Neighborhood-level characteristics as effect modifiers on the efficacy of the MyPEEPS mobile intervention in same-sex attracted adolescent men.

To estimate the effect of neighborhood-level modification on the efficacy of the MyPEEPS Mobile intervention on the reduction of condomless anal sex acts among same-sex attracted adolescent men. A series of generalized linear mixed model was used to examine if the effect of the MyPEEPS Mobile intervention on condomless anal sex acts was moderated by neighborhood-level factors using data from the 2019 American Community Survey US Census Bureau. "The magnitudes of intervention were significantly smaller at both 6- and 9-month follow-up among adolescents living in neighborhood with high proportions of Hispanic or Latino residents (IRR6M = 1.02, 95 % CI: 1.01, 1.02; IRR9M = 1.03, 95 % CI: 1.01, 1.05) and high proportions of families with income below the poverty level (IRR6M = 1.07, 95 % CI: 1.01, 1.12; IRR9M = 1.05, 95 % CI: 1.01, 1.10), which indicated that living in communities with a higher concentration of residents living under poverty or of Hispanic/and Latino ethnicity significantly modified the effective of program intervention on condomless sex among adolescent MSM. Understanding how neighborhood characteristics modify the effect of HIV prevention interventions may be useful in better targeting delivery and tailoring content of interventions based on neighborhood level characteristics such as the ones identified in this study.

Adverse childhood experiences among black sexually minoritized men and Black transgender women in Chicago.

BACKGROUND: Adverse childhood experiences (ACE) are important predictors of mental health outcomes in adulthood. However, commonly used ACE measures such as the Behavioural Risk Factor Surveillance System (BRFSS) have not been validated among Black sexually minoritized men (SMM) nor transgender women (TW), whom are known to have higher rates of ACE and poorer mental health outcomes. Assessing the psychometric properties of the measure is important for health equity research, as measurements that are not valid for some populations will render uninterpretable results. METHODS: Data are drawn from the Neighborhoods and Networks (N2) study, a longitudinal cohort of Black SMM and TW living in Southern Chicago. We conducted confirmatory factor analysis, correlation analysis and a two-parameter Item Response Theory (IRT) on the BRFSS ACE measure, an 11-item measure with 8 domains of ACE. RESULTS: One hundred forty seven participants (85% cisgender male) completed the BRFSS ACE measurement in the N2 study with age ranges from 16-34. The cohort were from a low socioeconomic background: about 40% of the cohort were housing insecure and made than $10,000 or less annually. They also have a high number of ACEs; 34% had endorsed 4 or more ACE domains. The three-factor structure fit the BRFSS ACE measure best; the measurement consisted of three subscales: of "Household Dysfunction", "Emotional / Physical", and "Sexual Abuse" (CFI = 0.975, TLI = 0.967, and RMSEA = 0.051). When the 8 domains of ACE were summed to one score, the total score was is correlated with depressive symptoms and anxiety scores, establishing concurrent validity. Item Response Theory model indicated that the "parental separation" domain had a low discrimination (slope) parameter, suggesting that this domain does not distinguish well between those with and without high ACE. CONCLUSIONS: The BRFFS ACE measure had adequate reliability, a well-replicated structure and some moderate evidence of concurrent validity among Black SMM and TW. The parental separation domain does not discriminate between those with high and low ACE experiences in this population. With changing population demographics and trends in marriage, further examination of this item beyond the current study is warranted to improve health equity research for all.

Police Harassment and Psychiatric, Sexual, and Substance Use Risk Among Black Sexual Minority Men and Black Transgender Women in the HIV Prevention Trials 061 Cohort.

