilitate patient-centered care and suggest that the process of personalized goal-setting itself may facilitate goal attainment. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Toto, Pamela E.; Skidmore, Elizabeth R.; Terhorst, Lauren] Univ Pittsburgh, Dept Occupat Therapy, Pittsburgh, PA 15260 USA. [Rosen, Jules] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. [Weiner, Debra K.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Weiner, Debra K.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA 15260 USA. RP Toto, PE (reprint author), Univ Pittsburgh, Dept Occupat Therapy, 5038 Forbes Tower, Pittsburgh, PA 15260 USA. EM pet3@pitt.edu FU Aging Institute of UPMC Senior Services; University of Pittsburgh FX This work was supported by a pilot seed grant from the Aging Institute of UPMC Senior Services and the University of Pittsburgh. NR 39 TC 3 Z9 3 U1 2 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-4943 EI 1872-6976 J9 ARCH GERONTOL GERIAT JI Arch. Gerontol. Geriatr. PD JAN-FEB PY 2015 VL 60 IS 1 BP 16 EP 21 DI 10.1016/j.archger.2014.10.022 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AW1TH UT WOS:000346072400003 PM 25465505 ER PT J AU Kubinski, SN McQueen, CA Sittloh, KA Dean, JC AF Kubinski, Samantha N. McQueen, Christina A. Sittloh, Keir A. Dean, Jesse C. TI Walking with wider steps increases stance phase gluteus medius activity SO GAIT & POSTURE LA English DT Article DE Biomechanics; Gluteus medius; Hip abduction; Locomotion; Step width ID BALANCE; STABILIZATION; COORDINATION; INDICATORS; STABILITY; TREADMILL; STRATEGY; STROKE; ADULTS; SPEED AB Increases in step width have been reported for several clinical populations, including older adults and stroke survivors. These populations often also exhibit decreased hip abductor strength, suggesting that walking with wider steps may be an adaptive response in order to reduce the mechanical demands on the hip abductors. The purpose of this study was to quantify the relationship between step width and gluteus medius (GM) activity during walking. Fourteen young, uninjured adults walked on a treadmill at 1.25 m/s for four step width conditions (Normal, Narrow, Medium, and Wide) while step width and stance phase GM electromyographic (EMG) activity were quantified. We also measured hip abduction torque and GM activity during maximum voluntary isometric contractions (MVICs) at three hip angles (neutral, abducted 108, and abducted 20 degrees). During walking trials, GM activity was significantly (p < 0.0001) influenced by step width; compared to Normal walking, GM activity was 47% higher with Wide steps and 24% lower with Narrow steps. We also observed a weak positive correlation (r = 0.18 +/- 0.14) between step width and GM activity during Normal walking, as GM activity was higher with wider steps. These results cannot be attributed to changes in GM conformation under the recording electrode, as GM activity was not influenced by hip angle during MVICs. The increased GM activity with wider steps does not support the proposal that increasing step width would be a beneficial adaptation to weakened hip abductors. A likely alternative explanation is that increased step width is a response to decreased gait balance. Published by Elsevier B.V. C1 [Kubinski, Samantha N.; McQueen, Christina A.; Sittloh, Keir A.; Dean, Jesse C.] Med Univ S Carolina, Coll Hlth Profess, Div Phys Therapy, Charleston, SC 29425 USA. [Dean, Jesse C.] Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. RP Dean, JC (reprint author), 77 President St,MSC700, Charleston, SC 29425 USA. EM deaje@musc.edu OI Dean, Jesse/0000-0003-2034-4217 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service [IK2 RX000750]; National Institutes of Health [R21 HD064964] FX This work was partially supported by grants from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service (IK2 RX000750) and the National Institutes of Health (R21 HD064964). The funding sources had no involvement in the study design; collection, analysis, and interpretation of data; writing of the manuscript; or decision to submit the manuscript for publication. The contents of this manuscript do not represent the views of the Department of Veterans Affairs or the United States Government. NR 30 TC 5 Z9 5 U1 0 U2 15 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 EI 1879-2219 J9 GAIT POSTURE JI Gait Posture PD JAN PY 2015 VL 41 IS 1 BP 130 EP 135 DI 10.1016/j.gaitpost.2014.09.013 PG 6 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA AW2MQ UT WOS:000346122800023 PM 25300241 ER PT J AU Provost, SM Lanham, HJ Leykum, LK McDaniel, RR Pugh, J AF Provost, Shannon M. Lanham, Holly J. Leykum, Luci K. McDaniel, Reuben R., Jr. Pugh, Jacqueline TI Health care huddles: Managing complexity to achieve high reliability SO HEALTH CARE MANAGEMENT REVIEW LA English DT Article DE complex adaptive systems; conversation; health care huddles; high reliability organizations; relationships ID CULTURE; ORGANIZATIONS; HOSPITALS; DYNAMICS; SAFETY; SYSTEM AB Background: Health care huddles are increasingly employed in a range of formats but theoretical mechanisms underlying huddles remain relatively uncharted. Purpose: A complexity science view implies that essential managerial strategies for high-performing health care organizations include meaningful conversations, enhanced relationships, and a learning culture. These three dimensions informed our approach to studying huddles. We explore new theories for how and why huddles have been useful in health care organizations. Methods: We used a study design incorporating literature review, direct observation, and semistructured interviews. A complexity science framework guided data collection in three health care settings; we also incorporated theories on high-reliability organizations to analyze our observations and interpret huddle participants' perspectives. Findings: We identify theoretical paths that could link huddles to improvement in patient safety outcomes. Huddles create time and space for conversations, enhance relationships, and strengthen a culture of safety. Huddles can be of particular value to health care organizations seeking or sustaining high reliability. Practice Implications: Achieving high reliability, the organizational capacity to deliver what is intended to be delivered every time is difficult in complex systems. Managers have potential to create conditions from which huddle outcomes that support high reliability are more likely to emerge. Huddles support efforts to improve patient safety when they afford opportunities for heedful interactions to take place among individuals caring for patients and embed mindfulness into the organization. C1 [Provost, Shannon M.; Lanham, Holly J.] Univ Texas Austin, Dept Informat Risk & Operat Management, McCombs Sch Business, Austin, TX 78712 USA. [Lanham, Holly J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Leykum, Luci K.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, Dept Med, San Antonio, TX 78229 USA. [McDaniel, Reuben R., Jr.] Univ Texas Austin, McCombs Sch Business, Austin, TX 78712 USA. [Pugh, Jacqueline] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Pugh, Jacqueline] South Texas Vet Hlth Care Syst, Res, San Antonio, TX USA. RP Provost, SM (reprint author), Univ Texas Austin, Dept Informat Risk & Operat Management, McCombs Sch Business, Austin, TX 78712 USA. EM shannon.provost@phd.mccombs.utexas.edu OI Pugh, Jacqueline/0000-0003-4933-141X NR 49 TC 5 Z9 5 U1 3 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0361-6274 EI 1550-5030 J9 HEALTH CARE MANAGE R JI Health Care Manage. Rev. PD JAN-MAR PY 2015 VL 40 IS 1 BP 2 EP 12 DI 10.1097/HMR.0000000000000009 PG 11 WC Health Policy & Services SC Health Care Sciences & Services GA AW2LW UT WOS:000346120400002 PM 24589926 ER PT J AU Jia, HG Phipps, M Bravata, D Castro, J Li, XL Ordin, D Myers, J Vogel, WB Williams, L Chumbler, N AF Jia, Huanguang Phipps, Michael Bravata, Dawn Castro, Jaime Li, Xinli Ordin, Diana Myers, Jennifer Vogel, W. Bruce Williams, Linda Chumbler, Neale TI Inpatient stroke care quality for veterans: are there differences between Veterans Affairs medical centers in the stroke belt and other areas? SO INTERNATIONAL JOURNAL OF STROKE LA English DT Article DE acute stroke therapy; acute; ischemic stroke; stroke; facilities; stroke units; treatment ID CLINICAL-PRACTICE GUIDELINE; AMERICAN-HEART-ASSOCIATION; ACADEMY-OF-NEUROLOGY; ISCHEMIC-STROKE; UNITED-STATES; REHABILITATION CARE; MORTALITY; MANAGEMENT; COUNCIL; PROFESSIONALS AB Background Stroke mortality has been found to be much higher among residents in the stroke belt region than in the rest of United States, but it is not known whether differences exist in the quality of stroke care provided in Department of Veterans Affairs medical centers in states inside and outside this region. Objective We compared mortality and inpatient stroke care quality between Veterans Affairs medical centers inside and outside the stroke belt region. Methods Study patients were veterans hospitalized for ischemic stroke at 129 Veterans Affairs medical centers. Inpatient stroke care quality was assessed by 14 quality indicators. Multivariable logistic regression models were fit to examine differences in quality between facilities inside and outside the stroke belt, adjusting for patient characteristics and Veterans Affairs medical centers clustering effect. Results Among the 3909 patients, 28.1% received inpatient ischemic stroke care in 28 stroke belt Veterans Affairs medical centers, and 71.9% obtained care in 101 non-stroke belt Veterans Affairs medical centers. Patients cared for in stroke belt Veterans Affairs medical centers were more likely to be younger, Black, married, have a higher stroke severity, and less likely to be ambulatory pre-stroke. We found no statistically significant differences in short-and long-term post-admission mortality and inpatient care quality indicators between the patients cared for in stroke belt and non-stroke belt Veterans Affairs medical centers after risk adjustment. Conclusions These data suggest that a stroke belt does not exist within the Veterans Affairs health care system in terms of either post-admission mortality or inpatient care quality. C1 [Jia, Huanguang; Castro, Jaime; Vogel, W. Bruce] US Dept Vet Affairs, North Florida South Georgia Vet Hlth Syst, Rehabil Outcomes Res Ctr, Gainesville, FL 32608 USA. [Phipps, Michael] Yale Univ, Robert Wood Johnson Fdn, Sch Med, Clin Scholars Program, New Haven, CT USA. [Phipps, Michael] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. [Phipps, Michael] VA Connecticut Healthcare Syst, West Haven, CT USA. [Bravata, Dawn; Myers, Jennifer; Williams, Linda; Chumbler, Neale] Vet Affairs VA Hlth Serv Res & Dev HSR&D, Ctr Excellence Implementing Evidence Based Practi, Indianapolis, IN USA. [Bravata, Dawn; Myers, Jennifer; Williams, Linda; Chumbler, Neale] VA HSR&D Stroke Qual Enhancement Res Initiat Stro, Indianapolis, IN USA. [Bravata, Dawn; Williams, Linda; Chumbler, Neale] Regenstrief Inst Hlth Care, Indianapolis, IN USA. [Li, Xinli] VA Natl Surg Off, Denver, CO USA. [Ordin, Diana] US Dept Vet Affairs, Vet Hlth Adm, Off Analyt & Business Intelligence, Washington, DC USA. [Williams, Linda] Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN 46202 USA. [Chumbler, Neale] Indiana Univ Purdue Univ, Indiana Univ Sch Liberal Arts, Dept Sociol, Indianapolis, IN 46202 USA. RP Jia, HG (reprint author), US Dept Vet Affairs, North Florida South Georgia Vet Hlth Syst, Rehabil Outcomes Res Ctr, 1601 SW Archer Rd, Gainesville, FL 32608 USA. EM huanguang.jia@va.gov FU Department of Veterans Affairs Health Services Research and Development (VA HSR D Grant) [RRP 09-184] FX This research was supported through the Department of Veterans Affairs Health Services Research and Development (VA HSR& D Grant RRP 09-184). The views and opinions expressed in this manuscript reflect those of the authors and do not necessarily reflect those of the Department of Veterans Affairs. NR 24 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD JAN PY 2015 VL 10 IS 1 BP 67 EP 72 DI 10.1111/j.1747-4949.2012.00861.x PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW3AA UT WOS:000346156500020 PM 22974516 ER PT J AU Campbell, SN Zhang, C Monte, L Roe, AD Rice, KC Tache, Y Masliah, E Rissman, RA AF Campbell, Shannon N. Zhang, Cheng Monte, Louise Roe, Allyson D. Rice, Kenner C. Tache, Yvette Masliah, Eliezer Rissman, Robert A. TI Increased Tau Phosphorylation and Aggregation in the Hippocampus of Mice Overexpressing Corticotropin-Releasing Factor SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; corticotropin-releasing factor (CRF); corticotropin-releasing factor receptor (CRFR); electron microscopy; hippocampus; immunohistochemistry; stress; tau phosphorylation (tau-P); western blot ID COLD-WATER STRESS; ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; TRANSGENIC MICE; CRF RECEPTORS; MOUSE-BRAIN; MICROTUBULE-BINDING; PROTEIN-TAU; FETAL-TAU; HYPERPHOSPHORYLATION AB Clinical and basic science research suggests that stress and/or changes in central stress signaling intermediates may be involved in Alzheimer's disease (AD) pathogenesis. Although the links between stress and AD remain unsettled, data from our group and others have established that stress exposure in rodents may confer susceptibility to AD pathology by inducing hippocampal tau phosphorylation (tau-P). Work in our laboratory has shown that stress-induced tau-P requires activation of the type-1 corticotropin-releasing factor receptor (CRFR1). CRF overexpressing (CRF-OE) mice are a model of chronic stress that display cognitive impairment at 9-10 month of age. In this study we used 6-7 month old CRF-OE mice to examine whether sustained exposure to CRF and stress steroids would impact hippocampal tau-P and kinase activity in the presence or absence of the CRFR1-specific antagonist, R121919, given daily for 30 days. CRF-OE mice had significantly elevated tau-P compared to wild type (WT) mice at the AT8 (S-202/T-204), PHF-1 (S-396/404), S-262, and S-422 sites. Treating CRF-OE mice with R121919 blocked phosphorylation at the AT8 (S-202/T-204) and PHF-1 (S-396/404) sites, but not at the S-262 and S-422 sites and reduced phosphorylation of c-Jun N Terminal Kinase (JNK). Examination of hippocampal extracts from CRF-OE mice at the ultrastructural level revealed negatively stained round/globular aggregates that were positively labeled by PHF-1. These data suggest critical roles for CRF and CRFR1 in tau-P and aggregation and may have implications for the development of AD cognitive decline. C1 [Campbell, Shannon N.; Zhang, Cheng; Monte, Louise; Roe, Allyson D.; Masliah, Eliezer; Rissman, Robert A.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Masliah, Eliezer] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. [Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Branch, NIH, Bethesda, MD USA. [Tache, Yvette] NIAAA, Chem Biol Res Branch, NIH, Bethesda, MD USA. [Tache, Yvette] Univ Calif Los Angeles, Dept Med, Ctr Neurobiol Stress & Womens Hlth, Los Angeles, CA 90024 USA. [Tache, Yvette] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. [Tache, Yvette] Univ Calif Los Angeles, Ctr Neurobiol Stress, Div Digest Dis, Los Angeles, CA 90024 USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Rissman, RA (reprint author), UCSD, Sch Med, Dept Neurosci, 9500 Gilman Dr,MTF 314 M-C 0624, La Jolla, CA 92037 USA. EM rrissman@ucsd.edu FU NIA [AG032755]; Alzheimer's Art Quilt Initiative (AAQI); Alzheimer's Association; Shiley-Marcos Alzheimer's Disease Research Center at UCSD [AG005131]; Intramural Research Programs of the National Institute on Drug Abuse; National Institute on Alcohol Abuse and Alcoholism; Veteran Administration FX This work was supported by grants to RAR from NIA AG032755, the Alzheimer's Art Quilt Initiative (AAQI), the Alzheimer's Association and the Shiley-Marcos Alzheimer's Disease Research Center at UCSD (AG005131). The authors thank Drs. P. E. Sawchenko (Salk Inst) and L. Wang (UCLA) for helpful discussions. We also thank Dr. P. Davies for antibody PHF-1. A portion of this work was supported by the Intramural Research Programs of the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism. YT is in receipt of the senior Career Scientist Award from Veteran Administration. NR 67 TC 8 Z9 8 U1 0 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2015 VL 43 IS 3 BP 967 EP 976 DI 10.3233/JAD-141281 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AU8PG UT WOS:000345858000024 PM 25125464 ER PT J AU Scheff, SW Price, DA Ansari, MA Roberts, KN Schmitt, FA Ikonomovic, MD Mufson, EJ AF Scheff, Stephen W. Price, Douglas A. Ansari, Mubeen A. Roberts, Kelly N. Schmitt, Frederick A. Ikonomovic, Milos D. Mufson, Elliott J. TI Synaptic Change in the Posterior Cingulate Gyrus in the Progression of Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; dementia; memory; mild cognitive impairment; synapses ID MILD COGNITIVE IMPAIRMENT; MITOCHONDRIAL CASCADE HYPOTHESIS; POSITRON-EMISSION-TOMOGRAPHY; AMYLOID-BETA-PEPTIDE; OXIDATIVE STRESS; A-BETA; ELDERLY SUBJECTS; NEUROPATHOLOGIC ASSESSMENT; ASSOCIATION GUIDELINES; PRESYNAPTIC PROTEINS AB Mild cognitive impairment (MCI) is considered to be an early stage in the progression of Alzheimer's disease (AD) providing an opportunity to investigate brain pathogenesis prior to the onset of dementia. Neuroimaging studies have identified the posterior cingulate gyrus (PostC) as a cortical region affected early in the onset of AD. This association cortex is involved in a variety of different cognitive tasks and is intimately connected with the hippocampal/entorhinal cortex region, a component of the medial temporal memory circuit that displays early AD pathology. We quantified the total number of synapses in lamina 3 of the PostC using unbiased stereology coupled with electron microscopy from short postmortem autopsy tissue harvested from cases at different stage of AD progression. Individuals in the early stages of AD showed a significant decline in synaptic numbers compared to individuals with no cognitive impairment (NCI). Subjects with MCI exhibited synaptic numbers that were between the AD and NCI cohorts. Adjacent tissue was evaluated for changes in both pre and postsynaptic proteins levels. Individuals with MCI demonstrated a significant loss in presynaptic markers synapsin-1 and synaptophysin and postsynaptic markers PSD-95 and SAP-97. Levels of [H-3]PiB binding was significantly increased in MCI and AD and correlated strongly with levels of synaptic proteins. All synaptic markers showed a significant association with Mini-Mental Status Examination scores. These results support the idea that the PostC synaptic function is affected during the prodromal stage of the disease and may underlie some of the early clinical sequelae associated with AD. C1 [Scheff, Stephen W.; Price, Douglas A.; Ansari, Mubeen A.; Roberts, Kelly N.; Schmitt, Frederick A.] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Mufson, Elliott J.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. RP Scheff, SW (reprint author), Univ Kentucky, Ctr Aging, 101 Sanders Brown, Lexington, KY 40536 USA. EM sscheff@email.uky.edu FU National Institute of Health [AG028383, PO1AG014449, AG027219, AG042475, AG025204, AG043375]; Mansbach Chair in Alzheimer's Disease FX This work was supported by the National Institute of Health grants: AG028383, PO1AG014449, AG027219, AG042475, AG025204, and AG043375, and the Mansbach Chair in Alzheimer's Disease. We are indebted to the altruism of the participants in the Sanders-Brown Center on Aging and the Religious Orders Study (P30AG10161). NR 140 TC 20 Z9 20 U1 1 U2 7 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2015 VL 43 IS 3 BP 1073 EP 1090 DI 10.3233/JAD-141518 PG 18 WC Neurosciences SC Neurosciences & Neurology GA AU8PG UT WOS:000345858000032 PM 25147118 ER PT J AU Solimeo, SL Ono, SS Lampman, MAM Paez, MBW Stewart, GL AF Solimeo, Samantha L. Ono, Sarah S. Lampman, Michelle A. M. Paez, Monica B. W. Stewart, Gregory L. TI The empowerment paradox as a central challenge to patient centered medical home implementation in the veteran's health administration SO JOURNAL OF INTERPROFESSIONAL CARE LA English DT Article DE Health and social care; interprofessional collaboration; mixed methods; patient centered practice; professional identity; team-based care ID PRIMARY-CARE; INTERPROFESSIONAL EDUCATION; ROLE-CONFLICT; ROLE STRESS; TEAMS; WORK; ANTECEDENTS; ENGAGEMENT; AMBIGUITY; BURNOUT AB In this paper we present results of a mixed methods study conducted to identify barriers to team function among staff implementing patient aligned care teams - the Department of Veterans Affairs' patient centered medical home (PCMH) model. Using a convergent mixed methods design, we administered a standardized survey measure (Team and Individual Role Perception Survey) to assess work role challenge and engagement; and conducted discussion groups to gather context pertaining to role change. We found that the role of primary care providers is highly challenging and did not become less difficult over the initial year of implementation. Unexpectedly over the course of the first year nurse care managers reported a decrease in their perceptions of empowerment and clerical associates reported less skill variety. Qualitative data suggest that more skilled team members fail to delegate and share tasks within their teams. We characterize this interprofessional knowledge factor as an empowerment paradox where team members find it difficult to share tasks in ways that are counter to traditionally structured hierarchical roles. Health care systems seeking to implement PCMH should dedicate resources to facilitating within-team role knowledge and negotiation. C1 [Solimeo, Samantha L.; Ono, Sarah S.; Lampman, Michelle A. M.; Paez, Monica B. W.; Stewart, Gregory L.] US Dept Vet Affairs, VISN Patient Aligned Care Team Demonstrat Lab 23, Iowa City, IA USA. [Solimeo, Samantha L.; Ono, Sarah S.; Paez, Monica B. W.] US Dept Vet Affairs, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City, IA USA. [Ono, Sarah S.] US Dept Vet Affairs, Off Rural Hlth Cent Reg, Iowa City, IA USA. [Stewart, Gregory L.] Univ Iowa, Henry B Tippie Coll Business, Iowa City, IA USA. RP Solimeo, SL (reprint author), Iowa City VA Hlth Care Syst, Dept Vet Affairs, VISN Patient Aligned Care Team Demonstrat Lab 23, 601 Highway 6 West, Iowa City, IA 52246 USA. EM Samantha.Solimeo@va.gov FU VISN 23 Patient Aligned Care Team Demonstration Lab - VA Office of Patient Care Services; Center for Comprehensive Access & Delivery Research and Evaluation - VA Health Services Research and Development Service FX The authors report no declarations of interest. The authors arc responsible for the writing and content of this paper. This study was supported by the VISN 23 Patient Aligned Care Team Demonstration Lab, funded by the VA Office of Patient Care Services. Additional support was provided by the Center for Comprehensive Access & Delivery Research and Evaluation, funded by the VA Health Services Research and Development Service. None of these sponsors had any role in the study design, methods, analyses, or interpretation or in the preparation of the manuscript and the decision to submit it 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 United States government. NR 35 TC 5 Z9 5 U1 0 U2 17 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1356-1820 EI 1469-9567 J9 J INTERPROF CARE JI J. Interprofessional Care PD JAN PY 2015 VL 29 IS 1 BP 26 EP 33 DI 10.3109/13561820.2014.937480 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AW1WU UT WOS:000346080000006 PM 25052920 ER PT J AU Stein, BD Gordon, AJ Dick, AW Burns, RM Pacula, RL Farmer, CM Leslie, DL Sorbero, M AF Stein, Bradley D. Gordon, Adam J. Dick, Andrew W. Burns, Rachel M. Pacula, Rosalie Liccardo Farmer, Carrie M. Leslie, Douglas L. Sorbero, Mark TI Supply of buprenorphine waivered physicians: The influence of state policies SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE Opioid use disorder; Buprenorphine; Medication assisted treatment; Medicaid; State policy ID OFFICE-BASED TREATMENT; OPIOID ADDICTION TREATMENT; 1ST 3 YEARS; METHADONE-MAINTENANCE; COST-EFFECTIVENESS; HEROIN DEPENDENCE; OPIATE ADDICTION; RANDOMIZED-TRIAL; UNITED-STATES; CARE AB Buprenorphine, an effective opioid use disorder treatment, can be prescribed only by buprenorphine-waivered physicians. We calculated the number of buprenorphine-waivered physicians/100,000 county residents using 2008-11 Buprenorphine Waiver Notification System data, and used multivariate regression models to predict number of buprenorphine-waivered physicians/100,000 residents in a county as a function of county characteristics, state policies and efforts to promote buprenorphine use. In 2011, 43% of US counties had no buprenorphine-waivered physicians and 7% had 20 or more waivered physicians. Medicaid funding, opioid overdose deaths, and specific state guidance for office-based buprenorphine use were associated with more buprenorphine-waivered physicians, while encouraging methadone programs to promote buprenorphine use had no impact. Our findings provide important empirical information to individuals seeking to identify effective approaches to increase the number of physicians able to prescribe buprenorphine. (C) 2014 Elsevier Inc. All rights reserved. C1 [Stein, Bradley D.; Dick, Andrew W.; Burns, Rachel M.; Pacula, Rosalie Liccardo; Farmer, Carrie M.; Sorbero, Mark] RAND Corp, Pittsburgh, PA 15219 USA. [Stein, Bradley D.; Gordon, Adam J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15261 USA. [Leslie, Douglas L.] Penn State Coll Med, Hershey, PA 17033 USA. RP Stein, BD (reprint author), RAND Corp, 4570 Fifth Ave, Pittsburgh, PA 15219 USA. EM stein@rand.org FU NIDA NIH HHS [R01DA032881-01A1, R01 DA032881] NR 77 TC 19 Z9 19 U1 5 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD JAN PY 2015 VL 48 IS 1 SI SI BP 104 EP 111 DI 10.1016/j.jsat.2014.07.010 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA AW3ZL UT WOS:000346221400016 PM 25218919 ER PT J AU Rosell, DR Zaluda, LC McClure, MM Perez-Rodriguez, MM Strike, KS Barch, DM Harvey, PD Girgis, RR Hazlett, EA Mailman, RB Abi-Dargham, A Lieberman, JA Siever, LJ AF Rosell, Daniel R. Zaluda, Lauren C. McClure, Margaret M. Perez-Rodriguez, M. Mercedes Strike, K. Sloan Barch, Deanna M. Harvey, Philip D. Girgis, Ragy R. Hazlett, Erin A. Mailman, Richard B. Abi-Dargham, Anissa Lieberman, Jeffrey A. Siever, Larry J. TI Effects of the D-1 Dopamine Receptor Agonist Dihydrexidine (DAR-0100A) on Working Memory in Schizotypal Personality Disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID FUNCTIONAL SELECTIVITY; SCHIZOPHRENIA SPECTRUM; NEUROPSYCHOLOGICAL PERFORMANCE; COGNITIVE PERFORMANCE; HIGH-POTENCY; D1; EFFICACY; AMPHETAMINE; RATS; SPECIFICITY AB Pharmacological enhancement of prefrontal D-1 dopamine receptor function remains a promising therapeutic approach to ameliorate schizophrenia-spectrum working memory deficits, but has yet to be rigorously evaluated clinically. This proof-of-principle study sought to determine whether the active enantiomer of the selective and full D-1 receptor agonist dihydrexidine (DAR-0100A) could attenuate working memory impairments in unmedicated patients with schizotypal personality disorder (SPD). We performed a randomized, double-blind, placebo-controlled trial of DAR-0100A (15 mg/150 ml of normal saline administered intravenously over 30 min) in medication-free patients with SPD (n = 16) who met the criteria for cognitive impairment (ie, scoring below the 25th percentile on tests of working memory). We employed two measures of verbal working memory that are salient to schizophrenia-spectrum cognitive deficits, and that clinical data implicate as being associated with prefrontal D-1 availability: (1) the Paced Auditory Serial Addition Test (PASAT); and (2) the N-back test (ratio of 2-back: 0-back scores). Study procedures occurred over four consecutive days, with working memory testing on Days 1 and 4, and DAR-0100A/placebo administration on Days 2-4. Treatment with DAR-0100A was associated with significantly improved PASAT performance relative to placebo, with a very large effect size (Cohen's d = 1.14). Performance on the N-back ratio was also significantly improved; however, this effect rested on both a non-significant enhancement and diminution of 2-back and 0-back performance, respectively; therefore interpretation of this finding is more complicated. DAR-0100A was generally well tolerated, with no serious medical or psychiatric adverse events; common side effects were mild to moderate and transient, consisting mainly of sedation, lightheadedness, tachycardia, and hypotension; however, we were able to minimize these effects, without altering the dose, with supportive measures, eg, co-administered normal saline. Although preliminary, these findings lend further clinical support to the potential of D-1 receptor agonists to treat schizophrenia-spectrum working memory impairments. These data suggest a need for further studies with larger group sizes, serum DAR-0100A levels, and a more comprehensive neuropsychological battery. C1 [Rosell, Daniel R.; Zaluda, Lauren C.; McClure, Margaret M.; Perez-Rodriguez, M. Mercedes; Strike, K. Sloan; Hazlett, Erin A.; Siever, Larry J.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Rosell, Daniel R.] James J Peters VA Med Ctr, Dept Outpatient Psychiat, Bronx, NY USA. [Zaluda, Lauren C.; McClure, Margaret M.; Perez-Rodriguez, M. Mercedes; Strike, K. Sloan; Hazlett, Erin A.; Siever, Larry J.] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr MIRECC VISN 3, Bronx, NY USA. [Barch, Deanna M.] Washington Univ, Dept Psychol, St Louis, MO 63130 USA. [Harvey, Philip D.] Univ Miami, Miller Sch Med, Dept Psychiat, Miami, FL 33136 USA. [Harvey, Philip D.] Bruce W Carter VA Med Ctr, Res Serv, Miami, FL USA. [Girgis, Ragy R.; Abi-Dargham, Anissa; Lieberman, Jeffrey A.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Girgis, Ragy R.; Abi-Dargham, Anissa; Lieberman, Jeffrey A.] Columbia Univ, Dept Psychiat, Med Ctr, New York, NY USA. [Mailman, Richard B.] Penn State Univ, Dept Pharmacol, Coll Med, Hershey, PA USA. RP Siever, LJ (reprint author), Vet Affairs Med Ctr, James J Peters Dept, 130 West Kingsbridge Rd,Room 6A-44, Bronx, NY 10468 USA. EM larry.siever@va.gov RI Perez Rodriguez, Maria/B-9410-2013; Girgis, Ragy/N-3271-2016 OI Perez Rodriguez, Maria/0000-0001-5137-1993; Mailman, Richard/0000-0003-1353-2738 FU Veterans Affairs VISN3 Mental Illness Research, Education, and Clinical Center; Department of Veterans Affairs Office of Academic Affiliations Psychiatric Research/Neurosciences Advanced Fellowship; National Center for Research Resources (NCRR) [MO1-RR-00071]; National Institutes of Health (NIH) FX We thank Drs Luis Ripoll and Amir Garakani for medical assistance; Dr Katherine Burdick for statistical consultation; and Nabila Hoque for technical assistance. This work was supported by the Veterans Affairs VISN3 Mental Illness Research, Education, and Clinical Center. Writing of this manuscript was supported by The Department of Veterans Affairs Office of Academic Affiliations Psychiatric Research/Neurosciences Advanced Fellowship. This publication was made possible by Grant Number MO1-RR-00071 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). NR 48 TC 10 Z9 11 U1 1 U2 5 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 JAN PY 2015 VL 40 IS 2 BP 446 EP 453 DI 10.1038/npp.2014.192 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AW2WQ UT WOS:000346147800021 PM 25074637 ER PT J AU Patterson, BJ Solimeo, SL Stewart, KR Rosenthal, GE Kaboli, PJ Lund, BC AF Patterson, Brandon J. Solimeo, Samantha L. Stewart, Kenda R. Rosenthal, Gary E. Kaboli, Peter J. Lund, Brian C. TI Perceptions of pharmacists' integration into patient-centered medical home teams SO RESEARCH IN SOCIAL & ADMINISTRATIVE PHARMACY LA English DT Article DE Patient-centered medical home; Pharmacy services; Veteran affairs; Health care teams ID HEALTH-CARE TEAM; THERAPY MANAGEMENT; PHYSICIANS PERCEPTIONS; COMMUNITY PHARMACISTS; GENERAL-PRACTITIONERS; CLINICAL PHARMACISTS; QUALITATIVE-ANALYSIS; FAMILY-PRACTICE; SERVICES; EXPECTATIONS AB Background: Patient-centered medical homes (PCMHs) are a newer paradigm of health care service delivery. Team-based care that includes pharmacists has been implemented in several countries. Subsequently studies have successfully identified challenges and barriers with team-based care. Research on pharmacists' integration into PCMH is warranted to help bridge knowledge from earlier studies exploring team-based care. In 2010, the Department of Veteran Affairs (VA) began a national PCMH implementation, operationalized as "Patient-Aligned Care Teams" (PACTs). The VA's national PACT implementation presents an opportunity to describe other persistent barriers to effective coordination between primary care and pharmacy providers. Objective: To identify perceived barriers and facilitators to pharmacist integration into VA PACTs from the perspective of non-pharmacist team members. Methods: Semi-structured interviews were conducted as part of a formative evaluation of PCMH implementation. Participants were from VA medical centers and community-based outpatient clinics in the Midwestern United States and included physicians, nurses, associated health care professionals, and health system administrators. Results: In working toward pharmacy service integration, role clarity and work activities were influenced by team member attitudes toward and previous experiences with pharmacists. Interviewees reported that coordination with pharmacists was hindered if communication placed extra burdens on other team members. Interviewees reported collaboration was easier when pharmacists were onsite, but that technology helped facilitate off-site access to pharmacy services. Finally, some team members characterized pharmacist integration as essential while others failed to integrate pharmacists at all. Conclusion: Non-pharmacist members of PACT teams reported some reluctance in pharmacists' integration. They attributed this reluctance to knowledge deficits, limited participation in PACT training by pharmacists, an imbalance in effort expended for pharmacists' integration, and coordination or communication challenges. While there may be unique opportunities for pharmacists to improve patient care through participation in PCMHs, work remains to improve other health professionals' knowledge of and attitudes toward pharmacists' roles on health care teams. (C) 2015 Elsevier Inc. All rights reserved. C1 [Patterson, Brandon J.] Univ Sci, Philadelphia Coll Pharm, Philadelphia, PA 19104 USA. [Solimeo, Samantha L.; Stewart, Kenda R.; Rosenthal, Gary E.] US Dept Vet Affairs, VISN Patient Aligned Care Team 23, Demonstrat Lab, Iowa City, VA USA. [Stewart, Kenda R.; Rosenthal, Gary E.; Kaboli, Peter J.; Lund, Brian C.] US Dept Vet Affairs, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City, VA USA. [Solimeo, Samantha L.; Stewart, Kenda R.; Kaboli, Peter J.; Lund, Brian C.] US Dept Vet Affairs, Vet Rural Hlth Resource Ctr Cent Reg, Iowa City, IA 52246 USA. [Rosenthal, Gary E.; Kaboli, Peter J.] Univ Iowa, Coll Med, Iowa City, IA 52242 USA. [Rosenthal, Gary E.; Lund, Brian C.] Univ Iowa, Coll Publ Hlth, Iowa City, IA 52242 USA. RP Lund, BC (reprint author), Iowa City Vet Affairs Hlth Care Syst, Mailstop 152,601 Hwy 6 W, Iowa City, IA 52246 USA. EM brian.lund@va.gov NR 62 TC 7 Z9 7 U1 6 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7411 EI 1934-8150 J9 RES SOC ADMIN PHARM JI Res. Soc. Adm. Pharm. PD JAN-FEB PY 2015 VL 11 IS 1 BP 85 EP 95 DI 10.1016/j.sapharm.2014.05.005 PG 11 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AW1MB UT WOS:000346052400008 PM 24954185 ER PT J AU Kotova, S Wong, RM Cameron, RB AF Kotova, Svetlana Wong, Raymond M. Cameron, Robert B. TI New and emerging therapeutic options for malignant pleural mesothelioma: review of early clinical trials SO CANCER MANAGEMENT AND RESEARCH LA English DT Review DE MPM; new targeted; systemic; local therapies AB Malignant pleural mesothelioma (MPM) is a rare tumor that is challenging to control. Despite some benefit from using the multimodality-approach (surgery, combination chemotherapy and radiation), survival remains poor. However, current research produced a list of potential therapies. Here, we summarize significant new preclinical and early clinical developments in treatment of MPM, which include mesothelin specific antibody and toxin therapies, interleukin-4 (IL-4) receptor toxins, dendritic cell vaccines, immune checkpoint inhibitors, and gene-based therapies. In addition, several local modalities such as photodynamic therapy, postoperative lavage using betadine, and cryotherapy for local recurrence, have also shown to be effective for local control of disease. C1 [Kotova, Svetlana; Wong, Raymond M.; Cameron, Robert B.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Thorac Surg, Los Angeles, CA USA. [Kotova, Svetlana; Wong, Raymond M.; Cameron, Robert B.] Univ Calif Los Angeles, Div Thorac Surg, Los Angeles, CA USA. [Kotova, Svetlana; Wong, Raymond M.; Cameron, Robert B.] Comprehens Mesothelioma Program, Los Angeles, CA USA. [Wong, Raymond M.] Pacific Heart Lung & Blood Inst, Pacific Meso Ctr, Los Angeles, CA USA. RP Cameron, RB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Thorac Surg, Ctr Hlth Sci, 10833 Le Conte Ave,Room 64-128,POB 957313, Los Angeles, CA 90095 USA. EM skotova@mednet.ucla.edu; rcameron@mednet.ucla.edu NR 100 TC 10 Z9 10 U1 0 U2 4 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1179-1322 J9 CANCER MANAG RES JI Cancer Manag. Res. PY 2015 VL 7 BP 51 EP 63 DI 10.2147/CMAR.S72814 PG 13 WC Oncology SC Oncology GA V46LK UT WOS:000209885500006 PM 25670913 ER PT J AU Guizzetti, M Zhang, X Goeke, C Gavin, DP AF Guizzetti, Marina Zhang, Xiaolu Goeke, Calla Gavin, David P. TI Gila and neurodevelopment. focus on fetal alcohol spectrum disorders (vol 2, 123, 2014) SO FRONTIERS IN PEDIATRICS LA English DT Correction DE fetal alcohol spectrum disorders; glia; astrocytes; microglia; oligodendrocytes C1 [Guizzetti, Marina; Zhang, Xiaolu; Goeke, Calla; Gavin, David P.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Guizzetti, Marina; Zhang, Xiaolu; Goeke, Calla; Gavin, David P.] US Dept Vet Affairs, Jesse Brown VA Med Ctr, Chicago, IL USA. [Guizzetti, Marina] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. RP Guizzetti, M (reprint author), Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. EM guizzett@ohsu.edu FU National Institute of Alcoholism and Alcohol Abuse, Department of Veterans Affairs [AA021876, 101BX001819, IK2BX001650] FX This study was supported in part by grant AA021876 from the National Institute of Alcoholism and Alcohol Abuse, Department of Veterans Affairs Merit Review Awards #101BX001819 (MG) and Career Development Award (CDA-2) #IK2BX001650 (DG). The authors are extremely grateful to Mr. Jeff Frkonja for the graphic design of Figures 1, 3, and 4. NR 1 TC 0 Z9 0 U1 0 U2 0 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 2296-2360 J9 FRONT PEDIATR JI Front. Pediatr. PY 2015 VL 3 AR 27 DI 10.3389/fped.2015.00027 PG 1 WC Pediatrics SC Pediatrics GA V46PZ UT WOS:000209897400025 PM 25954735 ER PT J AU Valencia, CA Husami, A Holle, J Johnson, JA Qian, YP Mathur, A Wei, C Indugula, SR Zou, FG Meng, HY Wang, LJ Li, X Fisher, R Tan, T Begtrup, AH Collins, K Wusik, KA Neilson, D Burrow, T Schorry, E Hopkin, R Keddache, M Harley, JB Kaufman, KM Zhang, KJ AF Valencia, C. Alexander Husami, Ammar Holle, Jennifer Johnson, Judith A. Qian, Yaping Mathur, Abhinav Wei, Chao Indugula, Subba Rao Zou, Fanggeng Meng, Haiying Wang, Lijun Li, Xia Fisher, Rachel Tan, Tony Begtrup, Amber Hogart Collins, Kathleen Wusik, Katie A. Neilson, Derek Burrow, Thomas Schorry, Elizabeth Hopkin, Robert Keddache, Mehdi Harley, John Barker Kaufman, Kenneth M. Zhang, Kejian TI Clinical impact and cost-effectiveness of whole exome sequencing as a diagnostic tool: a pediatric center's experience SO FRONTIERS IN PEDIATRICS LA English DT Article DE whole exome sequencing; next generation sequencing; diagnosis; children; clinical utility; pediatrics AB Background: There are limited reports of the use of whole exome sequencing (WES) as a clinical diagnostic tool. Moreover, there are no reports addressing the cost burden associated with genetic tests performed prior to WES. Objective: We demonstrate the performance characteristics of WES in a pediatric setting by describing our patient cohort, calculating the diagnostic yield, and detailing the patients for whom clinical management was altered. Moreover, we examined the potential cost-effectiveness of WES by examining the cost burden of diagnostic workups. Methods: To determine the clinical utility of our hospital's clinical WES, we performed a retrospective review of the first 40 cases. We utilized dual bioinformatics analyses pipelines based on commercially available software and in-house tools. Results: Of the first 40 clinical cases, we identified genetic defects in 12 (30%) patients, of which 47% of the mutations were previously unreported in the literature. Among the 12 patients with positive findings, seven have autosomal dominant disease and five have autosomal recessive disease. Ninety percent of the cohort opted to receive secondary findings and of those, secondary medical actionable results were returned in three cases. Among these positive cases, there are a number of novel mutations that are being reported here. The diagnostic workup included a significant number of genetic tests with microarray and single-gene sequencing being the most popular tests. Significantly, genetic diagnosis from WES led to altered patient medical management in positive cases. Conclusion: We demonstrate the clinical utility of WES by establishing the clinical diagnostic rate and its impact on medical management in a large pediatric center. The cost-effectiveness of WES was demonstrated by ending the diagnostic odyssey in positive cases. Also, in some cases it may be most cost-effective to directly perform WES. WES provides a unique glimpse into the complexity of genetic disorders. C1 [Valencia, C. Alexander; Husami, Ammar; Holle, Jennifer; Johnson, Judith A.; Mathur, Abhinav; Wei, Chao; Indugula, Subba Rao; Zou, Fanggeng; Meng, Haiying; Wang, Lijun; Li, Xia; Fisher, Rachel; Tan, Tony; Begtrup, Amber Hogart; Collins, Kathleen; Wusik, Katie A.; Neilson, Derek; Burrow, Thomas; Schorry, Elizabeth; Hopkin, Robert; Keddache, Mehdi; Zhang, Kejian] Cincinnati Childrens Hosp Med Ctr, Div Human Genet, 3333 Burnet Ave,MLC7016, Cincinnati, OH 45229 USA. [Valencia, C. Alexander; Husami, Ammar; Holle, Jennifer; Johnson, Judith A.; Mathur, Abhinav; Wei, Chao; Indugula, Subba Rao; Zou, Fanggeng; Meng, Haiying; Wang, Lijun; Li, Xia; Fisher, Rachel; Tan, Tony; Begtrup, Amber Hogart; Collins, Kathleen; Wusik, Katie A.; Neilson, Derek; Burrow, Thomas; Schorry, Elizabeth; Hopkin, Robert; Keddache, Mehdi; Harley, John Barker; Kaufman, Kenneth M.; Zhang, Kejian] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA. [Qian, Yaping] Myriad Genet Labs Inc, Salt Lake City, UT USA. [Harley, John Barker; Kaufman, Kenneth M.] Cincinnati Childrens Hosp Med Ctr, CAGE, Cincinnati, OH 45229 USA. [Harley, John Barker; Kaufman, Kenneth M.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. RP Valencia, CA (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Human Genet, 3333 Burnet Ave,MLC7016, Cincinnati, OH 45229 USA. EM alexander.valencia@cchmc.org FU National Human Genome Research Institute [U01 HG006828] FX JH and KK are partially supported by the National Human Genome Research Institute (U01 HG006828). NR 55 TC 12 Z9 12 U1 1 U2 1 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 2296-2360 J9 FRONT PEDIATR JI Front. Pediatr. PY 2015 VL 3 AR 67 DI 10.3389/fped.2015.00067 PG 15 WC Pediatrics SC Pediatrics GA V46PZ UT WOS:000209897400065 PM 26284228 ER PT J AU Baughman, E Tan, Y Ahmed, J Chatterjee, S Jackson, GR Ambegaokar, SS AF Baughman, E. Tan, Y. Ahmed, J. Chatterjee, S. Jackson, G. R. Ambegaokar, S. S. TI Negative feedback between miR-7 and its host gene hnRNP K/bancal by competitve binding to target mRNA, chico (insulin receptor substrate): implications for ERK, GSK-3beta and tau neurotoxicity SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Baughman, E.; Tan, Y.; Ahmed, J.; Ambegaokar, S. S.] Ohio Wesleyan Univ, Bot Microbiol, Delaware, OH 43015 USA. [Chatterjee, S.] Univ Texas Med Branch, Neurol, Galveston, TX 77555 USA. [Jackson, G. R.] DeBakey VA Med Ctr, Neurol, Houston, TX USA. [Jackson, G. R.] Baylor Coll Med, Neurol, Houston, TX 77030 USA. [Ambegaokar, S. S.] Ohio Wesleyan Univ, Neurosci, Delaware, OH 43015 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1341 PG 1 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500527 ER PT J AU Saez, JC Cisterna, B Vargas, AA Cardozo, C AF Saez, J. C. Cisterna, B. Vargas, A. A. Cardozo, C. TI Acetylcholine prevents the expression of connexin hemichannels in denervated skeletal myofibers SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Saez, J. C.; Cisterna, B.; Vargas, A. A.] Pontificia Univ Catolica Chile, Dept Fisiol, Santiago, Chile. [Saez, J. C.; Cisterna, B.; Vargas, A. A.] Univ Valparaiso, Ctr Interdisciplinario Neurociencias Valparaiso, Milenio 4Inst, Valparaiso, Chile. [Cardozo, C.] James J Peters Vet Affairs Med Ctr, Excellence Med Consequences Spinal Cord 2Ctr, Bronx, NY USA. [Cardozo, C.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Cardozo, C.] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P2212 PG 2 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600477 ER PT B AU Yang, EY Nambi, V AF Yang, Eric Y. Nambi, Vijay BE Wong, ND Amsterdam, EA Blumenthal, RS TI Role of Carotid Intima-Media Thickness Assessment in Preventative Cardiology SO ASPC MANUAL OF PREVENTIVE CARDIOLOGY LA English DT Article; Book Chapter ID CORONARY-HEART-DISEASE; SERVICES TASK-FORCE; ATHEROSCLEROSIS RISK; CARDIOVASCULAR-DISEASE; WALL THICKNESS; 3-DIMENSIONAL ULTRASOUND; VASCULAR MEDICINE; AMERICAN SOCIETY; ARTERY-DISEASE; PLAQUE C1 [Yang, Eric Y.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Nambi, Vijay] Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr,Sect Cardio, Ctr Cardiovasc Prevent,Methodist DeBakey Heart &, Houston, TX 77030 USA. RP Yang, EY (reprint author), Baylor Coll Med, Dept Med, Houston, TX 77030 USA. NR 46 TC 0 Z9 0 U1 0 U2 1 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-86-4 PY 2015 BP 118 EP 129 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BB5RG UT WOS:000344034500014 ER PT J AU Hsiao, JJ Lu, PH Grill, JD Teng, E AF Hsiao, Julia J. Lu, Po H. Grill, Joshua D. Teng, Edmond TI Longitudinal Declines in Instrumental Activities of Daily Living in Stable and Progressive Mild Cognitive Impairment SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Mild cognitive impairment; Dementia; Diagnosis; Activities of daily living; Functional abilities; Assessment measures ID ALZHEIMERS ASSOCIATION WORKGROUPS; VASCULAR RISK-FACTORS; DIAGNOSTIC GUIDELINES; FUNCTIONAL-ACTIVITIES; NATIONAL INSTITUTE; EVERYDAY FUNCTION; SYDNEY MEMORY; OLDER-ADULTS; DISEASE; DEMENTIA AB Background: Previous cross-sectional studies suggest that assessments of instrumental activities of daily living (IADLs) may be useful for operationalizing the differences in functional deficits seen in mild cognitive impairment (MCI) and dementia. However, their utility for longitudinal changes in IADLs in the transition between MCI and dementia remains unclear. Methods: We analyzed longitudinal IADL data with the Functional Activities Questionnaire (FAQ) in stable (MCI-S; n = 1,318) or progressive (MCI-P; n = 1,108) MCI patients. Results: Larger increases in FAQ scores were seen in the MCI-P group across a 14.5-month interval, but overlapping distributions in the two groups yielded poorer discriminatory power than prior cross-sectional reports. Conclusion: Our findings emphasize the difficulties in operationalizing the criterion of 'essentially intact' IADLs in MCI, which may complicate the interpretation of disease progression in MCI treatment trials. (C) 2014 S. Karger AG, Basel C1 [Hsiao, Julia J.; Lu, Po H.; Grill, Joshua D.; Teng, Edmond] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Hsiao, Julia J.; Teng, Edmond] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Teng, E (reprint author), West Los Angeles VA Healthcare Ctr, Neurobehav Serv, 116AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM eteng@ucla.edu FU National Institute on Aging (NIA, AFAR, the John A. Haratford Foundation, the Atlantic Philanthropies, the Starr Foundation) [P50 AG16570, K23 AG028727, K08 AG34628]; Alzheimer's Disease Research Centers of California; Sidell-Kagan Foundation; NIA [U01 AG016976] FX Support from the National Institute on Aging [P50 AG16570, K23 AG028727 to P.H.L. and K08 AG34628 to E.T. (jointly sponsored by NIA, AFAR, the John A. Haratford Foundation, the Atlantic Philanthropies, the Starr Foundation, and an anonymous donor)], the Alzheimer's Disease Research Centers of California, and the Sidell-Kagan Foundation is acknowledged. The NACC database is funded by NIA (U01 AG016976). NR 50 TC 1 Z9 1 U1 1 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 EI 1421-9824 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2015 VL 39 IS 1-2 BP 12 EP 24 DI 10.1159/000365587 PG 13 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA AU5LZ UT WOS:000345649800002 PM 25300404 ER PT J AU Schultz, HY Dutz, JP Furukawa, F Goodfield, MJ Kuhn, A Lee, LA Nyberg, F Szepietowski, JC Sontheimer, RD Werth, VP AF Schultz, Heather Y. Dutz, Jan P. Furukawa, Fukumi Goodfield, Mark J. Kuhn, Annegret Lee, Lela A. Nyberg, Filippa Szepietowski, Jacek C. Sontheimer, Richard D. Werth, Victoria P. TI From Pathogenesis, Epidemiology, and Genetics to Definitions, Diagnosis, and Treatments of Cutaneous Lupus Erythematosus and Dermatomyositis: A Report from the 3rd International Conference on Cutaneous Lupus Erythematosus (ICCLE) 2013 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID QUALITY-OF-LIFE; REGENERATING MUSCLE; EUROPEAN-SOCIETY; CONTROLLED-TRIAL; MURINE MODEL; POLYMYOSITIS; MULTICENTER; EXPRESSION; HYDROXYCHLOROQUINE; ASSOCIATION C1 [Dutz, Jan P.] Univ British Columbia, Dept Dermatol & Skin Sci, Vancouver, BC V5Z 1M9, Canada. [Furukawa, Fukumi] Wakayama Med Univ, Dept Dermatol, Wakayama, Japan. [Goodfield, Mark J.] Leeds Gen Infirm, Dept Dermatol, Leeds, W Yorkshire, England. [Kuhn, Annegret] Univ Munster, Dept Dermatol, D-48149 Munster, Germany. [Lee, Lela A.] Univ Colorado, Dept Dermatol, Denver, CO 80202 USA. [Nyberg, Filippa] Danderyd Hosp, Karolinska Inst, Stockholm, Sweden. [Szepietowski, Jacek C.] Med Univ, Dept Dermatol Venereol & Allergol, Wroclaw, Poland. [Sontheimer, Richard D.] Univ Utah, Dept Dermatol, Salt Lake City, UT USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Werth, Victoria P.] Univ Penn, Sch Med, Philadelphia, PA 19104 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 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 We thank Sean Wood for great secretarial assistance and Advancing Innovation in Dermatology, Biogen, Celgene, Genzyme, Pfizer, Rigel, and Stiefel for supporting this meeting. Funds were used in part to support the work of HYS who summarized the meeting and wrote the initial draft of this communication. Support was also provided by 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. NR 36 TC 4 Z9 5 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2015 VL 135 IS 1 BP 7 EP 12 DI 10.1038/jid.2014.316 PG 6 WC Dermatology SC Dermatology GA AW4AX UT WOS:000346225000002 PM 25501376 ER PT J AU Agarwala, A Jones, P Nambi, V AF Agarwala, Anandita Jones, Peter Nambi, Vijay TI The Role of Antisense Oligonucleotide Therapy in Patients with Familial Hypercholesterolemia: Risks, Benefits, and Management Recommendations SO CURRENT ATHEROSCLEROSIS REPORTS LA English DT Article DE Familial hypercholesterolemia; LDL cholesterol; ASO; Antisense oligonucleotide therapy; Mipomersen ID DENSITY-LIPOPROTEIN CHOLESTEROL; ASSOCIATION EXPERT PANEL; PLACEBO-CONTROLLED TRIAL; CORONARY-HEART-DISEASE; B SYNTHESIS INHIBITION; APOLIPOPROTEIN-B; ANDROGEN RECEPTOR; LDL CHOLESTEROL; PROSTATE-CANCER; MIPOMERSEN AB Antisense oligonucleotide therapy is a promising approach for the treatment of a broad variety of medical conditions. It functions at the cellular level by interfering with RNA function, often leading to degradation of specifically targeted abnormal gene products implicated in the disease process. Mipomersen is a novel antisense oligonucleotide directed at apolipoprotein (apoB)-100, the primary apolipoprotein associated with low-density lipoprotein cholesterol (LDL-C), which has recently been approved for the treatment of familial hypercholesterolemia. A number of clinical studies have demonstrated its efficacy in lowering LDL-C and apoB levels in patients with elevated LDL-C despite maximal medical therapy using conventional lipid-lowering agents. This review outlines the risks and benefits of therapy and provides recommendations on the use of mipomersen. C1 [Agarwala, Anandita] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. [Jones, Peter; Nambi, Vijay] Baylor Coll Med, Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Dept Med, Houston, TX 77030 USA. RP Nambi, V (reprint author), Baylor Coll Med, Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Dept Med, 6565 Fannin St,STE B 160, Houston, TX 77030 USA. EM anandita.kulkarni@bcm.edu; jones@bcm.edu; vnambi@bcm.edu FU Sanofi; Gillson Longenbaugh Foundation; Gulf Coast Regional Foundation; Methodist Hospital Research institute; NIH/ NHLBI K23 FX Vijay Nambi has a provisional patent on the use of biomarkers in heart failure with Roche; research collaboration with GE; received personal fees from Sanofi for serving on the regional advisory board; received grants from Gillson Longenbaugh Foundation, Gulf Coast Regional Foundation, Methodist Hospital Research institute, and NIH/ NHLBI K23; national monitor for Anthera and research collaboration with Tomtec. NR 45 TC 5 Z9 5 U1 0 U2 5 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1523-3804 EI 1534-6242 J9 CURR ATHEROSCLER REP JI Curr. Atheroscleros. Rep. PD JAN PY 2015 VL 17 IS 1 AR 467 DI 10.1007/s11883-014-0467-4 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AU0NZ UT WOS:000345321300003 PM 25398643 ER PT J AU Hanson, AJ Craft, S Banks, WA AF Hanson, Angela J. Craft, Suzanne Banks, William A. TI The APOE Genotype: Modification of Therapeutic Responses in Alzheimer's Disease SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Alzheimer's disease; treatments; APOE genotype ID APOLIPOPROTEIN-E GENOTYPE; MILD COGNITIVE IMPAIRMENT; AMYLOID-BETA; INTRANASAL INSULIN; LOWERING TREATMENT; EPSILON-4 ALLELE; OLDER-ADULTS; DOUBLE-BLIND; VITAMIN-E; DEMENTIA AB The translation of promising preclinical treatments into effective drugs for Alzheimer's disease (AD) has been challenging. One of the most potent risk factors for sporadic AD is carrier status of the epsilon 4 allele of the apolipoprotein E gene (E4). E4 carriers show a differential response to several therapies which are being investigated as AD treatments, including acetylcholinesterase inhibitors and therapeutics with vascular and metabolic targets. The differential treatment responses of E4 carriers may partially explain why some treatments show a null effect in clinical trials. Understanding the reasons behind these responses is not only important for clinical practice, but may also help us elucidate mechanisms for this neurodegenerative disease. C1 [Hanson, Angela J.; Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Hanson, Angela J.; Banks, William A.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Craft, Suzanne] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. RP Hanson, AJ (reprint author), 325 9th Ave,Box 359755, Seattle, WA 98104 USA. EM hansonaj@uw.edu NR 73 TC 7 Z9 7 U1 4 U2 19 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2015 VL 21 IS 1 BP 114 EP 120 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AU2GM UT WOS:000345434600011 PM 25330331 ER PT J AU Wang, X Lopez, OL Sweet, RA Becker, JT DeKosky, ST Barmada, MM Demirci, FY Kamboh, MI AF Wang, Xingbin Lopez, Oscar L. Sweet, Robert A. Becker, James T. DeKosky, Steven T. Barmada, Mahmud M. Demirci, F. Yesim Kamboh, M. Ilyas TI Genetic Determinants of Disease Progression in Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease progression; genome-wide association studies; late-onset Alzheimer's disease; Mini-Mental State Examination ID GENOME-WIDE ASSOCIATION; SYNDROME TYPE-I; IDENTIFIES VARIANTS; COMMON VARIANTS; BRAIN ATROPHY; PAX3; POPULATION; MUTATIONS; CD2AP; EPHA1 AB There is a strong genetic basis for late-onset Alzheimer's disease (LOAD); thus far 22 genes/loci have been identified that affect the risk of LOAD. However, the relationships among the genetic variations at these loci and clinical progression of the disease have not been fully explored. In the present study, we examined the relationships of 22 known LOAD genes to the progression of AD in 680 AD patients recruited from the University of Pittsburgh Alzheimer's Disease Research Center. Patients were classified as "rapid progressors" if the Mini-Mental State Examination (MMSE) changed >= 3 points in 12 months and "slow progressors" if the MMSE changed <= 2 points. We also performed a genome-wide association study in this cohort in an effort to identify new loci for AD progression. Association analysis between single nucleotide polymorphisms (SNPs) and the progression status of the AD cases was performed using logistic regression model controlled for age, gender, dementia medication use, psychosis, and hypertension. While no significant association was observed with either APOE*4 (p = 0.94) or APOE*2 (p = 0.33) with AD progression, we found multiple nominally significant associations (p < 0.05) either within or adjacent to seven known LOAD genes (INPP5D, MEF2C, TREM2, EPHA1, PTK2B, FERMT2, and CASS4) that harbor both risk and protective SNPs. Genome-wide association analyses identified four suggestive loci (PAX3, CCRN4L, PIGQ, and ADAM19) at p < 1E-05. Our data suggest that short-term clinical disease progression in AD has a genetic basis. Better understanding of these genetic factors could help to improve clinical trial design and potentially affect the development of disease modifying therapies. C1 [Wang, Xingbin; Barmada, Mahmud M.; Demirci, F. Yesim; Kamboh, M. Ilyas] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15261 USA. [Wang, Xingbin] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Lopez, Oscar L.; Sweet, Robert A.; Becker, James T.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15261 USA. [Lopez, Oscar L.; Sweet, Robert A.; Becker, James T.; Kamboh, M. Ilyas] Univ Pittsburgh, Alzheimers Dis Res Ctr, Pittsburgh, PA 15261 USA. [Sweet, Robert A.; Kamboh, M. Ilyas] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15261 USA. [DeKosky, Steven T.] Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA USA. RP Kamboh, MI (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. EM kamboh@pitt.edu OI Demirci, F. Yesim/0000-0001-6907-9843; Kamboh, M. Ilyas/0000-0002-3453-1438; Barmada, M Michael/0000-0002-3604-6460 FU National Institutes of Health [AG030653, AG041718, AG005133, AG027224] FX This study was supported by the National Institutes of Health grants AG030653, AG041718, AG005133, and AG027224. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs, the National Institutes of Health, or the United States Government. NR 37 TC 11 Z9 12 U1 1 U2 10 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2015 VL 43 IS 2 BP 649 EP 655 DI 10.3233/JAD-140729 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AU2NM UT WOS:000345455300027 PM 25114068 ER PT J AU Park, LG Howie-Esquivel, J Dracup, K AF Park, Linda G. Howie-Esquivel, Jill Dracup, Kathleen TI Electronic Measurement of Medication Adherence SO WESTERN JOURNAL OF NURSING RESEARCH LA English DT Article DE medication; medication adherence; measurement; electronic monitoring device ID DIABETES PATIENTS; DRUG ADHERENCE; THERAPY; DISEASE; DEVICE; TRIAL; INTERVENTIONS; PREVENTION; MANAGEMENT; CORONARY AB The measurement of medication adherence is important in both clinical practice and research settings to offer effective medical therapy, improve clinical outcomes, and determine the efficacy of therapy. The aims of this article are to (a) present an overview of current and developing electronic methods of medication measurement, (b) explore the advantages and disadvantages to each approach, and (c) discuss the implications of using electronic monitoring devices for clinical practice and research. A comprehensive review of electronic forms of medication measurement was performed. A description of each method is presented including oral medication monitors, personal electronic devices, electronic blisters, wirelessly observed therapy, inhaled medication monitors, mobile phones, video/photo-assisted observation, and electronic health records. Familiarity with using electronic devices and advances in technology will continue to develop and influence the measurement of medication adherence. C1 [Park, Linda G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Park, Linda G.; Howie-Esquivel, Jill; Dracup, Kathleen] Univ Calif San Francisco, San Francisco, CA 94121 USA. RP Park, LG (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Div Geriatr, 4150 Clement St 181G, San Francisco, CA 94121 USA. EM linda.park@ucsf.edu RI Emchi, Karma/Q-1952-2016 NR 47 TC 4 Z9 4 U1 2 U2 14 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0193-9459 EI 1552-8456 J9 WESTERN J NURS RES JI West. J. Nurs. Res. PD JAN PY 2015 VL 37 IS 1 BP 28 EP 49 DI 10.1177/0193945914524492 PG 22 WC Nursing SC Nursing GA AU4NU UT WOS:000345589200003 PM 24577868 ER PT J AU Paintlia, MK Singh, I Singh, AK AF Paintlia, Manjeet K. Singh, Inderjit Singh, Avtar K. TI Effect of Vitamin D3 Intake on the Onset of Disease in a Murine Model of Human Krabbe Disease SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE Krabbe disease; twitcher mouse; demyelinating disease; oligodendrocyte; psychosine ID GLOBOID-CELL LEUKODYSTROPHY; BONE-MARROW-TRANSPLANTATION; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL NERVOUS-SYSTEM; TANDEM MASS-SPECTROMETRY; TWITCHER MOUSE; MULTIPLE-SCLEROSIS; 1,25-DIHYDROXYVITAMIN D-3; GENE-THERAPY; OXIDATIVE STRESS AB Low vitamin D level is a risk factor for various late-onset CNS demyelinating disorders. We investigated whether vitamin D deficiency influences disease in twitcher mice (GALC(twi/twi); twi), a murine model of Krabbe disease (KD), an inherited disorder caused by galactocerebrosidase (GALC) deficiency that leads to psychosine accumulation, oligodendrocyte (OL) loss, and CNS demyelination. We found that the in situ 1,25-dihydroxyvitamin D3 level was reduced, with a parallel increase in the expression of inflammatory cytokines and vitamin D-catabolizing enzymes in the brains of KD and twi mice compared with age-matched controls. Pups maintained on milk from lactating heterozygous (GALC(twi/+)) mothers that were fed a vitamin D3-supplemented diet until weaning and then fed a vitamin D3-supplemented diet demonstrated delayed body weight loss and development of disease in twi mice. This delayed the onset of tremors and locomotor disabilities that eventually impacted the life span of twi mice (502 days). Accordingly, the expression of antioxidant enzymes was increased with delayed psychosine accumulation, lipid peroxidation, and inflammatory response that eventually protected CNS myelin and axonal integrity in twi mice. In vitro studies revealed that 1,25-dihydroxyvitamin D3 enhances antioxidant defenses in OLs deficient for GALC or incubated with psychosine. Together these data provide the first evidence that vitamin D deficiency affects disease development in twi mice and that vitamin D3 supplementation has the potential to improve the efficacy of KD therapeutics. (c) 2014 Wiley Periodicals, Inc. C1 [Paintlia, Manjeet K.; Singh, Inderjit; Singh, Avtar K.] Med Univ S Carolina, Dept Pediat, Darby Childrens Res Inst, Charleston, SC 29425 USA. [Singh, Avtar K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Singh, Avtar K.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Singh, AK (reprint author), Med Univ S Carolina, Dept Pediat, 173 Ashley Ave, Charleston, SC 29425 USA. EM singhi@musc.edu FU National Institutes of Health [NS064195, NS072511] FX Contract grant sponsor: National Institutes of Health; Contract grant number: NS064195; Contract grant number: NS072511. NR 69 TC 4 Z9 4 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0360-4012 EI 1097-4547 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JAN PY 2015 VL 93 IS 1 BP 28 EP 42 DI 10.1002/jnr.23476 PG 15 WC Neurosciences SC Neurosciences & Neurology GA AU0IR UT WOS:000345307200003 PM 25236689 ER PT J AU Martin, JT Collins, CM Ikuta, K Mauck, RL Elliott, DM Zhang, Y Anderson, DG Vaccaro, AR Albert, TJ Arlet, V Smith, HE AF Martin, John T. Collins, Christopher M. Ikuta, Kensuke Mauck, Robert L. Elliott, Dawn M. Zhang, Yeija Anderson, D. Greg Vaccaro, Alexander R. Albert, Todd J. Arlet, Vincent Smith, Harvey E. TI Population Average T2 MRI Maps Reveal Quantitative Regional Transformations in the Degenerating Rabbit Intervertebral Disc That Vary by Lumbar Level SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE intervertebral disc; degeneration; rabbit; MRI; T2 mapping ID LOW-BACK-PAIN; RELAXATION-TIMES; NEEDLE PUNCTURE; ANIMAL-MODEL; CARTILAGE; SPINE; INJURY; AGE; REPAIR; MOUSE AB Magnetic resonance imaging (MRI) with T2-weighting is routinely performed to assess intervertebral disc degeneration. Standard clinical evaluations of MR images are qualitative, however, and do not focus on region-specific alterations in the disc. Utilizing a rabbit needle puncture model, T2 mapping was performed on injured discs to develop a quantitative description of the degenerative process following puncture. To do so, an 18G needle was inserted into four discs per rabbit (L3/L4 to L6/L7) and T2 maps were generated pre- and 4 weeks post-injury. Individual T2 maps were normalized to a disc-specific coordinate system and then averaged for pre- and post-injury population composite T2 maps. We also developed a method to automatically segment the nucleus pulposus by fitting the NP region of the T2 maps with modified 2-D and 3-D Gaussian distribution functions. Puncture injury produced alterations in MR signal intensity in a region-specific manner mirroring human degeneration. Population average T2 maps provided a quantitative representation of the injury response, and identified deviations of individual degenerate discs from the pre-injury population. We found that the response to standardized injury was modest at lower lumbar levels, likely as a result of increased disc dimensions. These tools will be valuable for the quantitative characterization of disc degeneration in future clinical and pre-clinical studies. (c) 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:140-148, 2015. C1 [Martin, John T.; Ikuta, Kensuke; Mauck, Robert L.; Zhang, Yeija; Smith, Harvey E.] Philadelphia VA Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA. [Martin, John T.; Ikuta, Kensuke; Mauck, Robert L.; Zhang, Yeija; Arlet, Vincent; Smith, Harvey E.] Univ Penn, Dept Orthopaed Surg, Philadelphia, PA 19104 USA. [Martin, John T.; Mauck, Robert L.] Univ Penn, Dept Mech Engn & Appl Mech, Philadelphia, PA 19104 USA. [Collins, Christopher M.] NYU, Dept Radiol, New York, NY 10016 USA. [Mauck, Robert L.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. [Elliott, Dawn M.] Univ Delaware, Dept Biomed Engn, Newark, DE USA. [Vaccaro, Alexander R.] Univ Penn, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. [Anderson, D. Greg; Vaccaro, Alexander R.; Albert, Todd J.] Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. RP Smith, HE (reprint author), Philadelphia VA Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA. EM harvey.smith@uphs.upenn.edu FU NIAMS NIH HHS [P30 AR050950]; NIBIB NIH HHS [P41 EB017183, R01 EB000454]; NICHD NIH HHS [K08 HD049598, 5K08HD049598]; RRD VA [IK2 RX001476] NR 49 TC 4 Z9 4 U1 7 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 EI 1554-527X J9 J ORTHOP RES JI J. Orthop. Res. PD JAN PY 2015 VL 33 IS 1 BP 140 EP 148 DI 10.1002/jor.22737 PG 9 WC Orthopedics SC Orthopedics GA AU0WT UT WOS:000345343600019 PM 25273831 ER PT J AU Radwan, FFY Hossain, A God, JM Leaphart, N Elvington, M Nagarkatti, M Tomlinson, S Haque, A AF Radwan, Faisal F. Y. Hossain, Azim God, Jason M. Leaphart, Nathan Elvington, Michelle Nagarkatti, Mitzi Tomlinson, Stephen Haque, Azizul TI Reduction of Myeloid-Derived Suppressor Cells and Lymphoma Growth by a Natural Triterpenoid SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE TRITERPENOID; LYMPHOMA; MITOCHONDRIA; CASPASES; APOPTOSIS; T CELLS; HLA CLASS II PROTEINS; MYELOID-DERIVED SUPPRESSOR CELLS; STAT3 ID II ANTIGEN PRESENTATION; BREAST-CANCER CELLS; LYSOSOMAL THIOL REDUCTASE; BH3-ONLY PROTEIN BIM; GANODERMA-LUCIDUM; ANTITUMOR IMMUNITY; SIGNALING PATHWAY; RECOGNITION; APOPTOSIS; ACID AB Lymphoma is a potentially life threatening disease. The goal of this study was to investigate the therapeutic potential of a natural triterpenoid, Ganoderic acid A (GA-A) in controlling lymphoma growth both in vitro and in vivo. Here, we show that GA-A treatment induces caspase-dependent apoptotic cell death characterized by a dose-dependent increase in active caspases 9 and 3, up-regulation of pro-apoptotic BIM and BAX proteins, and a subsequent loss of mitochondrial membrane potential with release of cytochrome c. In addition to GA-A's anti-growth activity, we show that lower doses of GA-A enhance HLA class II-mediated antigen (Ag) presentation and CD4+ T cell recognition of lymphoma cells in vitro. The therapeutic relevance of GA-A treatment was also tested in vivo using the EL4 syngeneic mouse model of metastatic lymphoma. GA-A-treatment significantly prolonged survival of EL4 challenged mice and decreased tumor metastasis to the liver, an outcome accompanied by a marked down-regulation of STAT3 phosphorylation, reduction myeloid-derived suppressor cells (MDSCs), and enhancement of cytotoxic CD8+ T cells in the host. Thus, GA-A not only selectively induces apoptosis in lymphoma cells, but also enhances cell-mediated immune responses by attenuating MDSCs, and elevating Ag presentation and T cell recognition. The demonstrated therapeutic benefit indicates that GA-A is a candidate for future drug design for the treatment of lymphoma. J. Cell. Biochem. 116: 102-114, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Radwan, Faisal F. Y.; Hossain, Azim; God, Jason M.; Leaphart, Nathan; Elvington, Michelle; Tomlinson, Stephen; Haque, Azizul] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Radwan, Faisal F. Y.; Hossain, Azim; God, Jason M.; Leaphart, Nathan; Elvington, Michelle; Tomlinson, Stephen; Haque, Azizul] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Radwan, Faisal F. Y.; Hossain, Azim; God, Jason M.; Leaphart, Nathan; Elvington, Michelle; Tomlinson, Stephen; Haque, Azizul] Med Univ S Carolina, Childrens Res Inst, Charleston, SC 29425 USA. [Nagarkatti, Mitzi] Univ S Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC 29208 USA. [Tomlinson, Stephen] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Haque, A (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, 173 Ashley Ave,BS 208, Charleston, SC 29425 USA. EM haque@musc.edu OI Nagarkatti, Mitzi/0000-0002-5977-5615 FU National Institutes of Health [R01 CA129560, R01 CA129560-S1, R01 CA158179]; Cancer Center Support Grant [P30 CA138313] FX Grant sponsor: National Institutes of Health; Grant numbers: R01 CA129560, R01 CA129560-S1, R01 CA158179; Grant sponsor: Cancer Center Support Grant; Grant number: P30 CA138313. NR 59 TC 7 Z9 8 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-2312 EI 1097-4644 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN PY 2015 VL 116 IS 1 BP 102 EP 114 DI 10.1002/jcb.24946 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AT2YB UT WOS:000344799200011 PM 25142864 ER PT B AU Mulroy, SJ Kautz, SA Sullivan, KJ AF Mulroy, Sara J. Kautz, Steven A. Sullivan, Katherine J. BE Stein, J Harvey, RL Winstein, CJ Zorowitz, RD Wittenberg, GF TI Walking Recovery and Rehabilitation After Stroke SO STROKE RECOVERY AND REHABILITATION, SECOND EDITION LA English DT Article; Book Chapter ID RANDOMIZED CONTROLLED-TRIAL; FUNCTIONAL ELECTRICAL-STIMULATION; WEIGHT-SUPPORTED TREADMILL; CORTICOSPINAL TRACT INTEGRITY; ABNORMAL SYNERGY PATTERNS; PERONEAL NERVE STIMULATOR; IMPROVES MUSCLE STRENGTH; GROUND REACTION FORCES; GAIT FOLLOWING STROKE; POSTSTROKE HEMIPARESIS C1 [Mulroy, Sara J.] Rancho Los Amigos Natl Rehabil Ctr, Pathokinesiol Lab, Downey, CA 90242 USA. [Mulroy, Sara J.] Univ So Calif, Herman Ostrow Sch Dent, Div Biokinesiol & Phys Therapy, Los Angeles, CA USA. [Kautz, Steven A.] Med Univ S Carolina, Coll Hlth Profess, Charleston, SC 29425 USA. [Kautz, Steven A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Sullivan, Katherine J.] MetroHlth Stn Jefferson Pk BTL Hlth Inc, Los Angeles, CA USA. RP Mulroy, SJ (reprint author), Rancho Los Amigos Natl Rehabil Ctr, Pathokinesiol Lab, Downey, CA 90242 USA. NR 165 TC 0 Z9 0 U1 2 U2 8 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-006-8 PY 2015 BP 384 EP 406 PG 23 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BB2VG UT WOS:000342391500024 ER PT B AU Cooper, RA Cooper, R Hill, K Karg, P Karmarkar, A Lane, AK Little, R Pelleschi, TL AF Cooper, Rory A. Cooper, Rosemarie Hill, Katya Karg, Patricia Karmarkar, Amol Lane, Amy Karas Little, Roger Pelleschi, Tamara L. BE Stein, J Harvey, RL Winstein, CJ Zorowitz, RD Wittenberg, GF TI Seating, Assistive Technology, and Equipment SO STROKE RECOVERY AND REHABILITATION, SECOND EDITION LA English DT Article; Book Chapter ID UNILATERAL NEGLECT; WHEELCHAIR; STROKE; LANGUAGE C1 [Cooper, Rory A.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15260 USA. [Cooper, Rory A.; Cooper, Rosemarie; Karg, Patricia; Lane, Amy Karas; Little, Roger] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Hill, Katya] AAC Inst, Pittsburgh, PA USA. [Karmarkar, Amol] Univ Texas Med Branch, Div Rehabil Sci, Galveston, TX 77555 USA. [Pelleschi, Tamara L.] Univ Pittsburgh, Hiram G Andrews Ctr, Johnstown, PA 15902 USA. RP Cooper, RA (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15260 USA. NR 42 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-006-8 PY 2015 BP 623 EP 643 PG 21 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BB2VG UT WOS:000342391500038 ER PT B AU Handler, G Boninger, ML AF Handler, Grace Boninger, Michael L. BE Hammond, FM Malec, JF Nick, TG Buschbacher, RM TI Special Issues in Randomized Controlled Trials SO HANDBOOK FOR CLINICAL RESEARCH: DESIGN, STATISTICS, AND IMPLEMENTATION LA English DT Article; Book Chapter C1 [Handler, Grace] UPMC, UPMC Rehabil Inst, Pittsburgh, PA 15213 USA. [Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Boninger, Michael L.] VA Ctr Excellence Wheelchairs & Related Mobil, VA Pittsburgh Hlth Care Syst, Dept Vet Affairs, Pittsburgh, PA USA. RP Handler, G (reprint author), UPMC, UPMC Rehabil Inst, Pittsburgh, PA 15213 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-54-3 PY 2015 BP 43 EP 45 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BB1YS UT WOS:000341461600012 ER PT J AU Michaels, TM Horan, WP Ginger, EJ Martinovich, Z Pinkham, AE Smith, MJ AF Michaels, Tania M. Horan, William P. Ginger, Emily J. Martinovich, Zoran Pinkham, Amy E. Smith, Matthew J. TI Cognitive empathy contributes to poor social functioning in schizophrenia: Evidence from a new self-report measure of cognitive and affective empathy SO PSYCHIATRY RESEARCH LA English DT Article DE Schizophrenia; Empathy; Social functioning; Social cognition; QCAE ID EMOTION REGULATION; PSYCHOSIS; DEFICITS; METAANALYSIS; NEUROSCIENCE; SUPPRESSION; PERCEPTION; MECHANISMS; ABILITIES; ACCURACY AB Cognitive empathy impairments have been linked to poor social functioning in schizophrenia. However, prior studies primarily used self-reported empathy measures developed decades ago that are not well-aligned with contemporary models of empathy. We evaluated empathy and its relationship to social functioning in schizophrenia using the recently developed Questionnaire of Cognitive and Affective Empathy (QCAE). Schizophrenia (n=52) and healthy comparison (n=37) subjects completed the QCAE, Interpersonal Reactivity Index (IRI), and measures of neurocognition, symptoms, and social functioning. Between-group differences on the QCAE, and relationships between QCAE and IRI subscales, neurocognition, symptoms, and social functioning were examined. The schizophrenia group reported significantly lower cognitive empathy than comparison subjects, which was driven by low online simulation scores. Cognitive empathy explained significant variance in social functioning after accounting for neurocognition and symptoms. Group differences for affective empathy were variable; the schizophrenia group reported similar proximal responsivity, but elevated emotion contagion relative to comparison subjects. These findings bolster support for the presence and functional significance of impaired cognitive empathy in schizophrenia using a contemporary measure of empathy. Emerging evidence that some aspects of affective empathy may be unimpaired or hyper-responsive in schizophrenia and implications for the assessment and treatment of empathy in schizophrenia are discussed. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Michaels, Tania M.; Ginger, Emily J.; Martinovich, Zoran; Smith, Matthew J.] Northwestern Univ, Dept Psychiat & Behav Sci, Feinberg Sch Med, 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.] VA Greater Los Angeles Healthcare Syst, VISN22, MIRECC, Los Angeles, CA USA. [Pinkham, Amy E.] Univ Texas Dallas, Sch Behav & Brain Sci, Richardson, TX 75083 USA. [Smith, Matthew J.] Northwestern Univ, Warren Wright Adolescent Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. RP Smith, MJ (reprint author), Northwestern Univ, Dept Psychiat & Behav Sci, Feinberg Sch Med, Abbott Hall 13th Floor, Chicago, IL 60611 USA. EM matthewsmith@northwestem.edu OI Smith, Matthew/0000-0002-0079-1477 FU Department of Psychiatry and Behavioral Sciences at Northwestern University Feinberg School of Medicine; Warren Wright Adolescent Center at Northwestern Medicine's Stone Institute of Psychiatry FX We would like to acknowledge the research staff at the Northwestern University Schizophrenia Research Group-for study coordination and data collection, and our participants for volunteering their time. This work was funded by the Department of Psychiatry and Behavioral Sciences at Northwestern University Feinberg School of Medicine. Additional support for this study was provided by Warren Wright Adolescent Center at Northwestern Medicine's Stone Institute of Psychiatry. NR 68 TC 11 Z9 11 U1 6 U2 27 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 DEC 30 PY 2014 VL 220 IS 3 BP 803 EP 810 DI 10.1016/j.psychres.2014.08.054 PG 8 WC Psychiatry SC Psychiatry GA AY1OD UT WOS:000347361300011 PM 25632418 ER PT J AU Lindqvist, D Mueller, S Mellon, SH Su, YL Epel, ES Reus, VI Rosser, R Mahan, L Mackin, RS Yang, TT Wolkowitz, OM AF Lindqvist, Daniel Mueller, Susanne Mellon, Synthia H. Su, Yali Epel, Elissa S. Reus, Victor I. Rosser, Rebecca Mahan, Laura Mackin, R. Scott Yang, Tony T. Wolkowitz, Owen M. TI Peripheral antioxidant markers are associated with total hippocampal and CA3/dentate gyrus volume in MDD and healthy controls-preliminary findings SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Oxidative Stress; Glutathione; Vitamin C; Hippocampus; Subfields; Aging ID MAJOR DEPRESSIVE DISORDER; OXIDATIVE STRESS; PSYCHIATRIC-DISORDERS; ALZHEIMERS-DISEASE; ASCORBIC-ACID; GLUTATHIONE; BRAIN; NEURONS; IMPAIRMENT; DEFICIENCY AB Several psychiatric disorders, including major depressive disorder (MDD), are associated with increased blood markers of oxidative stress. The relevance of this to the oxidation-sensitive hippocampus (DC) is unknown. We investigated the relationship between peripheral oxidative stress markers and HC volume in unmedicated individuals with MDD (n = 16) and healthy controls (n = 19). To conserve power, our primary analysis was carried out in the combined group of subjects, and secondary analyses examined each group separately. Oxidative stress markers (oxidized glutathione (GSSG)) and antioxidants (reduced glutathione (GSH), glutathione peroxidase (Gpx), and Vitamin C) were assessed, and a "total net antioxidant score" was calculated. 4-T MRI estimated total HC volume and HC subfield (CA1, CAl-CA2 transition zone, subiculum and CA3/dentate gyms [CA3&DG]) volumes. Across groups, the antioxidant score was significantly and positively correlated with total HC volume and CA3&DG subfield volume (normalized to total intracranial volume), adjusting for age and sex. Similar relationships were observed in each individual group but missed statistical significance, likely due to type II errors, with the exception of a significant correlation between the antioxidant score and CA3&DG volume in the MDD group. These preliminary data are consistent with oxidative stress being associated with smaller total HC and CA3&DG subfield volumes. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Lindqvist, Daniel; Epel, Elissa S.; Reus, Victor I.; Rosser, Rebecca; Mahan, Laura; Mackin, R. Scott; Yang, Tony T.; Wolkowitz, Owen M.] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. [Lindqvist, Daniel] Lund Univ, Dept Clin Sci, Sect Psychiat, SE-22185 Lund, Sweden. [Mueller, Susanne] Univ Calif San Francisco, Sch Med, Dept Radiol, San Francisco, CA 94143 USA. [Mueller, Susanne; Mackin, R. Scott] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. [Mellon, Synthia H.] Univ Calif San Francisco, Sch Med, Dept OB GYN & Reprod Sci, San Francisco, CA 94143 USA. [Su, Yali] Silver Creek Technol, Gilbert, AZ USA. RP Lindqvist, D (reprint author), Lund Univ, Dept Clin Sci, Sect Psychiat, Baravagen 1, SE-22185 Lund, Sweden. EM Daniel.Lindqvist@med.lu.se RI reus, victor/I-7923-2015 OI reus, victor/0000-0002-8193-5697 FU NIMH [RO1 MH083784]; Swedish Society of Medicine [SLS-244821]; Sjobring Foundation; OM Persson Foundation; province of Scania (Sweden) state grants (ALF); National Center for Research Resources; National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI [UL1 RR024131]; O'Shaughnessy Foundation; Tinberg family; [R01-NS31966]; [K08 (MH081065)]; [R01 (0977669)] FX This project was funded by NIMH Grant 1 RO1 MH083784 (co-Pl's: OMW, SHM and ESE), and by donations from the O'Shaughnessy Foundation and the Tinberg family. DL received post-doctoral grants from the Swedish Society of Medicine (SLS-244821), the Sjobring Foundation, the OM Persson Foundation and the province of Scania (Sweden) state grants (ALF).; SM has the following funding: R01-NS31966.; RSM has the following funding: K08 (MH081065) and R01 (0977669).; This project was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1 RR024131. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. NR 39 TC 6 Z9 6 U1 0 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 EI 1872-7506 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD DEC 30 PY 2014 VL 224 IS 3 BP 168 EP 174 DI 10.1016/j.pscychresns.2014.09.002 PG 7 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AU3QG UT WOS:000345527900004 PM 25266915 ER PT J AU Rustgi, AK El-Serag, HB AF Rustgi, Anil K. El-Serag, Hashem B. TI Esophageal Carcinoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID SQUAMOUS-CELL CARCINOMA; GENOME-WIDE ASSOCIATION; HELICOBACTER-PYLORI INFECTION; GASTROESOPHAGEAL-REFLUX DISEASE; NUTRITION INTERVENTION TRIALS; HIGH-RISK POPULATION; BARRETTS-ESOPHAGUS; SUSCEPTIBILITY LOCI; GASTRIC CARDIA; ORAL BISPHOSPHONATES C1 [Rustgi, Anil K.] Univ Penn, Dept Med, Div Gastroenterol, Abramson Canc Ctr,Perelman Sch Med, Philadelphia, PA 19104 USA. [Rustgi, Anil K.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Dept Genet, Philadelphia, PA 19104 USA. [El-Serag, Hashem B.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM hasheme@bcm.edu NR 97 TC 121 Z9 134 U1 9 U2 31 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 25 PY 2014 VL 371 IS 26 BP 2499 EP 2509 DI 10.1056/NEJMra1314530 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AX4RZ UT WOS:000346920300009 PM 25539106 ER PT J AU Dodge, HH Katsumata, Y Zhu, J Mattek, N Bowman, M Gregor, M Wild, K Kaye, JA AF Dodge, Hiroko H. Katsumata, Yuriko Zhu, Jian Mattek, Nora Bowman, Molly Gregor, Mattie Wild, Katherine Kaye, Jeffrey A. TI Characteristics associated with willingness to participate in a randomized controlled behavioral clinical trial using home-based personal computers and a webcam SO TRIALS LA English DT Article DE Sample recruitment selection bias; Volunteer bias; Behavioral randomized controlled trial; PC; Internet; Webcam; Conversation-based social interaction; Cognitive function; Mild cognitive impairment ID OLDER-ADULTS; RECRUITMENT; DEMENTIA; RETENTION; SELECTION; ANXIETY AB Background: Trials aimed at preventing cognitive decline through cognitive stimulation among those with normal cognition or mild cognitive impairment are of significant importance in delaying the onset of dementia and reducing dementia prevalence. One challenge in these prevention trials is sample recruitment bias. Those willing to volunteer for these trials could be socially active, in relatively good health, and have high educational levels and cognitive function. These participants' characteristics could reduce the generalizability of study results and, more importantly, mask trial effects. We developed a randomized controlled trial to examine whether conversation-based cognitive stimulation delivered through personal computers, a webcam and the internet would have a positive effect on cognitive function among older adults with normal cognition or mild cognitive impairment. To examine the selectivity of samples, we conducted a mass mail-in survey distribution among community-dwelling older adults, assessing factors associated with a willingness to participate in the trial. Methods: Two thousand mail-in surveys were distributed to retirement communities in order to collect data on demographics, the nature and frequency of social activities, personal computer use and additional health-related variables, and interest in the prevention study. We also asked for their contact information if they were interested in being contacted as potential participants in the trial. Results: Of 1,102 surveys returned (55.1% response rate), 983 surveys had complete data for all the variables of interest. Among them, 309 showed interest in the study and provided their contact information (operationally defined as the committed with interest group), 74 provided contact information without interest in the study (committed without interest group), 66 showed interest, but provided no contact information (interest only group), and 534 showed no interest and provided no contact information (no interest group). Compared with the no interest group, the committed with interest group were more likely to be personal computer users (odds ratio (OR) = 2.78), physically active (OR = 1.03) and had higher levels of loneliness (OR = 1.16). Conclusion: Increasing potential participants' familiarity with a personal computer and the internet before trial recruitment could increase participation rates and improve the generalizability of future studies of this type. C1 [Dodge, Hiroko H.; Mattek, Nora; Bowman, Molly; Gregor, Mattie; Wild, Katherine; Kaye, Jeffrey A.] Oregon Hlth & Sci Univ, Dept Neurol, Layton Aging & Alzheimers Dis Ctr, Portland, OR 97201 USA. [Dodge, Hiroko H.] Univ Michigan, Dept Neurol, Michigan Alzheimers Dis Ctr, Ann Arbor, MI USA. [Dodge, Hiroko H.; Mattek, Nora; Bowman, Molly; Wild, Katherine; Kaye, Jeffrey A.] Oregon Hlth & Sci Univ, Oregon Ctr Aging & Technol, Portland, OR 97201 USA. [Katsumata, Yuriko] Univ Kentucky, Coll Publ Hlth, Lexington, KY USA. [Zhu, Jian] Univ Michigan, Grad Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Kaye, Jeffrey A.] Portland VA Med Ctr, Portland, OR USA. RP Dodge, HH (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Layton Aging & Alzheimers Dis Ctr, Portland, OR 97201 USA. EM dodgeh@ohsu.edu FU National Institute on Aging [R01AG033581, P30AG008017, P30AG024978, R01AG024059]; National Institutes of Health; US Department of Health and Human Services FX Funding sources: R01AG033581, P30AG008017, P30AG024978, and R01AG024059 from National Institute on Aging, National Institutes of Health, US Department of Health and Human Services. NR 18 TC 3 Z9 3 U1 4 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6215 J9 TRIALS JI Trials PD DEC 23 PY 2014 VL 15 AR 508 DI 10.1186/1745-6215-15-508 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AY9FA UT WOS:000347853900002 PM 25539637 ER PT J AU Gori, M Senni, M Gupta, DK Charytan, DM Kraigher-Krainer, E Pieske, B Claggett, B Shah, AM Santos, ABS Zile, MR Voors, AA McMurray, JJV Packer, M Bransford, T Lefkowitz, M Solomon, SD AF Gori, Mauro Senni, Michele Gupta, Deepak K. Charytan, David M. Kraigher-Krainer, Elisabeth Pieske, Burkert Claggett, Brian Shah, Amil M. Santos, Angela B. S. Zile, Michael R. Voors, Adriaan A. McMurray, John J. V. Packer, Milton Bransford, Toni Lefkowitz, Martin Solomon, Scott D. CA PARAMOUNT Investigators TI Association between renal function and cardiovascular structure and function in heart failure with preserved ejection fraction SO EUROPEAN HEART JOURNAL LA English DT Article DE Heart failure with preserved ejection fraction; Chronic kidney disease; Albuminuria; Glomerular filtration rate; Cardiovascular structure and function ID LEFT-VENTRICULAR HYPERTROPHY; URINARY ALBUMIN EXCRETION; CHRONIC KIDNEY-DISEASE; CARDIAC ABNORMALITIES; HYPERTENSIVE PATIENTS; CYSTATIN-C; PREVALENCE; MORTALITY; DYSFUNCTION; IMPAIRMENT AB Aim Renal dysfunction is a common comorbidity in patients with heart failure and preserved ejection fraction (HFpEF). We sought to determine whether renal dysfunction was associated with measures of cardiovascular structure/function in patients with HFpEF. Methods We studied 217 participants from the PARAMOUNT study with HFpEF who had echocardiography and measures of kidney function. We evaluated the relationships between renal dysfunction [estimated glomerular filtration rate (eGFR)>30 and <60 mL/min/1.73 m(2) and/or albuminuria] and cardiovascular structure/function. Results The mean age of the study population was 71 years, 55% were women, 94% hypertensive, and 40% diabetic. Impairment of at least one parameter of kidney function was present in 62% of patients (16% only albuminuria, 23% only lowe GFR, 23% both). Renal dysfunction was associated with abnormal LV geometry (defined as concentric hypertrophy, or eccentric hypertrophy, or concentric remodelling) (adjusted P = 0.048), lower midwall fractional shortening (MWFS) (P = 0.009), and higherNT-proBNP (P = 0.006). Compared with patients without renal dysfunction, those with lowe GFR and no albuminuria had a higher prevalence of abnormal LV geometry (P = 0.032) and lower MWFS (P< 0.01), as opposed to those with only albuminuria. Conversely, albuminuria alone was associated with greater LV dimensions (P< 0.05). Patients with combined renal impairment had mixed abnormalities (higher LV wall thicknesses, NT-proBNP; lower MWFS). Conclusion Renal dysfunction, as determined by both eGFR and albuminuria, is highly prevalent in HFpEF, and associated with cardiac remodelling and subtle systolic dysfunction. The observed differences in cardiac structure/function between each type of renal damage suggest that both parameters of kidney function might play a distinct role in HFpEF. C1 [Gori, Mauro; Gupta, Deepak K.; Claggett, Brian; Shah, Amil M.; Santos, Angela B. S.; Solomon, Scott D.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02445 USA. [Senni, Michele] Azienda Osped Papa Giovanni XXIII, Cardiovasc Dept, Bergamo, Italy. [Charytan, David M.] Brigham & Womens Hosp, Div Renal, Boston, MA 02445 USA. [Charytan, David M.] Brigham & Womens Hosp, Boston, MA 02445 USA. [Kraigher-Krainer, Elisabeth; Pieske, Burkert] Med Univ Graz, Graz, Austria. [Zile, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Zile, Michael R.] Ralph H Johnson VA Med Ctr, US Dept Vet Affairs, Charleston, SC USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [McMurray, John J. V.] Univ Glasgow, Glasgow, Lanark, Scotland. [Packer, Milton] Univ Texas Southwestern, Dallas, TX USA. [Bransford, Toni; Lefkowitz, Martin] Novartis Pharmaceut, E Hanover, NJ USA. RP Solomon, SD (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02445 USA. EM ssolomon@rics.bwh.harvard.edu OI mcmurray, john/0000-0002-6317-3975 FU NHLBI NIH HHS [T32 HL094301, K08 HL116792] NR 39 TC 14 Z9 18 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD DEC 21 PY 2014 VL 35 IS 48 BP 3442 EP 3451 DI 10.1093/eurheartj/ehu254 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AX9JW UT WOS:000347220200015 PM 24980489 ER PT J AU Jones, A Kainz, D Khan, F Lee, C Carrithers, MD AF Jones, Alexis Kainz, Danielle Khan, Faatima Lee, Cara Carrithers, Michael D. TI Human Macrophage SCN5A Activates an Innate Immune Signaling Pathway for Antiviral Host Defense SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Adenylate Cyclase; Double-stranded RNA (dsRNA); Innate Immunity; Interferon; Sodium Channel ID SODIUM-CHANNEL NAV1.5; EXPRESSION; PROTEIN; RECOGNITION; INFECTION; NUCLEAR; BINDING; SYSTEM; CELLS AB Pattern recognition receptors contain a binding domain for pathogen-associated molecular patterns coupled to a signaling domain that regulates transcription of host immune response genes. Here, a novel mechanism that links pathogen recognition to channel activation and downstream signaling is proposed. We demonstrate that an intracellular sodium channel variant, human macrophage SCN5A, initiates signaling and transcription through a calcium-dependent isoform of adenylate cyclase, ADCY8, and the transcription factor, ATF2. Pharmacological stimulation with a channel agonist or treatment with cytoplasmic poly(I:C), a mimic of viral dsRNA, activates this pathway to regulate expression of SP100-related genes and interferon . Electrophysiological analysis reveals that the SCN5A variant mediates nonselective outward currents and a small, but detectable, inward current. Intracellular poly(I:C) markedly augments an inward voltage-sensitive sodium current and inhibits the outward nonselective current. These results suggest human macrophage SCN5A initiates signaling in an innate immune pathway relevant to antiviral host defense. It is postulated that SCN5A is a novel pathogen sensor and that this pathway represents a channel activation-dependent mechanism of transcriptional regulation. C1 [Jones, Alexis; Kainz, Danielle; Khan, Faatima; Lee, Cara; Carrithers, Michael D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, Madison, WI 53706 USA. [Jones, Alexis; Kainz, Danielle; Khan, Faatima; Lee, Cara; Carrithers, Michael D.] Univ Wisconsin, Sch Med & Publ Hlth, Program Cellular & Mol Pathol, Madison, WI 53706 USA. [Carrithers, Michael D.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Carrithers, MD (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, 1300 Univ Ave,Rm 2679, Madison, WI 53706 USA. EM carrithers@neurology.wisc.edu OI Lee, Cara/0000-0003-0614-9060 FU Department of Veterans Affairs; University of Wisconsin at Madison FX This work was supported by a Merit Award from the Department of Veterans Affairs and the University of Wisconsin at Madison. NR 24 TC 2 Z9 2 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 19 PY 2014 VL 289 IS 51 BP 35326 EP 35340 DI 10.1074/jbc.M114.611962 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AX0RT UT WOS:000346660200024 PM 25368329 ER PT J AU Mariappan, MM Prasad, S D'Silva, K Cedillo, E Sataranatarajan, K Barnes, JL Choudhury, GG Kasinath, BS AF Mariappan, Meenalakshmi M. Prasad, Sanjay D'Silva, Kristin Cedillo, Esteban Sataranatarajan, Kavithalakshmi Barnes, Jeffrey L. Choudhury, Goutam Ghosh Kasinath, Balakuntalam S. TI Activation of Glycogen Synthase Kinase 3 beta Ameliorates Diabetes-induced Kidney Injury SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Cell Signaling; Eukaryotic Translation Initiation; Extracellular Matrix Protein; Glycogen Synthase Kinase 3 (GSK-3); Kidney; Mammalian Target of Rapamycin (mTOR); Type 1 Diabetes; Diabetic Nephropathy; Sodium Nitroprusside; Kidney Hypertrophy ID MESSENGER-RNA TRANSLATION; RENAL EPITHELIAL-CELLS; PROTEIN-SYNTHESIS; HIGH GLUCOSE; HIGH INSULIN; AKT KINASE; PHOSPHORYLATION; NEPHROPATHY; INITIATION; GROWTH AB Increase in protein synthesis contributes to kidney hypertrophy and matrix protein accumulation in diabetes. We have previously shown that high glucose-induced matrix protein synthesis is associated with inactivation of glycogen synthase kinase 3 (GSK3) in renal cells and in the kidneys of diabetic mice. We tested whether activation of GSK3 by sodium nitroprusside (SNP) mitigates kidney injury in diabetes. Studies in kidney-proximal tubular epithelial cells showed that SNP abrogated high glucose-induced laminin increment by stimulating GSK3 and inhibiting Akt, mTORC1, and events in mRNA translation regulated by mTORC1 and ERK. NONOate, an NO donor, also activated GSK3, indicating that NO may mediate SNP stimulation of GSK3. SNP administered for 3 weeks to mice with streptozotocin-induced type 1 diabetes ameliorated kidney hypertrophy, accumulation of matrix proteins, and albuminuria without changing blood glucose levels. Signaling studies showed that diabetes caused inactivation of GSK3 by activation of Src, Pyk2, Akt, and ERK; GSK3 inhibition activated mTORC1 and downstream events in mRNA translation in the kidney cortex. These reactions were abrogated by SNP. We conclude that activation of GSK3 by SNP ameliorates kidney injury induced by diabetes. C1 [Mariappan, Meenalakshmi M.; Prasad, Sanjay; D'Silva, Kristin; Cedillo, Esteban; Sataranatarajan, Kavithalakshmi; Barnes, Jeffrey L.; Choudhury, Goutam Ghosh; Kasinath, Balakuntalam S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78245 USA. [Choudhury, Goutam Ghosh] South Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. [Mariappan, Meenalakshmi M.; Choudhury, Goutam Ghosh; Kasinath, Balakuntalam S.] South Texas Vet Hlth Care Syst, Med Serv, San Antonio, TX 78229 USA. RP Kasinath, BS (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med MC7882, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kasinath@uthscsa.edu FU Veterans Affairs Merit Review Program; National Institutes of Health [DK077295, RC2AG036613, DK050190]; American Diabetes Association; Juvenile Diabetes Research Foundation; Veterans Affairs Merit Review Grant [5I01BX000926]; Veterans Affairs Senior Research Career Scientist Award FX This work was supported, in whole or in part, by the Veterans Affairs Merit Review Program (to B. S. K.), National Institutes of Health Grants DK077295 (to B. S. K.) and RC2AG036613 (to B. S. K.). This work was also supported by the American Diabetes Association (to B. S. K.) and the Juvenile Diabetes Research Foundation (to M. M. M.).; Supported by National Institutes of Health R01 Grant DK050190 and Veterans Affairs Merit Review Grant 5I01BX000926; recipient of a Veterans Affairs Senior Research Career Scientist Award. NR 51 TC 6 Z9 6 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 19 PY 2014 VL 289 IS 51 BP 35363 EP 35375 DI 10.1074/jbc.M114.587840 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AX0RT UT WOS:000346660200027 PM 25339176 ER PT J AU Singh, JA Lewallen, DG AF Singh, Jasvinder A. Lewallen, David G. TI Increasing obesity and comorbidity in patients undergoing primary total hip arthroplasty in the US: A 13-year study of time trends SO BMC MUSCULOSKELETAL DISORDERS LA English DT Article DE Total hip replacement; Time trends; Arthroplasty; Joint replacement; Diagnosis; Obesity; Comorbidity; Osteoarthritis ID TOTAL KNEE ARTHROPLASTY; TOTAL JOINT ARTHROPLASTY; MODIFYING ANTIRHEUMATIC DRUGS; RHEUMATOID-ARTHRITIS; UNITED-STATES; PAIN MEDICATIONS; DEMOGRAPHICS; REPLACEMENT; POPULATION; MORBIDITY AB Background: Few, if any data are available are available regarding the time-trends in characteristics of patients who have undergone primary THA. Our objective was to examine the time-trends in key demographic and clinical characteristics of patients undergoing primary total hip arthroplasty (THA). Methods: We used the data from the Mayo Clinic Total Joint Registry from 1993-2005 to examine the time-trends in demographics (age, body mass index (BMI)), medical (Deyo-Charlson index) and psychological comorbidity (anxiety, depression) and underlying diagnosis of patients undergoing primary THA. Chi-square test and analysis for variance were used. Multivariable-adjusted logistic regression (age, sex, comorbidity-adjusted) compared 1993-95 to other study periods. Odds ratio (OR) and 95% confidence interval (CI) are presented. Results: The primary THA cohort consisted of 6,168 patients with 52% women. In unadjusted analyses, compared to 1993-95, significantly more patients (by > 2-times for most) in 2002-05 had: BMI >= 40, 2.3% vs. 6.3%; depression, 4.1% vs. 9.8%; and anxiety, 3.4% vs. 5.7%; and significantly fewer had an underlying diagnosis of rheumatoid/inflammatory arthritis, 3.7% vs. 1.5% (p <= 0.01 for all). In multivariable-adjusted models, compared to 1993-95, significantly more patients in 2003-05 had (all p-values <= 0.01): BMI >= 40, OR, 2.79 (95% CI: 1.85, 4.22); Deyo-Charlson Index >= 3, 1.32 (1.07, 1.63); depression, 2.25 (1.66, 3.05); and anxiety, 1.71 (1.19, 2.15). Respectively, fewer patients had a diagnosis of RA/inflammatory arthritis: 0.28 (0.17, 0.46; p < 0.01). Over the 13-year study period, Deyo-Charlson index increased by 22% (0.9 to 1.1) and the mean age decreased by 0.7 years (65.0 to 64.3) (p < 0.01 for both). Conclusions: Obesity, medical and psychological comorbidity increased and the underlying diagnosis of RA/inflammatory arthritis decreased rapidly in primary THA patients over 13-years. Our cohort characteristics are similar to previously described characteristics of national U. S. cohort, suggesting that these trends may be national rather than local trends. This is important information for policy makers to take into account for resource allocation. Studies of THA outcomes and utilization should take these rapidly changing patient characteristics into account. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Lewallen, David G.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. EM Jasvinder.md@gmail.com FU Mayo Clinic Orthopedic Surgery research funds; Birmingham VA Medical Center, Alabama, USA; Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) [U19 HS021110]; National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) [P50 AR060772, U34 AR062891]; National Institute of Aging (NIA) [U01 AG018947]; National Cancer Institute (NCI) [U10 CA149950]; Patient Centered Outcomes Research Institute (PCORI) [CE-1304-6631] FX This material is the result of work supported Mayo Clinic Orthopedic Surgery research funds and the resources and use of facilities at the Birmingham VA Medical Center, Alabama, USA. J.A.S. is also supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) U19 HS021110, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) P50 AR060772 and U34 AR062891, National Institute of Aging (NIA) U01 AG018947, and National Cancer Institute (NCI) U10 CA149950, and research contract CE-1304-6631 from the Patient Centered Outcomes Research Institute (PCORI). NR 46 TC 6 Z9 6 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2474 J9 BMC MUSCULOSKEL DIS JI BMC Musculoskelet. Disord. PD DEC 17 PY 2014 VL 15 AR 441 DI 10.1186/1471-2474-15-441 PG 9 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA AZ8JI UT WOS:000348461200001 PM 25519434 ER PT J AU Jin, ZC Wu, C Zhou, XH He, J AF Jin, Zhi-Chao Wu, Cheng Zhou, Xiao-Hua He, Jia TI A modified regression method to test publication bias in meta-analyses with binary outcomes SO BMC MEDICAL RESEARCH METHODOLOGY LA English DT Article DE Meta-analysis; Observational studies; Publication bias; Smoothed variance; Weighted regression ID STATISTICAL TESTS; CLINICAL-RESEARCH; CONTROLLED-TRIALS AB Background: The tendency towards publication bias is greater for observational studies than for randomized clinical trials. Several statistical methods have been developed to test the publication bias. However, almost all existing methods exhibit rather low power or have inappropriate type I error rates. Methods: We propose a modified regression method, which used a smoothed variance to estimate the precision of a study, to test for publication bias in meta-analyses of observational studies. A comprehensive simulation study is carried out, and a real-world example is considered. Results: The simulation results indicate that the performance of tests varies with the number of included studies, level of heterogeneity, event rates, and sample size ratio between two groups. Neither the existing tests nor the newly developed method is particularly powerful in all simulation scenarios. However, our proposed method has a more robust performance across different settings. In the presence of heterogeneity, the arcsine-Thompson test is a suitable alternative, and Peters' test can be considered as a complementary method when mild or no heterogeneity is present. Conclusions: Several factors should be taken into consideration when employing asymmetry tests for publication bias. Based on our simulation results, we provide a concise table to show the appropriate use of regression methods to test for publication bias based on our simulation results. C1 [Jin, Zhi-Chao; Wu, Cheng; He, Jia] Second Mil Med Univ, Dept Hlth Stat, Shanghai 200433, Peoples R China. [Zhou, Xiao-Hua] Vet Affairs Puget Sound Hlth Care Syst, Biostat Unit, HSR&D Ctr Excellence, Seattle, WA 98101 USA. [Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Zhou, XH (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Biostat Unit, HSR&D Ctr Excellence, Seattle, WA 98101 USA. EM azhou@u.washington.edu; hejia63@yahoo.com FU Department of Veterans Affairs, Veterans Health Administration, Health Service Research and Development [RCS 05-196]; National Natural Science Foundation, China [81001287]; key discipline construction of evidence-based public health in Shanghai [12GWZX0602]; Ministry of Science and Technology of China [2009ZX09312-025, 2008ZX09312-007, 2008ZX10002-018]; China Scholarship Council FX This work was supported by Department of Veterans Affairs, Veterans Health Administration, Health Service Research and Development [Research Career Scientist Award RCS 05-196]; National Natural Science Foundation [grant number 81001287], China; the key discipline construction of evidence-based public health in Shanghai [grant number 12GWZX0602]; The Ministry of Science and Technology of China [grant number 2009ZX09312-025, 2008ZX09312-007, 2008ZX10002-018]. We thank China Scholarship Council for sponsoring the first author's visiting in University of Washington. NR 33 TC 2 Z9 2 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2288 J9 BMC MED RES METHODOL JI BMC Med. Res. Methodol. PD DEC 17 PY 2014 VL 14 AR 132 DI 10.1186/1471-2288-14-132 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AZ1IM UT WOS:000347993100001 PM 25516509 ER PT J AU Bekelman, JE Sylwestrzak, G Barron, J Liu, JA Epstein, AJ Freedman, G Malin, J Emanuel, EJ AF Bekelman, Justin E. Sylwestrzak, Gosia Barron, John Liu, Jinan Epstein, Andrew J. Freedman, Gary Malin, Jennifer Emanuel, Ezekiel J. TI Uptake and Costs of Hypofractionated vs Conventional Whole Breast Irradiation After Breast Conserving Surgery in the United States, 2008-2013 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RANDOMIZED-TRIAL; RADIOTHERAPY HYPOFRACTIONATION; UK STANDARDIZATION; RADIATION-THERAPY; CANCER; FRACTIONATION; WOMEN; MASTECTOMY AB IMPORTANCE Based on randomized evidence, expert guidelines in 2011 endorsed shorter, hypofractionated whole breast irradiation (WBI) for selected patients with early-stage breast cancer and permitted hypofractionated WBI for other patients. OBJECTIVES To examine the uptake and costs of hypofractionated WBI among commercially insured patients in the United States. DESIGN, SETTING, AND PARTICIPANTS Retrospective, observational cohort study, using administrative claims data from 14 commercial health care plans covering 7.4% of US adult women in 2013, we classified patients with incident early-stage breast cancer treated with lumpectomy and WBI from 2008 and 2013 into 2 cohorts: (1) the hypofractionation-endorsed cohort (n = 8924) included patients aged 50 years or older without prior chemotherapy or axillary lymph node involvement and (2) the hypofractionation-permitted cohort (n = 6719) included patients younger than 50 years or those with prior chemotherapy or axillary lymph node involvement. EXPOSURES Hypofractionated WBI (3-5 weeks of treatment) vs conventional WBI (5-7 weeks of treatment). MAIN OUTCOMES AND MEASURES Use of hypofractionated and conventional WBI, total and radiotherapy-related health care expenditures, and patient out-of-pocket expenses. Patient and clinical characteristics included year of treatment, age, comorbid disease, prior chemotherapy, axillary lymph node involvement, intensity-modulated radiotherapy, practice setting, and other contextual variables. RESULTS Hypofractionated WBI increased from 10.6% (95% Cl, 8.8%-12.5%) in 2008 to 34.5% (95% Cl, 32.2%-36.8%) in 2013 in the hypofractionation-endorsed cohort and from 8.1% (95% Cl, 6.0%-10.2%) in 2008 to 21.2% (95% Cl, 18.9%-23.6%) in 2013 in the hypofractionation-permitted cohort. Adjusted mean total health care expenditures in the 1 year after diagnosis were $28 747 for hypofractionated and $31 641 for conventional WBI in the hypofractionation-endorsed cohort (difference, $2894; 95% Cl, $1610-$4234; P < .001) and $64 273 for hypofractionated and $72 860 for conventional WBI in the hypofractionation-permitted cohort (difference, $8587; 95% Cl, $5316-$12 017; P < .001). Adjusted mean total 1-year patient out-of-pocket expenses were not significantly different between hypofractionated vs conventional WBlin either cohort. CONCLUSIONS AND RELEVANCE Hypofractionated WBI after breast conserving surgery increased among women with early-stage breast cancer in 14 US commercial health care plans between 2008 and 2013. However, only 34.5% of patients with hypofractionation-endorsed and 21.2% with hypofractionation-permitted early-stage breast cancer received hypofractionated WBI in 2013. C1 [Bekelman, Justin E.; Freedman, Gary] Univ Penn, Perelman Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Bekelman, Justin E.; Emanuel, Ezekiel J.] Univ Penn, Perelman Sch Med, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Bekelman, Justin E.; Epstein, Andrew J.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Sylwestrzak, Gosia; Barron, John; Liu, Jinan] HealthCore, Wilmington, DE USA. [Epstein, Andrew J.] Univ Penn, Div Gen Internal Med, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Epstein, Andrew J.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Malin, Jennifer] WellPoint Inc, Indianapolis, IN USA. RP Bekelman, JE (reprint author), Univ Penn, Perelman Ctr Adv Med, Dept Radiat Oncol, Perelman Sch Med, 3400 Civ Ctr Blvd,4 West, Philadelphia, PA 19104 USA. EM bekelman@uphs.upenn.edu FU National Cancer Institute [K07-CA163616]; WellPoint FX Dr Bekelman received support from grant K07-CA163616 from the National Cancer Institute. WellPoint provided funds to support research at HealthCore, a wholly-owned WellPoint subsidiary. NR 27 TC 40 Z9 40 U1 1 U2 4 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 DEC 17 PY 2014 VL 312 IS 23 BP 2542 EP 2550 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AW5YN UT WOS:000346346900017 PM 25494006 ER PT J AU Cunningham, MA Wirth, JR Freeman, LR Boger, HA Granholm, AC Gilkeson, GS AF Cunningham, Melissa A. Wirth, Jena R. Freeman, Linnea R. Boger, Heather A. Granholm, Ann-Charlotte Gilkeson, Gary S. TI Estrogen receptor alpha deficiency protects against development of cognitive impairment in murine lupus SO JOURNAL OF NEUROINFLAMMATION LA English DT Article DE Estrogen receptor alpha (ERa); Neuropsychiatric lupus (NP-SLE); Microglia ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; RADIAL-ARM MAZE; DENDRITIC CELL-DIFFERENTIATION; MEMORY LOAD INCREASES; MRL-LPR MICE; NEUROPSYCHIATRIC SYNDROMES; OBJECT-RECOGNITION; WORKING-MEMORY; GLUTAMATE-RECEPTOR; DNA ANTIBODIES AB Background: One of the more profound features of systemic lupus erythematosus (SLE) is that females have a 9: 1 prevalence of this disease over males. Up to 80% of SLE patients have cognitive defects or affective disorders. The mechanism of CNS injury responsible for cognitive impairment is unknown. We previously showed that ERa deficiency significantly reduced renal disease and increased survival in lupus-prone mice. We hypothesized that ERa deficiency would be similarly protective in the brain, and that ERa may play a role in modulating blood-brain barrier (BBB) integrity and/or neuroinflammation in lupus-prone mice. Methods: MRL/lpr ERa+/+ and ERaKO mice (n = 46) were ovariectomized, received 17 beta-estradiol pellets, and underwent radial arm water maze (WRAM) and novel object recognition (NOR) testing starting at eight weeks of age. Mice were sacrificed and brains were hemisected and processed for either immunohistochemistry, or hippocampus and parietal cortex dissection for Western blotting. Results: MRL/lpr ERaKO mice (n = 21) performed significantly better in WRAM testing than wild-type MRL/lpr mice (n = 25). There was a significant reduction in reference memory errors (P < 0.007), working memory errors (P < 0.05), and start arm errors (P < 0.02) in ERaKO mice. There were significant differences in NOR testing, particularly total exploration time, with ERa deficiency normalizing behavior. No significant differences were seen in markers of tight junction, astrogliosis, or microgliosis in the hippocampus or cortex by Western blot, however, there was a significant reduction in numbers of Iba1+ activated microglia in the hippocampus of ERaKO mice, as evidenced by immunohistochemietry (IHC). Conclusion: ERa deficiency provides significant protection against cognitive deficits in MRL/lpr mice as early as eight weeks of age. Additionally, the significant reduction in Iba1+ activated microglia in the MRL/lpr ERaKO mice was consistent with reduced inflammation, and may represent a biological mechanism for the cognitive improvement observed. C1 [Cunningham, Melissa A.] Med Univ S Carolina, Dept Neurosci, Div Rheumatol & Immunol, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Vet Affairs Hosp, Charleston, SC 29425 USA. RP Cunningham, MA (reprint author), Med Univ S Carolina, Dept Neurosci, Div Rheumatol & Immunol, 96 Jonathan Lucas St,Suite 814,MSC637, Charleston, SC 29425 USA. EM cunnima@musc.edu OI Wirth, Jena/0000-0001-6094-8336; Cunningham, Melissa/0000-0002-9207-1986 FU Office of Research on Women's Health: Specialized Centers of Research on Sex and Gender Factors Affecting Women's Health (NIH/NIAMS - National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin diseases) [P50 DA016511]; South Carolina Clinical & Translational Research Institute, with an academic home at the Medical University of South Carolina (NIH/NCRR - National Instititutes of Health/National Center for Research Resources) [UL1 RR029880, UL1 RR029882]; VA Medical Research Service merit award [1I01BX000470-01] FX The authors wish to thank Ms Claudia Umphlet and Dr Michael Smith for help with tissue processing. This publication was supported by the Office of Research on Women's Health: Specialized Centers of Research on Sex and Gender Factors Affecting Women's Health (NIH/NIAMS - National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin diseases, grant number: P50 DA016511); The South Carolina Clinical & Translational Research Institute, with an academic home at the Medical University of South Carolina (NIH/NCRR - National Instititutes of Health/National Center for Research Resources, grant numbers: UL1 RR029880 and UL1 RR029882); and a VA Medical Research Service merit award (grant number: 1I01BX000470-01). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or NCRR. NR 76 TC 3 Z9 3 U1 0 U2 9 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 DEC 16 PY 2014 VL 11 AR 171 DI 10.1186/s12974-014-0171-x PG 15 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA CC5ZS UT WOS:000350444700001 PM 25510908 ER PT J AU Backus, LI Belperio, PS Loomis, TP Han, SH Mole, LA AF Backus, Lisa I. Belperio, Pamela S. Loomis, Timothy P. Han, Steven-Huy Mole, Larry A. TI Screening for and Prevalence of Hepatitis B Virus Infection Among High-Risk Veterans Under the Care of the US Department of Veterans Affairs: A Case Report SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID UNITED-STATES C1 [Backus, Lisa I.; Belperio, Pamela S.; Loomis, Timothy P.; Mole, Larry A.] Vet Affairs Palo Alto Hlth Care Syst, Off Publ Hlth Populat Hlth, Palo Alto, CA 94304 USA. [Mole, Larry A.] Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Hlthcare Syst, Los Angeles, CA 90095 USA. [Mole, Larry A.] Univ Calif Los Angeles, David Geffen Sch Med, Pfleger Liver Inst, Los Angeles, CA 90095 USA. RP Backus, LI (reprint author), Vet Affairs Palo Alto Hlth Care Syst, Off Publ Hlth Populat Hlth, Palo Alto, CA 94304 USA. NR 5 TC 1 Z9 1 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 DEC 16 PY 2014 VL 161 IS 12 BP 926 EP 928 DI 10.7326/L14-5036 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AX9UW UT WOS:000347248400046 PM 25506867 ER PT J AU Hsu, A Conell-Price, J Cenzer, IS Eng, C Huang, AJ Rice-Trumble, K Lee, SJ AF Hsu, Amy Conell-Price, Jessamyn Cenzer, Irena Stijacic Eng, Catherine Huang, Alison J. Rice-Trumble, Kathy Lee, Sei J. TI Predictors of urinary incontinence in communityd-welling frail older adults with diabetes mellitus in a cross-sectional study SO BMC GERIATRICS LA English DT Article DE Urinary incontinence; Frail older adults; Diabetes mellitus ID QUALITY-OF-LIFE; NURSING-HOME RESIDENTS; POSTMENOPAUSAL WOMEN; GERIATRIC SYNDROMES; OVERACTIVE BLADDER; UNITED-STATES; HEALTH; RISK; PREVALENCE; CARE AB Background: Diabetes mellitus is a potent risk factor for urinary incontinence. Previous studies of incontinence in patients with diabetes have focused on younger, healthier patients. Our objective was to characterize risk factors for urinary incontinence among frail older adults with diabetes mellitus in a real-world clinical setting. Methods: We performed a cross-sectional analysis on enrollees at On Lok (the original Program for All-Inclusive Care of the Elderly) between October 2004 and December 2010. Enrollees were community-dwelling, nursing home-eligible older adults with diabetes mellitus (N = 447). Our outcome was urinary incontinence measures (n = 2602) assessed every 6 months as "never incontinent", "seldom incontinent" (occurring less than once per week), or "often incontinent" (occurring more than once per week). Urinary incontinence was dichotomized ("never" versus "seldom" and "often" incontinent). We performed multivariate mixed effects logistic regression analysis with demographic (age, gender and ethnicity), geriatric (dependence on others for ambulation or transferring; cognitive impairment), diabetes-related factors (hemoglobin A1c level; use of insulin and other glucose-lowering medications; presence of renal, ophthalmologic, neurological and peripheral vascular complications), depressive symptoms and diuretic use. Results: The majority of participants were 75 years or older (72%), Asian (65%) and female (66%). Demographic factors independently associated with incontinence included older age (OR for age >85, 3.13, 95% CI: 2.15-4.56; Reference: Age <75) and African American or other race (OR 2.12, 95% CI: 1.14-3.93; Reference: Asian). Geriatric factors included: dependence on others for ambulation (OR 1.48, 95% CI: 1.19-1.84) and transferring (OR 2.02, 95% CI: 1.58-2.58) and being cognitively impaired (OR 1.41, 95% CI: 1.15-1.73). Diabetes-related factors associated included use of insulin (OR 2.62, 95% CI: 1.67-4.13) and oral glucose-lowering agents (OR 1.81, 95% CI: 1.33-2.45). Urinary incontinence was not associated with gender, hemoglobin A1c level or depressive symptoms. Conclusions: Geriatric factors such as the inability to ambulate or transfer independently are important predictors of urinary incontinence among frail older adults with diabetes mellitus. Clinicians should address mobility and cognitive impairment as much as diabetes-related factors in their assessment of urinary incontinence in this population. C1 [Hsu, Amy; Cenzer, Irena Stijacic; Lee, Sei J.] San Francisco VA Med Ctr, San Francisco, CA 94122 USA. [Hsu, Amy; Cenzer, Irena Stijacic; Eng, Catherine; Lee, Sei J.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Conell-Price, Jessamyn] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Eng, Catherine; Rice-Trumble, Kathy] On Lok Lifeways, San Francisco, CA USA. [Huang, Alison J.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. RP Hsu, A (reprint author), San Francisco VA Med Ctr, 4150 Clement St,181G, San Francisco, CA 94122 USA. EM Amy.Hsu@ucsf.edu FU Beeson Career Development Award - National Institution on Aging [K23AG040779]; American Federation of Aging Research FX This material is the result of work supported with resources and the use of facilities at the San Francisco VA Medical Center. Dr. Sei Lee's effort was supported by the Beeson Career Development Award (K23AG040779) funded by the National Institution on Aging and the American Federation of Aging Research. NR 36 TC 2 Z9 3 U1 3 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2318 J9 BMC GERIATR JI BMC Geriatr. PD DEC 16 PY 2014 VL 14 AR 137 DI 10.1186/1471-2318-14-137 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AX2AU UT WOS:000346746300001 PM 25514968 ER PT J AU Lamming, DW AF Lamming, Dudley W. TI Diminished mTOR signaling: a common mode of action for endocrine longevity factors SO SPRINGERPLUS LA English DT Review DE Calorie restriction; Rapamycin; Insulin resistance; Longevity ID AMES DWARF MICE; GLUCAGON-LIKE PEPTIDE-1; IMPROVES INSULIN SENSITIVITY; BETA-CELL PROLIFERATION; MAMMALIAN LIFE-SPAN; CALORIC RESTRICTION; DIETARY RESTRICTION; FAT-METABOLISM; EXTENDS LIFE; ALZHEIMERS-DISEASE AB Since the initial observation that a calorie-restricted (CR) diet can extend rodent lifespan, many genetic and pharmaceutical interventions that also extend lifespan in mammals have been discovered. The mechanism by which CR and these other interventions extend lifespan is the subject of significant debate and research. One proposed mechanism is that CR promotes longevity by increasing insulin sensitivity, but recent findings that dissociate longevity and insulin sensitivity cast doubt on this hypothesis. These findings can be reconciled if longevity is promoted not via increased insulin sensitivity, but instead via decreased PI3K/Akt/mTOR pathway signaling. This review presents a unifying hypothesis that explains the lifespan-extending effects of a variety of genetic mutations and pharmaceutical interventions and points towards new molecular pathways which may also be leveraged to promote healthy aging. C1 [Lamming, Dudley W.] Univ Wisconsin, Dept Med, Div Endocrinol, Madison, WI 53706 USA. [Lamming, Dudley W.