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BackgroundThe opioid epidemic has ravaged rural communities in the United States. Despite extensive literature relating the physical environment to substance use in urban areas, little is known about the role of physical environment on the opioid epidemic in rural areas. ObjectiveThis study aimed to examine the reliability of Google Earth to collect data on the physical environment related to substance use in rural areas. MethodsSystematic virtual audits were performed in 5 rural Kentucky counties using Google Earth between 2017 and 2018 to capture land use, health care facilities, entertainment venues, and businesses. In-person audits were performed for a subset of the census blocks. ResultsWe captured 533 features, most of which were images taken before 2015 (71.8%, 383/533). Reliability between the virtual audits and the gold standard was high for health care facilities (>83%), entertainment venues (>95%), and businesses (>61%) but was poor for land use features (>18%). Reliability between the virtual audit and in-person audit was high for health care facilities (83%) and entertainment venues (62%) but was poor for land use (0%) and businesses (12.5%). ConclusionsPoor reliability for land use features may reflect difficulty characterizing features that require judgment or natural changes in the environment that are not reflective of the Google Earth imagery because it was captured several years before the audit was performed. Virtual Google Earth audits were an efficient way to collect rich neighborhood data that are generally not available from other sources. However, these audits should use caution when the images in the observation area are dated.

Recent advances in cancer therapeutics clearly demonstrate the need for innovative multiplex therapies that attack the tumour on multiple fronts. Oncolytic or "cancer-killing" viruses (OVs) represent up-and-coming multi-mechanistic immunotherapeutic drugs for the treatment of cancer. In this study, we perform an in-vitro screen based on virus-encoded artificial microRNAs (amiRNAs) and find that a unique amiRNA, herein termed amiR-4, confers a replicative advantage to the VSVΔ51 OV platform. Target validation of amiR-4 reveals ARID1A, a protein involved in chromatin remodelling, as an important player in resistance to OV replication. Virus-directed targeting of ARID1A coupled with small-molecule inhibition of the methyltransferase EZH2 leads to the synthetic lethal killing of both infected and uninfected tumour cells. The bystander killing of uninfected cells is mediated by intercellular transfer of extracellular vesicles carrying amiR-4 cargo. Altogether, our findings establish that OVs can serve as replicating vehicles for amiRNA therapeutics with the potential for combination with small molecule and immune checkpoint inhibitor therapy.

The liver plays a central role in metabolism and produces important hormones. Hepatic estrogen receptors and the release of insulin-like growth factor 1 (IGF1) are critical links between liver function and the reproductive system. However, the role of liver in pubertal development is not fully understood. To explore this question, we applied transcriptomic analyses to liver samples of pre- and post-pubertal Brahman heifers and identified differentially expressed (DE) genes and genes encoding transcription factors (TFs). Differential expression of genes suggests potential biological mechanisms and pathways linking liver function to puberty. The analyses identified 452 DE genes and 82 TF with significant contribution to differential gene expression by using a regulatory impact factor metric. Brain-derived neurotrophic factor was observed as the most down-regulated gene (P = 0.003) in post-pubertal heifers and we propose this gene influences pubertal development in Brahman heifers. Additionally, co-expression network analysis provided evidence for three TF as key regulators of liver function during pubertal development: the signal transducer and activator of transcription 6, PBX homeobox 2, and polybromo 1. Pathway enrichment analysis identified transforming growth factor-beta and Wnt signaling pathways as significant annotation terms for the list of DE genes and TF in the co-expression network. Molecular information regarding genes and pathways described in this work are important to further our understanding of puberty onset in Brahman heifers.

Objectives. To analyze War on Drugs encounters and their relationships to health care utilization among White people who use drugs (PWUD) in 22 Appalachian rural counties in Kentucky, West Virginia, Ohio, and North Carolina. Methods. We recruited White PWUD using chain referral sampling in 2018 to 2020. Surveys asked about criminal–legal encounters, unmet health care needs, and other covariates. We used generalized estimating equations to regress unmet need on criminal–legal encounters in multivariable models. Results. In this sample (n = 957), rates of stop and search, arrest, incarceration, and community supervision were high (44.0%, 26.8%, 36.3%, and 31.1%, respectively), as was unmet need (68.5%). Criminal–legal encounters were unrelated to unmet need (stops: adjusted prevalence ratio [APR] = 1.13; 95% confidence interval [CI] = 0.97, 1.32; arrest: APR = 0.95; 95% CI = 0.78, 1.15; incarceration: APR = 1.01; 95% CI = 0.89, 1.14; community supervision: APR = 0.99; 95% CI = 0.90, 1.09). Conclusions. Contrasting with findings from predominantly Black urban areas, criminal–legal encounters and unmet need were unrelated among White Appalachian PWUD. Research should explore whether and under what conditions White supremacy's benefits might buffer adverse impacts of the War on Drugs in Appalachia. (Am J Public Health. 2024;114(10):1086–1096. https://doi.org/10.2105/AJPH.2024.307744) [ABSTRACT FROM AUTHOR]