BACKGROUND: Black sexual minority men and Black transgender women (BSMM/BTW) experience disproportionate levels of HIV/STI-related risk factors as well as police harassment (PH). PH is linked to psychiatric risk and could play a role in substance use, sexual risk behavior, and HIV/STI risk. METHODS: We used data from the HIV Prevention Trials Network 061(HPTN 061) study to examine associations between PH and HIV/STI-related outcomes. Using PH exposure measured at baseline and 6-month study visits, we examined an ordinal exposure (PH reported at both visits, PH reported at either visit, versus PH reported at neither baseline nor 6 months) and a binary exposure of persistent PH reported at both visits (yes versus no). We estimate risk ratios (RR) for associations between PH and depression, use of alcohol and methamphetamine, multiple partnerships, condomless sex, and syphilis. RESULTS: Persistent PH (binary) was associated with a 20% or greater increase in the risk of depression (RR, 1.26 (1.07, 1.47)) and multiple partnerships (RR, 1.20 (1.05, 1.39)). There was evidence that ordinal PH was associated with elevated risk of alcohol use (RR, 1.17 (1.00, 1.36)); the point estimate for the association between persistent PH and alcohol use was similar but the imprecision was greater (RR, 1.16 (0.95, 1.42)). CONCLUSION: PH may influence not only mental health but also behavioral risks that contribute to HIV/STI among BSMM/BTW, highlighting the potential wide-ranging and downstream effects of PH on health. Further research is required to confirm associations and elucidate pathways through which PH may influence HIV/STI among BSMM/BTW.

Neighborhood violent crime exposure is associated with PrEP non-use among black sexually minoritized men and transgender women: A GPS Study.

OBJECTIVE: The objective of this study is to use GPS technology to determine if violent and property crime exposure to participants activity spaces affect outcomes of the HIV prevention and care continuum (PCC) among Young Black sexually minoritized men (YBSMM) and Transgender women (TW), a subgroup at high vulnerability for new HIV diagnoses. Exposure to violent and property crime adversely affects a variety of acute and chronic medical conditions; however the relationship between exposure to violent and property crime and HIV risk (e.g., PrEP non use) is unknown. Spatial analytic analysis using dynamic Global Position Systems (GPS) technology can accurately detect geospatial associations between the crime exposure and objective HIV related outcomes. METHODS: With the Neighborhoods and Networks (N2) Cohort Study, GPS technology to identify the activity space of 286 (123 PLWH and 163 PWoH) YBSMM & TW living in Chicago, IL, to identified spatial associations between violent and property crime exposures with HIV PCC outcomes. RESULTS: We found that YBSMM & TGW with higher exposure areas with higher levels of violent crime were less likely to use HIV preexposure prophylaxis (PrEP) therapy (aOR 0.76, 95% CI 0.63-0.91, p = 0.03). CONCLUSION: This study demonstrates the importance of clinical providers to consider violent crime as a potential sociostructural barrier that may impact medication adherence and health care outcomes among vulnerable populations. Additionally, GPS technology offers an alternative data analytic process that may be used to future studies to assist in identifying barriers to ending the HIV epidemic.

Reversible Covalent Inhibition─Desired Covalent Adduct Formation by Mass Action.

Covalent inhibition has seen a resurgence in the last several years. Although long-plagued by concerns of off-target effects due to nonspecific reactions leading to covalent adducts, there has been success in developing covalent inhibitors, especially within the field of anticancer therapy. Covalent inhibitors can have an advantage over noncovalent inhibitors since the formation of a covalent adduct may serve as an additional mode of selectivity due to the intrinsic reactivity of the target protein that is absent in many other proteins. Unfortunately, many covalent inhibitors form irreversible adducts with off-target proteins, which can lead to considerable side-effects. By designing the inhibitor to form reversible covalent adducts, one can leverage competing on/off kinetics in complex formation by taking advantage of the law of mass action. Although covalent adducts do form with off-target proteins, the reversible nature of inhibition prevents accumulation of the off-target adduct, thus limiting side-effects. In this perspective, we outline important characteristics of reversible covalent inhibitors, including examples and a guide for inhibitor development.

The burden of Cardiovascular diseases in Jordan: a longitudinal analysis from the global burden of disease study, 1990-2019.

