Rapamycin limits CD4+ T cell proliferation in simian immunodeficiency virus–infected rhesus macaques on antiretroviral therapy

Proliferation of latently infected CD4⁺ T cells with replication-competent proviruses is an important mechanism contributing to HIV persistence during antiretroviral therapy (ART). One approach to targeting this latent cell expansion is to inhibit mTOR, a regulatory kinase involved with cell growth, metabolism, and proliferation. Here, we determined the effects of chronic mTOR inhibition with rapamycin with or without T cell activation in SIV-infected rhesus macaques (RMs) on ART. Rapamycin perturbed the expression of multiple genes and signaling pathways important for cellular proliferation and substantially decreased the frequency of proliferating CD4⁺ memory T cells (TM cells) in blood and tissues. However, levels of cell-associated SIV DNA and SIV RNA were not markedly different between rapamycin-treated RMs and controls during ART. T cell activation with an anti-CD3LALA antibody induced increases in SIV RNA in plasma of RMs on rapamycin, consistent with SIV production. However, upon ART cessation, both rapamycin and CD3LALA–treated and control-treated RMs rebounded in less than 12 days, with no difference in the time to viral rebound or post-ART viral load set points. These results indicate that, while rapamycin can decrease the proliferation of CD4⁺ TM cells, chronic mTOR inhibition alone or in combination with T cell activation was not sufficient to disrupt the stability of the SIV reservoir.     

Donation after cardiac death liver transplantation is associated with increased risk of end‐stage renal disease

Limited organ supply has led to greater use of liver allografts with higher donor risk indices (DRI) and/or donated after cardiac death (DCD). DCD status is associated with acute kidney injury after liver transplantation; however, less is known about the association between donor quality and end‐stage renal disease (ESRD). Using SRTR data, we assembled a cohort of liver transplant recipients from 2/2002 to 12/2010. We fit multivariable Cox regression models for ESRD. Model 1 included total DRI; model 2 included components of DRI, including DCD, as separate variables. Forty thousand four hundred and sixty‐three liver transplant recipients were included. Median DRI was 1.40 (IQR 1.14, 1.72); 1822 (5%) received DCD livers. During median follow‐up of 3.93 years, ESRD occurred in 2008 (5%) and death in 11 075 (27%) subjects. There was a stepwise increase in ESRD risk with higher DRI (DRI ≥1.14 and <1.40: HR 1.17, P = 0.06; DRI ≥1.40 and <1.72: HR 1.29, P = 0.003; DRI ≥1.72: HR 1.39, P < 0.001, compared with DRI <1.14). Adjusting for DRI components separately, DCD status was most strongly associated with ESRD (HR 1.40, P = 0.008). Higher DRI is associated with ESRD after liver transplantation, driven in part by DCD status. Donor quality is an important predictor of long‐term renal outcomes in liver transplant recipients.     

Can trained volunteers provide psychosocial support to patients undergoing radiotherapy? The perspective of patients and volunteers

PurposeClinic-based psychosocial interventions, including volunteer-based ones, may be a cost-efficient and acceptable means of integrating psychosocial support into cancer care during radiotherapy. The present study evaluated a new psychosocial volunteer support program in a large radiotherapy clinic.Methods and MaterialsPatients were asked to complete a demographic and satisfaction with care questionnaire. Clinic volunteers were asked to report their interactions with patients on shift logs.ResultsOf the 182 participating patients, 93 (51%) recalled meeting a volunteer in the clinic, with the 2 most common support types provided being the following: “listening and caring,” and “information on services.” Analysis of 224 volunteers' shift logs indicated that almost all interactions (94%) were initiated by the volunteers, and almost half (47%) involved the patients' companions in the clinic. The most common support type documented was “information and navigation” (71%), followed by “emotional” (47%), “diversional” (21%), and “physical/practical” (17%) support.ConclusionsTrained volunteers can effectively provide clinic-based psychosocial support and information to a high proportion of radiotherapy patients. These findings demonstrate that volunteer support is a feasible means of meeting the psychosocial needs of patients with cancer attending outpatient radiotherapy clinics, who may not require or want professional psychosocial support.     

Purposiveness and Leisure-Time Physical Activity in Women in Early Midlife

Physical activity in early midlife has important implications for women's health. The present cross-sectional study investigated the relation of purposiveness to leisure-time physical activity, as mediated by health investment, in a sample of women in early midlife. Participants were 211 women between the ages of 35 and 45 years (mean 40.55 years, SD = 3.11) who responded to the second wave of the study of Midlife Development in the United States. Participants were originally selected by means of a nationally representative random-digit-dialing procedure. A structural equation analysis of data with latent variables was conducted with MPLUS. Purposiveness was indexed by measures of purpose in life, personal growth, and future planning. Health investment was indexed by thought and effort committed to health and the extent to which individuals worked hard to stay healthy. Leisure-time physical activity was indexed by both moderate and vigorous leisure-time activity. Results, controlling for sociodemographic factors, showed that purposiveness was associated with more physical activity and that the relation between purposiveness and leisure-time physical activity was fully mediated by health investment. These results suggest that women with a sense of purpose may be better able to achieve acceptable levels of physical activity.