The World Health Organization has issued an early release revision to its antiretroviral guidelines in which PrEP (Pre-exposure prophylaxis in the form of daily oral, fixed dose combination tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)) is recommended as a prevention option to all people at substantial risk of acquiring HIV. However, lack of effectiveness in two major women-only PrEP trials, VOICE and FEM PrEP, continue to be a cause for concern about achieving effectiveness for women in Southern Africa. We conducted a series of meta-analyses of oral TDF/FTC effectiveness in women including all five randomized placebo-controlled trials that included women. An adherence-based meta-analysis model showed that with high levels of adherence (75%), oral PrEP is estimated to be effective (RR=0.39, 95% CI 0.25 to 0.60). Provided that these results apply to women in Southern Africa, future prevention trial designs in that region should account for potentially reduced HIV incidence when PrEP is available.
Bi CEBPA mutations in patients with AML are strongly associated with a favorable prognosis, which suggested that bi CEBPA mutations would potentially serve as a novel prognostic marker in AML.
Emphysema is a T-cell mediated autoimmune disease caused predominantly by cigarette smoking. Th17 cells and related cytokines may contribute to this disorder. However, the possible implication of Th17 cells in regulating inflammatory response in emphysema remains to be elucidated. In the current study, we tested the protein levels of IL-17 and IL-21 in peripheral blood and lung tissues from cigarette-smoke- (CS-) exposed mice and air-exposed mice, analyzed the frequencies of CD4+IL-17+(Th17) cells, IL-21+Th17 cells, and CD8+IL-21R+ T cells in peripheral blood and lung tissues of mice, and their relationship with emphysematous lesions, and explored the impact of IL-21 on cytotoxic CD8+ T cells function in vitro. It was found that the frequencies of Th17, IL-21+Th17, and CD8+IL-21R+ T cells and the levels of IL-17 and IL-21 of CS-exposed mice were much higher than those of the air-exposed mice and correlated with emphysematous lesions. Additionally, the number of IL-21+Th17 cells positively correlated with the number of CD8+IL-21R+ T cells. The in vitro experiments showed that IL-21 significantly augmented the secretion of perforin and granzyme B in CD8+ T cells from CS-exposed mice. These data indirectly provide evidence that Th17 cells could be involved in the control of the local and system inflammatory response in emphysema by regulating CD8+ cytotoxic T-cell function.
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