Astroglial conditional Slc13a3 knockout is therapeutic in murine Canavan leukodystrophy.

Canavan disease is a leukodystrophy caused by ASPA mutations that diminish oligodendroglial aspartoacylase activity, and is characterized by markedly elevated brain concentrations of the aspartoacylase substrate N-acetyl-l-aspartate (NAA) and by astroglial and intramyelinic vacuolation. Astroglia express NaDC3 (encoded by SLC13A3), a sodium-coupled transporter for NAA and other dicarboxylates. Astroglial conditional Slc13a3 deletion in aspartoacylase-deficient Canavan disease model mice ("CD mice") reversed brain NAA elevation and improved motor function. These results demonstrate that astroglial NaDC3 contributes to brain NAA elevation in CD mice, and suggest that suppressing astroglial NaDC3 activity would ameliorate human Canavan disease.

Resident Perceptions of Virtual Reality Versus Dry Lab Simulation for Advanced Shoulder Arthroscopy Resident Training.

INTRODUCTION: Surgical training using simulation can fill gaps in traditional surgical residency learning. We hypothesize that arthroscopy training conducted on a virtual reality simulator will be preferred by orthopaedic surgery residents over a traditional dry lab simulation model. METHODS: 38 orthopaedic surgery residents at a single U.S. residency program were randomized to train for a shoulder arthroscopy procedure using either a virtual reality simulator or a table-top dry lab simulator. Training and learning preferences were then asked of the resident participants. RESULTS: Junior residents were likely to report training preference for the virtual reality simulator compared to senior residents [15/24 (62.5%) v. 8/14 (57.1%); P = .043]. Simulator preference was not influenced by subspecialty interest, prior arthroscopy experience, or simulator experience. Virtual reality simulation was associated with positive attitude towards arthroscopy and high chance of reporting learning gains on general arthroscopic understanding. Senior residents were 4.7 times more likely than juniors to report learning gains via staff discussion pre- and post-operatively. A majority of residents [34/38 (89.5%)] reported, however, wanting more simulation for training surgical skills. CONCLUSION: Simulation is a desired and potentially valuable adjunct to training orthopaedic residents in arthroscopy. Training needs do evolve; and junior arthroscopists may benefit more from virtual reality platforms for general skills. Senior residents preferred dry lab simulation, possibly because it allowed for handling of actual instruments and implants.

Pathological Bergmann glia alterations and disrupted calcium dynamics in ataxic Canavan disease mice.

Canavan disease (CD) is a recessively inherited pediatric leukodystrophy resulting from inactivating mutations to the oligodendroglial enzyme aspartoacylase (ASPA). ASPA is responsible for hydrolyzing the amino acid derivative N-acetyl-L-aspartate (NAA), and without it, brain NAA concentrations increase by 50% or more. Infants and children with CD present with progressive cognitive and motor delays, cytotoxic edema, astroglial vacuolation, and prominent spongiform brain degeneration. ASPA-deficient CD mice (Aspanur7/nur7 ) present similarly with elevated NAA, widespread astroglial dysfunction, ataxia, and Purkinje cell (PC) dendritic atrophy. Bergmann glia (BG), radial astrocytes essential for cerebellar development, are intimately intertwined with PCs, where they regulate synapse stability, functionality, and plasticity. BG damage is common to many neurodegenerative conditions and frequently associated with PC dysfunction and ataxia. Here, we report that, in CD mice, BG exhibit significant morphological alterations, decreased structural associations with PCs, loss of synaptic support proteins, and altered calcium dynamics. We also find that BG dysfunction predates cerebellar vacuolation and PC damage in CD mice. Previously, we developed an antisense oligonucleotide (ASO) therapy targeting Nat8l (N-acetyltransferase-8-like, "Nat8l ASO") that inhibits the production of NAA and reverses ataxia and PC atrophy in CD mice. Here, we show that Nat8l ASO administration in adult CD mice also leads to BG repair. Furthermore, blocking astroglial uptake of NAA is neuroprotective in astroglia-neuron cocultures exposed to elevated NAA. Our findings suggest that restoration of BG structural and functional integrity could be a mechanism for PC regeneration and improved motor function.

Presentation and Surgical Management of Multiple Ligament Knee Injuries: A Multicenter Study from the Surgical Timing and Rehabilitation (STaR) Trial for MLKIs Network.

