Identifying and Responding to Lead in Drinking Water in a University Setting

Lead is an established neurotoxicant, and it has known associations with adverse neurodevelopmental and reproductive outcomes. Exposure to lead at any level is unsafe, and the United States (US) has enacted various federal and state legislations to regulate lead levels in drinking water in K-12 schools and childcare facilities; however, no regulations exist for higher education settings. Upon the discovery of lead in drinking water fixtures in the University of North Carolina at Chapel Hill (UNC-CH) campus, a cross-campus water testing network and sampling plan was developed and deployed. The campaign was based on the US Environmental Protection Agency’s (EPA) 3Ts (Training, Testing, and Taking Action) guidance. The seven-month campaign involved 5954 tests on 3825 drinking water fixtures across 265 buildings. A total of 502 (8.43%) tests showed lead above the limit of detection (1 part per billion, ppb), which represented 422 (11.03%) fixtures. Fewer than 1.5% of the tests were above the EPA action level for public water systems (15 ppb). In conclusion, systematic testing of all the fixtures across campus was required to identify localized contamination, and each entity in the cross-campus network undertook necessary roles to generate a successful testing campaign. UNC-CH established preventative measures to test drinking water fixtures every three years, which provide a framework for other higher education institutions in responding to lead contamination

Evaluating protein cross-linking as a therapeutic strategy to stabilize SOD1 variants in a mouse model of familial ALS

Mutations in the gene encoding Cu-Zn superoxide dismutase 1 (SOD1) cause a subset of familial amyotrophic lateral sclerosis (fALS) cases. A shared effect of these mutations is that SOD1, which is normally a stable dimer, dissociates into toxic monomers that seed toxic aggregates. Considerable research effort has been devoted to developing compounds that stabilize the dimer of fALS SOD1 variants, but unfortunately, this has not yet resulted in a treatment. We hypothesized that cyclic thiosulfinate cross-linkers, which selectively target a rare, 2 cysteine-containing motif, can stabilize fALS-causing SOD1 variants in vivo. We created a library of chemically diverse cyclic thiosulfinates and determined structure-cross-linking-activity relationships. A pre-lead compound, “S-XL6,” was selected based upon its cross-linking rate and drug-like properties. Co-crystallographic structure clearly establishes the binding of S-XL6 at Cys 111 bridging the monomers and stabilizing the SOD1 dimer. Biophysical studies reveal that the degree of stabilization afforded by S-XL6 (up to 24°C) is unprecedented for fALS, and to our knowledge, for any protein target of any kinetic stabilizer. Gene silencing and protein degrading therapeutic approaches require careful dose titration to balance the benefit of diminished fALS SOD1 expression with the toxic loss-of-enzymatic function. We show that S-XL6 does not share this liability because it rescues the activity of fALS SOD1 variants. No pharmacological agent has been proven to bind to SOD1 in vivo. Here, using a fALS mouse model, we demonstrate oral bioavailability; rapid engagement of SOD1G93A by S-XL6 that increases SOD1G93A’s in vivo half-life; and that S-XL6 crosses the blood–brain barrier. S-XL6 demonstrated a degree of selectivity by avoiding off-target binding to plasma proteins. Taken together, our results indicate that cyclic thiosulfinate-mediated SOD1 stabilization should receive further attention as a potential therapeutic approach for fALS

Patient Characteristics Associated With Phone and Video Visits at a Tele-Urgent Care Center During the Initial COVID-19 Response: Cross-Sectional Study

Background Health systems rapidly adopted telemedicine as an alternative health care delivery modality in response to the COVID-19 pandemic. Demographic factors, such as age and gender, may play a role in patients’ choice of a phone or video visit. However, it is unknown whether there are differences in utilization between phone and video visits. Objective This study aimed to investigate patients’ characteristics, patient utilization, and service characteristics of a tele-urgent care clinic during the initial response to the pandemic. Methods We conducted a cross-sectional study of urgent care patients using a statewide, on-demand telemedicine clinic with board-certified physicians during the initial phases of the pandemic. The study data were collected from March 3, 2020, through May 3, 2020. Results Of 1803 telemedicine visits, 1278 (70.9%) patients were women, 730 (40.5%) were aged 18 to 34 years, and 1423 (78.9%) were uninsured. There were significant differences between telemedicine modalities and gender (P<.001), age (P<.001), insurance status (P<.001), prescriptions given (P<.001), and wait times (P<.001). Phone visits provided significantly more access to rural areas than video visits (P<.001). Conclusions Our findings suggest that offering patients a combination of phone and video options provided additional flexibility for various patient subgroups, particularly patients living in rural regions with limited internet bandwidth. Differences in utilization were significant based on patient gender, age, and insurance status. We also found differences in prescription administration between phone and video visits that require additional investigation

Perspectives From Public Health Practitioners and Advocates on Community Development for Active Living: What are the Lasting Impacts?

