Department of Medicine

Existing research highlights TB's economic and social stigma burdens and impacts behavior in households, but virtually unexplored is the dynamics of TB and parenthood. This qualitative study examines the interplay between TB diagnosis and treatment, and parenting experiences, focusing on the intersections of individual agency, societal expectations, and access to resources. From March 2021 to January 2022, we conducted in-depth interviews with 98 TB patients in Buffalo City, South Africa, including 44 mothers and 54 fathers. Guided by the Network-Individual-Resource (NIR) model, we applied layered coding, memoing, and causal mapping to analyze experiences through the lens of agency and societal expectations. Mothers reported primary caregiving responsibilities, drawing motivation from their children, and relying on multigenerational family support for childcare and treatment-adherence. Children frequently provided emotional and practical care, such as cooking and medication reminders. Fathers more often distanced themselves to protect families from infection, faced isolation, and struggled to fulfill provider roles due to job loss. Extended family support for fathers was limited, with financial pressures exacerbating treatment challenges. These results illustrate how gender norms and resources structure the TB experience. Strengthening maternal caregiving networks and reimagining fatherhood beyond economic provision can foster better adherence and more equitable health outcomes.

Post acute sequelae of SARS-CoV-2 infection (also known as Long COVID) have been defined as symptoms that persist after 3 months from initial acute episode of COVID-19. While the pathophysiology and mechanisms that cause Long COVID are hypothesized as secondary to persistent inflammation and immune dysregulation, the burden of this disease remains difficult to estimate due to varied symptomatology. Solid-organ transplant recipients in particular remain a vulnerable population that has been disproportionately affected by the COVID-19 pandemic, and the impact of Long COVID among orthotopic heart transplant recipients (OHTRs)-a patient population on chronic immunosuppressive therapy-remains incompletely characterized. We sought to evaluate patient-reported Long COVID symptoms between OHTRs compared to patients with baseline cardiomyopathy. We conducted a prospective survey-based study of adult OHTRs and cardiomyopathy control patients with documented SARS-CoV-2 infection. Participants completed telephone surveys, which included questionnaires of symptoms, quality of life (QOL), and mental health assessment. Between-group differences were evaluated using multivariable models adjusting for baseline characteristics. Our results show that the prevalence of Long COVID symptoms did not significantly differ between OHTRs and patients with cardiomyopathy. Dyspnea was reported more frequently in the non-OHTR group; however, this association was attenuated after adjusting for a higher burden of underlying pulmonary disease. No evidence of increased overall symptom burden was observed among OHTRs. In this first comparative analysis of Long COVID among OHTRs and control cardiomyopathy patients, OHTRs demonstrated no increase in symptom burden and may experience fewer persistent symptoms.

Exercise reduces cardiovascular events, yet its interactions with parathyroid hormone (PTH) and atherosclerotic calcification as well as their combined effects on cardiac remodeling remain unclear. Thus, we tested effects of constitutive activation of the PTH type I receptor (PTH1R) with and without exercise on aortic calcification and cardiovascular remodeling in a mouse model of atherosclerotic calcification. Female Ldlr^{-/-;Tagln-PTH1R} transgenic (Tg) and Ldlr^-/- littermate control (Ctrl) mice were fed a Western diet beginning at 9-10 weeks of age. At age 40 weeks, mice were assigned to sedentary (SED) or treadmill exercise (TM) regimens for 9 weeks. MicroPET/CT and echocardiography were performed at baseline and study completion. By microCT, aortic calcium content increased in all four groups. However, ¹⁸F-NaF uptake, reflecting mineral surface area, increased only in Ctrl/TM mice. Systolic function improved and left ventricular (LV) mass decreased in Tg/TM and Ctrl/TM groups. However, in Ctrl/TM mice, LV chamber diameter increased while anterior wall thickness decreased, consistent with eccentric remodeling. In contrast, in Tg/TM mice, diastolic wall thickness decreased without chamber enlargement, indicating preserved geometry and enhanced contractile efficiency. In sedentary mice (Tg/SED and Ctrl/SED), diastolic LV diameter increased without changes in wall thickness or systolic function, consistent with ventricular remodeling due to aortic stiffening in hyperlipidemia. These findings suggest that vascular PTH1R signaling selectively modulates cardiovascular adaptation to exercise. By preserving geometry and improving contractile efficiency, PTH1R activation augments the beneficial effects of exercise on adverse cardiac remodeling in atherosclerotic calcification, supporting endocrine and exercise contributions to ventricular-vascular coupling.

