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Sexual minority women (SMW; women who self-identify as lesbian, queer, etc., as well as heterosexually-identified women who experience attraction to romantic or sexual partnerships with women) and vulnerabilized women (those marginalized due to structural forces such as housing insecurity, violence, sex exchange, drug use, or HIV positive status) experience a range of mental health challenges compared to their heterosexual and general population counterparts. General populations studies show a positive relationship between social support and mental health; less is known about SMW experiencing intersecting multi-layered vulnerabilities. This study characterizes mental health stressors, identifies social support sources and forms, and explores the relationship between social support and mental health among vulnerabilized SMW in Baltimore, MD. We conducted virtual, in-depth semi-structured interviews with vulnerabilized cisgender SMW (n = 25) between June and October 2021. We utilized an inductive analytical approach to identify central themes and develop a categorization structure. Results are presented using narrative synthesis and illustrative quotes. To understand different forms of mental health-related social support provided across sources, data was sorted into a matrix and analyzed. Vulnerabilized SMW commonly self-reported depression and anxiety. Participants identified three primary mental health stressors: 1) managing identity-related stigma; 2) relationships, loss, and isolation; and 3) financial struggles. The most important type of social support for mental health was non-judgement related to sexual orientation and/or mental health struggles. Family, friends, and partners were providing similar amounts of support, primarily emotional support. Vulnerabilized SMW have unique mental health and social support-related experiences and needs, potentially attributed to experiences with multiple marginalization, compounded by struggles with intersecting structural vulnerabilities. More research is warranted to explore different sources and forms of social support as predictors of mental health. Findings indicate need for public health interventions that address sexual orientation and mental health stigma.

Obwohl kunstbasierte Verfahren in der Gesundheitsforschung an Popularität gewonnen haben, werden sie eher selten systematisch integriert. Gerade weil menschliches Erleben jedoch komplex und emotional ist, wäre es unangemessen, auf Methoden zu verzichten, die unterschiedliche Erfahrensweisen mobilisieren. Ich diskutiere deshalb in diesem Beitrag, wie diese Verfahren kreativ und konsequent im Forschungsprozess genutzt werden können. Hierzu nutze ich Beispiele aus meiner Masterarbeit, in der mich mit den Liebesbeziehungen von Frauen beschäftigt habe, die an einem Reizdarmsyndrom leiden. Die Ergebnisse veranschaulichen, dass mittels kunstbasierter Ansätze unterschiedliche Wissensformen sowie der Ausdruck von persönlichem Denken und Fühlen eruiert werden können, wenn über herkömmliche Wege der Wissensgenerierung hinausgegangen wird. Ich zeige, wie dies in jedem Abschnitt des Forschungsprozesses gelingen kann.

Accumulation of somatic mutations in the mitochondrial genome (mtDNA) has long been proposed as a possible mechanism of mitochondrial and tissue dysfunction that occurs during aging. A thorough characterization of age-associated mtDNA somatic mutations has been hampered by the limited ability to detect low-frequency mutations. Here, we used Duplex Sequencing on eight tissues of an aged mouse cohort to detect >89,000 independent somatic mtDNA mutations and show significant tissue-specific increases during aging across all tissues examined which did not correlate with mitochondrial content and tissue function. G→A/C→T substitutions, indicative of replication errors and/or cytidine deamination, were the predominant mutation type across all tissues and increased with age, whereas G→T/C→A substitutions, indicative of oxidative damage, were the second most common mutation type, but did not increase with age regardless of tissue. We also show that clonal expansions of mtDNA mutations with age is tissue- and mutation type-dependent. Unexpectedly, mutations associated with oxidative damage rarely formed clones in any tissue and were significantly reduced in the hearts and kidneys of aged mice treated at late age with elamipretide or nicotinamide mononucleotide. Thus, the lack of accumulation of oxidative damage-linked mutations with age suggests a life-long dynamic clearance of either the oxidative lesions or mtDNA genomes harboring oxidative damage.

