Endogenous adenine mediates kidney injury in diabetic models and predicts diabetic kidney disease in patients

Diabetic kidney disease (DKD) can lead to end-stage kidney disease (ESKD) and mortality; however, few mechanistic biomarkers are available for high-risk patients, especially those without macroalbuminuria. Urine from participants with diabetes from the Chronic Renal Insufficiency Cohort (CRIC) study, the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes (SMART2D), and the American Indian Study determined whether urine adenine/creatinine ratio (UAdCR) could be a mechanistic biomarker for ESKD. ESKD and mortality were associated with the highest UAdCR tertile in the CRIC study and SMART2D. ESKD was associated with the highest UAdCR tertile in patients without macroalbuminuria in the CRIC study, SMART2D, and the American Indian study. Empagliflozin lowered UAdCR in nonmacroalbuminuric participants. Spatial metabolomics localized adenine to kidney pathology, and single-cell transcriptomics identified ribonucleoprotein biogenesis as a top pathway in proximal tubules of patients without macroalbuminuria, implicating mTOR. Adenine stimulated matrix in tubular cells via mTOR and stimulated mTOR in mouse kidneys. A specific inhibitor of adenine production was found to reduce kidney hypertrophy and kidney injury in diabetic mice. We propose that endogenous adenine may be a causative factor in DKD.</p

Measuring Five Dimensions of Religiosity Across Adolescence

This paper theorizes and tests a latent variable model of adolescent religiosity in which five dimensions of religiosity are interrelated: religious beliefs, religious exclusivity, external religiosity, private practice, and religious salience. Research often theorizes overlapping and independent influences of single items or dimensions of religiosity on outcomes such as adolescent sexual behavior, but rarely operationalizes the dimensions in a measurement model accounting for their associations with each other and across time. We use longitudinal structural equation modeling (SEM) with latent variables to analyze data from two waves of the National Study of Youth and Religion. We test our hypothesized measurement model as compared to four alternate measurement models and find that our proposed model maintains superior fit. We then discuss the associations between the five dimensions of religiosity we measure and how these change over time. Our findings suggest how future research might better operationalize multiple dimensions of religiosity in studies of the influence of religion in adolescence

Association of sex, age and education level with patient reported outcomes in atrial fibrillation

Abstract Background In atrial fibrillation (AF), there are known sex and sociodemographic disparities in clinical outcomes such as stroke. We investigate whether disparities also exist with respect to patient-reported outcomes. We explored the association of sex, age, and education level with patient-reported outcomes (AF-related quality of life, symptom severity, and emotional and functional status). Methods The PaTH AF cohort study recruited participants (N = 953) with an AF diagnosis and age ≥ 18 years across 4 academic medical centers. We performed longitudinal multiple regression with random effects to determine if individual characteristics were associated with patient-reported outcomes. Results Women reported poorer functional status (β − 2.23, 95% CI: -3.52, − 0.94) and AF-related quality of life (β − 4.12, 95% CI: -8.10, − 0.14), and higher symptoms of anxiety (β 2.08, 95% CI: 0.76, 3.40), depression (β 1.44, 95% CI: 0.25, 2.63), and AF (β 0.29, 95% CI: 0.08, 0.50). Individuals < 60 years were significantly (p < 0.05) more likely to report higher symptoms of depression, anxiety, and AF, and poorer AF-related quality of life. Lack of college education was associated with reporting higher symptoms of AF (β 0.42, 95% CI: 0.17, 0.68), anxiety (β 1.86, 95% CI: 0.26, 3.45), and depression (β 1.11, 95% CI: 0.15, 2.38), and lower AF-related quality of life (β − 4.41, 95% CI: -8.25, − 0.57) and functional status. Conclusion Women, younger adults, and individuals with lower levels of education reported comparatively poor patient-reported outcomes. These findings highlight the importance of understanding why individuals experience AF differently based on certain characteristics