Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Compartmentalized CNS inflammation involving B cells is implicated in gray matter injury and disease progression in multiple sclerosis (MS). Products secreted by B cells of patients with MS can kill oligodendrocytes and neurons, a cytotoxicity conferred by their exosome-enriched extracellular vesicle (Ex En) fraction. METHODS:To explore the potential molecular mediators of this cytotoxicity, we profiled proteomic and transcriptomic cargo of Ex En isolated from B cells of patients with treatment-naive MS and matched healthy controls. RESULTS:MS B-cell-derived Ex En appeared enriched in cell-death-associated proteins (including fibrinogen, complement C9, APP, and SPARC) and deficient in cell-survival-associated proteins (such as galectin-3). Abnormal enrichment for cell-death proteins was supported by gene set enrichment analysis. Protein pathway analysis revealed densely connected prodeath modules in the MS B-cell-derived Ex En, contrasting with homeostatic signatures in controls. Transcriptomic analysis further revealed that Ex En of MS B cells appeared to carry reduced levels of miRNAs (miR-182, miR-212, and miR-1270) known to inhibit apoptosis. DISCUSSION/CONCLUSIONS:Our findings indicate that B-cell-derived Ex En of patients with MS, previously shown to impair neuronal and glial survival, harbor an abnormal cytotoxic molecular profile that may contribute to CNS-compartmentalized injury and progressive MS biology.

INTRODUCTION/UNASSIGNED:Current disability questions used in many US federal surveys exclusively measure disability as having 1 or more of 6 functional limitations. This strategy is at odds with who is disabled as some disabled people do not experience these limitations. METHODS/UNASSIGNED:Using data from a nationally representative survey of 2169 adults, this study describes the potential of a comprehensive disability status question to improve the measurement of disability. RESULTS/UNASSIGNED:Results from this study demonstrate that a comprehensive disability status question successfully identifies disabled people who both do, and do not, experience limitations. CONCLUSION/UNASSIGNED:These findings suggest that a single comprehensive disability status question may provide a viable and more inclusive alternative to identifying the disabled population in US federal surveys.

Immune-mediated protection generated to COVID-19 mRNA vaccines is associated with anti-Spike (S) protein neutralizing antibodies. However, humoral immunity is compromised in B cell depleting (BCD) therapies, used to treat autoimmune diseases such as Multiple Sclerosis (MS). To study the effect of BCD on the durability and protective efficacy of vaccine-induced immunity, we evaluated S-reactive antibodies and T cell responses 1-70 weeks post-vaccination in MS cohorts treated with BCD compared to non-BCD therapies from four centers. BCD-treated participants had significantly reduced antibody levels and enhanced frequencies of S-reactive CD4⁺ and CD8⁺ memory T cells to COVID-19 vaccination compared to the non-BCD group, with some variations among different BCD formulations. T cell memory responses persisted up to 14 months post-vaccination in both BCD and non-BCD cohorts, who experienced similar clinical protection from COVID-19. Together, our results establish a critical role for T cell-mediated immunity in anti-viral protection independent of humoral immunity.

Health professions educators are continuing to develop training programs for future health care professionals to understand social determinants of health and address practical needs of their training institutions via service-oriented learning. Although individual U.S. programs have piloted different models, evaluations of programs that have demonstrated longitudinal growth and sustainability in the community are lacking, which is important because these programs can have long-term impacts not only on students but also on the communities they serve. In this article, the authors describe the long-term impacts of the Bridging the Gaps (BTG) program. First established in 1991 as an academic health institution and community organization collaborative, by 2019, the BTG program encompassed 9 academic health institution-based programs, partnering with 96 community organizations and employing 187 health professions students across 15 disciplines. By 2019, the program had 5,648 alumni. Of 3,104 alumni, 2,848 (91.8%) felt that the program broadened their understanding of health issues encountered by vulnerable and/or economically disadvantaged populations, and 2,767 of 3,101 (89.2%) felt that the program increased their interest in working with these populations. A total of 142 of 156 (91.0%) reported an effect on their clinical practice, 169 of 180 (93.9%) reported an effect on their professional role, and 64 of 109 (58.7%) reported an effect on their research careers. Of the community partners, 1,401 of 1,441 (97.2%) felt that the partnership between their organization and the BTG program was beneficial, 955 of 1,423 (67.1%) felt that BTG students brought resources to their organization that had previously been unavailable, and 1,095 of 1,421 (77.1%) felt that the linkages between their agency and other organizations were strengthened. The BTG program demonstrates growth and sustainability in its ongoing efforts to integrate training on social determinants of health via service-oriented learning into health professions education.