BACKGROUND: Multiple ligament knee injuries (MLKIs) represent a spectrum of injury patterns that are often associated with concomitant musculoskeletal and neurovascular injuries, complex treatment, and postoperative complications. However, there has not been high-level evidence describing the presentation and treatment of MLKIs. The purpose of this multicenter retrospective study was to describe characteristics of MLKIs, their management, and related complications using a pathoanatomic MLKI classification system based on the Schenck Knee Dislocation classification system. METHODS: This review identified and analyzed MLKIs that occurred between 2011 and 2015. Cases with an MLKI were included in this study if there was a complete tear of ≥2 ligaments and at least 1 ligament was repaired or reconstructed. Cases in which a ligament was deemed clinically incompetent due to a partial ligament tear and required surgical repair or reconstruction were considered equivalent to grade-III tears for inclusion and classification. Demographic information, the mechanism of injury, times from injury to presentation to an orthopaedic surgeon and to surgery, the ligament injury pattern, associated injuries, surgical procedures, and complications were captured. Data were analyzed descriptively. RESULTS: A total of 773 individuals from 14 centers who underwent surgery for an MLKI were reviewed. The mean age of the individuals was 30.5 ± 12.7 years, and 74.2% were male. The most common mechanism involved sports (43.2%). The median time from injury to presentation to the orthopaedic surgeon was 11 days (interquartile range [IQR], 3 to 48 days), and the time to initial ligament surgery was 64 days (IQR, 23 to 190 days). While the most common injury patterns were an anterior cruciate ligament tear combined with either a medial-sided (MLK 1-AM, 20.7%) or lateral-sided (MLK 1-AL, 23.2%) injury, one-third (34.7%) were bicruciate injuries. Associated injuries most often involved menisci (55.6%), nerves (18.5%) and tendons (15.6%). The method of surgical intervention (repair versus reconstruction), external fixator use, and staging of procedures varied by MLKI classification. Loss of motion (11.4%) was the most common postoperative complication. CONCLUSIONS: A better understanding of the clinical characteristics and management of the various MLKI patterns can be used to support clinical decision-making and individualized treatment of these complex injuries, and may ultimately lead to enhanced outcomes and reduced associated risks. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Pharmacokinetics and clinical efficacy of acetaminophen (paracetamol) in adult horses with mechanically induced lameness.

BACKGROUND: Acetaminophen has been used clinically in horses alone or combined with traditional non-steroidal anti-inflammatory drugs for treatment of musculoskeletal pain in horses. OBJECTIVES: To determine the pharmacokinetics and efficacy of acetaminophen at two doses in horses with mechanically induced lameness compared with phenylbutazone or placebo control. STUDY DESIGN: In vivo experiment. METHODS: Nine healthy mares with mechanical lameness induced via a reversible sole pressure horseshoe model were treated with acetaminophen (20 mg/kg PO; A20), acetaminophen (30 mg/kg PO; A30), phenylbutazone (2.2 mg/kg, PO; PB) and oral placebo (C) in a randomised four-way Latin square model. Plasma concentrations for A20 and A30 were analysed via LC-MS/MS and noncompartmental pharmacokinetic analysis. Heart rate and heart rate variability were measured using a portable telemetry. Lameness was scored by three blinded boarded equine surgeons using the AAEP and 10-point scales. RESULTS: Mean maximum plasma concentration (Cmax ) for A20 was 20.01 µg/ml within 0.66 h (Tmax ) after administration; The mean Cmax for A30 was 30.02 µg/ml with a Tmax of 0.43 h. Post-treatment heart rate for A30 was significantly lower than A20 at 1 and 7 h; lower than PB at 2, 3, 4.5 and 7 h; lower than C at 2, 3.5, 4.5, 6, 7 and 8 h. 10-point Lameness scores were significantly improved for A30 than C at 2 and 4 h post-treatment; PB was significantly improved than C at 8 h post treatment. There were no significant differences in lameness between A20, A30 and PB. MAIN LIMITATIONS: Small sample size, lack of objective lameness measurement. CONCLUSIONS: Acetaminophen at 30 mg/kg produced a more rapid improvement in lameness scores and heart rate compared with other treatments in this model. Further evaluation of the pharmacokinetics and safety of repeated oral dosing of acetaminophen at 30 mg/kg is needed to determine clinical utility.

