Concise review of end of life and palliative care in neuromuscular pathologies: still a long pathway ahead.

Introduction: Neuromuscular diseases (NMD) include different types of diseases depending on the deficient component of the motor unit involved. They may all be interested by a progressive and sometimes irreversible pump respiratory failure which unfortunately for some NMD may start soon after the diagnosis. Within this vast group of patients those affected by muscle diseases are a subgroup who comprises patients with an average earlier onset of symptoms compared to other NMD. Indeed it is also important to comprehend not just the patient's burden but also the surrounding families'. Defining the end of life (EoL) phase in these patients is not simple especially in the young patient population. Consequently, the late stage of disease remains poorly defined and challenging. Objectives: The aim of this review is to describe the EoL phase in NMD patients with attention to QoL and psycological status. Methods: The focus would be on one hand on the management of the psychological burden, the communication barriers, and tone of humor. Results: Those topics have been described being crucial in this group of patients as they increase tensions and burden of both patient and family, and between them and the outside world. Thus also causing their social isolation, increasing anxiety and reducing their quality of life. On the other hand the use of cough clearance devices and all the respiratory supports and their withdrawn are carefully evaluated in the view of alleviating respiratory symptoms, improving patient quality of life and above all reaching the patient's goals of care. Conclusions: Although there is no cure, the advent of supportive interventions including multidisciplinary care (MDC) has improved all the aspects of dying for patients affected by NMD; nevertheless there still a long pathway ahead.

The Revolution of exosomes: From biological functions to therapeutic applications in skeletal muscle diseases.

Skeletal muscle diseases, a broad category encompassing a myriad of afflictions such as acute muscle injury and muscular dystrophies, pose a significant health burden globally. These conditions often lead to muscle weakness, compromised mobility, and a diminished quality of life. In light of this, innovative and effective therapeutic strategies are fervently sought after. Exosomes, naturally extracellular vesicles with a diameter of 30-150 nm, pervade biological fluids. These microscopic entities harbor a host of biological molecules, including proteins, nucleic acids, and lipids, bearing a significant resemblance to their parent cells. The roles they play in the biological theater are manifold, influencing crucial physiological and pathological processes within the organism. In the context of skeletal muscle diseases, their potential extends beyond these roles, as they present a promising therapeutic target and a vehicle for targeted drug delivery. This potentially paves the way for significant clinical applications. This review aims to elucidate the mechanisms underpinning exosome action, their myriad biological functions, and the strides made in exosome research and application. A comprehensive exploration of the part played by exosomes in skeletal muscle repair and regeneration is undertaken. In addition, we delve into the use of exosomes in the therapeutic landscape of skeletal muscle diseases, providing a valuable reference for a deeper understanding of exosome applications in this realm. The concluding section encapsulates the prospective avenues for exosome research and the promising future they hold, underscoring the tremendous potential these diminutive vesicles possess in the field of skeletal muscle diseases. The Translational Potential of this Article. The comprehensive exploration of exosome's diverse biological functions and translational potential in the context of skeletal muscle diseases presented in this review underscores their promising future as a therapeutic target with significant clinical applications, thus paving the way for innovative and effective therapeutic strategies in this realm.

[Management of cardiomyopathies : New ESC guidelines 2023]. / Management von Kardiomyopathien : Neue ESC-Leitlinie 2023.

The group of cardiomyopathies has received increasing attention over the last few years after some of the causes were identified and they could be characterized more exactly using modern imaging methods. New definitions and classification schemes were regularly provided by national and international cardiac societies. The new guidelines of the European Society of Cardiology (ESC) from 2023 on the management of cardiomyopathies are the first guidelines that comprehensively address all cardiomyopathies in one document. As these are new guidelines most of the recommendations are also new. An exception is the section on hypertrophic cardiomyopathy (HCM), which provides a targeted update of the 2014 ESC guidelines on the diagnosis and treatment of HCM. The main aim of the guidelines is to provide clear guidance for the diagnosis of cardiomyopathies, to highlight general assessment and management problems and to point out the relevant scientific evidence for the recommendations to the readership. Due to the magnitude detailed descriptions and recommendations cannot be provided for each individual cardiomyopathy phenotype; however, reference is made to the relevant literature.

