Genetic variant rs1205 is associated with COVID-19 outcomes: The Strong Heart Study and Strong Heart Family Study.

BACKGROUND: Although COVID-19 infection has been associated with a number of clinical and environmental risk factors, host genetic variation has also been associated with the incidence and morbidity of infection. The CRP gene codes for a critical component of the innate immune system and CRP variants have been reported associated with infectious disease and vaccination outcomes. We investigated possible associations between COVID-19 outcome and a limited number of candidate gene variants including rs1205. METHODOLOGY/PRINCIPAL FINDINGS: The Strong Heart and Strong Heart Family studies have accumulated detailed genetic, cardiovascular risk and event data in geographically dispersed American Indian communities since 1988. Genotypic data and 91 COVID-19 adjudicated deaths or hospitalizations from 2/1/20 through 3/1/23 were identified among 3,780 participants in two subsets. Among 21 candidate variants including genes in the interferon response pathway, APOE, TMPRSS2, TLR3, the HLA complex and the ABO blood group, only rs1205, a 3' untranslated region variant in the CRP gene, showed nominally significant association in T-dominant model analyses (odds ratio 1.859, 95%CI 1.001-3.453, p = 0.049) after adjustment for age, sex, center, body mass index, and a history of cardiovascular disease. Within the younger subset, association with the rs1205 T-Dom genotype was stronger, both in the same adjusted logistic model and in the SOLAR analysis also adjusting for other genetic relatedness. CONCLUSION: A T-dominant genotype of rs1205 in the CRP gene is associated with COVID-19 death or hospitalization, even after adjustment for relevant clinical factors and potential participant relatedness. Additional study of other populations and genetic variants of this gene are warranted.

Effect of an Arsenic Mitigation Program on Arsenic Exposure in American Indian Communities: A Cluster Randomized Controlled Trial of the Community-Led Strong Heart Water Study Program.

BACKGROUND: Chronic arsenic exposure has been associated with an increased risk of cardiovascular disease; diabetes; cancers of the lung, pancreas and prostate; and all-cause mortality in American Indian communities in the Strong Heart Study. OBJECTIVE: The Strong Heart Water Study (SHWS) designed and evaluated a multilevel, community-led arsenic mitigation program to reduce arsenic exposure among private well users in partnership with Northern Great Plains American Indian Nations. METHODS: A cluster randomized controlled trial (cRCT) was conducted to evaluate the effectiveness of the SHWS arsenic mitigation program over a 2-y period on a) urinary arsenic, and b) reported use of arsenic-safe water for drinking and cooking. The cRCT compared the installation of a point-of-use arsenic filter and a mobile Health (mHealth) program (3 phone calls; SHWS mHealth and Filter arm) to a more intensive program, which included this same program plus three home visits (3 phone calls and 3 home visits; SHWS Intensive arm). RESULTS: A 47% reduction in urinary arsenic [geometric mean (GM)=13.2 to 7.0µg/g creatinine] was observed from baseline to the final follow-up when both study arms were combined. By treatment arm, the reduction in urinary arsenic from baseline to the final follow-up visit was 55% in the mHealth and Filter arm (GM=14.6 to 6.55µg/g creatinine) and 30% in the Intensive arm (GM=11.2 to 7.82µg/g creatinine). There was no significant difference in urinary arsenic levels by treatment arm at the final follow-up visit comparing the Intensive vs. mHealth and Filter arms: GM ratio of 1.21 (95% confidence interval: 0.77, 1.90). In both arms combined, exclusive use of arsenic-safe water from baseline to the final follow-up visit significantly increased for water used for cooking (17% to 53%) and drinking (12% to 46%). DISCUSSION: Delivery of the interventions for the community-led SHWS arsenic mitigation program, including the installation of a point-of-use arsenic filter and a mHealth program on the use of arsenic-safe water (calls only, no home visits), resulted in a significant reduction in urinary arsenic and increases in reported use of arsenic-safe water for drinking and cooking during the 2-y study period. These results demonstrate that the installation of an arsenic filter and phone calls from a mHealth program presents a promising approach to reduce water arsenic exposure among private well users. https://doi.org/10.1289/EHP12548.

The Contribution of Declines in Blood Lead Levels to Reductions in Blood Pressure Levels: Longitudinal Evidence in the Strong Heart Family Study.

