Engagement Along the PrEP Care Continuum Among Men Who Have Sex with Men in China: A Systematic Review and Meta-analysis.

Pre-exposure prophylaxis (PrEP), including daily oral, on-demand, and long-acting injectable (LAI), is a promising HIV prevention intervention for men who have sex with men (MSM). We conducted a systematic review on engagement with the PrEP continuum among MSM in China. A total of 756 studies were initially identified and 36 studies were included (N = 26,021). In the 20 studies (N = 13,886) examining PrEP awareness, 32.4% (95% CI: 25.1-40.7) of MSM were aware of PrEP. In the 25 studies (N = 18,587) examining willingness, 54.5% (95% CI: 41.9-66.5) MSM indicated they were willing to use PrEP. The pooled prevalence of PrEP uptake from 9 studies (N = 6,575) was 4.9% (95% CI: 1.4-15.8%), while pooled estimates of adequate adherence from five studies (N = 2,344) among MSM on PrEP was 40.7% (95% CI: 20.0-65.2%). Subgroup analyses suggested studies conducted after 2015 (versus before) tended to report higher awareness and uptake. Awareness was highest for daily oral PrEP, followed by on-demand, and LAI PrEP; willingness to use was highest for LAI PrEP. The operationalization of willingness and adherence constructs varied across studies and complicated the interpretation of pooled estimates. This review revealed gaps in the PrEP care continuum among MSM in China, with relatively low awareness and uptake (in contrast to willingness and adherence) as the major potential barriers to widespread implementation and the need for a unified approach to defining and measuring PrEP outcomes.

Navigating Barriers and Opportunities: Perceptions of the Non-Occupational Post-Exposure Prophylaxis Care Continuum Among Young Sexual Minority Men, Aged 17-24, in the United States.

Human immunodeficiency virus (HIV) is a public health concern among young sexual minority men (YSMM), ages 17 to 24, in the United States. Biomedical prevention methods, such as pre-exposure prophylaxis (PrEP) and non-occupational post-exposure prophylaxis (nPEP), can help reduce the risk of HIV transmission among this population. However, there is limited awareness and use of nPEP by YSMM. This study aims to explore the perceptions of YSMM regarding the nPEP care continuum, which consists of three areas of focus: awareness, uptake, and linkage to other HIV prevention services. This study draws on synchronous online focus groups with a sample of 41 YSMM in the United States. Transcripts from the focus groups were analyzed using reflexive thematic analysis. Participants reported limited nPEP awareness and prior use, a process of personal appraisal of nPEP need based on HIV risk and costs, and a preference for PrEP over PEP for long-term HIV prevention. Interventions should be tailored to increase awareness of nPEP among YSMM and reduce addressable barriers to nPEP use for YSMM, including cost and confidentiality concerns, in situations where nPEP is warranted. Finally, more research is needed on how nPEP use can act as a bridge to PrEP initiation for this population.

"That's My Girl; I love her": The Promise of Compassionate, Inclusive Healthcare for Black Transgender Women to Support PrEP Use.

There are significant disparities in HIV pre-exposure prophylaxis (PrEP) use that disproportionately impact Black transgender women. Medical mistrust and discriminatory experiences in healthcare settings have been identified as critical barriers to equitable PrEP implementation. This qualitative study examines Black transgender women's experiences in healthcare to better understand how patient-provider relationships can help overcome the challenges brought on by medical mistrust. We interviewed 42 Black transgender women about their experiences with healthcare and PrEP access. Data were analyzed using inductive thematic content analysis to develop the following themes: (1) historical and ongoing marginalization and exclusion from healthcare remains a barrier to PrEP use; (2) Many providers continue to be unprepared to prescribe PrEP; (3) Providers can act as important advocates and sources of support; and (4) Compassionate, trusting patient-provider relationships can facilitate PrEP use. Our results highlight the importance of supportive and positive patient-provider relationships and demonstrate how providers can build trusting relationships with Black transgender women to help overcome barriers to healthcare and PrEP use.

Factors Influencing Engagement Across the Motivational PrEP Cascade Among Latino SMM: A Mixed-Methods Analysis from the Perspectives of Community Providers and Latino SMM.

