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Dyspnea is a common symptom in neuromuscular disorders and, although multifactorial, it is usually due to respiratory muscle involvement, associated musculoskeletal changes such as scoliosis or, in certain neuromuscular conditions, cardiomyopathy. Clinical history can elicit symptoms such as orthopnea, trepopnea, sleep disruption, dysphagia, weak cough, and difficulty with secretion clearance. The examination is essential to assist with the diagnosis of an underlying neurologic disorder and determine whether dyspnea is from a cardiac or pulmonary origin. Specific attention should be given to possible muscle loss, use of accessory muscles of breathing, difficulty with neck flexion/extension, presence of thoraco-abdominal paradox, conversational dyspnea, cardiac examination, and should include a detailed neurological examination directed at the suspected differential diagnosis. Pulmonary function testing including sitting and supine spirometry, measures of inspiratory and expiratory muscle strength, cough peak flow, sniff nasal inspiratory pressure, pulse oximetry, transcutaneous CO 2 , and arterial blood gases will help determine the extent of the respiratory muscle involvement, assess for hypercapnic or hypoxemic respiratory failure, and qualify the patient for noninvasive ventilation when appropriate. Additional testing includes dynamic imaging with sniff fluoroscopy or diaphragm ultrasound, and diaphragm electromyography. Polysomnography is indicated for sleep related symptoms that are not otherwise explained. Noninvasive ventilation alleviates dyspnea and nocturnal symptoms, improves quality of life, and prolongs survival. Therapy targeted at neuromuscular disorders may help control the disease or favorably modify its course. For patients who have difficulty with secretion clearance, support of expiratory function with mechanical insufflation-exsufflation, oscillatory devices can reduce the aspiration risk., (© 2024 by the American Association of Neuromuscular & Electrodiagnostic Medicine, Inc. All rights reserved.)

Neisseria gonorrhoeae causes a common sexually transmitted infection with manifestations ranging from asymptomatic to urethritis and pelvic inflammatory disease to disseminated infections including septic arthritis. Serious complications may arise in unrecognised or inappropriately treated infections.We report a young, healthy woman who developed fever and joint pain and was diagnosed with an inflammatory arthritis. After starting immune suppressing treatments, she experienced right wrist drop and progressive muscle atrophy, joint contractures and sensory loss. Electrodiagnostic studies showed patchy, mixed neurogenic and myopathic features. Areas of muscle oedema on extremity MRI led to a right brachioradialis biopsy, which showed only nonspecific changes. Other testing, including lumbar puncture and MRI of the brain/spine was noncontributory. Additional history revealed unprotected intercourse with a new partner prior to symptom onset. Urine gonorrhoeae PCR was positive, and right shoulder arthrocentesis confirmed septic arthritis. After intravenous antibiotic treatment with ceftriaxone, she demonstrated slow, incomplete symptomatic improvement., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Exercise improves many comorbidities associated with epilepsy in addition to seizure control. Despite the ILAE consensus statement noting the positive effects of exercise in patients with epilepsy (PWE) and individual assessment of risks pertaining to these activities, many healthcare professionals, including neurologists, are unfamiliar with these guidelines. Neurostimulation is an increasingly prevalent treatment option for refractory epilepsy. To date, no literature exists regarding how PWE treated with neurostimulation devices view and participate in exercise. We surveyed 36 adult PWE treated with neurostimulation (11 VNS, 21 RNS, 3 DBS, 1 VNS+RNS) on their barriers, beliefs, activity levels, and interests in exercise. Forty-three percent of patients reported meeting AHA guidelines for physical activity. Ninety percent of participants noted at least one barrier to exercise with transportation being most common. Fear of embarrassment of a seizure during exercise was reported by 44% with 39% endorsing prior seizure while exercising. Device-specific barriers included fear of device damage or avoidance of specific exercises. There was a statistically significant effect on activity level and prior seizure while exercising. Only 8% of participants reported knowledge of exercise guidelines for PWE. This data provides insight into the views of PWE treated with neurostimulation devices on exercise., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Tissue transglutaminase (tTG) is a multifunctional enzyme with a plethora of potential applications in regenerative medicine and tissue bioengineering. In this study, we examined the role of tTG as a regulator of chondrogenesis in human mesenchymal stem cells (MSC) using nanofibrous scaffolds coated with collagen type XI. Transient treatment of collagen type XI films and 3D scaffolds with tTG results in enhanced attachment of MSC and supports rounded cell morphology compared to the untreated matrices or those incubated in the continuous presence of tTG. Accordingly, enhanced cell aggregation and augmented chondrogenic differentiation have been observed on the collagen type XI-coated poly-(L-lactide) nanofibrous scaffolds treated with tTG prior to cell seeding. These changes implicate that MSC chondrogenesis is enhanced by the tTG-mediated modifications of the collagen matrix. For example, exogenous tTG increases resistance to collagenolysis in collagen type XI matrices by catalyzing intermolecular cross-linking, detected by a shift in the denaturation temperature. In addition, tTG auto-crosslinks to collagen type XI as detected by western blot and immunofluorescent analysis. This study identifies tTG as a novel regulator of MSC chondrogenesis further contributing to the expanding use of these cells in cartilage bioengineering.

Ubiquitin carboxy-terminal hydrolase L5 (UCHL5) is a proteasome-associated deubiquitinating enzyme, which, along with RPN11 and USP14, is known to carry out deubiquitination on proteasome. As a member of the ubiquitin carboxy-terminal hydrolase (UCH) family, UCHL5 is unusual because, unlike UCHL1 and UCHL3, it can process polyubiquitin chain. However, it does so only when it is bound to the proteasome; in its free form, it is capable of releasing only relatively small leaving groups from the C-terminus of ubiquitin. Such a behavior might suggest at least two catalytically distinct forms of the enzyme, an apo form incapable of chain processing activity, and a proteasome-induced activated form capable of cleaving polyubiquitin chain. Through the crystal structure analysis of two truncated constructs representing the catalytic domain (UCH domain) of this enzyme, we were able to visualize a state of this enzyme that we interpret as its inactive form, because the catalytic cysteine appears to be in an unproductive orientation. While this work was in progress, the structure of a different construct representing the UCH domain was reported; however, in that work the structure reported was that of an inactive mutant [catalytic Cys to Ala; Nishio K et al. (2009) Biochem Biophys Res Commun 390, 855-860], which precluded the observation that we are reporting here. Additionally, our structures reveal conformationally dynamic parts of the enzyme that may play a role in the structural transition to the more active form., (© 2011 The Authors Journal compilation © 2011 FEBS.)