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Athletes use creatine monohydrate (CM) to enhance high‐intensity exercise performance by increasing creatine phosphate availability. While CM supplementation is known to raise muscle creatine levels in vegans and vegetarians, its impact on exercise performance remains uncertain. We examined the effects of CM supplementation on muscle creatine content and exercise performance in vegans and vegetarians. In a randomized, double‐blind placebo‐controlled design, 15 healthy vegans and vegetarians consumed CM (0.3 g/kg/day, n = 7) or placebo (PLA, 0.3 g maltodextrin/kg/day, n = 8) four times a day for 7 days. Before and after supplementation, repeated sprint capacity was determined. Body mass and fat‐free mass (FFM) were assessed by dual‐energy x‐ray absorptiometry. The CM group increased body mass (1.56 ± 0.57 kg, p < 0.01) and FFM (1.15 ± 0.94 kg, p < 0.05), while the PLA group showed no changes. In the CM group, muscle creatine (Cr) and total muscle creatine (TCr) increased by 18.8 ± 13.1 mmol/kg (p < 0.05) and 30.8 ± 21.2 mmol/kg (p < 0.01), respectively. The PLA group showed no changes in Cr and TCr (−4.6 ± 13.1 mmol/kg and 2.9 ± 11.6 mmol/kg, respectively). Phosphocreatine levels remained consistent within and between groups. There were no observed changes in peak and mean power output during repeated sprints. A seven‐day CM supplementation in healthy vegans and vegetarians increased Cr and TCr whereas Phosphocreatine, peak and mean power output during repeated sprints was unchanged.

Whereas the diagnosis of moderate and severe traumatic brain injury (TBI) is readily visible on current medical imaging paradigms (magnetic resonance imaging [MRI] and computed tomography [CT] scanning), a far greater challenge is associated with the diagnosis and subsequent management of mild TBI (mTBI), especially concussion which, by definition, is characterized by a normal CT. To investigate whether the integrity of the blood–brain barrier (BBB) is altered in a high-risk population for concussions, we studied professional mixed martial arts (MMA) fighters and adolescent rugby players. Additionally, we performed the linear regression between the BBB disruption defined by increased gadolinium contrast extravasation on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) on MRI and multiple biomechanical parameters indicating the severity of impacts recorded using instrumented mouthguards in professional MMA fighters. MMA fighters were examined pre-fight for a baseline and again within 120 h post–competitive fight, whereas rugby players were examined pre-season and again post-season or post-match in a subset of cases. DCE-MRI, serological analysis of BBB biomarkers, and an analysis of instrumented mouthguard data, was performed. Here, we provide pilot data that demonstrate disruption of the BBB in both professional MMA fighters and rugby players, dependent on the level of exposure. Our data suggest that biomechanical forces in professional MMA and adolescent rugby can lead to BBB disruption. These changes on imaging may serve as a biomarker of exposure of the brain to repetitive subconcussive forces and mTBI.

Traumatic brain injury is the leading cause of death in children and young adults globally. Malignant cerebral oedema has a major role in the pathophysiology that evolves after severe traumatic brain injury. Added to this is the significant morbidity and mortality from cerebral oedema associated with acute stroke, hypoxic ischemic coma, neurological cancers and brain infection. Therapeutic strategies to prevent cerebral oedema are limited and, if brain swelling persists, the risks of permanent brain damage or mortality are greatly exacerbated. Here we show that a temporary and size-selective modulation of the blood-brain barrier allows enhanced movement of water from the brain to the blood and significantly impacts on brain swelling. We also show cognitive improvement in mice with focal cerebral oedema following administration in these animals of short interfering RNA directed against claudin-5. These observations may have profound consequences for early intervention in cases of traumatic brain injury, or indeed any neurological condition where cerebral oedema is the hallmark pathology. Claudin-5 is a component of tight junctions and has important roles in mediating the permeability of the blood-brain barrier. Campbell and co-workers administer short interfering RNA against claudin-5 in a model of brain injury, finding that it enhances water movement from the brain to the blood and alleviates swelling.

BackgroundNitrous oxide (N2O) is increasingly being used as a recreational drug of abuse. It can induce a functional B12 deficiency, which may present clinically as subacute combined degeneration of the cord (SACD).MethodsWe conducted a prospective case series of patients presenting with N2O-associated SACD to three large Dublin teaching hospitals, between October 2021 and January 2023. Data were gathered regarding clinical presentation, investigations, and management of patients.ResultsSixteen patients were identified (81% male, mean age 20 years). The most common neuro- logic symptoms at presentation to the hospital included gait impairment (12/16), paresthesia (10/16) or numbness (11/16), and weakness (8/16). All patients reported heavy pre-presentation use of inhaled nitrous oxide. Serum vitamin B12 was low in nine cases and borderline low in six cases. Homocysteine and/or methylmalonic acid was raised in all cases where it was measured (10/15). Abnormal signal intensity was seen on MRI of cervical cord in 93% of cases where imaging was available (13/14). Four cases demonstrated additional thoracic cord involvement. Nerve conduction studies demonstrated motor-predominant axonal neuropathy in 64% of cases.ConclusionThis study highlights a remarkable prevalence of nitrous oxide abuse with obvious public health implications. Physicians should be aware of its potential to cause SACD and the need for prompt Vitamin B12 replacement to minimise long term disability.