Latino sexual minority men (SMM) are a highly vulnerable population to HIV, and while pre-exposure prophylaxis (PrEP) has emerged as a promising biomedical tool for HIV prevention among them, its utilization remains disproportionately low in this community despite its potential. Understanding the barriers along the PrEP continuum of care, known as the "PrEP cascade," is crucial for effectively implementing PrEP interventions. Therefore, the objective of our study was twofold: first, to explore the stage of Latino SMM in the PrEP cascade by examining disparities in demographics, social factors, and healthcare aspects; second, to gain insights from healthcare providers who have direct clinical experience with our population regarding the challenges faced by Latino SMM in accessing and adhering to PrEP. Based on the study findings, the majority of participants (n = 74; 49%) were in the contemplation stage, and only one in ten Latino SMM (10.6%) were currently adherent to PrEP. Compared to those who were at least second-generation, first-generation status had a positive association (B = 0.699, SE = 0.208, ß = 0.351, p < .001) with engagement along the PrEP Contemplation Ladder. Conversely, having at least one parent who did not have legal residency, relative to those whose parents were both U.S. citizens or held legal residency documentation, was found to have a negative association (B = - 0.689, SE = 0.245, ß = 0.245, p = .006) with engagement along the PrEP Contemplation Ladder. Additionally, discussing PrEP with a healthcare provider had a positive association (B = 0.374, SE = 0.179, ß = 0.185, p = .038) with engagement along the PrEP Contemplation Ladder. Qualitative results from our study suggest that some Latinos who initially agreed to start using PrEP ended up getting lost in the care pipeline and failed to attend their scheduled appointments. Providers also noted that many patients lacked access to a pharmacy where they felt comfortable obtaining their PrEP prescription, leading them to discontinue use after only a few months. These findings emphasize the importance of considering the unique needs, culture, and background of Latinos, including care delivery and provider attitudes that can facilitate progress through the PrEP cascade.

Correlates of intention to screen for cervical cancer among adult women in Kyotera District, Central Uganda: a community based cross-sectional study.

INTRODUCTION: Cervical cancer continues to pose a major public health challenge in low-income countries. Cervical cancer screening programs enable early detection and effectively reduce the incidence of cervical cancer as well as late-stage diagnosis and mortality. However, screening uptake remains suboptimal in Uganda. This study assessed correlates of intention to screen for cervical cancer among women in the Kyotera district of Central Uganda. METHODS: We analyzed cross-sectional data collected to determine the effectiveness of community audio towers (CATs) as a modality of health communication to support cervical cancer prevention. Women (n = 430) aged 21-60 years without a prior history of cervical cancer screening were surveyed about demographics, sources of health information and cervical cancer screening intentions in 2020. We used generalized linear modelling with modified Poisson regression and backwards variable elimination to identify adjusted prevalence ratios and 95% confidence intervals (CI) to determine factors associated with intention to screen for cervical cancer. RESULTS: Half (50.2%) of the participants had intentions to screen for cervical cancer within twelve months and 26.5% had moderate knowledge about cervical cancer. Nearly half (46.0%) considered themselves at risk of cervical cancer. Compared to residents who primarily received their health information from social media and radio, participants who received health information primarily from CATs (aPR:0.64, 95% CI:0.52-0.80, p < 0.001) and TV (aPR:0.52, 95% CI:0.34-0.82, p = 0.005) had a lower prevalence of intention to screen for cervical cancer. The prevalence of intentions to screen for cervical cancer in twelve months was higher among those resided in town councils (aPR:1.44, 95% CI:1.12-1.86, p = 0.004) compared to rural areas, and higher among those who considered themselves to be at risk of cervical cancer (aPR:1.74, 95% CI:1.28-2.36, p < 0.001) compared to those who did not. CONCLUSIONS: We found suboptimal prevalence of intentions to screen for cervical cancer among women in central Uganda. Additional research and implementation projects are needed to increase cervical cancer screening. Targeting risk perceptions and behavioral approaches to increase intentions could be effective in future intervention work. Based on urban-rural differences, additional work is needed to support equitable sharing of information to support cancer prevention messaging; CATs and TV may best help reach those with lower intentions to screen based on our research.

Mining cholesterol genes from thousands of mouse livers identifies aldolase C as a regulator of cholesterol biosynthesis.

