Faculty Bibliography

BACKGROUND:South Asians face a high prevalence of type II diabetes (DMII) and comorbid hypertension (HTN). Community health worker (CHW) interventions have the potential to improve chronic disease outcomes, yet few have been tailored to South Asian populations in the United States. OBJECTIVE:To test the effectiveness of an evidence-based CHW-led and culturally-tailored HTN and DMII management program for South Asian adults with diabetes and comorbid uncontrolled HTN (systolic blood pressure (SBP) > 130 mmHg or diastolic blood pressure (DBP) > 80 mmHg). DESIGN/METHODS:Randomized-controlled Trial. PARTICIPANTS/METHODS:South Asian adults with DMII and comorbid HTN. INTERVENTION/METHODS:The Diabetes Research, Education, and Action for Minorities (DREAM) Atlanta intervention was a CHW telehealth intervention designed to improve blood pressure (BP). The treatment group received five virtual group-based health education sessions, an action plan, and follow-up calls to assess goal setting activities. The control group received only the first session. Main Measures included: feasibility, improvement in BP control, and decreases in SBP, DBP, weight, and hemoglobin A1c (HbA1c). KEY RESULTS/RESULTS:A total of 190 South Asian adults were randomized (97 to the treatment group and 93 to the control group); 94% of treatment group participants completed all 5 telehealth sessions. At endpoint, BP control increased 33.7% (95% CI: 22.5, 44.9, p < 0.001) in the treatment group and 16.5% (95%: 6.2, 26.8, p = 0.003) in the control group; the adjusted intervention effect was 1.8 (95% CI: 1.0, 3.2, p = 0.055). Mean weight decreased by 4.8 pounds (95% CI: -8.2, -1.4, p = 0.006) in the treatment group, and the adjusted intervention effect was -5.2 (95% CI: -9.0, -1.4, p = 0.007. The intervention had an overall retention of 95%. CONCLUSIONS:A culturally-tailored, CHW-led telehealth intervention is feasible and can improve BP control among South Asian Americans with DMII. GOV REGISTRATION/UNASSIGNED:NCT04263311.

A wooden house frame consists of many different lumber pieces, but because of the regularity of these building blocks, the structure can be designed using straightforward geometrical principles. The design of multicomponent protein assemblies, in comparison, has been much more complex, largely owing to the irregular shapes of protein structures¹. Here we describe extendable linear, curved and angled protein building blocks, as well as inter-block interactions, that conform to specified geometric standards; assemblies designed using these blocks inherit their extendability and regular interaction surfaces, enabling them to be expanded or contracted by varying the number of modules, and reinforced with secondary struts. Using X-ray crystallography and electron microscopy, we validate nanomaterial designs ranging from simple polygonal and circular oligomers that can be concentrically nested, up to large polyhedral nanocages and unbounded straight 'train track' assemblies with reconfigurable sizes and geometries that can be readily blueprinted. Because of the complexity of protein structures and sequence-structure relationships, it has not previously been possible to build up large protein assemblies by deliberate placement of protein backbones onto a blank three-dimensional canvas; the simplicity and geometric regularity of our design platform now enables construction of protein nanomaterials according to 'back of an envelope' architectural blueprints.

BACKGROUND:Cardiometabolic risk factors diabetes, obesity, and hypertension are highly prevalent and contribute to increased cardiovascular disease (CVD). Endothelial dysfunction precedes CVD development. The current study aimed to investigate the EC transcriptome among individuals with varying degree of cardiometabolic risk. METHODS:Adult participants without CVD and various degrees of cardiometabolic risk factor burden (hypertension, diabetes, obesity) were included. Participants underwent brachial vein EC harvesting followed by RNA sequencing. To evaluate the association between cardiometabolic comorbidity burden and outcome transcripts we performed linear regression with multivariable models, adjusting for age, sex, and race/ethnicity. RESULTS:A total of 18 individuals were included in the present analysis (mean age 47 ± 14, 44% female, and 61% White adults). Endothelial cell RNA sequencing revealed 588 differentially expressed transcripts (p-adj <0.05) with excellent discrimination in unsupervised hierarchical clustering analysis. Gene ontology enrichment analysis revealed upregulated pathways associated with T-cell activation (NES = 2.22, p<0.001), leukocyte differentiation (NES= 2.16, p<0.001), leukocyte migration (NES= 2.12, p<0.001), regulation of cell-cell adhesion (NES= 1.91, p=0.006). Downregulated pathways of interest included endothelial cell proliferation (NES= -1.68, p=0.03) and response to interleukin-1 (NES= -1.61, p=0.04). Upregulated genes included VCAM1, CEACAM1, ADAM 17, and CD99L2, all with a log-2-fold change >3 and p-adj <0.05. These genes demonstrated a graded increase in mean normalized counts with increasing number of risk factors. CONCLUSIONS:We demonstrate a proinflammatory and pro-adhesive EC transcriptome associated with increased cardiometabolic risk factor burden offering insight into a potential mechanism linking these risk factors with the development of CVD.

