Modulating fast skeletal muscle contraction protects skeletal muscle in animal models of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a lethal muscle disease caused by absence of the protein dystrophin, which acts as a structural link between the basal lamina and contractile machinery to stabilize muscle membranes in response to mechanical stress. In DMD, mechanical stress leads to exaggerated membrane injury and fiber breakdown, with fast fibers being the most susceptible to damage. A major contributor to this injury is muscle contraction, controlled by the motor protein myosin. However, how muscle contraction and fast muscle fiber damage contribute to the pathophysiology of DMD has not been well characterized. We explored the role of fast skeletal muscle contraction in DMD with a potentially novel, selective, orally active inhibitor of fast skeletal muscle myosin, EDG-5506. Surprisingly, even modest decreases of contraction (<15%) were sufficient to protect skeletal muscles in dystrophic mdx mice from stress injury. Longer-term treatment also decreased muscle fibrosis in key disease-implicated tissues. Importantly, therapeutic levels of myosin inhibition with EDG-5506 did not detrimentally affect strength or coordination. Finally, in dystrophic dogs, EDG-5506 reversibly reduced circulating muscle injury biomarkers and increased habitual activity. This unexpected biology may represent an important alternative treatment strategy for Duchenne and related myopathies.

The sound of migration: exploring data sonification as a means of interpreting multivariate salmon movement datasets.

The migration of Pacific salmon is an important part of functioning freshwater ecosystems, but as populations have decreased and ecological conditions have changed, so have migration patterns. Understanding how the environment, and human impacts, change salmon migration behavior requires observing migration at small temporal and spatial scales across large geographic areas. Studying these detailed fish movements is particularly important for one threatened population of Chinook salmon in the Snake River of Idaho whose juvenile behavior may be rapidly evolving in response to dams and anthropogenic impacts. However, exploring movement data sets of large numbers of salmon can present challenges due to the difficulty of visualizing the multivariate, time-series datasets. Previous research indicates that sonification, representing data using sound, has the potential to enhance exploration of multivariate, time-series datasets. We developed sonifications of individual fish movements using a large dataset of salmon otolith microchemistry from Snake River Fall Chinook salmon. Otoliths, a balance and hearing organ in fish, provide a detailed chemical record of fish movements recorded in the tree-like rings they deposit each day the fish is alive. This data represents a scalable, multivariate dataset of salmon movement ideal for sonification. We tested independent listener responses to validate the effectiveness of the sonification tool and mapping methods. The sonifications were presented in a survey to untrained listeners to identify salmon movements with increasingly more fish, with and without visualizations. Our results showed that untrained listeners were most sensitive to transitions mapped to pitch and timbre. Accuracy results were non-intuitive; in aggregate, respondents clearly identified important transitions, but individual accuracy was low. This aggregate effect has potential implications for the use of sonification in the context of crowd-sourced data exploration. The addition of more fish, and visuals, to the sonification increased response time in identifying transitions.

Delayed Presentation of Isolated Sagittal Synostosis With Raised Intracranial Pressure and Secondary Chiari Malformation With Cervical Syringomyelia.

Sagittal craniosynostosis (SC) is the most common type of premature suture fusion presenting in approximately 1 in every 5000 births with a 3:1 male:female ratio. The most common indication for surgery is the improvement of the cosmetic appearance of the skull, since a cranial deformation may have a significant psychosocial impact on affected patients. Relief from raised intracranial pressure is a further indication for surgery, although an increased intracranial pressure (ICP) can be demonstrated only in a minority of affected children at diagnosis. It is even more rare to have Chiari malformations (CMs) secondary to ICP in an isolated SC, as shown in a study by Strahle et al (Neurosurg Focus 2011;31:E2), demonstrating only 5 (3%) of the 183 with isolated sagittal synostosis having a CM. The authors present the rare case of a 4-year-old boy presenting late with raised intracranial pressure (40 mm Hg) and his management with 1 stage vault expansion and decompression of CM.

Outcome after knee dislocations: a 2-9 years follow-up of 85 consecutive patients.

Dislocation of the knee is a relatively rare injury with modern arthroscopic techniques, operative reconstruction has become the standard of care. The primary aim of this study was to prospectively follow a large, consecutive series of patients with knee dislocation to document associated injuries, surgical treatment, knee function, and knee osteoarthritis (OA) at a minimum of 2 years follow-up. Hundred and twenty-two consecutive patients with a traumatic knee dislocation (Schenck II-IV) were treated at the Oslo University Hospital, Ulleval, between May 1996 and December 2004. Follow-up evaluation of 85 patients consisted of evaluation of knee joint laxity using the KT1000, the Lachman test, the pivot shift test, the reversed pivot shift, the posterior drawer test, the dial test, and the varus-valgus tests compared to the uninjured knee. Knee function was evaluated using the Lysholm score, the Tegner activity level score, the IKDC2000 score, and four single leg hop tests. Radiographic evaluation was performed using the Kellgren & Lawrence classification grade 0-4. Knee function at a minimum of 2 years after surgery disclosed a Lysholm score of a median of 83, a Tegner activity score of 5, and above 83% on all single leg hop tests compared to the uninjured side. Knee function was lower in the patients with a knee dislocation caused by high-energy trauma compared to low energy trauma. Eighty-seven percent had Kellgren & Lawrence grade 2 or higher for the injured knee compared to 35% for the uninjured knee.