Development of capsid- and genome-modified optimized AAVrh74 vectors for muscle gene therapy.

The first generation of adeno-associated virus (AAV) vectors composed of the naturally occurring capsids and genomes, although effective in some instances, are unlikely to be optimal for gene therapy in humans. The use of the first generation of two different AAV serotype vectors (AAV9 and AAVrh74) in four separate clinical trials failed to be effective in patients with Duchenne muscular dystrophy, although some efficacy was observed in a subset of patients with AAVrh74 vectors leading to US Food and Drug Administration approval (Elevidys). In two trials with the first generation of AAV9 vectors, several serious adverse events were observed, including the death of a patient in one trial, and more recently, in the death of a second patient in an N-of-1 clinical trial. In a fourth trial with the first generation of AAVrh74 vectors, myositis and myocarditis were also observed. Here, we report that capsid- and genome-modified optimized AAVrh74 vectors are significantly more efficient in transducing primary human skeletal muscle cells in vitro and in all major muscle tissues in vivo following systemic administration in a murine model. The availability of optimized AAVrh74 vectors promises to be safe and effective in the potential gene therapy of muscle diseases in humans.

The Mitochondrial Calcium Uniporter (MCU): Molecular Identity and Role in Human Diseases.

Calcium (Ca2+) ions act as a second messenger, regulating several cell functions. Mitochondria are critical organelles for the regulation of intracellular Ca2+. Mitochondrial calcium (mtCa2+) uptake is ensured by the presence in the inner mitochondrial membrane (IMM) of the mitochondrial calcium uniporter (MCU) complex, a macromolecular structure composed of pore-forming and regulatory subunits. MtCa2+ uptake plays a crucial role in the regulation of oxidative metabolism and cell death. A lot of evidence demonstrates that the dysregulation of mtCa2+ homeostasis can have serious pathological outcomes. In this review, we briefly discuss the molecular structure and the function of the MCU complex and then we focus our attention on human diseases in which a dysfunction in mtCa2+ has been shown.

Putative malignant hyperthermia mutation CaV1.1-R174W is insufficient to trigger a fulminant response to halothane or confer heat stress intolerance.

Malignant hyperthermia susceptibility (MHS) is an autosomal dominant pharmacogenetic disorder that manifests as a hypermetabolic state when carriers are exposed to halogenated volatile anesthetics or depolarizing muscle relaxants. In animals, heat stress intolerance is also observed. MHS is linked to over 40 variants in RYR1 that are classified as pathogenic for diagnostic purposes. More recently, a few rare variants linked to the MHS phenotype have been reported in CACNA1S, which encodes the voltage-activated Ca2+ channel CaV1.1 that conformationally couples to RyR1 in skeletal muscle. Here, we describe a knock-in mouse line that expresses one of these putative variants, CaV1.1-R174W. Heterozygous (HET) and homozygous (HOM) CaV1.1-R174W mice survive to adulthood without overt phenotype but fail to trigger with fulminant malignant hyperthermia when exposed to halothane or moderate heat stress. All three genotypes (WT, HET, and HOM) express similar levels of CaV1.1 by quantitative PCR, Western blot, [3H]PN200-110 receptor binding and immobilization-resistant charge movement densities in flexor digitorum brevis fibers. Although HOM fibers have negligible CaV1.1 current amplitudes, HET fibers have similar amplitudes to WT, suggesting a preferential accumulation of the CaV1.1-WT protein at triad junctions in HET animals. Never-the-less both HET and HOM have slightly elevated resting free Ca2+ and Na+ measured with double barreled microelectrode in vastus lateralis that is disproportional to upregulation of transient receptor potential canonical (TRPC) 3 and TRPC6 in skeletal muscle. CaV1.1-R174W and upregulation of TRPC3/6 alone are insufficient to trigger fulminant malignant hyperthermia response to halothane and/or heat stress in HET and HOM mice.

Sarcoplasmic Reticulum Ca2+ Buffer Proteins: A Focus on the Yet-To-Be-Explored Role of Sarcalumenin in Skeletal Muscle Health and Disease.

