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Abstract Background Prior reports indicate that modulation of the endocannabinoid system (ECS) may have a protective benefit for Covid-19 patients. However, associations between cannabis use (CU) or CU not in remission (active cannabis use (ACU)), and Covid-19-related outcomes among hospitalized patients is unknown. Methods In this multicenter retrospective observational cohort analysis of adults (≥ 18 years-old) identified from 2020 National Inpatient Sample database, we utilize multivariable regression analyses and propensity score matching analysis (PSM) to analyze trends and outcomes among Covid-19-related hospitalizations with CU and without CU (N-CU) for primary outcome of interest: Covid-19-related mortality; and secondary outcomes: Covid-19-related hospitalization, mechanical ventilation (MV), and acute pulmonary embolism (PE) compared to all-cause admissions; for CU vs N-CU; and for ACU vs N-ACU. Results There were 1,698,560 Covid-19-related hospitalizations which were associated with higher mortality (13.44% vs 2.53%, p ≤ 0.001) and worse secondary outcomes generally. Among all-cause hospitalizations, 1.56% of CU and 6.29% of N-CU were hospitalized with Covid-19 (p ≤ 0.001). ACU was associated with lower odds of MV, PE, and death among the Covid-19 population. On PSM, ACU(N(unweighted) = 2,382) was associated with 83.97% lower odds of death compared to others(N(unweighted) = 282,085) (2.77% vs 3.95%, respectively; aOR:0.16, [0.10–0.25], p ≤ 0.001). Conclusions These findings suggest that the ECS may represent a viable target for modulation of Covid-19. Additional studies are needed to further explore these findings.

The United States witnessed a nearly 4‐fold increase in personal health care expenditures between 1980 and 2010. Despite innovations and obvious benefits to health, participants enrolled in clinical trials still do not accurately represent the racial and ethnic composition of patients nationally or globally. This lack of diversity in cohorts limits the generalizability and significance of results among all populations and has deep repercussions for patient equity. To advance diversity in clinical trials, robust evidence for the most effective strategies for recruitment of diverse participants is needed. A major limitation of previous literature on clinical trial diversity is the lack of control or comparator groups for different strategies. To date, interventions have focused primarily on (1) community‐based interventions, (2) institutional practices, and (3) digital health systems. This review article outlines prior intervention strategies across these 3 categories and considers health policy and ethical incentives for substantiation before US Food and Drug Administration approval. There are no current studies that comprehensively compare these interventions against one another. The American Heart Association Strategically Focused Research Network on the Science of Diversity in Clinical Trials represents a multicenter, collaborative network between Stanford School of Medicine and Morehouse School of Medicine created to understand the barriers to diversity in clinical trials by contemporaneous head‐to‐head interventional strategies accessing digital, institutional, and community‐based recruitment strategies to produce informed recruitment strategies targeted to improve underrepresented patient representation in clinical trials.

Understanding HIV-1 persistence despite antiretroviral therapy (ART) is of paramount importance. Both single-genome sequencing (SGS) and integration site analysis (ISA) provide useful information regarding the structure of persistent HIV DNA populations; however, until recently, there was no way to link integration sites to their cognate proviral sequences. Here, we used multiple-displacement amplification (MDA) of cellular DNA diluted to a proviral endpoint to obtain full-length proviral sequences and their corresponding sites of integration. We applied this method to lymph node and peripheral blood mononuclear cells from 5 ART-treated donors to determine whether groups of identical subgenomic sequences in the 2 compartments are the result of clonal expansion of infected cells or a viral genetic bottleneck. We found that identical proviral sequences can result from both cellular expansion and viral genetic bottlenecks occurring prior to ART initiation and following ART failure. We identified an expanded T cell clone carrying an intact provirus that matched a variant previously detected by viral outgrowth assays and expanded clones with wild-type and drug-resistant defective proviruses. We also found 2 clones from 1 donor that carried identical proviruses except for nonoverlapping deletions, from which we could infer the sequence of the intact parental virus. Thus, MDA-SGS can be used for "viral reconstruction" to better understand intrapatient HIV-1 evolution and to determine the clonality and structure of proviruses within expanded clones, including those with drug-resistant mutations. Importantly, we demonstrate that identical sequences observed by standard SGS are not always sufficient to establish proviral clonality.