Given the worldwide adverse impact of traumatic brain injury (TBI) on the human population, its diagnosis and prediction are of utmost importance. Historically, many studies have focused on associating head kinematics to brain injury risk. Recently, there has been a push toward using computationally expensive finite element (FE) models of the brain to create tissue deformation metrics of brain injury. Here, we develop a new brain injury metric, the brain angle metric (BAM), based on the dynamics of a 3 degree-of-freedom lumped parameter brain model. The brain model is built based on the measured natural frequencies of an FE brain model simulated with live human impact data. We show that it can be used to rapidly estimate peak brain strains experienced during head rotational accelerations that cause mild TBI. In our data set, the simplified model correlates with peak principal FE strain (R2  = 0.82). Further, coronal and axial brain model displacement correlated with fiber-oriented peak strain in the corpus callosum (R2  = 0.77). Our proposed injury metric BAM uses the maximum angle predicted by our brain model and is compared against a number of existing rotational and translational kinematic injury metrics on a data set of head kinematics from 27 clinically diagnosed injuries and 887 non-injuries. We found that BAM performed comparably to peak angular acceleration, translational acceleration, and angular velocity in classifying injury and non-injury events. Metrics that separated time traces into their directional components had improved model deviance compare with those that combined components into a single time trace magnitude. Our brain model can be used in future work to rapidly approximate the peak strain resulting from mild to moderate head impacts and to quickly assess brain injury risk.

BackgroundThe radiological trajectory of post-COVID-19 is uncertain. We present a prospective, observational, multicentre cohort study using multimodality imaging to describe the pulmonary sequelae of patients hospitalised with COVID-19, predictors of persistent abnormal radiology and implications on health status.MethodsIn survivors of COVID-19, we performed convalescent CT pulmonary angiogram and high-resolution CT imaging as part of the CISCO-19 study (ClinicalTrials.gov ID NCT04403607). This included serial blood biomarkers and patient-reported outcomes 28–60 days following discharge from hospital.ResultsOf the COVID-19 cohort, 88 (56%) patients of the COVID-19 cohort (n = 159; mean age, 55 years; 43% female) had persisting radiological abnormalities at 28–60 days postdischarge. This included ground-glass opacification (45%), reticulation/architectural distortion (30%) or mixed pattern (19%). These features were very infrequent among a group of age-matched, sex-matched and cardiovascular risk factor-matched controls (n=29). The majority of COVID-19 cohort (68%) had less than 20% persisting radiological abnormalities, with 67% demonstrating overall improvement compared with admission imaging. Older age, premorbid performance status, typical acute COVID-19 radiological features, markers of severe acute COVID-19, convalescent ICAM-1 and P-selectin were associated with persisting lung abnormalities (all p<0.05). Patients with persisting abnormalities were shown to have lower levels of physical activity and predicted maximal oxygen utilisation (derived VO2) (both p<0.05). Higher percentage of abnormal lung parenchyma was associated with lower patient-assessed quality of life (EQ-5D-5L) score (p=0.03).ConclusionsPersistent radiological abnormalities post-COVID-19 were common at 28–60 days postdischarge from hospital, although most improved. Patients with persisting radiological abnormalities 28–60 days postdischarge are at risk of persisting health impairment in the longer term and represent a population for targeted intervention.Trial registration numberNCT04403607.

To the Editor: The trial by Wiebe et al. (Aug. 2 issue) 1 of surgery as compared with prolonged medical treatment for temporal-lobe seizures clearly demonstrated the superiority of surgical intervention and illustrated the feasibility of conducting randomized controlled trials in patients with epilepsy. In the accompanying editorial, Engel 2 urges that more studies be performed to define more precisely the role and timing of conventional surgery in drug-resistant epilepsy. Other approaches to treatment, such as gamma-knife radiosurgery, are not considered. Gamma-knife radiosurgery is a noninvasive technique involving the selective delivery of concentrated radiation to a stereotactically defined intracranial target. The use . . .

Sequencing-based studies have identified novel risk genes for rare, severe epilepsies and revealed a role of rare deleterious variation in common epilepsies. To identify the shared and distinct ultra-rare genetic risk factors for rare and common epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals and 8,364 controls of European ancestry. We focused on three phenotypic groups; the rare but severe developmental and epileptic encephalopathies (DEE), and the commoner phenotypes of genetic generalized epilepsy (GGE) and non-acquired focal epilepsy (NAFE). We observed that compared to controls, individuals with any type of epilepsy carried an excess of ultra-rare, deleterious variants in constrained genes and in genes previously associated with epilepsy, with the strongest enrichment seen in DEE and the least in NAFE. Moreover, we found that inhibitory GABAA receptor genes were enriched for missense variants across all three classes of epilepsy, while no enrichment was seen in excitatory receptor genes. The larger gene groups for the GABAergic pathway or cation channels also showed a significant mutational burden in DEE and GGE. Although no single gene surpassed exome-wide significance among individuals with GGE or NAFE, highly constrained genes and genes encoding ion channels were among the top associations, including CACNA1G, EEF1A2, and GABRG2 for GGE and LGI1, TRIM3, and GABRG2 for NAFE. Our study confirms a convergence in the genetics of common and rare epilepsies associated with ultra-rare coding variation and highlights a ubiquitous role for GABAergic inhibition in epilepsy etiology in the largest epilepsy WES study to date.