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Lamming, DW (reprint author), Univ Wisconsin, Dept Med, Div Endocrinol, Madison, WI 53706 USA. EM dlamming@medicine.wisc.edu OI Lamming, Dudley/0000-0002-0079-4467 FU National Institute of Health [AG041765]; UW-Madison School of Medicine and Public Health; UW-Madison Department of Medicine; William S. Middleton Memorial Veterans Hospital FX This review benefited greatly from the advice of D.E. Cohen, and we also thank A.K. Linnemann for helpful suggestions about CCK and E.L. Baar for critical reading of the manuscript. The Lamming lab is supported by a grant from the National Institute of Health (AG041765) and startup funds from the UW-Madison School of Medicine and Public Health and the UW-Madison Department of Medicine. This work was supported using facilities and resources from the William S. Middleton Memorial Veterans Hospital. This work does not represent the views of the Department of Veterans Affairs or the United States Government. NR 112 TC 13 Z9 15 U1 1 U2 4 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 2193-1801 J9 SPRINGERPLUS JI SpringerPlus PD DEC 15 PY 2014 VL 3 AR 735 DI 10.1186/2193-1801-3-735 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO4HY UT WOS:000359123000002 PM 25674466 ER PT J AU Jin, L Datta, PK AF Jin, Lin Datta, Pran K. TI Oncogenic STRAP functions as a novel negative regulator of E-cadherin and p21(Cip1) by modulating the transcription factor Sp1 SO CELL CYCLE LA English DT Article DE STRAP; Sp1; transcription factor; cell cycle; ubiquitination; STRAP; serine threonine kinase receptor-associated protein; Sp1; specificity protein 1; Sp; KLF; specificity protein; Kruppel-like factor; SWI; SNF; SWItch; Sucrose nonfermentable; p300; CBP; p300; CREB-binding protein; TSS; transcription start site; MEF; mouse embryonic fibroblast; HNF4; hepatocyte nuclear factor 4; TSA; trichostatin A; HDAC1; histone deacetylase 1; HDAC2; histone deacetylase 2; HDAC3; histone deacetylase 3; NF-YA; nuclear transcription factor Y subunit alpha; TR I; II; TGF- receptor I; II; RNase; A ribonuclease A; CDK2; cyclin-dependent kinase 2; CDK4; cyclin-dependent kinase 4; PARP; poly (ADP-ribose) polymerase; RhoA; Ras homolog gene family; member A ID GENE-TRANSCRIPTION; CANCER-CELLS; LUNG-CANCER; EXPRESSION; PROTEINS; PROMOTER; BINDING; OVEREXPRESSION; PROGRESSION; INHIBITION AB We have previously reported the identification of a novel WD-domain protein, STRAP that plays a role in maintenance of mesenchymal morphology by regulating E-cadherin and that enhances tumorigenicity partly by downregulating CDK inhibitor p21(Cip1). However, the functional mechanism of regulation of E-cadherin and p21(Cip1) by STRAP is unknown. Here, we have employed STRAP knock out and knockdown cell models (mouse embryonic fibroblast, human cancer cell lines) to show how STRAP downregulates E-cadherin and p21(Cip1) by abrogating the binding of Sp1 to its consensus binding sites. Moreover, ChIP assays suggest that STRAP recruits HDAC1 to Sp1 binding sites in p21(Cip1) promoter. Interestingly, loss of STRAP can stabilize Sp1 by repressing its ubiquitination in G1 phase, resulting in an enhanced expression of p21(Cip1) by >4.5-fold and cell cycle arrest. Using Bioinformatics and Microarray analyses, we have observed that 87% mouse genes downregulated by STRAP have conserved Sp1 binding sites. In NSCLC, the expression levels of STRAP inversely correlated with that of Sp1 (60%). These results suggest a novel mechanism of regulation of E-cadherin and p21(Cip1) by STRAP by modulating Sp1-dependent transcription, and higher expression of STRAP in lung cancer may contribute to downregulation of E-cadherin and p21(Cip1) and to tumor progression. C1 [Jin, Lin; Datta, Pran K.] Univ Alabama Birmingham, Dept Med, Div Hematol & Oncol, UAB Comprehens Canc Ctr, Birmingham, AL 35294 USA. [Jin, Lin; Datta, Pran K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Datta, PK (reprint author), Univ Alabama Birmingham, Dept Med, Div Hematol & Oncol, UAB Comprehens Canc Ctr, Birmingham, AL 35294 USA. EM prandatta@uabmc.edu FU Veterans Affairs Merit Review Award; [R01 CA095195] FX This study was supported by R01 CA095195, and Veterans Affairs Merit Review Award (to PK Datta). NR 36 TC 4 Z9 4 U1 1 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD DEC 15 PY 2014 VL 13 IS 24 BP 3909 EP 3920 DI 10.4161/15384101.2014.973310 PG 12 WC Cell Biology SC Cell Biology GA AZ6KU UT WOS:000348329600020 PM 25483064 ER PT J AU Fogelgren, B Zuo, XF Buonato, JM Vasilyev, A Baek, JI Choi, SY Chacon-Heszele, MF Palmyre, A Polgar, N Drummond, I Park, KM Lazzara, MJ Lipschutz, JH AF Fogelgren, Ben Zuo, Xiaofeng Buonato, Janine M. Vasilyev, Aleksandr Baek, Jeong-In Choi, Soo Young Chacon-Heszele, Maria F. Palmyre, Aurelien Polgar, Noemi Drummond, Iain Park, Kwon Moo Lazzara, Matthew J. Lipschutz, Joshua H. TI Exocyst Sec10 protects renal tubule cells from injury by EGFR/MAPK activation and effects on endocytosis SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE AKI; EGFR; exocyst; MAPK ID GROWTH-FACTOR RECEPTOR; ACUTE KIDNEY INJURY; CRITICALLY-ILL PATIENTS; EPITHELIAL-CELLS; PRIMARY CILIOGENESIS; EARLY PHASE; IN-VITRO; FAILURE; RECOVERY; COMPLEX AB Acute kidney injury is common and has a high mortality rate, and no effective treatment exists other than supportive care. Using cell culture models, we previously demonstrated that exocyst Sec10 overexpression reduced damage to renal tubule cells and speeded recovery and that the protective effect was mediated by higher basal levels of mitogen-activated protein kinase (MAPK) signaling. The exocyst, a highly-conserved eight-protein complex, is known for regulating protein trafficking. Here we show that the exocyst biochemically interacts with the epidermal growth factor receptor (EGFR), which is upstream of MAPK, and Sec10-overexpressing cells express greater levels of phosphorylated (active) ERK, the final step in the MAPK pathway, in response to EGF stimulation. EGFR endocytosis, which has been linked to activation of the MAPK pathway, increases in Sec10-overexpressing cells, and gefitinib, a specific EGFR inhibitor, and Dynasore, a dynamin inhibitor, both reduce EGFR endocytosis. In turn, inhibition of the MAPK pathway reduces ligand-mediated EGFR endocytosis, suggesting a potential feedback of elevated ERK activity on EGFR endocytosis. Gefitinib also decreases MAPK signaling in Sec10-overexpressing cells to levels seen in control cells and, demonstrating a causal role for EGFR, reverses the protective effect of Sec10 overexpression following cell injury in vitro. Finally, using an in vivo zebrafish model of acute kidney injury, morpholino-induced knockdown of sec10 increases renal tubule cell susceptibility to injury. Taken together, these results suggest that the exocyst, acting through EGFR, endocytosis, and the MAPK pathway is a candidate therapeutic target for acute kidney injury. C1 [Fogelgren, Ben; Polgar, Noemi] Univ Hawaii, Dept Anat, Dept Biochem & Physiol, Honolulu, HI 96822 USA. [Zuo, Xiaofeng; Baek, Jeong-In; Choi, Soo Young; Lipschutz, Joshua H.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Buonato, Janine M.] Univ Penn, Dept Chem & Biomol Engn, Philadelphia, PA USA. [Vasilyev, Aleksandr; Palmyre, Aurelien] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Chacon-Heszele, Maria F.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Drummond, Iain] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Drummond, Iain] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Park, Kwon Moo] Kyungpook Natl Univ, Sch Med, Dept Anat & Plus BK21, Taegu, South Korea. [Lipschutz, Joshua H.] Ralph H Johnson Vet Affairs Med Ctr, Dept Med, Charleston, SC USA. RP Lipschutz, JH (reprint author), Med Univ S Carolina, Clin Sci Bldg 829,96 Jonathan Lucas St, Charleston, SC 29425 USA. EM Lipschut@musc.edu OI Polgar, Noemi/0000-0002-8400-162X FU Veterans Affairs (Merit Award); National Institute of Diabetes and Digestive and Kidney Diseases [DK-069909, DK-070980, K01-DK-087852, R0-3DK-100738] FX This work was supported in part by grants from the Veterans Affairs (Merit Award to J. H. Lipschutz), National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-069909 and DK-070980 (to J. H. Lipschutz) and K01-DK-087852 and R0-3DK-100738 (to B. Fogelgren F.), Satellite Healthcare (Norman S. Coplon Extramural Research Grant to J. H. Lipschutz), Hawaii Community Foundation (12ADVC-51347 to B. F.), March of Dimes (Basil O'Connor No. 5-FY14-56 to B. Fogelgren), University of Hawaii RCMI-BRIDGES (5G12MD007601, Pilot Award to B. Fogelgren), Hepato/Renal Fibrocystic Diseases Core Center at the University of Alabama at Birmingham (5P30-DK-074038, Pilot Award to B. Fogelgren), National Science Foundation (Graduate Research Fellowship Award to J. M. Buonato), and the Korean Government (National Research Foundation Grant NRF-2011-220-E00001 to K. Park). NR 52 TC 3 Z9 3 U1 1 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD DEC 15 PY 2014 VL 307 IS 12 BP F1334 EP F1341 DI 10.1152/ajprenal.00032.2014 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA AW7ZS UT WOS:000346480900003 PM 25298525 ER PT J AU Lapidus, KAB Levitch, CF Perez, AM Brallier, JW Parides, MK Soleimani, L Feder, A Iosifescu, DV Charney, DS Murrough, JW AF Lapidus, Kyle A. B. Levitch, Cara F. Perez, Andrew M. Brallier, Jess W. Parides, Michael K. Soleimani, Laili Feder, Adriana Iosifescu, Dan V. Charney, Dennis S. Murrough, James W. TI A Randomized Controlled Trial of Intranasal Ketamine in Major Depressive Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Antidepressant; depression; glutamate; intranasal; ketamine; treatment resistant ID TREATMENT-RESISTANT DEPRESSION; D-ASPARTATE ANTAGONIST; MAGNETIC-RESONANCE-SPECTROSCOPY; RAPID ANTIDEPRESSANT RESPONSE; ADD-ON TRIAL; UNIPOLAR DEPRESSION; BIPOLAR DEPRESSION; GLUTAMATE; EFFICACY; PREMEDICATION AB Background: The N-methyl-D-aspartate glutamate receptor antagonist ketamine, delivered via an intravenous route, has shown rapid antidepressant effects in patients with treatment-resistant depression. The current study was designed to test the safety, tolerability, and efficacy of intranasal ketamine in patients with depression who had failed at least one prior antidepressant trial. Methods: In a randomized, double-blind, crossover study, 20 patients with major depression were randomly assigned, and 18 completed 2 treatment days with intranasal ketamine hydrochloride (50 mg) or saline solution. The primary efficacy outcome measure was change in depression severity 24 hours after ketamine or placebo, measured using the Montgomery-Asberg Depression Rating Scale. Secondary outcomes included persistence of benefit, changes in self-reports of depression, changes in anxiety, and proportion of responders. Potential psychotomimetic, dissociative, hemodynamic, and general adverse effects associated with ketamine were also measured. Results: Patients showed significant improvement in depressive symptoms at 24 hours after ketamine compared to placebo (t = 4.39, p < .001; estimated mean Montgomery-Asberg Depression Rating Scale score difference of 7.6 +/- 3.7; 95% confidence interval, 3.9-11.3). Response criteria were met by 8 of 18 patients (44%) 24 hours after ketamine administration compared with 1 of 18 (6%) after placebo (p = .033). Intranasal ketamine was well tolerated with minimal psychotomimetic or dissociative effects and was not associated with clinically significant changes in hemodynamic parameters. Conclusions: This study provides the first controlled evidence for the rapid antidepressant effects of intranasal ketamine. Treatment was associated with minimal adverse effects. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with major depression. C1 [Lapidus, Kyle A. B.; Levitch, Cara F.; Soleimani, Laili; Iosifescu, Dan V.; Charney, Dennis S.; Murrough, James W.] Icahn Sch Med Mt Sinai, Dept Psychiat, Mood & Anxiety Disorders Program, New York, NY 10029 USA. [Lapidus, Kyle A. B.; Iosifescu, Dan V.; Charney, Dennis S.; Murrough, James W.] Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA. [Perez, Andrew M.; Brallier, Jess W.] Icahn Sch Med Mt Sinai, Dept Anesthesiol, New York, NY 10029 USA. [Parides, Michael K.] Icahn Sch Med Mt Sinai, Dept Hlth Evidence & Policy, New York, NY 10029 USA. [Charney, Dennis S.] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [Iosifescu, Dan V.; Murrough, James W.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Soleimani, Laili] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Murrough, JW (reprint author), 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM james.murrough@mssm.edu RI Murrough, James/J-7129-2013 OI Murrough, James/0000-0001-6286-1242 FU National Institutes of Health [UL1TR000067, K23MH094707]; National Alliance for Research on Schizophrenia and Depression Young Investigator Award from the Brain and Behavior Research Foundation; National Institutes of Health; National Institute of Mental Health; Department of Veterans Affairs; Doris Duke Charitable Foundation; American Foundation for Suicide Prevention; Brain and Behavior Research Foundation; Janssen Research and Development; Avanir Pharmaceuticals; American Psychiatric Institute for Research and Education Janssen Resident Psychiatric Research Scholars; Le Foundation; LCN Consulting; Icahn School of Medicine at Mount Sinai from AstraZeneca; Brainsway; Euthymics Bioscience; NeoSync; Roche; Shire; CNS Response; Otsuka Pharmaceutical Co, Ltd; Servier Laboratories; Sunovion Pharmaceuticals, Inc.; United States Department of Defense; National Alliance for Research on Schizophrenia and Depression; United States Army Medical Research Acquisition Activity; CNS Spectrums FX This work was supported by National Institutes of Health Grant Nos. UL1TR000067 (Mount Sinai Clinical and Translational Science Award) and K23MH094707 (JWM) and a National Alliance for Research on Schizophrenia and Depression Young Investigator Award from the Brain and Behavior Research Foundation (KABL). A portion of the data from the current study was previously presented at the 52nd annual meeting of the American College of Neuropsychopharmacology.; The content of this article is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health or other sponsoring entity. In the past 2 years, JWM has received research support from the National Institutes of Health, the National Institute of Mental Health, the Department of Veterans Affairs, the Doris Duke Charitable Foundation, the American Foundation for Suicide Prevention, the Brain and Behavior Research Foundation, Janssen Research and Development, and Avanir Pharmaceuticals; he has served on advisory boards for Janssen Research and Development and Genentech and has provided consultation services for ProPhase, LLC, and Impel NeuroPharma. KABL has received research support from the Brain and Behavior Research Foundation, American Psychiatric Institute for Research and Education Janssen Resident Psychiatric Research Scholars, and the Le Foundation; he has received consulting fees from LCN Consulting and serves on the advisory board for Halo Neuro Inc. DVI has received research funding through Icahn School of Medicine at Mount Sinai from AstraZeneca, Brainsway, Euthymics Bioscience, NeoSync, Roche, and Shire; he has received consulting fees for Avanir Pharmaceuticals, CNS Response, Otsuka Pharmaceutical Co, Ltd, Servier Laboratories, and Sunovion Pharmaceuticals, Inc. DSC has received consulting fees or research support from the United States Department of Defense, National Institutes of Health, National Institute of Mental Health, National Alliance for Research on Schizophrenia and Depression, United States Army Medical Research Acquisition Activity, and CNS Spectrums; he a member of the Advisory and Editorial Boards of the Institute of Medicine Committee on Department of Homeland Security Workforce Resilience. DSC (Dean of Icahn School of Medicine at Mount Sinai and coinvestigator on this study) and Icahn School of Medicine at Mount Sinai have been named on a use patent on ketamine for the treatment of depression. The Icahn School of Medicine has entered into a licensing agreement for the use of ketamine as therapy for treatment-resistant depression. DSC and Icahn School of Medicine at Mount Sinai could potentially benefit from the results of this study. DSC and AF (a coinvestigator on this study) are named coinventors on a use patent application filed by Mount Sinai for the use of ketamine as a treatment for posttraumatic stress disorder. If ketamine were shown to be effective in the treatment of posttraumatic stress disorder and received approval from the U.S. Food and Drug Administration for this indication, DSC, AF, and the Icahn School of Medicine at Mount Sinai could benefit financially. All other authors report no biomedical financial interests or potential conflicts of interest. NR 38 TC 73 Z9 75 U1 9 U2 43 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 2014 VL 76 IS 12 BP 970 EP 976 DI 10.1016/j.biopsych.2014.03.026 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AU2DY UT WOS:000345427500009 PM 24821196 ER PT J AU Gros, DF AF Gros, Daniel F. TI Development and initial evaluation of Transdiagnostic Behavior Therapy (TBT) for veterans with affective disorders SO PSYCHIATRY RESEARCH LA English DT Article DE Transdiagnostic Behavior Therapy TBT; Anxiety disorders; Depression; Posttraumatic stress disorder ID POSTTRAUMATIC-STRESS-DISORDER; COMORBIDITY SURVEY REPLICATION; RANDOMIZED CONTROLLED-TRIAL; MENTAL-HEALTH PROBLEMS; PRIMARY-CARE CLINICS; DSM-IV DISORDERS; EMOTIONAL DISORDERS; ANXIETY DISORDER; UNIFIED PROTOCOL; PANIC DISORDER AB Considerable attention has focused on the growing need for evidence-based psychotherapy for veterans with affective disorders within the Department of Veteran Affairs. Despite, and possibly due to, the large number of evidence-based protocols available, several obstacles remain in their widespread delivery within Veterans Affairs Medical Centers. In part as an effort to address these concerns, newer transdiagnostic approaches to psychotherapy have been developed to provide a single treatment that is capable of addressing several, related disorders. The goal of the present investigation was to develop and evaluate a transdiagnostic psychotherapy, Transdiagnostic Behavior Therapy (TBT), in veterans with affective disorders. Study 1 provided initial support for transdiagnostic presentation of evidence-based psychotherapy components in veterans with principal diagnoses of affective disorders (n=15). These findings were used to inform the development of the TBT protocol. In Study 2, an initial evaluation of TBT was completed in a second sample of veterans with principal diagnoses of affective disorders (n=29). The findings of Study 2 demonstrated significant improvements in symptoms of depression, anxiety, stress, posttraumatic stress, and related impairment across participants with various principal diagnoses. Together, the investigation provided preliminary support for effectiveness of TBT in veterans with affective disorders. Published by Elsevier Ireland Ltd. C1 [Gros, Daniel F.] Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC USA. [Gros, Daniel F.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Gros, DF (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu FU CSRD VA [IK2 CX000845] NR 42 TC 10 Z9 10 U1 3 U2 10 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 DEC 15 PY 2014 VL 220 IS 1-2 BP 275 EP 282 DI 10.1016/j.psychres.2014.08.018 PG 8 WC Psychiatry SC Psychiatry GA AT6OJ UT WOS:000345058400044 PM 25193379 ER PT J AU Kasckow, J Morse, J Begley, A Anderson, S Bensasi, S Thomas, S Quinn, SC Reynolds, CF AF Kasckow, John Morse, Jennifer Begley, Amy Anderson, Stewart Bensasi, Salem Thomas, Stephen Quinn, Sandra C. Reynolds, Charles F., III TI Treatment of post traumatic stress disorder symptoms in emotionally distressed individuals SO PSYCHIATRY RESEARCH LA English DT Article DE Post traumatic stress disorder; Dietary education; Problem solving therapy ID RANDOMIZED CONTROLLED-TRIAL; PROBLEM-SOLVING THERAPY; PRIMARY-CARE PATIENTS; SUBSYNDROMAL DEPRESSION; MAJOR DEPRESSION; RATING-SCALE; PREVENTION; VETERANS; PTSD; INTERVENTION AB Older individuals with emotional distress and a history of psychologic trauma are at risk for post traumatic stress disorder (PTSD) and major depression. This study was an exploratory, secondary analysis of data from the study "Prevention of Depression in Older African Americans". It examined whether Problem Solving Therapy-Primary Care (PST-PC) would lead to improvement in PTSD symptoms in patients with subsyndromal depression and a history of psychologic trauma. The control condition was dietary education (DIET). Participants (n=60) were age 50 or older with scores on the Center for Epidemiologic Studies -Depression scale of 11 or greater and history of psychologic trauma. Exclusions stipulated no major depression and substance dependence within a year. Participants were randomized to 6-8 sessions of either PST-PC or DIET and followed 2 years with booster sessions every 6 months; 29 participants were in the PST-PC group and 31 were in the DIET group. Mixed effects models showed that improvement of PTSD Check List scores was significantly greater in the DIET group over two years than in the PST-PC group (based on a group time interaction). We observed no intervention*time interactions in Beck Depression Inventory or Brief Symptom Inventory-Anxiety subscale scores. Published by Elsevier Ireland Ltd. C1 [Kasckow, John] VA Pittsburgh Hlth Care Syst, MIRECC & Behav Hlth, Pittsburgh, PA 15240 USA. [Kasckow, John; Morse, Jennifer; Begley, Amy; Bensasi, Salem; Reynolds, Charles F., III] UPMC Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. [Anderson, Stewart] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Thomas, Stephen; Quinn, Sandra C.] Univ Maryland, Ctr Hlth Equ, College Pk, MD 20742 USA. [Thomas, Stephen] Univ Maryland, Dept Hlth Serv Adm, Sch Publ Hlth, College Pk, MD 20742 USA. [Quinn, Sandra C.] Univ Maryland, Dept Family Sci, Sch Publ Hlth, College Pk, MD 20742 USA. RP Kasckow, J (reprint author), VA Pittsburgh Hlth Care Syst, MIRECC & Behav Hlth, Univ Dr C, Pittsburgh, PA 15240 USA. EM kasckowjw@upmc.edu OI Anderson, Stewart/0000-0001-8948-0650 FU NCATS NIH HHS [UL1 TR000005]; NIMH NIH HHS [P30 MH090333, P30MH090333]; NIMHD NIH HHS [P20 MD006737, P60 MD000207, P60MD000207] NR 36 TC 1 Z9 1 U1 1 U2 28 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 DEC 15 PY 2014 VL 220 IS 1-2 BP 370 EP 375 DI 10.1016/j.psychres.2014.06.043 PG 6 WC Psychiatry SC Psychiatry GA AT6OJ UT WOS:000345058400058 PM 25107318 ER PT J AU Veena, MS Wilken, R Zheng, JY Gholkar, A Venkatesan, N Vira, D Ahmed, S Basak, SK Dalgard, CL Ravichandran, S Batra, RK Kasahara, N Elashoff, D Fishbein, MC Whitelegge, JP Torres, JZ Wang, MB Srivatsan, ES AF Veena, Mysore S. Wilken, Reason Zheng, Jun-Ying Gholkar, Ankur Venkatesan, Natarajan Vira, Darshni Ahmed, Sameer Basak, Saroj K. Dalgard, Clifton L. Ravichandran, Sandhiya Batra, Raj K. Kasahara, Noriyuki Elashoff, David Fishbein, Michael C. Whitelegge, Julian P. Torres, Jorge Z. Wang, Marilene B. Srivatsan, Eri S. TI p16 Protein and Gigaxonin Are Associated with the Ubiquitination of NF kappa B in Cisplatin-induced Senescence of Cancer Cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Cancer Stem Cells; Cellular Senescence; Chemoresistance; Head and Neck Cancer; Ubiquitination; Cisplatin; Gigaxonin; NFB; p16 Suppressor Gene ID CURCUMIN SUPPRESSES GROWTH; RANDOMIZED PHASE-II; TRANSCRIPTION FACTOR; NECK-CANCER; OROPHARYNGEAL CANCER; HUMAN-PAPILLOMAVIRUS; INDUCTION CHEMOTHERAPY; INDEPENDENT PATHWAY; HUMAN HEAD; IN-VITRO AB Background: Molecular mechanism of p16-mediated cellular senescence in cisplatin-treated cells is not known. Results: Cisplatin treatment leads to p16 nuclear transport and association with gigaxonin for the ubiquitination of NFB. Conclusion: A protein associated with neural diseases is involved in cisplatin-mediated cellular senescence. Significance: Nuclear expression of p16 and gigaxonin is a useful marker of cancer cell chemosensitivity. The molecular mechanism of p16-mediated senescence in cisplatin-treated cancer cells is not fully understood. Here we show that cisplatin treatment of head and neck cancer cells results in nuclear transport of p16 leading to a molecular modification of NFB. Chromatin immunoprecipitation assays show that this modification is associated with the inhibition of NFB interacting with its DNA binding sequences, leading to decreased expression of NFB-transcribed proteins. LCMS proteomic analysis of LAP-TAP-purified proteins from HeLa cells containing a tetracycline-inducible GFP-S peptide-NFB expression system identified gigaxonin, an ubiquitin E3 ligase adaptor, as an NFB-interacting protein. Immunoblotting and siRNA studies confirmed the NFB-gigaxonin interaction and the dependence of this binding on p16-NFB binding. Using gel shift assays, we have confirmed p16-NFB and gigaxonin-NFB interactions. Furthermore, we have observed increased NFB ubiquitination with cisplatin treatment that is abolished in the absence of p16 and gigaxonin expression. Analysis of 103 primary tumors has shown that increased nuclear p16 expression correlates with enhanced survival of head and neck cancer patients (p < 0.0000542), indicating the importance of nuclear p16 expression in prognosis. Finally, p16 expression is associated with reduced cytokine expression and the presence of human papilloma virus in chemoradiation-sensitive basaloid tumors. However, the absence of p16 expression is associated with enhanced cytokine expression and the absence of human papilloma virus in aggressive tumors. These results clearly demonstrate that nuclear p16 and gigaxonin play an important role in chemosensitivity of head and neck cancers through ubiquitination of NF kappa B. C1 [Veena, Mysore S.; Wilken, Reason; Zheng, Jun-Ying; Venkatesan, Natarajan; Vira, Darshni; Basak, Saroj K.; Ravichandran, Sandhiya; Wang, Marilene B.; Srivatsan, Eri S.] UCLA, David Geffen Sch Med, VAGLAHS, Dept Surg, Los Angeles, CA 90073 USA. [Gholkar, Ankur; Torres, Jorge Z.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. [Vira, Darshni; Ahmed, Sameer; Wang, Marilene B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Head & Neck Surg, Los Angeles, CA 90095 USA. [Dalgard, Clifton L.] Uniformed Serv Univ Hlth Sci, Dept Anat, Bethesda, MD 20814 USA. [Dalgard, Clifton L.] Uniformed Serv Univ Hlth Sci, Dept Physiol, Bethesda, MD 20814 USA. [Dalgard, Clifton L.] Uniformed Serv Univ Hlth Sci, Dept Genet, Bethesda, MD 20814 USA. [Batra, Raj K.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Pulm & Crit Care Med, Dept Med, Los Angeles, CA 90073 USA. [Batra, Raj K.; Kasahara, Noriyuki; Elashoff, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Fishbein, Michael C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Whitelegge, Julian P.] UCLA, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Batra, Raj K.; Torres, Jorge Z.; Wang, Marilene B.; Srivatsan, Eri S.] UCLA, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. RP Srivatsan, ES (reprint author), UCLA, David Geffen Sch Med, VAGLAHS, Dept Surg, Bldg 304,Rm E2-218,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM esrivats@ucla.edu FU National Institutes of Health [R21 CA116826-01]; Veterans Affairs, Washington, D. C.; Veterans Affairs Greater Los Angeles Healthcare System; West Los Angeles Surgical Education Research Center; UCLA Academic Senate grant FX This work was supported, in whole or in part, by National Institutes of Health Grant R21 CA116826-01 (to M. W.). This work was also supported by a merit grant from Veterans Affairs, Washington, D. C. (to E. S. S.), by funds from Veterans Affairs Greater Los Angeles Healthcare System, West Los Angeles Surgical Education Research Center, and by a UCLA Academic Senate grant (to M. W.). NR 59 TC 8 Z9 9 U1 0 U2 13 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 12 PY 2014 VL 289 IS 50 BP 34921 EP 34937 DI 10.1074/jbc.M114.568543 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AW4OP UT WOS:000346260800042 PM 25331947 ER PT J AU Korn, LL Hubbeling, HG Porrett, PM Yang, Q Barnett, LG Laufer, TM AF Korn, Lisa L. Hubbeling, Harper G. Porrett, Paige M. Yang, Qi Barnett, Lisa G. Laufer, Terri M. TI Regulatory T Cells Occupy an Isolated Niche in the Intestine that Is Antigen Independent SO CELL REPORTS LA English DT Article ID THYMIC EMIGRANTS; ULCERATIVE-COLITIS; COMMENSAL BACTERIA; COLONIC-MUCOSA; GENERATION; IL-2; INDUCTION; METABOLITES; EXPRESSION; EPITHELIUM AB Regulatory T cells (Tregs) are CD4(+) T cells that maintain immune homeostasis and prevent autoimmunity. Like all CD4(+) T cells, Tregs require antigenspecific signals via T cell receptor-major histocompatibility complex class II (TCR-MHCII) interactions for their development. However, the requirement for MHCII in Treg homeostasis in tissues such as intestinal lamina propria (LP) is unknown. We examined LP Treg homeostasis in a transgenic mouse model that lacks peripheral TCR-MHCII interactions and generation of extrathymic Tregs (iTregs). Thymically generated Tregs entered the LP of weanlings and proliferated independently of MHCII to fill the compartment. The adult LP was a closed niche; new thymic Tregs were excluded, and Tregs in parabiotic pairs were LP resident. The isolated LP niche was interleukin-2 (IL-2) independent but dependent on commensal bacteria. Thus, an LP Treg niche can be filled, isolated, and maintained independently of antigen signals and iTregs. This niche may represent a tissue-specific mechanism for maintaining immune tolerance. C1 [Korn, Lisa L.; Hubbeling, Harper G.; Barnett, Lisa G.; Laufer, Terri M.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Porrett, Paige M.] Univ Penn, Perelman Sch Med, Dept Surg, Philadelphia, PA 19104 USA. [Yang, Qi] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Laufer, Terri M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Laufer, TM (reprint author), Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. EM tlaufer@mail.med.upenn.edu FU Penn-CHOP Joint Center for Digestive, Liver and Pancreatic Medicine [P30DK050306]; Training Program in Rheumatic Disease [5T32AR007442-25] FX The authors would like to thank Yasmine Belkaid, Nicolas Bouladoux, Tim Hand, and Sean Spencer for helpful discussions, Amy Wagers for technical advice, and Chris Hunter and Helen Simkins for critical reading of the manuscript. This work was initiated with support from pilot grant from the Penn-CHOP Joint Center for Digestive, Liver and Pancreatic Medicine (P30DK050306). L. L. K. was supported by the Training Program in Rheumatic Disease (5T32AR007442-25). NR 35 TC 4 Z9 4 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD DEC 11 PY 2014 VL 9 IS 5 BP 1567 EP 1573 DI 10.1016/j.celrep.2014.11.006 PG 7 WC Cell Biology SC Cell Biology GA AX3PR UT WOS:000346851900001 PM 25482559 ER PT J AU Trivedi, AN Nsa, W Hausmann, LRM Lee, JS Ma, A Bratzler, DW Mor, MK Baus, K Larbi, F Fine, MJ AF Trivedi, Amal N. Nsa, Wato Hausmann, Leslie R. M. Lee, Jonathan S. Ma, Allen Bratzler, Dale W. Mor, Maria K. Baus, Kristie Larbi, Fiona Fine, Michael J. TI Quality and Equity of Care in US Hospitals SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TO-BALLOON TIME; ACUTE MYOCARDIAL-INFARCTION; HEALTH-CARE; OF-CARE; ETHNIC DISPARITIES; RACIAL DISPARITIES; BLACK PATIENTS; PERFORMANCE; RACE; VACCINATION AB BACKGROUND Nearly every U.S. hospital publicly reports its performance on quality measures for patients who are hospitalized for acute myocardial infarction, heart failure, or pneumonia. Because performance rates are not reported according to race or ethnic group, it is unclear whether improvements in equity of care have accompanied aggregate improvements in health care quality over time. METHODS We assessed performance rates for quality measures covering three conditions (six measures for acute myocardial infarction, four for heart failure, and seven for pneumonia). These rates, adjusted for patient-and hospital-level covariates, were compared among non-Hispanic white, non-Hispanic black, and Hispanic patients who received care between 2005 and 2010 in acute care hospitals throughout the United States. RESULTS Adjusted performance rates for the 17 quality measures improved by 3.4 to 57.6 percentage points between 2005 and 2010 for white, black, and Hispanic adults (P<0.001 for all comparisons). In 2005, as compared with adjusted performance rates for white patients, adjusted performance rates were more than 5 percentage points lower for black patients on 3 measures (range of differences, 12.3 to 14.2) and for Hispanic patients on 6 measures (5.6 to 14.5). Gaps decreased significantly on all 9 of these measures between 2005 and 2010, with adjusted changes for differences between white patients and black patients ranging from -8.5 to -11.8 percentage points and from -6.2 to -15.1 percentage points for differences between white patients and Hispanic patients. Decreasing differences according to race or ethnic group were attributable to more equitable care for white patients and minority patients treated in the same hospital, as well as to greater performance improvements among hospitals that disproportionately serve minority patients. CONCLUSIONS Improved performance on quality measures for white, black, and Hispanic adults hospitalized for acute myocardial infarction, heart failure, or pneumonia was accompanied by increased racial and ethnic equity in performance rates both within and among U.S. hospitals. C1 [Trivedi, Amal N.] Brown Univ, Sch Publ Hlth, Providence Vet Affairs VA Med Ctr, Providence, RI 02903 USA. [Trivedi, Amal N.] Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, Providence, RI 02903 USA. [Nsa, Wato; Ma, Allen] Oklahoma Fdn Med Qual, Oklahoma City, OK USA. [Bratzler, Dale W.] Univ Oklahoma, Hlth Sci Ctr, Coll Med, Oklahoma City, OK 73190 USA. [Bratzler, Dale W.] Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Oklahoma City, OK 73190 USA. [Hausmann, Leslie R. M.; Mor, Maria K.; Fine, Michael J.] VA Ctr Hlth Equ Res & Promot, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Hausmann, Leslie R. M.; Lee, Jonathan S.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Baus, Kristie; Larbi, Fiona] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. RP Trivedi, AN (reprint author), Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, 121 S Main St,6th Fl, Providence, RI 02903 USA. EM amal_trivedi@brown.edu FU Centers for Medicare and Medicaid Services; Veterans Affairs Health Services Research and Development Career Development Program FX Funded by the Centers for Medicare and Medicaid Services and the Veterans Affairs Health Services Research and Development Career Development Program. NR 39 TC 11 Z9 11 U1 0 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 11 PY 2014 VL 371 IS 24 BP 2298 EP 2308 DI 10.1056/NEJMoa1405003 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AW1KQ UT WOS:000346048800010 PM 25494269 ER PT J AU Kraut, JA Madias, NE AF Kraut, Jeffrey A. Madias, Nicolaos E. TI DISORDERS OF FLUIDS AND ELECTROLYTES Lactic Acidosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID CRITICALLY-ILL PATIENTS; VENOUS OXYGEN-SATURATION; SEPTIC SHOCK; METABOLIC-ACIDOSIS; LACTATE CLEARANCE; MICROCIRCULATORY ALTERATIONS; SEVERE SEPSIS; ANION GAP; HOSPITAL MORTALITY; CONTROLLED-TRIAL C1 [Kraut, Jeffrey A.] Univ Calif Los Angeles, Med Serv, Membrane Biol Lab, Los Angeles, CA USA. [Kraut, Jeffrey A.] Univ Calif Los Angeles, Res Serv, Membrane Biol Lab, Los Angeles, CA USA. [Kraut, Jeffrey A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Nephrol, Los Angeles, CA 90095 USA. [Kraut, Jeffrey A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Madias, Nicolaos E.] St Elizabeths Med Ctr, Dept Med, Div Nephrol, Boston, MA USA. [Madias, Nicolaos E.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. RP Kraut, JA (reprint author), VHAGLA Healthcare Syst, Div Nephrol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jkraut@ucla.edu; nicolaos.madias@steward.org NR 61 TC 63 Z9 64 U1 5 U2 34 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 11 PY 2014 VL 371 IS 24 BP 2309 EP 2319 DI 10.1056/NEJMra1309483 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AW1KQ UT WOS:000346048800011 PM 25494270 ER PT J AU Cisterna, BA Cardozo, C Saez, JC AF Cisterna, Bruno A. Cardozo, Christopher Saez, Juan C. TI Neuronal involvement in muscular atrophy SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Review DE acetylcholine; hemichannels; connexins; trophic factors; electrical activity ID SPINAL-CORD-INJURY; CILIARY NEUROTROPHIC FACTOR; RAT SKELETAL-MUSCLE; FUNCTIONAL ELECTRICAL-STIMULATION; CHOLINERGIC SYNAPTIC VESICLES; RECEPTOR GENE-EXPRESSION; CONNEXIN-43 HEMICHANNELS MEDIATE; PHOSPHATE ADENINE-NUCLEOTIDES; MYOGENIC REGULATORY FACTORS; IN-SITU HYBRIDIZATION AB The innervation of skeletal myofibers exerts a crucial influence on the maintenance of muscle tone and normal operation. Consequently, denervated myofibers manifest atrophy, which is preceded by an increase in sarcolemma permeability. Recently, de novo expression of hemichannels (HCs) formed by connexins (Cxs) and other none selective channels, including P2X(7) receptors (P2X(7)Rs), and transient receptor potential, sub family V, member 2 (TRPV2) channels was demonstrated in denervated fast skeletal muscles. The denervation-induced atrophy was drastically reduced in denervated muscles deficient in Cxs 43 and 45. Nonetheless, the transduction mechanism by which the nerve represses the expression of the above mentioned non selective channels remains unknown. The paracrine action of extracellular signaling molecules including ATR neurotrophic factors (i.e., brain-derived neurotrophic factor (BDNF)), agrin/LDL receptor-related protein 4 (Lrp4)/muscle-specific receptor kinase (MuSK) and acetylcholine (Ach) are among the possible signals for repression for connexin expression. This review discusses the possible role of relevant factors in maintaining the normal functioning of fast skeletal muscles and suppression of connexin hemichannel expression. C1 [Cisterna, Bruno A.; Saez, Juan C.] Pontificia Univ Catolica Chile, Dept Fisiol, Santiago 8331150, Chile. [Cardozo, Christopher] James J Peters Vet Affairs Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY USA. [Cardozo, Christopher] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Cardozo, Christopher] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. [Saez, Juan C.] Univ Valparaiso, Ctr Interdisciplinario Neurociencias Valparaiso, Valparaiso, Chile. RP Cisterna, BA (reprint author), Pontificia Univ Catolica Chile, Dept Fisiol, Alameda 340, Santiago 8331150, Chile. EM bcisterna@uc.cl FU FONDECYT [1111033]; millennium institute; CONICYT; Department of Veterans Affairs Rehabilitation Research and Development Service [B9212C]; James J. Peters VA Medical Center FX This work was partially funded by FONDECYT grants 1111033 (to Juan C. Saez), millennium institute (to Juan C. Saez), and Bruno A. Cisterna acknowledge the support of a CONICYT fellowship, and the Department of Veterans Affairs Rehabilitation Research and Development Service (B9212C) and the James J. Peters VA Medical Center. NR 182 TC 6 Z9 6 U1 1 U2 18 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5102 J9 FRONT CELL NEUROSCI JI Front. Cell. Neurosci. PD DEC 10 PY 2014 VL 8 AR 405 DI 10.3389/fncel.2014.00405 PG 11 WC Neurosciences SC Neurosciences & Neurology GA AX9QE UT WOS:000347236200001 PM 25540609 ER PT J AU Hayes, J Jackson, JL McNutt, GM Hertz, BJ Ryan, JJ Pawlikowski, SA AF Hayes, John Jackson, Jeffrey L. McNutt, Gail M. Hertz, Brian J. Ryan, Jeffrey J. Pawlikowski, Scott A. TI Association Between Physician Time-Unlimited vs Time-Limited Internal Medicine Board Certification and Ambulatory Patient Care Quality SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; OF-CARE; HEALTH-CARE; PREVENTION; METAANALYSIS; MAINTENANCE; OUTCOMES; DISEASE; SCORES AB IMPORTANCE American Board of Internal Medicine (ABIM) initiatives encourage internists with time-unlimited certificates to recertify. However, there are limited data evaluating differences in performance between internists with time-limited or time-unlimited board certification. OBJECTIVE To determine whether there are differences in primary care quality between physicians holding time-limited or time-unlimited certification. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of performance data from 1 year (2012-2013) at 4 Veterans Affairs (VA) medical centers. Participants were internists with time-limited (n = 71) or time-unlimited (n = 34) ABIM certification providing primary care to 68 213 patients. Median physician panel size was 610 patients (range, 19-1316), with no differences between groups (P = .90). MAIN OUTCOMES AND MEASURES Ten primary care performance measures: colorectal screening rates; diabetes with glycated hemoglobin (HbA(1c) level) less than 9.0%; diabetes with blood pressure less than 140/90 mmHg; diabetes with low-density lipoprotein cholesterol (LDL-C) level less than 100 mg/dL; hypertension with blood pressure less than 140/90 mmHg; thiazide diuretics used in multidrug hypertensive regimen; atherosclerotic coronary artery disease and LDL-C level less than 100 mg/dL; post-myocardial infarction use of aspirin; post-myocardial infarction use of beta-blockers; congestive heart failure (CHF) with use of angiotensin-converting enzyme (ACE) inhibitor. RESULTS After adjustment for practice site, panel size, years since certification, and clustering by physician, there were no differences in outcomes for patients cared for by internists with time-limited or time-unlimited certification for any performance measure: colorectal screening (odds ratio [OR], 0.95 [95% CI, 0.89-1.01]); diabetes with HbA1c level less than 9.0% (OR, 0.96 [95% CI, 0.74-1.2]); blood pressure control (OR, 0.99 [95% CI, 0.69-1.4]); LDL-C level less than 100 mg/dL (OR, 1.1 [95% CI, 0.79-1.5]); hypertension with blood pressure less than 140/90 mmHg (OR, 1.0 [95% CI, 0.92-1.2]); thiazide use (OR, 1.0 [95% CI, 0.8-1.3]); atherosclerotic coronary artery disease with LDL-C level less than 100 mg/dL (OR, 1.1 [95% CI, 0.75-1.7]); post-myocardial infarction use of aspirin (OR, 0.98 [95% CI, 0.58-1.68]) or beta-blockers (OR, 1.0 [95% CI, 0.57-1.9]); CHF with use of ACE inhibitor (OR, 0.98 [95% CI, 0.61-1.6]). CONCLUSIONS AND RELEVANCE Among internists providing primary care at 4 VA medical centers, there were no significant differences between those with time-limited ABIM certification and those with time-unlimited ABIM certification on 10 primary care performance measures. Additional research to examine the difference in patient outcomes among holders of time-limited and time-unlimited certificates in non-VA and nonacademic settings and the association with other ABIM goals may help clarify the potential benefit of Maintenance of Certification participation. Copyright 2014 American Medical Association. All rights reserved. C1 [Hayes, John] Clement J Zablocki VA Med Ctr, Milwaukee, WI 53295 USA. [Jackson, Jeffrey L.] Clement J Zablocki VA Med Ctr, GIM Sect, Milwaukee, WI 53295 USA. [McNutt, Gail M.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Hertz, Brian J.; Pawlikowski, Scott A.] Hines VA Med Ctr, Chicago, IL USA. [Ryan, Jeffrey J.] Jesse Brown VA Med Ctr, Chicago, IL USA. RP Hayes, J (reprint author), Clement J Zablocki VA Med Ctr, 5000 W Natl Ave, Milwaukee, WI 53295 USA. EM john.hayes3@va.gov NR 28 TC 13 Z9 13 U1 0 U2 7 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 DEC 10 PY 2014 VL 312 IS 22 BP 2358 EP 2363 DI 10.1001/jama.2014.13992 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA AW5YB UT WOS:000346345700010 PM 25490326 ER PT J AU Patel, MS Volpp, KG Small, DS Hill, AS Even-Shoshan, O Rosenbaum, L Ross, RN Bellini, L Zhu, JS Silber, JH AF Patel, Mitesh S. Volpp, Kevin G. Small, Dylan S. Hill, Alexander S. Even-Shoshan, Orit Rosenbaum, Lisa Ross, Richard N. Bellini, Lisa Zhu, Jingsan Silber, Jeffrey H. TI Association of the 2011 ACGME Resident Duty Hour Reforms With Mortality and Readmissions Among Hospitalized Medicare Patients SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; QUALITY-OF-CARE; ADMINISTRATIVE DATA; COMORBIDITY MEASURES; INTERNAL-MEDICINE; BENEFICIARIES; ICD-9-CM; CONSEQUENCES; INFORMATION; EDUCATION AB IMPORTANCE Patient outcomes associated with the 2011 Accreditation Council for Graduate Medical Education (ACGME) duty hour reforms have not been evaluated at a national level. OBJECTIVE To evaluate the association of the 2011 ACGME duty hour reforms with mortality and readmissions. DESIGN, SETTING, AND PARTICIPANTS Observational study of Medicare patient admissions (6 384 273 admissions from 2 790 356 patients) to short-term, acute care, nonfederal hospitals (n = 3104) with principal medical diagnoses of acute myocardial infarction, stroke, gastrointestinal bleeding, or congestive heart failure or a Diagnosis Related Group classification of general, orthopedic, or vascular surgery. Of the hospitals, 96 (3.1%) were very major teaching, 138 (4.4%) major teaching, 442 (14.2%) minor teaching, 443 (14.3%) very minor teaching, and 1985 (64.0%) nonteaching. EXPOSURE Resident-to-bed ratio as a continuous measure of hospital teaching intensity. MAIN OUTCOMES AND MEASURES Change in 30-day all-location mortality and 30-day all-cause readmission, comparing patients in more intensive relative to less intensive teaching hospitals before (July 1, 2009-June 30, 2011) and after (July 1, 2011-June 30, 2012) duty hour reforms, adjusting for patient comorbidities, time trends, and hospital site. RESULTS In the 2 years before duty hour reforms, there were 4 325 854 admissions with 288 422 deaths and 602 380 readmissions. In the first year after the reforms, accounting for teaching hospital intensity, there were 2 058 419 admissions with 133 547 deaths and 272 938 readmissions. There were no significant postreform differences in mortality accounting for teaching hospital intensity for combined medical conditions (odds ratio [OR], 1.00; 95% CI, 0.96-1.03), combined surgical categories (OR, 0.99; 95% CI, 0.94-1.04), or any of the individual medical conditions or surgical categories. There were no significant postreform differences in readmissions for combined medical conditions (OR, 1.00; 95% CI, 0.97-1.02) or combined surgical categories (OR, 1.00; 95% CI, 0.98-1.03). For the medical condition of stroke, there were higher odds of readmissions in the postreform period (OR, 1.06; 95% CI, 1.001-1.13). However, this finding was not supported by sensitivity analyses and there were no significant postreform differences for readmissions for any other individual medical condition or surgical category. CONCLUSIONS AND RELEVANCE Among Medicare beneficiaries, there were no significant differences in the change in 30-day mortality rates or 30-day all-cause readmission rates for those hospitalized in more intensive relative to less intensive teaching hospitals in the year after implementation of the 2011 ACGME duty hour reforms compared with those hospitalized in the 2 years before implementation. Copyright 2014 American Medical Association. All rights reserved. C1 [Patel, Mitesh S.; Volpp, Kevin G.] Vet Adm Hosp, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Patel, Mitesh S.; Volpp, Kevin G.; Bellini, Lisa; Zhu, Jingsan] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Patel, Mitesh S.; Volpp, Kevin G.; Silber, Jeffrey H.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Patel, Mitesh S.; Volpp, Kevin G.; Small, Dylan S.; Zhu, Jingsan] Univ Penn, Leonard Davis Inst, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Small, Dylan S.] Univ Penn, Wharton Sch, Dept Stat, Philadelphia, PA 19104 USA. [Hill, Alexander S.; Even-Shoshan, Orit; Ross, Richard N.; Silber, Jeffrey H.] Childrens Hosp Philadelphia, Ctr Outcomes Res, Philadelphia, PA 19104 USA. [Even-Shoshan, Orit; Silber, Jeffrey H.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Rosenbaum, Lisa] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Silber, Jeffrey H.] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Silber, Jeffrey H.] Univ Penn, Perelman Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. RP Patel, MS (reprint author), Univ Penn, 423 Guardian Dr,12th Floor,Blockley Hall, Philadelphia, PA 19104 USA. EM mpatel@upenn.edu FU National Heart, Lung, and Blood Institute [RO1-HLO94593]; Department of Veteran Affairs; Robert Wood Johnson Foundation FX This project was funded in part through National Heart, Lung, and Blood Institute grant RO1-HLO94593. Dr Patel was supported by the Department of Veteran Affairs and the Robert Wood Johnson Foundation. NR 46 TC 29 Z9 29 U1 0 U2 4 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 DEC 10 PY 2014 VL 312 IS 22 BP 2364 EP 2373 DI 10.1001/jama.2014.15273 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AW5YB UT WOS:000346345700011 PM 25490327 ER PT J AU Rajaram, R Chung, JW Jones, AT Cohen, ME Dahlke, AR Ko, CY Tarpley, JL Lewis, FR Hoyt, DB Bilimoria, KY AF Rajaram, Ravi Chung, Jeanette W. Jones, Andrew T. Cohen, Mark E. Dahlke, Allison R. Ko, Clifford Y. Tarpley, John L. Lewis, Frank R. Hoyt, David B. Bilimoria, Karl Y. TI Association of the 2011 ACGME Resident Duty Hour Reform With General Surgery Patient Outcomes and With Resident Examination Performance SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SURGICAL QUALITY; WORK HOURS; RESTRICTIONS; MORTALITY; EDUCATION; INTERNS; CARE; REGULATIONS; MEDICINE; FAILURES AB IMPORTANCE In 2011, the Accreditation Council for Graduate Medical Education (ACGME) restricted resident duty hour requirements beyond those established in 2003, leading to concerns about the effects on patient care and resident training. OBJECTIVE To determine if the 2011 ACGME duty hour reform was associated with a change in general surgery patient outcomes or in resident examination performance. DESIGN, SETTING, AND PARTICIPANTS Quasi-experimental study of general surgery patient outcomes 2 years before (academic years 2009-2010) and after (academic years 2012-2013) the 2011 duty hour reform. Teaching and nonteaching hospitals were compared using a difference-in-differences approach adjusted for procedural mix, patient comorbidities, and time trends. Teaching hospitals were defined based on the proportion of cases at which residents were present intraoperatively. Patients were those undergoing surgery at hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). General surgery resident performance on the annual in-training, written board, and oral board examinations was assessed for this same period. EXPOSURES National implementation of revised resident duty hour requirements on July 1, 2011, in all ACGME accredited residency programs. MAIN OUTCOMES AND MEASURES Primary outcome was a composite of death or serious morbidity; secondary outcomes were other postoperative complications and resident examination performance. RESULTS In the main analysis, 204 641 patients were identified from 23 teaching (n = 102 525) and 31 nonteaching (n = 102 116) hospitals. The unadjusted rate of death or serious morbidity improved during the study period in both teaching (11.6%[95% CI, 11.3%-12.0%] to 9.4%[95% CI, 9.1%-9.8%], P < .001) and nonteaching hospitals (8.7%[95% CI, 8.3%-9.0%] to 7.1% [95% CI, 6.8%-7.5%], P < .001). In adjusted analyses, the 2011 ACGME duty hour reform was not associated with a significant change in death or serious morbidity in either postreform year 1 (OR, 1.12; 95% CI, 0.98-1.28) or postreform year 2 (OR, 1.00; 95% CI, 0.86-1.17) or when both postreform years were combined (OR, 1.06; 95% CI, 0.93-1.20). There was no association between duty hour reform and any other postoperative adverse outcome. Mean (SD) in-training examination scores did not significantly change from 2010 to 2013 for first-year residents (499.7 [85.2] to 500.5 [84.2], P = .99), for residents from other postgraduate years, or for first-time examinees taking the written or oral board examinations during this period. CONCLUSIONS AND RELEVANCE Implementation of the 2011 ACGME duty hour reform was not associated with a change in general surgery patient outcomes or differences in resident examination performance. The implications of these findings should be considered when evaluating the merit of the 2011 ACGME duty hour reform and revising related policies in the future. Copyright 2014 American Medical Association. All rights reserved. C1 [Rajaram, Ravi; Cohen, Mark E.; Ko, Clifford Y.; Hoyt, David B.; Bilimoria, Karl Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Rajaram, Ravi; Chung, Jeanette W.; Dahlke, Allison R.; Bilimoria, Karl Y.] Northwestern Univ, Dept Surg, SOQIC, Chicago, IL 60611 USA. [Rajaram, Ravi; Chung, Jeanette W.; Dahlke, Allison R.; Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Inst Publ Hlth & Med, Ctr Healthcare Studies, Chicago, IL 60611 USA. [Jones, Andrew T.; Lewis, Frank R.] Amer Board Surg, Philadelphia, PA USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Tarpley, John L.] Vanderbilt Univ, Med Ctr, Dept Surg, Nashville, TN USA. RP Bilimoria, KY (reprint author), Northwestern Univ, Dept Surg, SOQIC, 633 N St Clair St,20th Floor, Chicago, IL 60611 USA. EM k-bilimoria@northwestern.edu FU Agency for Healthcare Research and Quality [T32HS000078]; American College of Surgeons Clinical Scholars in Residence Program; Merck FX Dr Rajaramis supported by grant T32HS000078 from the Agency for Healthcare Research and Quality, the American College of Surgeons Clinical Scholars in Residence Program, and an unrestricted educational grant from Merck. NR 38 TC 40 Z9 40 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 DEC 10 PY 2014 VL 312 IS 22 BP 2374 EP 2384 DI 10.1001/jama.2014.15277 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AW5YB UT WOS:000346345700012 PM 25490328 ER PT J AU Wheeler, SE Clark, AM Taylor, DP Young, CL Pillai, VC Stolz, DB Venkataramanan, R Lauffenburger, D Griffith, L Wells, A AF Wheeler, S. E. Clark, A. M. Taylor, D. P. Young, C. L. Pillai, V. C. Stolz, D. B. Venkataramanan, R. Lauffenburger, D. Griffith, L. Wells, A. TI Spontaneous dormancy of metastatic breast cancer cells in an all human liver microphysiologic system SO BRITISH JOURNAL OF CANCER LA English DT Article DE bioreactor; 3D culture systems; mammary carcinoma; liver; hepatocytes ID EPITHELIAL-MESENCHYMAL TRANSITION; BALANCED PROLIFERATION; CULTURE MODELS; TUMOR DORMANCY; E-CADHERIN; PROGRESSION; THERAPY; TISSUE; MORPHOGENESIS; CHEMOTHERAPY AB Background: Metastatic outgrowth in breast cancer can occur years after a seeming cure. Existing model systems of dormancy are limited as they do not recapitulate human metastatic dormancy without exogenous manipulations and are unable to query early events of micrometastases. Methods: Here, we describe a human ex vivo hepatic microphysiologic system. The system is established with fresh human hepatocytes and non-parenchymal cells (NPCs) creating a microenvironment into which breast cancer cells (MCF7 and MDA-MB-231) are added. Results: The hepatic tissue maintains function through 15 days as verified by liver-specific protein production and drug metabolism assays. The NPCs form an integral part of the hepatic niche, demonstrated within the system through their participation in differential signalling cascades and cancer cell outcomes. Breast cancer cells intercalate into the hepatic niche without interfering with hepatocyte function. Examination of cancer cells demonstrated that a significant subset enter a quiescent state of dormancy as shown by lack of cell cycling (EdU(-) or Ki67(-)). The presence of NPCs altered the cancer cell fraction entering quiescence, and lead to differential cytokine profiles in the microenvironment effluent. Conclusions: These findings establish the liver microphysiologic system as a relevant model for the study of breast cancer metastases and entry into dormancy. C1 [Wheeler, S. E.; Clark, A. M.; Taylor, D. P.; Stolz, D. B.; Venkataramanan, R.; Wells, A.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15260 USA. [Taylor, D. P.; Wells, A.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Young, C. L.; Lauffenburger, D.; Griffith, L.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Pillai, V. C.; Venkataramanan, R.] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA USA. [Stolz, D. B.] Univ Pittsburgh, Dept Cell Biol, Pittsburgh, PA USA. [Stolz, D. B.; Wells, A.] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA USA. [Stolz, D. B.; Wells, A.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Wells, A.] VA Pittsburgh Healthcare Syst, Pittsburgh VA Med Ctr, Pittsburgh, PA USA. RP Wells, A (reprint author), Univ Pittsburgh, Dept Pathol, S711 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15260 USA. EM wellsa@upmc.edu OI Clark, Amanda/0000-0003-1590-2560; Wells, Alan/0000-0002-1637-8150 FU NIH [1UH2TR000496-01]; VA Merit Award; DARPA [BAA-11-73, W911NF-12-2-0039] FX The authors thank other members of their laboratories for thoughtful discussions. The work described herein is being funded by grants from the NIH (1UH2TR000496-01), a VA Merit Award, and DARPA (BAA-11-73 Microphysiological Systems: W911NF-12-2-0039). NR 45 TC 11 Z9 11 U1 1 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD DEC 9 PY 2014 VL 111 IS 12 BP 2342 EP 2350 DI 10.1038/bjc.2014.533 PG 9 WC Oncology SC Oncology GA AW4JJ UT WOS:000346247000018 PM 25314052 ER PT J AU Lee, SJ Ritchie, CS Yaffe, K Cenzer, IS Barnes, DE AF Lee, Sei J. Ritchie, Christine S. Yaffe, Kristine Cenzer, Irena Stijacic Barnes, Deborah E. TI A Clinical Index to Predict Progression from Mild Cognitive Impairment to Dementia Due to Alzheimer's Disease SO PLOS ONE LA English DT Article ID OLDER-ADULTS; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; RISK; RECOMMENDATIONS; CLASSIFICATION; VALIDATION; BIOMARKERS; CONVERSION AB Background: Mild cognitive impairment is often a precursor to dementia due to Alzheimer's disease, but many patients with mild cognitive impairment never develop dementia. New diagnostic criteria may lead to more patients receiving a diagnosis of mild cognitive impairment. Objective: To develop a prediction index for the 3-year risk of progression from mild cognitive impairment to dementia relying only on information that can be readily obtained in most clinical settings. Design and Participants: 382 participants diagnosed with amnestic mild cognitive impairment enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI), a multi-site, longitudinal, observational study. Main Predictors Measures: Demographics, comorbid conditions, caregiver report of participant symptoms and function, and participant performance on individual items from basic neuropsychological scales. Main Outcome Measure: Progression to probable Alzheimer's disease. Key Results: Subjects had a mean (SD) age of 75 (7) years and 43% progressed to probable Alzheimer's disease within 3 years. Important independent predictors of progression included being female, resisting help, becoming upset when separated from caregiver, difficulty shopping alone, forgetting appointments, number of words recalled from a 10-word list, orientation and difficulty drawing a clock. The final point score could range from 0 to 16 (mean [SD]: 4.2 [2.9]). The optimism-corrected Harrell's c-statistic was 0.71(95% CI: 0.68-0.75). Fourteen percent of subjects with low risk scores (0-2 points, n=124) converted to probable Alzheimer's disease over 3 years, compared to 51% of those with moderate risk scores (3-8 points, n=223) and 91% of those with high risk scores (9-16 points, n=35). Conclusions: An index using factors that can be obtained in most clinical settings can predict progression from amnestic mild cognitive impairment to probable Alzheimer's disease and may help clinicians differentiate between mild cognitive impairment patients at low vs. high risk of progression. C1 [Lee, Sei J.; Ritchie, Christine S.; Cenzer, Irena Stijacic] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Lee, Sei J.; Ritchie, Christine S.; Yaffe, Kristine; Cenzer, Irena Stijacic; Barnes, Deborah E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Ritchie, Christine S.] Jewish Home San Francisco, San Francisco, CA USA. [Yaffe, Kristine; Barnes, Deborah E.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine; Barnes, Deborah E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Lee, SJ (reprint author), Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. EM sei.lee@ucsf.edu FU S.D. Bechtel, Jr. Foundation; National Institutes of Health [K24-AG031155, R01-DK69406, R01-AG26720]; Veterans Health Administration FX SJL was supported by the S.D. Bechtel, Jr. Foundation (http://sdbjrfoundation.org/). KY was supported for this study by the National Institutes of Health (K24-AG031155, R01-DK69406 and R01-AG26720) and the Veterans Health Administration. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 4 Z9 4 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 DEC 8 PY 2014 VL 9 IS 12 AR e113535 DI 10.1371/journal.pone.0113535 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX4MX UT WOS:000346907600021 PM 25486250 ER PT J AU Freytes, CO Callander, NS Goodman, SA Luo, SH Toro, JJ Carson, KR AF Freytes, Cesar O. Callander, Natalie S. Goodman, Stacey A. Luo, Suhong Toro, Juan J. Carson, Kenneth R. TI The Veterans Health Administration Provides Equal Access to Autologous Hematopoietic Stem Cell Transplantation for Patients with Multiple Myeloma SO BLOOD LA English DT Meeting Abstract C1 [Freytes, Cesar O.; Toro, Juan J.] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. [Freytes, Cesar O.; Toro, Juan J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Callander, Natalie S.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Callander, Natalie S.] Univ Wisconsin, Madison, WI USA. [Goodman, Stacey A.] Nashville VA Med Ctr, Nashville, TN USA. [Goodman, Stacey A.] Vanderbilt Univ, Nashville, TN 37235 USA. [Luo, Suhong; Carson, Kenneth R.] St Louis VA Med Ctr, Res Serv, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242706152 ER PT J AU Garbati, MR Rathbun, RK Yates, JE Yang, WJ Bagby, GC AF Garbati, Michael R. Rathbun, R. K. Yates, Jane E. Yang, Wenjin Bagby, Grover C. TI ALDH1A1 Dysfunction in FA-Deficient Macrophages Contributes to Aberrant Activation of the Innate Immune Response SO BLOOD LA English DT Meeting Abstract C1 [Garbati, Michael R.; Bagby, Grover C.] Portland VA Med Ctr, Portland, OR USA. [Rathbun, R. K.; Yates, Jane E.; Bagby, Grover C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Yang, Wenjin] Aldea Pharmaceut, Redwood City, CA USA. [Bagby, Grover C.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707171 ER PT J AU Lai, HY Morse, SJ Luty, SB Garbati, MR Edmiston, JB Bagby, GC Druker, BJ Fleischman, AG AF Lai, Hew Yeng Morse, Sarah J. Luty, Samuel B. Garbati, Michael R. Edmiston, J. Blair Bagby, Grover C. Druker, Brian J. Fleischman, Angela G. TI Exaggerated Response to Toll-like Receptor Agonist Contributes to Excessive TNF Production in Myeloproliferative Neoplasm SO BLOOD LA English DT Meeting Abstract C1 [Lai, Hew Yeng; Morse, Sarah J.; Fleischman, Angela G.] Univ Calif Irvine, Irvine, CA USA. [Luty, Samuel B.; Edmiston, J. Blair; Bagby, Grover C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Garbati, Michael R.] Portland VA Med Ctr, Portland, OR USA. [Druker, Brian J.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242702116 ER PT J AU Newell, LF Rathbun, RK Garbati, MR Dao, KHT Holtan, SG Cook, RJ Meyers, G Bagby, GC AF Newell, Laura F. Rathbun, R. K. Garbati, Michael R. Dao, Kim-Hien T. Holtan, Shernan G. Cook, Rachel J. Meyers, Gabrielle Bagby, Grover C. TI The Contribution of Toll-like Receptor (TLR) Pathway Hyper-Reactivity to Clonal Selection in Secondary MDS and AML SO BLOOD LA English DT Meeting Abstract C1 [Newell, Laura F.; Rathbun, R. K.; Cook, Rachel J.; Meyers, Gabrielle; Bagby, Grover C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Garbati, Michael R.; Bagby, Grover C.] Portland VA Med Ctr, Portland, OR USA. [Dao, Kim-Hien T.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Holtan, Shernan G.] Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242708115 ER PT J AU Bagby, GC AF Bagby, Grover C. TI The Role of Innate Immune Dysfunction in Inherited Bone Marrow Failure SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Bagby, Grover C.] Portland VA Med Ctr, Portland, OR USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233802005 ER PT J AU Carey, A Edwards, D Eide, CA Traer, E Tyner, JW Bagby, GC Druker, BJ Agarwal, A AF Carey, Alyssa Edwards, David Eide, Christopher A. Traer, Elie Tyner, Jeffrey W. Bagby, Grover C. Druker, Brian J. Agarwal, Anupriya TI Targeted Suppression of Interleukin-1 Signaling Attenuates Leukemic Cellular Growth and Disease Progression in Primary Human Cells and Murine Models of Acute Myeloid leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Carey, Alyssa; Edwards, David; Eide, Christopher A.; Traer, Elie; Tyner, Jeffrey W.; Bagby, Grover C.; Druker, Brian J.; Agarwal, Anupriya] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Eide, Christopher A.; Druker, Brian J.] Howard Hughes Med Inst, Portland, OR USA. [Bagby, Grover C.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243503028 ER PT J AU Cassaday, RD Stevenson, PA Gooley, TA Chauncey, T Pagel, J Till, BG Philip, M Orozco, JJ Bensinger, WI Holmberg, L Shustov, AR Green, DJ Smith, SD Libby, EN Maloney, DG Soma, LA Press, OW Gopal, AK AF Cassaday, Ryan D. Stevenson, Philip A. Gooley, Theodore A. Chauncey, Thomas Pagel, John Till, Brian G. Philip, Mary Orozco, Johnnie J. Bensinger, William I. Holmberg, Leona Shustov, Andrei R. Green, Damian J. Smith, Stephen D. Libby, Edward N. Maloney, David G. Soma, Lorinda A. Press, Oliver W. Gopal, Ajay K. TI Long Term Follow-up of High-Dose CD20-Targeted Radioimmunotherapy-Based Autologous Transplantation for Patients with Mantle Cell Lymphoma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Cassaday, Ryan D.; Gooley, Theodore A.; Pagel, John; Till, Brian G.; Bensinger, William I.; Green, Damian J.; Smith, Stephen D.; Maloney, David G.; Press, Oliver W.; Gopal, Ajay K.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Cassaday, Ryan D.; Stevenson, Philip A.; Gooley, Theodore A.; Chauncey, Thomas; Pagel, John; Till, Brian G.; Philip, Mary; Orozco, Johnnie J.; Bensinger, William I.; Shustov, Andrei R.; Green, Damian J.; Smith, Stephen D.; Libby, Edward N.; Soma, Lorinda A.; Press, Oliver W.; Gopal, Ajay K.] Univ Washington, Seattle, WA 98195 USA. [Chauncey, Thomas] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Holmberg, Leona] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Maloney, David G.] Univ Washington, Sch Med, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233808151 ER PT J AU Viel, KR Kim, B Tejero, ME Cole, SS Howard, TE Ortiz, AS AF Viel, Kevin R. Kim, Benjamin Elizabeth Tejero, Maria Cole, Shelley S. Howard, Tom E. Santamaria Ortiz, Amparo TI The Spectrum of Amino Acid Substitutions Resulting from Single Nucleotide Substitutions in the Coagulation Biosystem: Impact on Identification By Mass Spectrometry SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Viel, Kevin R.] Histonis Inc, Atlanta, GA USA. [Kim, Benjamin] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Elizabeth Tejero, Maria] Inst Nacl Med Genom, Mexico City, DF, Mexico. [Cole, Shelley S.] Texas Biomed Res Inst, San Antonio, TX USA. [Howard, Tom E.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Santamaria Ortiz, Amparo] Hosp Valle De Hebron, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243502119 ER PT J AU Zhang, QS Benedetti, E Deater, M Schubert, K Major, A Pelz, C Impey, S Marquez-Loza, L Rathbun, K Kato, S Bagby, GC Grompe, M AF Zhang, Qingshuo Benedetti, Eric Deater, Matthew Schubert, Kathryn Major, Angela Pelz, Carl Impey, Soren Marquez-Loza, Laura Rathbun, Keaney Kato, Shigeaki Bagby, Grover C. Grompe, Markus TI Oxymetholone Therapy of Fanconi Anemia Induces Hematopoietic Stem Cell Cycling By Suppressing Osteopontin Transcription SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Zhang, Qingshuo; Benedetti, Eric; Deater, Matthew; Schubert, Kathryn; Pelz, Carl; Impey, Soren; Marquez-Loza, Laura; Grompe, Markus] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Major, Angela] Texas Childrens Hosp, Houston, TX 77030 USA. [Rathbun, Keaney; Bagby, Grover C.] Portland VA Med Ctr, Portland, OR USA. [Kato, Shigeaki] Univ Tokyo, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806030 ER PT J AU Li, W Long, JA Watts, LT Jiang, Z Shen, Q Li, YX Duong, TQ AF Li, Wei Long, Justin Alexander Watts, Lora Talley Jiang, Zhao Shen, Qiang Li, Yunxia Duong, Timothy Q. TI A Quantitative MRI Method for Imaging Blood-Brain Barrier Leakage in Experimental Traumatic Brain Injury SO PLOS ONE LA English DT Article ID REPERFUSION INJURY; MODEL SELECTION; PATLAK PLOTS; RAT MODEL; GD-DTPA; PERMEABILITY; STROKE; PARAMETERS; DIFFUSION; BREAKDOWN AB Blood-brain barrier (BBB) disruption is common following traumatic brain injury (TBI). Dynamic contrast enhanced (DCE) MRI can longitudinally measure the transport coefficient K-trans which reflects BBB permeability. K-trans measurements however are not widely used in TBI research because it is generally considered to be noisy and possesses low spatial resolution. We improved spatiotemporal resolution and signal sensitivity of K-trans MRI in rats by using a high-sensitivity surface transceiver coil. To overcome the signal drop off profile of the surface coil, a pre-scan module was used to map the flip angle (B-1 field) and magnetization (M-0) distributions. A series of T-1-weighted gradient echo images were acquired and fitted to the extended Kety model with reversible or irreversible leakage, and the best model was selected using F-statistics. We applied this method to study the rat brain one hour following controlled cortical impact (mild to moderate TBI), and observed clear depiction of the BBB damage around the impact regions, which matched that outlined by Evans Blue extravasation. Unlike the relatively uniform T-2 contrast showing cerebral edema, K-trans shows a pronounced heterogeneous spatial profile in and around the impact regions, displaying a nonlinear relationship with T-2. This improved K-trans MRI method is also compatible with the use of high-sensitivity surface coil and the high-contrast two-coil arterial spin-labeling method for cerebral blood flow measurement, enabling more comprehensive investigation of the pathophysiology in TBI. C1 [Li, Wei; Long, Justin Alexander; Watts, Lora Talley; Jiang, Zhao; Shen, Qiang; Li, Yunxia; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Li, Wei; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Watts, Lora Talley] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Watts, Lora Talley; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. RP Li, W (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. EM liw5@uthscsa.edu; duongt@uthscsa.edu RI Shen, Qiang/B-8784-2008 OI Shen, Qiang/0000-0002-4287-3403 FU NIH/NINDS [R01 NS45879, UL1 TR001119, TL1TR001119, KL2 TR001118]; NIH/NINDS via the Clinical Translational Science Awards (CTSA) [TL1TR001119, UL1TR001119, 8UL1TR000149] FX The study was supported in part by grants from NIH/NINDS R01 NS45879 (TQD), UL1 TR001119 (WL), TL1TR001119 (JAL), and KL2 TR001118 (LTW) via the Clinical Translational Science Awards (CTSA, parent grant UL1TR001119, 8UL1TR000149, and TL1TR001119). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 26 TC 8 Z9 10 U1 2 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 DEC 5 PY 2014 VL 9 IS 12 AR e114173 DI 10.1371/journal.pone.0114173 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX4MS UT WOS:000346907200050 PM 25478693 ER PT J AU Woody, G Bruce, D Korthuis, PT Chhatre, S Hillhouse, M Jacobs, P Sorensen, J Saxon, AJ Poole, S Metzger, D Ling, W AF Woody, George Bruce, Douglas Korthuis, P. Todd Chhatre, Sumedha Hillhouse, Maureen Jacobs, Petra Sorensen, James Saxon, Andrew J. Poole, Sabrina Metzger, David Ling, Walter TI Authors' Reply: "Risk Reduction With Buprenorphine-Naloxone and Methadone: Patient's Choice" SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter C1 [Woody, George; Chhatre, Sumedha; Poole, Sabrina; Metzger, David] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Woody, George; Chhatre, Sumedha; Jacobs, Petra; Metzger, David] Treatment Res Inst, Philadelphia, PA USA. [Bruce, Douglas] Yale Univ, Sch Med, New Haven, CT USA. [Korthuis, P. Todd] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Hillhouse, Maureen; Ling, Walter] Univ Calif Los Angeles, Los Angeles, CA USA. [Sorensen, James] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Saxon, Andrew J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Woody, G (reprint author), Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RI Metzger, David/D-9499-2012 FU NIAID NIH HHS [P30 AI045008]; NIDA NIH HHS [K05 DA-17009, K05 DA017009, U10 DA-13043, U10 DA013043, U10 DA013714, U10-DA013714, UG1 DA013714]; NIMH NIH HHS [P30 MH097488] NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 5 PY 2014 VL 67 IS 5 BP E142 EP E143 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AT2NW UT WOS:000344772300003 PM 25243431 ER PT J AU Pan, H He, MH Liu, RX Brecha, NC Yu, ACH Pu, ML AF Pan, Hong He, Meihua Liu, Ruixing Brecha, Nicholas C. Yu, Albert Cheung Hoi Pu, Mingliang TI Sulforaphane Protects Rodent Retinas against Ischemia-Reperfusion Injury through the Activation of the Nrf2/HO-1 Antioxidant Pathway SO PLOS ONE LA English DT Article ID NRF2-DEPENDENT PHASE-2 ENZYME; OXIDATIVE STRESS; HEME OXYGENASE-1; ISCHEMIA/REPERFUSION INJURY; PHARMACOLOGICAL INDUCTION; CALCIUM DOBESILATE; RESPONSE ELEMENT; KAPPA-B; CELLS; GENE AB Retinal ischemia-reperfusion (I/R) injury induces oxidative stress, leukocyte infiltration, and neuronal cell death. Sulforaphane (SF), which can be obtained in cruciferous vegetables such as broccoli, exerts protective effects in response to oxidative stress in various tissues. These effects can be initiated through nuclear factor E2-related factor 2 (Nrf2)-mediated induction of heme oxygenase-1 (HO-1). This investigation was designed to elucidate the neural protective mechanisms of SF in the retinal I/R rat model. Animals were intraperitoneally (i.p.) injected with SF (12.5 mg/kg) or vehicle (corn oil) once a day for 7 consecutive days. Then, retinal I/R was made by elevating the intraocular pressure (IOP) to 130 mmHg for 1 h. To determine if HO-1 was involved in the Nrf2 antioxidant pathway, rats were subjected to protoporphyrin IX zinc (II) (ZnPP, 30 mg/kg, i.p.) treatments at 24 h before retinal ischemia. The neuroprotective effects of SF were assessed by determining the morphology of the retina, counting the infiltrating inflammatory cells and the surviving retinal ganglion cells (RGCs) and amacrine cells, and measuring apoptosis in the retinal layers. The expression of Nrf2 and HO-1 was studied by immunofluorescence analysis and western blotting. I/R induced a marked increase of ROS generation, caused pronounced inflammation, increased the apoptosis of RGCs and amacrine cells and caused the thinning of the inner retinal layer (IRL), and these effects were diminished or abolished by SF pretreatment. Meanwhile, SF pretreatment significantly elevated the nuclear accumulation of Nrf2 and the level of HO-1 expression in the I/R retinas; however, ZnPP reversed the protective effects of SF on I/R retinas. Together, we offer direct evidence that SF had protective effects on I/R retinas, which could be attributed, at least in part, to the activation of the Nrf2/HO-1 antioxidant pathway. C1 [Pan, Hong; Yu, Albert Cheung Hoi] Peking Univ, Neurosci Res Inst, Dept Neurobiol, Sch Basic Med Sci, Beijing 100871, Peoples R China. [Pan, Hong; He, Meihua; Liu, Ruixing; Pu, Mingliang] Peking Univ, Dept Anat Embryol, Sch Basic Med Sci, Beijing 100871, Peoples R China. [Pan, Hong] Binzhou Med Coll, Dept Phys, Yantai, Shandong, Peoples R China. [Pan, Hong; He, Meihua; Liu, Ruixing; Pu, Mingliang] Peking Univ, Key Lab Machine Percept, Minist Educ, Beijing 100871, Peoples R China. [Pan, Hong; He, Meihua; Liu, Ruixing; Pu, Mingliang] Peking Univ, Key Lab Visual Impairment & Restorat, Minist Educ, Beijing 100871, Peoples R China. [Brecha, Nicholas C.] Univ Calif Los Angeles, Dept Med, David Geffen Sch Med Los Angeles, Jules Stein Eye Inst,CURE Digest Dis Res Ctr,Dept, Los Angeles, CA 90024 USA. [Brecha, Nicholas C.] Vet Adm Greater Los Angeles Hlth Syst, Los Angeles, CA USA. RP Pu, ML (reprint author), Peking Univ, Dept Anat Embryol, Sch Basic Med Sci, Beijing 100871, Peoples R China. EM mpu@hsc.pku.edu.cn RI He, Meihua/D-4312-2017 FU National Basic Research Program of China (973 Program) [2011CB510206]; National Science Foundation of China [30831160516, 81200691]; Ministry of Education of China [20090001120075]; Azalea Endowment Fund; Fundamental Research Fund for the Central Universities [21609101]; NIH [EY04067]; VA Merit Review FX This study was supported by grants obtained from the National Basic Research Program of China (973 Program, 2011CB510206 [MP]), the National Science Foundation of China (30831160516 [MP] and 81200691 [MH]), the Ministry of Education of China (20090001120075 [MH]), Azalea (1972) Endowment Fund (KS & RC), and the Fundamental Research Fund for the Central Universities (21609101, KS), NIH EY04067 (NCB) and VA Merit Review (NB). NCB is a VA Career Research Scientist. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 18 Z9 20 U1 2 U2 10 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 DEC 3 PY 2014 VL 9 IS 12 AR e114186 DI 10.1371/journal.pone.0114186 PG 24 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA7WS UT WOS:000349128700082 PM 25470382 ER PT J AU de Lima-Pardini, AC Coelho, DB Silva, MB Azzi, NM Martinelli, AR Horak, FB Teixeira, LA AF de Lima-Pardini, Andrea Cristina Coelho, Daniel Boari Silva, Marina Brito Azzi, Nametala Maia Martinelli, Alessandra Rezende Horak, Fay Bahling Teixeira, Luis Augusto TI Aging increases flexibility of postural reactive responses based on constraints imposed by a manual task SO FRONTIERS IN AGING NEUROSCIENCE LA English DT Article DE postural control; manual constraint; dual task; elderly; postural adaptation; balance control ID AGE-RELATED-CHANGES; PARKINSONIAN SUBJECTS; FALLS PREVENTION; BALANCE CONTROL; GRIP FORCE; LIFE-SPAN; COORDINATION; MOVEMENT; SET; ATTENTION AB This study compared the effect of stability constraints imposed by a manual task on the adaptation of postural responses between 16 healthy elderly (7.38) and 16 healthy young (mean age = 22.94 years, SD = 4.82) individuals. Postural stability was perturbed through unexpected release of a load attached to the participant's trunk while performing two versions of a voluntary task: holding a tray with a cylinder placed with its flat side down (low constraint) or with its rolling round side down (high constraint). Low and high constraint tasks were performed in alternate blocks of trials. Results showed that young participants adapted muscular activation and kinematics of postural responses in association with previous experience with the first block of manual task constraint, whereas the elderly modulated postural responses based on the current manual constraint. This study provides evidence for flexibility of postural strategies in the elderly to deal with constraints imposed by a manual task. C1 [de Lima-Pardini, Andrea Cristina] Univ Sao Paulo, Fac Med, Inst Radiol, Lab Med Invest LIM44, BR-05403900 Sao Paulo, Brazil. [Coelho, Daniel Boari; Silva, Marina Brito; Azzi, Nametala Maia; Martinelli, Alessandra Rezende; Teixeira, Luis Augusto] Univ Sao Paulo, Sch Phys Educ & Sport, Dept Human Movement Biodynam, Human Motor Syst Lab, BR-05403900 Sao Paulo, Brazil. [Horak, Fay Bahling] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. [Horak, Fay Bahling] Oregon Hlth & Sci Univ, Sch Med, Dept Neurol, Balance Disorders Lab, Portland, OR 97201 USA. RP de Lima-Pardini, AC (reprint author), Univ Sao Paulo, Fac Med, Inst Radiol, Lab Med Invest LIM44, Av Dr Eneas de Carvalho Aguiar,S-N Rua1, BR-05403900 Sao Paulo, Brazil. EM aclfisio@yahoo.com.br RI Coelho, Daniel/I-9369-2012 OI Coelho, Daniel/0000-0001-8758-6507; Teixeira, Luis/0000-0003-4132-0484 FU Coordination for the Improvement of Higher Level Personnel (CAPES, Brazil); Foundation for Research Advancement of the State of Sao Paulo (FAPESP, Brazil) [2009/11319-2]; Brazilian Council for Scientific and Technological Development (CNPq, Brazil) [200321/2010-2] FX We thank Coordination for the Improvement of Higher Level Personnel (CAPES, Brazil) for a studentship granted to the first author, the Foundation for Research Advancement of the State of Sao Paulo (FAPESP, Brazil), process number 2009/11319-2, and the Brazilian Council for Scientific and Technological Development (CNPq, Brazil), process number 200321/2010-2, for funding this research. We are also thankful to the great contribution in the review process given by the professor Kim Barrett from the University of California San Diego, USA, and to the participants of this study. NR 48 TC 2 Z9 2 U1 1 U2 6 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1663-4365 J9 FRONT AGING NEUROSCI JI Front. Aging Neurosci. PD DEC 3 PY 2014 VL 6 AR 327 DI 10.3389/fnagi.2014.00327 PG 9 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AY9RN UT WOS:000347888100001 PM 25520656 ER PT J AU Bharadwaj, R Peter, CJ Jiang, Y Roussos, P Vogel-Ciernia, A Shen, EY Mitchell, AC Mao, WJ Whittle, C Dincer, A Jakovcevski, M Pothula, V Rasmussen, TP Giakoumaki, SG Bitsios, P Sherif, A Gardner, PD Ernst, P Ghose, S Sklar, P Haroutunian, V Tamminga, C Myers, RH Futai, K Wood, MA Akbarian, S AF Bharadwaj, Rahul Peter, Cyril J. Jiang, Yan Roussos, Panos Vogel-Ciernia, Annie Shen, Erica Y. Mitchell, Amanda C. Mao, Wenjie Whittle, Catheryne Dincer, Aslihan Jakovcevski, Mira Pothula, Venu Rasmussen, Theodore P. Giakoumaki, Stella G. Bitsios, Panos Sherif, Ajfar Gardner, Paul D. Ernst, Patricia Ghose, Subroto Sklar, Pamela Haroutunian, Vahram Tamminga, Carol Myers, Richard H. Futai, Kensuke Wood, Marcelo A. Akbarian, Schahram TI Conserved Higher-Order Chromatin Regulates NMDA Receptor Gene Expression and Cognition SO NEURON LA English DT Article ID DE-NOVO MUTATIONS; GENOME-WIDE; SYNAPTIC-TRANSMISSION; SCHIZOPHRENIA RISK; PREFRONTAL CORTEX; ENERGY-METABOLISM; MAMMALIAN GENOMES; ENHANCER FUNCTION; SUBUNIT GENES; CYTOCHROME-C AB Three-dimensional chromosomal conformations regulate transcription by moving enhancers and regulatory elements into spatial proximity with target genes. Here we describe activity-regulated long-range loopings bypassing up to 0.5 Mb of linear genome to modulate NMDA glutamate receptor GRIN2B expression in human and mouse prefrontal cortex. Distal intronic and 3' intergenic loop formations competed with repressor elements to access promoter-proximal sequences, and facilitated expression via a "cargo'' of AP-1 and NRF-1 transcription factors and TALE-based transcriptional activators. Neuronal deletion or overexpression of Kmt2a/Mll1 H3K4-and Kmt1e/Setdb1 H3K9-methyl-transferase was associated with higher-order chromatin changes at distal regulatory Grin2b sequences and impairments in working memory. Genetic polymorphisms and isogenic deletions of loop-bound sequences conferred liability for cognitive performance and decreased GRIN2B expression. Dynamic regulation of chromosomal conformations emerges as a novel layer for transcriptional mechanisms impacting neuronal signaling and cognition. C1 [Bharadwaj, Rahul; Peter, Cyril J.; Jiang, Yan; Roussos, Panos; Shen, Erica Y.; Mitchell, Amanda C.; Dincer, Aslihan; Pothula, Venu; Sherif, Ajfar; Sklar, Pamela; Haroutunian, Vahram; Akbarian, Schahram] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Bharadwaj, Rahul; Peter, Cyril J.; Jiang, Yan; Roussos, Panos; Shen, Erica Y.; Mitchell, Amanda C.; Dincer, Aslihan; Pothula, Venu; Sherif, Ajfar; Sklar, Pamela; Haroutunian, Vahram; Akbarian, Schahram] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Roussos, Panos; Sklar, Pamela] Icahn Sch Med Mt Sinai, Inst Multiscale Biol, New York, NY 10029 USA. [Roussos, Panos; Haroutunian, Vahram] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Mao, Wenjie; Whittle, Catheryne; Gardner, Paul D.; Futai, Kensuke] Univ Massachusetts, Sch Med, Brudnick Neuropsychiat Res Inst, Worcester, MA 01604 USA. [Bitsios, Panos] Fdn Res & Technol Hellas, Inst Comp Sci, Computat Med Lab, Iraklion 71003, Greece. [Rasmussen, Theodore P.] Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT 06269 USA. [Rasmussen, Theodore P.] Univ Connecticut, Univ Conn Stem Cell Inst, Storrs, CT 06269 USA. [Jakovcevski, Mira] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Giakoumaki, Stella G.; Bitsios, Panos] Univ Crete, Dept Psychiat, Iraklion 71003, Greece. [Giakoumaki, Stella G.] Univ Crete, Dept Psychol, Iraklion 71003, Greece. [Ernst, Patricia] Geisel Sch Med Dartmouth, Norris Cotton Canc Ctr, Dept Genet, Hanover, NH 03755 USA. [Ernst, Patricia] Geisel Sch Med Dartmouth, Norris Cotton Canc Ctr, Dept Microbiol & Immunol, Hanover, NH 03755 USA. [Ghose, Subroto; Tamminga, Carol] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Myers, Richard H.] Boston Univ, Dept Neurol, Boston, MA 02118 USA. [Vogel-Ciernia, Annie; Wood, Marcelo A.] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92697 USA. RP Akbarian, S (reprint author), Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. EM schahram.akbarian@mssm.edu RI Dincer, Aslihan/N-4435-2015; Ghose, Subroto/J-6732-2016; Roussos, Panos/J-7090-2013 OI Dincer, Aslihan/0000-0002-4971-1597; Roussos, Panos/0000-0002-4640-6239; Peter, Cyril/0000-0001-9190-8724 FU National Institute of Mental Health [R01 MH086509, P50 MH096890]; National Institute of Neurological Disorders and Stroke [R01 NS073947-04]; National Institute of Drug Abuse [R01 DA036984]; NIH Brain and Tissue Repository grant [HHSN271201300031C]; VA; Veterans Affairs Merit grant [BX002395]; BBRF; APA-Merck & Co. Early Academic Career Research Award; Connecticut State Stem Cell Research Program [09-SCB-UCON-18]; Whitehall Foundation; University of Crete Research Funds Account [E.L.K.E. 1348] FX This work was supported by National Institute of Mental Health grants R01 MH086509 and P50 MH096890 (S.A.); National Institute of Neurological Disorders and Stroke grant R01 NS073947-04 (R.H.M.); National Institute of Drug Abuse grant R01 DA036984 (M.A.W. and S.A.); NIH Brain and Tissue Repository grant HHSN271201300031C and the VA, and Veterans Affairs Merit grant BX002395, BBRF, the APA-Merck & Co. Early Academic Career Research Award (P.R.); the Connecticut State Stem Cell Research Program (09-SCB-UCON-18) (T.P.R.); the Whitehall Foundation (K.F.); and the University of Crete Research Funds Account (E.L.K.E. 1348). The authors thank the participants and the personnel of the Military Training Camp of Candidate, Supply Army officers (SEAP) in Heraklion, Crete, for their help with the LOGOS study. NR 74 TC 13 Z9 13 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD DEC 3 PY 2014 VL 84 IS 5 BP 997 EP 1008 DI 10.1016/j.neuron.2014.10.032 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AW9JW UT WOS:000346574300012 PM 25467983 ER PT J AU Keyhani, S Myers, LJ Cheng, E Hebert, P Williams, LS Bravata, DM AF Keyhani, Salomeh Myers, Laura J. Cheng, Eric Hebert, Paul Williams, Linda S. Bravata, Dawn M. TI Effect of Clinical and Social Risk Factors on Hospital Profiling for Stroke Readmission A Cohort Study SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID MEDICARE BENEFICIARIES; 30-DAY READMISSION; HEART-FAILURE; CARE; PREDICTION; MORTALITY; IDENTIFY; PATIENT; MODELS; SCALE AB Background: The Centers for Medicare & Medicaid Services (CMS) and Veterans Health Administration (VA) will report 30-day stroke readmission rates as a measure of hospital quality. A national debate on whether social risk factors should be included in models developed for hospital profiling is ongoing. Objective: To compare a CMS-based model of 30-day readmission with a more comprehensive model that includes measures of social risk (such as homelessness) or clinical factors (such as stroke severity and functional status). Design: Data from a retrospective cohort study were used to develop a CMS-based 30-day readmission model that included age and comorbid conditions based on codes from the International Classification of Diseases, Ninth Revision, Clinical Modification (model 1). This model was then compared with one that included administrative social risk factors (model 2). Finally, the CMS model (model 1) was compared with a model that included social risk and clinical factors from chart review (model 3). These 3 models were used to rank hospitals by 30-day risk-standardized readmission rates and examine facility rankings among the models. Setting: Hospitals in the VA. Participants: Patients hospitalized with stroke in 2007. Measurements: 30-day readmission rates. Results: The 30-day readmission rate was 12.8%. The c-statistics for the 3 models were 0.636, 0.646, and 0.661, respectively. All hospitals were classified as performing "as expected" using all 3 models (that is, performance did not differ from the VA national average); therefore, the addition of detailed clinical information or social risk factors did not alter assessment of facility performance. Limitation: A predominantly male veteran cohort limits the generalizability of these findings. Conclusion: In the VA, more comprehensive models that included social risk and clinical factors did not affect hospital comparisons based on 30-day readmission rates. C1 [Keyhani, Salomeh] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Indiana Univ Sch Med, Vet Hlth Adm Hlth Serv Res & Dev, Stroke Qual Enhancement Res Initiat Program, Indianapolis, IN 46202 USA. Indiana Univ Sch Med, Ctr Excellence Implementing Evidence Based Practi, Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA. Regenstrief Inst Hlth Care, Indianapolis, IN USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Washington, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Keyhani, S (reprint author), San Francisco VA Med Ctr, 4150 Clement,111A1, San Francisco, CA 94121 USA. EM salomeh.keyhani@va.gov FU Veterans Health Administration Office of Quality and Performance; Health Services Research and Development Service Quality Enhancement Research Initiative of the Department of Veterans Affairs [RRP 12-192]; National Heart, Lung, and Blood Institute, U. S. Department of Health and Human Services [1R01HL116522-01A1] FX By the Veterans Health Administration Office of Quality and Performance and Health Services Research and Development Service Quality Enhancement Research Initiative of the Department of Veterans Affairs (RRP 12-192) and the National Heart, Lung, and Blood Institute, U.S. Department of Health and Human Services (1R01HL116522-01A1). NR 27 TC 9 Z9 9 U1 0 U2 5 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 DEC 2 PY 2014 VL 161 IS 11 BP 775 EP U51 DI 10.7326/M14-0361 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA AX9UJ UT WOS:000347247200006 PM 25437405 ER PT J AU Rubenstein, LV Danz, MS Crain, AL Glasgow, RE Whitebird, RR Solberg, LI AF Rubenstein, Lisa V. Danz, Marjorie S. Crain, A. Lauren Glasgow, Russell E. Whitebird, Robin R. Solberg, Leif I. TI Assessing organizational readiness for depression care quality improvement: relative commitment and implementation capability SO IMPLEMENTATION SCIENCE LA English DT Article DE Depression; Primary care; Quality improvement; Readiness; Measurement ID COLLABORATIVE CARE; RANDOMIZED-TRIAL; INTERVENTION; COSTS; MODEL AB Background: Depression is a major cause of morbidity and cost in primary care patient populations. Successful depression improvement models, however, are complex. Based on organizational readiness theory, a practice s commitment to change and its capability to carry out the change are both important predictors of initiating improvement. We empirically explored the links between relative commitment (i.e., the intention to move forward within the following year) and implementation capability. Methods: The DIAMOND initiative administered organizational surveys to medical and quality improvement leaders from each of 83 primary care practices in Minnesota. Surveys preceded initiation of activities directed at implementation of a collaborative care model for improving depression care. To assess implementation capability, we developed composites of survey items for five types of organizational factors postulated to be collaborative care barriers and facilitators. To assess relative commitment for each practice, we averaged leader ratings on an identical survey question assessing practice priorities. We used multivariable regression analyses to assess the extent to which implementation capability predicted relative commitment. We explored whether relative commitment or implementation capability measures were associated with earlier initiation of DIAMOND improvements. Results: All five implementation capability measures independently predicted practice leaders? relative commitment to improving depression care in the following year. These included the following: quality improvement culture and attitudes (p = 0.003), depression culture and attitudes (p < 0.001), prior depression quality improvement activities (p < 0.001), advanced access and tracking capabilities (p = 0.03), and depression collaborative care features in place (p = 0.03). Higher relative commitment (p = 0.002) and prior depression quality improvement activities appeared to be associated with earlier participation in the DIAMOND initiative. Conclusions: The study supports the concept of organizational readiness to improve quality of care and the use of practice leader surveys to assess it. Practice leaders relative commitment to depression care improvement may be a useful measure of the likelihood that a practice is ready to initiate evidence-based depression care changes. A comprehensive organizational assessment of implementation capability for depression care improvement may identify specific barriers or facilitators to readiness that require targeted attention from implementers. C1 [Rubenstein, Lisa V.; Danz, Marjorie S.] RAND Corp, Santa Monica, CA 90401 USA. [Rubenstein, Lisa V.; Danz, Marjorie S.] Vet Affairs Greater Los Angeles Healthcare Syst, North Hills, CA 91343 USA. [Crain, A. Lauren; Whitebird, Robin R.; Solberg, Leif I.] HealthPartners Res Fdn, Minneapolis, MN 55440 USA. [Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. RP Rubenstein, LV (reprint author), RAND Corp, 1776 Main St, Santa Monica, CA 90401 USA. EM lisar@rand.org FU National Institute of Mental Health [5R01MH080692] FX This research would not have been possible without the active support of many leaders and staff at the Institute for Clinical Systems Improvement, payers (Blue Cross and Blue Shield of Minnesota, First Plan, HealthPartners, Medica, Minnesota Department of Human Services, Preferred One, and U Care), and the medical groups and clinics. The success of the complex process for the clinical leader surveys is a tribute to both the leaders and study staff, in particular Kris Ohnsorg, Beth Molitor, and David Butani. The Veterans Affairs Center for Implementation Practice and Research Support (CIPRS) investigators and staff supported the manuscript development and preparation. The opinions expressed are those of the authors and do not necessarily represent those of the funding agency or the NIH. The support was provided by the National Institute of Mental Health grant number 5R01MH080692. NR 32 TC 2 Z9 2 U1 0 U2 10 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 DEC 2 PY 2014 VL 9 AR 173 DI 10.1186/s13012-014-0173-1 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AY2PT UT WOS:000347432600001 PM 25443652 ER PT J AU Rosendorff, C AF Rosendorff, Clive TI Blood Pressure Targets Still Struggling for the Right Answer SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE diabetes; elderly; goals; guidelines; hypertension ID HYPERTENSION; MANAGEMENT; GUIDELINES; SOCIETY C1 [Rosendorff, Clive] Icahn Sch Med Mt Sinai, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA. [Rosendorff, Clive] Icahn Sch Med Mt Sinai, Marie Josee & Henry R Kravis Ctr Cardiovasc Hlth, New York, NY 10029 USA. [Rosendorff, Clive] James J Peters VA Med Ctr, Bronx, NY 10468 USA. RP Rosendorff, C (reprint author), James J Peters VA Med Ctr, Med 110,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM clive.rosendorff@va.gov NR 13 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 2 PY 2014 VL 64 IS 21 BP 2204 EP 2206 DI 10.1016/j.jacc.2014.07.994 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AW0EA UT WOS:000345961900005 PM 25447262 ER PT J AU Gutierrez, B Kaatz, A Chu, S Ramirez, D Samson-Samuel, C Carnes, M AF Gutierrez, Belinda Kaatz, Anna Chu, Sarah Ramirez, Dennis Samson-Samuel, Clem Carnes, Molly TI "Fair Play'': A Videogame Designed to Address Implicit Race Bias Through Active Perspective Taking SO GAMES FOR HEALTH JOURNAL LA English DT Article ID ASSOCIATION TEST; ACADEMIC MEDICINE; STIGMATIZED GROUP; MINORITY FACULTY; RACIAL BIAS; EMPATHY; ATTITUDES; STEREOTYPES; INFORMATION; PREJUDICE AB Objective: Having diverse faculty in academic health centers will help diversify the healthcare workforce and reduce health disparities. Implicit race bias is one factor that contributes to the underrepresentation of Black faculty. We designed the videogame "Fair Play'' in which players assume the role of a Black graduate student named Jamal Davis. As Jamal, players experience subtle race bias while completing "quests'' to obtain a science degree. We hypothesized that participants randomly assigned to play the game would have greater empathy for Jamal and lower implicit race bias than participants randomized to read narrative text describing Jamal's experience. Materials and Methods: University of Wisconsin-Madison graduate students were recruited via e-mail and randomly assigned to play "Fair Play'' or read narrative text through an online link. Upon completion, participants took an Implicit Association Test to measure implicit bias and answered survey questions assessing empathy toward Jamal and awareness of bias. Results: As hypothesized, gameplayers showed the least implicit bias but only when they also showed high empathy for Jamal (P = 0.013). Gameplayers did not show greater empathy than text readers, and women in the text condition reported the greatest empathy for Jamal (P = 0.008). However, high empathy only predicted lower levels of implicit bias among those who actively took Jamal's perspective through gameplay (P = 0.014). Conclusions: A videogame in which players experience subtle race bias as a Black graduate student has the potential to reduce implicit bias, possibly because of a game's ability to foster empathy through active perspective taking. C1 [Gutierrez, Belinda; Carnes, Molly] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Gutierrez, Belinda; Kaatz, Anna; Carnes, Molly] Univ Wisconsin, Ctr Womens Hlth Res, Madison, WI 53715 USA. [Chu, Sarah; Ramirez, Dennis; Samson-Samuel, Clem] Univ Wisconsin, Games Learning & Soc, Madison, WI 53715 USA. [Chu, Sarah; Ramirez, Dennis; Samson-Samuel, Clem] Univ Wisconsin, Dept Curriculum & Instruct, Madison, WI 53715 USA. [Carnes, Molly] Univ Wisconsin, Dept Med, Madison, WI 53715 USA. [Carnes, Molly] Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. [Carnes, Molly] Univ Wisconsin, Dept Ind & Syst Engn, Madison, WI 53706 USA. RP Gutierrez, B (reprint author), Univ Wisconsin, Ctr Womens Hlth Res, 700 Regent St,Suite 301, Madison, WI 53715 USA. EM bgutierrez@wisc.edu FU NIGMS NIH HHS [DP4 GM096822, R25 GM083252] NR 67 TC 3 Z9 3 U1 2 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2161-783X EI 2161-7856 J9 GAMES HEALTH J JI Games Health J. PD DEC PY 2014 VL 3 IS 6 BP 371 EP 378 DI 10.1089/g4h.2013.0071 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Rehabilitation SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Rehabilitation GA CU2WW UT WOS:000363385400006 PM 26192644 ER PT J AU Jones, BL Smith, SM AF Jones, Brian L. Smith, Stephen M. TI Choice of Crystalloid and Mortality in Sepsis-All in the Timing? SO CRITICAL CARE MEDICINE LA English DT Letter C1 [Jones, Brian L.; Smith, Stephen M.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA. [Smith, Stephen M.] Portland VA Med Ctr, Sect Pulm & Crit Care Med, Portland, OR USA. RP Jones, BL (reprint author), Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA. OI Smith, Stephen/0000-0002-0331-7615 NR 3 TC 2 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 BP E796 EP E796 DI 10.1097/CCM.0000000000000594 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA CS4XX UT WOS:000362080700008 PM 25402300 ER PT J AU Byne, W AF Byne, William TI The First Year of LGBT Health: A Year of LGBT Progress in the United States SO LGBT HEALTH LA English DT Editorial Material DE LGBT; Medicare; same-sex marriage; sex reassignment surgery; pre-exposure prophylaxis C1 [Byne, William] James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY USA. [Byne, William] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. RP Byne, W (reprint author), James J Peters VAMC, Res Bldg,Room 2F39 130 West Kingsbridge Rd, Bronx, NY 10467 USA. EM william.byne@mssm.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2325-8292 EI 2325-8306 J9 LGBT HEALTH JI LGBT Health PD DEC PY 2014 VL 1 IS 4 BP 239 EP 241 DI 10.1089/lgbt.2014.0085 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CR9QK UT WOS:000361691400001 PM 26789849 ER PT J AU Blosnich, JR Brown, GR Wojcio, S Jones, KT Bossarte, RM AF Blosnich, John R. Brown, George R. Wojcio, Sybil Jones, Kenneth T. Bossarte, Robert M. TI Mortality Among Veterans with Transgender-Related Diagnoses in the Veterans Health Administration, FY2000-2009 SO LGBT HEALTH LA English DT Article DE mortality; suicide; transgender persons; veterans ID GENDER IDENTITY DISORDER; PSYCHIATRIC COMORBIDITY; SUICIDAL IDEATION; RISK BEHAVIORS; HIV PREVALENCE; UNITED-STATES; CARE; SYSTEM; TRANSSEXUALISM; PEOPLE AB Purpose: The aims of this project were to document all-cause and suicide mortality among Veteran Healthcare Administration (VHA) utilizers with The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis consistent with transgender status. Methods: The study population consisted of VHA patients identified as having any one of four diagnosis codes indicating transgender status (n = 5,117) gathered from the VA National Patient Care Database. Mortality data were gathered from the National Death Index from 2000-2009 for 1,277 veterans with transgender-related ICD-9-CM diagnoses. The remaining 3,840 were not searched because they had VHA utilization after 2009 (indicating they were alive). Person-time at risk (person-years) for crude rates were calculated based on the time from an individual's index diagnosis to either death or the end of FY 2009. Causes of death were categorized using ICD-10 code groups. Results: Approximately 9.3% (n = 309) veterans with transgender-related ICD-9-CM diagnoses died across the study period. Although diseases of the circulatory system and neoplasms were the first and second leading causes of death, respectively, the other ranked causes of mortality differed somewhat from patterns for the US during the same time span. The crude suicide rate among veterans with transgender-related ICD-9-CM diagnoses across the 10-year period was approximately 82/100,000 person-years, which approximated the crude suicide death rates for other serious mental illness in VHA (e.g., depression, schizophrenia). The average age of suicide decedents was 49.4 years. Conclusion: The crude suicide rate among veterans with transgender-related ICD-9-CM diagnoses is higher than in the general population, and they may be dying by suicide at younger ages than their veteran peers without transgender-related ICD-9-CM diagnoses. Future research, such as age-adjusted rates or accounting for psychiatric co-morbidities, will help to better clarify if the all-cause and suicide mortality rates are elevated for veterans with transgender-related ICD-9-CM diagnoses. C1 [Blosnich, John R.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Blosnich, John R.; Bossarte, Robert M.] Univ Rochester, Dept Psychiat, Rochester, NY USA. [Blosnich, John R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA USA. [Brown, George R.; Jones, Kenneth T.] VA Cent Off, Off Hlth Equ, Washington, DC USA. [Brown, George R.] E Tennessee State Univ, Dept Psychiat & Behav Sci, Johnson City, TN 37614 USA. [Wojcio, Sybil; Bossarte, Robert M.] VISN2 Ctr Excellence Suicide Prevent, Canandaigua, NY USA. RP Blosnich, JR (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C 151C-U,Bldg 30, Pittsburgh, PA 15240 USA. EM john.blosnich@va.gov FU VISN2 Center of Excellence for Suicide Prevention; Department of Veterans Affairs Office of Academic Affiliations; Center for Health Equity Research and Promotion at the VA Pittsburgh Healthcare System FX This work was partially supported by the VISN2 Center of Excellence for Suicide Prevention and a postdoctoral fellowship to JRB through the Department of Veterans Affairs Office of Academic Affiliations and the Center for Health Equity Research and Promotion at the VA Pittsburgh Healthcare System. NR 56 TC 5 Z9 5 U1 0 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2325-8292 EI 2325-8306 J9 LGBT HEALTH JI LGBT Health PD DEC PY 2014 VL 1 IS 4 BP 269 EP 276 DI 10.1089/lgbt.2014.0050 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CR9QK UT WOS:000361691400007 PM 26789855 ER PT J AU Liu, M Bashir, M Williams, KJ Werth, VP AF Liu, M. Bashir, M. Williams, K. J. Werth, V. P. TI Novel roles for cholesterol and the cytoskeleton in the formation of neutrophil extracellular traps. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Liu, M.; Bashir, M.; Werth, V. P.] Univ Penn, Dermatol, Philadelphia, PA 19104 USA. [Liu, M.; Bashir, M.; Werth, V. P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Liu, M.; Williams, K. J.] Temple Univ, Med, Philadelphia, PA 19122 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1678 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094104143 ER PT J AU Shelton, JB Skolarus, TA Ordin, D Malin, J Antonio, A Ryoo, J Saigal, CS AF Shelton, Jeremy B. Skolarus, Ted A. Ordin, Diana Malin, Jennifer Antonio, AnnaLiza Ryoo, Joan Saigal, Christopher S. TI Validating Electronic Cancer Quality Measures at Veterans Health Administration SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID SURGERY REPORT CARDS; MEDICAL-RECORDS; PROSTATE-CANCER; CLINICAL-DATA; PERFORMANCE; DELIVERY; VALIDITY; AFFAIRS; REFORM AB Objectives To assess the feasibility and validity of developing electronic clinical quality measures (eCQMs) of cancer care quality from existing metrics, using electronic health records, administrative, and cancer registry data. Study Design Retrospective comparison of quality indicators using chart abstracted versus electronically available data from multiple sources. Methods We compared the sensitivity and specificity of eCQMs created from structured data from electronic health records (EHRs) linked to administrative and cancer registry data to data abstracted from patients' electronic health records. Twenty-nine measures of care were assessed in 15,394 patients with either incident lung or prostate cancer from 2007 and 2008, respectively, and who were treated in the Veteran's Health Administration (VHA). Results It was feasible to develop eCQMs for 11 of 18 (61%) lung cancer measures, 4 (22%) of which were considered to be valid measures of the care constructs. Among prostate cancer measures, 6 of 11 (55%) were feasible, and 4 (36%) were both feasible and valid. Of the 29 metrics, data was available to create eCQMs for 17 (59%) cancer care metrics, and 8 (28%) were considered valid. Conclusions In a large integrated healthcare system with nationally standardized electronic health records, administrative, and cancer registry data, 28% of cancer quality measures developed for chart abstraction could be translated into valid eCQMs. These results raise much concern about the development of electronic clinical quality measures for cancer care, particularly in healthcare environments where data are disparate in both form and location C1 [Antonio, AnnaLiza] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Shelton, Jeremy B.] VA Greater Los Angeles Healthcare Syst, Urol, Informat, HSR&D, Los Angeles, CA USA. [Malin, Jennifer] VA Greater Los Angeles Healthcare Syst, Oncol, Los Angeles, CA USA. [Skolarus, Ted A.] Univ Michigan, VA Ann Arbor Healthcare Syst, Urol, HSR&D, Ann Arbor, MI 48109 USA. [Ordin, Diana] VA, Washington, DC USA. [Ryoo, Joan] Kaiser Permanente Med Ctr, Los Angeles, CA 90034 USA. [Saigal, Christopher S.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Shelton, JB (reprint author), Vet Affairs Surg, 13301 Wilshire Blvd,Bldg 500, Los Angeles, CA 90073 USA. EM jeremy.shelton@va.gov FU Veterans Affairs Office of Analytics and Business Intelligence; UCLA Career Development Program in Cancer Prevention and Control Research R25 Grant [CA 087949-13] FX This study was funded by the Veterans Affairs Office of Analytics and Business Intelligence. This study was supported in part by the UCLA Career Development Program in Cancer Prevention and Control Research R25 Grant CA 087949-13 (JBS). NR 42 TC 1 Z9 1 U1 2 U2 3 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD DEC PY 2014 VL 20 IS 12 BP 1041 EP + PG 16 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CD3TS UT WOS:000351005400013 PM 25526392 ER PT J AU Sturmberg, J Lanham, HJ AF Sturmberg, Joachim Lanham, Holly J. TI Understanding health care delivery as a complex system Achieving best possible health outcomes for individuals and communities by focusing on interdependencies SO JOURNAL OF EVALUATION IN CLINICAL PRACTICE LA English DT Article DE complexity in health; efficient and effective health system; health care reform; health systems reform; non-linear dynamics; patient-centred care; person-centred medicine ID SOCIAL SUPPORT; MEDICAL HOMES; MORTALITY; CONSULTATION; LESSONS; ECOLOGY; CANCER AB Rationale, aims and objectives The concept of emergence offers a new way of thinking about multimorbidity and chronic disease. Results and conclusions Multimorbidity and chronic disease are the end results of ongoing perturbations and interconnected activities of simpler substructures that collectively constitute the complex adaptive superstructure known as us, the person or patient. Medical interventions cause perturbations of many different subsystems within the patient, hence they are not limited to the person's bodily function, but also affect his general health perception and his interactions with his external environments. Changes in these domains inevitably have consequences on body function, and close the feedback loop of illness/disease, recovery and regained health. C1 [Sturmberg, Joachim] Univ Newcastle, Dept Gen Practice, Newcastle, NSW 2260, Australia. [Lanham, Holly J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Lanham, Holly J.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Sturmberg, J (reprint author), Univ Newcastle, Dept Gen Practice, Newcastle, NSW 2260, Australia. EM jp.sturmberg@gmail.com NR 45 TC 3 Z9 3 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1356-1294 EI 1365-2753 J9 J EVAL CLIN PRACT JI J. Eval. Clin. Pract. PD DEC PY 2014 VL 20 IS 6 BP 1005 EP 1009 DI 10.1111/jep.12142 PG 5 WC Health Care Sciences & Services; Medical Informatics; Medicine, General & Internal SC Health Care Sciences & Services; Medical Informatics; General & Internal Medicine GA CC6BS UT WOS:000350450200043 PM 24797788 ER PT J AU Kerns, E Patel, S Cohen, DM AF Kerns, Eric Patel, Shweta Cohen, David M. TI Hourly oral sodium chloride for the rapid and predictable treatment of hyponatremia SO CLINICAL NEPHROLOGY LA English DT Article DE osmoregulation; arginine vasopressin; hyponatremia; sodium chloride ID OPTIC CHIASM GLIOMA; INAPPROPRIATE SECRETION; NONOBSTRUCTIVE HYDROCEPHALUS; ANTIDIURETIC-HORMONE; HYPERTONIC SALINE; WATER; OVERCORRECTION; VALPROATE; ASCITES; ABNORMALITIES AB Hypertonic NaCl is first-line therapy for acute, severe and symptomatic hyponatremia; however, its use is often restricted to the intensive care unit (ICU). A 35-year-old female inpatient with an optic chiasm glioma and ventriculoperitoneal shunt for hydrocephalus developed acute hyponatremia (sodium 122 mEq/L) perhaps coinciding with haloperidol treatment. The sum of her urinary sodium and potassium concentrations was markedly hypertonic vis-a-vis plasma; it was inferred that serum sodium concentration would continue to fall even in the complete absence of fluid intake. Intravenous (IV) 3% NaCl was recommended; however, a city-wide public health emergency precluded her transfer to the ICU. She was treated with hourly oral NaCl tablets in a dose calculated to deliver the equivalent of 0.5 mL/kg/h of 3% NaCl with an objective of increasing the serum sodium concentration by 6 mEq/L. She experienced a graded and predictable increase in serum sodium concentration. A slight overshoot to 129 mEq/L was rapidly corrected with 0.25 l of D5W, and she stabilized at 127 mEq/L. We conclude that hourly oral NaCl, in conjunction with careful monitoring of the serum sodium concentration, may provide an attractive alternative to IV 3% NaCl for selected patients with severe hyponatremia. C1 [Kerns, Eric; Patel, Shweta; Cohen, David M.] Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97239 USA. [Cohen, David M.] Portland VA Med Ctr, Portland, OR USA. RP Cohen, DM (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Mailcode CH12R,3303 SW Bond Ave, Portland, OR 97239 USA. EM cohend@ohsu.edu FU National Institutes of Health; Department of Veterans Affairs; American Heart Association FX This work is supported by grants from the National Institutes of Health, the Department of Veterans Affairs, and the American Heart Association. The authors have no conflict of interest related to the contents of this manuscript. NR 33 TC 2 Z9 2 U1 2 U2 3 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD DEC PY 2014 VL 82 IS 6 BP 397 EP 401 DI 10.5414/CN108014 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA AZ6SM UT WOS:000348350000008 PM 23816479 ER PT J AU Carrithers, MD AF Carrithers, Michael D. TI Update on Disease-Modifying Treatments for Multiple Sclerosis SO CLINICAL THERAPEUTICS LA English DT Review DE immune therapy; multiple sclerosis; interferon; glatiramer; natalizumab; fumarate ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PLACEBO-CONTROLLED TRIAL; INTERFERON BETA-1A THERAPY; CONTROLLED PHASE-3 TRIAL; QUALITY-OF-LIFE; DOUBLE-BLIND; GLATIRAMER ACETATE; IMMUNE SURVEILLANCE; ORAL TERIFLUNOMIDE; DIMETHYL FUMARATE AB Purpose: The purpose of this review is to discuss the selection and use of disease- modifying treatments for patients with relapsing forms of multiple sclerosis (MS). Methods: PubMed was searched (1966-2014) using the terms multiple sclerosis, treatment, interferon, glatiramer acetate, dimethyl fumarate, fingolimod, teri-flunomide, natalizumab, rituximab, and alemtuzumab. Findings: MS is a chronic neurological disorder that can cause a substantial degree of disability. Because of its usual onset in young adults, patients may require treatment for several decades. Currently available agents include platform injectable therapies, newer oral agents, and second-line monoclonal antibody treatments. Treatment decisions have become more complex with the introduction of new approaches, and a major goal is to balance perceived efficacy and tolerability in a specific patient with the relative impact of disease activity and adverse events on quality of life. Here the options for disease-modifying treatments for relapsing forms of MS are reviewed, and current and future challenges are discussed. Implications: An evidence-based approach can be used for the selection of disease-modifying treatments based on disease phenotype and severity, adverse events, and perceived efficacy. Published by Elsevier HS Journals, Inc. C1 [Carrithers, Michael D.] Univ Wisconsin, Sch Med & Publ Hlth, Neurol Serv, William S Middleton Mem Vet Hosp,Dept Neurol, Madison, WI 53706 USA. [Carrithers, Michael D.] Univ Wisconsin, Sch Med & Publ Hlth, Neurol Serv, William S Middleton Mem Vet Hosp,Dept Pathol, Madison, WI 53706 USA. [Carrithers, Michael D.] Univ Wisconsin, Sch Med & Publ Hlth, Program Cellular & Mol Pathol, Madison, WI 53706 USA. RP Carrithers, MD (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, 1300 Univ Ave,Room 2679, Madison, WI 53706 USA. EM carrithers@neurology.wisc.edu FU Biogen-Idec/Elan; U.S. Department of Veterans Affairs; National Multiple Sclerosis Society; NIH FX Dr. Carrithers has currently or previously received research funding from Biogen-Idec/Elan, the U.S. Department of Veterans Affairs, the National Multiple Sclerosis Society, and NIH. NR 65 TC 17 Z9 18 U1 2 U2 22 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD DEC PY 2014 VL 36 IS 12 BP 1938 EP 1945 DI 10.1016/j.clinthera.2014.08.006 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AZ2OK UT WOS:000348072500009 PM 25218310 ER PT J AU Bott, NT Johnson, ET Schutt, N Galifianakis, N Subas, T Pollock, J Pressman, P Kramer, JH Possin, KL AF Bott, Nicholas T. Johnson, Erica T. Schutt, Norbert Galifianakis, Nicholas Subas, Trishna Pollock, Jessica Pressman, Peter Kramer, Joel H. Possin, Katherine L. TI Sensitive measures of executive dysfunction in non-demented Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease; Mild cognitive impairment; Executive function; Cognitive control; Working memory ID MILD COGNITIVE IMPAIRMENT; RIVASTIGMINE; DEMENTIA AB Background: We examined the sensitivity of different executive function measures for detecting deficits in Parkinson's disease patients without dementia. Methods: Twenty-one non-demented PD subjects and 21 neurologically healthy controls were administered widely used clinical executive functioning measures as well as the NIH EXAMINER battery, which produces Cognitive Control, Working Memory, and Verbal Fluency scores, along with an overall Executive Composite score, using psychometrically matched scales. Results: No significant differences between groups were observed on widely used clinical measures. The PD patients scored lower than controls on the EXAMINER Executive Composite, Cognitive Control, and Working Memory Scores. Conclusions: The NIH EXAMINER Executive Composite and Cognitive Control Scores are sensitive measures of executive dysfunction in non-demented PD, and may be more sensitive than several widely used measures. Results highlight the importance of careful test selection when evaluating for mild cognitive impairment in PD. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Bott, Nicholas T.; Johnson, Erica T.; Subas, Trishna; Pressman, Peter; Kramer, Joel H.; Possin, Katherine L.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA. [Schutt, Norbert; Pollock, Jessica] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Schutt, Norbert; Pollock, Jessica] Dept Vet Affairs Med Ctr, San Francisco, CA USA. [Galifianakis, Nicholas] San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA USA. RP Bott, NT (reprint author), 675 Nelson Rising Lane,Suite 190,Box 1207, San Francisco, CA 94158 USA. EM nbott@stanford.edu FU National Institute on Aging [K23AG037566, R01AG032289, P50AG023501]; Larry L Hillblom Foundation (Miller); Hellman Family Foundation; Michael J. Fox Foundation FX This study was supported by the National Institute on Aging (Possin: K23AG037566; Kramer: R01AG032289; Miller: P50AG023501), the Larry L Hillblom Foundation (Miller, 2007/21), the Hellman Family Foundation, and MJFF2011, MRI signature of Parkinson's disease from the Michael J. Fox Foundation. NR 16 TC 2 Z9 2 U1 1 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD DEC PY 2014 VL 20 IS 12 BP 1430 EP 1433 DI 10.1016/j.parkreldis.2014.10.007 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA AY6FF UT WOS:000347662000021 PM 25454318 ER PT J AU Clark, KB AF Clark, Kevin B. TI Evolution of affective and linguistic disambiguation under social eavesdropping pressures SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material ID NONHUMAN PRIMATE; INFORMATION; LANGUAGE; VOCALIZATIONS; COMPREHENSION; STRATEGIES; RESOLUTION; MONKEYS AB Contradicting new dual-pathway models of language evolution, cortico-striatal-thalamic circuitry disambiguate uncertainties in affective prosody and propositional linguistic content of language production and comprehension, predictably setting limits on useful complexity of articulate phonic and/or signed speech. Such limits likely evolved to ensure public information is discriminated by intended communicants and safeguarded against the ecological pressures of social eavesdropping within and across phylogenetic boundaries. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Res & Dev Serv, Los Angeles, CA 90073 USA. RP Clark, KB (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Res & Dev Serv, Los Angeles, CA 90073 USA. EM kbclarkphd@yahoo.com NR 32 TC 0 Z9 0 U1 1 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0140-525X EI 1469-1825 J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD DEC PY 2014 VL 37 IS 6 DI 10.1017/S0140525X13003993 PG 6 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA AZ2IE UT WOS:000348056700007 ER PT J AU Chiang, S Stern, JM Engel, J Levin, HS Haneef, Z AF Chiang, Sharon Stern, John M. Engel, Jerome, Jr. Levin, Harvey S. Haneef, Zulfi TI Differences in graph theory functional connectivity in left and right temporal lobe epilepsy SO EPILEPSY RESEARCH LA English DT Article DE Brain imaging; Epilepsy; Functional MRI; Graph theory; Functional reorganization ID STRUCTURAL CONNECTIVITY; COGNITIVE DECLINE; HUMAN BRAIN; SMALL-WORLD; NETWORKS; MRI; MEMORY; FMRI; LATERALIZATION; ABNORMALITIES AB Purpose: To investigate lateralized differences in limbic system functional connectivity between left and right temporal lobe epilepsy (TLE) using graph theory. Methods: Interictal resting state fMRI was performed in 14 left TLE patients, 11 right TLE patients, and 12 controls. Graph theory analysis of 10 bilateral limbic regions of interest was conducted. Changes in edgewise functional connectivity, network topology, and regional topology were quantified, and then left and right TLE were compared. Results: Limbic edgewise functional connectivity was predominantly reduced in both left and right TLE. More regional connections were reduced in right TLE, most prominently involving reduced interhemispheric connectivity between the bilateral insula and bilateral hippocampi. A smaller number of limbic connections were increased in TLE, more so in left than in right TLE. Topologically, the most pronounced change was a reduction in average network betweenness centrality and concurrent increase in left hippocampal betweenness centrality in right TLE. In contrast, left TLE exhibited a weak trend toward increased right hippocampal betweenness centrality, with no change in average network betweenness centrality. Conclusion: Limbic functional connectivity is predominantly reduced in both left and right TLE, with more pronounced reductions in right TLE. In contrast, left TLE exhibits both edgewise and topological changes that suggest a tendency toward reorganization. Network changes in TLE and lateralized differences thereof may have important diagnostic and prognostic implications. Published by Elsevier B.V. C1 [Chiang, Sharon] Rice Univ, Dept Stat, Houston, TX 77251 USA. [Stern, John M.; Engel, Jerome, Jr.