CONTEXTO: Acetaminofeno tem sido usado rotineiramente em cavalos com dor musculoesquelética, tanto como terapia solo quanto em associação com outros anti-inflamatórios não esteroides tradicionais. OBJETIVOS: Determinar a farmacocinética e eficácia de duas doses de acetaminofeno em cavalos com claudicação mecanicamente induzida, e comparar com fenilbutazona e placebo. DELINEAMENTO DO ESTUDO: Estudo randomizado, cego e controlado utilizando quadrado latino. METODOLOGIA: Nove éguas adultas com claudicação induzida mecanicamente pelo método de aplicação de pressão na sola através de ferradura foram tratadas com acetaminofeno (20 mg/kg VO; A20), acetaminofeno (30 mg/kg VO; A30), fenilbutazona (2.2 mg/kg, VO; PB) e placebo oral (C) em um estudo quadrado latino de forma randômica. Concentração plasmática dos grupos A20 e A30 foram analisadas pelo método LC-MS/MS e análise farmacocinética não compartimentar. Frequência cardíaca e variação da frequência cardíaca foram mensuradas usando telemetria portátil. O grau de claudicação foi avaliado usando a escala de 10 pontos da AAEP por três cirurgiões especialistas (board-certified) que estavam cegos ao tratamento. RESULTADOS: A média máxima da concentração plasmática (Cmax ) do grupo A20 foi 20.01 µg/ml dentro de 0.66 h (Tmax ) da administração. A média Cmax do grupo A30 foi 30.02 µg/ml dentro da Tmax de 0.43 h. A frequência cardíaca do grupo A30 foi significativamente mais baixa do que a do grupo A20 nos momentos 1 e 7 h; mais baixa do que o grupo PB nos momentos 2, 3, 4.5 e 7 h; e mais baixa do que as do grupo C nos momentos 2, 3.5, 4.5, 6, 7 e 8 h. O grau de claudicação diminuiu significativamente no grupo A30 quando comparado com o grupo C nos momentos 2 e 4 h pós tratamento, e no grupo PB quando comparado com o grupo C no momento 8 h pós tratamento. Não houve diferença significativa em grau de claudicação quando os grupos A20, A30 e PB foram comparados. PRINCIPAIS LIMITAÇÕES: Número pequeno de animais, ausência de mensuração de claudicação objetiva. CONCLUSÕES: A dose de 30 mg/kg de acetaminofeno proporcionou uma superior melhora na escala de claudicação e frequência cardíaca quando comparada com os outros tratamentos avaliados neste estudo. Mais informações sobre a farmacocinética e efeitos da repetida dosagem de 30 mg/kg de acetaminofeno precisam ser avaliadas para determinar a sua aplicabilidade clínica.

The Military Orthopedics Tracking Injuries and Outcomes Network: A Solution for Improving Musculoskeletal Care in the Military Health System.

INTRODUCTION: Musculoskeletal injuries are an endemic amongst U.S. Military Service Members and significantly strain the Department of Defense's Military Health System. The Military Health System aims to provide Service Members, military retirees, and their families the right care at the right time. The Military Orthopedics Tracking Injuries and Outcomes Network (MOTION) captures the data that can optimize musculoskeletal care within the Military Health System. This report provides MOTION structural framework and highlights how it can be used to optimize musculoskeletal care. MATERIALS AND METHODS: MOTION established an internet-based data capture system, the MOTION Musculoskeletal Data Portal. All adult Military Health System patients who undergo orthopedic surgery are eligible for entry into the database. All data are collected as routine standard of care, with patients and orthopedic surgeons inputting validated global and condition-specific patient reported outcomes and operative case data, respectively. Patients have the option to consent to allow their standard of care data to be utilized within an institutional review board approved observational research study. MOTION data can be merged with other existing data systems (e.g., electronic medical record) to develop a comprehensive dataset of relevant information. In pursuit of enhancing musculoskeletal injury patient outcomes MOTION aims to: (1) identify factors which predict favorable outcomes; (2) develop models which inform the surgeon and military commanders if patients are behind, on, or ahead of schedule for their targeted return-to-duty/activity; and (3) develop predictive models to better inform patients and surgeons of the likelihood of a positive outcome for various treatment options to enhance patient counseling and expectation management. RESULTS: This is a protocol article describing the intent and methodology for MOTION; thus, to date, there are no results to report. CONCLUSIONS: MOTION was established to capture the data that are necessary to improve military medical readiness and optimize medical resource utilization through the systematic evaluation of short- and long-term musculoskeletal injury patient outcomes. The systematic enhancement of musculoskeletal injury care through data analyses aligns with the National Defense Authorization Act (2017) and Defense Health Agency's Quadruple Aim, which emphasizes optimizing healthcare delivery and Service Member medical readiness. This transformative approach to musculoskeletal care can be applied across disciplines within the Military Health System.