BACKGROUND: Cardiovascular Disease (CVD) is the leading cause of mortality worldwide. While countries in the Arab world continue to lack public health data and be severely understudied in health research, previous research has shown that compared to 1990, CVDs had a higher burden of disease in the Arab World in 2010. Jordan, a middle-income Arab country, is profiled with unique attributes such as a dual-sector healthcare system, political stability, and its role as a haven for refugees and migrants. These distinctive factors emphasize Jordan's suitability as a case study. This investigation aims to quantify CVD burden in Jordan and identify risk factors, contributing to a broader understanding of health challenges in the Arab region and beyond. METHODS: The Global Burden of Disease (GBD) dataset was used to estimate prevalence, death, and disability-adjusted life-years (DALYs) as age-standardized rates from 1990 to 2019. We calculated percentage change for nine specific CVDs and reported trends by gender and age groups. Additionally, data on twelve a priori selected behavioral, clinical, and environmental risk factors attributing to overall age-standardized CVDs DALY were reported per 100,00 population. RESULTS: In 2019, the age-standardized CVD prevalence, death, and DALYs rates in Jordan were 7980 (95% uncertainty interval [UI] 7629, 8360), 248 (95% UI 211, 288), and 4647 (95% UI 4028, 5388), respectively. Despite an increase in the absolute number of mortality and prevalence, between 1990 and 2019, the age-standardized prevalence, death, and DALYs rates all decreased by 5.5%, 45.1%, and 46.7%, respectively. In 2019, the leading risk factors contributing to overall age-standardized CVDs DALY per 100,000 population were high systolic blood pressure, high BMI, dietary risks, and high LDL cholesterol. CONCLUSION: Despite decreasing burden rate of CVDs in Jordan between 1990 and 2019, CVDs remain the leading cause of mortality in Jordan, with an increase in the total number of prevalence and mortality. Overall, this contributes to increased healthcare costs. Further research is required to quantify the burden of CVDs and understand it better. Intervention measures and policies tailored to specific CVDs should be designed to reduce the burden of CVDs in Jordan.

Defining Spatial Epidemiology: A Systematic Review and Re-Orientation.

BACKGROUND: Spatial epidemiology has emerged as an important subfield of epidemiology over the past quarter century. We trace the origins of spatial epidemiology and note that its emergence coincided with technological developments in spatial statistics and geography. We hypothesize that spatial epidemiology makes important contributions to descriptive epidemiology and analytic risk factor studies, but is not yet aligned with epidemiology's current focus on causal inference and intervention. METHODS: We conducted a systematic review of studies indexed in PubMed that used the term "spatial epidemiolog*" in the title, abstract, or keywords. Excluded papers were not written in English, examined disease in animals, or reported biologic pathogen distribution only. We coded the included papers into five categories (review, demonstration of method, descriptive, analytic, intervention) and recorded the unit of analysis (i.e., individual vs. ecological). We additionally examined papers coded as analytic ecologic studies using scales for lexical content. RESULTS: A total of 482 papers met the inclusion criteria, including 76 reviews, 117 demonstrations of methods, 122 descriptive studies, 167 analytic studies, and 0 intervention studies. Demonstration studies were most common from 2006 to 2014, and analytic studies were most common after 2015. Among the analytic ecologic studies, those published in later years used more terms relevant to spatial statistics (IRR =1.3, 95%CI: 1.1, 1.5) and causal inference (IRR =1.1, 95%CI: 1.1, 1.2). CONCLUSIONS: Spatial epidemiology is an important and growing subfield of epidemiology. We suggest a re-orientation to help align its practice with the goals of contemporary epidemiology.

A chemical screen identifies structurally diverse metal chelators with activity against the fungal pathogen Candida albicans.

