Protocol for generating splice isoform-specific mouse mutants using CRISPR-Cas9 and a minigene splicing reporter.

Here, we present a protocol to alter the production of alternatively spliced mRNA variants, without affecting the overall gene expression, through CRISPR-Cas9-engineered genomic mutations in mice. We describe steps for designing guide RNA to direct Cas9 endonuclease to consensus splice sites, producing transgenic mice through pronuclear injection, and screening for desired mutations in cultured mammalian cells using a minigene splicing reporter. Splice isoform-specific mouse mutants provide valuable tools for genetic analyses beyond loss-of-function and transgenic alleles.

The effect of age and bracing on vehicle occupant responses during sled-simulated evasive swerving.

Objective: Bracing can reduce adult occupants' out-of-position postures, but it is unclear if this finding can be extended to child occupants. We investigated the effect of bracing, and age on the motion of vehicle occupants of different ages during sled-simulated pre-crash maneuvers.

Methods: Forty seatbelt restrained subjects (9-40 y.

Interactions between rearward-facing child restraint systems and the center console in frontal impact sled tests.

Objective: To quantify the head and chest injury metrics associated with a pediatric anthropomorphic test device (ATD) in rearward-facing infant child restraint system (CRS) models positioned directly behind a center console during frontal impact sled tests.

Methods: Sled tests using the Federal Motor Vehicle Safety Standard (FMVSS) 213 frontal crash pulse were performed. The test buck comprised a second row middle seat and center console from the same 2023 model mid-size SUV spaced as per the in-vehicle relative dimensions, a force plate covered with an automotive floor mat, a post-mounted shoulder belt simulating the in-vehicle roof-mounted seatbelt and an array of high-speed cameras.

Community and Patient Features and Health Care Point of Entry for Pediatric Concussion.

Importance: Many recent advances in pediatric concussion care are implemented by specialists; however, children with concussion receive care across varied locations. Thus, it is critical to identify which children have access to the most up-to-date treatment strategies.

Objective: To evaluate differences in the sociodemographic and community characteristics of pediatric patients who sought care for concussion across various points of entry into a regional health care network.

Factors Influencing Length of Care in Physical Therapy After Pediatric and Adolescent Concussion.

Context: Social determinants of health including insurance type, income, race, and ethnicity have been shown to influence the utilization of physical therapy and recovery after an orthopedic injury. The influence of social determinants of health on the utilization of physical therapy and recovery from concussion is not well understood.

Design: Prospective observational registry study in a specialty concussion program.

Model based fitting of pattern reversal visually evoked potentials provides a reliable characterization of waveform components.

Objective: To introduce a novel approach to analyzing pattern reversal visual evoked potentials (prVEPs) using a difference-of-gammas model-based fitting method.

Methods: prVEP was recorded from uninjured youth ages 11-19 years during pre- or postseason sports evaluation. A difference-of-gammas model fit was used to extract the amplitude, peak time, and peak width of each of four gamma components.

Age-Related Variations in Clinical Profiles for Children with Sports- and Recreation-Related Concussions.

Objective: The purpose was to examine clinical profiles in concussed children aged 5-9 and 10-12 years and compare them with those of adolescents >12 years.

Methods: This study included patients aged 5-18 years presenting to a specialty care concussion program with a sports- and recreation-related (SRR) concussion ≤28 days postinjury. Demographics, injury mechanisms, symptoms, and clinical features were assessed.

Trajectory of Health-Related Quality of Life Following Pediatric Concussion.

Objective: To assess changes in health-related quality of life (HRQOL) across a 12-month period following pediatric concussion and to explore whether psychological factors (ie, preinjury mental health history, current symptoms of anxiety and depression, sleep disturbance, or grit) were associated with HRQOL.

Study Design: Prospective cohort study design using data collected from patients presenting to a specialty care concussion program, with each patient followed for 12 months after initial presentation. Comparison data were collected from nonconcussed controls recruited from the community.

