Importance: Bioenergetic failure has been proposed as a driver of amyotrophic lateral sclerosis (ALS). CNM-Au8 is a suspension of gold nanocrystals that catalyzes the conversion of nicotinamide adenine dinucleotide hydride into NAD+, resulting in an increase of cellular adenosine triphosphate production.
Objective: To determine the effects of CNM-Au8 on ALS disease progression.
Importance: Amyotrophic lateral sclerosis (ALS) is a fatal disease. The sigma-1 (σ1) receptor emerged as a target for intervention.
Objective: To determine the effects of pridopidine, a σ1-receptor agonist, in ALS.
JAMA Neurol
February 2025
Importance: Myeloperoxidase is one of the most abundant peroxidase enzymes in activated myeloid cells. Myeloperoxidase inhibitors may have a clinical benefit in amyotrophic lateral sclerosis (ALS) by slowing neurodegeneration via reduced neuroinflammation and oxidative stress.
Objective: To determine the safety, tolerability, and efficacy of verdiperstat, a selective myeloperoxidase inhibitor, in ALS.
Introduction: Reliable assessments of learning ability in preclinical models are essential for studying neurodegenerative, developmental, and inflammatory disorders. However, many inbred strains of mice present background pathologies that interfere with traditional learning tests. The C57BL/6 J mouse, a widely used laboratory strain, sporadically develops auditory and visual impairments that complicate interpretation.
View Article and Find Full Text PDFBrain network dynamics have been extensively explored in patients with subjective cognitive decline (SCD). However, these studies are susceptible to individual differences, scanning parameters, and other confounding factors. Therefore, how to reveal subtle SCD-related subtle changes remains unclear.
View Article and Find Full Text PDFCalreticulin (CALR) mutations are detected in around 20% of patients with primary and post-essential thrombocythemia myelofibrosis (MF). Regardless of driver mutations, patients with splenomegaly and symptoms are generally treated with JAK2-inhibitors, most commonly ruxolitinib. Recently, new therapies specifically targeting the CALR mutant clone have entered clinical investigation.
View Article and Find Full Text PDFVery-low-carbohydrate diets (LCHF; <50 g/day) have been debated for their potential to lower pre-exercise muscle and liver glycogen stores and metabolic efficiency, risking premature fatigue. It is also hypothesized that carbohydrate ingestion during prolonged exercise delays fatigue by increasing carbohydrate oxidation, thereby sparing muscle glycogen. Leveraging a randomized crossover design, we evaluated performance during strenuous time-to-exhaustion (70% V̇o) tests in trained triathletes following 6-wk high-carbohydrate (HCLF, 380 g/day) or very-low-carbohydrate (LCHF, 40 g/day) diets to determine ) if adoption of the LCHF diet impairs time-to-exhaustion performance, ) whether carbohydrate ingestion (10 g/h) 6-12× lower than current CHO fueling recommendations during low glycogen availability (>15-h pre-exercise overnight fast and/or LCHF diet) improves time to exhaustion by preventing exercise-induced hypoglycemia (EIH; <3.
View Article and Find Full Text PDFUstekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist approved for the treatment of Crohn's disease (CD). Only limited real-life data on the long-term outcomes of CD patients treated with UST are available. This study assessed UST's long-term effectiveness and safety in a large population-based cohort of moderate to severe CD patients.
View Article and Find Full Text PDFThis study demonstrates a simple approach to synthesize green Cu particles stabilized by poly(n-vinyl)pyrrolidone (PVP): the latter acts as stabilizer and dispersant, and its presence in solution eliminates the need for an inert atmosphere. Synthetic parameters were tuned to obtain particles with diameters >200 nm, to be human-safe and prevent nano-cytotoxicity. PVP and reductant concentrations, with reaction times, were varied to investigate their effect on colloidal stability, kinetics, and particles size.
View Article and Find Full Text PDFPharmaceuticals (Basel)
August 2024
Ketone bodies are considered alternative fuels for the brain when glucose availability is limited. To determine the neuroregenerative potential of D,L-sodium-beta-hydroxybutyrate (D/L-BHB), Sprague Dawley rat primary cortical neurons were exposed to simulated central nervous system injury using a scratch assay. The neuronal cell migration, cell density and degree of regeneration in the damaged areas (gaps) in the absence (control) and presence of BHB (2 mM) were documented with automated live-cell imaging by the CytoSMART system over 24 h, which was followed by immunocytochemistry, labeling synapsin-I and β3-tubulin.
View Article and Find Full Text PDFApproximately 30% of patients with epilepsy are drug-refractory. There is an urgent need to elucidate the exact pathophysiology of different types of epilepsies and the mechanisms of action of both antiseizure medication and metabolic therapies to treat patients more effectively and safely. For example, it has been demonstrated that exogenous ketone supplement (EKS)-generated therapeutic ketosis, as a metabolic therapy, may decrease epileptic activity in both animal models and humans, but its exact mechanism of action is unknown.
View Article and Find Full Text PDFArtificial intelligence (AI) has been extensively researched in medicine, but its practical application remains limited. Meanwhile, there are various disparities in existing AI-enabled clinical studies, which pose a challenge to global health equity. In this study, we conducted an in-depth analysis of the geo-economic distribution of 159 AI-enabled clinical studies, as well as the gender disparities among these studies.
View Article and Find Full Text PDFNeurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder caused by loss-of-function variants in the gene. As of 20 November 2023, over 5000 distinct pathogenic or likely pathogenic variants have been reported in public databases. However, only a few genotype-phenotype correlations have been established so far.
View Article and Find Full Text PDFAdvances in immunosuppression have extended patient and graft survival rates after solid organ transplantation; however, this is not free of side effects. Balancing safety and efficacy is of paramount importance, particularly in the pediatric setting. Current literature comparing different protocols is scarce, and decisions are mostly guided by physician preference.
View Article and Find Full Text PDFJ Int Soc Sports Nutr
December 2024
Position Statement: The International Society of Sports Nutrition (ISSN) provides an objective and critical review of the use of a ketogenic diet in healthy exercising adults, with a focus on exercise performance and body composition. However, this review does not address the use of exogenous ketone supplements. The following points summarize the position of the ISSN.
View Article and Find Full Text PDFThe global rise in type 2 diabetes (T2D) and obesity necessitates innovative dietary interventions. This study investigates the effects of allulose, a rare sugar shown to reduce blood glucose, in a rat model of diet-induced obesity and T2D. Over 12 weeks, we hypothesized that allulose supplementation would improve body weight, insulin sensitivity, and glycemic control.
View Article and Find Full Text PDFIntroduction/aims: Expanded access (EA) is a Food and Drug Administration-regulated pathway to provide access to investigational products (IPs) to individuals with serious diseases who are ineligible for clinical trials. The aim of this report is to share the design and operations of a multicenter, multidrug EA program for amyotrophic lateral sclerosis (ALS) across nine US centers.
Methods: A central coordination center was established to design and conduct the program.
Providing a model that achieves a strong predictive performance and is simultaneously interpretable by humans is one of the most difficult challenges in machine learning research due to the conflicting nature of these two objectives. To address this challenge, we propose a modification of the radial basis function neural network model by equipping its Gaussian kernel with a learnable precision matrix. We show that precious information is contained in the spectrum of the precision matrix that can be extracted once the training of the model is completed.
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