e Preexposure prophylaxis (PrEP) with 1% tenofovir (TFV) vaginal gel has failed in clinical trials. To improve TFV efficacy in vaginal gel, we formulated tenofovir disoproxil fumarate nanoparticles in a thermosensitive (TMS) gel (TDF-NP-TMS gel). TDF-NPs were fabricated using poly(lactic-co-glycolic acid) (PLGA) polymer and an ion-pairing agent by oil-in-water emulsification. The efficacy of TDF-NP-TMS gel was tested in humanized bone marrow-liver-thymus (hu-BLT) mice. Hu-BLT mice in the treatment group (Rx; n ؍ 15) were administered TDF-NP-TMS gel intravaginally, having TDF at 0.1%, 0.5%, and 1% (wt/vol) concentrations, whereas the control (Ctr; n ؍ 8) group received a blank TMS gel. All Rx mice ( Presently, a total of 36.9 million people worldwide are living with HIV-1 (1). Topical preexposure prophylaxis (PrEP) currently is a promising preventative strategy (2). The basic idea is to protect the vagina (and/or rectum) from HIV-1 infection by applying gel containing antiretroviral drug(s) around the time of sexual intercourse. This topical preparation is considered a microbicide, inhibiting infection by blocking viral transmission at the mucosal surface. To date, tenofovir (TFV) is the only drug administered locally as a 1% vaginal gel shown to be effective at preventing heterosexual contraction of HIV-1 (3). TFV tissue concentrations indicate a direct relationship between levels of TFV in genitals and protection (4-7). The minimum amount of TFV in cervicovaginal fluid levels when associated with gel that shows protection against HIV-1 infection has been reported to be Ͼ1,000 ng/ml (4). This level is greater than 10 times that seen in patients receiving oral TDF and emtricitabine (4). In female macaques given 1% TFV gel, the intracellular half-life for the active metabolite, tenofovir diphosphate, is significantly shorter (averaging 25 h) in vaginal lymphocytes than peripheral PBMCs (averaging 49 h) (7). A coitally independent strategy using 1% TFV gel has not shown efficacy in several clinical trials (8,9). Based on the dramatic negative results of the Vaginal and Oral Interventions to Control the Epidemic (VOICE) trial, it is important to consider female attitudes and opinions for a vaginal gel-based prevention delivery system. A safe and effective female-controlled, discrete gel-based delivery system has the potential to prevent millions of HIV-1 infections worldwide annually.When designing female-controlled preventative delivery systems, the gel-based system should have features important for the female user. Namely, the delivery system should be (i) easy to administer; (ii) adherent to the mucosal surface once applied vaginally; (iii) low seepage; and (iv) free of side effects or cytotoxicity to the mucosal surfaces of the female genital tract (10). All of these factors, if not optimized, could diminish gel effectiveness or lead to gel aversion. Finally, a long-acting preparation would be highly desirable if it offered long-term protection from HIV-1 (11).Our laboratory has been developing a nanotechn...
The multisystem inflammatory syndrome in adults (MIS-A) came to attention back in June 2020, when the United States Center for Disease Control and Prevention (CDC) got initial reports regarding the patients who had delayed and multisystem involvement of the disease with clinical course resembling the multisystem inflammatory syndrome in children (MIS-C). We share a case of MIS-A, where the patient presented three weeks after the initial COVID19 exposure. His clinical course was consistent with the working definition of MIS-A as specified by CDC. Aggressive supportive care in the intensive care unit, utilization of advanced heart failure devices, and immunomodulatory therapeutics (high dose steroids, anakinra, intravenous immunoglobulin) led to clinical recovery. Management of MIS-A is a topic of ongoing research and needs more studies to elaborate on the treatment modalities and clinical predictors.
The results of our meta-analysis suggest that early surgical intervention is associated with significantly lower risk of mortality in patients with infective endocarditis.
The motivational face-to-face communication technique was particularly useful in conveying ASP team member recommendations to the primary medical or surgical teams. Communicating recommendations as a multidisciplinary team in an educational manner seems to have resulted in to greater acceptance of recommendations.
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