eIF3 Associates with 80S Ribosomes to Promote Translation Elongation, Mitochondrial Homeostasis, and Muscle Health.

eIF3, a multi-subunit complex with numerous functions in canonical translation initiation, is known to interact with 40S and 60S ribosomal proteins and translation elongation factors, but a direct involvement in translation elongation has never been demonstrated. We found that eIF3 deficiency reduced early ribosomal elongation speed between codons 25 and 75 on a set of ∼2,700 mRNAs encoding proteins associated with mitochondrial and membrane functions, resulting in defective synthesis of their encoded proteins. To promote elongation, eIF3 interacts with 80S ribosomes translating the first ∼60 codons and serves to recruit protein quality-control factors, functions required for normal mitochondrial physiology. Accordingly, eIF3e+/- mice accumulate defective mitochondria in skeletal muscle and show a progressive decline in muscle strength. Hence, eIF3 interacts with 80S ribosomes to enhance, at the level of early elongation, the synthesis of proteins with membrane-associated functions, an activity that is critical for mitochondrial physiology and muscle health.

Potential Diaphragm Muscle Weakness-related Dyspnea Persists Two Years after COVID-19 and Could Be Improved by Inspiratory Muscle Training: Results of an Observational and an Interventional Trial.

RATIONALE: Diaphragm muscle weakness might underly persistent exertional dyspnea despite normal lung/cardiac function in individuals previously hospitalized for acute COVID-19 illness. OBJECTIVES: Firstly, to determine the persistence and pathophysiological nature of diaphragm muscle weakness and its association with exertional dyspnea two years after hospitalization for COVID-19, and secondly to investigate the impact of inspiratory muscle training (IMT) on diaphragm and inspiratory muscle weakness and exertional dyspnea in individuals with long COVID. METHODS: ~2 years after hospitalization for COVID-19, 30 individuals (11 female, median age 58 [interquartile range (IQR) 51-63] years) underwent comprehensive (invasive) respiratory muscle assessment and evaluation of dyspnea. Eighteen with persistent diaphragm muscle weakness and exertional dyspnea were randomized to 6 weeks of IMT or sham training; assessments were repeated immediately after and 6 weeks after IMT completion. The primary endpoint was change in inspiratory muscle fatiguability immediately after IMT. RESULTS: At median 31 [IQR 23-32] months after hospitalization, 21/30 individuals reported relevant persistent exertional dyspnea. Diaphragm muscle weakness on exertion and reduced diaphragm cortical activation were potentially related to exertional dyspnea. Compared with sham control, IMT improved diaphragm and inspiratory muscle function (sniff transdiaphragmatic pressure 83 [IQR 75-91] vs. 100 [IQR 81-113] cmH2O; p=0.02), inspiratory muscle fatiguability (time to task failure 365 [IQR 284-701] vs. 983 [IQR 551-1494] sec; p=0.05), diaphragm voluntary activation index (79 [IQR 63-92] vs 89 [IQR 75-94]%; p=0.03), and dyspnea (Borg score 7 [IQR 5.5-8] vs. 6 [IQR 4-7]; p=0.03); improvements persisted for 6 weeks after IMT completion. CONCLUSIONS: This study is the first to identify a potential treatment for persisting exertional dyspnea in long COVID, and provide a possible pathophysiological explanation for the treatment benefit. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Alterations in neuromuscular junction morphology with ageing and endurance training modulate neuromuscular transmission and myofibre composition.

Both ageing and exercise training affect the neuromuscular junction (NMJ) structure. Morphological alterations in the NMJ have been considered to influence neuromuscular transmission and myofibre properties, but the direct link between the morphology and function has yet to be established. We measured the neuromuscular transmission, myofibre composition and NMJ structure of 5-month-old (young) and 24-month-old untrained (aged control) and trained (aged trained) mice. Aged trained mice were subjected to 2 months of endurance training before the measurement. Neuromuscular transmission was evaluated in vivo as the ratio of ankle plantar flexion torque evoked by the sciatic nerve stimulation to that by direct muscle stimulation. The torque ratio was significantly lower in aged mice than in young and aged trained mice at high-frequency stimulations, showing a significant positive correlation with voluntary grip strength. The degree of pre- to post-synaptic overlap of the NMJ was also significantly lower in aged mice and positively correlated with the torque ratio. We also found that the proportion of fast-twitch fibres in the soleus muscle decreased with age, and that age-related denervation occurred preferentially in fast-twitch fibres. Age-related denervation and a shift in myofibre composition were partially prevented by endurance training. These results suggest that age-related deterioration of the NMJ structure impairs neuromuscular transmission and alters myofibre composition, but these alterations can be prevented by structural amelioration of NMJ with endurance training. Our findings highlight the importance of the NMJ as a major determinant of age-related deterioration of skeletal muscles and the clinical significance of endurance training as a countermeasure. KEY POINTS: The neuromuscular junction (NMJ) plays an essential role in neuromuscular transmission and the maintenance of myofibre properties. We show that neuromuscular transmission is impaired with ageing but recovered by endurance training, which contributes to alterations in voluntary strength. Neuromuscular transmission is associated with the degree of pre- to post-synaptic overlap of the NMJ. Age-related denervation of fast-twitch fibres and a shift in myofibre composition toward a slower phenotype are partially prevented by endurance training. Our study provides substantial evidence that age-related and exercise-induced alterations in neuromuscular transmission and myofibre properties are associated with morphological changes in the NMJ.

