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Context: Sex differences in lower extremity landing mechanics and muscle activation have been identified as potential causative factors leading to the increased incidence of anterior cruciate ligament injuries in female athletes. Valgus knee alignment places greater strain on the anterior cruciate ligament than a more neutral alignment. Gluteus medius (GM) activation may stabilize the leg and pelvis during landing, limiting valgus knee motion and potentially preventing anterior cruciate ligament injury.Objective: To determine if frontal-plane knee angle and GM activation differ between the sexes at initial contact and maximal knee flexion during a single-leg drop landing.Design: Between-groups design. Setting: Motion analysis laboratory.Patients or Other Participants: Thirty-two healthy subjects between the ages of 18 and 30 years.Intervention(s): The independent variables were sex (male or female) and position (initial contact or maximal knee flexion).Main Outcome Measure(s): Frontal-plane knee angle and GM average root mean square (aRMS) amplitude.Results: At initial contact, women landed in knee valgus and men landed in knee varus (P < .025). At maximal knee flexion, both men and women were in a position of knee varus, but the magnitude of varus was less in women than in men (P < .025). The GM aRMS amplitude was greater at maximal knee flexion than at initial contact (P < .025); however, male GM aRMS did not differ from female GM aRMS amplitude at either position (P > .025).Conclusions: Women tended to land in more knee valgus before and at impact than men. The GM muscle activation did not differ between the sexes and, thus, does not appear to be responsible for the sex differences in knee valgus. The excessive valgus knee angles displayed in women may help to explain the sex disparity in anterior cruciate ligament injury. [ABSTRACT FROM AUTHOR]

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a motor neuron disease that leads to rapid degeneration of nerves in the brain and spinal cord, with eventual loss of voluntary movements, including breathing. This retrospective study of medical record data from 105 US veterans diagnosed with ALS at the Oklahoma City VA Medical Center between 2010 and 2021 aimed to identify patient demographics, and the causes and places of death for these veterans. MATERIAL AND METHODS Data from 105 US veterans diagnosed with ALS by the El Escorial criteria and supported by neurophysiology testing was reviewed. The information about the place and cause of death was obtained from each patient's care provider and death certificate. Crude mortality rates (per 100 person-years) and standardized mortality ratios (SMRs) were calculated for the causes of death, by sex, age group, and location of death. RESULTS During the 11-year follow-up period, 80 (76.2%) veterans with ALS died. The mean (SD) follow-up time was 4.53 (4.55) years. Most of the deaths were due to respiratory failure and pneumonia (n=43, mortality rate=9.21 per 100 person-years). Most patients died at home (n=71, 88.7%). The annual crude mortality rate was 16.7 and the all-cause death SMR was 25.63 (95% CI, 20.32-31.55). CONCLUSIONS This study's findings are that in veterans with ALS, the main cause of death is respiratory disease (failure). The main location of death was the home, with their family members. The all-cause mortality rate among veterans with ALS was 26 times greater than for the general Oklahoma population.

Purpose: To identify genetic etiologies and genotype/phenotype associations for unsolved ocular congenital cranial dysinnervation disorders (oCCDDs)., Methods: We coupled phenotyping with exome or genome sequencing of 467 probands (550 affected and 1108 total individuals) with genetically unsolved oCCDDs, integrating analyses of pedigrees, human and animal model phenotypes, and de novo variants to identify rare candidate single nucleotide variants, insertion/deletions, and structural variants disrupting protein-coding regions. Prioritized variants were classified for pathogenicity and evaluated for genotype/phenotype correlations., Results: Analyses elucidated phenotypic subgroups, identified pathogenic/likely pathogenic variant(s) in 43/467 probands (9.2%), and prioritized variants of uncertain significance in 70/467 additional probands (15.0%). These included known and novel variants in established oCCDD genes, genes associated with syndromes that sometimes include oCCDDs (e.g., MYH10, KIF21B, TGFBR2, TUBB6), genes that fit the syndromic component of the phenotype but had no prior oCCDD association (e.g., CDK13, TGFB2), genes with no reported association with oCCDDs or the syndromic phenotypes (e.g., TUBA4A, KIF5C, CTNNA1, KLB, FGF21), and genes associated with oCCDD phenocopies that had resulted in misdiagnoses., Conclusion: This study suggests that unsolved oCCDDs are clinically and genetically heterogeneous disorders often overlapping other Mendelian conditions and nominates many candidates for future replication and functional studies., (Copyright © 2024. Published by Elsevier Inc.)