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Engel, Jerome, Jr.] Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA USA. [Engel, Jerome, Jr.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Engel, Jerome, Jr.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. [Levin, Harvey S.] Baylor Coll Med, Dept Phys Med, Houston, TX 77030 USA. [Levin, Harvey S.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Haneef, Zulfi] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Haneef, Zulfi] VA Med Ctr, Neurol Care Line, Houston, TX USA. RP Haneef, Z (reprint author), Baylor Coll Med, Dept Neurol, One Baylor Plaza,MS NB302, Houston, TX 77030 USA. EM zulfi.haneef@bcm.edu OI Chiang, Sharon/0000-0002-4548-4550 FU Epilepsy Foundation of America; National Library of Medicine Training Fellowship in Biomedical Informatics, Gulf Coast Consortia for Quantitative Biomedical Sciences [2T15LM007093-21]; National Institute of Health [5T32CA096520-07]; Leff Family Foundation; National Institute of Neurological Disorders and Stroke [P01 NS02808, R01 NS33310, U01 NS42372, P20 NS80181]; Moody Foundation; Baylor College of Medicine Computational and Integrative Biomedical Research Center FX Funding for design and conduct of this study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript was provided by the Epilepsy Foundation of America. Support for this publication was provided by the National Library of Medicine Training Fellowship in Biomedical Informatics, Gulf Coast Consortia for Quantitative Biomedical Sciences (Grant #2T15LM007093-21) (SC); the National Institute of Health (Grant #5T32CA096520-07) (SC); the Leff Family Foundation (JMS); the National Institute of Neurological Disorders and Stroke (Grants #P01 NS02808, R01 NS33310, U01 NS42372, P20 NS80181) (JE); the Moody Foundation (HSL); Epilepsy Foundation of America (Research Grants Program) (ZH); and the Baylor College of Medicine Computational and Integrative Biomedical Research Center Seed Grant Awards (ZH). NR 51 TC 7 Z9 7 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 EI 1872-6844 J9 EPILEPSY RES JI Epilepsy Res. PD DEC PY 2014 VL 108 IS 10 BP 1770 EP 1781 DI 10.1016/j.eplepsyres.2014.09.023 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA AY3RP UT WOS:000347500600011 PM 25445238 ER PT J AU Lankford, HV Swenson, ER AF Lankford, Harvey V. Swenson, Erik R. TI Dilated Hearts at High Altitude: Words From On High SO HIGH ALTITUDE MEDICINE & BIOLOGY LA English DT Article DE altitude; cor pulmonale; dilated; Everest; heart; pulmonary; ventricle ID OPERATION EVEREST-II; MOUNTAIN-SICKNESS; EXTREME ALTITUDE; FAILURE; MASS AB Lankford, Harvey V, Erik R Swenson. Dilated hearts at high altitude: Words from on high. High Alt Med Biol 15:511-519, 2014.From the time of the turn of the twentieth century, dilated hearts and presumed cardiac fatigue in expeditionary climbers and scientists have been the subject of much commentary in the medical and mountaineering literature. Although largely attributed by most, but not all, to left heart strain, the description of dilated hearts in these accounts is clearly that of right heart dilation as a consequence of high and sustained hypoxic pulmonary vasoconstriction with hypertensive remodeling. This essay will feature quotations from the writings of high altitude pioneers about dilated, strained, or enlarged hearts. It will give some brief physiology of the right side of the heart as background, but will focus on the words of mountaineers and mountaineering physicians as color commentary. C1 [Swenson, Erik R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Lankford, HV (reprint author), 8001 Riverside Dr, Richmond, VA 23225 USA. EM h.lankford@gmail.com NR 62 TC 2 Z9 2 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1527-0297 EI 1557-8682 J9 HIGH ALT MED BIOL JI High Alt. Med. Biol. PD DEC 1 PY 2014 VL 15 IS 4 BP 511 EP 519 PG 9 WC Biophysics; Public, Environmental & Occupational Health; Sport Sciences SC Biophysics; Public, Environmental & Occupational Health; Sport Sciences GA AX0HB UT WOS:000346632500032 PM 25369424 ER PT J AU Vick, JC Campbell, TF Shriberg, LD Green, JR Truemper, K Rusiewicz, HL Moore, CA AF Vick, Jennell C. Campbell, Thomas F. Shriberg, Lawrence D. Green, Jordan R. Truemper, Klaus Rusiewicz, Heather Leavy Moore, Christopher A. TI Data-Driven Subclassification of Speech Sound Disorders in Preschool Children SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article ID CLASSIFICATION-SYSTEM SDCS; UNDIFFERENTIATED LINGUAL GESTURES; LIP MUSCLE-ACTIVITY; LANGUAGE IMPAIRMENT; CHILDHOOD APRAXIA; DEVELOPMENTAL APRAXIA; RELIABILITY; COORDINATION; EXTENSIONS; KINEMATICS AB Purpose: The purpose of the study was to determine whether distinct subgroups of preschool children with speech sound disorders (SSD) could be identified using a subgroup discovery algorithm (SUBgroup discovery via Alternate Random Processes, or SUBARP). Of specific interest was finding evidence of a subgroup of SSD exhibiting performance consistent with atypical speech motor control. Method: Ninety-seven preschool children with SSD completed speech and nonspeech tasks. Fifty-three kinematic, acoustic, and behavioral measures from these tasks were input to SUBARP. Results: Two distinct subgroups were identified from the larger sample. The 1st subgroup (76%; population prevalence estimate = 67.8%-84.8%) did not have characteristics that would suggest atypical speech motor control. The 2nd subgroup (10.3%; population prevalence estimate = 4.3%-16.5%) exhibited significantly higher variability in measures of articulatory kinematics and poor ability to imitate iambic lexical stress, suggesting atypical speech motor control. Both subgroups were consistent with classes of SSD in the Speech Disorders Classification System (SDCS; Shriberg et al., 2010a). Conclusion: Characteristics of children in the larger subgroup were consistent with the proportionally large SDCS class termed speech delay; characteristics of children in the smaller subgroup were consistent with the SDCS subtype termed motor speech disorder-not otherwise specified. The authors identified candidate measures to identify children in each of these groups. C1 [Vick, Jennell C.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Campbell, Thomas F.; Truemper, Klaus] Univ Texas Dallas, Richardson, TX 75083 USA. [Shriberg, Lawrence D.] Univ Wisconsin, Waisman Ctr, Madison, WI 53706 USA. [Green, Jordan R.] MGH Inst Hlth Profess, Boston, MA USA. [Rusiewicz, Heather Leavy] Duquesne Univ, Pittsburgh, PA 15219 USA. [Moore, Christopher A.] US Dept Vet Affairs, Washington, DC USA. RP Vick, JC (reprint author), Case Western Reserve Univ, Cleveland, OH 44106 USA. EM jennell@case.edu FU National Institute on Deafness and Other Communication Disorders [R01 DC00822]; American Speech-Language-Hearing Foundation FX Funding for this project was provided by the National Institute on Deafness and Other Communication Disorders (Grant R01 DC00822; principal investigator, Christopher A. Moore) and the American Speech-Language-Hearing Foundation (New Century Scholars Doctoral Scholarship to Jennell C. Vick). We are especially grateful to the participants and their families, who graciously volunteered their time for this project. In addition, we gratefully acknowledge those whose work was critical for participant recruitment, data acquisition, data extraction, and computer programming: Tammy Nash, Jill Brady, Dayna Pitcairn, Denise Balason, Stacey Pavelko, Mitzi Kweder, Katherine Moreland, Lakshmi Venkatesh, Sharon Gretz, Kevin Reilly, Roger Steeve, Kathryn Connaghan, Yumi Sumida, Alyssa Mosely, Rossella Belli, Ettore Cavallaro, Jeanette Wu, Jenny Morus, Kelsey Moore, Mary Reeves, Nicholas Moon, Dennis Tang, Adam Politis, Andrea Kettler, Laura Worthen, Dara Cohen, Heather Mabie, Rebecca Mental, Michelle Foye, and Greg Lee. NR 60 TC 3 Z9 3 U1 2 U2 9 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 EI 1558-9102 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD DEC PY 2014 VL 57 IS 6 BP 2033 EP 2050 DI 10.1044/2014_JSLHR-S-12-0193 PG 18 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AZ4MK UT WOS:000348195300001 PM 25076005 ER PT J AU Lee, LY Koehler, UA Zhang, L Roenneburg, D Werner, S Johnson, JA Foley, DP AF Lee, Lung-Yi Koehler, Ulrike A. Zhang, Li Roenneburg, Drew Werner, Sabine Johnson, Jeffrey A. Foley, David P. TI Activation of the Nrf2-ARE Pathway in Hepatocytes Protects Against Steatosis in Nutritionally Induced Non-alcoholic Steatohepatitis in Mice SO TOXICOLOGICAL SCIENCES LA English DT Article DE liver; Nrf2; antioxidants; steatosis; NASH; transgenic mice ID HIGH-FAT DIET; OXIDATIVE STRESS; LIPID-ACCUMULATION; HEPATIC STEATOSIS; NRF2-NULL MICE; LIVER-DISEASE; ALPHA-SMA; EXPRESSION; GENES; KEAP1 AB Oxidative stress is implicated in the development of non-alcoholic steatohepatitis (NASH). The Nrf2-antioxidant response element pathway protects cells from oxidative stress. Studies have shown that global Nrf2 deficiency hastens the progression of NASH. The purpose of this study was to determine whether long-term hepatocyte-specific activation of Nrf2 mitigates NASH progression. Transgenic mice expressing a constitutively active Nrf2 construct in hepatocytes (AlbCre+/caNrf2+) and littermate controls were generated. These mice were fed standard or methionine-choline-deficient (MCD) diet, a diet used to induce NASH development in rodents. After 28 days of MCD dietary feeding, mice developed significant increases in steatosis, inflammation, oxidative stress, and HSC activation compared with those mice on standard diet. AlbCre+/caNrf2+ animals had significantly decreased serum transaminases and reduced steatosis when compared with the AlbCre+/caNrf2- animals. This significant reduction in steatosis was associated with increased expression of genes involved in triglyceride export (MTTP) and beta-oxidation (CPT2). However, there were no differences in the increased oxidative stress, inflammation, and HSC activation from MCD diet administration between the AlbCre+/caNrf2- and AlbCre+/caNrf2+ animals. We conclude that hepatocyte-specific activation of Nrf2-mediated gene expression decreased hepatocellular damage and steatosis in a dietary model of NASH. However, hepatocyte-specific induction of Nrf2-mediated gene expression alone is insufficient to mitigate inflammation, oxidative stress, and HSC activation in this nutritional NASH model. C1 [Lee, Lung-Yi; Zhang, Li; Roenneburg, Drew; Foley, David P.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI 53726 USA. [Koehler, Ulrike A.; Werner, Sabine] Swiss Fed Inst Technol, Inst Mol Hlth Sci, Dept Biol, CH-8093 Zurich, Switzerland. [Johnson, Jeffrey A.] Univ Wisconsin, Div Pharmaceut Sci, Madison, WI 53705 USA. [Johnson, Jeffrey A.] Univ Wisconsin, Mol & Environm Toxicol Ctr, Madison, WI 53705 USA. [Johnson, Jeffrey A.] Univ Wisconsin, Ctr Neurosci, Madison, WI 53705 USA. [Johnson, Jeffrey A.] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA. [Foley, David P.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. RP Foley, DP (reprint author), Clin Sci Ctr H4 766, 600 Highland Ave, Madison, WI 53792 USA. EM foley@surgery.wisc.edu FU Clinical and Translational Science Award (CTSA) program through National Institutes of Health National Center for Advancing Translational Sciences (NCATS) [UL1TR000427]; American Society of Transplant Surgeons-Pfizer Mid-Level Faculty Award; National Institutes of Health [T32 CA090217]; American College of Surgeons Resident Research Scholarship; Swiss National Science Foundation [310030_132884]; Boehringer Ingelheim Fonds FX The Clinical and Translational Science Award (CTSA) program, through the National Institutes of Health National Center for Advancing Translational Sciences (NCATS) (UL1TR000427 to D.P.F.); the American Society of Transplant Surgeons-Pfizer Mid-Level Faculty Award (to D.P.F.), National Institutes of Health (T32 CA090217 to L.-Y.L.), the American College of Surgeons Resident Research Scholarship (to L.-Y.L.), the Swiss National Science Foundation (310030_132884 to S.W.); and a predoctoral fellowship from the Boehringer Ingelheim Fonds (U.A.K.). NR 37 TC 6 Z9 6 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2014 VL 142 IS 2 BP 361 EP 374 DI 10.1093/toxsci/kfu184 PG 14 WC Toxicology SC Toxicology GA AY5MZ UT WOS:000347617800006 PM 25294219 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Ruling in or out a source of gastrointestinal bleeding SO UNITED EUROPEAN GASTROENTEROLOGY JOURNAL LA English DT Article DE Bayes' formula; gastrointestinal bleeding; gastrointestinal endoscopy; medical decision analysis; outcome research AB Background and aims: The search for a source of gastrointestinal bleeding is associated with two distinct approaches of trying to rule in a specific diagnosis or rule out any potential source of bleeding. The study aim was to understand the conceptual differences underlying the two searches. Methods: The performance of endoscopy as diagnostic test is analyzed in terms of Bayes' formula. Results: The performance of gastrointestinal endoscopy to rule in a suspected lesion is mostly influenced by its underlying specificity. Because the specificity of endoscopy is less likely to be affected by procedural exigencies, the demands on pre-procedural prep and general quality can be more relaxed. In contradistinction, the performance of endoscopy to rule out a suspected bleeding site is mostly influenced by its sensitivity, which can easily be compromised by suboptimal procedural conditions. Conclusions: Paradoxically, the more urgent, focused, and important search (to rule in a bleeding site), carries less stringent criteria for its execution than the more general and aimless search (to rule out a bleeding site) that frequently ends up just empty handed. C1 [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Div Gastroenterol Hepatol, 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 NR 6 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2050-6406 EI 2050-6414 J9 UNITED EUR GASTROENT JI United European Gastroenterol. J. PD DEC PY 2014 VL 2 IS 6 BP 471 EP 474 DI 10.1177/2050640614557319 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AY8AS UT WOS:000347777400003 PM 25436110 ER PT J AU Sartor, CE Wang, ZH Xu, K Kranzler, HR Gelernter, J AF Sartor, Carolyn E. Wang, Zuoheng Xu, Ke Kranzler, Henry R. Gelernter, Joel TI The Joint Effects of ADH1B Variants and Childhood Adversity on Alcohol Related Phenotypes in African-American and European-American Women and Men SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Childhood Adversity; ADH1B; Alcohol; African Americans ID NATIONAL COMORBIDITY SURVEY; SUBSTANCE USE DISORDERS; MAO-A GENE; SEXUAL-ABUSE; PSYCHIATRIC-DISORDER; SEMISTRUCTURED ASSESSMENT; JEWISH POPULATION; DRINKING HABITS; YOUNG ADULTHOOD; DRUG-DEPENDENCE AB BackgroundThe ADH1B gene has consistently been implicated in problem drinking, but rarely incorporated into gene by environment investigations of alcohol phenotypes. This study examined the joint effects of variation in ADH1B and childhood adversitya well-documented risk factor for alcohol problems and moderator of genetic liability to psychiatric outcomeson maximum drinks consumed in a 24-hour period (maxdrinks) and alcohol use disorder (AUD) symptoms. MethodsData were drawn from 2,617 African-American (AA) and 1,436 European-American (EA) participants (42% female) in a multisite genetic study of substance dependence. We tested the most significant ADH1B single nucleotide polymorphisms for alcohol dependence from a genomewide association study with this sample, ADH1B-rs1229984 (Arg48His) and ADH1B-rs2066702 (Arg370Cys), in EA and AA subsamples, respectively. ResultsOrdinal regression analyses conducted separately by sex and population revealed significant main effects for childhood adversity for both alcohol phenotypes in AA women and men and for maxdrinks in EA women. A significant rs1229984 by childhood adversity interaction was observed for AUD symptoms in EA men. Unexposed His-allele carriers reported a mean of 3.6 AUD criteria, but adversity-exposed His-allele carriers endorsed approximately the same number (6.3) as those without the protective allele (6.3 and 7.0 for adversity-exposed and -unexposed groups, respectively). ConclusionsResults suggest that under conditions of childhood adversity, the His allele does not exert its protective effects in EA men (OR=0.57, CI: 0.32 to 1.01; p=0.056). Findings highlight the robust risk effect conferred by childhood adversity and the importance of considering population and sex in genetically informative investigations of its association with alcohol outcomes. C1 [Sartor, Carolyn E.; Xu, Ke; Gelernter, Joel] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Wang, Zuoheng] Yale Univ, Sch Med, Dept Biostat, New Haven, CT USA. [Kranzler, Henry R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kranzler, Henry R.] Philadelphia VA Med Ctr, Educ & Clin Ctr, Mental Illness Res VISN4, Philadelphia, PA USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA. [Gelernter, Joel] VA Connecticut Healthcare Syst, West Haven, CT USA. RP Sartor, CE (reprint author), Yale Univ, Sch Med, VA Connecticut Healthcare Syst, Dept Psychiat, 950 Campbell Ave 151D, West Haven, CT 06516 USA. EM carolyn.sartor@yale.edu FU NIH [DA12849, DA00167, DA12690, AA017921, AA11330, AA13736]; CTSA [KL2 RR024138]; Robert E. Leet and Clara Guthrie Patterson Trust; APA/Merck Early Academic Career Award Program; VA CT and Philadelphia VA Mental Illness Research, Education, and Clinical Centers FX The following investigators oversaw subject recruitment and assessment at their respective sites: Roger Weiss, M.D. (McLean Hospital), Kathleen Brady, M.D., Ph.D. and Raymond Anton, M.D. (Medical University of South Carolina), and David Oslin, M.D. (University of Pennsylvania). This work was supported by NIH grants DA12849, DA00167, DA12690, AA017921, AA11330, and AA13736, CTSA KL2 RR024138, the Robert E. Leet and Clara Guthrie Patterson Trust, the APA/Merck Early Academic Career Award Program, and the VA CT and Philadelphia VA Mental Illness Research, Education, and Clinical Centers. NR 47 TC 4 Z9 4 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2014 VL 38 IS 12 BP 2907 EP 2914 DI 10.1111/acer.12572 PG 8 WC Substance Abuse SC Substance Abuse GA AY4IN UT WOS:000347541500006 PM 25410943 ER PT J AU Metten, P Iancu, OD Spence, SE Walter, NAR Oberbeck, D Harrington, CA Colville, A McWeeney, S Phillips, TJ Buck, KJ Crabbe, JC Belknap, JK Hitzemann, RJ AF Metten, Pamela Iancu, Ovidiu D. Spence, Stephanie E. Walter, Nicole A. R. Oberbeck, Denesa Harrington, Christina A. Colville, Alexandre McWeeney, Shannon Phillips, Tamara J. Buck, Kari J. Crabbe, John C. Belknap, John K. Hitzemann, Robert J. TI Dual-Trait Selection for Ethanol Consumption and Withdrawal: Genetic and Transcriptional Network Effects SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Consumption and Withdrawal; Weighted Gene Co-Expression Network Analysis; Dual-Trait Selective Breeding; Mouse; Microarray ID MAP KINASE PATHWAY; ALCOHOL-WITHDRAWAL; VOLUNTARY CONSUMPTION; C57BL/6J MICE; MOUSE LINES; DRINKING; LOCI; DEPENDENCE; SUSCEPTIBILITY; PREFERENCE AB BackgroundData from C57BL/6J (B6)xDBA/2J (D2) F-2 intercrosses (B6xD2F(2)), standard and recombinant inbred strains, and heterogeneous stock mice indicate that a reciprocal (or inverse) genetic relationship exists between alcohol consumption and withdrawal severity. Furthermore, some genetic studies have detected reciprocal quantitative trait loci (QTLs) for these traits. We used a novel mouse model developed by simultaneous selection for both high alcohol consumption/low withdrawal and low alcohol consumption/high withdrawal and analyzed the gene expression and genome-wide genotypic differences. MethodsRandomly chosen third selected generation (S-3) mice (N=24/sex/line), bred from a B6xD2F(2), were genotyped using the Mouse Universal Genotyping Array, which provided 2,760 informative markers. QTL analysis used a marker-by-marker strategy with the threshold for a significant log of the odds (LOD) set at 10. Gene expression in the ventral striatum was measured using the Illumina Mouse 8.2 array. Differential gene expression and the weighted gene co-expression network analysis (WGCNA) were implemented. ResultsSignificant QTLs for consumption/withdrawal were detected on chromosomes (Chr) 2, 4, 9, and 12. A suggestive QTL mapped to Chr 6. Some of the QTLs overlapped with known QTLs mapped for 1 of the traits individually. One thousand seven hundred and forty-five transcripts were detected as being differentially expressed between the lines; there was some overlap with known withdrawal genes (e.g., Mpdz) located within QTL regions. WGCNA revealed several modules of co-expressed genes showing significant effects in both differential expression and intramodular connectivity; a module richly annotated with kinase-related annotations was most affected. ConclusionsMarked effects of selection on expression and network structure were detected. QTLs overlapping with differentially expressed genes on Chr 2 (distal) and 4 suggest that these are cis-eQTLs (Chr 2: Kif3b, Kcnq2; Chr 4: Mpdz, Snapc3). Other QTLs identified were on Chr 2 (proximal), 9, and 12. Network results point to involvement of kinase-related mechanisms and outline the need for further efforts such as interrogation of noncoding RNAs. C1 [Metten, Pamela; Iancu, Ovidiu D.; Spence, Stephanie E.; Walter, Nicole A. R.; Oberbeck, Denesa; Colville, Alexandre; McWeeney, Shannon; Phillips, Tamara J.; Buck, Kari J.; Crabbe, John C.; Belknap, John K.; Hitzemann, Robert J.] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Portland Alcohol Res Ctr, Portland, OR 97201 USA. [Metten, Pamela; Iancu, Ovidiu D.; Spence, Stephanie E.; Walter, Nicole A. R.; Oberbeck, Denesa; Colville, Alexandre; Phillips, Tamara J.; Buck, Kari J.; Crabbe, John C.; Belknap, John K.; Hitzemann, Robert J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Harrington, Christina A.] Oregon Hlth & Sci Univ, Integrated Genom Lab, Portland, OR 97201 USA. [McWeeney, Shannon] Oregon Hlth & Sci Univ, Div Biostat Publ Hlth & Preventat Med, Portland, OR 97201 USA. [McWeeney, Shannon] Oregon Hlth & Sci Univ, Div Bioinformat & Computat Biol Med Informat & Cl, Portland, OR 97201 USA. RP Metten, P (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,R&D 12, Portland, OR 97239 USA. EM mettenp@ohsu.edu FU Department of Veterans Affairs [P60 AA010760, R01 AA011034, R01 AA013484, R01 AA006243, R01 AA011114, 5UL1 RR024140, U01 AA013519, R24 AA020245]; Department of the Army/Department of Defense-TATRC [10245005.05] FX The authors are grateful for the assistance of Mr. Jason Schlumbohm, Mr. Larry Huang, Ms. Karen Shepherdson, Mr. Jason Erk, Mr. Andy-Jade Cameron, and Dr. Mark Rutledge-Gorman in performance of these experiments, sample preparation, assistance with data presentation, and manuscript submission. This study was supported by P60 AA010760, R01 AA011034, R01 AA013484, R01 AA006243, R01 AA011114, 5UL1 RR024140, U01 AA013519, R24 AA020245, grants from the Department of Veterans Affairs, and grant 10245005.05 from the Department of the Army/Department of Defense-TATRC. NR 44 TC 4 Z9 4 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2014 VL 38 IS 12 BP 2915 EP 2924 DI 10.1111/acer.12574 PG 10 WC Substance Abuse SC Substance Abuse GA AY4IN UT WOS:000347541500007 PM 25581648 ER PT J AU Chalmers, JR Schmitt, J Apfelbacher, C Dohil, M Eichenfield, LF Simpson, EL Singh, J Spuls, P Thomas, KS Admani, S Aoki, V Ardeleanu, M Barbarot, S Berger, T Bergman, JN Block, J Borok, N Burton, T Chamlin, SL Deckert, S DeKlotz, CC Graff, LB Hanifin, JM Hebert, AA Humphreys, R Katoh, N Kisa, RM Margolis, DJ Merhand, S Minnillo, R Mizutani, H Nankervis, H Ohya, Y Rodgers, P Schram, ME Stalder, JF Svensson, A Takaoka, R Teper, A Tom, WL von Kobyletzki, L Weisshaar, E Zelt, S Williams, HC AF Chalmers, J. R. Schmitt, J. Apfelbacher, C. Dohil, M. Eichenfield, L. F. Simpson, E. L. Singh, J. Spuls, P. Thomas, K. S. Admani, S. Aoki, V. Ardeleanu, M. Barbarot, S. Berger, T. Bergman, J. N. Block, J. Borok, N. Burton, T. Chamlin, S. L. Deckert, S. DeKlotz, C. C. Graff, L. B. Hanifin, J. M. Hebert, A. A. Humphreys, R. Katoh, N. Kisa, R. M. Margolis, D. J. Merhand, S. Minnillo, R. Mizutani, H. Nankervis, H. Ohya, Y. Rodgers, P. Schram, M. E. Stalder, J. F. Svensson, A. Takaoka, R. Teper, A. Tom, W. L. von Kobyletzki, L. Weisshaar, E. Zelt, S. Williams, H. C. TI Report from the third international consensus meeting to harmonise core outcome measures for atopic eczema/dermatitis clinical trials (HOME) SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID B-VIRUS-INFECTION; HUMAN-IMMUNODEFICIENCY-VIRUS; VARICELLA-ZOSTER VIRUS; STRONGYLOIDES-STERCORALIS INFECTION; EPIDERMOLYSIS-BULLOSA-ACQUISITA; FORCE RECOMMENDATION STATEMENT; MODIFYING ANTIRHEUMATIC DRUGS; DOSE METHOTREXATE THERAPY; HEPATITIS-B; PEMPHIGUS-VULGARIS AB This report provides a summary of the third meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in San Diego, CA, U.S.A., 6-7 April 2013 (HOME III). The meeting addressed the four domains that had previously been agreed should be measured in every eczema clinical trial: clinical signs, patient-reported symptoms, long-term control and quality of life. Formal presentations and nominal group techniques were used at this working meeting, attended by 56 voting participants (31 of whom were dermatologists). Significant progress was made on the domain of clinical signs. Without reference to any named scales, it was agreed that the intensity and extent of erythema, excoriation, oedema/papulation and lichenification should be included in the core outcome measure for the scale to have content validity. The group then discussed a systematic review of all scales measuring the clinical signs of eczema and their measurement properties, followed by a consensus vote on which scale to recommend for inclusion in the core outcome set. Research into the remaining three domains was presented, followed by discussions. The symptoms group and quality of life groups need to systematically identify all available tools and rate the quality of the tools. A definition of long-term control is needed before progress can be made towards recommending a core outcome measure. C1 [Chalmers, J. R.; Thomas, K. S.; Burton, T.; Nankervis, H.; Williams, H. C.] Univ Nottingham, Ctr Evidence Based Dermatol, Nottingham NG7 2RD, England. [Schmitt, J.; Deckert, S.] Univ Dresden, Ctr Evidence Based Healthcare, Dresden, Germany. [Apfelbacher, C.] Univ Regensburg, Dept Epidemiol & Prevent Med, D-93053 Regensburg, Germany. [Dohil, M.; Eichenfield, L. F.; Admani, S.; Borok, N.; DeKlotz, C. C.; Tom, W. L.] Univ Calif San Diego, Rady Childrens Hosp, San Diego, CA 92103 USA. [Simpson, E. L.; Hanifin, J. M.] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA. [Singh, J.] Univ Alabama Birmingham, Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, J.] Univ Alabama Birmingham, Dept Med, Birmingham, AL USA. [Spuls, P.; Schram, M. E.] Univ Amsterdam, Acad Med Ctr, Dept Dermatol, NL-1105 AZ Amsterdam, Netherlands. [Aoki, V.; Takaoka, R.] Univ Sao Paulo, Dept Dermatol, Sao Paulo, Brazil. [Ardeleanu, M.] Regeneron Pharmaceut Inc, Immunol & Inflammat, Clin Sci, Tarrytown, NY 10591 USA. [Barbarot, S.] CHU Nantes, Dept Dermatol, F-44035 Nantes 01, France. [Berger, T.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Bergman, J. N.] Univ British Columbia, Pediat Allergy & Dermatol Ctr, Vancouver, BC V5Z 1M9, Canada. [Block, J.] Natl Eczema Assoc, San Rafael, CA USA. [Chamlin, S. L.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL USA. [Graff, L. B.] LEO Pharma AS, Ballerup, Denmark. [Hebert, A. A.] Univ Texas Houston, Sch Med, Dept Dermatol, Houston, TX USA. [Humphreys, R.] Natl Eczema Soc, London, England. [Katoh, N.] Kyoto Prefectural Univ Med, Dept Dermatol, Kyoto, Japan. [Kisa, R. M.] Pierre Fabre Pharmaceut, New York, NY USA. [Margolis, D. J.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Merhand, S.] French Assoc Eczema, Redon, France. [Minnillo, R.] Soc Investigat Dermatol, Cleveland, OH USA. [Mizutani, H.] Mie Univ, Dept Dermatol, Tsu, Mie 514, Japan. [Ohya, Y.] Natl Ctr Child Hlth & Dev, Div Allergy, Tokyo, Japan. [Rodgers, P.] LEO Pharma, Parsippany, NJ USA. [Stalder, J. F.] Nantes Univ Hosp, Dept Dermatol, Nantes, France. [Svensson, A.] Malmo Univ Hosp, Dept Dermatol, Malmo, Sweden. [Teper, A.] Sanofi Aventis, Hastings On Hudson, NY USA. [von Kobyletzki, L.] Lund Univ, Dept Dermatol & Venerol, Lund, Sweden. [Weisshaar, E.] Univ Heidelberg Hosp, Dept Clin Social Med, Heidelberg, Germany. [Zelt, S.] Stiefel Labs, Res Triangle Pk, NC USA. RP Chalmers, JR (reprint author), Univ Nottingham, Ctr Evidence Based Dermatol, Nottingham NG7 2RD, England. EM Joanne.Chalmers@nottingham.ac.uk RI Aoki, Valeria/H-1415-2012 OI Schram, Miranda/0000-0003-0515-4124; Chalmers, Joanne/0000-0002-2281-7367; Apfelbacher, Christian/0000-0003-3805-8219; DeKlotz, Cynthia/0000-0002-6410-8710 FU National Institute for Health Research (NIHR) [RP-PG-0407-10177] FX This report represents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (RP-PG-0407-10177). The views expressed in this report are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. NR 100 TC 25 Z9 25 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD DEC PY 2014 VL 171 IS 6 BP 1318 EP 1325 DI 10.1111/bjd.13237 PG 8 WC Dermatology SC Dermatology GA AX9QD UT WOS:000347236100172 PM 24980543 ER PT J AU Stengel, A Tache, Y AF Stengel, Andreas Tache, Yvette TI Brain peptides and the modulation of postoperative gastric ileus SO CURRENT OPINION IN PHARMACOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; PLASMA GHRELIN LEVELS; GENE-RELATED PEPTIDE; INCREASES FOOD-INTAKE; BODY-MASS INDEX; ABDOMINAL-SURGERY; GROWTH-HORMONE; GASTROINTESTINAL MOTILITY; INSULIN-SECRETION; ACYLATED PEPTIDE AB Postoperative ileus (POI) develops after abdominal surgery irrespective of the site of surgery. When prolonged, POI can lead to longer hospitalization times and higher healthcare costs. Moreover, it is associated with complaints for the patient. In order to develop new strategies to treat this condition, a deeper understanding of the pathophysiology of the POI is necessary. This review will focus on brain peptides (ghrelin, nesfatin-1, somatostatin, corticotropin-releasing factor, thyrotropin-releasing hormone and calcitonin gene-related peptide) involved in the mediation of POI and the possible modulation of these pathways to shorten the time of POI. Lastly, the role of vagal signaling or chewing gum as potential treatment strategies of alleviating symptoms of POI is discussed. C1 [Stengel, Andreas] Charite, Campus Benjamin Franklin, Div Gen Internal & Psychosomat Med, Charite Ctr Internal Med & Dermatol, D-13353 Berlin, Germany. [Tache, Yvette] Univ Calif Los Angeles, Div Digest Dis, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress & Womens Hlth,Dept Med, Los Angeles, CA 90073 USA. [Tache, Yvette] VA Greater Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), Univ Calif Los Angeles, Div Digest Dis, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress & Womens Hlth,Dept Med, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU NIH [R01 DK-33061]; NIH Center [DK-41301]; VA Research Career Scientist; German Research Foundation [STE 1765/3-1]; Charite University Funding [UFF 89-441-176] FX This work was supported by NIH R01 DK-33061, NIH Center Grant DK-41301 (Animal Core), VA Research Career Scientist (Y.T.), VA Merit Award (Y.T.) German Research Foundation STE 1765/3-1 (A.S.) and Charite University Funding UFF 89-441-176 (AS.). NR 85 TC 4 Z9 5 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 EI 1471-4973 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD DEC PY 2014 VL 19 BP 31 EP 37 DI 10.1016/j.coph.2014.06.006 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AY3UO UT WOS:000347508000008 PM 24999843 ER PT J AU Ronnestad, I Akiba, Y Kaji, I Kaunitz, JD AF Ronnestad, Ivar Akiba, Yasutada Kaji, Izumi Kaunitz, Jonathan D. TI Duodenal luminal nutrient sensing SO CURRENT OPINION IN PHARMACOLOGY LA English DT Article ID CHAIN FATTY-ACIDS; PROTEIN-COUPLED RECEPTOR; INTESTINAL GLUCOSE-ABSORPTION; RAT SMALL-INTESTINE; ENTEROENDOCRINE CELLS; PEPTIDE-1 SECRETION; TASTE RECEPTOR; AMINO-ACID; GASTROINTESTINAL-TRACT; BICARBONATE SECRETION AB The gastrointestinal mucosa is exposed to numerous chemical substances and microorganisms, including macronutrients, micronutrients, bacteria, endogenous ions, and proteins. The regulation of mucosal protection, digestion, absorption and motility is signaled in part by luminal solutes. Therefore, luminal chemosensing is an important mechanism enabling the mucosa to monitor luminal conditions, such as pH, ion concentrations, nutrient quantity, and microflora. The duodenal mucosa shares luminal nutrient receptors with lingual taste receptors in order to detect the five basic tastes, in addition to essential nutrients, and unwanted chemicals. The recent 'de-orphanization' of nutrient sensing G protein-coupled receptors provides an essential component of the mechanism by which the mucosa senses luminal nutrients. In this review, we will update the mechanisms of and underlying physiological and pathological roles in luminal nutrient sensing, with a main focus on the duodenal mucosa. C1 [Akiba, Yasutada; Kaunitz, Jonathan D.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA. [Ronnestad, Ivar; Akiba, Yasutada; Kaji, Izumi; Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Dept Surg, Los Angeles, CA 90024 USA. [Akiba, Yasutada; Kaji, Izumi; Kaunitz, Jonathan D.] Brentwood Biomed Res Inst, Los Angeles, CA 90073 USA. [Ronnestad, Ivar] Univ Bergen, Dept Biol, N-5020 Bergen, Norway. RP Kaunitz, JD (reprint author), Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA. EM jake@ucla.edu RI Ronnestad, Ivar/A-1774-2013 OI Ronnestad, Ivar/0000-0001-8789-0197; Akiba, Yasutada/0000-0001-5731-1019 FU Ajinomoto, Inc., Japan; Department of Veterans Affairs Merit Review Award; Research Council of Norway [208352, 199482]; University of Bergen; Department of Veterans Affairs Merit Review Award, NIH-NIDDK [R01 DK54221] FX Supported by a research grant from Ajinomoto, Inc., Japan (Y Akiba), Department of Veterans Affairs Merit Review Award, NIH-NIDDK R01 DK54221 (J Kaunitz), the funding from a Grant-in-Aid for Japan Society for the Promotion of Science Fellow (I Kaji), and funding from Research Council of Norway, 208352; 199482, and University of Bergen, Sabbatical Grant (I Ronnestad). NR 60 TC 6 Z9 6 U1 1 U2 26 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 EI 1471-4973 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD DEC PY 2014 VL 19 BP 67 EP 75 DI 10.1016/j.coph.2014.07.010 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AY3UO UT WOS:000347508000013 PM 25113991 ER PT J AU Struzyna, LA Katiyar, K Cullen, DK AF Struzyna, Laura A. Katiyar, Kritika Cullen, D. Kacy TI Living scaffolds for neuroregeneration SO CURRENT OPINION IN SOLID STATE & MATERIALS SCIENCE LA English DT Review DE Tissue engineering; Cell transplant; Biomaterials; Regeneration; Neurotrauma; Neurodegeneration; Axon pathfinding; Cell migration ID PERIPHERAL-NERVE REGENERATION; NEURAL STEM-CELLS; LONG-TERM SURVIVAL; NEURITE OUTGROWTH; IN-VITRO; NEURONAL MIGRATION; NEUROTROPHIC FACTOR; GRASSHOPPER EMBRYOS; SUBSTRATE CURVATURE; FUNCTIONAL RECOVERY AB Neural tissue engineers are exploiting key mechanisms responsible for neural cell migration and axonal pathfinding during embryonic development to create living scaffolds for neuroregeneration following injury and disease. These mechanisms involve the combined use of haptotactic, chemotactic, and mechanical cues to direct cell movement and re-growth. Living scaffolds provide these cues through the use of cells engineered in a predefined architecture, generally in combination with biomaterial strategies. Although several hurdles exist in the implementation of living regenerative scaffolds, there are considerable therapeutic advantages to using living cells in conjunction with biomaterials. The leading contemporary living scaffolds for neurorepair are utilizing aligned glial cells and neuronal/axonal tracts to direct regenerating axons across damaged tissue to appropriate targets, and in some cases to directly replace the function of lost cells. Future advances in technology, including the use of exogenous stimulation and genetically engineered stem cells, will further the potential of living scaffolds and drive a new era of personalized medicine for neuroregeneration. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Struzyna, Laura A.; Katiyar, Kritika; Cullen, D. Kacy] Univ Penn, Dept Neurosurg, Perelman Sch Med, Ctr Brain Injury & Repair, Philadelphia, PA 19104 USA. [Struzyna, Laura A.; Cullen, D. Kacy] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Katiyar, Kritika] Drexel Univ, Sch Biomed Engn, Philadelphia, PA 19104 USA. RP Cullen, DK (reprint author), 105E Hayden Hall 3320 Smith Walk, Philadelphia, PA 19104 USA. EM lstruz@mail.med.upenn.edu; kritikak@mail.med.upenn.edu; dkacy@mail.med.upenn.edu FU U.S. Army Medical Research and Materiel Command through the Armed Forces Institute of Regenerative Medicine [W81XWH-08-2-0034]; Congressionally Directed Medical Research Program [W81XWH-10-1-0941]; Axonia Medical, Inc.; Department of Veterans Affairs (RRD Merit Review) [B1097-I]; National Institutes of Health/NINDS [T32-NS043126]; National Science Foundation (Graduate Research Fellowship) [DGE-1321851] FX This work was made possible due to financial support provided by the U.S. Army Medical Research and Materiel Command through the Armed Forces Institute of Regenerative Medicine (#W81XWH-08-2-0034) and the Congressionally Directed Medical Research Program (#W81XWH-10-1-0941); Axonia Medical, Inc., through a sponsored research agreement; Department of Veterans Affairs (RR&D Merit Review #B1097-I); National Institutes of Health/NINDS (T32-NS043126); and the National Science Foundation (Graduate Research Fellowship DGE-1321851). NR 101 TC 7 Z9 8 U1 0 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-0286 EI 1879-0348 J9 CURR OPIN SOLID ST M JI Curr. Opin. Solid State Mat. Sci. PD DEC PY 2014 VL 18 IS 6 BP 308 EP 318 DI 10.1016/j.cossms.2014.07.004 PG 11 WC Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Materials Science; Physics GA AY3QU UT WOS:000347498600002 ER PT J AU Mancuso, JJ Halaney, DL Elahi, S Ho, D Wang, TY Ouyang, YJ Dijkstra, J Milner, TE Feldman, MD AF Mancuso, J. Jacob Halaney, David L. Elahi, Sahar Ho, Derek Wang, Tianyi Ouyang, Yongjian Dijkstra, Jouke Milner, Thomas E. Feldman, Marc D. TI Intravascular optical coherence tomography light scattering artifacts: merry-go-rounding, blooming, and ghost struts SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE imaging; lasers; stents; tomography ID ACCURACY; REPRODUCIBILITY AB We sought to elucidate the mechanisms underlying two common intravascular optical coherence tomography (IV-OCT) artifacts that occur when imaging metallic stents: "merry-go-rounding" (MGR), which is an increase in strut arc length (SAL), and "blooming," which is an increase in the strut reflection thickness (blooming thickness). Due to uncontrollable variables that occur in vivo, we performed an in vitro assessment of MGR and blooming in stented vessel phantoms. Using Xience V and Driver stents, we examined the effects of catheter offset, intimal strut coverage, and residual blood on SAL and blooming thickness in IV-OCT images. Catheter offset and strut coverage both caused minor MGR, while the greatest MGR effect resulted from light scattering by residual blood in the vessel lumen, with 1% hematocrit (Hct) causing a more than fourfold increase in SAL compared with saline (p < 0.001). Residual blood also resulted in blooming, with blooming thickness more than doubling when imaged in 0.5% Hct compared with saline (p < 0.001). We demonstrate that a previously undescribed mechanism, light scattering by residual blood in the imaging field, is the predominant cause of MGR. Light scattering also results in blooming, and a newly described artifact, three-dimensional-MGR, which results in " ghost struts" in B-scans. (C) 2014 Society of Photo-Optical Instrumentation Engineers (SPIE). C1 [Mancuso, J. Jacob; Halaney, David L.; Ouyang, Yongjian; Feldman, Marc D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Cardiol, San Antonio, TX 78229 USA. [Mancuso, J. Jacob; Halaney, David L.; Feldman, Marc D.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX 78229 USA. [Elahi, Sahar; Ho, Derek; Wang, Tianyi; Milner, Thomas E.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. [Dijkstra, Jouke] Leiden Univ, Med Ctr, Dept Radiol, Div Image Proc, NL-2333 ZA Leiden, Netherlands. RP Feldman, MD (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Cardiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM feldmanm@uthscsa.edu OI Halaney, David/0000-0003-4437-0516 FU South Texas Veterans Health Care System (VA Merit Grant, San Antonio, Texas); Janey and Dolph Briscoe Center for Cardiovascular Research (San Antonio, Texas); Volcano Corporation (San Diego, California); Clayton Foundation for Biomedical Research (Houston, Texas) FX This work was supported by the South Texas Veterans Health Care System (VA Merit Grant, San Antonio, Texas), the Janey and Dolph Briscoe Center for Cardiovascular Research (San Antonio, Texas), Volcano Corporation (San Diego, California), and the Clayton Foundation for Biomedical Research (Houston, Texas). Disclosures: None. NR 17 TC 0 Z9 0 U1 0 U2 3 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD DEC PY 2014 VL 19 IS 12 AR 126017 DI 10.1117/1.JBO.19.12.126017 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AY2TS UT WOS:000347442600022 PM 25545341 ER PT J AU Merchant, RM Ha, YP Wong, CA Schwartz, HA Sap, M Ungar, LH Asch, DA AF Merchant, Raina M. Ha, Yoonhee P. Wong, Charlene A. Schwartz, H. Andrew Sap, Maarten Ungar, Lyle H. Asch, David A. TI The 2013 US Government Shutdown (#Shutdown) and Health: An Emerging Role for Social Media SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID EMERGENCY-PREPAREDNESS AB In October 2013, multiple United States (US) federal health departments and agencies posted on Twitter, "We're sorry, but we will not be tweeting or responding to @ replies during the shutdown. We'll be back as soon as possible!" These "last tweets" and the millions of responses they generated revealed social media's role as a forum for sharing and discussing information rapidly. Social media are now among the few dominant communication channels used today. We used social media to characterize the public discourse and sentiment about the shutdown. The 2013 shutdown represented an opportunity to explore the role social media might play in events that could affect health. C1 [Merchant, Raina M.; Ha, Yoonhee P.; Wong, Charlene A.] Univ Penn, Penn Med Social Media & Hlth Innovat Lab, Penn Med Ctr Hlth Care Innovat, Philadelphia, PA 19104 USA. [Schwartz, H. Andrew; Sap, Maarten; Ungar, Lyle H.] Univ Penn, Dept Comp & Informat Sci, Posit Psychol Ctr, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Merchant, RM (reprint author), Univ Penn, Penn Med Social Media & Hlth Innovat Lab, 423 Guardian Dr, Philadelphia, PA 19104 USA. EM Raina.Merchant@uphs.upenn.edu FU NHLBI NIH HHS [K23 HL109083] NR 11 TC 2 Z9 2 U1 1 U2 13 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2014 VL 104 IS 12 BP 2248 EP 2250 DI 10.2105/AJPH.2014.302118 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AX9GB UT WOS:000347210500027 PM 25322303 ER PT J AU Merchant, RM Griffis, HM Ha, YP Kilaru, AS Sellers, AM Hershey, JC Hill, SS Kramer-Golinkoff, E Nadkarni, L Debski, MM Padrez, KA Becker, LB Asch, DA AF Merchant, Raina M. Griffis, Heather M. Ha, Yoonhee P. Kilaru, Austin S. Sellers, Allison M. Hershey, John C. Hill, Shawndra S. Kramer-Golinkoff, Emily Nadkarni, Lindsay Debski, Margaret M. Padrez, Kevin A. Becker, Lance B. Asch, David A. TI Hidden in Plain Sight: A Crowdsourced Public Art Contest to Make Automated External Defibrillators More Visible SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HOSPITAL CARDIAC-ARREST; AMERICAN-HEART-ASSOCIATION; ACCESS DEFIBRILLATION; IMPROVING SURVIVAL; UNITED-STATES; HEALTH; PROFESSIONALS; SURVEILLANCE; CHALLENGE; COMMUNITY AB Objectives. We sought to explore the feasibility of using a crowdsourcing study to promote awareness about automated external defibrillators (AEDs) and their locations. Methods. The Defibrillator Design Challenge was an online initiative that asked the public to create educational designs that would enhance AED visibility, which took place over 8 weeks, from February 6, 2014, to April 6, 2014. Participants were encouraged to vote for AED designs and share designs on social media for points. Using a mixed-methods study design, we measured participant demographics and motivations, design characteristics, dissemination, and Web site engagement. Results. Over 8 weeks, there were 13 992 unique Web site visitors; 119 submitted designs and 2140 voted. The designs were shared 48 254 times on Facebook and Twitter. Most designers-voters reported that they participated to contribute to an important cause (44%) rather than to win money (0.8%). Design themes included: empowerment, location awareness, objects (e.g., wings, lightning, batteries, life-buoys), and others. Conclusions. The Defibrillator Design Challenge engaged a broad audience to generate AED designs and foster awareness. This project provides a framework for using design and contest architecture to promote health messages. C1 [Merchant, Raina M.; Griffis, Heather M.; Ha, Yoonhee P.; Kilaru, Austin S.; Sellers, Allison M.; Hershey, John C.; Hill, Shawndra S.; Kramer-Golinkoff, Emily; Nadkarni, Lindsay; Debski, Margaret M.; Padrez, Kevin A.] Univ Penn, Social Media & Hlth Innovat Lab, Penn Med Ctr Hlth Care Innovat, Philadelphia, PA 19104 USA. [Becker, Lance B.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Merchant, RM (reprint author), Univ Penn, Social Media & Hlth Innovat Lab, 1022 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM Raina.Merchant@uphs.upenn.edu FU Leonard Davis Institute of Health Economics Pilot Grant, Physio-Control, Seattle, WA; Zoll Medical, Boston, MA; Cardiac Science, Bothell, WA; Philips Medical, Seattle, WA; Heartsine, Belfast, Northern Ireland; National Institutes of Health [10714038]; Physio-Control, Seattle, WA; Philips Healthcare, Seattle, WA; Laerdal Medical, Stavanger, Norway; National Institutes of Health, Bethesda, MD; Medtronic Foundation, Minneapolis, MN FX This work was supported by Leonard Davis Institute of Health Economics Pilot Grant, Physio-Control, Seattle, WA; Zoll Medical, Boston, MA; Cardiac Science, Bothell, WA; Philips Medical, Seattle, WA; and Heartsine, Belfast, Northern Ireland. R. M. Merchant was supported by the National Institutes of Health (K23 grant 10714038); Physio-Control, Seattle, WA; Zoll Medical, Boston, MA; Cardiac Science, Bothell, WA; Philips Medical, Seattle, WA; and Heartsine, Belfast, Northern Ireland. L. B. Becker was supported by Philips Healthcare, Seattle, WA; Laerdal Medical, Stavanger, Norway; the National Institutes of Health, Bethesda, MD; Cardiac Science, Bothell, WA; and Medtronic Foundation, Minneapolis, MN. NR 34 TC 4 Z9 4 U1 1 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2014 VL 104 IS 12 BP 2306 EP 2312 DI 10.2105/AJPH.2014.302211 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AX9GB UT WOS:000347210500037 PM 25320902 ER PT J AU Attia, EF Akgun, KM Wongtrakool, C Goetz, MB Rodriguez-Barradas, MC Rimland, D Brown, ST Hoo, GWS Kim, J Lee, PJ Schnapp, LM Sharafkhaneh, A Justice, AC Crothers, K AF Attia, Engi F. Akguen, Kathleen M. Wongtrakool, Cherry Goetz, Matthew Bidwell Rodriguez-Barradas, Maria C. Rimland, David Brown, Sheldon T. Hoo, Guy W. Soo Kim, Joon Lee, Patty J. Schnapp, Lynn M. Sharafkhaneh, Amir Justice, Amy C. Crothers, Kristina TI Increased Risk of Radiographic Emphysema in HIV Is Associated With Elevated Soluble CD14 and Nadir CD4 SO CHEST LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; LIPOPOLYSACCHARIDE-BINDING PROTEIN; RESOLUTION COMPUTED-TOMOGRAPHY; AIRWAY WALL THICKNESS; ANTIRETROVIRAL THERAPY; DIFFUSING-CAPACITY; LUNG-FUNCTION; INFECTION; INFLAMMATION; SMOKERS AB BACKGROUND: The association between HIV and emphysema remains incompletely understood. We sought to determine whether HIV is an independent risk factor for emphysema severity and whether markers of HIV severity and systemic biomarkers of inflammation (IL-6), altered coagulation (D-dimer), and immune activation (soluble CD14) are associated with emphysema. METHODS: We performed a cross-sectional analysis of 114 participants with HIV infection and 89 participants without HIV infection in the Examinations of HIV-Associated Lung Emphysema (EXHALE) study. Participants underwent chest CT imaging with blinded semi-quantitative interpretation of emphysema severity, distribution, and type. We generated multivariable logistic regression models to determine the risk of HIV for radiographic emphysema, defined as >10% lung involvement. Similar analyses examined associations of plasma biomarkers, HIV RNA, and recent and nadir CD4 cell counts with emphysema among participants with HIV infection. RESULTS: Participants with HIV infection had greater radiographic emphysema severity with increased lower lung zone and diffuse involvement. HIV was associated with significantly increased risk for >10% emphysema in analyses adjusted for cigarette smoking pack-years (OR, 2.24; 95% CI, 1.12-4.48). In multivariable analyses restricted to participants with HIV infection, nadir CD4 < 200 cells/mu L (OR, 2.98; 95% CI, 1.14-7.81), and high soluble CD14 level (upper 25th percentile) (OR, 2.55; 95% CI, 1.04-6.22) were associated with increased risk of >10% emphysema. IL-6 and D-dimer were not associated with emphysema in HIV. CONCLUSIONS: HIV is an independent risk factor for radiographic emphysema. Emphysema severity was significantly greater among participants with HIV infection. Among those with HIV, nadir CD4 < 200 cells/mu L and elevated soluble CD14 level were associated with emphysema, highlighting potential mechanisms linking HIV with emphysema. C1 [Attia, Engi F.; Schnapp, Lynn M.; Crothers, Kristina] Univ Washington, Dept Med, Seattle, WA 98104 USA. [Akguen, Kathleen M.; Justice, Amy C.] Vet Affairs Connecticut Healthcare Syst, Dept Med, West Haven, CT USA. [Akguen, Kathleen M.; Lee, Patty J.; Justice, Amy C.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. [Wongtrakool, Cherry; Rimland, David] Atlanta Vet Affairs Med Ctr, Atlanta, GA USA. [Wongtrakool, Cherry; Rimland, David] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA. [Goetz, Matthew Bidwell; Hoo, Guy W. Soo] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Goetz, Matthew Bidwell; Hoo, Guy W. Soo] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Rodriguez-Barradas, Maria C.; Sharafkhaneh, Amir] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Rodriguez-Barradas, Maria C.; Sharafkhaneh, Amir] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Brown, Sheldon T.; Kim, Joon] James J Peters Vet Affairs Med Ctr, Dept Med, Bronx, NY USA. [Brown, Sheldon T.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. RP Crothers, K (reprint author), Univ Washington, Harborview Med Ctr, 325 Ninth Ave,Campus Box 359762, Seattle, WA 98104 USA. EM crothk@uw.edu OI Attia, Engi/0000-0002-5044-9602; Justice, Amy/0000-0003-0139-5502; Crothers, Kristina/0000-0001-9702-0371 FU National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH) [R21 HL120391, R01 HL090342]; University of Washington Center for AIDS Research; NIH [P30-AI-027757]; National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Institute of Mental Health; National Institute on Drug Abuse; Eunice Kennedy Shriver National Institute of Child Health and Human Development; NHLBI; National Institute on Aging FX This work was supported by the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH) [R21 HL120391 to Dr Schnapp and R01 HL090342 to Dr Crothers]. This research was funded in part by a 2012 developmental grant from the University of Washington Center for AIDS Research, an NIH-funded program under award number P30-AI-027757, which is supported by the following NIH institutes and centers: National Institute of Allergy and Infectious Diseases, National Cancer Institute, National Institute of Mental Health, National Institute on Drug Abuse, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NHLBI, and National Institute on Aging. NR 54 TC 23 Z9 23 U1 2 U2 4 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2014 VL 146 IS 6 BP 1543 EP 1553 DI 10.1378/chest.14-0543 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AX9IU UT WOS:000347217600042 PM 25080158 ER PT J AU Guerrero-Berroa, E Schmeidler, J Beeri, MS AF Guerrero-Berroa, Elizabeth Schmeidler, James Beeri, Michal Schnaider TI Neuropathology of type 2 diabetes: a short review on insulin-related mechanisms SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Review DE Type 2 diabetes; Cerebrovascular disease; Alzheimer's disease; Neuropathology; Review ID ADVANCED GLYCATION ENDPRODUCTS; AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; DEGRADING ENZYME; COGNITIVE DECLINE; OXIDATIVE STRESS; ANIMAL-MODELS; MOUSE MODEL; MELLITUS; BETA AB Postmortem studies have shown that cerebrovascular disease (CVD) neuropathology occurs frequently in type 2 diabetes (T2D) through mechanisms associated with chronic hyperglycemia such as advanced glycation end-products (AGES). The involvement of T2D in Alzheimer's disease (AD)-type neuropathology has been more controversial. While postmortem data from animal studies have supported the involvement of T2D in AD-type neuropathology through insulin mechanism that may affect the development of neuritic plaques and neurofibrillary tangles (NFTs), findings from postmortem studies in humans, of the association of T2D with AD, have been mainly negative. To complicate matters, medications to treat T2D have been implicated in reduced AD-type neuropathology. In this review we summarize the literature on animal and human postmortem studies of T2D neuropathology, mainly the mechanisms involved in hyperglycemiarelated CVD neuropathology and hyperinsulinemia-related AD-type neuropathology. (C) 2014 Elsevier B.V. and ECNR All rights reserved. C1 [Guerrero-Berroa, Elizabeth; Schmeidler, James; Beeri, Michal Schnaider] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Beeri, Michal Schnaider] Chaim Sheba Med Ctr, Joseph Sagol Neurosci Ctr, Ramat Gan, Israel. RP Guerrero-Berroa, E (reprint author), James J Peters VA Med Ctr, 130 West Kingsbridge Rd,Room 1F-01, Bronx, NY 10468 USA. EM elizabeth.guerrero-berroa@mssm.edu FU NIA [R01 AG034087, P50 AG005138]; Helen Bader Foundation; Irma T. Hirschl Scholar award FX This study was supported by NIA Grants R01 AG034087 to Dr. Beeni and P50 AG005138 to Dr. Sano, the Helen Bader Foundation and the Irma T. Hirschl Scholar award to Dr. Been. NR 58 TC 0 Z9 0 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD DEC PY 2014 VL 24 IS 12 BP 1961 EP 1966 DI 10.1016/j.euroneuro.2014.01.019 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AX7LJ UT WOS:000347097200011 PM 24529419 ER PT J AU Sudore, RL Casarett, D Smith, D Richardson, DM Ersek, M AF Sudore, Rebecca L. Casarett, David Smith, Dawn Richardson, Diane M. Ersek, Mary TI Family Involvement at the End-of-Life and Receipt of Quality Care SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE End-of-life care; communication; quality assessment; veterans ID SURROGATE DECISION-MAKING; HOSPITALIZED ADULTS; ADVANCE DIRECTIVES; ETHNIC-DIFFERENCES; CANCER; NATIONWIDE; VETERANS; COMORBIDITY; CAPACITY; IMPACT AB Context. Most patients will lose decision-making capacity at the end of life. Little is known about the quality of care received by patients who have family involved in their care. Objectives. To evaluate differences in the receipt of quality end-of-life care for patients who died with and without family involvement. Methods. We retrospectively reviewed the charts of 34,290 decedents from 146 acute and long-term care Veterans Affairs facilities between 2010 and 2011. Outcomes included: 1) palliative care consult, 2) chaplain visit, and 3) death in an inpatient hospice or palliative care unit. We also assessed "do not resuscitate" (DNR) orders. Family involvement was defined as documented discussions with the health care team in the last month of life. We used logistic regression adjusted for demographics, comorbidity, and clustered by facility. For chaplain visit, hospice or palliative care unit death, and DNR, we additionally adjusted for palliative care consults. Results. Mean (SD) age was 74 (+/- 12) years, 98% were men, and 19% were nonwhite. Most decedents (94.2%) had involved family. Veterans with involved family were more likely to have had a palliative care consult, adjusted odds ratio (AOR) 4.31 (95% CI 3.90-4.76); a chaplain visit, AOR 1.18 (95% CI 1.07-1.31); and a DNR order, AOR 4.59 (95% CI 4.08-5.16) but not more likely to die in a hospice or palliative care unit. Conclusion. Family involvement at the end of life is associated with receipt of palliative care consultation and a chaplain visit and a higher likelihood of a DNR order. Clinicians should support early advance care planning for vulnerable patients who may lack family or friends. Published by Elsevier Inc. on behalf of American Academy of Hospice and Palliative Medicine. C1 [Sudore, Rebecca L.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA 94121 USA. [Sudore, Rebecca L.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Casarett, David] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ersek, Mary] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Smith, Dawn; Richardson, Diane M.; Ersek, Mary] Dept Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA. RP Sudore, RL (reprint author), San Francisco VA Med Ctr, Div Geriatr, 4150 Clement St,151R, San Francisco, CA 94121 USA. EM rebecca.sudore@ucsf.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, HSRD FX The authors have no conflicts of interest to disclose. This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, HSR&D, which 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; and decision to submit the manuscript for publication. All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 33 TC 5 Z9 5 U1 2 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD DEC PY 2014 VL 48 IS 6 BP 1108 EP 1116 DI 10.1016/j.jpainsymman.2014.04.001 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA AX1ZG UT WOS:000346742300010 PM 24793077 ER PT J AU Goldstein, NE Kalman, J Kutner, JS Fromme, EK Hutchinson, MD Lipman, HI Matlock, DD Swetz, KM Lampert, R Herasme, O Morrison, RS AF Goldstein, Nathan E. Kalman, Jill Kutner, Jean S. Fromme, Erik K. Hutchinson, Mathew D. Lipman, Hannah I. Matlock, Daniel D. Swetz, Keith M. Lampert, Rachel Herasme, Omarys Morrison, R. Sean TI A Study to Improve Communication Between Clinicians and Patients With Advanced Heart Failure: Methods and Challenges Behind the Working to Improve Discussions About Defibrillator Management Trial SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Heart failure; communication; randomized controlled trial; palliative care; methods; intervention; IRB ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; QUALITY-OF-LIFE; EXPERT CONSENSUS STATEMENT; VENTRICULAR ASSIST DEVICES; SERIOUSLY-ILL PATIENTS; PATIENTS NEARING END; PALLIATIVE CARE; REQUESTING WITHDRAWAL; TREATMENT PREFERENCES; ELECTRONIC DEVICES AB We report the challenges of the Working to Improve Discussions About Defibrillator Management trial, our novel, multicenter trial aimed at improving communication between cardiology clinicians and their patients with advanced heart failure (HF) who have implantable cardioverter defibrillators (ICDs). The study objectives are (1) to increase ICD deactivation conversations, (2) to increase the number of ICDs deactivated, and (3) to improve psychological outcomes in bereaved caregivers. The unit of randomization is the hospital, the intervention is aimed at HF clinicians, and the patient and caregiver are the units of analysis. Three hospitals were randomized to usual care and three to intervention. The intervention consists of an interactive educational session, clinician reminders, and individualized feedback. We enroll patients with advanced HF and their caregivers, and then we regularly survey them to evaluate whether the intervention has improved communication between them and their HF providers. We encountered three implementation barriers. First, there were institutional review board concerns at two sites because of the palliative nature of the study. Second, we had difficulty in creating entry criteria that accurately identified an HF population at high risk of dying. Third, we had to adapt our entry criteria to the changing landscape of ventricular assist devices and cardiac transplant eligibility. Here we present our novel solutions to the difficulties we encountered. Our work has the ability to enhance conduct of future studies focusing on improving care for patients with advanced illness. Published by Elsevier Inc. on behalf of American Academy of Hospice and Palliative Medicine. C1 [Goldstein, Nathan E.; Herasme, Omarys; Morrison, R. Sean] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Kalman, Jill] Icahn Sch Med Mt Sinai, Div Cardiol, Samuel Bronfman Dept Med, New York, NY 10029 USA. [Goldstein, Nathan E.; Morrison, R. Sean] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Kutner, Jean S.; Matlock, Daniel D.] Univ Colorado, Sch Med, Dept Med, Div Gen Internal Med, Aurora, CO USA. [Fromme, Erik K.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR USA. [Fromme, Erik K.] Oregon Hlth & Sci Univ, Dept Radiat Med, Portland, OR USA. [Fromme, Erik K.] Oregon Hlth & Sci Univ, Dept Nursing, Portland, OR USA. [Hutchinson, Mathew D.] Univ Penn, Dept Med, Div Cardiovasc, Philadelphia, PA 19104 USA. [Lipman, Hannah I.] Montefiore Med Ctr, Div Geriatr, Bronx, NY 10467 USA. [Lipman, Hannah I.] Montefiore Med Ctr, Div Cardiol, Bronx, NY 10467 USA. [Lipman, Hannah I.] Montefiore Med Ctr, Montefiore Einstein Ctr Bioeth, Bronx, NY 10467 USA. [Swetz, Keith M.] Mayo Clin, Sect Palliat Med, Dept Med, Div Gen Internal Med, Rochester, MN USA. [Lampert, Rachel] Yale Univ, Sch Med, Dept Internal Med, Cardiol Sect, New Haven, CT 06510 USA. RP Goldstein, NE (reprint author), Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, Box 1070,1 Gustave L Levy Pl, New York, NY 10029 USA. EM nathan.goldstein@mssm.edu FU National Heart, Lung, and Blood Institute [R01HL102084] FX Research reported in this publication was supported by a grant from the National Heart, Lung, and Blood Institute (R01HL102084). The content is solely the responsibility of the authors and does not represent the views of the National Institutes of Health or the Department of Veterans Affairs. The investigators have no conflicts of interest to disclose. NR 52 TC 3 Z9 3 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 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD DEC PY 2014 VL 48 IS 6 BP 1236 EP 1246 DI 10.1016/j.jpainsymman.2014.03.005 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA AX1ZG UT WOS:000346742300021 PM 24768595 ER PT J AU Muller, M Hess, L Tardivo, A Lajmanovich, R Attademo, A Poletta, G Simoniello, MF Yodice, A Lavarello, S Chialvo, D Scremin, O AF Muller, Marie Hess, Leonardo Tardivo, Agostina Lajmanovich, Rafael Attademo, Andres Poletta, Gisela Fernanda Simoniello, Maria Yodice, Agustina Lavarello, Simona Chialvo, Dante Scremin, Oscar TI Neurologic dysfunction and genotoxicity induced by low levels of chlorpyrifos SO NEUROTOXICOLOGY LA English DT Article DE Acetylcholinesterase inhibitors; Evoked potentials; Comet assay; Auditory startle; EEG ID ACETYLCHOLINESTERASE INHIBITOR CHLORPYRIFOS; SOMATOSENSORY-EVOKED-POTENTIALS; HIPPOCAMPAL THETA-RHYTHM; ACOUSTIC STARTLE REFLEX; ANESTHETIZED RAT; CHOLINERGIC MODULATION; SENSORY-INTERFERENCE; PREPULSE INHIBITION; REPEATED EXPOSURES; BEHAVIORAL STATES AB Chlorpyrifos (CPF) is an organophosphorus cholinesterase inhibitor widely used as an insecticide. Neuro and genotoxicity of this agent were evaluated following daily subcutaneous injections at 0.1, 1 and 10 mg/kg or its vehicle to laboratory rats during one week, at the end of which somatosensory evoked potentials (SEP) and power spectrum of the electroencephalogram (EEGp) were recorded under urethane anesthesia. In another group of conscious animals, auditory startle reflex (ASR) was evaluated followed, after euthanasia, with measurements of plasma B-esterases, and genotoxicity with the alkaline comet assay (ACA) at the same CPF doses. The results indicated a CPF dose related inhibition of B-esterases. Enhanced inhibition of the ASR by a subthreshold pre-pulse was observed at all doses and ACA showed a significant higher DNA damage than vehicle controls in animals exposed to 10 mg/kg CPF. A trend to higher frequencies of EEGp and an increase in amplitude of the first negative wave of the SEP were found at all doses. The first positive wave of the SEP decreased at the CPF dose of 10 mg/kg. In summary, a shift to higher EEG frequencies and alterations of somatosensory and auditory input to the central nervous system were sensitive manifestations of CPF toxicity, associated with depression of B-esterases. The changes in electrical activity of the cerebral cortex and DNA damage observed at doses that do not elicit overt toxicity may be useful in the detection of CPF exposure before clinical signs appear. Published by Elsevier Inc. C1 [Muller, Marie; Hess, Leonardo; Tardivo, Agostina; Yodice, Agustina; Lavarello, Simona; Chialvo, Dante; Scremin, Oscar] Univ Natl Rosario, Fac Ciencias Med, PROFISIO, RA-3100 Rosario, Argentina. [Lajmanovich, Rafael; Attademo, Andres; Poletta, Gisela; Fernanda Simoniello, Maria] Univ Nacl Litoral, Fac Bioquim & Ciencias Biol, Santa Fe, Argentina. [Lajmanovich, Rafael; Attademo, Andres; Poletta, Gisela; Chialvo, Dante; Scremin, Oscar] Consejo Nacl Invest Cient & Tecn, RA-1033 Buenos Aires, DF, Argentina. [Scremin, Oscar] Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90073 USA. [Scremin, Oscar] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90073 USA. RP Scremin, O (reprint author), Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, 11301 Wilshire Bldg, Los Angeles, CA 90073 USA. EM oscremin@ucla.edu RI Chialvo, Dante/A-4658-2009 OI Chialvo, Dante/0000-0002-1038-3637 FU National Research Council of Argentina (CONICET); Capacitacion e Investigacion para la Medicina Argentina (CIMA) FX The work was supported by the National Research Council of Argentina (CONICET) and funds from Capacitacion e Investigacion para la Medicina Argentina (CIMA) a non-profit academic organization. NR 83 TC 6 Z9 7 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X EI 1872-9711 J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2014 VL 45 BP 22 EP 30 DI 10.1016/j.neuro.2014.08.012 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA AX5GQ UT WOS:000346955100003 PM 25196089 ER PT J AU Liachko, NF McMillan, PJ Strovas, TJ Loomis, E Greenup, L Murrell, JR Ghetti, B Raskind, MA Montine, TJ Bird, TD Leverenz, JB Kraemer, BC AF Liachko, Nicole F. McMillan, Pamela J. Strovas, Timothy J. Loomis, Elaine Greenup, Lynne Murrell, Jill R. Ghetti, Bernardino Raskind, Murray A. Montine, Thomas J. Bird, Thomas D. Leverenz, James B. Kraemer, Brian C. TI The Tau Tubulin Kinases TTBK1/2 Promote Accumulation of Pathological TDP-43 SO PLOS GENETICS LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION; ALZHEIMERS-DISEASE BRAIN; HELICAL FILAMENT-TAU; CAENORHABDITIS-ELEGANS; PHOSPHORYLATION SITES; INDUCED NEUROTOXICITY; TARDBP MUTATIONS; DNA-BINDING; IN-VIVO AB Pathological aggregates of phosphorylated TDP-43 characterize amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP), two devastating groups of neurodegenerative disease. Kinase hyperactivity may be a consistent feature of ALS and FTLD-TDP, as phosphorylated TDP-43 is not observed in the absence of neurodegeneration. By examining changes in TDP-43 phosphorylation state, we have identified kinases controlling TDP-43 phosphorylation in a C. elegans model of ALS. In this kinome-wide survey, we identified homologs of the tau tubulin kinases 1 and 2 (TTBK1 and TTBK2), which were also identified in a prior screen for kinase modifiers of TDP-43 behavioral phenotypes. Using refined methodology, we demonstrate TTBK1 and TTBK2 directly phosphorylate TDP-43 in vitro and promote TDP-43 phosphorylation in mammalian cultured cells. TTBK1/2 overexpression drives phosphorylation and relocalization of TDP-43 from the nucleus to cytoplasmic inclusions reminiscent of neuropathologic changes in disease states. Furthermore, protein levels of TTBK1 and TTBK2 are increased in frontal cortex of FTLD-TDP patients, and TTBK1 and TTBK2 co-localize with TDP-43 inclusions in ALS spinal cord. These kinases may represent attractive targets for therapeutic intervention for TDP-43 proteinopathies such as ALS and FTLD-TDP. C1 [Liachko, Nicole F.; Strovas, Timothy J.; Loomis, Elaine; Bird, Thomas D.; Leverenz, James B.; Kraemer, Brian C.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Liachko, Nicole F.; Raskind, Murray A.; Bird, Thomas D.; Kraemer, Brian C.] Univ Washington, Dept Med, Seattle, WA USA. [McMillan, Pamela J.; Greenup, Lynne; Raskind, Murray A.; Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [McMillan, Pamela J.; Leverenz, James B.; Kraemer, Brian C.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Murrell, Jill R.; Ghetti, Bernardino] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA. [Montine, Thomas J.; Bird, Thomas D.; Leverenz, James B.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Montine, Thomas J.; Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. [Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Liachko, NF (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. EM kraemerb@u.washington.edu FU Department of Veterans Affairs [1147891, I01BX007080]; National Institutes of Health [R01NS064131, AG 000057-31, 2P50AG005136-27, 5P50NS2062684-02] FX This work was supported by grants from the Department of Veterans Affairs [Merit Review Grant #1147891 to BCK and CDA2 Award #I01BX007080 to NFL] and National Institutes of Health [R01NS064131 to BCK, AG 000057-31 to NFL, 2P50AG005136-27 and 5P50NS2062684-02 to JBL]). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 14 Z9 14 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD DEC PY 2014 VL 10 IS 12 AR e1004803 DI 10.1371/journal.pgen.1004803 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA AX0NW UT WOS:000346649900015 PM 25473830 ER PT J AU Deng, LQ Bensing, BA Thamadilok, S Yu, H Lau, K Chen, X Ruhl, S Sullam, PM Varki, A AF Deng, Lingquan Bensing, Barbara A. Thamadilok, Supaporn Yu, Hai Lau, Kam Chen, Xi Ruhl, Stefan Sullam, Paul M. Varki, Ajit TI Oral Streptococci Utilize a Siglec-Like Domain of Serine-Rich Repeat Adhesins to Preferentially Target Platelet Sialoglycans in Human Blood SO PLOS PATHOGENS LA English DT Article ID VIRIDANS GROUP STREPTOCOCCI; SUBMANDIBULAR-SUBLINGUAL SALIVA; SURFACE GLYCOPROTEINS GSPB; SIALIC-ACID DIVERSITY; INFECTIVE ENDOCARDITIS; STAPHYLOCOCCAL ENDOCARDITIS; CARDIOVASCULAR-DISEASE; ANTIMICROBIAL THERAPY; CONTAINING RECEPTORS; HEART-ASSOCIATION AB Damaged cardiac valves attract blood-borne bacteria, and infective endocarditis is often caused by viridans group streptococci. While such bacteria use multiple adhesins to maintain their normal oral commensal state, recognition of platelet sialoglycans provides an intermediary for binding to damaged valvular endocardium. We use a customized sialoglycan microarray to explore the varied binding properties of phylogenetically related serine-rich repeat adhesins, the GspB, Hsa, and SrpA homologs from Streptococcus gordonii and Streptococcus sanguinis species, which belong to a highly conserved family of glycoproteins that contribute to virulence for a broad range of Gram-positive pathogens. Binding profiles of recombinant soluble homologs containing novel sialic acid-recognizing Siglec-like domains correlate well with binding of corresponding whole bacteria to arrays. These bacteria show multiple modes of glycan, protein, or divalent cation-dependent binding to synthetic glycoconjugates and isolated glycoproteins in vitro. However, endogenous asialoglycan-recognizing clearance receptors are known to ensure that only fully sialylated glycans dominate in the endovascular system, wherein we find these particular streptococci become primarily dependent on their Siglec-like adhesins for glycan-mediated recognition events. Remarkably, despite an excess of alternate sialoglycan ligands in cellular and soluble blood components, these adhesins selectively target intact bacteria to sialylated ligands on platelets, within human whole blood. These preferred interactions are inhibited by corresponding recombinant soluble adhesins, which also preferentially recognize platelets. Our data indicate that circulating platelets may act as inadvertent Trojan horse carriers of oral streptococci to the site of damaged endocardium, and provide an explanation why it is that among innumerable microbes that gain occasional access to the bloodstream, certain viridans group streptococci have a selective advantage in colonizing damaged cardiac valves and cause infective endocarditis. C1 [Deng, Lingquan; Varki, Ajit] Univ Calif San Diego, Dept Med, Glycobiol Res & Training Ctr, San Diego, CA 92103 USA. [Deng, Lingquan; Varki, Ajit] Univ Calif San Diego, Dept Cellular & Mol Med, Glycobiol Res & Training Ctr, San Diego, CA 92103 USA. [Bensing, Barbara A.; Sullam, Paul M.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Bensing, Barbara A.; Sullam, Paul M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Thamadilok, Supaporn; Ruhl, Stefan] SUNY Buffalo, Sch Dent Med, Dept Oral Biol, Buffalo, NY 14260 USA. [Yu, Hai; Lau, Kam; Chen, Xi] Univ Calif Davis, Dept Chem, Davis, CA 95616 USA. RP Varki, A (reprint author), Univ Calif San Diego, Dept Med, Glycobiol Res & Training Ctr, San Diego, CA 92103 USA. EM a1varki@ucsd.edu OI Ruhl, Stefan/0000-0003-3888-4908 FU G. Harold and Leila Y. Mathers foundation; NIH [P01HL107150, R01-AI41513, R01-AI106987, R01HD065122]; NIH/NIDCR [DE019807]; Department of Veterans Affairs; Northern California Institute for Research and Education, VA Merit Review Award FX This work was supported by grants from the G. Harold and Leila Y. Mathers foundation and NIH P01HL107150 (to AV), R01-AI41513 and R01-AI106987 (to PMS), NIH/NIDCR DE019807 (to SR), NIH R01HD065122 (to XC), and in part by the Department of Veterans Affairs and the Northern California Institute for Research and Education, in particular a VA Merit Review Award to PMS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 68 TC 11 Z9 11 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD DEC PY 2014 VL 10 IS 12 AR e1004540 DI 10.1371/journal.ppat.1004540 PG 15 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AX1JB UT WOS:000346702400027 PM 25474103 ER PT J AU Gonzalez, DA Jenkins, SR AF Gonzalez, David Andres Jenkins, Sharon Rae TI Cross-Measure Equivalence and Communicability in the Assessment of Depression: A Focus on Factor-Based Scales SO ASSESSMENT LA English DT Article DE depression assessment; factors; BDI-II; CES-D; IDAS; IDS ID INVENTORY-II; ANXIETY DISORDERS; DSM-V; BECK; SYMPTOMATOLOGY; SYMPTOMS; QUESTIONNAIRES; DIMENSIONALITY; VALIDITY; HAMILTON AB All measures of depression yield a global summary scale indicating the severity of depressive symptoms, implicitly conceptualized as a homogeneous construct. However, depression is a heterogeneous construct, with different presentations, subtypes, correlates, and responses to interventions. In response, the National Institute of Mental Health (NIMH) has suggested changes in the way depression is assessed, moving the focus to specific factors, such as cognitive, somatic, or affective symptoms. Still, there is little factor overlap between measures, and shared factors are weighted differently. To help fulfill NIMH's strategic plan, this study used canonical correlation analysis (CCA) to explore shared latent variables and redundancy across the measures. It also analyzed the psychometric properties of factor-based subscales in the Beck Depression Inventory-2nd edition (BDI-II), Center for Epidemiologic Studies Depression scale (CES-D), Inventory for Depression and Anxiety Symptoms (IDAS), and Inventory of Depressive Symptomatology (IDS). Using a diverse sample of 218 students who reported at least mild depressive symptoms, this study found that the IDAS was best aligned with NIMH's strategic plan; it has complete DSM-IV/DSM-5 symptom coverage and content-valid, psychometrically sound subscales. The BDI-II, CES-D, and IDS did not have consistent subscales, nor had incomplete or incongruent coverage of DSM criteria. Furthermore, CCA revealed low redundancy across measures (23% to 41% shared variance). These results suggest that different measures of depression do not measure the same construct. As a partial solution, empirical conversion tables were provided for researchers and clinicians to empirically compare total scores from different measures. C1 [Gonzalez, David Andres; Jenkins, Sharon Rae] Univ N Texas, Denton, TX 76203 USA. [Gonzalez, David Andres] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Gonzalez, DA (reprint author), Univ N Texas, Dept Psychol, 1155 Union Circle 311280, Denton, TX 76203 USA. EM davidgonzalez@my.unt.edu NR 44 TC 1 Z9 1 U1 1 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-1911 EI 1552-3489 J9 ASSESSMENT JI Assessment PD DEC PY 2014 VL 21 IS 6 BP 731 EP 741 DI 10.1177/1073191114524018 PG 11 WC Psychology, Clinical SC Psychology GA AX0LS UT WOS:000346644500010 PM 24586091 ER PT J AU Budde, KS Barron, DS Fox, PT AF Budde, Kristin S. Barron, Daniel S. Fox, Peter T. TI Stuttering, induced fluency, and natural fluency: A hierarchical series of activation likelihood estimation meta-analyses SO BRAIN AND LANGUAGE LA English DT Article DE Persistent developmental stuttering; Functional neuroimaging; Meta-analysis; Activation likelihood estimation; ALE ID POSITRON-EMISSION-TOMOGRAPHY; NONSTUTTERING ADULTS; SPEECH PRODUCTION; ALE METAANALYSIS; SINGLE; AREAS; SUPPLEMENTARY; CONNECTIVITY; VALIDATION; PATTERNS AB Developmental stuttering is a speech disorder most likely due to a heritable form of developmental dysmyelination impairing the function of the speech-motor system. Speech-induced brain-activation patterns in persons who stutter (PWS) are anomalous in various ways; the consistency of these aberrant patterns is a matter of ongoing debate. Here, we present a hierarchical series of coordinate-based meta-analyses addressing this issue. Two tiers of meta-analyses were performed on a 17-paper dataset (202 PWS; 167 fluent controls). Four large-scale (top-tier) meta-analyses were performed, two for each subject group (PWS and controls). These analyses robustly confirmed the regional effects previously postulated as "neural signatures of stuttering" (Brown, Ingham, Ingham, Laird, & Fox, 2005) and extended this designation to additional regions. Two smaller-scale (lower-tier) meta-analyses refined the interpretation of the large-scale analyses: (1) a between-group contrast targeting differences between PWS and controls (stuttering trait); and (2) a within-group contrast (PWS only) of stuttering with induced fluency (stuttering state). (C) 2014 Elsevier Inc. All rights reserved. C1 [Budde, Kristin S.; Barron, Daniel S.; Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Budde, Kristin S.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Barron, Daniel S.] Yale Univ, Sch Med, New Haven, CT USA. [Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX USA. [Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX USA. [Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Fox, Peter T.] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China. [Fox, Peter T.] Univ Hong Kong, Dept Linguist, Hong Kong, Hong Kong, Peoples R China. RP Budde, KS (reprint author), 300 George St,Suite 901, New Haven, CT 06511 USA. EM kristin.budde@yale.edu FU National Institute of Health (NIMH) [RO1 MH074457] FX We thank Juan Saenz, Michaela Robertson and P. Mickle Fox for technical assistance. This study was supported by funds from the National Institute of Health (NIMH: RO1 MH074457), P. Fox PI. NR 50 TC 12 Z9 12 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 0093-934X EI 1090-2155 J9 BRAIN LANG JI Brain Lang. PD DEC PY 2014 VL 139 BP 99 EP 107 DI 10.1016/j.bandl.2014.10.002 PG 9 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA AX4FK UT WOS:000346888900009 PM 25463820 ER PT J AU Qureshi, S Galiveeti, S Bichet, DG Roth, J AF Qureshi, Sana Galiveeti, Sneha Bichet, Daniel G. Roth, Jesse TI Diabetes Insipidus: Celebrating a Century of Vasopressin Therapy SO ENDOCRINOLOGY LA English DT Article ID CYCLIC ADENINE RIBONUCLEOTIDE; HUMAN ANTIDIURETIC-HORMONE; ISOLATED TOAD BLADDER; WATER-CHANNEL; ARGININE-VASOPRESSIN; SYNTHETIC ANALOG; PLASMA-MEMBRANE; RECEPTOR GENE; RAT-KIDNEY; PHARMACOLOGICAL CHAPERONES AB Diabetes mellitus, widely known to the ancients for polyuria and glycosuria, budded off diabetes insipidus (DI) about 200 years ago, based on the glucose-free polyuria that characterized a subset of patients. In the late 19th century, clinicians identified the posterior pituitary as the site of pathology, and pharmacologists found multiple bioactivities there. Early in the 20th century, the amelioration of the polyuria with extracts of the posterior pituitary inaugurated a new era in therapy and advanced the hypothesis that DI was due to a hormone deficiency. Decades later, a subset of patients with polyuria unresponsive to therapy were recognized, leading to the distinction between central DI and nephrogenic DI, an early example of a hormone-resistant condition. Recognition that the posterior pituitary had 2 hormones was followed by du Vigneaud's Nobel Prize winning isolation, sequencing, and chemical synthesis of oxytocin and vasopressin. The pure hormones accelerated the development of bioassays and immunoassays that confirmed the hormone deficiency in vasopressin-sensitive DI and abundant levels of hormone in patients with the nephrogenic disorder. With both forms of the disease, acquired and inborn defects were recognized. Emerging concepts of receptors and of genetic analysis led to the recognition of patients with mutations in the genes for 1) arginine vasopressin (AVP), 2) the AVP receptor 2 (AVPR2), and 3) the aquaporin 2 water channel (AQP2). We recount here the multiple skeins of clinical and laboratory research that intersected frequently over the centuries since the first recognition of DI. C1 [Qureshi, Sana; Galiveeti, Sneha; Roth, Jesse] North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Lab Diabet & Diabet Related Disorders, Manhasset, NY 11030 USA. [Qureshi, Sana; Roth, Jesse] Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY 10461 USA. [Galiveeti, Sneha] Mt Sinai Med Ctr Hlth Syst, James J Peters VA Med Ctr, Bronx, NY 10029 USA. [Bichet, Daniel G.] Univ Montreal, Hop Sacre Coeur Montreal, Grp Prot Membranaires, Montreal, PQ H4J 1C5, Canada. [Roth, Jesse] North Shore Long Isl Jewish Hlth Syst, Hofstra North Shore Long Isl Jewish Sch Med, Hempstead, NY 11549 USA. RP Roth, J (reprint author), Yeshiva Univ, Feinstein Inst Med Res North Shore Long Isl Jewis, Albert Einstein Coll Med, 149-37 Powells Cove Blvd, Whitestone, NY 11357 USA. EM jesserothmd@hotmail.com FU Feinstein Institute for Medical Research, Manhasset, NY; Russell Berrie Foundation, Teaneck, NJ; Alan and Tatyana Forman family FX J.R.'s academic program receives support from the Feinstein Institute for Medical Research, Manhasset, NY, Russell Berrie Foundation, Teaneck, NJ, and the Alan and Tatyana Forman family. NR 201 TC 11 Z9 11 U1 0 U2 8 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2014 VL 155 IS 12 BP 4605 EP 4621 DI 10.1210/en.2014-1385 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX0UN UT WOS:000346668000002 PM 25211589 ER PT J AU Schnabolk, G Stauffer, K O'Quinn, E Coughlin, B Kunchithapautham, K Rohrer, B AF Schnabolk, Gloriane Stauffer, Kimberly O'Quinn, Elizabeth Coughlin, Beth Kunchithapautham, Kannan Rohrer, Baerbel TI A comparative analysis of C57BL/6J and 6N substrains; chemokine/cytokine expression and susceptibility to laser-induced choroidal neovascularization SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE rd8 mutation; Choroidal neovascularization; Age-related macular degeneration; Para-inflammation; Pre-conditioning ID DIET-INDUCED OBESITY; MACULAR DEGENERATION; MOUSE MODEL; MUTATION; GENE; INFLAMMATION; COMPLEMENT; THERAPY; RETINA; CELLS AB Age-related macular degeneration (AMD) is the most prevalent cause of blindness in the elderly. To study potential underlying mechanisms of AMD, animal models are utilized, focusing mostly on mice. Recently, genomic and phenotypic differences between the so-called control substrains, C57BL/6J and C57BL/6N, have been described in models of ocular and non-ocular diseases. In particular, the rd8 mutation of the Crb 1 gene present in the C57BL/6N has been shown to impact certain ocular phenotypes and appears to augment phenotypes generally associated with inflammation. Here, we investigated angiogenic factor and cytokine expression using pathway arrays as well as the susceptibility to laser-induced choroidal neovascularization (CNV), a model of wet AMD, in the two substrains. Age-matched 3-month-old C57BL/ 6J and C57BL/6N animals differed in gene expression levels for angiogenic factors and cytokines, with 6N animals expressing higher levels of inflammatory markers than 6Js. Yet laser-induced CNV was comparable in size between the two substrains. This lack of difference in CNV size was correlated with a gene expression profile that was comparable between the two substrains, due to the fact that the degree of change in gene expression of inflammatory markers after CNV was blunted in 6N mice. In summary, significant gene expression differences exist between C57BL/6J and C57BL/6N animals, reinforcing the notion that appropriate litter-mate controls or genetic background controls need to be used. Contrary to our expectation, CNV was not augmented in 6N animals, suggesting that low chronic inflammation in the RPE might provide a level of pre-conditioning and protection against stress. Published by Elsevier Ltd. C1 [Schnabolk, Gloriane; Rohrer, Baerbel] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC 29401 USA. [Stauffer, Kimberly; O'Quinn, Elizabeth; Coughlin, Beth; Kunchithapautham, Kannan; Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. RP Rohrer, B (reprint author), Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA. EM rohrer@musc.edu FU National Institutes of Health (NIH) [R01EY019320]; Department for Veteran Affairs [RX000444]; Beckman Initiative for Macular Research [1202]; Research to Prevent Blindness (PRB), New York, NY,; Foundation Fighting Blindness, Columbia, MD; Wofford College to K.S. (John Rampey Fund); NIH [C06RR015455] FX We thank Luanna Bartholomew for critical review. This work was supported in the laboratory of B.R. in part by the National Institutes of Health (NIH R01EY019320), a Department for Veteran Affairs merit award RX000444, the Beckman Initiative for Macular Research (1202), an unrestricted grant to MUSC from Research to Prevent Blindness (RPB), New York, NY, Foundation Fighting Blindness, Columbia, MD, and a summer undergraduate stipend from Wofford College to K.S. (John Rampey Fund). Animal studies were conducted in a facility constructed with support from the NIH C06RR015455. NR 29 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 EI 1096-0007 J9 EXP EYE RES JI Exp. Eye Res. PD DEC PY 2014 VL 129 BP 18 EP 23 DI 10.1016/j.exer.2014.10.005 PG 6 WC Ophthalmology SC Ophthalmology GA AX4HJ UT WOS:000346893800004 PM 25305577 ER PT J AU Willauer, P Sangeorzan, BJ Whittaker, EC Shofer, JB Ledoux, WR AF Willauer, Patrick Sangeorzan, Bruce J. Whittaker, Eric C. Shofer, Jane B. Ledoux, William R. TI The Sensitivity of Standard Radiographic Foot Measures to Misalignment SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE foot; X-ray; radiograph; misalignment ID ALIGNMENT; RELIABILITY; FLATFOOT; HINDFOOT AB Background: The purpose of this study was to identify the effects that X-ray source misalignment has on common measurements made from anterior-poster (AP) and medial-lateral (ML) view foot radiographs. Methods: A cadaveric foot model was used to obtain ML radiographs with +/- 25 degree transverse plane misalignment. From these images the calcaneal pitch angle (CPA) and lateral talometatarsal angle (LTMA) were measured. AP images were captured with up to 30 degree sagittal plane misalignment as well as +/- 15 degree misalignment in the transverse plane at each sagittal angle. From these images the talonavicular coverage angle (TNCA) and talometatarsal angle (TMA) were measured. Results: On the ML images, the CPA was sensitive to transverse plane misalignment from -10 to -25 degrees and from 15 to 25 degrees (P < .005). The LTMA was a more reliable measurement than the CPA and did not demonstrate sensitivity to transverse plane misalignment. On the AP images, the TNCA and TMA were not sensitive to sagittal plane misalignment alone. However, at 0, 10, and 15 degrees sagittal misalignment the TNCA showed sensitivity to transverse plane misalignment (P < .0083). Conclusion: Misalignment of an X-ray source can lead to errors in the measurement of foot radiographic parameters, especially the CPA when there is transverse plane misalignment and the TNCA when there is both sagittal and transverse plane misalignment. The LTMA and TMA can be measured reliably, even with significant misalignment present. C1 [Willauer, Patrick; Sangeorzan, Bruce J.; Whittaker, Eric C.; Shofer, Jane B.; Ledoux, William R.] RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Dept Vet Affairs, Seattle, WA USA. [Willauer, Patrick] Univ Washington, Sch Med, Seattle, WA USA. [Sangeorzan, Bruce J.; Ledoux, William R.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. [Ledoux, William R.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. RP Sangeorzan, BJ (reprint author), VA Puget Sound, Ms 151,1660 S Columbian Way, Seattle, WA 98108 USA. EM bsangeor@uw.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 FU Department of Veterans Affairs [A4843C]; University of Washington Medical Student Research and Training Program FX The author(s) received the following financial support for the research, authorship, and/or publication of this article: his research was partially supported by the Department of Veterans Affairs, RR&D grant A4843C and the University of Washington Medical Student Research and Training Program. NR 19 TC 2 Z9 2 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1071-1007 EI 1944-7876 J9 FOOT ANKLE INT JI Foot Ankle Int. PD DEC PY 2014 VL 35 IS 12 BP 1334 EP 1340 DI 10.1177/1071100714549188 PG 7 WC Orthopedics SC Orthopedics GA AX1FL UT WOS:000346693300016 PM 25237177 ER PT J AU Tsai, J Pilver, CE Hoff, RA AF Tsai, Jack Pilver, Corey E. Hoff, Rani A. TI Potential Mental Health Needs of US Adult Residents Under Different Provisions of the Affordable Care Act SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID NATIONAL EPIDEMIOLOGIC SURVEY; PERSONALITY-DISORDER; UNITED-STATES; MEDICAID; PREVALENCE; DISABILITY; ALCOHOL; POVERTY; INDIVIDUALS; COMORBIDITY AB Objective: This study examined different groups of the US population who may be affected by the expansion of Medicaid and creation of health insurance exchanges under the Affordable Care Act (ACA). Method: Data were based on structured interviews with a nationally representative sample of 34,587 adults from the 2004-2005 Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Psychiatric diagnoses were assessed with the Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV. Results: Of the total sample, 6.4% were currently on Medicaid; 3.9% were uninsured and likely eligible for the Medicaid expansion (LEME); 8.6% were uninsured and not LEME but likely to participate in the health insurance exchanges; 4.6% were insured and LEME; and 76.6% were insured and not LEME. Among those uninsured, those LEME had a significantly higher prevalence of mood and anxiety disorders than those not LEME (odds ratios = 1.26-1.41). Among those insured, those LEME had a higher prevalence of mood, anxiety, substance use, and personality disorders than those not LEME (odds ratios = 1.78-2.41). Although there were few clinical differences between those currently on Medicaid and those LEME, those currently on Medicaid were more likely to use all types of services for mood, anxiety, and substance use disorders. Conclusions: The ACA may directly affect the 12.5% of the US adult population who are uninsured by requiring them to obtain insurance coverage. Given the high prevalence for various psychiatric disorders among those uninsured, state plans to expand Medicaid and create health insurance exchanges have potential to offer coverage to many adults with mental health needs, and states should carefully plan for comprehensive services. (C) Copyright 2014 Physicians Postgraduate Press, Inc. C1 [Tsai, Jack] US Dept Vet Affairs, New England Mental Illness Res Educ & Clin Ctr, West Haven, CT USA. [Tsai, Jack; Hoff, Rani A.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Pilver, Corey E.] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT USA. [Hoff, Rani A.] US Dept Vet Affairs, Northeast Program Evaluat Ctr, West Haven, CT USA. RP Tsai, J (reprint author), 950 Campbell Ave,151D, West Haven, CT 06516 USA. EM jack.tsai@yale.edu FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development FX This work was supported by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development. Role of the sponsor: The funding agencies had no role in the conduct or publication of the study. NR 28 TC 5 Z9 5 U1 1 U2 6 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2014 VL 75 IS 12 BP 1402 EP 1410 DI 10.4088/JCP.13m08885 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AX3RL UT WOS:000346856500017 PM 25271598 ER PT J AU Zorick, T Mandelkern, MA Brody, AL AF Zorick, Todd Mandelkern, Mark A. Brody, Arthur L. TI A Naturalistic Study of the Association Between Antidepressant Treatment and Outcome of Smoking Cessation Treatment SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; ALCOHOL DEPENDENCE; MENTAL-ILLNESS; DOUBLE-BLIND; TOBACCO USE; SERTRALINE; METHAMPHETAMINE; PREDICTORS; DISORDERS; HEALTH AB Objective: Psychiatric, medical, and substance use comorbidities are highly prevalent among smokers, and many of these comorbidities have been found to be associated with reduced rate of success in clinical trials for smoking cessation. While much has been established about the best available treatments from these clinical trials, little is known about the effect of concomitant psychiatric medications on quit rates in smoking cessation programs. On the basis of results in populations with tobacco dependence and other substance use disorders, we hypothesized that smokers taking antidepressants would have a lower rate of quitting in an outpatient smoking cessation program. Method: We performed a naturalistic chart review of veterans (N = 144) enrolled in the Veterans Affairs Greater Los Angeles Mental Health Clinic Smoking Cessation Program from March 2011 through July 2013, who met DSM-IV-TR criteria for nicotine dependence. The primary outcome was smoking cessation with treatment, as evidenced by a patient report of at least 1 week of abstinence and an exhaled carbon monoxide level of = 6 ppm (if available) at the end of acute treatment, with comparators including concomitant psychotropic medication treatment, psychiatric and medical comorbidities, and the presence of a substance use disorder history. We utilized stepwise binary logistic regression as the main statistical technique. Results: We found that current antidepressant treatment (P =.003) and history of substance use disorder (P = .01) (particularly cocaine [P = .02]) were associated with a lower rate of quitting smoking. Furthermore, the association between antidepressant treatment and reduced rate of smoking cessation was primarily seen in patients with a history of substance use disorder (P =.003). Conclusions: While preliminary, these results suggest an important clinical interaction meriting future study. If these findings are confirmed, clinicians may want to consider the risk of reduced ability to quit smoking in patients with a history of substance use disorder who are taking antidepressants. (C) Copyright 2014 Physicians Postgraduate Press, Inc. C1 [Zorick, Todd] VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA 90073 USA. [Mandelkern, Mark A.] VA Greater Los Angeles Healthcare Syst, Dept Imaging, Los Angeles, CA 90073 USA. [Zorick, Todd; Brody, Arthur L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Zorick, T (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Psychiat, 11301 Wilshire Blvd,B210-2nd Floor, Los Angeles, CA 90073 USA. EM tzorick@mednet.ucla.edu FU VA Career Development Award [I01 BX007080]; National Institute on Drug Abuse [R01 DA20872]; Tobacco-Related Disease Research Program [23XT-0002]; VA Merit Review Award [I01 CX000412] FX Dr Zorick is supported by a VA Career Development Award (I01 BX007080). Dr Brody receives grant funding from the National Institute on Drug Abuse (R01 DA20872), the Tobacco-Related Disease Research Program (23XT-0002), and a VA Merit Review Award (I01 CX000412). NR 25 TC 1 Z9 1 U1 0 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2014 VL 75 IS 12 BP E1433 EP E1438 DI 10.4088/JCP.14m09012 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AX3RL UT WOS:000346856500003 PM 25551240 ER PT J AU Akiba, Y Kaunitz, JD AF Akiba, Yasutada Kaunitz, Jonathan D. TI Prostaglandin pathways in duodenal chemosensing SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article; Proceedings Paper CT 15th Taishotoyama International Symposium on Gastroenterology CY SEP 26-28, 2013 CL Tokyo, JAPAN DE acid sensing; ATP-P2Y signal; bacterial sensing; dual oxidase ID COLONIC EPITHELIAL-CELLS; ARACHIDONIC-ACID RELEASE; HYDROGEN-PEROXIDE; BICARBONATE SECRETION; RAT DUODENUM; BACTERIAL OVERGROWTH; DUAL OXIDASE; CHLORIDE SECRETION; EXTRACELLULAR ATP; SENSING PATHWAYS AB Acid-sensing pathways, which trigger mucosal defense mechanisms in response to luminal acid, involve the rapid afferent-mediated capsaicin pathway and the sustained prostaglandin (PG) pathway. Luminal acid quickly increases protective PG synthesis and release from epithelia, although the mechanism by which luminal acid induces PG synthesis is still mostly unknown. Acid exposure augments purinergic ATP-P2Y signaling by inhibition of intestinal alkaline phosphatase activity. Since P2Y activation increases intracellular Ca2+, we further hypothesized that ATP-P2Y signals increase the generation of H2O2 derived from dual oxidase, a member of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family activated by Ca2+. Our recent studies suggest that acid exposure increases H2O2 output, followed by phospholipase A(2) and cyclooxygenase activation, increasing PG synthesis. Released prostaglandin E2 augments protective HCO3- and mucus secretion via EP4 receptor activation. Thus, the PG pathway as a component of duodenal acid sensing consists of acid-related intestinal alkaline phosphatase inhibition, ATP-P2Y signals, dual oxidase 2-derived H2O2 production, phospholipase A(2) activation, prostaglandin E2 synthesis, and EP4 receptor activation. The PG pathway is also involved in luminal bacterial sensing in the duodenum via activation of pattern recognition receptors, including Toll-like receptors and nucleotide-binding oligomerization domain 2. The presence of acute mucosal responses to luminal bacteria suggests that the duodenum is important for host defenses and may reduce bacterial loading to the hindgut using H2O2, complementing gastric acidity and anti-bacterial bile acids. C1 [Akiba, Yasutada; Kaunitz, Jonathan D.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Akiba, Yasutada; Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Akiba, Yasutada; Kaunitz, Jonathan D.] Brentwood Biomed Res Inst, Los Angeles, CA USA. RP Akiba, Y (reprint author), Univ Calif Los Angeles, Sch Med, Dept Med, Vet Affairs Greater Los Angles Healthcare Syst, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM yakiba@mednet.ucla.edu FU BLRD VA [I01 BX001245]; NIDDK NIH HHS [P30 DK041301, R01 DK054221, R01 DK54221] NR 67 TC 2 Z9 2 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0815-9319 EI 1440-1746 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD DEC PY 2014 VL 29 SU 4 SI SI BP 93 EP 98 DI 10.1111/jgh.12731 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AW9MA UT WOS:000346580200018 PM 25521740 ER PT J AU Tenhula, WN Nezu, AM Nezu, CM Stewart, MO Miller, SA Steele, J Karlin, BE AF Tenhula, Wendy N. Nezu, Arthur M. Nezu, Christine Maguth Stewart, Michael O. Miller, Sarah A. Steele, Jennifer Karlin, Bradley E. TI Moving Forward: A Problem-Solving Training Program to Foster Veteran Resilience SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article DE veterans; problem solving; resilience; social problem solving; readjustment ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL THERAPY; PATIENT-LEVEL OUTCOMES; NATIONAL DISSEMINATION; DEPRESSION; HEALTH; METAANALYSIS; CARE; PHQ-9 AB It is vital for mental health professionals serving veterans to be able to address the full range of needs presented by returning veterans, including those that affect a veterans' daily life (e.g., relationships, employment, and community functioning) but may not rise to the level of requiring specialty mental health care. This article describes the development and evaluation of an innovative Veterans Affairs program, Moving Forward, which focuses on building resilience and reducing emotional distress. Moving Forward is based on the principles of problem-solving therapy that have been adapted for use in a four-session, classroom-based training program for veterans. The program evaluation results indicate that Moving Forward is feasible, well-received by veterans, and yields improvements in social problem solving, resilience, and overall distress levels. Although there is a strong evidence base for problem-solving therapy in a range of clinical settings and with a variety of patient populations (Nezu et al., 2013), this represents the first effort to apply these principles in a program focusing on the readjustment and resilience of our nation's veterans. We include several recommendations for building on these results, including the use of Internet-based training, inclusion of family members in training, and recommendations for research in this important area. C1 [Tenhula, Wendy N.] US Dept Vet Affairs, Vet Affairs Dept Def Integrated Mental Hlth, Vet Hlth Adm, Washington, DC 20240 USA. [Nezu, Arthur M.; Nezu, Christine Maguth] Drexel Univ, Philadelphia, PA USA. [Stewart, Michael O.] US Dept Vet Affairs, Vet Hlth Adm, Washington, DC 20240 USA. [Miller, Sarah A.] US Dept Vet Affairs, Cent Off, Washington, DC 20240 USA. [Steele, Jennifer; Karlin, Bradley E.] US Dept Vet Affairs, Washington, DC 20240 USA. RP Tenhula, WN (reprint author), US Dept Vet Affairs, VA Dept Def Integrated Mental Hlth, Mental Hlth Serv 10P4M, Cent Off, 810 Vermont Ave NW, Washington, DC 20240 USA. EM wendy.tenhula@va.gov NR 31 TC 4 Z9 4 U1 2 U2 17 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 EI 1939-1323 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD DEC PY 2014 VL 45 IS 6 SI SI BP 416 EP 424 DI 10.1037/a0037150 PG 9 WC Psychology, Multidisciplinary SC Psychology GA AX0HS UT WOS:000346634200005 ER PT J AU Maguen, S Madden, E Neylan, TC Cohen, BE Bertenthal, D Seal, KH AF Maguen, Shira Madden, Erin Neylan, Thomas C. Cohen, Beth E. Bertenthal, Daniel Seal, Karen H. TI Timing of Mental Health Treatment and PTSD Symptom Improvement Among Iraq and Afghanistan Veterans SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; PRIMARY-CARE; GENDER-DIFFERENCES; MILITARY SERVICE; US VETERANS; COMBAT; TRAJECTORIES; SCREEN; CHECKLIST; DIAGNOSES AB Objective: This study examined demographic, military, temporal, and logistic variables associated with improvement of posttraumatic stress disorder (PTSD) among Iraq and Afghanistan veterans who received mental health outpatient treatment from the U.S. Department of Veterans Affairs (VA) health care system. The authors sought to determine whether time between last deployment and initiating mental health treatment was associated with a lack of improvement in PTSD symptoms. Methods: The authors conducted a retrospective analysis of existing medical records of Iraq and Afghanistan veterans who enrolled in VA health care, received a postdeployment PTSD diagnosis, and initiated treatment for one or more mental health problems between October 1, 2007, and December 31, 2011, and whose records contained results of PTSD screening at the start of treatment and approximately one year later (N=39,690). Results: At the start of treatment, 75% of veterans diagnosed as having PTSD had a positive PTSD screen. At follow-up, 27% of those with a positive screen at baseline had improved, and 43% of those with a negative screen at baseline remained negative. A negative PTSD screen at follow-up was associated with female gender, older age, white race, having never married, officer rank, non-Army service, closer proximity to the nearest VA facility, and earlier initiation of treatment after the end of the last deployment. Conclusions: Interventions to reduce delays in initiating mental health treatment may improve veterans' treatment response. Further studies are needed to test interventions for particular veteran subgroups who were less likely than others to improve with treatment. C1 [Maguen, Shira; Madden, Erin; Neylan, Thomas C.; Cohen, Beth E.; Bertenthal, Daniel; Seal, Karen H.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Maguen, Shira; Madden, Erin; Neylan, Thomas C.] Mental Illness Res Educ & Clin Ctr, Dept Mental Hlth, San Francisco, CA USA. [Cohen, Beth E.; Seal, Karen H.] Mental Illness Res Educ & Clin Ctr, Dept Med, San Francisco, CA USA. [Maguen, Shira; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Cohen, Beth E.; Seal, Karen H.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, San Francisco, CA 94121 USA. EM shira.maguen@va.gov FU VA Health Services Research and Development Service (HSR& D) Career Development Award [RCD 06-042]; HSR& D Service Directed Research Award [SDR-08-408]; Department of Defense Mental Health Research Infrastructure Award [W81XWH-11-2-0189]; Department of Defense; VA FX This research was supported by VA Health Services Research and Development Service (HSR& D) Career Development Award (RCD 06-042) to Dr. Maguen, an HSR& D Service Directed Research Award (SDR-08-408) to Dr. Seal, and a Department of Defense Mental Health Research Infrastructure Award (W81XWH-11-2-0189) to Dr. Neylan. The authors thank Julie Dinh, B.A., for assistance.; Dr. Neylan has received study medication for a study funded by the Department of Defense and study medication for a study funded by the VA. The other authors report no competing interests. NR 31 TC 7 Z9 7 U1 1 U2 17 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD DEC PY 2014 VL 65 IS 12 BP 1414 EP 1419 DI 10.1176/appi.ps.201300453 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA AW9TG UT WOS:000346599500017 PM 25082217 ER PT J AU Rosen, MI Ablondi, K Black, AC Mueller, L Serowik, KL Martino, S Mobo, B Rosenheck, RA AF Rosen, Marc I. Ablondi, Karen Black, Anne C. Mueller, Lisa Serowik, Kristin L. Martino, Steve Mobo, Ben Hur Rosenheck, Robert A. TI Work Outcomes After Benefits Counseling Among Veterans Applying for Service Connection for a Psychiatric Condition SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SUPPORTED EMPLOYMENT; DISABILITY COMPENSATION; SOCIAL-SECURITY; MENTAL-ILLNESS; SUBSTANCE-ABUSE; PSYCHOMETRIC PROPERTIES; HOMELESS VETERANS; BENEFICIARIES; SEEKING AB Objective: This study's objective was to determine the efficacy of benefits counseling in a clinical trial. There has been concern that disability payments for psychiatric disorders reduce incentives for employment and rehabilitation. Benefits counseling, with education about opportunities to work and the financial implications of work on receipt of disability benefits, may counter these disincentives. Methods: This single-blind, six-month randomized clinical trial enrolled 84 veterans who had applied for service-connected compensation for a psychiatric condition. Veterans were randomly assigned to either four sessions of benefits counseling or of a control condition involving orientation to the U.S Department of Veterans Affairs health care system and services. Days of paid work and work-related activities were assessed at follow-up visits by using a time-line follow-back calendar. Results: Veterans assigned to benefits counseling worked for pay for significantly more days than did veterans in the control group (effect size=.69, p<.05), reflecting an average of three more days of paid employment during the 28 days preceding the six-month follow-up. Benefits counseling was associated with increased use of mental health services, but this correlation did not mediate the effect of benefits counseling on working. Conclusions: Barriers to employment associated with disability payments are remediable with basic counseling. More research is needed to understand the active ingredient of this counseling and to strengthen the intervention. C1 [Rosen, Marc I.; Ablondi, Karen; Black, Anne C.; Serowik, Kristin L.; Martino, Steve; Rosenheck, Robert A.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. [Rosen, Marc I.; Ablondi, Karen; Black, Anne C.; Serowik, Kristin L.; Martino, Steve] VA Connecticut Healthcare Syst, US Dept Vet Affairs, Dept Psychiat, West Haven, CT USA. [Rosenheck, Robert A.] VA New England Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Bedford, MA USA. [Mueller, Lisa] Edith Nourse Rogers Mem Vet Hosp, Bedford, MA USA. [Mobo, Ben Hur] Christiana Care Hlth Syst, Newark, DE USA. RP Rosen, MI (reprint author), Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. EM marc.rosen@yale.edu FU VA Rehabilitation Research and Development grant [D6432]; National Institute of Mental Health [R25 DA026636]; Veterans Integrated Service Network 1 Mental Illness Research, Education and Clinical Center FX The authors acknowledge the contributions of Rani Hoff, Ph.D., to the VA service use analyses in this study. This work was supported by VA Rehabilitation Research and Development grant D6432 to Dr. Rosen, National Institute of Mental Health grant R25 DA026636 to Dr. Martino, and the Veterans Integrated Service Network 1 Mental Illness Research, Education and Clinical Center. NR 47 TC 3 Z9 3 U1 3 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD DEC PY 2014 VL 65 IS 12 BP 1426 EP 1432 DI 10.1176/appi.ps.201300478 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA AW9TG UT WOS:000346599500019 PM 25082304 ER PT J AU Bodell, L Forney, KJ Keel, P Gutierrez, P Joiner, TE AF Bodell, Lindsay Forney, Katherine Jean Keel, Pamela Gutierrez, Peter Joiner, Thomas E. TI Consequences of Making Weight: A Review of Eating Disorder Symptoms and Diagnoses in the United States Military SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Review DE eating disorder symptoms; eating disorders; military; purging; risk factors; veterans ID CONTRIBUTING FACTORS; PSYCHIATRIC COMORBIDITY; BODY DISSATISFACTION; HEALTH BEHAVIORS; BULIMIA-NERVOSA; AIR-FORCE; FOLLOW-UP; PREVALENCE; VETERANS; FEMALE AB Eating disorders are serious psychiatric illnesses associated with health problems. Such problems may compromise military performance, highlighting the need to establish the level of eating pathology that exists in military samples. This article qualitatively reviews prevalence estimates of eating disorder symptoms and diagnoses in military samples, providing nonmilitary estimates for context. Findings suggest that eating disorder symptoms are prevalent in cadets and active duty service members, especially when using self-report measures. The increased salience of weight in the military and increased exposure to trauma may influence risk for eating disorders. Alternatively, individuals at risk for eating disorders may self-select into the military. Overall, this review suggests that eating disorder symptoms are common in military samples and that further research is warranted. C1 [Bodell, Lindsay; Forney, Katherine Jean; Keel, Pamela; Joiner, Thomas E.] Florida State Univ, Tallahassee, FL 32306 USA. [Gutierrez, Peter] Denver VA Med Ctr, Denver, CO USA. RP Joiner, TE (reprint author), Florida State Univ, Dept Psychol, 1107 West Call St, Tallahassee, FL 32306 USA. EM joiner@psy.fsu.edu OI Gutierrez, Peter/0000-0001-8981-8404 FU NIMH NIH HHS [T32 MH093311] NR 46 TC 6 Z9 6 U1 3 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0969-5893 EI 1468-2850 J9 CLIN PSYCHOL-SCI PR JI Clin. Psychol.-Sci. Pract. PD DEC PY 2014 VL 21 IS 4 BP 398 EP 409 DI 10.1111/cpsp.12082 PG 12 WC Psychology, Clinical SC Psychology GA AW5UC UT WOS:000346338200006 PM 25642105 ER PT J AU Han, S Snavely, C Jerome, J Mallampalli, R AF Han, SeungHye Snavely, Courtney Jerome, Jake Mallampalli, Rama TI LIPOPOLYSACCHARIDE PRIMES THE INFLAMMASOME BY INCREASING LEVELS OF IMMUNOREACTIVE NALP3 SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Han, SeungHye] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Snavely, Courtney; Jerome, Jake; Mallampalli, Rama] Univ Pittsburgh, Pittsburgh, PA USA. [Mallampalli, Rama] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 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 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 47 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211800048 ER PT J AU Kirschen, M Elkind, J Lim, M Putnam, B Cohen, A AF Kirschen, Matthew Elkind, Jaclynn Lim, Miranda Putnam, Brendan Cohen, Akiva TI THE ROLE OF BRANCHED CHAIN AMINO ACIDS IN THE FUNCTIONAL RECOVERY FROM TRAUMATIC BRAIN INJURY SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Kirschen, Matthew; Elkind, Jaclynn; Putnam, Brendan; Cohen, Akiva] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Lim, Miranda] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 108 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211800073 ER PT J AU Soble, JR Eichstaedt, KE Waseem, H Mattingly, ML Benbadis, SR Bozorg, AM Vale, FL Schoenberg, MR AF Soble, Jason R. Eichstaedt, Katie E. Waseem, Hena Mattingly, Michelle L. Benbadis, Selim R. Bozorg, Ali M. Vale, Fernando L. Schoenberg, Mike R. TI Clinical utility of the Wechsler Memory Scale-Fourth Edition (WMS-IV) in predicting laterality of temporal lobe epilepsy among surgical candidates SO EPILEPSY & BEHAVIOR LA English DT Article DE Temporal lobe epilepsy; Neuropsychological assessment; Presurgical evaluation; Wechsler Memory Scale-Fourth Edition (WMS-IV); Rey Auditory Verbal Learning Test (RAVLT) ID BOSTON NAMING TEST; NEUROPSYCHOLOGICAL ASSESSMENT; ULTIMATE SIDE; SURGERY; PERFORMANCE; VALIDATION; LOBECTOMY; OUTCOMES; ABILITY; EEG AB This study evaluated the accuracy of the Wechsler Memory Scale-Fourth Edition (WMS-IV) in identifying functional cognitive deficits associated with seizure laterality in localization-related temporal lobe epilepsy (TLE) relative to a previously established measure, the Rey Auditory Verbal Learning Test (RAVLT). Emerging WMS-IV studies have highlighted psychometric improvements that may enhance its ability to identify lateralized memory deficits. Data from 57 patients with video-EEG-confirmed unilateral TLE who were administered the WMS-IV and RAVLT as part of a comprehensive presurgical neuropsychological evaluation for temporal resection were retrospectively reviewed. We examined the predictive accuracy of the WMS-IV not only in terms of verbal versus visual composite scores but also using individual subtests. A series of hierarchal logistic regression models were developed, including the RAVLT, WMS-IV delayed subtests (Logical Memory, Verbal Paired Associates, Designs, Visual Reproduction), and a WMS-IV verbal-visual memory difference score. Analyses showed that the RAVLT significantly predicted laterality with overall classification rates of 69.6% to 70.2%, whereas neither the individual WMS-IV subtests nor the verbal-visual memory difference score accounted for additional significant variance. Similar to previous versions of the WMS, findings cast doubt as to whether the WMS-IV offers significant incremental validity in discriminating seizure laterality in TLE beyond what can be obtained from the RAVLT. (C) 2014 Elsevier Inc. All rights reserved. C1 [Soble, Jason R.] South Texas Vet Hlth Care Syst, Psychol Serv 116B, San Antonio, TX 78229 USA. [Eichstaedt, Katie E.; Mattingly, Michelle L.; Schoenberg, Mike R.] Univ S Florida, Morsani Coll Med, Dept Psychiat & Behav Sci, Tampa, FL 33613 USA. [Waseem, Hena; Vale, Fernando L.; Schoenberg, Mike R.] Univ S Florida, USF Hlth, Morsani Coll Med, Dept Neurosurg & Brain Repair, Tampa, FL 33606 USA. [Benbadis, Selim R.; Bozorg, Ali M.; Schoenberg, Mike R.] Univ S Florida, USF Hlth, Morsani Coll Med, Dept Neurol, Tampa, FL 33606 USA. RP Schoenberg, MR (reprint author), Univ S Florida, Morsani Coll Med, Dept Psychiat & Behav Sci, 3515 East Fletcher Ave, Tampa, FL 33613 USA. EM Jason.Soble@va.gov; keichsta@health.usf.edu; hwaseem@health.usf.edu; mmatting@health.usf.edu; sbenbadi@health.usf.edu; abozorg@health.usf.edu; fvale@health.usf.edu; mschoenb@health.usf.edu RI Schoenberg, Mike/J-9018-2012 OI Schoenberg, Mike/0000-0003-1355-3651 NR 38 TC 4 Z9 4 U1 2 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD DEC PY 2014 VL 41 BP 232 EP 237 DI 10.1016/j.yebeh.2014.10.014 PG 6 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA AW3LH UT WOS:000346187700045 PM 25461222 ER PT J AU Albergotti, WG Byrd, JK De Almeida, JR Kim, S Duvvuri, U AF Albergotti, W. Greer Byrd, J. Kenneth De Almeida, John R. Kim, Seungwon Duvvuri, Umamaheswar TI Robot-assisted level II-IV neck dissection through a modified facelift incision: initial North American experience SO INTERNATIONAL JOURNAL OF MEDICAL ROBOTICS AND COMPUTER ASSISTED SURGERY LA English DT Article DE head and neck surgery; robotic neck dissection; cancer ID THYROIDECTOMY; CARCINOMA; SURGERY AB BackgroundCosmesis is of increasing importance to the otolaryngology patient population. This is the first report of clinical outcomes of robot-assisted neck dissection by North American groups. MethodsThis is a retrospective case-control study. Cases included three patients who underwent isolated, ipsilateral robot-assisted neck dissection. Operative time, estimated blood loss, lymph node retrieval, total drainage, hospital stay and complications from this group were compared against the outcomes of six consecutive patients who underwent conventional neck dissection. ResultsOperative times were longer in robot-assisted neck dissection (mean 234min) compared with the conventional neck dissection (mean 110min). There were no significant differences between the two groups in other outcomes. ConclusionsRobot-assisted selective neck dissection of levels II-IV is feasible through a modified facelift incision. Our initial data suggest that this procedure is surgically sound. It should be applied by experienced surgeons who wish to avoid a cervical incision. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Albergotti, W. Greer; Byrd, J. Kenneth; Duvvuri, Umamaheswar] Vet Affairs Pittsburgh Hlth Syst, Pittsburgh, PA USA. [Duvvuri, Umamaheswar] Univ Pittsburgh, Med Ctr, Dept Otolaryngol, Pittsburgh, PA 15213 USA. [De Almeida, John R.] Univ Toronto, Dept Otolaryngology Head & Neck Surg, Toronto, ON, Canada. RP Duvvuri, U (reprint author), Univ Pittsburgh, Med Ctr, Inst Eye & Ear, Dept Otolaryngol, 200 Lothrop St,Suite 500, Pittsburgh, PA 15213 USA. EM duvuriu@upmc.edu FU Department of Veterans Affairs; PNC Foundation; Intuitive Surgical Inc. FX This study was supported in part by funds from the Department of Veterans Affairs, the PNC Foundation, and a research grant from Intuitive Surgical Inc. The funding organizations had no role in the design or conduct of the study, collection, management, analysis or interpretation of the data. They had no role in the preparation, review or approval of this manuscript and the decision to submit this manuscript was solely the decision of the authors. NR 17 TC 6 Z9 7 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1478-5951 EI 1478-596X J9 INT J MED ROBOT COMP JI Int. J. Med. Robot. Comput. Assist. Surg. PD DEC PY 2014 VL 10 IS 4 BP 391 EP 396 DI 10.1002/rcs.1585 PG 6 WC Surgery SC Surgery GA AW4TG UT WOS:000346272700002 ER PT J AU Byrd, JK Leonardis, RL Bonawitz, SC Losee, JE Duvvuri, U AF Byrd, James K. Leonardis, Rachel L. Bonawitz, Steven C. Losee, Joseph E. Duvvuri, Umamaheswar TI Transoral robotic surgery for pharyngeal stenosis SO INTERNATIONAL JOURNAL OF MEDICAL ROBOTICS AND COMPUTER ASSISTED SURGERY LA English DT Article DE robotics; pharyngoplasty; local flaps ID ACQUIRED NASOPHARYNGEAL STENOSIS; BALLOON DILATION AB BackgroundPharyngeal stenosis is a complication of head and neck cancer and sleep apnea treatment that results in functional impairment. Due to the location of the stenosis and tendency to recur, surgical management is challenging. Robotic surgery may allow these areas to be treated with surgical technique that would be difficult using traditional approaches. MethodsA retrospective chart review was performed to identify patients who underwent transoral robotic surgery (TORS) for pharyngeal stenosis at a tertiary hospital system. ResultsFive patients were identified, ages 8-75years. Length of follow-up ranged from 1-12months. There was one failure, a 74year old male with a history of chemoradiation to the area who has required additional procedures. ConclusionTORS may offer improved surgical access to the pharynx in patients who require complex reconstruction that would otherwise be very difficult. Appropriate patient selection is necessary and long-term follow-up is warranted for the selected cases. