BNip3 regulates mitochondrial function and lipid metabolism in the liver

BNip3 localizes to the outer mitochondrial membrane, where it functions in mitophagy and mitochondrial dynamics. While the BNip3 protein is constitutively expressed in adult liver from fed mice, we have shown that its expression is superinduced by fasting of mice, consistent with a role in responses to nutrient deprivation. Loss of BNip3 resulted in increased lipid synthesis in the liver that was associated with elevated ATP levels, reduced AMP-regulated kinase (AMPK) activity, and increased expression of lipogenic enzymes. Conversely, there was reduced β-oxidation of fatty acids in BNip3 null liver and also defective glucose output under fasting conditions. These metabolic defects in BNip3 null liver were linked to increased mitochondrial mass and increased hepatocellular respiration in the presence of glucose. However, despite elevated mitochondrial mass, an increased proportion of mitochondria exhibited loss of mitochondrial membrane potential, abnormal structure, and reduced oxygen consumption. Elevated reactive oxygen species, inflammation, and features of steatohepatitis were also observed in the livers of BNip3 null mice. These results identify a role for BNip3 in limiting mitochondrial mass and maintaining mitochondrial integrity in the liver that has consequences for lipid metabolism and disease

Structured inquiry-based learning: Drosophila GAL4 enhancer trap characterization in an undergraduate laboratory course.

We have developed and tested two linked but separable structured inquiry exercises using a set of Drosophila melanogaster GAL4 enhancer trap strains for an upper-level undergraduate laboratory methods course at Bucknell University. In the first, students learn to perform inverse PCR to identify the genomic location of the GAL4 insertion, using FlyBase to identify flanking sequences and the primary literature to synthesize current knowledge regarding the nearest gene. In the second, we cross each GAL4 strain to a UAS-CD8-GFP reporter strain, and students perform whole mount CNS dissection, immunohistochemistry, confocal imaging, and analysis of developmental expression patterns. We have found these exercises to be very effective in teaching the uses and limitations of PCR and antibody-based techniques as well as critical reading of the primary literature and scientific writing. Students appreciate the opportunity to apply what they learn by generating novel data of use to the wider research community

Trends in Moral Injury, Distress, and Resilience Factors among Healthcare Workers at the Beginning of the COVID-19 Pandemic

The coronavirus severe acute respiratory syndrome (COVID-19) pandemic has placed increased stress on healthcare workers (HCWs). While anxiety and post-traumatic stress have been evaluated in HCWs during previous pandemics, moral injury, a construct historically evaluated in military populations, has not. We hypothesized that the experience of moral injury and psychiatric distress among HCWs would increase over time during the pandemic and vary with resiliency factors. From a convenience sample, we performed an email-based, longitudinal survey of HCWs at a tertiary care hospital between March and July 2020. Surveys measured occupational and resilience factors and psychiatric distress and moral injury, assessed by the Impact of Events Scale-Revised and the Moral Injury Events Scale, respectively. Responses were assessed at baseline, 1-month, and 3-month time points. Moral injury remained stable over three months, while distress declined. A supportive workplace environment was related to lower moral injury whereas a stressful, less supportive environment was associated with increased moral injury. Distress was not affected by any baseline occupational or resiliency factors, though poor sleep at baseline predicted more distress. Overall, our data suggest that attention to improving workplace support and lowering workplace stress may protect HCWs from adverse emotional outcomes

A Novel Capacity-Strengthening Intervention for Frontline Harm Reduction Workers to Support Pre-exposure Prophylaxis Awareness-Building and Promotion Among People Who Use Drugs: Formative Research and Intervention Development

