The Dynamic Interaction Between Psychological Health and Sleep Symptoms Following Adolescent Concussion.

Objectives: To evaluate changes in psychological symptoms and sleep quality at three clinically relevant milestones following adolescent concussion: while symptomatic, at symptom resolution, and about 2 months after symptom resolution.

Study Design: We conducted a secondary analysis of a multisite, longitudinal investigation of adolescent concussion recovery. Participants enrolled < 21 days following concussion and completed self-report questionnaires (Patient-Reported Outcomes Measurement Information System [PROMIS] Pediatric Global 25 anxiety and depressive symptom domains, and the Pittsburgh Sleep Quality Index [PSQI]) at three time points: visit 1 (symptomatic), visit 2 (<14 days after symptom resolution), and visit 3 (2 months after symptom resolution).

Examining muscle synergy composition and segmental coordination during overground walking in individuals with a rotationplasty about the knee.

Rotationplasty is a surgical technique used to salvage the limb following resection of a sarcoma or to address congenital defects. The procedure repurposes the ankle as a new knee, while fusing the thigh and shank musculature to achieve 'knee' flexion/extension. Most unique is the retainment of original innervations of the distal and proximal musculature, thus requiring spinal reorganization to coordinate the separate muscles as a single tensile unit.

Differences in immune cell profiles around the time of islet autoimmunity seroconversion in children with and without type 1 diabetes: Immune cell changes around islet autoimmunity.

Seroconversion (SV) marks the initiation of islet autoimmunity (IA) and pre-clinical phase of type 1 diabetes, yet the contributions of immune cells beyond cytotoxic T cells remain unclear. We applied high-resolution immune cell-type deconvolution using peripheral blood DNA methylation data from nested case-control samples of the Diabetes Autoimmunity Study in the Young (DAISY; n=151) and The Environmental Determinants of Diabetes in the Young (TEDDY; n=166) to estimate immune cell proportions across pre-SV and SV timepoints and construct functional ratios, such as the neutrophil-to-lymphocyte ratio (NLR). Using linear models, we evaluated differences between type 1 diabetes cases and controls at pre-SV, SV, and the change across timepoints.

Ancestry Calibration of Polygenic Risk Scores Improves Risk Stratification and Effect Estimation in African American Adults.

Polygenic risk score (PRS) distributions vary across populations, complicating PRS risk assessment. We evaluated the impact of PRS calibration according to individualized genetic ancestry estimates on PRS performance using two large multi-ethnic PRS for type 2 diabetes (T2D) (PRS) and height (PRS), in 8,841 African American (AA) individuals from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. We calibrated each participant's score as a function of estimated genetic similarity to the Yoruba (GSYRI) cohort in the 1000 Genomes Project.

Re-Evaluating the Impact of Including Patients with Bilateral Conditions in Orthopaedic Clinical Research Studies: When 1 + 1 Does Not Equal 2.

Background: Orthopaedic studies frequently include subjects with bilateral conditions. Failure to account for bilateral conditions can lead to spurious associations. The performance of different methods for addressing this issue, especially in populations that include subjects with unilateral and bilateral conditions, has not been rigorously evaluated.

Longitudinal changes in DNA methylation during the onset of islet autoimmunity differentiate between reversion versus progression of islet autoimmunity.

Background: Type 1 diabetes (T1D) is preceded by a heterogenous pre-clinical phase, islet autoimmunity (IA). We aimed to identify pre vs. post-IA seroconversion (SV) changes in DNAm that differed across three IA progression phenotypes, those who lose autoantibodies (reverters), progress to clinical T1D (progressors), or maintain autoantibody levels (maintainers).

Rare Coding Variants in Patients with Non-Syndromic Vestibular Dysfunction.

Vertigo due to vestibular dysfunction is rare in children. The elucidation of its etiology will improve clinical management and the quality of life of patients. Genes for vestibular dysfunction were previously identified in patients with both hearing loss and vertigo.

Investigating iron intake in risk of progression from islet autoimmunity to type 1 diabetes: The diabetes autoimmunity study in the young.