BACKGROUND: Chronic lead exposure is associated with both subclinical and clinical cardiovascular disease. We evaluated whether declines in blood lead were associated with changes in systolic and diastolic blood pressure in adult American Indian participants from the SHFS (Strong Heart Family Study). METHODS AND RESULTS: Lead in whole blood was measured in 285 SHFS participants in 1997 to 1999 and 2006 to 2009. Blood pressure and measures of cardiac geometry and function were obtained in 2001 to 2003 and 2006 to 2009. We used generalized estimating equations to evaluate the association of declines in blood lead with changes in blood pressure; cardiac function and geometry measures were considered secondary. Mean blood lead was 2.04 µg/dL at baseline. After ≈10 years, mean decline in blood lead was 0.67 µg/dL. In fully adjusted models, the mean difference in systolic blood pressure comparing the highest to lowest tertile of decline (>0.91 versus <0.27 µg/dL) in blood lead was -7.08 mm Hg (95% CI, -13.16 to -1.00). A significant nonlinear association between declines in blood lead and declines in systolic blood pressure was detected, with significant linear associations where blood lead decline was 0.1 µg/dL or higher. Declines in blood lead were nonsignificantly associated with declines in diastolic blood pressure and significantly associated with declines in interventricular septum thickness. CONCLUSIONS: Declines in blood lead levels in American Indian adults, even when small (0.1-1.0 µg/dL), were associated with reductions in systolic blood pressure. These findings suggest the need to further study the cardiovascular impacts of reducing lead exposures and the importance of lead exposure prevention.

Comparison of circulating and excreted metals and of autoimmunity between two Great Plains Tribal communities.

Metals contaminants of the environment from mine waste have been implicated as contributing agents in autoimmune disease. The current study compares metals and autoimmunity in two Tribal communities residing in the Black Hills and the Bighorn Mountains geographical regions that are scattered with extant hard rock mines. With documented drinking water contamination in both communities, in vivo levels of more than half of the measured serum and urine metals differed between the two communities and were substantially different from their national median values. Serum autoantibodies associated with systemic autoimmune disease were rare or at low-level, but antibodies to denatured (single-stranded) DNA and thyroid-specific autoantibodies were commonly elevated, especially in women. A three-tier statistical modeling process was carried out to examine individual metals exposure as predictors of autoantibody levels. For the most part only weak positive associations between individual metals and systemic autoantibodies were found, although univariate quantile regression analysis showed positive statistical associations of serum lead and antimony with anti-chromatin and anti-histone autoantibodies. Using age and gender-adjusted multivariable statistical models, metals did not predict anti-thyroglobulin or -thyroid peroxidase significantly and metals were generally negative predictors of the other autoantibodies. Overall these results suggest that elevated levels of environmental metals and metalloids in these communities may result in suppression of autoantibodies associated with systemic autoimmune disease.

Return of Participants' Incidental Genetic Research Findings: Experience from a Case-Control Study of Asthma in an American Indian Community.

The proper communication of clinically actionable findings to participants of genetic research entails important ethical considerations, but has been challenging for a variety of reasons. We document an instance of the return of individual genetic results in the context of a very rural American Indian community, in hopes of providing insight to other investigators about potentially superior or inferior courses of action. This was a case/control study of asthma among 324 pediatric participants. Subsequently, microarray genotype data became available, providing over 2 million variants, incidentally including some conferring risk for conditions for which the American College of Medical Genetics recommends return of results. The study investigators engaged in extensive consultation with the IRB, the tribal government, and local clinicians to better inform our approach. We were able to notify the two participants heterozygous for the one clinically actionable variant identified. One participant welcomed this information and proceeded to obtain further clinical work-up; the other participant declined further follow-up. While demanding considerable time and effort, the return of clinically actionable genetic results is important from both an ethical perspective and to provide an improved trust relationship with the community of research participants.

Depression, physical activity, and incident cardiovascular disease among American Indians: The strong heart family study.