A High-Sensitivity International Knee Documentation Committee Survey Index From the PROMIS System: The Next-Generation Patient-Reported Outcome for a Knee Injury Population.

BACKGROUND: Patient-reported outcomes (PROs) measure progression and quality of care. While legacy PROs such as the International Knee Documentation Committee (IKDC) survey are well-validated, a lengthy PRO creates a time burden on patients, decreasing adherence. In recent years, PROs such as the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function and Pain Interference surveys were developed as computer adaptive tests, reducing time to completion. Previous studies have examined correlation between legacy PROs and PROMIS; however, no studies have developed effective prediction models utilizing PROMIS to create an IKDC index. While the IKDC is the standard knee PRO, computer adaptive PROs offer numerous practical advantages. PURPOSE: To develop a nonlinear predictive model utilizing PROMIS Physical Function and Pain Interference to estimate IKDC survey scores and examine algorithm sensitivity and validity. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: The MOTION (Military Orthopaedics Tracking Injuries and Outcomes Network) database is a prospectively collected repository of PROs and intraoperative variables. Patients undergoing knee surgery completed the IKDC and PROMIS surveys at varying time points. Nonlinear multivariable predictive models using Gaussian and beta distributions were created to establish an IKDC index score, which was then validated using leave-one-out techniques and minimal clinically important difference analysis. RESULTS: A total of 1011 patients completed the IKDC and PROMIS Physical Function and Pain Interference, providing 1618 complete observations. The algorithms for the Gaussian and beta distribution were validated to predict the IKDC (Pearson = 0.84-0.86; R2 = 0.71-0.74; root mean square error = 9.3-10.0). CONCLUSION: The publicly available predictive models can approximate the IKDC score. The results can be used to compare PROMIS Physical Function and Pain Interference against historical IKDC scores by creating an IKDC index score. Serial use of the IKDC index allows for a lower minimal clinically important difference than the conventional IKDC. PROMIS can be substituted to reduce patient burden, increase completion rates, and produce orthopaedic-specific survey analogs.

Ablating the Transporter Sodium-Dependent Dicarboxylate Transporter 3 Prevents Leukodystrophy in Canavan Disease Mice.

Canavan disease is caused by ASPA mutations that diminish brain aspartoacylase activity, and it is characterized by excessive brain storage of the aspartoacylase substrate, N-acetyl-l-aspartate (NAA), and by astroglial and intramyelinic vacuolation. Astroglia and the arachnoid mater express sodium-dependent dicarboxylate transporter (NaDC3), encoded by SLC13A3, a sodium-coupled transporter for NAA and other dicarboxylates. Constitutive Slc13a3 deletion in aspartoacylase-deficient Canavan disease mice prevents brain NAA overaccumulation, ataxia, and brain vacuolation. ANN NEUROL 2021;90:845-850.

The Immediate Effect of Routine Hoof Trimming and Shoeing on Horses' Gait.

Evaluation of the effect of changes in the horses' feet after routine trimming and shoeing on gait at the trot is needed improve routine foot care. Evaluate changes in foot conformation and gait after routine farriery. Correlate alterations in a horse's gait before and after routine hoof trimming and shoe application. Fifteen horses received routine hoof trimming and horseshoe application. Dorsal and lateral photographs of the right and left front feet and inertial gait analysis at the trot were completed before and after trimming and shoeing. Measurements were made of hoof photos using a calibrated system. Gait and hoof measurements before and after farrier intervention were compared. Hoof measurement changes in relation to gait changes before and after farrier intervention were analyzed for significant associations. Mean medial to lateral coronary band length (P = .02), lateral (P = .01) and medial (P = .03) coronary band height, dorsal hoof wall length (P = .0004), heel length (P = .0002), heel overhang length (P < .0001), palmar coronary band height (P = .01), and hoof angle (P = .03) in each foot were significantly different pre- and post- farrier intervention. There was no statistical difference in the total head and pelvis movement before and after farrier intervention. The difference in the pooled mean of heel length before and after intervention was correlated with difference in maximum head movement (P = .03.) Pooled mean differences for dorsal hoof wall length (P = .04), heel length and heel overhang length (P = .006) before and after trimming were correlated with differences in maximum pelvis movement. Pooled mean differences for heel length (P = .005) and hoof angle (P = .04) before and after trimming were correlated with difference in minimum pelvis movement. Change in hoof conformation due to routine hoof trimming and shoeing does not change the gait in non-lame horses; however, some hoof characteristics measurements are correlated with immediate change in stride parameters. Use of hoof measurements may assist farriers and veterinarians in applying routine hoof care. Further studies could help determine what hoof conformation changes may be helpful to treat lame horses.