In a pilot study providing HIV self-testing to persons who use drugs (N = 40), we identified 3 new HIV cases when partnering with a community-based organization. Most (82%) participants were interested in preexposure prophylaxis. HIV self-testing could contribute to efforts to Ending the HIV Epidemic in the United States. ClinicalTrials.gov registration: NCT05528562 [ABSTRACT FROM AUTHOR]

Black men who have sex with men (BMSM) are at higher risk of HIV transmission than any other group; however, their uptake of the highly effective HIV prevention medication, pre-exposure prophylaxis (PrEP), is low. In collaboration with a communitybased organization in Atlanta, Georgia, we explored ten HIV-negative BMSM's willingness to obtain PrEP in pharmacies using standard open-ended and vignette qualitative methods. Three overarching themes were identified: privacy, patient-pharmacist interactions, and HIV/STI screening. While open-ended questions allowed participants to provide broad answers on their willingness to receive prevention services at a pharmacy, the vignette drew out specific responses to facilitate in-pharmacy PrEP delivery. Using both openended questions and vignette data collection strategies, BMSM reported high willingness to screen for and uptake PrEP in pharmacies. However, the vignette method allowed for greater depth. Open-ended questions elicited responses that highlighted general barriers and facilitators of PrEP dispensing in pharmacies. However, the vignette allowed participants to customize a plan of action that would best fit their needs. Vignette methods are underutilized in HIV research and may be helpful in supplementing standard open-ended interview questions to uncovering unknown challenges about health behaviors and obtain more robust data on highly sensitive research topics in HIV research. [ABSTRACT FROM AUTHOR]

The perverseness of racial and ethnic inequities in the United States continues to implore the investigation of their causes. While there have been improvements in the health of the US population, these improvements have not been equally distributed. To commemorate the 100th anniversary of the American Journal of Epidemiology , in this commentary, we aim to highlight the Journal 's contributions to: 1) the definition and use of race and ethnicity in research, and 2) understanding racial and ethnic inequities, both empirically and methodologically, over the past decade. We commend the Journal for its contributions and for spearheading many of the challenges related to measuring and interpreting racial and ethnic data for the past 20 years. We identify 3 additional areas in which the Journal could make further impact to address racial and ethnic inequities: 1) devote a section in every issue of the Journal to scientific papers that make substantive epidemiologic or methodological contributions to racial and ethnic inequities in health; 2) update the Journal 's guidelines for authors to include justifying the use of race and ethnicity; and 3) diversify the field of epidemiology by bringing a new cadre of scholars from minoritized racial and ethnic groups who represent the most affected communities into the research process. [ABSTRACT FROM AUTHOR]

Objectives: In an effort to reduce HIV transmission among injection drug users (IDUs), New York State deregulated pharmacy syringe sales in 2001 through the Expanded Syringe Access Program by removing the requirement of a prescription. With evidence suggesting pharmacists' ability to expand their public health role, a structural, pharmacy-based intervention was implemented to determine whether expanding pharmacy practice to include provision of HIV risk reduction and social/medical services information during the syringe sale would (a) improve pharmacy staff attitudes toward IDUs (b) increase IDU syringe customers, and (c) increase prescription customer base in New York City neighborhoods with high burden of HIV and illegal drug activity. Methods: Pharmacies (n = 88) were randomized into intervention (recruited IDU syringe customers into the study and delivered intervention activities), primary control (recruited IDU syringe customers only) and secondary control (did not recruit IDUs or deliver intervention activities) arms. Results: Pharmacy staff in the intervention versus secondary control pharmacies showed significant decreases in the belief that selling syringes to IDUs causes community loitering. Conclusions: Structural interventions may be optimal approaches for changing normative attitudes about highly stigmatized populations.

This study examines the association between race and self-rated health status among Hispanic and non-Hispanic adults in the 2003 Behavioral Risk Factor Surveillance System survey (N = 241,038). Logistic regression was used to estimate the odds of self-rated health as fair/poor for Hispanic Blacks, Hispanic Whites, and non-Hispanic Blacks as compared with non-Hispanic Whites. This study found that, first, Hispanic Blacks were more likely to rate their health as fair/poor than Hispanic and non-Hispanic Whites, and second, there was no difference between Hispanic and non-Hispanic Blacks. Specifically, when compared with non-Hispanic Whites, Hispanic Blacks and Whites were more likely to report their health as fair/poor. However, this association was stronger for Hispanic Blacks. More careful examination of race among Hispanics is imperative to unmask important health variations. (Contains 1 figure and 3 tables.)