Background: Little is known about the relationship of depression with incident cardiovascular disease (CVD) among American Indians (AIs), a population with a high burden of depressive symptoms and CVD. In this study, we examined the association of depressive symptoms with CVD risk among AIs and assessed whether an objective marker of ambulatory activity influenced the relationship. Methods: The study comprised participants from the Strong Heart Family Study, a longitudinal study of CVD risk among AIs free of CVD at baseline (2001-2003) and who participated in a follow-up examination (n = 2209). The Center for Epidemiologic Studies of Depression Scale (CES-D) was used to assess depressive symptoms and depressive affect. Ambulatory activity was measured using Accusplit AE120 pedometers. Incident CVD was defined as new myocardial infarction, coronary heart disease, or stroke (through 2017). Generalized estimating equations were used to examine the association of depressive symptoms with incident CVD. Results: 27.5% of participants reported moderate or severe depressive symptoms at baseline and 262 participants developed CVD during follow-up. Compared to participants who reported no depressive symptoms, the odds ratios for developing CVD among those who reported mild, moderate, or severe symptoms were: 1.19 (95% CI: 0.76, 1.85), 1.61 (95% CI: 1.09, 2.37), and 1.71 (95% CI: 1.01, 2.91), respectively. Adjustment for activity did not alter findings. Limitations: CES-D is a tool used to identify individuals with depressive symptoms and not a measure of clinical depression. Conclusion: Higher levels of reported depressive symptoms were positively associated with CVD risk in a large cohort of AIs.

Feasibility and Acceptability of Using Ecological Momentary Assessment to Evaluate Alcohol Use with American Indian Women.

BACKGROUND: Ecological momentary assessments (EMA) are one way to collect timely and accurate alcohol use data, as they involve signaling participants via cell phones to report on daily behaviors in real-time and in a participant's natural environment. EMA has never been used with American Indian populations to evaluate alcohol consumption. The purpose of this project was to determine the feasibility and acceptability of EMA for American Indian women. METHODS: Eligible participants were American Indian women between the ages of 18 and 44 who were not pregnant and had consumed more than one drink within the past month. All participants received a TracFone and weekly automated messages. Self-reported measures of daily quantity and frequency of alcohol consumption, alcohol type, and context were assessed once per week for four weeks. Baseline measurements also included the Drinking Motives Questionnaire-Revised (DMQ-R) and the Interpersonal Support Evaluation List (ISEL). RESULTS: Fifteen participants were enrolled in the study. All but one participant completed all data collection time points, and drinking patterns were consistent across the study period. A total of 420 records were completed across 86 drinking days and 334 non-drinking days. Participants reported drinking an average of 5.7 days over the 30-day period and typically consumed 3.99 drinks per drinking occasion. Sixty-six percent of participants met gender-specific cut-points for heavy episodic drinking, with an average of 2.46 binge drinking occasions across the four week study period. CONCLUSIONS: This proof-of-concept project showed that EMA was both feasible and acceptable for collecting alcohol data from American Indian women. Additional studies are necessary to fully implement EMA with American Indian women to better understand the drinking motives, contexts, patterns, and risk factors in this population.

Behavioral determinants of arsenic-safe water use among Great Plains Indian Nation private well users: results from the Community-Led Strong Heart Water Study Arsenic Mitigation Program.

BACKGROUND: The objective of this study was to evaluate the behavioral determinants associated with exclusive use of arsenic-safe water in the community-led Strong Heart Water Study (SHWS) arsenic mitigation program. METHODS: The SHWS is a randomized controlled trial of a community-led arsenic mitigation program designed to reduce arsenic exposure among private well users in American Indian Great Plains communities. All households received point-of-use (POU) arsenic filters installed at baseline and were followed for 2 years. Behavioral determinants selected were those targeted during the development of the SHWS program, and were assessed at baseline and follow-up. RESULTS: Among participants, exclusive use of arsenic-safe water for drinking and cooking at follow-up was associated with higher self-efficacy for accessing local resources to learn about arsenic (OR: 5.19, 95% CI: 1.48-18.21) and higher self-efficacy to resolve challenges related to arsenic in water using local resources (OR: 3.11, 95% CI: 1.11-8.71). Higher commitment to use the POU arsenic filter faucet at baseline was also a significant predictor of exclusive arsenic-safe water use for drinking (OR: 32.57, 95% CI: 1.42-746.70) and cooking (OR: 15.90, 95% CI: 1.33-189.52) at follow-up. From baseline to follow-up, the SHWS program significantly increased perceived vulnerability to arsenic exposure, self-efficacy, descriptive norms, and injunctive norms. Changing one's arsenic filter cartridge after installation was associated with higher self-efficacy to obtain arsenic-safe water for drinking (OR: 6.22, 95% CI: 1.33-29.07) and cooking (OR: 10.65, 95% CI: 2.48-45.68) and higher perceived vulnerability of personal health effects (OR: 7.79, 95% CI: 1.17-51.98) from drinking arsenic-unsafe water. CONCLUSIONS: The community-led SHWS program conducted a theory-driven approach for intervention development and evaluation that allowed for behavioral determinants to be identified that were associated with the use of arsenic safe water and changing one's arsenic filter cartridge. These results demonstrate that theory-driven, context-specific formative research can influence behavior change interventions to reduce water arsenic exposure. The SHWS can serve as a model for the design of theory-driven intervention approaches that engage communities to reduce arsenic exposure. TRIAL REGISTRATION: The SHWS is registered with ClinicalTrials.gov (Identifier: NCT03725592).