Shoulder Arthroscopy Simulator Training Improves Surgical Procedure Performance: A Controlled Laboratory Study.

BACKGROUND: Previous simulation studies evaluated either dry lab (DL) or virtual reality (VR) simulation, correlating simulator training with the performance of arthroscopic tasks. However, these studies did not compare simulation training with specific surgical procedures. PURPOSE/HYPOTHESIS: To determine the effectiveness of a shoulder arthroscopy simulator program in improving performance during arthroscopic anterior labral repair. It was hypothesized that both DL and VR simulation methods would improve procedure performance; however, VR simulation would be more effective based on the validated Arthroscopic Surgery Skill Evaluation Tool (ASSET) Global Rating Scale. STUDY DESIGN: Controlled laboratory study. METHODS: Enrolled in the study were 38 orthopaedic residents at a single institution, postgraduate years (PGYs) 1 to 5. Each resident completed a pretest shoulder stabilization procedure on a cadaveric model and was then randomized into 1 of 2 groups: VR or DL simulation. Participants then underwent a 4-week arthroscopy simulation program and completed a posttest. Sports medicine-trained orthopaedic surgeons graded the participants on completeness of the surgical repair at the time of the procedure, and a single, blinded orthopaedic surgeon, using the ASSET Global Rating Scale, graded participants' arthroscopy skills. The procedure step and ASSET grades were compared between simulator groups and between PGYs using paired t tests. RESULTS: There was no significant difference between the groups in pretest performance in either the procedural steps or ASSET scores. Overall procedural step scores improved after combining both types of simulator training (P = .0424) but not in the individual simulation groups. The ASSET scores improved across both DL (P = .0045) and VR (P = .0003), with no significant difference between the groups. CONCLUSION: A 4-week simulation program can improve arthroscopic skills and performance during a specific surgical procedure. This study provides additional evidence regarding the benefits of simulator training in orthopaedic surgery for both novice and experienced arthroscopic surgeons. There was no statistically significant difference between the VR and DL models, which disproved the authors' hypothesis that the VR simulator would be the more effective simulation tool. CLINICAL RELEVANCE: There may be a role for simulator training in the teaching of arthroscopic skills and learning of specific surgical procedures.

Generating the American Shoulder and Elbow Surgeons Score Using Multivariable Predictive Models and Computer Adaptive Testing to Reduce Survey Burden.

BACKGROUND: The preferred patient-reported outcome measure for the assessment of shoulder conditions continues to evolve. Previous studies correlating the Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive tests (CATs) to the American Shoulder and Elbow Surgeons (ASES) score have focused on a singular domain (pain or physical function) but have not evaluated the combined domains of pain and physical function that compose the ASES score. Additionally, previous studies have not provided a multivariable prediction tool to convert PROMIS scores to more familiar legacy scores. PURPOSE: To establish a valid predictive model of ASES scores using a nonlinear combination of PROMIS domains for physical function and pain. STUDY DESIGN: Cohort study (Diagnosis); Level of evidence, 3. METHODS: The Military Orthopaedics Tracking Injuries and Outcomes Network (MOTION) database is a prospectively collected repository of patient-reported outcomes and intraoperative variables. Patients in MOTION research who underwent shoulder surgery and completed the ASES, PROMIS Physical Function, and PROMIS Pain Interference at varying time points were included in the present analysis. Nonlinear multivariable predictive models were created to establish an ASES index score and then validated using "leave 1 out" techniques and minimal clinically important difference /substantial clinical benefit (MCID/SCB) analysis. RESULTS: A total of 909 patients completed the ASES, PROMIS Physical Function, and PROMIS Pain Interference at presurgery, 6 weeks, 6 months, and 1 year after surgery, providing 1502 complete observations. The PROMIS CAT predictive model was strongly validated to predict the ASES (Pearson coefficient = 0.76-0.78; R2 = 0.57-0.62; root mean square error = 13.3-14.1). The MCID/SCB for the ASES was 21.7, and the best ASES index MCID/SCB was 19.4, suggesting that the derived ASES index is effective and can reliably re-create ASES scores. CONCLUSION: The PROMIS CAT predictive models are able to approximate the ASES score within 13 to 14 points, which is 7 points more accurate than the ASES MCID/SCB derived from the sample. Our ASES index algorithm, which is freely available online (https://osf.io/ctmnd/), has a lower MCID/SCB than the ASES itself. This algorithm can be used to decrease patient survey burden by 11 questions and provide a reliable ASES analog to clinicians.

