Exploring Health Literacy, Transition Readiness, and Healthcare Utilization in Medicaid Chronically Ill Youth.

PURPOSE: Youths with special healthcare needs face challenges transitioning from pediatric to adult health care. Understanding possible mechanisms contributing to poor healthcare transition could improve care. This study explores associations between health literacy (HL), transition readiness, and healthcare utilization. METHODS: Youths with special healthcare needs aged 12-18 years were recruited from a Medicaid accountable care organization (2012-2017). Outcome measures included transition readiness (Transition Readiness Assessment Questionnaire), and healthcare utilization (any well-check, hospitalization, emergency department [ED] visit, or ambulatory sensitive condition ED visit). Multivariate regression analyses examined whether HL (adequate vs. inadequate) predicted outcomes, after adjusting for covariates. Models were then created to examine whether the effect of HL on healthcare utilization was mediated by transition readiness. RESULTS: Among 417 youths with special healthcare needs, 67.1% reported adequate HL. Relative to inadequate HL, teens with adequate HL had significantly higher average Transition Readiness Assessment Questionnaire-20 scores (ß = .34, p < .001). Controlling for covariates, HL was a significant predictor of having an ambulatory sensitive condition ED visit and having any ED visits neared significance. There was a positive transition readiness mediation effect on having an ED visit, with higher transition readiness being associated with higher odds of having any ED visit in the mediation analysis. CONCLUSIONS: HL is independently associated with higher transition readiness and lower ambulatory sensitive condition ED use, but pathways of action require further study.

Do health literacy disparities explain racial disparities in family-centered care for youths with special health care needs?

OBJECTIVE: To explore the relationship among youth health literacy, parental health literacy, and family-centered care (FCC) for youth with special health care needs (YSHCN) and assess potential racial disparities. METHODS: HL and FCC were assessed in 486 Medicaid-enrolled YSHCN (ages 12-18) and their healthcare-responsible parent/caregiver. Analyses assessed racial differences in HL and FCC for parents and youth using logistic regression. RESULTS: Half of youth and over 80 percent of parents had adequate HL (REALM score ≥62). Adequate HL was significantly lower in African Americans (AA) for both YSHCN and parents. Only 57 % of parents and 29 % of YSHCN reported FCC. AA YSHCN reported significantly lower levels of FCC compared to White YSHCN. AA parents trended lower for FCC compared to Whites, though the disparity was not significant. AA youth and parents had significantly lower odds of reporting that doctors spent enough time with them compared to Whites. CONCLUSION: Results suggest that AA and those with less than adequate health literacy experience lower FCC, however the relationship between race and health literacy does not explain the racial disparity in FCC. PRACTICAL IMPLICATIONS: Provider time spent focused on HL may not reduce the racial disparity in FCC, but opportunities for improvement exist.

Insights into the base-pairing preferences of 8-oxoguanosine on the ribosome.

Of the four bases, guanine is the most susceptible to oxidation, which results in the formation of 8-oxoguanine (8-oxoG). In protein-free DNA, 8-oxodG adopts the syn conformation more frequently than the anti one. In the syn conformation, 8-oxodG base pairs with dA. The equilibrium between the anti and syn conformations of the adduct are known to be altered by the enzyme recognizing 8-oxodG. We previously showed that 8-oxoG in mRNA severely disrupts tRNA selection, but the underlying mechanism for these effects was not addressed. Here, we use miscoding antibiotics and ribosome mutants to probe how 8-oxoG interacts with the tRNA anticodon in the decoding center. Addition of antibiotics and introduction of error-inducing mutations partially suppressed the effects of 8-oxoG. Under these conditions, rates and/or endpoints of peptide-bond formation for the cognate (8-oxoG•C) and near-cognate (8-oxoG•A) aminoacyl-tRNAs increased. In contrast, the antibiotics had little effect on other mismatches, suggesting that the lesion restricts the nucleotide from forming other interactions. Our findings suggest that 8-oxoG predominantly adopts the syn conformation in the A site. However, its ability to base pair with adenosine in this conformation is not sufficient to promote the necessary structural changes for tRNA selection to proceed.

Decoding on the ribosome depends on the structure of the mRNA phosphodiester backbone.

During translation, the ribosome plays an active role in ensuring that mRNA is decoded accurately and rapidly. Recently, biochemical studies have also implicated certain accessory factors in maintaining decoding accuracy. However, it is currently unclear whether the mRNA itself plays an active role in the process beyond its ability to base pair with the tRNA. Structural studies revealed that the mRNA kinks at the interface of the P and A sites. A magnesium ion appears to stabilize this structure through electrostatic interactions with the phosphodiester backbone of the mRNA. Here we examined the role of the kink structure on decoding using a well-defined in vitro translation system. Disruption of the kink structure through site-specific phosphorothioate modification resulted in an acute hyperaccurate phenotype. We measured rates of peptidyl transfer for near-cognate tRNAs that were severely diminished and in some instances were almost 100-fold slower than unmodified mRNAs. In contrast to peptidyl transfer, the modifications had little effect on GTP hydrolysis by elongation factor thermal unstable (EF-Tu), suggesting that only the proofreading phase of tRNA selection depends critically on the kink structure. Although the modifications appear to have no effect on typical cognate interactions, peptidyl transfer for a tRNA that uses atypical base pairing is compromised. These observations suggest that the kink structure is important for decoding in the absence of Watson-Crick or G-U wobble base pairing at the third position. Our findings provide evidence for a previously unappreciated role for the mRNA backbone in ensuring uniform decoding of the genetic code.

Uniformity of Peptide Release Is Maintained by Methylation of Release Factors.

Termination of protein synthesis on the ribosome is catalyzed by release factors (RFs), which share a conserved glycine-glycine-glutamine (GGQ) motif. The glutamine residue is methylated in vivo, but a mechanistic understanding of its contribution to hydrolysis is lacking. Here, we show that the modification, apart from increasing the overall rate of termination on all dipeptides, substantially increases the rate of peptide release on a subset of amino acids. In the presence of unmethylated RFs, we measure rates of hydrolysis that are exceptionally slow on proline and glycine residues and approximately two orders of magnitude faster in the presence of the methylated factors. Structures of 70S ribosomes bound to methylated RF1 and RF2 reveal that the glutamine side-chain methylation packs against 23S rRNA nucleotide 2451, stabilizing the GGQ motif and placing the side-chain amide of the glutamine toward tRNA. These data provide a framework for understanding how release factor modifications impact termination.