Characteristics of Pediatric Concussion across Different Mechanisms of Injury in 5 through 12-Year-Olds.

Objective: To investigate characteristics of sport-related concussion (SRC), recreation-related concussion (RRC), and nonsport or recreation-related concussion (non-SRRC) in patients 5 through 12 years old, an understudied population in youth concussion.

Study Design: This observational study included patients aged 5 through 12 years presenting to a specialty care concussion setting at ≤28 days postinjury from 2018 through 2022. The following characteristics were assessed: demographics, injury mechanism (SRC, RRC, or SRRC), point of healthcare entry, and clinical signs and symptoms.

Response Rate Patterns in Adolescents With Concussion Using Mobile Health and Remote Patient Monitoring: Observational Study.

Background: A concussion is a common adolescent injury that can result in a constellation of symptoms, negatively affecting academic performance, neurobiological development, and quality of life. Mobile health (mHealth) technologies, such as apps for patients to report symptoms or wearables to measure physiological metrics like heart rate, have been shown to be promising in health maintenance. However, there is limited evidence about mHealth engagement in adolescents with a concussion during their recovery course.

Mechanisms of Injury Leading to Concussions in Collegiate Soccer Players: A CARE Consortium Study.

Background: Few previous studies have investigated how different injury mechanisms leading to sport-related concussion (SRC) in soccer may affect outcomes.

Purpose: To describe injury mechanisms and evaluate injury mechanisms as predictors of symptom severity, return to play (RTP) initiation, and unrestricted RTP (URTP) in a cohort of collegiate soccer players.

Study Design: Cohort study; Level of evidence, 2.

Head Impact Kinematics and Brain Tissue Strains in High School Lacrosse.

Male lacrosse and female lacrosse have differences in history, rules, and equipment. There is current debate regarding the need for enhanced protective headwear in female lacrosse like that worn by male lacrosse players. To inform this discussion, 17 high school lacrosse players (6 female and 11 male) wore the Stanford Instrumented Mouthguard during 26 competitive games over the 2021 season.

Neurovascular Coupling in Acutely Concussed Adolescent Patients.

Neurovascular coupling (NVC) uniquely describes cerebrovascular response to neural activation and has demonstrated impairments following concussion in adult patients. It is currently unclear how adolescent patients experience impaired NVC acutely following concussion during this dynamic phase of physiological development. The purpose of this study was to investigate NVC in acutely concussed adolescent patients relative to controls.

Head Injury Treatment With Healthy and Advanced Dietary Supplements: A Pilot Randomized Controlled Trial of the Tolerability, Safety, and Efficacy of Branched Chain Amino Acids in the Treatment of Concussion in Adolescents and Young Adults.

Concussion is a common injury in the adolescent and young adult populations. Although branched chain amino acid (BCAA) supplementation has shown improvements in neurocognitive and sleep function in pre-clinical animal models of mild-to-moderate traumatic brain injury (TBI), to date, no studies have been performed evaluating the efficacy of BCAAs in concussed adolescents and young adults. The goal of this pilot trial was to determine the efficacy, tolerability, and safety of varied doses of oral BCAA supplementation in a group of concussed adolescents and young adults.

Dose-Response Effect of Mental Health Diagnoses on Concussion Recovery in Children and Adolescents.

Background: Pre-existing mental health diagnoses may contribute to greater emotional symptom burden and prolonged recovery after concussion.

Hypothesis: Youth with pre-existing mental health diagnoses will have greater emotional symptom burden, greater risk for delayed return to exercise, and more prolonged recovery from concussion than those without those diagnoses.

Study Design: Prospective cohort.

Optimizing the Combination of Common Clinical Concussion Batteries to Predict Persistent Postconcussion Symptoms in a Prospective Cohort of Concussed Youth.