Candida albicans, one of the most prevalent human fungal pathogens, causes diverse diseases extending from superficial infections to deadly systemic mycoses. Currently, only three major classes of antifungal drugs are available to treat systemic infections: azoles, polyenes, and echinocandins. Alarmingly, the efficacy of these antifungals against C. albicans is hindered both by basal tolerance toward the drugs and the development of resistance mechanisms such as alterations of the drug's target, modulation of stress responses, and overexpression of efflux pumps. Thus, the need to identify novel antifungal strategies is dire. To address this challenge, we screened 3,049 structurally-diverse compounds from the Boston University Center for Molecular Discovery (BU-CMD) chemical library against a C. albicans clinical isolate and identified 17 molecules that inhibited C. albicans growth by >80% relative to controls. Among the most potent compounds were CMLD013360, CMLD012661, and CMLD012693, molecules representing two distinct chemical scaffolds, including 3-hydroxyquinolinones and a xanthone natural product. Based on structural insights, CMLD013360, CMLD012661, and CMLD012693 were hypothesized to exert antifungal activity through metal chelation. Follow-up investigations revealed all three compounds exerted antifungal activity against non-albicans Candida, including Candida auris and Candida glabrata, with the xanthone natural product CMLD013360 also displaying activity against the pathogenic mould Aspergillus fumigatus. Media supplementation with metallonutrients, namely ferric or ferrous iron, rescued C. albicans growth, confirming these compounds act as metal chelators. Thus, this work identifies and characterizes two chemical scaffolds that chelate iron to inhibit the growth of the clinically relevant fungal pathogen C. albicansIMPORTANCEThe worldwide incidence of invasive fungal infections is increasing at an alarming rate. Systemic candidiasis caused by the opportunistic pathogen Candida albicans is the most common cause of life-threatening fungal infection. However, due to the limited number of antifungal drug classes available and the rise of antifungal resistance, an urgent need exists for the identification of novel treatments. By screening a compound collection from the Boston University Center for Molecular Discovery (BU-CMD), we identified three compounds representing two distinct chemical scaffolds that displayed activity against C. albicans. Follow-up analyses confirmed these molecules were also active against other pathogenic fungal species including Candida auris and Aspergillus fumigatus. Finally, we determined that these compounds inhibit the growth of C. albicans in culture through iron chelation. Overall, this observation describes two novel chemical scaffolds with antifungal activity against diverse fungal pathogens.

A Network Science Approach to Sex-Polydrug Use Among Black Sexually Minoritized Men and Transgender Women: The N2 Cohort Study.

Black sexually minoritized men (SMM) and transgender women (TW) are subgroups with lower rates of substance use and comparable rates of condom use relative to White SMM and TW yet experience heightened vulnerability to HIV. This study sought to explore associations of substance use, including sex-drug use (i.e., drug or alcohol use during sex to enhance sex), and condomless sex among Black SMM and TW. Data were collected from Black SMM and TW living in Chicago, Illinois, enrolled in the Neighborhoods and Networks (N2) cohort study, from November 2018 to April 2019. We used bivariate analyses followed by a multilevel egocentric network analysis to identify factors associated with condomless sex. We conducted Spearman correlation coefficients to examine correlations between pairs of sex-drugs to enhance sex. We used a bipartite network analysis to identify correlates of sex-drug use and condomless sex. A total of 352 Black SMM and TW (egos) provided information about 933 sexual partners (alters). Of respondents, 45% reported condomless sex and 61% reported sex-drug use. In unadjusted analyses, marijuana (34%) and cocaine/crack (5%) sex-drug use were associated with condomless sex (p < 0.05). Condomless sex was positively associated with sex-polydrug use, or the use of 2+ drugs or 1 drug and alcohol (OR = 1.48; 95% CI: 1.02-2.14; p = 0.039), and negatively associated with sharing an HIV-negative serostatus with a sexual partner (OR = 0.57; 95% CI: 0.33-0.98; p = 0.041), having a different HIV serostatus with a sexual partner (OR = 0.37; 95% CI: 0.21-0.64; p < 0.001) or not knowing the HIV serostatus of a sexual partner (OR = 0.47; 95% CI: 0.26-0.84; p = 0.011). The following pairs of sex-polydrug use had Spearman correlation coefficients higher than 0.3: marijuana and alcohol, ecstasy and alcohol, cocaine/crack and ecstasy, and methamphetamine and poppers (p < 0.05). HIV prevention interventions for Black SMM and TW designed to reduce HIV transmission through egocentric sexual networks could address sex-drug use through sex-positive and pleasure-centered harm reduction strategies and provide and promote biomedical prevention and care options at supraoptimal levels.