Purpose Evidence suggests differential impacts of community development, including gentrification and displacement. Public health practitioners and advocates are key stakeholders involved in the community development process related to active living, yet little is known about their perceptions of its impacts. We explored the perspectives of relevant leaders of public health departments and key community and advocacy organizations on community development, gentrification, and displacement. Approach Purposive key informant interviews. Setting CDC State Physical Activity and Nutrition (SPAN) funding recipients. Participants CDC SPAN recipient leadership (n = 10 of 16) and advocacy organizations they partnered with (n = 7 of 16). Method Interviews were recorded, transcribed, coded, and thematically analyzed with direct quotes representing key themes. Results Both groups felt community development held important benefits, specifically by creating healthy living opportunities, but also potentially leading to the displacement of long-time residents. Practitioners reported the benefits were for all community members, whereas advocates noted the benefits were seen in those with privilege, and the consequences were disproportionately seen in disadvantaged communities. Both mentioned the importance and difficulty of getting diverse representation for community engagement. Conclusions Learning how key stakeholders perceive and navigate the community development process can help inform recommendations for better equity in active living community improvements. More work is needed to further elucidate best practices for health and social equity in the community development process

The Social Fabric of Watershed Management: Comparison of Citizen-Based and Agency-Based Organizations

This research offers an exploration of the social networks within two distinct watershed groups in the Hudson River, New York State, USA: citizen-based and agency-based organizations. Through a social network analysis of their operations and interactions, this study unveils the complex dynamics and roles of individual nodes in facilitating nine types of connections, such as political and financial, within these networks. The citizen-based organization demonstrated denser and more cohesive networks, suggesting robust relationships and enhanced resilience and adaptability. In contrast, the agency-based organization exhibited more hierarchical networks. This study employs both network-level and node-level analyses to examine the social networks within watershed groups. Our network-level analysis focuses on metrics such as density, average degree, and hierarchy, while our node-level analysis examines clustering coefficients and influence. It also explores ego networks through an analysis of their density and the effective size of structural holes. Our finding is that the social networks of the two groups are quite distinct, and there is limited exchange of information and resources between them. However, we discovered that effective communication among a few well-connected individuals (e.g., those with high influence values) within each group can enhance the effectiveness and resilience of these networks. These analyses aim to provide a detailed understanding of the social dynamics within regional watershed groups

Racial and ethnic differences in the degree of participation and retention in a decentralized cohort study of COVID-19 immunization in patients with inflammatory bowel diseases

Introduction: Disparities in the recruitment of minority populations in research are well-documented. However, the degree of participation and retention of minorities following enrollment is less known, particularly in decentralized studies. Although decentralized clinical research methods may allow researchers to engage broader study populations with less participation burden, they may present different retention challenges. To evaluate racial and ethnic differences in the degree of participation after enrollment in a decentralized study, we analyzed data from a cohort of patients with inflammatory bowel diseases following COVID-19 immunization. Methods: We compared by race and ethnicity the following post-enrollment participation metrics: response to > 50% of follow-up surveys, donation of a blood sample for antibody testing, consent to use of bio samples for future research, and withdrawal prior to study completion. Results: Overall, we observed higher levels of post-enrollment study participation among non-Hispanic White (NHW) participants as compared to Black or Hispanic participants: 95% of NHW participants completed follow-up versus 87% of Black participants and 91% of Hispanic participants, 73% of NHW participants provided bio samples versus 64% Black participants and 67% Hispanic participants, and 65% of NHW participants provided consent for future research versus 62% of Black participants and 52% of Hispanic participants. Conclusions: Our findings demonstrate that the degree of study participation after enrollment in this decentralized study differed by race and ethnicity, indicating that attention to diversity, equity, and inclusion is needed not only in clinical research recruitment but also throughout study administration