Objective: We sought to characterize the clinical prognostic factors in veterans with amyotrophic lateral sclerosis (ALS) followed in our ALS clinic., Background: ALS is a rare, progressive neurodegenerative condition associated with decreased survival compared to that in the normal population., Method: The electronic medical records of 105 veterans diagnosed with ALS who are followed in our ALS clinic between 2010 and 2021 were reviewed. Approval from the institutional review board was obtained from the study protocol. Demographic and clinical variables included age at symptom onset, age at initial evaluation, survival (from symptom onset to death), gender, site of onset (appendicular, bulbar, and respiratory), initial amyotrophic lateral sclerosis functional-related score-revised (ALSFRS-R), total functional independence measure (TFIM) scores, initial forced vital capacity (FVC), and interventions (Riluzole, gastrostomy, noninvasive ventilation [NIV], and tracheostomy). Normally distributed data was expressed as mean ± standard deviation. Fischer's exact analysis of the distribution differences of categorical data. The Kaplan-Meier plot analyzed the time-to-event., Results: The mean (SD) age at symptom onset was 62.0 (11.1) years, age at diagnosis was 65 (11) years, with 72% of the patients being over 60 years at diagnosis. The median survival time from symptom onset was 4.12 (3) years. Limb-onset ALS (appendicular) was the most frequent (52%) followed by bulbar-onset ALS (43%). The mean ALSFRS-R and TFIM scores were 31 (8) and 91 (25), respectively. Family history (familial), bulbar, and respiratory presentation at diagnosis were associated with shorter survival times., Conclusion: This study suggests that of the clinical prognostic factors veterans with familial ALS, bulbar, and respiratory onset at presentations had shorter survival. The presence of Agent Orange, PEG placement, and NIV did not affect survival., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Genetic variants that cause rare disorders may remain elusive even after expansive testing, such as exome sequencing. The diagnostic yield of genome sequencing, particularly after a negative evaluation, remains poorly defined., Methods: We sequenced and analyzed the genomes of families with diverse phenotypes who were suspected to have a rare monogenic disease and for whom genetic testing had not revealed a diagnosis, as well as the genomes of a replication cohort at an independent clinical center., Results: We sequenced the genomes of 822 families (744 in the initial cohort and 78 in the replication cohort) and made a molecular diagnosis in 218 of 744 families (29.3%). Of the 218 families, 61 (28.0%) - 8.2% of families in the initial cohort - had variants that required genome sequencing for identification, including coding variants, intronic variants, small structural variants, copy-neutral inversions, complex rearrangements, and tandem repeat expansions. Most families in which a molecular diagnosis was made after previous nondiagnostic exome sequencing (63.5%) had variants that could be detected by reanalysis of the exome-sequence data (53.4%) or by additional analytic methods, such as copy-number variant calling, to exome-sequence data (10.8%). We obtained similar results in the replication cohort: in 33% of the families in which a molecular diagnosis was made, or 8% of the cohort, genome sequencing was required, which showed the applicability of these findings to both research and clinical environments., Conclusions: The diagnostic yield of genome sequencing in a large, diverse research cohort and in a small clinical cohort of persons who had previously undergone genetic testing was approximately 8% and included several types of pathogenic variation that had not previously been detected by means of exome sequencing or other techniques. (Funded by the National Human Genome Research Institute and others.)., (Copyright © 2024 Massachusetts Medical Society.)

Over the past 2 decades, equine veterinarians are turning increasingly to stem cell therapies to repair damaged tissues or to promote healing through modulation of the immune system. Research is ongoing into optimizing practices associated with stem cell product transport, dosage, and administration. Culture-expanded equine mesenchymal stem cell therapies seem safe, even when used allogeneically, but various safety concerns should be considered. Stem cells and cellular reprogramming tools hold great promise for future equine therapies., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To investigate the craniofacial growth outcomes of early secondary alveolar bone grafting(ABG) around 6 years of age., Design: Retrospective cohort study., Setting: 1 North-American and 5 Northern-European cleft centers., Subjects: 33 subjects with CUCLP consecutively treated with secondary ABG around 6 years of age were compared to 105 subjects from 4 centers treated with late secondary ABG and 19 subjects from 1 center with primary ABG., Methods: Preorthodontic standardized lateral cephalometric radiographs taken after 12 years of age were traced and analyzed according to the Eurocleft Study protocol. Fourteen angular and two proportional measurements were performed. Measurement means from the Study Center(SC) were compared to 5 Northern-European centers using analysis of variance and Welch's modified t -tests, and P  < .05 was considered statistically significant., Results: For the SC, the mean age ± SD at the time of bone graft was 5.85 ± 0.71 years and the mean age at the time of the lateral cephalogram was 13.4 ± 1.8 years. The sagittal maxillary prominence of the SC was favorably comparable to the 5 Northern-European centers. The mean SNA (78.1 ± 4.3) for the SC was significantly higher compared to 4 of the 5 Northern-European centers(all P  < .05), and the mean ANB angle was comparable to 4 of the 5 centers. Similarly, the mean soft tissue ANB angle was not significantly different to the 5 centers. The soft tissue vertical proportions compared favorably to all 5 Northern-European centers(all P  < .01)., Conclusions: Craniofacial growth outcomes of early secondary ABG around 6 years compare favorably to the outcomes of late secondary ABG.