Aims Epigenetic regulators, including microRNAs(miRNAs), are implicated in type 2 diabetes, but evidence linking circulating miRNAs in pregnancy and risk of gestational diabetes(GDM) is sparse. Potential modifiers, including pre-pregnancy overweight/obesity and offspring sex, are unexamined. We hypothesized that circulating levels of early-mid-pregnancy(range 7-23 weeks of gestation) candidate miRNAs are related to subsequent development of GDM. We also hypothesized that miRNA-GDM associations might vary by pre-pregnancy body-mass index(ppBMI) or offspring sex. Methods In a case-control analysis(36 GDM cases/80 controls) from the Omega study, a prospective cohort study of pregnancy complications, we measured early–mid-pregnancy plasma levels of 10 miRNAs chosen for potential roles in pregnancy course and complications(miR-126-3p, -155-5p, -21-3p, -146b-5p, -210-3p, -222-3p, -223-3p, -517-5p, -518a-3p, and 29a-3p) using qRT-PCR. Logistic regression models adjusted for gestational age at blood draw (GA) were fit to compare circulating miRNAs between cases and controls. We repeated analyses among overweight/obese(ppBMI≥25kg/m2) or lean(ppBMI<25kg/m2) women, and women with male or female offspring separately. Results Mean age was 34.3 years(cases) and 32.9 years(controls). GA-adjusted miR-155-5p(β=0.260/p=0.028) and - 21-3p(β=0.316/p=0.005) levels were positively associated with GDM. MiR-146b-5p(β=0.266/p=0.068) and miR-517-5p(β=0.196/p=0.074) were borderline. Associations of miR-21-3p and miR-210-3p with GDM were observed among overweight/obese but not lean women. Associations of six miRNAs(miR-155-5p, -21-3p, - 146b-5p, -223-3p, -517-5p, and -29a-3p) with GDM were present only among women carrying male fetuses(all p<0.05). Conclusions Circulating early–mid-pregnancy miRNAs are associated with GDM, particularly among women who are overweight/obese pre-pregnancy or pregnant with male offspring. This area has potential to clarify mechanisms underlying GDM pathogenesis and identify at-risk mothers earlier in pregnancy.

Background Methods of sustaining the deimplementation of overused medical practices (i.e., practices not supported by evidence) are understudied. In pediatric hospital medicine, continuous pulse oximetry monitoring of children with the common viral respiratory illness bronchiolitis is recommended only under specific circumstances. Three national guidelines discourage its use for children who are not receiving supplemental oxygen, but guideline-discordant practice (i.e., overuse) remains prevalent. A 6-hospital pilot of educational outreach with audit and feedback resulted in immediate reductions in overuse; however, the best strategies to optimize sustainment of deimplementation success are unknown. Methods The Eliminating Monitor Overuse (EMO) trial will compare two deimplementation strategies in a hybrid type III effectiveness-deimplementation trial. This longitudinal cluster-randomized design will be conducted in Pediatric Research in Inpatient Settings (PRIS) Network hospitals and will include baseline measurement, active deimplementation, and sustainment phases. After a baseline measurement period, 16–19 hospitals will be randomized to a deimplementation strategy that targets unlearning (educational outreach with audit and feedback), and the other 16–19 will be randomized to a strategy that targets unlearning and substitution (adding an EHR-integrated clinical pathway decision support tool). The primary outcome is the sustainment of deimplementation in bronchiolitis patients who are not receiving any supplemental oxygen, analyzed as a longitudinal difference-in-differences comparison of overuse rates across study arms. Secondary outcomes include equity of deimplementation and the fidelity to, and cost of, each deimplementation strategy. To understand how the deimplementation strategies work, we will test hypothesized mechanisms of routinization (clinicians developing new routines supporting practice change) and institutionalization (embedding of practice change into existing organizational systems). Discussion The EMO trial will advance the science of deimplementation by providing new insights into the processes, mechanisms, costs, and likelihood of sustained practice change using rigorously designed deimplementation strategies. The trial will also advance care for a high-incidence, costly pediatric lung disease. Trial registration ClinicalTrials.gov,NCT05132322. Registered on November 10, 2021.

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Summary: Background: The MC3R haplotype C17A+G241A, which encodes a partially-inactivated receptor, has high prevalence in Individuals of predominately African ancestry. In pediatric cohorts, homozygosity for this common variant has been associated with obesity, reduced lean mass, and greater fasting insulin. However, metabolic and body composition measures have not been well studied in adults with this haplotype. Methods: A convenience sample of 237 healthy African American adult volunteers was studied. Taqman assays were used to genotype MC3R variants. Labs were drawn in the morning in the fasted state. Body composition data was obtained via dual-energy X-ray absorptiometry. An analysis of covariance was used to examine the associations of genotype with metabolic and body composition measures controlling for age and sex. Results: Individuals homozygous for the MC3R C17A+G241A haplotype had significantly greater body mass index, fat mass, fat mass percentage, and C-Reactive Protein, with reduced lean mass percentage as compared to heterozygous and wild-type participants (all p’s<0.05); fasting insulin was marginally non-significant between groups (p=0.053). After adjusting for fat mass, laboratory differences no longer remained significant. Conclusions: Homozygosity for MC3R C17A+G241A is associated with increased adiposity in African American adults. Further studies are needed to elucidate the mechanisms behind these associations.