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1.
Sepsis-Induced Myopathy and Gut Microbiome Dysbiosis: Mechanistic Links and Therapeutic Targets.
Mankowski, RT, Laitano, O, Darden, D, Kelly, L, Munley, J, Loftus, TJ, Mohr, AM, Efron, PA, Thomas, RM
Shock (Augusta, Ga.). 2022;(1):15-23
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Abstract
Sepsis is currently defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The skeletal muscle system is among the host organ systems compromised by sepsis. The resulting neuromuscular dysfunction and impaired regenerative capacity defines sepsis-induced myopathy and manifests as atrophy, loss of strength, and hindered regeneration after injury. These outcomes delay recovery from critical illness and confer increased vulnerability to morbidity and mortality. The mechanisms underlying sepsis-induced myopathy, including the potential contribution of peripheral organs, remain largely unexplored. The gut microbiome is an immunological and homeostatic entity that interacts with and controls end-organ function, including the skeletal muscle system. Sepsis induces alterations in the gut microbiota composition, which is globally termed a state of "dysbiosis" for the host compared to baseline microbiota composition. In this review, we critically evaluate existing evidence and potential mechanisms linking sepsis-induced myopathy with gut microbiota dysbiosis.
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Structure and Function of the Human Ryanodine Receptors and Their Association with Myopathies-Present State, Challenges, and Perspectives.
Bauerová-Hlinková, V, Hajdúchová, D, Bauer, JA
Molecules (Basel, Switzerland). 2020;(18)
Abstract
Cardiac arrhythmias are serious, life-threatening diseases associated with the dysregulation of Ca2+ influx into the cytoplasm of cardiomyocytes. This dysregulation often arises from dysfunction of ryanodine receptor 2 (RyR2), the principal Ca2+ release channel. Dysfunction of RyR1, the skeletal muscle isoform, also results in less severe, but also potentially life-threatening syndromes. The RYR2 and RYR1 genes have been found to harbor three main mutation "hot spots", where mutations change the channel structure, its interdomain interface properties, its interactions with its binding partners, or its dynamics. In all cases, the result is a defective release of Ca2+ ions from the sarcoplasmic reticulum into the myocyte cytoplasm. Here, we provide an overview of the most frequent diseases resulting from mutations to RyR1 and RyR2, briefly review some of the recent experimental structural work on these two molecules, detail some of the computational work describing their dynamics, and summarize the known changes to the structure and function of these receptors with particular emphasis on their N-terminal, central, and channel domains.
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Corticosteroid-sparing benefit of intravenous immunoglobulin in systemic sclerosis-associated myopathy: A comparative study in 52 patients.
Chaigne, B, Rodeia, S, Benmostefa, N, Bérézné, A, Authier, J, Cohen, P, Régent, A, Terrier, B, Costedoat-Chalumeau, N, Guillevin, L, et al
Autoimmunity reviews. 2020;(1):102431
Abstract
INTRODUCTION Little is known about systemic sclerosis (SSc)-associated myopathy (SScAM) treatment. Herein we evaluated the use of intravenous immunoglobulin (IVIg) in SScAM. METHODS We conducted a retrospective study of patients with SScAM in the Internal medicine department of Cochin University Hospital between 1993 and 2017. RESULTS Fifty-two patients were included comprising 18 (34.6%) with limited SSc and 34 (65.4%) with diffuse SSc. SScAM occurred at a median [interquartile range (IQR)] time of 1 month [0-15] after SSc diagnosis. Thirty-four patients (65.4%) had muscle weakness, 28 (53.8%) had myalgia and 24 (46.2%) had dysphagia. Fifty patients (96.2%) had increased creatine kinase, 22/26 (84.6%) had myopathic electromyography, 10/12 (83.3%) had a high intensity signal of girdle muscles on MRI and 49/50 (98%) had abnormal muscle biopsy. Eighteen (34.6%) patients received IVIg. Severe adverse events occurred in 3/18 (16.7%) patients. When compared to patients who did not receive IVIg, patients who received IVIg had a significantly higher maximal corticosteroid (CS) dose ever, a greater decrease of CS at 3 months, and a lower CS dose at one year and at the end of follow up. CONCLUSIONS This study suggests the benefit of IVIg as adjunctive therapy, with an acceptable tolerance profile, and supports its use as a CS-sparing agent, in SScAM.
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Nutritional interventions for reducing the signs and symptoms of exercise-induced muscle damage and accelerate recovery in athletes: current knowledge, practical application and future perspectives.