Implementing a Community-Led Arsenic Mitigation Intervention for Private Well Users in American Indian Communities: A Qualitative Evaluation of the Strong Heart Water Study Program.

Arsenic is a naturally occurring toxicant in groundwater, which increases cancer and cardiovascular disease risk. American Indian populations are disproportionately exposed to arsenic in drinking water. The Strong Heart Water Study (SHWS), through a community-centered approach for intervention development and implementation, delivered an arsenic mitigation program for private well users in American Indian communities. The SHWS program comprised community-led water arsenic testing, point-of-use arsenic filter installation, and a mobile health program to promote sustained filter use and maintenance (i.e., changing the filter cartridge). Half of enrolled households received additional in-person behavior change communication and videos. Our objectives for this study were to assess successes, barriers, and facilitators in the implementation, use, and maintenance of the program among implementers and recipients. We conducted 45 semi-structured interviews with implementers and SHWS program recipients. We analyzed barriers and facilitators using the Consolidated Framework for Implementation Research and the Risks, Attitudes, Norms, Abilities, and Self-regulation model. At the implementer level, facilitators included building rapport and trust between implementers and participating households. Barriers included the remoteness of households, coordinating with community plumbers for arsenic filter installation, and difficulty securing a local supplier for replacement filter cartridges. At the recipient level, facilitators included knowledge of the arsenic health risks, perceived effectiveness of the filter, and visual cues to promote habit formation. Barriers included attitudes towards water taste and temperature and inability to procure or install replacement filter cartridges. This study offers insights into the successes and challenges of implementing an arsenic mitigation program tailored to American Indian households, which can inform future programs in partnership with these and potentially similar affected communities. Our study suggests that building credibility and trust between implementers and participants is important for the success of arsenic mitigation programs.

Return of Participants' Incidental Genetic Research Findings: Experience from a Case-Control Study of Asthma in an American Indian Community.

PURPOSE: The proper communication of clinically actionable findings to participants of genetic research entails important ethical considerations, but has been challenging for a variety of reasons. We document an instance of return of individual genetic results in the context of a very rural American Indian community, in hopes of providing insight to other investigators about potentially superior or inferior courses of action. METHODS: The original study was a case/control study of asthma among 324 pediatric participants. The study utilized a genotyping microarray assessing over 2 million variants, including one conferring risk for hypertrophic cardiomyopathy for which the American College of Medical Genetics recommends return of results to participants. The study investigators engaged in extensive consultation with the IRB, the Tribal government and local clinicians to better inform our approach. RESULTS: With some difficulty we were able to notify the 2 participants heterozygous for this variant. One participant welcomed this information and proceeded to obtain further clinical work-up; the other participant declined further follow-up. CONCLUSION: While demanding of considerable time and effort, the return of clinically actionable genetic results is important from both an ethical perspective and to provide an improved trust relationship with the community of research participants.

Evaluation of a water arsenic filter in a participatory intervention to reduce arsenic exposure in American Indian communities: The Strong Heart Water Study.

