In Our Sacred Voice - An Exploration of Tribal and Community Leader Perceptions as Health Communicators of Disease Prevention among American Indians in the Plains.

American Indians (AI) are disproportionately and significantly impacted by disease morbidity, mortalityand poor behavioral health outcomes. Health promotion and health communication programs exist to address these health disparities and health conditions; however, few programs fully integrate holistic approaches when targeting AI populations. The objective of this study was to explore how tribal and community leaders throughout the Central Plains (Kansas, Iowa, Missouri, and South Dakota) viewed themselves as health communicators and health promoters within their communities. Members of the Center for American Indian Community Health (CAICH) conducted 39 in-depth interviews with members of federally recognized tribes living in reservation communities as well as urban tribal communities across the region. Results from the sample show that these individuals do not necessarily see themselves as the "authority" health communicator or health promoter within their tribe or community. They did perceive themselves and others as gatekeepers of pertinent health information. Social and cultural authority within culturally centered messaging and collective delivery of this type of health information from trusted sources within tribes and communities is perceived to bolster health communication programs and positively impact health outcomes among AI populations.

Targeted Next-Generation Sequencing Identifies Pathogenic Variants in Diabetic Kidney Disease.

INTRODUCTION: Diabetes is the most common cause of chronic kidney disease (CKD). For patients with diabetes and CKD, the underlying cause of their kidney disease is often assumed to be a consequence of their diabetes. Without histopathological confirmation, however, the underlying cause of their disease is unclear. Recent studies have shown that next-generation sequencing (NGS) provides a promising avenue toward uncovering and establishing precise genetic diagnoses in various forms of kidney disease. METHODS: Here, we set out to investigate the genetic basis of disease in nondiabetic kidney disease (NDKD) and diabetic kidney disease (DKD) patients by performing targeted NGS using a custom panel comprising 345 kidney disease-related genes. RESULTS: Our analysis identified rare diagnostic variants based on ACMG-AMP guidelines that were consistent with the clinical diagnosis of 19% of the NDKD patients included in this study. Similarly, 22% of DKD patients were found to carry rare pathogenic/likely pathogenic variants in kidney disease-related genes included on our panel. Genetic variants suggestive of NDKD were detected in 3% of the diabetic patients included in this study. DISCUSSION/CONCLUSION: Our findings suggest that rare variants in kidney disease-related genes in a diabetic background may play a role in the pathogenesis of DKD and NDKD in patients with diabetes.

Densitometric and local histogram based analysis of computed tomography images in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Prior studies of clinical prognostication in idiopathic pulmonary fibrosis (IPF) using computed tomography (CT) have often used subjective analyses or have evaluated quantitative measures in isolation. This study examined associations between both densitometric and local histogram based quantitative CT measurements with pulmonary function test (PFT) parameters and mortality. In addition, this study sought to compare risk prediction scores that incorporate quantitative CT measures with previously described systems. METHODS: Forty six patients with biopsy proven IPF were identified from a registry of patients with interstitial lung disease at Brigham and Women's Hospital in Boston, MA. CT scans for each subject were visually scored using a previously published method. After a semi-automated method was used to segment the lungs from the surrounding tissue, densitometric measurements including the percent high attenuating area, mean lung density, skewness and kurtosis were made for the entirety of each patient's lungs. A separate, automated tool was used to detect and quantify the percent of lung occupied by interstitial lung features. These analyses were used to create clinical and quantitative CT based risk prediction scores, and the performance of these was compared to the performance of clinical and visual analysis based methods. RESULTS: All of the densitometric measures were correlated with forced vital capacity and diffusing capacity, as were the total amount of interstitial change and the percentage of interstitial change that was honeycombing measured using the local histogram method. Higher percent high attenuating area, higher mean lung density, lower skewness, lower kurtosis and a higher percentage of honeycombing were associated with worse transplant free survival. The quantitative CT based risk prediction scores performed similarly to the clinical and visual analysis based methods. CONCLUSIONS: Both densitometric and feature based quantitative CT measures correlate with pulmonary function test measures and are associated with transplant free survival. These objective measures may be useful for identifying high risk patients and monitoring disease progression. Further work will be needed to validate these measures and the quantitative imaging based risk prediction scores in other cohorts.

Suppression of Cardiac Autophagy by Hyperinsulinemia in Insulin Receptor-Deficient Hearts Is Mediated by Insulin-Like Growth Factor Receptor Signaling.

Aims: Autophagy is a catabolic process required for the maintenance of cardiac health. Insulin and insulin-like growth factor 1 (IGF-1) are potent inhibitors of autophagy and as such, one would predict that autophagy will be increased in the insulin-resistant/diabetic heart. However, autophagy is rather decreased in the hearts of diabetic/insulin-resistant mice. The aim of this study is to determine the contribution of IGF-1 receptor signaling to autophagy suppression in insulin receptor (IR)-deficient hearts. Results: Absence of IRs in the heart was associated with reduced autophagic flux, and further inhibition of autophagosome clearance reduced survival, impaired contractile function, and enhanced myocyte loss. Contrary to the in vivo setting, isolated cardiomyocytes from IR-deficient hearts exhibited unrestrained autophagy in the absence of insulin, whereas addition of insulin was able to suppress autophagy. To investigate the mechanisms involved in the maintenance of the responsiveness to insulin in IR-deficient hearts, we generated mice lacking both IRs and one copy of the IGF-1 receptor (IGF-1R) in cardiac cells and showed that these mice had increased autophagy. Innovation and Conclusion: This study unveils a new mechanism by which IR-deficient hearts can still respond to insulin to suppress autophagy, in part, through activation of IGF-1R signaling. This is a highly significant observation because it is the first to show that systemic hyperinsulinemia can suppress autophagy in IR-deficient hearts through IGF-1R signaling.