Extracellular Vesicle-Encapsulated microRNAs and Respiratory Health Among American Indian Participants in the Strong Heart Study.

Background: American Indian populations have experienced marked disparities in respiratory disease burden. Extracellular vesicle-encapsulated microRNAs (EV-miRNAs) are a novel class of biomarkers that may improve recognition of lung damage in indigenous populations in the United States.

Research Question: Are plasma EV-miRNAs viable biomarkers of respiratory health in American Indian populations?

Study Design And Methods: The Strong Heart Study is a prospective cohort study that enrolled American Indian patients aged 45 to 74 years.

Geographic and dietary differences of urinary uranium levels in the Strong Heart Family Study.

Background: American Indian (AI) communities are affected by uranium exposure from abandoned mines and naturally contaminated drinking water. Few studies have evaluated geographical differences across AI communities and the role of dietary exposures.

Objective: We evaluated differences in urinary uranium levels by diet and geographical area among AI participants from the Northern Plains, the Southern Plains, and the Southwest enrolled in the Strong Heart Family Study (SHFS).

Expanded phenotype and cancer risk in patients with Beckwith-Wiedemann spectrum caused by CDKN1C variants.

Beckwith-Wiedemann spectrum (BWSp) is caused by genetic and epigenetic alterations on chromosome 11 that regulate cell growth and division. Considering the diverse phenotypic landscape in BWSp, the characterization of the CDKN1C molecular subtype remains relatively limited. Here, we investigate the role of CDKN1C in the broader BWSp phenotype.

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.

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 ) urinary arsenic, and ) reported use of arsenic-safe water for drinking and cooking.

Plasma lipidomic markers of diet quality are associated with incident coronary heart disease in American Indian adults: the Strong Heart Family Study.

Background: Identifying lipidomic markers of diet quality is needed to inform the development of biomarkers of diet, and to understand the mechanisms driving the diet- coronary heart disease (CHD) association.

Objectives: This study aimed to identify lipidomic markers of diet quality and examine whether these lipids are associated with incident CHD.

Methods: Using liquid chromatography-mass spectrometry, we measured 1542 lipid species from 1694 American Indian adults (aged 18-75 years, 62% female) in the Strong Heart Family Study.

Dietary magnesium, C-reactive protein and interleukin-6: The Strong Heart Family Study.

Objectives: To examine the associations of dietary Mg intake with inflammatory biomarkers (C-reactive protein (CRP) and interleukin 6 (IL-6)), and the interaction of dietary Mg intake with single nucleotide polymorphism (SNP) rs3740393, a SNP related to Mg metabolism and transport, on CRP and IL-6 among American Indians (AIs).

Methods: This cross-sectional study included AI participants (n = 1,924) from the Strong Heart Family Study (SHFS). Mg intake from foods and dietary supplements was ascertained using a 119-item Block food frequency questionnaire, CRP and IL-6 were measured from blood, and SNP rs3740393 was genotyped using MetaboChip.

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.

Fine particulate matter composition in American Indian vs. Non-American Indian communities.

Background: Fine particulate matter (PM) exposure is a known risk factor for numerous adverse health outcomes, with varying estimates of component-specific effects. Populations with compromised health conditions such as diabetes can be more sensitive to the health impacts of air pollution exposure. Recent trends in PM in primarily American Indian- (AI-) populated areas examined in previous work declined more gradually compared to the declines observed in the rest of the US.

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.

Ambulatory Activity and Risk of Premature Mortality Among Young and Middle-aged American Indian Individuals.

Importance: To our knowledge, no published studies have investigated the association of ambulatory activity with risk of death among young and middle-aged American Indian individuals. The burden of chronic disease and risk of premature death is higher among American Indian individuals than among the general US population, so better understanding of the association of ambulatory activity with risk of death is needed to inform public health messaging in tribal communities.

Objective: To examine the association of objectively measured ambulatory activity (ie, steps per day) with risk of death among young and middle-aged American Indian individuals.

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.

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.

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.

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.

Adapting a cooking, food budgeting and nutrition intervention for a rural community of American Indians with type 2 diabetes in the North-Central United States.

American Indian (AI) communities experience persistent diabetes-related disparities, yet few nutrition interventions are designed for AI with type 2 diabetes or address socio-contextual barriers to healthy eating. We describe our process of adapting the evidence-based Cooking Matters® program for use by AI adults with type 2 diabetes in a rural and resource-limited setting in the North-Central United States. We conducted three focus groups with AI adults with diabetes to (i) identify Cooking Matters® adaptations and (ii) gather feedback on appropriateness of the adapted intervention using Barrera and Castro's cultural adaptation framework.

Familial Beckwith-Wiedemann syndrome in a multigenerational family: Forty years of careful phenotyping.

Beckwith-Wiedemann Spectrum (BWSp) is an overgrowth and cancer predisposition disorder characterized by a wide spectrum of phenotypic manifestations including macroglossia, abdominal wall defects, neonatal hypoglycemia, and predisposition to embryonal tumors. In 1981, Best and Hoekstra reported four patients with BWSp in a single family which suggested autosomal dominant inheritance, but standard clinical testing for BWSp was not available during this time. Meticulous phenotyping of this family has occurred over the past 40 years of follow-up with additional family members being identified and samples collected for genetic testing.

Lipidomics profiling of biological aging in American Indians: the Strong Heart Family Study.

Telomeres shorten with age and shorter leukocyte telomere length (LTL) has been associated with various age-related diseases. Thus, LTL has been considered a biomarker of biological aging. Dyslipidemia is an established risk factor for most age-related metabolic disorders.

Exploring Clinical Risk Factors for Breast Cancer Among American Indian Women.

Objective: Very little is known about the breast cancer risk profile among American Indian women. Previous research shows that the proportion of American Indian/Alaska Native women with baseline characteristics (commonly known breast cancer risk factors) differs from other ethnicities. This retrospective case control study was designed to the explore the association of these factors among American Indian women with and without breast cancer.

Association of protein function-altering variants with cardiometabolic traits: the strong heart study.

Clinical and biomarker phenotypic associations for carriers of protein function-altering variants may help to elucidate gene function and health effects in populations. We genotyped 1127 Strong Heart Family Study participants for protein function-altering single nucleotide variants (SNV) and indels selected from a low coverage whole exome sequencing of American Indians. We tested the association of each SNV/indel with 35 cardiometabolic traits.