The availability of genome-wide transcriptomic and proteomic datasets is ever-increasing and often not used beyond initial publication. Here, we applied module-based coexpression network analysis to a comprehensive catalog of 35 mouse genome-wide liver expression datasets (encompassing more than 3800 mice) with the goal of identifying and validating unknown genes involved in cholesterol metabolism. From these 35 datasets, we identified a conserved module of genes enriched with cholesterol biosynthetic genes. Using a systematic approach across the 35 datasets, we identified three genes (Rdh11, Echdc1, and Aldoc) with no known role in cholesterol metabolism. We then performed functional validation studies and show that each gene is capable of regulating cholesterol metabolism. For the glycolytic gene, Aldoc, we demonstrate that it contributes to de novo cholesterol biosynthesis and regulates cholesterol and triglyceride levels in mice. As Aldoc is located within a genome-wide significant genome-wide association studies locus for human plasma cholesterol levels, our studies establish Aldoc as a causal gene within this locus. Through our work, we develop a framework for leveraging mouse genome-wide liver datasets for identifying and validating genes involved in cholesterol metabolism.

Preoperative Alcohol Use, Postoperative Pain, and Opioid Use After Coronary Artery Bypass Surgery.

OBJECTIVES: Chronic alcohol use is associated with chronic pain and increased opioid consumption. The association between chronic alcohol use and acute postoperative pain has been studied minimally. The authors' objective was to explore the association among preoperative alcohol use, postoperative pain, and opioid consumption after coronary artery bypass grafting (CABG). DESIGN: A retrospective cohort study. SETTING: At a single academic medical center. PARTICIPANTS: Patients having isolated CABG. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics, comorbidities, and baseline alcohol consumption were recorded. Primary outcomes were mean pain score and morphine milligram equivalent (MME) consumption on postoperative day 0. Among 1,338 patients, there were 764 (57.1%) who had no weekly preoperative alcohol use, 294 (22.0%) who drank ≤1 drink per week, 170 (12.7%) who drank 2-to-7 drinks per week, and 110 (8.2%) who drank 8 or more drinks per week. There was no significant difference in mean pain score on postoperative day 0 in patients who consumed different amounts of alcohol (no alcohol = 5.3 ± 2.2, ≤1 drink = 5.2 ± 2.1, 2 to 7 drinks = 5.3 ± 2.3, 8 or more drinks = 5.4 ± 1.9, p = 0.66). There was also no significant difference in median MME use on postoperative day 0 in patients who consumed different amounts of alcohol (no alcohol = 22.5 mg, ≤1 drink = 21.1 mg, 2-to-7 drinks = 24.8 mg, 8 or more drinks = 24.5 mg, p = 0.14). CONCLUSIONS: There is no apparent association among mild-to-moderate preoperative alcohol consumption and early postoperative pain and opioid use in patients who underwent CABG.

Acceptability, Feasibility, and Preliminary Impact of 4 Remotely-Delivered Interventions for Rural Older Adults Living with HIV.

People living with HIV (PLH) who live in rural areas of the United States (US) face more challenges to obtaining medical care and suffer higher mortality rates compared to non-rural PLH. Compared with younger PLH, older PLH (age 50+) also face additional challenges to maintaining their health and wellbeing. Despite the heightened barriers to receiving care and remaining adherent to treatment among older rural PLH, few interventions to increase viral suppression and improve quality of life exist for this population. We pilot-tested four remotely-delivered interventions-group-based social support, group-based stigma-reduction, individual strengths-based case management, and individual technology detailing-aimed to improve care engagement and quality of life in rural older PLH in the southern US. Participants (N = 61, Mage = 58, 75% male) completed surveys and self-collected blood specimens at baseline and 3 months; in between, they were randomized to 0-4 interventions. We assessed feasibility, acceptability, and preliminary impact on medication adherence, viral suppression, quality of life, depressive symptoms, and hypothesized mediating mechanisms. More than 80% participated in assigned intervention(s), and 84% completed the study. Interventions were highly acceptable to participants, with more than 80% reporting they would recommend interventions to peers. More than 80% found the social support and case management interventions to be relevant and enjoyable. We found promising preliminary impact of interventions on quality of life, medication adherence, depressive symptoms, internalized stigma, and loneliness. Remotely-delivered interventions targeting rural older PLH are feasible to conduct and acceptable to participants. Larger scale study of these interventions is warranted.