Rest-Activity Rhythms Are Associated With Prevalent Cardiovascular Disease, Hypertension, Obesity, and Central Adiposity in a Nationally Representative Sample of US Adults.

BACKGROUND: Rest-activity rhythms (RARs), a measure of circadian rhythmicity in the free-living setting, are related to mortality risk, but evidence is limited on associations with cardiovascular disease (CVD) and its risk factors. METHODS AND RESULTS: Participants included 4521 adults from the 2013 to 2014 National Health and Nutrition Examination Survey physical activity monitoring examination. Wrist-worn ActiGraph GT3X+ data were used to estimate RARs. Multivariable logistic models evaluated associations of RARs with prevalent CVD, hypertension, obesity, and central adiposity. Participants (mean age, 49 years) in the highest versus lowest tertile of relative amplitude (greater circadian rhythmicity) had 39% to 62% lower odds of prevalent CVD, hypertension, obesity, and central adiposity. A more active wake period was associated with 19% to 72% lower CVD, hypertension, obesity, and central adiposity odds. Higher interdaily stability (regular sleep-wake and rest-activity patterns) was related to 52% and 23% lower CVD and obesity odds, respectively. In contrast, participants in the highest versus lowest tertile of intradaily variability (fragmented RAR and inefficient sleep) had >3-fold and 24% higher CVD and obesity odds, respectively. A later and less restful sleep period was associated with 36% to 2-fold higher CVD, hypertension, obesity, and central adiposity odds. A statistically significant linear trend was observed for all associations (P-trend<0.05). CONCLUSIONS: A robust, stable, and less fragmented RAR, an active wake period, and an earlier and more restful sleep period are associated with lower prevalent CVD, hypertension, obesity, and central adiposity, with evidence of a dose-response relationship. The magnitude, timing, and regularity of sleep-wake and rest-activity patterns may be important targets for reducing cardiovascular risk.

HIV Prevention and Care Among Black Cisgender Sexual Minority Men and Transgender Women: Protocol for an HIV Status-Neutral Cohort Study Using an Observational-Implementation Hybrid Approach.

BACKGROUND: Black cisgender gay, bisexual, and other sexual minority men (SMM) and transgender women (TW) continue to be heavily affected by HIV. Further research is needed to better understand HIV prevention and care outcomes in this population. In particular, there is a need for research examining the impact of substance use and sleep health on HIV prevention and treatment outcomes among Black SMM and TW. OBJECTIVE: This paper outlines the study methods being used in the recently launched follow-up study to the Neighborhoods and Networks (N2) study, which we refer to as N2 Part 2 (N2P2). N2P2 aims to address this gap in the literature, build off the findings of the original N2 study, and identify socioenvironmental determinants of health, including whether neighborhood and network factors mediate and moderate these relationships. METHODS: Building on the N2 cohort study in Chicago from 2018 to 2022, N2P2 used a prospective longitudinal cohort design and an observational-implementation hybrid approach. With sustained high levels of community engagement, we aim to recruit a new sample of 600 Black SMM and TW participants residing in the Chicago metropolitan statistical area. Participants are asked to participate in 3 study visits across an 18-month study period (1 visit every 9 months). Four different forms of data are collected per wave: (1) an in-person survey, (2) biological specimen collection, (3) a daily remote ecological momentary assessment for 14 days after each study visit, and (4) data from electronic health records. These forms of data collection continue to assess neighborhood and network factors and specifically explore substance use, sleep, immune function, obesity, and the implementation of potential interventions that address relevant constructs (eg, alcohol use and pre-exposure prophylaxis adherence). RESULTS: The N2P2 study was funded in August 2021 by the National Institute of Drug Abuse (R01DA054553 and R21DA053156) and National Heart, Lung, and Blood Institute (R01HL160325). This study was launched in November 2022. Recruitment and enrollment for the first wave of data collection are currently ongoing. CONCLUSIONS: The N2P2 study is applying innovative methods to comprehensively explore the impacts of substance use and sleep health on HIV-related outcomes among an HIV status-neutral cohort of Black SMM and TW in Chicago. This study is applying an observational-implementation hybrid design to help us achieve findings that support rapid translation, a critical priority among populations such as Black SMM and TW that experience long-standing inequities with regard to HIV and other health-related outcomes. N2P2 will directly build off the findings that have resulted from the original N2 study among Black SMM and TW in Chicago. These findings provide a better understanding of multilevel (eg, individual, network, and neighborhood) factors that contribute to HIV-related outcomes and viral suppression among Black SMM and TW. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48548.