Background: Studies have evaluated individual factors associated with persistent postconcussion symptoms (PPCS) in youth concussion, but no study has combined individual elements of common concussion batteries with patient characteristics, comorbidities, and visio-vestibular deficits in assessing an optimal model to predict PPCS.

Purpose: To determine the combination of elements from 4 commonly used clinical concussion batteries and known patient characteristics and comorbid risk factors that maximize the ability to predict PPCS.

Study Design: Cohort study; Level of evidence, 2.

Neurophysiological and gait outcomes during a dual-task gait assessment in concussed adolescents.

Background: Gait deficits are common after concussion in adolescents. However, the neurophysiological underpinnings of these gait deficiencies are currently unknown. Thus, the goal of this study was to compare spatiotemporal gait metrics, prefrontal cortical activation, and neural efficiency between concussed adolescents several weeks from injury and uninjured adolescents during a dual-task gait assessment.

Postinjury Outcomes After Non-Sport-Related Concussion: A CARE Consortium Study.

Context: Concussion research has primarily focused on sport-related mechanisms and excluded non-sport-related mechanisms. In adult populations, non-sport-related concussions (non-SRCs) demonstrated worse clinical outcomes compared with sport-related concussions (SRCs); however, investigations of non-SRCs in college-aged patients are limited.

Objectives: To examine clinical outcomes in collegiate athletes with non-SRCs compared with SRCs and explore sex differences in outcomes among collegiate athletes with non-SRCs.

Altered Auditory and Visual Evoked Potentials following Single and Repeated Low-Velocity Head Rotations in 4-Week-Old Swine.

Auditory and visually evoked potentials (EP) have the ability to monitor cognitive changes after concussion. In the literature, decreases in EP are commonly reported; however, a subset of studies shows increased cortical activity after injury. We studied auditory and visual EP in 4-week-old female Yorkshire piglets (N = 35) divided into anesthetized sham, and animals subject to single (sRNR) and repeated (rRNR) rapid non-impact head rotations (RNR) in the sagittal direction.

Finite element brain deformation in adolescent soccer heading.

Finite element (FE) modeling provides a means to examine how global kinematics of repetitive head loading in sports influences tissue level injury metrics. FE simulations of controlled soccer headers in two directions were completed using a human head FE model to estimate biomechanical loading on the brain by direction. Overall, headers were associated with 95th percentile peak maximum principal strains up to 0.

Use of functional near-infrared spectroscopy to quantify neurophysiological deficits after repetitive head impacts in adolescent athletes.

There is concern that repetitive head impact exposure (RHIE) may lead to neurophysiological deficits in adolescents. Twelve high school varsity soccer players (5 female) completed the King-Devick (K-D) and complex tandem gait (CTG) assessments pre- and post-season while wearing a functional near-infrared spectroscopy (fNIRS) sensor. The average head impact load (AHIL) for each athlete-season was determined via a standardised protocol of video-verification of headband-based head impact sensor data.

Frontal-oblique impact sled tests of a rearward-facing child restraint system with and without a support leg.

Objective: To quantify the head and neck injury metrics of an anthropometric test device (ATD) in a rearward-facing child restraint system (CRS), with and without a support leg, in frontal-oblique impacts.

Methods: Sled tests using the Federal Motor Vehicle Safety Standards (FMVSS) 213 frontal crash pulse (48 km/h, 23 g) were performed with a simulated Consumer Reports test buck, which comprised a test bench that mimics the rear outboard vehicle seat of a sport utility vehicle (SUV). The test bench was rigidised to increase durability for repeated testing and the seat springs and cushion were replaced every five tests.

Neurophysiological Effects of Repeated Soccer Heading in Youth.

Repeated head loading in sports is associated with negative long-term brain health, and there is growing evidence of short-term neurophysiological changes after repeated soccer heading. The objective of this study was to quantify the head kinematics and effects of repetitive soccer headers in adolescents using an instrumented mouthguard. Adolescent soccer players aged 13-18 years were randomly assigned to a kicking control, frontal heading, or oblique heading group.