Background: Studies of the role of iron in the risk of type 1 diabetes (T1D) have been inconsistent. Given that iron generates reactive oxygen radicals, which can lead to oxidative damage and apoptosis in the beta cells of the pancreas, we examined whether iron intake was associated with the risk of progressing to T1D in individuals with islet autoimmunity (IA), the pre-clinical phase of T1D.

Methods: DAISY is a prospective cohort following 2,547 children at increased risk for IA and progression to T1D.

Pediatric and Adult Fracture Incidence: A Decreasing Trend With Increasing Hospital Admissions.

Large-scale studies examining fracture trends and epidemiological data are lacking. The purpose of this study was to evaluate the incidence of fractures presenting to US emergency departments using the National Electronic Injury Surveillance System. A total of 7,109,078 pediatric and 13,592,548 adult patients presenting to US emergency departments with a fracture between 2008 and 2017 were analyzed for patterns.

Propensity scores as a novel method to guide sample allocation and minimize batch effects during the design of high throughput experiments.

Background: We developed a novel approach to minimize batch effects when assigning samples to batches. Our algorithm selects a batch allocation, among all possible ways of assigning samples to batches, that minimizes differences in average propensity score between batches. This strategy was compared to randomization and stratified randomization in a case-control study (30 per group) with a covariate (case vs control, represented as β1, set to be null) and two biologically relevant confounding variables (age, represented as β2, and hemoglobin A1c (HbA1c), represented as β3).

An Oxylipin-Related Nutrient Pattern and Risk of Type 1 Diabetes in the Diabetes Autoimmunity Study in the Young (DAISY).

Oxylipins, pro-inflammatory and pro-resolving lipid mediators, are associated with the risk of type 1 diabetes (T1D) and may be influenced by diet. This study aimed to develop a nutrient pattern related to oxylipin profiles and test their associations with the risk of T1D among youth. The nutrient patterns were developed with a reduced rank regression in a nested case-control study ( = 335) within the Diabetes Autoimmunity Study in the Young (DAISY), a longitudinal cohort of children at risk of T1D.

Prediction of Late Dysplasia Based on Ultrasound and Plain X-Ray at 6 Months.

Background: Developmental dysplasia of the hip represents a spectrum of deformity. Residual dysplasia at 2 years of age is associated with an increased risk for osteoarthritis and functional limitations. We compared the prognostic value of 6-month imaging modalities and aimed to identify optimal diagnostic metrics for the prediction of residual dysplasia.

DNA Methylation Near May Mediate the Relationship between Family History of Type 1 Diabetes and Type 1 Diabetes Risk.

Given the differential risk of type 1 diabetes (T1D) in offspring of affected fathers versus affected mothers and our observation that T1D cases have differential DNA methylation near the imprinted gene compared to controls, we examined whether methylation near mediates the association between T1D family history and T1D risk. In a nested case-control study of 87 T1D cases and 87 controls from the Diabetes Autoimmunity Study in the Young, we conducted causal mediation analyses at 12 region CpGs to decompose the effect of family history on T1D risk into indirect and direct effects. These effects were estimated from two regression models adjusted for the human leukocyte antigen DR3/4 genotype: a linear regression of family history on methylation (mediator model) and a logistic regression of family history and methylation on T1D (outcome model).

Application of Accepted Use Criteria for the Treatment of Developmental Dysplasia of the Hip Decreases the Number of Infants Treated With a Pavlik Harness.

Background: This analysis examined how the application of the American Academy of Orthopedic Surgeons appropriate use criteria (AUC) for developmental dysplasia of the hip in infants would change treatment patterns and outcomes for Graf IIA hips at a single quaternary pediatric hospital.

Methods: After Institutional Review Board approval, patient medical records were reviewed and data were collected. Graf IIa hips were defined as alpha angle (AA) 50 to 59 degrees.

Changes in the Coexpression of Innate Immunity Genes During Persistent Islet Autoimmunity Are Associated With Progression of Islet Autoimmunity: Diabetes Autoimmunity Study in the Young (DAISY).