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Byrd, James K.; Leonardis, Rachel L.; Duvvuri, Umamaheswar] Univ Pittsburgh, Med Ctr, Vet Affairs Pittsburgh Hlth Syst, Pittsburgh, PA 15213 USA. [Byrd, James K.; Leonardis, Rachel L.; Duvvuri, Umamaheswar] Univ Pittsburgh, Med Ctr, Dept Otolaryngol, Pittsburgh, PA 15213 USA. [Bonawitz, Steven C.] Johns Hopkins Univ, Dept Plast & Reconstruct, Baltimore, MD USA. [Losee, Joseph E.] Childrens Hosp Pittsburgh, Div Pediat Plast Surg, Pittsburgh, PA 15213 USA. RP Byrd, JK (reprint author), Univ Pittsburgh, Med Ctr, Dept Otolaryngol, 200 Lothrop St,Suite 500, Pittsburgh, PA 15213 USA. EM byrdjk@upmc.edu NR 7 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1478-5951 EI 1478-596X J9 INT J MED ROBOT COMP JI Int. J. Med. Robot. Comput. Assist. Surg. PD DEC PY 2014 VL 10 IS 4 BP 418 EP 422 DI 10.1002/rcs.1591 PG 5 WC Surgery SC Surgery GA AW4TG UT WOS:000346272700006 PM 24737499 ER PT J AU Zhang, JM Sheerin, C Mandel, H Banducci, AN Myrick, H Acierno, R Amstadter, AB Wang, ZW AF Zhang, Jingmei Sheerin, Christina Mandel, Howard Banducci, Anne N. Myrick, Hugh Acierno, Ronald Amstadter, Ananda B. Wang, Zhewu TI Variation in SLC1A1 is related to combat-related posttraumatic stress disorder SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Posttraumatic stress disorder; SLC1A1; Combat stress disorders; Genes; Veterans ID OBSESSIVE-COMPULSIVE DISORDER; GENOME-WIDE ASSOCIATION; ENVIRONMENTAL CONTRIBUTIONS; TRAUMA EXPOSURE; 2 GENERATIONS; PTSD; SYMPTOMS; TWIN; GLUTAMATE; SAMPLE AB Candidate gene studies have yet to investigate the glutamate system, the primary excitatory neurotransmitter of the HPA-axis related to PTSD risk. We investigated 13 SNPs in the glutamate transporter gene (SLC1A1) in relation to PTSD among combat-exposed veterans. Participants (n = 418) completed a diagnostic interview and provided a blood sample for DNA isolation and genotyping. A subset of participants (n = 391) had severity and combat exposure data available. In the primary logistic regression gender and rsl 0739062 were significant predictors of PTSD diagnosis (OR = 0.50; OR = 1.43). In the linear regression analysis, combat exposure was the only significant predictor (beta = 0.16) of severity. A computed genetic risk sum score was significant in relation to PTSD diagnosis (OR = 1.15) and severity scores (beta = 0.14) above and beyond the effects of combat exposure. This study provides preliminary support for the relationship of glutamate transporter polymorphisms to PTSD risk and the need for further genetic studies within this system. Published by Elsevier Ltd: C1 [Zhang, Jingmei; Myrick, Hugh; Acierno, Ronald; Wang, Zhewu] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Mandel, Howard; Myrick, Hugh; Acierno, Ronald; Wang, Zhewu] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Amstadter, Ananda B.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. [Sheerin, Christina] McGuire VA Med Ctr, Richmond, VA USA. [Banducci, Anne N.] Univ Maryland, Ctr Addict Personal & Emot Res, College Pk, MD 20742 USA. RP Wang, ZW (reprint author), Med Univ S Carolina, Dept Psychiat, 67 President St, Charleston, SC 29425 USA. EM wanzh@musc.edu OI Banducci, Anne N/0000-0003-1213-7998 NR 38 TC 1 Z9 1 U1 3 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 EI 1873-7897 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD DEC PY 2014 VL 28 IS 8 BP 902 EP 907 DI 10.1016/j.janxdis.2014.09.013 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AW8WM UT WOS:000346540200021 PM 25445080 ER PT J AU First, MB Bhat, V Adler, D Dixon, L Goldman, B Koh, S Levine, B Oslin, D Siris, S AF First, Michael B. Bhat, Venkat Adler, David Dixon, Lisa Goldman, Beth Koh, Steve Levine, Bruce Oslin, David Siris, Sam TI How Do Clinicians Actually Use the Diagnostic and Statistical Manual of Mental Disorders in Clinical Practice and Why We Need to Know More SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE DSM-IV; clinical use; DSM-5; use of DSM in clinical practice ID DSM-III-R; PSYCHIATRIC-DIAGNOSIS; UNITED-STATES; GLOBAL SURVEY; RELIABILITY; CRITERIA; CLASSIFICATION; CARE; INTERVIEWS; ATTITUDES AB The clinical use of the Diagnostic and Statistical Manual of Mental Disorders (DSM) is explicitly stated as a goal for both the DSM Fourth Edition and DSM Fifth Edition (DSM-5) revisions. Many uses assume a relatively faithful application of the DSM diagnostic definitions. However, studies demonstrate significant discrepancies between clinical psychiatric diagnoses with those made using structured interviews suggesting that clinicians do not systematically apply the diagnostic criteria. The limited information regarding how clinicians actually use the DSM raises important questions: a) How can the clinical use be improved without first having a baseline assessment? b) How can potentially significant shifts in practice patterns based on wording changes be assessed without knowing the extent to which the criteria are used as written? Given the American Psychiatric Association's plans for interim revisions to the DSM-5, the value of a detailed exploration of its actual use in clinical practice remains a significant ongoing concern and deserves further study including a number of survey and in vivo studies. C1 [First, Michael B.; Dixon, Lisa] Columbia Univ, Med Ctr, New York State Psychiat Inst, Dept Psychiat, New York, NY 10032 USA. [Bhat, Venkat] McGill Univ, Dept Psychiat, Montreal, PQ, Canada. [Adler, David] Tufts Univ, Sch Med, Dept Psychiat, Tufts Med Ctr, Boston, MA 02111 USA. [Goldman, Beth] Blue Cross Blue Shield Michigan, Behav Hlth, Detroit, MI USA. [Koh, Steve] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Levine, Bruce] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Oslin, David] Univ Penn, Philadelphia VA Med Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. [Siris, Sam] Zucker Hillside Hosp, Glen Oaks, NY USA. RP First, MB (reprint author), Columbia Univ, Med Ctr, New York State Psychiat Inst, Dept Psychiat, 1051 Riverside Dr,Unit 60, New York, NY 10032 USA. EM mbf2@columbia.edu NR 34 TC 6 Z9 6 U1 4 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD DEC PY 2014 VL 202 IS 12 BP 841 EP 844 DI 10.1097/NMD.0000000000000210 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AW4QJ UT WOS:000346265400001 PM 25390931 ER PT J AU Ward, RE Boudreau, RM Caserotti, P Harris, TB Zivkovic, S Goodpaster, BH Satterfield, S Kritchevsky, SB Schwartz, AV Vinik, AI Cauley, JA Simonsick, EM Newman, AB Strotmeyer, ES AF Ward, Rachel E. Boudreau, Robert M. Caserotti, Paolo Harris, Tamara B. Zivkovic, Sasa Goodpaster, Bret H. Satterfield, Suzanne Kritchevsky, Stephen B. Schwartz, Ann V. Vinik, Aaron I. Cauley, Jane A. Simonsick, Eleanor M. Newman, Anne B. Strotmeyer, Elsa S. CA Hlth Aging Body Composition Study TI Sensory and Motor Peripheral Nerve Function and Incident Mobility Disability SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE peripheral nerve function; disability; older adults; longitudinal analysis; muscle strength ID MUSCLE STRENGTH; OLDER-ADULTS; BODY-COMPOSITION; PHYSICAL PERFORMANCE; DIABETIC-NEUROPATHY; WOMENS HEALTH; AGE; CONDUCTION; BLACK; DEGENERATION AB ObjectivesTo assess the relationship between sensorimotor nerve function and incident mobility disability over 10years. DesignProspective cohort study with longitudinal analysis. SettingTwo U.S. clinical sites. ParticipantsPopulation-based sample of community-dwelling older adults with no mobility disability at 2000/01 examination (N=1,680; mean age SD 76.52.9, body mass index 27.14.6; 50.2% female, 36.6% black, 10.7% with diabetes mellitus). MeasurementsMotor nerve conduction amplitude (poor <1 mV) and velocity (poor <40m/s) were measured on the deep peroneal nerve. Sensory nerve function was measured using 10- and 1.4-g monofilaments and vibration detection threshold at the toe. Lower extremity symptoms included numbness or tingling and aching or burning pain. Incident mobility disability assessed semiannually over 8.5years (interquartile range 4.5-9.6years) was defined as two consecutive self-reports of a lot of difficulty or inability to walk one-quarter of a mile or climb 10 steps. ResultsNerve impairments were detected in 55% of participants, and 30% developed mobility disability. Worse motor amplitude (HR=1.29 per SD, 95% CI=1.16-1.44), vibration detection threshold (HR=1.13 per SD, 95% CI=1.04-1.23), symptoms (HR=1.65, 95% CI=1.26-2.17), two motor impairments (HR=2.10, 95% CI=1.43-3.09), two sensory impairments (HR=1.91, 95% CI=1.37-2.68), and three or more nerve impairments (HR=2.33, 95% CI=1.54-3.53) predicted incident mobility disability after adjustment. Quadriceps strength mediated relationships between certain nerve impairments and mobility disability, although most remained significant. ConclusionPoor sensorimotor nerve function independently predicted mobility disability. Future work should investigate modifiable risk factors and interventions such as strength training for preventing disability and improving function in older adults with poor nerve function. C1 [Ward, Rachel E.] Spaulding Rehabil Hosp, Cambridge, England. [Ward, Rachel E.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Boudreau, Robert M.; Cauley, Jane A.; Newman, Anne B.; Strotmeyer, Elsa S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Caserotti, Paolo] Univ Southern Denmark, Inst Sports Sci & Clin Biomech, Odense, Denmark. [Harris, Tamara B.] NIA, Lab Epidemiol Biometry & Demog, NIH, Bethesda, MD USA. [Zivkovic, Sasa] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Zivkovic, Sasa] Vet Affairs Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Goodpaster, Bret H.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. [Kritchevsky, Stephen B.] Wake Forest, Div Gerontol & Geriatr Med, Dept Internal Med, Winston Salem, NC USA. [Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Vinik, Aaron I.] Eastern Virginia Med Sch, Dept Neurobiol, Norfolk, VA 23501 USA. [Simonsick, Eleanor M.] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. RP Strotmeyer, ES (reprint author), Univ Pittsburgh, Dept Epidemiol, 130 N Bellefield Ave,Rm 515, Pittsburgh, PA 15213 USA. EM StrotmeyerE@edc.pitt.edu RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408; Newman, Anne B./0000-0002-0106-1150; Strotmeyer, Elsa/0000-0002-4093-6036; Boudreau, Robert/0000-0003-0162-5187 FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, 1-R01-AG 028050]; National Institute of Nursing Research Grant [R01-NR012459]; Intramural Research Program of the National Institutes of Health, National Institute on Aging; University of Pittsburgh Claude D. Pepper Older Americans Independence Center [P30-AG024827]; American Diabetes Association [1-04-JF-46] FX This research was supported by National Institute on Aging Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106 and Grant 1-R01-AG 028050 (to ESS) and National Institute of Nursing Research Grant R01-NR012459 and supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging, the University of Pittsburgh Claude D. Pepper Older Americans Independence Center (P30-AG024827) Pilot Grant (to ESS), and the American Diabetes Association (1-04-JF-46 to ESS). NR 33 TC 10 Z9 10 U1 1 U2 6 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 DEC PY 2014 VL 62 IS 12 BP 2273 EP 2279 DI 10.1111/jgs.13152 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AW8FX UT WOS:000346497600005 PM 25482096 ER PT J AU Pa, J Goodson, W Bloch, A King, AC Yaffe, K Barnes, DE AF Pa, Judy Goodson, William Bloch, Andrew King, Abby C. Yaffe, Kristine Barnes, Deborah E. TI Effect of Exercise and Cognitive Activity on Self-Reported Sleep Quality in Community-Dwelling Older Adults with Cognitive Complaints: A Randomized Controlled Trial SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE physical activity; cognition; sleep; aging; intervention ID MODERATE-INTENSITY EXERCISE; NONPHARMACOLOGIC TREATMENT; NEUROPSYCHIATRIC SYMPTOMS; BEHAVIORAL TREATMENT; PRACTICE PARAMETERS; CHRONIC INSOMNIA; ELDERLY PERSONS; RATED QUALITY; TAI-CHI; IMPAIRMENT AB ObjectivesTo compare the effects of different types of physical and mental activity on self-reported sleep quality over 12weeks in older adults with cognitive and sleep complaints. DesignRandomized controlled trial. SettingGeneral community. ParticipantsSeventy-two inactive community-dwelling older adults with self-reported sleep and cognitive problems (mean age 73.36.1; 60% women). InterventionRandom allocation to four arms using a two-by-two factorial design: aerobic+cognitive training, aerobic+educational DVD, stretching+cognitive training, and stretching+educational DVD arms (60min/d, 3d/wk for physical and mental activity for 12weeks). MeasurementsChange in sleep quality using seven questions from the Sleep Disorders Questionnaire on the 2005 to 2006 National Health and Nutrition Examination Survey (range 0-28, with higher scores reflecting worse sleep quality). Analyses used intention-to-treat methods. ResultsSleep quality scores did not differ at baseline, but there was a significant difference between the study arms in change in sleep quality over time (P<.005). Mean sleep quality scores improved significantly more in the stretching+educational DVD arm (5.1 points) than in the stretching+cognitive training (1.2 points), aerobic+educational DVD (1.1 points), or aerobic+cognitive training (0.25 points) arms (all P<.05, corrected for multiple comparisons). Differences between arms were strongest for waking at night (P=.02) and taking sleep medications (P=.004). ConclusionSelf-reported sleep quality improved significantly more with low-intensity physical and mental activities than with moderate- or high-intensity activities in older adults with self-reported cognitive and sleep difficulties. Future longer-term studies with objective sleep measures are needed to corroborate these results. C1 [Pa, Judy; Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Pa, Judy] Univ So Calif, Inst Neuroimaging & Informat, Dept Neurol, Los Angeles, CA USA. [Goodson, William] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Bloch, Andrew] James Quillen Vet Affairs Med Ctr, Mountain Home, TN USA. [King, Abby C.] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [King, Abby C.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Yaffe, Kristine; Barnes, Deborah E.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine; Barnes, Deborah E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine; Barnes, Deborah E.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Barnes, DE (reprint author), San Francisco VA Med Ctr, 4150 Clement St 151R, San Francisco, CA 94121 USA. EM Deborah.Barnes@ucsf.edu FU Alzheimer's Association [IIRG-06-27306, NIRP-12-259277]; National Institutes of Health (NIH) [K01-AG024069, K01-AG034175, R01-AG026720]; NIH/National Center for Research Resources/University of California, San Francisco-Clinical and Translational Science Institute [KL2 RR024130] FX This work was supported by the Alzheimer's Association (IIRG-06-27306, NIRP-12-259277) and the National Institutes of Health (NIH; K01-AG024069, K01-AG034175, R01-AG026720). This work also was supported by NIH/National Center for Research Resources/University of California, San Francisco-Clinical and Translational Science Institute (KL2 RR024130). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Exercise space and equipment donated by the YMCA of San Francisco, California. Computer equipment donated by Posit Science Corp., San Francisco, California. NR 42 TC 5 Z9 7 U1 3 U2 29 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 DEC PY 2014 VL 62 IS 12 BP 2319 EP 2326 DI 10.1111/jgs.13158 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AW8FX UT WOS:000346497600011 PM 25516028 ER PT J AU Kinosian, B AF Kinosian, Bruce TI Twenty-First Century Home-Centered Medicine: It's About the Touch, Not the Tech... SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material ID PRIMARY-CARE; TECHNOLOGY; TRIAL C1 [Kinosian, Bruce] Univ Penn, Leonard Davis Inst Hlth Econ, Perelman Sch Med, Div Geriatr, Philadelphia, PA 19104 USA. [Kinosian, Bruce] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Geriatr & Extended Care Data Anal Ctr, Philadelphia, PA USA. RP Kinosian, B (reprint author), Univ Penn, Leonard Davis Inst Hlth Econ, Perelman Sch Med, Div Geriatr, Philadelphia, PA 19104 USA. NR 13 TC 1 Z9 1 U1 1 U2 4 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 DEC PY 2014 VL 62 IS 12 BP 2433 EP 2435 DI 10.1111/jgs.13176 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AW8FX UT WOS:000346497600030 PM 25516039 ER PT J AU Liao, W Jordaan, G Coriaty, N Sharma, S AF Liao, Wei Jordaan, Gwen Coriaty, Natalie Sharma, Sanjai TI Amplification of B cell receptor-Erk signaling by Rasgrf-1 overexpression in chronic lymphocytic leukemia SO LEUKEMIA & LYMPHOMA LA English DT Article DE CLL; B cell receptor; guanine exchange factor; Rasgrf-1; Erk pathway ID EXCHANGE FACTOR; TYROSINE KINASE; RAS PROTEINS; DEPENDENT ACTIVATION; THERAPEUTIC TARGET; GDP/GTP EXCHANGE; DOWN-REGULATION; UP-REGULATION; IN-VITRO; EXPRESSION AB Rasgrf-1 is a guanine exchange factor (GEF) that catalyzes the exchange of GDP for GTP. In a RNA microarray analysis of chronic lymphocytic leukemia (CLL) specimens (n = 5), this gene was found to be overexpressed in CLL as compared to normal peripheral blood mononuclear cell (PBMC) CD19 + B cells (n = 3). CLL specimens (n = 29) expressed Rasgrf-1 RNA at levels 5-300-fold higher as compared to normal B cells. CLL specimens expressed a 75 kDa isoform that was smaller than the expected full-length protein (140 kDa) and the truncated variant had higher GEF activity. Knockdown of Rasgrf-1 in CLL specimens inhibited active GTP-bound Ras and the Ras/Erk/mitogen-activated protein kinase (MAPK) pathway. Rasgrf-1 was phosphorylated and activated by B cell receptor (BCR) signaling that increased its GEF function, and this phosphorylation was blocked by Src and Bruton's tyrosine kinase (BTK) inhibitors. Rasgrf-1 is a novel GEF protein that has a role in BCR signaling and its overexpression further activates the Ras/Erk/MAPK pathway in CLL specimens. C1 [Liao, Wei; Jordaan, Gwen; Coriaty, Natalie; Sharma, Sanjai] Univ Calif Los Angeles, Sch Med, Greater Los Angeles VA Healthcare Ctr, Div Hematol Oncol, Los Angeles, CA 90073 USA. RP Sharma, S (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,Bldg 304,Rm E1-115, Los Angeles, CA 90073 USA. EM sasharma@mednet.ucla.edu FU Flight Attendant Medical Research Institute Fund (FAMRI); Veterans Administration Merit Review Grant FX We thank Dr. Alan Lichtenstein for useful discussions regarding this project. This work was supported by a grant from the Flight Attendant Medical Research Institute Fund (FAMRI) and a Veterans Administration Merit Review Grant to S.S. NR 58 TC 1 Z9 3 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD DEC PY 2014 VL 55 IS 12 BP 2907 EP 2916 DI 10.3109/10428194.2014.898759 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA AW9IQ UT WOS:000346571100036 PM 24597981 ER PT J AU Bascom, PB Bordley, JL Lawton, AJ AF Bascom, Paul B. Bordley, Jessica L. Lawton, Andrew J. TI High-Dose Neuroleptics and Neuroleptic Rotation for Agitated Delirium Near the End of Life SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Article DE agitated delirium; terminal delirium; palliative sedation; chlorpromazine; olanzapine; end-of-life care ID PALLIATIVE SEDATION; ADVANCED CANCER; OLANZAPINE; CHLORPROMAZINE; HALOPERIDOL; TRIAL AB Reason for the study: Agitated delirium presents unique challenges for hospice and palliative care clinicians. Haloperidol, the recommended neuroleptic, may be ineffective at low dose, or poorly tolerated at higher doses. Main Findings: This article reports on two patients with refractory agitated delirium. Both developed extrapyramidal symptoms from haloperidol and required rotation to an alternate neuroleptic. Patient #1 received 2000 mg/day oral chlorpromazine. Patient #2 received greater than 200 mg/day sublingual olanzapine. Control of agitation was achieved, though the doses were substantially higher than has previously reported in the literature. Each patient experienced considerable sedation, though this was an acceptable side effect for the family. Each patient was transferred from the acute care hospital to a location of family preference. There they died within a week of transfer. Conclusions: Agitated delirium is a palliative care emergency. High doses of neuroleptic medications, with rotation to an alternate neuroleptic when side effects occur with standard haloperidol, may effectively palliate agitated delirium. This remedy can provide the patient with a peaceful dying in a place of their choosing. C1 [Bascom, Paul B.] Palliat Care Phys, Portland, OR USA. [Bordley, Jessica L.] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97232 USA. [Lawton, Andrew J.] Oregon Hlth & Sci Univ, Portland, OR 97232 USA. RP Bascom, PB (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd, Portland, OR 97232 USA. EM paulbbascom@gmail.com NR 21 TC 1 Z9 1 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-9091 EI 1938-2715 J9 AM J HOSP PALLIAT ME JI Am. J. Hosp. Palliat. Med. PD DEC PY 2014 VL 31 IS 8 BP 808 EP 811 DI 10.1177/1049909113507124 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AW2AR UT WOS:000346091100004 PM 24081790 ER PT J AU Svenson, J Cunningham, M Dasgupta, S Gilkeson, GS AF Svenson, John Cunningham, Melissa Dasgupta, Subhajit Gilkeson, Gary S. TI Estrogen Receptor Alpha Modulates Mesangial Cell Responses to Toll-Like Receptor Ligands SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Mesangial cells; Estrogen receptors; Toll-like receptors; Innate immunity ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; AUTOIMMUNE-DISEASE; EXPRESSION; ACID; MOUSE; 17-BETA-ESTRADIOL; PHOSPHORYLATION; DIFFERENTIATION; RECOGNITION; DEFICIENCY AB The female predominance in lupus is incompletely understood. The mechanisms for this difference are multifactorial involving the sex chromosomes, the hormones, and their receptors. We, and others, demonstrated that estrogen receptor alpha (ER)-deficient female mice developed significantly less lupus-like renal disease. This protective effect of ER deficiency occurred despite no impact on glomerular immune complex deposition. We hypothesized that decreased renal disease in ER-deficient mice was due to a dampened renal response to inflammatory stimuli. Given the role of Toll-like receptors (TLRs) in lupus, we assessed whether there was an interaction between TLR responses and ER. Herein, we show that TLR3, 4, and 7 ligands all enhanced mesangial cell (MC) ER expression, whereas neither estrogen, nor ER, impacted TLR3, 4, or 7 expression in MCs. The lack of ER markedly decreased MC production of interleukin 6 and monocyte chemoattractant protein 1 (MCP-1) following addition of TLR3, 4, and 7 ligands. In MCs, TLR ligands induced ER phosphorylation and nuclear localization. TLR3-induced nuclear factor B nuclear translocation in MCs was not significantly affected by estrogen or ER. Finally, we demonstrate that female MCs express more TLR3 and respond to TLR ligands with a significantly increased production of interleukin-6 compared with male MCs. These results identify a significant impact/interaction of ER in TLR-mediated inflammatory responses in MCs. C1 Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Gilkeson, GS (reprint author), 96 Jonathan Lucas St,Suite 816,MSC 637, Charleston, SC 29425 USA. EM gilkeson@musc.edu OI Cunningham, Melissa/0000-0002-9207-1986 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Biomedical Laboratory Research and Development [I01BX000470] FX Supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Biomedical Laboratory Research and Development, I01BX000470. NR 35 TC 5 Z9 5 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD DEC PY 2014 VL 348 IS 6 BP 492 EP 500 DI 10.1097/MAJ.0000000000000339 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AW0XK UT WOS:000346014300008 PM 25343264 ER PT J AU Jain, S Khera, R Corrales-Medina, VF Townsend, RR Chirinos, JA AF Jain, Snigdha Khera, Rohan Corrales-Medina, Vicente F. Townsend, Raymond R. Chirinos, Julio A. TI "Inflammation and arterial stiffness in humans" SO ATHEROSCLEROSIS LA English DT Review DE Arterial stiffness; Inflammation; Pulse wave velocity; Cardiovascular risk ID PULSE-WAVE VELOCITY; NITRIC-OXIDE SYNTHASE; C-REACTIVE PROTEIN; SYSTEMIC-LUPUS-ERYTHEMATOSUS; RANDOMIZED CONTROLLED-TRIAL; TYPE-2 DIABETES-MELLITUS; FACTOR-ALPHA THERAPY; SMOOTH-MUSCLE-CELLS; RHEUMATOID-ARTHRITIS; AORTIC STIFFNESS AB Arterial stiffness is an established marker of cardiovascular morbidity and mortality and a potential therapeutic target. While hypertension and aging are established factors contributing to arterial stiffness, the role of inflammation in stiffening of the arteries is less well understood. We summarize existing literature regarding inflammation and arterial stiffness, including a discussion of the potential mechanisms by which inflammation may lead to arterial stiffening and studies assessing: (1) The association between subclinical inflammation and arterial stiffness in the general population; (2) The presence of increased arterial stiffness in primary inflammatory diseases; (3) The effect of anti-inflammatory therapy on arterial stiffness in primary inflammatory disease including the effect of statins; (4) Experimental evidence of immunization-induced arterial stiffening in normal adults. We discuss potential opportunities to assess the impact of anti-inflammatory interventions on arterial stiffness in subjects without primary inflammatory conditions. We also review the effect of inflammation on wave reflections. Published by Elsevier Ireland Ltd. C1 [Jain, Snigdha; Khera, Rohan] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [Corrales-Medina, Vicente F.] Univ Ottawa, Ottawa, ON, Canada. [Corrales-Medina, Vicente F.] Ottawa Hosp, Res Inst, Ottawa, ON, Canada. [Townsend, Raymond R.; Chirinos, Julio A.] Univ Penn, Philadelphia, PA 19060 USA. [Townsend, Raymond R.; Chirinos, Julio A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Chirinos, JA (reprint author), Univ Penn, Philadelphia, PA 19060 USA. EM julio.chirinos@uphs.upenn.edu RI Khera, Rohan/H-9029-2012 OI Khera, Rohan/0000-0001-9467-6199; Corrales-Medina, Vicente/0000-0002-9691-491X FU NIH [1R21AG043802] FX This work was supported by NIH grant 1R21AG043802 (JAC). NR 94 TC 34 Z9 35 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD DEC PY 2014 VL 237 IS 2 BP 381 EP 390 DI 10.1016/j.atherosclerosis.2014.09.011 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW1RG UT WOS:000346066600031 PM 25463062 ER PT J AU Hajsadeghi, F Nabavi, V Bhandari, A Choi, A Vincent, H Flores, F Budoff, M Ahmadi, N AF Hajsadeghi, Fereshteh Nabavi, Vahid Bhandari, Ajay Choi, Andrew Vincent, Hunter Flores, Ferdinand Budoff, Matthew Ahmadi, Naser TI Increased epicardial adipose tissue is associated with coronary artery disease and major adverse cardiovascular events SO ATHEROSCLEROSIS LA English DT Article DE Epicardial adipose tissue (EAT); Computed tomography angiography (CTA); Major adverse cardiac event (MACE); Coronary artery disease (CAD) ID PERICARDIAL FAT; RISK-FACTORS; ADIPOCYTES AB Background: Increased-epicardial-adipose tissue (EAT) is associated with the presence and severity of subclinical-atherosclerosis. This study investigates the long-term clinical-outcome of subjects with and without increased-EAT. Methods: Two hundred and forty-five subjects, aged 61 +/- 9 years and 34% women underwent clinically-indicated computed-tomography-angiography (CTA), and body-surfacearea adjusted EAT was measured and were followed prospectively. CTA-diagnosed coronary-arterydisease (CAD) was defined as obstructive (luminal-stenosis >= 50%), non-obstructive (luminal-stenosis: 1 -49%) and zero-obstruction. Major-adverse-cardiac-event (MACE) was defined as myocardial-infarction or cardiovascular-death. Results: EAT increased significantly from subjects with zero-obstructioncoronaries (93 +/- 37 cm(3)/m(2)) to non-obstructive-CAD (132 +/- 25 cm(3)/m(2)) to obstructive-CAD (145 +/- 35 cm(3)/m(2)) (P = 0.01). During the 48-month follow-up, the event-rate was 8.6% (21). The event free survival-rate decreased significantly from 99% in the lowest-quartile to 86.6% in the highestquartile of EAT. After adjustment for risk-factors, the hazard ratio of MACE was 1.4, 3.1 and 5.7 in lower mid-, upper mid-and highest-quartiles of EAT as compared to lowest-quartile of EAT (P < 0.05). Conclusion: Increased EAT is directly associated with CAD and predicts MACE independent of the age, gender and conventional-risk-factors. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Hajsadeghi, Fereshteh; Nabavi, Vahid; Bhandari, Ajay; Choi, Andrew; Vincent, Hunter; Flores, Ferdinand; Budoff, Matthew; Ahmadi, Naser] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90073 USA. RP Hajsadeghi, F (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Greater Los Angeles VA Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM drfsadeghi@gmail.com NR 10 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD DEC PY 2014 VL 237 IS 2 BP 486 EP 489 DI 10.1016/j.atherosclerosis.2014.09.037 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW1RG UT WOS:000346066600047 PM 25463078 ER PT J AU Friedlander, AH AF Friedlander, A. H. TI The need to develop a strategy for managing incidental findings on maxillofacial imaging studies: a call for action SO DENTOMAXILLOFACIAL RADIOLOGY LA English DT Letter ID TOMOGRAPHY; CT C1 [Friedlander, A. H.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. [Friedlander, A. H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Friedlander, AH (reprint author), Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. EM arthur.friedlander@med.va.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0250-832X EI 1476-542X J9 DENTOMAXILLOFAC RAD JI Dentomaxillofac. Radiol. PD DEC PY 2014 VL 43 IS 8 AR 20140284 DI 10.1259/dmfr.20140284 PG 2 WC Dentistry, Oral Surgery & Medicine; Radiology, Nuclear Medicine & Medical Imaging SC Dentistry, Oral Surgery & Medicine; Radiology, Nuclear Medicine & Medical Imaging GA AW4DL UT WOS:000346231400009 PM 25299932 ER PT J AU Waltz, TJ Campbell, DG Kirchner, JE Lombardero, A Bolkan, C Zivin, K Lanto, AB Chaney, EF Rubenstein, LV AF Waltz, Thomas J. Campbell, Duncan G. Kirchner, JoAnn E. Lombardero, Anayansi Bolkan, Cory Zivin, Kara Lanto, Andrew B. Chaney, Edmund F. Rubenstein, Lisa V. TI Veterans With Depression in Primary Care: Provider Preferences, Matching, and Care Satisfaction SO FAMILIES SYSTEMS & HEALTH LA English DT Article DE care satisfaction; patient centered care; primary care mental health; treatment matching; treatment preference ID MENTAL-HEALTH; PATIENT PREFERENCE; COLLABORATIVE CARE; AUDIT-C; DSM-IV; DISORDERS; AFFAIRS; INTERVENTIONS; COMORBIDITY; AFGHANISTAN AB Primary care is often the first point of care for individuals with depression. Depressed patients often have comorbid alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD). Understanding variations in treatment preferences and care satisfaction in this population can improve care planning and outcomes. The design involved a cross-sectional comparison of veterans screening positive for depression. Veterans receiving primary care during the previous year were contacted (n = 10, 929) and were screened for depression using the PHQ-2/PHQ-9. Those with probable depression (n = 761) underwent a comprehensive assessment including screens for AUD and PTSD, treatment provider preferences, treatments received, and satisfaction with care. Treatment provider preferences differed based on specific mental health comorbidities, and satisfaction with care was associated with receipt of preferred care. Depressed veterans with comorbid PTSD were more likely to prefer care from more than one provider type (e.g., a psychiatrist and a primary care provider) and were more likely to receive treatment that matched their preferences than veterans without comorbid PTSD. Veterans receiving full or partial treatment matches affirmed satisfaction with care at higher rates, and veterans with comorbid PTSD were least satisfied when care did not match their preferences. Patient satisfaction with care is an increasingly important focus for health care systems. This study found significant variations in depressed patients' satisfaction with care in terms of treatment matching, particularly among those with comorbid PTSD. Delivery of care that matches patient treatment preferences is likely to improve depressed patient's satisfaction with the care provided. C1 [Waltz, Thomas J.] Eastern Michigan Univ, Dept Psychol, Ypsilanti, MI 48197 USA. [Waltz, Thomas J.; Kirchner, JoAnn E.] Arkansas Dept Vet Affairs, Mental Hlth QUERI, HSR&D, North Little Rock, AR USA. [Campbell, Duncan G.; Lombardero, Anayansi] Univ Montana, Dept Psychol, Missoula, MT 59812 USA. [Kirchner, JoAnn E.] Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. [Bolkan, Cory] Washington State Univ Vancouver, Dept Human Dev, Vancouver, BC 98686, Canada. [Zivin, Kara] Vet Affairs Ann Arbor, CCMR, HSR&D, Ann Arbor, MI USA. [Zivin, Kara] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Zivin, Kara] Univ Michigan, Dept Hlth Management & Policy, Ann Arbor, MI 48109 USA. [Zivin, Kara] Univ Michigan, Inst Social Res, Ann Arbor, MI 48109 USA. [Lanto, Andrew B.] Vet Affairs Greater Los Angeles, HSR&D, Los Angeles, CA USA. [Chaney, Edmund F.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Rubenstein, Lisa V.] Vet Affairs Greater Los Angeles, HSR&D Ctr Implementat Practice & Res Support, Los Angeles, CA USA. [Rubenstein, Lisa V.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. [Rubenstein, Lisa V.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Waltz, TJ (reprint author), Eastern Michigan Univ, Dept Psychol, 341 Sci Complex, Ypsilanti, MI 48197 USA. EM twaltz1@emich.edu OI Waltz, Thomas/0000-0001-7976-430X FU Department of Veterans Affairs (VA) Health Services Research and Development (HSRD) Service; VA Quality Enhancement Research Initiative (QUERI) [MHI 99-375, MNT 01-027, MHQ 10-06]; Department of Veterans Affairs [CD2 07-206-1, IIR 10-176-3]; VA Office of Academic Affiliations (OAA) Associated Health Postdoctoral Fellowship Program at the HSR&D Center for Mental Healthcare Outcomes Research (CeMHOR) FX The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. This project was funded by the Department of Veterans Affairs (VA) Health Services Research and Development (HSR&D) Service and the VA Quality Enhancement Research Initiative (QUERI) (Project nos. MHI 99-375, MNT 01-027, MHQ 10-06) and Department of Veterans Affairs CD2 07-206-1 and IIR 10-176-3. Dr. Waltz was funded by a VA Office of Academic Affiliations (OAA) Associated Health Postdoctoral Fellowship Program at the HSR&D Center for Mental Healthcare Outcomes Research (CeMHOR). We thank Valorie Shue for editorial comments on a draft of this article. NR 37 TC 2 Z9 2 U1 1 U2 13 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1091-7527 EI 1939-0602 J9 FAM SYST HEALTH JI Fam. Syst. Health PD DEC PY 2014 VL 32 IS 4 BP 367 EP 377 DI 10.1037/fsh0000071 PG 11 WC Health Care Sciences & Services; Family Studies; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Family Studies; Public, Environmental & Occupational Health GA AW1US UT WOS:000346076900002 PM 25090611 ER PT J AU Gardner, RC Burke, JF Nettiksimmons, J Kaup, A Barnes, DE Yaffe, K AF Gardner, Raquel C. Burke, James F. Nettiksimmons, Jasmine Kaup, Allison Barnes, Deborah E. Yaffe, Kristine TI Dementia Risk After Traumatic Brain Injury vs Nonbrain Trauma The Role of Age and Severity SO JAMA NEUROLOGY LA English DT Article ID YOUNG ONSET DEMENTIA; ALZHEIMERS-DISEASE; HEAD-INJURY; ADMINISTRATIVE DATA; PARKINSONS-DISEASE; OLDER-ADULTS; POPULATION; COHORT; MORTALITY; ACCURACY AB IMPORTANCE Epidemiologic evidence regarding the importance of traumatic brain injury (TBI) as a risk factor for dementia is conflicting. Few previous studies have used patients with non-TBI trauma (NTT) as controls to investigate the influence of age and TBI severity. OBJECTIVE To quantify the risk of dementia among adults with recent TBI compared with adults with NTT. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study was performed from January 1, 2005, through December 31, 2011 (follow-up, 5-7 years). All patients 55 years or older diagnosed as having TBI or NTT in 2005 and 2006 and who did not have baseline dementia or die during hospitalization (n = 164 661) were identified in a California statewide administrative health database of emergency department (ED) and inpatient visits. EXPOSURES Mild vs moderate to severe TBI diagnosed by Centers for Disease Control and Prevention criteria using International Classification of Diseases, Ninth Revision (ICD-9) codes, and NTT, defined as fractures excluding fractures of the head and neck, diagnosed using ICD-9 codes. MAIN OUTCOMES AND MEASURES Incident ED or inpatient diagnosis of dementia (using ICD-9 codes) 1 year or more after initial TBI or NTT. The association between TBI and risk of dementia was estimated using Cox proportional hazards models before and after adjusting for common dementia predictors and potential confounders. We also stratified by TBI severity and age category (55-64, 65-74, 75-84, and >85 years). RESULTS A total of 51 799 patients with trauma (31.5%) had TBI. Of these, 4361 (8.4%) developed dementia compared with 6610 patients with NTT (5.9%) (P < .001). We found that TBI was associated with increased dementia risk (hazard ratio [HR], 1.46; 95% CI, 1.41-1.52; P < .001). Adjustment for covariates had little effect except adjustment for age category (fully adjusted model HR, 1.26; 95% CI, 1.21-1.32; P < .001). In stratified adjusted analyses, moderate to severe TBI was associated with increased risk of dementia across all ages (age 55-64: HR, 1.72; 95% CI, 1.40-2.10; P < .001; vs age 65-74: HR, 1.46; 95% CI, 1.30-1.64; P < .001), whereas mild TBI may be a more important risk factor with increasing age (age 55-64: HR, 1.11; 95% CI, 0.80-1.53; P = .55; vs age 65-74: HR, 1.25; 95% CI, 1.04-1.51; P = .02; age interaction P < .001). CONCLUSIONS AND RELEVANCE Among patients evaluated in the ED or inpatient settings, those with moderate to severe TBI at 55 years or older or mild TBI at 65 years or older had an increased risk of developing dementia. Younger adults may be more resilient to the effects of recent mild TBI than older adults. C1 [Gardner, Raquel C.; Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA. [Gardner, Raquel C.; Nettiksimmons, Jasmine; Kaup, Allison; Barnes, Deborah E.; Yaffe, Kristine] San Francisco VA Med Ctr, Dept Vet Affairs, San Francisco, CA 94121 USA. [Burke, James F.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Burke, James F.] Ann Arbor Vet Affairs Healthcare Syst, Vet Affairs Ctr Clin Management & Res, Dept Vet Affairs, Ann Arbor, MI USA. [Nettiksimmons, Jasmine; Barnes, Deborah E.; Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Kaup, Allison; Barnes, Deborah E.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Gardner, RC (reprint author), San Francisco VA Med Ctr, Dept Vet Affairs, 4150 Clement St,Campus Mailbox 127, San Francisco, CA 94121 USA. EM raquel.gardner@ucsf.edu FU Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment; Medical Research Service of the San Francisco Veterans Affairs Medical Center; Department of Veterans Affairs Sierra-Pacific Mental Illness Research, Education, and Clinical Center; National Institutes of Health [K24 AG031155, K08 NS082597]; Department of Defense, the Department of Veterans Affairs [W81XWH-12-1-0581]; California Department of Public Health; Bright Focus Foundation; Alzheimer's Association FX Drs Gardner and Kaup reported having received support from the Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment, the Medical Research Service of the San Francisco Veterans Affairs Medical Center, and the Department of Veterans Affairs Sierra-Pacific Mental Illness Research, Education, and Clinical Center. Dr Yaffe reported having received research support from grant K24 AG031155 from the National Institutes of Health, grant W81XWH-12-1-0581 from the Department of Defense, the Department of Veterans Affairs, the California Department of Public Health, the Bright Focus Foundation, and the Alzheimer's Association. Dr Burke reported having received research support from grant K08 NS082597 from the National Institutes of Health. No other disclosures were reported. NR 42 TC 51 Z9 53 U1 2 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD DEC PY 2014 VL 71 IS 12 BP 1490 EP 1497 DI 10.1001/jamaneurol.2014.2668 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AW1YA UT WOS:000346083500006 PM 25347255 ER PT J AU Williams, BA Ahalt, C Stijacic-Cenzer, I Smith, AK Goldenson, J Ritchie, CS AF Williams, Brie A. Ahalt, Cyrus Stijacic-Cenzer, Irena Smith, Alexander K. Goldenson, Joe Ritchie, Christine S. TI Pain Behind Bars: The Epidemiology of Pain in Older Jail Inmates in a County Jail SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID HEALTH-CARE; PALLIATIVE CARE; NONMALIGNANT PAIN; SCREENING-TEST; MANAGEMENT; ADULTS; PRISON; POPULATIONS; GUIDELINES; DISTRESS AB Background: The number of older jail inmates in poor health is increasing rapidly. Among older adults, pain is common and leads to greater acute care use. In jail, pain management is complicated by concerns about misuse and diversion. A lack of data about the prevalence and management of pain in older jail inmates limits our ability to develop optimal palliative care strategies for this population. Objective: To describe the prevalence of and factors associated with pain and analgesic use in a population of older jail inmates. Design: Cross-sectional study. chi(2) tests assessed association between characteristics, pain, and analgesic use. Setting/Subjects: Two hundred ten jail inmates age 55 or older. Measurements: "Severe frequent pain" defined as "severe or very severe" pain experienced "frequently or constantly" using the validated Memorial Symptom Assessment Scale. Medical conditions, substance use, and analgesic treatment determined through self-report and jail medical records. Results: Participants' mean age was 59 years; 69% had multimorbidity; 75% reported any pain; 39% reported severe frequent pain. Report of severe frequent pain was associated with multimorbidity, functional impairment, and pre-jail acute care use (p<0.05), but not with substance use (57% versus 56%, p=0.89). Within a week of their interview, most participants with severe frequent pain had received an analgesic (87%) and many received an opioid (70%). Conclusion: High rates of pain in a rapidly growing population of older jail inmates with multimorbidity and functional impairment suggest that jails are an important site for assessing symptom burden and developing appropriate palliative care interventions. C1 [Williams, Brie A.; Ahalt, Cyrus; Stijacic-Cenzer, Irena; Smith, Alexander K.; Ritchie, Christine S.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94118 USA. [Williams, Brie A.; Smith, Alexander K.; Ritchie, Christine S.] San Francisco VA Med Ctr, San Francisco, CA USA. [Goldenson, Joe] San Francisco Dept Publ Hlth, Jail Hlth Serv, San Francisco, CA USA. RP Williams, BA (reprint author), Univ Calif San Francisco, Div Geriatr, 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; UCSF Program for the Aging Century; National Palliative Care Research Center (NPCRC) FX B.A.W received support from the National Institute of Aging (K23AG033102), The Jacob & Valeria Langeloth Foundation, and The UCSF Program for the Aging Century. This project was also supported in part by a Pilot and Exploratory Project Support Grant from the National Palliative Care Research Center (NPCRC). Sponsors played no role in the design, methods, subject recruitment, data collection, analysis, or preparation of this manuscript. NR 58 TC 4 Z9 4 U1 1 U2 7 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD DEC 1 PY 2014 VL 17 IS 12 BP 1336 EP 1343 DI 10.1089/jpm.2014.0160 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AW5TH UT WOS:000346336200010 PM 25265035 ER PT J AU DiMartino, LD Weiner, BJ Mayer, DK Jackson, GL Biddle, AK AF DiMartino, Lisa D. Weiner, Bryan J. Mayer, Deborah K. Jackson, George L. Biddle, Andrea K. TI Do Palliative Care Interventions Reduce Emergency Department Visits among Patients with Cancer at the End of Life? A Systematic Review SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Review ID LUNG-CANCER; QUALITY; IMPROVEMENT; POPULATION; INDICATORS; FRAMEWORK; SERVICES; OUTCOMES; TRIAL; DEATH AB Background: Frequent emergency department (ED) visits are an indicator of poor quality of cancer care. Coordination of care through the use of palliative care teams may limit aggressive care and improve outcomes for patients with cancer at the end of life. Objectives: To systematically review the literature to determine whether palliative care interventions implemented in the hospital, home, or outpatient clinic are more effective than usual care in reducing ED visits among patients with cancer at the end of life. Eligibility Criteria: PubMed, EMBASE, and CINAHL databases were searched from database inception to May 7, 2014. Only randomized/non-randomized controlled trials (RCTs) and observational studies examining the effect of palliative care interventions on ED visits among adult patients with cancer with advanced disease were considered. Data Extraction and Data Synthesis: Data were abstracted from the articles that met all the inclusion criteria. A second reviewer independently abstracted data from 2 articles and discrepancies were resolved. From 464 abstracts, 2 RCTs, 10 observational studies, and 1 non-RCT/quasi-experimental study were included. Overall there is limited evidence to support the use of palliative care interventions to reduce ED visits, although studies examining effect of hospice care and those conducted outside of the United States reported a statistically significant reduction in ED visits. Conclusions: Evidence regarding whether palliative care interventions implemented in the hospital, home or outpatient clinic are more effective than usual care at reducing ED visits is not strongly substantiated based on the literature reviewed. Improvements in the quality of reporting for studies examining the effect of palliative care interventions on ED use are needed. C1 [DiMartino, Lisa D.; Weiner, Bryan J.; Biddle, Andrea K.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC 27599 USA. [Mayer, Deborah K.] Univ N Carolina, Sch Nursing, Chapel Hill, NC 27599 USA. [Jackson, George L.] US Dept Vet Affairs, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Jackson, George L.] Duke Univ, Div Gen Internal Med, Durham, NC USA. RP DiMartino, LD (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Campus Box 7411, Chapel Hill, NC 27599 USA. EM lisa.dimartino@unc.edu OI Biddle, Andrea/0000-0003-0273-7439 NR 32 TC 3 Z9 3 U1 2 U2 10 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD DEC 1 PY 2014 VL 17 IS 12 BP 1384 EP 1399 DI 10.1089/jpm.2014.0092 PG 16 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AW5TH UT WOS:000346336200017 PM 25115197 ER PT J AU Beckson, M Tucker, D AF Beckson, Mace Tucker, Douglas TI Commentary: Craving Diagnostic Validity in DSM-5 Substance Use Disorders SO JOURNAL OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW LA English DT Editorial Material ID DEPENDENCE SYNDROME; ALCOHOL DEPENDENCE; CRITERIA; CLASSIFICATION; ADOLESCENTS; CANNABIS; COCAINE; ABUSE AB Drs. Norko and Fitch examine questions raised by DSM-5 in the forensic context of criminal defendant diversion to treatment, where eligibility has commonly relied on the view that addiction to alcohol or drugs is distinct from alcohol or drug use, misuse, and abuse. The creation in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), of the new unidimensional spectrum diagnosis of Substance Use Disorder (SUD), which includes three Abuse criteria from DSM-IV, has resulted in a need to re-examine policies that evolved with the DSM-III-R/DSM-IV biaxial abuse-dependence conceptual paradigm. DSM-5 acknowledges the common usage of the term addiction to describe severe problems, and that some clinicians choose to use the word to describe more extreme presentations. Limiting the concept of addiction to the severe form of DSM-5 SUD would maximize validity and support for an expert opinion that an individual has an addiction, as well as facilitate research inquiry into the underlying psychobiological nature of addiction. However, in some contexts, such as criminal diversion, achieving such specificity at the expense of sensitivity may be undesirably restrictive if it excludes appropriate candidates. Future research and experience in both clinical and forensic settings are needed for a fuller understanding of the DSM-5 SUD diagnoses and associated real-world implications. C1 [Beckson, Mace] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Beckson, Mace] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90024 USA. [Tucker, Douglas] Univ Calif San Francisco, Sch Med, Program Psychiat & Law, San Francisco, CA USA. RP Tucker, D (reprint author), 2930 Domingo Ave 306, Berkeley, CA 94705 USA. EM dtuckermd@gmail.com NR 26 TC 1 Z9 1 U1 0 U2 9 PU AMER ACAD PSYCHIATRY & LAW PI BLOOMFIELD PA ONE REGENCY DR, PO BOX 30, BLOOMFIELD, CT 06002 USA SN 1093-6793 EI 1943-3662 J9 J AM ACAD PSYCHIATRY JI J. Am. Acad. Psychiatry Law PD DEC 1 PY 2014 VL 42 IS 4 BP 453 EP 458 PG 6 WC Law; Psychiatry SC Government & Law; Psychiatry GA AW2XD UT WOS:000346149100008 PM 25492071 ER PT J AU Macleod, AC Klug, LR Patterson, J Griffith, DJ Beadling, C Town, A Heinrich, MC AF Macleod, Alison C. Klug, Lillian R. Patterson, Janice Griffith, Diana J. Beadling, Carol Town, Ajia Heinrich, Michael C. TI Combination Therapy for KIT-Mutant Mast Cells: Targeting Constitutive NFAT and KIT Activity SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID RECEPTOR TYROSINE KINASE; PROTOONCOGENE C-KIT; CYCLOSPORINE-A; TRANSCRIPTION FACTOR; ACTIVATING MUTATION; CATALYTIC DOMAIN; POINT MUTATION; LEUKEMIA-CELL; T-CELLS; MASTOCYTOSIS AB Resistant KIT mutations have hindered the development of KIT kinase inhibitors for treatment of patients with systemic mastocytosis. The goal of this research was to characterize the synergistic effects of a novel combination therapy involving inhibition of KIT and calcineurin phosphatase, a nuclear factor of activated T cells (NFAT) regulator, using a panel of KIT-mutant mast cell lines. The effects of monotherapy or combination therapy on the cellular viability/survival of KIT-mutant mast cells were evaluated. In addition, NFAT-dependent transcriptional activity was monitored in a representative cell line to evaluate the mechanisms responsible for the efficacy of combination therapy. Finally, shRNA was used to stably knockdown calcineurin expression to confirm the role of calcineurin in the observed synergy. The combination of a KIT inhibitor and a calcineurin phosphatase inhibitor (CNPI) synergized to reduce cell viability and induce apoptosis in six distinct KIT-mutant mast cell lines. Both KIT inhibitors and CNPIs were found to decrease NFAT-dependent transcriptional activity. NFAT-specific inhibitors induced similar synergistic apoptosis induction as CNPIs when combined with a KIT inhibitor. Notably, NFAT was constitutively active in each KIT-mutant cell line tested. Knockdown of calcineurin subunit PPP3R1 sensitized cells to KIT inhibition and increased NFAT phosphorylation and cytoplasmic localization. Constitutive activation of NFAT appears to represent a novel and targetable characteristic of KIT-mutant mast cell disease. Our studies suggest that combining KIT inhibition with NFAT inhibition might represent a new treatment strategy for mast cell disease. (C) 2014 AACR. C1 [Macleod, Alison C.; Klug, Lillian R.; Patterson, Janice; Griffith, Diana J.; Beadling, Carol; Town, Ajia; Heinrich, Michael C.] Portland VA Med Ctr, Portland, OR 97239 USA. [Macleod, Alison C.; Klug, Lillian R.; Patterson, Janice; Griffith, Diana J.; Beadling, Carol; Town, Ajia; Heinrich, Michael C.] OHSU Knight Canc Inst, Portland, OR USA. RP Heinrich, MC (reprint author), Portland VA Med Ctr, R&D 19,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM heinrich@ohsu.edu OI Patterson, Janice/0000-0002-8969-2933 FU VA Merit Review grant; Life Raft Group; GIST Cancer Research Fund FX This work was supported in part by funding from a VA Merit Review grant (to M.C. Heinrich), the Life Raft Group (to M.C. Heinrich), and the GIST Cancer Research Fund (to M.C. Heinrich) NR 49 TC 2 Z9 2 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2014 VL 13 IS 12 BP 2840 EP 2851 DI 10.1158/1535-7163.MCT-13-0830 PG 12 WC Oncology SC Oncology GA AW2QH UT WOS:000346132900007 PM 25253785 ER PT J AU van Steenoven, I Aarsland, D Hurtig, H Chen-Plotkin, A Duda, JE Rick, J Chahine, LM Dahodwala, N Trojanowski, JQ Roalf, DR Moberg, PJ Weintraub, D AF van Steenoven, Inger Aarsland, Dag Hurtig, Howard Chen-Plotkin, Alice Duda, John E. Rick, Jacqueline Chahine, Lama M. Dahodwala, Nabila Trojanowski, John Q. Roalf, David R. Moberg, Paul J. Weintraub, Daniel TI Conversion Between Mini-Mental State Examination, Montreal Cognitive Assessment, and Dementia Rating Scale-2 Scores in Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; Mini-Mental State Examination; Montreal Cognitive Assessment; Dementia Rating Scale-2; cognitive screening scales ID SOCIETY TASK-FORCE; DIAGNOSTIC-CRITERIA; ALZHEIMERS-DISEASE; IMPAIRMENT; MOCA; MULTICENTER; VALIDITY; PROFILE AB Cognitive impairment is one of the earliest, most common, and most disabling non-motor symptoms in Parkinson's disease (PD). Thus, routine screening of global cognitive abilities is important for the optimal management of PD patients. Few global cognitive screening instruments have been developed for or validated in PD patients. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Dementia Rating Scale-2 (DRS-2) have been used extensively for cognitive screening in both clinical and research settings. Determining how to convert the scores between instruments would facilitate the longitudinal assessment of cognition in clinical settings and the comparison and synthesis of cognitive data in multicenter and longitudinal cohort studies. The primary aim of this study was to apply a simple and reliable algorithm for the conversion of MoCA to MMSE scores in PD patients. A secondary aim was to apply this algorithm for the conversion of DRS-2 to both MMSE and MoCA scores. The cognitive performance of a convenience sample of 360 patients with idiopathic PD was assessed by at least two of these cognitive screening instruments. We then developed conversion scores between the MMSE, MoCA, and DRS-2 using equipercentile equating and log-linear smoothing. The conversion score tables reported here enable direct and easy comparison of three routinely used cognitive screening assessments in PD patients. (C) 2014 International Parkinson and Movement Disorder Society C1 [van Steenoven, Inger; Aarsland, Dag] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Neurogeriatr, Stockholm, Sweden. [Aarsland, Dag] Stavanger Univ Hosp, Ctr Age Related Dis, Stavanger, Norway. [Aarsland, Dag] Akershus Univ Hosp, Dept Neurol, Oslo, Norway. [Hurtig, Howard; Chen-Plotkin, Alice; Rick, Jacqueline; Chahine, Lama M.; Dahodwala, Nabila; Trojanowski, John Q.] Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Duda, John E.; Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [Trojanowski, John Q.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Roalf, David R.; Moberg, Paul J.] Univ Penn, Perelman Sch Med, Dept Psychiat, Neuropsychiat Sect, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. [Weintraub, Daniel] Univ Penn, Perelman Sch Med, Dept Psychiat, Geriatr Psychiat Sect, Philadelphia, PA 19104 USA. RP van Steenoven, I (reprint author), Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Neurogeriatr, Stockholm, Sweden. EM ingervansteenoven@gmail.com OI Aarsland, Dag/0000-0001-6314-216X FU NIA NIH HHS [K23 AG034236]; NIMH NIH HHS [K01 MH102609]; NINDS NIH HHS [U01 NS082134, P50 NS053488] NR 47 TC 13 Z9 14 U1 2 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD DEC PY 2014 VL 29 IS 14 BP 1809 EP 1815 DI 10.1002/mds.26062 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AW1EY UT WOS:000346034400016 PM 25381961 ER PT J AU Jimenez, A Lee, J Wynn, J Horan, W Bender, A McGee, M Engel, S Glahn, D Nuechterlein, K Cohen, M Green, M AF Jimenez, Amy Lee, Junghee Wynn, Jonathan Horan, William Bender, Amanda McGee, Mark Engel, Stephen Glahn, David Nuechterlein, Keith Cohen, Mark Green, Michael TI Deficits at the Perception-Attention Interface in Schizophrenia: An fMRI Study SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE schizophrenia; fMRI; cognition C1 [Jimenez, Amy; Lee, Junghee; Wynn, Jonathan; Horan, William; Bender, Amanda; McGee, Mark; Engel, Stephen; Glahn, David; Nuechterlein, Keith; Cohen, Mark; Green, Michael] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 DEC PY 2014 VL 39 SU 1 MA W49 BP S504 EP S504 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905002049 ER PT J AU McFadden, K Tregellas, J AF McFadden, Kristina Tregellas, Jason TI Neuronal and Behavioral Effects of an Implicit Priming Intervention to Reduce High-calorie Food Appeal SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE implicit priming; obesity; food preferences; fMRI C1 [McFadden, Kristina; Tregellas, Jason] Univ Colorado, Denver VA Med Ctr, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC PY 2014 VL 39 SU 1 MA W147 BP S567 EP S568 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905002146 ER PT J AU Mitchell, J Weinstein, D Arcuni, P Woolley, J AF Mitchell, Jennifer Weinstein, Dawn Arcuni, Peter Woolley, Joshua TI Intranasal Oxytocin Selectively Modulates Social Perception, Approach Behavior, and Craving in Human Alcohol Abusers SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE oxytocin; alcohol abuse; social perception; cue reactivity C1 [Mitchell, Jennifer; Weinstein, Dawn; Arcuni, Peter; Woolley, Joshua] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 9 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 DEC PY 2014 VL 39 SU 1 MA T261 BP S467 EP S467 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905001259 ER PT J AU Ozburn, A Kern, J Parekh, P Logan, R Liu, Z Purohit, K Huang, YH McClung, C AF Ozburn, Angela Kern, Joseph Parekh, Puja Logan, Ryan Liu, Zheng Purohit, Kush Huang, Yanhua McClung, Colleen TI Mechanisms Mediating Circadian Gene Effects on Anxiety-like behavior: Focus on NPAS2 & GABAA SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE anxiety; circadian; GABAA; NPAS2 C1 [Ozburn, Angela; Kern, Joseph; Parekh, Puja; Logan, Ryan; Liu, Zheng; Purohit, Kush; Huang, Yanhua; McClung, Colleen] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA T36 BP S313 EP S314 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905001036 ER PT J AU Peskind, E Petrie, E Mayer, C Pagulayan, K Huber, B Meabon, J Raskind, M Cook, D Zhang, J Banks, W AF Peskind, Elaine Petrie, Eric Mayer, Cynthia Pagulayan, Kathleen Huber, Bertram Meabon, James Raskind, Murray Cook, David Zhang, Jin Banks, William TI Cerebrospinal Fluid Biomarkers in Iraq and Afghanistan Veterans: Effects of Deployment and Blast Concussion Mild Traumatic Brain Injury SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE CSF; biomarker; veterans; concussion C1 [Peskind, Elaine; Petrie, Eric; Mayer, Cynthia; Pagulayan, Kathleen; Huber, Bertram; Meabon, James; Raskind, Murray; Cook, David; Zhang, Jin; Banks, William] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA W121 BP S549 EP S550 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905002120 ER PT J AU Raskind, M Peskind, E Millard, S Petrie, E AF Raskind, Murray Peskind, Elaine Millard, Steve Petrie, Eric TI Baseline Blood Pressure is Associated with PTSD Symptom Response to Prazosin in Active Duty Combat Soldiers SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE prazosin; PTSD; combat; soldiers C1 [Raskind, Murray; Peskind, Elaine; Millard, Steve; Petrie, Eric] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 5 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 DEC PY 2014 VL 39 SU 1 MA T136 BP S384 EP S384 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905001135 ER PT J AU Wynn, J Davis, M Weiner, K Maes, L Green, M Marder, S AF Wynn, Jonathan Davis, Michael Weiner, Katherine Maes, Lauryn Green, Michael Marder, Stephen TI Oxytocin Modulates EEG and Pupillary Responses to Social Stimuli in Schizophrenia: A Pilot Within-Subject Double-blind Crossover Study SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE oxytocin; schizophrenia; EEG; pupillometry C1 [Wynn, Jonathan; Davis, Michael; Weiner, Katherine; Maes, Lauryn; Green, Michael; Marder, Stephen] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 DEC PY 2014 VL 39 SU 1 MA W46 BP S502 EP S502 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905002046 ER PT J AU Yang, Y Lee, J Narr, K Leaver, A Myers, AC Green, M AF Yang, Yvonne Lee, Junghee Narr, Katherine Leaver, Amber Myers, Ana Ceci Green, Michael TI GABA Assessed by Magnetic Resonance Spectroscopy in Visual Cortex in Schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 07-11, 2014 CL Phoenix, AZ SP Amer Coll Neuropsychopharmacol DE magnetic resonance spectroscopy; schizophrenia; GABA; visual cortex C1 [Yang, Yvonne; Lee, Junghee; Narr, Katherine; Leaver, Amber; Myers, Ana Ceci; Green, Michael] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 SU 1 MA M116 BP S186 EP S187 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AU9IJ UT WOS:000345905000324 ER PT J AU Nguyen, C Wang, M AF Chau Nguyen Wang, Marilene TI Practice Patterns in the Surgical Treatment of Papillary Thyroid Microcarcinoma SO THYROID LA English DT Letter ID GUIDELINES; CANCER C1 [Chau Nguyen] Ventura Cty Med Ctr, Div Otolaryngol Head & Neck Surg, Ventura, CA 93003 USA. [Wang, Marilene] Univ Calif Los Angeles, David Geffen Sch Med, Dept Head & Neck Surg, Los Angeles, CA 90095 USA. [Wang, Marilene] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Nguyen, C (reprint author), Ventura Cty Med Ctr, Div Otolaryngol Head & Neck Surg, 3291 Loma Vista Rd Ste 401, Ventura, CA 93003 USA. EM chau.nguyen@ventura.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD DEC 1 PY 2014 VL 24 IS 12 BP 1816 EP 1817 DI 10.1089/thy.2014.0388 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AW4KL UT WOS:000346249900013 PM 25232803 ER PT J AU Chan, ED Kinney, WH Honda, JR Bishwakarma, R Gangavelli, A Mya, J Bai, XY Ordway, DJ AF Chan, Edward D. Kinney, William H. Honda, Jennifer R. Bishwakarma, Raju Gangavelli, Avani Mya, Jenny Bai, Xiyuan Ordway, Diane J. TI Tobacco exposure and susceptibility to tuberculosis: Is there a smoking gun? SO TUBERCULOSIS LA English DT Review DE Cigarette smoke; Mycobacterium tuberculosis; Host-defense; Air-pollution ID OBSTRUCTIVE PULMONARY-DISEASE; REGULATORY T-CELLS; NICOTINIC ACETYLCHOLINE-RECEPTOR; CIGARETTE-SMOKE; MYCOBACTERIUM-TUBERCULOSIS; ALVEOLAR MACROPHAGES; IN-VITRO; INCREASES SUSCEPTIBILITY; ACTIVE TUBERCULOSIS; CYTOKINE RESPONSES AB In many regions of the world, there is a great overlap between the prevalence of cigarette smoke exposure and tuberculosis. Despite the large body of epidemiologic evidence that tobacco smoke exposure is associated with increased tuberculosis infection, active disease, severity of disease, and mortality from tuberculosis, these studies cannot distinguish whether the mechanism is principally through direct impairment of anti-tuberculosis immunity by cigarette smoke or due to potential confounders that increase risk for tuberculosis and are commonly associated with smoking - such as poverty, malnutrition, and crowded living conditions. While there are several in vivo murine and in vitro macrophage studies showing cigarette smoke impairs control of tuberculous infection, little is known of the molecular and cellular mechanisms by which this impairment occurs. Herein, we highlight the key findings of these studies. Additionally, we review key immune cells that play critical roles in host-defense or pathogenesis of tuberculosis and generate a hypothesis-driven discussion of the possible mechanisms by which cigarette smoke impairs or enhances their functions, respectively, ultimately resulting in compromised immunity against tuberculosis. Published by Elsevier Ltd. C1 [Chan, Edward D.] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO 80220 USA. [Chan, Edward D.; Kinney, William H.; Bishwakarma, Raju; Gangavelli, Avani; Mya, Jenny; Bai, Xiyuan] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. [Chan, Edward D.; Kinney, William H.; Bishwakarma, Raju; Gangavelli, Avani; Mya, Jenny; Bai, Xiyuan] Natl Jewish Hlth, Dept Acad Affairs, Denver, CO 80206 USA. [Chan, Edward D.; Honda, Jennifer R.] Univ Colorado, Div Pulm Sci & Crit Care Med, Aurora, CO 80045 USA. [Ordway, Diane J.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Mycobacteria Res Labs, Ft Collins, CO 80523 USA. RP Chan, ED (reprint author), Natl Jewish Hlth, D509,Neustadt Bldg,1400 Jackson St, Denver, CO 80206 USA. EM chane@njhealth.org FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development FX This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, but this funding had no influence in the content of the manuscript. NR 89 TC 10 Z9 10 U1 0 U2 10 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PD DEC PY 2014 VL 94 IS 6 BP 544 EP 550 DI 10.1016/j.tube.2014.08.010 PG 7 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA AW0KB UT WOS:000345979900003 PM 25305002 ER PT J AU Yeo, KK Maddox, TM Carey, E Low, RI Shunk, KA AF Yeo, Khung Keong Maddox, Thomas M. Carey, Evan Low, Reginald I. Shunk, Kendrick A. TI Right- and Left-Sided Heart Catheterization as a Quality Marker for Catheterization Laboratories (from the National Veterans Affairs Clinical Assessment Reporting and Tracking Program) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIAC-CATHETERIZATION; PULMONARY-HYPERTENSION; CORONARY-ANGIOGRAPHY; DISEASE AB The rate of concurrent right-heart catheterization (RHC) in patients undergoing left-heart catheterization (LHC) for coronary artery disease (CAD) indications or bilateral heart catheterization (BHC) is recommended as a measure of hospital quality, with higher rates suggesting over utilization. Our aim was to describe the prevalence of BHC and abnormal RHC findings in patients undergoing BHC with a primary indication for LHC. A retrospective analysis was performed for patients undergoing cardiac catheterization for CAD indications using the Department of Veterans Affairs Clinical Assessment Reporting and Tracking Program. Patients undergoing catheterization from October 2007 to September 2011 in 76 Veterans Affairs hospitals were included. Among 95,656 patients undergoing catheterization for CAD, 6,611 (6.9%) underwent BHC and 88,929 (93.0%) LHC. Among the patients undergoing BHC, 61.3% had at least 1 of the following abnormal RHC values: mean pulmonary artery (PA) pressure >25 mm Hg, pulmonary capillary wedge pressure (PCWP) >15 mm Hg, or pulmonary vascular resistance (PVR) >3 Woods units. A total of 37.5% of patients had mean PA pressures of 26 to 40 mm Hg and 11.1% had mean PA pressures >40 mm Hg. A total of 34.4% of patients had mean PCWP of 16 to 25 mm Hg and 13.6% had mean PAWP >25 mm Hg. A total of 16.5% of patients had PVR between 3 and 6 WU and 2.9% had PVR >6 WU. A total of 4.3% of patients met formal criteria for pulmonary arterial hypertension (defined as the combination of PA mean >25 mm Hg, PCWP <= 15 mm Hg, and PVR >3). In conclusion, these findings suggest that most BHC were performed for appropriate clinical reasons. Future studies should further explore BHC rate as an effective quality indicator. (C) 2014 Elsevier Inc. All rights reserved. C1 [Yeo, Khung Keong; Low, Reginald I.] Univ Calif Davis, Med Ctr, Div Cardiovasc Med, Sacramento, CA 95817 USA. [Yeo, Khung Keong] Natl Heart Ctr Singapore, Dept Cardiol, Singapore, Singapore. [Maddox, Thomas M.] Vet Affairs Eastern Colorado Hlth Care Syst, Cardiol Sect, Denver, CO USA. [Maddox, Thomas M.] Univ Colorado, Sch Med, Div Cardiol, Denver, CO USA. [Carey, Evan] Vet Affairs Clin Assessment Reporting & Tracking, Denver, CO USA. [Shunk, Kendrick A.] San Francisco VA Med Ctr, Dept Cardiol, San Francisco, CA USA. [Shunk, Kendrick A.] Univ Calif San Francisco, Dept Med, Div Cardiol, San Francisco, CA 94143 USA. RP Yeo, KK (reprint author), Univ Calif Davis, Med Ctr, Div Cardiovasc Med, Sacramento, CA 95817 USA. EM khung.yeo@ucdmc.ucdavis.edu FU VA Health Services Research and Development FX Dr Maddox is supported by a VA Health Services Research and Development career development award. The other authors have no relevant conflicts of interest. NR 11 TC 0 Z9 0 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 2014 VL 114 IS 11 BP 1758 EP 1762 DI 10.1016/j.amjcard.2014.08.047 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AU6RJ UT WOS:000345729300021 PM 25316348 ER PT J AU Chaudhry, SI Lien, C Ehrlich, J Lane, S Cordasco, K McDonald, FS Arora, VM Steinmann, A AF Chaudhry, Saima I. Lien, Cynthia Ehrlich, Jason Lane, Susan Cordasco, Kristina McDonald, Furman S. Arora, Vineet M. Steinmann, Alwin TI Curricular Content of Internal Medicine Residency Programs: A Nationwide Report SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID PREPAREDNESS; EDUCATION C1 [Chaudhry, Saima I.; Lien, Cynthia; Ehrlich, Jason] Hofstra North Shore LIJ Sch Med, Hempstead, NY USA. [Lane, Susan] SUNY Stony Brook, Med Ctr, Stony Brook, NY 11794 USA. [Cordasco, Kristina] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Cordasco, Kristina] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Cordasco, Kristina] RAND Corp, Santa Monica, CA USA. [McDonald, Furman S.] Mayo Clin, Coll Med, Rochester, MN USA. [Arora, Vineet M.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Steinmann, Alwin] Exempla St Joseph Hosp, Denver, CO USA. [Steinmann, Alwin] Univ Colorado, Sch Med, Denver, CO USA. RP Chaudhry, SI (reprint author), Dept Med, 270-05 76th Ave,Res Bldg,2nd Fl, New Hyde Pk, NY 11040 USA. EM schaudhr@nshs.edu OI Arora, Vineet/0000-0002-4745-7599 NR 22 TC 5 Z9 5 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD DEC PY 2014 VL 127 IS 12 BP 1247 EP 1254 DI 10.1016/j.amjmed.2014.08.009 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AW1CY UT WOS:000346029400044 PM 25168079 ER PT J AU Backhus, LM Farjah, F Zeliadt, SB Varghese, TK Cheng, A Kessler, L Au, DH Flum, DR AF Backhus, Leah M. Farjah, Farhood Zeliadt, Steven B. Varghese, Thomas K. Cheng, Aaron Kessler, Larry Au, David H. Flum, David R. TI Predictors of Imaging Surveillance for Surgically Treated Early-Stage Lung Cancer SO ANNALS OF THORACIC SURGERY LA English DT Article ID FOLLOW-UP; CURATIVE INTENT; UNITED-STATES; COLORECTAL-CANCER; CLINICAL-PRACTICE; SURVIVORS; RESECTION; ROUTINE; RECURRENCE; SURGERY AB Background. Current guidelines recommend routine imaging surveillance for patients with non-small cell lung cancer (NSCLC) after treatment. Little is known about surveillance patterns for patients with surgically resected early-stage lung cancer in the community at large. We sought to characterize surveillance patterns in a national cohort. Methods. We conducted a retrospective study using the Surveillance, Epidemiology, and End-Results (SEER)Medicare database (1995-2010). Patients with stage I/II NSCLC treated with surgical resection were included. Our primary outcome was receipt of imaging between 4 and 8 months after the surgical procedure. Covariates included demographics and comorbidities. Results. Chest radiography (CXR) was the most frequent initial modality (60%), followed by chest computed tomography (CT) (25%). Positron emission tomography (PET) was least frequent as an initial imaging modality (3%). A total of 13% of patients received no imaging within the initial surveillance period. Adherence to National Comprehensive Cancer Network (NCCN) guidelines for imaging by overall prevalence was 47% for receipt of CT; however, rates of CT increased over time from 28% to 61% (p < 0.01). Reduced rates of CT were associated with stage I disease and surgical resection as the sole treatment modality. Conclusions. Imaging after definitive surgical treatment for NSCLC predominantly used CXR rather than CT. Most of this imaging is likely for surveillance, and in that context CXR has inferior detection rates for recurrence and new cancers. Adherence to guideline-recommended CT surveillance after surgical treatment is poor, but the reasons are multifactorial. Efforts to improve adherence to imaging surveillance must be coupled with greater evidence demonstrating improved long-term outcomes. (C) 2014 by The Society of Thoracic Surgeons C1 VA Puget Sound Hlth Care Syst, Surg Serv, Seattle, WA USA. Univ Washington, Dept Surg, Div Cardiothorac Surg, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA USA. Univ Washington, Sch Publ Hlth, Dept Med, Dept Hlth Serv,Div Pulm & Crit Care, Seattle, WA 98195 USA. Univ Washington, Dept Surg, Seattle, WA 98195 USA. RP Backhus, LM (reprint author), Univ Washington, Dept Surg, Div Cardiothorac Surg, 1959 NE Pacific St, Seattle, WA 98195 USA. EM lbackhus@u.washington.edu FU NIH/NCATS National Center for Research Resources [2 KL2 TR000421-06 KL2] FX This work was funded by NIH/NCATS National Center for Research Resources 2 KL2 TR000421-06 KL2 Scholar ITHS Multidisciplinary Clinical Research Training Program. 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 41 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2014 VL 98 IS 6 BP 1944 EP 1952 DI 10.1016/j.athoracsur.2014.06.067 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AU6WX UT WOS:000345743200017 PM 25282167 ER PT J AU Sayegh, P Arentoft, A Thaler, NS Dean, AC Thames, AD AF Sayegh, Philip Arentoft, Alyssa Thaler, Nicholas S. Dean, Andy C. Thames, April D. TI Quality of Education Predicts Performance on the Wide Range Achievement Test-4th Edition Word Reading Subtest SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Literacy; Academic achievement; Neurocognition; High schools; Multiple regression; Test validity ID NEUROPSYCHOLOGICAL TEST-PERFORMANCE; AFRICAN-AMERICAN ELDERS; LEVEL AB The current study examined whether self-rated education quality predicts Wide Range Achievement Test-4th Edition (WRAT-4) Word Reading subtest and neurocognitive performance, and aimed to establish this subtest's construct validity as an educational quality measure. In a community-based adult sample (N = 106), we tested whether education quality both increased the prediction of Word Reading scores beyond demographic variables and predicted global neurocognitive functioning after adjusting for WRAT-4. As expected, race/ethnicity and education predicted WRAT-4 reading performance. Hierarchical regression revealed that when including education quality, the amount of WRAT-4's explained variance increased significantly, with race/ethnicity and both education quality and years as significant predictors. Finally, WRAT-4 scores, but not education quality, predicted neurocognitive performance. Results support WRAT-4 Word Reading as a valid proxy measure for education quality and a key predictor of neurocognitive performance. Future research should examine these findings in larger, more diverse samples to determine their robust nature. C1 [Sayegh, Philip; Arentoft, Alyssa; Thaler, Nicholas S.; Dean, Andy C.; Thames, April D.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Sayegh, Philip; Arentoft, Alyssa; Thaler, Nicholas S.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Thames, AD (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza,C8-226, Los Angeles, CA 90095 USA. EM athames@mednet.ucla.edu OI Arentoft, Alyssa/0000-0002-4235-4638 FU National Institutes of Health (National Institute of Mental Health) [K23 MH095661] FX This work was supported by the National Institutes of Health (National Institute of Mental Health) Career Development Award (grant number K23 MH095661) to A.D.T. NR 17 TC 4 Z9 4 U1 5 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD DEC PY 2014 VL 29 IS 8 BP 731 EP 736 DI 10.1093/arclin/acu059 PG 6 WC Psychology, Clinical; Psychology SC Psychology GA AU9DD UT WOS:000345890900001 PM 25404004 ER PT J AU Patrick, RE Horner, MD AF Patrick, Regan E. Horner, Michael D. TI Psychological Characteristics of Individuals Who Put Forth Inadequate Cognitive Effort in a Secondary Gain Context SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Malingering; Test validity; Neuropsychological assessment; Behavioral economics; Minnesota multiphasic personality inventory; Personality processes ID SYMPTOM VALIDITY TESTS; MALINGERED NEUROCOGNITIVE DYSFUNCTION; RESPONSE BIAS SCALE; MMPI-2-RF VALIDITY; MENTAL-RETARDATION; FORENSIC SETTINGS; MILITARY SAMPLE; TEST FAILURE; CHRONIC PAIN; RC SCALES AB The current study sought to characterize the psychological architecture of individuals who put forth inadequate effort. The Minnesota Multiphasic Personality Inventory, 2nd Edition-Restructured Form was used to identify dimensions of psychological functioning in a mixed outpatient sample of U.S. Veterans referred for neuropsychological evaluation as part of their clinical care. After accounting for external financial incentive and symptom overreporting, results showed that the inadequate effort group (n = 23, mean age = 42.48) scored higher than the adequate effort group (n = 29, mean age = 44.31) on neurologic complaints (NUC) and lower on behavioral/externalizing dysfunction (BXD), antisocial behaviors (RC4), and disconstraint (DISC-r). Lower scores on BXD, RC4, and DISC-r could indicate higher behavioral constraint-a psychological characteristic that has been linked to the pursuit of high-value future rewards. Alternatively, lower scores on these scales could have reflected a self-presentation strategy aimed at minimizing externalizing and RC4 in order to appear more psychological healthy. Implications of each of these interpretations are discussed. C1 [Patrick, Regan E.; Horner, Michael D.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Patrick, Regan E.; Horner, Michael D.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Patrick, RE (reprint author), McLean Hosp, Dept Neuropsychol, 115 Mill St,Mailstop 234, Belmont, MA 02452 USA. EM rpatrick@partners.org NR 60 TC 0 Z9 0 U1 3 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD DEC PY 2014 VL 29 IS 8 BP 754 EP 766 DI 10.1093/arclin/acu054 PG 13 WC Psychology, Clinical; Psychology SC Psychology GA AU9DD UT WOS:000345890900004 PM 25318597 ER PT J AU Barsuglia, JP Kaiser, NC Wilkins, SS Joshi, A Barrows, RJ Paholpak, P Panchal, HV Jimenez, EE Mather, MJ Mendez, MF AF Barsuglia, Joseph P. Kaiser, Natalie C. Wilkins, Stacy Schantz Joshi, Aditi Barrows, Robin J. Paholpak, Pongsatorn Panchal, Hemali Vijay Jimenez, Elvira E. Mather, Michelle J. Mendez, Mario F. TI A Scale of Socioemotional Dysfunction in Frontotemporal Dementia SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Dementia; Neurodegenerative diseases; Social behavior; Behavioral assessment; Semantic dementia; Presenile dementia ID ONSET ALZHEIMERS-DISEASE; BEHAVIORAL VARIANT; DIAGNOSTIC-CRITERIA; SOCIAL COGNITION; CLINICAL-DIAGNOSIS; LOBAR DEGENERATION; EMOTIONAL ASSESSMENT; OLDER-ADULTS; SENSITIVITY; INVENTORY AB Early social dysfunction is a hallmark symptom of behavioral variant frontotemporal dementia (bvFTD); however, validated measures for assessing social deficits in dementia are needed. The purpose of the current study was to examine the utility of a novel informant-based measure of social impairment, the Socioemotional Dysfunction Scale (SDS) in early-onset dementia. Sixteen bvFTD and 18 early-onset Alzheimer's disease (EOAD) participants received standard clinical neuropsychological measures and neuroimaging. Caregiver informants were administered the SDS. Individuals with bvFTD exhibited greater social dysfunction on the SDS compared with the EOAD group; t(32) = 6.32, p < .001. The scale demonstrated preliminary evidence for discriminating these frequently misdiagnosed groups (area under the curve = 0.920, p = < .001) and internal consistency alpha = 0.977. The SDS demonstrated initial evidence as an effective measure for detecting abnormal social behavior and discriminating bvFTD from EOAD. Future validation is recommended in larger and more diverse patient groups. C1 [Barsuglia, Joseph P.; Kaiser, Natalie C.; Wilkins, Stacy Schantz; Joshi, Aditi; Barrows, Robin J.; Paholpak, Pongsatorn; Panchal, Hemali Vijay; Jimenez, Elvira E.; Mather, Michelle J.; Mendez, Mario F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Barsuglia, Joseph P.; Kaiser, Natalie C.; Joshi, Aditi; Barrows, Robin J.; Paholpak, Pongsatorn; Jimenez, Elvira E.; Mather, Michelle J.; Mendez, Mario F.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Mendez, Mario F.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Wilkins, Stacy Schantz] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Barsuglia, JP (reprint author), West Los Angeles VA Healthcare Ctr, Neurobehav Serv 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM joseph.barsuglia@va.gov FU National Institutes of Health [R01AG034499-04]; VA Geriatric Research Education and Clinical Centers (GRECC) FX This work was supported by the National Institutes of Health (grant number R01AG034499-04); and JPB and NCK were funded through VA Geriatric Research Education and Clinical Centers (GRECC) Advanced Fellowship in Geriatrics Awards. NR 73 TC 5 Z9 5 U1 1 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD DEC PY 2014 VL 29 IS 8 BP 793 EP 805 DI 10.1093/arclin/acu050 PG 13 WC Psychology, Clinical; Psychology SC Psychology GA AU9DD UT WOS:000345890900007 PM 25331776 ER PT J AU Sato, S Richard, ML Brandon, D Buie, JNJ Oates, JC Gilkeson, GS Zhang, XK AF Sato, Shuzo Richard, Mara Lennard Brandon, Danielle Buie, Joy N. Jones Oates, Jim C. Gilkeson, Gary S. Zhang, Xian K. TI A Critical Role of the Transcription Factor Fli-1 in Murine Lupus Development by Regulation of Interleukin-6 Expression SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID MESENCHYMAL STEM-CELLS; B-CELLS; BONE-MARROW; ANTIBODY-PRODUCTION; STROMAL CELLS; ERYTHEMATOSUS; DIFFERENTIATION; MECHANISMS; OAZ; DNA AB Objective. The Fli-1 transcription factor is implicated in the pathogenesis of systemic lupus erythematosus (SLE), both in humans and in animal models. Dysregulation of interleukin-6 (IL-6) is also associated with SLE. The purpose of this study was to investigate whether Fli-1 directly regulates the expression of IL-6. Methods. Sera were collected from wild-type and Fli-1-heterozygous (Fli-1 /) MRL/lpr mice, and the concentration of IL-6 was measured by enzyme-linked immunosorbent assay (ELISA). Expression of IL-6 in the kidney was measured by real-time polymerase chain reaction analysis. T cells were isolated from wild-type and Fli-1 / MRL/lpr mice and stimulated with CD3/CD28 beads, and the concentration of IL-6 in the supernatants was measured by ELISA. MS1 endothelial cells were transfected with Fli-1 and control small interfering RNA, and the production of IL-6 was compared after lipopolysaccharide stimulation. A chromatin immunoprecipitation (ChIP) assay was performed to determine whether Fli-1 binds to the IL-6 promoter region. Transient transfections with the NIH3T3 cell line were performed to examine whether Fli-1 regulates the expression of IL-6. Results. Fli-1 / MRL/lpr mice had significantly decreased IL-6 levels in sera and reduced expression of IL-6 in kidneys as compared to their wild-type littermates. T cells isolated from Fli-1 / MRL/lpr mice produced less IL-6 than did those from wild-type mice. Inhibiting the expression of Fli-1 in endothelial cells resulted in reduced production of IL-6. The ChIP assay revealed direct binding of Fli-1 to 3 regions within the IL-6 promoter. Fli-1 activated transcription from the IL-6 promoter in a dose-dependent manner. Conclusion. The direct regulation of IL-6 expression by Fli-1 represents one possible mechanism for the protective effect of decreased Fli-1 expression in lupus. C1 [Sato, Shuzo; Richard, Mara Lennard; Brandon, Danielle; Buie, Joy N. Jones; Oates, Jim C.; Gilkeson, Gary S.; Zhang, Xian K.] Med Univ S Carolina, Charleston, SC 29425 USA. [Oates, Jim C.; Gilkeson, Gary S.; Zhang, Xian K.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Zhang, XK (reprint author), Med Univ S Carolina, Div Rheumatol & Immunol, 96 Jonathan Lucas St,Suite 912,MSC 637, Charleston, SC 29425 USA. EM zhangjo@musc.edu FU Medical Research Service, Department of Veterans Affairs; NIH [AR-056670] FX Supported in part by the Medical Research Service, Department of Veterans Affairs (grant to Drs. Gilkeson and Zhang) and the NIH (grant AR-056670 to Dr. Zhang). NR 38 TC 9 Z9 9 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD DEC PY 2014 VL 66 IS 12 BP 3436 EP 3444 DI 10.1002/art.38818 PG 9 WC Rheumatology SC Rheumatology GA AU4HK UT WOS:000345571200021 PM 25155007 ER PT J AU Khamashta, M Merrill, JT Werth, VP Furie, R Kalunian, K Illei, GG Drappa, J Wang, LW Greth, W AF Khamashta, Munther Merrill, Joan T. Werth, Victoria P. Furie, Richard Kalunian, Kenneth Illei, Gabor G. Drappa, Jorn Wang, Liangwei Greth, Warren TI Safety and Efficacy of Sifalimumab, an Anti IFN-Alpha Monoclonal Antibody, in a Phase 2b Study of Moderate to Severe Systemic Lupus Erythematosus (SLE) SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Khamashta, Munther] Kings Coll London, Graham Hughes Lupus Res Lab, London, England. [Merrill, Joan T.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Furie, Richard] North Shore LIJ Hlth Syst, Lake Success, NY USA. [Kalunian, Kenneth] UCSD, Sch Med, La Jolla, CA USA. [Illei, Gabor G.; Drappa, Jorn; Wang, Liangwei; Greth, Warren] MedImmune LLC, Gaithersburg, MD USA. NR 0 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD DEC PY 2014 VL 66 IS 12 MA L4 BP 3530 EP 3531 PG 2 WC Rheumatology SC Rheumatology GA AU4HK UT WOS:000345571200041 ER PT J AU Andersen, RE Lim, DA AF Andersen, Rebecca E. Lim, Daniel A. TI An ingredient for the elixir of youth SO CELL RESEARCH LA English DT Editorial Material ID COGNITIVE FUNCTION; REJUVENATION; MUSCLE; CELLS AB Emerging evidence indicates that there are factors within the blood of young animals that have the ability to restore youthful characteristics to a number of organ systems in older animals. Growth/differentiation factor 11 (GDF11) is the first of such factors to be identified, and two new studies demonstrate that this "factor of youth" rejuvenates stem cells found in the skeletal muscle and brain of aged mice. C1 [Andersen, Rebecca E.; Lim, Daniel A.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Andersen, Rebecca E.; Lim, Daniel A.] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA. [Andersen, Rebecca E.] Univ Calif San Francisco, Dev & Stem Cell Biol Grad Program, San Francisco, CA 94143 USA. [Lim, Daniel A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Lim, DA (reprint author), Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. EM LimD@neurosurg.ucsf.edu FU NICHD NIH HHS [T32 HD007470] NR 10 TC 3 Z9 4 U1 0 U2 27 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD DEC PY 2014 VL 24 IS 12 BP 1381 EP 1382 DI 10.1038/cr.2014.107 PG 2 WC Cell Biology SC Cell Biology GA AU9EP UT WOS:000345894800002 PM 25112712 ER PT J AU Yenchek, R Ix, JH Rifkin, DE Shlipak, MG Sarnak, MJ Garcia, M Patel, KV Satterfield, S Harris, TB Newman, AB Fried, LF AF Yenchek, Robert Ix, Joachim H. Rifkin, Dena E. Shlipak, Michael G. Sarnak, Mark J. Garcia, Melissa Patel, Kashang V. Satterfield, Suzanne Harris, Tamara B. Newman, Anne B. Fried, Linda F. CA Hlth Aging Body Composition Study TI Association of Serum Bicarbonate with Incident Functional Limitation in Older Adults SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; METABOLIC-ACIDOSIS; DISABILITY; PERFORMANCE; INCREASES; HUMANS; PEOPLE; FALLS AB Background and objectives Cross-sectional studies have found that low serum bicarbonate is associated with slower gait speed. Whether bicarbonate levels independently predict the development of functional limitation has not been previously studied. Whether bicarbonate was associated with incident persistent lower extremity functional limitation and whether the relationship differed in individuals with and without CKD were assessed in participants in the Health, Aging, and Body Composition study, a prospective study of well functioning older individuals Design, setting, participants, & measurements Functional limitation was defined as difficulty in walking 0.25 miles or up 10 stairs on two consecutive reports 6 months apart in the same activity (stairs or walking). Kidney function was measured using eGFR by the Chronic Kidney Disease Epidemiology Collaboration creatinine equation, and CKD was defined as an eGFR<60 ml/min per 1.73 m(2). Serum bicarbonate was measured using arterialized venous blood gas. Cox proportional hazards analysis was used to assess the association of bicarbonate (<23, 23-25.9, and >= 26 mEq/L) with functional limitation. Mixed model linear regression was performed to assess the association of serum bicarbonate on change in gait speed over time. Results Of 1544 participants, 412 participants developed incident persistent functional limitation events over a median 4.4 years (interquartile range, 3.1 to 4.5). Compared with >= 26 mEq/L, lower serum bicarbonate was associated with functional limitation. After adjustment for demographics, CKD, diabetes, body mass index, smoking, diuretic use, and gait speed, lower serum bicarbonate was significantly associated with functional limitation (hazard ratio, 1.35; 95% confidence interval, 1.08 to.1.68 and hazard ratio, 1.58; 95% confidence interval, 1.12 to 2.22 for bicarbonate levels from 23 to 25.9 and <23, respectively). There was not a significant interaction of bicarbonate with CKD. In addition, bicarbonate was not significantly associated with change in gait speed. Conclusions Lower serum bicarbonate was associated with greater risk of incident, persistent functional limitation. This association was present in individuals with and without CKD. C1 [Fried, Linda F.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. RP Fried, LF (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Univ Dr, Pittsburgh, PA 15240 USA. EM Linda.Fried@va.gov RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIA [R01-AG028050, R01-AG029364]; National Institute of Nursing Research (NINR) [R01-NR012459]; Intramural Research Program of the National Institutes of Health, National Institute on Aging; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [T3-2DK061296] FX This research was supported by National Institute on Aging (NIA) Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; NIA Grants R01-AG028050 and R01-AG029364; and National Institute of Nursing Research (NINR) Grant R01-NR012459. This research was supported, in part, by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. R.Y. was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Grant T3-2DK061296. NR 21 TC 3 Z9 3 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD DEC PY 2014 VL 9 IS 12 BP 2111 EP 2116 DI 10.2215/CJN.05480614 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA AU9YL UT WOS:000345947800015 PM 25381341 ER PT J AU Subramanya, AR Ellison, DH AF Subramanya, Arohan R. Ellison, David H. TI Distal Convoluted Tubule SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID NA-CL COTRANSPORTER; SODIUM-CHLORIDE COTRANSPORTER; FAMILIAL HYPERKALEMIC HYPERTENSION; CORTICAL COLLECTING DUCT; RETICULUM-ASSOCIATED DEGRADATION; PSEUDOHYPOALDOSTERONISM TYPE-II; CELL-SURFACE EXPRESSION; RECTIFIER K+ CHANNEL; KELCH-LIKE 3; SENSORINEURAL DEAFNESS AB The distal convoluted tubule is the nephron segment that lies immediately downstream of the macula densa. Although short in length, the distal convoluted tubule plays a critical role in sodium, potassium, and divalent cation homeostasis. Recent genetic and physiologic studies have greatly expanded our understanding of how the distal convoluted tubule regulates these processes at the molecular level. This article provides an update on the distal convoluted tubule, highlighting concepts and pathophysiology relevant to clinical practice. C1 [Subramanya, Arohan R.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15261 USA. [Subramanya, Arohan R.] Univ Pittsburgh, Sch Med, Dept Cell Biol, Pittsburgh, PA 15261 USA. [Subramanya, Arohan R.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Ellison, David H.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Ellison, David H.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. [Ellison, David H.] Portland VA Med Ctr, Portland, OR USA. RP Subramanya, AR (reprint author), Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Dept Med, S828A Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM ars129@pitt.edu FU National Institutes of Health [R01-DK51496, R01-DK095841, P30-DK079307, R01-DK098145]; Mid-Level Veterans Affairs Career Development Grant FX This work was supported, in part, by the National Institutes of Health Grants R01-DK51496 (to D.H.E.), R01-DK095841 (to D.H.E.), and P30-DK079307 (to the Pittsburgh Center for Kidney Research), R01-DK098145 (to A.R.S.), and a Mid-Level Veterans Affairs Career Development Grant (to A.R.S.). NR 120 TC 23 Z9 23 U1 0 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD DEC PY 2014 VL 9 IS 12 BP 2147 EP 2163 DI 10.2215/CJN.05920613 PG 17 WC Urology & Nephrology SC Urology & Nephrology GA AU9YL UT WOS:000345947800020 PM 24855283 ER PT J AU O'Hare, AM Armistead, N Schrag, WLF Diamond, L Moss, AH AF O'Hare, Ann M. Armistead, Nancy Schrag, Wendy L. Funk Diamond, Louis Moss, Alvin H. TI Patient-Centered Care: An Opportunity to Accomplish the "Three Aims" of the National Quality Strategy in the Medicare ESRD Program SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; OF-LIFE CARE; PALLIATIVE CARE; UNITED-STATES; CONSERVATIVE CARE; DECISION-MAKING; DIALYSIS INITIATION; STARTING DIALYSIS; OLDER-ADULTS; END AB In light of mounting federal government debt and levels of Medicare spending that are widely viewed as unsustainable, commentators have called for a transformation of the United States health care system to deliver better care at lower costs. This article presents the priorities of the Coalition for Supportive Care of Kidney Patients for how clinicians might achieve this transformation for patients with advanced CKD and their families. The authors suspect that much of the high-intensity, high-cost care currently delivered to patients with advanced kidney disease may be unwanted and that the "Three Aims" put forth by the National Quality Strategy of better care for the individual, better health for populations, and reduced health care costs may be within reach for patients with CKD and ESRD. This work describes the coalition's vision for a more patient-centered approach to the care of patients with kidney disease and argues for more concerted efforts to align their treatments with their goals, values, and preferences. Key priorities to achieve this vision include using improved prognostic models and decision science to help patients, their families, and their providers better understand what to expect in the future; engaging patients and their families in shared decision-making before the initiation of dialysis and during the course of dialysis treatment; and tailoring treatment strategies throughout the continuum of their care to address what matters most to individual patients. C1 [O'Hare, Ann M.] Univ Washington, Dept Med, Seattle, WA USA. [O'Hare, Ann M.] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. [Armistead, Nancy] Midatlantic Renal Coalit, Richmond, VA USA. [Schrag, Wendy L. Funk] Fresenius Med Care, Newton, KS USA. [Diamond, Louis] Qual Hlth Care Advisory Grp, Rockville, MD USA. [Moss, Alvin H.] W Virginia Univ, Sch Med, Nephrol Sect, Morgantown, WV 26506 USA. RP Moss, AH (reprint author), W Virginia Univ, Sch Med, Nephrol Sect, POB 9022, Morgantown, WV 26506 USA. EM amoss@hsc.wvu.edu FU MARC FX In 2007, the Mid-Atlantic Renal Coalition (MARC) established the Coalition for Supportive Care of Kidney Patients (CSCKP; formerly the Kidney End-of-Life Coalition) in recognition that end-of-life care is an essential component of the continuum of quality care. The coalition maintains a resource-rich website that encourages active engagement in meaningful shared decision-making. MARC is a nonprofit subsidiary of West Virginia Medical Institute/Quality Insights Holdings and serves as an ESRD Network organization. The CSCKP is supported by MARC from reserve funds. NR 63 TC 17 Z9 17 U1 0 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD DEC PY 2014 VL 9 IS 12 BP 2189 EP 2194 DI 10.2215/CJN.01930214 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA AU9YL UT WOS:000345947800023 PM 25035275 ER PT J AU Cotter, G Metra, M Davison, BA Senger, S Bourge, RC Cleland, JGF Jondeau, G Krum, H O'Connor, CM Parker, JD Torre-Amione, G van Veldhuisen, DJ Milo, O Kobrin, I Rainisio, M McMurray, JJV Teerlink, JR AF Cotter, Gad Metra, Marco Davison, Beth A. Senger, Stefanie Bourge, Robert C. Cleland, John G. F. Jondeau, Guillaume Krum, Henry O'Connor, Christopher M. Parker, John D. Torre-Amione, Guillermo van Veldhuisen, Dirk J. Milo, Olga Kobrin, Isaac Rainisio, Maurizio McMurray, John J. V. Teerlink, John R. CA VERITAS Investigators TI Worsening heart failure, a critical event during hospital admission for acute heart failure: results from the VERITAS study SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Acute heart failure; Outcome; VERITAS study; Worsening heart failure; Death ID TASK-FORCE; GUIDELINES AB AimsWorsening heart failure (WHF) in the first 7 days after an admission for acute HF (AHF) has been proposed as a therapeutic target in several recent AHF studies and was a co-primary endpoint of the VERITAS studies. Methods and resultsPatients were randomized within 24h of admission for AHF. WHF was defined as worsening or persistent signs and symptoms of HF requiring additional intravenous or mechanical therapy for HF or death within 7 days of randomization. Multivariable models were developed to predict the time to WHF through day 7. Unadjusted and multivariable-adjusted associations of WHF with the length of stay (LOS) of the index hospitalization, and 30- and 90-day outcomes were estimated. WHF occurred by day 7 in 27% of the 1347 patients enrolled. Age, co-morbidities, and markers of HF severity were moderately predictive of WHF; the C-index for a multivariable model for WHF was 0.66. After multivariable adjustment for baseline characteristics, WHF was associated with an increase in LOS of 4.33days [95% confidence interval (CI) 3.54-5.13days], a hazard ratio (HR) for 30-day HF readmission or death of 2.43 (95% CI 1.75-3.40), and a HR for 90-day mortality of 2.57 (95% CI 1.81-3.65), all with P < 0.0001.The associations of WHF with these outcomes remained largely unchanged after adjustment for both baseline characteristics and changes in markers of renal and hepatic dysfunction during the first day of admission. ConclusionsIn patients admitted for AHF, WHF is a significant clinical event that is associated with delays in discharge and higher rates for readmission and death. C1 [Cotter, Gad; Davison, Beth A.; Senger, Stefanie; Milo, Olga] Momentum Res, Durham, NC 27707 USA. [Metra, Marco] Univ Brescia, Piazza Spedali Civili, Brescia, Italy. [Bourge, Robert C.] Univ Alabama Birmingham, Birmingham, AL USA. [Cleland, John G. F.] Univ Hull, Kingston Upon Hull, Yorks, England. [Cleland, John G. F.] Univ London Imperial Coll Sci Technol & Med, Royal Brompton & Harefield Hosp NHS Trust, Natl Heart & Lung Inst, London, England. [Jondeau, Guillaume] Hop Bichat Claude Bernard, Serv Cardiol, F-75877 Paris 18, France. [Krum, Henry] Monash Univ, Alfred Hosp, Dept Epidemiol & Prevent Med, Monash Ctr Cardiovasc Res & Educ Therapeut, Melbourne, Vic 3181, Australia. [O'Connor, Christopher M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Parker, John D.] Mt Sinai Hosp, Div Cardiol, Toronto, ON M5G 1X5, Canada. [Torre-Amione, Guillermo] Methodist Hosp, Methodist DeBakey Heart & Vasc Ctr, Houston, TX 77030 USA. [van Veldhuisen, Dirk J.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Kobrin, Isaac] Kobrin Associates GmbH, Basel, Switzerland. [Rainisio, Maurizio] Abanovus Srl, San Remo, Imperia, Italy. [McMurray, John J. V.] Univ Glasgow, Glasgow, Lanark, Scotland. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Cotter, G (reprint author), Momentum Res, 3100 Tower Blvd, Durham, NC 27707 USA. EM gadcotter@momentum-research.com OI Metra, Marco/0000-0001-6691-8568; Davison, Beth/0000-0003-2374-6449; Cleland, John/0000-0002-1471-7016; Parker, John/0000-0003-1949-2669; Senger, Stefanie/0000-0003-4144-1040; mcmurray, john/0000-0002-6317-3975 FU Novartis; Corthera; Novocardia; Trevena; Merck; Angen; ChanRX; Cardio 3; Sorbent; Singulex; Actelion; Gilead; Amgen; Cytokinetics FX O.M.C., G.C., B.A.D., and S.S. are employees of Momentum Research Inc. which has received research grants from Novartis, Corthera, Novocardia, Trevena, Merck, Angen, ChanRX, Cardio 3, Sorbent, and Singulex. M.M. has received honoraria from Bayer as DMC Chairman, Novartis as EC Co-chairman. and Servier as a steering committee member. R.B. has conducted research sponsored by Actelion, has ongoing research sponsored by Gilead, a competitor of Actelion, and has served on Gilead's speaker's bureau. J.C., H.K., and J.D.P. have received honoraria from Actelion for steering committee activities. J.T. has received funds from Actelion and is currently conducting research funded by Amgen, Cytokinetics, Novartis, and Trevena. All other authors report no potential conflict of interest. NR 19 TC 10 Z9 10 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD DEC PY 2014 VL 16 IS 12 BP 1362 EP 1371 DI 10.1002/ejhf.186 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AU7BJ UT WOS:000345755200015 PM 25371147 ER PT J AU Reddy, AT Lakshmi, SP Zhang, YZ Reddy, RC AF Reddy, Aravind T. Lakshmi, Sowmya P. Zhang, Yingze Reddy, Raju C. TI Nitrated fatty acids reverse pulmonary fibrosis by dedifferentiating myofibroblasts and promoting collagen uptake by alveolar macrophages SO FASEB JOURNAL LA English DT Article DE TGF; collagen; MFG-E8 ID ACTIVATED-RECEPTOR-GAMMA; GROWTH-FACTOR-BETA; HEPATIC STELLATE CELLS; GENE-EXPRESSION; LUNG FIBROSIS; MURINE MODEL; INFLAMMATION; INJURY; DIFFERENTIATION; MECHANISMS AB Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disease, thought to be largely transforming growth factor beta (TGF beta) driven, for which there is no effective therapy. We assessed the potential benefits in IPF of nitrated fatty acids (NFAs), which are unique endogenous agonists of peroxisome proliferator- activated receptor gamma (PPAR gamma), a nuclear hormone receptor that exhibits wound-healing and antifibrotic properties potentially useful for IPF therapy. We found that pulmonary PPAR gamma is down-regulated in patients with IPF. In vitro, knockdown or knockout of PPAR gamma expression in isolated human and mouse lung fibroblasts induced a profibrotic phenotype, whereas treating human fibroblasts with NFAs up-regulated PPAR gamma and blocked TGF beta signaling and actions. NFAs also converted TGF beta to inactive monomers in cell-free solution, suggesting an additional mechanism through which they may inhibit TGF beta. In vivo, treating mice bearing experimental pulmonary fibrosis with NFAs reduced disease severity. Also, NFAs up-regulated the collagen-targeting factor milk fat globule-EGF factor 8 (MFG-E8), stimulated collagen uptake and degradation by alveolar macrophages, and promoted myofibroblast dedifferentiation. Moreover, treating mice with established pulmonary fibrosis using NFAs reversed their existing myofibroblast differentiation and collagen deposition. These findings raise the prospect of treating IPF with NFAs to halt and perhaps even reverse the progress of IPF. C1 [Reddy, Aravind T.; Lakshmi, Sowmya P.; Zhang, Yingze; Reddy, Raju C.] Univ Pittsburgh, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15213 USA. [Reddy, Aravind T.; Lakshmi, Sowmya P.; Reddy, Raju C.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Reddy, RC (reprint author), Univ Pittsburgh, Sch Med, Div Pulm Allergy & Crit Care Med, 3459 Fifth Ave, Pittsburgh, PA 15213 USA. EM reddyrc@upmc.edu FU U.S. Department of Veterans Affairs; U.S. National Institutes of Health [HL-093196] FX This work was supported by a Merit Review Award from the U.S. Department of Veterans Affairs and by U.S. National Institutes of Health grant HL-093196 (to R.C.R). NR 38 TC 7 Z9 7 U1 1 U2 10 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD DEC PY 2014 VL 28 IS 12 BP 5299 EP 5310 DI 10.1096/fj.14-256263 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AU9EN UT WOS:000345894500024 PM 25252739 ER PT J AU Lee, JS Fine, MJ AF Lee, Jonathan S. Fine, Michael J. TI The Debate on Antibiotic Therapy for Patients Hospitalized for Pneumonia Where Should We Go From Here? SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID AZITHROMYCIN C1 [Lee, Jonathan S.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Fine, Michael J.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. RP Fine, MJ (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Bldg 30,Univ Dr 151C, Pittsburgh, PA 15240 USA. EM michael.fine@va.gov NR 8 TC 2 Z9 2 U1 0 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD DEC PY 2014 VL 174 IS 12 BP 1901 EP 1903 DI 10.1001/jamainternmed.2014.3996 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AU9KI UT WOS:000345911000008 PM 25285980 ER PT J AU Jones, M Huttner, B Leecaster, M Huttner, A Damal, K Tanner, W Nielson, C Rubin, MA Goetz, MB Madaras-Kelly, K Samore, MH AF Jones, Makoto Huttner, Benedikt Leecaster, Molly Huttner, Angela Damal, Kavitha Tanner, Windy Nielson, Christopher Rubin, Michael A. Goetz, Matthew Bidwell Madaras-Kelly, Karl Samore, Matthew H. TI Does universal active MRSA surveillance influence anti-MRSA antibiotic use? A retrospective analysis of the treatment of patients admitted with suspicion of infection at Veterans Affairs Medical Centers between 2005 and 2010 SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE vancomycin; empirical treatment; definitive treatment ID RESISTANT STAPHYLOCOCCUS-AUREUS; SOFT-TISSUE INFECTIONS; INTENSIVE-CARE UNITS; ANTIMICROBIAL SUSCEPTIBILITY; LATIN-AMERICA; THERAPY; SKIN; TRANSMISSION; PERFORMANCE; PNEUMONIA AB After the implementation of an active surveillance programme for MRSA in US Veterans Affairs (VA) Medical Centers, there was an increase in vancomycin use. We investigated whether positive MRSA admission surveillance tests were associated with MRSA-positive clinical admission cultures and whether the availability of surveillance tests influenced prescribers' ability to match initial anti-MRSA antibiotic use with anticipated MRSA results from clinical admission cultures. Analyses were based on barcode medication administration data, microbiology data and laboratory data from 129 hospitals between January 2005 and September 2010. Hospitalized patient admissions were included if clinical cultures were obtained and antibiotics started within 2 days of admission. Mixed-effects logistic regression was used to examine associations between positive MRSA admission cultures and (i) admission MRSA surveillance test results and (ii) initial anti-MRSA therapy. Among 569aEuroS815 included admissions, positive MRSA surveillance tests were strong predictors of MRSA-positive admission cultures (OR 8.5; 95% CI 8.2-8.8). The negative predictive value of MRSA surveillance tests was 97.6% (95% CI 97.5%-97.6%). The diagnostic OR between initial anti-MRSA antibiotics and MRSA-positive admission cultures was 3.2 (95% CI 3.1-3.4) for patients without surveillance tests and was not significantly different for admissions with surveillance tests. The availability of nasal MRSA surveillance tests in VA hospitals did not seem to improve the ability of prescribers to predict the necessity of initial anti-MRSA treatment despite the high negative predictive value of MRSA surveillance tests. Prospective trials are needed to establish the safety and effectiveness of using MRSA surveillance tests to guide antibiotic therapy. C1 [Jones, Makoto; Huttner, Benedikt; Leecaster, Molly; Huttner, Angela; Damal, Kavitha; Rubin, Michael A.; Samore, Matthew H.] VA Salt Lake City Hlth Care Syst, Salt Lake City, UT 84148 USA. [Jones, Makoto; Huttner, Benedikt; Leecaster, Molly; Huttner, Angela; Damal, Kavitha; Rubin, Michael A.; Samore, Matthew H.] Univ Utah, Salt Lake City, UT USA. [Tanner, Windy] Univ Utah, Dept Family & Preventat Med, Salt Lake City, UT USA. [Nielson, Christopher] VA Reno Med Ctr, Reno, NV USA. [Nielson, Christopher] Univ Nevada, Reno, NV 89557 USA. [Goetz, Matthew Bidwell] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Madaras-Kelly, Karl] Vet Affairs Med Ctr, Clin Pharm Serv, Boise, ID USA. RP Jones, M (reprint author), VA Salt Lake City Hlth Care Syst, 500 Foothill Dr, Salt Lake City, UT 84148 USA. EM makoto.jones@va.gov RI Huttner, Benedikt/M-5616-2014 OI Huttner, Benedikt/0000-0002-1749-9464 FU VA Consortium for Health Informatics Research (CHIR) [HIR 09-001, HIR 09-003]; VA Informatics and Computing Infrastructure (VINCI) [HIR 08-204]; Centers for Disease Control and Prevention Epicenter [5U01CI000334, 07FED706504]; Geneva University Hospitals, Switzerland; [CDA 10-030-02] FX This work was supported by using resources and facilities at the VA Salt Lake City Health Care System. Funding was provided by the VA Consortium for Health Informatics Research (CHIR) (grant numbers HIR 09-001 and HIR 09-003), the VA Informatics and Computing Infrastructure (VINCI) (HIR 08-204) and the Centers for Disease Control and Prevention Epicenter (5U01CI000334 and 07FED706504). In addition, M. J. was supported by a career development award (CDA 10-030-02) and B. H. was supported in part by a fellowship grant from Geneva University Hospitals, Switzerland. NR 29 TC 2 Z9 2 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 EI 1460-2091 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD DEC PY 2014 VL 69 IS 12 BP 3401 EP 3408 DI 10.1093/jac/dku299 PG 8 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA AU7FX UT WOS:000345767300032 PM 25103488 ER PT J AU McAllister, C Leykum, LK Lanham, H Reisinger, HS Kohn, JL Palmer, R Pezzia, C Agar, M Parchman, M Pugh, J McDaniel, RR AF McAllister, Caitlin Leykum, Luci K. Lanham, Holly Reisinger, Heather Schacht Kohn, Jamie L. Palmer, Ray Pezzia, Carla Agar, Michael Parchman, Michael Pugh, Jacqueline McDaniel, Reuben R., Jr. TI Relationships Within Inpatient Physician Housestaff Teams and Their Association With Hospitalized Patient Outcomes SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID HEALTH-CARE; QUALITY; IMPLEMENTATION; KNOWLEDGE; MORTALITY; FAILURE; PROGRAM AB IMPORTANCEImproving inpatient care delivery has historically focused on improving individual components of the system. Applying the complexity science framework to clinical systems highlights the important role of relationships among providers in influencing system function and clinical outcomes. OBJECTIVETo understand whether inpatient medical physician teams can be differentiated based on the relationships among team members, and whether these relationships are associated with patient outcomes, including length of stay (LOS), unnecessary length of stay (ULOS), and complication rates. DESIGNEleven inpatient medicine teams were observed daily during attending rounds for 2- to 4-week periods from September 2008 through June 2011. Detailed field notes were taken regarding patient care activities, team behaviors, and patient characteristics and outcomes. Behaviors were categorized using the Lanham relationship framework, giving each team a relationship score. We used factor analysis to assess the pattern of relationship characteristics and assessed the association between relationship characteristics and patient outcomes. SETTINGObservations occurred at the Audie L. Murphy Veterans Affairs Hospital and University Hospital in San Antonio, Texas. PARTICIPANTSPhysicians were chosen based on rotation schedules, experience, and time of year. Patients were included based on their admission to the inpatient medicine teams that were being observed. MAIN MEASURESRelationship scores were based on the presence or absence of 7 relationship characteristics. LOS, ULOS, and complication rates were assessed based on team discussions and chart review. The association between relationships and outcomes was assessed using the Kruskal-Wallis rank sum test. RESULTSWe observed 11 teams over 352.9 hours, observing 1941 discussions of 576 individual patients. Teams exhibited a range of 0 to 7 relationship characteristics. Relationship scores were significantly associated with complication rates, and presence of trust and mindfulness among teams was significantly associated with ULOS and complication rates. CONCLUSIONSOur findings are an important step in understanding the impact of relationships on the outcomes of hospitalized medical patients. This understanding could expand the scope of interventions to improve hospital care to include not only process improvement but also relationships among providers. Journal of Hospital Medicine 2014;9:764-771. (c) 2014 Society of Hospital Medicine C1 [McAllister, Caitlin] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, San Antonio, TX 78229 USA. [Leykum, Luci K.; Lanham, Holly; Pezzia, Carla; Pugh, Jacqueline] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Leykum, Luci K.; Pezzia, Carla; Pugh, Jacqueline] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Lanham, Holly; McDaniel, Reuben R., Jr.] Univ Texas Austin, McCombs Sch Business, Dept Management Sci & Informat Syst, Austin, TX 78712 USA. [Reisinger, Heather Schacht] Iowa City VA Hlth Care Syst, Dept Med, Iowa City, IA USA. [Reisinger, Heather Schacht] Univ Iowa, Carver Coll Med, Iowa City, IA USA. [Kohn, Jamie L.] Univ N Carolina, Kenan Flagler Business Sch, Chapel Hill, NC USA. [Palmer, Ray] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Agar, Michael] Ethknoworks LLC, Santa Fe, NM USA. [Parchman, Michael] Grp Hlth Res Inst, MacColl Ctr Hlth Care Innovat, Seattle, WA USA. RP Leykum, LK (reprint author), 7400 Merton Minter, San Antonio, TX 78229 USA. EM leykum@uthscsa.edu OI Pugh, Jacqueline/0000-0003-4933-141X; Parchman, Michael/0000-0001-7129-2889 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [CDA 07-022] FX The research reported herein was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (CDA 07-022). Investigator salary support was provided through this funding, and through the South Texas Veterans Health Care System. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. Dr. McDaniel receives support from the IC2 Institute of the University of Texas at Austin. Dr. Luci Leykum 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. The authors report no conflicts of interest. NR 35 TC 7 Z9 7 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD DEC PY 2014 VL 9 IS 12 BP 764 EP 771 DI 10.1002/jhm.2274 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AU9LE UT WOS:000345913400004 PM 25355652 ER PT J AU Jenkins, TC Knepper, BC Moore, SJ Saveli, CC Pawlowski, SW Perlman, DM McCollister, BD Burman, WJ AF Jenkins, Timothy C. Knepper, Bryan C. Moore, S. Jason Saveli, Carla C. Pawlowski, Sean W. Perlman, Daniel M. McCollister, Bruce D. Burman, William J. TI Comparison of the Microbiology and Antibiotic Treatment Among Diabetic and Nondiabetic Patients Hospitalized for Cellulitis or Cutaneous Abscess SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID SOFT-TISSUE INFECTIONS; DISEASES SOCIETY; COMPLICATED SKIN; PRACTICE GUIDELINES; FOOT INFECTIONS; AMERICA; MULTICENTER; MANAGEMENT; DIAGNOSIS; MORTALITY AB BACKGROUNDAmong diabetics, complicated skin infections may involve gram-negative pathogens; however, the microbiology of cellulitis and cutaneous abscess is not well established. OBJECTIVETo compare the microbiology and prescribing patterns between diabetics and nondiabetics hospitalized for cellulitis or abscess. DESIGNSecondary analysis of 2 published retrospective cohorts. SETTING/PATIENTSAdults hospitalized for cellulitis or abscess, excluding infected ulcers or deep tissue infections, at 7 academic and community facilities. METHODSMicrobiological findings and antibiotic use were compared among diabetics and nondiabetics. Multivariable logistic regression was performed to identify factors associated with exposure to broad gram-negative therapy, defined as receipt of at least 2 calendar days of -lactamase inhibitors, second- to fifth-generation cephalosporins, fluoroquinolones, carbapenems, tigecycline, aminoglycosides, or colistin. RESULTSOf 770 total patients with cellulitis or abscess, 167 (22%) had diabetes mellitus. Among the 38% of cases with a positive culture, an aerobic gram-positive organism was isolated in 90% of diabetics and 92% of nondiabetics (P=0.59); aerobic gram-negative organisms were isolated in 7% and 12%, respectively (P=0.28). Overall, diabetics were more likely than nondiabetics to be exposed to broad gram-negative therapy (54% vs 44% of cases, P=0.02). By logistic regression, diabetes mellitus was independently associated with exposure to broad gram-negative therapy (odds ratio: 1.66, 95% confidence interval: 1.15-2.40). CONCLUSIONIn cases of cellulitis or abscess associated with a positive culture, gram-negative pathogens were not more common among diabetics compared with nondiabetics. However, diabetics were overall more likely to be exposed to broad gram-negative therapy suggesting this prescribing practice may not be not warranted. Journal of Hospital Medicine 2014;9:788-794. (c) 2014 Society of Hospital Medicine C1 [Jenkins, Timothy C.; Burman, William J.] Denver Hlth, Dept Med, Denver, CO USA. [Jenkins, Timothy C.; Burman, William J.] Denver Hlth, Div Infect Dis, Denver, CO USA. [Jenkins, Timothy C.; Saveli, Carla C.; McCollister, Bruce D.; Burman, William J.] Univ Colorado, Sch Med, Dept Med, Aurora, CO USA. [Jenkins, Timothy C.; Saveli, Carla C.; McCollister, Bruce D.; Burman, William J.] Univ Colorado, Sch Med, Div Infect Dis, Aurora, CO USA. [Knepper, Bryan C.] Denver Hlth, Dept Patient Safety & Qual, Denver, CO USA. [Moore, S. Jason] Vail Valley Med Ctr, Dept Trauma & Crit Care Serv, Vail, CO USA. [Pawlowski, Sean W.] Colorado Infect Dis Associates, Denver, CO USA. [Perlman, Daniel M.] Porter Adventist Med Ctr, Dept Med, Denver, CO USA. [McCollister, Bruce D.] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO USA. [McCollister, Bruce D.] Denver Vet Affairs Med Ctr, Div Infect Dis, Denver, CO USA. [Burman, William J.] Denver Hlth, Denver Publ Hlth, Denver, CO USA. RP Jenkins, TC (reprint author), 660 Bannock St, Denver, CO 80204 USA. EM timothy.jenkins@dhha.org FU National Institute of Allergy and Infectious Diseases, National Institute of Health [TCJ: K23 AI099082] FX This work was supported by the National Institute of Allergy and Infectious Diseases, National Institute of Health (TCJ: K23 AI099082). D.M.P. reports potential conflicts of interests with Optimer, Cubist, and Forest Pharmaceuticals. The authors report no other conflicts of interest. NR 16 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD DEC PY 2014 VL 9 IS 12 BP 788 EP 794 DI 10.1002/jhm.2267 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA AU9LE UT WOS:000345913400007 PM 25266293 ER PT J AU Wang, C Abdel-Mohsen, M Strain, MC Lada, SM Yukl, S Cockerham, LR Pilcher, CD Hecht, FM Sinclair, E Liegler, T Richman, DD Deeks, SG Pillai, SK AF Wang, Charlene Abdel-Mohsen, Mohamed Strain, Matthew C. Lada, Steven M. Yukl, Steven Cockerham, Leslie R. Pilcher, Christopher D. Hecht, Frederick M. Sinclair, Elizabeth Liegler, Teri Richman, Douglas D. Deeks, Steven G. Pillai, Satish K. TI Decreased HIV Type 1 Transcription in CCR5-Delta 32 Heterozygotes During Suppressive Antiretroviral Therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE HIV; CCR5; Delta 32; coreceptor; reservoir; latency; eradication; NF-kappa B; HIV transcription; HIV replication ID T-CELL-ACTIVATION; DISEASE PROGRESSION; CCR5; REPLICATION; INFECTION; RNA AB Individuals who are heterozygous for the CCR5-Delta 32 mutation provide a natural model to examine the effects of reduced CCR5 expression on human immunodeficiency virus (HIV) persistence. We evaluated the HIV reservoir in 18 CCR5-Delta 32 heterozygotes and 54 CCR5 wild-type individuals during suppressive antiretroviral therapy. Cell-associated HIV RNA levels (P = .035), RNA to DNA transcriptional ratios (P = .013), and frequency of detectable HIV 2-long terminal repeat circular DNA (P = .013) were significantly lower in CD4(+) T cells from CCR5-Delta 32 heterozygotes. Cell-associated HIV RNA was significantly correlated with CCR5 surface expression on CD4(+) T cells (r(2) = 0.136; P = .002). Our findings suggest that curative strategies should further explore manipulation of CCR5. C1 [Wang, Charlene] Emory Univ, Atlanta, GA 30322 USA. [Wang, Charlene; Abdel-Mohsen, Mohamed; Pillai, Satish K.] Blood Syst Res Inst, San Francisco, CA USA. [Abdel-Mohsen, Mohamed; Yukl, Steven; Cockerham, Leslie R.; Pilcher, Christopher D.; Hecht, Frederick M.; Sinclair, Elizabeth; Liegler, Teri; Deeks, Steven G.; Pillai, Satish K.] Univ Calif San Francisco, San Francisco, CA 94118 USA. [Yukl, Steven] San Francisco VA Med Ctr, San Francisco, CA USA. [Strain, Matthew C.; Lada, Steven M.; Richman, Douglas D.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Strain, Matthew C.; Lada, Steven M.; Richman, Douglas D.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. RP Pillai, SK (reprint author), Univ Calif San Francisco, Blood Syst Res Inst, 270 Masonic Ave, San Francisco, CA 94118 USA. EM satish.pillai@ucsf.edu FU American Foundation for AIDS Research; FAIR [108545]; National Institutes of Health [R21 AI108503, R01 HD074511]; University of California-San Francisco Gladstone Institute of Virology and Immunology Center for AIDS Research [P30 AI027763]; Delaney AIDS Research Enterprise [U19 AI096109]; Collaboratory of AIDS Researchers for Eradication [U19 AI096113]; University of California-San Diego Center for AIDS Research [P30 AI036214]; James Pendleton Charitable Trust; U.S. Department of Veterans Affairs [1 IK2 CX000520-01] FX This work was supported by American Foundation for AIDS Research, with support from FAIR (grant 108545 to S. K. P.) and the National Institutes of Health (grants R21 AI108503 [to S. K. P.] and R01 HD074511 [to C. D. P.]); the University of California-San Francisco Gladstone Institute of Virology and Immunology Center for AIDS Research (grant P30 AI027763); the Delaney AIDS Research Enterprise (grant U19 AI096109); the Collaboratory of AIDS Researchers for Eradication (grant U19 AI096113); the University of California-San Diego Center for AIDS Research (grant P30 AI036214 to D. D. R.); the James Pendleton Charitable Trust (support to D. D. R.); and the U.S. Department of Veterans Affairs (grant 1 IK2 CX000520-01 to S. Y.). NR 15 TC 5 Z9 5 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 1 PY 2014 VL 210 IS 11 BP 1838 EP 1843 DI 10.1093/infdis/jiu338 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AU7HI UT WOS:000345771000018 PM 24935955 ER PT J AU Zong, P Zhang, LL Shaban, NM Pena, J Jiang, L Taub, CC AF Zong, Pu Zhang, Lili Shaban, Nada M. Pena, Jessica Jiang, Leng Taub, Cynthia C. TI Left Heart Chamber Quantification in Obese Patients: How Does Larger Body Size Affect Echocardiographic Measurements? SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Echocardiography; Left heart; Obesity; Isometric scaling; Allometric scaling ID LEFT ATRIAL VOLUME; LEFT-VENTRICULAR MASS; SURFACE-AREA; CARDIAC DIMENSIONS; WEIGHT; CHILDREN; HEIGHT; ADULTS; ASSOCIATION; POPULATION AB Background: Accurate normalization of cardiac chamber size in the obese population is a challenge. The aim of this study was to develop and assess the performance of allometric models for scaling left heart chamber sizes, including left atrial anteroposterior dimension (LAD(AP)), left atrial volume (LAV), left ventricular end-diastolic volume (LVEDV), and left ventricular end-diastolic dimension (LVEDD), in an obese population. Methods: To normalize left heart chamber measurements (Y: LAD(AP), LAV, LVEDV, and LVEDD) to body size variables (X: height, weight, body mass index, and body surface area), both isometric models (Y = aX) and optimal allometric models (Y = aX(b)) were tested. A logarithmic transformation (LnY = Lna + b x LnX) and ordinary least squares linear regression was performed to estimate the allometric scaling exponents. Pearson's correlation coefficients were obtained for measured and indexed left chamber sizes using both isometric and allometric models against body size variables. Gender-specific allometric models were also derived as sensitivity analyses. Results: A total of 717 healthy obese subjects were included in the analysis. The mean body surface area and body mass index were 2.3 m(2) and 42.2 kg/m(2), respectively. Measured LAD(AP), LAV, LVEDD, and LVEDV were positively correlated with body size variables. Allometric scaling of LAD(AP), LAV, LVEDD, and LVEDV showed stronger correlation with measured chamber sizes compared with isometric scaling. The overcorrection caused by isometric scaling significantly improved after allometric models were used. The sensitivity analysis showed no significant differences in scaling exponents between men and women. Conclusions: Normalizing cardiac chamber measurements with allometric scaling methods is superior to the use of isometric methods in removing the effects of body size and minimizing overcorrection in the obese population. Using an allometric model with height provides the most accurate results. C1 [Zong, Pu] James J Peters VA Med Ctr, Dept Med, Bronx, NY USA. [Zhang, Lili] Jacobi Med Ctr, Dept Med, Bronx, NY USA. [Shaban, Nada M.; Pena, Jessica; Taub, Cynthia C.] Montefiore Med Ctr, Dept Cardiol, Bronx, NY 10467 USA. [Jiang, Leng] Baystate Med Ctr, Dept Cardiol, Springfield, MA USA. RP Taub, CC (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, 1845 Eastchester Rd, Bronx, NY 10461 USA. EM ctaub@montefiore.org OI Zhang, Lili/0000-0002-9341-5832 NR 24 TC 5 Z9 5 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD DEC PY 2014 VL 27 IS 12 BP 1267 EP 1274 DI 10.1016/j.echo.2014.07.015 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AU9GI UT WOS:000345899400003 PM 25193637 ER PT J AU Andeen, NK Lann, DY de Boer, IH Nicosia, RF AF Andeen, Nicole K. Lann, Daniel Y. de Boer, Ian H. Nicosia, Roberto F. TI Renal ApoA-1 Amyloidosis with Glu34Lys Mutation and Intra-amyloid Lipid Accumulation SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID APOLIPOPROTEIN-A-I; HIGH-DENSITY-LIPOPROTEIN; HEREDITARY AMYLOIDOSIS; VARIANT; RECEPTOR; CUBILIN AB Apolipoprotein A-1 (ApoA-1) amyloidosis occurs as a nonhereditary condition in atherosclerotic plaques, but it can also manifest as a hereditary disorder caused by mutations of the APOA1 gene. Hereditary ApoA-1 amyloidosis presents with diverse organ involvement based on the position of the mutation. We describe a case of ApoA-1 amyloidosis with a Glu34Lys mutation; testicular, conjunctival, and renal involvement; and the notable finding of lipid deposition within the amyloid deposits. C1 [Andeen, Nicole K.; Nicosia, Roberto F.