Myostatin gene invalidation does not prevent skeletal muscle mass loss during experimental sepsis in mice.

Loss of muscle mass and function induced by sepsis contributes to physical inactivity and disability in intensive care unit patients. Limiting skeletal muscle deconditioning may thus be helpful in reducing the long-term effect of muscle wasting in patients. We tested the hypothesis that invalidation of the myostatin gene, which encodes a powerful negative regulator of skeletal muscle mass, could prevent or attenuate skeletal muscle wasting and improve survival of septic mice. Sepsis was induced by caecal ligature and puncture (CLP) in 13-week-old C57BL/6J wild-type and myostatin knock-out male mice. Survival rates were similar in wild-type and myostatin knock-out mice seven days after CLP. Loss in muscle mass was also similar in wild-type and myostatin knock-out mice 4 and 7 days after CLP. The loss in muscle mass was molecularly supported by an increase in the transcript level of E3-ubiquitin ligases and autophagy-lysosome markers. This transcriptional response was blunted in myostatin knock-out mice. No change was observed in the protein level of markers of the anabolic insulin/IGF1-Akt-mTOR pathway. Muscle strength was similarly decreased in wild-type and myostatin knock-out mice 4 and 7 days after CLP. This was associated with a modified expression of genes involved in ion homeostasis and excitation-contraction coupling, suggesting that a long-term functional recovery following experimental sepsis may be impaired by a dysregulated expression of molecular determinants of ion homeostasis and excitation-contraction coupling. In conclusion, myostatin gene invalidation does not provide any benefit in preventing skeletal muscle mass loss and strength in response to experimental sepsis. KEY POINTS: Survival rates are similar in wild-type and myostatin knock-out mice seven days after the induction of sepsis. Loss in muscle mass and muscle strength are similar in wild-type and myostatin knock-out mice 4 and 7 days after the induction of an experimental sepsis. Despite evidence of a transcriptional regulation, the protein level of markers of the anabolic insulin/IGF1-Akt-mTOR pathway remained unchanged. RT-qPCR analysis of autophagy-lysosome pathway markers indicates that activity of the pathway may be altered by experimental sepsis in wild-type and myostatin knock-out mice. Experimental sepsis induces greater variations in the mRNA levels of wild-type mice than those of myostatin knock-out mice, without providing any significant catabolic resistance or functional benefits.

BMAL1 and CLOCK proteins exhibit differential association with mitochondrial dynamics, protein synthesis pathways and muscle strength in human muscle.

Murine models lacking CLOCK/BMAL1 proteins in skeletal muscle (SkM) present muscle deterioration and mitochondria abnormalities. It is unclear whether humans with lower levels of these proteins in the SkM have similar alterations. Here we evaluated the association between BMAL1 and CLOCK protein mass with mitochondrial dynamics parameters and molecular and functional SkM quality markers in males. SkM biopsies were taken from the vastus lateralis of 16 male (non-athletes, non-obese and non-diabetic) subjects (8-9 a.m.). The morphology of mitochondria and their interaction with the sarcoplasmic reticulum (mitochondria-SR) were determined using transmission electron microscopy images. Additionally, protein abundance of the OXPHOS complex, mitochondria fusion/fission regulators, mitophagy and signalling proteins related to muscle protein synthesis were measured. To evaluate the quality of SkM, the cross-sectional area and maximal SkM strength were also measured. The results showed that BMAL1 protein mass was positively associated with mitochondria-SR distance, mitochondria size, mitochondria cristae density and mTOR protein mass. On the other hand, CLOCK protein mass was negatively associated with mitochondria-SR interaction, but positively associated with mitochondria complex III, OPA1 and DRP1 protein mass. Furthermore, CLOCK protein mass was positively associated with the protein synthesis signalling pathway (total mTOR, AKT and P70S6K protein mass) and SkM strength. These findings suggest that the BMAL1 and CLOCK proteins play different roles in regulating mitochondrial dynamics and SkM function in males, and that modulation of these proteins could be a potential therapeutic target for treating muscle diseases. KEY POINTS: In murine models, reductions in BMAL1 and CLOCK proteins lead to changes in mitochondria biology and a decline in muscle function. However, this association has not been explored in humans. We found that in human skeletal muscle, a decrease in BMAL1 protein mass is linked to smaller intermyofibrillar mitochondria, lower mitochondria cristae density, higher interaction between mitochondria and sarcoplasmic reticulum, and reduced mTOR protein mass. Additionally, we found that a decrease in CLOCK protein mass is associated with a higher interaction between mitochondria and sarcoplasmic reticulum, lower protein mass of OPA1 and DRP1, which regulates mitochondria fusion and fission, lower protein synthesis signalling pathway (mTOR, AKT and P70S6K protein mass), and decreased skeletal muscle strength. According to our findings in humans, which are supported by previous studies in animals, the mitochondrial dynamics and skeletal muscle function could be regulated differently by BMAL1 and CLOCK proteins. As a result, targeting the modulation of these proteins could be a potential therapeutic approach for treating muscle diseases and metabolic disorders related to muscle.