RESUMEN: A pesar de las múltiples barreras para la adherencia a la medicación y la recepción de atención entre las personas mayores de zonas rurales que viven con el VIH, existen pocas intervenciones para mejorar la supresión viral y la calidad de vida para esta población. Realizamos pruebas piloto de intervenciones realizadas de forma remota (grupos de apoyo social, grupos de reducción del estigma, manejo de casos basado en los puntos fuertes y "technology detailing") entre las personas que viven con el VIH en zonas rurales del sur de Estados Unidos. Los participantes (N = 61, Medad = 58, 75% hombres) completaron encuestas y recolectaron muestras de sangre al inicio y a los 3 meses; en el medio, fueron asignados al azar a 0­4 intervenciones. Evaluamos la viabilidad, la aceptabilidad y el impacto preliminar. Más del 80% participó en la(s) intervención(es) y el 84% completó el estudio. Las intervenciones fueron muy aceptables para los participantes; más del 80% consideró que las intervenciones de apoyo social y gestión de casos eran relevantes y agradables. Las intervenciones tuvieron un impacto preliminar prometedor sobre la calidad de vida, la adherencia a la medicación, los síntomas depresivos, el estigma y la soledad. Las intervenciones realizadas a distancia dirigidas a las personas que viven con el VIH en zonas rurales de edad avanzada son viables y aceptables, y se justifica un estudio a mayor escala.

Heme biosynthesis regulates BCAA catabolism and thermogenesis in brown adipose tissue.

With age, people tend to accumulate body fat and reduce energy expenditure 1 . Brown (BAT) and beige adipose tissue dissipate heat and increase energy expenditure via the activity of the uncoupling protein UCP1 and other thermogenic futile cycles 2,3 . The activity of brown and beige depots inversely correlates with BMI and age 4-11 , suggesting that promoting thermogenesis may be an effective approach for combating age-related metabolic disease 12-15 . Heme is an enzyme cofactor and signaling molecule that we recently showed to regulate BAT function 16 . Here, we show that heme biosynthesis is the primary contributor to intracellular heme levels in brown adipocytes. Inhibition of heme biosynthesis leads to mitochondrial dysfunction and reduction in UCP1. Although supplementing heme can restore mitochondrial function in heme-synthesis-deficient cells, the downregulation of UCP1 persists due to the accumulation of the heme precursors, particularly propionyl-CoA, which is a product of branched-chain amino acids (BCAA) catabolism. Cold exposure promotes BCAA uptake in BAT, and defects in BCAA catabolism in this tissue hinder thermogenesis 17 . However, BCAAs' contribution to the TCA cycle in BAT and WAT never exceeds 2% of total TCA flux 18 . Our work offers a way to integrate current literature by describing heme biosynthesis as an important metabolic sink for BCAAs.

Preferred Characteristics for mHealth Interventions Among Young Sexual Minoritized Men to Support HIV Testing and PrEP Decision-Making: Focus Group Study.

BACKGROUND: Epidemiological trends in the United States have shown an increase in HIV cases among young sexual minoritized men. Using mobile health (mHealth), which refers to health services and information delivered or enhanced through the internet and related technologies, is a crucial strategy to address HIV disparities. However, despite its potential, the practical implementation of mHealth remains limited. Additionally, it is important to consider that young individuals may become accustomed to, distracted from, or lose interest in these apps, highlighting the need for regular updates and monitoring of relevant content. OBJECTIVE: In this study, we sought to highlight the voices of young sexual minoritized men aged 17-24 years and explored preferred mHealth intervention characteristics and willingness to adopt these technologies among a diverse, nationwide sample of young sexual minoritized men. METHODS: From April to September 2020, we recruited participants through web-based platforms such as social media and geosocial networking apps for men. These individuals were invited to participate in synchronous web-based focus group discussions centered around topics pertaining to HIV testing and prevention and their preferences for mHealth technologies. RESULTS: A total of 41 young sexual minoritized men, aged between 17 and 24 years, participated in 9 focus group discussions spanning April to September 2020, with 3-7 participants in each group. The findings shed light on three key insights regarding young sexual minoritized men's preferences: (1) the need for personalized and representative content, (2) a preference for mobile and web-based simulation of prevention scenarios, and (3) a preference for digital software with individually tailored content. As expected, preference for mHealth apps was high, which supports the potential and need to develop or adapt interventions that use smartphones as a platform for engaging young sexual minoritized men in HIV prevention. This study expands on previous research in multiple meaningful ways, delving into the use and perceptions of mHealth information amid the COVID-19 pandemic. This study also highlighted the importance of streamlined access to health care providers, especially in light of the barriers faced by young people during the COVID-19 pandemic. In terms of presentation and navigation, participants favored a user-friendly design that was easy to use and appropriate for their age, which was effectively addressed through the implementation of web-based simulations. CONCLUSIONS: Ultimately, this study provides valuable insight into the preferences of young sexual minoritized men when it comes to mHealth interventions and highlights the need for further research in order to develop effective and tailored HIV prevention tools. A future direction for researchers is to evaluate how best to address participants' desire for personalized content within mHealth apps. Additionally, as technology rapidly evolves, there is a need to re-assess the effectiveness of web-based simulations, particularly those that are used in HIV prevention.