Lateral External-fixation Adjacent to Radial Nerve.

Introduction The aim of our study was to describe the injury pattern and outcomes of active-duty subjects that underwent humeral external fixation and to determine if the placement of external fixator pins outside of the radial nerve safe zones is correlated with injury to the radial nerve. Materials and methods We examined all US Service members treated with humeral external fixation at our facility from June 2005 through June 2015. The mechanism of injury, injury pattern, location of external fixation application, pre- and postoperative radial nerve function, presence or absence of radial nerve transection from injury or external fixation, anatomic location of pins in relation to the radial nerve safe zone, and final radial nerve outcomes were recorded. We defined the proximal safe zone as 5 cm distal to the acromion to 14.8 cm proximal to the lateral epicondyle, and we defined the distal safe zone as the proximal 70% of the transepicondylar width of the humerus when projected proximally from the lateral epicondyle. Results  For our study, 123 patients were identified over our date range, and 16 subjects were included with documentation regarding nerve function/injury characteristics, appropriate radiographs, and active duty status. Around 80% of injuries resulted from a blast mechanism, and 80% of injury patterns included either an intraarticular or open fracture. The radial nerve safe zone was violated in 15 of the 16 subjects (94%). The one subject with a safe construct did not sustain a nerve injury. Complete preoperative documentation on nerve function was only available for half of the subjects. Two of five subjects known to have intact function prior to external fixation had a postoperative neurologic deficit (40%). Of eight subjects with unknown radial nerve function prior to external fixation, seven subjects had full nerve function at the final follow up, and one subject had partial sensory function only. Of the three subjects with impaired preoperative radial nerve function, two made a full recovery, and the third recovered sensory function only. Around 50% of all subjects required medical retirement. Conclusion External fixation of upper extremity injuries in combat is rarely absolutely indicated, often results in the placement of pins outside of the radial nerve safe zone, and is associated with up to a 40% incidence of radial nerve injury.

Antisense Oligonucleotide Reverses Leukodystrophy in Canavan Disease Mice.

Marked elevation in the brain concentration of N-acetyl-L-aspartate (NAA) is a characteristic feature of Canavan disease, a vacuolar leukodystrophy resulting from deficiency of the oligodendroglial NAA-cleaving enzyme aspartoacylase. We now demonstrate that inhibiting NAA synthesis by intracisternal administration of a locked nucleic acid antisense oligonucleotide to young-adult aspartoacylase-deficient mice reverses their pre-existing ataxia and diminishes cerebellar and thalamic vacuolation and Purkinje cell dendritic atrophy. Ann Neurol 2020;87:480-485.

Conjoint Tendon Tenotomy for Glenoid Exposure in the Setting of Previous Coracoid Transfer.

Surgical exposure of the glenoid after previous coracoid process transfer is technically challenging as a result of distorted anatomy, obliterated soft-tissue planes, and adhesive scar tissue, which poses additional risk to adjacent neurovascular structures. The purpose of this article is to present a technique for glenoid exposure following coracoid transfer that involves tenotomy of the conjoint tendon to minimize the risk for neurovascular injury while leaving the well-healed coracoid bone graft in place.

Correction: Mice Hemizygous for a Pathogenic Mitofusin-2 Allele Exhibit Hind Limb/Foot Gait Deficits and Phenotypic Perturbations in Nerve and Muscle.

[This corrects the article DOI: 10.1371/journal.pone.0167573.].

Brain Nat8l Knockdown Suppresses Spongiform Leukodystrophy in an Aspartoacylase-Deficient Canavan Disease Mouse Model.