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Lann, Daniel Y.; de Boer, Ian H.] Vet Affairs Puget Sound Hlth Care Syst, Hosp & Specialty Med Serv, Seattle, WA USA. [Nicosia, Roberto F.] Vet Affairs Puget Sound Hlth Care Syst, Pathol & Lab Med Serv, Seattle, WA USA. RP Andeen, NK (reprint author), Univ Washington, Dept Pathol, 1959 NE Pacific St,Box 356100, Seattle, WA 98195 USA. EM nandeen@u.washington.edu NR 19 TC 0 Z9 2 U1 2 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2014 VL 25 IS 12 BP 2703 EP 2705 DI 10.1681/ASN.2013060651 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA AU4UT UT WOS:000345607500006 PM 24925720 ER PT J AU Chung, SA Brown, EE Williams, AH Ramos, PS Berthier, CC Bhangale, T Alarcon-Riquelme, ME Behrens, TW Criswell, LA Graham, DC Demirci, FY Edberg, JC Gaffney, PM Harley, JB Jacob, CO Kamboh, MI Kelly, JA Manzi, S Moser-Sivils, KL Russell, LP Petri, M Tsao, BP Vyse, TJ Zidovetzki, R Kretzler, M Kimberly, RP Freedman, BI Graham, RR Langefeld, CD AF Chung, Sharon A. Brown, Elizabeth E. Williams, Adrienne H. Ramos, Paula S. Berthier, Celine C. Bhangale, Tushar Alarcon-Riquelme, Marta E. Behrens, Timothy W. Criswell, Lindsey A. Graham, Deborah Cunninghame Demirci, F. Yesim Edberg, Jeffrey C. Gaffney, Patrick M. Harley, John B. Jacob, Chaim O. Kamboh, M. Ilyas Kelly, Jennifer A. Manzi, Susan Moser-Sivils, Kathy L. Russell, Laurie P. Petri, Michelle Tsao, Betty P. Vyse, Tim J. Zidovetzki, Raphael Kretzler, Matthias Kimberly, Robert P. Freedman, Barry I. Graham, Robert R. Langefeld, Carl D. CA Int Consortium Systemic TI Lupus Nephritis Susceptibility Loci in Women with Systemic Lupus Erythematosus SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; RENAL-DISEASE; GENE-EXPRESSION; GROWTH-FACTOR; METAANALYSIS; POLYMORPHISM; POPULATIONS; VARIANTS; ITGAM; SCANS AB Lupus nephritis is a manifestation of SLE resulting from glomerular immune complex deposition and inflammation. Lupus nephritis demonstrates familial aggregation and accounts for significant morbidity and mortality. We completed a meta-analysis of three genome-wide association studies of SLE to identify lupus nephritis-predisposing loci. Through genotyping and imputation, >1.6 million markers were assessed in 2000 unrelated women of European descent with SLE (588 patients with lupus nephritis and 1412 patients with lupus without nephritis). Tests of association were computed using logistic regression adjusting for population substructure. The strongest evidence for association was observed outside the MHC and included markers localized to 4q11-q13 (PDGFRA, GSX2; P=4.5 X 10(-7)), 16p12 (SLC5A11; P=5.1 X 10(-7)), 6p22 (ID4; P=7.4 X 10(-7)), and 8q24.12 (HAS2, SNTB1; P=1.1 X 10(-6)). Both HLA-DR2 and HLA-DR3, two well established lupus susceptibility loci, showed evidence of association with lupus nephritis (P=0.06 and P=3.7 X 10(-5), respectively). Within the class I region, rs9263871 (C6orf15-HCG22) had the strongest evidence of association with lupus nephritis independent of HLA-DR2 and HLA-DR3 (P=8.5 X 10(-6)). Consistent with a functional role in lupus nephritis, intra-renal mRNA levels of PDGFRA and associated pathway members showed significant enrichment in patients with lupus nephritis (n=32) compared with controls (n=15). Results from this large-scale genome-wide investigation of lupus nephritis provide evidence of multiple biologically relevant lupus nephritis susceptibility loci. C1 [Chung, Sharon A.; Criswell, Lindsey A.] Univ Calif San Francisco, Div Rheumatol, Rosalind Russell Ephraim P Engleman Med Res Ctr A, San Francisco, CA USA. [Brown, Elizabeth E.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Brown, Elizabeth E.; Edberg, Jeffrey C.; Kimberly, Robert P.] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Williams, Adrienne H.; Russell, Laurie P.; Langefeld, Carl D.] Wake Forest Sch Med, Ctr Publ Hlth Gen, Dept Biostatist Sci, Winston Salem, NC USA. [Ramos, Paula S.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Berthier, Celine C.; Kretzler, Matthias] Univ Michigan, Dept Internal Med, Div Nephrol, Ann Arbor, MI 48109 USA. [Alarcon-Riquelme, Marta E.; Gaffney, Patrick M.; Harley, John B.; Kelly, Jennifer A.; Moser-Sivils, Kathy L.] Oklahoma Med Res Fdn, Arthritis & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [Alarcon-Riquelme, Marta E.] Pfizer Univ Granada Andalusian, Ctr Genom & Oncol Res, Granada, Spain. [Bhangale, Tushar] Genentech Inc, Dept Bioinformat & Computat Biol, San Francisco, CA 94080 USA. [Behrens, Timothy W.] Genentech Inc, Immunol Tissue Growth & Repair Human Genet Grp, San Francisco, CA 94080 USA. [Demirci, F. Yesim; Kamboh, M. Ilyas] Kings Coll London, Div Genet & Mol Med & Immunol Infect & Inflammato, London, England. [Harley, John B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Ctr Autoimmune Genom & Etiol, Div Rheumatol, Cincinnati, OH USA. [Harley, John B.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Jacob, Chaim O.] Univ So Calif, Dept Med, Los Angeles, CA USA. [Manzi, Susan] W Penn Allegheny Hlth Syst, Dept Med, Pittsburgh, PA USA. [Manzi, Susan] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [Moser-Sivils, Kathy L.] Univ Oklahoma, Hlth Sci Ctr, Coll Med, Oklahoma City, OK 73190 USA. [Petri, Michelle] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Tsao, Betty P.] Univ Calif Los Angeles, Dept Med, Div Rheumatol, Los Angeles, CA 90024 USA. [Zidovetzki, Raphael] Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA. [Freedman, Barry I.] Wake Forest Sch Med, Dept Internal Med, Nephrol Sect, Winston Salem, NC USA. RP Langefeld, CD (reprint author), Wake Forest Sch Med, Dept Biostatist Sci, Div Publ Hlth Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM clangefe@wakehealth.edu OI Demirci, F. Yesim/0000-0001-6907-9843; Kamboh, M. Ilyas/0000-0002-3453-1438; Alarcon Riquelme, Marta Eugenia/0000-0002-7632-4154; Kimberly, Robert/0000-0002-5330-3086 FU Genentech; International Consortium for Systemic Lupus Erythematosus Genetics; National Institutes of Health [AI063274, AR052125, AR043247, KL2-TR000143, R01-AR033062, N01-AR062277, RC2-AR058951, UL1-TR000165, P60-AR053308, K24-AR02175]; National Institutes of Health (National Research Service) [5F32-AR50927]; Lupus Foundation of Minnesota; Arthritis Foundation; National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK079912, P30-DK081943]; Alliance for Lupus Research; Swedish Research Council of Medicine; National Kidney Foundation [FLB1245]; Arthritis Research UK Special Strategic Award [19289]; Kirkland Scholar Award; National Institutes of Health (National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS] Progression of Cardiovascular Disease in Lupus) [K24-AR002213, AR43727, UL1-RR025005, R01-AR043814, R01-AR057172, R01-HL56266, R01-DK070941]; National Institutes of Health. [R01-AR057172, R01-AR052300, UL1-TR000004, AR057028, IMMA9, 5R37AI024717-25, 5P01AI083194, 5P01AR049084, PR094002, 3R37AI024717-23S1, HL092397, R01-AR046588] FX The authors gratefully acknowledge the following funding sources for this research. Genotyping funds for set I were provided by Genentech. The Alliance for Lupus Research funded the International Consortium for Systemic Lupus Erythematosus Genetics and the genotyping for set II. Set III was funded by grants from the National Institutes of Health (AI063274 and AR052125 to P.M.G. and AR043247 to K.L.M.; National Research Service Award 5F32-AR50927 to R.R.G.), the Lupus Foundation of Minnesota (to P.M.G. and K.L.M.-S.), and the Arthritis Foundation (to K.L.M.-S.). This study Was also supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK079912 and P30-DK081943 to M.K.), the Alliance for Lupus Research (M.K., B.P.T., L.A.C., and M.K.), and the Swedish Research Council of Medicine (to M.E.A.-R.), as well as a research fellowship from the National Kidney Foundation (FLB1245 to C.C.B.), an Arthritis Research UK Special Strategic Award (19289 to T.J.V.), and a Kirkland Scholar Award (to L.A.C). Sample collections and additional financial support were also obtained from grants from the National Institutes of Health (KL2-TR000143 to S.A.C.; R01-AR033062, N01-AR062277, RC2-AR058951, and UL1-TR000165 to E.E.B. and R.P.K.; P60-AR053308, K24-AR02175, R01-AR052300, and UL1-TR000004 to L.A.C.; AR057028 to F.Y.D.; IMMA9, 5R37AI024717-25, 5P01AI083194, 5P01AR049084, PR094002, and 3R37AI024717-23S1 to J.B.H.; R01-AR057172 to C.O.J.; HL092397 to M.I.K.; R01-AR046588, National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS] Progression of Cardiovascular Disease in Lupus K24-AR002213 to S.M.; AR43727 and UL1-RR025005 to M.P.; R01-AR043814 to B.P.T.; R01-AR057172 to C.O.J.; and R01-HL56266 and R01-DK070941 to B.I.F.). NR 47 TC 21 Z9 22 U1 0 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2014 VL 25 IS 12 BP 2859 EP 2870 DI 10.1681/ASN.2013050446 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA AU4UT UT WOS:000345607500020 PM 24925725 ER PT J AU Sui, YT Bullock, KM Erickson, MA Zhang, J Banks, WA AF Sui, Yu-Ting Bullock, Kristin M. Erickson, Michelle A. Zhang, Jing Banks, W. A. TI Alpha synuclein is transported into and out of the brain by the blood-brain barrier SO PEPTIDES LA English DT Article DE Blood-brain barrier; Alpha-synuclein; LRP-1; p-Glycoprotein; Parkinson's disease ID CARRIER-MEDIATED TRANSPORT; DOPAMINERGIC NEURON LOSS; MULTIPLE SYSTEM ATROPHY; PARKINSONS-DISEASE; MOUSE MODEL; CEREBROSPINAL-FLUID; ALZHEIMERS-DISEASE; SUBSTANTIA-NIGRA; LOCUS TRIPLICATION; HUMAN PLASMA AB Alpha-synuclein (alpha-Syn), a small protein with multiple physiological and pathological functions, is one of the dominant proteins found in Lewy Bodies, a pathological hallmark of Lewy body disorders, including Parkinson's disease (PD). More recently, alpha-Syn has been found in body fluids, including blood and cerebrospinal fluid, and is likely produced by both peripheral tissues and the central nervous system. Exchange of alpha-Syn between the brain and peripheral tissues could have important pathophysiologic and therapeutic implications. However, little is known about the ability of alpha-Syn to cross the blood-brain barrier (BBB). Here, we found that radioactively labeled alpha-Syn crossed the BBB in both the brain-to-blood and the blood-to-brain directions at rates consistent with saturable mechanisms. Low-density lipoprotein receptor-related protein-1 (LRP-1), but not p-glycoprotein, may be involved in alpha-Syn efflux and lipopolysaccharide (LPS)-induced inflammation could increase alpha-Syn uptake by the brain by disrupting the BBB. Published by Elsevier Inc. C1 [Sui, Yu-Ting; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA. [Bullock, Kristin M.; Erickson, Michelle A.; Banks, W. A.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Banks, W. A.] Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. RP Banks, WA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Room 810 Bldg 1,1660 S Columbian Way, Seattle, WA 98108 USA. EM wabanks1@uw.edu FU NIN [U01 N5082137]; VA Merit Review; NIH [AG029834 (WAB)] FX This study was supported by NIN U01 N5082137 (JZ), VA Merit Review (WAB) and NIH RO-1 AG029834 (WAB). NR 62 TC 8 Z9 8 U1 3 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 EI 1873-5169 J9 PEPTIDES JI Peptides PD DEC PY 2014 VL 62 BP 197 EP 202 DI 10.1016/j.peptides.2014.09.018 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA AU4YQ UT WOS:000345614700020 PM 25278492 ER PT J AU Atwood, CW AF Atwood, Charles W., Jr. TI How Few Signals are Needed to Diagnose Sleep Apnea? SO SLEEP LA English DT Editorial Material ID POLYSOMNOGRAPHY; AUTOTITRATION; HOME C1 [Atwood, Charles W., Jr.] Univ Pittsburgh, Pittsburgh, PA 15213 USA. [Atwood, Charles W., Jr.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Atwood, CW (reprint author), Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, 3459 Fifth Ave,NW628 MUH, Pittsburgh, PA 15213 USA. EM atwoodcw@upmc.edu NR 9 TC 1 Z9 1 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD DEC 1 PY 2014 VL 37 IS 12 BP 1883 EP 1884 DI 10.5665/sleep.4232 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AU8DW UT WOS:000345827600004 PM 25406117 ER PT J AU Luciano, JA Zuckerbraun, BS AF Luciano, Jason A. Zuckerbraun, Brian S. TI Clostridium Difficile Infection Prevention, Treatment, and Surgical Management SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article DE Vancomycin; Fecal microbiota therapy; Ileostomy; Colectomy ID FULMINANT PSEUDOMEMBRANOUS COLITIS; FECAL MICROBIOTA TRANSPLANTATION; PLACEBO-CONTROLLED TRIAL; RISK-FACTORS; BINARY TOXIN; MONOCLONAL-ANTIBODIES; CARE FACILITIES; UNITED-STATES; DISEASE; DIARRHEA AB Clostridium difficile is increasing in both incidence and severity. Although metronidazole and vancomycin remain the gold standard for medical management, and surgical colectomy remains the gold standard for surgical management, new treatment alternatives, including the creation of a diverting loop ileostomy along with colonic lavage and vancomycin enemas, are being investigated. These alternatives may lead to changes in the current treatment algorithms. The most exciting development in the treatment options for C difficile infection, however, is likely to be novel immunologic agents, which hold the potential to reduce the incidence, mortality, and costs associated with C difficile. C1 [Luciano, Jason A.; Zuckerbraun, Brian S.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. [Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Dept Surg, Pittsburgh, PA 15240 USA. RP Zuckerbraun, BS (reprint author), F1271 PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM zuckerbraunbs@upmc.edu NR 90 TC 4 Z9 4 U1 1 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0039-6109 EI 1558-3171 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD DEC PY 2014 VL 94 IS 6 BP 1335 EP + DI 10.1016/j.suc.2014.08.006 PG 16 WC Surgery SC Surgery GA AU7YO UT WOS:000345814400015 PM 25440127 ER PT J AU Park, M Vittinghoff, E Shlipak, MG Mishra, R Whooley, M Bansal, N AF Park, Meyeon Vittinghoff, Eric Shlipak, Michael G. Mishra, Rakesh Whooley, Mary Bansal, Nisha TI Associations of N-terminal pro-B-type natriuretic peptide with kidney function decline in persons without clinical heart failure in the Heart and Soul Study SO AMERICAN HEART JOURNAL LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; CORONARY-ARTERY-DISEASE; SUBCLINICAL CARDIAC ABNORMALITIES; GLOMERULAR-FILTRATION-RATE; CARDIOVASCULAR EVENTS; RENAL-FUNCTION; CYSTATIN-C; PLASMA; BNP; MORTALITY AB Background Subclinical volume overload in the absence of diagnosed heart failure (HF) may be an underrecognized contributor to kidney function decline in coronary artery disease (CAD) patients. We evaluated associations of circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP), a marker of ventricular stretch, with change in estimated glomerular filtration rate (eGFR). Methods We evaluated 535 patients with stable CAD and no history of HF, who were enrolled in the Heart and Soul Study and followed for 5 years. N-terminal pro-B-type natriuretic peptide was measured at baseline. We evaluated the associations of NT-proBNP with change in kidney function over 5 years: (a) annual percent change in eGFR, (b) rapid kidney function loss (>3% per year for 5 years), and (c) incident eGFR <60 mL/min per 1.73 m(2). In multivariable models, we adjusted for demographics, comorbid conditions, echocardiographic parameters, medications, and baseline kidney function. Results Among 535 participants, medianNT-proBNP was 130.6 (interquartile range 61.8-280.9) pg/mL, and median B-type natriuretic peptide (BNP) was 32.5 (14.4-75.9) pg/mL. Individuals with NT-proBNP levels in the highest quartile (>280.9 pg/mL) had a greater odds of rapid kidney function loss after full adjustment (odds ratio 2.95; 95% CI 1-8.65; P = .0492). Associations with incident eGFR <60 mL/min per 1.73 m(2) were also significant (adjusted odds ratio 4.23; 95% CI 1.05-16.98; P = .0422). Results were similar when analyzed using BNP as the predictor. Conclusions N-terminal pro-B-type natriuretic peptide and BNP are strongly and independently associated with accelerated kidney function loss, even in the absence of clinical HF. These findings suggest that subclinical cardiovascular dysfunction may contribute to elevated kidney disease risk in persons with CAD. C1 [Park, Meyeon] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Vittinghoff, Eric; Shlipak, Michael G.; Whooley, Mary] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Shlipak, Michael G.; Mishra, Rakesh; Whooley, Mary] San Francisco VA Med Ctr, San Francisco, CA USA. [Shlipak, Michael G.; Whooley, Mary] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Mishra, Rakesh] Univ Calif San Francisco, Div Cardiol, San Francisco, CA USA. [Bansal, Nisha] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. RP Park, M (reprint author), 521 Parnassus Ave,C443,Box 0532, San Francisco, CA 94143 USA. EM meyeon.park@ucsf.edu FU NHLBI NIH HHS [R01 HL079235]; NIA NIH HHS [R01 AG034853, R01 AG027002]; NIDDK NIH HHS [R01 DK087961, K23 DK088865, K23 DK099238] NR 45 TC 2 Z9 2 U1 2 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD DEC PY 2014 VL 168 IS 6 BP 931 EP + DI 10.1016/j.ahj.2014.09.008 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AU3IN UT WOS:000345506100017 PM 25458658 ER PT J AU Freytes, CO Toro, JJ Yeh, RF Stadtmauer, EA Ratanatharathorn, V Akpek, G Sahovic, E Tricot, GJ Shaughnessy, PJ White, DJ Rodriguez, TE Solomon, SR Yu, LH Zhao, C Patil, S Armstrong, E Smith, A Elekes, A Kato, K Reece, DE AF Freytes, Cesar O. Toro, Juan J. Yeh, Rosa F. Stadtmauer, Edward A. Ratanatharathorn, Voravit Akpek, Goerguen Sahovic, Entezam Tricot, Guido J. Shaughnessy, Paul J. White, Darrell J. Rodriguez, Tulio E. Solomon, Scott R. Yu, Louie H. Zhao, Cathy Patil, Shiva Armstrong, Elizabeth Smith, Angela Elekes, Agnes Kato, Kazunobu Reece, Donna E. TI Safety and Efficacy of Targeted-Dose Busulfan and Bortezomib as a Conditioning Regimen for Patients with Relapsed Multiple Myeloma Undergoing a Second Autologous Blood Progenitor Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Multiple myeloma; Autologous transplantation; Busulfan; Bortezomib ID BONE-MARROW-TRANSPLANTATION; HEPATIC VENOOCCLUSIVE DISEASE; DAILY INTRAVENOUS BUSULFAN; ORAL BUSULFAN; PREPARATIVE REGIMEN; DECREASED INCIDENCE; SYSTEMIC EXPOSURE; MELPHALAN; CYCLOPHOSPHAMIDE; SCHEDULE AB Patients with multiple myeloma (MM) who relapse after autologous transplantation have limited therapeutic options. We conducted a prospective, multicenter, phase ha study to investigate the safety and efficacy of i.v. busulfan (Bu) in combination with bortezomib as a conditioning regimen for a second autotransplantation. Because a safe Bu exposure was unknown in patients receiving this combination, Bu was initially targeted to a total area under the concentration time curve (AUC) of 20,000 mu M x minute. As no concentration-limiting toxicity was observed in 6 patients, this Bu exposure was utilized in the following treatment cohort (n = 24). Individualized Bu dose, based on test dose.8 mg/kg pharmacokinetics (PR), was administered daily for 4 consecutive days starting 5 days before transplantation, followed by a single dose of bortezomib (1.3 mg/m(2)) 1 day before transplantation. The total mean dose of i.v. Bu (including the test dose and 4-day administration) was 142 mg/kg (standard deviation = 2.48; range, 8.7 to 19.2). Confirmatory PR demonstrated that only 2 of 30 patients who underwent transplantation were dosed outside the Bu AUC target and dose adjustments were made for the last 2 doses of i.v. Bu. The median age was 59 years (range, 48 to 73). Median time from first to second transplantation was 28.0 months (range, 12 to 119). Of 26 evaluable patients, 10 patients attained a partial response (PR) or better at 3 months after transplantation, with 2 patients attaining a complete response. At 6 months after transplantation, 5 of 12 evaluable patients had maintained or improved their disease status. Median progression-free survival was 191 days, whereas median overall survival was not reached during the study period. The most common grade 3 and 4 toxicities were febrile neutropenia (50.0%) and stomatitis (43.3%). One transplantation-related death was observed. A combination of dose-targeted i.v. Bu and bortezomib induced PR or better in one third of patients with MM who underwent a second autotransplantation, with acceptable toxicity. Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation. C1 [Freytes, Cesar O.; Toro, Juan J.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Yeh, Rosa F.; Yu, Louie H.] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA 98104 USA. [Stadtmauer, Edward A.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Ratanatharathorn, Voravit] Karmanos Canc Inst, Detroit, MI USA. [Akpek, Goerguen] Univ Maryland, Dept Med Oncol, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Sahovic, Entezam] Western Penn Hosp, Pittsburgh, PA 15224 USA. [Tricot, Guido J.] Univ Utah, Sch Med, Div Hematol BMT, Dept Internal Med Hematol, Salt Lake City, UT USA. [Tricot, Guido J.] Univ Utah, Sch Med, Myeloma Program, Dept Internal Med Hematol, Salt Lake City, UT USA. [Shaughnessy, Paul J.] Texas Transplant Inst, San Antonio, TX USA. [White, Darrell J.] Queen Elizabeth 2 Hlth Sci Ctr, Div Hematol, Halifax, NS, Canada. [Rodriguez, Tulio E.] Loyola Univ, Chicago Med Ctr, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. [Solomon, Scott R.] Northside Hosp, Blood & Marrow Transplant Program, Atlanta, GA USA. [Zhao, Cathy; Patil, Shiva; Armstrong, Elizabeth; Smith, Angela; Elekes, Agnes; Kato, Kazunobu] Otsuka Pharmaceut Dev & Commercializat Inc, Princeton, NJ USA. [Reece, Donna E.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. RP Freytes, CO (reprint author), BMT 111,7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM cesar.freytes@va.gov FU Otsuka; Sanofi; Celgene and Janssen; Millennium; Merck; Novartis; BMS; Johnson and Johnson FX grant/research support from Otsuka and Merck; consultant for Otsuka; speakers bureau for Sanofi; advisory board for Spectrum Pharmaceuticals; and other for Cardiovascular Clinical Science Foundation. R.F.Y. reports consultancy for Otsuka. E.S. reports activity with the Millennium speakers bureau and advisory boards with honoraria. P.J.S. reports honoraria from Sanofi and Millenium and research funding from Sanofi. D.J.W. reports honoraria from Otsuka. T.E.R. reports grant/research support from Millennium and Otsuka; consultancy for Celgene, Millennium, and Otsuka; speakers bureau participation for Celgene, Millennium, and Onyx; and advisory board position for Celgene and Millennium. D.E.R. reports research funding, consultant/advisory role, and honoraria from Celgene and Janssen; research funding from Millennium, Merck, Novartis, and BMS; consultancy and advisory role for Onyx; honoraria from Amgen; research funding and honoraria from Otsuka; and research funding from and consultant/advisory role for Johnson and Johnson. C.Z., S.P. E.A., A.S., A.E., and K.K. report Otsuka employment. J.J.T., E.A.S, V.R., G.A., G.J.T., S.R.S., and L.H.Y. report no financial disclosures. NR 33 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD DEC PY 2014 VL 20 IS 12 BP 1949 EP 1957 DI 10.1016/j.bbmt.2014.08.007 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA AU4UJ UT WOS:000345606500013 PM 25139216 ER PT J AU Gaensbauer, JT Rakhola, JT Onyango-Makumbi, C Mubiru, M Westcott, JE Krebs, NF Asturias, EJ Fowler, MG McFarland, E Janoff, EN AF Gaensbauer, James T. Rakhola, Jeremy T. Onyango-Makumbi, Carolyne Mubiru, Michael Westcott, Jamie E. Krebs, Nancy F. Asturias, Edwin J. Fowler, Mary Glenn McFarland, Elizabeth Janoff, Edward N. TI Impaired Haemophilus influenzae Type b Transplacental Antibody Transmission and Declining Antibody Avidity through the First Year of Life Represent Potential Vulnerabilities for HIV-Exposed but - Uninfected Infants SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CONJUGATE VACCINE; MATERNAL IMMUNIZATION; POLYSACCHARIDE VACCINE; ROUTINE IMMUNIZATION; PLACENTAL-TRANSFER; IGG ANTIBODIES; CHILDREN; INFECTION; RESPONSES AB To determine whether immune function is impaired among HIV-exposed but - uninfected (HEU) infants born to HIV-infected mothers and to identify potential vulnerabilities to vaccine-preventable infection, we characterized the mother-to-infant placental transfer of Haemophilus influenzae type b-specific IgG (Hib-IgG) and its levels and avidity after vaccination in Ugandan HEU infants and in HIV-unexposed U. S. infants. Hib-IgG was measured by enzyme-linked immunosorbent assay in 57 Ugandan HIV-infected mothers prenatally and in their vaccinated HEU infants and 14 HIV-unexposed U. S. infants at birth and 12, 24, and 48 weeks of age. Antibody avidity at birth and 48 weeks of age was determined with 1 M ammonium thiocyanate. A median of 43% of maternal Hib-IgG was transferred to HEU infants. Although its level was lower in HEU infants than in U. S. infants at birth (P < 0.001), Hib-IgG was present at protective levels (> 1.0 mu g/ml) at birth in 90% of HEU infants and all U. S. infants. HEU infants had robust Hib-IgG responses to a primary vaccination. Although Hib-IgG levels declined from 24 to 48 weeks of age in HEU infants, they were higher than those in U. S. infants (P = 0.002). Antibody avidity, comparable at birth, declined by 48 weeks of age in both populations. Early vaccination of HEU infants may limit an initial vulnerability to Hib disease resulting from impaired transplacental antibody transfer. While initial Hib vaccine responses appeared adequate, the confluence of lower antibody avidity and declining Hib-IgG levels in HEU infants by 12 months support Hib booster vaccination at 1 year. Potential immunologic impairments of HEU infants should be considered in the development of vaccine platforms for populations with high maternal HIV prevalence. C1 [Gaensbauer, James T.; Westcott, Jamie E.; Krebs, Nancy F.; Asturias, Edwin J.; McFarland, Elizabeth] Univ Colorado Denver, Dept Pediat, Aurora, CO 80045 USA. [Rakhola, Jeremy T.; Janoff, Edward N.] Univ Colorado Denver, Dept Med, Aurora, CO USA. [Onyango-Makumbi, Carolyne; Mubiru, Michael; Fowler, Mary Glenn] Johns Hopkins Univ, Res Collaborat, Makerere Univ, Kampala, Uganda. [Gaensbauer, James T.; Asturias, Edwin J.] Colorado Sch Publ Hlth, Ctr Global Hlth, Aurora, CO USA. [Rakhola, Jeremy T.; McFarland, Elizabeth; Janoff, Edward N.] Mucosal & Vaccine Res Colorado MAVRC, Aurora, CO USA. [Janoff, Edward N.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Gaensbauer, JT (reprint author), Univ Colorado Denver, Dept Pediat, Aurora, CO 80045 USA. EM james.gaensbauer@childrenscolorado.org FU National Institutes of Health [R01 HD059527, R21AI083615, NIH K24 DK083772]; Elisabeth Glaser Pediatric AIDS Foundation [MV-00-9-900-01432-0-00]; National Institutes of Health/National Center for Advancing Translational Sciences, Colorado Clinical and Translational Sciences Institute [UL1 TR000154, UL1 RR025780]; Mucosal and Vaccine Research Colorado program; Veterans Affairs Research Service FX This work was supported by the National Institutes of Health (R01 HD059527 and R21AI083615 to E.J., NIH K24 DK083772 to N.F.K.), the Elisabeth Glaser Pediatric AIDS Foundation (MV-00-9-900-01432-0-00 to E.J.), the National Institutes of Health/National Center for Advancing Translational Sciences, Colorado Clinical and Translational Sciences Institute (UL1 TR000154 to J.T.G. and UL1 RR025780 to E.J.), the Mucosal and Vaccine Research Colorado program, and the Veterans Affairs Research Service. The contents of this report are solely our responsibility and do not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs. NR 49 TC 9 Z9 9 U1 1 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 EI 1556-679X J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD DEC PY 2014 VL 21 IS 12 BP 1661 EP 1667 DI 10.1128/CVI.00356-14 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AU3RX UT WOS:000345532300008 PM 25298109 ER PT J AU Graff, JN Beer, TM AF Graff, Julie N. Beer, Tomasz M. TI Pharmacotherapeutic Management of Metastatic, Castration-Resistant Prostate Cancer in the Elderly: Focus on Non-Chemotherapy Agents SO DRUGS & AGING LA English DT Review ID PHASE-III TRIAL; I CLINICAL-TRIAL; ABIRATERONE ACETATE; DOUBLE-BLIND; OPEN-LABEL; DENDRITIC CELLS; PLUS PREDNISONE; DOCETAXEL; PLACEBO; ENZALUTAMIDE AB In the past 4 years, five new agents have been approved for metastatic, castration-resistant prostate cancer. Four of them are non-chemotherapeutic and generally well tolerated. However, each has toxicities that can negatively impact patients, particularly the elderly. This review covers the epidemiology of prostate cancer in elderly men. It discusses the efficacy data for sipuleucel-T, abiraterone in chemotherapy-naive patients, enzalutamide in chemotherapy-naive patients and radium-223 and presents any additional studies done for those over 75 years of age. Disease burden, such as the presence or absence of visceral disease, and comorbid conditions weigh into the selection of therapy and are discussed here. Drug-drug interactions between these agents and other drugs commonly used in the elderly population are also considered. The emerging therapies tasquinimod and ipilimumab are reviewed. With the arrival of so many agents for prostate cancer, selection of the most appropriate agent can be perplexing, particularly because these agents were tested against placebo, not one another. Furthermore, the study population differs significantly from those seen in clinical practice. This review addresses these issues. C1 [Graff, Julie N.; Beer, Tomasz M.] Portland VA Med Ctr, Portland, OR USA. [Graff, Julie N.; Beer, Tomasz M.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. RP Graff, JN (reprint author), Oregon Hlth & Sci Univ, Knight Canc Inst, 3710 SW US Vet Hosp Rd,P3CHEMO, Portland, OR 97239 USA. EM graffj@ohsu.edu FU Medivation; Sanofi; Janssen; Astellas; Dendreon; Bayer; Astellas/Medivation FX J.N. Graff (JNG) and T.M. Beer (TMB) have received research funding from Medivation. JNG also received research funding from Sanofi. TMB also received research funding from Janssen, Astellas and Dendreon. TMB received consulting fees from Bayer, Dendreon, Janssen. TMB participated in a certified nursing program that received support from Astellas/Medivation, Bayer and Dendreon. JNG and TMB received an honorarium from Bayer for writing an educational piece. JNG and TMB received money from Bayer to travel to a research-related meeting. No funding was used in the preparation of this manuscript. NR 52 TC 3 Z9 3 U1 1 U2 5 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1170-229X EI 1179-1969 J9 DRUG AGING JI Drugs Aging PD DEC PY 2014 VL 31 IS 12 BP 873 EP 882 DI 10.1007/s40266-014-0224-y PG 10 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA AU1PH UT WOS:000345392100003 PM 25387443 ER PT J AU Dawes, AJ Louie, R Nguyen, DK Maggard-Gibbons, M Parikh, P Ettner, SL Ko, CY Zingmond, DS AF Dawes, Aaron J. Louie, Rachel Nguyen, David K. Maggard-Gibbons, Melinda Parikh, Punam Ettner, Susan L. Ko, Clifford Y. Zingmond, David S. TI The Impact of Continuous Medicaid Enrollment on Diagnosis, Treatment, and Survival in Six Surgical Cancers SO HEALTH SERVICES RESEARCH LA English DT Article DE Medicaid; cancer; surgery; access to care; survival ID HEALTH-INSURANCE COVERAGE; SERVICES TASK-FORCE; COLORECTAL-CANCER; RACIAL DISPARITIES; BREAST-CANCER; SOCIOECONOMIC-STATUS; AMERICAN-COLLEGE; LUNG-CANCER; CARE; QUALITY AB ObjectiveTo examine the effect of Medicaid enrollment on the diagnosis, treatment, and survival of six surgically relevant cancers among poor and underserved Californians. Data SourcesCalifornia Cancer Registry (CCR), California's Patient Discharge Database (PDD), and state Medicaid enrollment files between 2002 and 2008. Study DesignWe linked clinical and administrative records to differentiate patients continuously enrolled in Medicaid from those receiving coverage at the time of their cancer diagnosis. We developed multivariate logistic regression models to predict death within 1year for each cancer after controlling for sociodemographic and clinical variables. Data Collection/Extraction MethodsAll incident cases of six cancers (colon, esophageal, lung, pancreas, stomach, and ovarian) were identified from CCR. CCR records were linked to hospitalizations (PDD) and monthly Medicaid enrollment. Principal FindingsContinuous enrollment in Medicaid for at least 6months prior to diagnosis improves survival in three surgically relevant cancers. Discontinuous Medicaid patients have higher stage tumors, undergo fewer definitive operations, and are more likely to die even after risk adjustment. ConclusionsExpansion of continuous insurance coverage under the Affordable Care Act is likely to improve both access and clinical outcomes for cancer patients in California. C1 [Dawes, Aaron J.; Nguyen, David K.; Maggard-Gibbons, Melinda; Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Dawes, Aaron J.] Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90095 USA. [Dawes, Aaron J.; Maggard-Gibbons, Melinda; Ko, Clifford Y.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Louie, Rachel; Parikh, Punam; Ettner, Susan L.; Zingmond, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Dept Med, Los Angeles, CA 90095 USA. [Ettner, Susan L.] Univ Calif Los Angeles, Jonathan & Karin Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90095 USA. RP Dawes, AJ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 757 Westwood Plaza,B711, Los Angeles, CA 90095 USA. EM adawes@mednet.ucla.edu OI Dawes, Aaron/0000-0003-4574-6765 FU VA Office of Academic Affiliations through VA/Robert Wood Johnson Clinical Scholars Program; American Cancer Society [RSGI-11-005-01-CPHPS] FX This manuscript reflects work that was a presented at the 2014 AcademyHealth Annual Research Meeting. Dr. Dawes was supported by the VA Office of Academic Affiliations through the VA/Robert Wood Johnson Clinical Scholars Program. Dr. Zingmond was supported by a grant from the American Cancer Society (RSGI-11-005-01-CPHPS). NR 50 TC 5 Z9 5 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 EI 1475-6773 J9 HEALTH SERV RES JI Health Serv. Res. PD DEC PY 2014 VL 49 IS 6 BP 1787 EP 1811 DI 10.1111/1475-6773.12237 PG 25 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AU0XT UT WOS:000345346300006 PM 25256223 ER PT J AU Poordad, F Sievert, W Mollison, L Brau, N Levin, JM Sepe, TE Lee, SS Boyer, N Bronowicki, JP Jacobson, IM Boparai, N Hughes, EA Swenson, ES Yin, PD AF Poordad, Fred Sievert, William Mollison, Lindsay Brau, Norbert Levin, James M. Sepe, Thomas E. Lee, Samuel S. Boyer, Nathalie Bronowicki, Jean-Pierre Jacobson, Ira M. Boparai, Navdeep Hughes, Eric A. Swenson, Eugene S. Yin, Philip D. TI All-oral, fixed-dose combination therapy with daclatasvir/asunaprevir/BMS-791325 for non-cirrhotic patients with chronic HCV genotype 1 infection: UNITY-1 Phase 3 SVR12 results SO HEPATOLOGY LA English DT Meeting Abstract C1 [Poordad, Fred] Univ Texas Hlth Sci Ctr San Antonio, Texas Liver Inst, San Antonio, TX 78229 USA. [Sievert, William] Monash Hlth, Melbourne, Vic, Australia. [Sievert, William] Monash Univ, Melbourne, Vic 3004, Australia. [Mollison, Lindsay] Fremantle Hosp, Fremantle Hepatitis Serv, Fremantle, WA, Australia. [Brau, Norbert] Bronx Vet Affairs Med Ctr, New York, NY USA. [Levin, James M.] Dean Fdn, Madison, WI USA. [Sepe, Thomas E.] Univ Gastroenterol, Providence, RI USA. [Lee, Samuel S.] Univ Calgary, Calgary, AB, Canada. [Boyer, Nathalie] Hop Beaujon, Serv Hepatol, Clichy, France. [Bronowicki, Jean-Pierre] Univ Lorraine, Ctr Hosp Univ Nancy, Vandoeuvre Les Nancy, France. [Jacobson, Ira M.] Weill Cornell Med Coll, New York, NY USA. [Boparai, Navdeep; Hughes, Eric A.] Bristol Myers Squibb Co, Princeton, NJ USA. [Swenson, Eugene S.; Yin, Philip D.] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. NR 0 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD DEC PY 2014 VL 60 IS 6 MA LB-7 BP 1271A EP 1272A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AU3MI UT WOS:000345517000008 ER PT J AU Harrison, SA Castiblanco, JE Park, S Handler, TE Barstow, K He, WJ Harper, N Ahuja, SK AF Harrison, Stephen A. Castiblanco, John E. Park, Stephen Handler, Tristan E. Barstow, Karol He, Weijing Harper, Nathan Ahuja, Sunil K. TI Whole Genome RNA Sequencing (RNA-seq) Identifies CHI3L1 Gene Expression as a Stronger Discriminator of Isolated Steatosis vs. NASH Compared with Established Biomarker Scoring Systems SO HEPATOLOGY LA English DT Meeting Abstract C1 [Harrison, Stephen A.; Park, Stephen; Handler, Tristan E.; Barstow, Karol] Brooke Army Med Ctr, Ft Sam Houston, TX 78234 USA. [Castiblanco, John E.; He, Weijing; Harper, Nathan] South Texas Vet Hlth Care Syst, Vet Adm Ctr Personalized Med, San Antonio, TX USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD DEC PY 2014 VL 60 IS 6 MA LB-41 BP 1290A EP 1290A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AU3MI UT WOS:000345517000041 ER PT J AU Deberry, JJ Bielefeldt, K Davis, BM Szigethy, EM Hartman, DJ Coates, MD AF Deberry, Jennifer J. Bielefeldt, Klaus Davis, Brian M. Szigethy, Eva M. Hartman, Douglas J. Coates, Matthew D. TI Abdominal Pain and the Neurotrophic System in Ulcerative Colitis SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE inflammatory bowel disease; ulcerative colitis; abdominal pain; cytokines; nerve-gut interactions ID IRRITABLE-BOWEL-SYNDROME; QUALITY-OF-LIFE; FUNCTIONAL GASTROINTESTINAL DISORDERS; NERVE GROWTH-FACTOR; MAJOR DEPRESSION; COLON AFFERENTS; MOOD DISORDERS; SENSORY FIBERS; DISEASE; INFLAMMATION AB Background:We undertook a study to test the hypothesis that inflammation alters peripheral sensory mechanisms, thereby contributing to chronic abdominal pain in ulcerative colitis (UC).Methods:Patients with UC and healthy individuals rated abdominal pain using a visual analog scale and completed surveys describing anxiety or depression (Hospital Anxiety and Depression Score) and gastrointestinal symptoms (Rome III questionnaire). Patient age, sex, and severity of inflammation were determined. Rectal biopsies were processed using immunohistochemical techniques to assess nerve fiber density and real-time PCR to determine transcript expression of neurotrophins (nerve growth factor, glial cell-derived neurotrophic factor, artemin, neurturin), ion channels (transient receptor potential vanilloid type 1, transient receptor potential ankyrin 1) and inflammatory mediators (tumor necrosis factor-, interleukin [IL]-1, IL-6, IL-10, IL-17).Results:A total of 77 patients with UC (27 female, 50 male) and 21 controls (10 female, 11 male) were enrolled. Patients with UC with pain had significantly higher depression scores than controls and patients with UC without pain (P < 0.05). There was no correlation between any of the inflammatory markers and pain scores. Visual analog scale pain scores significantly correlated with younger age, higher depression scores, increased expression of neurturin and decreased expression of transient receptor potential ankyrin 1 in the mucosa. Mucosal nerve fiber density did not correlate with any measures of inflammation or pain. Only higher depression scores independently predicted pain in UC (r > 0.5).Conclusions:We did not observe changes in mucosal innervation and did not see a significant relationship between nerve fiber density, inflammatory mediators, neurotrophic factors, or mucosal ion channel expression and pain. In contrast, the importance of depression as the only independent predictor of pain ratings mirrors functional disorders, where central processes significantly contribute to symptom development and/or perpetuation. C1 [Deberry, Jennifer J.] Univ Alabama Birmingham, Dept Psychol, Birmingham, AL 35294 USA. [Bielefeldt, Klaus; Szigethy, Eva M.] Univ Pittsburgh, Med Ctr, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. [Davis, Brian M.] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA USA. [Hartman, Douglas J.] Univ Pittsburgh, Dept Pathol, Med Ctr, Pittsburgh, PA USA. [Coates, Matthew D.] VA Pittsburgh Healthcare Syst, Div Gastroenterol, Dept Med, Pittsburgh, PA USA. RP Coates, MD (reprint author), VA Pittsburgh Healthcare Syst, Div Gastroenterol, Univ Dr, Pittsburgh, PA 15240 USA. EM Matthew.Coates@va.gov OI Davis, Brian/0000-0002-4646-0569 FU NIH [DK063922]; BaCCoR grant from the University of Pittsburgh; Inflammatory Bowel Disease Working Group GI Fellows Research Award grant FX Supported by NIH grant DK063922, a BaCCoR grant from the University of Pittsburgh and an Inflammatory Bowel Disease Working Group GI Fellows Research Award grant. NR 57 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD DEC PY 2014 VL 20 IS 12 BP 2330 EP 2339 DI 10.1097/MIB.0000000000000207 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AU3ND UT WOS:000345519400020 PM 25358061 ER PT J AU Stewart, MO Raffa, SD Steele, JL Miller, SA Clougherty, KF Hinrichsen, GA Karlin, BE AF Stewart, Michael O. Raffa, Susan D. Steele, Jennifer L. Miller, Sarah A. Clougherty, Kathleen F. Hinrichsen, Gregory A. Karlin, Bradley E. TI National Dissemination of Interpersonal Psychotherapy for Depression in Veterans: Therapist and Patient-Level Outcomes SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE interpersonal psychotherapy; depression; dissemination; training; veterans ID WORKING ALLIANCE INVENTORY; HEALTH-CARE-SYSTEM; PSYCHOMETRIC PROPERTIES; IMPLEMENTATION AB Objective: To evaluate the effects of training in and delivery of interpersonal psychotherapy (IPT) for depression throughout the U. S. Department of Veterans Affairs health care system on therapists' competency and patients' clinical outcomes. Method: Participants included 124 therapists and 241 veteran patients. Therapists participated in a 3-day workshop followed by 6 months of weekly group consultation. Therapy session tapes were rated by expert IPT training consultants using a standardized competency rating form. Patient outcomes were assessed with the Beck Depression Inventory-II and the World Health Organization Quality of Life-BREF. Therapeutic alliance was assessed with the Working Alliance Inventory-Short Revised. Results: Of the 124 therapists receiving IPT training, 115 (93%) completed all training requirements. Therapist competence in IPT increased from their 1st patient to their 2nd for both initial (d = 0.36) and intermediate (d = 0.24) treatment phases. Of the 241 veteran patients treated with IPT, 167 (69%) completed = 12 sessions. Intent-to-treat analyses indicated large overall reductions in depression (d = 1.26) and significant improvements in quality of life (d = 0.57 to 0.86) and the therapeutic alliance (d = 0.50 to 0.83). Conclusions: National IPT training in the VA health care system was associated with significant increases in therapist competencies to deliver IPT, as well as large overall reductions in depression and improvements in quality of life among veterans, many of whom presented with high levels of depression. Results support the feasibility and effectiveness of broad dissemination of IPT in routine clinical settings. C1 [Stewart, Michael O.; Raffa, Susan D.; Steele, Jennifer L.; Miller, Sarah A.; Karlin, Bradley E.] US Dept Vet Affairs, Cent Off, Washington, DC USA. [Raffa, Susan D.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Clougherty, Kathleen F.] Columbia Univ, Sch Social Work, New York, NY 10027 USA. [Hinrichsen, Gregory A.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Karlin, Bradley E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. RP Karlin, BE (reprint author), Educ Dev Ctr Inc, 96 Morton St,7th Floor, New York, NY 10014 USA. EM bkarlin@edc.org NR 18 TC 3 Z9 3 U1 0 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X EI 1939-2117 J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 2014 VL 82 IS 6 BP 1201 EP 1206 DI 10.1037/a0037410 PG 6 WC Psychology, Clinical SC Psychology GA AU2MQ UT WOS:000345452900024 PM 25045906 ER PT J AU Jackevicius, CA Glassman, P AF Jackevicius, Cynthia A. Glassman, Peter TI Laboratory Monitoring for Pharmaceuticals: Familiarity Does Not Breed Contempt SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID THERAPY C1 [Jackevicius, Cynthia A.] Western Univ Hlth Sci, Pomona, CA USA. [Jackevicius, Cynthia A.; Glassman, Peter] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Jackevicius, Cynthia A.] Univ Toronto, Inst Clin Evaluat Sci, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Univ Toronto, Fac Med, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Univ Hlth Network, Toronto, ON, Canada. [Glassman, Peter] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Glassman, P (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med 111G, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Peter.Glassman@va.gov NR 9 TC 0 Z9 0 U1 1 U2 3 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 DEC PY 2014 VL 29 IS 12 BP 1574 EP 1576 DI 10.1007/s11606-014-3048-x PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AU1PY UT WOS:000345393700002 PM 25287479 ER PT J AU Dhaliwal, G AF Dhaliwal, Gurpreet TI Capsule Commentary on Guerrasio and Aagaard, Methods and Outcomes for the Remediation of Clinical Reasoning SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 [Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA. RP Dhaliwal, G (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. EM gurpreet.dhaliwal@ucsf.edu NR 4 TC 1 Z9 1 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 DEC PY 2014 VL 29 IS 12 BP 1687 EP 1687 DI 10.1007/s11606-014-2971-1 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AU1PY UT WOS:000345393700020 PM 25183473 ER PT J AU Giridhar, KV Dhaliwal, G Tierney, L AF Giridhar, Karthik V. Dhaliwal, Gurpreet Tierney, Lawrence TI Split Decision SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE shared decision making; flank pain; radiation safety ID RENAL-ARTERY DISSECTION; INFARCTION; CANCER C1 [Giridhar, Karthik V.; Dhaliwal, Gurpreet; Tierney, Lawrence] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Dhaliwal, Gurpreet; Tierney, Lawrence] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA. RP Giridhar, KV (reprint author), Univ Calif San Francisco, Dept Med, 505 Parnassus Ave, San Francisco, CA 94143 USA. EM Karthik.giridhar@ucsf.edu OI Giridhar, Karthik/0000-0003-4640-9197 NR 12 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 DEC PY 2014 VL 29 IS 12 BP 1707 EP 1710 DI 10.1007/s11606-014-2874-1 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AU1PY UT WOS:000345393700027 PM 24913002 ER PT J AU Dobscha, SK Denneson, LM Kovas, AE Teo, A Forsberg, CW Kaplan, MS Bossarte, R McFarland, BH AF Dobscha, Steven K. Denneson, Lauren M. Kovas, Anne E. Teo, Alan Forsberg, Christopher W. Kaplan, Mark S. Bossarte, Robert McFarland, Bentson H. TI Correlates of Suicide Among Veterans Treated in Primary Care: Case-Control Study of a Nationally Representative Sample SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE mental health; veterans; primary care health services research ID POSTTRAUMATIC-STRESS-DISORDER; RISK-ASSESSMENT; HEALTH SYSTEM; MENTAL-HEALTH; DEPRESSION; IDEATION; MORTALITY; DEATH; PATTERNS; CONTACT AB BACKGROUND: Veterans receiving Veterans Affairs (VA) healthcare have increased suicide risk compared to the general population. Many patients see primary care clinicians prior to suicide. Yet little is known about the correlates of suicide among patients who receive primary care treatment prior to death. OBJECTIVE: Our aim was to describe characteristics of veterans who received VA primary care in the 6 months prior to suicide: and to compare these to characteristics of control patients who also received VA primary care. DESIGN: This was a retrospective case-control study. SUBJECTS: The investigators partnered with VA operations leaders to obtain death certificate data from 11 states for veterans who died by suicide in 2009. Cases were matched 1:2 to controls based on age, sex, and clinician. MAIN MEASURES: Demographic, diagnosis, and utilization data were obtained from VA's Corporate Data Warehouse. Additional clinical and psychosocial context data were collected using manual medical record review. Multivariate conditional logistic, regression was used to examine associations between potential predictor variables and suicide. KEY RESULTS: Two hundred and sixty-nine veteran cases were matched to 538 controls. Average subject age was 63 years; 97 % were male. Rates of mental health conditions, functional decline, sleep disturbance, suicidal ideation, and psychosocial stressors were all significantly greater in cases compared to controls. In the final model describing men in the sample, non-white race (OR=0.51; 95 % CI=0.27-0.98) and VA service-connected disability (OR= 0.54: 95 % CI=0.36-0.80) were associated with decreased odds of suicide, while anxiety disorder (OR= 3.52: 95 % Cl= 1.79-6.92), functional decline (OR=2.52; 95 % CI = 1.55-4.10), depression (OR=1.82; 95 % CI= 1.073.10). and endorsement of suicidal ideation (OR= 2.27: 95 % CI= 1.07-4.83) were associated with greater odds of suicide. CONCLUSIONS: Assessment for anxiety disorders and functional decline in addition to suicidal ideation and depression may be especially important for determining suicide risk in this population. Continued development of interventions that support identifying and addressing these conditions in primary care is indicated. C1 [Dobscha, Steven K.; Denneson, Lauren M.; Kovas, Anne E.; Teo, Alan; Forsberg, Christopher W.] Portland VA Med Ctr, Ctr Improve Vet Involvement Care, Portland, OR 97207 USA. [Dobscha, Steven K.; Denneson, Lauren M.; Teo, Alan; McFarland, Bentson H.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Kaplan, Mark S.] UCLA Luskin Sch Publ Affairs, Dept Social Welf, Los Angeles, CA USA. [Bossarte, Robert] VISN, Ctr Excellence Suicide Prevent 2, Canandaigua, NY USA. RP Dobscha, SK (reprint author), Portland VA Med Ctr, Ctr Improve Vet Involvement Care, POB 1034 R&D 66, Portland, OR 97207 USA. EM steven.dobscha@va.gov FU Department of Veterans Affairs; Veterans Health Administration; Health Services Research and Development Service Project [IIR 10-331]; VA Mental Health Services-Suicide Prevention Program; VISN 2 Center of Excellence for Suicide Prevention FX This material is based upon work supported by the Department of Veterans Affairs, the Veterans Health Administration, and Health Services Research and Development Service Project IIR 10-331, VA Mental Health Services-Suicide Prevention Program, and VISN 2 Center of Excellence for Suicide Prevention. Dr Dobscha is the Director of the Center to Improve Veteran Involvement in Care (CIVIC) at the Portland VA Medical Center. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Affairs or the United States government. NR 45 TC 9 Z9 9 U1 4 U2 10 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 DEC PY 2014 VL 29 SU 4 BP S853 EP S860 DI 10.1007/s11606-014-3028-1 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AU1XG UT WOS:000345410200009 PM 25355088 ER PT J AU Elwy, AR Bokhour, BG Maguire, EM Wagner, TH Asch, SM Gifford, AL Gallagher, TH Durfee, JM Martinello, RA Schiffner, S Jesse, RL AF Elwy, A. Rani Bokhour, Barbara G. Maguire, Elizabeth M. Wagner, Todd H. Asch, Steven M. Gifford, Allen L. Gallagher, Thomas H. Durfee, Janet M. Martinello, Richard A. Schiffner, Susan Jesse, Robert L. TI Improving Healthcare Systems' Disclosures of Large-Scale Adverse Events: A Department of Veterans Affairs Leadership, Policymaker, Research and Stakeholder Partnership SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE adverse events Veterans; qualitative; communication: partnered-based research AB BACKGROUND: The Department of Veterans Affairs (VA) mandates disclosure of large-scale adverse events to patients, even if risk of harm is not clearly present. Concerns about past disclosures warranted further examination of the impact of this policy. OBJECTIVE: Through a collaborative partnership between VA leaders, policymakers, researchers and stakeholders, the objective was to empirically identify critical aspects of disclosure processes as a first step towards improving future disclosures. DESIGN: Semi-structured interviews were conducted with participants at nine VA facilities where recent disclosures took place. PARTICIPANTS: Ninety-seven stakeholders participated in the interviews: 38 employees, 28 leaders (from facilities, regions and national offices), 27 Veteran patients and family members, and four congressional staff members. APPROACH: Facility and regional leaders were interviewed by telephone, followed by a two-day site visit where employees, patients and family members were interviewed face-to-face. National leaders and congressional staff also completed telephone interviews. Interviews were analyzed using rapid qualitative assessment processes. Themes were mapped to the stages of the Crisis and Emergency Risk Communication model: pre-crisis, initial event, maintenance, resolution and evaluation. KEY RESULTS: Many areas for improvement during disclosure were identified, such as preparing facilities better (pre-crisis), creating rapid communications, modifying disclosure language, addressing perceptions of harm, reducing complexity, and seeking assistance from others (initial event), managing communication with other stakeholders (maintenance), minimizing effects on staff and improving trust (resolution), and addressing facilities' needs (evaluation). CONCLUSIONS: Through the partnership, five recommendations to improve disclosures during each stage of communication have been widely disseminated throughout the VA using non-academic strategies. Some improvements have been made; other recommendations will be addressed through implementation of a large-scale adverse event disclosure toolkit. These toolkit strategies will enable leaders to provide timely and transparent information to patients and families, while reducing the burden on employees and the healthcare system during these events. C1 [Elwy, A. Rani; Bokhour, Barbara G.; Maguire, Elizabeth M.; Gifford, Allen L.] Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Healthcare Org & Implementat Res, Bedford, MA 01730 USA. [Elwy, A. Rani; Bokhour, Barbara G.; Gifford, Allen L.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Elwy, A. Rani; Bokhour, Barbara G.; Asch, Steven M.; Gifford, Allen L.] Vet Hlth Adm, HIV Hepatitis Qual Enhancement Res Initiat, Washington, DC USA. [Wagner, Todd H.] VA Palo Alto Healthcare Syst, Hlth Econ Resource Ctr, Menlo Pk, CA USA. [Wagner, Todd H.; Asch, Steven M.] VA Palo Alto Healthcare Syst, Ctr Innovat Implementat, Menlo Pk, CA USA. [Wagner, Todd H.; Asch, Steven M.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Gallagher, Thomas H.] Univ Washington, Sch Med, Seattle, WA USA. [Durfee, Janet M.; Martinello, Richard A.] US Dept Vet Affairs, Clin Publ Hlth Program, Off Publ Hlth, Vet Hlth Adm, Washington, DC USA. [Martinello, Richard A.] Yale Univ, Sch Med, New Haven, CT USA. [Schiffner, Susan; Jesse, Robert L.] US Dept Vet Affairs, Off Principal Deputy Secretary Hlth, Vet Hlth Adm, Washington, DC USA. RP Elwy, AR (reprint author), Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Healthcare Org & Implementat Res, 200 Springs Rd,Mailstop152, Bedford, MA 01730 USA. EM Rani.Elwy@va.gov FU Department of Veterans Affairs, Health Services Research and Development Service [SDR 11-440]; HIV/Hepatitis Quality Enhancement Research Initiative, Veterans Health Administration; National Institute of Mental Health [R25 MH080916-01A2]; Department of Veterans Affairs, Health Services Research & Development Service, Quality Enhancement Research Initiative FX This study was supported by the Department of Veterans Affairs, Health Services Research and Development Service, SDR 11-440. The views, opinions, and content of this publication are those of the authors and do not necessarily reflect the views, opinions, or policies of the Department of Veterans Affairs or the United States Government.; Drs. Elwy, Bokhow, Maguire, Asch and Gifford are supported by the HIV/Hepatitis Quality Enhancement Research Initiative, Veterans Health Administration.; Dr. Elwy is also an investigator with the Implementation Research Institute, at the George Warren Brown School of Social Work, Washington University in St. Louis, through an award from the National Institute of Mental Health (R25 MH080916-01A2) and the Department of Veterans Affairs, Health Services Research & Development Service, Quality Enhancement Research Initiative. NR 15 TC 3 Z9 3 U1 2 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 DEC PY 2014 VL 29 SU 4 BP S895 EP S903 DI 10.1007/s11606-014-3034-3 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AU1XG UT WOS:000345410200014 PM 25355090 ER PT J AU Kertesz, SG Austin, EL Holmes, SK Pollio, DE Schumacher, JE White, B Lukas, AV AF Kertesz, Stefan G. Austin, Erika Laine Holmes, Sally K. Pollio, David E. Schumacher, Joseph E. White, Bert Lukas, Andcarol VanDeusen TI Making Housing First Happen: Organizational Leadership in VA's Expansion of Permanent Supportive Housing SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE homeless persons; organizational behavior; implementation; community health; veterans; housing policy ID HEALTH-CARE; CONSOLIDATED FRAMEWORK; HOMELESS; IMPLEMENTATION; OUTCOMES; FIDELITY; SERVICES; PROGRAM; IMPACT; CHALLENGES AB BACKGROUND: While most organizational literature has focused on initiatives that transpire inside the hospital walls, the redesign of American health care increasingly asks that health care institutions address matters outside their walls, targeting the health of populations. The US Department of Veterans Affairs (VA)'s national effort to end Veteran homelessness represents an externally focused organizational endeavor. OBJECTIVE: Our aim was to evaluate the role of organizational practices in the implementation of Housing First (MI, an evidence-based homeless intervention for chronically homeless individuals. DESIGN: This was an interview-based comparative case study conducted across eight VA Medical Centers (VAMCs). PARTICIPANTS: Front line staff, mid-level managers, and senior leaders at VA Medical Centers were interviewed between February and December 2012. APPROACH: Using a structured narrative and numeric scoring, we assessed the correlation between successful HF implementation and organizational practices devised according to the organizational transformation model (OTM). KEY RESULTS: Scoring results suggested a strong association between HF implementation and OTM practice. Strong impetus to house Veterans came from national leadership, reinforced by Medical Center directors closely tracking results. More effective Medical Center leaders differentiated themselves by joining front-line staff in the work (at public events and in process improvement exercises), by elevating homeless-knowledgeable persons into senior leadership, and by exerting themselves to resolve logistic challenges. Vertical alignment and horizontal integration advanced at sites that fostered work groups cutting across service lines and hierarchical levels. By contrast, weak alignment from top to bottom typically also hindered cooperation across departments. Staff commitment to ending homelessness was high, though sustainability planning was limited in this baseline year of observation. CONCLUSION: Key organizational practices correlated with more successful implementation of HF for homeless Veterans. Medical Center directors substantively influenced the success of this endeavor through their actions to foster impetus, demonstrate commitment and support alignment and integration. C1 [Kertesz, Stefan G.; Austin, Erika Laine] Birmingham VA Med Ctr, Birmingham, AL 35233 USA. [Kertesz, Stefan G.; Austin, Erika Laine; Pollio, David E.; Schumacher, Joseph E.] Univ Alabama Birmingham, Birmingham, AL USA. [Holmes, Sally K.; White, Bert] Boston VA Med Ctr, CHOIR, Jamaica Plain, MA USA. [Holmes, Sally K.; Lukas, Andcarol VanDeusen] Boston Univ, Boston, MA 02215 USA. RP Kertesz, SG (reprint author), Birmingham VA Med Ctr, 700 19th St S,REAP Mailstop 151, Birmingham, AL 35233 USA. EM skertesz@uabmc.edu OI Kertesz, Stefan/0000-0001-6101-8421 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development branch [SDR-11233] FX This study was funded by grant SDR-11233 from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development branch. The authors thank the many VA staff who graciously shared their observations and experiences with this research team. The authors also thank Vincent Kane, MSW, National Center on Homelessness Among Veterans, Department of Veterans Affairs, and Keith Harris, PhD, National Director of Clinical Operations, Mental Health Homeless and Residential Rehabilitation Treatment Programs, Department of Veterans Affairs, for their partnership in this study. They also thank N. Kay Johnson, BSN, MPH and Carolyn Ray, JD for their assistance with the study. NR 33 TC 3 Z9 3 U1 11 U2 30 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 DEC PY 2014 VL 29 SU 4 BP S835 EP S844 DI 10.1007/s11606-014-3025-4 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AU1XG UT WOS:000345410200007 PM 25355085 ER PT J AU Kilbourne, AM Atkins, D AF Kilbourne, Amy M. Atkins, David TI Partner or Perish: VA Health Services and the Emerging Bi-Directional Paradigm SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID MEDICAL HOME; VETERANS; CARE C1 [Kilbourne, Amy M.; Atkins, David] US Dept Vet Affairs, VA Hlth Serv Res & Dev Serv, Washington, DC 20420 USA. [Kilbourne, Amy M.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Kilbourne, AM (reprint author), US Dept Vet Affairs, Hlth Serv Res & Dev Serv, 810 Vermont Ave NW, Washington, DC 20420 USA. NR 15 TC 2 Z9 2 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 DEC PY 2014 VL 29 SU 4 BP S817 EP S819 DI 10.1007/s11606-014-3050-3 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AU1XG UT WOS:000345410200003 PM 25355094 ER PT J AU Midboe, AM Elwy, AR Durfee, JM Gifford, AL Yakovchenko, V Martinello, RA Ross, D Czarnogorski, M Goetz, MB Asch, SM AF Midboe, Amanda M. Elwy, A. Rani Durfee, Janet M. Gifford, Allen L. Yakovchenko, Vera Martinello, Richard A. Ross, David Czarnogorski, Maggie Goetz, Matthew B. Asch, Steven M. TI Building Strong Research Partnerships Between Public Health and Researchers: A VA Case Study SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE Partner-based research; Public health; Infectious disease ID HIV; QUERI AB We are in a new era of partner-based implementation research, and we need clear strategies for how to navigate this new era. Drawing on principles from community-based participatory research, the Clinical Public Health group of the Department of Veterans Affairs and the HIV/Hepatitis Quality Enhancement Research Initiative (HHQUERI) forged a longstanding partnership that has improved the care of Veterans with Human immunodeficiency Virus (HIV) and Hepatitis C Virus. An exemplar HIV testing project epitomizes this partnership and is discussed in terms of the lessons learned as a result of our high level of collaboration around design, analysis, implementation, and dissemination across projects over the past several years. Lessons learned through this partnered testing program involve respecting different time horizons among the partners, identifying relevant research questions for both parties, designing flexible studies, engaging all partners throughout the research, and placing an emphasis on relationship building at all times. These lessons and strategies can benefit others conducting partner-based research both within the Veterans Health Administration (VA) and in other integrated healthcare systems. C1 [Midboe, Amanda M.; Asch, Steven M.] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat Ci2i, Menlo Pk, CA 94025 USA. [Elwy, A. Rani; Gifford, Allen L.; Yakovchenko, Vera] Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Care Org & Implementat Res, Bedford, MA USA. [Elwy, A. Rani; Gifford, Allen L.; Yakovchenko, Vera] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Durfee, Janet M.; Martinello, Richard A.; Ross, David; Czarnogorski, Maggie] VA Cent Off Publ Hlth Clin Publ Hlth Grp, Charlottesville, VA USA. [Martinello, Richard A.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Martinello, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [Goetz, Matthew B.] VA Greater Los Angeles Healthcare Syst, Infect Dis Sect, Los Angeles, CA USA. [Goetz, Matthew B.] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Goetz, Matthew B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Asch, Steven M.] Stanford Univ, Div Gen Med Disciplines, Stanford, CA 94305 USA. RP Midboe, AM (reprint author), VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat Ci2i, 795 Willow Rd,152, Menlo Pk, CA 94025 USA. EM amanda.midboe@va.gov OI Goetz, Matthew/0000-0003-4542-992X FU Department of Veterans Affairs, Veterans Health Administration's Quality Enhancement Research Initiative (QUERI) Program FX This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration's Quality Enhancement Research Initiative (QUERI) Program, which has supported the HIV/Hepatitis is QUERI. NR 13 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 DEC PY 2014 VL 29 SU 4 BP S831 EP S834 DI 10.1007/s11606-014-3017-4 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AU1XG UT WOS:000345410200006 PM 25355082 ER PT J AU Nieuwsma, JA Jackson, GL DeKraai, MB Bulling, DJ Cantrell, WC Rhodes, JE Bates, MJ Ethridge, K Lane, ME Tenhula, WN Batten, SV Meador, KG AF Nieuwsma, Jason A. Jackson, George L. DeKraai, Mark B. Bulling, Denise J. Cantrell, William C. Rhodes, Jeffrey E. Bates, Mark J. Ethridge, Keith Lane, Marian E. Tenhula, Wendy N. Batten, Sonja V. Meador, Keith G. TI Collaborating Across the Departments of Veterans Affairs and Defense to Integrate Mental Health and Chaplaincy Services SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE mental health; spirituality; patient centered care. veterans; implementation research ID POSTTRAUMATIC-STRESS-DISORDER; CARE-SYSTEM; UNITED-STATES; BARRIERS; STIGMA; FORGIVENESS; SOLDIERS; COMBAT; PTSD; PERCEPTIONS AB BACKGROUND: Recognizing that clergy and spiritual care providers are a key part of mental health care systems, the Department of Veterans Affairs (VA) and Department of Defense (DoD) jointly examined chaplains' current and potential roles in caring for veterans and service members with mental health needs. OBJECTIVE: Our aim was to evaluate the intersection of chaplain and mental health care practices in VA and DoD in order to determine if improvement is needed, and if so, to develop actionable recommendations as indicated by evaluation findings. DESIGN: A 38-member multidisciplinary task group partnered with researchers in designing, implementing, and interpreting a mixed methods study that included: 1) a quantitative survey of VA and DoD chaplains; and 2) qualitative interviews with mental health providers and chaplains. PARTICIPANTS: Quantitative: the survey included all full-time VA chaplains and all active duty military chaplains (n=2,163 completed of 3,464 invited; 62 % response rate). Qualitative: a total of 291 interviews were conducted with mental health providers and chaplains during site visits to 33 VA and DoD facilities. MAIN MEASURES: Quantitative: the online survey assessed intersections between chaplaincy and mental health care and took an average of 37 mm to complete. Qualitative: the interviews assessed current integration of mental health and chaplain services and took an average of 1 h to complete. KEY RESULTS:When included on interdisciplinary mental health care teams, chaplains feel understood and valued (82.8-100 % of chaplains indicated this, depending on the team). However, findings from the survey and site visits suggest that integration of services is often lacking and can be improved. CONCLUSIONS: Closely coordinating with a multidisciplinary task group in conducting a mixed method evaluation of chaplain-mental health integration in VA and DoD helped to ensure that researchers assessed relevant domains and that findings could be rapidly translated into actionable recommendations. C1 [Nieuwsma, Jason A.; Cantrell, William C.; Meador, Keith G.] Mid Atlantic Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs, Durham, NC USA. [Nieuwsma, Jason A.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Jackson, George L.] Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Jackson, George L.] Duke Univ, Med Ctr, Div Gen Internal Med, Durham, NC USA. [DeKraai, Mark B.; Bulling, Denise J.] Univ Nebraska, Publ Policy Ctr, Lincoln, NE USA. [Cantrell, William C.] US Navy, Chaplain Corps, Marine Forces Reserve, New Orleans, LA USA. [Rhodes, Jeffrey E.; Bates, Mark J.] Def Ctr Excellence Psychol Hlth & Traumat Brain I, Deployment Hlth Clin Ctr, Silver Spring, MD USA. [Ethridge, Keith] Natl Chaplain Ctr, Dept Vet Affairs, Hampton, VA USA. [Lane, Marian E.] RTI Int, Durham, NC USA. [Tenhula, Wendy N.] US Dept Vet Affairs, Mental Hlth Serv, Washington, DC USA. [Batten, Sonja V.] Booz Allen Hamilton, Washington, DC USA. [Meador, Keith G.] Vanderbilt Univ, Ctr Biomed Eth & Soc, Dept Psychiat, Nashville, TN 37235 USA. [Meador, Keith G.] Vanderbilt Univ, Ctr Biomed Eth & Soc, Dept Hlth Policy, Nashville, TN 37235 USA. [Meador, Keith G.] Vanderbilt Univ, Grad Dept Relig, Nashville, TN 37235 USA. RP Nieuwsma, JA (reprint author), VA Mid Atlantic MIRECC, Legacy Towers 800B,411 West Chapel Hill St, Durham, NC 27701 USA. EM jason.nieuwsma@duke.edu FU Department of Veterans Affairs and Department of Defense Integrated Mental Health Strategy (VA/DoD IMHS); VA/DoD Joint Incentive Fund FX Funding support provided by Department of Veterans Affairs and Department of Defense Integrated Mental Health Strategy (VA/DoD IMHS) and the VA/DoD Joint Incentive Fund. NR 46 TC 3 Z9 3 U1 2 U2 4 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 DEC PY 2014 VL 29 SU 4 BP S885 EP S894 DI 10.1007/s11606-014-3032-5 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AU1XG UT WOS:000345410200013 PM 25355089 ER PT J AU Tallaj, JA Pamboukian, SV George, JF Kirklin, JK Brown, RN McGiffin, DC Acharya, D Loyaga-Rendon, R Melby, SJ Bourge, RC Naftel, DC AF Tallaj, Jose A. Pamboukian, Salpy V. George, James F. Kirklin, James K. Brown, Robert N. McGiffin, David C. Acharya, Deepak Loyaga-Rendon, Renzo Melby, Spencer J. Bourge, Robert C. Naftel, David C. TI Have risk factors for mortality after heart transplantation changed over time? Insights from 19 years of Cardiac Transplant Research Database study SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article DE Heart Transplantation; Survival post-transplantation; Left ventricular assist device; Pulmonary hypertension; Heart failure; Immunosuppression; Allograft rejection; Racial disparities ID LUNG TRANSPLANTATION; DEATH; RECIPIENTS; REJECTION; HYPERTENSION; TRIAL AB BACKGROUND: The Cardiac Transplant Research Database (CTRD) collected data from 26 U.S. institutions from January 1, 1990 to December 31, 2008 providing the opportunity for construction of a comprehensive multivariable model of risk for death after transplantation. We analyzed risk factors for death over 19 years of experience to determine how risk profiles have changed over time and how they interact with age. METHODS: A multivariable parametric hazard model for death was created for 7,015 patients entered into the CTRD. Variables collected over 19 years of experience were examined as potential risk factors and tested for interaction with date of transplantation to determine if their relative risk (RR) changed over time. RESULTS: The hazard for death post-transplant occurred in 2 phases: an early phase of acute risk lasting <1 year, and a late phase of relatively low, gradually increasing risk (<0.1 event/year). In the early phase, predictive models showed that ventricular assist device (VAD) at the time of transplant did not increase the RR of death for recipient transplant at 30 years of age, but the RR of death was increased by 60% (p = 0.04) at 60 years of age. Of the late-phase variables found to be risk factors, the RR of age, date of transplant and pulmonary vascular resistance changed with respect to transplant year. The overall risk of death dropped importantly over the study period, but the RR of all other variables remained unchanged. RR was 2.6 (p < 0.0001) for 25-year-old African-American (AA) versus non-AA recipients and 1.6 for 60-year-old AA recipients (p = 0.02). CONCLUSION: Over 19 years, the baseline risk of death has decreased, but the specific risk factors and the magnitudes of their RR have remained unchanged. Therefore, despite advances in clinical management and improvement in overall survival, the risk profile for death after cardiac transplantation is similar to that in 1990. (C) 2014 International Society for Heart and Lung Transplantation. All rights reserved. C1 [Tallaj, Jose A.; Pamboukian, Salpy V.; Acharya, Deepak; Loyaga-Rendon, Renzo; Bourge, Robert C.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Tallaj, Jose A.] Birmingham VA Med Ctr, Dept Med, Birmingham, AL USA. [George, James F.; Kirklin, James K.; Brown, Robert N.; McGiffin, David C.; Melby, Spencer J.; Naftel, David C.] Univ Alabama Birmingham, Dept Surg, Div Cardiothorac Surg, Birmingham, AL 35294 USA. RP Tallaj, JA (reprint author), Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, THT 338,1900 Univ Blvd, Birmingham, AL 35294 USA. EM jtallaj@uab.edu NR 23 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD DEC PY 2014 VL 33 IS 12 BP 1304 EP 1311 DI 10.1016/j.healun.2014.08.014 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA AU3XS UT WOS:000345544600014 PM 25443871 ER PT J AU Martini, RP Ward, J Siler, DA Eastman, JM Nelson, JW Borkar, RN Alkayed, NJ Dogan, A Cetas, JS AF Martini, Ross P. Ward, Jonathan Siler, Dominic A. Eastman, Jamie M. Nelson, Jonathan W. Borkar, Rohan N. Alkayed, Nabil J. Dogan, Aclan Cetas, Justin S. TI Genetic variation in soluble epoxide hydrolase: association with outcome after aneurysmal subarachnoid hemorrhage SO JOURNAL OF NEUROSURGERY LA English DT Article DE soluble epoxide hydrolase; epoxyeicosatrienoic acids; subarachnoid hemorrhage; vascular disorders ID DELAYED CEREBRAL-ISCHEMIA; EPOXYEICOSATRIENOIC ACIDS; STROKE; EPHX2; RISK; POLYMORPHISMS; PREDICTORS; VASOSPASM; PLATELET AB Object. Patients with aneurysmal subarachnoid hemorrhage (SAH) are at high risk for delayed cerebral ischemia (DCI) and stroke. Epoxyeicosatrienoic acids (EETs) play an important role in cerebral blood flow regulation and neuroprotection after brain injury. Polymorphisms in the gene for the enzyme soluble epoxide hydrolase (sEH), which inactivates EETs, are associated with ischemic stroke risk and neuronal survival after ischemia. This prospective observational study of patients with SAH compares vital and neurologic outcomes based on functional polymorphisms of sEH. Methods. Allelic discrimination based on quantitative real-time polymerase chain reaction was used to differentiate wild-type sEH from K55R heterozygotes (predictive of increased sEH activity and reduced EETs) and R287Q heterozygotes (predictive of decreased sEH activity and increased EETs). The primary outcome was new stroke after SAH. Secondary outcomes were death, Glasgow Outcome Scale score, and neurological deterioration attributable to DCI. Results. Multivariable logistic regression models adjusted for age at admission and Glasgow Coma Scale scores revealed an increase in the odds of new stroke (OR 5.48 [95% CI 1.51-19.91]) and death (OR 7.52 [95% CI 1.27- 44.46]) in the K55R group, but no change in the odds of new stroke (OR 0.56 [95% CI 0.16-1.96]) or death (OR 3.09 [95% CI 0.51-18.52]) in patients with R287Q genotype, compared with wild-type sEH. The R287Q genotype was associated with reduced odds of having a Glasgow Outcome Scale score of <= 3 (OR 0.23 [95% CI 0.06-0.82]). There were no significant differences in the odds of neurological deterioration due to DCI. Conclusions. Genetic polymorphisms of sEH are associated with neurological and vital outcomes after aneurysmal SAH. C1 [Martini, Ross P.; Ward, Jonathan; Siler, Dominic A.; Eastman, Jamie M.; Nelson, Jonathan W.; Borkar, Rohan N.; Alkayed, Nabil J.] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. [Dogan, Aclan; Cetas, Justin S.] Oregon Hlth & Sci Univ, Dept Neurol Surg, Portland, OR 97239 USA. [Cetas, Justin S.] Portland VA Med Ctr, Portland, OR USA. RP Cetas, JS (reprint author), Oregon Hlth & Sci Univ, Dept Neurol Surg, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM cetasj@ohsu.edu OI Robertson, Jamie/0000-0001-8252-6644 FU Brain Aneurysm Foundation FX This study was supported by a grant from the Brain Aneurysm Foundation (Dr. Cetas). NR 33 TC 2 Z9 2 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 EI 1933-0693 J9 J NEUROSURG JI J. Neurosurg. PD DEC PY 2014 VL 121 IS 6 BP 1359 EP 1366 DI 10.3171/2014.7.JNS131990 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AU3CP UT WOS:000345490700011 PM 25216066 ER PT J AU Boyers, LN Karimkhani, C Naghavi, M Sherwood, D Margolis, DJ Hay, RJ Williams, HC Naldi, L Coffeng, LE Weinstock, MA Dunnick, CA Pederson, H Vos, T Dellavalle, RP AF Boyers, Lindsay N. Karimkhani, Chante Naghavi, Mohsen Sherwood, David Margolis, David J. Hay, Roderick J. Williams, Hywel C. Naldi, Luigi Coffeng, Luc E. Weinstock, Martin A. Dunnick, Cory A. Pederson, Hannah Vos, Theo Dellavalle, Robert P. TI Global mortality from conditions with skin manifestations SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE basal cell carcinoma; burden of disease; dermatology; developed countries; developing countries; epidemiology; Global Burden of Disease Study 2010; measles; melanoma; mortality; non-melanoma; skin cancer; rate of death; squamous cell carcinoma; syphilis ID SYSTEMATIC ANALYSIS; 187 COUNTRIES; RISK-FACTORS; CUTANEOUS MELANOMA; UNITED-STATES; GBD 2010; BURDEN; DISEASE; PREVALENCE; CHALLENGES AB Background: Global Burden of Disease Study is a research database containing systematically compiled information from vital statistics and epidemiologic literature to inform research, public policy, and resource allocation. Objective: We sought to compare mortality among conditions with skin manifestations in 50 developed and 137 developing countries from 1990 to 2010. Methods: This was a cross-sectional study to calculate mean age-standardized mortality (per 100,000 persons) across countries for 10 disease categories with skin manifestations. We compared differences in mortality from these disorders by time period (year 1990 vs year 2010) and by developing versus developed country status. Results: Melanoma death rates were 5.6 and 4.7 times greater in developed compared with developing countries in 1990 and 2010, respectively. Measles death rates in 1990 and 2010 were 345 and 197 times greater in developing countries, and corresponding syphilis death rates were 33 and 45 times greater. Limitations: Inability to adjust for patient-, provider-, and geographic-level confounders may limit the accuracy and generalizability of these results. Conclusion: The mortality burden from skin-related conditions differs between developing and developed countries, with the greatest differences observed for melanoma, measles, and syphilis. These results may help prioritize and optimize efforts to prevent and treat these disorders. C1 [Boyers, Lindsay N.] Georgetown Univ, Sch Med, Washington, DC USA. [Karimkhani, Chante] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Naghavi, Mohsen; Coffeng, Luc E.; Vos, Theo] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA. [Sherwood, David] Univ Colorado, Dept Integrat Physiol, Boulder, CO 80309 USA. [Margolis, David J.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol & Dermatol, Philadelphia, PA 19104 USA. [Hay, Roderick J.] Kings Coll Hosp Natl Hlth Serv Trust, Dept Dermatol, London, England. [Williams, Hywel C.] Univ Nottingham, Ctr Evidence Based Dermatol, Nottingham NG7 2RD, England. [Naldi, Luigi] Azienda Osped Papa Giovanni XXIII, Dept Dermatol, Bergamo, Italy. [Weinstock, Martin A.] US Dept Vet Affairs, Med Ctr Providence, Dermatoepidemiol Unit, Washington, DC USA. [Weinstock, Martin A.] Rhode Isl Hosp, Dept Dermatol, Providence, RI 02903 USA. [Weinstock, Martin A.] Brown Univ, Dept Dermatol, Providence, RI 02912 USA. [Weinstock, Martin A.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. [Dunnick, Cory A.; Dellavalle, Robert P.] Univ Colorado, Dept Dermatol, Aurora, CO USA. [Dunnick, Cory A.; Dellavalle, Robert P.] Eastern Colorado Hlth Care Syst, US Dept Vet Affairs, Dermatol Serv, Denver, CO USA. [Pederson, Hannah] Univ Colorado, Sch Med, Aurora, CO USA. [Dellavalle, Robert P.] Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA. RP Dellavalle, RP (reprint author), US Dept Vet Affairs, Med Ctr, Dermatol Serv, 1055 Clermont St,Box 165, Denver, CO 80220 USA. EM robert.dellavalle@ucdenver.edu RI Naldi, Luigi/K-6343-2016 OI Naldi, Luigi/0000-0002-3160-2835 FU Bill and Melinda Gates Foundation [OPP43650_01] FX The Global Burden of Disease Study 2010 was supported in part by the Bill and Melinda Gates Foundation (grant number: OPP43650_01). NR 45 TC 7 Z9 9 U1 3 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD DEC PY 2014 VL 71 IS 6 BP 1137 EP U168 DI 10.1016/j.jaad.2014.08.022 PG 24 WC Dermatology SC Dermatology GA AT9FD UT WOS:000345232400023 PM 25282129 ER PT J AU Mayer, VL Hillier, A Bachhuber, MA Long, JA AF Mayer, Victoria L. Hillier, Amy Bachhuber, Marcus A. Long, Judith A. TI Food Insecurity, Neighborhood Food Access, and Food Assistance in Philadelphia SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article DE Environment and public health; Nutrition policy; Hunger; Food assistance ID PHYSICAL-ACTIVITY; GLYCEMIC CONTROL; HEALTHY FOODS; STAMPS; US AB An estimated 17.6 million American households were food insecure in 2012, meaning they were unable to obtain enough food for an active and healthy life. Programs to augment local access to healthy foods are increasingly widespread, with unclear effects on food security. At the same time, the US government has recently enacted major cuts to federal food assistance programs. In this study, we examined the association between food insecurity (skipping or reducing meal size because of budget), neighborhood food access (self-reported access to fruits and vegetables and quality of grocery stores), and receipt of food assistance using the 2008, 2010, and 2012 waves of the Southeastern Pennsylvania Household Health Survey. Of 11,599 respondents, 16.7 % reported food insecurity; 79.4 % of the food insecure found it easy or very easy to find fruits and vegetables, and 60.6 % reported excellent or good quality neighborhood grocery stores. In our regression models adjusting for individual- and neighborhood-level covariates, compared to those who reported very difficult access to fruits and vegetables, those who reported difficult, easy or very easy access were less likely to report food insecurity (OR 0.62: 95 % CI 0.43-0.90, 0.33: 95 % CI 0.23-0.47, and 0.28: 95 % CI 0.20-0.40). Compared to those who reported poor stores, those who reported fair, good, and excellent quality stores were also less likely to report food insecurity (OR 0.81: 95 % CI 0.60-1.08, 0.58: 95 % CI 0.43-0.78, and 0.43: 95 % CI 0.31-0.59). Compared to individuals not receiving food assistance, those receiving Supplemental Nutrition Assistance Program (SNAP) benefits were significantly more likely to be food insecure (OR 1.36: 95 % CI 1.11-1.67), while those receiving benefits from the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) (OR 1.17: 95 % CI 0.77-1.78) and those receiving both SNAP and WIC (OR 0.84: 95 % CI 0.61-1.17) did not have significantly different odds of food insecurity. In conclusion, better neighborhood food access is associated with lower risk of food insecurity. However, most food insecure individuals reported good access. Improving diet in communities with high rates of food insecurity likely requires not only improved access but also greater affordability. C1 [Mayer, Victoria L.; Long, Judith A.] Univ Penn, Div Gen Internal Med, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Mayer, Victoria L.; Bachhuber, Marcus A.; Long, Judith A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Hillier, Amy] Univ Penn, Dept City & Reg Planning, Sch Design, Philadelphia, PA 19104 USA. [Bachhuber, Marcus A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Bachhuber, Marcus A.] Univ Penn, Robert Wood Johnson Fdn, Clin Scholars Program, Philadelphia, PA 19104 USA. RP Mayer, VL (reprint author), Univ Penn, Div Gen Internal Med, Dept Med, Perelman Sch Med, 1205 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM vmayer@mail.med.upenn.edu OI Bachhuber, Marcus/0000-0002-5610-8382 FU Division of General Internal Medicine Matt Slap Award from the Perelman School of Medicine at the University of Pennsylvania; National Institutes of Health Institutional Training Grant [5-T32-HP-100296-20-00] FX The authors would like to thank Christopher Wirtalla for assistance with developing Stata programming. V.L.M. was supported with funding from the Division of General Internal Medicine Matt Slap Award from the Perelman School of Medicine at the University of Pennsylvania and the National Institutes of Health Institutional Training Grant 5-T32-HP-100296-20-00. NR 28 TC 8 Z9 8 U1 4 U2 29 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1099-3460 EI 1468-2869 J9 J URBAN HEALTH JI J. Urban Health PD DEC PY 2014 VL 91 IS 6 BP 1087 EP 1097 DI 10.1007/s11524-014-9887-2 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA AU1RA UT WOS:000345396700005 PM 25047157 ER PT J AU Gowda, C Compher, C Amorosa, VK Lo Re, V AF Gowda, C. Compher, C. Amorosa, V. K. Lo Re, V., III TI Association between chronic hepatitis C virus infection and low muscle mass in US adults SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE chronic hepatitis C; low muscle mass; malnutrition; NHANES ID HUMAN-IMMUNODEFICIENCY-VIRUS; NUTRITIONAL-STATUS; HIV-INFECTION; LIVER-CIRRHOSIS; BODY-COMPOSITION; PRIMARY-CARE; WEIGHT-LOSS; MALNUTRITION; DISEASE; TUBERCULOSIS AB Given that low muscle mass can lead to worse health outcomes in patients with chronic infections, we assessed whether chronic hepatitis C virus (HCV) infection was associated with low muscle mass among US adults. We performed a cross-sectional study of the National Health Examination and Nutrition Study (1999-2010). Chronic HCV-infected patients had detectable HCV RNA. Low muscle mass was defined as <10th percentile for mid-upper arm circumference (MUAC). Multivariable logistic regression was used to determine adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of low muscle mass associated with chronic HCV. Among 18513 adults, chronic HCV-infected patients (n=303) had a higher prevalence of low muscle mass than uninfected persons (13.8% vs 6.7%; aOR, 2.22; 95% CI, 1.39-3.56), and this association remained when analyses were repeated among persons without significant liver fibrosis (aOR, 2.12; 95% CI, 1.30-3.47). This study demonstrates that chronic HCV infection is associated with low muscle mass, as assessed by MUAC measurements, even in the absence of advanced liver disease. C1 [Gowda, C.; Amorosa, V. K.; Lo Re, V., III] Univ Penn, Perelman Sch Med, Div Infect Dis, Dept Med, Philadelphia, PA 19104 USA. [Gowda, C.; Lo Re, V., III] Univ Penn, Perelman Sch Med, Dept Biostatist & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Compher, C.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Amorosa, V. K.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Gowda, C (reprint author), Univ Penn, Div Infect Dis, 3400 Spruce St,Ste D, Philadelphia, PA 19104 USA. EM gowdac@uphs.upenn.edu RI Lo Re, Vincent/N-7817-2015 FU National Institutes of Health [T32-AI-055435, K01-AI070001] FX This work was supported by the National Institutes of Health research Grants T32-AI-055435 (to C.G.) and K01-AI070001 (to V.L.R.). NR 38 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1352-0504 EI 1365-2893 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD DEC PY 2014 VL 21 IS 12 BP 938 EP 943 DI 10.1111/jvh.12273 PG 6 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA AU1YP UT WOS:000345413700018 PM 24989435 ER PT J AU Sylling, PW Wong, ES Liu, CF Hernandez, SE Batten, AJ Helfrich, CD Nelson, K Fihn, SD Hebert, PL AF Sylling, Philip W. Wong, Edwin S. Liu, Chuan-Fen Hernandez, Susan E. Batten, Adam J. Helfrich, Christian D. Nelson, Karin Fihn, Stephan D. Hebert, Paul L. TI Patient-Centered Medical Home Implementation and Primary Care Provider Turnover SO MEDICAL CARE LA English DT Article DE primary care provider; turnover; patient-centered medical home; Veterans Health Administration ID PHYSICIAN TURNOVER; EMPLOYEE TURNOVER; JOB-SATISFACTION; PREDICTORS; COMMITMENT; BEHAVIOR; LESSONS; BURNOUT; MODELS; COSTS AB Background: The Veterans Health Administration (VHA) began implementing a patient-centered medical home (PCMH) model of care delivery in April 2010 through its Patient Aligned Care Team (PACT) initiative. PACT represents a substantial system reengineering of VHA primary care and its potential effect on primary care provider (PCP) turnover is an important but unexplored relationship. This study examined the association between a system-wide PCMH implementation and PCP turnover. Methods: This was a retrospective, longitudinal study of VHA-employed PCPs spanning 29 calendar quarters before PACT and eight quarters of PACT implementation. PCP employment periods were identified from administrative data and turnover was defined by an indicator on the last quarter of each uncensored period. An interrupted time series model was used to estimate the association between PACT and turnover, adjusting for secular trend and seasonality, provider and job characteristics, and local unemployment. We calculated average marginal effects (AME), which reflected the change in turnover probability associated with PACT implementation. Results: The quarterly rate of PCP turnover was 3.06% before PACT and 3.38% after initiation of PACT. In adjusted analysis, PACT was associated with a modest increase in turnover (AME = 4.0 additional PCPs per 1000 PCPs per quarter, P = 0.004). Models with interaction terms suggested that the PACT-related change in turnover was increasing in provider age and experience. Conclusions: PACT was associated with a modest increase in PCP turnover, concentrated among older and more experienced providers, during initial implementation. Our findings suggest that policymakers should evaluate potential workforce effects when implementing PCMH. C1 [Sylling, Philip W.; Wong, Edwin S.; Liu, Chuan-Fen; Hernandez, Susan E.; Batten, Adam J.; Helfrich, Christian D.; Nelson, Karin; Hebert, Paul L.] VA Puget Sound Healthcare Syst, Northwest HSR&D Ctr Innovat, Seattle, WA 98101 USA. [Wong, Edwin S.; Liu, Chuan-Fen; Hernandez, Susan E.; Helfrich, Christian D.; Fihn, Stephan D.; Hebert, Paul L.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Nelson, Karin; Fihn, Stephan D.] VA Puget Sound Healthcare Syst, Gen Internal Med Serv, Seattle, WA 98101 USA. [Nelson, Karin; Fihn, Stephan D.] Univ Washington, Dept Med, Sch Med, Seattle, WA 98195 USA. [Fihn, Stephan D.] VA Puget Sound Healthcare Syst, VHA Off Analyt & Business Intelligence, Seattle, WA 98101 USA. RP Sylling, PW (reprint author), VA Puget Sound Healthcare Syst, Northwest HSR&D Ctr Innovat, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM philip.sylling@va.gov FU Veterans Health Administration Patient Centered Medical Home Demonstration Laboratory Coordination Center [XVA-61-041] FX Supported by the Veterans Health Administration Patient Centered Medical Home Demonstration Laboratory Coordination Center (XVA-61-041). NR 30 TC 4 Z9 4 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD DEC PY 2014 VL 52 IS 12 BP 1017 EP 1022 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AU0DP UT WOS:000345294100003 PM 25271536 ER PT J AU Hwang, U Belland, LK Handel, DA Yadav, K Heard, K Rivera-Reyes, L Eisenberg, A Noble, MJ Mekala, S Valley, M Winkel, G Todd, KH Morrison, RS AF Hwang, Ula Belland, Laura K. Handel, Daniel A. Yadav, Kabir Heard, Kennon Rivera-Reyes, Laura Eisenberg, Amanda Noble, Matthew J. Mekala, Sudha Valley, Morgan Winkel, Gary Todd, Knox H. Morrison, R. Sean TI Is all pain is treated equally? A multicenter evaluation of acute pain care by age SO PAIN LA English DT Article DE Acute pain care; Emergency department; Geriatrics ID EMERGENCY-DEPARTMENT ANALGESIA; DISPARITIES; ETHNICITY; MEDICINE; QUALITY AB Pain is highly prevalent in health care settings; however, disparities continue to exist in pain care treatment. Few studies have investigated if differences exist based on patient-related characteristics associated with aging. The objective of this study was to determine if there are differences in acute pain care for older vs younger patients. This was a multicenter, retrospective, cross-sectional observation study of 5 emergency departments across the United States evaluating the 2 most commonly presenting pain conditions for older adults, abdominal and fracture pain. Multivariable adjusted hierarchical modeling was completed. A total of 6,948 visits were reviewed. Older (>= 65 years) and oldest (>= 85 years) were less likely to receive analgesics compared to younger patients (<65 years), yet older patients had greater reductions in final pain scores. When evaluating pain treatment and final pain scores, differences appeared to be based on type of pain. Older patients with abdominal pain were less likely to receive pain medications, while older patients with fracture were more likely to receive analgesics and opioids compared to younger patients. Differences in pain care for older patients appear to be driven by the type of presenting pain. Published by Elsevier B.V. on behalf of International Association for the Study of Pain. C1 [Hwang, Ula; Belland, Laura K.; Rivera-Reyes, Laura] Icahn Sch Med Mt Sinai, Dept Emergency Med, New York, NY 10029 USA. [Hwang, Ula; Morrison, R. Sean] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Hwang, Ula; Morrison, R. Sean] James J Peters VAMC, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Handel, Daniel A.] Med Univ S Carolina, Charleston, SC 29425 USA. [Handel, Daniel A.; Noble, Matthew J.; Mekala, Sudha] Oregon Hlth & Sci Univ, Dept Emergency Med, Portland, SC USA. [Yadav, Kabir; Eisenberg, Amanda] George Washington Univ, Med Ctr, Dept Emergency Med, Washington, DC 20037 USA. [Heard, Kennon; Valley, Morgan] Univ Colorado, Dept Emergency Med, Aurora, CO USA. [Winkel, Gary] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Todd, Knox H.] Univ Texas MD Anderson Canc Ctr, Dept Emergency Med, Houston, TX 77030 USA. RP Hwang, U (reprint author), Dept Emergency Med, One Gustave L Levy Pl,Box 1062, New York, NY 10029 USA. EM ula.hwang@mountsinai.org OI Yadav, Kabir/0000-0002-1092-9935 FU National Institute on Aging [K23 AG031218, K24 AG022345] FX UH was supported by a K23 award from the National Institute on Aging (K23 AG031218), and RSM by a K24 from the National Institute on Aging (K24 AG022345). NR 26 TC 8 Z9 8 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD DEC PY 2014 VL 155 IS 12 BP 2568 EP 2574 DI 10.1016/j.pain.2014.09.017 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA AU1YZ UT WOS:000345414700019 PM 25244947 ER PT J AU Starkstein, SE Dragovic, M Dujardin, K Marsh, L Martinez-Martin, P Pontone, GM Richard, IH Weintraub, D Leentjens, AFG AF Starkstein, Sergio E. Dragovic, Milan Dujardin, Kathy Marsh, Laura Martinez-Martin, Pablo Pontone, Gregory M. Richard, Irene H. Weintraub, Daniel Leentjens, Albert F. G. TI Anxiety Has Specific Syndromal Profiles in Parkinson Disease: A Data-Driven Approach SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Parkinson disease; anxiety; depression; diagnosis; phenomenology ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; PSYCHOMETRIC PROPERTIES; RATING-SCALES; DSM-IV; DISORDERS; DEPRESSION; MINI; COMORBIDITY; PREVALENCE; VALIDATION AB Background: Anxiety symptoms are common in Parkinson disease (PD). Recent evidence suggests that anxiety syndromes as encountered in clinical practice may not correspond to the DSM-IV classification of anxiety disorders. Objective: To examine the syndromal pattern of the anxiety spectrum in a large series of patients with PD, as determined with a data-driven approach using latent class analysis (LCA). Methods: 342 patients with PD were recruited from referrals to movement disorders or psychiatry clinics at six tertiary centers. Participants were assessed with a structured psychiatric interview and specific scales rating the severity of anxiety, depression, cognition and parkinsonism. The main outcome measure was classes of patients with a specific syndromal profile of anxiety symptoms based on LCA. Results: LCA identified four classes that were interpreted as "no anxiety or depression", "episodic anxiety without depression", "persistent anxiety with depression", and "both persistent and episodic anxiety with depression". Symptoms of persistent anxiety were almost invariably associated with symptoms of depression. There were significant differences between classes in terms of history of depression and anxiety, use of psychoactive medication, and on the Mentation and Complications sections of the Unified Parkinson Disease Rating Scale. Conclusions: Patients with PD show different syndromic profiles of anxiety that do not align with the symptom profiles represented by DSM-IV anxiety disorders and major depression. Accordingly, DSM-IV criteria for anxiety disorders may not be clinically useful in PD. The different classes identified here provide empirically validated phenotypes for future research. C1 [Starkstein, Sergio E.; Dragovic, Milan] Univ Western Australia, Sch Psychiat & Clin Neurosci, Fremantle, WA, Australia. [Starkstein, Sergio E.; Dragovic, Milan] Fremantle Hosp, Fremantle, WA 6959, Australia. [Dujardin, Kathy] Univ Lille 2, Lab Neurosci Fonct & Pathol, Lille, France. [Marsh, Laura] Mental Hlth Care Line, Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA. [Marsh, Laura] Baylor Coll Med, Menninger Dept Psychiat, Houston, TX 77030 USA. [Martinez-Martin, Pablo] Alzheimer Ctr Reina Sofia Fdn, Madrid, Spain. [Martinez-Martin, Pablo] Carlos III Inst Hlth, Consortium Biomed Res Neurodegenerat Dis CIBERNED, Madrid, Spain. [Pontone, Gregory M.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Richard, Irene H.] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. [Richard, Irene H.] Univ Rochester, Sch Med & Dent, Dept Psychiat, Rochester, NY 14642 USA. [Weintraub, Daniel] Univ Penn, Pereleman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia VA Med Ctr, Parkinson Dis & Mental Illness Clin Res & Educ Ct, Philadelphia, PA USA. [Leentjens, Albert F. G.] Maastricht Univ, Med Ctr, Dept Psychiat, Maastricht, Netherlands. RP Starkstein, SE (reprint author), Fremantle Hosp, Educ Bldg T-7, Fremantle, WA 6959, Australia. EM sergio.starkstein@uwa.edu.au NR 25 TC 9 Z9 9 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD DEC PY 2014 VL 22 IS 12 BP 1410 EP 1417 DI 10.1016/j.jagp.2013.09.006 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AT7LO UT WOS:000345118500005 PM 24200594 ER PT J AU Lin, F Roiland, R Polesskaya, O Chapman, B Johnson, M Brasch, J Chen, DG Mapstone, M AF Lin, Feng Roiland, Rachel Polesskaya, Oksana Chapman, Benjamin Johnson, Melissa Brasch, Judith Chen, Ding-Geng Mapstone, Mark TI Fatigability Disrupts Cognitive Processes' Regulation of Inflammatory Reactivity in Old Age SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Fatigability; aging; attention; speed of processing; executive function; interleukin-6 reactivity ID ACUTE PSYCHOLOGICAL STRESS; SOCIOECONOMIC-STATUS; ASSESS FATIGUE; INTERLEUKIN-6; ADULTS; RESPONSES; BRAIN; METAANALYSIS; CYTOKINES; MARKERS AB Objective: High fatigability, a dysfunctional adaption to fatigue, may lead to difficulties performing otherwise regularly encountered cognitive activities and may be related to pro-inflammatory reactivity. The purpose of the study was to investigate the effect of fatigability on cognitive processes and inflammatory response after an acute cognitive stress task in older adults. Methods: In an observational stress reactivity study conducted in a light-and temperature-controlled laboratory, we measured IL-6, self-reported acute fatigue, and frontally oriented cognitive processes in 55 community-dwelling individuals aged 75 years or older as part of a demanding set of cognitive tasks intended to induce stress. Results: Subjects were classified into groups of low and high fatigability based on cluster analysis of their self-report acute fatigue before and after the cognitive tasks. The two clusters were comparable on levels of baseline IL-6 and cognitive processes; however, the high fatigability cluster had significantly higher levels of IL-6 response than the low fatigability cluster. After controlling for multiple covariates, fatigability moderated the relationship between speed of processing and IL-6 reactivity. Further exploratory analyses indicated significant adverse associations between speed of processing and attention and IL-6 reactivity in the group with low but not high fatigability. Conclusion: Although observational, these data are consistent with the notion that pro-inflammatory states in older adults might be reduced by improvements in cognitive processes. Because fatigability was associated with increased acute inflammatory response and disrupted the normal stress regulation provided by the cognitive processes, future randomized studies might examine whether fatigability alleviation reduces IL-6. C1 [Lin, Feng; Polesskaya, Oksana; Johnson, Melissa; Brasch, Judith; Chen, Ding-Geng] Univ Rochester, Sch Nursing, Rochester, NY 14414 USA. [Lin, Feng; Chapman, Benjamin] Univ Rochester, Sch Med & Dent, Dept Psychiat, Rochester, NY 14414 USA. [Polesskaya, Oksana] Univ Rochester, Sch Med & Dent, Dept Microbiol & Immunol, Rochester, NY 14414 USA. [Chen, Ding-Geng] Univ Rochester, Sch Med & Dent, Dept Biostat & Computat Biol, Rochester, NY 14414 USA. [Mapstone, Mark] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14414 USA. [Roiland, Rachel] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Lin, F (reprint author), Univ Rochester, Med Ctr, HWH 2w128,601 Elmwood Ave, Rochester, NY 14414 USA. EM vankee_lin@urmc.rochester.edu FU University of Rochester CTSA award from the National Center for Advancing Translational Sciences of the National Institutes of Health [KL2 TR000095]; [K08AG031328]; [R01AG044588] FX Data collection of the present project was supported by Sigma Theta Tau International Small Grants (to FL). The manuscript preparation of the project was supported by the University of Rochester CTSA award number KL2 TR000095 from the National Center for Advancing Translational Sciences of the National Institutes of Health (to FL) and K08AG031328 and R01AG044588 (to BC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the U.S. government, or the Department of Veterans Affairs. NR 52 TC 0 Z9 0 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD DEC PY 2014 VL 22 IS 12 BP 1544 EP 1554 DI 10.1016/j.jagp.2013.12.003 PG 11 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AT7LO UT WOS:000345118500020 PM 24388221 ER PT J AU Hoang, TD Byers, AL Barnes, DE Yaffe, K AF Hoang, Tina D. Byers, Amy L. Barnes, Deborah E. Yaffe, Kristine TI Alcohol Consumption Patterns and Cognitive Impairment in Older Women SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Cognitive impairment; dementia; alcohol ID DRINKING PATTERNS; LATE-LIFE; ADULTS; RISK; DEMENTIA AB Objective: Few studies have investigated changes in alcohol consumption and risk of cognitive impairment among oldest old adults. Methods: In a prospective study of 1309 women >= 65 years old, alcohol use was assessed at repeated visits and used to estimate average change in alcohol consumption over 16 years. Clinically significant cognitive impairment (mild cognitive impairment and dementia) was assessed at year 20. Results: Compared with the reference group (slight decrease in alcohol consumption by 0-0.5 drinks/week, 60.4%), increasing consumption over time (>0 drinks/week) was not associated with risk of cognitive impairment (5.0%, odds ratio [OR]: 1.00, 95% confidence interval [CI]: 0.54-1.85). Decreasing consumption by >0.5 drinks/week was associated with increased risk (34.5%, OR: 1.34, 95% CI: 1.05-1.70). Adjustment for age, education, diabetes, smoking, BMI, and physical activity attenuated the magnitude of the effect slightly and resulted in borderline statistical significance. Conclusion: Women in their ninth and tenth decade of life who decrease alcohol use may be at risk of cognitive impairment. C1 [Hoang, Tina D.] Northern Calif Inst Res & Educ, San Francisco, CA USA. [Byers, Amy L.; Barnes, Deborah E.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Hoang, TD (reprint author), 4150 Clement St,VAMC 116-H, San Francisco, CA 94121 USA. EM tina.hoang@va.gov FU National Institutes of Health funding; National Institute on Aging (NIA) [R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576, R01 AG026720]; NIA [AG026720, K24 AG031155]; Independent Investigator Award from the Alzheimer's Association; National Institute on Aging [R01 AG026720]; National Institute of Mental Health [R01 MH086498]; National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK069406]; Department of Defense; Department of Veterans Affairs; BrightFocus Foundation; National Institutes of Health; Department of Defense grant [W81XWH-11-2-0189]; National Institute on Minority Health and Health Disparities grant [R01 MD007019]; Department of Veterans Affairs Mental Illness Research, Educational, and Clinical Center; National Institutes of Health [R01 AG045043]; Department of Defense [W81XWH-11-2-0189]; Brain and Behavior Research Foundation; Department of Veterans Affairs [REA 01-097, 1IO1HX000694]; UCB Pharma; S.D. Bechtel, Jr., Foundation; philanthropic fund of the Osher Center for Integrative Medicine FX The Study of Osteoporotic Fractures (SOF) is supported by National Institutes of Health funding. The National Institute on Aging (NIA) provides support under the following grant numbers: R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576, and R01 AG026720. In addition, this study was supported by NIA AG026720.; Dr. Kristine Yaffe is supported in part by NIA grant K24 AG031155 and an Independent Investigator Award from the Alzheimer's Association. She has also received grants from National Institute on Aging R01 AG026720, the National Institute of Mental Health R01 MH086498, National Institute of Diabetes and Digestive and Kidney Diseases R01 DK069406, Department of Defense, Department of Veterans Affairs, and the BrightFocus Foundation. She serves on data safety monitoring boards for Takeda, Inc., and a study sponsored by the National Institutes of Health and has served as a consultant for Novartis, Inc., and Pfizer.; Dr. Byers is supported by a Department of Defense grant (W81XWH-11-2-0189) and a National Institute on Minority Health and Health Disparities grant (R01 MD007019), which are administered by the Northern California Institute for Research and Education and with resources of the San Francisco Veterans Affairs Medical Center. In addition, she is supported in part by the Department of Veterans Affairs Mental Illness Research, Educational, and Clinical Center.; Dr. Barnes is supported in part by research grants from the National Institutes of Health R01 AG045043 Department of Defense (W81XWH-11-2-0189), Brain and Behavior Research Foundation (formerly NARSAD), Department of Veterans Affairs (REA 01-097, 1IO1HX000694), UCB Pharma, the S.D. Bechtel, Jr., Foundation, and the philanthropic fund of the Osher Center for Integrative Medicine. NR 18 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD DEC PY 2014 VL 22 IS 12 BP 1663 EP 1667 DI 10.1016/j.jagp.2014.04.006 PG 5 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AT7LO UT WOS:000345118500032 PM 24862680 ER PT J AU Winston, DJ Limaye, AP Pelletier, S Safdar, N Morris, MI Meneses, K Busuttil, RW Singh, N AF Winston, D. J. Limaye, A. P. Pelletier, S. Safdar, N. Morris, M. I. Meneses, K. Busuttil, R. W. Singh, N. TI Randomized, Double-Blind Trial of Anidulafungin Versus Fluconazole for Prophylaxis of Invasive Fungal Infections in High-Risk Liver Transplant Recipients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Clinical research; practice; fungal; infection and infectious agents; infectious disease ID AMPHOTERICIN-B; ANTIFUNGAL PROPHYLAXIS; CELL TRANSPLANTATION; OPEN-LABEL; MICAFUNGIN; CANDIDA; ASPERGILLOSIS; PREVENTION; ECHINOCANDIN; ITRACONAZOLE AB Invasive fungal infections (IFIs) are a common complication in liver transplant recipients. There are no previous randomized trials of an echinocandin for the prevention of IFIs in solid organ transplant recipients. In a randomized, double-blind trial conducted at University-affiliated transplant centers, 200 high-risk liver transplant recipients (100 patients per group) received either anidulafungin or fluconazole for antifungal prophylaxis. Randomization was stratified by Model for End-Stage Liver Disease score 30 and receipt of a pretransplant antifungal agent. The primary end point was IFI in a modified intent-to-treat analysis. The overall incidence of IFI was similar for the anidulafungin (5.1%) and the fluconazole groups (8.0%) (OR 0.61, 95% CI 0.19-1.94, p=0.40). However, anidulafungin prophylaxis was associated with less Aspergillus colonization or infection (3% vs. 9%, p=0.08), lower breakthrough IFIs among patients who had received pretransplant fluconazole (0% vs. 27%, p=0.07), and fewer cases of antifungal resistance (no cases vs. 5 cases). Both drugs were well-tolerated. Graft rejection, fungal-free survival, and mortality were similar for both groups. Thus, anidulafungin and fluconazole have similar efficacy for antifungal prophylaxis in most liver transplant recipients. Anidulafungin may be beneficial if the patient has an increased risk for Aspergillus infection or received fluconazole before transplantation. This randomized, double-blind trial shows that anidulafungin and fluconazole have similar efficacy for antifungal prophylaxis in most liver transplant recipients at high risk for invasive fungal infections, although anidulafungin may be beneficial for patients who have an increased risk for Aspergillus infection or received fluconazole before transplantation. See editorial by Huprikar on page . C1 [Winston, D. J.; Meneses, K.; Busuttil, R. W.] Univ Calif Los Angeles, Med Ctr, Dept Surg, Los Angeles, CA 90024 USA. [Limaye, A. P.] Univ Washington, Dept Med, Seattle, WA USA. [Pelletier, S.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Safdar, N.] Univ Wisconsin, Dept Med, Madison, WI USA. [Morris, M. I.] Univ Miami, Dept Med, Miami, FL USA. [Singh, N.] VA Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA 15261 USA. [Singh, N.] Univ Pittsburgh, Pittsburgh, PA USA. RP Singh, N (reprint author), VA Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA 15261 USA. EM nis5@pitt.edu FU Pfizer, Inc. [GA8851MQ] FX We thank Marilyn Wagener, MPH, for statistical analyses. We are also grateful to the transplant physicians and nurses for their assistance and care of the patients during the study. The study was supported by an Investigator-Initiated Research Grant from Pfizer, Inc. (GA8851MQ). The sponsor had no role in the design and conduct of the study, data collection, analysis and interpretation of the data orpreparation of the manuscript. The study was registered at ClinicalTrials.gov #NCT00841971. NR 33 TC 14 Z9 14 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD DEC PY 2014 VL 14 IS 12 BP 2758 EP 2764 DI 10.1111/ajt.12963 PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA AU0DR UT WOS:000345294300013 PM 25376267 ER PT J AU Singh, JA Lu, X Rosenthal, GE Ibrahim, S Cram, P AF Singh, Jasvinder A. Lu, Xin Rosenthal, Gary E. Ibrahim, Said Cram, Peter TI Racial disparities in knee and hip total joint arthroplasty: an 18-year analysis of national medicare data SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID CARDIAC RISK-ASSESSMENT; SURGEON PROCEDURE VOLUME; ETHNIC DISPARITIES; AFRICAN-AMERICANS; UNITED-STATES; OSTEOARTHRITIS PHENOTYPES; REPLACEMENT SURGERY; ADMINISTRATIVE DATA; NONCARDIAC SURGERY; EUROPEAN-SOCIETY AB Objective To examine whether racial disparities in usage and outcomes of total knee and total hip arthroplasty (TKA and THA) have declined over time. Methods We used data from the US Medicare Program (MedPAR data) for years 1991-2008 to identify four separate cohorts of patients (primary TKA, revision TKA, primary THA, revision THA). For each cohort, we calculated standardised arthroplasty usage rates for Caucasian and African-American Medicare beneficiaries for each calendar year, and examined changes in disparities over time. We examined unadjusted and adjusted outcomes (30-day readmission rate, discharge disposition etc.) for Caucasians and African-Americans, and whether disparities decreased over time. Results In 1991, the use of primary TKA was 36% lower for African-Americans compared with Caucasians (20.6 per 10 000 for African-Americans; 32.1 per 10 000 for Caucasians; p<0.0001); in 2008, usage of primary TKA was 40% lower for African-Americans (41.5 per 10 000 for African-Americans; 68.8 per 10 000 for Caucasians; p<0.0001) with similar findings for the other cohorts. Black-White disparities in 30-day hospital readmission increased significantly from 19912008 among three patient cohorts. For example in 1991 30-day readmission rates for African-Americans receiving primary TKA were 6% higher than for Caucasians; by 2008 readmission rates for African-Americans were 24% higher (p<0.05 for change in disparity). Similarly, black-white disparities in the proportion of patients discharged to home after surgery increased across the study period for all cohorts (p<0.05). Conclusions In an 18-year analysis of US Medicare data, we found little evidence of declines in racial disparities for joint arthroplasty usage or outcomes. C1 [Singh, Jasvinder A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. [Lu, Xin; Rosenthal, Gary E.; Cram, Peter] Univ Iowa, Dept Internal Med, Carver Coll Med, Div Gen Internal Med, Iowa City, IA 52242 USA. [Lu, Xin; Rosenthal, Gary E.; Cram, Peter] Iowa City Vet Adm Med Ctr, CADRE, Iowa City, IA USA. [Ibrahim, Said] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Ibrahim, Said] Perelman Univ Penn, Sch Med, Philadelphia, PA USA. RP Singh, JA (reprint author), Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. OI singh, jasvinder/0000-0003-3485-0006 FU National Institute of Aging; National Cancer Institute; Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs); Department of Veterans Affairs; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Heart, Lung and Blood Institute FX National Institute of Aging, National Cancer Institute, Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs), Department of Veterans Affairs, National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Heart, Lung and Blood Institute. NR 75 TC 31 Z9 31 U1 2 U2 7 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD DEC PY 2014 VL 73 IS 12 BP 2107 EP 2115 DI 10.1136/annrheumdis-2013-203494 PG 9 WC Rheumatology SC Rheumatology GA AT2RY UT WOS:000344783900013 PM 24047869 ER PT J AU Bremmer, DN Clancy, CJ Press, EG Almaghrabi, R Chen, L Doi, YH Nguyen, H Shields, RK AF Bremmer, Derek N. Clancy, Cornelius J. Press, Ellen G. Almaghrabi, Reem Chen, Liang Doi, Yohei Hong Nguyen Shields, Ryan K. TI KPC-Producing Klebsiella pneumoniae Strains That Harbor AAC(6 ')-Ib Exhibit Intermediate Resistance to Amikacin SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CRITICALLY-ILL PATIENTS; COLISTIN; GENE; AMINOGLYCOSIDES; COMBINATIONS; DORIPENEM; RMTB AB The aminoglycoside-modifying enzyme AAC(6')-Ib is common among carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strains. We investigated amikacin (AMK) activity against 20 AAC(6')-Ib-producing CR-Kp strains. MICs clustered at 16 to 32 mu g/ml. By the time-kill study, AMK (1x and 4x the MIC) was bactericidal against 30% and 85% of the strains, respectively. At achievable human serum concentrations, however, the majority of strains showed regrowth, suggesting that AAC(6')-Ib confers intermediate AMK resistance. AMK and trimethoprim-sulfamethoxazole (TMP-SMX) were synergistic against 90% of the strains, indicating that the combination may overcome resistance. C1 [Bremmer, Derek N.] Univ Pittsburgh, Dept Pharm & Therapeut, Pittsburgh, PA USA. [Clancy, Cornelius J.; Press, Ellen G.; Almaghrabi, Reem; Doi, Yohei; Hong Nguyen; Shields, Ryan K.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Hong Nguyen; Shields, Ryan K.] Univ Pittsburgh, Med Ctr, XDR Pathogen Lab, Pittsburgh, PA USA. [Clancy, Cornelius J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Chen, Liang] Rutgers State Univ, New Jersey Med Sch, Publ Hlth Res Inst, Newark, NJ 07102 USA. RP Shields, RK (reprint author), Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. EM shieldsrk@upmc.edu FU National Institutes of Health [KL2TR000146]; University of Pittsburgh Medical Center XDR Pathogen Laboratory FX This project was supported by the National Institutes of Health through grant no. KL2TR000146 awarded to R. K. S. and by the University of Pittsburgh Medical Center XDR Pathogen Laboratory. NR 20 TC 5 Z9 6 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2014 VL 58 IS 12 BP 7597 EP 7600 DI 10.1128/AAC.03831-14 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA AT9AW UT WOS:000345221000076 PM 25288089 ER PT J AU Shields, RK Nguyen, MH Press, EG Clancy, CJ AF Shields, Ryan K. Hong Nguyen, M. Press, Ellen G. Clancy, Cornelius J. TI Abdominal Candidiasis Is a Hidden Reservoir of Echinocandin Resistance SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INVASIVE CANDIDIASIS; CASPOFUNGIN MICS; GLABRATA; OUTCOMES; THERAPY; SUSCEPTIBILITY; PERSISTENCE; CANDIDEMIA; MICAFUNGIN; FAILURE AB FKS mutant Candida isolates were recovered from 24% (6/25) of abdominal candidiasis patients exposed to echinocandin. Candida glabrata (29%) and Candida albicans (14%) mutants were identified. Multidrug-resistant bacteria were recovered from 83% of FKS mutant infections. Mutations were associated with prolonged echinocandin exposure (P = 0.01), breakthrough infections (P = 0.03), and therapeutic failures despite source control interventions (100%). Abdominal candidiasis is a hidden reservoir for the emergence of echinocandin-resistant Candida. C1 [Shields, Ryan K.; Hong Nguyen, M.; Press, Ellen G.; Clancy, Cornelius J.