Overamped: Stimulant Use and HIV Pathogenesis.

PURPOSE OF REVIEW: In the era of HIV treatment as prevention (TasP), more clarity is needed regarding whether people with HIV who use stimulants (i.e., methamphetamine, powder cocaine, and crack cocaine) display elevated HIV viral load and greater immune dysregulation. RECENT FINDINGS: Although rates of viral suppression have improved in the TasP era, stimulant use was independently associated with elevated viral load in 23 of 28 studies included in our review. In the 12 studies examining other HIV disease markers, there was preliminary evidence for stimulant-associated alterations in gut-immune dysfunction and cellular immunity despite effective HIV treatment. Studies generally focused on documenting the direct associations of stimulant use with biomarkers of HIV pathogenesis without placing these in the context of social determinants of health. Stimulant use is a key barrier to optimizing the effectiveness of TasP. Elucidating the microbiome-gut-brain axis pathways whereby stimulants alter neuroimmune functioning could identify viable targets for pharmacotherapies for stimulant use disorders. Examining interpersonal, neighborhood, and structural determinants that could modify the associations of stimulant use with biomarkers of HIV pathogenesis is critical to guiding the development of comprehensive, multi-level interventions.

Church Closings Were Associated with Higher COVID-19 Infection Rates: Implications for Community Health Equity.

This study investigates the changes in physical church closings years 2013 to 2019 in New York City (NYC), Philadelphia, and Baltimore and the association with COVID-19 infection rates. We applied Bayesian spatial binomial models to analyze confirmed cases of COVID-19 as of February 28, 2022, in each city at the zip code-level. A one unit increase in the number of churches closed corresponded to a 5% higher COVID-19 infection rate, in NYC (rate ratio = 1.05, 95% credible interval = 1.02-1.08%), where the association was significant. Church closings appears to be an important indicator of neighborhood social vulnerability. Church closings should be routinely monitored as a structural determinant of community health and to advance health equity.

Alignment of Ending the HIV Epidemic Priority Jurisdictions With Availability of HIV Service Organizations: An Ecological Study.

We sought to describe and quantify the association between HIV service organization availability, HIV burden, and HIV awareness and prevention in the 57 priority jurisdictions selected as part of the U.S. Ending the HIV Epidemic initiative. On average, jurisdictions with more per capita organizations had more people living with HIV, more individuals aware of their positive status, and more individuals prescribed PrEP (b = 0.3; 95% CI [0.2, 0.5] for each additional case per 1,000 people in the first metric, and b = 0.3; 95% CI [0.2, 0.4] and b = 0.1; 95% CI [< 0.1, 0.1], respectively, for each percentage point change in the second two metrics), accounting for jurisdiction size. Several jurisdictions were outliers in the modeled associations and may reflect comparatively better, or worse, performance than similar jurisdictions. This information can assist in evaluating resource allocation and determining whether availability translates to accessibility.

Use of geofencing interventions in population health research: a scoping review.

