Provider and Practice Factors Associated With On-Time HPV Vaccination in Primary Care.

BACKGROUND: In 2018, only one third of girls and boys completed the 2-dose series of the human papillomavirus vaccine by their 13th birthday, the target for on-time vaccination. The study objective was to identify key patient, provider and practice-level factors associated with on-time vaccination in the primary care setting. METHODS: We examined data from 20 primary care pediatric practices (89 providers) in St. Louis including: the percentage of eligible patients with on-time vaccination assessed from medical records; providers' knowledge, attitudes and behaviors regarding on-time vaccination assessed with a survey; and practice-level strategies used to optimize vaccine delivery assessed with a 19-item vaccine delivery system score (VDSS). Factors that increased on-time vaccination were identified using logistic regression, controlling for clustering within providers. RESULTS: Completion of on-time vaccination occurred in 1347/3125 (43.10%) of patients (95% confidence interval [CI], 41.36%-44.86%) and varied among practices (7.39%-64.24%) and among providers (2.63%-82.50%). Independent predictors for higher completion of on-time vaccination included more frequent use by providers of the announcement style for vaccine recommendation (odds ratio [OR] 1.18, 95% CI, 1.04, 1.35), higher provider self-efficacy to deliver the vaccine according to guideline recommendations if parents were hesitant (OR 1.21, 95% CI, 1.05, 1.40), and higher VDSS (OR 1.20, 95% CI, 1.10, 1.31). CONCLUSIONS: Provider and practice-level factors were identified that may represent modifiable targets for improvement in on-time vaccine uptake. Future research is needed to test interventions built on these findings.

CARM1-mediated methylation of protein arginine methyltransferase 5 represses human γ-globin gene expression in erythroleukemia cells.

Protein arginine methyltransferase 5 (PRMT5) is a member of the arginine methyltransferase protein family that critically mediates the symmetric dimethylation of Arg-3 at histone H4 (H4R3me2s) and is involved in many key cellular processes, including hematopoiesis. However, the post-translational modifications (PTMs) of PRMT5 that may affect its biological functions remain less well-understood. In this study, using MS analyses, we found that PRMT5 itself is methylated in human erythroleukemia Lys-562 cells. Biochemical assays revealed that coactivator-associated arginine methyltransferase 1 (CARM1) interacts directly with and methylates PRMT5 at Arg-505 both in vivo and in vitro. Substitutions at Arg-505 significantly reduced PRMT5's methyltransferase activity, decreased H4R3me2s enrichment at the γ-globin gene promoter, and increased the expression of the γ-globin gene in Lys-562 cells. Moreover, CARM1 knockdown consistently reduced PRMT5 activity and activated γ-globin gene expression. Importantly, we show that CARM1-mediated methylation of PRMT5 is essential for the intracellular homodimerization of PRMT5 to its active form. These results thus reveal a critical PTM of PRMT5 that represses human γ-globin gene expression. We conclude that CARM1-mediated asymmetric methylation of PRMT5 is critical for its dimerization and methyltransferase activity leading to the repression of γ-globin expression. Given PRMT5's crucial role in diverse cellular processes, these findings may inform strategies for manipulating its methyltransferase activity for managing hemoglobinopathy or cancer.