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Shields, Ryan K.; Hong Nguyen, M.] Univ Pittsburgh, Med Ctr, XDR Pathogen Lab, Pittsburgh, PA USA. [Clancy, Cornelius J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Nguyen, MH (reprint author), Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. EM mhn5@pitt.edu FU Astellas; Merck; National Institutes of Health [KL2TR000146] FX This work was supported by investigator-initiated grants from Astellas and Merck and by the National Institutes of Health through grant KL2TR000146, awarded to R.K.S. NR 19 TC 18 Z9 19 U1 2 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2014 VL 58 IS 12 BP 7601 EP 7605 DI 10.1128/AAC.04134-14 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA AT9AW UT WOS:000345221000077 PM 25288081 ER PT J AU Wilking, MJ Singh, C Nihal, M Zhong, WX Ahmad, N AF Wilking, Melissa J. Singh, Chandra Nihal, Minakshi Zhong, Weixiong Ahmad, Nihal TI SIRT1 deacetylase is overexpressed in human melanoma and its small molecule inhibition imparts anti-proliferative response via p53 activation SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE SIRT1; Melanoma; p53; p21; Tenovin-1 ID PROSTATE-CANCER CELLS; MALIGNANT-MELANOMA; IN-VITRO; APOPTOSIS; EXPRESSION; ACETYLATION; SENESCENCE; SIRTUINS; INSIGHTS; ROLES AB Melanoma causes more deaths than any other skin cancer, and its incidence in the US continues to rise. Current medical therapies are insufficient to control this deadly neoplasm, necessitating the development of new target-based approaches. The objective of this study was to determine the role and functional significance of the class III histone deacetylase SIRT1 in melanoma. We have found that SIRT1 is overexpressed in clinical human melanoma tissues and human melanoma cell lines (Sk-Mel-2, WM35, G361, A375, and Hs294T) compared to normal skin and normal melanocytes, respectively. In addition, treatment of melanoma cell lines A375, Hs294T, and G361 with Tenovin-1, a small molecule SIRT1 inhibitor, resulted in a significant decrease in cell growth and cell viability. Further, Tenovin-1 treatment also resulted in a marked decrease in the clonogenic survival of melanoma cells. Further experiments showed that the anti-proliferative response of Tenovin-1 was accompanied by an increase in the protein as well as activity of the tumor suppressor p53. This increase in p53 activity was substantiated by an increase in the protein level of its downstream target p21. Overall, these data suggest that small molecule inhibition of SIRT1 causes anti-proliferative effects in melanoma cells. SIRT1 appears to be acting through the activity of the tumor suppressor p53, which is not mutated in the majority of melanomas. However, future detailed studies are needed to further explore the role and mechanism of SIRT1 in melanoma development and progression and its usefulness in melanoma treatment. (C) 2014 Elsevier Inc. All rights reserved. C1 [Wilking, Melissa J.; Singh, Chandra; Nihal, Minakshi; Ahmad, Nihal] Univ Wisconsin, Dept Dermatol, Madison, WI 53706 USA. [Zhong, Weixiong] Univ Wisconsin, Dept Pathol, Madison, WI 53706 USA. [Ahmad, Nihal] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Ahmad, N (reprint author), Univ Wisconsin, Med Sci Ctr, Dept Dermatol, 1300 Univ Ave,Room 423, Madison, WI 53706 USA. EM nahmad@wisc.edu FU NIH [R01AR059130, R01CA176748]; Department of Veterans Affairs [1I01BX001008] FX This work was partially supported by funding from the NIH (R01AR059130 and R01CA176748 and the Department of Veterans Affairs (VA Merit Review Award 1I01BX001008). NR 37 TC 12 Z9 15 U1 0 U2 8 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 DEC 1 PY 2014 VL 563 SI SI BP 94 EP 100 DI 10.1016/j.abb.2014.04.001 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AT8QT UT WOS:000345198000013 PM 24751483 ER PT J AU Singh, RP Hasan, S Sharma, S Nagra, S Yamaguchi, DT Wong, DTW Hahn, BH Hossain, A AF Singh, Ram Pyare Hasan, Sascha Sharma, Sherven Nagra, Saranpreet Yamaguchi, Dean T. Wong, David T. W. Hahn, Bevra H. Hossain, Awlad TI Th17 cells in inflammation and autoimmunity SO AUTOIMMUNITY REVIEWS LA English DT Review DE Th17; Sex hormones; Autoimmunity; Systemic lupus erythematosus; Cancer; Mesenchymal stem cells ID MESENCHYMAL STEM-CELLS; REGULATORY T-CELLS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CENTRAL-NERVOUS-SYSTEM; TUMOR-INFILTRATING LYMPHOCYTES; HELPER 17 CELLS; SJOGRENS-SYNDROME; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS; HEPATOCELLULAR-CARCINOMA AB T helper 17 (Th17), a distinct subset of CD4(+) T cells with IL-17 as their major cytokine, orchestrate the pathogenesis of inflammatory and autoimmune diseases. Dysregulated Th17 cells contribute to inflammatory and autoimmune diseases. Candidate biologics are in development for targeting IL-17, IL-17 receptors or IL-17 pathways. Several drugs that impact the IL-17 pathway are already in clinical trials for the treatment of autoimmune diseases. In this review we provide evidence for the role of Th17 cells in immune-mediated diseases. An understanding of the role of Th17 in these conditions will provide important insights and unravel novel targets for therapeutic intervention. (C) 2014 Elsevier B.V. All rights reserved. C1 [Singh, Ram Pyare; Nagra, Saranpreet; Hahn, Bevra H.; Hossain, Awlad] Univ Calif Los Angeles, David Geffen Sch Med, Div Rheumatol, Los Angeles, CA 90095 USA. [Hasan, Sascha] Univ Calif Los Angeles, David Geffen Sch Med, Sanguine Biosci Inc, Los Angeles, CA 90095 USA. [Sharma, Sherven; Yamaguchi, Dean T.] Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Hlth Care Syst, Res Serv, Los Angeles, CA 90095 USA. [Wong, David T. W.] Univ Calif Los Angeles, David Geffen Sch Med, Sch Dent, 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 rsingh@ucla.edu FU NIH [AR54034, AI 083894, AI65645]; UCLA Senate Core Grant; UCLA Oppenheimer Clinical Seed Grant; American Autoimmune Related Disease Association; Lupus Foundation of America; VA Merit Review Award [2101 BX000170-05] FX Supported by NIH grants AR54034, AI 083894, AI65645 to RPS, UCLA Senate Core Grant to BHH and RPS, UCLA Oppenheimer Clinical Seed Grant and American Autoimmune Related Disease Association and the Lupus Foundation of America Awards to RPS, and VA Merit Review Award 2101 BX000170-05 to DTY. NR 117 TC 47 Z9 57 U1 6 U2 36 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-9972 EI 1873-0183 J9 AUTOIMMUN REV JI Autoimmun. Rev. PD DEC PY 2014 VL 13 IS 12 BP 1174 EP 1181 DI 10.1016/j.autrev.2014.08.019 PG 8 WC Immunology SC Immunology GA AT8TC UT WOS:000345203800002 PM 25151974 ER PT J AU Zephyrin, LC Katon, JG Yano, EM AF Zephyrin, Laurie C. Katon, Jodie G. Yano, Elizabeth M. TI Strategies for transforming reproductive healthcare delivery in an integrated healthcare system: a national model with system-wide implications SO CURRENT OPINION IN OBSTETRICS & GYNECOLOGY LA English DT Review DE health policy; health system; programmatic development; reproductive health; women Veterans ID LIFE-COURSE APPROACH; WOMEN VETERANS; FEMALE VETERANS; RESEARCH AGENDA; MILITARY; TRAUMA AB Purpose of review As the number of women serving in the US military has grown, so too has the number of women using the US Department of Veterans Affairs Healthcare System (VA). This poses tremendous opportunity to integrate reproductive health services across a national healthcare system. This review summarizes the approaches used to assess, rapidly design, and integrate VA's first National Reproductive Health Program. Recent findings Compared with the civilian population, women Veterans have poorer health status including increased likelihood of medical comorbidities and mental health conditions. Given these complex health needs, a health systems approach that integrates reproductive health with other needs is essential in this vulnerable population. Summary Delivery of high-quality reproductive healthcare must incorporate a systems perspective. Promoting major organizational and cultural change in a national system has required use of an evidence-based strategic framework, which has relied on several key tenets including the following: understanding the population of women Veterans served, developing research clinical partnerships, building interdisciplinary initiatives for system-wide integration of reproductive healthcare, and developing innovative tools for enhancing care delivery. This approach can serve as a model for other healthcare systems committed to developing an integrated system of reproductive healthcare and addressing reproductive health conditions in women with complex needs. C1 [Zephyrin, Laurie C.; Katon, Jodie G.] Womens Hlth Serv, Off Patient Care Serv, US Dept Vet Affairs, Washington, DC 20420 USA. [Zephyrin, Laurie C.] NYU, Dept Obstet & Gynecol, Langone Sch Med, New York, NY 10016 USA. [Katon, Jodie G.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Katon, Jodie G.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, VA HSR Ctr Study Healthcare Innovat Implementat &, Los Angeles, CA USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA USA. RP Zephyrin, LC (reprint author), Womens Hlth Serv, Off Patient Care Serv, US Dept Vet Affairs, 810 Vermont Ave, Washington, DC 20420 USA. EM Laurie.Zephyrin@va.gov FU US Department of Veteran Affairs, Office of Research and Development, Health Services Research and Development Senior Career Scientist Award [RCS 05-195] FX E.M.Y.'s time was supported by the US Department of Veteran Affairs, Office of Research and Development, Health Services Research and Development Senior Career Scientist Award to E.M.Y. (grant RCS 05-195). NR 27 TC 3 Z9 3 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-872X EI 1473-656X J9 CURR OPIN OBSTET GYN JI Curr. Opin. Obstet. Gynecol. PD DEC PY 2014 VL 26 IS 6 BP 503 EP 510 DI 10.1097/GCO.0000000000000124 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AT5KL UT WOS:000344982000012 PM 25333678 ER PT J AU Brooks-Worrell, BM Boyko, EJ Palmer, JP AF Brooks-Worrell, Barbara M. Boyko, Edward J. Palmer, Jerry P. TI Impact of Islet Autoimmunity on the Progressive beta-Cell Functional Decline in Type 2 Diabetes SO DIABETES CARE LA English DT Article ID GLUTAMIC-ACID DECARBOXYLASE; INSULIN REQUIREMENT; ADULTS LADA; AUTOANTIBODIES; ANTIBODIES; MELLITUS; RESPONSES; PREVALENCE; DIAGNOSIS; PROTEINS AB OBJECTIVE Cross-sectional studies have suggested that islet autoimmunity may be more prevalent in type 2 diabetes (T2D) than previously appreciated and may contribute to the progressive decline in beta-cell function. In this study, we longitudinally evaluated the effect of islet autoimmune development on the progressive beta-cell dysfunction in T2D patients. RESEARCH DESIGN AND METHODS Twenty-three T2D patients negative for islet autoantibodies (GAD antibody and insulinoma-associated protein 2) and islet-specific T cells were evaluated prospectively for up to 36 months. We investigated the percentage of patients who developed islet autoantibodies (Ab+) and/or islet-reactive T cells (T+) and the effect of the islet autoimmunity on fasting and glucagon-stimulated C-peptide responses. We defined positive islet autoimmunity as Ab+ and/or T+ for at least two study visits. RESULTS Of the 23 patients, 6(26%) remained negative for islet autoimmunity (Ab T), 14 (61%) developed Ab+ and/or T+, and 3 (13%) were unclassifiable because they developed islet autoimmunity at only one study visit. Islet Ab+ was observed to be less stable than islet-specific T-cell responses. Development of islet autoimmunity was significantly associated with a more rapid decline in fasting (P < 0.0001) and glucagon-stimulated (P < 0.05) C-peptide responses. CONCLUSIONS These pilot data suggest that the development of islet autoimmunity in T2D is associated with a significantly more rapid beta-cell functional decline. C1 [Brooks-Worrell, Barbara M.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. RP Brooks-Worrell, BM (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. EM bbrooks@u.washington.edu FU National Institutes of Health [P01-DK-053004, P30-DK-017047] FX This work was supported by resources from the VA Puget Sound Health Care System, Seattle, WA. In addition, partial support was provided by National Institutes of Health grants P01-DK-053004 and P30-DK-017047. NR 38 TC 10 Z9 10 U1 1 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD DEC PY 2014 VL 37 IS 12 BP 3286 EP 3293 DI 10.2337/dc14-0961 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AU0SQ UT WOS:000345335200038 PM 25239783 ER PT J AU Garvey, WT Ryan, DH Bohannon, NJV Kushner, RF Rueger, M Dvorak, RV Troupin, B AF Garvey, W. Timothy Ryan, Donna H. Bohannon, Nancy J. V. Kushner, Robert F. Rueger, Miriam Dvorak, Roman V. Troupin, Barbara TI Weight-Loss Therapy in Type 2 Diabetes: Effects of Phentermine and Topiramate Extended Release SO DIABETES CARE LA English DT Article ID CARDIOVASCULAR RISK-FACTORS; LIFE-STYLE INTERVENTION; EUROPEAN-ASSOCIATION; CONSENSUS STATEMENT; METABOLIC SYNDROME; OBESE ADULTS; OVERWEIGHT; MANAGEMENT; ALGORITHM; MELLITUS AB Treatment algorithms for type 2 diabetes recommend weight loss for disease management. The safety and efficacy of treatment with phentermine (PHEN)/topiramate (TPM) extended release (ER) plus lifestyle modification for weight loss and glycemic benefits were assessed in two randomized, double-blind, placebo-controlled 56-week studies of obese/overweight adults with type 2 diabetes. RESEARCH DESIGN AND METHODS The OB-202/DM-230 Study was a 56-week phase 2 trial that randomized subjects to receive once-daily placebo or PHEN/TPMER 15 mg/92 mg (15/92). The primary end point was change in HbA(1c) level. A post hoc analysis of a subpopulation with type 2 diabetes from a second study, CONQUER, is also presented. All subjects made lifestyle modifications, and comorbidities were managed to the standard of care. RESULTS The study groups comprised 130 subjects with type 2 diabetes enrolled in the OB-202/DM-230 Study (mean baseline HbA(1c) 8.7% [72 mmol/mol]) and 388 subjects with type 2 diabetes in the CONQUER Study (mean baseline HbA1c 6.8% [51 mmol/mol]). At week 56 in the OB-202/DM-230, change in weight (from intent-to-treat sample with last observation carried forward [ITT-LOCF]) was - 22.7% for placebo and -9.4% for PHEN/TPM ER 15/92 (P < 0.0001 vs. placebo). Change in HbA(1c) level (from ITT-LOCF) was 21.2% (-13.1 mmol/mol) for placebo and -1.6% (-17.5 mmol/mol) for PHEN/TPM ER 15/92 (P = 0.0381). In both the OB-202/DM-230 and CONQUER, greater numbers of patients randomized to receive PHEN/TPM ER treatment achieved HbA(1c) targets with reduced need for diabetic medications when compared with the placebo group. Common adverse events included paraesthesia, constipation, and insomnia. CONCLUSIONS PHEN/TPM ER plus lifestyle modification can effectively promote weight loss and improve glycemic control as a treatment approach in obese/overweight patients with type 2 diabetes. C1 [Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Garvey, W. Timothy] Birmingham VA Med Ctr, Birmingham, AL USA. [Ryan, Donna H.] Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Bohannon, Nancy J. V.] Monteagle Med Ctr, San Francisco, CA USA. [Kushner, Robert F.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Rueger, Miriam] Univ Alabama Birmingham, Birmingham, AL USA. [Dvorak, Roman V.; Troupin, Barbara] VIVUS Inc, Mountain View, CA USA. RP Garvey, WT (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. EM garveyt@uab.edu FU VIVUS, Inc. FX Funding for the study and for editorial assistance was provided by VIVUS, Inc. NR 28 TC 19 Z9 19 U1 2 U2 12 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 DEC PY 2014 VL 37 IS 12 BP 3309 EP 3316 DI 10.2337/dc14-0930 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AU0SQ UT WOS:000345335200041 PM 25249652 ER PT J AU Ambwani, S Slane, JD Thomas, KM Hopwood, CJ Grilo, CM AF Ambwani, Suman Slane, Jennifer D. Thomas, Katherine M. Hopwood, Christopher J. Grilo, Carlos M. TI Interpersonal dysfunction and affect-regulation difficulties in disordered eating among men and women SO EATING BEHAVIORS LA English DT Article DE Interpersonal functioning; Negative affect; Emotion regulation; Disordered eating; Gender differences ID ANOREXIA-NERVOSA; BODY DISSATISFACTION; EMOTIONAL EXPRESSION; MODEL; MAINTENANCE; PSYCHOPATHOLOGY; QUESTIONNAIRE; DYSREGULATION; VALIDATION; PATHOLOGY AB Although several studies suggest that negative affect and interpersonal problems serve as important contributors for eating-related problems, much of this research has been conducted among women and less is known about their roles in precipitating and maintaining eating problems among men. Previous studies with undergraduate men suggest that difficulties in emotion regulation are associated with disordered eating even after controlling for differences in body mass index (BMI) and negative affect. The present study sought to replicate these findings and extend them to assess any unique variance explained by problems in interpersonal functioning among both men and women. Participants were men (n = 213) and women (n = 521) undergraduates at a large Midwestern university who completed a demographic information form, the Eating Disorder Examination-Questionnaire (EDE-Q), the Difficulties in Emotion Regulation Scale (DERS), the Positive and Negative Affect Schedule, and the Inventory of Interpersonal Problems-Short Circumplex Form(IIP-SC). A series of hierarchical regression analyses indicated that DERS and IIP-SC significantly predicted EDE-Q global scores after controlling for variability in BMI and negative affect and that the results were similar for men and women. Our findings offer preliminary support for models that highlight emotional vulnerability and interpersonal problems for disordered eating for young adult men. Future research extending these findings among treatment-seeking samples and employing multi-method assessment would serve to further clarify the tenability of these theoretical models for both men and women. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Ambwani, Suman] Dickinson Coll, Dept Psychol, Carlisle, PA 17013 USA. [Slane, Jennifer D.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. [Slane, Jennifer D.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. [Thomas, Katherine M.; Hopwood, Christopher J.] Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA. [Grilo, Carlos M.] Yale Univ, Dept Psychiat, Sch Med, New Haven, CT 06511 USA. RP Ambwani, S (reprint author), Dickinson Coll, Dept Psychol, POB 1773, Carlisle, PA 17013 USA. EM Ambwanis@dickinson.edu NR 34 TC 5 Z9 5 U1 3 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1471-0153 EI 1873-7358 J9 EAT BEHAV JI Eat. Behav. PD DEC PY 2014 VL 15 IS 4 BP 550 EP 554 DI 10.1016/j.eatbeh.2014.08.005 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AU1TJ UT WOS:000345402700007 PM 25194562 ER PT J AU Anderson, JA Godwin, KM Saleem, JJ Russell, S Robinson, JJ Kimmel, B AF Anderson, Jane A. Godwin, Kyler M. Saleem, Jason J. Russell, Scott Robinson, Joshua J. Kimmel, Barbara TI Accessibility, usability, and usefulness of a Web-based clinical decision support tool to enhance provider-patient communication around Self-management TO Prevent (STOP) Stroke SO HEALTH INFORMATICS JOURNAL LA English DT Article DE Clinical decision support tool; clinical-practice guidelines; prevention; provider-patient communication; stroke ID CARE; IMPACT AB This article reports redesign strategies identified to create a Web-based user-interface for the Self-management TO Prevent (STOP) Stroke Tool. Members of a Stroke Quality Improvement Network (N = 12) viewed a visualization video of a proposed prototype and provided feedback on implementation barriers/facilitators. Stroke-care providers (N = 10) tested the Web-based prototype in think-aloud sessions of simulated clinic visits. Participants' dialogues were coded into themes. Access to comprehensive information and the automated features/systematized processes were the primary accessibility and usability facilitator themes. The need for training, time to complete the tool, and computer-centric care were identified as possible usability barriers. Patient accountability, reminders for best practice, goal-focused care, and communication/counseling themes indicate that the STOP Stroke Tool supports the paradigm of patient-centered care. The STOP Stroke Tool was found to prompt clinicians on secondary stroke-prevention clinical-practice guidelines, facilitate comprehensive documentation of evidence-based care, and support clinicians in providing patient-centered care through the shared decision-making process that occurred while using the action-planning/goal-setting feature of the tool. C1 [Anderson, Jane A.; Godwin, Kyler M.] Baylor Coll Med, VA Hlth Serv Res & Dev, Houston Ctr Innovat Qual Effectiveness & Safety, Michael E Debark VAMC, Houston, TX 77030 USA. [Saleem, Jason J.] Regenstrief Inst Inc, VA Hlth Serv Res & Dev, Ctr Implementing Evidence Based Practice, Richard Roudebush VAMC, Indianapolis, IN USA. [Russell, Scott] Richard L Roudebush Vet Affairs Med Ctr, Hlth Serv Res & Dev, Ctr Implementing Evidence Based Practice, Indianapolis, IN USA. [Robinson, Joshua J.] US Dept Vet Affairs, Washington, DC 20420 USA. [Kimmel, Barbara] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. RP Anderson, JA (reprint author), Baylor Coll Med, Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM Jane.Anderson@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [RRP 09-147]; Health Services Research & Development Houston VA Center of Excellence [HFP90-020]; National Research Service Award [T32 HP10031] FX This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (RRP 09-147). This work was partly supported by the Health Services Research & Development Houston VA Center of Excellence (HFP90-020) and by the National Research Service Award (T32 HP10031). NR 18 TC 0 Z9 0 U1 2 U2 12 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1460-4582 EI 1741-2811 J9 HEALTH INFORM J JI Health Inform. J. PD DEC PY 2014 VL 20 IS 4 BP 261 EP 274 DI 10.1177/1460458213493195 PG 14 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA AU0UB UT WOS:000345339000003 PM 24352597 ER PT J AU Pandit, LM Lloyd, EE Reynolds, JO Lawrence, WS Reynolds, C Wehrens, XHT Bryan, RM AF Pandit, Lavannya M. Lloyd, Eric E. Reynolds, Julia O. Lawrence, William S. Reynolds, Corey Wehrens, Xander H. T. Bryan, Robert M. TI TWIK-2 Channel Deficiency Leads to Pulmonary Hypertension Through a Rho-Kinase-Mediated Process SO HYPERTENSION LA English DT Article DE KCNK6; potassium channel; pulmonary hypertension; Rho-kinase; TWIK-2 ID ARTERY SMOOTH-MUSCLE; DOMAIN POTASSIUM CHANNELS; K+ CHANNELS; VASOCONSTRICTION; MICE; INHIBITOR; CELLS; TASK-1; PATHOGENESIS; CONTRACTION AB TWIK-2 (KCNK6) is a member of the 2-pore domain (K-2P) family of potassium channels, which are highly expressed in the vascular system. We tested the hypothesis that TWIK-2 deficiency leads to pulmonary hypertension. TWIK-2 knockout mice and their wildtype littermates at 8 weeks of age had similar mean right ventricular systolic pressures (24 +/- 3 and 21 +/- 3 mm Hg, respectively.) Significantly, by 20 weeks of age, the mean right ventricular systolic pressures in TWIK-2 knockout mice increased to 35 +/- 3 mm Hg (P <= 0.036), whereas mean right ventricular systolic pressures in wildtype littermates remained at 22 +/- 3 mm Hg. Elevated mean right ventricular systolic pressures in the TWIK-2 knockout mice was accompanied by pulmonary vascular remodeling as determined by a 25% increase in the cross-sectional area of the vessels occupied by the vessel wall. Additionally, secondary branches of the pulmonary artery from 20-week-old TWIK-2 knockout mice showed an enhanced contractile response to U46619 (10(-6) moles/L), a thromboxane A2 mimetic, which was completely abolished with the Rho-kinase inhibitor, Y27632 (10(-6) and 10(-5) moles/L). Treatment of TWIK-2 knockout mice with the Rho-kinase inhibitor, fasudil, in the drinking water for 12 weeks, abolished the development of pulmonary hypertension and attenuated the vessel remodeling. We concluded that mice deficient in the TWIK-2 channel develop pulmonary hypertension between 8 and 20 weeks of age through a mechanism involving Rho-kinase. Our results suggest that downregulation of TWIK-2 in the pulmonary vasculature may be an underlying mechanism in the development of pulmonary hypertension. C1 [Pandit, Lavannya M.; Wehrens, Xander H. T.; Bryan, Robert M.] Baylor Coll Med, Dept Internal Med, Houston, TX 77030 USA. [Lloyd, Eric E.; Bryan, Robert M.] Baylor Coll Med, Dept Anesthesiol, Houston, TX 77030 USA. [Reynolds, Julia O.; Reynolds, Corey; Wehrens, Xander H. T.; Bryan, Robert M.] Baylor Coll Med, Cardiovasc Res Inst, Dept Mol Physiol & Biophys, Houston, TX 77030 USA. [Lawrence, William S.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX USA. RP Pandit, LM (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, One Baylor Plaza,Jones Bldg Suite 535e, Houston, TX 77030 USA. EM lpandit@bcm.edu FU Baylor College of Medicine; Veterans Affairs Career Development Award Program; [R21 HL098921] FX The studies were supported by R21 HL098921 (R. M. Bryan), Baylor College of Medicine Seed Funding Award 2011-2012 (L. M. Pandit), and Veterans Affairs Career Development Award Program (L. M. Pandit). NR 42 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD DEC PY 2014 VL 64 IS 6 BP 1260 EP U216 DI 10.1161/HYPERTENSIONAHA.114.03406 PG 13 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AT7PL UT WOS:000345129900024 PM 25245387 ER PT J AU McDonald, CC Sommers, MS Fargo, JD AF McDonald, Catherine C. Sommers, Marilyn S. Fargo, Jamison D. TI Risky driving, mental health, and health-compromising behaviours: risk clustering in late adolescents and adults SO INJURY PREVENTION LA English DT Article ID HIGH-SCHOOL-STUDENTS; RANDOMIZED CONTROLLED-TRIAL; MOTOR-VEHICLE CRASHES; EMERGENCY-DEPARTMENT; TEENAGE DRIVERS; NOVICE DRIVERS; SLEEP QUALITY; UNITED-STATES; YOUNG-ADULTS; ALCOHOL AB Background Health-compromising behaviours in adolescents and adults co-occur. Because motor vehicle crashes are the leading cause of death and disability for these age groups, understanding the association between risky driving and other health-compromising behaviours is critical. Methods We performed a secondary analysis of data from a randomised controlled trial of an intervention for participants who screened positive for risky driving and problem drinking. Using baseline data, we examined relationships among conduct behaviour problems before and after age 15 years, depressive symptoms, sleep, problem drinking, and risky driving (hostile, reckless and drinking and driving) in late adolescents ages 18-24 (n=110) years, and adults ages 25-44 (n=202) years. We developed a measurement model for the entire sample using confirmatory factor analysis, which was then specified as a multigroup structural equation model. Results Late adolescents and adults had some similar associations for pathways through problem drinking to drinking and driving; depression to reckless driving; and conduct behaviour problems after 15 years of age to hostile driving. Late adolescents, however, had more complex relationships: depressive symptoms and conduct behaviour problems before 15 years of age were associated with more risky driving behaviours through multiple pathways, and males reported more risky driving. Conclusions Risky driving is associated with other health-compromising behaviours and mental health factors. It is a multidimensional phenomenon more pronounced in late adolescence than adulthood. In order to promote safe driving, the findings support the need to consider behaviours that are a health threat in the late adolescent population during driving training and licensure. C1 [McDonald, Catherine C.; Sommers, Marilyn S.] Univ Penn, Sch Nursing, Ctr Global Womens Hlth, Philadelphia, PA 19104 USA. [McDonald, Catherine C.] Univ Penn, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. [Fargo, Jamison D.] Utah State Univ, Dept Psychol, Logan, UT 84322 USA. RP McDonald, CC (reprint author), Univ Penn, Sch Nursing, Ctr Global Womens Hlth, Claire Fagin Hall,418 Curie Blvd,4012a, Philadelphia, PA 19104 USA. EM mcdonalc@nursing.upenn.edu FU Centers for Disease Control and Prevention [R49CE523225]; University of Pennsylvania, School of Nursing through the National Institute of Nursing Research [T32NR007100, K99NR013548] FX We would like to acknowledge that the study was funded by the Centers for Disease Control and Prevention, Grants for Unintentional Injury Prevention and Control Research (R49CE523225) (PI: Marilyn S. Sommers). The analyses presented here was supported by the postdoctoral research training for Catherine C. McDonald at the University of Pennsylvania, School of Nursing on T32NR007100 (PI: Marilyn S. Sommers) and K99NR013548 (PI: Catherine C. McDonald) through the National Institute of Nursing Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Nursing Research or the National Institutes of Health. NR 44 TC 2 Z9 2 U1 2 U2 21 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1353-8047 EI 1475-5785 J9 INJURY PREV JI Inj. Prev. PD DEC PY 2014 VL 20 IS 6 BP 365 EP 372 DI 10.1136/injuryprev-2014-041150 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AT9XB UT WOS:000345276000001 PM 24814717 ER PT J AU Giordano, S Dodson, M Ravi, S Redmann, M Ouyang, XS Usmar, VMD Zhang, JH AF Giordano, Samantha Dodson, Matthew Ravi, Saranya Redmann, Matthew Ouyang, Xiaosen Usmar, Victor M. Darley Zhang, Jianhua TI Bioenergetic adaptation in response to autophagy regulators during rotenone exposure SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE 3-methyladenine; autophagy; mitochondria; primary neuron; rapamycin; rotenone ID MITOCHONDRIAL QUALITY-CONTROL; PARKINSONS-DISEASE; OXIDATIVE STRESS; COMPLEX-I; CELLULAR BIOENERGETICS; CELLS; MITOPHAGY; MECHANISMS; SH-SY5Y; MODEL AB Parkinson's disease is the second most common neurodegenerative disorder with both mitochondrial dysfunction and insufficient autophagy playing a key role in its pathogenesis. Among the risk factors, exposure to the environmental neurotoxin rotenone increases the probability of developing Parkinson's disease. We previously reported that in differentiated SH-SY5Y cells, rotenone-induced cell death is directly related to inhibition of mitochondrial function. How rotenone at nM concentrations inhibits mitochondrial function, and whether it can engage the autophagy pathway necessary to remove damaged proteins and organelles, is unknown. We tested the hypothesis that autophagy plays a protective role against rotenone toxicity in primary neurons. We found that rotenone (10-100nM) immediately inhibited cellular bioenergetics. Concentrations that decreased mitochondrial function at 2h, caused cell death at 24h with an LD50 of 10nM. Overall, autophagic flux was decreased by 10nM rotenone at both 2 and 24h, but surprisingly mitophagy, or autophagy of the mitochondria, was increased at 24h, suggesting that a mitochondrial-specific lysosomal degradation pathway may be activated. Up-regulation of autophagy by rapamycin protected against cell death while inhibition of autophagy by 3-methyladenine exacerbated cell death. Interestingly, while 3-methyladenine exacerbated the rotenone-dependent effects on bioenergetics, rapamycin did not prevent rotenone-induced mitochondrial dysfunction, but caused reprogramming of mitochondrial substrate usage associated with both complex I and complex II activities. Taken together, these data demonstrate that autophagy can play a protective role in primary neuron survival in response to rotenone; moreover, surviving neurons exhibit bioenergetic adaptations to this metabolic stressor. C1 [Giordano, Samantha; Dodson, Matthew; Ravi, Saranya; Redmann, Matthew; Ouyang, Xiaosen; Usmar, Victor M. Darley; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Giordano, Samantha; Dodson, Matthew; Ravi, Saranya; Redmann, Matthew; Ouyang, Xiaosen; Usmar, Victor M. Darley; Zhang, Jianhua] Univ Alabama Birmingham, Ctr Free Radical Biol, Birmingham, AL 35294 USA. [Ouyang, Xiaosen; Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL USA. RP Zhang, JH (reprint author), Univ Alabama Birmingham, Dept Pathol, BMRII-534,901 19th St S, Birmingham, AL 35294 USA. EM zhanja@uab.edu OI Zhang, Jianhua/0000-0002-2128-9574 FU NIH [NIHR01-NS064090]; VA merit award FX We thank members of the Zhang and the Darley-Usmar laboratories for discussions and technical help. This work was supported by NIH (NIHR01-NS064090) and a VA merit award (to JZ). NR 42 TC 7 Z9 7 U1 0 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2014 VL 131 IS 5 BP 625 EP 633 DI 10.1111/jnc.12844 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA AU0YQ UT WOS:000345348500010 PM 25081478 ER PT J AU Jesinkey, SR Korrapati, MC Rasbach, KA Beeson, CC Schnellmann, RG AF Jesinkey, Sean R. Korrapati, Midhun C. Rasbach, Kyle A. Beeson, Craig C. Schnellmann, Rick G. TI Atomoxetine Prevents Dexamethasone-Induced Skeletal Muscle Atrophy in Mice SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID MITOCHONDRIAL BIOGENESIS; BETA(2)-ADRENOCEPTOR AGONISTS; CELLULAR MECHANISMS; UBIQUITIN LIGASES; GENE-EXPRESSION; ERR-ALPHA; HYPERTROPHY; NOREPINEPHRINE; METABOLISM; FORMOTEROL AB Skeletal muscle atrophy remains a clinical problem in numerous pathologic conditions. beta(2)-Adrenergic receptor agonists, such as formoterol, can induce mitochondrial biogenesis (MB) to prevent such atrophy. Additionally, atomoxetine, an FDA-approved norepinephrine reuptake inhibitor, was positive in a cellular assay for MB. We used a mouse model of dexamethasone-induced skeletal muscle atrophy to investigate the potential role of atomoxetine and formoterol to prevent muscle mass loss. Mice were administered dexamethasone once daily in the presence or absence of formoterol (0.3 mg/kg), atomoxetine (0.1 mg/kg), or sterile saline. Animals were euthanized at 8, 16, and 24 hours or 8 days later. Gastrocnemius muscle weights, changes in mRNA and protein expression of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) isoforms, ATP synthase beta, cytochrome c oxidase subunit I, NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 8, ND1, insulin-like growth factor 1 (IGF-1), myostatin, muscle Ring-finger protein-1 (muscle atrophy), phosphorylated forkhead box protein O 3a (p-FoxO3a), Akt, mammalian target of rapamycin (mTOR), and ribosomal protein S6 (rp-S6; muscle hypertrophy) in naive and muscle-atrophied mice were measured. Atomoxetine increased p-mTOR 24 hours after treatment in naive mice, but did not change any other biomarkers. Formoterol robustly activated the PGC-1 alpha-4-IGF1-Akt-mTOR-rp-S6 pathway and increased p-FoxO3a as early as 8 hours and repressed myostatin at 16 hours. In contrast to what was observed with acute treatment, chronic treatment (7 days) with atomoxetine increased p-Akt and p-FoxO3a, and sustained PGC-1 alpha expression and skeletal muscle mass in dexamethasone-treated mice, in a manner comparable to formoterol. In conclusion, chronic treatment with a low dose of atomoxetine prevented dexamethasone-induced skeletal muscle wasting and supports a potential role in preventing muscle atrophy. C1 [Jesinkey, Sean R.; Korrapati, Midhun C.; Rasbach, Kyle A.; Beeson, Craig C.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM schnell@musc.edu FU National Institutes of Health National Institute of General Medical Sciences [R01-GM084147]; National Institutes of Health National Center for Research Resources [UL1-RR029882, C06-RR015455]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs [BX-000851]; SC COBRE in Oxidants, Redox Balance, and Stress Signaling [P20 GM103542-02]; South Carolina Clinical and Translational Research Institute at the Medical University of South Carolina FX This work was supported by the National Institutes of Health National Institute of General Medical Sciences [Grant R01-GM084147]; the National Institutes of Health National Center for Research Resources [Grant UL1-RR029882]; the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs [BX-000851]; an SC COBRE in Oxidants, Redox Balance, and Stress Signaling [P20 GM103542-02]; and the South Carolina Clinical and Translational Research Institute, which has an academic home at the Medical University of South Carolina. Animal facilities were funded by National Institutes of Health National Center for Research Resources [Grant C06-RR015455]. NR 43 TC 7 Z9 7 U1 1 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2014 VL 351 IS 3 BP 663 EP 673 DI 10.1124/jpet.114.217380 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AT9AK UT WOS:000345219800019 PM 25292181 ER PT J AU Malnar, M Hecimovic, S Mattsson, N Zetterberg, H AF Malnar, Martina Hecimovic, Silva Mattsson, Niklas Zetterberg, Henrik TI Bidirectional links between Alzheimer's disease and Niemann-Pick type C disease SO NEUROBIOLOGY OF DISEASE LA English DT Review DE Alzheimer's disease; Amyloid-beta; Niemann-Pick type C disease; NPC1; Tau; Cholesterol; Lipids ID AMYLOID-PRECURSOR-PROTEIN; INTRACELLULAR CHOLESTEROL TRANSPORT; GENOME-WIDE ASSOCIATION; A-BETA PRODUCTION; APOLIPOPROTEIN-E; NEUROFIBRILLARY TANGLES; IN-VIVO; ENDOCYTIC PATHWAY; ALPHA-SYNUCLEIN; DOWN-SYNDROME AB Alzheimer's disease (AD) and Niemann-Pick type C (NPC) disease are progressive neurodegenerative diseases with very different epidemiology and etiology. AD is a common cause of dementia with a complex polyfactorial etiology, including both genetic and environmental risk factors, while NPC is a very rare autosomal recessive disease. However, the diseases share some disease-related molecular pathways, including abnormal cholesterol metabolism, and involvement of amyloid-beta (A beta) and tau pathology. Here we review recent studies on these pathological traits, focusing on studies of A beta and tau pathology in NPC, and the importance of the NPC1 gene in AD. Further studies of similarities and differences between AD and NPC may be useful to increase the understanding of both these devastating neurological diseases. (C) 2014 Elsevier Inc. All rights reserved. C1 [Malnar, Martina; Hecimovic, Silva] Rudjer Boskovic Inst, Div Mol Med, Zagreb 10000, Croatia. [Mattsson, Niklas; Zetterberg, Henrik] Univ Gothenburg, Sahlgrenska Acad, Dept Psychiat & Neurochem, Clin Neurochem Lab,Inst Neurosci & Physiol, Gothenburg, Sweden. [Mattsson, Niklas] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. [Mattsson, Niklas] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Zetterberg, Henrik] UCL Inst Neurol, London WC1N 3BG, England. RP Hecimovic, S (reprint author), Rudjer Boskovic Inst, Div Mol Med, Zagreb 10000, Croatia. EM silva.hecimovic@irb.hr; henrik.zetterberg@gu.se FU Swedish Research Council Formas; Knut and Alice Wallenberg Foundation; Wolfson Foundation; Ministry of Science, Education and Sports of the Republic of Croatia; Unity through Knowledge Fund; Swedish State Support for Clinical Research FX Work in the authors' laboratories is supported by the Swedish Research Council Formas, Swedish State Support for Clinical Research, the Knut and Alice Wallenberg Foundation, the Wolfson Foundation (to N.M. and H.Z.), the Ministry of Science, Education and Sports of the Republic of Croatia and the Unity through Knowledge Fund (to S.H.). NR 122 TC 15 Z9 15 U1 0 U2 8 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 DEC PY 2014 VL 72 SI SI BP 37 EP 47 DI 10.1016/j.nbd.2014.05.033 PN A PG 11 WC Neurosciences SC Neurosciences & Neurology GA AT8QX UT WOS:000345198300005 PM 24907492 ER PT J AU Yakabi, K Harada, Y Takayama, K Ro, S Ochiai, M Iizuka, S Hattori, T Wang, LX Tache, Y AF Yakabi, Koji Harada, Yumi Takayama, Kiyoshige Ro, Shoki Ochiai, Mitsuko Iizuka, Seiichi Hattori, Tomohisa Wang, Lixin Tache, Yvette TI Peripheral alpha(2)-beta(1) adrenergic interactions mediate the ghrelin response to brain urocortin 1 in rats SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Atylated ghrelin; Adrenergit receptors; Food intake; Urocortin 1; Stress; Rikkunshito ID CORTICOTROPIN-RELEASING-FACTOR; EDINGER-WESTPHAL NUCLEUS; AUTONOMIC NERVOUS-SYSTEM; DES-ACYL GHRELIN; FOOD-INTAKE; CRF2 RECEPTORS; GASTROINTESTINAL-TRACT; CIRCULATING GHRELIN; ENERGY-METABOLISM; INDUCED ANOREXIA AB The autonomic nervous system (ANS) conveys neuronal input from the brain to the stomach. We investigated mechanisms through which urocortin 1 (UCN1) injected intracerebroventricularly (ICV, 300 pmol/rat) inhibits circulating ghrelin in rats. This was achieved by assessing (1) the induction of c-fos gene expression as a marker of neuronal activation in specific hypothalamic and caudal brainstem regulating ANS; (2) the influence of vagotomy and pharmacological blockade of central and peripheral alpha- and beta-adrenergic receptor (AR) on ICY UCN1-induced reduction of plasma ghrelin levels (determined by ELISA); and (3) the relevance of this pathway in the feeding response to a fast in rats. UCN1 increased c-fos mRNA expression in key brain sites influencing sympathetic activity namely the hypothalamic paraventricular and ventromedial nuclei, locus coeruleus, nucleus of the solitary tract, and rostral ventrolateral medulla, by 16-, 29-, 6-, 37-, and 13-fold, respectively. In contrast, the dorsal motor nucleus of the vagus had little c-fos mRNA expression and ICY UCN1 induced a similar reduction in acylated ghrelin in the sham-operated (31%) and vagotomized (41%) rats. An intraperitoneal (IP) injection of either a non-selective alpha- or selective alpha(2)-AR antagonist reduced, while a selective alpha(2)-AR agonist enhanced ICV UCN1-induced suppression of plasma acylated ghrelin levels. In addition, IP injection of a non-selective beta- or selective beta(1)-AR agonist blocked, and selective beta(1)-AR antagonist augmented, the ghrelin response to ICV UCN1. The IP injections of a selective alpha(1)- or non-selective beta or beta(2)-AR antagonists, or any of the pretreatments given ICV had no effect. ICV UCN1 reduced the 2-h food intake in response to a fast by 80%, and this effect was partially prevented by a selective alpha(2)-AR antagonist. These data suggest that ICV UCN1 reduces plasma ghrelin mainly through the brain sympathetic component of the ANS and peripheral AR specifically alpha(2)-AR activation and inactivation of beta(1)-AR. The alpha(2)-AR pathway contributes to the associated reduction in food intake. (C) 2014 The Authors. Published by Elsevier Ltd. C1 [Yakabi, Koji; Harada, Yumi; Takayama, Kiyoshige; Ro, Shoki; Ochiai, Mitsuko] Saitama Med Univ, Dept Gastroenterol & Hepatol, Saitama Med Ctr, Saitama 3508550, Japan. [Harada, Yumi; Iizuka, Seiichi; Hattori, Tomohisa] Tsumura & Co, Tsumura Res Labs, Ami, Ibaraki 3001192, Japan. [Takayama, Kiyoshige] Gunma Univ, Sch Hlth Sci, Dept Lab Sci, Gunma 3718511, Japan. [Ro, Shoki] Teikyo Univ, Chiba Med Ctr, Cent Res Labs, Chiba 2990111, Japan. [Wang, Lixin; Tache, Yvette] Univ Calif Los Angeles, CURE Digest Dis Ctr, Dept Med, Div Digest Dis, Los Angeles, CA 90078 USA. [Wang, Lixin; Tache, Yvette] Univ Calif Los Angeles, Ctr Neurobiol Stress, Dept Med, Div Digest Dis, Los Angeles, CA 90078 USA. [Wang, Lixin; Tache, Yvette] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90078 USA. RP Harada, Y (reprint author), Tsumura & Co, Tsumura Res Labs, 3586 Yoshiwara, Ami, Ibaraki 3001192, Japan. EM harada_yumi@mail.tsumura.co.jp FU Saitama Medical Center, Saitama Medical University (Japan); Tsumura Co. (Japan); Senior Research Career Scientist Award FX This work was supported in part by Saitama Medical Center, Saitama Medical University (Japan), a grant from Tsumura & Co. (Japan) and the Senior Research Career Scientist Award (YT). NR 53 TC 3 Z9 3 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD DEC PY 2014 VL 50 BP 300 EP 310 DI 10.1016/j.psyneuen.2014.09.003 PG 11 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA AT6PJ UT WOS:000345061000029 PM 25265283 ER PT J AU Lin, HZ Zhou, L Zhou, XH AF Lin, Huazhen Zhou, Ling Zhou, Xiaohua TI Semiparametric Regression Analysis of Longitudinal Skewed Data SO SCANDINAVIAN JOURNAL OF STATISTICS LA English DT Article DE additive model; longitudinal data; multiplicative model; semiparametric; transformation model ID TRANSFORMATION MODELS; CENSORED-DATA; RETRANSFORMATION AB In this paper, we develop a semiparametric regression model for longitudinal skewed data. In the new model, we allow the transformation function and the baseline function to be unknown. The proposed model can provide a much broader class of models than the existing additive and multiplicative models. Our estimators for regression parameters, transformation function and baseline function are asymptotically normal. Particularly, the estimator for the transformation function converges to its true value at the rate n(-1/2), the convergence rate that one could expect for a parametric model. In simulation studies, we demonstrate that the proposed semiparametric method is robust with little loss of efficiency. Finally, we apply the new method to a study on longitudinal health care costs. C1 [Lin, Huazhen; Zhou, Ling] Southwestern Univ Finance & Econ, Sch Stat, Ctr Stat Res, Chengdu, Peoples R China. [Zhou, Xiaohua] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Zhou, Xiaohua] VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA USA. RP Zhou, XH (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98195 USA. EM azhou@u.washington.edu FU Chinese Natural Science Foundation [11125104, 30728019]; Fundamental Research Funds for the Central Universities of China; US Department of Veterans Affairs, Veterans Affairs Health Administration, HSRD [IIR 07-235-1] FX Lin's research is supported in part by the Chinese Natural Science Foundation (11125104) and the Fundamental Research Funds for the Central Universities of China. Zhou's work was supported in part by the Chinese Natural Science Foundation (30728019), and US Department of Veterans Affairs, Veterans Affairs Health Administration, HSR&D grant IIR 07-235-1. This paper presents the findings and conclusions of the authors. It does not necessarily represent those of VA HSR&D Service. We would like to thank Dr Liu at University of Virginia for providing us the data set used in this paper and Shili Fan for her help in analysing the real data. This paper presents the findings and conclusions of the authors. NR 35 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6898 EI 1467-9469 J9 SCAND J STAT JI Scand. J. Stat. PD DEC PY 2014 VL 41 IS 4 BP 1031 EP 1050 DI 10.1111/sjos.12080 PG 20 WC Statistics & Probability SC Mathematics GA AT3UO UT WOS:000344860800010 ER PT J AU Akgun, KM Tate, JP Crothers, K Crystal, S Leaf, DA Womack, J Brown, TT Justice, AC Oursler, KK AF Akguen, Kathleen M. Tate, Janet P. Crothers, Kristina Crystal, Stephen Leaf, David A. Womack, Julie Brown, Todd T. Justice, Amy C. Oursler, Krisann K. TI An Adapted Frailty-Related Phenotype and the VACS Index as Predictors of Hospitalization and Mortality in HIV-Infected and Uninfected Individuals SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE adapted frailty-related phenotype; physiologic frailty; HIV; VACS risk index; hospitalization; mortality ID VETERANS AGING COHORT; HUMAN-IMMUNODEFICIENCY-VIRUS; INDEPENDENT RISK-FACTOR; ANTIRETROVIRAL THERAPY; DEFICIT ACCUMULATION; ELDERLY-PEOPLE; OLDER-ADULTS; MEN; CARE; ASSOCIATION AB Background: Frailty is a geriatric syndrome of decreased physiologic reserve and a risk factor for hospitalization and mortality. We hypothesized that an adapted survey-based frailty-related phenotype (aFRP) predicts hospitalization and mortality among HIV-infected and uninfected individuals in adjusted models but is uncommon among those achieving undetectable HIV-1 RNA. Methods: Defined from self-reported domains of physical shrinking, exhaustion, slowness, and low physical activity in Veterans Aging Cohort Study (VACS) participants, aFRP was considered present with >= 3 domains and prefrailty with 1-2 domains. Cox survival analysis determined hazard ratios (HRs) for 5-year hospitalization and mortality risk adjusting for frailty states, demographics, health behaviors, comorbidities, and a validated risk index incorporating HIV-specific and general organ system biomarkers, the VACS Index. Model discrimination was assessed. Results: Participants with complete data were included [6515/7324 (89%)]. Of these, 3.9% of HIV-infected individuals with HIV-1 RNA >400 copies per milliliter; 2.0% of HIV-infected individuals with HIV-1 RNA <= 400 copies per milliliter; and 2.8% of uninfected individuals met aFRP criteria (P = 0.01). After adjustment for other covariates, aFRP was associated with hospitalization (HR = 1.78; 95% confidence interval: 1.48 to 2.13) and mortality (HR = 1.75; 95% confidence interval: 1.28 to 2.40). C-statistics for the VACS Index for hospitalization (0.633) and for mortality (0.756) were higher than for aFRP (0.565 and 0.584, respectively). C-statistic for hospitalization improved modestly when VACS Index and aFRP were both included (0.646) and minimally for mortality (0.761). Conclusions: aFRP was independently associated with adverse health outcomes among HIV-infected and uninfected individuals. aFRP modestly improved prediction for hospitalization. However, the aFRP is rare among HIV-infected individuals with undetectable HIV-1 RNA. C1 [Akguen, Kathleen M.] VA Connecticut Healthcare Syst, Dept Internal Med & Gen Internal Med, West Haven, CT 06516 USA. [Akguen, Kathleen M.; Tate, Janet P.; Justice, Amy C.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Tate, Janet P.; Justice, Amy C.] VA Connecticut Healthcare Syst, Dept Internal Med, West Haven, CT USA. [Crothers, Kristina] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Crystal, Stephen] Rutgers State Univ, Inst Hlth Healthcare Policy & Aging Res, New Brunswick, NJ 08903 USA. [Leaf, David A.] Univ Calif Los Angeles, Sch Med, Dept Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. [Womack, Julie] Yale Univ, Sch Nursing, New Haven, CT 06536 USA. [Brown, Todd T.] Johns Hopkins Univ, Div Endocrinol Diabet & Metab, Baltimore, MD USA. [Oursler, Krisann K.] Univ Maryland SOM, VA Maryland Hlth Care Syst, Dept Med, Baltimore, MD USA. RP Akgun, KM (reprint author), VA Connecticut West Haven, 950 Campbell Ave,MS 11 ACSLG, West Haven, CT 06516 USA. EM kathleen.akgun@yale.edu OI Crothers, Kristina/0000-0001-9702-0371 FU Department of Veterans Affairs, Veterans Health Administration [V1CDA2012-20, I01 RX000667]; Association of Subspecialty Physicians; CHEST Foundation of the American College of Chest Physicians T. Franklin Williams Award; National Institute on Alcohol Abuse and Alcoholism [U24-AA020794, U01-AA020790, U10 AA013566]; National Institutes of Health and National Heart, Lung, and Blood Institute [R01 HL090342]; National Institutes of Health [K23 AG02489] FX K.M.A. is currently receiving a grant [VISN 1 Career Development Award (V1CDA2012-20)] from the Department of Veterans Affairs, Veterans Health Administration, and previously was supported with a grant from the Association of Subspecialty Physicians and CHEST Foundation of the American College of Chest Physicians T. Franklin Williams Award. A.C.J. is currently receiving a grant [U24-AA020794, U01-AA020790, and U10 AA013566-completed] from the National Institute on Alcohol Abuse and Alcoholism. K. C. was receiving a grant (R01 HL090342) from the National Institutes of Health and National Heart, Lung, and Blood Institute. K.K.O. is currently receiving a grant (I01 RX000667) from the Department of Veterans Affairs, Veterans Health Administration, and previously was supported with a grant (K23 AG02489) from the National Institutes of Health. The remaining authors have no funding or conflicts of interest to disclose. NR 37 TC 16 Z9 17 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 1 PY 2014 VL 67 IS 4 BP 397 EP 404 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AT2NR UT WOS:000344771900010 PM 25202921 ER PT J AU Lewis, MS McMillan, GP Hutter, M Folmer, RL Wilmington, D Casiana, L Fitzpatrick, M Lilly, DJ Bourdette, D Overs, S Cameron, M Fausti, S AF Lewis, M. Samantha McMillan, Garnett P. Hutter, Michele Folmer, Robert L. Wilmington, Debra Casiana, Linda Fitzpatrick, Mary Lilly, David J. Bourdette, Dennis Overs, Shannon Cameron, Michelle Fausti, Stephen TI Does Interferon Beta-1a Impact Pure-Tone Hearing Sensitivity Among Individuals With Multiple Sclerosis? SO JOURNAL OF NEUROSCIENCE NURSING LA English DT Article DE adverse effects; disease attributes; hearing; hearing loss; interferon beta-1a; multiple sclerosis; toxicology ID CHRONIC HEPATITIS-C; RIBAVIRIN COMBINATION THERAPY; PEGYLATED INTERFERON/RIBAVIRIN; AURAL ATTENUATION; OTOTOXICITY; PATIENT; THRESHOLDS; ALPHA; PEGINTERFERON; DEAFNESS AB Background: Previous studies reported that particular types of interferon medications might contribute to hearing loss in some patients. The package insert included in the original Food and Drug Administration application for intramuscular interferon beta-1a (Avonex) stated that some patients in the treatment group reported decreased hearing sensitivity. Objective: The purpose of the present investigation was to assess if individuals with multiple sclerosis (MS) taking intramuscular interferon beta-1a have significantly poorer hearing thresholds than those not currently using any disease-modifying therapies. Methods: This was a secondary analysis of data collected as part of two larger studies evaluating auditory function in patients with MS. The goal of this analysis was to determine if users of interferon beta-1a do not have significantly worse hearing thresholds than nonusers of disease-modifying therapies, after adjusting for potential confounders. A linear mixed model was fit to the audiometric thresholds of our subjects. This model included interferon beta-1a use, MS disease subtype, gender, test frequency, age, disease duration (number of years), and the Expanded Disability Status Scale score. Results and Conclusions: With all subjects included, there is insufficient evidence to say that intramuscular interferon-beta 1a is not ototoxic (in relation to nonuse of a disease-modifying therapy) at all frequencies tested except 3000 and 6000 Hz. After removing two influential subjects, the results indicated that there is statistical support for no ototoxic effect of intramuscular interferon beta-1a at test frequencies from 250 to 6000 Hz. There is insufficient evidence, however, to rule out an ototoxic effect at 8000 Hz. Future studies should further evaluate the effect of interferon on auditory function in patients with MS. Neuroscience nurses should monitor their patients' hearing throughout the course of treatment. C1 [Lewis, M. Samantha; McMillan, Garnett P.; Hutter, Michele; Folmer, Robert L.; Wilmington, Debra; Casiana, Linda; Lilly, David J.; Fausti, Stephen] Portland VA Med Ctr, NCRAR, Portland, OR 97239 USA. [Lewis, M. Samantha] Oregon Hlth & Sci Univ, Dept Otolarynol Head Neck Surg, Portland, OR 97201 USA. [Folmer, Robert L.; Wilmington, Debra; Fausti, Stephen] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA. [Fitzpatrick, Mary; Overs, Shannon; Cameron, Michelle] Portland VA Med Ctr, Neurol Serv, Portland, OR USA. [Lilly, David J.] Univ Iowa, Dept Otolaryngol Head & Neck Surg, Iowa City, IA 52242 USA. [Bourdette, Dennis] Portland VA Med Ctr, Multiple Sclerosis Ctr Excellence West, Portland, OR USA. [Bourdette, Dennis; Overs, Shannon; Cameron, Michelle; Fausti, Stephen] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Overs, Shannon] Novant Hlth Neurol Specialists, Charlotte, NC USA. RP Lewis, MS (reprint author), Portland VA Med Ctr, NCRAR, Portland, OR 97239 USA. EM Michele.Lewis3@med.va.gov FU U.S. Department of Veterans Affairs (VA) Rehabilitation Research and Development (RR&D) Service Merit Review grants [B2568R, C4488R]; VA RR&D Career Development Awards [C3293H, C3758V, C7067W, E7244-W]; VA RR&D National Center for Rehabilitative Auditory Research [C9230C]; Biogen Idec FX This work was supported by U.S. Department of Veterans Affairs (VA) Rehabilitation Research and Development (RR&D) Service Merit Review grants (#B2568R, #C4488R), VA RR&D Career Development Awards to the 1st (M. S. L.) author (#C3293H, #C3758V, #C7067W) and the 11th (M. C.) author (#E7244-W), and the VA RR&D National Center for Rehabilitative Auditory Research (#C9230C). In addition, some of the members of the study team were recognized with the Biogen Idec award for best poster presentation at the 2008 meeting of the Consortium of Multiple Sclerosis Centers in Denver, CO, which resulted in travel funds for the first author to attend the 2009 meeting The 9th (D. B.) and 10th (S. O.) authors of this article, also, have received honoraria for speaking, consultant fees, and/or educational grants from Biogen Idec. The 7th (M. F.) author now works for Biogen Idec. NR 64 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0888-0395 EI 1945-2810 J9 J NEUROSCI NURS JI J. Neurosci. Nurs. PD DEC PY 2014 VL 46 IS 6 BP 351 EP 360 DI 10.1097/JNN.0000000000000096 PG 10 WC Clinical Neurology; Nursing SC Neurosciences & Neurology; Nursing GA AT4XK UT WOS:000344945200010 PM 25365049 ER PT J AU Hage, FG AF Hage, Fadi G. TI Regadenoson for myocardial perfusion imaging: Is it safe? (vol 21, pg 871, 2014) SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Correction C1 [Hage, Fadi G.] Univ Alabama Birmingham, Div Cardiovasc Dis, Dept Med, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, AL USA. RP Hage, FG (reprint author), Univ Alabama Birmingham, Div Cardiovasc Dis, Dept Med, Lyons Harrison Res Bldg 314,1900 Univ BLVD, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI Hage, Fadi/0000-0002-1397-4942 NR 1 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD DEC PY 2014 VL 21 IS 6 BP 1266 EP 1266 DI 10.1007/s12350-014-9993-2 PG 1 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AT2GG UT WOS:000344750700026 ER PT J AU Minzenberg, MJ Yoon, JH Cheng, YA Carter, CS AF Minzenberg, Michael J. Yoon, Jong H. Cheng, Yaoan Carter, Cameron S. TI Modafinil Effects on Middle-Frequency Oscillatory Power During Rule Selection in Schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID INDEPENDENT COMPONENT ANALYSIS; INTERNEURON DIVERSITY SERIES; PREFRONTAL CORTEX; COGNITIVE CONTROL; WORKING-MEMORY; THETA OSCILLATIONS; LOCUS-COERULEUS; NETWORK OSCILLATIONS; BAND OSCILLATIONS; DOUBLE-BLIND AB Control-related cognitive processes such as rule selection are associated with cortical oscillations in the theta, alpha and, beta ranges, and modulated by catecholamine neurotransmission. Thus, a potential strategy for improving cognitive control deficits in schizophrenia would be to use pro-catecholamine pharmacological agents to augment these control-related oscillations. In a double-blind, placebo-controlled (within-subjects) study, we tested the effects of adjunctive single-dose modafinil 200 mg on rule-related 4-30 Hz oscillations in 23 stable schizophrenia patients, using EEG during cognitive control task performance. EEG data underwent time-frequency decomposition with Morlet wavelets to determine the power of 4-30 Hz oscillations. Modafinil (relative to placebo) enhanced oscillatory power associated with high-control rule selection in theta, alpha, and beta ranges, with modest effects during rule maintenance. Modafinil treatment in schizophrenia augments middle-frequency cortical oscillatory power associated with rule selection, and may subserve diverse subcomponent processes in proactive cognitive control. C1 [Minzenberg, Michael J.; Cheng, Yaoan] Univ Calif San Francisco, Dept Psychiat, San Francisco Sch Med, San Francisco, CA USA. [Minzenberg, Michael J.; Cheng, Yaoan] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Yoon, Jong H.] Stanford Univ, Sch Med, Dept Psychiat, Palo Alto, CA 94304 USA. [Yoon, Jong H.] Palo Alto Vet Affairs Med Ctr, Palo Alto, CA USA. [Carter, Cameron S.] Calif State Univ Sacramento, Davis Sch Med, Dept Psychiat, Sacramento, CA 95819 USA. [Carter, Cameron S.] Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. RP Minzenberg, MJ (reprint author), San Francisco VA Med Ctr, Outpatient Mental Hlth Serv, 116C,4150 Clement St, San Francisco, CA 94121 USA. EM Michael.minzenberg@ucsf.edu FU Clinical Scientist Development Award from the Doris Duke Charitable Foundation; Young Investigator award from NARSAD (Brain and Behavior Foundation); [5RO1 MH059883] FX This work was supported by a Clinical Scientist Development Award from the Doris Duke Charitable Foundation, and a Young Investigator award from NARSAD (Brain and Behavior Foundation), both to MJM, and 5RO1 MH059883 to CSC. The authors have no competing financial interests. NR 69 TC 2 Z9 2 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2014 VL 39 IS 13 BP 3018 EP 3026 DI 10.1038/npp.2014.155 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AT3KT UT WOS:000344834600010 PM 24964814 ER PT J AU Slade, EP Becker, KD AF Slade, Eric P. Becker, Kimberly D. TI Understanding Proximal-Distal Economic Projections of the Benefits of Childhood Preventive Interventions SO PREVENTION SCIENCE LA English DT Article DE Prevention; Proximal-distal modeling; Economic projection ID PERRY PRESCHOOL PROGRAM; COST-EFFECTIVENESS; FOLLOW-UP; SCHOOL; CRIME; METAANALYSIS; 1ST-GRADE; CHILDREN; VIOLENCE; HEALTH AB This paper discusses the steps and decisions involved in proximal-distal economic modeling, in which social, behavioral, and academic outcomes data for children may be used to inform projections of the economic consequences of interventions. Economic projections based on proximal-distal modeling techniques may be used in cost-benefit analyses when information is unavailable for certain long-term outcomes data in adulthood or to build entire cost-benefit analyses. Although examples of proximal-distal economic analyses of preventive interventions exist in policy reports prepared for governmental agencies, such analyses have rarely been completed in conjunction with research trials. The modeling decisions on which these prediction models are based are often opaque to policymakers and other end-users. This paper aims to illuminate some of the key steps and considerations involved in constructing proximal-distal prediction models and to provide examples and suggestions that may help guide future proximal-distal analyses. C1 [Slade, Eric P.] US Dept Vet Affairs, VA Capitol Healthcare Network VISN5 Mental Illnes, Educ & Clin Ctr, Baltimore, MD 21201 USA. [Slade, Eric P.; Becker, Kimberly D.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. RP Slade, EP (reprint author), US Dept Vet Affairs, VA Capitol Healthcare Network VISN5 Mental Illnes, Educ & Clin Ctr, 737 W Lombard St,Room 526, Baltimore, MD 21201 USA. EM eslade@psych.umaryland.edu FU NIMH NIH HHS [P30 MH086043] NR 44 TC 1 Z9 1 U1 3 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1389-4986 EI 1573-6695 J9 PREV SCI JI Prev. Sci. PD DEC PY 2014 VL 15 IS 6 BP 807 EP 817 DI 10.1007/s11121-013-0445-z PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AT3AN UT WOS:000344806700004 PM 24337979 ER PT J AU Ford, JM AF Ford, Judith M. TI Decomposing P300 to identify its genetic basis SO PSYCHOPHYSIOLOGY LA English DT Article DE EEG; P300 amplitude; Genetic basis; SNPs ID SCHIZOPHRENIA; AMPLITUDE; ENDOPHENOTYPES; DISORDERS; RISK AB In this commentary, I explore reasons why it has been difficult to associate P300 amplitude with a gene or a single nucleotide polymorphism (SNP). I suggest we decompose P300 into the factors that contribute to it to get better traction on its genetic basis. Specifically, I note that we can improve the measurement of P300 to remove state-dependent contributions by including more than one measurement occasion; we can identify and extract the neural components contributing to P300 amplitude by estimating EEG power in specific bands of the P300; we can adjust P300 for single-trial variability; we can extract single-trial variability; and we can refine the tasks to isolate the separate psychological processes that P300 reflects. In the end, each of these factors that contribute to the conglomerate P300 may be a separate endophenotype mapping onto a separate SNP or gene. C1 [Ford, Judith M.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Ford, Judith M.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Ford, JM (reprint author), San Francisco VA Med Ctr, Psychiat Serv 116D, 4150 Clement St, San Francisco, CA 94121 USA. EM Judith.Ford@ucsf.edu NR 20 TC 2 Z9 2 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD DEC PY 2014 VL 51 IS 12 SI SI BP 1325 EP 1326 DI 10.1111/psyp.12353 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA AT2SL UT WOS:000344785500014 PM 25387713 ER PT J AU Guerrero-Berroa, E Kluger, A Schmeidler, J Sailor, K Lizardi, H Golomb, J Ferris, S Reisberg, B AF Guerrero-Berroa, Elizabeth Kluger, Alan Schmeidler, James Sailor, Kevin Lizardi, Humberto Golomb, James Ferris, Steven Reisberg, Barry TI Neuropsychological and Neuropsychiatric Prediction of Global Cognitive Status Among Older Spanish-Speaking Hispanics and English-Speaking Whites SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE neuropsychology; neuropsychiatric symptoms; depression; cognitive status; dementia; Hispanic elderly ID LATE-LIFE DEPRESSION; PRIMARY DEGENERATIVE DEMENTIA; ALZHEIMERS-DISEASE; TEST-PERFORMANCE; DETERIORATION SCALE; MEXICAN-AMERICANS; MEMORY IMPAIRMENT; AFRICAN-AMERICAN; ELDERLY PERSONS; PRIMARY-CARE AB Background: Neuropsychological and depression measures have been found to predict cognitive functioning. We compared these associations among whites and Spanish-speaking Hispanics. Methods: Fifty-two pairs of whites and Hispanics were matched demographically and clinically in a cross-sectional study. Hierarchical regression analyses predicted Global Deterioration Scale (GDS) rating by baseline neuropsychological tests and depression symptoms. Results: Neuropsychological tests predicted GDS better in whites; depression symptomsspecifically retardationpredicted well in Hispanics but not whites. Immediate recall of the New York University (NYU)-Paragraph Test and the Retardation item of the Hamilton Depression Rating Scale were associated with GDS in Hispanics and delayed recall of the NYU-Paragraph Test and Wechsler Adult Intelligence Scale-Digit Symbol in whites. Neuropsychological tests and depression symptoms predicted GDS differently in Hispanics and whites. Discussion: These results suggest that other measures should be considered to increase the predictive accuracy of neuropsychological tests when assessing cognitive status in Spanish-speaking Hispanics. Additional studies of specific ethnic/racial and sociodemographic subgroups are warranted. C1 [Guerrero-Berroa, Elizabeth; Schmeidler, James] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Kluger, Alan; Sailor, Kevin; Lizardi, Humberto] CUNY Herbert H Lehman Coll, Dept Psychol, New York, NY USA. [Kluger, Alan; Golomb, James; Ferris, Steven; Reisberg, Barry] NYU, Langone Med Ctr, Comprehens Ctr Brain Aging, Alzheimers Dis Ctr, New York, NY USA. RP Guerrero-Berroa, E (reprint author), James J Peters VA Med Ctr, 130 West Kingsbridge Rd,Room 1F-01, Bronx, NY 10468 USA. EM elizabeth.guerrero-berroa@mssm.edu OI Reisberg, Barry/0000-0002-9104-7423; Ferris, Steven/0000-0001-8641-6223 FU NIH [S06 GM 08225, 12, P30 AG 08051, AG-R01-03051, MH R29 44697]; National Science Foundation/ Alliance for Graduate Education and the Professoriate [HRD 0450360] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by NIH grants S06 GM 08225 (Project 12); P30 AG 08051; AG-R01-03051; MH R29 44697; and the National Science Foundation/ Alliance for Graduate Education and the Professoriate (HRD 0450360). NR 64 TC 0 Z9 0 U1 2 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 EI 1552-5708 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD DEC PY 2014 VL 27 IS 4 BP 266 EP 275 DI 10.1177/0891988714532020 PG 10 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA AS9MW UT WOS:000344567700006 PM 24759088 ER PT J AU Sumner, JA Pietrzak, RH Danielson, CK Adams, ZW Ruggiero, KJ AF Sumner, Jennifer A. Pietrzak, Robert H. Danielson, Carla Kmett Adams, Zachary W. Ruggiero, Kenneth J. TI Elucidating dimensions of posttraumatic stress symptoms and their functional correlates in disaster-exposed adolescents SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Posttraumatic stress disorder; Disasters; Adolescents; Dysphoric arousal model; Confirmatory factor analysis ID CONFIRMATORY FACTOR-ANALYSIS; DISORDER SYMPTOMS; FACTORIAL INVARIANCE; EARTHQUAKE SURVIVORS; DYSPHORIC AROUSAL; 5-FACTOR MODEL; PTSD; SAMPLE; VETERANS; CHILDREN AB The aim of this study was to elucidate the dimensional structure of posttraumatic stress disorder (PTSD) and potential moderators and functional correlates of this structure in disaster-affected adolescents. A population-based sample of 2000 adolescents aged 12-17 years (M = 14.5 years; 51% female) completed interviews on post-tornado PTSD symptoms, substance use, and parent adolescent conflict between 4 and 13 months (M = 8.8, SD = 2.6) after tornado exposure. Confirmatory factor analyses revealed that all models fit well but a 5-factor dysphoric arousal model provided a statistically significantly better representation of adolescent PTSD symptoms compared to 4-factor dysphoria and emotional numbing models. There was evidence of measurement invariance of the dysphoric arousal model across gender and age, although girls and older adolescents aged 15-17 years had higher mean scores than boys and younger adolescents aged 12-14 years, respectively, on some PTSD dimensions. Differential magnitudes of association between PTSD symptom dimensions and functional correlates were observed, with emotional numbing symptoms most strongly positively associated with problematic substance use since the tornado, and dysphoric arousal symptoms most strongly positively associated with parent-adolescent conflict; both correlations were significantly larger than the corresponding correlations with anxious arousal. Taken together, these results suggest that the dimensional structure of tornado-related PTSD symptomatology in adolescents is optimally characterized by five separate clusters of re-experiencing, avoidance, numbing, dysphoric arousal, and anxious arousal symptoms, which showed unique associations with functional correlates. Findings emphasize that PTSD in disaster-exposed adolescents is not best conceptualized as a homogenous construct and highlight potential differential targets for post-disaster assessment and intervention. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Sumner, Jennifer A.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. [Pietrzak, Robert H.] Natl Ctr Posttraumat Stress Disorder, Vet Affairs Connecticut Healthcare Syst, Clin Neurosci Div, West Haven, CT 06516 USA. [Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA. [Danielson, Carla Kmett; Adams, Zachary W.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Ruggiero, Kenneth J.] Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA. [Ruggiero, Kenneth J.] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Sumner, JA (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, 722 W 168th St, New York, NY 10032 USA. EM js4456@columbia.edu FU National Institute of Mental Health [R01-MH081056, T32-MH18869, R21-MH086313]; National Institute on Drug Abuse [R01-DA031285] FX This work was supported by National Institute of Mental Health grants R01-MH081056, T32-MH18869, R21-MH086313 and National Institute on Drug Abuse grant R01-DA031285. The funding sources did not have any involvement in study design, data collection, analysis, or interpretation, writing of the manuscript, or the decision to submit the manuscript for publication. NR 48 TC 7 Z9 7 U1 4 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD DEC PY 2014 VL 59 BP 85 EP 92 DI 10.1016/j.jpsychires.2014.09.003 PG 8 WC Psychiatry SC Psychiatry GA AS3WJ UT WOS:000344205700012 PM 25248557 ER PT J AU Thase, ME AF Thase, Michael E. TI Using biomarkers to predict treatment response in major depressive disorder: evidence from past and present studies SO DIALOGUES IN CLINICAL NEUROSCIENCE LA English DT Article DE biomarker; antidepressant; cognitive behavior therapy; prediction; treatment response AB Major depressive disorder (MDD) is a heterogeneous condition with a variable response to a wide range of treatments. Despite intensive efforts, no biomarker has been identified to date that can reliably predict response or nonresponse to any form of treatment, nor has one been identified that can be used to identify those at high risk of developing treatment-resistant depression (ie, nonresponse to a sequence of treatments delivered for adequate duration and intensity). This manuscript reviews some past areas of research that have proved informative, such as studies using indexes of hypercortisolism or sleep disturbance, and more recent research findings using measures of inflammation and different indicators of regional cortical activation to predict treatment response. It is concluded that, although no method has yet been demonstrated to be sufficiently accurate to be applied in clinical practice, progress has been made. It thus seems likely that-at some point in the not-too-distant future-it will be possible to prospectively identify, at least for some MDD patients, the likelihood of response or nonresponse to cognitive therapy or various antidepressant medications. (C) 2014, AICH - Servier Research Group C1 [Thase, Michael E.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Thase, Michael E.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. RP Thase, ME (reprint author), Dept Psychiat, Mood & Anxiety Disorders Sect, 3535 Market St,Suite 670, Philadelphia, PA 19104 USA. EM thase@mail.med.upenn.edu FU Agency for Healthcare Research and Quality; Eli Lilly Company; National Institute of Mental Health; Otsuka Pharmaceuticals; PharmaNeuroboost [03/13]; Roche [06/13] FX Dr Thase has provided scientific consultation to Alkermes, Astra-Zeneca, Bristol-Myers Squibb Company, Eli Lilly & Company, Forest Pharmaceuticals, Inc, Gerson Lehman Group, GlaxoSmithKline, Guidepoint Global, H. Lundbeck A/S, MedAvante, Inc, Merck and Co. Inc, Neronetics, Inc, Novartis, Otsuka, Ortho-McNeil Pharmaceuticals, Pfizer (formerly Wyeth-Ayerst Laboratories), Shire US Inc, Sunovion Pharmaceuticals, Inc, and Takeda. Dr Thase receives grant funding from the Agency for Healthcare Research and Quality, Eli Lilly & Company, National Institute of Mental Health, Otsuka Pharmaceuticals, PharmaNeuroboost (ended 03/13), and Roche (ended 06/13). He has equity holdings in MedAvante, Inc and receives royalty income from American Psychiatric Foundation, Inc, Guilford Publications, Herald House, Oxford University Press, and W.W. Norton & Company. His wife is employed as the Group Scientific Director for Peloton Advantage which does business with Pfizer. NR 29 TC 7 Z9 7 U1 2 U2 3 PU INST CONFERENCE HIPPOCRATE PI SURESNESS-CEDEX PA 50 RUE CARNOT, SURESNESS-CEDEX, 92284, FRANCE SN 1294-8322 EI 1958-5969 J9 DIALOGUES CLIN NEURO JI Dialogues Clin. Neurosci. PD DEC PY 2014 VL 16 IS 4 BP 539 EP 544 PG 6 WC Neurosciences SC Neurosciences & Neurology GA V45QS UT WOS:000209831700008 PM 25733957 ER PT J AU Elwy, AR Johnston, JM Bormann, JE Hull, A Taylor, SL AF Elwy, A. Rani Johnston, Jennifer M. Bormann, Jill E. Hull, Amanda Taylor, Stephanie L. TI A Systematic Scoping Review of Complementary and Alternative Medicine Mind and Body Practices to Improve the Health of Veterans and Military Personnel SO MEDICAL CARE LA English DT Review DE complementary and alternative medicine (CAM); veterans; military; systematic review; methods AB Background: Meditation, imagery, acupuncture, and yoga are the most frequently offered mind and body practices in the Department of Veterans Affairs. Yet, the research on mind and body practices has been critiqued as being too limited in evidence and scope to inform clinical treatment. Objectives: We conducted a systematic scoping review of mind and body practices used with veterans or active duty military personnel to identify gaps in the literature and make recommendations for future primary research. Research Design: Following systematic literature review methodology, we searched 5 databases using 27 different National Center for Complementary and Alternative Medicine-defined mind and body practices as text words, keywords, and MeSH terms through June 30, 2014. We also conducted handsearches of 4 previous reviews. Subjects: Active duty military members or veterans 18 years or older participating in mind and body practice interventions globally. Measures: Data were extracted from studies meeting 5 inclusion criteria. The quality of randomized controlled trials (RCTs) was assessed using an existing checklist. Results: Of 1819 studies identified, 89 interventions (50 RCTs) published between 1976 and 2014, conducted in 9 countries, using 152 different measures to assess 65 health and well-being outcomes met our inclusion criteria. Most interventions took place in the United States (n = 78). Meditation practices (n = 25), relaxation techniques including imagery (n = 20), spinal manipulation including physical therapy (n = 16), and acupuncture (n = 11) were the most frequently studied practices. Methodological quality of most RCTs was rated poorly. Conclusions: Meditation and acupuncture practices are among the most frequently offered and studied mind and body practices. Future research should include yoga as it is currently understudied among veterans and military personnel. A repository of mind and body intervention outcome measures may further future research efforts, as would conducting pragmatic trials and more robust RCTs. C1 [Elwy, A. Rani] Edith Nourse Rogers Mem Vet Hosp, Ctr Healthcare Org & Implementat Res, 200 Springs Rd,Mailstop 152, Bedford, MA 01730 USA. [Elwy, A. Rani] Boston Univ, Sch Med, Dept Hlth Policy & Management, Boston, MA 02118 USA. [Johnston, Jennifer M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Bormann, Jill E.] VA San Diego Healthcare Syst, Ctr Excellence Stress & Mental Hlth, San Diego, CA USA. [Bormann, Jill E.] Univ San Diego, Hahn Sch Nursing & Hlth Sci, San Diego, CA 92110 USA. [Hull, Amanda] Washington DC VA Med Ctr, Integrat Hlth & Wellness Program, War Related Injuries & Illness Ctr, Washington, DC USA. [Taylor, Stephanie L.] Greater Los Angeles VA Med Ctr, Ctr Study Healthcare Innovat Implementat & Policy, North Hills, CA USA. [Taylor, Stephanie L.] RAND Corp, Santa Monica, CA USA. RP Elwy, AR (reprint author), Edith Nourse Rogers Mem Vet Hosp, Ctr Healthcare Org & Implementat Res, 200 Springs Rd,Mailstop 152, Bedford, MA 01730 USA. EM rani.elwy@va.gov FU Department of Veterans Affairs, Health Services Research and Development Service [SDR 13-424]; National Institute of Mental Health [R25 MH080916-01A2]; Department of Veterans Affairs, Health Services Research & Development Service, Quality Enhancement Research Initiative FX Supported by the Department of Veterans Affairs, Health Services Research and Development Service, SDR 13-424.; A.R.E. is also an investigator with the Implementation Research Institute, at the George Warren Brown School of Social Work, Washington University in St. Louis, through an award from the National Institute of Mental Health (R25 MH080916-01A2) and the Department of Veterans Affairs, Health Services Research & Development Service, Quality Enhancement Research Initiative. The remaining authors declare no conflict of interest. NR 127 TC 6 Z9 6 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD DEC PY 2014 VL 52 IS 12 SU 5 BP S70 EP S82 PG 13 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA V45TM UT WOS:000209838900013 PM 25397827 ER PT J AU Goldstein, JN Long, JA Arevalo, D Ibrahim, SA Mao, JJ AF Goldstein, Jennifer N. Long, Judith A. Arevalo, Doris Ibrahim, Said A. Mao, Jun J. TI US Veterans Use Vitamins and Supplements as Substitutes for Prescription Medication SO MEDICAL CARE LA English DT Article AB Background: Vitamins and supplements are the most commonly used form of complementary and alternative medicine in the United States. Growing research suggests that patients substitute vitamins and supplements for their prescription medications. The reasons might include cost of prescription medications and discordant patient and doctor health belief systems. Objectives: To investigate the prevalence of substitution of vitamins and supplements for prescription medications among veterans who receive care in the VA health care system and whether substitution is associated with prescription rationing due to cost, treatment beliefs, or distrust of the health system. Research Design: Cross-sectional observational survey. Subjects: Primary care patients (n = 275) at the Philadelphia VA Medical Center. Measures: Medication substitution, prescription medication rationing, treatment beliefs, and health system distrust were measured with structured instruments. Multivariate logistic regression was performed with substitution as the dependent variable. Results: A significant number of primary care patients in the VA system use vitamins and supplements 206 (75%). The prevalence of medication substitution is high 48 (18%). Medication substitution is strongly associated with prescription rationing due to cost (adjusted odds ratio 6.3, 95% confidence interval: 2.0-19.5, P = 0.001). Similarly, greater belief in complementary and alternative approaches to care positively predicts medication substitution (adjusted odds ratio 1.08, 95% confidence interval: 1.01-1.15, P = 0.011). There is no significant association between health system distrust and likelihood of medication substitution. Conclusions: Medication substitution is prevalent in this sample of inner city primary care patients who receive care in the VA system. Cost of prescriptions and belief in the value of complementary and alternative approaches to care appear to be associated with this patient-driven treatment decision. C1 [Goldstein, Jennifer N.] Christiana Hosp, Dept Med, Ammon Bldg,Suite 2E72A,4755 Ogletown Stanton Rd, Newark, DE 19718 USA. [Long, Judith A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Long, Judith A.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Arevalo, Doris] Univ Illinois, Urbana, IL 61801 USA. [Ibrahim, Said A.] Philadelphia VA Med Ctr, Ctr Hlth Equ & Promot, Philadelphia, PA USA. [Mao, Jun J.] Univ Penn, Dept Family & Community Med, Philadelphia, PA 19104 USA. RP Goldstein, JN (reprint author), Christiana Hosp, Dept Med, Ammon Bldg,Suite 2E72A,4755 Ogletown Stanton Rd, Newark, DE 19718 USA. EM jennifer.n.goldstein@gmail.com FU Ruth L. Kirschstein National Research Service Award (NRSA) [T32HP10026] FX The Ruth L. Kirschstein National Research Service Award (NRSA): Grant #: T32HP10026 funded the fellowship of J.N.G. and therefore this research. NR 24 TC 1 Z9 1 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD DEC PY 2014 VL 52 IS 12 SU 5 BP S65 EP S69 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA V45TM UT WOS:000209838900012 PM 25397826 ER PT J AU Kearney, DJ McManus, C Malte, CA Martinez, ME Felleman, B Simpson, TL AF Kearney, David J. McManus, Carolyn Malte, Carol A. Martinez, Michelle E. Felleman, Benjamin Simpson, Tracy L. TI Loving-Kindness Meditation and the Broaden-and-Build Theory of Positive Emotions Among Veterans Disorder SO MEDICAL CARE LA English DT Article DE emotions; meditation; social support; post-traumatic stress disorder (PTSD); veterans AB Background: Loving-kindness meditation (LKM) is a practice intended to enhance feelings of kindness and compassion for self and others. Objectives: To assess whether participation in a 12-week course of LKM for veterans with posttraumatic stress disorder (PTSD) is associated with improved positive emotions, decentering, and personal resources. Research Design: In an open-pilot trial, veterans were assessed at baseline, after the course, and 3 months later. Effect sizes were calculated from baseline to each follow-up point for each construct of interest. Measures were chosen as an initial investigation of the broaden-and-build theory of positive emotions. Subjects: A total of 42 veterans with active PTSD (40% female) participated. Measures: Emotions, decentering, psychological wellbeing including autonomy, environmental mastery, personal growth, positive relations, purpose in life, self-acceptance, and sense of social support were measured at each time point. Results: Significant increases in unactivated pleasant (d = 0.73), but not activated pleasant, emotions were found over time. Activated and unactivated unpleasant emotions decreased over time (d = -0.69 and -0.53, respectively). There were also increases in environmental mastery (d = 0.61), personal growth (d = 0.54), purpose in life (d = 0.71), self-acceptance (d = 0.68), and decentering (d = 0.96) at 3-month follow-up. Conclusions: Overall, positive emotions increased, and enhancement of personal resources occurred over time. Further investigation of LKM for PTSD is warranted. C1 [Kearney, David J.] VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [Kearney, David J.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [McManus, Carolyn] Swedish Med Ctr, Dept Phys Therapy, Seattle, WA USA. [Malte, Carol A.] CESATE, Seattle, WA USA. [Martinez, Michelle E.; Felleman, Benjamin] VA Puget Sound Hlth Care Syst, Dept Res & Dev, Seattle, WA USA. [Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Dept Mental Hlth, Seattle, WA USA. [Simpson, Tracy L.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Kearney, DJ (reprint author), VA Puget Sound Hlth Care Syst, 1660 South Columbian Way,S-111-GI, Seattle, WA 98108 USA. EM david.kearney@va.gov NR 50 TC 5 Z9 5 U1 4 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD DEC PY 2014 VL 52 IS 12 SU 5 BP S32 EP S38 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA V45TM UT WOS:000209838900007 PM 25397820 ER PT J AU Lisi, AJ Khorsan, R Smith, MM Mittman, BS AF Lisi, Anthony J. Khorsan, Raheleh Smith, Monica M. Mittman, Brian S. TI Variations in the Implementation and Characteristics of Chiropractic Services in VA SO MEDICAL CARE LA English DT Article DE Department of Veterans Affairs; chiropractic; health services research; rehabilitation services; complementary therapies; program evaluation AB Background: In 2004, the US Department of Veterans Affairs expanded its delivery of chiropractic care by establishing onsite chiropractic clinics at select facilities across the country. Systematic information regarding the planning and implementation of these clinics and describing their features and performance is lacking. Objectives: To document the planning, implementation, key features and performance of VA chiropractic clinics, and to identify variations and their underlying causes and key consequences as well as their implications for policy, practice, and research on the introduction of new clinical services into integrated health care delivery systems. Research Design, Methods, and Subjects: Comparative case study of 7 clinics involving site visit-based and telephone-based interviews with 118 key stakeholders, including VA clinicians, clinical leaders and administrative staff, and selected external stakeholders, as well as reviews of key documents and administrative data on clinic performance and service delivery. Interviews were recorded, transcribed, and analyzed using a mixed inductive (exploratory) and deductive approach. Results and Conclusions: Interview data revealed considerable variations in clinic planning and implementation processes and clinic features, as well as perceptions of clinic performance and quality. Administrative data showed high variation in patterns of clinic patient care volume over time. A facility's initial willingness to establish a chiropractic clinic, along with a higher degree of perceived evidence-based and collegial attributes of the facility chiropractor, emerged as key factors associated with higher and more consistent delivery of chiropractic services and higher perceived quality of those services. C1 [Lisi, Anthony J.] Vet Hlth Adm, Chiropract Serv, Rehabil Serv, Washington, DC USA. [Lisi, Anthony J.] Vet Hlth Adm, Chiropract Serv, Prosthet Serv, Washington, DC USA. [Lisi, Anthony J.] VA Connecticut Healthcare Syst, Chiropract Serv, 950 Campbell Ave, West Haven, CT 06516 USA. [Khorsan, Raheleh] Samueli Inst, Mil Med Res Program, Corona Del Mar, CA USA. [Khorsan, Raheleh; Smith, Monica M.; Mittman, Brian S.] VA Greater Los Angeles Healthcare Syst, VA Ctr Implementat Practice & Res Support, Los Angeles, CA USA. [Mittman, Brian S.] Kaiser Permanente Southern Calif, Dept Res & Evaluat, Pasadena, CA USA. RP Lisi, AJ (reprint author), VA Connecticut Healthcare Syst, Chiropract Serv, 950 Campbell Ave, West Haven, CT 06516 USA. EM anthony.lisi@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research Development Service; Samueli Institute; US Army Medical Research and Materiel Command [W81XWH-06-1-0279]; National Institutes of Health National Center for Complementary and Alternative Medicine (NIH-NCCAM) [K01-AT002391] FX This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research Development Service. In addition, this work was supported, in part, by a grant to Brian S. Mittman by the Samueli Institute. This grant is supported by the US Army Medical Research and Materiel Command under Award no. W81XWH-06-1-0279. M.M.S. was supported in this work by Grant no. K01-AT002391, a grant from National Institutes of Health National Center for Complementary and Alternative Medicine (NIH-NCCAM). NR 15 TC 2 Z9 2 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD DEC PY 2014 VL 52 IS 12 SU 5 BP S97 EP S104 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA V45TM UT WOS:000209838900016 PM 25397831 ER PT J AU Reinhard, MJ Nassif, TH Bloeser, K Dursa, EK Barth, SK Benetato, B Schneiderman, A AF Reinhard, Matthew J. Nassif, Thomas H. Bloeser, Katharine Dursa, Erin K. Barth, Shannon K. Benetato, Bonnie Schneiderman, Aaron TI CAM Utilization Among OEF/OIF Veterans Findings From the National Health Study for a New Generation of US Veterans SO MEDICAL CARE LA English DT Article DE complementary therapies; alternative medicine; veterans health; health surveys; population characteristics; CAM AB Background: Complementary and alternative medicine (CAM) is increasingly seen as an adjunct to traditional plans of care. This study utilized a representative sample of Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) veterans and OEF/OIF-era veterans to explore the prevalence and characteristics of CAM users. Research Design: The National Health Study for a New Generation of US Veterans (NewGen) is a longitudinal health study of a population-based cohort of OEF/OIF (deployed) and OEF/OIF-era (nondeployed) veterans. Data from the 2009-2011 NewGen survey (n = 20,563) were analyzed to determine prevalence of CAM use by demographic and military characteristics, the types of CAM modalities used, and where the modalities were sought. Results were weighted to the entire population of OEF/OIF and OEF/OIF-era veterans. Results: There was no statistically significant association between CAM use and deployment. Those who used Department of Veterans Affairs (VA) health care after separation were more likely to be CAM users compared with those who did not use VA care; however, the majority of veterans using CAM are using it outside the VA health care system. Massage was the most prevalent CAM modality followed by chiropractic treatment; males were less likely to use CAM than women. Conclusions: CAM modalities are being utilized by OEF/OIF veterans for health problems mainly outside the VA. Policy-makers should determine appropriate use of these modalities. C1 [Reinhard, Matthew J.; Nassif, Thomas H.; Bloeser, Katharine] Washington DC Vet Affairs Med Ctr, WRIISC, Washington, DC USA. [Reinhard, Matthew J.] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA. [Nassif, Thomas H.] Amer Univ, Sch Educ Teaching & Hlth, Washington, DC 20016 USA. [Dursa, Erin K.; Barth, Shannon K.; Schneiderman, Aaron] US Dept Vet Affairs, Off Publ Hlth, Post Deployment Hlth, Program Epidemiol, Washington, DC USA. [Benetato, Bonnie] Vet Affairs Greenville NC CBOC, Greenville, NC USA. [Benetato, Bonnie] East Carolina Univ, Coll Nursing, Greenville, NC USA. RP Reinhard, MJ (reprint author), Vet Affairs Med Ctr, War Related Illness & Injury Study Ctr, Room 3B 203,Mail Stop 127,50 Irving St NW, Washington, DC 20422 USA. EM matthew.reinhard@va.gov FU Department of Veterans Affairs Office of Public Health; War Related Illness and Injury Study Center FX Supported by the Department of Veterans Affairs Office of Public Health and the War Related Illness and Injury Study Center. NR 50 TC 4 Z9 4 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD DEC PY 2014 VL 52 IS 12 SU 5 BP S45 EP S49 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA V45TM UT WOS:000209838900009 PM 25397822 ER PT J AU Serpa, JG Taylor, SL Tillisch, K AF Serpa, J. Greg Taylor, Stephanie L. Tillisch, Kirsten TI Mindfulness-based Stress Reduction (MBSR) Reduces Anxiety, Depression, and Suicidal Ideation in Veterans SO MEDICAL CARE LA English DT Article DE mindfulness; meditation; veterans; depression; anxiety; pain; suicidal ideation AB Introduction: Anxiety, depression, and pain are major problems among veterans, despite the availability of standard medical options within the Veterans Health Administration. Complementary and alternative approaches for these symptoms have been shown to be appealing to veterans. One such complementary and alternative approach is mindfulness-based stress reduction (MBSR), a brief course that teaches mindfulness meditation with demonstrated benefits for mood disorders and pain. Methods: We prospectively collected data on MBSR's effectiveness among 79 veterans at an urban Veterans Health Administration medical facility. The MBSR course had 9 weekly sessions that included seated and walking meditations, gentle yoga, body scans, and discussions of pain, stress, and mindfulness. Pre-MBSR and post-MBSR questionnaires investigating pain, anxiety, depression, suicidal ideation, and physical and mental health functioning were obtained and compared for individuals. We also conducted a mediation analysis to determine whether changes in mindfulness were related to changes in the other outcomes. Results: Significant reductions in anxiety, depression, and suicidal ideation were observed after MBSR training. Mental health functioning scores were improved. Also, mindfulness interacted with other outcomes such that increases in mindfulness were related to improvements in anxiety, depression, and mental health functionality. Pain intensity and physical health functionality did not show improvements. Discussion: This naturalistic study in veterans shows that completing an MBSR program can improve symptoms of anxiety and depression, in addition to reducing suicidal ideations, all of which are of critical importance to the overall health of the patients. C1 [Serpa, J. Greg; Taylor, Stephanie L.; Tillisch, Kirsten] Vet Adm Greater Los Angeles, Los Angeles, CA USA. [Serpa, J. Greg] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA USA. [Taylor, Stephanie L.] RAND Corp, Santa Monica, CA USA. [Tillisch, Kirsten] Univ Calif Los Angeles, David Geffen Sch Med, Oppenheimer Ctr Neurobiol Stress, Los Angeles, CA 90095 USA. RP Serpa, JG (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd 116B, Los Angeles, CA 90073 USA. EM john.serpa@va.gov FU VA Office of Patient Centered Care & Cultural Transformation FX The authors thank Sandy Robertson RN, MSN, PH-CNS for her support in the delivery of MBSR and the preparation of this manuscript and the VA Office of Patient Centered Care & Cultural Transformation for funding to provide MBSR and prepare the manuscript. We also would like to thank Christiane Wolf, MD, PhD, lead consultant of VA-CALM and Insight LA MBSR teacher trainer as well as the co-facilitators of the MBSR classes: Najwa Culver, PhD; Sarah Duman, PhD; Sara Gilbert, PhD; Morgan Kay, PhD; Jeanette Lantz, PhD; Shirley Pakdaman, Psy. D; Nissa Perez, MD; Debra Sobol, PhD. We also grateful to Alexis Huynh, PhD; Michele Solloway, PhD; and Nui Brown MA for their assistance. NR 38 TC 11 Z9 11 U1 7 U2 26 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD DEC PY 2014 VL 52 IS 12 SU 5 BP S19 EP S24 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA V45TM UT WOS:000209838900005 PM 25397818 ER PT J AU Taylor, SL Elwy, AR AF Taylor, Stephanie L. Elwy, A. Rani TI Complementary and Alternative Medicine for US Veterans and Active Duty Military Personnel Promising Steps to Improve Their Health SO MEDICAL CARE LA English DT Editorial Material C1 [Taylor, Stephanie L.] Greater Los Angeles VA Healthcare Syst, Ctr Study Healthcare Innovat Implementat & Policy, 16111 Plummer St,Mailstop 152, North Hills, CA 91343 USA. [Elwy, A. Rani] Edith Nourse Rogers Mem Vet Hosp, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. [Elwy, A. Rani] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. RP Taylor, SL (reprint author), Greater Los Angeles VA Healthcare Syst, Ctr Study Healthcare Innovat Implementat & Policy, 16111 Plummer St,Mailstop 152, North Hills, CA 91343 USA. EM stephanie.taylor8@va.gov FU Department of Veterans Affairs, Office of Patient Centered Care and Cultural Transformation FX Funding for this research was provided by the Department of Veterans Affairs, Office of Patient Centered Care and Cultural Transformation. NR 72 TC 2 Z9 2 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD DEC PY 2014 VL 52 IS 12 SU 5 BP S1 EP S4 PG 4 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA V45TM UT WOS:000209838900001 PM 25397816 ER PT J AU Shukla, S Meeran, SM Katiyar, SK AF Shukla, Samriddhi Meeran, Syed M. Katiyar, Santosh K. TI Epigenetic regulation by selected dietary phytochemicals in cancer chemoprevention SO CANCER LETTERS LA English DT Review DE Epigenetics; Phytochemicals; DNA methylation; Histone deacetylation; Cancer ID TUMOR-SUPPRESSOR GENES; GREEN TEA POLYPHENOL; HISTONE DEACETYLASE INHIBITORS; MOUSE ERYTHROLEUKEMIA-CELLS; FACTOR-KAPPA-B; BREAST-CANCER; DNA METHYLATION; PROSTATE-CANCER; SKIN-CANCER; PREVENTS PHOTOCARCINOGENESIS AB The growing interest in cancer epigenetics is largely due to the reversible nature of epigenetic changes which tend to alter during the course of carcinogenesis. Major epigenetic changes including DNA methylation, chromatin modifications and miRNA regulation play important roles in tumorigenic process. There are several epigenetically active synthetic molecules such as DNA methyltransferase (DNMTs) and histone deacetylases (HDACs) inhibitors, which are either approved or, are under clinical trials for the treatment of various cancers. However, most of the synthetic inhibitors have shown adverse side effects, narrow in their specificity and also expensive. Hence, bioactive phytochemicals, which are widely available with lesser toxic effects, have been tested for their role in epigenetic modulatory activities in gene regulation for cancer prevention and therapy. Encouragingly, many bioactive phytochemicals potentially altered the expression of key tumor suppressor genes, tumor promoter genes and oncogenes through modulation of DNA methylation and chromatin modification in cancer. These bioactive phytochemicals either alone or in combination with other phytochemicals showed promising results against various cancers. Here, we summarize and discuss the role of some commonly investigated phytochemicals and their epigenetic targets that are of particular interest in cancer prevention and cancer therapy. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Shukla, Samriddhi; Meeran, Syed M.] CSIR, Cent Drug Res Inst, Canc Epigenet Lab, Div Endocrinol, Lucknow 226021, Uttar Pradesh, India. [Katiyar, Santosh K.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. RP Katiyar, SK (reprint author), Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU National Institutes of Health/NCI [CA140832, CA140197]; Veterans Administration Merit Review Award [1I01BX001410]; Council of Scientific and Industrial Research (CSIR), Government of India, India [EpiHeD (BSC0118), UNDO (BSC0103), BioPROS (BSC0106)] FX The work reported from Dr. Katiyar's laboratory was supported by National Institutes of Health/NCI (CA140832, CA140197) and Veterans Administration Merit Review Award (1I01BX001410). The work reported from Dr. Meeran's laboratory was supported in part by grants from the Council of Scientific and Industrial Research (CSIR), Government of India, India network grants-EpiHeD (BSC0118), UNDO (BSC0103), and BioPROS (BSC0106). CSIR-CDRI communication #8790. The content of this article does not necessarily reflect the views or policies of the funding sources. NR 109 TC 27 Z9 27 U1 1 U2 42 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 EI 1872-7980 J9 CANCER LETT JI Cancer Lett. PD DEC 1 PY 2014 VL 355 IS 1 BP 9 EP 17 DI 10.1016/j.canlet.2014.09.017 PG 9 WC Oncology SC Oncology GA AR7TO UT WOS:000343782900002 PM 25236912 ER PT J AU Kaiser, NC Liang, LJ Melrose, RJ Wilkins, SS Sultzer, DL Mendez, MF AF Kaiser, Natalie C. Liang, Li-Jung Melrose, Rebecca J. Wilkins, Stacy S. Sultzer, David L. Mendez, Mario F. TI Differences in Anxiety Among Patients With Early- Versus Late-Onset Alzheimer's Disease SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID BEHAVIOR RATING-SCALE; NEUROPSYCHIATRIC INVENTORY; PSYCHIATRIC-SYMPTOMS; VASCULAR DEMENTIA; CACHE COUNTY; PREVALENCE; DISTURBANCES; DEPRESSION; MEMORY; PSYCHOPATHOLOGY AB The authors sought to evaluate the incidence and correlates of anxiety in early-onset Alzheimer's disease (EOAD) versus the more typical late-onset AD (LOAD). A group of 23 EOAD and 22 LOAD patients were compared by the Neuropsychiatric Inventory Anxiety subscale. Demographic and disease-related relationships with anxiety were evaluated, as well as types of anxiety symptoms that were endorsed. EOAD patients had significantly more anxiety symptoms than LOAD patients. Among those with EOAD, anxiety was associated with male gender, higher Mini-Mental State Exam score, and separation from caregivers. Among LOAD patients, anxiety was associated with psychotic and activating psychiatric symptoms. These results have implications for the management and alleviation of anxiety in AD. C1 [Kaiser, Natalie C.; Wilkins, Stacy S.; Sultzer, David L.; Mendez, Mario F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Liang, Li-Jung; Melrose, Rebecca J.; Sultzer, David L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Kaiser, NC (reprint author), VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. EM Natalie.Kaiser@va.gov FU National Institutes of Health [R01AG034499-3]; Dept. of Veterans Affairs VA Merit Review; Career Development Award; National Institute of Mental Health [R01-MH56031]; GRECC Fellowship Award FX This research was supported by National Institutes of Health Grant #R01AG034499-3 (M. Mendez PI); Dept. of Veterans Affairs VA Merit Review (two separate awards; one to M. Mendez and one to D. Sultzer); Career Development Award to R. Melrose; National Institute of Mental Health #R01-MH56031 (D. Sultzer, PI); GRECC Fellowship Award to N. Kaiser. NR 46 TC 5 Z9 6 U1 4 U2 162 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 EI 1545-7222 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 2014 VL 26 IS 1 BP 73 EP 80 PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AB9OW UT WOS:000332125500041 PM 24515678 ER PT J AU Izquierdo, A Sarkisian, C Ryan, G Wells, KB Miranda, J AF Izquierdo, Adriana Sarkisian, Catherine Ryan, Gery Wells, Kenneth B. Miranda, Jeanne TI OLDER DEPRESSED LATINOS' EXPERIENCES WITH PRIMARY CARE VISITS FOR PERSONAL, EMOTIONAL AND/OR MENTAL HEALTH PROBLEMS: A QUALITATIVE ANALYSIS SO ETHNICITY & DISEASE LA English DT Article DE Depression; Aging; Latino; Primary Care ID RANDOMIZED CONTROLLED-TRIAL; POPULATION; SYMPTOMS; IMPACT AB Objective: To describe salient experiences with a primary care visit (eg, the context leading up to the visit, the experience and/or outcomes of that visit) for emotional, personal and/or mental health problems older Latinos with a history of depression and recent depressive symptoms and/or antidepressant medication use reported 10 years after enrollment into a randomized controlled trial of quality-improvement for depression in primary care. Design: Secondary analysis of existing qualitative data from the second stage of the continuation study of Partners in Care (PIC). Participants: Latino ethnicity, aged >= 50 years, recent depressive symptoms and/or antidepressant medication use, and a recent primary care visit for mental health problems. Of 280 second-stage participants, 47 were eligible. Both stages of the continuation study included participants from the PIC parent study control and 2 intervention groups, and all had a history of depression. Methods: Data analyzed by a multidisciplinary team using grounded theory methodology. Results: Five themes were identified: beliefs about the nature of depression; prior experiences with mental health disorders/treatments; sociocultural context (eg, social relationships, caregiving, the media); clinic-related features (eg, accessibility of providers, staff continuity, amount of visit time); and provider attributes (eg, interpersonal skills, holistic care approach). Conclusions: Findings emphasize the importance of key features for shaping the context leading up to primary care visits for help-seeking for mental health problems, and the experience and/or outcomes of those visits, among older depressed Latinos at long-term follow-up, and may help tailor chronic depression care for the clinical management of this vulnerable population. C1 [Izquierdo, Adriana] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Sarkisian, Catherine] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. [Sarkisian, Catherine] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ Clin Ctr, Los Angeles, CA USA. [Ryan, Gery] RAND Corp, Santa Monica, CA USA. [Izquierdo, Adriana; Wells, Kenneth B.; Miranda, Jeanne] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Ctr Hlth Serv & Soc, Los Angeles, CA 90024 USA. RP Izquierdo, A (reprint author), 10920 Wilshire Blvd,Suite 300, Los Angeles, CA 90024 USA. EM aizquierdo@mednet.ucla.edu FU Diversity Supplement (NIMH) [P30-MH082760-04]; UCLA Resource Centers for Minority Aging Research/Center for Health Improvement of Minority Elderly (RCMAR/CHIME) (NIH/NIA) [P30-AG021684]; UCLA-CTSI (NIH/NCRR/NCATS [ULITR000124] FX Dr. Izquierdo was supported by a Diversity Supplement (NIMH Grant P30-MH082760-04), the UCLA Resource Centers for Minority Aging Research/Center for Health Improvement of Minority Elderly (RCMAR/CHIME) (NIH/NIA Grant P30-AG021684), and the UCLA-CTSI (NIH/NCRR/NCATS Grant ULITR000124). NR 16 TC 1 Z9 1 U1 3 U2 99 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X EI 1945-0826 J9 ETHNIC DIS JI Ethn. Dis. PD WIN PY 2014 VL 24 IS 1 BP 84 EP 91 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AB3IA UT WOS:000331683300013 PM 24620453 ER PT J AU Taylor, JJ Neitzke, DJ Khouri, G Borckardt, JJ Acierno, R Tuerk, PW Schmidt, M George, MS AF Taylor, Joseph J. Neitzke, Daniel J. Khouri, George Borckardt, Jeffrey J. Acierno, Ron Tuerk, Peter W. Schmidt, Matthew George, Mark S. TI A pilot study to investigate the induction and manipulation of learned helplessness in healthy adults SO PSYCHIATRY RESEARCH LA English DT Article DE Learned helplessness; Stress; rTMS; Prefrontal cortex; Post-traumatic stress disorder; Depression ID TRANSCRANIAL MAGNETIC STIMULATION; POSTTRAUMATIC-STRESS-DISORDER; MEDIAL PREFRONTAL CORTEX; DORSAL RAPHE NUCLEUS; BRAIN ACTIVATION; PRIMARY-CARE; DEPRESSION; RTMS; PTSD; CONTROLLABILITY AB Eliminating the controllability of a noxious stimulus may induce a learned helplessness (LH) that resembles aspects of depression and post-traumatic stress disorder (PTSD). This study examined whether repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) promotes resilience in an aversive stimulus model of LH. All 55 participants were told that an undisclosed sequence of button presses would terminate an aversive stimulus on their forearm. In truth, only half had control (+C). The other half had no control (-C). All participants received real (R) or sham (S) left DLPFC rTMS during the paradigm (+C/R, -C/S, +C/S, -C/R). We evaluated the cognitive effects of LH using an anagram task. The LH paradigm successfully reduced perceived control in the -C groups. As predicted, the +C/R and +C/S groups tended to give up less quickly and take less time to solve each anagram than did the -C/S group. Superior anagram performance in the -C/R group approached statistical significance. Our preliminary results suggest that manipulating the controllability of an aversive stimulus may induce an LH effect that manifests as impaired anagram performance. Further research is needed to refine this model and determine if DLPFC rTMS mitigates any LH effects. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Taylor, Joseph J.; Neitzke, Daniel J.; Khouri, George; Borckardt, Jeffrey J.; Acierno, Ron; Tuerk, Peter W.; Schmidt, Matthew; George, Mark S.] Med Univ S Carolina, Charleston, SC 29425 USA. [Acierno, Ron; Tuerk, Peter W.; George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP George, MS (reprint author), Med Univ S Carolina, Brain Stimulat Lab, 67 President St, Charleston, SC 29425 USA. EM georgem@musc.edu FU NIDA [F30DA033748]; NIGMS [T32 GM008716]; USAMRAA/TATRC [W81XWH-10-2-0194] FX JT was funded by NIDA (Grant no. F30DA033748). DN was funded by NIGMS (Grant no. T32 GM008716). MG was partially funded through USAMRAA/TATRC W81XWH-10-2-0194. MG would like to acknowledge Dr. John Carney for many interesting brainstorming sessions about resiliency and brain circuits and stimulation. NR 37 TC 1 Z9 1 U1 1 U2 27 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 NOV 30 PY 2014 VL 219 IS 3 BP 631 EP 637 DI 10.1016/j.psychres.2014.05.045 PG 7 WC Psychiatry SC Psychiatry GA AP2KR UT WOS:000341901600035 PM 25023370 ER PT J AU Greene, M Covinsky, K Astemborski, J Piggott, DA Brown, T Leng, S Galai, N Mehta, SH Guralnik, J Patel, KV Kirk, GD AF Greene, Meredith Covinsky, Kenneth Astemborski, Jacquie Piggott, Damani A. Brown, Todd Leng, Sean Galai, Noya Mehta, Shruti H. Guralnik, Jack Patel, Kushang V. Kirk, Gregory D. TI The relationship of physical performance with HIV disease and mortality SO AIDS LA English DT Article DE aging; HIV; injection drug use; mortality; physical function ID LOWER-EXTREMITY FUNCTION; EFFECTIVE ANTIRETROVIRAL THERAPY; INJECTION-DRUG USERS; SUBSEQUENT DISABILITY; FUNCTIONAL IMPAIRMENT; OLDER PERSONS; IL-6 LEVELS; INFECTION; FRAILTY; AGE AB Objective: To evaluate whether HIV infection was associated with reduced physical performance, and to examine if reduced physical performance predicted mortality in our aging cohort of HIV-infected and HIV-uninfected persons. Design: Prospective, observational cohort of current and former injection drug users in the AIDS Linked to the IntraVenous Experience study in Baltimore, Maryland, USA. Methods: The Short Physical Performance Battery (SPPB) was used as an objective measure of physical performance and measured semiannually along with behavioral and demographic data. Correlates of reduced physical performance (SPPB score < 10) were identified and the relationship between reduced physical performance, HIV infection and mortality was analyzed by Cox regression. Results: Among 12 270 person-visits contributed by 1627 participants, the median age was 51, 30.3% were HIV-infected and 32.6% had an SPPB score 10 or less. In multivariable models, HIV infection was independently associated with 30% increased odds of reduced physical performance [odds ratio 1.30; 95% confidence interval (CI): 1.12-1.52]. Reduced physical performance predicted mortality in a dose-response manner and within all HIV disease strata. Whereas reduced physical performance alone (hazard ratio 2.52, 95% CI: 1.59-4.00) and HIV infection alone (hazard ratio 2.78, 95% CI: 1.70-4.54) increased mortality, HIV-infected participants with reduced physical performance had a six-fold increased mortality risk (hazard ratio 6.03, 95% CI: 3.80-10.0) compared with HIV-uninfected participants with higher physical performance. Conclusion: HIV infection was independently associated with reduced physical performance. HIV and reduced physical performance have independent and joint effects on mortality. Physical performance measurement may be an important research and clinical tool to predict adverse outcomes among aging HIV-infected persons. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Greene, Meredith; Covinsky, Kenneth] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [Greene, Meredith; Covinsky, Kenneth] San Francisco VA Med Ctr, San Francisco, CA USA. [Astemborski, Jacquie; Piggott, Damani A.; Galai, Noya; Mehta, Shruti H.; Kirk, Gregory D.] Johns Hopkins Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Piggott, Damani A.; Kirk, Gregory D.] Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA. [Brown, Todd] Johns Hopkins Univ, Sch Med, Dept Med, Div Endocrinol & Metab, Baltimore, MD 21205 USA. [Leng, Sean] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr & Gerontol, Baltimore, MD 21205 USA. [Galai, Noya] Univ Haifa, Dept Stat, Har Hakarmel, Israel. [Guralnik, Jack] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Patel, Kushang V.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. RP Kirk, GD (reprint author), Johns Hopkins Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,E-6533, Baltimore, MD 21205 USA. EM gkirk@jhsph.edu FU National Institutes of Health [U01-DA-036297, R01-DA-0433, R01-DA-12568, RC1-AI-086053, 5-T32-AG000212] FX This work was supported by the National Institutes of Health (grants U01-DA-036297, R01-DA-0433, R01-DA-12568, RC1-AI-086053, and 5-T32-AG000212 [MG]). T. B. is a consultant for EMD-Serono, ViiV Healthcare, Gilead, Merck, and Abbvie. M. G. received one-time honoraria for reviewing IAS-USA cases on the web. NR 40 TC 10 Z9 10 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD NOV 28 PY 2014 VL 28 IS 18 BP 2711 EP 2719 DI 10.1097/QAD.0000000000000507 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AT9XO UT WOS:000345277300009 PM 25493597 ER PT J AU Spicer, TP Jiang, JW Taylor, AB Choi, JY Hart, PJ Roush, WR Fields, GB Hodder, PS Minong, D AF Spicer, Timothy P. Jiang, Jianwen Taylor, Alexander B. Choi, Jun Yong Hart, P. John Roush, William R. Fields, Gregg B. Hodder, Peter S. Minong, Dmitriy TI Characterization of Selective Exosite-Binding Inhibitors of Matrix Metalloproteinase 13 That Prevent Articular Cartilage Degradation in Vitro SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PYRIMIDINETRIONE-BASED INHIBITORS; CHELATING MMP-13 INHIBITORS; HUMAN COLLAGENASE-3 MMP-13; CRYSTAL-STRUCTURES; CATALYTIC DOMAIN; STRUCTURAL BASIS; DRUG DISCOVERY; CANCER-THERAPY; POTENT; OSTEOARTHRITIS AB Matrix metalloproteinase 13 (MMP-13) has been shown to be the main collagenase responsible for degradation of articular cartilage during osteoarthritis and therefore represents a target for drug development. As a result of high-throughput screening and structureactivity relationship studies, we identified a novel, highly selective class of MMP-13 inhibitors (compounds 1 (Q), 2 (Q1), and 3 (Q2)). Mechanistic characterization revealed a noncompetitive nature of these inhibitors with binding constants in the low micromolar range. Crystallographic analyses revealed two binding modes for compound 2 in the MMP-13 S-1' subsite and in an S-1/S-2* subsite. Type II collagen- and cartilage-protective effects exhibited by compounds 1, 2, and 3 suggested that these compounds might be efficacious in future in vivo studies. Finally, these compounds were also highly selective when tested against a panel of 30 proteases, which, in combination with a good CYP inhibition profile, suggested low off-target toxicity and drugdrug interactions in humans. C1 [Spicer, Timothy P.; Hodder, Peter S.; Minong, Dmitriy] Scripps Res Inst, Translat Res Inst, Lead Identificat Div, Jupiter, FL 33458 USA. [Hodder, Peter S.] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA. [Choi, Jun Yong; Roush, William R.] Scripps Res Inst, Scripps Florida, Dept Chem, Jupiter, FL 33458 USA. [Fields, Gregg B.; Minong, Dmitriy] Torrey Pines Inst Mol Studies, Dept Chem, Port St Lucie, FL 34987 USA. [Fields, Gregg B.; Minong, Dmitriy] Torrey Pines Inst Mol Studies, Dept Biol, Port St Lucie, FL 34987 USA. [Jiang, Jianwen; Taylor, Alexander B.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Jiang, Jianwen; Taylor, Alexander B.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Xray Crystallog Core Lab, San Antonio, TX 78229 USA. [Hart, P. John] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX 78229 USA. RP Minong, D (reprint author), Scripps Res Inst, Translat Res Inst, Lead Identificat Div, Jupiter, FL 33458 USA. EM dminond@tpims.org FU National Institutes of Health (Florida) [MH078948-01, U54MH074404, CA098799, AR063795]; Robert A. Welch Foundation [AQ-1399]; National Center for Research Resources at the National Institutes of Health [RR-15301]; U.S. Department of Energy, Office of Basic Energy Sciences [W-31-109-ENG-38]; Cancer Therapy & Research Center (CTRC) Cancer Center Support Grant [NCI P30CA054174]; UTHSCSA Executive Research Committee FX The National Institutes of Health (Grants MH078948-01, U54MH074404, CA098799, and AR063795) supported this work (Florida). Dr. Louis Scampavia, Pierre Baillargeon, and Lina DeLuca (Lead Identification Division, Translational Research Institute, Scripps Florida) are thanked for their assistance with compound management. This work was also supported in part by a grant from the Robert A. Welch Foundation (AQ-1399) (to P.J.H.) and is based in part upon research conducted at the Northeastern Collaborative Access Team beamlines of the Advanced Photon Source, supported by Award RR-15301 from the National Center for Research Resources at the National Institutes of Health. Use of the Advanced Photon Source is supported by the U.S. Department of Energy, Office of Basic Energy Sciences, under Contract No. W-31-109-ENG-38. Support for the X-ray Crystallography Core Laboratory by the UTHSCSA Executive Research Committee and by a Cancer Therapy & Research Center (CTRC) Cancer Center Support Grant (NCI P30CA054174) is also acknowledged. NR 66 TC 10 Z9 10 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD NOV 27 PY 2014 VL 57 IS 22 BP 9598 EP 9611 DI 10.1021/jm501284e PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AU6ON UT WOS:000345722200027 PM 25330343 ER PT J AU Leykum, LK Lanham, HJ Provost, SM McDaniel, RR Pugh, J AF Leykum, Luci K. Lanham, Holly J. Provost, Shannon M. McDaniel, Reuben R., Jr. Pugh, Jacqueline TI Improving outcomes of hospitalized patients: the Physician Relationships, Improvising, and Sensemaking intervention protocol SO IMPLEMENTATION SCIENCE LA English DT Article DE Complexity science; Inpatient care; Physician teams ID QUALITY-OF-CARE; HEALTH-CARE; COMPLEXITY; MORTALITY; FAILURE; PROGRAM; SCIENCE; TEAMS; JAZZ AB Background: Our goal is to improve the safety and effectiveness of inpatient care. Rather than focus on improving process of care, we focus on the social structure within physician teams. We have developed the Physician Relationships, Improvising, and Sensemaking (PRISm) intervention to improve the way physician teams round, enabling them to better relate, make sense of their patients' conditions, and improvise in uncertain clinical situations. We are currently studying the impact of PRISm on adverse events and complications in hospitalized patients. This manuscript describes the PRISm intervention. Methods/design: PRISm is a structured communication tool consisting of three components: daily briefings before rounds; use of the Situation, Task, Intent, Concern, and Calibrate (STICC) framework during rounds as part of the discussion of individual patients; and debriefings after rounds. We are implementing the PRISm intervention on eight inpatient medical and surgical physician teams in the South Texas Veterans Health Care System. We are assessing PRISm impact on the way team members relate to each other, round, and discuss patients through pre- and post-implementation observations and surveys. We are also assessing PRISm impact on complications and adverse events. Finally, we are interviewing physicians regarding their experience using the intervention. Discussion: Our results will allow us to begin to understand the potential impact of interventions designed to improve how providers relate to each other, improvise, and make sense of what is happening as a strategy for improving inpatient care. Our in-depth data collection will enable us to assess how relationships, improvising, and sensemaking influence patient outcomes, potentially through creating shared mental models or enhancing distributed cognition during clinical reasoning. Finally, our results will lay the groundwork for larger implementation studies to improve clinical outcomes through improving how providers, and providers, patients, and caregivers, relate. C1 [Leykum, Luci K.; Lanham, Holly J.; Pugh, Jacqueline] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Leykum, Luci K.; Lanham, Holly J.; Pugh, Jacqueline] Univ Texas San Antonio, Hlth Sci Ctr, Sch Med, San Antonio, TX 78229 USA. [Leykum, Luci K.; Lanham, Holly J.; Provost, Shannon M.; McDaniel, Reuben R., Jr.] Univ Texas Austin, Austin, TX 78712 USA. RP Leykum, LK (reprint author), South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. EM Leykum@uthscsa.edu NR 38 TC 1 Z9 2 U1 1 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 NOV 26 PY 2014 VL 9 AR 171 DI 10.1186/s13012-014-0171-3 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AY2PR UT WOS:000347432400002 PM 25424007 ER PT J AU Williams, JS Lynch, CP Knapp, RG Egede, LE AF Williams, Joni S. Lynch, Cheryl P. Knapp, Rebecca G. Egede, Leonard E. TI Technology-Intensified Diabetes Education Study (TIDES) in African Americans with type 2 diabetes: study protocol for a randomized controlled trial SO TRIALS LA English DT Article DE Diabetes; Education; Skills training; Technology; Telehealth; Telemedicine ID GLYCEMIC CONTROL; CARE MANAGEMENT; FOLLOW-UP; SUPPORT; SCALE; VETERANS; MELLITUS; VALIDITY; DESIGN; IMPACT AB Background: Compared to American Whites, African Americans have a higher prevalence of type 2 diabetes mellitus (T2DM), experiencing poorer metabolic control and greater risks for complications and death. Patient-level factors, such as diabetes knowledge, self-management skills, empowerment, and perceived control, account for > 90% of the variance observed in outcomes between these racial groups. There is strong evidence that self-management interventions that include telephone-delivered diabetes education and skills training are effective at improving metabolic control in diabetes. Web-based home telemonitoring systems in conjunction with active care management are also effective ways to lower glycosylated hemoglobin A1c values when compared to standard care, and provide feedback to patients; however, there are no studies in African Americans with poorly controlled T2DM that examine the use of technology-based feedback to tailor or augment diabetes education and skills training. This study provides a unique opportunity to address this gap in the literature. Methods: We describe an ongoing 4-year randomized clinical trial, which will test the efficacy of a technology intensified diabetes education and skills training (TIDES) intervention in African Americans with poorly controlled T2DM. Two hundred male and female AfricanAmerican participants, 21 years of age or older and with a glycosylated hemoglobin A1c level = 8%, will be randomized into one of two groups for 12 weeks of telephone interventions: (1) TIDES intervention group or (2) a usual-care group. Participants will be followed for 12 months to ascertain the effect of the interventions on glycemic control. Our primary hypothesis is that, among African Americans with poorly controlled T2DM, patients randomized to the TIDES intervention will have significantly greater reduction in glycosylated hemoglobin A1c at 12 months of follow-up compared to the usual-care group. Discussion: Results from this study will add to the current literature examining how best to deliver diabetes education and skills training and provide important insight into effective strategies to improve metabolic control and hence reduce diabetes complications and mortality rates in African Americans with poorly controlled T2DM. C1 [Williams, Joni S.; Lynch, Cheryl P.; Knapp, Rebecca G.; Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. [Williams, Joni S.; Lynch, Cheryl P.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Lynch, Cheryl P.; Egede, Leonard E.] Ralph H Johnson VAMC, Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC 29401 USA. [Knapp, Rebecca G.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Div Gen Internal Med & Geriatr, 135 Rutledge Ave, Charleston, SC 29425 USA. EM Egedel@musc.