Interrogating the “Ivorian Miracle”: From Independence Success to Civil Wars

Post-colonial Côte d’Ivoire represents the story of an economically prosperous nation succumbing to the negative effects of economic globalization led by the IMF’s structural adjustment reforms. Internal divisions over ethnic tensions fueled by the politicization of citizenship and belonging added to this trajectory. From the “Ivorian miracle,” an autonomous agricultural economy led by small cocoa farmers, to the country’s involvement with the IMF and the push for economic and political liberalization, the post-colonial history of Cote D’Ivoire has included major episodes of turbulence. The introduction of the concept of Ivoirité—a nativist ideology aimed at classifying between native Ivorians and Ivorians with immigrant ancestry with regard to citizenship status and political participation—would cause ethnic and regional tensions in the country to boil over. Françafrique and other myriad forms of neocolonialist politics that ensure the maintenance of French influence in West Africa also undermined the economic development of the Ivorian state. This article focuses on the involvement of international institutions in the post-colonial journey of the Ivorian state, analyzing the discourse of democracy in the African continent, in a state where the fluidity of citizenship and ethnicity has always created tensions and civil wars

Caspase-1 activates gasdermin A in non-mammals

Gasdermins oligomerize to form pores in the cell membrane, causing regulated lytic cell death called pyroptosis. Mammals encode five gasdermins that can trigger pyroptosis: GSDMA, B, C, D, and E. Caspase and granzyme proteases cleave the linker regions of and activate GSDMB, C, D, and E, but no endogenous activation pathways are yet known for GSDMA. Here, we perform a comprehensive evolutionary analysis of the gasdermin family. A gene duplication of GSDMA in the common ancestor of caecilian amphibians, reptiles, and birds gave rise to GSDMA-D in mammals. Uniquely in our tree, amphibian, reptile, and bird GSDMA group in a separate clade than mammal GSDMA. Remarkably, GSDMA in numerous bird species contain caspase-1 cleavage sites like YVAD or FASD in the linker. We show that GSDMA from birds, amphibians, and reptiles are all cleaved by caspase-1. Thus, GSDMA was originally cleaved by the host-encoded protease caspase-1. In mammals the caspase-1 cleavage site in GSDMA is disrupted; instead, a new protein, GSDMD, is the target of caspase-1. Mammal caspase-1 uses exosite interactions with the GSDMD C-terminal domain to confer the specificity of this interaction, whereas we show that bird caspase-1 uses a stereotypical tetrapeptide sequence to confer specificity for bird GSDMA. Our results reveal an evolutionarily stable association between caspase-1 and the gasdermin family, albeit a shifting one. Caspase-1 repeatedly changes its target gasdermin over evolutionary time at speciation junctures, initially cleaving GSDME in fish, then GSDMA in amphibians/reptiles/birds, and finally GSDMD in mammals

Work-Related Stress and Psychological Distress among Law Enforcement Officers: The Carolina Blue Project

Law enforcement is a stressful occupation that places significant psychological demands on those serving in this role. However, little is known about the severity of work-related stress and psychological distress among law enforcement officers (LEOs) in North Carolina (NC). This cross-sectional study examined the severity of work-related stress and psychological distress among 283 LEOs in NC. The Maslach Burnout Inventory, the Operational Police Stress Questionnaire, the Depression, Anxiety, and Stress Scale, and the Post-Traumatic Stress Disorder (PTSD) Checklist were used to assess burnout, operational police stress, depression, anxiety, stress, and PTSD among LEOs. Descriptive statistics, independent t-tests, Mann–Whitney U tests, one-way ANOVA, and Kruskal–Wallis tests were performed. Rural and male LEOs reported higher burnout levels related to depersonalization (i.e., increased mental distance from one’s job) compared with their urban and female counterparts. LEOs exposed to toxic materials or performing patrol duties exhibited higher operational police stress levels than those who did not. Caucasian LEOs exhibited higher depression, anxiety, and stress than their African American counterparts. Rural LEOs and LEOs who were exposed to toxic materials displayed higher levels of PTSD than their counterparts. Our findings highlight the need for increased mental health support and better working environments for LEOs