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BackgroundThere is a need for medical education on health care transitions for youth with special health care needs. The Texas Transition Toolkit (the tool) supports providers through a one-stop shop for researching literature on care transitions, a catalog of care transition tools, and guides for developing care transition programs. ObjectiveThis study aims to assess the functionality and usability of the tool with providers working with transition-aged children and youth with special health care needs (representative users). MethodsThe tool was evaluated using a triangulated mixed methods case study approach consisting of a concurrent think-aloud phase, a satisfaction survey, and a survey of problem relevance and task performance to operationalize and capture functionality and usability. Our mixed methods deep dive into the functionality and usability of the tool focused on 10 representative users from one medical home in Texas and 5 website design experts. ResultsRepresentative users found the tool to be highly relevant, as demonstrated by the satisfaction score for relevance (138/150, 92%). According to the users, the tool provided comprehensive information related to health care transitions for youth with special health care needs, with a satisfaction score of 87.3% (131/150) for comprehensive. Overall satisfaction with the tool was high at 81.92% (1065/1300) with a cutoff score of 73.33% (953.4/1300) indicating high satisfaction, but users reported relatively lower satisfaction with search (114/150, 76%) and navigation (ease of use: 114/150, 76%; hyperlinks: 163/200, 81.5%; structure: 159/200, 79.5%). They experienced search- and navigation-related problems (total problems detected: 21/31, 68%) and, based on quality checks, had a relatively low task completion rate for tasks involving finding information (60/80, 75%), which required searching and navigation. The problems identified around search and navigation functionality were relevant (relevance scores ranging from 14.5 to 22, with a cutoff score of 11.7 indicating relevance). ConclusionsThe tool may help bridge the gaps in training on health care transitions for youth with special health care needs in US medical education. The tool can be used to create structured protocols to help improve provider knowledge, collaboration across pediatric and adult care providers, and the continuity of care as youth with special health care needs transition from pediatric to adult care. The results provided a road map for optimizing the tool and highlighted the importance of evaluating eHealth technologies with representative users.

Tourette disorder (TD) is poorly understood, despite affecting 1/160 children. A lack of animal models possessing construct, face, and predictive validity hinders progress in the field. We used CRISPR/Cas9 genome editing to generate mice with mutations orthologous to human de novo variants in two high-confidence Tourette genes, CELSR3 and WWC1. Mice with human mutations in Celsr3 and Wwc1 exhibit cognitive and/or sensorimotor behavioral phenotypes consistent with TD. Sensorimotor gating deficits, as measured by acoustic prepulse inhibition, occur in both male and female Celsr3 TD models. Wwc1 mice show reduced prepulse inhibition only in females. Repetitive motor behaviors, common to Celsr3 mice and more pronounced in females, include vertical rearing and grooming. Sensorimotor gating deficits and rearing are attenuated by aripiprazole, a partial agonist at dopamine type II receptors. Unsupervised machine learning reveals numerous changes to spontaneous motor behavior and less predictable patterns of movement. Continuous fixed-ratio reinforcement shows that Celsr3 TD mice have enhanced motor responding and reward learning. Electrically evoked striatal dopamine release, tested in one model, is greater. Brain development is otherwise grossly normal without signs of striatal interneuron loss. Altogether, mice expressing human mutations in high-confidence TD genes exhibit face and predictive validity. Reduced prepulse inhibition and repetitive motor behaviors are core behavioral phenotypes and are responsive to aripiprazole. Enhanced reward learning and motor responding occur alongside greater evoked dopamine release. Phenotypes can also vary by sex and show stronger affection in females, an unexpected finding considering males are more frequently affected in TD. [ABSTRACT FROM AUTHOR]