Canavan disease, a leukodystrophy caused by loss-of-function ASPA mutations, is characterized by brain dysmyelination, vacuolation, and astrogliosis ("spongiform leukodystrophy"). ASPA encodes aspartoacylase, an oligodendroglial enzyme that cleaves the abundant brain amino acid N-acetyl-L-aspartate (NAA) to L-aspartate and acetate. Aspartoacylase deficiency results in a 50% or greater elevation in brain NAA concentration ([NAAB]). Prior studies showed that homozygous constitutive knockout of Nat8l, the gene encoding the neuronal NAA synthesizing enzyme N-acetyltransferase 8-like, prevents aspartoacylase-deficient mice from developing spongiform leukodystrophy. We now report that brain Nat8l knockdown elicited by intracerebroventricular/intracisternal administration of an adeno-associated viral vector carrying a short hairpin Nat8l inhibitory RNA to neonatal aspartoacylase-deficient AspaNur7/Nur7 mice lowers [NAAB] and suppresses development of spongiform leukodystrophy.

Iatrogenic Hip Instability Treated With Periacetabular Osteotomy.

Hip dislocation following hip arthroscopy is a devastating complication. Previous reports of arthroscopy-related iatrogenic instability have focused on strategies aimed at restoring the stabilizing effects of the hip joint capsuloligamentous complex. Less has been written about treatment options for patients in whom deficient acetabular coverage of the femoral head is implicated in the functionally unstable hip joint. Given this relative paucity of information, an optimal treatment approach has yet to be elucidated for these patients. Periacetabular osteotomy has been described as a treatment for iatrogenic hip instability related to surgical hip dislocation; however, to our knowledge, this is the first case of a patient with hip arthroscopy-related iatrogenic instability manifesting as recurrent, frank dislocations treated with periacetabular osteotomy.

Assessment of Disability Related to Femoroacetabular Impingement Syndrome by Use of the Patient-Reported Outcome Measure Information System (PROMIS) and Objective Measures of Physical Performance.

BACKGROUND: The National Institutes of Health (NIH)-sponsored Patient-Reported Outcomes Measurement System (PROMIS) has been described as a valuable tool for characterizing outcomes among patients with specific musculoskeletal conditions. Additionally, previously proposed objective measures of physical performance among patients with nonarthritic hip abnormalities are costly and not practically incorporated into routine clinical practice. PURPOSE: (1) To determine the ability of the PROMIS to differentiate between patients with femoroacetabular impingement (FAI) and asymptomatic controls, (2) to determine the effect of FAI on subjects' completion of timed physical performance measures, and (3) to determine whether associations exist between established patient-reported outcome (PRO) measures and subjects' completion of physical performance measures. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Twenty-two asymptomatic controls (CON group) and 20 patients with FAI completed multiple activities to assess physical ability: self-selected walking velocity (SSWV), timed stair ascent (TSA), four-square step test (FSST), and sit-to-stand five times test (STS5). All subjects also underwent a battery of PRO questionnaires: Visual Analog Scale for Pain (VAS), Modified Harris Hip Score (mHHS), International Hip Outcome Tool (iHOT-33), Hip Disability and Osteoarthritis Outcome Score (HOOS), and PROMIS. Descriptive analyses were performed and comparisons between groups were made by use of paired t tests with Bonferroni-Holm correction. Spearman's rank correlation coefficients were used to determine associations between physical performance measures and PRO. The magnitude of differences between groups for each measured variable was calculated by use of Cohen's d. RESULTS: Significant differences between CON and FAI groups were observed for all hip-specific PRO measures (CON vs FAI for all; HOOS 99.2 vs 42.8, P < .001, iHOT-33 99.0 vs 26.6, P < .001, mHHS 99.6 vs 62.2, P < .001). Similarly, PROMIS scores were significantly different between groups for 8 of 9 tested domains. Patients with FAI demonstrated significant decrements in performance of all tested physical measures compared with asymptomatic controls (CON vs FAI, SSWV: 1.51 vs 1.32 m/s, P = .002; TSA: 3.05 vs 5.92 s, P = .017; FSST: 4.83 vs 8.89 s, P = .006; STS5: CON 5.53 vs FAI 10.75 s, P = .005.) Deficits in activities involving hip flexion-TSA, STS5-were strongly associated ( r < -0.7, P < .001) with increased reports of disability. CONCLUSION: FAI has a negative effect on patient-reported and objectively measured function. Hip-specific and general measures such as PROMIS, FSST, TSA, and STS5 are responsive to FAI-associated debility and may be used to objectively assess surgical or rehabilitative outcomes.