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Aims: This study assesses whether changes in body composition - lean body mass (LBM) and body fat % (BF%) - and body mass index (BMI), in patients undergoing cardiac rehabilitation (CR), are associated with long-term outcomes. Methods: In this cohort study of 1234 adults with coronary artery disease (CAD) who participated in CR from April 2012 to June 2024, bioelectric impedance analysis was used at baseline and after CR to assess body composition. Outcomes assessed included net adverse cardiovascular events (NACE) and all-cause mortality. Results: Subjects were followed for a mean of 5.9 years (SD 3.2). We found that those who had an increase in BF% during CR had a higher risk of NACE (adjusted HR 1.44, 95% CI: 1.10, 1.90) compared to those who had a decrease in BF%. There was also a trend towards decreased mortality in patients with a moderate increase in LBM (adjusted HR 0.49, 95% CI 0.23, 1.02). There were no associations between changes in body mass index and any outcomes. When the cohort was stratified by sex, both males and females had higher adjusted risk of NACE with BF% increase, but the finding was only statistically significant in males. Conclusion: An increase in BF% during CR was associated with increased NACE in patients with CAD. Overall, these findings suggest that interventions to address body composition change, particularly decreasing BF%, may be important in mitigating cardiovascular events in patients undergoing CR.

Ca²⁺ signaling and its regulation are important for endothelial cell (EC) function and signaling. Yet, the spatiotemporal organization of Ca²⁺ activity and its regulation across a vascular plexus is poorly understood in an in vivo mammalian context. To overcome this gap in knowledge, we developed an intravital imaging approach to resolve Ca²⁺ activity with single-cell resolution in skin vasculature of adult mice via multiphoton microscopy. Here, we tracked thousands of Ca²⁺ events in the skin capillary plexus during homeostasis and observed signaling heterogeneity between ECs, with just over half displaying Ca²⁺ activity at any given time. Longitudinal tracking of the same mice revealed that the same capillary ECs maintain Ca²⁺ activity over days to weeks. Interestingly, activity dynamics, such as frequency and event duration, are not conserved at a single-cell level but are maintained at an EC population level. Molecularly, conditional deletion of the gap junction protein Connexin 43 (Cx43cKO) in ECs leads to a subset of ECs displaying sustained Ca²⁺ activity, biasing signaling dynamics of the whole network toward chronically persistent activity over time. Sustained capillary Ca²⁺ activity results in vascular permeability and flow dysregulation. Last, through pharmacological targeting of known agonists/antagonists, we showed that inhibition of L-type Voltage Gated Ca²⁺ channels non-cell-autonomously restores Ca²⁺ activity, blood flow, and barrier function in Cx43cKO mice. Collectively, our work provides insight into the spatial and temporal characteristics, extent, and regulation of Ca²⁺ activity in skin capillaries of live mice.

