REV7-p53 interaction inhibits ATM-mediated DNA damage signaling.

REV7 is an abundant, multifunctional protein that is a known factor in cell cycle regulation and in several key DNA repair pathways including Trans-Lesion Synthesis (TLS), the Fanconi Anemia (FA) pathway, and DNA Double-Strand Break (DSB) repair pathway choice. Thus far, no direct role has been studied for REV7 in the DNA damage response (DDR) signaling pathway. Here we describe a novel function for REV7 in DSB-induced p53 signaling. We show that REV7 binds directly to p53 to block ATM-dependent p53 Ser15 phosphorylation. We also report that REV7 is involved in the destabilization of p53. These findings affirm REV7's participation in fundamental cell cycle and DNA repair pathways. Furthermore, they highlight REV7 as a critical factor for the integration of multiple processes that determine viability and genome stability.

Reliability and Differences Between Sexes in Landing Mechanics when Performing the Lateral Bound Test.

Background and Purpose: Anterior cruciate ligament injuries are prevalent among the athletic population, imposing a heavy economic burden, and the risk of re-injury. Most current biomechanical screening tasks are performed in the sagittal plane, and there is a need for more screening tools that assess sports specific movements in the frontal plane. The purpose of this study was to determine the reliability of and examine differences between sexes in the performance of the Lateral Bound Test (LBT). Materials/Methods: Each subject performed three trials of a LBT which included jumping laterally from one leg over a hurdle and landing on the opposite leg. Two cameras were placed six feet from the landing marker. Maximum dynamic knee valgus using the frontal plane projection angle and knee flexion angle at initial contact and maximal knee flexion were measured upon landing leg using 2D video analysis software. Additionally, video of 10 individuals' trials were analyzed twice with one week between the analyses to obtain intra-rater reliability while 12 participants were retested one week later to determine test-retest reliability. Results: Thirty healthy subjects, 16 males, 14 females participated. Intra-rater reliability was determined to be excellent for all variables (ICC>0.96). In contrast, the test-retest reliability had greater disparity. Test-retest reliability ranged from poor (ICC = 0.47) to excellent (ICC > 0.90). Significant differences existed between the sexes, including males being significantly taller, weighing more, and demonstrating greater bilateral dynamic knee valgus (p < 0.05). No significant differences existed between sexes for knee flexion angles. Conclusion: The new LBT had excellent intra-rater reliability for assessing dynamic knee valgus and initial and maximum knee flexion angle when performing a functional movement in the frontal plane. Furthermore, males landed with more dynamic knee valgus than females which is contradictory to what has been observed with functional screening tools performed in the sagittal plane. Level of Evidence: 3b (reliability study).

Litigation to Access Health Services: Ally or Enemy of Global Public Health?

Background: Some scholars and global health advocates argue that litigation is a strategy to advance public health care, especially in those countries that do not have specific legislation to guarantee access to basic health care services. However, strategic litigation has another side, known as judicialization of the right to health, particularly present in the Latin American region where most countries incorporate the right to health into their constitutions, but their citizens still struggle with health disparities. Objectives: Considering these two perspectives on litigation in health care, this paper examines the phenomenon of litigation in health care and its impact on public health in Brazil, where there is an ambiguous process of litigation in health care. Methods: Comparing the literature of both the use of strategic litigation for advancing public health and the judicialization of the right to health, this paper develops an ethical analysis of the impacts of strategic litigation for individuals and societies, using Brazil's public health care system and its policies as case-study of the impact of court decisions on the management of the system. Findings: Supporters of strategic litigation present experiences in African countries using this strategy to access a specific medical service led to enforce the creation of health-related policies by authorities and policymakers. However, in Brazil, a country with the right to health guaranteed by its Constitution, strategic litigation creates access to health care for some individuals, but also results in complex sociomedical challenges with significant impact for public administration and distributive justice. Conclusions: Strategic litigation can lead to ambiguous results, which will depend on the local context and the existence or not of public health services and health-related policies. When this strategy is considered, ethical analysis helps to understand how litigation can both benefit and damage individuals' health and the public health system in the complex context and diverse reality of Brazil. As a result, strategic litigation must be considered from an ethical perspective of prudence and discernment in a close interaction with the local reality, its particular circumstances, culture, policies, and laws.

Implementation of Quality-of-Life Assessment Increases Referrals for Intervention in Patients with Tetralogy of Fallot.