Analysis of system-wide cellular communication changes in Alzheimer’s disease (AD) has recently been enabled by single nucleus RNA sequencing (snRNA-seq) and new computational methods. Here, we combined these to analyze data from postmortem human tissue from the entorhinal cortex of people with AD and compared our findings to those from multiomic data from the 5xFAD amyloidogenic mouse model at two different time points. Using the cellular communication inference tool CellChat we found that disease-related changes were largely related to neuronal excitability as well as synaptic communication, with specific signaling pathways including BMP, EGF, and EPHA, and relatively poor conservation of glial-related changes during disease. Further analysis using the neuron-specific NeuronChat revealed changes relating to metabotropic glutamate receptors as well as neuronal adhesion molecules including neurexins and neuroligins. Our results that cellular processes relating to excitotoxicity are the best conserved between 5xFAD mice and AD suggest that excitotoxicity is the main common feature between pathogenesis in 5xFAD mice and people with AD.

COVID-19 testing is an important risk mitigation strategy for COVID-19 prevention in school settings, where the virus continues to pose a public health challenge for in-person learning. Socially vulnerable school communities with the highest proportion of low-income, minority, and non-English speaking families have the least testing access despite shouldering a disproportionate burden of COVID-19 morbidity and mortality. Through the Safer at School Early Alert (SASEA) program, we investigated community perceptions of testing in San Diego County schools, with a focus on barriers and facilitators from the perspective of socially vulnerable parents and school staff. Using a mixed-methods approach, we administered a community survey and conducted focus group discussions (FGDs) with staff and parents from SASEA-affiliated schools and childcares. We recruited 299 survey respondents and 42 FGD participants. Protecting one’s family (96.6%) and protecting one’s community (96.6%) were marked as key motivators to testing uptake. School staff in particular reported that the reassurance of a negative status mitigated concerns about COVID-19 infection in schools. Participants expressed that COVID-19-related stigma, loss of income as a result of isolation/quarantine requirements, and lack of multilingual materials were the most significant barriers to testing. Our findings suggest that the testing barriers faced by school community members are predominantly structural. Testing uptake efforts must provide support and resources to manage the social and financial consequences of testing while continuously communicating its benefits. There is a clear need to continue to incorporate testing as a strategy to maintain school safety and facilitate access for vulnerable community members.

Background Before SARS-CoV-2 vaccination availability, medical center employees were at high risk of COVID-19. However, risk factors for SARS-CoV-2 infection in medical center employees, both healthcare and non-healthcare workers, are poorly understood. Methods From September-December 2020, free IgG antibody testing was offered to all employees at a large urban medical center. Participants were asked to complete a questionnaire on work and non-work related risk factors for COVID-19 infection. Results SARS-CoV-2 seropositivity was found in 4.7%. Seropositivity was associated with close contact with COVID-19 cases with or without the use of adequate personal protective equipment (PPE), (OR 3.1 [95% CI 1.4–6.9] and OR 4.7 [95% CI 2.0–11.0] respectively), never wearing a mask outside of work (OR 10.1 [95% CI 1.9–57]), and Native Hawaiian/Pacific Islander race (OR 6.3 95% CI (1.6–25)]. Conclusions Among workers in a large urban medical center, SARS-CoV-2 seropositivity was associated with work-related COVID-19 close contacts and low mask use outside of work, suggesting that non-workplace close contacts are also relevant routes of COVID-19 spread among healthcare workers.

Background Sexual minority women (SMW) experience higher rates of substance use relative to heterosexual women in the U.S. but remain an under-studied population. SMW who inject drugs (SMWWID) navigate an unpredictable drug market and may experience complex relationships within their social spheres. We explore cisgender SMWWID’s strategies to maintain safety while injecting drugs, and the influence of their social support systems on those strategies. Methods We conducted N  = 16 phone-based, semi-structured, in-depth interviews with SMWWID in Baltimore, Maryland between June-October 2021. The interviews explored participants’ sexual orientation and gender identities, social networks and support systems, drug use behaviors and HIV risk, and experiences accessing services. Using an inductive thematic analysis approach, we examined emergent themes related to drug use, social support, safety, and HIV and identified key safety strategies and social support experiences for SMWWID. Results SMWWID employed various strategies to “stay safe,” which they primarily interpreted as ensuring overdose safety (i.e., using drugs in the presence of others, carrying Naloxone, purchasing strategies), and additionally as infectious disease safety (i.e., avoiding syringe sharing, using sterile syringes) and avoiding threats of violence (i.e., maintaining situational awareness while using drugs). Romantic or sexual partners, family and friends, and the wider community were sources of social support for overdose safety, and family and friends also provided material support (e.g., financial, housing). Syringe sharing with romantic partners and threats of violence from people in the community detracted from SMWWID’s safety. Conclusion SMWWID in this sample reported strong safety prioritization while using drugs, often facilitated by their social support systems. Harm reduction interventions that consider SMWWID’s relationships, including those that aim to improve social connectedness, may better meet the needs of SMWWID, thereby enhancing safety.