Sarcalumenin (SAR) is a luminal Ca2+ buffer protein with high capacity but low affinity for calcium binding found predominantly in the longitudinal sarcoplasmic reticulum (SR) of fast- and slow-twitch skeletal muscles and the heart. Together with other luminal Ca2+ buffer proteins, SAR plays a critical role in modulation of Ca2+ uptake and Ca2+ release during excitation-contraction coupling in muscle fibers. SAR appears to be important in a wide range of other physiological functions, such as Sarco-Endoplasmic Reticulum Calcium ATPase (SERCA) stabilization, Store-Operated-Calcium-Entry (SOCE) mechanisms, muscle fatigue resistance and muscle development. The function and structural features of SAR are very similar to those of calsequestrin (CSQ), the most abundant and well-characterized Ca2+ buffer protein of junctional SR. Despite the structural and functional similarity, very few targeted studies are available in the literature. The present review provides an overview of the role of SAR in skeletal muscle physiology, as well as of its possible involvement and dysfunction in muscle wasting disorders, in order to summarize the current knowledge on SAR and drive attention to this important but still underinvestigated/neglected protein.

Identification of vacuolar autophagic aggregates in the skeletal muscles of inbred C57BL/6NCrl mice.

A comprehensive pathological analysis of inbred strains is essential to define strain-specific spontaneous lesions and to understand whether a specific phenotype results from experimental intervention or reflects a naturally occurring disease. This study aimed to report and describe a novel condition affecting the skeletal muscles of an inbred C57BL/6NCrl mouse colony characterised by large sarcoplasmic vacuoles in the muscle fibres of male mice in the subsarcolemmal spaces and the intermyofibrillary network. There was no muscle weakness, loss of ambulation or cardiac/respiratory involvement. Post-mortem evaluation and histological analysis excluded the presence of pathological accumulations or lesions in other tissues and organs. Changes were seen in fibre size, with many hypotrophic and some slightly hypertrophic fibres. Histological, immunohistochemical and molecular analyses of the vacuolar content revealed dysregulation of the autophagy machinery while ruling out a morphologically similar condition marked by the accumulation of tubular aggregates.

A randomised controlled trial of acceptance and commitment therapy for improving quality of life in people with muscle diseases.

Abstract. BACKGROUND: Chronic muscle diseases (MD) are progressive and cause wasting and weakness in muscles and are associated with reduced quality of life (QoL). The ACTMuS trial examined whether Acceptance and Commitment Therapy (ACT) as an adjunct to usual care improved QoL for such patients as compared to usual care alone. METHODS: This two-arm, randomised, multicentre, parallel design recruited 155 patients with MD (Hospital and Depression Scale ⩾ 8 for depression or ⩾ 8 for anxiety and Montreal Cognitive Assessment ⩾ 21/30). Participants were randomised, using random block sizes, to one of two groups: standard medical care (SMC) (n = 78) or to ACT in addition to SMC (n = 77), and were followed up to 9 weeks. The primary outcome was QoL, assessed by the Individualised Neuromuscular Quality of Life Questionnaire (INQoL), the average of five subscales, at 9-weeks. Trial registration was NCT02810028. RESULTS: 138 people (89.0%) were followed up at 9-weeks. At all three time points, the adjusted group difference favoured the intervention group and was significant with moderate to large effect sizes. Secondary outcomes (mood, functional impairment, aspects of psychological flexibility) also showed significant differences between groups at week 9. CONCLUSIONS: ACT in addition to usual care was effective in improving QoL and other psychological and social outcomes in patients with MD. A 6 month follow up will determine the extent to which gains are maintained.

Differential Analysis of Gly211Val and Gly286Val Mutations Affecting Sarco(endo)plasmic Reticulum Ca2+-ATPase (SERCA1) in Congenital Pseudomyotonia Romagnola Cattle.