Implementation determinants of HIV Self-Testing among young sexual minority men.

BACKGROUND: HIV self-testing (HIVST) has shown the potential for reaching people with heightened vulnerability to HIV, including young sexual minority men (YSMM), yet implementation of HIVST among YSMM aged 17-24 is scarce as a prevention method. Moreover, despite the consistent finding that offering HIVST increases HIV testing rates, barriers remain that need to be reduced in order to maximize the potential of this biomedical technology. Such information is necessary to direct implementation efforts to increase HIVST among YSMM, including HIV counseling and linkage to care. The current study was therefore intended to investigate perspectives for HIVST among YSMM and how HIVST can be marketed to increase implementation. METHODS: Between March and September 2020, we enrolled 41 YSMM to participate in one of nine online synchronous focus group discussions about their general experience with HIV preventive services. Guided by the Consolidated Framework (CFIR) for Implementation Research, we explored YSMM perspectives on facilitators and barriers to HIVST implementation. Data were analyzed using a deductive thematic content analysis approach. RESULTS: Many participants had never used HIVST before their participation in this study (n = 30; 73.2%). Qualitative results exhibited a variety of implementation determinants across the five CFIR 2.0 domains. Barriers included concerns about the format in which the testing materials would be provided (i.e., nature of packaging) and about the method in which the sample would need to be collected, particularly for those who had the testing kit mailed to their home address. These reservations were nested in the fear of unwanted disclosure of their sexual behavior, namely among the respondents who had to cohabitate with family due to the COVID-19 pandemic. Participants also discussed the limited local resources for HIVST. Many participants suggested programs that could be implemented to support HIVST, such as collaborations with trusted community agencies. CONCLUSIONS: Understanding YSMM' perspectives of HIVST may help identify implementation deficiencies within the delivery system and aid the development of implementation strategies to promote reach of HIVST.

Analysis of the rat chorda tympani nerve response to "super salty" sodium carbonate.

In behavioral experiments, rats perceive sodium carbonate (Na2CO3) as super salty. In fact, when the dissociated Na+ ions are accounted for, rats perceive Na2CO3 as 5× saltier than equinormal concentrations of NaCl. The chorda tympani nerve (CT) responds to salts through at least two receptor mechanisms and is a model system for understanding how salt taste is transmitted to the brain. Here, we recorded CT nerve activity to a broad range of NaCl (3-300 mM) and Na2CO3 (3-300 mN) to investigate why Na2CO3 tastes so salty to rats. Benzamil, a specific epithelial sodium channel (ENaC) antagonist, was used to determine the relative contribution of apical ENaCs in Na2CO3 transduction. The benzamil-insensitive component of CT nerve responses was enhanced by increasing the adapted tongue temperature from 23°C to 30°C. Na2CO3 solutions are alkaline, so we compared neural responses (with and without benzamil) to 100 mM NaCl alone (6.2 pH) and at a pH (11.2 pH) that matched 100 mN Na2CO3. As expected, NaCl responses increased progressively with increasing concentration and temperature. Responses to 3 mN Na2CO3 were greater than 3 mM NaCl with and without benzamil, but the shape of the first log-fold range of was relatively flat. Adjusting the pH of NaCl to 11.2 abolished the thermal enhancement of 100 mN NaCl through the benzamil-insensitive pathway. Rinsing Na2CO3 off the tongue resulted in robust aftertaste that was concentration dependent, thermally sensitive, and benzamil-insensitive. Responses to alkaline NaCl did not recapitulate Na2CO3 responses or aftertaste, suggesting multiple transduction mechanisms for the cations (2Na+) and anion (CO3-2).