Bongiovanni, T, Genovesi, F, Nemmer, M, Carling, C, Alberti, G, Howatson, G
European journal of applied physiology. 2020;(9):1965-1996
Abstract
PURPOSE This review provides an overview of the current knowledge of the nutritional strategies to treat the signs and symptoms related to EIMD. These strategies have been organized into the following sections based upon the quality and quantity of the scientific support available: (1) interventions with a good level of evidence; (2) interventions with some evidence and require more research; and (3) potential nutritional interventions with little to-no-evidence to support efficacy. METHOD Pubmed, EMBASE, Scopus and Web of Science were used. The search terms 'EIMD' and 'exercise-induced muscle damage' were individually concatenated with 'supplementation', 'athletes', 'recovery', 'adaptation', 'nutritional strategies', hormesis'. RESULT Supplementation with tart cherries, beetroot, pomegranate, creatine monohydrate and vitamin D appear to provide a prophylactic effect in reducing EIMD. β-hydroxy β-methylbutyrate, and the ingestion of protein, BCAA and milk could represent promising strategies to manage EIMD. Other nutritional interventions were identified but offered limited effect in the treatment of EIMD; however, inconsistencies in the dose and frequency of interventions might account for the lack of consensus regarding their efficacy. CONCLUSION There are clearly varying levels of evidence and practitioners should be mindful to refer to this evidence-base when prescribing to clients and athletes. One concern is the potential for these interventions to interfere with the exercise-recovery-adaptation continuum. Whilst there is no evidence that these interventions will blunt adaptation, it seems pragmatic to use a periodised approach to administering these strategies until data are in place to provide and evidence base on any interference effect on adaptation.
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Polyphenols: Potential Beneficial Effects of These Phytochemicals in Athletes.
D'Angelo, S
Current sports medicine reports. 2020;(7):260-265
Abstract
An athlete's dietary requirements depend on several aspects, including the environment, the sport, and the athlete's goals. Although it is recognized that regular exercise improves muscle performance and energy metabolism, unaccustomed or excessive exercise may cause cell damage and impair muscle function by triggering tissue inflammation and oxidative stress. Supplement use among athletes is widespread and recently new attention has been applied to polyphenols. Polyphenols are a class of organic chemical compounds, mainly found in plants, characterized by the presence of multiples of phenol structural units, and over recent decades, special attention has been paid to the healthy role of fruit-derived polyphenols in the human diet. This article will summarize latest knowledge on polyphenolic compounds that have been demonstrated both to exert an effect in exercise-induced muscle damage and to play a biological/physiological role in improving physical performance.
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Protein and amino acids for skeletal muscle health in aging.
Thalacker-Mercer, A, Riddle, E, Barre, L
Advances in food and nutrition research. 2020;:29-64
Abstract
Proteins and its building blocks, amino acids, have many physiological roles in the body. While some amino acids can be synthesized endogenously, exogenous protein and amino acids are necessary to maintain homeostasis. Because skeletal muscle contains a large portion of endogenous protein and plays important roles in movement, regulation, and metabolism, imbalanced protein and amino acid availability may result in clinical conditions including skeletal muscle atrophy, impaired muscle growth or regrowth, and functional decline. Aging is associated with changes in protein metabolism and multiple physiological and functional alterations in the skeletal muscle that are accentuated by decreased dietary protein intake and impaired anabolic responses to stimuli. Inactivity and chronically elevated inflammation of the skeletal muscle can initiate and/or augment pathological remodeling of the tissue (i.e., increase of fat and fibrotic tissues and atrophy of the muscle). Defining an adequate amount of dietary protein that is appropriate to maintain the availability of amino acids for biological needs is necessary but is still widely debated for older adults. This chapter will provide (i) an overview of dietary protein and amino acids and their role in skeletal muscle health; (ii) an overview of skeletal muscle structure and function and the deterioration of muscle that occurs with advancing age; (iii) a discussion of the relationship between protein/amino acid metabolism and skeletal muscle decline with aging; and (iv) a brief discussion of optimal protein intakes for older adults to maintain skeletal muscle health in aging.
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The increasing role of muscle MRI to monitor changes over time in untreated and treated muscle diseases.