The hepatitis C virus (HCV) infects more than 180 million people worldwide, with long-term consequences including liver failure and hepatocellular carcinoma. Quercetin bioflavonoids can decrease HCV production in tissue culture, in part through inhibition of heat shock proteins. If quercetin demonstrates safety and antiviral activity in patients, then it could be developed into an inexpensive HCV treatment for third world countries or other affected populations that lack financial means to cover the cost of mainstream antivirals. A phase 1 dose escalation study was performed to evaluate the safety of quercetin in 30 untreated patients with chronic HCV infection and to preliminarily characterize quercetin's potential in suppressing viral load and/or liver injury. Quercetin displayed safety in all trial participants. Additionally, 8 patients showed a "clinically meaningful" 0.41-log viral load decrease. There was a positive correlation (r = 0.41, p = 0.03) indicating a tendency for HCV decrease in patients with a lower ratio of plasma quercetin relative to dose. No significant changes in aspartate transaminase and alanine transaminase were detected. In conclusion, quercetin exhibited safety (up to 5 g daily) and there was a potential for antiviral activity in some hepatitis C patients.

Food insecurity is a risk factor for morbidity and mortality leading to high medical expenditures, but race/ethnicity was used as adjustments in the literature. The study sought to use race/ethnicity as a key predictor to compare racial differences in associations between food insecurity and expenditures of seven health services among non-institutionalized adults. This cross-sectional study used Medical Expenditure Panel Survey that collects information on food insecurity in 2016 (n=24,179) and 2017 (n=22,539). We examined the association between race/ethnicity and food insecurity status and documented the extent to which impacts of food insecurity on medical expenditures varied by race/ethnicity. We fit multivariable models for each racial group, adjusting for states, age, gender, insurance, and education. Adults older than 18 years were included. The results show that blacks experienced an inter-racial disparity in food insecurity whereas Hispanics experienced intra-racial disparity. A higher percentage of blacks (28.7%) reported at least one type of food insecurity (11.2% of whites). Around 20% of blacks reported being worried about running out of food and the corresponding number is 8.4% among whites. Hispanics reported more food insecurity issues than whites. Moreover, food insecurity is positively associated with expenditures on emergency room utilization (99% increase for other races vs. 51% increase for whites) but is negatively associated with dental care utilization (43% decrease for blacks and 44% for whites). Except for Hispanics, prescription expenditure has the most positive association with food insecurity, and food insecure blacks are the only group that did not significantly use home health. The study expanded our understanding of food insecurity by investigating how it affected seven types of medical expenditures for each of four racial populations. An interdisciplinary effort is needed to enhance the food supply for minorities. Policy interventions to address intra-racial disparities among Hispanics and inter-racial disparities among African Americans are imperative to close the gap. [ABSTRACT FROM AUTHOR]

Immunoglobulin heavy chain variable region exons are assembled in progenitor-B cells, from VH, D, and JH gene segments located in separate clusters across the Igh locus. RAG endonuclease initiates V(D)J recombination from a JH-based recombination center (RC). Cohesin-mediated extrusion of upstream chromatin past RC-bound RAG presents Ds for joining to JHs to form a DJH-RC. Igh has a provocative number and organization of CTCF-binding elements (CBEs) that can impede loop extrusion. Thus, Igh has two divergently oriented CBEs (CBE1 and CBE2) in the IGCR1 element between the VH and D/JH domains, over 100 CBEs across the VH domain convergent to CBE1, and 10 clustered 3'Igh-CBEs convergent to CBE2 and VH CBEs. IGCR1 CBEs segregate D/JH and VH domains by impeding loop extrusion-mediated RAG-scanning. Downregulation of WAPL, a cohesin unloader, in progenitor-B cells neutralizes CBEs, allowing DJH-RC-bound RAG to scan the VH domain and perform VH-to-DJH rearrangements. To elucidate potential roles of IGCR1-based CBEs and 3'Igh-CBEs in regulating RAG-scanning and elucidate the mechanism of the ordered transition from D-to-JH to VH-to-DJH recombination, we tested effects of inverting and/or deleting IGCR1 or 3'Igh-CBEs in mice and/or progenitor-B cell lines. These studies revealed that normal IGCR1 CBE orientation augments RAG-scanning impediment activity and suggest that 3'Igh-CBEs reinforce ability of the RC to function as a dynamic loop extrusion impediment to promote optimal RAG scanning activity. Finally, our findings indicate that ordered V(D)J recombination can be explained by a gradual WAPL downregulation mechanism in progenitor-B cells as opposed to a strict developmental switch. [ABSTRACT FROM AUTHOR]