Exploring preferences and decision-making about long-acting injectable HIV pre-exposure prophylaxis (PrEP) among young sexual minority men 17-24 years old.

Intramuscular cabotegravir for long-acting injectable HIV pre-exposure prophylaxis (i.e., LAI-PrEP) was approved by the U.S. FDA in 2021. We sought to explore LAI-PrEP decision-making among a nationwide sample of young sexual minority men (YSMM) 17-24 years old. In 2020, HIV-negative/unknown YSMM (n = 41) who met CDC criteria for PrEP were recruited online to participate in synchronous online focus groups eliciting preferences and opinions about LAI-PrEP, as well as the impact of a potential self-administered option. Data were analyzed using inductive and deductive thematic analysis with constant comparison. Preferences and decision-making about LAI-PrEP varied widely among YSMM, with participants frequently comparing LAI-PrEP to oral PrEP regimens. We identified five key themes related to LAI-PrEP decision-making including concerns about adherence to PrEP dosing and clinic appointments, awareness and knowledge of PrEP safety and efficacy data, comfort with needles, minimizing PrEP stigma, and considerations of self-administration. YSMM acknowledged more PrEP options as beneficial to supporting uptake and persistence.

Trends in sepsis and pneumonia during COVID-19: lessons from BPCIA.

OBJECTIVES: The COVID-19 pandemic affected care delivery nationwide for all patients, influencing cost and utilization for patients both with and without COVID-19. Our first analysis assessed changes in utilization for patients with sepsis without COVID-19 prior to vs during the pandemic. Our second analysis assessed cost and utilization changes during the pandemic for patients with sepsis or pneumonia both with and without COVID-19. STUDY DESIGN: A retrospective case-control study was utilized to determine differences in cost and utilization for patients with sepsis or pneumonia, relative to a COVID-19 diagnosis. METHODS: Claims data from 8 teaching hospitals participating in sepsis and pneumonia episodes in the Bundled Payments for Care Improvement Advanced (BPCIA) model were utilized. BPCIA is a Medicare value-based care bundled payment program that aims to decrease costs and increase quality of care through a 90-day total cost of care model. RESULTS: The first analysis (N = 1092) found that non-COVID-19 patients with sepsis had 26% higher hospice utilization (P < .05) and 38% higher mortality (P < .0001) during the pandemic vs the prepandemic period. The second analysis (N = 640) found that during the pandemic, patients with sepsis or pneumonia with COVID-19 had 70% more skilled nursing facility (SNF) use (P < .0001), 132% higher SNF costs (P < .0001), and 21% higher total episode costs (P < .0001) compared with patients without COVID-19. CONCLUSIONS: COVID-19 has affected care patterns for all patients. Patients without COVID-19 postponed care and used lower-acuity care settings, whereas patients with COVID-19 were more costly and utilized postacute care at a higher rate. These analyses inform future care coordination initiatives, given the ongoing pandemic.

Intersectional Discrimination and PrEP uSe Among Young Black Sexual Minority Individuals: The Importance of Black LGBTQ Communities and Social Support.

Intersectional stigma and discrimination have increasingly been recognized as impediments to the health and well-being of young Black sexual minority men (YBSMM) and transgender women (TW). However, little research has examined the relationship between intersectional discrimination and HIV pre-exposure prophylaxis (PrEP) outcomes. This study with 283 YBSMM and TW examines the relationship between intersectional discrimination and current PrEP use and likelihood of future PrEP use. Path models were used to test associations between intersectional discrimination, resilience and social support, and PrEP use and intentions. Individuals with higher levels of anticipated discrimination were less likely to be current PrEP users (OR = 0.59, p = .013), and higher levels of daily discrimination were associated with increased likelihood of using PrEP in the future (B = 0.48 (0.16), p = .002). Greater discrimination was associated with higher levels of resilience, social support, and connection to the Black LGBTQ community. Social support mediated the effect of day-to-day discrimination on likelihood of future PrEP use. Additionally, there was a significant and negative indirect effect of PrEP social concerns on current PrEP use via Black LGBTQ community connectedness. The results of this study highlight the complexity of the relationships between discrimination, resilience, and health outcomes.