Nuñez-Peralta, C, Alonso-Pérez, J, Díaz-Manera, J
Current opinion in neurology. 2020;(5):611-620
Abstract
PURPOSE OF REVIEW This review aims to discuss the recent results of studies published applying quantitative MRI sequences to large cohorts of patients with neuromuscular diseases. RECENT FINDINGS Quantitative MRI sequences are now available to identify and quantify changes in muscle water and fat content. These two components have been associated with acute and chronic injuries, respectively. Studies show that the increase in muscle water is not only reversible if therapies are applied successfully but can also predict fat replacement in neurodegenerative diseases. Muscle fat fraction correlates with muscle function tests and increases gradually over time in parallel with the functional decline of patients with neuromuscular diseases. There are new spectrometry-based sequences to quantify other components, such as glycogen, electrolytes or the pH of the muscle fibre, extending the applicability of MRI to the study of several processes in neuromuscular diseases. SUMMARY The latest results obtained from the study of long cohorts of patients with various neuromuscular diseases open the door to the use of this technology in clinical trials, which would make it possible to obtain a new measure for assessing the effectiveness of new treatments. The challenge is currently the popularization of these studies and their application to the monitoring of patients in the daily clinic.
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8.
Diagnostic challenges in metabolic myopathies.
Angelini, C, Marozzo, R, Pegoraro, V, Sacconi, S
Expert review of neurotherapeutics. 2020;(12):1287-1298
Abstract
INTRODUCTION Metabolic myopathies comprise a clinically etiological diverse group of disorders caused by defects in cellular energy metabolism including the breakdown of carbohydrates and fatty acids, which include glycogen storage diseases and fatty acid oxidation disorders. Their wide clinical spectrum ranges from infantile severe multisystemic disorders to adult-onset myopathies. To suspect in adults these disorders, clinical features such as exercise intolerance and recurrent myoglobinuria need investigation while another group presents fixed weakness and cardiomyopathy as a clinical pattern. AREAS COVERED In metabolic myopathies, clinical manifestations are important to guide diagnostic tests used in order to lead to the correct diagnosis. The authors searched in literature the most recent techniques developed. The authors present an overview of the most common phenotypes of Pompe disease and what is currently known about the mechanism of ERT treatment. The most common disorders of lipid metabolism are overviewed, with their possible dietary or supplementary treatments. EXPERT COMMENTARY The clinical suspicion is the clue to conduct in-depth investigations in suspected cases of metabolic myopathies that lead to the final diagnosis with biochemical molecular studies and often nowadays by the use of Next Generation Sequencing (NGS) to determine gene mutations.
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9.
[Valproic acid-induced hyperammonemic encephalopathy in a patient receiving valproic acid monotherapy].
Yamada, H, Shishido, T, Mukai, T, Araki, M, Naka, H, Tokinobu, H
Rinsho shinkeigaku = Clinical neurology. 2019;(5):258-263
Abstract
A 79-year-old female was diagnosed with epilepsy because she experienced loss of consciousness twice in January and February and then had a seizure in June 2016. She was treated with 800 mg sodium valproate (sustained release). After 3 days, she experienced loss of appetite, and more than 3 days later, disturbance of consciousness. Serum valproic acid (VPA) concentration was 128.3 μg/ml and serum ammonia was 404 μmol/l. Cerebral edema and status epilepticus occurred. Severe neurological dysfunction remained, even after treatment with continuous hemodiafiltration and levocarnitine. VPA is widely used for the treatment of generalized epilepsy. VPA-induced hyperammonemic encephalopathy is a rare but serious adverse event of VPA. Thus, we must pay attention to serum ammonia levels when using VPA, even VPA monotherapy.
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10.
Can exercise and nutrition stimulate muscle protein gain in the ICU patient?
Sundström-Rehal, M, Tardif, N, Rooyackers, O
Current opinion in clinical nutrition and metabolic care. 2019;(2):146-151
Abstract
PURPOSE OF REVIEW The intended purpose of nutritional and exercise interventions during ICU stay is often to limit the muscle loss associated with critical illness. Unfortunately, direct measurements of muscle protein turnover or potential surrogates have often been neglected in clinical trials. RECENT FINDINGS We discuss the potential advantages and drawbacks of common outcome measures for assessing changes in muscle structure and function over time, and how temporal changes in patient physiology require consideration. There is an increasing awareness of emphasizing functional outcomes in recent clinical trials. We here summarize the latest research on therapies attempting to limit muscle loss in ICU patients, with a focus on muscle protein metabolism. No recent or older studies show any effect of nutritional interventions on muscle protein gain, although some smaller studies show a promising positive effect on muscle thickness and function. Some studies show a positive effect of increased physical activity in the ICU on muscle mass and function but heterogeneity of the interventions and outcome measures make any general conclusions impossible. SUMMARY Several knowledge gaps remain regarding the importance of muscle protein regulation as a driver of improved physical function following ICU discharge. In our opinion, physiological investigations are needed to guide the design and interpretation of future clinical trials.