BackgroundHip fracture is a global public health concern, with over 10 million cases worldwide in 2019. Post-hip fracture outcomes, including mortality, vary by type 2 diabetes (T2D) co-diagnosis and patient demographics.ObjectiveTo examine post-hip fracture outcomes and identify factors modifying mortality differences in a racially and ethnically diverse population of older United States (US) adults with T2D.DesignRetrospective cohort study using Medicare fee-for-service data from 2014 to 2020.ParticipantsMen and women aged > 65 years, with T2D diagnosis who had experienced a non-traumatic hip fracture.Main Measure(s)We evaluated associations between race and ethnicity and one-year mortality, dual energy x-ray absorptiometry (DXA) testing, osteoporosis treatment, and incident destitution post-hip fracture using multivariable Cox proportional hazards models.Key ResultsAmong 159,699 older adults with T2D, one-year post-hip fracture mortality was 30.4%. In age- and sex-adjusted models, mortality was higher in Black individuals (HR 1.26 [95% CI, 1.22–1.31) and lower in Asian and Hispanic individuals (HR 0.78 [95% CI, 0.73–0.83] and 0.91 [95% CI,0.86–0.96], respectively) compared with White individuals. Elevated mortality in Black individuals persisted across subgroups stratified by sex, age, region, BMI, and frailty, but not among those with advanced chronic kidney disease (CKD stages 4–5; HR 1.01 [0.93–1.09]) or low socioeconomic status (SES; Medicaid eligibility; HR 1.00 [0.88–1.14]). Models adjusting for important demographic and clinical covariates mitigated mortality differences between Black and White individuals. DXA testing and osteoporosis treatment initiation rates were low overall (7.3% and 5.6%, respectively). Black individuals had lower DXA testing (HR 0.51 [0.45–0.56]) and treatment (HR 0.58 [0.51–0.65]) rates, and higher incident destitution (HR 1.41 [1.29–1.55]) than White individuals in all models.ConclusionsOverall mortality was high and guideline-concordant care was low in the first year post-hip fracture in Medicare-insured older adults with T2D. Furthermore, racial and ethnic differences in post-hip fracture mortality and management exist.

Systemic administration of antibodies that target immune checkpoint inhibitor pathways is a highly effective approach to cancer immunotherapy, but systemic toxicity can limit clinical utility. In preclinical testing, a peri-tumor injection of a low dose of hydrogel-encapsulated cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody was shown to selectively activate T cells in tumor-draining lymph nodes, induce tumor infiltration by cytotoxic T cells, and result in tumor regression, protective immunity, and long-term survival. In contrast to systemic therapy, there was limited systemic exposure or risk for autoimmune toxicity. The current study focuses on translating this platform into a biocompatible human therapeutic. The hydrogel matrix was reformulated using a low-molecular-weight hyaluronic acid. A recombinant human hyaluronidase (rHuPH20) was incorporated to promote lymph node targeting and self-resorbing features. Formulations were optimized to operate at neutral pH and with gelation kinetics allowing a 5 to 10 min administration window. Performance features were assessed including the capacity to encapsulate human IgG or ipilimumab antibody at proposed therapeutic doses (1–15 mg/mL), impact of rHuPH20 and antibody on rheologic properties and three-dimensional microstructure, and payload delivery profiles in vitro and in vivo. Results confirm the capacity for this unique hydrogel platform to be adapted for human testing.

Background Sexual and gender minority (SGM) individuals in South Africa's Eastern Cape face dual challenges navigating progressive constitutional protections alongside persistent cultural conservatism. Traditional Xhosa practices, including initiation schools (Ulwaluko) and ceremonial rituals, enforce rigid gender roles that conflict with SGM identities. With HIV prevalence reaching 49.5 % among men who have sex with men yet only 25.7 % achieving viral suppression, understanding how SGM individuals negotiate cultural traditions while managing HIV remains critically understudied. Methods This qualitative study explored post-intervention experiences of 31 SGM individuals living with HIV in the Eastern Cape following participation in the SOAR (Speaking Out & Allying Relationships) intervention. Semi-structured interviews, guided by Social Cognitive Theory, were conducted in participants' preferred language by trained local interviewers. Thematic analysis through the Minority Stress Model examined four domains: traditional practices, family dynamics, community perceptions, and intervention impact. Results Participants demonstrated resilience through selective participation in cultural practices, balancing ancestral reverence with identity authenticity. Family acceptance was often conditional, tied to economic contributions or heteronormative expectations. Health communication barriers persisted due to stigma and traditional beliefs linking HIV to moral failing. SOAR enhanced participants' status-sharing confidence, treatment adherence, and skills for navigating cultural tensions, though community stigma remained pronounced in rural areas. Conclusion SGM individuals exhibit remarkable adaptability in negotiating intersecting cultural, familial, and health challenges. While SOAR effectively builds individual resilience and HIV management skills, findings underscore the need for multi-level interventions combining skill-building with community mobilization and cultural sensitization to address structural barriers in traditional contexts.