Many rural populations, including American Indian communities, that use private wells from groundwater for their source of drinking and cooking water are disproportionately exposed to elevated levels of arsenic. However, programs aimed at reducing arsenic in American Indian communities are limited. The Strong Heart Water Study (SHWS) is a randomized controlled trial aimed at reducing arsenic exposure among private well users in American Indian Northern Great Plains communities. The community-led SHWS program installed point-of-use (POU) arsenic filters in the kitchen sink of households, and health promoters delivered arsenic health communication programs. In this study we evaluated the efficacy of these POU arsenic filters in removing arsenic during the two-year installation period. Participants were randomized into two arms. In the first arm households received a POU arsenic filter, and 3 calls promoting filter use (SHWS mobile health (mHealth) & filter arm). The second arm received the same filter and phone calls, and 3 in-person home visits and 3 Facebook messages (SHWS intensive arm) for program delivery. Temporal variability in water arsenic concentrations from the main kitchen faucet was also evaluated. A total of 283 water samples were collected from 50 households with private wells from groundwater (139 filter and 144 kitchen faucet samples). Ninety-three percent of households followed after baseline had filter faucet water arsenic concentrations below the arsenic maximum contaminant level of 10 µg/L at the final visit during our 2 year study period with no difference between study arms (98 % in the intensive arm vs. 94 % in the mHealth & filter arm). No significant temporal variation in kitchen arsenic concentration was observed over the study period (intraclass correlation coefficient = 0.99). This study demonstrates that POU arsenic filters installed for the community participatory SHWS program were effective in reducing water arsenic concentration in study households in both arms, even with delivery of the POU arsenic filter and mHealth program only. Furthermore, we observed limited temporal variability of water arsenic concentrations from kitchen faucet samples collected over time from private wells in our study setting.

Efficacy and feasibility of the BREATHE asthma intervention with American Indian children: a randomized controlled trial.

American Indian (AI) children experience significant disparities in asthma prevalence, severity, and burden of disease, yet few asthma education interventions are tested in this population. This study aimed to evaluate the efficacy and feasibility of the BREATHE intervention with parents and AI children, during a 3-year follow-up period (n = 108), using a randomized controlled design. Children with asthma identified by electronic medical records (EMR) were screened and matched with 2 controls. The intervention included an initial educational and 24 months of follow-up. The control group continued their usual care. The primary outcome was the frequency of EMR documented, emergency department (ED) visits or hospitalization for respiratory complaints. There was no statistical difference in mean primary outcomes (1.34 (1.98) vs 1.22 (1.95), - 0.88 to 0.63, 95% CI of the difference, p = 0.75), nor percent with any ED visit or hospitalization (29/53, 55% vs 30/55, 54%, p = 0.99) between the intervention or control groups respectively. After 365 days, there was a borderline significant difference in time to primary outcome. Although limited in power, the present study did not demonstrate a persistent effect of this intervention. We recommend that AI pediatric asthma interventions are culturally-designed, use feasible procedures, and repeat education at least every 12 months.

Tapwater Exposures, Effects Potential, and Residential Risk Management in Northern Plains Nations.

In the United States (US), private-supply tapwater (TW) is rarely monitored. This data gap undermines individual/community risk-management decision-making, leading to an increased probability of unrecognized contaminant exposures in rural and remote locations that rely on private wells. We assessed point-of-use (POU) TW in three northern plains Tribal Nations, where ongoing TW arsenic (As) interventions include expansion of small community water systems and POU adsorptive-media treatment for Strong Heart Water Study participants. Samples from 34 private-well and 22 public-supply sites were analyzed for 476 organics, 34 inorganics, and 3 in vitro bioactivities. 63 organics and 30 inorganics were detected. Arsenic, uranium (U), and lead (Pb) were detected in 54%, 43%, and 20% of samples, respectively. Concentrations equivalent to public-supply maximum contaminant level(s) (MCL) were exceeded only in untreated private-well samples (As 47%, U 3%). Precautionary health-based screening levels were exceeded frequently, due to inorganics in private supplies and chlorine-based disinfection byproducts in public supplies. The results indicate that simultaneous exposures to co-occurring TW contaminants are common, warranting consideration of expanded source, point-of-entry, or POU treatment(s). This study illustrates the importance of increased monitoring of private-well TW, employing a broad, environmentally informative analytical scope, to reduce the risks of unrecognized contaminant exposures.

Diet Quality and Depression in a Cohort of American Indians: The Strong Heart Family Study.