Congenital pseudomyotonia in cattle (PMT) is a rare skeletal muscle disorder, clinically characterized by stiffness and by delayed muscle relaxation after exercise. Muscle relaxation impairment is due to defective content of the Sarco(endo)plasmic Reticulum Ca2+ ATPase isoform 1 (SERCA1) protein, caused by missense mutations in the ATP2A1 gene. PMT represents the only mammalian model of human Brody myopathy. In the Romagnola breed, two missense variants occurring in the same allele were described, leading to Gly211Val and Gly286Val (G211V/G286V) substitutions. In this study, we analyzed the consequences of G211V and G286V mutations. Results support that the reduced amount of SERCA1 is a consequence of the G211V mutation, the G286V mutation almost being benign and the ubiquitin-proteasome system (UPS) being involved. After blocking the proteasome using a proteasome inhibitor, we found that the G211V mutant accumulates in cells at levels comparable to those of WT SERCA1. Our conclusion is that G211/286V mutations presumably originate in a folding-defective SERCA1 protein, recognized and diverted to degradation by UPS, although still catalytically functional, and that the main role is played by G211V mutation. Rescue of mutated SERCA1 to the sarcoplasmic reticulum membrane can re-establish resting cytosolic Ca2+ concentration and prevent the appearance of pathological signs, paving the way for a possible therapeutic approach against Brody disease.

Impact of the COVID-19 pandemic on neuromuscular rehabilitation setting. Part 2: patients and families' views on the received health care during the pandemic.

This study explored views of users with muscular dystrophies and their caregivers on staff-user relationships and the treatments provided by a Rehabilitation Centre during the pandemic. Patients and relatives were asked to anonymously complete an open-ended questionnaire exploring their views on these aspects. Fifty-four patients and 40 caregivers gave their informed consent and participated in the survey. Fifty-three patients were adults, 28% suffering from Duchenne/Becker muscular dystrophy. Patients reported 269 comments on health care services provided during the pandemic, 132 (49%) concerning positive aspects and 137 (51%) negative aspects. The prompt restart of the rehabilitation therapies and the staff closeness over the pandemic were the practical aspects most frequently appreciated (46.9%), while closer family contacts and the perception of being able to rely on the Centre's constant support were the most cited psychological aspects (53.1%). Architectural barriers, difficulties in accessing public health services, economic difficulties, and lack of support from welfare and other agencies were the practical critical points most frequently reported (89%). In addition, social isolation, and loneliness due to fear of contagion were the most negative psychological aspects (10.1%). As regard the caregivers' views, participants reported 151 comments. Of these, 86 (56.9%) were positive and 65 (43.1%) were negative. Among the positive aspects, the psychological ones - such as closer family contacts, not feeling abandoned and counting on the constant Centre's professional support prevailed (53.5%). As for the negative aspects, most caregivers (92.6%) believe that the pandemic exacerbated their financial and bureaucratic difficulties, particularly in poorer families.

Genetic Appraisal of Hereditary Muscle Disorders In A Cohort From Mumbai, India.

BACKGROUND: Hereditary muscle disorders are clinically and genetically heterogeneous. Limited information is available on their genetic makeup and their prevalence in India. OBJECTIVE: To study the genetic basis of prevalent hereditary myopathies. MATERIAL AND METHODS: This is a retrospective study conducted at a tertiary care center. The study was approved by the institutional ethics board. The point of the collection was the genetic database. The genetic data of myopathy patients for the period of two and half years (2019 to mid-2021) was evaluated. Those with genetic diagnoses of DMD, FSHD, myotonic dystrophies, mitochondriopathies, and acquired myopathies were excluded. The main outcome measures were diagnostic yield and the subtype prevalence with their gene variant spectrum. RESULTS: The definitive diagnostic yield of the study was 39% (cases with two pathogenic variants in the disease-causing gene). The major contributing genes were GNE (15%), DYSF (13%), and CAPN3 (7%). Founder genes were documented in Calpainopathy and GNE myopathy. The uncommon myopathies identified were Laminopathy (0.9%), desminopathy (0.9%), and GMPPB-related myopathy (1.9%). Interestingly, a small number of patients showed pathogenic variants in more than one myopathy gene, the multigenic myopathies. CONCLUSION: This cohort study gives hospital-based information on the prevalent genotypes of myopathies (GNE, Dysferlinopathy, and calpainopathy), founder mutations, and also newly documents the curious occurrence of multigenicity in a small number of myopathies.

NAD+ centric mechanisms and molecular determinants of skeletal muscle disease and aging.

