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Background Floreciendo is a sexual and reproductive health program for Latina teens (14–18 years) and their female caregivers adapted from the evidence-based IMARA intervention. We report on our experience theater testing Floreciendo during the preparation phase of the multiphase optimization strategy (MOST) framework. Floreciendo includes four two-hour sessions (i.e., intervention components). Our aims were to: (1) examine the preliminary acceptability, appropriateness, and feasibility of the intervention components, including the acceptability of the implementation plan (i.e., logistics, strategies), and (2) systematically report on curriculum modifications made based on findings. Methods Using a community-based participatory research approach, we theater tested the program at a community organization over one weekend with three teen-caregiver dyads ( n  = 6) using mixed methods. Immediately following the delivery of each intervention component, teens and caregivers completed surveys and engaged in feedback sessions. Observers ( n  = 8) and facilitators ( n  = 2) completed surveys, recorded activity start and end times, and participated in a post-program discussion. Survey item ratings were on four-point Likert scales, with higher scores indicating more favorable results. Feedback informed subsequent curriculum modifications, which were documented using the FRAME. Results We found high satisfaction with the intervention components among all surveyed ( n  = 16) and with the implementation plan among teens and caregivers ( n  = 6) (≥ 3.7/4.0). Teens and caregivers described sessions as “educational,” “motivating,” “interactive,” and “fun”; all (100%; n  = 6) reported that they would recommend the program to others. Teens and caregivers rated the appropriateness of the material and language/wording highly (4.0/4.0; n  = 6), although caregivers expressed difficulty understanding “passive communication” given translation difficulties. Feasibility was also rated highly across groups (≥ 3.8/4.0; n  = 16); 18% of activities were 10 + minutes longer than planned based on observer reports but the sessions overall remained within 2 min of the allotted time. We modified the intervention components based on the feedback received. For example, we moved discussions about sex to come later in the foundational session to increase participant comfort. Conclusions Findings offer preliminary evidence of Floreciendo’s acceptability, appropriateness, and feasibility. Theater testing is a valuable tool for intervention adaptation and FRAME is useful for tracking curriculum modifications over time. MOST researchers could consider theater testing while carrying out preparation-phase activities.

A novel coronavirus—severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—emerged in humans in Wuhan, China, in December 2019 and has since disseminated globally 1 , 2 . As of April 16, 2020, the confirmed case count of coronavirus disease 2019 (COVID-19) had surpassed 2 million. Based on full-genome sequence analysis, SARS-CoV-2 shows high homology to SARS-related coronaviruses identified in horseshoe bats 1 , 2 . Here we show the establishment and characterization of expandable intestinal organoids derived from horseshoe bats of the Rhinolophus sinicus species that can recapitulate bat intestinal epithelium. These bat enteroids are fully susceptible to SARS-CoV-2 infection and sustain robust viral replication. Development of gastrointestinal symptoms in some patients with COVID-19 and detection of viral RNA in fecal specimens suggest that SARS-CoV-2 might cause enteric, in addition to respiratory, infection 3 , 4 . Here we demonstrate active replication of SARS-CoV-2 in human intestinal organoids and isolation of infectious virus from the stool specimen of a patient with diarrheal COVID-19. Collectively, we established the first expandable organoid culture system of bat intestinal epithelium and present evidence that SARS-CoV-2 can infect bat intestinal cells. The robust SARS-CoV-2 replication in human intestinal organoids suggests that the human intestinal tract might be a transmission route of SARS-CoV-2. Bat and human intestinal organoids can support replication of SARS-CoV-2, enabling further characterization of the virus lifecycle and investigation of potential mechanisms of enteric infection in COVID-19.

This study aimed to determine the role of DHEA-S in coping against the exercise training mixing aerobic and resistance components. During 5-day successive exercise training, 16 young male participants (19.2 ± 1.2 years) received either a placebo (flour capsule) or DHEA (100 mg/day) in a double-blinded and placebo-controlled design. Oral DHEA supplementation significantly increased circulating DHEA-S by 2.5-fold, but a protracted drop (~35 %) was observed from Day 3 during training. In the Placebo group, only a minimal DHEA-S reduction (~17 %) was observed. Changes in testosterone followed a similar pattern as DHEA-S. Muscle soreness was elevated significantly on Day 2 for both groups to a similar extent. Lower muscle soreness was observed in the DHEA-supplemented group on Day 3 and Day 6. In the Placebo group, training increased circulating creatine kinase (CK) levels by approximately ninefold, while only a threefold increase was observed in the DHEA-supplemented group. This mix-type exercise training improved glucose tolerance in both groups, while lowering the insulin response to the glucose challenge, but no difference between treatments was observed. Our results suggest that DHEA-S may play a role in protecting skeletal muscle from exercise training-induced muscle damage.

A novel coronavirus--severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)--emerged in humans in Wuhan, China, in December 2019 and has since disseminated globally.sup.1,2. As of April 16, 2020, the confirmed case count of coronavirus disease 2019 (COVID-19) had surpassed 2 million. Based on full-genome sequence analysis, SARS-CoV-2 shows high homology to SARS-related coronaviruses identified in horseshoe bats.sup.1,2. Here we show the establishment and characterization of expandable intestinal organoids derived from horseshoe bats of the Rhinolophus sinicus species that can recapitulate bat intestinal epithelium. These bat enteroids are fully susceptible to SARS-CoV-2 infection and sustain robust viral replication. Development of gastrointestinal symptoms in some patients with COVID-19 and detection of viral RNA in fecal specimens suggest that SARS-CoV-2 might cause enteric, in addition to respiratory, infection.sup.3,4. Here we demonstrate active replication of SARS-CoV-2 in human intestinal organoids and isolation of infectious virus from the stool specimen of a patient with diarrheal COVID-19. Collectively, we established the first expandable organoid culture system of bat intestinal epithelium and present evidence that SARS-CoV-2 can infect bat intestinal cells. The robust SARS-CoV-2 replication in human intestinal organoids suggests that the human intestinal tract might be a transmission route of SARS-CoV-2. Bat and human intestinal organoids can support replication of SARS-CoV-2, enabling further characterization of the virus lifecycle and investigation of potential mechanisms of enteric infection in COVID-19.

Objectives: Overexpression and aberrant activation of Src promote the development of oral squamous cell carcinoma (OSCC), thus therapies targeting Src-related kinases may afford an improvement in patient survival. However, limited clinical activity of the Src-targeted drug, dasatinib, in cancer patients warrants further investigation to better understand the underlying basis of resistance to dasatinib in OSCC. Methods: Response to dasatinib was evaluated in a panel of oral cancer cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, DNA synthesis, cell cycle and apoptosis analysis. The underlying mechanism of drug response was investigated using immunoblotting. Xenograft models were used to test efficacy. Results: All cell lines were sensitive to dasatinib (IC50 < 250 nM), but this was not associated with CDKN2a/p14ARF mutations. Dasatinib-induced cell cycle arrest and apoptosis, while inhibiting Src, Akt and FAK activity in all lines tested. However, dasatinib failed to inhibit tumour growth in xenograft models and treated tissues showed Akt activity despite the loss of Src activity. Conclusions: Our data revealed that reactivation of Akt (Ser473) could be a compensatory mechanism that bypasses Src inhibition by dasatinib, providing important clues that could improve treatment strategies to overcome dasatinib resistance.