Validation of the Gait Outcomes Assessment List questionnaire and caregiver priorities for individuals with cerebral palsy.

AIM: To expand upon previous validation of the Gait Outcomes Assessment List (GOAL) questionnaire in individuals with cerebral palsy (CP), to rank items by importance, and to summarize written-in (free text) goals. METHOD: For this cross-sectional study, the parent-version 5.0 of the GOAL was completed by 310 consecutive caregivers of 310 individuals aged 3 to 25 years with CP (189 males, 121 females; mean [SD] age: 10y [4y 2mo]; Gross Motor Function Classification System [GMFCS] levels I-IV) concurrent with a gait analysis. Distribution properties and validity were quantified using questionnaires, kinematics, and oxygen consumption. Items classified as at least 'difficult' to perform and 'very important' to improve were considered caregiver priorities and rank ordered. Free text goals were categorized. Results were summarized for everyone and by GMFCS level. RESULTS: Most scores were normally distributed. Validity was acceptable, with concurrent greater than construct validity. Among all 310 caregivers, fatigue was the highest priority, followed by gait pattern and appearance items. The rank of priorities varied by GMFCS level. Common free text goals included toileting independently as well as improved fine motor and ball sport skills. INTERPRETATION: The GOAL is a valid tool that can help prioritize goals across GMFCS levels I to IV. Identifying the top goals may improve shared decision-making and prioritize research for this sample.

A Nationwide Survey of Program Directors on Resident Attrition in Emergency Medicine.

INTRODUCTION: Despite the burdens that resident attrition places upon programs and fellow trainees, emergency medicine (EM) as a specialty has only begun to explore the issue. Our primary objectives were to quantify attrition in EM residency programs and elucidate the reasons behind it. Our secondary objectives were to describe demographic characteristics of residents undergoing attrition, personal factors associated with attrition, and methods of resident replacement. METHODS: We conducted a national survey study of all EM program directors (PDs) during the 2018-2019 academic year. PDs were asked to identify all residents who had left their program prior to completion of training within the last four academic years (2015-2016 to 2018-2019), provide relevant demographic information, select perceived reasons for attrition, and report any resident replacements. Frequencies, percentages, proportions, and 95% confidence intervals were obtained for program- and resident-specific demographics. We performed Fisher's exact tests to compare reasons for attrition between age groups. RESULTS: Of 217 PDs successfully contacted, 118 completed the questionnaire (response rate of 54%). A third of programs (39 of 118) reported at least one resident attrition. A total of 52 residents underwent attrition. Attrition was most likely to occur prior to completion of two years of training. Gender and underrepresented minority status were not associated with attrition. Older residents were more likely to leave due to academic challenges. The most common reported reason for attrition was to switch specialties. Resident replacement was found in 42% of cases. CONCLUSION: One-third of programs were affected by resident attrition. Gender and underrepresented minority status were not associated with attrition.

Neuromuscular effects of G93A-SOD1 expression in zebrafish.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal disorder involving the degeneration and loss of motor neurons. The mechanisms of motor neuron loss in ALS are unknown and there are no effective treatments. Defects in the distal axon and at the neuromuscular junction are early events in the disease course, and zebrafish provide a promising in vivo system to examine cellular mechanisms and treatments for these events in ALS pathogenesis. RESULTS: We demonstrate that transient genetic manipulation of zebrafish to express G93A-SOD1, a mutation associated with familial ALS, results in early defects in motor neuron outgrowth and axonal branching. This is consistent with previous reports on motor neuron axonal defects associated with familial ALS genes following knockdown or mutant protein overexpression. We also demonstrate that upregulation of growth factor signaling is capable of rescuing these early defects, validating the potential of the model for therapeutic discovery. We generated stable transgenic zebrafish lines expressing G93A-SOD1 to further characterize the consequences of G93A-SOD1 expression on neuromuscular pathology and disease progression. Behavioral monitoring reveals evidence of motor dysfunction and decreased activity in transgenic ALS zebrafish. Examination of neuromuscular and neuronal pathology throughout the disease course reveals a loss of neuromuscular junctions and alterations in motor neuron innervations patterns with disease progression. Finally, motor neuron cell loss is evident later in the disease. CONCLUSIONS: This sequence of events reflects the stepwise mechanisms of degeneration in ALS, and provides a novel model for mechanistic discovery and therapeutic development for neuromuscular degeneration in ALS.

A novel approach to study motor neurons from zebrafish embryos and larvae in culture.

Zebrafish are becoming increasingly popular models for examining the mechanisms of and treatments for neurological diseases. The available methods and technology to examine disease processes in vivo are increasing, however, detailed observations of subcellular structures and processes are complex in whole organisms. To address this need, we developed a primary motor neuron (MN) culture technique for utilization with zebrafish neurological disease models. Our protocol enables the culturing of cells from embryos older than 24h post-fertilization, at points after MN axonal development and outgrowth begins, which enables MN axons to develop in vivo in the context of the normal endogenous cues of the model organism, while also providing the accessibility of an in vitro system. When utilized with the increasing number of genetically modified or transgenic models of neurological diseases, this approach provides a novel tool for the examination of cellular and subcellular disease mechanisms, and offers a new platform for therapeutic discoveries in zebrafish.