The nicotinamide adenine dinucleotide (NAD+) is an essential redox cofactor, involved in various physiological and molecular processes, including energy metabolism, epigenetics, aging, and metabolic diseases. NAD+ repletion ameliorates muscular dystrophy and improves the mitochondrial and muscle stem cell function and thereby increase lifespan in mice. Accordingly, NAD+ is considered as an anti-oxidant and anti-aging molecule. NAD+ plays a central role in energy metabolism and the energy produced is used for movements, thermoregulation, and defense against foreign bodies. The dietary precursors of NAD+ synthesis is targeted to improve NAD+ biosynthesis; however, studies have revealed conflicting results regarding skeletal muscle-specific effects. Recent advances in the activation of nicotinamide phosphoribosyltransferase in the NAD+ salvage pathway and supplementation of NAD+ precursors have led to beneficial effects in skeletal muscle pathophysiology and function during aging and associated metabolic diseases. NAD+ is also involved in the epigenetic regulation and post-translational modifications of proteins that are involved in various cellular processes to maintain tissue homeostasis. This review provides detailed insights into the roles of NAD+ along with molecular mechanisms during aging and disease conditions, such as the impacts of age-related NAD+ deficiencies on NAD+-dependent enzymes, including poly (ADP-ribose) polymerase (PARPs), CD38, and sirtuins within skeletal muscle, and the most recent studies on the potential of nutritional supplementation and distinct modes of exercise to replenish the NAD+ pool.

Alpha B-Crystallin in Muscle Disease Prevention: The Role of Physical Activity.

HSPB5 or alpha B-crystallin (CRYAB), originally identified as lens protein, is one of the most widespread and represented of the human small heat shock proteins (sHSPs). It is greatly expressed in tissue with high rates of oxidative metabolism, such as skeletal and cardiac muscles, where HSPB5 dysfunction is associated with a plethora of human diseases. Since HSPB5 has a major role in protecting muscle tissues from the alterations of protein stability (i.e., microfilaments, microtubules, and intermediate filament components), it is not surprising that this sHSP is specifically modulated by exercise. Considering the robust content and the protective function of HSPB5 in striated muscle tissues, as well as its specific response to muscle contraction, it is then realistic to predict a specific role for exercise-induced modulation of HSPB5 in the prevention of muscle diseases caused by protein misfolding. After offering an overview of the current knowledge on HSPB5 structure and function in muscle, this review aims to introduce the reader to the capacity that different exercise modalities have to induce and/or activate HSPB5 to levels sufficient to confer protection, with the potential to prevent or delay skeletal and cardiac muscle disorders.

Embedded Psychiatric Services in a Multidisciplinary Amyotrophic Lateral Sclerosis Clinic: An Assessment of Patient Needs and Perceptions.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is often associated with a range of difficult neuropsychiatric symptoms and conditions, including depression, apathy, pseudobulbar affect, and frontotemporal dementia (FTD). Despite the potential role for psychiatrists in the treatment of ALS, they are not typically involved in the ALS clinical team. The investigators describe a quality improvement intervention providing embedded psychiatric services within a multidisciplinary clinic (MDC). METHODS: A psychiatrist working within an ALS MDC evaluated patients (N=116) over a 1-year period. The clinic assessed the prevalence of neuropsychiatric symptoms and conditions in patients with ALS (depression, anxiety, pseudobulbar affect, and cognitive impairment, including FTD) using standardized screening methods. Fifty-five patients and 47 family members completed surveys about perceptions of their need for psychiatric care, their experience of meeting with a psychiatrist, and their desire for future access to psychiatric care. RESULTS: Prevalence rates for neuropsychiatric symptoms were 14.9% for depression, 11.3% for anxiety, 19% for cognitive impairment (including FTD, 8.6%), and 36.2% for pseudobulbar affect; 62.0% of patients were being prescribed at least one psychotropic medication. Both patients and family members reported that meeting with a psychiatrist was helpful, that the treatment provided was helpful, and that they would prefer continued availability of psychiatric services in the future. The presence of cognitive impairment and use of antidepressants increased the likelihood of patients reporting a benefit from psychiatric care. CONCLUSIONS: Patients with ALS report a benefit from increased access to psychiatric services. The inclusion of a psychiatrist within the ALS MDC model should be considered to improve quality of care for this patient population.

The Importance of mTORC1-Autophagy Axis for Skeletal Muscle Diseases.