Diet quality has been shown to be inversely associated with depression, but this has not been studied in American Indians (AIs). We examined the prospective association of diet quality and probable depression in a family-based cohort of rural AIs. Using data from the Strong Heart Family Study, we included 1,100 AIs ≥14 years old who were free of probable depression at baseline. We defined probable depression as the presence of moderate or severe depressive symptoms on the Center for Epidemiologic Studies Depression Scale or current use of antidepressant medications. We calculated baseline diet quality from food frequency questionnaires using the Alternative Healthy Eating Index-2010 (AHEI). We used GEE-based multivariate logistic regression to estimate the odds ratio of probable depression at follow up associated with a 10-point higher AHEI score at baseline, adjusted for demographic, psychosocial, and health factors. At follow up, 19% (n = 207) of the sample reported probable depression. Diet quality was not associated with report of probable depression at follow up (OR = 1.16, 95% CI [0.96, 1.39]). Research is needed to examine other temporal dimensions of this relationship and unique aspects of rural AI diets and psychosocial factors that may influence depression.

Blood cadmium, lead, manganese, mercury, and selenium levels in American Indian populations: The Strong Heart Study.

BACKGROUND: Many American Indian (AI) communities are in areas affected by environmental contamination, such as toxic metals. However, studies assessing exposures in AI communities are limited. We measured blood metals in AI communities to assess historical exposure and identify participant characteristics associated with these levels in the Strong Heart Study (SHS) cohort. METHOD: Archived blood specimens collected from participants (n = 2014, all participants were 50 years of age and older) in Arizona, Oklahoma, and North and South Dakota during SHS Phase-III (1998-1999) were analyzed for cadmium, lead, manganese, mercury, and selenium using inductively coupled plasma triple quadrupole mass spectrometry. We conducted descriptive analyses for the entire cohort and stratified by selected subgroups, including selected demographics, health behaviors, income, waist circumference, and body mass index. Bivariate associations were conducted to examine associations between blood metal levels and selected socio-demographic and behavioral covariates. Finally, multivariate regression models were used to assess the best model fit that predicted blood metal levels. FINDINGS: All elements were detected in 100% of study participants, with the exception of mercury (detected in 73% of participants). The SHS population had higher levels of blood cadmium and manganese than the general U.S. population 50 years and older. The median blood mercury in the SHS cohort was at about 30% of the U.S. reference population, potentially due to low fish consumption. Participants in North Dakota and South Dakota had the highest blood cadmium, lead, manganese, and selenium, and the lowest total mercury levels, even after adjusting for covariates. In addition, each of the blood metals was associated with selected demographic, behavioral, income, and/or weight-related factors in multivariate models. These findings will help guide the tribes to develop education, outreach, and strategies to reduce harmful exposures and increase beneficial nutrient intake in these AI communities.

Adaptations of an RCT during COVID: Case Study in one Rural American Indian Community.

The COVID-19 pandemic is global in nature but especially threatens American Indian and Alaska Native (AI/AN) communities due to pre-existing conditions and social determinants of health. Because of the higher risk to AI/AN communities, many tribal nations have been proactive in their policies to keep the virus at bay, including travel restrictions and lockdowns. This affected tribal programs as well as collaborative research projects. One project impacted is the Native CHOICES project, an ongoing randomized controlled trial with an AI/AN community that is focused on the prevention of alcohol-exposed pregnancies. Originally designed to be conducted via in-person motivational interviewing sessions, COVID-19 restrictions precluded the intervention from being delivered in-person as it was designed. The study team received valuable input from the project's Community Advisory Board (CAB) and community-based staff to establish a feasible and acceptable way of conducting the intervention while respecting tribally-enacted COVID-19 restrictions. The goal of this brief report is to outline not just the process to adapting to COVID-19 but also to provide recommendations for future public health programs, including the ongoing need to consider gaps in access affecting resource-poor settings.

Psychological and social support associations with mortality and cardiovascular disease in middle-aged American Indians: the Strong Heart Study.

PURPOSE: Our study examined psychosocial risk and protective features affecting cardiovascular and mortality disparities in American Indians, including stress, anger, cynicism, trauma, depression, quality of life, and social support. METHODS: The Strong Heart Family Study cohort recruited American Indian adults from 12 communities over 3 regions in 2001-2003 (N = 2786). Psychosocial measures included Cohen Perceived Stress, Spielberger Anger Expression, Cook-Medley cynicism subscale, symptoms of post-traumatic stress disorder, Centers for Epidemiologic Studies Depression scale, Short Form 12-a quality of life scale, and the Social Support and Social Undermining scale. Cardiovascular events and all-cause mortality were evaluated by surveillance and physician adjudication through 2017. RESULTS: Participants were middle-aged, 40% male, with mean 12 years formal education. Depression symptoms were correlated with anger, cynicism, poor quality of life, isolation, criticism; better social support was correlated with lower cynicism, anger, and trauma. Adjusted time-to-event regressions found that depression, (poor) quality of life, and social isolation scores formed higher risk for mortality and cardiovascular events, and social support was associated with lower risk. Social support partially explained risk associations in causal mediation analyses. CONCLUSION: Altogether, our findings suggest that social support is associated with better mood and quality of life; and lower cynicism, stress, and disease risk-even when said risk may be increased by comorbidities. Future research should examine whether enhancing social support can prospectively reduce risk, as an efficient, cost-effective intervention opportunity that may be enacted at the community level.