Mortality from surgical repair of tetralogy of Fallot (TOF) has decreased dramatically over the last several decades. Despite excellent surgical outcomes, studies reveal that patients with TOF continue to have decreased physical functioning, academic difficulties, and psychosocial impairments. We hypothesized that administering a validated quality-of-life assessment to patients with TOF during routine cardiology follow-up visits would help identify deficits and increase referrals to appropriate interventional programs. Between May 2017 and November 2018, TOF patients (5-20 years) and/or their families completed a standardized quality-of-life assessment (PedsQL 4.0) during cardiology clinic visits. Providers were encouraged to refer patients with abnormal PedsQL 4.0 scores to appropriate services including cardiovascular rehabilitation, psychological evaluation, neurodevelopmental testing, and school intervention. Referrals for the intervention group were compared to those of a control group using χ2 analysis. The PedsQL 4.0 was completed by 79 patients at 90 clinic visits. At least one abnormal PedsQL 4.0 score was identified in 58% (52/90) of patient encounters, and of those 52 encounters, 38% (20/52) received at least one referral for intervention. The most commonly placed referrals were for neurodevelopmental testing (16) and school intervention (11). When comparing the number of referrals from the intervention group to those of the control group, referrals to all intervention services were statistically significant (p < 0.05). Our quality improvement initiative successfully utilized a quality-of-life assessment to detect deficits and subsequently increased the number of referrals to intervention services. Future studies will address barriers that prevent completion of the PedsQL and assess how interventions impact quality-of-life scores.

Neurodevelopmental outcomes at 2 and 4 years in children with congenital heart disease.

BACKGROUND AND OBJECTIVES: Children with congenital heart disease (CHD) are at risk for neurodevelopmental (ND) delays. The purpose of this study is to compare the ND testing results of children with CHD at 2 and 4 years of age and determine if rates of ND delays change over time. METHODS: Children with CHD completed the Bayley Scales of Infant Development-III (BSID-III) at 2 years of age, and standardized neuropsychological measures at 4 years. Scores were compared with test norms and were classified as: average (within one SD of test mean); at risk (1-2 SDs from the test mean); and delayed (>2 SD from test mean). Pearson correlations and McNemar's exact tests were performed to determine the relationship between test scores at the two times of assessment. RESULTS: Sixty-four patients completed evaluations at 24 ± 3 months of age and 4 years of age. BSID-III cognitive and fine motor scores were correlated with preschool IQ and fine motor scores, r = .75 to .87, P < .0001. Agreement in score categories was 79% for cognitive and 61% for fine motor. More patients had at risk or delayed scores at age 4 vs age 2 (P ≤ .01). CONCLUSION(S): Despite significant correlations between 2- and 4-year-old test scores, many patients who scored in the average range at age 2 showed deficits at age 4. BSID-III scores at age 2 may underestimate delays. Therefore, longitudinal ND assessment is recommended.

Preschool Neurodevelopmental Outcomes in Children with Congenital Heart Disease.

OBJECTIVE: To describe preschool neurodevelopmental outcomes of children with complex congenital heart disease (CHD), who were evaluated as part of a longitudinal cardiac neurodevelopmental follow-up program, as recommended by the American Heart Association and the American Academy of Pediatrics, and identify predictors of neurodevelopmental outcomes in these children. STUDY DESIGN: Children with CHD meeting the American Heart Association/American Academy of Pediatrics high-risk criteria for neurodevelopmental delay were evaluated at 4-5 years of age. Testing included standardized neuropsychological measures. Parents completed measures of child functioning. Scores were compared by group (single ventricle [1V]; 2 ventricles [2V]; CHD plus known genetic condition) to test norms and classified as: normal (within 1 SD of mean); at risk (1-2 SD from mean); and impaired (>2 SD from mean). RESULTS: Data on 102 patients were analyzed. Neurodevelopmental scores did not differ based on cardiac anatomy (1V vs 2V); both groups scored lower than norms on fine motor and adaptive behavior skills, but were within 1 SD of norms. Patients with genetic conditions scored significantly worse than 1V and 2V groups and test norms on most measures. CONCLUSIONS: Children with CHD and genetic conditions are at greatest neurodevelopmental risk. Deficits in children with CHD without genetic conditions were mild and may not be detected without formal longitudinal testing. Parents and providers need additional education regarding the importance of developmental follow-up for children with CHD.