The study aims to develop an abnormal body temperature probability (ABTP) model for dairy cattle, utilizing environmental and physiological data. This model is designed to enhance the management of heat stress impacts, providing an early warning system for farm managers to improve dairy cattle welfare and farm productivity in response to climate change. The study employs the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm to analyze environmental and physiological data from 320 dairy cattle, identifying key factors influencing body temperature anomalies. This method supports the development of various models, including the Lyman Kutcher-Burman (LKB), Logistic, Schultheiss, and Poisson models, which are evaluated for their ability to predict abnormal body temperatures in dairy cattle effectively. The study successfully validated multiple models to predict abnormal body temperatures in dairy cattle, with a focus on the temperature-humidity index (THI) as a critical determinant. These models, including LKB, Logistic, Schultheiss, and Poisson, demonstrated high accuracy, as measured by the AUC and other performance metrics such as the Brier score and Hosmer-Lemeshow (HL) test. The results highlight the robustness of the models in capturing the nuances of heat stress impacts on dairy cattle. The research develops innovative models for managing heat stress in dairy cattle, effectively enhancing detection and intervention strategies. By integrating advanced technologies and novel predictive models, the study offers effective measures for early detection and management of abnormal body temperatures, improving cattle welfare and farm productivity in changing climatic conditions. This approach highlights the importance of using multiple models to accurately predict and address heat stress in livestock, making significant contributions to enhancing farm management practices.

Pathogenic variants in LMNA have been associated with a wide spectrum of muscular conditions: the laminopathies. LMNA-related congenital muscular dystrophy is a laminopathy characterised by the early onset of symptoms and often leads to a fatal outcome at young ages. Children face a heightened risk of malignant arrhythmias. No established paediatric protocols for managing this condition are available. We review published cases and provide insights into disease progression in two twin sisters with LMNA-related muscular dystrophy. Our objective is to propose a cardiac surveillance and management plan tailored specifically for paediatric patients. We present a family of five members, including two twin sisters with LMNA-related muscular dystrophy. A comprehensive neuromuscular and cardiac work-up was performed in all family members. Genetic analysis using massive sequencing technology was performed in both twins. Clinical assessment showed that only the twins showed diagnoses of LMNA-related muscular dystrophy. Follow-up showed an early onset of symptoms and life-threatening arrhythmias, with differing disease progressions despite both twins passing away. Genetic analysis identified a de novo rare missense deleterious variant in the LMNA gene. Other additional rare variants were identified in genes associated with myasthenic syndrome. Early-onset neuromuscular symptoms could be related to a prognosis of worse life-threatening arrhythmias in LMNA related muscular dystrophy. Being a carrier of other rare variants may be a modifying factor in the progression of the phenotype, although further studies are needed. There is a pressing need for specific cardiac recommendations tailored to the paediatric population to mitigate the risk of malignant arrhythmias.

Dysferlin is a large transmembrane protein involved in critical cellular processes including membrane repair and vesicle fusion. Mutations in the dysferlin gene (DYSF) can result in rare forms of muscular dystrophy; Miyoshi myopathy; limb girdle muscular dystrophy type 2B (LGMD2B); and distal myopathy. These conditions are collectively known as dysferlinopathies and are caused by more than 600 mutations that have been identified across the DYSF gene to date. In this review, we discuss the key molecular and clinical features of LGMD2B, the causative gene DYSF, and the associated dysferlin protein structure. We also provide an update on current approaches to LGMD2B diagnosis and advances in drug development, including splice switching antisense oligonucleotides. We give a brief update on clinical trials involving adeno-associated viral gene therapy and the current progress on CRISPR/Cas9 mediated therapy for LGMD2B, and then conclude by discussing the prospects of antisense oligomer-based intervention to treat selected mutations causing dysferlinopathies.