OBJECTIVES: Technological advancements that use global positioning system (GPS), such as geofencing, provide the opportunity to examine place-based context in population health research. This review aimed to systematically identify, assess and synthesise the existing evidence on geofencing intervention design, acceptability, feasibility and/or impact. DESIGN: Scoping review, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidance for reporting. DATA SOURCES: PubMed, CINAHL, EMBASE, Web of Science, Cochrane and PsycINFO for articles in English published up to 31 December 2021. ELIGIBILITY CRITERIA: Articles were included if geofencing was used as a mechanism for intervention delivery. EXCLUSION CRITERIA: (1) a component or combination of GPS, geographical information system or ecological momentary assessment was used without delivery of an intervention; (2) did not include a health or health-related outcome from the geofencing intervention; or (3) was not a peer-reviewed study. DATA EXTRACTION AND SYNTHESIS: Several researchers independently reviewed all abstracts and full-text articles for final inclusion. RESULTS: A total of 2171 articles were found; after exclusions, nine studies were included in the review. The majority were published in 5 years preceding the search (89%). Geofences in most studies (n=5) were fixed and programmed in the mobile application carried by participants without their input. Mechanisms of geofencing interventions were classified as direct or indirect, with five studies (56%) using direct interventions. There were several different health outcomes (from smoking to problematic alcohol use) across the five studies that used a direct geofencing intervention. CONCLUSIONS: This scoping review found geofencing to be an emerging technology that is an acceptable and feasible intervention applied to several different populations and health outcomes. Future studies should specify the rationale for the locations that are geofenced and user input. Moreover, attention to mechanisms of actions will enable scientists to understand not only whether geofencing is an appropriate and effective intervention but why it works to achieve the outcomes observed.

Associations between police harassment and distrust in and reduced access to healthcare among Black sexual minority men: A longitudinal analysis of HPTN 061.

OBJECTIVE: Evaluate associations between racialized and homophobia-based police harassment (RHBPH) and healthcare distrust and utilization among Black Sexual Minority Men (BSMM). METHODS: We utilized data from a longitudinal cohort study from HIV Prevention Trials Network (HPTN) 061 with baseline, six and 12 month follow-up assessments. Using multivariable analysis, we evaluated associations between RHBPH and healthcare distrust and utilization reported at the 6 and 12 month visits. RESULTS: Of 1553 BSMM present at baseline, 1160 were available at six-month follow-up. In multivariable analysis, increasing frequency of RHBPH was associated with increasing levels of distrust in healthcare providers (aOR 1.31, 95% CI: 1.00, 1.74) and missing 50% or more of healthcare visits at six-month follow-up (aOR 1.93, 95% CI: 1.09, 3.43). CONCLUSIONS: Recent experiences of RHBPH are associated with reduced trust in and access to healthcare among BSMM, with more frequent RHBPH associated with greater vulnerability.

Potent Antifungal Activity of Penta-O-galloyl-ß-d-Glucose against Drug-Resistant Candida albicans, Candida auris, and Other Non-albicans Candida Species.

Among fungal pathogens, infections by drug-resistant Candida species continue to pose a major challenge to healthcare. This study aimed to evaluate the activity of the bioactive natural product, penta-O-galloyl-ß-d-glucose (PGG) against multidrug-resistant (MDR) Candida albicans, MDR Candida auris, and other MDR non-albicans Candida species. Here, we show that PGG has a minimum inhibitory concentration (MIC) of 0.25-8 µg mL-1 (0.265-8.5 µM) against three clinical strains of C. auris and a MIC of 0.25-4 µg mL-1 (0.265-4.25 µM) against a panel of other MDR Candida species. Our cytotoxicity studies found that PGG was well tolerated by human kidney, liver, and epithelial cells with an IC50 > 256 µg mL-1 (>272 µM). We also show that PGG is a high-capacity iron chelator and that deletion of key iron homeostasis genes in C. albicans rendered strains hypersensitive to PGG. In conclusion, PGG displayed potent anti-Candida activity with minimal cytotoxicity for human cells. We also found that the antifungal activity of PGG is mediated through an iron-chelating mechanism, suggesting that the compound could prove useful as a topical treatment for superficial Candida infections.

Spatial accessibility of pre-exposure prophylaxis (PrEP): different measure choices and the implications for detecting shortage areas and examining its association with social determinants of health.

