Preadmission Metformin Use Is Associated with Reduced Mortality in Patients with Diabetes Mellitus Hospitalized with COVID-19.

BACKGROUND: Observational studies have reported an association between metformin and improved outcomes in COVID-19, but most have been small and with significant limitations. OBJECTIVE: To evaluate the association between preadmission metformin exposure and mortality in patients with diabetes mellitus hospitalized with coronavirus disease 2019 (COVID-19) infection. DESIGN: Retrospective cohort analysis using electronic health records extracted from the American Heart Association COVID-19 Registry. PARTICIPANTS: Adults (n = 11,993) with diabetes mellitus but without chronic kidney disease (CKD) or need for hemodialysis who were hospitalized with COVID-19 between January 25, 2020, and February 9, 2022. MAIN MEASURES: We used propensity score modeling to address differences between metformin and non-metformin users prior to multivariable log-binomial models to examine the association between metformin use at time of hospital admission for COVID-19 infection and in-hospital death; composite of in-hospital death or discharge to hospice; composite of in-hospital death, discharge to hospice, or ICU admission; and composite of in-hospital death, discharge to hospice, ICU admission, or mechanical ventilation. KEY RESULTS: Compared to metformin non-use, pre-admission metformin use was associated with lower risk of in-hospital death (risk ratio (RR) 0.81 [95% CI 0.75-0.90]); composite of in-hospital death or discharge to hospice (RR 0.79 [95% CI 0.74-0.87]); composite of in-hospital death, discharge to hospice, or ICU admission (RR 0.90 [95% CI 0.86-0.95]); and composite of in-hospital death, discharge to hospice, ICU admission, or mechanical ventilation (RR 0.9 [95% CI 0.84-0.98]). Metformin use was also associated with lower risk of death due to respiratory cause (RR 0.86 [95% CI 0.74-0.97]) but not cardiovascular (RR 0.84 [95% CI 0.58-1.2]) or other (RR 0.78 [95% CI 0.60-1.0]) causes. CONCLUSIONS: Pre-admission metformin use was associated with lower risk of in-hospital mortality and markers of disease severity among adults with diabetes mellitus without CKD and not requiring hemodialysis who were hospitalized with COVID-19 infection.

An AML1-ETO/miR-29b-1 regulatory circuit modulates phenotypic properties of acute myeloid leukemia cells.

Acute myeloid leukemia (AML) is characterized by an aggressive clinical course and frequent cytogenetic abnormalities that include specific chromosomal translocations. The 8;21 chromosomal rearrangement disrupts the key hematopoietic RUNX1 transcription factor, and contributes to leukemia through recruitment of co-repressor complexes to RUNX1 target genes, altered subnuclear localization, and deregulation of the myeloid gene regulatory program. However, a role of non-coding microRNAs (miRs) in t(8;21)-mediated leukemogenesis is minimally understood. We present evidence of an interplay between the tumor suppressor miR-29b-1 and the AML1-ETO (also designated RUNX1-RUNX1T1) oncogene that is encoded by the t(8;21). We find that AML1-ETO and corepressor NCoR co-occupy the miR-29a/b-1 locus and downregulate its expression in leukemia cells. Conversely, re-introduction of miR-29b-1 in leukemia cells expressing AML1-ETO causes significant downregulation at the protein level through direct targeting of the 3' untranslated region of the chimeric transcript. Restoration of miR-29b-1 expression in leukemia cells results in decreased cell growth and increased apoptosis. The AML1-ETO-dependent differentiation block and transcriptional program are partially reversed by miR-29b-1. Our findings establish a novel regulatory circuit between the tumor-suppressive miR-29b-1 and the oncogenic AML1-ETO that controls the leukemic phenotype in t(8;21)-carrying acute myeloid leukemia.

A Mixed Methods Approach to Equity and Justice Research: Insights from Research on Children's Reasoning About Economic Inequality.

Mixed methods research approaches are gaining traction across various social science disciplines, including among developmental scientists. In this chapter, we discuss the utility of a mixed methods research approach in examining issues related to equity and justice. We incorporate a brief overview of quantitative and qualitative monomethod research approaches in our larger discussion of the advantages, procedures, and considerations of employing a mixed methods design to advance developmental science from an equity and justice perspective. To better illustrate the theoretical and practical significance of a mixed methods research approach, we include examples of research conducted on children and adolescents' conceptions of economic inequality as one example of developmental science research with an equity and justice frame.

Elementary School Children's Reasoning About Social Class: A Mixed-Methods Study.

The current study examined children's identification and reasoning about their subjective social status (SSS), their beliefs about social class groups (i.e., the poor, middle class, and rich), and the associations between the two. Study participants were 117 10- to 12-year-old children of diverse racial, ethnic, and socioeconomic backgrounds attending a laboratory elementary school in Southern California. Results indicated that children's SSS ratings correlated with indicators of family socioeconomic status and were informed by material possessions, lifestyle characteristics, and social and societal comparisons. Children rated the poor as having fewer positive attributes and more negative attributes than the middle class, and fewer positive attributes than the rich. Lower SSS children held less positive attitudes toward the poor than children with middle SSS ratings.

A longitudinal study of the simultaneous influence of mothers' and teachers' educational expectations on low-income youth's academic achievement.

This short-term longitudinal study investigated the simultaneous influences of adults' (mothers and teachers) educational expectations and youth's achievement (standardized test scores and teachers' ratings of academic performance) across a 3-year time span on youth's performance in school (GPA). Participants were an ethnically diverse sample of 426 low-income urban youth, ages 6 through 16 at T1. Results from cross-lagged and autoregressive path analyses indicated stability in adults' expectations and youth's standardized test scores; cross-lagged influences of teachers', but not mothers', expectations across time; and effects of youth's achievement outcomes on adults' expectations at T2, but not vice versa. Overall, the pattern of findings demonstrate that adults' educational expectations are dynamic and responsive to how youth are faring in school and to changes in academic performance across time.