Building Environmental Health and Genomics Literacy among Healthcare Providers Serving Vulnerable Communities: An Innovative Educational Framework.

This study addresses healthcare providers' knowledge deficits in environmental health and genetics, and primarily focuses on student nurses and nurses serving marginalized, low-income communities frequently exposed to environmental toxicants. Our approach to improve public health is unique, combining hands-on modeling exercises with case-based lessons in addition to three targeted 40 min lectures on toxicology. These lectures included the team's community-based environmental health research among Indigenous peoples of the U.S. The hands-on approach employed DNA and protein molecular models designed to demonstrate normal and dysfunctional molecules, as well as genetic variants in world populations. The models provided learners with visuals and an experience of "learning by doing." Increased awareness of the effects of environmental toxicants is the first step toward improving health care for exposed communities. We measured knowledge gains by pre- and post-tests among student nurses and nurses serving Native Americans living both in urban and rural areas of the U.S. (n = 116). The modeling lessons illustrated genetic variants in liver proteins common in Native peoples and their resulting health vulnerabilities. Participants were engaged and enthusiastic; and pre- and post-test results reported substantial knowledge gains and a greater understanding of genetic susceptibility (p < 0.0001). Our study demonstrates the utility of this framework across diverse populations and remote communities.

Alcohol Consumption during COVID among Women with an Existing Alcohol-Use Disorder.

Prior to the pandemic, our research team implemented a randomized controlled trial of an intervention to reduce risk for alcohol-exposed pregnancy (AEP) in American Indian women. When active recruitment for the in-person trial was paused due to COVID, the research team moved to conducting follow-up surveys with participants who had completed the intervention to better understand changes to their alcohol use during the pandemic. We collected surveys from 62 American Indian women who had completed the Native CHOICES intervention. Baseline data collected pre-COVID included demographics and scores on the Alcohol Use Disorders Identification Test (AUDIT). Follow-up surveys conducted during the active pandemic period included a self-reported questionnaire about changes in drinking patterns. At pre-COVID baseline, all participants were engaged in heavy or binge drinking. At follow-up during COVID, 24.2% reported drinking more, and over half had at least one binge drinking episode. Approximately half reported reduced drinking. We found that risky drinking remained an issue during the pandemic for many American Indian women who had engaged in this behavior pre-COVID, while others reported reducing their alcohol consumption. As the pandemic abates, concerted efforts must be made to reach those with identified alcohol use disorders to offer resources and intervention as needed.

Spatial relationship between well water arsenic and uranium in Northern Plains native lands.

Arsenic and uranium in unregulated private wells affect many rural populations across the US. The distribution of these contaminants in the private wells of most American Indian communities is poorly characterized, and seldom studied together. Here, we evaluate the association between drinking water arsenic and uranium levels in wells (n = 441) from three tribal regions in North Dakota and South Dakota participating in the Strong Heart Water Study. Groundwater contamination was extensive; 29% and 7% of wells exceeded maximum contaminant levels for arsenic and uranium respectively. 81% of wells had both arsenic and uranium concentrations at one-tenth of their human-health benchmark (arsenic, 1 µg/L; uranium 3 µg/L). Well arsenic and uranium concentrations were uncorrelated (rs = 0.06); however, there appeared to be a spatial correlation of wells co-contaminated by arsenic and uranium associated with flow along a geologic contact. These findings indicate the importance of measuring multiple metals in well water, and to understand underlying hydrogeological conditions. The underlying mechanisms for the prevalence of arsenic and uranium across Northern Plains Tribal Lands in the US, and in particular the occurrence of both elevated arsenic and uranium in drinking water wells in this region, demands further study.