The mechanistic target of rapamycin (mTOR) complex 1, mTORC1, integrates nutrient and growth factor signals with cellular responses and plays critical roles in regulating cell growth, proliferation, and lifespan. mTORC1 signaling has been reported as a central regulator of autophagy by modulating almost all aspects of the autophagic process, including initiation, expansion, and termination. An increasing number of studies suggest that mTORC1 and autophagy are critical for the physiological function of skeletal muscle and are involved in diverse muscle diseases. Here, we review recent insights into the essential roles of mTORC1 and autophagy in skeletal muscles and their implications in human muscle diseases. Multiple inhibitors targeting mTORC1 or autophagy have already been clinically approved, while others are under development. These chemical modulators that target the mTORC1/autophagy pathways represent promising potentials to cure muscle diseases.

Impact of the COVID-19 pandemic on rehabilitation setting. Part 1: professionals' views on the changes in routine care provided by a rehabilitation centre for patients with muscle diseases.

The outbreak of COVID-19 has forced the health care system to undergo profound rearrangements in services and facilities, especially during the periods of lockdown. In this context, inpatient and outpatient services had to rethink and reorganize their activities to meet the needs of severely disabled patients, as those affected by Muscular Dystrophies (MDs). We present the preliminary results of a survey aiming to explore the staff views on the changes in the care provided by the Gaetano Torre Rehabilitation Centre, and, the impact of these changes on professionals, patients and their families. The survey was carried out using an open-ended questionnaire including six-items, on the practical and psychological aspects emerged during the pandemic in relation to the healthcare services provided by the Centre and to the patients/caregivers conditions. The participants, most of them physiotherapists, highlighted 169 aspects emerging in the pandemic, 48.5% referring to the resources used to cope with critical issues and 51.5% concerning the difficulties encountered. Emotional aspects prevailed on practical aspects both in resources (52.4 vs 47.6%) and in difficulties (57.5 vs 42.5%) categories. In particular, with regard to patients' resources, psychological benefits, despite the burden, were greater than practical ones (87 vs 13%), in the form of improved intra-family relationships, feeling more cared for, and satisfaction for the received care. As for the patients' relatives, the staff indicated more resources than difficulties (72.8 vs 17.2%). Among the former, 75% concerned the emotional sphere, such as the perception of having a point of reference even in such a difficult time.

Alteration of STIM1/Orai1-Mediated SOCE in Skeletal Muscle: Impact in Genetic Muscle Diseases and Beyond.

Intracellular Ca2+ ions represent a signaling mediator that plays a critical role in regulating different muscular cellular processes. Ca2+ homeostasis preservation is essential for maintaining skeletal muscle structure and function. Store-operated Ca2+ entry (SOCE), a Ca2+-entry process activated by depletion of intracellular stores contributing to the regulation of various function in many cell types, is pivotal to ensure a proper Ca2+ homeostasis in muscle fibers. It is coordinated by STIM1, the main Ca2+ sensor located in the sarcoplasmic reticulum, and ORAI1 protein, a Ca2+-permeable channel located on transverse tubules. It is commonly accepted that Ca2+ entry via SOCE has the crucial role in short- and long-term muscle function, regulating and adapting many cellular processes including muscle contractility, postnatal development, myofiber phenotype and plasticity. Lack or mutations of STIM1 and/or Orai1 and the consequent SOCE alteration have been associated with serious consequences for muscle function. Importantly, evidence suggests that SOCE alteration can trigger a change of intracellular Ca2+ signaling in skeletal muscle, participating in the pathogenesis of different progressive muscle diseases such as tubular aggregate myopathy, muscular dystrophy, cachexia, and sarcopenia. This review provides a brief overview of the molecular mechanisms underlying STIM1/Orai1-dependent SOCE in skeletal muscle, focusing on how SOCE alteration could contribute to skeletal muscle wasting disorders and on how SOCE components could represent pharmacological targets with high therapeutic potential.

Coping in Children and Adolescents with a Genetic Muscle Disorder -Findings from a Population-Based Study.