BackgroundHIV prevalence among people who use drugs (PWUD) in Baltimore, Maryland, is higher than among the general population. Pre-exposure prophylaxis (PrEP) is a widely available medication that prevents HIV transmission, yet its usefulness is low among PWUD in Baltimore City and the United States. Community-level interventions to promote PrEP uptake and adherence among PWUD are limited. ObjectiveWe describe the development of a capacity-strengthening intervention designed for frontline harm reduction workers (FHRWs) to support PrEP awareness-building and promotion among PWUD. MethodsOur study was implemented in 2 phases in Baltimore City, Maryland. The formative phase focused on a qualitative exploration of the PrEP implementation environment, as well as facilitators and barriers to PrEP willingness and uptake, among cisgender women who use drugs. This work, as well as the existing literature, theory, and feedback from our community partners, informed the intervention development phase, which used an academic-community partnership model. The intervention involved a 1-time, 2-hour training with FHRWs aimed at increasing general PrEP knowledge and developing self-efficacy promoting PrEP in practice (eg, facilitating PrEP dialogues with clients, supporting client advancement along a model of PrEP readiness, and referring clients to PrEP services). In a separate paper, we describe the conduct and results of a mixed methods evaluation to assess changes in PrEP-related knowledge, attitudes, self-efficacy, and promotion practices among FHRWs participating in the training. ResultsThe pilot was developed from October to December 2021 and implemented from December 2021 through April 2022. We leveraged existing relationships with community-based harm reduction organizations to recruit FHRWs into the intervention. A total of 39 FHRWs from 4 community-based organizations participated in the training across 4 sessions (1 in-person, 2 online synchronous, and 1 online asynchronous). FHRW training attendees represented a diverse range of work cadres, including peer workers, case managers, and organizational administrators. ConclusionsThis intervention could prevent the HIV burden among PWUD by leveraging the relationships that FHRWs have with PWUD and by supporting advancement along the PrEP continuum. Given suboptimal PrEP uptake among PWUD and the limited number of interventions designed to address this gap, our intervention offers an innovative approach to a burgeoning public health problem. If effective, our intervention has the potential to be further developed and scaled up to increase PrEP awareness and uptake among PWUD worldwide

Type of Exchange Sex and Associated Behaviors and Outcomes Among Cisgender Men and Women at Increased Risk for HIV via Heterosexual Transmission in Six U.S. Metropolitan Areas

Exchange sex is associated with sexual risk behaviors and poor outcomes and different types may incur different levels of risk. We assessed risk profiles of different types of exchange sex among non-injecting cisgender men and women who participated in the 2019 National HIV Behavioral Surveillance project at six sites. Six percent of men and 19% of women reported exchange sex in the past year; most engaged in non-commercial exchange sex for drugs/money with smaller percentages reporting formal sex work or non-commercial exchange sex for goods or services other than drugs/money. Exchange sex was associated with sexual risk and prevention behaviors and psychosocial and sexual health outcomes and associations varied by type of exchange sex. Efforts to improve access to STI/HIV testing and PrEP may benefit from tailoring based on type of exchange sex. Findings indicate value in a broader definition of exchange sex with follow-up assessment of exchange sex typology

HIV Among MSM and Heterosexual Women in the United States: An Ecologic Analysis.

Phylogenetic studies show links between heterosexual women and men who have sex with men (MSM) that are more numerous than from heterosexual men to women suggesting that HIV infections among heterosexual women may stem from MSM. Poor communities have been associated with high rates of HIV among heterosexual women. Our analysis investigates potential transmission of HIV between MSM and female heterosexuals. National HIV Behavioral Surveillance data describe transmission risk behaviors of MSM, and HIV case reporting data describe the percentages of cases that are attributed to transmission risk categories. We examined correlations between the percentages of men who were MSM who also have sex with women and female heterosexual cases. We also examined census data to characterize each city in terms of poverty level and race/ethnicity makeup. There was a high correlation (0.93) between the percentage of reported living HIV cases attributed to male heterosexual contact and female heterosexual contact and a moderate nonsignificant correlation (0.49) between the percentage of MSM who were men who have sex with men and women (MSMW) in National HIV Behavioral Surveillance and the percentage of reported cases that were attributed to female heterosexual contact suggesting some potential overlap. Cities with high levels of poverty and African American/Black residents had higher levels of MSMW and higher levels of heterosexual female cases. Addressing HIV in cities with high levels of MSMW may have the dual effect of improving the health of MSM populations that have a high burden of HIV and to improve the health of their larger communities