BACKGROUND. HIV-1 viremia that is not suppressed by combination antiretroviral therapy (ART) is generally attributed to incomplete medication adherence and/or drug resistance. We evaluated individuals referred by clinicians for nonsuppressible viremia (plasma HIV-1 RNA above 40 copies/mL) despite reported adherence to ART and the absence of drug resistance to the current ART regimen. METHODS. Samples were collected from at least 2 time points from 8 donors who had nonsuppressible viremia for more than 6 months. Single templates of HIV-1 RNA obtained from plasma and viral outgrowth of cultured cells and from proviral DNA were amplified by PCR and sequenced for evidence of clones of cells that produced infectious viruses. Clones were confirmed by host-proviral integration site analysis. RESULTS. HIV-1 genomic RNA with identical sequences were identified in plasma samples from all 8 donors. The identical viral RNA sequences did not change over time and did not evolve resistance to the ART regimen. In 4 of the donors, viral RNA sequences obtained from plasma matched those sequences from viral outgrowth cultures, indicating that the viruses were replication competent. Integration sites for infectious proviruses from those 4 donors were mapped to the introns of the MATR3, ZNF268, ZNF721/ABCA11P, and ABCA11Pgenes. The sizes of the clones were estimated to be from 50 million to 350 million cells. CONCLUSION. These findings show that clones of HIV-1-infected cells producing virus can cause failure of ART to suppress viremia. The mechanisms involved in clonal expansion and persistence need to be defined to effectively target viremia and the HIV-1 reservoir. FUNDING. National Cancer Institute, NIH; Howard Hughes Medical Research Fellows Program, Howard Hughes Medical Institute; Bill and Melinda Gates Foundation; Office of AIDS Research; American Cancer Society; National Cancer Institute through a Leidos subcontract; National Institute for Allergy and Infectious Diseases, NIH, to the I4C Martin Delaney Collaboratory; University of Rochester Center for AIDS Research and University of Rochester HIV/ AIDS Clinical Trials Unit., Introduction In most individuals, combination antiretroviral therapy (ART) suppresses HIV-1 viremia, measured as plasma HIV-1 RNA, to below the limit of detection of commercial assays (20-40 copies/mL), and confers major [...]

This study examines the differences among students in terms of self-reported leadership characteristics. It was conducted among all three programs and four generations of undergraduates at RIT Croatia. The goal of this study is to determine the differences among students who report being more and less leadership prone (Potential Future Leaders and Followers, respectively) with regard to demographic characteristics, reported self-reliance socialization pattern, college level and program choice, career focus attainment and development, and reported attitudes regarding the importance of specific personality traits in leadership, the importance of specific career development factors and success indicators. Research showed that generation and college program are not related to student reported leadership proneness, suggesting that college education's impact on leadership traits is not significant. Only one socio-demographic factor considered was significantly different between clusters; namely, the respondents who had moved once were significantly more represented in the Potential Future Leaders cluster, suggesting that study-abroad programs might play a role in leadership development. In terms of ranking career development factors, success indicators, the importance of emotional stability and openness to experience as a specific leadership trait, Potential Future Leaders reported higher scores in comparison with Followers cluster, potentially resulting from their forward-looking, goal-oriented attitude. Keywords: Leadership characteristics, Student leadership profile, Student development, Career development, Personal success., 1. INTRODUCTION 1.1. Theoretical background The major challenge that inspired this study is how educators might facilitate student leadership development and how they might understand and improve student experiences in [...]

Flexible polyimide probes, used for neuronal signal acquisition, are thought to reduce signal deteriorating gliosis, improving the quality of recordings in brain machine interfacing applications. These probes suffer from the disadvantage that they cannot penetrate brain tissue on their own, owing to their limited stiffness and low buckling forces. A microfluidic device as an external micro-drive which aids in the insertion of flexible polyimide neural probes in 0.6% Agarose gel is presented here.

This study examines the differences among students in terms of self-reported leadership characteristics. It was conducted among all three programs and four generations of undergraduates at RIT Croatia. The goal of this study is to determine the differences among students who report being more and less leadership prone (Potential Future Leaders and Followers, respectively) with regard to demographic characteristics, reported self reliance socialization pattern, college level and program choice, career focus attainment and development, and reported attitudes regarding the importance of specific personality traits in leadership, the importance of specific career development factors and success indicators. Research showed that generation and college program are not related to student reported leadership proneness, suggesting that college education’s impact on leadership traits is not significant. Only one socio-demographic factor considered was significantly different between clusters; namely, the respondents who had moved once were significantly more represented in the Potential Future Leaders cluster, suggesting that study-abroad programs might play a role in leadership development. In terms of ranking career development factors, success indicators, the importance of emotional stability and openness to experience as a specific leadership trait, Potential Future Leaders reported higher scores in comparison with Followers cluster, potentially resulting from their forwardlooking, goal-oriented attitude.

Deep brain stimulation (DBS) is based on the effect of high frequency stimulation (HFS) in neuronal tissue. As a therapy option for patients suffering from e.g. Parkinson’s disease, DBS has been used for decades. Despite the widespread use, the effect of HFS on neurons is not fully investigated. Improving the stimulation efficiency und specificity could increase the efficiency of the INS (internal neuronal stimulator) as well as potentially reduce unwanted side effects. The effect of HFS on the GABAergic system was quantified using whole cell patch clamp electrophysiology during HFS stimulation in cortical human brain slices in vitro. Rectangular, sine, sawtooth and triangular waveforms were applied extracellularly. Since HFS has been hypothesized to increase the activity of the axons of GABAergic interneurons, a decrease in activity can be observed in the pyramidal cells that the interneurons project to. By isolating the incoming non- GABAergic events, we can filter out only the GABAA currents which can be verified using a GABAA antagonist. The results show that all the waveforms effectively increase the GABAA currents. The triangle waveform causes the highest significant increase in the activity which further increases over time after the stimulation was turned off.

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