BACKGROUND: African cities, particularly Abidjan and Johannesburg, face challenges of rapid urban growth, informality and strained health services, compounded by increasing temperatures due to climate change. This study aims to understand the complexities of heat-related health impacts in these cities. The objectives are: (1) mapping intraurban heat risk and exposure using health, socioeconomic, climate and satellite imagery data; (2) creating a stratified heat-health forecast model to predict adverse health outcomes; and (3) establishing an early warning system for timely heatwave alerts. The ultimate goal is to foster climate-resilient African cities, protecting disproportionately affected populations from heat hazards.
METHODS: The research will acquire health-related datasets from eligible adult clinical trials or cohort studies conducted in Johannesburg and Abidjan between 2000 and 2022. Additional data will be collected, including socioeconomic, climate datasets and satellite imagery. These resources will aid in mapping heat hazards and quantifying heat-health exposure, the extent of elevated risk and morbidity. Outcomes will be determined using advanced data analysis methods, including statistical evaluation, machine learning and deep learning techniques.
BACKGROUND: The study has been approved by the Wits Human Research Ethics Committee (reference no: 220606). Data management will follow approved procedures. The results will be disseminated through workshops, community forums, conferences and publications. Data deposition and curation plans will be established in line with ethical and safety considerations.

BACKGROUND: Muscle diseases are of various types, viz., muscular dystrophies, inflammatory myopathies, myotonic disorders, congenital myopathies, and metabolic myopathies. They all present with muscle weakness, be it proximal or distal. The assessment of muscle biopsy with the help of enzyme histochemistry, histopathological, and immunohistochemical methods is an essential component in the diagnosis of neuromuscular disorders. The authors outline brief data on muscle diseases prevalent in the North Indian region.
METHODS: Muscle biopsy was done, and the biopsy was freshly frozen in liquid nitrogen and sections were taken on a cryostat. Slides were then stained with hematoxylin and eosin (H&E), modified Gomori trichome (MGT), nicotinamide adenine dinucleotide hydrogenase (NADH), and succinic dehydrogenase (SDH) stains. Further specific immunohistochemistry tests were also done.
RESULTS: Out of n=16 cases, three cases were diagnosed as Becker\'s muscular dystrophy, two cases were diagnosed as inflammatory myopathy, four cases were diagnosed as Facioscapulohumeral muscular dystrophy, and one each case of dysferlinopathy and alpha sarcoglycanopathy.
CONCLUSIONS: Muscle diseases can cause different levels of physical disability and thus it is important to diagnose at the appropriate time to ensure proper treatment.

Skeletal muscle regeneration relies on the intricate interplay of various cell populations within the muscle niche-an environment crucial for regulating the behavior of muscle stem cells (MuSCs) and ensuring postnatal tissue maintenance and regeneration. This review delves into the dynamic interactions among key players of this process, including MuSCs, macrophages (MPs), fibro-adipogenic progenitors (FAPs), endothelial cells (ECs), and pericytes (PCs), each assuming pivotal roles in orchestrating homeostasis and regeneration. Dysfunctions in these interactions can lead not only to pathological conditions but also exacerbate muscular dystrophies. The exploration of cellular and molecular crosstalk among these populations in both physiological and dystrophic conditions provides insights into the multifaceted communication networks governing muscle regeneration. Furthermore, this review discusses emerging strategies to modulate the muscle-regenerating niche, presenting a comprehensive overview of current understanding and innovative approaches.

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UNASSIGNED: Muscular dystrophies and congenital myopathies encompass various inherited muscular disorders that present diagnostic challenges due to clinical complexity and genetic heterogeneity.
UNASSIGNED: This study aimed to investigate the use of whole exome sequencing (WES) in diagnosing muscular disorders in pediatric patients in Taiwan. Out of 161 pediatric patients suspected to have genetic/inherited myopathies, 115 received a molecular diagnosis through conventional tests, single gene testing, and gene panels. The remaining 46 patients were divided into three groups: Group 1 (multiplex ligation-dependent probe amplification-negative Duchenne muscular dystrophy) with three patients (6.5%), Group 2 (various forms of muscular dystrophies) with 21 patients (45.7%), and Group 3 (congenital myopathies) with 22 patients (47.8%).
UNASSIGNED: WES analysis of these groups found pathogenic variants in 100.0% (3/3), 57.1% (12/21), and 68.2% (15/22) of patients in Groups 1 to 3, respectively. WES had a diagnostic yield of 65.2% (30 patients out of 46), detecting 30 pathogenic or potentially pathogenic variants across 28 genes.
UNASSIGNED: WES enables the diagnosis of rare diseases with symptoms and characteristics similar to congenital myopathies and muscular dystrophies, such as muscle weakness. Consequently, this approach facilitates targeted therapy implementation and appropriate genetic counseling.