Psychosocial and environmental factors, including loss of natural reward, contribute to the risk of drug abuse. Reward loss has been modeled in animals by removal from social or sexual contact, transfer from enriched to impoverished housing, or restriction of food. We previously showed that food restriction increases the unconditioned rewarding effects of abused drugs and the conditioned incentive effects of drug-paired environments. Mechanistic studies provided evidence of decreased basal dopamine (DA) transmission, adaptive upregulation of signaling downstream of D1 DA receptor stimulation, synaptic upscaling and incorporation of calcium-permeable AMPA receptors (CP-AMPARs) in medium spiny neurons (MSNs) of nucleus accumbens (NAc). These findings align with the still evolving 'reward deficiency' hypothesis of drug abuse. The present study tested whether a compound natural reward that is known to increase DA utilization, environmental enrichment, would prevent the persistent expression of cocaine conditioned place preference (CPP) otherwise observed in food restricted rats, along with the mechanistic underpinnings. Because nearly all prior investigations of both food restriction and environmental enrichment effects on cocaine CPP were conducted in male rodents, both sexes were included in the present study. Results indicate that environmental enrichment curtailed the persistence of CPP expression, decreased signaling downstream of the D1R, and decreased the amplitude and frequency of spontaneous excitatory postsynaptic currents (EPSCs) in NAc MSNs of food restricted male, but not female, rats. The failure of environmental enrichment to significantly decrease food restriction-induced synaptic insertion of CP-AMPARs, and how this may accord with previous pharmacological findings that blockade of CP-AMPARs reverses behavioral effects of food restriction is discussed. In addition, it is speculated that estrous cycle-dependent fluctuations in DA release, receptor density and MSN excitability may obscure the effect of increased DA signaling during environmental enrichment, thereby interfering with development of the cellular and behavioral effects that enrichment produced in males.

PURPOSE/UNASSIGNED:Although the majority of US adults obtain health information on the internet, the quality of information about prostate cancer is highly variable. Black adults are underrepresented in online content about prostate cancer despite a higher incidence of and mortality from the disease. The goal of this study was to explore the perspectives of Black patients with prostate cancer on the importance of racial representation in online content and other factors influencing trust. MATERIALS AND METHODS/UNASSIGNED:We conducted 7 virtual focus groups with Black patients with prostate cancer in 2022 and 2023. Participants completed an intake questionnaire with demographics followed by a group discussion, including feedback on purposefully selected online content. Transcripts were independently analyzed by 2 investigators experienced in qualitative research using a constant comparative method. RESULTS/UNASSIGNED:Most participants use online sources to look for prostate cancer information. Racial representation is an important factor affecting trust in the content. A lack of Black representation has consequences, including misperceptions about a lower risk of prostate cancer and discouraging further information-seeking. Other key themes affecting trust in online content included the importance of a reputable source of information, professional website structure, and soliciting money. CONCLUSIONS/UNASSIGNED:Underrepresentation of Black adults in prostate cancer content has the potential to worsen health disparities. Optimal online communications should include racially diverse representation and evidence-based information in a professional format from reputable sources without financial conflict.

BACKGROUND:Parents of children with special health care needs (CSHCN) are at risk of poorer health outcomes. Material hardships also pose significant health risks to parents. Little is known about how protective factors may mitigate these risks, and if effects are similar between mothers and fathers. METHODS:This was a cross-sectional survey study conducted using the US 2018/2019 National Survey of Children's Health, including parents of children 0-17 with income <200% of the Federal Poverty Level. Separately, for parents of children with and without special health care needs (N-CSHCN), weighted logistic regression measured associations between material hardship, protective factors (family resilience, neighborhood cohesion and receipt of family-centered care) and two outcomes: mental and physical health of mothers and fathers. Interactions were assessed between special health care needs status, material hardship and protective factors. RESULTS:Sample consisted of parents of 16,777 children, 4,440 were parents of CSHCN. Most outcomes showed similar associations for both mothers and fathers of CSHCN and N-CSHCN: material hardship was associated with poorer health outcomes, and family resilience and neighborhood cohesion associated with better parental health outcomes. Family-centered care was associated with better health of mothers but not fathers. Interaction testing showed that the protective effects of family resilience were lower among fathers of CSHCN experiencing material hardship. CONCLUSIONS:Family resilience and neighborhood cohesion are associated with better health outcomes for all parents, though these effects may vary by experience of special health care needs, parent gender and material hardship. WHAT'S NEW/UNASSIGNED:Protective factors such as family relationships, neighborhood cohesion and family-centered care are associated with better health outcomes for most parents. Particularly for fathers, experience of material hardship may reduce these protective effects.

Obesity is a chronic, relapsing disease that increases the risks of living kidney donation; at the same time, transplant centers have liberalized body mass index constraints for donors. With the increasing number of anti-obesity medications available, the treatment of obesity with anti-obesity medications may increase the pool of potential donors and enhance donor safety. Anti-obesity medications are intended for long-term use given the chronic nature of obesity. Cessation of treatment can be expected to lead to weight regain and increases the risk of comorbidity rebound/development. In addition, anti-obesity medications are meant to be used in conjunction with-rather than in replacement of-diet and physical activity optimization. Anti-obesity medication management includes selecting medications that may ameliorate any co-existing medical conditions, avoiding those that are contraindicated in such conditions, and being sensitive to any out-of-pocket expenses that may be incurred by the potential donor. A number of questions remain regarding who will and should shoulder the costs of long-term obesity treatment for donors. In addition, future studies are needed to quantify the degree of weight loss and duration of weight loss maintenance needed to normalize the risk of adverse kidney outcomes relative to comparable non-donors and lower weight donors.