BACKGROUND:Health insurance in the United States varies in coverage of essential diagnostic tests, therapies, and specialists. Health disparities between privately and publicly insured patients with MS have not been comprehensively assessed. The objective of this study is to evaluate the impact of public versus private insurance on longitudinal brain outcomes in MS. METHODS:Lesional, thalamic, and gray and white matter volumes were extracted from longitudinal MRI of 710 MS patients. Baseline volumes and atrophy rates of lesional, thalamic, and gray and white matter volumes were compared across insurance groups. RESULTS:After image quality assessment, 376 (284 private / 92 public), 638 (499 / 139), and 331 (250 / 81), patients were in MS lesion, thalamic, gray and white matter analyses respectively. Baseline lesion volume was higher for publicly insured patients but increased at a slightly higher rate in those privately insured (p = 0.01). Baseline gray matter measurements were lower for patients with public insurance, but thalamic (p < 0.01) and gray matter (p < 0.01) atrophy rates were slightly higher in the private insurance group. CONCLUSION/CONCLUSIONS:Insurance type was associated with lesion, thalamic, and gray matter volumes. The results suggest that patients with public insurance may present with more advanced disease.

IMPORTANCE/UNASSIGNED:People with disabilities experience pervasive health disparities driven by adverse social determinants of health, such as unemployment. Section 14(c) of the 1938 Fair Labor Standards Act has been a controversial policy that allows people with disabilities to be paid below the prevailing minimum wage, but its impact on employment remains unknown despite ongoing national debates about its repeal. OBJECTIVE/UNASSIGNED:To estimate whether state-level repeal of Section 14(c) was associated with employment-related outcomes for people with cognitive disability. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This quasi-experimental, synthetic difference-in-differences study used individual-level data from the 2010-2019 American Community Surveys. Outcomes before and after subminimum wage law repeal in 2 states (New Hampshire and Maryland) that repealed Section 14(c) were compared with a synthetic group of control states that did not implement repeal. Individuals aged 18 to 45 years who reported having a cognitive disability were included. Data were analyzed from May 2023 to May 2024. EXPOSURE/UNASSIGNED:Repeal of Section 14(c) in New Hampshire (2015) and Maryland (2016). MAIN OUTCOMES AND MEASURES/UNASSIGNED:Primary outcomes were labor force participation and employment rates. Secondary outcomes were annual wages, annual hours worked, hourly wages, and proportion earning above state minimum wage among employed individuals. RESULTS/UNASSIGNED:The sample included 450 838 individuals. Of these, 253 157 (55.7%) were male, and the mean (SD) age was 31.3 (8.4) years. In state-specific analyses, New Hampshire's labor force participation and employment had a statistically significant increase by 5.2 percentage points (β = 0.05; 95% CI, 0-0.10; P = .04) and 7 percentage points (β = 0.07; 95% CI, 0.01-0.13; P = .03), respectively, following Section 14(c) repeal. Labor force participation and employment both increased in Maryland, although estimates were not statistically significant. Pooling both states, Section 14(c) repeal was associated with a statistically significant 4.7-percentage point (β = 0.05; 95% CI, 0.01-0.08; P = .01) increase in labor force participation and a nonsignificant 4.3-percentage point (β = 0.04; 95% CI, 0-0.09; P = .07) increase in employment. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this study, repeal of Section 14(c), a policy allowing subminimum wages for people with disabilities, led to increases in labor force participation, though with heterogeneity at the state level. These findings suggest the importance of state-level factors in shaping program effects, especially as national-level Section 14(c) repeal is being debated.