UNASSIGNED: Calpainopathy, also known as limb-girdle muscular dystrophy recessive type 1, is a progressive muscle disorder that impacts the muscles around the hips and shoulders. The disease is caused by defects in the CAPN3 gene and can be inherited in both recessive and dominant forms. In this retrospective study, we aimed to evaluate the clinical and molecular results of our patients with calpainopathy and to examine the CAPN3 variants in Turkish and global populations.
UNASSIGNED: Molecular analyses were performed using the next-generation sequencing (NGS) method. CAPN3 variants were identified through the examination of various databases.
UNASSIGNED: In this retrospective study, the cohort consisted of seven patients exhibiting the CAPN3 (NM_000070.3) mutation and a phenotype compatible with calpainopathy at a single center in Türkiye. All patients displayed high CK levels and muscle weakness. We report a novel missense c.2437G>A variant that causes the autosomal dominant form of calpainopathy. Interestingly, the muscle biopsy report for the patient with the novel mutation indicated sarcoglycan deficiency. Molecular findings for the remaining individuals in the cohort included a compound heterozygous variant (frameshift and missense), one homozygous nonsense, one homozygous intronic deletion, and three homozygous missense variants. The most common variant in the Turkish population was c.550del. In both populations, pathogenic variants were most frequently located in exon 21, according to exon length. Variants were stochastically distributed based on consequences in CAPN3 domains.
UNASSIGNED: Therefore, the NGS method proves highly effective in diagnosing rare diseases characterized by clinical heterogeneity. Assessing variants based on ethnicity holds significance in the development of precise therapies.

Pressure to reduce the use of antibiotics in the poultry industry has intensified research on alternative solutions to support intestinal health, including but not limited to direct fed microbials (DFM). Heat stress is known to impact intestinal health and function. The aim of this study was to determine efficacy of a water applied DFM product on broiler performance during the summer period. One of two treatments were randomly allocated to 12 replicate floor pens each: a control treatment and a treatment provided daily with a dual strain DFM comprised of Lactobacillus acidophilus AG01 and Bifidobacterium animalis AG02 at 1 × 108 CFU/bird/d. Each pen contained 20 Ross 308 broilers. All birds were fed the same three-phased wheat- and soybean meal-based diets. Body weight, feed intake, feed conversion ratio, and mortality were measured at d 0, 10, 24, 35, and 42. Due to natural extreme external temperature conditions, all birds were subject to heat stress during the end of the grower phase up to and including the finisher phase. Temperature was on average 5°C higher compared to industry recommendation. No significant differences were found in growth performance between the control and DFM treatment, yet BW at d 42 in both treatments was reduced by 19% compared to the breed standard. The DFM treatment significantly reduced mortality among the birds. Overall mortality from d 1 to d 35 was reduced from 4.58% to 0.42% (P = 0.023) and overall mortality from d 1 to d 42 was reduced from 5.83 to 0.83% (P = 0.027). This was driven by the difference in heat-stress related mortality in the finisher phase from d 25 to d 42, where mortality reached only 0.44% in the DFM treatment versus 2.88% in the unsupplemented control treatment. Post-mortem analysis confirmed heat-stress related hypoxia. In conclusion, the dual strain DFM may have provided improved (intestinal) homeostasis and barrier function allowing increased resilience to heat stress in broilers.