Nitric oxide-driven modifications of lipoic arm inhibit α-ketoacid dehydrogenases.

Pyruvate dehydrogenase complex (PDHC) and oxoglutarate dehydrogenase complex (OGDC), which belong to the mitochondrial α-ketoacid dehydrogenase family, play crucial roles in cellular metabolism. These multi-subunit enzyme complexes use lipoic arms covalently attached to their E2 subunits to transfer an acyl group to coenzyme A (CoA). Here, we report a novel mechanism capable of substantially inhibiting PDHC and OGDC: reactive nitrogen species (RNS) can covalently modify the thiols on their lipoic arms, generating a series of adducts that block catalytic activity. S-Nitroso-CoA, a product between RNS and the E2 subunit's natural substrate, CoA, can efficiently deliver these modifications onto the lipoic arm. We found RNS-mediated inhibition of PDHC and OGDC occurs during classical macrophage activation, driving significant rewiring of cellular metabolism over time. This work provides a new mechanistic link between RNS and mitochondrial metabolism with potential relevance for numerous physiological and pathological conditions in which RNS accumulate.

Factors associated with lack of care engagement among older, rural-dwelling adults living with HIV in the United States.

PURPOSE: Most people living with HIV (PLH) in the United States are over age 50 and this sector of PLH continues to grow. Aging with HIV can be challenging due to comorbid medical conditions, mental health disorders, substance use, and lack of social and practical support. Additional challenges are faced by older PLH living in the rural United States, such as longer distances to health care, concerns over privacy and stigma, and social isolation. PLH in rural areas have higher mortality rates than urban PLH. We aimed to understand factors associated with HIV care engagement and quality of life in rural US adults over age 50. METHODS: We conducted a cross-sectional study to evaluate the association between patient-level factors and a combined outcome variable encompassing multiple aspects of care engagement. FINDINGS: Either online or on paper, 446 participants completed our survey. One-third of the participants (33%) were from the southern United States; one-third were women; one-third were non-White; and 24% completed the survey on paper. In multiple regression analysis, lower income, residing in the southern United States, lacking internet access at home, not having an HIV specialist provider, higher levels of stress, living alone, and longer distance to an HIV provider were all associated with lower engagement in HIV care. CONCLUSIONS: Our findings demonstrated multiple potential options for interventions that could improve care engagement, such as providing and enhancing access to technology for health care engagement and remotely delivering social support and mental health services. Research on such potential interventions is needed for older, rural PLH.

Factors associated with quality of life, depressive symptoms, and perceived stress among rural older adults living with HIV in the United States.

PURPOSE: Rural older people living with HIV (PLH) in the United States are a population of growing size and significance. A better understanding of factors associated with quality of life (QOL), depressive symptoms, and stress in this population-especially modifiable factors-could inform future interventions. METHODS: Online or on paper, we surveyed 446 PLH aged 50+ residing in rural counties across the United States (Mage = 56, 67% male, 67% White, and 23% Black). Associations between social support, HIV stigma, satisfaction with medical care, discrimination in health care settings, and structural barriers and health-related QOL, depressive symptoms, and perceived stress were assessed using multiple linear regressions. FINDINGS: Controlling for demographics, greater social support was associated with better QOL, fewer depressive symptoms, and less stress. Greater HIV stigma was associated with more depressive symptoms and stress. Satisfaction with care was associated with better QOL and less stress. Discrimination in medical settings was associated with lower QOL and more depressive symptoms and stress. Finally, experiencing more structural barriers was associated with lower QOL and more depressive symptoms and stress. CONCLUSIONS: In addition to engagement in care and viral suppression, QOL and mental health are also critical considerations for rural older PLH. Increasing social support, reducing or providing skills to cope with HIV stigma, improving quality of care, reducing discrimination and stigma in medical settings, and reducing or mitigating the impact of structural barriers present potential targets for interventions aiming to improve the well-being of older rural PLH.