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Rosas S.E.,Philadelphia Veterans Administration Medical Center | Reese P.P.,University of Pennsylvania | Huan Y.,Thomas Jefferson University | Doria C.,Thomas Jefferson University | And 2 more authors.
American Journal of Nephrology | Year: 2012

Background: Low physical activity (PA) has been associated with higher rates of cardiovascular disease (CVD) and mortality in the general population. Despite the benefits of kidney transplantation, kidney transplant recipients (KTRs) remain at elevated risk for CVD and mortality compared to individuals without kidney disease. Methods: A prospective cohort of 507 adult KTRs from three academic centers completed the Physical Activity Scale for the Elderly (PASE) at transplantation. PASE scores were divided into tertiles. Results: PA was lower with older age, history of CVD, smoking, and diabetes. During the median 8-year follow-up period, 128 individuals died, among whom 101 had a functioning allograft. In multivariable Cox regression for all-cause mortality, greater PA was strongly associated with better survival (HR: 0.52 for most active vs. inactive tertiles, 95% CI: 0.31-0.87, p = 0.01). Secondary analyses, in which (1) death with a functioning graft was the primary outcome, and (2) PASE scores were converted to the metabolic equivalent of task, revealed similar results. We did not find an association between change of PA after transplantation and mortality. Conclusions: PA at the time of kidney transplantation is a strong predictor of all-cause mortality and death with graft function. Evaluation of PA level among kidney transplant candidates may be a useful method to risk-stratify patients for survival after kidney transplantation. Kidney transplant candidates and recipients should also be encouraged to be physically active. Copyright © 2011 S. Karger AG, Basel.


Shen J.C.,University of Pennsylvania | Chen B.,University of Pennsylvania | Cohen N.A.,University of Pennsylvania | Cohen N.A.,Philadelphia Veterans Administration Medical Center
International Forum of Allergy and Rhinology | Year: 2012

Background: Chronic rhinosinusitis is a multifactorial disease characterized by a local inflammatory response and impaired mucociliary clearance. Our prior work suggests that nonpolypoid inflammation can blunt ciliary dynamics. Thus, we set out to determine whether exogenously applied recombinant keratinocyte chemoattractant (KC), mouse homologue of interleukin-8 (IL-8), modulates ciliary function. Methods: Murine primary sinonasal cultures were established in an air-liquid interface. Exogenous KC was administered to apical and basal surfaces at 500 pg/mL (n = 6) or 5 ng/mL (n = 3). Basal and stimulated cilia beat frequency (CBF) was recorded at 6, 12, 24, and 48 hours after exposure. Control groups were treated with buffered saline solution (n = 6). Cilia were mechanically stimulated with bursts of pressurized air (55 mmHg). CBF after prolonged KC exposure (96 hours) was also measured. Results: KC-treated cultures had significantly increased basal CBF at 24 hours and 48 hours. KC (500 pg/mL) yielded a 41.6% ± 9.5 increase in basal CBF (p < 0.001) at 24 hours, which persisted at 48 hours, 35.8% ± 10.2 (p < 0.05), while high-concentration KC (5 ng/mL) yielded a 50.2% ± 6.6 (p < 0.01) increase in basal CBF at 24 hours, which declined to 15.2% ± 5.2 (p < 0.01) at 48 hours. After 48 hours, the KC group demonstrated decreased response to mechanical stimulus vs control (500 pg/mL: p < 0.01, 5 ng/mL: p ≤ 0.04). With prolonged KC exposure (500 pg/mL) CBF declined: -25.5% ± 6.9 (p < .001) at 72 hours, and -19.6% ± 5.4 (p < 0.01) at 96 hours. Conclusion: Our results demonstrate modulation of cilia function of murine sinonasal epithelial cells by the inflammatory cytokine KC, which acutely increases basal CBF while decreasing the response of cilia to mechanical stimulation. Prolonged KC exposure decreases basal CBF. © 2011 American Rhinologic Society-American Academy of Otolaryngic Allergy, LLC.


Adeseun G.A.,University of Pennsylvania | Rosas S.E.,University of Pennsylvania | Rosas S.E.,Philadelphia Veterans Administration Medical Center
Current Hypertension Reports | Year: 2010

Obstructive sleep apnea (OSA) is an important clinical problem in the chronic kidney disease (CKD) population. OSA is associated with hypoxemia and sleep fragmentation, which activates the sympathetic nervous system, the renin-angiotensin-aldosterone system, alters cardiovascular hemodynamics, and results in free radical generation. In turn, a variety of deleterious processes such as endothelial dysfunction, inflammation, platelet aggregation, atherosclerosis, and fibrosis are triggered, predisposing individuals to adverse cardiovascular events and likely renal damage. Independent of obesity, OSA is associated with glomerular hyperfiltration and may be an independent predictor of proteinuria, a risk factor for CKD progression. OSA is also associated with hypertension, another important risk factor for CKD progression, particularly proteinuric CKD. OSA may mediate renal damage via several mechanisms, and there is a need to better elucidate the impact of OSA on incident renal disease and CKD progression. © 2010 US Government.


Plebani J.G.,University of Pennsylvania | Oslin D.W.,University of Pennsylvania | Oslin D.W.,Philadelphia Veterans Administration Medical Center | Lynch K.G.,University of Pennsylvania
American Journal on Addictions | Year: 2011

Prior clinical findings have indicated a potential lack of naltrexone efficacy among African Americans with alcohol dependence. However, no definitive conclusions have been drawn due to the relatively small numbers of African Americans in most alcohol treatment trials. The purpose of this study was to examine alcohol and naltrexone effects on healthy African-American individuals in a laboratory environment. Nonalcohol-dependent social drinking adults of African descent (n = 43) were recruited for participation. After consenting and completing the baseline assessment, they participated in four separate alcohol challenge sessions each separated by at least 10 days. During each of the sessions, subjects were administered alcohol or sham drinks, after pretreatment with either naltrexone (50 mg/day) or placebo in a double-blind fashion. The order of the four sessions was randomly assigned. During each session, breath alcohol levels and subjective responses were measured. Results indicate an alcohol effect among these subjects for subjective responses, but no naltrexone effect. Similar to the apparent lack of clinical efficacy findings, naltrexone does not appear to impact alcohol effects in African-American social drinkers. Future studies should investigate African-American populations with heavy drinking as well as alcohol-dependent subjects in order to strengthen the parallels to clinical findings. © American Academy of Addiction Psychiatry.


Roalf D.R.,University of Pennsylvania | Gur R.E.,University of Pennsylvania | Ruparel K.,University of Pennsylvania | Calkins M.E.,University of Pennsylvania | And 6 more authors.
Neuropsychology | Year: 2014

Objective: The transition from childhood to adulthood is characterized by improved motor and cognitive performance in many domains. Developmental studies focus on average performance in single domains but ignore consistency of performance across domains. Within-individual variability (WIV) provides an index of that evenness and is a potential marker of development. Method: We gave a computerized battery of 14 neurocognitive tests to 9138 youths ages 8-21 from the Philadelphia Neurodevelopmental Cohort. Results: As expected, performance improved with age, with both accuracy and speed peaking in adulthood. WIV, however, showed a U-shaped course: highest in childhood, declining yearly into mid-adolescence, and increasing again into adulthood. Young females outperformed and were less variable than males, but by early adulthood male performance matched that of females despite being more variable. Conclusion: We conclude that WIV declines from childhood to adolescence as developmental lags are overcome, and then increases into adulthood reflecting the emergence of cognitive specializations related to skill-honing and brain maturation. © 2014 American Psychological Association.

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