Leishmania infantum Amastigotes Enhance HIV-1 Production in Cocultures of Human Dendritic Cells and CD4+ T Cells by Inducing Secretion of IL-6 and TNF-α

Visceral leishmaniasis (VL) is a potentially deadly parasitic disease afflicting millions worldwide. Although itself an important infectious illness, VL has also emerged as an opportunistic disease among patients infected with HIV-1. This is partly due to the increasing overlap between urban regions of high HIV-1 transmission and areas where Leishmania is endemic. Furthermore, VL increases the development and clinical progression of AIDS-related diseases. Conversely, HIV-1-infected individuals are at greater risk of developing VL or suffering relapse. Finally, HIV-1 and Leishmania can both productively infect cells of the macrophage-dendritic cell lineage, resulting in a cumulative deficiency of the immune response. We therefore studied the effect of Leishmania infantum on HIV-1 production when dendritic cells (DCs) are cocultured with autologous CD4+ T cells. We show that amastigotes promote virus replication in both DCs and lymphocytes, due to a parasite-mediated production of soluble factors by DCs. Micro-beads array analyses indicate that Leishmania infantum amastigotes infection induces a higher secretion of several cytokines in these cells, and use of specific neutralizing antibodies revealed that the Leishmania-induced increase in HIV-1 replication is due to IL-6 and TNF-α. These findings suggest that Leishmania's presence within DC/T-cell conjugates leads to an enhanced HIV-1 production

Effect of the 2011 vs 2003 duty hour regulation-compliant models on sleep duration, trainee education, and continuity of patient care among internal medicine house staff: a randomized trial

On July 1, 2011, the Accreditation Council for Graduate Medical Education implemented further restrictions of its 2003 regulations on duty hours and supervision. It remains unclear if the 2003 regulations improved trainee well-being or patient safety. To determine the effects of the 2011 Accreditation Council for Graduate Medical Education duty hour regulations compared with the 2003 regulations concerning sleep duration, trainee education, continuity of patient care, and perceived quality of care among internal medicine trainees. Crossover study design in an academic research setting. Medical house staff. General medical teams were randomly assigned using a sealed-envelope draw to an experimental model or a control model. We randomly assigned 4 medical house staff teams (43 interns) using a 3-month crossover design to a 2003-compliant model of every fourth night overnight call (control) with 30-hour duty limits or to one of two 2011-compliant models of every fifth night overnight call (Q5) or a night float schedule (NF), both with 16-hour duty limits. We measured sleep duration using actigraphy and used admission volumes, educational opportunities, the number of handoffs, and satisfaction surveys to assess trainee education, continuity of patient care, and perceived quality of care. RESULTS The study included 560 control, 420 Q5, and 140 NF days that interns worked and 834 hospital admissions. Compared with controls, interns on NF slept longer during the on call period (mean, 5.1 vs 8.3 hours; P = .003), and interns on Q5 slept longer during the postcall period (mean, 7.5 vs 10.2 hours; P = .05). However, both the Q5 and NF models increased handoffs, decreased availability for teaching conferences, and reduced intern presence during daytime work hours. Residents and nurses in both experimental models perceived reduced quality of care, so much so with NF that it was terminated early. Compared with a 2003-compliant model, two 2011 duty hour regulation-compliant models were associated with increased sleep duration during the on-call period and with deteriorations in educational opportunities, continuity of patient care, and perceived quality of care