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [R01DK098529, K24DK093699] FX The study is funded by grant #R01DK098529 from the National Institute of Diabetes and Digestive and Kidney Diseases. LEE is also partially supported by grant # K24DK093699 from the National Institute of Diabetes and Digestive and Kidney Diseases. NR 33 TC 0 Z9 0 U1 2 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6215 J9 TRIALS JI Trials PD NOV 25 PY 2014 VL 15 AR 460 DI 10.1186/1745-6215-15-460 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AW2DD UT WOS:000346097600001 PM 25425504 ER PT J AU Peterson, ED Ho, PM Barton, M Beam, C Burgess, LH Casey, DE Drozda, JP Fonarow, GC Goff, D Grady, KL King, DE King, ML Masoudi, FA Nielsen, DR Stanko, S AF Peterson, Eric D. Ho, P. Michael Barton, Mary Beam, Craig Burgess, L. Hayley Casey, Donald E., Jr. Drozda, Joseph P., Jr. Fonarow, Gregg C. Goff, David, Jr. Grady, Kathleen L. King, Dana E. King, Marjorie L. Masoudi, Frederick A. Nielsen, David R. Stanko, Stephen TI ACC/AHA/AACVPR/AAFP/ANA Concepts for Clinician-Patient Shared Accountability in Performance Measures A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures SO CIRCULATION LA English DT Article DE AHA Scientific Statements; quality indicators; quality measurement; shared accountability ID BEHAVIORAL ECONOMICS; OF-CARDIOLOGY; CARE; ADHERENCE; MEDICARE; QUALITY C1 [Ho, P. Michael] Denver VA Med Ctr, Denver, CO USA. [Ho, P. Michael] Univ Colorado Denver, Denver, CO USA. [Barton, Mary] Natl Comm Qual Assurance, Washington, DC USA. [Beam, Craig] Amer Heart Assoc, Dallas, TX USA. [Burgess, L. Hayley] HCA Clin Serv Grp, Nashville, TN USA. [Casey, Donald E., Jr.] NYUPN Clin Integrated Network, New York, NY USA. [Drozda, Joseph P., Jr.] Mercy Hlth Syst, Janesville, WI 53548 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. [Goff, David, Jr.] Colorado Sch Publ Hlth, Aurora, CO USA. [Grady, Kathleen L.] Northwestern Univ Feinberg, Sch Med, Chicago, IL USA. [Grady, Kathleen L.] NW Mem Hosp, Bluhm Cardiovasc Inst, Chicago, IL USA. [King, Dana E.] W Virginia Univ, Morgantown, WV 26506 USA. [King, Marjorie L.] Helen Hayes Hosp, West Haverstraw, NY USA. [Masoudi, Frederick A.] Univ Colorado, Denver, CO 80202 USA. [Nielsen, David R.] Amer Acad Otolaryngol, Alexandria, VA USA. [Stanko, Stephen] Mended Hearts Inc, Dallas, TX USA. FU NIGMS NIH HHS [U54 GM104942] NR 28 TC 12 Z9 12 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 25 PY 2014 VL 130 IS 22 BP 1984 EP + DI 10.1161/CIR.0000000000000139 PG 17 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AU3MJ UT WOS:000345517100014 PM 25366994 ER PT J AU Barton, JL Koenig, CJ Evans-Young, G Trupin, L Anderson, J Ragouzeos, D Breslin, M Morse, T Schillinger, D Montori, VM Yelin, EH AF Barton, Jennifer L. Koenig, Christopher J. Evans-Young, Gina Trupin, Laura Anderson, Jennie Ragouzeos, Dana Breslin, Maggie Morse, Timothy Schillinger, Dean Montori, Victor M. Yelin, Edward H. TI The design of a low literacy decision aid about rheumatoid arthritis medications developed in three languages for use during the clinical encounter SO BMC MEDICAL INFORMATICS AND DECISION MAKING LA English DT Article DE Decision aid; Rheumatoid arthritis; Health literacy AB Background: Shared decision-making in rheumatoid arthritis (RA) care is a priority among policy makers, clinicians and patients both nationally and internationally. Demands on patients to have basic knowledge of RA, treatment options, and details of risk and benefit when making medication decisions with clinicians can be overwhelming, especially for those with limited literacy or limited English language proficiency. The objective of this study is to describe the development of a medication choice decision aid for patients with rheumatoid arthritis (RA) in three languages using low literacy principles. Methods: Based on the development of a diabetes decision aid, the RA decision aid (RA Choice) was developed through a collaborative process involving patients, clinicians, designers, decision-aid and health literacy experts. A combination of evidence synthesis and direct observation of clinician-patient interactions generated content and guided an iterative process of prototype development. Results: Three iterations of RA Choice were developed and field-tested before completion. The final tool organized data using icons and plain language for 12 RA medications across 5 issues: frequency of administration, time to onset, cost, side effects, and special considerations. The tool successfully created a conversation between clinician and patient, and garnered high acceptability from clinicians. Conclusions: The process of collaboratively developing an RA decision aid designed to promote shared decision making resulted in a graphically-enhanced, low literacy tool. The use of RA Choice in the clinical encounter has the potential to enhance communication for RA patients, including those with limited health literacy and limited English language proficiency. C1 [Barton, Jennifer L.; Koenig, Christopher J.; Evans-Young, Gina; Trupin, Laura; Schillinger, Dean; Yelin, Edward H.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Barton, Jennifer L.] Portland VA Med Ctr, Div Hosp & Specialty Med, Portland, OR 97239 USA. [Evans-Young, Gina; Trupin, Laura; Yelin, Edward H.] Phillip R Lee Inst Hlth Policy Studies, San Francisco, CA USA. [Montori, Victor M.] Mayo Clin, Knowledge & Evaluat Res Unit, Rochester, MN 55905 USA. RP Barton, JL (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA USA. EM Jennifer.Barton@va.gov OI Barton, Jennifer/0000-0002-6771-3465; Koenig, Christopher J./0000-0003-0884-4120; Montori, Victor/0000-0003-0595-2898 FU Agency for Healthcare Research and Quality [R18 HS019209-01]; NIH [P60 AR053308] FX Funding for this project was from the Agency for Healthcare Research and Quality (R18 HS019209-01, PI Yelin). AHRQ had no role in study design; in collection, analysis and interpretation of data; in the writing of this manuscript; or in the decision to submit this paper for publication. Dr. Yelin, Ms. Trupin and Ms. Evans-Young also received funding from the NIH (NIAMS P60 AR053308). NR 45 TC 6 Z9 7 U1 2 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6947 J9 BMC MED INFORM DECIS JI BMC Med. Inform. Decis. Mak. PD NOV 25 PY 2014 VL 14 AR 104 DI 10.1186/s12911-014-0104-8 PG 14 WC Medical Informatics SC Medical Informatics GA V42AA UT WOS:000209585500001 PM 25649726 ER PT J AU Das, F Ghosh-Choudhury, N Dey, N Bera, A Mariappan, MM Kasinath, BS Choudhury, GG AF Das, Falguni Ghosh-Choudhury, Nandini Dey, Nirmalya Bera, Amit Mariappan, Meenalakshmi M. Kasinath, Balakuntalam S. Choudhury, Goutam Ghosh TI High Glucose Forces a Positive Feedback Loop Connecting Akt Kinase and FoxO1 Transcription Factor to Activate mTORC1 Kinase for Mesangial Cell Hypertrophy and Matrix Protein Expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA TRANSLATION; DIABETIC-NEPHROPATHY; OSTEOBLAST DIFFERENTIATION; GENE-TRANSCRIPTION; SIGNALING PATHWAY; EPITHELIAL-CELLS; TRANSGENIC MICE; HIGH INSULIN; SMAD 3; DISEASE AB High glucose-induced Akt acts as a signaling hub for mesangial cell hypertrophy and matrix expansion, which are recognized as cardinal signatures for the development of diabetic nephropathy. How mesangial cells sustain the activated state of Akt is not clearly understood. Here we show Akt-dependent phosphorylation of the transcription factor FoxO1 by high glucose. Phosphorylation-deficient, constitutively active FoxO1 inhibited the high glucose-induced phosphorylation of Akt to suppress the phosphorylation/inactivation of PRAS40 and mTORC1 activity. In contrast, dominant negative FoxO1 increased the phosphorylation of Akt, resulting in increased mTORC1 activity similar to high glucose treatment. Notably, FoxO1 regulates high glucose-induced protein synthesis, hypertrophy, and expression of fibronectin and PAI-1. High glucose paves the way for complications of diabetic nephropathy through the production of reactive oxygen species (ROS). We considered whether the FoxO1 target antioxidant enzyme catalase contributes to sustained activation of Akt. High glucose-inactivated FoxO1 decreases the expression of catalase to increase the production of ROS. Moreover, we show that catalase blocks high glucose-stimulated Akt phosphorylation to attenuate the inactivation of FoxO1 and PRAS40, resulting in the inhibition of mTORC1 and mesangial cell hypertrophy and fibronectin and PAI-1 expression. Finally, using kidney cortices from type 1 diabetic OVE26 mice, we show that increased FoxO1 phosphorylation is associated with decreased catalase expression and increased fibronectin and PAI-1 expression. Together, our results provide the first evidence for the presence of a positive feedback loop for the sustained activation of Akt involving inactivated FoxO1 and a decrease in catalase expression, leading to increased ROS and mesangial cell hypertrophy and matrix protein expression. C1 [Ghosh-Choudhury, Nandini; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh] South Texas Vet Hlth Care Syst, Vet Affairs Res & Geriatr Res, San Antonio, TX 78229 USA. [Choudhury, Goutam Ghosh] South Texas Vet Hlth Care Syst, Educ & Clin Ctr, San Antonio, TX 78229 USA. [Das, Falguni; Dey, Nirmalya; Bera, Amit; Mariappan, Meenalakshmi M.; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. RP Choudhury, GG (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. EM choudhuryg@uthscsa.edu FU National Institutes of Health [RO1 DK50190]; Veterans Affairs Research Service Merit Review Grant [5I01BX000926, 5I01BX000150, 5I01BX001340]; Veterans Affairs Senior Research Career Scientist Award FX This work was supported, in whole or in part, by National Institutes of Health Grant RO1 DK50190. This work was also supported by Veterans Affairs Research Service Merit Review Grant 5I01BX000926 (to G. G. C.).; Supported by Veterans Affairs Merit Review Grant 5I01BX000150.; Supported by Veterans Affairs Merit Review Grant 5I01BX001340.; Recipient of the Veterans Affairs Senior Research Career Scientist Award. NR 50 TC 9 Z9 9 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 21 PY 2014 VL 289 IS 47 DI 10.1074/jbc.M114.605196 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AU0SO UT WOS:000345335000027 PM 25288788 ER PT J AU Roussos, P Mitchell, AC Voloudakis, G Fullard, JF Pothula, VM Tsang, J Stahl, EA Georgakopoulos, A Ruderfer, DM Charney, A Okada, Y Siminovitch, KA Worthington, J Padyukov, L Klareskog, L Gregersen, PK Plenge, RM Raychaudhuri, S Fromer, M Purcell, SM Brennand, KJ Robakis, NK Schadt, EE Akbarian, S Sklar, P AF Roussos, Panos Mitchell, Amanda C. Voloudakis, Georgios Fullard, John F. Pothula, Venu M. Tsang, Jonathan Stahl, Eli A. Georgakopoulos, Anastasios Ruderfer, Douglas M. Charney, Alexander Okada, Yukinori Siminovitch, Katherine A. Worthington, Jane Padyukov, Leonid Klareskog, Lars Gregersen, Peter K. Plenge, Robert M. Raychaudhuri, Soumya Fromer, Menachem Purcell, Shaun M. Brennand, Kristen J. Robakis, Nikolaos K. Schadt, Eric E. Akbarian, Schahram Sklar, Pamela TI A Role for Noncoding Variation in Schizophrenia SO CELL REPORTS LA English DT Article ID GENOME-WIDE ASSOCIATION; BIPOLAR DISORDER; GENE-EXPRESSION; RISK LOCI; HEALTHY-INDIVIDUALS; PREFRONTAL CORTEX; CELL-TYPES; CACNA1C; IDENTIFICATION; TRANSCRIPTION AB A large portion of common variant loci associated with genetic risk for schizophrenia reside within noncoding sequence of unknown function. Here, we demonstrate promoter and enhancer enrichment in schizophrenia variants associated with expression quantitative trait loci (eQTL). The enrichment is greater when functional annotations derived from the human brain are used relative to peripheral tissues. Regulatory trait concordance analysis ranked genes within schizophrenia genome-wide significant loci for a potential functional role, based on colocalization of a risk SNP, eQTL, and regulatory element sequence. We identified potential physical interactions of noncontiguous proximal and distal regulatory elements. This was verified in prefrontal cortex and -induced pluripotent stem cell-derived neurons for the L-type calcium channel (CACNA1C) risk locus. Our findings point to a functional link between schizophrenia-associated noncoding SNPs and 3D genome architecture associated with chromosomal loopings and transcriptional regulation in the brain. C1 [Roussos, Panos; Mitchell, Amanda C.; Voloudakis, Georgios; Fullard, John F.; Pothula, Venu M.; Tsang, Jonathan; Stahl, Eli A.; Georgakopoulos, Anastasios; Ruderfer, Douglas M.; Charney, Alexander; Fromer, Menachem; Purcell, Shaun M.; Brennand, Kristen J.; Robakis, Nikolaos K.; Akbarian, Schahram; Sklar, Pamela] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Roussos, Panos; Stahl, Eli A.; Ruderfer, Douglas M.; Charney, Alexander; Fromer, Menachem; Purcell, Shaun M.; Schadt, Eric E.; Sklar, Pamela] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Roussos, Panos; Stahl, Eli A.; Ruderfer, Douglas M.; Charney, Alexander; Fromer, Menachem; Purcell, Shaun M.; Schadt, Eric E.; Sklar, Pamela] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, New York, NY 10029 USA. [Roussos, Panos; Mitchell, Amanda C.; Voloudakis, Georgios; Fullard, John F.; Pothula, Venu M.; Brennand, Kristen J.; Robakis, Nikolaos K.; Akbarian, Schahram; Sklar, Pamela] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Roussos, Panos] Mental Illness Res Educ & Clin Ctr, James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Mitchell, Amanda C.; Voloudakis, Georgios; Pothula, Venu M.; Brennand, Kristen J.; Robakis, Nikolaos K.; Akbarian, Schahram; Sklar, Pamela] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Okada, Yukinori] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Human Genet & Dis Divers, Tokyo 2300045, Japan. [Okada, Yukinori] RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa 2300045, Japan. [Siminovitch, Katherine A.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Siminovitch, Katherine A.] Toronto Gen Res Inst, Toronto, ON M5G 2M9, Canada. [Siminovitch, Katherine A.] Univ Toronto, Dept Med, Toronto, ON M5S 2J7, Canada. [Worthington, Jane] Univ Manchester, Arthrit Res UK Ctr Genet & Genom, Musculoskeletal Res Ctr, Inst Inflammat & Repair,Manchester Acad Hlth Sci, Manchester M13 9NT, Lancs, England. [Worthington, Jane] Cent Manchester Univ Hosp Natl Hlth Serv Fdn Trus, Natl Inst Hlth Res, Manchester Musculoskeletal Biomed Res Unit, Manchester Acad Hlth Sci Ctr, Manchester M13 9NT, Lancs, England. [Padyukov, Leonid; Klareskog, Lars] Karolinska Inst, Dept Med Solna, Rheumatol Unit, S-17176 Stockholm, Sweden. [Gregersen, Peter K.] North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA. [Plenge, Robert M.; Raychaudhuri, Soumya] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Plenge, Robert M.; Raychaudhuri, Soumya] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Plenge, Robert M.; Raychaudhuri, Soumya] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Raychaudhuri, Soumya] Cent Manchester NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, NIHR Manchester Musculoskeletal Biomed Res Unit, Manchester M13 9NT, Lancs, England. RP Roussos, P (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. EM panagiotis.roussos@mssm.edu; pamela.sklar@mssm.edu RI Brennand, Kristen/J-8704-2012; Siminovitch, Katherine/K-1475-2013; Ruderfer, Douglas/M-5795-2016; Roussos, Panos/J-7090-2013 OI Brennand, Kristen/0000-0003-0993-5956; Ruderfer, Douglas/0000-0002-2365-386X; Roussos, Panos/0000-0002-4640-6239; Klareskog, Lars/0000-0001-9601-6186; Padyukov, Leonid/0000-0003-2950-5670 FU NIH/National Institute of Mental Health (NIMH) grant [R01MH095034]; NIMH grant [R01MH097276, U01MH103392, P50 MH096890, R01 MH101454]; National Institute of Neurological Disorders and Stroke (NINDS) grant [R21 NS076958]; NINDS grant [R01 NS047229]; National Institute on Aging (NIA) grant [R37 AG017926]; NIA grant [P50 AG005138]; Veterans Affairs Merit grant [BX002395]; Brain Behavior Research Foundation; American Psychiatric Association-Merck & Co. Early Academic Career Research Award; New York Stem Cell Foundation; Alzheimer's Association grant [IIRG-11-205149]; Friedman Brain Institute at Icahn School of Medicine at Mount Sinai; Icahn Institute for Genomics and Multiscale Biology at Icahn School of Medicine at Mount Sinai; Department of Scientific Computing at the Icahn School of Medicine at Mount Sinai FX We thank Iris Cheung and Yin Guo for ChIP-seq assays on sorted brain nuclei. We thank all members of the Rheumatoid Arthritis Consortium for providing access to the GWAS data. Members of Rheumatoid Arthritis Consortium are Steve Eyre, John Bowes, Dorothee Diogo, Annette Lee, Anne Barton, Paul Martin, Alexandra Zhernakova, E. A. S., Sebastien Viatte, Kate McAllister, Christopher I. Amos, L. P., Rene E. M. Toes, Tom W. J. Huizinga, Cisca Wijmenga, Gosia Trynka, Lude Franke, Harm-Jan Westra, Lars Alfredsson, Xinli Hu, Cynthia Sandor, Paul I. W. de Bakker, Sonia Davila, Chiea Chuen Khor, Khai Koon Heng, Robert Andrews, Sarah Edkins, Sarah E. Hunt, Cordelia Langford, Deborah Symmons, Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate, Wellcome Trust Case Control Consortium, Pat Concannon, Suna Onengut-Gumuscu, Stephen S. Rich, Panos Deloukas, Miguel A. Gonzalez-Gay, Luis Rodriguez-Rodriguez, Lisbeth Arlsetig, Javier Martin, Solbritt Rantapaa-Dahlqvist, R. M. P., S. R., L. K., P. K. G., J. W., the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS), and the Wellcome Trust Case Control Consortium (WTCCC). We thank Dr. Ron Zielke and staff from the Brain and Tissue Bank for Developmental Disorders, and Dr. Andree Lessard from the Maryland Psychiatric Research Center, University of Maryland, for providing postmortem brain tissue. We acknowledge funding support from NIH/National Institute of Mental Health (NIMH) grant R01MH095034 (to P. S.), NIMH grant R01MH097276 (to P. S. and E. E. S.), NIMH grant U01MH103392 (to. S. A. and P. S.), NIMH grant P50 MH096890 (to S. A.), National Institute of Neurological Disorders and Stroke (NINDS) grant R21 NS076958 (to S. A.), NINDS grant R01 NS047229 (to N.K.R.), National Institute on Aging (NIA) grant R37 AG017926 (to N.K.R.), NIA grant P50 AG005138 (to N.K.R. and A. G.), Veterans Affairs Merit grant BX002395 (to P. R.), the Brain Behavior Research Foundation (to P. R., A. C. M., S. A., E. A. S., and K. B.), the American Psychiatric Association-Merck & Co. Early Academic Career Research Award (to P. R.), NIMH grant R01 MH101454 (to K. B.), the New York Stem Cell Foundation (to K. B.), Alzheimer's Association grant IIRG-11-205149 (to A. G.), the Friedman Brain Institute at Icahn School of Medicine at Mount Sinai, and the Icahn Institute for Genomics and Multiscale Biology at Icahn School of Medicine at Mount Sinai. This work was supported in part through the computational resources and staff expertise provided by the Department of Scientific Computing at the Icahn School of Medicine at Mount Sinai. The funders had no role in study design, execution, analysis, or manuscript preparation. NR 58 TC 46 Z9 46 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD NOV 20 PY 2014 VL 9 IS 4 BP 1417 EP 1429 DI 10.1016/j.celrep.2014.10.015 PG 13 WC Cell Biology SC Cell Biology GA AU3QW UT WOS:000345529600023 PM 25453756 ER PT J AU Leykum, LK Lanham, HJ Pugh, JA Parchman, M Anderson, RA Crabtree, BF Nutting, PA Miller, WL Stange, KC McDaniel, RR AF Leykum, Luci K. Lanham, Holly J. Pugh, Jacqueline A. Parchman, Michael Anderson, Ruth A. Crabtree, Benjamin F. Nutting, Paul A. Miller, William L. Stange, Kurt C. McDaniel, Reuben R., Jr. TI Manifestations and implications of uncertainty for improving healthcare systems: an analysis of observational and interventional studies grounded in complexity science SO IMPLEMENTATION SCIENCE LA English DT Article DE Complexity science; Relationships; Uncertainty; Healthcare systems; Implementation ID PREVENTIVE SERVICE DELIVERY; QUALITY-OF-CARE; CLINICAL-TRIAL; DIABETES CARE; NURSING-HOMES; MODEL; SCALE; IMPLEMENTATION; MEDICARE; INSIGHTS AB Background: The application of complexity science to understanding healthcare system improvement highlights the need to consider interdependencies within the system. One important aspect of the interdependencies in healthcare delivery systems is how individuals relate to each other. However, results from our observational and interventional studies focusing on relationships to understand and improve outcomes in a variety of healthcare settings have been inconsistent. We sought to better understand and explain these inconsistencies by analyzing our findings across studies and building new theory. Methods: We analyzed eight observational and interventional studies in which our author team was involved as the basis of our analysis, using a set theoretical qualitative comparative analytic approach. Over 16 investigative meetings spanning 11 months, we iteratively analyzed our studies, identifying patterns of characteristics that could explain our set of results. Our initial focus on differences in setting did not explain our mixed results. We then turned to differences in patient care activities and tasks being studied and the attributes of the disease being treated. Finally, we examined the interdependence between task and disease. Results: We identified system-level uncertainty as a defining characteristic of complex systems through which we interpreted our results. We identified several characteristics of healthcare tasks and diseases that impact the ways uncertainty is manifest across diverse care delivery activities. These include disease-related uncertainty (pace of evolution of disease and patient control over outcomes) and task-related uncertainty (standardized versus customized, routine versus non-routine, and interdependencies required for task completion). Conclusions: Uncertainty is an important aspect of clinical systems that must be considered in designing approaches to improve healthcare system function. The uncertainty inherent in tasks and diseases, and how they come together in specific clinical settings, will influence the type of improvement strategies that are most likely to be successful. Process-based efforts appear best-suited for low-uncertainty contexts, while relationship-based approaches may be most effective for high-uncertainty situations. C1 [Leykum, Luci K.; Lanham, Holly J.; Pugh, Jacqueline A.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Leykum, Luci K.; Lanham, Holly J.; Pugh, Jacqueline A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Leykum, Luci K.; Lanham, Holly J.; McDaniel, Reuben R., Jr.] Univ Texas Austin, Austin, TX 78712 USA. [Parchman, Michael] Grp Hlth Res Inst, MacColl Ctr Hlth Care Innovat, Seattle, WA USA. [Anderson, Ruth A.] Duke Univ, Durham, NC USA. [Crabtree, Benjamin F.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Family Med, New Brunswick, NJ USA. [Nutting, Paul A.] Univ Colorado, Dept Family Med, Sch Med, Aurora, CO USA. [Miller, William L.] Lehigh Valley Hlth Network, Lehigh, PA USA. [Stange, Kurt C.] Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Leykum, LK (reprint author), South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. EM Leykum@uthscsa.edu OI Parchman, Michael/0000-0001-7129-2889 FU Department of Veterans Affairs, Veterans Health Administration, and Health Services Research and Development Service [CDA 07-022]; South Texas Veterans Health Care System; IC2 Institute of the University of Texas at Austin; Clinical Research Professorship from the American Cancer Society FX The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, and Health Services Research and Development Service (CDA 07-022). Investigator salary support is provided through this funding and through the South Texas Veterans Health Care System. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. Dr. McDaniel receives support from the IC2 Institute of the University of Texas at Austin. Dr. Stange's time was supported in part by a Clinical Research Professorship from the American Cancer Society. NR 47 TC 7 Z9 7 U1 2 U2 12 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 NOV 19 PY 2014 VL 9 AR 165 DI 10.1186/s13012-014-0165-1 PG 13 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AY2PK UT WOS:000347431700001 PM 25407138 ER PT J AU Crandall, CJ Newberry, SJ Diamant, A Lim, YW Gellad, WF Booth, MJ Motala, A Shekelle, PG AF Crandall, Carolyn J. Newberry, Sydne J. Diamant, Allison Lim, Yee-Wei Gellad, Walid F. Booth, Marika J. Motala, Aneesa Shekelle, Paul G. TI Comparative Effectiveness of Pharmacologic Treatments to Prevent Fractures An Updated Systematic Review SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID BONE-MINERAL DENSITY; BISPHOSPHONATE-RELATED OSTEONECROSIS; ATYPICAL FEMORAL FRACTURES; YEARLY ZOLEDRONIC ACID; LONG-TERM ALENDRONATE; POSTMENOPAUSAL WOMEN; PRIMARY OSTEOPOROSIS; ATRIAL-FIBRILLATION; ORAL BISPHOSPHONATES; VERTEBRAL FRACTURE AB Background: Osteoporosis is a major contributor to the propensity to fracture among older adults, and various pharmaceuticals are available to treat it. Purpose: To update a review about the benefits and harms of pharmacologic treatments used to prevent fractures in adults at risk. Data Sources: Multiple computerized databases were searched between 2 January 2005 and 4 March 2014 for English-language studies. Study Selection: Trials, observational studies, and systematic reviews. Data Extraction: Duplicate extraction and assessment of data about study characteristics, outcomes, and quality. Data Synthesis: From more than 52 000 titles screened, 315 articles were included in this update. There is high-strength evidence that bisphosphonates, denosumab, and teriparatide reduce fractures compared with placebo, with relative risk reductions from 0.40 to 0.60 for vertebral fractures and 0.60 to 0.80 for nonvertebral fractures. Raloxifene has been shown in placebo-controlled trials to reduce only vertebral fractures. Since 2007, there is a newly recognized adverse event of bisphosphonate use: atypical subtrochanteric femur fracture. Gastrointestinal side effects, hot flashes, thromboembolic events, and infections vary among drugs. Limitations: Few studies have directly compared drugs used to treat osteoporosis. Data in men are very sparse. Costs were not assessed. Conclusion: Good-quality evidence supports that several medications for bone density in osteoporotic range and/or preexisting hip or vertebral fracture reduce fracture risk. Side effects vary among drugs, and the comparative effectiveness of the drugs is unclear. C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore. RAND Corp, Pittsburgh Vet Affairs Med Ctr, Pittsburgh, PA USA. Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. RP Crandall, CJ (reprint author), Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, David Geffen Sch Med, 911 Broxton Ave,1st Floor, Los Angeles, CA 90024 USA. EM ccrandall@mednet.ucla.edu FU Agency for Healthcare Research and Quality (AHRQ) [HHSA290200710062I] FX By the Agency for Healthcare Research and Quality (AHRQ) (HHSA290200710062I). No statement in this article should be construed as an official position of AHRQ or the U.S. Department of Health and Human Services. NR 157 TC 43 Z9 47 U1 1 U2 16 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 NOV 18 PY 2014 VL 161 IS 10 BP 711 EP U163 DI 10.7326/M14-0317 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA AX9TT UT WOS:000347245600028 PM 25199883 ER PT J AU Kullgren, JT Dicks, TN Fu, XY Richardson, D Tzanis, GL Tobi, M Marcus, SC AF Kullgren, Jeffrey T. Dicks, Tanisha N. Fu, Xiaoying Richardson, Diane Tzanis, George L. Tobi, Martin Marcus, Steven C. TI Financial Incentives for Completion of Fecal Occult Blood Tests Among Veterans A 2-Stage, Pragmatic, Cluster, Randomized, Controlled Trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID COLORECTAL-CANCER; LONGITUDINAL ADHERENCE; CLINICAL-TRIALS; WEIGHT-LOSS; INTERVENTION; DECISION; BEHAVIOR; QUALITY; IMPACT; COLON AB Background: Rates of patient completion of fecal occult blood tests (FOBTs) are often low. Objective: To examine whether financial incentives increase rates of FOBT completion. Design: A 2-stage, parallel-design, pragmatic, cluster, randomized, controlled trial with clustering by clinic day (ClinicalTrials.gov: NCT01516489). Setting: Primary care clinic of the Philadelphia Veterans Affairs Medical Center. Patients: 1549 patients who were prescribed an FOBT (unique samples of 713 patients for stage 1 and 836 patients for stage 2). Intervention: In stage 1, patients were assigned to usual care or receipt of $5, $10, or $20 for FOBT completion. In stage 2, different patients were assigned to usual care or receipt of $5, a 1 in 10 chance of $50, or entry into a $500 raffle for FOBT completion. Measurements: Primary outcome was FOBT completion within 30 days. Preplanned subgroup analyses examined 30-day FOBT completion by previous nonadherence to a prescribed FOBT. Results: In stage 1, none of the incentives increased rates of FOBT completion. In stage 2, a 1 in 10 chance of $50 increased FOBT completion compared with usual care (between-group difference, 19.6% [95% CI, 10.7% to 28.6%]; P < 0.001) but a $5 fixed payment and entry into a raffle for $500 did not. None of the incentives were more effective among patients who had previously been nonadherent to an FOBT than among patients who had previously completed an FOBT. Limitations: Single Veterans Affairs medical center setting, short follow-up, use of 3-sample rather than 1-sample immunochemical FOBTs, limited power to detect small effects of incentives, inability to evaluate cost-effectiveness. Conclusion: A 1 in 10 chance of receiving $50 was effective at increasing rates of FOBT completion, but 5 other tested incentives were not. C1 [Kullgren, Jeffrey T.] Vet Affairs Ann Arbor Healthcare Syst, Vet Affairs Ctr Clin Management Res, Ann Arbor, MI 48113 USA. Univ Michigan, Sch Med, Ann Arbor, MI USA. [Dicks, Tanisha N.; Fu, Xiaoying; Richardson, Diane; Tzanis, George L.; Tobi, Martin] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Kullgren, JT (reprint author), Vet Affairs Ann Arbor Healthcare Syst, Vet Affairs Ctr Clin Management Res, POB 130170, Ann Arbor, MI 48113 USA. EM jkullgre@med.umich.edu FU Veterans Affairs Center for Health Equity Research and Promotion FX Veterans Affairs Center for Health Equity Research and Promotion. NR 44 TC 7 Z9 7 U1 1 U2 3 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 NOV 18 PY 2014 VL 161 IS 10 SU S BP S35 EP S43 DI 10.7326/M13-3015 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CW3RR UT WOS:000364909900006 PM 25402401 ER PT J AU Patel, MS Day, S Small, DS Howell, JT Lautenbach, GL Nierman, EH Volpp, KG AF Patel, Mitesh S. Day, Susan Small, Dylan S. Howell, John T., III Lautenbach, Gillian L. Nierman, Eliot H. Volpp, Kevin G. TI Using Default Options Within the Electronic Health Record to Increase the Prescribing of Generic-Equivalent Medications A Quasi-experimental Study SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CARE; PHYSICIANS; DECISIONS; ECONOMICS; PATTERNS; POWER AB Background: Low-value services, such as prescribing brand-name medications that have existing generic equivalents, contribute to unnecessary health care spending. Objective: To evaluate the association of an intervention by using the electronic health record with provider prescription of generic-equivalent medications. Design: Quasi-experimental study. Setting: General internal medicine (IM) (n = 2) and family medicine (FM) (n = 2) clinics at the University of Pennsylvania from June 2011 to September 2012. Participants: Attending physicians (IM, n = 38; FM, n = 17) and residents (IM, n = 166; FM, n = 34). Intervention: In January 2012, the default in the electronic health record was changed for IM providers from displaying brand and generic medications to displaying initially only generics, with the ability to opt out. Measurements: Monthly prescriptions of brand-name and generic-equivalent beta-blockers, statins, and proton-pump inhibitors. Results: During the preintervention period, FM providers had slightly higher rates of generic medication prescribing (range, 80.8% to 85.5%) than did IM providers (range, 75.4% to 79.6%), but both groups had similar trends. In the postintervention period relative to the preintervention period, IM providers had an increase in generic prescribing compared with FM providers for all 3 medications combined (5.4 percentage points [95% CI, 2.2 to 8.7 percentage points]; P < 0.001), beta-blockers (10.5 percentage points [CI, 5.8 to 15.2 percentage points]; P < 0.001), and statins (4.0 percentage points [CI, 0.4 to 7.6 percentage points]; P = 0.002). Results for proton-pump inhibitors (2.1 percentage points [CI, -3.7 to 8.0 percentage points]; P = 0.47) were not significant. Subset analyses revealed similar findings for attending physicians. Among residents, however, results were imprecise, with wide CIs. Limitation: Observational single-center evaluation, comparison groups that represented different specialties, and a small subset of medication classes studied. Conclusion: The use of default options was an effective method to increase the odds of prescribing generic medication equivalents for beta-blockers and statins. C1 [Patel, Mitesh S.; Day, Susan; Lautenbach, Gillian L.; Nierman, Eliot H.; Volpp, Kevin G.] Univ Penn, Perelman Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Small, Dylan S.] Univ Penn, Dept Stat, Wharton Sch, Philadelphia, PA 19104 USA. [Howell, John T., III] Univ Penn, Off Chief Med Informat Officer, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Patel, MS (reprint author), Univ Penn, Perelman Sch Med, Div Gen Internal Med, 423 Guardian Dr,12th Floor,Blockley Hall, Philadelphia, PA 19104 USA. EM mpatel@upenn.edu FU U.S. Department of Veterans Affairs; Robert Wood Johnson Foundation FX U.S. Department of Veterans Affairs and Robert Wood Johnson Foundation. NR 35 TC 11 Z9 11 U1 2 U2 7 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 NOV 18 PY 2014 VL 161 IS 10 SU S BP S44 EP S52 DI 10.7326/M13-3001 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CW3RR UT WOS:000364909900007 PM 25402402 ER PT J AU Prasad, R Katiyar, SK AF Prasad, Ram Katiyar, Santosh K. TI Down-regulation of miRNA-106b inhibits growth of melanoma cells by promoting G1-phase cell cycle arrest and reactivation of p21/WAF1/Cip1 protein SO ONCOTARGET LA English DT Article DE Melanoma; MicroRNA-106b; cell cycle; tumor xenograft growth; grape seed proanthocyanidins ID MICRORNAS; CANCER; EXPRESSION; MIR-106B; CARCINOMA; ACQUISITION; EXTRACTION; CLUSTER AB MiR-106b is overexpressed in various types of cancers and is associated with the regulation of the carcinogenic processes. Using RT-PCR, we have identified overexpression of miRNA-106b in various melanoma cell lines (A375, Hs294t, SK-el28, SK-Mel 119, Mel 1241, Mel 1011 and Mel 928) as compared to its expression in normal human epidermal melanocytes (NHEM). The overexpression of miR-106b in melanoma cells (A375, Hs294t) was associated with greater cell proliferation capacity than NHEM. Treatment of A375 and Hs294t cells with anti-miR-106b resulted in inhibition of cell proliferation as well as G1-phase arrest. We determined the effects of grape seed proanthocyanidins (GSPs) on the expression of miRNA-106b and its underlying molecular targets. Treatment of A375 and Hs294t cells with GSPs resulted in suppression of the levels of miRNA-106b, cytotoxicity, G1-phase arrest and reactivation of p21/WAF1/Cip1. Dietary GSPs significantly inhibited growth of A375 melanoma cell tumor xenografts in nude mice, which was associated with reduction in the levels of miRNA-106b, tumor cell proliferation and increases in the levels of p21/WAF1/Cip1 protein. These studies suggest that miRNA-106b plays a crucial role in melanoma growth and that GSPs act as an inhibitor of miR-106b thereby blocking melanoma growth in vitro and in vivo models. C1 [Prasad, Ram; Katiyar, Santosh K.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU National Institutes of Health [CA166883]; Veterans Administration Merit Review Award [1I01BX001410] FX The study is partially supported by the funds from the National Institutes of Health (CA166883, S.K.K.), and Veterans Administration Merit Review Award (1I01BX001410, S.K.K.). Normal human melanocytes were obtained from the UAB Skin Diseases Research Center (AR050948). The content of this manuscript does not necessarily reflect the views or policies of the funding agencies. NR 33 TC 19 Z9 19 U1 1 U2 4 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD NOV 15 PY 2014 VL 5 IS 21 BP 10636 EP 10649 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AZ2AL UT WOS:000348036900033 PM 25361006 ER PT J AU Abreo, AP Glidden, D Painter, P Lea, J Herzog, CA Kutner, NG Johansen, KL AF Abreo, Adrian P. Glidden, David Painter, Patricia Lea, Janice Herzog, Charles A. Kutner, Nancy G. Johansen, Kirsten L. TI Association of physical function with predialysis blood pressure in patients on hemodialysis SO BMC NEPHROLOGY LA English DT Article DE Blood pressure; End-stage renal disease; Physical function ID STAGE RENAL-DISEASE; MORTALITY RISK; PERFORMANCE; DIALYSIS; HYPERTENSION; PREDICTION; DISABILITY; PATTERNS; OUTCOMES; ADULTS AB Background: New information from various clinical settings suggests that tight blood pressure control may not reduce mortality and may be associated with more side effects. Methods: We performed cross-sectional multivariable ordered logistic regression to examine the association between predialysis blood pressure and the short physical performance battery (SPPB) in a cohort of 749 prevalent hemodialysis patients in the San Francisco and Atlanta areas recruited from July 2009 to August 2011 to study the relationship between systolic blood pressure and objective measures of physical function. Mean blood pressure for three hemodialysis sessions was analyzed in the following categories: <110 mmHg, 110-129 mmHg (reference), 130-159 mmHg, and >= 160 mmHg. SPPB includes three components: timed repeated chair stands, timed 15-ft walk, and balance tests. SPPB was categorized into ordinal groups (<= 6, 7-9, 10-12) based on prior literature. Results: Patients with blood pressure 130-159 mmHg had lower odds (OR 0.57, 95% CI 0.35-0.93) of scoring in a lower SPPB category than those whose blood pressure was between 110 and 129 mmHg, while those with blood pressure >= 160 mmHg had 0.56 times odds (95% CI 0.33-0.94) of scoring in a lower category when compared with blood pressure 110-129 mmHg. When individual components were examined, blood pressure was significantly associated with chair stand (130-159 mmHg: OR 0.59, 95% CI 0.38-0.92) and gait speed (>= 160 mmHg: OR 0.59, 95% CI 0.35-0.98). Blood pressure >= 160 mmHg was not associated with substantially higher SPPB score compared with 130-159 mmHg. Conclusions: Patients with systolic blood pressure at or above 130 mmHg had better physical performance than patients with lower blood pressure in the normotensive range. The risk-benefit tradeoff of aggressive blood pressure control, particularly in low-functioning patients, should be reexamined. C1 [Abreo, Adrian P.] Univ Cincinnati, Coll Med, Dept Nephrol, Cincinnati, OH 45267 USA. [Glidden, David; Johansen, Kirsten L.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Painter, Patricia] Univ Utah, Dept Phys Therapy, Salt Lake City, UT USA. [Lea, Janice] Emory Univ, Div Nephrol, Atlanta, GA 30322 USA. [Herzog, Charles A.] Hennepin Cty Med Ctr, Div Cardiol, Minneapolis, MN 55415 USA. [Herzog, Charles A.] Univ Minnesota, Minneapolis, MN USA. [Herzog, Charles A.] US Renal Data Syst Cardiovasc Special Studies Ctr, Minneapolis, MN USA. [Kutner, Nancy G.; Johansen, Kirsten L.] US Renal Data Syst Rehabil Qual Life Special Stud, Atlanta, GA USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. [Johansen, Kirsten L.] US Renal Data Syst Nutr Special Studies Ctr, San Francisco, CA USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] Nephrol Sect, San Francisco, CA 94121 USA. RP Johansen, KL (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. EM kirsten.johansen@ucsf.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [N01-DK-7-0005, N01-DK-7-5004]; [K24DK085153] FX This work was supported through contracts N01-DK-7-0005 and N01-DK-7-5004 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and a K24DK085153 grant. The authors would like to thank Julie W. Doyle, MS for administrative support. NR 21 TC 1 Z9 1 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2369 J9 BMC NEPHROL JI BMC Nephrol. PD NOV 15 PY 2014 VL 15 AR 177 DI 10.1186/1471-2369-15-177 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AU7RN UT WOS:000345797700001 PM 25399253 ER PT J AU Arbabshirani, MR Damaraju, E Phlypo, R Plis, S Allen, E Ma, S Mathalon, D Preda, A Vaidya, JG Adali, T Calhoun, VD AF Arbabshirani, Mohammad R. Damaraju, Eswar Phlypo, Ronald Plis, Sergey Allen, Elena Ma, Sai Mathalon, Daniel Preda, Adrian Vaidya, Jatin G. Adali, Tuelay Calhoun, Vince D. TI Impact of autocorrelation on functional connectivity SO NEUROIMAGE LA English DT Article DE Autocorrelation; Functional connectivity; Independent component analysis; Autoregressive process; Resting-state fMRI ID FMRI TIME-SERIES; RESTING-STATE DATA; NETWORK CONNECTIVITY; TEMPORAL AUTOCORRELATION; EMPIRICAL ANALYSES; NULL-HYPOTHESIS; HUMAN BRAIN; NOISE; MRI; SCHIZOPHRENIA AB Although the impact of serial correlation (autocorrelation) in residuals of general linear models for fMRI time-series has been studied extensively, the effect of autocorrelation on functional connectivity studies has been largely neglected until recently. Some recent studies based on results from economics have questioned the conventional estimation of functional connectivity and argue that not correcting for autocorrelation in fMRI time-series results in "spurious" correlation coefficients. In this paper, first we assess the effect of autocorrelation on Pearson correlation coefficient through theoretical approximation and simulation. Then we present this effect on real fMRI data. To our knowledge this is the first work comprehensively investigating the effect of autocorrelation on functional connectivity estimates. Our results show that although FC values are altered, even following correction for autocorrelation, results of hypothesis testing on FC values remain very similar to those before correction. In real data we show this is true for main effects and also for group difference testing between healthy controls and schizophrenia patients. We further discuss model order selection in the context of autoregressive processes, effects of frequency filtering and propose a preprocessing pipeline for connectivity studies. (c) 2014 Elsevier Inc. All rights reserved. C1 [Arbabshirani, Mohammad R.; Damaraju, Eswar; Plis, Sergey; Allen, Elena; Calhoun, Vince D.] Mind Res Network, Albuquerque, NM 87106 USA. [Arbabshirani, Mohammad R.; Calhoun, Vince D.] Univ New Mexico, Dept ECE, Albuquerque, NM 87131 USA. [Phlypo, Ronald; Ma, Sai; Adali, Tuelay] Univ Maryland, Dept CSEE, Baltimore, MD USA. [Allen, Elena] Univ Bergen, KG Jebsen Cener Res Neuropsychiat Disorders, N-5020 Bergen, Norway. [Allen, Elena] Univ Bergen, Dept Biol & Med Psychol, N-5020 Bergen, Norway. [Mathalon, Daniel] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Mathalon, Daniel] San Francisco VA Med Ctr, San Francisco, CA USA. [Preda, Adrian] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [Vaidya, Jatin G.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. RP Arbabshirani, MR (reprint author), Mind Res Network, 1101 Yale Blvd NE, Albuquerque, NM 87106 USA. EM marbabshirani@mrn.org RI Preda, Adrian /K-8889-2013 OI Preda, Adrian /0000-0003-3373-2438; Plis, Sergey/0000-0003-0040-0365 FU NIH (NCRR) [U24-RR021992]; COBRE NIGMS [P20GM103472] FX We would like to acknowledge the efforts of all parties responsible for designing and implementing the experiment, collecting the data, and facilitating the brain imaging that made this study possible. Funding was provided by NIH for the FBIRN study (NCRR grant U24-RR021992) and COBRE NIGMS P20GM103472. NR 53 TC 11 Z9 11 U1 0 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD NOV 15 PY 2014 VL 102 BP 294 EP 308 DI 10.1016/j.neuroimage.2014.07.045 PN 2 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AU1PD UT WOS:000345391700006 PM 25072392 ER PT J AU Wheelock, MD Sreenivasan, KR Wood, KH Hoef, LWV Deshpande, G Knight, DC AF Wheelock, M. D. Sreenivasan, K. R. Wood, K. H. Hoef, L. W. Ver Deshpande, Gopikrishna Knight, D. C. TI Threat-related learning relies on distinct dorsal prefrontal cortex network connectivity SO NEUROIMAGE LA English DT Article DE Anxiety; Connectivity; Conditioning; Fear; fMRI ID GRANGER CAUSALITY ANALYSIS; ANTERIOR CINGULATE CORTEX; RESTING-STATE CONNECTIVITY; HUMAN AMYGDALA ACTIVITY; COGNITIVE CONTROL; CONDITIONED DIMINUTION; NEURAL MECHANISMS; ANXIETY DISORDER; FUNCTIONAL MRI; FEAR RESPONSES AB Conditioned changes in the emotional response to threat (e. g. aversive unconditioned stimulus; UCS) are mediated in part by the prefrontal cortex (PFC). Unpredictable threats elicit large emotional responses, while the response is diminished when the threat is predictable. A better understanding of how PFC connectivity to other brain regions varies with threat predictability would provide important insights into the neural processes that mediate conditioned diminution of the emotional response to threat. The present study examined brain connectivity during predictable and unpredictable threat exposure using a fear conditioning paradigm (previously published in Wood et al., 2012) in which unconditioned functional magnetic resonance imaging data were reanalyzed to assess effective connectivity. Granger causality analysis was performed using the time series data from 15 activated regions of interest after hemodynamic deconvolution, to determine regional effective connectivity. In addition, connectivity path weights were correlated with trait anxiety measures to assess the relationship between negative affect and brain connectivity. Results indicate the dorsomedial PFC (dmPFC) serves as a neural hub that influences activity in other brain regions when threats are unpredictable. In contrast, the dorsolateral PFC (dlPFC) serves as a neural hub that influences the activity of other brain regions when threats are predictable. These findings are consistent with the view that the dmPFC coordinates brain activity to take action, perhaps in a reactive manner, when an unpredicted threat is encountered, while the dlPFC coordinates brain regions to take action, in what may be a more proactive manner, to respond to predictable threats. Further, dlPFC connectivity to other brain regions (e. g. ventromedial PFC, amygdala, and insula) varied with negative affect (i.e. trait anxiety) when the UCS was predictable, suggesting that stronger connectivity may be required for emotion regulation in individuals with higher levels of negative affect. (C) 2014 Elsevier Inc. All rights reserved. C1 [Wheelock, M. D.; Wood, K. H.; Knight, D. C.] Univ Alabama Birmingham, Dept Psychol, Birmingham, AL 35233 USA. [Hoef, L. W. Ver] Univ Alabama Birmingham, Birmingham VA Med Ctr, Sch Med, Dept Neurol, Birmingham, AL 35233 USA. [Sreenivasan, K. R.; Deshpande, Gopikrishna] Auburn Univ, AU MRI Res Ctr, Dept Elect & Comp Engn, Auburn, AL 36849 USA. [Deshpande, Gopikrishna] Auburn Univ, Dept Psychol, Auburn, AL 36849 USA. RP Knight, DC (reprint author), Univ Alabama Birmingham, Dept Psychol, CIRC 235H,1720 2nd Ave S, Birmingham, AL 35233 USA. EM knightdc@uab.edu OI Deshpande, Gopikrishna/0000-0001-7471-5357 FU University of Alabama at Birmingham Faculty Development Grant Program; NIH [MH098348] FX This research was supported by the University of Alabama at Birmingham Faculty Development Grant Program and NIH grant MH098348 (D.C.K). NR 87 TC 13 Z9 13 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD NOV 15 PY 2014 VL 102 BP 904 EP 912 DI 10.1016/j.neuroimage.2014.08.005 PN 2 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AU1PD UT WOS:000345391700063 PM 25111474 ER PT J AU Garner, AP Gozgit, JM Anjum, R Vodala, S Schrock, A Zhou, TJ Serrano, C Eilers, G Zhu, MJ Ketzer, J Wardwell, S Ning, YY Song, Y Kohlmann, A Wang, F Clackson, T Heinrich, MC Fletcher, JA Bauer, S Rivera, VM AF Garner, Andrew P. Gozgit, Joseph M. Anjum, Rana Vodala, Sadanand Schrock, Alexa Zhou, Tianjun Serrano, Cesar Eilers, Grant Zhu, Meijun Ketzer, Julia Wardwell, Scott Ning, Yaoyu Song, Youngchul Kohlmann, Anna Wang, Frank Clackson, Tim Heinrich, Michael C. Fletcher, Jonathan A. Bauer, Sebastian Rivera, Victor M. TI Ponatinib Inhibits Polyclonal Drug-Resistant KIT Oncoproteins and Shows Therapeutic Potential in Heavily Pretreated Gastrointestinal Stromal Tumor (GIST) Patients SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; CHROMOSOME-POSITIVE LEUKEMIAS; C-KIT; IMATINIB RESISTANCE; MUTAGENESIS SCREEN; KINASE INHIBITOR; TYROSINE KINASE; MUTATIONS; SUNITINIB; EFFICACY AB Purpose: KIT is the major oncogenic driver of gastrointestinal stromal tumors (GIST). Imatinib, sunitinib, and regorafenib are approved therapies; however, efficacy is often limited by the acquisition of polyclonal secondary resistance mutations in KIT, with those located in the activation (A) loop (exons 17/18) being particularly problematic. Here, we explore the KIT-inhibitory activity of ponatinib in preclinical models and describe initial characterization of its activity in patients with GIST. Experimental Design: The cellular and in vivo activities of ponatinib, imatinib, sunitinib, and regorafenib against mutant KIT were evaluated using an accelerated mutagenesis assay and a panel of engineered and GIST-derived cell lines. The ponatinib-KIT costructure was also determined. The clinical activity of ponatinib was examined in three patients with GIST previously treated with all three FDA-approved agents. Results: In engineered and GIST-derived cell lines, ponatinib potently inhibited KIT exon 11 primary mutants and a range of secondary mutants, including those within the A-loop. Ponatinib also induced regression in engineered and GIST-derived tumor models containing these secondary mutations. In a mutagenesis screen, 40 nmol/L ponatinib was sufficient to suppress outgrowth of all secondary mutants except V654A, which was suppressed at 80 nmol/L. This inhibitory profile could be rationalized on the basis of structural analyses. Ponatinib (30 mg daily) displayed encouraging clinical activity in two of three patients with GIST. Conclusion: Ponatinib possesses potent activity against most major clinically relevant KIT mutants and has demonstrated preliminary evidence of activity in patients with refractory GIST. These data strongly support further evaluation of ponatinib in patients with GIST. Clin Cancer Res; 20(22); 5745-55. (C) 2014 AACR. C1 [Garner, Andrew P.; Gozgit, Joseph M.; Anjum, Rana; Vodala, Sadanand; Schrock, Alexa; Zhou, Tianjun; Wardwell, Scott; Ning, Yaoyu; Song, Youngchul; Kohlmann, Anna; Wang, Frank; Clackson, Tim; Rivera, Victor M.] ARIAD Pharmaceut Inc, Cambridge, MA 02139 USA. [Serrano, Cesar; Eilers, Grant; Zhu, Meijun; Fletcher, Jonathan A.] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA. [Ketzer, Julia; Bauer, Sebastian] Univ Duisburg Essen, West German Canc Ctr, Dept Med Oncol, Sarcoma Ctr, Essen, Germany. [Heinrich, Michael C.] Portland VA Med Ctr, Portland, OR USA. [Heinrich, Michael C.] OHSU Knight Canc Inst, Portland, OR USA. RP Rivera, VM (reprint author), ARIAD Pharmaceut Inc, Preclin & Translat Res, 26 Landsdowne St, Cambridge, MA 02139 USA. EM victor.rivera@ariad.com FU Deutsche Krebshilfe; U.S. NIH [1P50CA127003-07, 1P50CA168512-01]; Virginia and Daniel K. Ludwig Trust for Cancer Research; GIST Cancer Research Fund; Life Raft Group; ASCO Young Investigator Award; Spanish Society of Medical Oncology Translational Award; VA Merit Award from the Department of Veterans Affairs FX This work was supported by grants from Deutsche Krebshilfe (S.Bauer); the U.S. NIH, including 1P50CA127003-07 and 1P50CA168512-01 (J.A.Fletcher); the Virginia and Daniel K. Ludwig Trust for Cancer Research (J.A.Fletcher); the GIST Cancer Research Fund (M.C. Heinrich, J.A.Fletcher); the Life Raft Group (M.C.Heinrich, J.A.Fletcher, S.Bauer); an ASCO Young Investigator Award (C.Serrano); the Spanish Society of Medical Oncology Translational Award (C. Serrano); and a VA Merit Award Grant (M.C. Heinrich) from the Department of Veterans Affairs. NR 34 TC 15 Z9 17 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2014 VL 20 IS 22 BP 5745 EP 5755 DI 10.1158/1078-0432.CCR-14-1397 PG 11 WC Oncology SC Oncology GA AT7PT UT WOS:000345130800019 PM 25239608 ER PT J AU Kontoyiannis, DP Patterson, TF AF Kontoyiannis, Dimitrios P. Patterson, Thomas F. TI Diagnosis and Treatment of Invasive Fungal Infections in the Cancer Patient: Recent Progress and Ongoing Questions SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE cancer; Aspergillosis; candidiasis; treatment; diagnosis ID POLYMERASE-CHAIN-REACTION; HEMATOLOGICAL MALIGNANCIES; ANTIFUNGAL THERAPY; MOLD INFECTIONS; ASPERGILLOSIS; PULMONARY; GALACTOMANNAN; DISEASES; IDENTIFICATION; MUCORMYCOSIS AB In the last 5 years we have witnessed further developments in diagnosis and treatment of invasive fungal infections (IFIs) that complicate cancer chemotherapy. In this brief overview, we highlight some advancement, discuss future directions, and unmet needs in this complex area. C1 [Kontoyiannis, Dimitrios P.; Patterson, Thomas F.] Univ Texas MD Anderson Canc Ctr, Div Internal Med, Houston, TX 77030 USA. [Kontoyiannis, Dimitrios P.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Kontoyiannis, Dimitrios P.; Patterson, Thomas F.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Kontoyiannis, DP (reprint author), Univ Texas MD Anderson Canc Ctr, Div Internal Med, 1400 Pressler St,FCT 12-5069,Unit 1463, Houston, TX 77030 USA. EM dkontoyi@mdanderson.org FU National Institute of Health; Agency for Healthcare Research and Quality (AHRQ) [R13 HS021599] FX Funding for this conference was made possible [in part] by the National Institute of Health and by grant (R13 HS021599) from the Agency for Healthcare Research and Quality (AHRQ). NR 37 TC 4 Z9 4 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2014 VL 59 SU 5 BP S356 EP S359 DI 10.1093/cid/ciu591 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AT0TQ UT WOS:000344648100006 PM 25352631 ER PT J AU Lu, L Zheng, L Si, Y Luo, WY Dujardin, G Kwan, T Potochick, NR Thompson, SR Schneider, DA King, PH AF Lu, Liang Zheng, Lei Si, Ying Luo, Wenyi Dujardin, Gwendal Kwan, Thaddaeus Potochick, Nicholas R. Thompson, Sunnie R. Schneider, David A. King, Peter H. TI Hu Antigen R (HuR) Is a Positive Regulator of the RNA-binding Proteins TDP-43 and FUS/TLS IMPLICATIONS FOR AMYOTROPHIC LATERAL SCLEROSIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Amyotrophic Lateral Sclerosis (ALS) (Lou Gehrig Disease); Astrocyte; Neuron; RNA Processing; RNA Splicing; 3 Untranslated Region ID NUCLEAR FACTOR TDP-43; MESSENGER-RNA; MOTOR-NEURONS; TRANSLATIONAL CONTROL; STRESS GRANULES; RICH ELEMENTS; WIDE ANALYSIS; UP-REGULATION; CFTR EXON-9; STABILITY AB Background: RNA processing abnormalities have been linked to amyotrophic lateral sclerosis (ALS). Results: HuR promotes the expression of the ALS-associated TDP-43 and FUS/TLS RNA-binding proteins. Conclusion: Through its regulation of TDP-43 and FUS/TLS, HuR potentially impacts a wide range of molecular and cellular phenotypes. Significance: A network of proteins exists to maintain RNA processing, and ALS-associated abnormalities may stem from disruption of this network. Posttranscriptional gene regulation is governed by a network of RNA-binding proteins (RBPs) that interact with regulatory elements in the mRNA to modulate multiple molecular processes, including splicing, RNA transport, RNA stability, and translation. Mounting evidence indicates that there is a hierarchy within this network whereby certain RBPs cross-regulate other RBPs to coordinate gene expression. HuR, an RNA-binding protein we linked previously to aberrant VEGF mRNA metabolism in models of SOD1-associated amyotrophic lateral sclerosis, has been identified as being high up in this hierarchy, serving as a regulator of RNA regulators. Here we investigated the role of HuR in regulating two RBPs, TDP-43 and FUS/TLS, that have been linked genetically to amyotrophic lateral sclerosis. We found that HuR promotes the expression of both RBPs in primary astrocytes and U251 cells under normal and stressed (hypoxic) conditions. For TDP-43, we found that HuR binds to the 3 untranslated region (UTR) and regulates its expression through translational efficiency rather than RNA stability. With HuR knockdown, there was a shift of TDP-43 and FUS mRNAs away from polysomes, consistent with translational silencing. The TDP-43 splicing function was attenuated upon HuR knockdown and could be rescued by ectopic TDP-43 lacking the 3 UTR regulatory elements. Finally, conditioned medium from astrocytes in which HuR or TDP-43 was knocked down produced significant motor neuron and cortical neuron toxicity in vitro. These findings indicate that HuR regulates TDP-43 and FUS/TLS expression and that loss of HuR-mediated RNA processing in astrocytes can alter the molecular and cellular landscape to produce a toxic phenotype. C1 [Lu, Liang; Zheng, Lei; Si, Ying; Luo, Wenyi; Kwan, Thaddaeus; King, Peter H.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Lu, Liang; King, Peter H.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA. [King, Peter H.] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL 35294 USA. [Potochick, Nicholas R.; Thompson, Sunnie R.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. [Schneider, David A.] Univ Alabama Birmingham, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA. [Lu, Liang; King, Peter H.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. [Dujardin, Gwendal] Univ Buenos Aires, Fac Ciencias Exactas & Nat, Buenos Aires, DF, Argentina. RP Lu, L (reprint author), Sparks Ctr, Dept Neurol, Suite 260,1720 7th Ave S, Birmingham, AL 35233 USA. EM luliang@uab.edu; pking@uab.edu RI Dujardin, Gwendal/K-7464-2015 OI Dujardin, Gwendal/0000-0003-4320-6351; Schneider, David/0000-0003-0635-5091 FU NINDS, National Intitutes of Health [NS064133, R21NS081743, R21NS085497, NS057664]; Department of Veterans Affairs FX This work was supported, in whole or in part, by NINDS, National Intitutes of Health Grants NS064133, R21NS081743, and R21NS085497 (to P. H. K.) and NS057664 (to L. L.). This work was also supported by a Merit Review award from the Department of Veterans Affairs (to P. H. K.). NR 70 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 14 PY 2014 VL 289 IS 46 BP 31792 EP 31804 DI 10.1074/jbc.M114.573246 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AU0LP UT WOS:000345314700011 PM 25239623 ER PT J AU Hsu, C Lemon, JM Wong, ES Carson-Cheng, E Perkins, M Nordstrom, MS Liu, CF Sprague, C Bryson, CL AF Hsu, Clarissa Lemon, Jaclyn M. Wong, Edwin S. Carson-Cheng, Elizabeth Perkins, Mark Nordstrom, Margaret S. Liu, Chuan-Fen Sprague, Carol Bryson, Christopher L. TI Factors affecting medication adherence: patient perspectives from five veterans affairs facilities SO BMC HEALTH SERVICES RESEARCH LA English DT Article DE Diabetes; Medication adherence; Chronic disease management; Patient self-management; Delivery of care; Veterans; Health systems research; Pharmacy services research; Patient-oriented research ID TYPE-2 DIABETES-MELLITUS; SELF-MANAGEMENT; BARRIERS; CARE; OUTCOMES; NONADHERENCE; PERCEPTIONS; PREDICTORS; GUIDELINE; PROGRAM AB Background: In the United States, more than 25 million people have diabetes. Medication adherence is known to be important for disease control. However, factors that consistently predict medication adherence are unclear and the literature lacks patient perspectives on how health care systems affect adherence to oral hypoglycemic agents (OHAs). This study explored facilitators and barriers to OHA adherence by obtaining the perspectives of Veterans Affairs (VA) patients with OHA prescriptions. Methods: A total of 45 patients participated in 12 focus groups that explored a wide range of issues that might affect medication adherence. Participants were patients at clinics in Seattle, Washington; San Antonio, Texas; Portland, Oregon; Salem, Oregon, and Warrenton, Oregon. Results: Key system-level facilitators of OHA adherence included good overall pharmacy service and several specific mechanisms for ordering and delivering medications (automated phone refill service, Web-based prescription ordering), as well as providing pillboxes and printed lists of current medications to patients. Barriers mirrored many of the facilitators. Poor pharmacy service quality and difficulty coordinating multiple prescriptions emerged as key barriers. Conclusions: VA patient focus groups provided insights on how care delivery systems can encourage diabetes medication adherence by minimizing the barriers and enhancing the facilitators at both the patient and system levels. Major system-level factors that facilitated adherence were overall pharmacy service quality, availability of multiple systems for reordering medications, having a person to call when questions arose, counseling about the importance of adherence and providing tools such as pillboxes and updated medication lists. C1 [Hsu, Clarissa; Carson-Cheng, Elizabeth] Ctr Community Hlth & Evaluat, Grp Hlth Res Inst, Seattle, WA 98101 USA. [Lemon, Jaclyn M.; Wong, Edwin S.; Perkins, Mark; Nordstrom, Margaret S.; Liu, Chuan-Fen; Bryson, Christopher L.] VA Puget Sound Hlth Care Syst, Northwest Ctr Outcomes Res Older Adults, Seattle, WA 98108 USA. [Bryson, Christopher L.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Hsu, Clarissa; Wong, Edwin S.; Liu, Chuan-Fen] Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Serv, Seattle, WA 98195 USA. [Sprague, Carol] Portland VA Med Ctr, Portland, OR 97239 USA. [Sprague, Carol] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. RP Hsu, C (reprint author), Ctr Community Hlth & Evaluat, Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM hsu.c@ghc.org FU Investigator Initiated Research Award from the 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] FX This research was supported by an Investigator Initiated Research Award (IIR 07-068-2, PI: Bryson) 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. NR 39 TC 5 Z9 5 U1 2 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 NOV 13 PY 2014 VL 14 AR 533 DI 10.1186/s12913-014-0533-1 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AZ7ST UT WOS:000348418800001 PM 25391694 ER PT J AU Mayer, EA Knight, R Mazmanian, SK Cryan, JF Tillisch, K AF Mayer, Emeran A. Knight, Rob Mazmanian, Sarkis K. Cryan, John F. Tillisch, Kirsten TI Gut Microbes and the Brain: Paradigm Shift in Neuroscience SO JOURNAL OF NEUROSCIENCE LA English DT Article ID ANXIETY-LIKE BEHAVIOR; PROBIOTIC BIFIDOBACTERIUM-INFANTIS; IRRITABLE-BOWEL-SYNDROME; LACTOBACILLUS-HELVETICUS; MICE; AXIS; DISORDERS; STRESS; DISEASE; RATS AB The discovery of the size and complexity of the human microbiome has resulted in an ongoing reevaluation of many concepts of health and disease, including diseases affecting the CNS. A growing body of preclinical literature has demonstrated bidirectional signaling between the brain and the gut microbiome, involving multiple neurocrine and endocrine signaling mechanisms. While psychological and physical stressors can affect the composition and metabolic activity of the gut microbiota, experimental changes to the gut microbiome can affect emotional behavior and related brain systems. These findings have resulted in speculation that alterations in the gut microbiome may play a pathophysiological role in human brain diseases, including autism spectrum disorder, anxiety, depression, and chronic pain. Ongoing large-scale population-based studies of the gut microbiome and brain imaging studies looking at the effect of gut microbiome modulation on brain responses to emotion-related stimuli are seeking to validate these speculations. This article is a summary of emerging topics covered in a symposium and is not meant to be a comprehensive review of the subject. C1 [Mayer, Emeran A.; Tillisch, Kirsten] Univ Calif Los Angeles, David Geffen Sch Med, Oppenheimer Ctr Neurobiol Stress, Dept Med, Los Angeles, CA 90095 USA. [Mayer, Emeran A.; Tillisch, Kirsten] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. [Mayer, Emeran A.; Tillisch, Kirsten] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biobehav Sci, Div Digest Dis, Los Angeles, CA 90095 USA. [Knight, Rob] Univ Colorado, Howard Hughes Med Inst, Boulder, CO 80309 USA. [Knight, Rob] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA. [Knight, Rob] Univ Colorado, Dept Comp Sci, Boulder, CO 80309 USA. [Knight, Rob] Univ Colorado, BioFrontiers Inst, Boulder, CO 80309 USA. [Mazmanian, Sarkis K.] CALTECH, Dept Biol & Biol Engn, Pasadena, CA 91125 USA. [Cryan, John F.] Natl Univ Ireland Univ Coll Cork, Dept Anat & Neurosci, Cork, Ireland. [Cryan, John F.] Natl Univ Ireland Univ Coll Cork, Alimentary Pharmabiot Ctr, Cork, Ireland. [Tillisch, Kirsten] Vet Adm Greater Los Angeles Healthcare Syst, Div Integrat Med, Dept Med, Los Angeles, CA 90073 USA. RP Mayer, EA (reprint author), Univ Calif Los Angeles, CHS 42-210,MC737818,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM emayer@ucla.edu RI Knight, Rob/D-1299-2010 OI Cryan, John/0000-0001-5887-2723 FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Grant [R01 DK048351, P30 DK041301]; National Institutes of Health/National Institute of Mental Health Grant [R01 MH100556]; Simons Foundation SFARI Program; Howard Hughes Medical Institute; Autism Speaks FX This work was supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Grant R01 DK048351 to E. A. M., Grant P30 DK041301, National Institutes of Health/National Institute of Mental Health Grant R01 MH100556 to S. K. M., Autism Speaks to S. K. M., Simons Foundation SFARI Program to S. K. M., and Howard Hughes Medical Institute to R. K. NR 74 TC 107 Z9 110 U1 34 U2 263 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 12 PY 2014 VL 34 IS 46 BP 15490 EP 15496 DI 10.1523/JNEUROSCI.3299-14.2014 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AT9AU UT WOS:000345220900037 PM 25392516 ER PT J AU Ehdaie, A Rubin, SA AF Ehdaie, Ashkan Rubin, Stanley A. TI Letter by Ehdaie and Rubin Regarding Article, "Long-Term Arrhythmia-Free Survival in Patients With Severe Left Ventricular Dysfunction and No Inducible Ventricular Tachycardia After Myocardial Infarction" SO CIRCULATION LA English DT Letter ID RECOVERY C1 [Ehdaie, Ashkan] VA Greater Los Angeles Healthcare Syst, Cedars Sinai Heart Inst, Dept Cardiol, Los Angeles, CA 90073 USA. [Rubin, Stanley A.] UCLA Sch Med, Dept Cardiol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Ehdaie, A (reprint author), VA Greater Los Angeles Healthcare Syst, Cedars Sinai Heart Inst, Dept Cardiol, Los Angeles, CA 90073 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 11 PY 2014 VL 130 IS 20 BP E177 EP E177 DI 10.1161/CIRCULATIONAHA.114.009059 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AT4TZ UT WOS:000344936700003 PM 25385942 ER PT J AU Zheng, XJ Demirci, FY Barmada, MM Richardson, GA Lopez, OL Sweet, RA Kamboh, MI Feingold, E AF Zheng, Xiaojing Demirci, F. Yesim Barmada, M. Michael Richardson, Gale A. Lopez, Oscar L. Sweet, Robert A. Kamboh, M. Ilyas Feingold, Eleanor TI A Rare Duplication on Chromosome 16p11.2 Is Identified in Patients with Psychosis in Alzheimer's Disease SO PLOS ONE LA English DT Article ID COPY NUMBER VARIATION; MENTAL-RETARDATION; SEIZURE DISORDER; DOWN-REGULATION; SCHIZOPHRENIA; RISK; MICRODELETION; DELETIONS; AUTISM; ASSOCIATION AB Epidemiological and genetic studies suggest that schizophrenia and autism may share genetic links. Besides common single nucleotide polymorphisms, recent data suggest that some rare copy number variants (CNVs) are risk factors for both disorders. Because we have previously found that schizophrenia and psychosis in Alzheimer's disease (AD+P) share some genetic risk, we investigated whether CNVs reported in schizophrenia and autism are also linked to AD+P. We searched for CNVs associated with AD+P in 7 recurrent CNV regions that have been previously identified across autism and schizophrenia, using the Illumina HumanOmni1-Quad BeadChip. A chromosome 16p11.2 duplication CNV (chr16: 29,554,843-30,105,652) was identified in 2 of 440 AD+P subjects, but not in 136 AD subjects without psychosis, or in 593 AD subjects with intermediate psychosis status, or in 855 non-AD individuals. The frequency of this duplication CNV in AD+P (0.46%) was similar to that reported previously in schizophrenia (0.46%). This duplication CNV was further validated using the NanoString nCounter CNV Custom CodeSets. The 16p11.2 duplication has been associated with developmental delay, intellectual disability, behavioral problems, autism, schizophrenia (SCZ), and bipolar disorder. These two AD+P patients had no personal of, nor any identified family history of, SCZ, bipolar disorder and autism. To the best of our knowledge, our case report is the first suggestion that 16p11.2 duplication is also linked to AD+P. Although rare, this CNV may have an important role in the development of psychosis. C1 [Zheng, Xiaojing; Feingold, Eleanor] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Demirci, F. Yesim; Barmada, M. Michael; Kamboh, M. Ilyas; Feingold, Eleanor] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [Richardson, Gale A.; Sweet, Robert A.; Kamboh, M. Ilyas] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. [Lopez, Oscar L.; Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Lopez, Oscar L.; Sweet, Robert A.; Kamboh, M. Ilyas] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA USA. [Richardson, Gale A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Zheng, Xiaojing] Univ N Carolina, Sch Med, Dept Pediat, Chapel Hill, NC USA. RP Zheng, XJ (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. EM xiaojinz@email.unc.edu OI 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, AG041718, AG005133, AG027224]; NanoString award; NIMH Grant [T32 MH015169] FX This study was supported by the National Institute on Aging grants AG030653, AG041718 (MIK), AG005133 (OLL), and AG027224 (RAS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the Department of Veterans Affairs or the United States Government. Funding for experimental validation was provided by NanoString award. This work was conducted in partial fulfillment of requirements for the first author's doctoral degree, supported by NIMH Grant T32 MH015169 (G.A.R., Program Director). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 2 Z9 4 U1 3 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 7 PY 2014 VL 9 IS 11 AR e111462 DI 10.1371/journal.pone.0111462 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AT3WF UT WOS:000344863100030 PM 25379732 ER PT J AU Ibinson, JW Ezaru, CS Cormican, DS Mangione, MP AF Ibinson, James W. Ezaru, Catalin S. Cormican, Daniel S. Mangione, Michael P. TI GlideScope Use improves intubation success rates: an observational study using propensity score matching SO BMC ANESTHESIOLOGY LA English DT Article DE Airway management; Direct laryngoscopy; Difficult intubation ID DIFFICULT TRACHEAL INTUBATION; DIRECT LARYNGOSCOPY; VIDEO LARYNGOSCOPE; AIRWAY MANAGEMENT; VIDEOLARYNGOSCOPE; COMPLICATIONS; PERFORMANCE; PERFORATION; BLADE; TRIAL AB Background: Rigid video laryngoscopes are popular alternatives to direct laryngoscopy for intubation, but further large scale prospective studies comparing these devices to direct laryngoscopy in routine anesthesiology practice are needed. We hypothesized that the first pass success rate with one particular video laryngoscope, the GlideScope, would be higher than the success rate with direct laryngoscopy. Methods: 3831 total intubation attempts were tracked in an observational study comparing first-pass success rate using a Macintosh or Miller-style laryngoscope with the GlideScope. Propensity scoring was then used to select 626 subjects matched between the two groups based on their morphologic traits. Results: Comparing the GlideScope and direct laryngoscopy groups suggested that intubation would be more difficult in the GlideScope group based on the Mallampati class, cervical range of motion, mouth opening, dentition, weight, and past intubation history. Thus, a propensity score based on these factors was used to balance the groups into two 313 patient cohorts. Direct laryngoscopy was successful in 80.8% on the first-pass intubation attempt, while the GlideScope was successful in 93.6% (p < 0.001; risk difference of 0.128 with a 95% CI of 0.0771 - 0.181). Conclusion: A greater first-attempt success rate was found when using the GlideScope versus direct laryngoscopy. In addition, the GlideScope was found to be 99% successful for intubation after initial failure of direct laryngoscopy, helping to reduce the incidence of failed intubation. C1 [Ibinson, James W.; Ezaru, Catalin S.; Mangione, Michael P.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. [Ibinson, James W.; Ezaru, Catalin S.; Mangione, Michael P.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15261 USA. [Cormican, Daniel S.] Univ Pittsburgh, Med Ctr, Dept Anesthesiol, Pittsburgh, PA USA. RP Mangione, MP (reprint author), Univ Pittsburgh, Sch Med, Dept Anesthesiol, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. EM mangionemp@anes.upmc.edu OI Ibinson, James/0000-0002-5525-5225 FU NIH [T32GM075770]; Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, PA FX The authors would like to thank the Anesthesiologists and the Certified Registered Nurse Anesthetists of the VA Pittsburgh Healthcare System for their dedicated efforts toward the collection of the data for this project. During a portion of his work on this project, Dr Ibinson was supported by NIH Grant Number T32GM075770. This material is also the result of work supported with resources and the use of facilities at the VA Pittsburgh Health Care System. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. Other support includes the Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, PA. NR 22 TC 5 Z9 5 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2253 J9 BMC ANESTHESIOL JI BMC Anesthesiol. PD NOV 5 PY 2014 VL 14 AR 101 DI 10.1186/1471-2253-14-101 PG 8 WC Anesthesiology SC Anesthesiology GA AX4XS UT WOS:000346932800001 PM 25400507 ER PT J AU Spainhour, JCG Janech, MG Schwacke, JH Velez, JCQ Ramakrishnan, V AF Spainhour, John Christian G. Janech, Michael G. Schwacke, John H. Velez, Juan Carlos Q. Ramakrishnan, Viswanathan TI The Application of Gaussian Mixture Models for Signal Quantification in MALDI-ToF Mass Spectrometry of Peptides SO PLOS ONE LA English DT Article ID RENIN-ANGIOTENSIN SYSTEM; ASSISTED-LASER-DESORPTION/IONIZATION; COMPLEX PROTEIN MIXTURES; ABSOLUTE QUANTIFICATION; ENDOTHELIAL-CELLS; LC-MS; PROTEOMICS; IDENTIFICATION; ENZYME; PLASMA AB Matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) coupled with stable isotope standards (SIS) has been used to quantify native peptides. This peptide quantification by MALDI-TOF approach has difficulties quantifying samples containing peptides with ion currents in overlapping spectra. In these overlapping spectra the currents sum together, which modify the peak heights and make normal SIS estimation problematic. An approach using Gaussian mixtures based on known physical constants to model the isotopic cluster of a known compound is proposed here. The characteristics of this approach are examined for single and overlapping compounds. The approach is compared to two commonly used SIS quantification methods for single compound, namely Peak Intensity method and Riemann sum area under the curve (AUC) method. For studying the characteristics of the Gaussian mixture method, Angiotensin II, Angiotensin-2-10, and Angiotenisn-1-9 and their associated SIS peptides were used. The findings suggest, Gaussian mixture method has similar characteristics as the two methods compared for estimating the quantity of isolated isotopic clusters for single compounds. All three methods were tested using MALDI-TOF mass spectra collected for peptides of the renin-angiotensin system. The Gaussian mixture method accurately estimated the native to labeled ratio of several isolated angiotensin peptides (5.2% error in ratio estimation) with similar estimation errors to those calculated using peak intensity and Riemann sum AUC methods (5.9% and 7.7%, respectively). For overlapping angiotensin peptides, (where the other two methods are not applicable) the estimation error of the Gaussian mixture was 6.8%, which is within the acceptable range. In summary, for single compounds the Gaussian mixture method is equivalent or marginally superior compared to the existing methods of peptide quantification and is capable of quantifying overlapping (convolved) peptides within the acceptable margin of error. C1 [Spainhour, John Christian G.; Ramakrishnan, Viswanathan] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Janech, Michael G.; Velez, Juan Carlos Q.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Velez, Juan Carlos Q.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Schwacke, John H.] Sci Res Corp, N Charleston, SC USA. RP Spainhour, JCG (reprint author), Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. EM jcs21@musc.edu RI Velez, Juan Carlos/N-3782-2016 OI Janech, Michael/0000-0002-3202-4811 FU National Institute of General Medicine [5T32GM74934-8]; National Institutes of Health [5DK080944] FX JCGS was supported under a training grant from the National Institute of General Medicine (5T32GM74934-8) http://www.nigms.nih.gov/Pages/default.aspx. JCQV was supported by a grant from the National Institutes of Health (5DK080944) http://www.nih.gov/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 2 Z9 2 U1 2 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 NOV 5 PY 2014 VL 9 IS 11 AR e111016 DI 10.1371/journal.pone.0111016 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AS9IQ UT WOS:000344556900032 PM 25372836 ER PT J AU Maddox, TM Stanislawski, MA Grunwald, GK Bradley, SM Ho, PM Tsai, TT Patel, MR Sandhu, A Valle, J Magid, DJ Leon, B Bhatt, DL Fihn, SD Rumsfeld, JS AF Maddox, Thomas M. Stanislawski, Maggie A. Grunwald, Gary K. Bradley, Steven M. Ho, P. Michael Tsai, Thomas T. Patel, Manesh R. Sandhu, Amneet Valle, Javier Magid, David J. Leon, Benjamin Bhatt, Deepak L. Fihn, Stephan D. Rumsfeld, John S. TI Nonobstructive Coronary Artery Disease and Risk of Myocardial Infarction SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID COMPUTED TOMOGRAPHIC ANGIOGRAPHY; SECONDARY PREVENTION THERAPIES; CLINICAL-ASSESSMENT; MORTALITY RISK; CART PROGRAM; INSIGHTS; OUTCOMES; ANGINA; STRATIFICATION; IMPLEMENTATION AB IMPORTANCE Little is known about cardiac adverse events among patients with nonobstructive coronary artery disease (CAD). OBJECTIVE To compare myocardial infarction (MI) and mortality rates between patients with nonobstructive CAD, obstructive CAD, and no apparent CAD in a national cohort. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of all US veterans undergoing elective coronary angiography for CAD between October 2007 and September 2012 in the Veterans Affairs health care system. Patients with prior CAD events were excluded. EXPOSURES Angiographic CAD extent, defined by degree (no apparent CAD: no stenosis >20%; nonobstructive CAD: >= 1 stenosis >= 20% but no stenosis >= 70%; obstructive CAD: any stenosis >= 70% or left main [LM] stenosis >= 50%) and distribution (1, 2, or 3 vessel). MAIN OUTCOMES AND MEASURES The primary outcome was 1-year hospitalization for nonfatal MI after the index angiography. Secondary outcomes included 1-year all-cause mortality and combined 1-year MI and mortality. RESULTS Among 37 674 patients, 8384 patients (22.3%) had nonobstructive CAD and 20 899 patients (55.4%) had obstructive CAD. Within 1 year, 845 patients died and 385 were rehospitalized for MI. Among patients with no apparent CAD, the 1-year MI rate was 0.11% (n = 8, 95% CI, 0.10%-0.20%) and increased progressively by 1-vessel nonobstructive CAD, 0.24%(n = 10, 95% CI, 0.10%-0.40%); 2-vessel nonobstructive CAD, 0.56%(n = 13, 95% CI, 0.30%-1.00%); 3-vessel nonobstructive CAD, 0.59% (n = 6, 95% CI, 0.30%-1.30%); 1-vessel obstructive CAD, 1.18%(n = 101, 95% CI, 1.00%-1.40%); 2-vessel obstructive CAD, 2.18% (n = 110, 95% CI, 1.80%-2.60%); and 3-vessel or LM obstructive CAD, 2.47%(n = 137, 95% CI, 2.10%-2.90%). After adjustment, 1-year MI rates increased with increasing CAD extent. Relative to patients with no apparent CAD, patients with 1-vessel nonobstructive CAD had a hazard ratio (HR) for 1-year MI of 2.0 (95% CI, 0.8-5.1); 2-vessel nonobstructive HR, 4.6 (95% CI, 2.0-10.5); 3-vessel nonobstructive HR, 4.5 (95% CI, 1.6-12.5); 1-vessel obstructive HR, 9.0 (95% CI, 4.2-19.0); 2-vessel obstructive HR, 16.5 (95% CI, 8.1-33.7); and 3-vessel or LM obstructive HR, 19.5 (95% CI, 9.9-38.2). One-year mortality rates were associated with increasing CAD extent, ranging from 1.38% among patients without apparent CAD to 4.30% with 3-vessel or LM obstructive CAD. After risk adjustment, there was no significant association between 1-or 2-vessel nonobstructive CAD and mortality, but there were significant associations with mortality for 3-vessel nonobstructive CAD (HR, 1.6; 95% CI, 1.1-2.5), 1-vessel obstructive CAD (HR, 1.9; 95% CI, 1.4-2.6), 2-vessel obstructive CAD (HR, 2.8; 95% CI, 2.1-3.7), and 3-vessel or LM obstructive CAD (HR, 3.4; 95% CI, 2.6-4.4). Similar associations were noted with the combined outcome. CONCLUSIONS AND RELEVANCE In this cohort of patients undergoing elective coronary angiography, nonobstructive CAD, compared with no apparent CAD, was associated with a significantly greater 1-year risk of MI and all-cause mortality. These findings suggest clinical importance of nonobstructive CAD and warrant further investigation of interventions to improve outcomes among these patients. Copyright 2014 American Medical Association. All rights reserved. C1 [Maddox, Thomas M.; Stanislawski, Maggie A.; Grunwald, Gary K.; Bradley, Steven M.; Ho, P. Michael; Rumsfeld, John S.] VA Eastern Colorado Hlth Care Syst, Denver, CO USA. [Maddox, Thomas M.; Grunwald, Gary K.; Bradley, Steven M.; Ho, P. Michael; Sandhu, Amneet; Valle, Javier; Leon, Benjamin; Rumsfeld, John S.] Univ Colorado, Sch Med, Aurora, CO USA. [Grunwald, Gary K.; Magid, David J.] Colorado Sch Publ Hlth, Aurora, CO USA. [Tsai, Thomas T.; Magid, David J.] Kaiser Permanente Colorado, Denver, CO USA. [Patel, Manesh R.] Duke Univ, Durham, NC USA. [Magid, David J.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Heart & Vasc Ctr, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Fihn, Stephan D.] US Dept Vet Affairs, Off Analyt & Business Intelligence, Washington, DC USA. RP Maddox, TM (reprint author), Denver VA Med Ctr, Div Cardiol, Cardiol Sect 111B, 1055 Clermont St, Denver, CO 80220 USA. EM thomas.maddox@va.gov FU VA Health Services Research and Development career development awards FX The CART program is an operational program of the Department of Veterans Affairs Office of Information and Analytics. Drs Maddox and Bradley are supported with VA Health Services Research and Development career development awards. NR 40 TC 54 Z9 56 U1 4 U2 10 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 NOV 5 PY 2014 VL 312 IS 17 BP 1754 EP 1763 DI 10.1001/jama.2014.14681 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AS3QX UT WOS:000344194500013 PM 25369489 ER PT J AU Stewart, EH Davis, B Clemans-Taylor, BL Littenberg, B Estrada, CA Centor, RM AF Stewart, Emily H. Davis, Brian Clemans-Taylor, B. Lee Littenberg, Benjamin Estrada, Carlos A. Centor, Robert M. TI Rapid Antigen Group A Streptococcus Test to Diagnose Pharyngitis: A Systematic Review and Meta-Analysis SO PLOS ONE LA English DT Article ID PEDIATRIC EMERGENCY-DEPARTMENT; THROAT CULTURE; TEST ACCURACY; CHILDHOOD PHARYNGITIS; SPECTRUM BIAS; SENSITIVITY; MANAGEMENT; PERFORMANCE; VALIDATION; PYOGENES AB Background: Pharyngitis management guidelines include estimates of the test characteristics of rapid antigen streptococcus tests (RAST) using a non-systematic approach. Objective: To examine the sensitivity and specificity, and sources of variability, of RAST for diagnosing group A streptococcal (GAS) pharyngitis. Data Sources: MEDLINE, Cochrane Reviews, Centre for Reviews and Dissemination, Scopus, SciELO, CINAHL, guidelines, 2000-2012. Study Selection: Culture as reference standard, all languages. Data Extraction and Synthesis: Study characteristics, quality. Main Outcome(s) and Measure(s): Sensitivity, specificity. Results: We included 59 studies encompassing 55,766 patients. Forty three studies (18,464 patients) fulfilled the higher quality definition (at least 50 patients, prospective data collection, and no significant biases) and 16 (35,634 patients) did not. For the higher quality immunochromatographic methods in children (10,325 patients), heterogeneity was high for sensitivity (inconsistency [I-2] 88%) and specificity (I-2 86%). For enzyme immunoassay in children (342 patients), the pooled sensitivity was 86% (95% CI, 79-92%) and the pooled specificity was 92% (95% CI, 88-95%). For the higher quality immunochromatographic methods in the adult population (1,216 patients), the pooled sensitivity was 91% (95% CI, 87 to 94%) and the pooled specificity was 93% (95% CI, 92 to 95%); however, heterogeneity was modest for sensitivity (I-2 61%) and specificity (I-2 72%). For enzyme immunoassay in the adult population (333 patients), the pooled sensitivity was 86% (95% CI, 81-91%) and the pooled specificity was 97% (95% CI, 96 to 99%); however, heterogeneity was high for sensitivity and specificity (both, I-2 88%). Conclusions: RAST immunochromatographic methods appear to be very sensitive and highly specific to diagnose group A streptococcal pharyngitis among adults but not in children. We could not identify sources of variability among higher quality studies. The present systematic review provides the best evidence for the wide range of sensitivity included in current guidelines. C1 [Stewart, Emily H.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Davis, Brian] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Clemans-Taylor, B. Lee; Centor, Robert M.] Univ Alabama, Huntsville, AL 35899 USA. [Littenberg, Benjamin] Univ Vermont, Burlington, VT USA. [Estrada, Carlos A.] Univ Alabama Birmingham, Birmingham, AL 35233 USA. [Estrada, Carlos A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Estrada, Carlos A.] Vet Affairs Qual Scholar Program, Birmingham, AL USA. RP Estrada, CA (reprint author), Univ Alabama Birmingham, Birmingham, AL 35233 USA. EM cestrada@uab.edu FU Justin Rogers Foundation FX RMC received funding from Justin Rogers Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 82 TC 11 Z9 11 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 4 PY 2014 VL 9 IS 11 AR e111727 DI 10.1371/journal.pone.0111727 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AS6XG UT WOS:000344402000094 PM 25369170 ER PT J AU Egan, BM Li, JX Hutchison, FN Ferdinand, KC AF Egan, Brent M. Li, Jiexiang Hutchison, Florence N. Ferdinand, Keith C. TI Hypertension in the United States, 1999 to 2012 Progress Toward Healthy People 2020 Goals SO CIRCULATION LA English DT Article DE Healthy People Programs; hypertension; nutrition surveys; population characteristics ID DISEASE RISK-FACTORS; BODY-MASS-INDEX; BLOOD-PRESSURE; NATIONAL-HEALTH; RESISTANT HYPERTENSION; ADULTS; PREVALENCE; AWARENESS; TRENDS; INSURANCE AB Background-To reduce the cardiovascular disease burden, Healthy People 2020 established US hypertension goals for adults to (1) decrease the prevalence to 26.9% and (2) raise treatment to 69.5% and control to 61.2%, which requires controlling 88.1% on treatment. Methods and Results-To assess the current status and progress toward these Healthy People 2020 goals, time trends in National Health and Nutrition Examination Surveys 1999 to 2012 data in 2-year blocks were assessed in adults >= 18 years of age age-adjusted to US 2010. From 1999 to 2000 to 2011 to 2012, prevalent hypertension was unchanged (30.1% versus 30.8%, P=0.32). Hypertension treatment (59.8% versus 74.7%, P<0.001) and proportion of treated adults controlled (53.3%-68.9%, P=0.0015) increased. Hypertension control to <140/< 90 mm Hg rose every 2 years from 1999 to 2000 to 2009 to 2010 (32.2% versus 53.8%, P<0.001) before declining to 51.2% in 2011 to 2012. Modifiable factor(s) significant in multivariable logistic regression modeling include: (1) increasing body mass index with prevalent hypertension (odds ratio [OR], 1.44); (2) lack of health insurance (OR, 1.68) and <2 healthcare visits per year (OR, 4.24) with untreated hypertension; (3) healthcare insurance (OR, 1.69), >= 2 healthcare visits per year (OR, 3.23), and cholesterol treatment (OR, 1.90) with controlled hypertension. Conclusions-The National Health and Nutrition Examination Survey 1999 to 2012 analysis suggests that Healthy People 2020 goals for hypertension ([1] prevalence shows no progress, [2] treatment was exceeded, and [3] control) have flattened below target. Findings are consistent with evidence that (1) obesity prevention and treatment could reduce prevalent hypertension, and (2) healthcare insurance, >= 2 healthcare visits per year, and guideline-based cholesterol treatment could improve hypertension control. C1 [Egan, Brent M.] Care Coordinat Inst, Greenville, SC 29601 USA. [Egan, Brent M.] Univ S Carolina, Sch Med Greenville, Greenville Hlth Syst, Greenville, SC USA. [Li, Jiexiang] Coll Charleston, Dept Math, Charleston, SC 29424 USA. [Hutchison, Florence N.] Med Univ S Carolina, Charleston, SC 29425 USA. [Hutchison, Florence N.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Ferdinand, Keith C.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. RP Egan, BM (reprint author), Care Coordinat Inst, 300 East McBee Ave,4th Floor, Greenville, SC 29601 USA. EM began@ccihealth.org FU National Institutes of Health [HL105880]; United States Army [W81XWH-10-2-0057]; Centers for Disease Control, Atlanta, GA (Community Transformation Grant thru the South Carolina Department of Health and Environmental Control [SC DHEC]; State of South Carolina, Columbia, SC FX This work was supported in part by National Institutes of Health grant HL105880; United States Army, W81XWH-10-2-0057, Centers for Disease Control, Atlanta, GA (Community Transformation Grant thru the South Carolina Department of Health and Environmental Control [SC DHEC]), and the State of South Carolina, Columbia, SC. NR 36 TC 34 Z9 34 U1 4 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 4 PY 2014 VL 130 IS 19 BP 1692 EP + DI 10.1161/CIRCULATIONAHA.114.010676 PG 17 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AS1UJ UT WOS:000344067000012 PM 25332288 ER PT J AU Bratcher, PE Gaggar, A AF Bratcher, Preston E. Gaggar, Amit TI Factors Influencing the Measurement of Plasma/Serum Surfactant Protein D Levels by ELISA SO PLOS ONE LA English DT Article ID INTERSTITIAL LUNG-DISEASE; OBSTRUCTIVE PULMONARY-DISEASE; BRONCHOALVEOLAR LAVAGE FLUID; CLINICAL-SIGNIFICANCE; SYSTEMIC-SCLEROSIS; SERUM-LEVELS; RADIATION PNEUMONITIS; RHEUMATOID-ARTHRITIS; BIOMARKER PROFILES; CIRCULATING LEVELS AB Background: Extensive variations in human surfactant protein D (SP-D) levels in circulation as measured by ELISA exist in the published literature. In order to determine the source of these variations, factors influencing the measurement by ELISA were explored. Materials and Methods: Peripheral blood from healthy individuals was collected into various vacutainers during the same blood draw. Recombinant SP-D was diluted into different matrices and used for a standard curve. Samples were analyzed by capture ELISA using one of two distinct detection antibodies. Results: The type of matrix had some effects on detection of recombinant SP-D. The type of anticoagulant used and dilution factor had very little effect, except for in plasma collected in EDTA vacutainers. The extent of variation in published values seemed to be due to the ELISA configuration employed, and, in agreement with this, we found that by switching the detection antibody, there was a 50% decrease in the extrapolated SP-D value of serum and plasma samples. Storage of samples resulted in slight changes in measured SP-D levels. Conclusions: The ELISA configuration employed to measure circulating levels of SP-D has a significant effect on the extrapolated values. In both configurations tested, the use of EDTA as a coagulant resulted in inconsistent values, and we, therefore, suggest the avoidance of this anticoagulant when assaying for SP-D by ELISA. While the demonstrated effects of several factors on measurement of SP-D may not account for all the disparities amongst the previous studies, they stress that variations in methodologies for measuring the same protein can result in very inconsistent results. C1 [Bratcher, Preston E.; Gaggar, Amit] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Bratcher, Preston E.; Gaggar, Amit] Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. [Gaggar, Amit] Univ Alabama Birmingham, Gregory Fleming James Cyst Fibrosis Res Ctr, Birmingham, AL 35294 USA. [Gaggar, Amit] Univ Alabama Birmingham, UAB Lung Hlth Ctr, Birmingham, AL 35294 USA. [Gaggar, Amit] US Dept Vet Affairs, Med Serv, Med Ctr, Birmingham, AL USA. [Bratcher, Preston E.; Gaggar, Amit] Univ Alabama Birmingham, Program Protease & Matrix Biol, Birmingham, AL 35294 USA. RP Bratcher, PE (reprint author), Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. EM bratcher@uab.edu FU National Institutes of Health [HL102371, 5T32HL105346-02] FX This work is supported by the National Institutes of Health (HL102371 to AG and 5T32HL105346-02 to PEB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 92 TC 4 Z9 4 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 NOV 3 PY 2014 VL 9 IS 11 AR e111466 DI 10.1371/journal.pone.0111466 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AU4DB UT WOS:000345558100068 PM 25365324 ER PT J AU Merlin, JS Walcott, M Ritchie, C Herbey, I Kertesz, SG Chamot, E Saag, M Turan, JM AF Merlin, Jessica S. Walcott, Melonie Ritchie, Christine Herbey, Ivan Kertesz, Stefan G. Chamot, Eric Saag, Michael Turan, Janet M. TI 'Two Pains Together': Patient Perspectives on Psychological Aspects of Chronic Pain while Living with HIV SO PLOS ONE LA English DT Article ID PRIMARY-CARE PATIENTS; CHRONIC BACK-PAIN; MUSCULOSKELETAL PAIN; NONCANCER PAIN; OPIOID USE; GENERAL-POPULATION; DEPRESSION; MANAGEMENT; COMORBIDITY; ADULTS AB Objective: Chronic pain is common in HIV-infected individuals. Understanding HIV-infected patients' chronic pain experience not just from a biological, but also from a psychological perspective, is a critical first step toward improving care for this population. Our objective was to explore HIV-infected patients' perspectives on psychological aspects of chronic pain using in-depth qualitative interviews. Methods: Investigators engaged in an iterative process of independent and group coding until theme saturation was reached. Results: Of the 25 patients with chronic pain interviewed, 20 were male, 15 were younger than age 50, and 15 were African-American. Key themes that emerged included the close relationship between mood and pain; mood and pain in the context of living with HIV; use of alcohol/drugs to self-medicate for pain; and the challenge of receiving prescription pain medications while dealing with substance use disorders. Conclusions: The results suggest that psychological approaches to chronic pain treatment may be well received by HIV-infected patients. C1 [Merlin, Jessica S.; Walcott, Melonie; Herbey, Ivan; Saag, Michael] Univ Alabama Birmingham, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. [Merlin, Jessica S.] Univ Alabama Birmingham, Div Gerontol Geriatr & Palliat Care, Birmingham, AL USA. [Ritchie, Christine] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94143 USA. [Ritchie, Christine] Jewish Home San Francisco Ctr Res Aging, San Francisco, CA USA. [Kertesz, Stefan G.] Birmingham VA Med Ctr, Birmingham, AL USA. [Kertesz, Stefan G.] Univ Alabama Birmingham, Dept Med, Div Prevent Med, Birmingham, AL USA. [Chamot, Eric; Turan, Janet M.] Univ Alabama Birmingham, Sch Publ Hlth, Birmingham, AL USA. RP Merlin, JS (reprint author), Univ Alabama Birmingham, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. EM jmerlin@uab.edu FU University of Alabama at Birmingham (UAB) Center for AIDS Research (CFAR); National Institutes of Health funded program [P30 A1027767]; Agency for Healthcare Research and Quality [1K12HS02169401]; National Institute on Aging [7K07AG031779]; Mary Fisher CARE Fund at UAB FX This research was supported by the University of Alabama at Birmingham (UAB) Center for AIDS Research (CFAR), an National Institutes of Health funded program (P30 A1027767) that was made possible by the following institutes: National Institute of Allergy and Infectious Diseases, National Cancer Institute, National Institute of Child Health and Human Development, National Heart, Lung, and Blood Institute, National Institute on Drug Abuse, National Institute of Mental Health, National Institute on Aging, and the NIH Office of AIDS Research. JSM is supported by 1K12HS02169401 (Agency for Healthcare Research and Quality). CSR is supported by 7K07AG031779 (National Institute on Aging). Funding was also provided by the Mary Fisher CARE Fund at UAB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 3 Z9 3 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 NOV 3 PY 2014 VL 9 IS 11 AR e111765 DI 10.1371/journal.pone.0111765 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AU4DB UT WOS:000345558100116 PM 25365306 ER PT J AU Ahmad, I Ouyang, XS Wani, WY Zhang, JH AF Ahmad, Israr Ouyang, Xiaosen Wani, Willayat Y. Zhang, Jianhua TI NRBF-2 Regulates Autophagic Flux and Plays an Important Role in Neuronal Survival SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 [Ahmad, Israr; Ouyang, Xiaosen; Wani, Willayat Y.; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Ctr Free Radical Biol & Med, Birmingham, AL 35294 USA. [Ouyang, Xiaosen; Zhang, Jianhua] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV PY 2014 VL 76 SU 1 MA 18 BP S21 EP S21 DI 10.1016/j.freeradbiomed.2014.10.466 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA CO9WA UT WOS:000359525800038 ER PT J AU Dohi, K Kovac, A Erickson, M Kraemer, BC Ogawa, T Banks, WA AF Dohi, Kenji Kovac, Andrej Erickson, Michelle Kraemer, Brian C. Ogawa, Takeki Banks, William A. TI Hydrogen in Drinking Water Reduces Brain Edema after Traumatic Brain Injury in Mice SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 [Dohi, Kenji; Ogawa, Takeki] Jikei Univ, Tokyo, Japan. [Dohi, Kenji; Kovac, Andrej; Erickson, Michelle; Kraemer, Brian C.; Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Kraemer, Brian C.; Banks, William A.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV PY 2014 VL 76 SU 1 MA 23 BP S22 EP S22 DI 10.1016/j.freeradbiomed.2014.10.471 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA CO9WA UT WOS:000359525800043 ER PT J AU Boardman, CR Sonnenberg, A AF Boardman, Charles R. Sonnenberg, Amnon TI Magical Thinking SO CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY LA English DT Editorial Material ID RECTAL-CANCER; APPROPRIATENESS; ENDOSCOPY; COLON; RISK C1 [Boardman, Charles R.; Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 11 TC 1 Z9 1 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2155-384X J9 CLIN TRANSL GASTROEN JI Clin. Transl. Gastroenterol. PD NOV PY 2014 VL 5 AR e63 DI 10.1038/ctg.2014.15 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CJ5MI UT WOS:000355531300002 PM 25393587 ER PT J AU Kinkel, RP Simon, JH O'Connor, P Hyde, R Pace, A AF Kinkel, R. P. Simon, J. H. O'Connor, P. Hyde, R. Pace, A. TI Early MRI activity predicts treatment nonresponse with intramuscular interferon beta-1a in clinically isolated syndrome SO MULTIPLE SCLEROSIS AND RELATED DISORDERS LA English DT Article DE Multiple sclerosis; Magnetic resonance imaging; Intramuscular interferon beta-1a; Treatment response; Clinically isolated syndrome; Clinically definite multiple sclerosis ID RELAPSING MULTIPLE-SCLEROSIS; 1ST DEMYELINATING EVENT; 10-YEAR FOLLOW-UP; DIAGNOSTIC-CRITERIA; NATURAL-HISTORY; OPTIC NEURITIS; DISABILITY; MS; DEFINITE; RISK AB Objective: Determine whether MRI activity 6 months after treatment initiation in the Controlled High-Risk Subjects Avonex (R) Multiple Sclerosis Prevention Study (CHAMPS) predicted progression to clinically definite multiple sclerosis (CDMS) over the subsequent 30 months in intramuscular interferon beta-1a (IM IFN beta-1a)-treated patients vs placebo-treated patients. Methods: CHAMPS patients were randomized to once-weekly IM 30 mu g or placebo for up to 36 months. MRI was performed every 6 months until CDMS confirmation. Patient groups were defined based on new T2 and/or Gd + lesions at 6 months. Results: Thirteen IM IFN beta-1a patients (6.7%) and 24 placebo patients (12.6%) developed CDMS prior to month 6 and did not undergo the 6-month MRI. At 6 months, 29.7% of IM IFN beta-1a-treated patients vs 40.9% of placebo-treated patients were defined as having high MRI activity levels (>= 2 new T2 and/or >= 2 Gd+ lesions). In this subgroup, estimated cumulative probabilities of CDMS were similar between groups (HR=0.88 [0.44-1.77], p=0.7227). A significant treatment response was seen for patients with <2 new T2 and <2 Gd+ lesions at 6 months (HR=0.39 [0.19-0.82], p=0.0120). Conclusion: MRI scans 6 months after IM IFN beta-1 a initiation in CIS patients predict early treatment non-response. Standardized scanning and monitoring may facilitate early disease management. (C) 2014 Elsevier B.V. All rights reserved. C1 [Kinkel, R. P.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Simon, J. H.] Portland VA Med Ctr, Portland, OR 97239 USA. [O'Connor, P.] St Michaels Hosp, Multiple Sclerosis Clin, Toronto, ON M5B 1W8, Canada. [Hyde, R.; Pace, A.] Biogen Idec Inc, Cambridge, MA 02142 USA. RP Kinkel, RP (reprint author), Univ Calif San Diego, Dept Neurosci, 9500 Gilman Dr,MC 0662, La Jolla, CA 92093 USA. EM rkinkel@ucsd.edu; jacksimon1@me.com; OCONNORP@smh.toronto.on.ca; Robert.Hyde@biogenidec.com; Amy.Pace@biogenidec.com FU Biogen Idec FX Biogen Idec provided funding for editorial support in the development of this paper; Christopher Barnes of Infusion Communications wrote the first draft of the manuscript based on input from authors, Joshua Safran and Shannon Davis from Infusion Communications copyedited the manuscript, and Colin Mitchell of Biogen Idec styled the manuscript per journal requirements. Biogen Idec reviewed and provided feedback on the paper to the authors. The authors had full editorial control of the paper and provided their final approval of all content. NR 39 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2211-0348 EI 2211-0356 J9 MULT SCLER RELAT DIS JI Mult. Scler. Relat. Disord. PD NOV PY 2014 VL 3 IS 6 BP 712 EP 719 DI 10.1016/j.msard.2014.08.003 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CB5KO UT WOS:000349666100008 PM 25891550 ER PT J AU Wisneski, AD Mookhoek, A Chitsaz, S Hope, MD Guccione, JM Ge, L Tseng, EE AF Wisneski, Andrew D. Mookhoek, Aart Chitsaz, Sam Hope, Michael D. Guccione, Julius M. Ge, Liang Tseng, Elaine E. TI Patient-Specific Finite Element Analysis of Ascending Thoracic Aortic Aneurysm SO JOURNAL OF HEART VALVE DISEASE LA English DT Article ID WALL STRESS; MECHANICAL-PROPERTIES; INTIMAL TEARS; VALVE; DISSECTION; ROOT AB Background and aim of the study: Rupture/dissection of ascending thoracic aortic aneurysm (aTAA) is a cardiovascular emergency. Elective surgical repair is primarily based on maximum diameter, but complications have occurred under the size limits for surgical intervention. aTAA wall stress may be a better predictor of patient-specific rupture risk, but cannot be directly measured in vivo. The study aim was to develop an aTAA computational model associated with tricuspid aortic valve (TAV) to determine patient-specific wall stresses. Methods: A TAV-associated aTAA was excised intact during surgery. Zero-pressure geometry was generated from microcomputed tomography, and an opening angle was used to calculate residual stress. Material properties determined from stress-strain data were incorporated into an Ogden hyperelastic model. Wall stress distribution and magnitudes at systemic pressure were determined using finite element analyses (FEA) in LS-DYNA. Results: Regional material property differences were noted: the left aTAA region had a higher stiffness compared to the right, and anterior/posterior walls. During systole, the mean principal wall stresses were 172.0 kPa (circumferential) and 71.9 kPa (longitudinal), while peak wall stresses were 545.1 kPa (circumferential) and 430.1 kPa (longitudinal). Elevated wall stress pockets were seen in anatomic left and right aTAA regions. Conclusion: A validated computational approach was demonstrated to determine aTAA wall stresses in a patient-specific fashion, taking into account the required zero-stress geometry, wall thickness, material properties and residual stress. Regions of maximal wall stress may indicate the sites most prone to rupture. The creation of a patient-specific aTAA model based on a surgical specimen is necessary to serve as the 'gold standard' for comparing models based on in-vivo data alone. Validated data using the surgical specimen are essential for establishing wall stress and rupture-risk relationships. C1 [Wisneski, Andrew D.; Chitsaz, Sam; Guccione, Julius M.; Ge, Liang; Tseng, Elaine E.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Hope, Michael D.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. [Hope, Michael D.] San Francisco VA Med Ctr, San Francisco, CA USA. [Mookhoek, Aart] Erasmus Univ, Med Ctr, Dept Cardiothorac Surg, Rotterdam, Netherlands. RP Tseng, EE (reprint author), UCSF Med Ctr, Div Cardiothorac Surg, 500 Parnassus Ave,Suite 405W,Box 0118, San Francisco, CA 94143 USA. EM elaine.tseng@ucsfmedctr.org FU American Heart Association Western States Affiliate Medical Student Fellowship FX These studies were supported by an American Heart Association Western States Affiliate Medical Student Fellowship. NR 24 TC 2 Z9 2 U1 1 U2 6 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 NOV PY 2014 VL 23 IS 6 BP 765 EP 772 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CB4BM UT WOS:000349573200015 PM 25790625 ER PT J AU Caprio, TV Hung, WW Howe, JL Sun, D Deering, J Kochersberger, G Fell, S AF Caprio, T. V. Hung, W. W. Howe, J. L. Sun, D. Deering, J. Kochersberger, G. Fell, S. TI CASE-BASED TELECONFERENCE MODEL FOR GERIATRICS CONSULTATION AND EDUCATION: OUTREACH TO RURAL PRIMARY CARE PROVIDERS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Caprio, T. V.; Kochersberger, G.] Univ Rochester, Rochester, NY USA. [Caprio, T. V.; Kochersberger, G.; Fell, S.] Canandaigua VA Med Ctr, Canandaigua, NY USA. [Hung, W. W.; Howe, J. L.; Sun, D.; Deering, J.] James J Peters VA Med Ctr, Bronx, NY USA. [Hung, W. W.; Howe, J. L.] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2014 VL 54 SU 2 BP 120 EP 120 PG 1 WC Gerontology SC Geriatrics & Gerontology GA AW5TU UT WOS:000346337501270 ER PT J AU Rossi, MI Powers, BB Edmonds, N Dolbee, C Hennon, J Homer, MC AF Rossi, M. I. Powers, B. Brott Edmonds, N. Dolbee, C. Hennon, J. Homer, M. C. TI TELEDEMENTIA CLINIC: CLINICAL VIDEO TELEHEALTH TO DIAGNOSE & SUPPORT RURAL VETERANS WITH DEMENTIA SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Rossi, M. I.; Powers, B. Brott; Edmonds, N.; Dolbee, C.; Hennon, J.; Homer, M. C.] VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. [Rossi, M. I.; Hennon, J.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2014 VL 54 SU 2 BP 120 EP 120 PG 1 WC Gerontology SC Geriatrics & Gerontology GA AW5TU UT WOS:000346337501269 ER PT J AU Roiland, R Porter, J Polnaszek, B Hovanes, ML Jensen, LL Kind, A AF Roiland, R. Porter, J. Polnaszek, B. Hovanes, M. L. Jensen, L. L. Kind, A. TI FRAILTY AND TRANSITIONAL CARE OUTCOMES IN HOSPITALIZED, OLDER VETERANS: A FEASIBILITY STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Roiland, R.; Porter, J.; Hovanes, M. L.; Jensen, L. L.; Kind, A.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Porter, J.; Hovanes, M. L.; Kind, A.] Univ Madison Sch Med & Publ Hlth, Div Geriatr & Gerontol, Madison, WI USA. [Polnaszek, B.] Univ Madison Sch Med & Publ Hlth, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2014 VL 54 SU 2 BP 149 EP 149 PG 1 WC Gerontology SC Geriatrics & Gerontology GA AW5TU UT WOS:000346337501414 ER PT J AU Spira, JL Lathan, CE Bleiberg, J Tsao, JW AF Spira, James L. Lathan, Corinna E. Bleiberg, Joseph Tsao, Jack W. TI The Impact of Multiple Concussions on Emotional Distress, Post-Concussive Symptoms, and Neurocognitive Functioning in Active Duty United States Marines Independent of Combat Exposure or Emotional Distress SO JOURNAL OF NEUROTRAUMA LA English DT Article DE adult brain injury; behavioral assessments; cognitive function; head trauma; military injury ID TRAUMATIC BRAIN-INJURY; PROFESSIONAL FOOTBALL PLAYERS; DEPLOYED MILITARY PERSONNEL; HEAD-INJURY; RECURRENT CONCUSSION; NEUROPSYCHOLOGICAL OUTCOMES; POSTCONCUSSION SYNDROME; NCAA CONCUSSION; IRAQ; PERFORMANCE AB Controversy exists as to whether the lingering effects of concussion on emotional, physical, and cognitive symptoms is because of the effects of brain trauma or purely to emotional factors such as post-traumatic stress disorder or depression. This study examines the independent effects of concussion on persistent symptoms. The Defense Automated Neurobehavioral Assessment, a clinical decision support tool, was used to assess neurobehavioral functioning in 646 United States Marines, all of whom were fit for duty. Marines were assessed for concussion history, post-concussive symptoms, emotional distress, neurocognitive functioning, and deployment history. Results showed that a recent concussion or ever having experienced a concussion was associated with an increase in emotional distress, but not with persistent post-concussive symptoms (PPCS) or neurocognitive functioning. Having had multiple lifetime concussions, however, was associated with greater emotional distress, PPCS, and reduced neurocognitive functioning that needs attention and rapid discrimination, but not for memory-based tasks. These results are independent of deployment history, combat exposure, and symptoms of post-traumatic stress disorder and depression. Results supported earlier findings that a previous concussion is not generally associated with post-concussive symptoms independent of covariates. In contrast with other studies that failed to find a unique contribution for concussion to PPCS, however, evidence of recent and multiple concussion was seen across a range of emotional distress, post-concussive symptoms, and neurocognitive functioning in this study population. Results are discussed in terms of implications for assessing concussion on return from combat. C1 [Spira, James L.] US Dept Vet Affairs, Natl Ctr PTSD, Pacific Isl Div, Honolulu, HI 96819 USA. [Spira, James L.] Univ Hawaii, John A Burns Sch Med, Dept Psychiat, Honolulu, HI 96822 USA. [Lathan, Corinna E.] AnthroTronix Inc, Silver Spring, MD USA. [Bleiberg, Joseph] Walter Reed Natl Mil Med Ctr, Natl Intrepid Ctr Excellence Psychol Hlth & Traum, Bethesda, MD USA. [Tsao, Jack W.] US Navy Bur Med & Surg Falls Church, Traumat Brain Injury Program, Wounded Ill & Injured Directorate, Falls Church, VA USA. RP Spira, JL (reprint author), US Dept Vet Affairs, Natl Ctr PTSD, 3375 Koapaka St,I-560, Honolulu, HI 96819 USA. EM James.Spira@va.gov OI Bleiberg, Joseph/0000-0003-0867-5494 FU U.S. Navy Bureau of Medicine and Surgery, Wounded, Ill, and Injured Directorate FX This work was supported by the U.S. Navy Bureau of Medicine and Surgery, Wounded, Ill, and Injured Directorate, as well as with resources and the use of facilities at the US Department of Veterans Affairs, National Center for PTSD, Pacific Islands Health Care System. NR 56 TC 9 Z9 9 U1 0 U2 7 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD NOV 1 PY 2014 VL 31 IS 22 BP 1823 EP 1834 DI 10.1089/neu.2014.3363 PG 12 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA CB4ZO UT WOS:000349637400002 PM 25003552 ER PT J AU Haley, KP Blanz, EJ Gaddy, JA AF Haley, Kathryn Patricia Blanz, Eric Joshua Gaddy, Jennifer Angeline TI High Resolution Electron Microscopy of the Helicobacter pylori Cag Type IV Secretion System Pili Produced in Varying Conditions of Iron Availability SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Infection; Issue 93; Helicobacter pylori; iron acquisition; cag pathogenicity island; type IV secretion; pili ID CHEMICALLY-DEFINED MEDIA; IN-VIVO; DISEASE; DEFICIENCY; INFECTION; GENE AB Helicobacter pylori is a helical-shaped, gram negative bacterium that colonizes the human gastric niche of half of the human population(1,2). H. pylori is the primary cause of gastric cancer, the second leading cause of cancer-related deaths worldwide(3). One virulence factor that has been associated with increased risk of gastric disease is the Cag-pathogenicity island, a 40-kb region within the chromosome of H. pylori that encodes a type IV secretion system and the cognate effector molecule, CagA(4,5). The Cag-T4SS is responsible for translocating CagA and peptidoglycan into host epithelial cells(5,6). The activity of the Cag-T4SS results in numerous changes in host cell biology including upregulation of cytokine expression, activation of proinflammatory pathways, cytoskeletal remodeling, and induction of oncogenic cell-signaling networks(5-8). The Cag-T4SS is a macromolecular machine comprised of sub-assembly components spanning the inner and outer membrane and extending outward from the cell into the extracellular space. The extracellular portion of the Cag-T4SS is referred to as the "pilus" (5). Numerous studies have demonstrated that the Cag-T4SS pili are formed at the host-pathogen interface(9,10). However, the environmental features that regulate the biogenesis of this important organelle remain largely obscure. Recently, we reported that conditions of low iron availability increased the Cag-T4SS activity and pilus biogenesis. Here we present an optimized protocol to grow H. pylori in varying conditions of iron availability prior to co-culture with human gastric epithelial cells. Further, we present the comprehensive protocol for visualization of the hyper-piliated phenotype exhibited in iron restricted conditions by high resolution scanning electron microscopy analyses. C1 [Haley, Kathryn Patricia; Blanz, Eric Joshua; Gaddy, Jennifer Angeline] Vanderbilt Univ, Sch Med, Dept Med, Div Infect Dis, Nashville, TN 37235 USA. [Gaddy, Jennifer Angeline] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Washington, DC USA. RP Gaddy, JA (reprint author), Vanderbilt Univ, Sch Med, Dept Med, Div Infect Dis, Nashville, TN 37235 USA. EM jennifer.a.gaddy@vanderbilt.edu FU Department of Veterans Affairs Career Development Award [1IK2BX001701]; CTSA from the National Center for Advancing Translational Sciences [UL1TR000445]; NIH [CA68485, DK20593, DK58404, DK59637, EY08126] FX This research was supported by the Department of Veterans Affairs Career Development Award 1IK2BX001701 and the CTSA award UL1TR000445 from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. Scanning electron microscopy experiments were performed in part through the use of the VUMC Cell Imaging Shared Resource, supported by NIH grants CA68485, DK20593, DK58404, DK59637 and EY08126. NR 25 TC 4 Z9 4 U1 0 U2 1 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 NOV PY 2014 IS 93 AR e52122 DI 10.3791/52122 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CB0JH UT WOS:000349311400061 PM 25489938 ER PT J AU Muldoon, MF Ryan, CM Yao, JK Conklin, SM Manuck, SB AF Muldoon, Matthew F. Ryan, Christopher M. Yao, Jeffrey K. Conklin, Sarah M. Manuck, Stephen B. TI Long-Chain Omega-3 Fatty Acids and Optimization of Cognitive Performance SO MILITARY MEDICINE LA English DT Article ID N-3 FATTY-ACIDS; HEART-RATE-VARIABILITY; RANDOMIZED CONTROLLED-TRIAL; HEALTHY-YOUNG ADULTS; ETHYL-EICOSAPENTAENOIC ACID; FISH-OIL SUPPLEMENTATION; PLACEBO-CONTROLLED TRIAL; DOCOSAHEXAENOIC ACID; DOUBLE-BLIND; OLDER-ADULTS AB Low consumption of the omega-3 fatty acids, eicosapentaenoic and docosahexaenonic acids, is linked to delayed brain development and, in late life, increased risk for Alzheimer's disease. The current review focuses on cognitive functioning during midlife and summarizes available scientific evidence relevant to the hypothesis that adequate dietary consumption of the long-chain omega-3 fatty acids is necessary for optimal cognitive performance. Taken together, the findings suggest that raising the currently low consumption among healthy adults may improve some aspects of cognitive performance. Nonetheless, evidence from randomized clinical trials is comparatively sparse and leaves unclear: (a) whether such effects are clinically significant, (b) whether effects of eicosapentaenoic acid and DHA differ, (c) which dimensions of cognitive function are affected, (d) the dose-response relationships, or (e) the time course of the response. Clarification of these issues through both laboratory and clinical investigations is a priority given the broad implications for public health, as well as for military personnel and other positions of high performance demand and responsibility. C1 [Muldoon, Matthew F.] Univ Pittsburgh, Sch Med, Inst Heart & Vasc, Pittsburgh, PA 15260 USA. [Ryan, Christopher M.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15206 USA. [Conklin, Sarah M.] Allegheny Coll, Dept Psychol & Neurosci, Meadville, PA 16335 USA. [Manuck, Stephen B.] Univ Pittsburgh, Dept Psychol, Behav Physiol Lab, Pittsburgh, PA 15260 USA. RP Muldoon, MF (reprint author), Univ Pittsburgh, Sch Med, Inst Heart & Vasc, Old Engn Hall,Room 506, Pittsburgh, PA 15260 USA. FU IsodiNatura FX Dr. Conklin, Dr. Yao, and Dr. Muldoon report receipt of a $9,000 research grant in 2008 from IsodiNatura to support serum fatty acid determinations. NR 122 TC 2 Z9 2 U1 1 U2 16 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 NOV PY 2014 VL 179 IS 11 SU S BP 95 EP 105 DI 10.7205/MILMED-D-14-00168 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CA7LS UT WOS:000349099400007 PM 25373092 ER PT J AU Fredriksen-Goldsen, KI Simoni, JM Kim, HJ Lehavot, K Walters, KL Yang, J Hoy-Ellis, CP Muraco, A AF Fredriksen-Goldsen, Karen I. Simoni, Jane M. Kim, Hyun-Jun Lehavot, Keren Walters, Karina L. Yang, Joyce Hoy-Ellis, Charles P. Muraco, Anna TI The Health Equity Promotion Model: Reconceptualization of Lesbian, Gay, Bisexual, and Transgender (LGBT) Health Disparities SO AMERICAN JOURNAL OF ORTHOPSYCHIATRY LA English DT Article DE health equity; health disparities; mental and physical health; sexual orientation; sexual identity; gender identity; lesbain; gay; bisexual; transgender; minority health ID OF-THE-LITERATURE; SEXUAL ORIENTATION; MENTAL-HEALTH; PSYCHOLOGICAL DISTRESS; UNITED-STATES; OLDER-ADULTS; LIFE-COURSE; PSYCHIATRIC-DISORDERS; ALLOSTATIC LOAD; RISK BEHAVIORS AB National health initiatives emphasize the importance of eliminating health disparities among historically disadvantaged populations. Yet, few studies have examined the range of health outcomes among lesbian, gay, bisexual, and transgender (LGBT) people. To stimulate more inclusive research in the area, we present the Health Equity Promotion Model-a framework oriented toward LGBT people reaching their full mental and physical health potential that considers both positive and adverse health-related circumstances. The model highlights (a) heterogeneity and intersectionality within LGBT communities; (b) the influence of structural and environmental context; and (c) both health-promoting and adverse pathways that encompass behavioral, social, psychological, and biological processes. It also expands upon earlier conceptualizations of sexual minority health by integrating a life course development perspective within the health-promotion model. By explicating the important role of agency and resilience as well as the deleterious effect of social structures on health outcomes, it supports policy and social justice to advance health and well-being in these communities. Important directions for future research as well as implications for health-promotion interventions and policies are offered. C1 [Fredriksen-Goldsen, Karen I.; Kim, Hyun-Jun; Walters, Karina L.; Hoy-Ellis, Charles P.] Univ Washington, Sch Social Work, Seattle, WA 98105 USA. [Simoni, Jane M.; Yang, Joyce] Univ Washington, Dept Psychol, Seattle, WA 98105 USA. [Lehavot, Keren] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Lehavot, Keren] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98105 USA. [Muraco, Anna] Loyola Marymount Univ, Dept Sociol, Los Angeles, CA 90045 USA. RP Fredriksen-Goldsen, KI (reprint author), Univ Washington, Sch Social Work, 4101 15th Ave NE,Box 354900, Seattle, WA 98105 USA. EM fredrikk@u.washington.edu OI Simoni, Jane/0000-0002-8711-1576 FU National Institute on Aging [2R01AG026526-03A1]; Department of Veterans Affairs Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment; VA Puget Sound Health Care System, Seattle, Washington FX This research was supported in part by grants from the National Institute on Aging (2R01AG026526-03A1). The views expressed in this article are those of the authors and do not necessarily reflect the views of the National Institutes of Health, National Institute of Aging, University of Washington, Department of Veterans Affairs, or Loyola Marymount University. In addition, Keren Lehavot's contribution to this article is supported by resources from the Department of Veterans Affairs Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment and the VA Puget Sound Health Care System, Seattle, Washington. NR 124 TC 19 Z9 19 U1 8 U2 44 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0002-9432 EI 1939-0025 J9 AM J ORTHOPSYCHIAT JI Am. J. Orthopsychiatr. PD NOV PY 2014 VL 84 IS 6 BP 653 EP 663 DI 10.1037/ort0000030 PG 11 WC Psychiatry; Social Work SC Psychiatry; Social Work GA AX4TM UT WOS:000346924100008 PM 25545433 ER PT J AU Brent, GA AF Brent, Gregory A. TI Perchlorate Exposure in Pregnancy and Cognitive Outcomes in Children: It's Not Your Mother's Thyroid SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID THIOCYANATE EXPOSURE; HORMONE; WOMEN; ASSOCIATION; POSTPARTUM; MANAGEMENT; WATER C1 [Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. [Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. RP Brent, GA (reprint author), Dept Med, 111,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gbrent@ucla.edu FU NIDDK NIH HHS [R01 DK098576, R01 DK98576] NR 22 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2014 VL 99 IS 11 BP 4066 EP 4068 DI 10.1210/jc.2014-3673 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX1ZN UT WOS:000346743100020 PM 25372124 ER PT J AU McNabb, B Vittinghoff, E Eastell, R Schwartz, AV Bauer, DC Ensrud, K Barrett-Connor, E Black, DM AF McNabb, Brian Vittinghoff, Eric Eastell, Richard Schwartz, Ann V. Bauer, Douglas C. Ensrud, Kristine Barrett-Connor, Elizabeth Black, Dennis M. TI A Model of BMD Changes After Alendronate Discontinuation to Guide Postalendronate BMD Monitoring SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FRACTURE INTERVENTION TRIAL; LONG-TERM EXTENSION; POSTMENOPAUSAL OSTEOPOROSIS; RANDOMIZED-TRIAL; ZOLEDRONIC ACID; BISPHOSPHONATE THERAPY; VERTEBRAL FRACTURES; WOMEN; BONE; FLEX AB Context: Women stopping alendronate are commonly monitored with serial bone mineral density (BMD) measurements, yet no information exists on how frequently or for whom these measurements should be performed. Objective: The objective of the study was to develop a tool to guide post-alendronate BMD monitoring. Design: A predictive model was constructed to estimate the time until a given percentage of women's BMD T-scores drop below a given threshold that indicates a management change (such as retreatment) would be considered. This model was then used to estimate the time it would take for groups of women defined by their baseline BMDs to drop below the given threshold. Setting: Data were derived from the Fracture Intervention Trial Long Term Extension (FLEX), the largest multicenter clinical trial of its type to date. Participants: Four hundred four women who had received an average of 5.1 years of alendronate during the Fracture Intervention Trial and were subsequently observed for 5 treatment-free years (on placebo) during the FLEX trial were used to estimate the change in BMD over time. Results: If a management change such as alendronate reinitiation would be considered when BMDT-score drops below -2.5, the model shows that women with total hip BMD greater than -1.9 T-scores at the time of alendronate discontinuation have less than a 20% probability that at follow-up, monitoring BMD will be below the threshold within 5 years. The model performed similarly, and results are provided over a range of management change thresholds from -1.75 to -3 T-scores. Conclusions: Using the tool developed in this analysis, it is possible to estimate when BMD repeat measurement after alendronate discontinuation could potentially be useful. Measuring BMD within 5 years after alendronate discontinuation is unlikely to change management for women with total hip BMD 0.6 T-scores above a prespecified retreatment threshold within the range of -1.75 to -3 T-scores. C1 [McNabb, Brian] San Francisco VA Med Ctr, Dept Gen Internal Med, San Francisco, CA 94121 USA. [McNabb, Brian; Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94117 USA. [McNabb, Brian] Univ Calif San Francisco, Div Endocrinol, San Francisco, CA 94117 USA. [Vittinghoff, Eric; Schwartz, Ann V.; Bauer, Douglas C.; Black, Dennis M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94117 USA. [Eastell, Richard] Univ Sheffield, Dept Human Metab, Acad Unit Bone Metab, Sheffield S10 2JF, S Yorkshire, England. [Ensrud, Kristine] Univ Minnesota, Dept Med, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Ensrud, Kristine] Vet Affairs Hlth Care Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN 55417 USA. [Barrett-Connor, Elizabeth] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92093 USA. RP McNabb, B (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Mailing Code 111A1, San Francisco, CA 94121 USA. EM brian.mcnabb@ucsf.edu FU Veterans Affairs Advanced Women's Health Fellowship FX B.M. is supported by the Veterans Affairs Advanced Women's Health Fellowship. NR 30 TC 2 Z9 2 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2014 VL 99 IS 11 BP 4094 EP 4100 DI 10.1210/jc.2014-1193 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX1ZN UT WOS:000346743100024 PM 25127011 ER PT J AU Li, XB Fryml, L Rodriguez, JJ Taylor, J Borckardt, JJ Short, B Sahlem, G Roberts, D George, MS AF Li, Xingbao Fryml, Leah Rodriguez, Julia Jaskwich Taylor, Joseph Borckardt, Jeff J. Short, Baron Sahlem, Greg Roberts, Donna George, Mark S. TI Safe Management of a Bipolar Depressed Patient With Prefrontal Repetitive Transcranial Magnetic Stimulation (rTMS) Over 7 Years and > 2 Million Stimuli SO BRAIN STIMULATION LA English DT Letter ID MAJOR DEPRESSION; TMS; MULTISITE C1 [Li, Xingbao; Fryml, Leah; Rodriguez, Julia Jaskwich; Taylor, Joseph; Borckardt, Jeff J.; Short, Baron; Sahlem, Greg; Roberts, Donna; George, Mark S.] Med Univ S Carolina, Dept Psychiat, Brain Stimulat Div, Charleston, SC 29425 USA. [George, Mark S.] Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Li, XB (reprint author), MUSC, IOP, 502 N,67 President St, Charleston, SC 29425 USA. EM lixi@musc.edu NR 7 TC 1 Z9 1 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD NOV-DEC PY 2014 VL 7 IS 6 SI SI BP 919 EP 921 DI 10.1016/j.brs.2014.09.005 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AW7OZ UT WOS:000346455200027 PM 25440291 ER PT J AU Shim, EH Livi, CB Rakheja, D Tan, J Benson, D Parekh, V Kho, EY Ghosh, AP Kirkman, R Velu, S Dutta, S Chenna, B Rea, SL Mishur, RJ Li, QH Johnson-Pais, TL Guo, L Bae, S Wei, S Block, K Sudarshan, S AF Shim, Eun-Hee Livi, Carolina B. Rakheja, Dinesh Tan, Jubilee Benson, Daniel Parekh, Vishwas Kho, Eun-Young Ghosh, Arindam P. Kirkman, Richard Velu, Sadanan Dutta, Shilpa Chenna, Balachandra Rea, Shane L. Mishur, Robert J. Li, Qiuhua Johnson-Pais, Teresa L. Guo, Lining Bae, Sejong Wei, Shi Block, Karen Sudarshan, Sunil TI L-2-Hydroxyglutarate: An Epigenetic Modifier and Putative Oncometabolite in Renal Cancer SO CANCER DISCOVERY LA English DT Article ID CELL CARCINOMA; ALPHA-KETOGLUTARATE; MYELOID CANCERS; MUTATIONS; 2-HYDROXYGLUTARATE; ACIDURIA; TET2; DEHYDROGENASE; EXPRESSION; HISTONE AB Through unbiased metabolomics, we identified elevations of the metabolite 2-hydroxyglutarate (2HG) in renal cell carcinoma (RCC). 2HG can inhibit 2-oxoglutaratre (2-OG)-dependent dioxygenases that mediate epigenetic events, including DNA and histone demethylation. 2HG accumulation, specifically the d enantiomer, can result from gain-of-function mutations of isocitrate dehydrogenase (IDH1, IDH2) found in several different tumors. In contrast, kidney tumors demonstrate elevations of the l enantiomer of 2HG (l-2HG). High-2HG tumors demonstrate reduced DNA levels of 5-hydroxymethylcytosine (5hmC), consistent with 2HG-mediated inhibition of ten-eleven translocation (TET) enzymes, which convert 5-methylcytosine (5mC) to 5hmC. l-2HG elevation is mediated in part by reduced expression of l-2HG dehydrogenase (L2HGDH). L2HGDH reconstitution in RCC cells lowers l-2HG and promotes 5hmC accumulation. In addition, L2HGDH expression in RCC cells reduces histone methylation and suppresses in vitro tumor phenotypes. Our report identifies l-2HG as an epigenetic modifier and putative oncometabolite in kidney cancer. C1 [Shim, Eun-Hee; Tan, Jubilee; Benson, Daniel; Kho, Eun-Young; Ghosh, Arindam P.; Kirkman, Richard; Sudarshan, Sunil] Univ Alabama Birmingham, Dept Urol, Birmingham, AL 35294 USA. [Livi, Carolina B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Rakheja, Dinesh] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Parekh, Vishwas; Wei, Shi] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Velu, Sadanan; Dutta, Shilpa; Chenna, Balachandra] Univ Alabama Birmingham, Dept Chem, Birmingham, AL 35294 USA. [Rea, Shane L.; Mishur, Robert J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Li, Qiuhua; Johnson-Pais, Teresa L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Guo, Lining] Metabolon, Durham, NC USA. [Bae, Sejong] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Block, Karen] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Block, Karen] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Sudarshan, S (reprint author), Univ Alabama Birmingham, 1105 Fac Off Tower,510 20th St South, Birmingham, AL 35294 USA. EM sudarshan@uab.edu OI CHENNA, BALA CHANDRA/0000-0002-2660-5302 FU NIH [P30 CA013148, K08 CA138774, R01 NCI CA131272]; Urology Care Foundation; Astellas Pharrna Rising Star Award; American Cancer Society [RSG-12-127-01 CNE]; Clinical & Translational Science Awards/Institute for Integration of Medicine and Science [UL1RR025767]; Cancer Prevention Research Institute of Texas [RP120190] FX The research reported its this article was supported by the NIH (P30 CA013148). S. Sudarshan was supported by the NIH (K08 CA138774), the Urology Care Foundation, the Astellas Pharrna Rising Star Award, and the American Cancer Society (RSG-12-127-01 CNE). K. Block was supported by the NIH (R01 NCI CA131272). S. Sudarshan and C.B. Livi were supported by the Clinical & Translational Science Awards/Institute for Integration of Medicine and Science (UL1RR025767). C.B. Livi and K. Block were supported by the Cancer Prevention Research Institute of Texas (RP120190). NR 37 TC 36 Z9 36 U1 0 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD NOV PY 2014 VL 4 IS 11 BP 1290 EP 1298 DI 10.1158/2159-8290.CD-13-0696 PG 9 WC Oncology SC Oncology GA AW8GY UT WOS:000346500700024 PM 25182153 ER PT J AU Katz, KA Reid, EE Chren, MM AF Katz, Kenneth A. Reid, Erika E. Chren, Mary-Margaret TI The Good, the Bad, and the Ugly of Free Drug Samples Reply SO JAMA DERMATOLOGY LA English DT Letter ID PATTERNS C1 [Katz, Kenneth A.] Permanente Med Grp Inc, Dept Dermatol, Pleasanton, CA 94588 USA. [Reid, Erika E.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Chren, Mary-Margaret] San Francisco VA Med Ctr, San Francisco, CA USA. RP Katz, KA (reprint author), Permanente Med Grp Inc, Dept Dermatol, 7601 Stoneridge Dr,Second Floor,S Bldg, Pleasanton, CA 94588 USA. EM Kenneth.Katz@gmail.com NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD NOV PY 2014 VL 150 IS 11 BP 1238 EP 1238 DI 10.1001/jamadermatol.2014.1815 PG 1 WC Dermatology SC Dermatology GA AW4EP UT WOS:000346234300033 PM 25188905 ER PT J AU Ganguly, K Abrams, GM AF Ganguly, Karunesh Abrams, Gary M. TI Neurologic Rehabilitation Preface SO SEMINARS IN NEUROLOGY LA English DT Editorial Material C1 [Ganguly, Karunesh; Abrams, Gary M.] San Francisco VA Med Ctr, Neurol & Rehabil Serv, San Francisco, CA USA. [Ganguly, Karunesh; Abrams, Gary M.] UCSF, Dept Neurol, San Francisco, CA USA. RP Ganguly, K (reprint author), Neurol & Rehabil Serv, 1700 Owens St, San Francisco, CA 94158 USA. EM karunesh.ganguly@ucsf.edu 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 0271-8235 EI 1098-9021 J9 SEMIN NEUROL JI Semin. Neurol. PD NOV PY 2014 VL 34 IS 5 BP 483 EP 483 DI 10.1055/s-0034-1396001 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AW6YL UT WOS:000346411500002 PM 25520019 ER PT J AU Tsu, AP Abrams, GM Byl, NN AF Tsu, Adelyn P. Abrams, Gary M. Byl, Nancy N. TI Poststroke Upper Limb Recovery SO SEMINARS IN NEUROLOGY LA English DT Article DE stroke; upper limb rehabilitation; stroke management ID RANDOMIZED CONTROLLED-TRIAL; UPPER-EXTREMITY FUNCTION; SKILL ACQUISITION PROGRAM; ROBOT-ASSISTED THERAPY; STROKE REHABILITATION; MOTOR IMAGERY; COPENHAGEN STROKE; CLINICAL-TRIAL; BOBATH CONCEPT; OUTCOMES AB Upper limb recovery after a stroke is suboptimal. Only a few individuals achieve full functional use of the hemiparetic arm. Complex primary and secondary impairments may affect recovery of upper limb function in stroke survivors. In addition, multiple personal, social, behavioral, economic, and environmental factors may interact to positively or negatively influence recovery during the different stages of rehabilitation. The current management of upper limb dysfunction poststroke has become more evidence based. In this article, we review the standard of care for upper limb poststroke rehabilitation, the evidence supporting the treatment modalities that currently exist and the exciting new developments in the therapeutic pipeline. C1 [Tsu, Adelyn P.; Abrams, Gary M.] San Francisco VA Med Ctr, Dept Neurol, Rehabil Serv, San Francisco, CA 94121 USA. [Tsu, Adelyn P.; Abrams, Gary M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Byl, Nancy N.] Univ Calif San Francisco, Dept Phys Therapy & Rehabil Sci, San Francisco, CA 94143 USA. RP Tsu, AP (reprint author), San Francisco VA Med Ctr, Dept Neurol, Rehabil Serv, San Francisco, CA 94121 USA. EM adelyn.tsu@ucsf.edu NR 72 TC 1 Z9 2 U1 3 U2 11 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0271-8235 EI 1098-9021 J9 SEMIN NEUROL JI Semin. Neurol. PD NOV PY 2014 VL 34 IS 5 BP 485 EP 495 DI 10.1055/s-0034-1396002 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA AW6YL UT WOS:000346411500003 PM 25520020 ER PT J AU Williams-Sanchez, V McArdle, RA Wilson, RH Kidd, GR Watson, CS Bourne, AL AF Williams-Sanchez, Victoria McArdle, Rachel A. Wilson, Richard H. Kidd, Gary R. Watson, Charles S. Bourne, Andrea L. TI Validation of a Screening Test of Auditory Function Using the Telephone SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Article DE Diagnostic techniques and procedures; hearing loss; hearing test; screening; sensitivity and specificity; telephone; validation studies ID QUALITY-OF-LIFE; IN-NOISE TEST; HEARING-LOSS; OLDER-ADULTS; ELDERLY POPULATION; PRIMARY-CARE; TASK-FORCE; SPEECH; WORDS; LISTENERS AB Background: Several European countries have demonstrated successful use of telephone screening tests for auditory function. The screening test consists of spoken three-digit sequences presented in a noise background. The speech-to-noise ratios of the stimuli are determined by an adaptive tracking method that converges on the level required to achieve 50% correct recognition. Purpose: A version of the three-digit telephone screening protocol for the United States was developed: the US National Hearing Test (NHT). The objective of the current study was to determine the sensitivity and specificity as well as the feasibility of the NHT for use within the Department of Veterans Affairs (VA). Research Design and Study Sample: Using a multisite study design with convenience sampling, we used the NHT to collect data from 693 participants (1379 ears) from three geographical areas of the United States (Florida, Tennessee, and California). Data Collection and Analysis: The NHT procedures were as follows: the participants (1) called a toll-free telephone number, (2) entered their assigned ear-specific identification code, (3) listened to 40-sets of digit triplets presented in speech-spectrum background noise, and (4) entered in the numbers that they heard on the telephone key pad. The NHT was performed on each ear, either at home or in a VA clinic. In addition to collecting data from the experimental task, we gathered demographic data and the data from other standard-of-care tests (i.e., audiometric thresholds and speech recognition tests in quiet and in noise). Results: A total of 505 participants completed the NHT at a VA clinic, whereas 188 completed the test at home. Although the ear-specific NHT and mean pure-tone threshold all correlated significantly (p < 0.001), there were more modest correlations in the low- and high-frequency ranges with the highest correlation seen with the 2000 Hz mean pure-tone threshold. When the NHT 50% point or threshold was compared with the three-frequency PTA at 500, 1000, and 2000 Hz, the sensitivity was 0.87 and specificity was 0.54. When comparing the NHT with the four-frequency PTA at 500, 1000, 2000, and 4000 Hz, the sensitivity was 0.81 and specificity increased to 0.65. The NHT also correlated strongly with other speech-in-noise measures. Conclusions: The NHT was found to correlate with other audiometric measures, including pure-tone thresholds and speech recognition tests in noise, at sufficiently high correlation values to support its use as a screening test of auditory function. C1 [Williams-Sanchez, Victoria; McArdle, Rachel A.] Bay Pines VA HealthCare Syst, Bay Pines, FL 37710 USA. [Williams-Sanchez, Victoria; McArdle, Rachel A.] Univ S Florida, Dept Commun Sci & Disorders, Tampa, FL USA. [Wilson, Richard H.] James H Quillen VA Med Ctr, Mountain Home, TN USA. [Wilson, Richard H.] E Tennessee State Univ, Dept Audiol & Speech Language Pathol, Johnson City, TN USA. [Kidd, Gary R.; Watson, Charles S.] Commun Disorders Technol Inc, Bloomington, IN USA. [Kidd, Gary R.; Watson, Charles S.] Indiana Univ, Bloomington, IN USA. [Bourne, Andrea L.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Williams-Sanchez, V (reprint author), Bay Pines VA HealthCare Syst, Audiol 126,POB 5005, Bay Pines, FL 37710 USA. EM vawilli2@mail.usf.edu FU National Institutes of Health/National Institute on Deafness and Other Communication Disorders [R43DC009719]; Rehabilitation Research and Development Service, VA; Auditory and Vestibular Dysfunction Research Enhancement Award Program (REAP); Senior Research Career Scientist award FX The screening test used in this study was developed with funding provided by National Institutes of Health/National Institute on Deafness and Other Communication Disorders grant R43DC009719 to Communication Disorders Technology, Inc. (CDT), Bloomington, IN. Charles Watson is a stockholder of CDT and might benefit financially from the licensing, sale, or other commercial use of that test. The Rehabilitation Research and Development Service, VA, also supported this work through a Career Development Award to Rachel A. McArdle and a Merit Review, the Auditory and Vestibular Dysfunction Research Enhancement Award Program (REAP), and a Senior Research Career Scientist award to Richard H. Wilson. NR 58 TC 5 Z9 7 U1 3 U2 3 PU AMER ACAD AUDIOLOGY PI RESTON PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA SN 1050-0545 EI 2157-3107 J9 J AM ACAD AUDIOL JI J. Am. Acad. Audiol. PD NOV-DEC PY 2014 VL 25 IS 10 BP 937 EP 951 DI 10.3766/jaaa.25.10.3 PG 15 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA AW7RE UT WOS:000346461400003 PM 25514447 ER PT J AU Ojserkis, R McKay, D Badour, CL Feldner, MT Arocho, J Dutton, C AF Ojserkis, Rachel McKay, Dean Badour, Christal L. Feldner, Matthew T. Arocho, Justin Dutton, Courtney TI Alleviation of Moral Disgust, Shame, and Guilt in Posttraumatic Stress Reactions: An Evaluation of Comprehensive Distancing SO BEHAVIOR MODIFICATION LA English DT Article DE disgust; moral disgust; guilt; shame; trauma; acceptance and commitment therapy ID OBSESSIVE-COMPULSIVE DISORDER; COGNITIVE-PROCESSING THERAPY; RANDOMIZED CONTROLLED-TRIAL; LIFE EVENTS CHECKLIST; TRAUMA-RELATED GUILT; PSYCHOMETRIC PROPERTIES; MENTAL CONTAMINATION; COMMITMENT THERAPY; INDIVIDUAL-DIFFERENCES; PROLONGED EXPOSURE AB Research suggests that moral disgust, shame, and guilt are present in posttraumatic psychopathology. However, it is unclear that these emotional states are responsive to empirically supported interventions for posttraumatic stress symptoms (PTSS). This study explored the relations among moral disgust, shame, guilt, and PTSS, and examined comprehensive distancing (CD) as a novel intervention for these emotional states in undergraduates with elevated PTSS. Participants were randomly assigned to use a CD or a cognitive challenge task in response to personalized scripts of a traumatic event. Both interventions were associated with decreases in disgust, moral disgust, shame, and guilt. Contrary to predictions, there were no significant differences between the exercises in the reduction of negative emotions. In addition, PTSS severity was correlated with trauma-related guilt as well as state guilt and shame, but not trait or state measures of disgust or moral disgust. This proof of concept project sets the stage for further research examining CD as an alternative or adjunctive intervention for posttraumatic stress reactions with strong features of moral disgust, shame, and guilt. C1 [Ojserkis, Rachel; McKay, Dean; Arocho, Justin] Fordham Univ, Bronx, NY 10458 USA. [Badour, Christal L.; Dutton, Courtney] Univ Arkansas, Fayetteville, AR 72701 USA. [Feldner, Matthew T.] Univ Arkansas, Dept Psychol Sci, Fayetteville, AR 72701 USA. [Badour, Christal L.] Med Univ S Carolina, Charleston, SC 29425 USA. [Badour, Christal L.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Feldner, Matthew T.] Laureate Inst Brain Res, Tulsa, OK USA. RP Ojserkis, R (reprint author), Fordham Univ, Dept Psychol, 441 E Fordham Rd, Bronx, NY 10458 USA. EM rojserkis@fordham.edu NR 118 TC 2 Z9 2 U1 5 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-4455 EI 1552-4167 J9 BEHAV MODIF JI Behav. Modificat. PD NOV PY 2014 VL 38 IS 6 BP 801 EP 836 DI 10.1177/0145445514543465 PG 36 WC Psychology, Clinical SC Psychology GA AW0YH UT WOS:000346016700002 PM 25037054 ER PT J AU Boockvar, K AF Boockvar, Kenneth TI Impact of Depression and Mental Illness on Outcomes of Medical Illness in Older Adults SO CLINICAL THERAPEUTICS LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; CARE; SYMPTOMS; RISK; IMPAIRMENT; MORTALITY; DISEASE; SINGLE C1 [Boockvar, Kenneth] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Boockvar, Kenneth] James J Peters VA Med Ctr, Bronx, NY USA. [Boockvar, Kenneth] Jewish Home Lifecare, New York, NY USA. RP Boockvar, K (reprint author), Icahn Sch Med Mt Sinai, New York, NY 10029 USA. OI Boockvar, Kenneth/0000-0003-1165-5558 NR 25 TC 0 Z9 0 U1 2 U2 4 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD NOV PY 2014 VL 36 IS 11 BP 1486 EP 1488 DI 10.1016/j.clinthera.2014.10.010 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AU9YX UT WOS:000345948900002 PM 25455929 ER PT J AU Zahradnik, EK Grossman, H AF Zahradnik, Erin K. Grossman, Hillel TI Palliative Care as a Primary Therapeutic Approach in Advanced Dementia: A Narrative Review SO CLINICAL THERAPEUTICS LA English DT Review DE palliative care; dementia; Alzheimer's disease; geriatrics; geriatric psychiatry ID RANDOMIZED CONTROLLED-TRIAL; HOSPITALIZED OLDER-ADULTS; NURSING-HOME RESIDENTS; CELL LUNG-CANCER; ALZHEIMER-DISEASE; NEUROPSYCHIATRIC SYMPTOMS; BEHAVIORAL SYMPTOMS; TERMINALLY-ILL; DIGNITY THERAPY; CACHE COUNTY AB Purpose: The goal of this narrative review was to identify and summarize the ways in which palliative care could benefit patients who have advanced dementia. Methods: This case-based discussion article examines current literature on palliative care for dementia. Findings: Dementia is an incurable, progressive disease that affects millions of subjects. The prevalence has grown in the last decade and is projected to continue on this trajectory. In the later stages of dementia, subjects require increasing levels of care due to severe cognitive and functional impairment. Although the field of palliative medicine focuses on improving the quality of life of patients with life-limiting illnesses, many patients with advanced dementia do not receive palliative care services. (C) 2014 Elsevier HS Journals, Inc. All rights reserved. C1 [Zahradnik, Erin K.; Grossman, Hillel] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Grossman, Hillel] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Zahradnik, EK (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, One Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM erin.zahradnik@mssm.edu NR 71 TC 3 Z9 3 U1 3 U2 13 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD NOV PY 2014 VL 36 IS 11 BP 1512 EP 1517 DI 10.1016/j.clinthera.2014.10.006 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AU9YX UT WOS:000345948900004 PM 25457122 ER PT J AU Garrido, MM Prigerson, HG Penrod, JD Jones, SC Boockyar, KS AF Garrido, Melissa M. Prigerson, Holly G. Penrod, Joan D. Jones, Shatice C. Boockyar, Kenneth S. TI Benzodiazepine and Sedative-hypnotic Use Among Older Seriously Ill Veterans: Choosing Wisely? SO CLINICAL THERAPEUTICS LA English DT Article DE Benzodiazepine; inappropriate; sedative-hypnotic; veterans ID INAPPROPRIATE MEDICATION USE; RECEIVING PALLIATIVE CARE; BEERS CRITERIA; HEALTH-CARE; ELDERLY-PATIENTS; ADULTS; RISK; CANCER; SETTINGS; EXPOSURE AB Purpose: The 2014 American Geriatrics Society's Choosing Wisely list cautions against the use of any benzodiazepines or other sedative-hypnotics (BSHs) as initial treatments for agitation, insomnia, or delirium in older adults. Because these symptoms are prevalent among hospitalized patients, seriously ill older adults are at risk of receiving these potentially inappropriate medications. The objectives of this study were to understand the extent to which potentially inappropriate BSHs are being used in hospitalized, seriously ill, older veterans and to understand what clinical and sociodemographic characteristics are associated with potentially inappropriate BSH use. Methods: We reviewed medical records of 222 veterans aged >= 65 years who were hospitalized in an acute care facility in the New York New Jersey metropolitan region in fiscal years 2009 and 2010. Veterans had diagnoses of advanced cancer, chronic obstructive pulmonary disease, congestive heart failure, and/or HIV/AIDS and received inpatient palliative care. Associations among potentially inappropriate BSH use (BSHs for indications other than alcohol withdrawal and current generalized anxiety disorder or one-time use before a medical procedure) and clinical and sociodemographic characteristics were examined with multivariable logistic regression. Findings: One-fifth of the sample was prescribed a potentially inappropriate BSH during the index hospitalization during the study period (n = 47). The most commonly prescribed potentially inappropriate medications were zolpidem (n = 26 [11.7%]) and lorazepam (n = 19 [8.9%]). Hispanic ethnicity was significantly associated with prescription of potentially inappropriate BSHs among the entire sample (adjusted odds ratio [AOR] = 3.79; 95% CI, 1.32-10.88) and among patients who survived until discharge (n = 164; AOR = 5.28; 95% CI, 1.64-17.07). Among patients who survived until discharge, black patients were less likely to be prescribed potentially inappropriate BSHs than white patients (AOR = 0.35; 95% CI, 0.13 0.997), and patients who had past-year BSH prescriptions were more likely to be prescribed a potentially inappropriate BSH than patients without past-year BSH use. Implications: The potentially inappropriate BSHs documented in our sample included short-and intermediate-acting benzodiazepines, medications that were not identified as potentially inappropriate for older adults until after these data were collected. Few long-acting benzodiazepines were recorded, suggesting that the older veterans in our sample were receiving medications according to the guidelines in place at the time of hospitalization. Clinicians may be able to reduce prescriptions of newly identified inappropriate BSHs by being aware of medications patients received before hospitalization and by being cognizant of racial/ethnic disparities in symptom management. Future studies should explore reasons for disparities in BSH prescriptions. Published by Elsevier HS Journals, Inc. C1 [Garrido, Melissa M.; Penrod, Joan D.; Jones, Shatice C.; Boockyar, Kenneth S.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Garrido, Melissa M.; Penrod, Joan D.; Boockyar, Kenneth S.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Prigerson, Holly G.] Weill Cornell Med Coll, New York, NY USA. [Boockyar, Kenneth S.] Jewish Home Lifecare, New York, NY USA. RP Garrido, MM (reprint author), James J Peters VA Med Ctr, 4A-17,130 Kingsbridge Rd, Bronx, NY 10468 USA. EM melissa.garrido@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service [CDA 11-201/CDP 12255]; Greenwall Foundation; National Palliative Care Research Center FX Dr. Garrido is supported by CDA 11-201/CDP 12255, Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service. Dr. Boockvar is supported by the Greenwall Foundation. Data were collected with support from the National Palliative Care Research Center. NR 34 TC 6 Z9 7 U1 1 U2 5 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD NOV PY 2014 VL 36 IS 11 BP 1547 EP 1554 DI 10.1016/j.clinthera.2014.10.007 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AU9YX UT WOS:000345948900008 PM 25453732 ER PT J AU Redding, SE Liu, S Hung, WW Boockvar, KS AF Redding, Sarah E. Liu, Sophia Hung, William W. Boockvar, Kenneth S. TI Opioid Interruptions, Pain, and Withdrawal Symptoms in Nursing Home Residents SO CLINICAL THERAPEUTICS LA English DT Article DE opioid; withdrawal; pain management; nursing homes ID ADVERSE EVENTS; DRUG; RELIABILITY; MORPHINE; SCALE; CARE; MDS AB Purpose: Interruptions in opioid use have the potential to cause pain relapse and withdrawal symptoms. The objectives of this study were to observe patterns of opioid interruption during acute illness in nursing home residents and examine associations between interruptions and pain and withdrawal symptoms. Methods: Patients from 3 nursing homes in a metropolitan area who were prescribed opioids were assessed for symptoms of pain and withdrawal by researchers blinded to opioid dosage received, using the Brief Pain Inventory Scale and the Clinical Opioid Withdrawal Scale, respectively, during prespecified time periods. The prespecified time periods were 2 weeks after onset of acute illness (eg, urinary tract infection), and 2 weeks after hospital admission and nursing home readmission, if they occurred. Opioid dosing was recorded and a significant interruption was defined as a complete discontinuation or a reduction in dose of >50% for >= 1 day. The covariates age, sex, race, comorbid conditions, initial opioid dose, and initial pain level were recorded. Symptoms pre-and post-opioid interruptions were compared and contrasted with those in a group without opioid interruptions. Findings: Sixty-six patients receiving opioids were followed for a mean of 10.9 months and experienced a total of 104 acute illnesses. During 64 (62%) illnesses, patients experienced any reduction in opioid dosing, with a mean (SD) dose reduction of 63.9% (29.9%). During 39 (38%) illnesses, patients experienced a significant opioid interruption. In a multivariable model, residence at 1 of the 3 nursing homes was associated with a lower risk of interruption (odds ratio = 0.073; 95% CI, 0.009 to 0.597; P < 0.015). In patients with interruptions, there were statistically insignificant changes in mean (SD) pain score (difference 0.50 [2.66]; 95% CI, 3.16 to 2.16) and withdrawal-score (difference 0.91 [3.12]; 95% CI, 4.03 to 2.21) after the interruption as compared with before interruption. However, when compared with patients without interruptions, patients with interruptions experienced larger increases in pain scores during the follow-up periods (difference 0.09 points per day; 95% CI, 0.01 to 0.019; P = 0.08). In particular, patients who received the highest quartile of opioid dose before interruption experienced increases in pain scores over time that were 0.22 points per day larger (95% CI, 0.02 to 0.41; P = 0.03) than those without interruption. Withdrawal scores were not associated with opioid interruption regardless of dose before interruption. Published by Elsevier HS Journals, Inc. C1 [Redding, Sarah E.; Liu, Sophia; Hung, William W.; Boockvar, Kenneth S.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Hung, William W.; Boockvar, Kenneth S.] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Boockvar, Kenneth S.] Jewish Home Lifecare, New York, NY USA. RP Boockvar, KS (reprint author), James J Peters VA Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM Kenneth.boockvar@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU Veterans Affairs Health Services Research and Development Service [RCD 03-027-1, REA 08-260]; Greenwall Foundation FX This study was supported by Veterans Affairs Health Services Research and Development Service grants RCD 03-027-1 and REA 08-260. The study sponsor had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the mandscript for publication. One author (K. Boockvar) is also supported by the Greenwall Foundation. The contents do not represent the views of the US Department of Veterans Affairs or the United States Government. NR 21 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD NOV PY 2014 VL 36 IS 11 BP 1555 EP 1563 DI 10.1016/j.clinthera.2014.10.013 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AU9YX UT WOS:000345948900009 PM 25455930 ER PT J AU Durazzo, TC Pennington, DL Schmidt, TP Meyerhoff, DJ AF Durazzo, Timothy C. Pennington, David L. Schmidt, Thomas P. Meyerhoff, Dieter J. TI Effects of Cigarette Smoking History on Neurocognitive Recovery Over 8 Months of Abstinence in Alcohol-Dependent Individuals SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Dependence; Cigarette Smoking; Cognition; Recovery; Longitudinal ID BRAIN; DISORDERS; HMO AB BackgroundThis study compared the rate and extent of recovery on measures of learning and memory, processing speed, and working memory in treatment-seeking alcohol-dependent individuals (ALC) who were never smokers (nvsALC), former smokers (fsALC), and active smokers (asALC) over the first 8months of sustained abstinence from alcohol. Assessments after 1week, 1month, and 8months of abstinence in ALC enabled a comparison of the rates of neurocognitive changes from 1 week to 1 month versus 1 to 8months of abstinence. MethodsALC and never-smoking controls were administered standardized measures of auditory-verbal and visuospatial learning and memory, processing speed, and working memory. Controls completed a baseline assessment and a follow-up approximately 9months later. ResultsOver 8months of abstinence, asALC showed poorer recovery than nvsALC on visuospatial learning, and both fsALC and asALC recovered less than nvsALC on processing speed measures. The corresponding recovery rates for the ALC group, as a whole, were greater from 1 week to 1 month than from 1 to 8months of abstinence; these findings were largely driven by improvements in nvsALC. The recovery levels for fsALC on most measures were similar to those in asALC. Additionally, over 8months, asALC showed significantly less improvement with increasing age than nvsALC on measures of processing speed and learning and memory. At 8months of abstinence, asALC were inferior to controls and nvsALC on multiple measures, fsALC performed worse than nvsALC on several tests, but nvsALC were not different from controls on any measure. ConclusionsOverall, ALC showed rapid improvement on measures of visuospatial learning and processing speed during the first month of abstinence from alcohol. Results also provide robust evidence that smoking status influenced the rate and level of neurocognitive recovery over 8months of abstinence in this ALC cohort. C1 [Durazzo, Timothy C.; Pennington, David L.; Schmidt, Thomas P.; Meyerhoff, Dieter J.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. [Durazzo, Timothy C.; Pennington, David L.; Meyerhoff, Dieter J.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. RP Durazzo, TC (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis 114M, 4150 Clement St, San Francisco, CA 94121 USA. EM timothy.durazzo@ucsf.edu FU National Institutes of Health [DA24136, AA10788] FX This work was supported by grants from the National Institutes of Health (DA24136 to TCD and AA10788 to DJM) administered by the Northern California Institute for Research and Education and by the use of resources and facilities at the San Francisco Veterans Administration Medical Center. NR 28 TC 5 Z9 5 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 2014 VL 38 IS 11 BP 2816 EP 2825 DI 10.1111/acer.12552 PG 10 WC Substance Abuse SC Substance Abuse GA AU5AW UT WOS:000345620400016 PM 25336410 ER PT J AU Lee, JS Nsa, W Hausmann, LRM Trivedi, AN Bratzler, DW Auden, D Mor, MK Baus, K Larbi, FM Fine, MJ AF Lee, Jonathan S. Nsa, Wato Hausmann, Leslie R. M. Trivedi, Amal N. Bratzler, Dale W. Auden, Dana Mor, Maria K. Baus, Kristie Larbi, Fiona M. Fine, Michael J. TI Quality of Care for Elderly Patients Hospitalized for Pneumonia in the United States, 2006 to 2010 SO JAMA INTERNAL MEDICINE LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; ALL-CAUSE MORTALITY; PNEUMOCOCCAL VACCINATION; INFLUENZA VACCINATION; PERFORMANCE-MEASURES; MEDICARE PATIENTS; ADULTS; OUTCOMES; METAANALYSIS; ASSOCIATIONS AB IMPORTANCE Nearly every US acute care hospital reports publicly on adherence to recommended processes of care for patients hospitalized with pneumonia. However, it remains uncertain how much performance of these process measures has improved over time or whether performance is associated with superior patient outcomes. OBJECTIVES To describe trends in processes of care, mortality, and readmission for elderly patients hospitalized for pneumonia and to assess the independent associations between processes and outcomes of care. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study conducted from January 1, 2006, to December 31, 2010, at 4740 US acute care hospitals. The cohort included 1 818 979 cases of pneumonia in elderly (>= 65 years), Medicare fee-for-service patients who were eligible for at least 1 of 7 pneumonia inpatient processes of care tracked by the Centers for Medicare & Medicaid Services (CMS). MAIN OUTCOMES AND MEASURES Annual performance rates for 7 pneumonia processes of care and an all-or-none composite of these measures; and 30-day, all-cause mortality and hospital readmission, adjusted for patient and hospital characteristics. RESULTS Adjusted annual performance rates for all 7 CMS processes of care (expressed in percentage points per year) increased significantly from 2006 to 2010, ranging from 1.02 for antibiotic initiation within 6 hours to 5.30 for influenza vaccination (P < .001). All 7 measures were performed in more than 92% of eligible cases in 2010. The all-or-none composite demonstrated the largest adjusted relative increase over time (6.87 percentage points per year; P < .001) and was achieved in 87.4% of cases in 2010. Adjusted annual mortality decreased by 0.09 percentage points per year (P < .001), driven primarily by decreasing mortality in the subgroup not treated in the intensive care unit (ICU) (-0.18 percentage points per year; P < .001). Adjusted annual readmission rates decreased significantly by 0.25 percentage points per year (P < .001). All 7 processes of care were independently associated with reduced 30-day mortality, and 5 were associated with reduced 30-day readmission. CONCLUSIONS AND RELEVANCE Performance of processes of care for elderly patients hospitalized for pneumonia improved substantially from 2006 to 2010. Adjusted 30-day mortality declined slightly over time primarily owing to improved survival among non-ICU patients, and all individual processes of care were independently associated with reduced mortality. C1 [Lee, Jonathan S.; Hausmann, Leslie R. M.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Nsa, Wato; Auden, Dana] Oklahoma Fdn Med Qual, Oklahoma City, OK USA. [Hausmann, Leslie R. M.; Mor, Maria K.; Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Trivedi, Amal N.] Brown Univ, Dept Hlth Serv Policy & Practice, Providence, RI 02912 USA. [Bratzler, Dale W.] Univ Oklahoma, Hlth Sci Ctr, Coll Med & Publ Hlth, Oklahoma City, OK USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Baus, Kristie; Larbi, Fiona M.] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. RP Fine, MJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Bldg 30,Univ Dr 151C, Pittsburgh, PA 15240 USA. EM michael.fine@va.gov FU CMS, an agency of the US Department of Health and Human Services [HHSM-500-2011-OK10C] FX The analyses on which this study is based were performed under contract No. HHSM-500-2011-OK10C funded by the CMS, an agency of the US Department of Health and Human Services. NR 48 TC 12 Z9 12 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD NOV PY 2014 VL 174 IS 11 BP 1806 EP 1814 DI 10.1001/jamainternmed.2014.4501 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AU9KA UT WOS:000345909900021 PM 25201438 ER PT J AU Lyles, CR Schafer, AL Seligman, HK AF Lyles, Courtney R. Schafer, Anne L. Seligman, Hilary K. TI Income, Food Insecurity, and Osteoporosis among Older Adults in the 2007-2008 National Health and Nutrition Examination Survey (NHANES) SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Aging; disparities; osteoporosis; socioeconomic factors; nutrition; food insecurity ID BONE-MINERAL DENSITY; BODY-MASS INDEX; FRACTURE RISK; SOCIOECONOMIC-STATUS; UNITED-STATES; VITAMIN-D; METAANALYSIS; WOMEN; ASSOCIATION; EPIDEMIOLOGY AB Background. Low SES is associated with risk and protective factors for osteoporosis. However, there has been little examination of SES and osteoporosis in the U.S. Methods. We conducted a cross-sectional study of adults aged 50 or older in 2007-2008 NHANES, examining two predictors of SES: income and food insecurity. Our outcome was osteoporosis assessed from bone scans. Adjusted regression models (overall and gender-stratified) controlled for age, gender, race/ethnicity, education, BMI, smoking, alcohol consumption, physical activity, calcium and vitamin D, and medication use. Results. Of 2403 participants, 5% had osteoporosis. In adjusted models, there was a higher risk of osteoporosis in low-income (OR; 95% CI: 1.90;1.07-3.37) and food-insecure populations (3.48;1.43-8.48). There was a stronger association with food insecurity among women (4.91;2.40-10.0) than men (0.46;0.07-3.01). Conclusions. Income and food insecurity may have significant implications not just for immediate nutritional outcomes, but also for conditions such as osteoporosis that develop over the lifespan. C1 [Lyles, Courtney R.; Seligman, Hilary K.] San Francisco Gen Hosp, UCSF Dept Med, Div Gen Internal Med, San Francisco, CA USA. [Lyles, Courtney R.; Seligman, Hilary K.] UCSF Ctr Vulnerable Populat, San Francisco, CA USA. [Schafer, Anne L.] UCSF Dept Med, Div Endocrinol & Metab, San Francisco, CA USA. [Schafer, Anne L.] San Francisco VA Med Ctr, Endocrine Res Unit, San Francisco, VA USA. RP Lyles, CR (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Div Gen Internal Med, Ctr Vulnerable Populat, 1001 Potrero Ave Bldg 10,W13,Box 1364, San Francisco, CA 94110 USA. FU AHRQ HHS [K99HS022408]; NCRR NIH HHS [KL2RR024130] NR 42 TC 1 Z9 1 U1 1 U2 9 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 EI 1548-6869 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD NOV PY 2014 VL 25 IS 4 BP 1530 EP 1541 PG 12 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AU6SN UT WOS:000345732200007 PM 25418225 ER PT J AU Griffis, HM Kilaru, AS Werner, RM Asch, DA Hershey, JC Hill, S Ha, YP Sellers, A Mahoney, K Merchant, RM AF Griffis, Heather M. Kilaru, Austin S. Werner, Rachel M. Asch, David A. Hershey, John C. Hill, Shawndra Ha, Yoonhee P. Sellers, Allison Mahoney, Kevin Merchant, Raina M. TI Use of Social Media Across US Hospitals: Descriptive Analysis of Adoption and Utilization SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE social media; Internet; health information ID HEALTH-CARE; PATIENT RATINGS; QUALITY; ASSOCIATIONS; INTERNET; ONLINE AB Background: Use of social media has become widespread across the United States. Although businesses have invested in social media to engage consumers and promote products, less is known about the extent to which hospitals are using social media to interact with patients and promote health. Objective: The aim was to investigate the relationship between hospital social media extent of adoption and utilization relative to hospital characteristics. Methods: We conducted a cross-sectional review of hospital-related activity on 4 social media platforms: Facebook, Twitter, Yelp, and Foursquare. All US hospitals were included that reported complete data for the Centers for Medicare and Medicaid Services Hospital Consumer Assessment of Healthcare Providers and Systems survey and the American Hospital Association Annual Survey. We reviewed hospital social media webpages to determine the extent of adoption relative to hospital characteristics, including geographic region, urban designation, bed size, ownership type, and teaching status. Social media utilization was estimated from user activity specific to each social media platform, including number of Facebook likes, Twitter followers, Foursquare check-ins, and Yelp reviews. Results: Adoption of social media varied across hospitals with 94.41% (3351/3371) having a Facebook page and 50.82% (1713/3371) having a Twitter account. A majority of hospitals had a Yelp page (99.14%, 3342/3371) and almost all hospitals had check-ins on Foursquare (99.41%, 3351/3371). Large, urban, private nonprofit, and teaching hospitals were more likely to have higher utilization of these accounts. Conclusions: Although most hospitals adopted at least one social media platform, utilization of social media varied according to several hospital characteristics. This preliminary investigation of social media adoption and utilization among US hospitals provides the framework for future studies investigating the effect of social media on patient outcomes, including links between social media use and the quality of hospital care and services. C1 [Griffis, Heather M.; Sellers, Allison] Univ Penn, Penn Social Media & Hlth Innovat Lab, Philadelphia, PA 19104 USA. [Kilaru, Austin S.] Highland Hosp, Dept Emergency Med, Oakland, CA USA. [Werner, Rachel M.] Univ Penn, Perelman Sch Med, Ctr Hlth Equity Res & Promot, Philadelphia VA Med Ctr,Div Gen Internal Med, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Philadelphia VA Med Ctr, Penn Med Ctr Healthcare Innovat, Philadelphia, PA 19104 USA. [Hershey, John C.; Hill, Shawndra] Univ Penn, Wharton Sch, Penn Social Media & Hlth Innovat Lab, Philadelphia, PA 19104 USA. [Ha, Yoonhee P.] Univ Penn, Perelman Sch Med, Penn Social Media & Hlth Innovat Lab, Philadelphia, PA 19104 USA. [Mahoney, Kevin] Univ Penn, Penn Med, Philadelphia, PA 19104 USA. [Merchant, Raina M.] Univ Penn, Dept Emergency Med, Penn Social Media & Hlth Innovat Lab, Philadelphia, PA 19104 USA. RP Merchant, RM (reprint author), Univ Penn, Dept Emergency Med, Penn Social Media & Hlth Innovat Lab, 423 Guardian Dr,Room 1022, Philadelphia, PA 19104 USA. EM raina.merchant@uphs.upenn.edu NR 22 TC 12 Z9 12 U1 3 U2 29 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PD NOV PY 2014 VL 16 IS 11 AR e264 DI 10.2196/jmir.3758 PG 11 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA AU5FJ UT WOS:000345632300043 PM 25431831 ER PT J AU Maschmeyer, G Patterson, TF AF Maschmeyer, Georg Patterson, Thomas F. TI Our 2014 approach to breakthrough invasive fungal infections SO MYCOSES LA English DT Article DE Breakthrough fungal infection; liposomal AmB; fluconazole; posaconazole; voriconazole; echinocandins ID ACUTE MYELOID-LEUKEMIA; MINIMUM INHIBITORY CONCENTRATIONS; STEM-CELL TRANSPLANTATION; IN-VITRO ACTIVITY; AMPHOTERICIN-B; POSACONAZOLE PROPHYLAXIS; ASPERGILLUS-TERREUS; CANDIDA-GLABRATA; DRUG-RESISTANCE; HEMATOLOGICAL MALIGNANCIES AB Evidence-based clinical pathways to direct antifungal treatment options in patients with breakthrough fungal infections during current systemic antifungal therapy are not available. Nonetheless, for defined settings of such breakthrough infections approaches to management can be recommended based on clinical, epidemiological, pharmacological and in vitro susceptibility data. C1 [Maschmeyer, Georg] Charite, Klinikum Ernst von Bergmann, Dept Hematol Oncol & Palliat Care, Acad Teaching Hosp, D-14467 Potsdam, Germany. [Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, San Antonio Ctr Med Mycol, Div Infect Dis, San Antonio, TX 78229 USA. RP Maschmeyer, G (reprint author), Charite, Klinikum Ernst von Bergmann, Dept Hematol Oncol & Palliat Care, Acad Teaching Hosp, Charlottenstr 72, D-14467 Potsdam, Germany. EM gmaschmeyer@klinikumevb.de NR 55 TC 7 Z9 8 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0933-7407 EI 1439-0507 J9 MYCOSES JI Mycoses PD NOV PY 2014 VL 57 IS 11 BP 645 EP 651 DI 10.1111/myc.12213 PG 7 WC Dermatology; Mycology SC Dermatology; Mycology GA AU5LP UT WOS:000345648900001 PM 24963554 ER PT J AU Denny, BT Fan, J Liu, X Guerreri, S Mayson, SJ Rimsky, L New, AS Siever, LJ Koenigsberg, HW AF Denny, Bryan T. Fan, Jin Liu, Xun Guerreri, Stephanie Mayson, Sarah Jo Rimsky, Liza New, Antonia S. Siever, Larry J. Koenigsberg, Harold W. TI Insula-amygdala functional connectivity is correlated with habituation to repeated negative images SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE habituation; emotion; functional connectivity; insula; amygdala ID GILL-WITHDRAWAL REFLEX; OLD-WORLD MONKEY; EMOTION REGULATION; FACIAL EXPRESSIONS; BRAIN; APLYSIA; DISHABITUATION; PICTURES; CORTEX; METAANALYSIS AB Behavioral habituation during repeated exposure to aversive stimuli is an adaptive process. However, the way in which changes in self-reported emotional experience are related to the neural mechanisms supporting habituation remains unclear. We probed these mechanisms by repeatedly presenting negative images to healthy adult participants and recording behavioral and neural responses using functional magnetic resonance imaging. We were particularly interested in investigating patterns of activity in insula, given its significant role in affective integration, and in amygdala, given its association with appraisal of aversive stimuli and its frequent coactivation with insula. We found significant habituation behaviorally along with decreases in amygdala, occipital cortex and ventral prefrontal cortex (PFC) activity with repeated presentation, whereas bilateral posterior insula, dorsolateral PFC and precuneus showed increased activation. Posterior insula activation during image presentation was correlated with greater negative affect ratings for novel presentations of negative images. Further, repeated negative image presentation was associated with increased functional connectivity between left posterior insula and amygdala, and increasing insula-amygdala functional connectivity was correlated with increasing behavioral habituation. These results suggest that habituation is subserved in part by insula-amygdala connectivity and involves a change in the activity of bottom-up affective networks. C1 [Denny, Bryan T.; Fan, Jin; Guerreri, Stephanie; Mayson, Sarah Jo; Rimsky, Liza; New, Antonia S.; Siever, Larry J.; Koenigsberg, Harold W.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Fan, Jin] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Fan, Jin] CUNY Queens Coll, Dept Psychol, New York, NY 11367 USA. [Liu, Xun] Chinese Acad Sci, Inst Psychol, Beijing 100101, Peoples R China. [New, Antonia S.; Siever, Larry J.; Koenigsberg, Harold W.] James J Peters VA Med Ctr, Bronx, NY 10468 USA. RP Koenigsberg, HW (reprint author), James J Peters VA Med Ctr, Mental Hlth Patient Care Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM HWarrenK@nyc.rr.com RI Liu, Xun/C-2400-2009; Fan, Jin/A-6716-2009 OI Liu, Xun/0000-0003-1366-8926; Fan, Jin/0000-0001-9630-8330 FU National Institute of Mental Health [R01 MH077813]; National Center for Research Resources, National Institutes of Health for the Mount Sinai General Clinical Research Center [5M01 RR00071]; James J Peters Veterans Affairs Medical Center FX This work was supported by a grant from the National Institute of Mental Health (R01 MH077813 to Dr Koenigsberg); by the National Center for Research Resources, National Institutes of Health for the Mount Sinai General Clinical Research Center (5M01 RR00071) and by the James J Peters Veterans Affairs Medical Center. NR 51 TC 9 Z9 9 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 EI 1749-5024 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD NOV PY 2014 VL 9 IS 11 BP 1660 EP 1667 DI 10.1093/scan/nst160 PG 8 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AU8LA UT WOS:000345846800003 PM 24170933 ER PT J AU Foster-Chang, SA Manning, ML Chandler, L AF Foster-Chang, Sarah A. Manning, Mary L. Chandler, Laura TI Tuberculosis Screening of New Hospital Employees Compliance, Clearance to Work Time, and Cost Using Tuberculin Skin Test and Interferon-Gamma Release Assays SO WORKPLACE HEALTH & SAFETY LA English DT Article ID HEALTH-CARE WORKERS; QUANTIFERON-TB GOLD; LATENT TUBERCULOSIS; UNITED-STATES; DIAGNOSIS; INFECTION; ACCEPTABILITY; GUIDELINES; SPOT.TB; PROGRAM AB Selection of the most suitable test(s) for detection of Mycobacterium tuberculosis (TB) infection should be based on purpose, setting, effectiveness, and cost. Two tests are available to screen for latent TB: the tuberculin skin test (TST) and the more recent interferon-gamma release assays (IGRAs). Based on the administrative, logistic, and technical ease of use, an IGRA trial was initiated by the occupational health department at an urban Veteran's Administration health care facility for TB screening of new employees. As a result, new employees completing the pre-placement process within the organization's designated 14 days increased from 77% to 97%, new employee clearance to work time decreased from 13.18 to 5.91 days, and new employee TB screening costs were reduced by 40%. The IGRA is an acceptable alternative to the TST and has significant potential to improve the process of pre-placement TB screening. C1 [Foster-Chang, Sarah A.; Chandler, Laura] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Foster-Chang, Sarah A.] Natl VA Occupat & Environm Med Consult Grp, Natl VA Occupat Hlth Program, Philadelphia, PA USA. [Chandler, Laura] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Manning, Mary L.] Thomas Jefferson Univ, Jefferson Sch Nursing, Philadelphia, PA 19107 USA. RP Foster-Chang, SA (reprint author), Philadelphia VA Med Ctr, 3900 Woodland Ave,1B153, Philadelphia, PA 19104 USA. EM Sarah.Foster-Chang@va.gov NR 36 TC 1 Z9 1 U1 0 U2 4 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 2165-0799 EI 2165-0969 J9 WORKPLACE HEALTH SAF JI Workplace Health Saf. PD NOV PY 2014 VL 62 IS 11 BP 460 EP 467 DI 10.3928/21650799-20140902-02 PG 8 WC Nursing SC Nursing GA AW0BU UT WOS:000345956200004 PM 25207587 ER PT J AU Barnes, DE Cenzer, IS Yaffe, K Ritchie, CS Lee, SJ AF Barnes, Deborah E. Cenzer, Irena S. Yaffe, Kristine Ritchie, Christine S. Lee, Sei J. CA Alzheimer's Dis Neuroimaging Initi TI A point-based tool to predict conversion from mild cognitive impairment to probable Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Mild cognitive impairment; Prognostic modeling; Risk factors; Aged; Human; Magnetic resonance imaging; Neuropsychological tests; Disease progression ID ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; OLDER-ADULTS; AD; DEMENTIA; MRI; MCI; BIOMARKERS; RISK AB Background: Our objective in this study was to develop a point-based tool to predict conversion from amnestic mild cognitive impairment (MCI) to probable Alzheimer's disease (AD). Methods: Subjects were participants in the first part of the Alzheimer's Disease Neuroimaging Initiative. Cox proportional hazards models were used to identify factors associated with development of AD, and a point score was created from predictors in the final model. Results: The final point score could range from 0 to 9 (mean 4.8) and included: the Functional Assessment Questionnaire (2-3 points); magnetic resonance imaging (MRI) middle temporal cortical thinning (1 point); MRI hippocampal subcortical volume (1 point); Alzheimer's Disease Cognitive Scale cognitive subscale (2-3 points); and the Clock Test (1 point). Prognostic accuracy was good (Harrell's c = 0.78; 95% CI 0.75, 0.81); 3-year conversion rates were 6% (0-3 points), 53% (4-6 points), and 91% (7-9 points). Conclusions: A point-based risk score combining functional dependence, cerebral MRI measures, and neuropsychological test scores provided good accuracy for prediction of conversion from amnestic MCI to AD. (C) 2014 The Alzheimer's Association. All rights reserved. C1 [Barnes, Deborah E.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Barnes, Deborah E.; Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Barnes, Deborah E.; Cenzer, Irena S.; Yaffe, Kristine; Ritchie, Christine S.; Lee, Sei J.] San Francisco VA Med Ctr, San Francisco, CA USA. [Cenzer, Irena S.; Ritchie, Christine S.; Lee, Sei J.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Ritchie, Christine S.] Jewish Home San Francisco, San Francisco, CA USA. RP Barnes, DE (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. EM deborah.barnes@ucsf.edu FU Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; BioClinica, Inc.; Biogen Idec, Inc.; Bristol-Myers Squibb Company; Eisai, Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche, Ltd.; Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO, Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Medpace, Inc.; Merck Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer, Inc.; Piramal Imaging; Servier; Synarc, Inc.; Takeda Pharmaceutical Company; Canadian Institutes of Health Research; Northern California Institute for Research and Education; NIH [P30 AGO 10129, K01 AG030514]; S.D. Bechtel, Jr. Foundation; National Institutes of Health; Department of Veterans Affairs; Department of Defense; NARSAD; University of California School of Medicine, S.D.; NIH; Commonwealth Fund; Retirement Research Foundation; American Federation of Aging Research through the Beeson Career Development Award [K23AG040779]; [K24-AG031155] FX The authors thank Dr. John Boscardin, Professor of Medicine and Epidemiology & Biostatistics at the University of California, San Francisco, for guidance on statistical methods as well as the study participants. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). The ADNI is funded by the National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: the Alzheimer's Association; the Alzheimer's Drug Discovery Foundation; BioClinica, Inc.; Biogen Idec, Inc.; Bristol-Myers Squibb Company; Eisai, Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche, Ltd., and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO, Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer, Inc.; Piramal Imaging; Servier; Synarc, Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research provides funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (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 Neuroimaging at the University of California, Los Angeles. This research was also supported by NIH Grants P30 AGO 10129 and K01 AG030514. This study was supported by the S.D. Bechtel, Jr. Foundation. Dr. Yaffe was supported in part by Grant K24-AG031155.; Dr. Barnes reports research support from the National Institutes of Health, Alzheimer's Association, Department of Veterans Affairs, Department of Defense, NARSAD, University of California School of Medicine, S.D. Bechtel, Jr. Foundation, UCSF Osher Center for Integrative Medicine, and UCB Pharma, Inc., and serves as a study design consultant for the UCSF Clinical and Translational Sciences Institute. Dr. Yaffe reports serving on data safety monitoring boards for Takeda, Inc., and a study sponsored by the NIH and has served as a consultant for Novartis, Inc. Dr. Ritchie reports research funding from the National Institutes of Health, the Commonwealth Fund, the Retirement Research Foundation, programmatic funding support from the S.D. Bechtel, Jr. Foundation, and royalties from UptoDate. Dr. Lee reports funding from the National Institute on Aging and the American Federation of Aging Research through the Beeson Career Development Award (K23AG040779) and the S.D. Bechtel, Jr. Foundation. NR 50 TC 8 Z9 8 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD NOV PY 2014 VL 10 IS 6 BP 646 EP 655 DI 10.1016/j.jalz.2013.12.014 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA AU0KD UT WOS:000345310800009 PM 24495339 ER PT J AU Dodge, HH Zhu, J Harvey, D Saito, N Silbert, LC Kaye, JA Koeppe, RA Albin, RL AF Dodge, Hiroko H. Zhu, Jian Harvey, Danielle Saito, Naomi Silbert, Lisa C. Kaye, Jeffrey A. Koeppe, Robert A. Albin, Roger L. CA Alzheimer's Dis Neuroimaging Inita TI Biomarker progressions explain higher variability in stage-specific cognitive decline than baseline values in Alzheimer disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE ADNI; Cognitive declines; Biomarker; Biomarker progressions; ADNI-mem; ADNI-exe; MCI; FDG-PET; MRI volume ID NEUROIMAGING INITIATIVE ADNI; SMALL-VESSEL DISEASE; WHITE-MATTER; CORTICAL THICKNESS; CLINICAL CHARACTERIZATION; PATHOLOGICAL CASCADE; HYPOTHETICAL MODEL; DYNAMIC BIOMARKERS; EXECUTIVE FUNCTION; PROCESSING SPEED AB Background: It is unknown which commonly used Alzheimer disease (AD) biomarker values baseline or progression best predict longitudinal cognitive decline. Methods: 526 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). ADNI composite memory and executive scores were the primary outcomes. Individual-specific slope of the longitudinal trajectory of each biomarker was first estimated. These estimates and observed baseline biomarker values were used as predictors of cognitive declines. Variability in cognitive declines explained by baseline biomarker values was compared with variability explained by biomarker progression values. Results: About 40% of variability in memory and executive function declines was explained by ventricular volume progression among mild cognitive impairment patients. A total of 84% of memory and 65% of executive function declines were explained by fluorodeoxyglucose positron emission tomography (FDG-PET) score progression and ventricular volume progression, respectively, among AD patients. Conclusions: For most biomarkers, biomarker progressions explained higher variability in cognitive decline than biomarker baseline values. This has important implications for clinical trials targeted to modify AD biomarkers. (C) 2014 The Alzheimer's Association. All rights reserved. C1 [Dodge, Hiroko H.; Silbert, Lisa C.; Kaye, Jeffrey A.] Oregon Hlth & Sci Univ, Dept Neurol, Layton Aging & Alzheimers Dis Ctr, Portland, OR 97201 USA. [Dodge, Hiroko H.; Albin, Roger L.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Dodge, Hiroko H.; Albin, Roger L.] Univ Michigan, Michigan Alzheimers Dis Ctr, Ann Arbor, MI USA. [Zhu, Jian] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Harvey, Danielle; Saito, Naomi] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA. [Silbert, Lisa C.; Kaye, Jeffrey A.] Portland VA Med Ctr, Portland, OR USA. [Koeppe, Robert A.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Albin, Roger L.] Vet Affairs Ann Arbor Healthcare Syst, Neurol Serv & Geriatr Res Educ & Clin Ctr, Ann Arbor, MI USA. RP Dodge, HH (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Layton Aging & Alzheimers Dis Ctr, Portland, OR 97201 USA. EM dodgeh@ohsu.edu OI Kaye, Jeffrey/0000-0002-9971-3478 FU Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant) [U01 AG024904]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Alzheimer's Drug Discovery Foundation; Bio-Clinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly; F. Hoffmann-La Roche Ltd; Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; Takeda Pharmaceutical Company; Canadian Institutes of Health Research; National Institutes of Health grant [P30 AG010129]; National Institute on Aging [P30 AG008017, 1R01AG036772, R13 AG030995]; Michigan Alzheimer's Disease Center Pilot Grant FX Data collection and sharing for this project were funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Bio-Clinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; 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 (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 National Institutes of Health grant (P30 AG010129). Additional funding includes National Institute on Aging (P30 AG008017, 1R01AG036772, and R13 AG030995) and Michigan Alzheimer's Disease Center Pilot Grant. NR 37 TC 7 Z9 7 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD NOV PY 2014 VL 10 IS 6 BP 690 EP 703 DI 10.1016/j.jalz.2014.04.513 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA AU0KD UT WOS:000345310800014 PM 25022534 ER PT J AU Wyman, MF Kallio, P Allred, E Meyer, D AF Wyman, Mary F. Kallio, Peter Allred, Emily Meyer, Deborah TI A group-based brief intervention for surgery patients with high-risk substance use SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Substance use disorder; Surgery; Brief intervention; Health behavior; Veterans ID ALCOHOL-USE DISORDERS; MAJOR NONCARDIAC SURGERY; SELF-REPORTED DRINKING; EMERGENCY-DEPARTMENT; HEALTH-CARE; AT-RISK; AUDIT-C; CONSUMPTION; ABUSE; COMPLICATIONS AB Objective: This study examined the feasibility and efficacy of a psychosocial intervention to address high-risk substance use in patients scheduled for elective surgery. Method: A group-format intervention, based on motivational interviewing principles, was provided prior to elective surgery to 107 participants with at-risk substance use, identified using the Alcohol Use Disorders Identification Test - Condensed (AUDIT-C) and self-report of illicit drug use. Patient satisfaction was assessed with an anonymous survey. Within-subject comparisons of substance use at baseline and at a postoperative follow-up evaluation were conducted. A control group of 67 surgery patients reporting high-risk substance use completed baseline assessments and received usual care. Medical outcomes and measures of utilization were compared between groups. Results: Patient satisfaction with the brief intervention was high. A paired t test comparing average pre- and post-AUDIT-C scores showed significant reduction in substance use postsurgery (t=9.94, P=.000), and participants reported intention to maintain reduced substance use levels. Between-group analyses revealed no significant differences in medical complications or utilization. Conclusion: Findings suggest that a group-based intervention for substance use disorder can be implemented as part of preoperative care and may contribute to decreased substance use prior to and following surgery. Further work is needed to identify methods to reduce adverse medical outcomes in surgical patients. Published by Elsevier Inc. C1 [Wyman, Mary F.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. [Wyman, Mary F.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Psychiat, Madison, WI 53706 USA. [Kallio, Peter; Allred, Emily; Meyer, Deborah] Zablocki Vet Affairs Med Ctr, Milwaukee, WI USA. RP Wyman, MF (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA. EM mary.wyman@va.gov NR 29 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 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2014 VL 36 IS 6 BP 637 EP 643 DI 10.1016/j.genhosppsych.2014.08.002 PG 7 WC Psychiatry SC Psychiatry GA AU2GK UT WOS:000345434400016 PM 25264340 ER PT J AU Walker, RJ Gebregziabher, M Martin-Harris, B Egede, LE AF Walker, Rebekah J. Gebregziabher, Mulugeta Martin-Harris, Bonnie Egede, Leonard E. TI Independent effects of socioeconomic and psychological social determinants of health on self-care and outcomes in Type 2 diabetes SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Diabetes; Social determinants; Socioeconomic; Psychological; Self-care ID OF-THE-LITERATURE; PSYCHOMETRIC PROPERTIES; GLYCEMIC CONTROL; VALIDITY; SCALE; DEPRESSION; DISTRESS; ADULTS; QUESTIONNAIRE; METAANALYSIS AB Objective: The purpose of this study was to investigate the independent effects of socioeconomic and psychological social determinants of health on diabetes knowledge, self-care, diabetes outcomes and quality of life. Research design and methods: Cross-sectional sample of 615 adults from two adult primary care clinics in the southeastern United States. Primary outcome variables were diabetes knowledge, self-care behaviors (diet, exercise, medication adherence, blood sugar testing, foot care) and diabetes outcomes (HbA1c, low-density lipoprotein, blood pressure, physical component summary score of SF12 quality of life, mental component summary score of SF12 quality of life). Covariates included age, sex, race/ethnicity, marital status, health literacy and comorbidity. Linear regression models were used to assess independent associations controlling for covariates. Results: In final adjusted models, significant associations for HbA1c included education [beta=-0.72, 95% confidence interval (CI): -1.36 to -0.08], income (beta=-0.66, CI: -1.30 to -0.16), self-efficacy (beta=-0.12, CI: -0.15 to -0.08) and diabetes distress (beta=0.43, CI: 0.14 to 0.72). Significant associations for self-care included medication adherence with diabetes distress (beta=-0.58, CI: -0.91 to -0.25) and perceived stress (beta=-0.12, CI: -0.18 to -0.05) and exercise with depression (beta=-0.06, CI: -0.10 to-0.01) and self-efficacy (beta=0.06, CI: 0.01 to 0.10). Significant associations for quality of life included depression (beta=-0.08, CI: -0.12 to -0.03), serious psychological distress (beta=-0.09, CI: -0.12 to -0.05), social support (beta=0.01, CI: 0.001 to 0.02) and perceived stress (beta=-0.12, CI: -0.19 to -0.06). Conclusions: Social determinants of health were significantly associated with diabetes self-care and outcomes with socioeconomic factors being most often associated with diabetes outcomes and psychological factors, specifically self-efficacy and perceived stress being most often associated with self-care and quality of life. (C) 2014 Elsevier Inc. All rights reserved. C1 [Walker, Rebekah J.; Gebregziabher, Mulugeta; Egede, Leonard E.] Ralph H Johnson VAMC, Charleston VA HSR & D COIN, Hlth Equity & Rural Outreach Innovat Ctr, Charleston, SC USA. [Walker, Rebekah J.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Walker, Rebekah J.; Martin-Harris, Bonnie] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta] Med Univ S Carolina, Dept Med, Div Publ Hlth Sci, Charleston, SC 29425 USA. [Martin-Harris, Bonnie] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Egede, Leonard E.] Med Univ S Carolina, Dept Med, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu OI Gebregziabher, Mulugeta/0000-0002-4826-481X FU The National Institute of Diabetes and Digestive and Kidney Disease [K24DK093699-01] FX This study was supported by Grant K24DK093699-01 from The National Institute of Diabetes and Digestive and Kidney Disease (PI: Leonard Egede). NR 40 TC 13 Z9 13 U1 6 U2 33 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2014 VL 36 IS 6 BP 662 EP 668 DI 10.1016/j.genhosppsych.2014.06.011 PG 7 WC Psychiatry SC Psychiatry GA AU2GK UT WOS:000345434400020 PM 25103544 ER PT J AU Hershenberg, R Mavandadi, S Klaus, JR Oslin, DW Sayers, SL AF Hershenberg, Rachel Mavandadi, Shahrzad Klaus, Johanna R. Oslin, David W. Sayers, Steven L. TI Veteran preferences for romantic partner involvement in depression treatment SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Depression; Veterans; Social support; Treatment ID FAMILY INVOLVEMENT; PRIMARY-CARE; PRIME-MD; VALIDITY; UTILITY AB Objective: The objective was to examine Veterans' preferences for romantic partner involvement in depression treatment and patient characteristics that are associated with the likelihood of preferred involvement. Method: One hundred seventy-nine Veterans who met criteria for major or minor depression reported if they wanted their partners to give them medication reminders, accompany them to appointments, and speak with their treatment provider. Results: Greater depression severity and wanting a partner to be less critical and more encouraging were associated with greater preferences for involvement. Conclusion: Veterans may view their partners' involvement in depression treatment as one opportunity for partners to decrease blame or understand more about their problems. Published by Elsevier Inc. C1 Philadelphia VA Med Ctr, Educ & Clin Ctr, VISN Mental Illness Res 4, Philadelphia, PA USA. Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Sayers, SL (reprint author), Philadelphia VA Med Ctr, VISN MIRECC 4, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM steven.sayers@va.gov FU VISN 4 Mental Illness Research, Education, and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA FX Please do not cite without permission from the authors. This paper was prepared with the support of the VISN 4 Mental Illness Research, Education, and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA. The views expressed in the 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. There were no conflicts of interest related to this project or its authors. We would like to thank Shirley Leong for consultation on the preparation of this manuscript. NR 12 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2014 VL 36 IS 6 BP 757 EP 759 DI 10.1016/j.genhosppsych.2014.08.001 PG 3 WC Psychiatry SC Psychiatry GA AU2GK UT WOS:000345434400038 PM 25219288 ER PT J AU Graham, LA Singletary, BA Richman, JS Maddox, TM Itani, KMF Hawn, MT AF Graham, Laura A. Singletary, Brandon A. Richman, Joshua S. Maddox, Thomas M. Itani, Kamal M. F. Hawn, Mary T. TI Improved Adverse Postoperative Outcomes With Revised American College of Cardiology/American Heart Association Guidelines for Patients With Cardiac Stents SO JAMA SURGERY LA English DT Article ID DRUG-ELUTING STENTS; NONCARDIAC SURGERY; CORONARY STENTS; ANTIPLATELET THERAPY; BARE-METAL; PERIOPERATIVE MANAGEMENT; LATE THROMBOSIS; RISK; IMPLANTATION; EVENTS AB IMPORTANCE In 2007, the American College of Cardiology/American Heart Association guidelines were revised for patients with cardiac stents in need of subsequent surgery to recommend delaying elective noncardiac surgery by 365 days in patients with drug-eluting stents (DESs). OBJECTIVE To examine the effect of the guidelines on postoperative major adverse cardiac events (MACEs) in subsequent noncardiac surgery. DESIGN, SETTING, AND PARTICIPANTS Patients receiving a cardiac stent between fiscal years 2005 and 2010 were identified by International Classification of Diseases, Ninth Revision diagnosis codes in the Veterans Affairs Medical SAS data sets. The Veterans Affairs Surgical Quality Improvement Program data were used to identify subsequent operations in the 2 years following stenting. The preguideline period was defined as fiscal years 2005 through 2007 and the postguideline period was defined as fiscal years 2008 through 2010. Surgery patients admitted through the emergency department or transferred from another hospital were excluded from analyses. Overall, 16 634 elective noncardiac operations were identified (8034 [48.3%] in the preguideline period; 8600 [51.7%] in the postguideline period). MAIN OUTCOMES AND MEASURES Composite 30-day postoperative MACEs. We used chi(2) tests to examine differences in bivariate frequencies and used logistic models to examine adjusted associations with 2-year postoperative MACEs. RESULTS The median time to surgery was 364 days (interquartile range, 184-528 days). A total of 11 026 operations (66.3%) followed DES placement, and 5608 (33.7%) followed bare metal stent placement. After the guidelines' publication, surgery timing increased following DES placement from 323 to 404 days (P < .001) and decreased following bare metal stent placement from 402 to 309 days (P < .001). In addition, postoperative MACE rates decreased from 4.2% to 3.3%(P = .002). After adjusting for cardiac risk factors and procedure characteristics, there was an overall absolute risk reduction of 0.9% for MACEs (odds ratio = 0.74; 95% CI, 0.62-0.89). On further examination of trends across time, MACE rates with DES placement began to decrease prior to the guidelines' publication from 5.5% in 2005 to 4.3% in 2006 and remained stable through 2010. In contrast, MACE rates with bare metal stent placement increased from 4.3% in 2005 to 8.0% in 2007 but decreased to 4.8% following the guidelines' publication. CONCLUSIONS AND RELEVANCE After the guidelines' publication, noncardiac surgery was delayed in patients with DESs but not bare metal stents. With a 26% reduction in MACEs following the guidelines, it would appear that the guidelines did improve postoperative outcomes; however, when examined over time, it becomes evident that there are many more factors influencing management of patients with cardiac stents in need of subsequent surgery. C1 [Graham, Laura A.; Singletary, Brandon A.; Richman, Joshua S.; Hawn, Mary T.] Birmingham Vet Affairs Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USA. [Graham, Laura A.; Singletary, Brandon A.; Richman, Joshua S.; Hawn, Mary T.] Univ Alabama Birmingham, Sect Gastrointestinal Surg, Dept Surg, Birmingham, AL 35294 USA. [Maddox, Thomas M.] Vet Affairs Eastern Colorado Hlth Care Syst, Denver, CO USA. [Maddox, Thomas M.] Univ Colorado, Sch Med, Denver, CO USA. [Itani, Kamal M. F.] Boston Univ, Dept Surg, Vet Affairs Boston Healthcare Syst, Boston, MA 02215 USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. RP Hawn, MT (reprint author), Univ Alabama Birmingham, Sect Gastrointestinal Surg, Dept Surg, 1922 Seventh Ave S,KB 428, Birmingham, AL 35294 USA. EM mhawn@uab.edu FU VA Health Services Research and Development [IIR 09-347]; VA Health Services Research and Development FX This study is funded by grant IIR 09-347 from VA Health Services Research and Development. Drs Richman and Maddox are supported by career development awards from VA Health Services Research and Development. NR 23 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD NOV PY 2014 VL 149 IS 11 BP 1113 EP 1120 DI 10.1001/jamasurg.2014.2044 PG 8 WC Surgery SC Surgery GA AU2JI UT WOS:000345443800005 PM 25188466 ER PT J AU Ernst, KF Hall, DE Schmid, KK Seever, G Lavedan, P Lynch, TG Johanning, JM AF Ernst, Katherine F. Hall, Daniel E. Schmid, Kendra K. Seever, Georgia Lavedan, Pierre Lynch, Thomas G. Johanning, Jason Michael TI Surgical Palliative Care Consultations Over Time in Relationship to Systemwide Frailty Screening SO JAMA SURGERY LA English DT Article ID UNIT; SERVICES; OUTCOMES; PROJECT; TRAUMA AB IMPORTANCE The need for integrating palliative care into surgical services has been established within the surgical literature. The ability to effectively screen, obtain an appropriately timed consultation, and determine the effect of consultation remains problematic. OBJECTIVE To examine surgical palliative care consultations over time and their relationship to the initiation and implementation of a systemwide frailty-screening program. DESIGN, SETTING, AND PARTICIPANTS We reviewed all surgical palliative care consultations performed between January 1, 2006, and August 31, 2013, and abstracted the referring service (medicine/surgery), date of surgery (if any), date of death (if any), and all variables required to calculate a frailty score using the risk analysis index. We examined changes in mortality and referral patterns before and after implementation of the frailty-screening program using multivariable logistic regression. EXPOSURES Surgical palliative care consultations, including frailty screening. MAIN OUTCOMES AND MEASURES The primary study outcomes were 30-, 180-, and 360-day mortality. RESULTS From 2006 to 2013, a total of 310 palliative care consultations were ordered for surgical patients: 160 before initiation of frailty screening (January 1, 2011) and 150 after initiation of the program. The groups had similar demographics, comorbidities, and frailty scores. After initiation, we observed dramatically decreased mortality at 30, 180, and 360 days (21.3% vs 31.9%, 44.0% vs 70.6%, and 66.0% vs 78.8%, respectively; all P < .05). This coincided with an increased rate of palliative care consultations from 32 per year to 56 per year. After initiation of the program, consultations were more likely to be requested by surgeons (56.7% vs 24.4%; P < .05) and were more likely to occur before the index operation (52.0% vs 26.3%; P < .05). Implementation of the screening program was associated with a 33% reduction in 180-day mortality (odds ratio [OR], 0.37; 95% CI, 0.22-0.62; P < .001) even after controlling for age, frailty, and whether the patients had surgery. Modeled mortality was also reduced when the palliative care consultation was ordered by a surgeon (OR, 0.50; CI, 0.30-0.83; P = .007) or ordered before the operation (OR, 0.52; CI, 0.30-0.90; P = .02). CONCLUSIONS AND RELEVANCE Our data suggest that a systematic frailty-screening program effectively identifies at-risk surgical patients and is associated with a significant reduction in mortality for patients undergoing palliative care consultation. Analysis also suggests that preoperative palliative care consultations ordered by surgeons are associated with reduced mortality rates. C1 [Ernst, Katherine F.] Univ Nebraska Med Ctr, Coll Med, Omaha, NE 68105 USA. [Hall, Daniel E.] Univ Pittsburgh, Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Schmid, Kendra K.] Univ Nebraska Med Ctr, Dept Biostat, Coll Publ Hlth Masters Programs, Omaha, NE 68105 USA. [Seever, Georgia; Lavedan, Pierre; Johanning, Jason Michael] Nebraska Western Iowa Vet Affairs Med Ctr, Dept Surg, Omaha, NE USA. [Lynch, Thomas G.] Vet Hlth Adm, Washington, DC USA. [Johanning, Jason Michael] Univ Nebraska Med Ctr, Dept Surg, Omaha, NE 68105 USA. RP Johanning, JM (reprint author), Univ Nebraska Med Ctr, 4101 Woolworth Ave, Omaha, NE 68105 USA. EM jason.johanning@va.gov OI Hall, Daniel/0000-0001-6382-0522 FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and Health Services Research and Development [CDA 08-281] FX This research was supported in part by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and Health Services Research and Development (CDA 08-281). NR 16 TC 13 Z9 13 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD NOV PY 2014 VL 149 IS 11 BP 1121 EP 1126 DI 10.1001/jamasurg.2014.1393 PG 6 WC Surgery SC Surgery GA AU2JI UT WOS:000345443800006 PM 25207603 ER PT J AU Jacobs, MA Weinstein, S Hope, TA Aslam, R Yee, J Coakley, F AF Jacobs, Melissa A. Weinstein, Stefanie Hope, Thomas A. Aslam, Rizwan Yee, Judy Coakley, Fergus TI Neuroendocrine Tumors: Beyond the Abdomen SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Review DE lesion descriptors; breast carcinoma; BIRADS classification; scoring system; magnetic resonance imaging; specificity ID MERKEL CELL-CARCINOMA; MEDULLARY-THYROID CARCINOMA; RADIOLOGIC-PATHOLOGICAL CORRELATION; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; POSITRON-EMISSION-TOMOGRAPHY; LYMPH-NODE BIOPSY; OF-THE-LITERATURE; F-18-FDG PET-CT; PROGNOSTIC-FACTORS; OLFACTORY NEUROBLASTOMA AB Several classification systems for neuroendocrine tumors (NETs) exist, which use variable terminology and criteria for grading and staging. This variability in terminology can cause confusion and difficulty in recognizing which tumors are, in fact, members of this heterogeneous group of malignancies. The largest group of NETs, the gastroenteropancreatic NETs, has been well described and characterized; however, there are less-recognized extra-abdominal NETs that can arise from nearly any organ in the body. In this article, the clinical features and imaging appearances of the extra-abdominal NETs will be reviewed, compared, and contrasted. This diverse group consists of paragangliomas, Merkel cell carcinomas, esthesioneuroblastomas, NETs of the lung, and medullary thyroid carcinomas. Recognition of these tumors as part of the larger group of NETs is important for understanding how best to approach imaging for their diagnosis, staging, and potential treatment. Familiarity with the computed tomographic and magnetic resonance imaging appearances and the role of radionuclide imaging of these heterogeneous groups aids in the correct diagnosis and in treatment planning. C1 [Jacobs, Melissa A.; Coakley, Fergus] Oregon Hlth & Sci Univ, Dept Radiol, Pittsburgh, PA USA. [Weinstein, Stefanie; Hope, Thomas A.; Aslam, Rizwan; Yee, Judy] UCSF Med Ctr, Dept Radiol, San Francisco, CA 94121 USA. [Weinstein, Stefanie; Hope, Thomas A.; Aslam, Rizwan; Yee, Judy] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Weinstein, S (reprint author), UCSF Med Ctr, Dept Radiol, 4150 Clement St, San Francisco, CA 94121 USA. EM Stefanie.Weinstein@ucsf.edu NR 111 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 EI 1532-3145 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD NOV-DEC PY 2014 VL 38 IS 6 BP 898 EP 914 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AU2EW UT WOS:000345430200015 PM 25162290 ER PT J AU Hershenberg, R Davila, J Leong, SH AF Hershenberg, Rachel Davila, Joanne Leong, Shirley H. TI DEPRESSIVE SYMPTOMS IN WOMEN AND THE PREFERENCE AND EMOTIONAL BENEFITS OF DISCUSSING POSITIVE LIFE EVENTS SO JOURNAL OF SOCIAL AND CLINICAL PSYCHOLOGY LA English DT Article ID SELF-VERIFICATION STRIVINGS; THINGS GO RIGHT; INTERPERSONAL BENEFITS; NEGATIVE FEEDBACK; SEX-DIFFERENCES; GOOD-NEWS; RESPONSES; RUMINATION; GIRLS; MOOD AB Discussing positive life events with other people-a process referred to as capitalization-generally enhances positive emotions and well-being. We examined current symptoms of depression as an individual difference factor likely to be associated with the preference and emotional benefits of capitalization in a sample of women with a range of depressive symptoms. Specifically, when given a choice to capitalize on a positive life event or discuss a negative life event, we hypothesized that women with greater symptoms of depression would be more likely to choose to discuss a negative event. Next, regardless of preference, all participants completed a capitalization interaction with a highly supportive confederate. We tested competing hypotheses regarding the emotional consequences of capitalization, as greater depressive symptoms could interfere with the emotional benefit or, alternatively, could be associated with enhanced emotional benefits. As predicted, findings suggested that depressive symptoms were associated with a greater preference to discuss a negative rather than positive event. Notably, when examining change in emotion following capitalization, findings supported the benefit hypothesis. Together, findings suggested that women with greater depressive symptoms were less inclined to capitalize but, when prompted to do so, experienced greater improvements in current levels of positive and negative emotion. Clinical implications and ideas for continued systematic study of depression and this positive emotion regulation strategy are discussed. C1 [Hershenberg, Rachel; Leong, Shirley H.] Philadelphia VA Med Ctr, MIRECC, Philadelphia, PA 19104 USA. [Hershenberg, Rachel] Univ Penn, Philadelphia, PA 19104 USA. [Davila, Joanne] SUNY Stony Brook, Stony Brook, NY USA. RP Hershenberg, R (reprint author), Philadelphia VA Med Ctr, VISN MIRECC 4, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM rhersh@mail.med.upenn.edu NR 51 TC 1 Z9 1 U1 2 U2 9 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 370 SEVENTH AVE, SUITE 1200, NEW YORK, NY 10001-1020 USA SN 0736-7236 J9 J SOC CLIN PSYCHOL JI J. Soc. Clin. Psychol. PD NOV PY 2014 VL 33 IS 9 BP 767 EP 788 PG 22 WC Psychology, Clinical; Psychology, Social SC Psychology GA AU3BC UT WOS:000345486900001 ER PT J AU Spira, AP Stone, KL Rebok, GW Punjabi, NM Redline, S Ancoli-Israel, S Yaffe, K AF Spira, Adam P. Stone, Katie L. Rebok, George W. Punjabi, Naresh M. Redline, Susan Ancoli-Israel, Sonia Yaffe, Kristine TI Sleep-Disordered Breathing and Functional Decline in Older Women SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE sleep; apnea; function; IADLs; older women ID MILD COGNITIVE IMPAIRMENT; DAYTIME SLEEPINESS; STROKE; ADULTS; APNEA; HEALTH; DISTURBANCES; EPIDEMIOLOGY; DEMENTIA; OUTCOMES AB ObjectivesTo determine the association between sleep-disordered breathing (SDB) and decline in instrumental activities of daily living (IADLs) and mobility in older women. DesignProspective cohort. SettingMinneapolis and Pittsburgh sites of the Study of Osteoporotic Fractures, participants' homes. ParticipantsWomen with a mean agestandard deviation of 82.33.2 (N=302). MeasurementsParticipants completed a single night of unattended polysomnography and provided data regarding difficulty with IADLs and mobility. They repeated IADL and mobility measures 5.0 +/- 0.7years later. ResultsAfter adjustment for age, obesity, Mini-Mental State Examination score, depressive symptoms, history of hypertension and chronic obstructive pulmonary disease, and number of IADL impairments at baseline, women with an apnea-hypopnea index (AHI) of 15 or greater at baseline had more than twice the odds of an increase in number of IADL difficulties (adjusted odds ratio (aOR)=2.22, 95% confidence interval (CI)=1.09-4.53) and of incident IADL difficulty (aOR=2.43, 95% CI=1.00-5.92), of women with an AHI less than 5. There was no association between AHI and mobility difficulty. Women in the middle and highest tertiles of oxygen desaturation index had more than double the odds as those in the lowest tertile of an increase in number of IADL difficulties (middle tertile aOR=2.64, 95% CI=1.38-5.04, highest tertile aOR=2.17, 95% CI=1.13-4.17) and approximately three times the odds of incident IADL difficulty (middle tertile aOR=2.84, 95% CI=1.27-6.36, highest tertile aOR=3.07, 95% CI=1.31-7.18). Neither sleep fragmentation nor sleep duration was associated with IADL outcomes. ConclusionSDB and associated hypoxemia are risk factors for functional decline in older women. Research is needed to determine whether treatment of SDB prevents functional decline. C1 [Spira, Adam P.; Rebok, George W.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Stone, Katie L.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Punjabi, Naresh M.] Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Punjabi, Naresh M.] Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA. [Redline, Susan] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Redline, Susan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 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. San Francisco VA Med Ctr, San Francisco, CA USA. RP Spira, AP (reprint author), 624 N Broadway,Hampton House,Rm 794, Baltimore, MD 21205 USA. EM aspira@jhu.edu FU Mentored Research Scientist Development Award from the NIA [1K01AG033195]; NIH; NIA; NIH [2R01-HL075078]; ResMed; NIH National Heart, Lung, and Blood Institute; California Pacific Medical Center; ResMed Foundation; National Institute of Mental Health; National Institute of Diabetes and Digestive and Kidney Diseases; Department of Defense; Department of Veterans Affairs; Alzheimer's Association; National Institutes of Health (NIH) [AG026720, AG05394, AG05407, AR35582, AR35583, AR35584, R01 AG005407, R01 AG027576-22, 2 R01 AG005394-22A1, 2 R01 AG027574-22A1, HL40489, K24AG031155] FX Dr. Adam Spira is supported by Mentored Research Scientist Development Award 1K01AG033195 from the NIA. Dr. Katie Stone reports that NIH funding has been obtained for this work. Dr. George Rebok is supported by grants from the NIA. Dr. Naresh Punjabi is supported by NIH grant 2R01-HL075078 and has received grant support from ResMed for a multicenter clinical trial on the effects of positive airway pressure therapy for sleep apnea in individuals with type 2 diabetes mellitus. Dr. Susan 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 in this study. She also has received a research grant from the ResMed Foundation to support ancillary data collection for a NIH-funded clinical trial. She is a member of the board of directors for the American Academy of Sleep Medicine. Dr. Redline 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. Ancoli-Israel is supported by grants from NIH and is a consultant for Ferring Pharmaceuticals, Inc., Merck, NeuroVigil, Inc., and Purdue Pharma LP. Dr. 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, Alzheimer's Association, and an anonymous donor. She has served on data safety monitoring boards for Pfizer and Medivation and has 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.; Supported by National Institutes of Health (NIH) Grants AG026720, AG05394, AG05407, AR35582, AR35583, AR35584, R01 AG005407, R01 AG027576-22, 2 R01 AG005394-22A1, 2 R01 AG027574-22A1, HL40489, K24AG031155. The content is solely the responsibility of the authors and does not necessarily represent the official views of National Institute on Aging (NIA) or NIH. NR 23 TC 2 Z9 2 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2014 VL 62 IS 11 BP 2040 EP 2046 DI 10.1111/jgs.13108 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AU3GO UT WOS:000345500700002 PM 25376169 ER PT J AU Sowa, GA Perera, S Bechara, B Agarwal, V Boardman, J Huang, W Camacho-Soto, A Vo, N Kang, J Weiner, D AF Sowa, Gwendolyn A. Perera, Subashan Bechara, Bernard Agarwal, Vikas Boardman, John Huang, Wan Camacho-Soto, Alejandra Vo, Nam Kang, James Weiner, Debra TI Associations Between Serum Biomarkers and Pain and Pain-Related Function in Older Adults with Low Back Pain: A Pilot Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE low back pain; biomarkers; imaging ID HUMAN INTERVERTEBRAL DISC; KNEE OSTEOARTHRITIS; PHYSICAL FUNCTION; LUMBAR DISC; MATRIX METALLOPROTEINASES; ASYMPTOMATIC VOLUNTEERS; RHEUMATOID-ARTHRITIS; INFLAMMATORY MARKERS; MOLECULAR MARKERS; URINE BIOMARKERS AB ObjectivesTo examine the relationship between serum biomarkers and self-reported pain intensity and pain-related function, in addition to the contribution of magnetic resonance imaging (MRI) findings of lumbar spine degenerative changes, in older adults with chronic low back pain. DesignSingle-center cross-sectional cohort study. SettingAcademic medical center. ParticipantsIndividuals aged 60 and older with axial low back pain without radiculopathy or previously diagnosed osteoarthritis of the knee or hip or pain outside the low back that is more severe than the back pain (n=43). MeasurementsTo examine pain-related impairment, pain was measured on a pain thermometer and the McGill Pain Questionnaire Short Form was administered. To examine pain-related function or activity limitation, the Roland Morris Disability Questionnaire, Short Physical Performance Battery (SPPB), and repetitive trunk rotation were used. Single plasma samples were obtained before and after physical performance tests and analyzed for inflammatory markers (E-selectin and regulated on activation, normal T cell expressed and secreted (RANTES)), inhibitors of catabolic enzymes (tissue inhibitor of metalloproteinases-1 (TIMP-1)), markers of matrix turnover (C- telopeptide of type II collagen (CTX-II) and aggrecan chondroitin sulfate 846 (CS846)), and stress biomarkers (neuropeptide Y (NPY)). Conventional nongadolinium lumbar MRI was performed and analyzed quantitatively and clinically. ResultsComposite MRI measurements did not show significant correlation with pain or pain-related function. Basal levels and changes in serum biomarkers in response to activity, particularly NPY and RANTES, demonstrated associations with pain and pain-related function in addition to the explanatory power of MRI-based results. ConclusionSerum biomarkers may be a metric for assessment of active disease in older adults, in whom imaging changes are ubiquitous. In addition, changing levels of biomarkers in response to activity suggests that they may be useful as metrics to measure treatment responses in future studies and may reflect potential targets for use in designing personalized treatment for older adults with low back pain. C1 [Sowa, Gwendolyn A.; Huang, Wan; Camacho-Soto, Alejandra] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA. [Sowa, Gwendolyn A.; Bechara, Bernard; Huang, Wan; Camacho-Soto, Alejandra; Vo, Nam; Kang, James] Univ Pittsburgh, Dept Orthopaed, Ferguson Lab Orthopaed Res, Pittsburgh, PA 15213 USA. [Perera, Subashan; Weiner, Debra] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA. [Agarwal, Vikas; Boardman, John] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15213 USA. [Weiner, Debra] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. [Weiner, Debra] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA 15213 USA. [Weiner, Debra] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA 15213 USA. [Weiner, Debra] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Sowa, GA (reprint author), Univ Pittsburgh, Dept Phys Med & Rehabil, 3471 5th Ave,Suite 201, Pittsburgh, PA 15213 USA. EM sowaga@upmc.edu FU Dennis W. Jahnigen Career Development Scholars Award; American Geriatrics Society; Pittsburgh Claude D. Pepper Older Americans Independence Center [AG024827] FX Funded by the Dennis W. Jahnigen Career Development Scholars Award, the American Geriatrics Society, and the Pittsburgh Claude D. Pepper Older Americans Independence Center (AG024827). NR 50 TC 10 Z9 11 U1 4 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2014 VL 62 IS 11 BP 2047 EP 2055 DI 10.1111/jgs.13102 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AU3GO UT WOS:000345500700003 PM 25367206 ER PT J AU Brown, RT Pierluissi, E Guzman, D Kessell, ER Goldman, LE Sarkar, U Schneidermann, M Critchfield, JM Kushel, MB AF Brown, Rebecca T. Pierluissi, Edgar Guzman, David Kessell, Eric R. Goldman, L. Elizabeth Sarkar, Urmimala Schneidermann, Michelle Critchfield, Jeffrey M. Kushel, Margot B. TI Functional Disability in Late-Middle-Aged and Older Adults Admitted to a Safety-Net Hospital SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE disability; physical function; middle-aged; aged ID UNITED-STATES; INSTRUMENTAL ACTIVITIES; SOCIOECONOMIC-STATUS; HEALTH; VALIDITY; OUTCOMES; DECLINE; POPULATION; INDEX; RELIABILITY AB ObjectivesTo determine the prevalence of preadmission functional disability in late-middle-aged and older safety-net inpatients and to identify characteristics associated with functional disability by age. DesignCross-sectional analysis. SettingSafety-net hospital in San Francisco, California. ParticipantsEnglish-, Spanish-, and Chinese-speaking community-dwelling individuals aged 55 and older admitted to a safety-net hospital with anticipated return to the community (N=699). MeasurementsAt hospital admission, participants reported their need for help performing five activities of daily living (ADLs) and seven instrumental activities of daily living (IADLs) 2weeks before admission. ADL disability was defined as needing help performing one or more ADLs and IADL disability as needing help performing two or more IADLs. Participant characteristics were assessed, including sociodemographic characteristics, health status, health-related behaviors, and health-seeking behaviors. ResultsOverall, 28.3% of participants reported that they had an ADL disability 2weeks before admission, and 40.4% reported an IADL disability. The prevalence of preadmission ADL disability was 28.9% of those aged 55 to 59, 20.7% of those aged 60 to 69, and 41.2% of those aged 70 and older (P<.001). The prevalence of IADL disability had a similar distribution. The characteristics associated with functional disability differed according to age; in participants aged 55 to 59, African Americans had a higher odds of ADL and IADL disability, whereas in participants aged 60 to 69 and aged 70 and older, inadequate health literacy was associated with functional disability. ConclusionPreadmission functional disability is common in individuals aged 55 and older admitted to a safety-net hospital. Late-middle-aged individuals admitted to safety-net hospitals may benefit from models of acute care currently used for older adults that prevent adverse outcomes associated with functional disability. C1 [Brown, Rebecca T.; Pierluissi, Edgar] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Brown, Rebecca T.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Pierluissi, Edgar; Kessell, Eric R.; Schneidermann, Michelle; Critchfield, Jeffrey M.] Univ Calif San Francisco, Div Hosp Med, San Francisco, CA 94143 USA. [Guzman, David; Goldman, L. Elizabeth; Sarkar, Urmimala; Kushel, Margot B.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. San Francisco Gen Hosp & Trauma Ctr, San Francisco, CA USA. RP Brown, RT (reprint author), San Francisco VA Med Ctr, 181G,4150 Clement St, San Francisco, CA 94121 USA. EM rebecca.brown@ucsf.edu FU Gordon and Betty Moore Foundation; National Center for Advancing Translational Sciences, National Institutes of Health (NIH) through the University of California at San Francisco Clinical and Translational Sciences Institute [KL2TR000143]; National Institute on Aging (NIA), NIH [K23 AG045290]; National NIA, NIH [T32 AG000212, P30AG044281] FX This work was funded in part by the Gordon and Betty Moore Foundation (Mr. Guzman and Drs. Kessell, Goldman, Sarkar, Schneidermann, Critchfield, and Kushel); Grant KL2TR000143 from the National Center for Advancing Translational Sciences, National Institutes of Health (NIH) through the University of California at San Francisco Clinical and Translational Sciences Institute (Dr. Brown); Grant K23 AG045290 from the National Institute on Aging (NIA), NIH; and Grants T32 AG000212 (Dr. Brown) and P30AG044281 (Dr. Brown) from the National NIA, NIH. These funding sources had no role in the preparation, review, or approval of the manuscript. The opinions expressed in this manuscript may not represent those of the Department of Veterans Affairs. NR 50 TC 1 Z9 1 U1 1 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 NOV PY 2014 VL 62 IS 11 BP 2056 EP 2063 DI 10.1111/jgs.13103 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AU3GO UT WOS:000345500700004 PM 25367281 ER PT J AU Tschirhart, EC Du, QL Kelley, AS AF Tschirhart, Evan C. Du, Qingling Kelley, Amy S. TI Factors Influencing the Use of Intensive Procedures at the End of Life SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE end-of-life decisions; terminal care; intensive care; Medicare ID ADVANCE DIRECTIVES; MEDICARE EXPENDITURES; SUSTAINING TREATMENTS; REGIONAL-VARIATIONS; CANCER-PATIENTS; LAST YEAR; CARE; ILLNESS; DETERMINANTS; PREFERENCES AB ObjectivesTo examine individual and regional factors associated with the use of intensive medical procedures in the last 6months of life. DesignRetrospective cohort study. SettingThe Health and Retirement Study (HRS), a longitudinal nationally representative cohort of older adults. ParticipantsHRS decedents aged 66 and older (N=3,069). MeasurementsMultivariable logistic regression was used to evaluate associations between individual and regional factors and receipt of five intensive procedures: intubation and mechanical ventilation, tracheostomy, gastrostomy tube insertion, enteral and parenteral nutrition, or cardiopulmonary resuscitation in the last 6months of life. ResultsApproximately 18% of subjects (n=546) underwent at least one intensive procedure in the last 6months of life. Characteristics significantly associated with lower odds of an intensive procedure included aged 85-94 (vs 65-74, adjusted odds ratio (AOR)=0.67, 95% confidence interval (CI)=0.51-0.90), Alzheimer's disease (AOR=0.71, 95% CI=0.54-0.94), cancer (AOR=0.60, 95% CI=0.43-0.85), nursing home residence (AOR=0.70, 95% CI=0.50-0.97), and having an advance directive (AOR=0.71, 95% CI=0.57-0.89). In contrast, living in a region with higher hospital care intensity (AOR=2.16, 95% CI=1.48-3.13) and black race (AOR=2.02, 95% CI=1.52-2.69) each doubled one's odds of undergoing an intensive procedure. ConclusionIndividual characteristics and regional practice patterns are important determinants of intensive procedure use in the last 6months of life. The effect of nonclinical factors highlights the need to better align treatments with individual preferences. C1 [Tschirhart, Evan C.; Du, Qingling; Kelley, Amy S.] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Kelley, Amy S.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. RP Tschirhart, EC (reprint author), 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM evan.tschirhart@mssm.edu FU Medical Student Training in Aging Research Program, American Federation for Aging Research and National Institute on Aging [1K23AG040774-01A1] FX This work was supported by the Medical Student Training in Aging Research Program, American Federation for Aging Research and National Institute on Aging (1K23AG040774-01A1). NR 37 TC 8 Z9 9 U1 3 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2014 VL 62 IS 11 BP 2088 EP 2094 DI 10.1111/jgs.13104 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AU3GO UT WOS:000345500700008 PM 25376084 ER PT J AU Ramaswamy, R Williams, A Clark, EM Kelley, AS AF Ramaswamy, Ravishankar Williams, Alicia Clark, Elizabeth M. Kelley, Amy S. TI Communication Skills Curriculum for Foreign Medical Graduates in an Internal Medicine Residency Program SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE communication skills; foreign medical graduates; internal medicine residency ID FELLOWS AB Effective communication is an important aspect of caring for the elderly, who are more likely to have multimorbidity, limited health literacy, and psychosocial barriers to care. About half of Internal Medicine (IM) trainees in the United States are foreign medical graduates, and may not have been exposed to prior communication skills education. This novel communication skills curriculum for IM interns aimed to increase trainees' confidence and use of specific communication tools with older adults, particularly in delivering bad news and conducting family meetings. The workshop consisted of two interactive sessions in a small group with two learners and one or two facilitators, during the 4-week geriatrics block in IM internship training year. Twenty-three IM interns at an urban Veterans Affairs Medical Center were surveyed at the beginning and at the end of the 4-week block and 3months after completion of the workshop about their knowledge, confidence, and skill in communication and asked about challenges to effective communication with older adults. The primary outcome measure was change in self-reported confidence and behavior in communication at 4weeks. On a 4-point Likert scale, there was average improvement of 0.70 in self-reported confidence in communication, which was sustained 3months after completion of the workshop. Participants reported several patient, physician, and system barriers to effective communication. Communication skills education in a small-group setting and the opportunity for repeated practice and self-reflection resulted in a sustained increase in overall confidence in IM interns in communication with older adults and may help overcome certain patient- and physician-specific communication barriers. C1 [Ramaswamy, Ravishankar; Kelley, Amy S.] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Williams, Alicia] Columbia Univ, Bassett Med Ctr, Cooperstown, NY USA. [Clark, Elizabeth M.] Montefiore Med Ctr, Dept Med, Div Geriatr, Bronx, NY 10467 USA. [Kelley, Amy S.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ Ctr, Bronx, NY USA. [Kelley, Amy S.] James J Peters Vet Affairs Med Ctr, Ctr Clin, Bronx, NY USA. RP Ramaswamy, R (reprint author), Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, One Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM ravishankar.ramaswamy@mssm.edu FU Hartford Centers of Excellence career development award; American Federation for Aging Research; National Institute on Aging [1K23AG0407 74-01A1] FX Dr. Ramaswamy is supported by the Hartford Centers of Excellence career development award. Dr. Kelley is supported by the American Federation for Aging Research and National Institute on Aging (1K23AG0407 74-01A1). NR 19 TC 2 Z9 2 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2014 VL 62 IS 11 BP 2153 EP 2158 DI 10.1111/jgs.13094 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AU3GO UT WOS:000345500700018 PM 25354834 ER PT J AU Brown, RT Ahalt, C Steinman, MA Kruger, K Williams, BA AF Brown, Rebecca T. Ahalt, Cyrus Steinman, Michael A. Kruger, Kelly Williams, Brie A. TI Police on the Front Line of Community Geriatric Health Care: Challenges and Opportunities SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE geriatrics; police; public health policy ID NURSING-HOME PLACEMENT; OLDER-ADULTS; CRIME VICTIMIZATION; RESIDENTS; KNOWLEDGE; POPULATION; VALIDATION; ATTITUDES; VICTIMS; SERVICE AB As the population ages, police increasingly serve as first responders to incidents involving older adults in which aging-related health plays a critical role. The goals of this study were to assess police officers' knowledge of aging-related health, to identify challenges police experience in their encounters with older adults, and to describe their recommendations for how to address those challenges. This was a mixed-methods study of 141 San Francisco police officers recruited from mandatory police trainings between 2011 and 2013. Descriptive statistics were used to analyze 141 self-administered questionnaires, and principles of grounded theory were used to analyze open-ended questionnaire responses and 11 additional qualitative interviews. Eighty-nine percent of officers reported interacting with older adults at least monthly. Although 84% of police reported prior training in working with older adults, only 32% rated themselves as knowledgeable about aging-related health. Participants described themselves as first responders to medical and social emergencies involving older adults and identified several challenges, including identifying and responding to aging-related conditions and ensuring appropriate medical and social service handoffs. To address these challenges, officers recommended developing trainings focused on recognizing and responding to aging-related conditions and improving police knowledge of community resources for older adults. They also called for enhanced communication and collaboration between police and clinicians. These findings suggest that, because they assume a front-line role in responding to older adults with complex medical and social needs, many police may benefit from additional knowledge about aging-related health and community resources. Collaboration between police and healthcare providers presents an important opportunity to develop geriatrics training and interprofessional systems of care to support police work with a rapidly aging population. C1 [Brown, Rebecca T.; Ahalt, Cyrus; Steinman, Michael A.; Williams, Brie A.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Brown, Rebecca T.; Steinman, Michael A.; Williams, Brie A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Kruger, Kelly] San Francisco Police Dept, San Francisco, CA USA. RP Brown, RT (reprint author), San Francisco VA Med Ctr, 181G,4150 Clement St, San Francisco, CA 94121 USA. EM rebecca.brown@ucsf.edu FU National Institute on Aging (NIA), National Institutes of Health (NIH) [T32 AG000212]; National Center for Advancing Translational Sciences, NIH, through the University of California at San Francisco (UCSF) Clinical and Translational Sciences Institute [KL2TR000143]; NIA, NIH [P30AG044281, 1K23 AG030999]; John A. Hartford Foundation; Jacob & Valeria Langeloth Foundation; UCSF Program for the Aging Century; UCSF University Community Partnership Grant from NIA, NIH [K23 AG033102]; American Federation for Aging Research FX This work was supported by Grant T32 AG000212 from the National Institute on Aging (NIA), National Institutes of Health (NIH) (Dr. Brown), Grant KL2TR000143 from the National Center for Advancing Translational Sciences, NIH, through the University of California at San Francisco (UCSF) Clinical and Translational Sciences Institute (Dr. Brown), Grant P30AG044281 from the NIA, NIH (Drs. Brown, Steinman, and Williams), the John A. Hartford Foundation (Drs. Brown and Williams), the Jacob & Valeria Langeloth Foundation (Dr. Williams and Mr. Ahalt), the UCSF Program for the Aging Century (Drs. Brown and Williams and Mr. Ahalt), the UCSF University Community Partnership Grant, Grant K23 AG033102 from NIA, NIH (Dr. Williams), and Grant 1K23 AG030999 from NIA, NIH and the American Federation for Aging Research (Dr. Steinman). The opinions expressed in this manuscript may not represent those of the Department of Veterans Affairs. NR 31 TC 0 Z9 0 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2014 VL 62 IS 11 BP 2191 EP 2198 DI 10.1111/jgs.13093 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AU3GO UT WOS:000345500700024 PM 25378267 ER PT J AU Marina, A von Frankenberg, AD Suvag, S Callahan, HS Kratz, M Richards, TL Utzschneider, KM AF Marina, Anna von Frankenberg, Anize Delfino Suvag, Seda Callahan, Holly S. Kratz, Mario Richards, Todd L. Utzschneider, Kristina M. TI Effects of Dietary Fat and Saturated Fat Content on Liver Fat and Markers of Oxidative Stress in Overweight/Obese Men and Women under Weight-Stable Conditions SO NUTRIENTS LA English DT Article DE non-alcoholic fatty liver; dietary fat; saturated fat; oxidative stress ID NONALCOHOLIC STEATOHEPATITIS; INSULIN SENSITIVITY; EXERCISE INTERVENTION; LIPID-PEROXIDATION; DISEASE; RESISTANCE; SEVERITY; TRIAL AB Dietary fat and oxidative stress are hypothesized to contribute to non-alcoholic fatty liver disease and progression to steatohepatitis. To determine the effects of dietary fat content on hepatic triglyceride, body fat distribution and markers of inflammation and oxidative stress, overweight/obese subjects with normal glucose tolerance consumed a control diet (CONT: 35% fat/12% saturated fat/47% carbohydrate) for ten days, followed by four weeks on a low fat (LFD (n = 10): 20% fat/8% saturated fat/62% carbohydrate) or high fat diet (HFD (n = 10): 55% fat/25% saturated fat/27% carbohydrate). Hepatic triglyceride content was quantified by MRS and abdominal fat distribution by MRI. Fasting biomarkers of inflammation (plasma hsCRP, IL-6, IL-12, TNF alpha, IFN-gamma) and oxidative stress (urinary F2-alpha isoprostanes) were measured. Body weight remained stable. Compared to the CONT, hepatic triglyceride decreased on the LFD (mean (95% CI): change -2.13% (-3.74%, -0.52%)), but did not change on the HFD and there was no significant difference between the LFD and HFD. Intra-abdominal fat did not change significantly on either diet, but subcutaneous abdominal fat increased on the HFD. There were no significant changes in fasting metabolic markers, inflammatory markers and urinary F2-a isoprostanes. We conclude that in otherwise healthy overweight/obese adults under weight-neutral conditions, a diet low in fat and saturated fat has modest effects to decrease liver fat and may be beneficial. On the other hand, a diet very high in fat and saturated fat had no effect on hepatic triglyceride or markers of metabolism, inflammation and oxidative stress. C1 [Marina, Anna; von Frankenberg, Anize Delfino; Suvag, Seda; Kratz, Mario; Utzschneider, Kristina M.] Univ Washington, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA 98195 USA. [Callahan, Holly S.] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Kratz, Mario] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Kratz, Mario] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Richards, Todd L.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Utzschneider, Kristina M.] VA Puget Sound Hlth Care Syst, Endocrinol, Seattle, WA 98108 USA. RP Utzschneider, KM (reprint author), Univ Washington, Div Metab Endocrinol & Nutr, Dept Med, 1959 NE Pacific St, Seattle, WA 98195 USA. EM annam45@hotmail.com; anize.frankenberg@gmail.com; sedasuv@yahoo.com; hcal@uw.edu; mkratz@fhcrc.org; toddr@u.washington.edu; kutzschn@u.washington.edu FU Department of Veteran Affairs; Diabetes Research Center [P30DK017047]; Institute for Translational Health Sciences [UL1TR000423]; Nutrition Obesity Research Center [P30 DK035816]; Diagnostic Imaging Sciences Center at the University of Washington; Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES) FX We are grateful to the study participants for their contribution and time. This study was supported by funding and resources from the Department of Veteran Affairs, the Diabetes Research Center (P30DK017047), the Institute for Translational Health Sciences (UL1TR000423), the Nutrition Obesity Research Center (P30 DK035816), the Diagnostic Imaging Sciences Center at the University of Washington, and the Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES). NR 30 TC 8 Z9 8 U1 2 U2 9 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6643 J9 NUTRIENTS JI Nutrients PD NOV PY 2014 VL 6 IS 11 BP 4678 EP 4690 DI 10.3390/nu6114678 PG 13 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AU3RM UT WOS:000345531300004 PM 25353663 ER PT J AU Morasco, BJ O'Hearn, D Turk, DC Dobscha, SK AF Morasco, Benjamin J. O'Hearn, Daniel Turk, Dennis C. Dobscha, Steven K. TI Associations Between Prescription Opioid Use and Sleep Impairment among Veterans with Chronic Pain SO PAIN MEDICINE LA English DT Article DE Opioids; Sleep; Chronic Pain; Pittsburgh Sleep Quality Index ID CHRONIC NONCANCER PAIN; QUALITY-OF-LIFE; HEPATITIS-C; BACK-PAIN; THERAPY; DISORDERS; INSOMNIA; APNEA; COMORBIDITY; MEDICATIONS AB ObjectiveChronic pain is associated with impairments in sleep; however, the relationship between prescription opioid status and sleep is unclear. The primary aim of this study was to examine differences in self-reported sleep quality between groups of patients who varied based on chronic pain and prescription opioid status. DesignThis is a cross-sectional study with retrospective review of patient medical records. SettingThe study was performed in a single VA medical center located in the Pacific Northwest. SubjectsParticipants with chronic pain and a current prescription for opioid medications (N=72), chronic pain and no opioid prescription (N=104), or who did not report current chronic pain or opioid prescription (N=91) were included. MethodsAll participants completed self-report questionnaires assessing demographic characteristics, sleep parameters, pain-related variables, and psychiatric symptoms. Data on prescription opioid use were extracted from patients' medical records. ResultsIn unadjusted analyses, patients with chronic pain who were prescribed opioids were more likely to have sleep apnea diagnoses in their medical record and reported more impairment on sleep global score and across four sleep parameter subscales (subjective sleep quality, sleep latency, sleep disturbance, and use of sleeping medications). In linear regression analyses controlling for demographic and clinical covariates, prescription opioid status was associated with sleep latency, and opioid dose was significantly associated with sleep latency and sleep global score. ConclusionsPrescription opioid status and dose were associated with impairment in self-reported sleep. For patients with chronic pain, consideration should be given to use of nonpharmacological interventions to improve sleep. C1 [Morasco, Benjamin J.; Dobscha, Steven K.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA. [Morasco, Benjamin J.; Dobscha, Steven K.] Portland VA Med Ctr, Ctr Improve Vet Involvement Care, Portland, OR USA. [Morasco, Benjamin J.; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [O'Hearn, Daniel] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Turk, Dennis C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. RP Morasco, BJ (reprint author), Portland VA Med Ctr R&D99, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM benjamin.morasco@va.gov FU National Institute on Drug Abuse [DA023467, DA034083]; U.S. Food & Drug Administration [FD004508] FX This study was supported in part by awards from the National Institute on Drug Abuse (DA023467, DA034083) and from the U.S. Food & Drug Administration (FD004508). This material is also the result of work supported with resources and the use of facilities at the Portland VA Medical Center. NR 54 TC 3 Z9 3 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD NOV PY 2014 VL 15 IS 11 BP 1902 EP 1910 DI 10.1111/pme.12472 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AU4EI UT WOS:000345561700010 PM 24930962 ER PT J AU Hamza, TH Hill-Burns, EM Scott, WK Vance, JM Factor, SA Zabetian, CP Payami, H AF Hamza, Taye H. Hill-Burns, Erin M. Scott, William K. Vance, Jeffrey M. Factor, Stewart A. Zabetian, Cyrus P. Payami, Haydeh TI Glutamate Receptor Gene GRIN2A, Coffee, and Parkinson Disease SO PLOS GENETICS LA English DT Editorial Material ID CAFFEINE; RISK; SMOKING C1 [Hamza, Taye H.; Hill-Burns, Erin M.; Payami, Haydeh] New York State Dept Hlth, Wadsworth Ctr, Div Genet, Albany, NY 12205 USA. [Hamza, Taye H.] New England Res Inst Inc, Watertown, MA USA. [Scott, William K.; Vance, Jeffrey M.] Univ Miami, Miller Sch Med, Dr John T Macdonald Fdn Dept Human Genet, Miami, FL 33136 USA. [Scott, William K.; Vance, Jeffrey M.] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA. [Factor, Stewart A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Zabetian, Cyrus P.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Zabetian, Cyrus P.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Payami, Haydeh] SUNY Albany, Sch Publ Hlth, Dept Biomed Sci, Albany, NY USA. RP Hamza, TH (reprint author), New York State Dept Hlth, Wadsworth Ctr, Div Genet, Albany, NY 12205 USA. EM haydeh.payami@health.ny.gov OI Zabetian, Cyrus/0000-0002-7739-4306 FU NINDS NIH HHS [P50 NS071674, R01 NS036960, R01 NS067469] NR 11 TC 3 Z9 4 U1 1 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD NOV PY 2014 VL 10 IS 11 AR e1004774 DI 10.1371/journal.pgen.1004774 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA AU2NL UT WOS:000345455200025 PM 25411979 ER PT J AU Coutinho, ML Matsunaga, J Wang, LC Moctezuma, AD Lewis, MS Babbitt, JT Aleixo, JAG Haake, DA AF Coutinho, Mariana L. Matsunaga, James Wang, Long-Chieh de la Pena Moctezuma, Alejandro Lewis, Michael S. Babbitt, Jane T. Aleixo, Jose Antonio G. Haake, David A. TI Kinetics of Leptospira interrogans Infection in Hamsters after Intradermal and Subcutaneous Challenge SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID CELL MONOLAYERS; ICTEROHAEMORRHAGIAE; MODEL; DISSEMINATION; VIRULENCE; ETIOLOGY; DISEASE; CATTLE; WATER; HOST AB Background: Leptospirosis is a zoonosis caused by highly motile, helically shaped bacteria that penetrate the skin and mucous membranes through lesions or abrasions, and rapidly disseminate throughout the body. Although the intraperitoneal route of infection is widely used to experimentally inoculate hamsters, this challenge route does not represent a natural route of infection. Methodology/Principal Findings: Here we describe the kinetics of disease and infection in hamster model of leptospirosis after subcutaneous and intradermal inoculation of Leptospira interrogans serovar Copenhageni, strain Fiocruz L1-130. Histopathologic changes in and around the kidney, including glomerular and tubular damage and interstitial inflammatory changes, began on day 5, and preceded deterioration in renal function as measured by serum creatinine. Weight loss, hemoconcentration, increased absolute neutrophil counts (ANC) in the blood and hepatic dysfunction were first noted on day 6. Vascular endothelial growth factor, a serum marker of sepsis severity, became elevated during the later stages of infection. The burden of infection, as measured by quantitative PCR, was highest in the kidney and peaked on day 5 after intradermal challenge and on day 6 after subcutaneous challenge. Compared to subcutaneous challenge, intradermal challenge resulted in a lower burden of infection in both the kidney and liver on day 6, lower ANC and less weight loss on day 7. Conclusions/Significance: The intradermal and subcutaneous challenge routes result in significant differences in the kinetics of dissemination and disease after challenge with L. interrogans serovar Copenhageni strain Fiocruz L1-130 at an experimental dose of 2610 6 leptospires. These results provide new information regarding infection kinetics in the hamster model of leptospirosis. C1 [Coutinho, Mariana L.; Matsunaga, James; Wang, Long-Chieh; Lewis, Michael S.; Babbitt, Jane T.; Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Coutinho, Mariana L.; Aleixo, Jose Antonio G.] Univ Fed Pelotas, Ctr Desenvolvimento Tecnol, Pelotas, Brazil. [Coutinho, Mariana L.] Univ Fed Rio Grande do Sul, Fac Vet, Porto Alegre, RS, Brazil. [Matsunaga, James; Babbitt, Jane T.; Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [de la Pena Moctezuma, Alejandro] Univ Nacl Autonoma Mexico, Fac Med Vet & Zootecnia, CEIEPAA, Tequisquiapan, Queretaro, Mexico. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, Dept Microbiol, Los Angeles, CA 90024 USA. [Haake, David A.] Univ Calif Los Angeles, Dept Immunol, Los Angeles, CA USA. [Haake, David A.] Univ Calif Los Angeles, Dept Mol Genet, Los Angeles, CA USA. RP Coutinho, ML (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. EM dhaake@ucla.edu FU VA Medical Research Funds (United States Office of Veterans Affairs) [1I01BX002003, 5I01BX000119]; National Institute of Allergy and Infectious Diseases [R01 AI034431]; Brazilian Conselho Nacional de Pesquisa [201549/2008-5]; Direccion General de Asuntos del Personal Academico, UNAM FX This study was supported by VA Medical Research Funds (United States Office of Veterans Affairs Project Numbers 1I01BX002003 to DAH and 5I01BX000119 to JM; http://www.research.va.gov/), the National Institute of Allergy and Infectious Diseases (Grant #R01 AI034431 to DAH; http://www.niaid.nih.gov/), the Brazilian Conselho Nacional de Pesquisa (process number 201549/2008-5), the Direccion General de Asuntos del Personal Academico, UNAM (to AdlPM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 9 Z9 9 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD NOV PY 2014 VL 8 IS 11 AR e3307 DI 10.1371/journal.pntd.0003307 PG 9 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AU3LF UT WOS:000345514000036 PM 25411782 ER EF