Although antiretroviral therapy is highly effective in suppressing human immunodeficiency virus type-1 (HIV) replication, treatment has failed to eliminate viral reservoirs and discontinuation of treatment results in viral reactivation. Here, we demonstrate that peptides Tat-vFLIP-α2 and Tat-Beclin 1/BECN1 which have been shown to induce a Na/K-ATPase- and a macroautophagy/autophagy-dependent form of cell death, autosis, can preferentially kill HIV-infected macrophages while preventing virological rebound. To improve bioavailability and drug delivery, Tat-vFLIP-α2 was encapsulated into biodegradable PLGA (poly lactic-co-glycolic acid)-lipid-PEG (polyethylene glycol) nanoparticles for long-lasting intracellular delivery. After a single dose of NP-vFLIP-α2, HIV-infected macrophages were preferentially killed in a dose-dependent manner compared to uninfected or untreated HIV-infected cells with complete inhibition of HIV infection at 10 μM of peptide. HIV-infected macrophages treated with NP-vFLIP-α2 exhibited increased markers of autophagy including LC3B lipidation, SQSTM1/p62 degradation and Na/K-ATPase expression compared to untreated uninfected or infected cells. Moreover, the increased cell death observed in HIV-infected cells was not altered by treatment with bafilomycin A (BAF) or the caspase inhibitor Z-VAD-FMK, but could be reversed following treatment with the Na/K-ATPase inhibitor, digoxin, or knockdown of ATG5 or ATG7. NP-vFLIP-α2 induced preferential killing was also detected in HIV-infected macrophages under antiretroviral suppression without inducing viral reactivation. Additionally, we found that Na/K-ATPase was upregulated in HIV-infected cells, which enhanced NP-vFLIP-α2 induced cell death. These findings provide a novel strategy to eradicate HIV-infected macrophages by selectively killing infected cells through the induction of Na/K-ATPase dependent autophagy, while preventing reactivation of virus and new infection of uninfected bystander cells.

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Background: Throughout medical school students are exposed to a variety of fields within medicine, but structured leadership and teaching opportunities are limited. There is a need for more training to prepare students of all backgrounds to be future leaders in all healthcare realms, especially critical care medicine, in order to address the lack of diversity seen in leadership positions. Methods: Implemented entirely by students with faculty guidance, the Kern model was applied to develop a student-run longitudinal Designated Emphasis in Healthcare Leadership. This program was implemented at a medical school leading the nation in creating opportunities for diverse and underrepresented groups in medicine. Students are involved in structured leadership lectures, projects, and mentorship, and there is an emphasis on learning by doing. A survey was sent out to all present and past student participants to assess its acceptability and effectiveness. Results: A post-participation survey found that a total of 96% of participants identified themselves as healthcare leaders, felt confident leading a team, and felt comfortable working with a diverse team. Further, 96% of participants agreed or strongly agreed they would recommend the program to other medical students. Qualitative feedback revealed that participants felt they learned how to “apply leadership skills to the healthcare setting” and were provided an “environment to grow and practice vital leadership skills that will help [them] be effective clinicians.” Conclusions: Our initial research shows that introducing a longitudinal leadership program into Medical Education may allow participants to start developing personal and professional leadership qualities. The program is well-received by the students and preliminary data shows that there may be increase in leadership capabilities when participating in this program. Such a program can enable future healthcare providers to become leaders in their own fields, so that they can hone interpersonal communication skills, bridge the gap of representation in leadership positions, and lead teams effectively.

Objective: To evaluate an expedited “Brain Emergency Management Initiative (BEMI)” transfer process within a telestroke network with the goal of decreasing transfer delays and time to stroke embolectomy intervention. Methods: We conducted an exploratory, retrospective assessment of consecutive acute telestroke patients transferred for potential intervention to compare outcomes in pre-BEMI vs. BEMI periods. Baseline characteristics included age, sex, ethnicity, stroke risk factors, and NIHSS. Times included Spoke In, Spoke Out, Hub In, and groin puncture. Outcomes included discharge destination home, and Symptomatic Intracranial Hemorrhage (SxICH). Results: Overall, 68 transfers were assessed. There were no differences for age, sex, diabetes, hypertension, or atrial fibrillation. There was a higher NIHSS in BEMI (11 pre-BEMI vs. 20 BEMI;p=0.01). There was a shorter spoke door in to door out (143 vs 118 minutes; p=0.01) and spoke door out to hub door in (23min pre-BEMI vs. 21min BEMI;p=0.001). For embolectomy patients, there was a shorter hub door in to reperfusion (83min Pre-BEMI vs. 74min BEMI;p=.04), and rt-PA decision to groin puncture (155min Pre-BEMI vs.130min BEMI;p=.01). There were no sxICH or discharge home differences. Though NIHSS was correlated with home discharge destination (r=-0.26;p=0.04), Hispanic ethnicity (r=0.33;p=0.01), hub door in to reperfusion (r=0.11;p=0.04) and spoke out to reperfusion (r=0.28;p=0.04), no relationship was strong. Conclusions: In our Hub-EMS-Spoke telestroke network, BEMI led to improved evaluation times. Rapid transfer protocols are critical for improving outcomes. BEMI can serve as a model for future rapid stroke transfer pathways. Further work assessing generalizability and outcomes is underway.