Longitudinal changes in gene expression during islet autoimmunity (IA) may provide insight into biological processes that explain progression to type 1 diabetes (T1D). We identified individuals from Diabetes Autoimmunity Study in the Young (DAISY) who developed IA, autoantibodies present on two or more visits. Illumina's NovaSeq 6000 was used to quantify gene expression in whole blood.

Lower extremity physeal fractures and post-traumatic surgical deformities; National Trauma Data Bank and institutional cohorts.

Background: Pediatric lower extremity physeal fractures carry a risk of developing deformities. Most epidemiological evidence is over 25 years old, single institution, and lacks follow-up, while recent studies report variable results. Understanding their epidemiology and deformity risk is important for patient counseling and follow-up.

An 8-Week Neuromuscular Training Program After Concussion Reduces 1-Year Subsequent Injury Risk: A Randomized Clinical Trial.

Background: Existing data suggest that after concussion, athletes experience an increased risk of subsequent injury. Exploring methods that may reduce injury risk after successful postconcussion return to play may lead to new treatment approaches.

Purpose: To examine the efficacy of a neuromuscular training (NMT) intervention on acute sports-related time-loss injury over the subsequent year relative to standard of care.

How Do We Best Educate Our Patients' Caregivers? Comparing the Efficacy of Print Versus Media-based Education Materials in Peripheral Nerve Catheter and Pain Pump Education.

Background: Media-based educational materials (EMs) are becoming prominent. The purpose of this study was to compare print versus media-based EMs given to caregivers of pediatric and young adult patients undergoing surgery. We aimed to see whether print or media-based EMs lead to greater caregiver satisfaction, comfort, and preparedness for outpatient peripheral nerve catheter and pain pump management.

An effective processing pipeline for harmonizing DNA methylation data from Illumina's 450K and EPIC platforms for epidemiological studies.

Objective: Illumina BeadChip arrays are commonly used to generate DNA methylation data for large epidemiological studies. Updates in technology over time create challenges for data harmonization within and between studies, many of which obtained data from the older 450K and newer EPIC platforms. The pre-processing pipeline for DNA methylation is not trivial, and influences the downstream analyses.

Severity of Idiopathic Scoliosis Is Associated with Differential Methylation: An Epigenome-Wide Association Study of Monozygotic Twins with Idiopathic Scoliosis.

Epigenetic mechanisms may contribute to idiopathic scoliosis (IS). We identified 8 monozygotic twin pairs with IS, 6 discordant (Cobb angle difference > 10°) and 2 concordant (Cobb angle difference ≤ 2°). Genome-wide methylation in blood was measured with the Infinium HumanMethylation EPIC Beadchip.

A Mediation Approach to Discovering Causal Relationships between the Metabolome and DNA Methylation in Type 1 Diabetes.

Environmental factors including viruses, diet, and the metabolome have been linked with the appearance of islet autoimmunity (IA) that precedes development of type 1 diabetes (T1D). We measured global DNA methylation (DNAm) and untargeted metabolomics prior to IA and at the time of seroconversion to IA in 92 IA cases and 91 controls from the Diabetes Autoimmunity Study in the Young (DAISY). Causal mediation models were used to identify seven DNAm probe-metabolite pairs in which the metabolite measured at IA mediated the protective effect of the DNAm probe measured prior to IA against IA risk.

Inverse probability weighting is an effective method to address selection bias during the analysis of high dimensional data.

Omics studies frequently use samples collected during cohort studies. Conditioning on sample availability can cause selection bias if sample availability is nonrandom. Inverse probability weighting (IPW) is purported to reduce this bias.

Single season re-injury risk after concussion and lower extremity injury among male, collision sport, high school athletes.

Objectives: Research suggests that a recent concussion increases subsequent lower extremity injury risk; however, data in high school athletes is limited. This study evaluates the association between concussion and subsequent injury risk among male, collision sport, high school athletes over a single season.

Design: Retrospective cohort study.