BACKGROUND: The impacts of genetic muscle disorders on quality of life in affected children are well-documented. However, few studies have investigated children's coping strategies and relationships between coping and quality of life. OBJECTIVES: To determine coping strategy use, efficacy, and associations with quality of life in children with a genetic muscle disorder. METHODS: Forty-eight children (6-15 years, 58% male) with a genetic muscle disorder were identified as part of a national prevalence study. Children completed the Kidcope in response to a specific stressor (doctors visits) and the Pediatric Quality of Life Inventory Neuromuscular Module. RESULTS: 'Wishful thinking' (75%, 36/48) and 'cognitive restructuring' (71%, 34/48) were the most frequently used coping strategies. 'Self-criticism' (12%, 6/48), and 'blaming others' and 'resignation' (both 19%, 9/48) were the least used strategies. Coping strategy use did not differ across age and sex groups (p's from 0.08 to 1.00). Positive coping strategies tended to be more effective (medians ranged from 2.00 to 2.75) than negative strategies (medians ranged from 1.38 to 2.50). Using a greater number of different types of positive (F(4, 46) = 5.79, p = 0.001) and/or negative (F(4, 44) = 5.64, p 0.001) coping strategies was linked to poorer health-related quality of life. CONCLUSION: We conclude that children with genetic muscle disorders use a wide range of positive and/or negative coping strategies in response to stressors associated with a doctor visit and may benefit from greater support to improve health-related quality of life. Findings support the value of routine screening of children's coping to identify those who would benefit from support.

Validating muscle mass cutoffs of four international sarcopenia-working groups in Japanese people using DXA and BIA.

BACKGROUND: The Asian Working Group for Sarcopenia (AWGS) 2019 recommended the use of dual-energy X-ray absorptiometry (DXA) or bioelectrical impedance analysis (BIA) to assess appendicular lean mass (ALM). AWGS, European Working Group on Sarcopenia in Older People 2 (EWGSOP2), Foundation for the National Institutes of Health Sarcopenia Project (FNIH), and International Working Group on Sarcopenia (IWGS) reported different cutoff values for sarcopenia. We aimed to validate these cutoff values in a Japanese population using DXA and two different devices of segmental multi-frequency BIA (MF-BIA). METHODS: We examined the data of Japanese individuals aged 18-86 years using the DXA (n = 756) and two 8-electrode MF-BIA devices (InBody and TANITA MC) (n = 1884). To validate these cutoff values, we used a population aged 18-40 years, and calculated the 95% confidence intervals (CIs) of [mean-2SD]. RESULTS: In DXA, the 95%CIs of [mean-2SD] for ALM/Ht2 were 5.2-5.8 and 6.6-7.3 kg/m2 in women and men, respectively. The AWGS (<5.4 in women and <7.0 in men), and IWGS (≤5.67 in women and ≤7.23 in men) cutoffs were acceptable. Regarding TANITA MC, the 95%CIs of [mean-2SD] for ALM/Ht2 were 5.6-6.0 and 6.9-7.4 kg/m2 in women and men, respectively. The AWGS (<5.7 in women and <7.0 in men), EWGSOP2 (<6.0 in women and <7.0 in men), and IWGS cutoffs were acceptable. Regarding InBody, the 95%CIs of [mean-2SD] for ALM/Ht2 were 4.8-5.2 and 6.4-6.8 kg/m2 in young women and men, respectively. All cutoff values were too high compared to those measured by InBody. InBody and TANITA MC were highly correlated (P < 0.001), but the values by InBody were significantly lower than those by TANITA MC or DXA. Using Yamada's equation for InBody raw data, the AWGS, EWGSOP2, or IWGS cutoffs were acceptable. The BMI-adjusted muscle mass cutoff values were <0.60 and <0.82 m2 in women and men, respectively. We also obtained the 20th percentile in older adult population (ALM/Ht2 , <6.2 in women and <7.5 in men for TANITA MC; <5.4 in women and <7.0 in men for InBody). CONCLUSIONS: The AWGS and IWGS cutoffs were valid for DXA, and the AWGS, IWGS, and EWGSOP2 cutoffs were valid for TANITA MC in Japanese population. Because the prevalence of sarcopenia is too low particularly in women when using those criteria, the 20th percentile might be a good alternative criteria. If the ALM original InBody values are used, the cutoffs should be <5.0 kg/m2 in women and <6.6 kg/m2 in men.