PURPOSE: We examine how various pre-exposure prophylaxis (PrEP) accessibility measures impact the detection of PrEP shortage areas and the relation of shortage areas to social determinants of health (SDOH). METHODS: Using ZIP Code Tabulation Areas (ZCTAs) in New York City as a case study, we compared 25 measures of spatial PrEP accessibility across four categories, including density, proximity, two-step floating catchment area (2SFCA), and Gaussian 2SFCA (G2SFCA). Bayesian spatial regression models were used to examine how PrEP accessibility is associated with SDOH. RESULTS: Using density to measure PrEP accessibility for small areas such as ZCTAs poses challenges to statistical modeling because the measured accessibility values are highly skewed with excess zeros, leading to the necessity of using complex models such as the two-part mixture model. When G2SFCA measures are used, which account for distance decay effects and the competition from the PrEP demand side, findings on PrEP shortage area detection and the association between PrEP accessibility and SDOH were more consistent and less sensitive to spatial scales (i.e., varying from 10- to 30-minute driving). CONCLUSIONS: This research adds to the nascent research on PrEP accessibility measurement and sheds light on selecting an appropriate measure to assess spatial disparities in PrEP accessibility and its associations with SDOH.

Identification of triazenyl indoles as inhibitors of fungal fatty acid biosynthesis with broad-spectrum activity.

Rising drug resistance among pathogenic fungi, paired with a limited antifungal arsenal, poses an increasing threat to human health. To identify antifungal compounds, we screened the RIKEN natural product depository against representative isolates of four major human fungal pathogens. This screen identified NPD6433, a triazenyl indole with broad-spectrum activity against all screening strains, as well as the filamentous mold Aspergillus fumigatus. Mechanistic studies indicated that NPD6433 targets the enoyl reductase domain of fatty acid synthase 1 (Fas1), covalently inhibiting its flavin mononucleotide-dependent NADPH-oxidation activity and arresting essential fatty acid biosynthesis. Robust Fas1 inhibition kills Candida albicans, while sublethal inhibition impairs diverse virulence traits. At well-tolerated exposures, NPD6433 extended the lifespan of nematodes infected with azole-resistant C. albicans. Overall, identification of NPD6433 provides a tool with which to explore lipid homeostasis as a therapeutic target in pathogenic fungi and reveals a mechanism by which Fas1 function can be inhibited.

HIV Care Engagement Is Not Associated with COVID-19 Vaccination Hesitancy during the Initial Peak of the COVID-19 Pandemic among Black Cisgender Sexual Minority Men and Transgender Women in the N2 COVID Study.

BACKGROUND: Although there is limited literature on medication adherence (including HIV care engagement) and COVID-19 vaccine hesitancy in general populations (i.e., non-sexual or gender minority populations), even less is known about whether HIV care engagement correlates with COVID-19 vaccine hesitancy among sexual and gender minorities, especially those from intersectional backgrounds. The objective of the current study was to examine if an association exists between HIV status neutral care (i.e., current pre-exposure prophylaxis [PrEP] or antiretroviral therapy [ART] use) and COVID-19 vaccination hesitancy among Black cisgender sexual minority men and transgender women at the initial peak of the pandemic. METHODS: We conducted the N2 COVID Study in Chicago from 20 April 2020 to 31 July 2020 (analytic n = 222), including Black cisgender sexual minority men and transgender women who were vulnerable to HIV as well as those who were living with HIV. The survey included questions regarding HIV care engagement, COVID-19 vaccination hesitancy and COVID-19 related socio-economic hardships. Multivariable associations estimated adjusted risk ratios (ARRs) using modified Poisson regressions for COVID vaccine hesitancy adjusting for baseline socio-demographic characteristics and survey assessment time period. RESULTS: Approximately 45% of participants reported COVID-19 vaccine hesitancy. PrEP and ART use were not associated with COVID-19 vaccine hesitancy when examined separately or combined (p > 0.05). There were no significant multiplicative effects of COVID-19 related socio-economic hardships and HIV care engagement on COVID-19 vaccine hesitancy. CONCLUSIONS: Findings suggest no association between HIV care engagement and COVID-19 vaccine hesitancy among Black cisgender sexual minority men and transgender women at the initial peak of the pandemic. It is therefore essential that COVID-19 vaccine promotion interventions focus on all Black sexual and gender minorities regardless of HIV care engagement and COVID-19 vaccine uptake is likely related to factors other than engagement in HIV status neutral care.