ObjectivesTo evaluate the uptake of a platform for virtual visits in primary care, examine patient and physician preferences for virtual communication methods and report on characteristics of visits and patients experience of care.DesignA retrospective cohort study.SettingPrimary care practices within five regions in Ontario, Canada after 18 months of access to virtual care services.Participants326 primary care providers and 14 291 registered patients.InterventionsProviders used a platform that allowed them to connect with their patients through synchronous (audio/video) and/or asynchronous (secure messaging) communication.Main outcome measuresUser-level data from the platforms including patient demographics, practice characteristics, communication modality used, visit characteristics and patients’ satisfaction.ResultsAmong the participants, 44% of registered patients and 60% of registered providers used the platform at least once. Among patient users, 51% completed at least one virtual visit. The majority of virtual visits (94%) involved secure messaging. The most common patient requests were for medication prescriptions (24%) and follow-up from previous appointment (22%). The most common provider request was to follow-up on test results (59%). Providers indicated that 81% of virtual visits required no follow-up for that issue and 99% of patients reported that they would use virtual care services again.ConclusionsWhile there are a growing number of primary care video visit services, our study found that both patients and providers in rostered practices prefer secure messaging over video. Despite fears that virtual visits would be overused by patients, when patients connected with their own primary care provider, many virtual visits appeared to replace in-person visits, and patients did not overwhelm physicians with requests. This approach may improve access and continuity in primary care.

Aging is characterized by the accumulation of proteins that display amyloid-like behavior. However, the molecular mechanisms by which these proteins arise remain unclear. Here, we demonstrate that amyloid-like proteins are produced in a variety of human cell types, including stem cells, brain organoids and fully differentiated neurons by mistakes that occur in messenger RNA molecules. Some of these mistakes generate mutant proteins already known to cause disease, while others generate proteins that have not been observed before. Moreover, we show that these mistakes increase when cells are exposed to DNA damage, a major hallmark of human aging. When taken together, these experiments suggest a mechanistic link between the normal aging process and age-related diseases.

Introduction Adverse drug events (ADEs) are associated with poor outcomes and increased costs but may be prevented with prediction tools. With the National Institute of Health All of Us (AoU) database, we employed machine learning (ML) to predict selective serotonin reuptake inhibitor (SSRI)-associated bleeding. Methods The AoU program, beginning in 05/2018, continues to recruit ≥ 18 years old individuals across the United States. Participants completed surveys and consented to contribute electronic health record (EHR) for research. Using the EHR, we determined participants who were exposed to SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, vortioxetine). Features ( n  = 88) were selected with clinicians’ input and comprised sociodemographic, lifestyle, comorbidities, and medication use information. We identified bleeding events with validated EHR algorithms and applied logistic regression, decision tree, random forest, and extreme gradient boost to predict bleeding during SSRI exposure. We assessed model performance with area under the receiver operating characteristic curve statistic (AUC) and defined clinically significant features as resulting in > 0.01 decline in AUC after removal from the model, in three of four ML models. Results There were 10,362 participants exposed to SSRIs, with 9.6% experiencing a bleeding event during SSRI exposure. For each SSRI, performance across all four ML models was relatively consistent. AUCs from the best models ranged 0.632–0.698. Clinically significant features included health literacy for escitalopram, and bleeding history and socioeconomic status for all SSRIs. Conclusions We demonstrated feasibility of predicting ADEs using ML. Incorporating genomic features and drug interactions with deep learning models may improve ADE prediction.