Biochemical and biophysical characterization of the nucleic acid binding properties of the RNA/DNA binding protein EWS.

EWS is a member of the FET family of RNA/DNA binding proteins that regulate crucial phases of nucleic acid metabolism. EWS comprises an N-terminal low-complexity domain (LCD) and a C-terminal RNA-binding domain (RBD). The RBD is further divided into three RG-rich regions, which flank an RNA-recognition motif (RRM) and a zinc finger (ZnF) domain. Recently, EWS was shown to regulate R-loops in Ewing sarcoma, a pediatric bone and soft-tissue cancer in which a chromosomal translocation fuses the N-terminal LCD of EWS to the C-terminal DNA binding domain of the transcription factor FLI1. Though EWS was shown to directly bind R-loops, the binding mechanism was not elucidated. In the current study, the RBD of EWS was divided into several constructs, which were subsequently assayed for binding to various nucleic acid structures expected to form at R-loops, including RNA stem-loops, DNA G-quadruplexes, and RNA:DNA hybrids. EWS interacted with all three nucleic acid structures with varying affinities and multiple domains contributed to binding each substrate. The RRM and RG2 region appear to bind nucleic acids promiscuously while the ZnF displayed more selectivity for single-stranded structures. With these results, the structural underpinnings of EWS recognition and binding of R-loops and other nucleic acid structures is better understood.

Mutual Gaze: An Active Ingredient for Social Development in Toddlers with ASD: A Randomized Control Trial.

We examined the efficacy of an early autism intervention for use in early childhood intervention (ECI) and mutual gaze as a contributor to social development. Seventy-eight families were randomly assigned to one of three 12-week interventions: Pathways (with a mutual gaze component), communication, or services-as-usual (SAU). The Pathways/SAU comparison concerned the efficacy of Pathways for ECI, and the Pathways/communication comparison, mutual gaze. The Pathways group made significantly more change on social measures, communicative synchrony, and adaptive functioning compared with the SAU group and on social measures compared with the communication group. There were no group differences for communicative acts. The results support Pathways as a potential ECI program and mutual gaze as an active ingredient for social and communication development.

A Clinical Reminder Order Check Intervention to Improve Guideline-concordant Imaging Practices for Men With Prostate Cancer: A Pilot Study.

OBJECTIVE: To understand how to potentially improve inappropriate prostate cancer imaging rates we used National Comprehensive Cancer Network's guidelines to design and implement a Clinical Reminder Order Check (CROC) that alerts ordering providers of potentially inappropriate imaging orders in real-time based on patient features of men diagnosed with low-risk prostate cancer. METHODS: We implemented the CROC at VA New York Harbor Healthcare System from April 2, 2015 to November 15, 2017. We then used VA administrative claims from the VA's Corporate Data Warehouse to analyze imaging rates among men with low-risk prostate cancer at VA New York Harbor Healthcare System before and after CROC implementation. We also collected and cataloged provider responses in response to overriding the CROC in qualitative analysis. RESULTS FIFTY SEVEN PERCENT: (117/205) of Veterans before CROC installation and 73% (61/83) of Veterans post-intervention with low-risk prostate cancer received guideline-concordant care. CONCLUSION: While the decrease in inappropriate imaging during our study window was almost certainly due to many factors, a Computerized Patient Record System-based CROC intervention is likely associated with at least moderate improvement in guideline-concordant imaging practices for Veterans with low-risk prostate cancer.

Hepatitis C virus screening at a Veterans Administration Hospital in New York City.

BACKGROUND: Asymptomatic hepatitis C virus (HCV) infection has the highest prevalence in "baby boomers" born in 1945 through 1965. New York State mandates that all persons born during this period be screened at least once for hepatitis C. LOCAL PROBLEM: Military veteran HCV screening is often missed during primary care visits. METHODS: After baseline screening, provider education with and without an HCV education dashboard of information in the Electronic Medical Record system was used to determine if screening proportions could be improved. The Chi-square and Z-test for independent proportions compared after with before education screening. The odds ratio compared after versus before screening odds. INTERVENTIONS: Two interventions were tested. One was provider education with a 30-minute lecture. The second was the lecture with addition of an HCV education computer dashboard. RESULTS: The Chi-square test and Z-test comparing the month immediately after provider education was significant for increased screening (p < .01) compared with baseline. There was a 2.04-fold (95% confidence interval, 1.31-3.20) greater odds of screening in the month after education. If two or more months went by after education, the effect of education no longer improved screening proportions. Provider education plus the use of HCV education dashboard did not improve screening from baseline to the month immediately after screening (p = .95). CONCLUSION: Provider education significantly improved HCV screening the month immediately after education, then regressed toward baseline. Adding an HCV education dashboard to education did not improve screening. To maintain elevated screening proportions, provider screening education must be reinforced on a frequent basis for sustained effect.

A community-based early intervention program for toddlers with autism spectrum disorders.

This study examined Pathways Early Autism Intervention, a community-based, parent-mediated, intensive behavioral and developmental intervention program for children with autism spectrum disorders that could be used as a model for state-funded early intervention programs. A single-subject, multiple-baseline, across-participants design was used. Four boys with autism spectrum disorder and their mothers participated. Interventionists made weekly home visits and worked with caregivers to establish and maintain face-to-face reciprocal social interaction and eye contact. Each session included a 10-min video of parent-child interaction. Evidence of intervention effectiveness was measured by percentage of nonoverlapping data points. Social validity was measured using questionnaire items in regard to parents' perception of the intervention. The intervention was effective for the measures of eye contact, social engagement, and verbal reciprocity but not for nonverbal turn taking. Parents perceived the intervention as beneficial and easy to learn and incorporate into daily life.