Prefrontal cortex hemodynamic activity during a test of lower extremity functional muscle strength in children with cerebral palsy: A functional near-infrared spectroscopy study.

Children with cerebral palsy (CP) exhibit impaired motor control and significant muscle weakness due to a brain lesion. However, studies that assess the relationship between brain activity and performance on dynamic functional muscle strength assessments in CP are needed. The aim of this study was to determine the effect of a progressive lateral step-up test on prefrontal cortex (PFC) hemodynamic activity in children with CP. Fourteen ambulatory children with spastic CP (Gross Motor Function Classification System level I; 5-11 y) and 14 age- and sex-matched typically developing control children completed a progressive lateral step-up test at incremental step heights (0, 10, 15 and 20 cm) using their non-dominant lower limb. Hemodynamic activity in the PFC was assessed using non-invasive, portable functional neuroimaging (functional near-infrared spectroscopy). Children with CP completed fewer repetitions at each step height and exhibited lower PFC hemodynamic activity across step heights compared to controls. Lower PFC activation in CP was maintained after statistically controlling for the number of repetitions completed at each step height. PFC hemodynamic activity was not associated with LSUT task performance in children with CP, but a positive relationship was observed in controls at the most challenging 20 cm step height. The results suggest there is an altered PFC recruitment pattern in children with CP during a highly dynamic test of functional strength. Further studies are needed to explore the mechanisms underlying the suppressed PFC activation observed in children with CP compared to typically developing children.

Postnatal Pdzrn3 deficiency causes acute muscle atrophy without alterations in endplate morphology.

PDZ domain-containing RING finger family protein 3 (PDZRN3) is expressed in various tissues, including the skeletal muscle. Although PDZRN3 plays a crucial role in the terminal differentiation of myoblasts and synaptic growth/maturation in myogenesis, the role of this molecule in postnatal muscles is completely unknown despite its lifelong expression in myofibers. In this study, we aimed to elucidate the function of PDZRN3 in mature myofibers using myofiber-specific conditional knockout mice. After tamoxifen injection, PDZRN3 deficiency was confirmed in both fast and slow myofibers of Myf6-CreERT2; Pdzrn3flox/flox (Pdzrn3mcKO) mice. Transcriptome analysis of the skeletal muscles of Pdzrn3mcKO mice identified differentially expressed genes, including muscle atrophy-related genes such as Smox, Amd1/2, and Mt1/2, suggesting that PDZRN3 is involved in the homeostatic maintenance of postnatal muscles. PDZRN3 deficiency caused muscle atrophy, predominantly in fast-twitch (type II) myofibers, and reduced muscle strength. While myofiber-specific PDZRN3 deficiency did not influence endplate morphology or expression of neuromuscular synaptic formation-related genes in postnatal muscles, indicating that the relationship between PDZRN3 and neuromuscular junctions might be limited during muscle development. Considering that the expression of Pdzrn3 in skeletal muscles was significantly lower in aged mice than in mature adult mice, we speculated that the PDZRN3-mediated muscle maintenance system might be associated with the pathophysiology of age-related muscle decline, such as sarcopenia.

Association between hip muscle strength/function and hip cartilage defects in sub-elite football players with hip/groin pain.

OBJECTIVE: To explore associations between hip muscle strength and cartilage defects (presence and severity) on magnetic resonance imaging (MRI) in young adults with hip/groin pain participating in sub-elite football. DESIGN: Sub-elite football players with hip/groin pain (>6 months) completed assessments of isometric hip strength and functional task performance. Hip cartilage defects were assessed using the Scoring Hip Osteoarthritis with MRI tool. This exploratory, cross-sectional study used logistic and negative binomial models to assess the relationships between hip muscle strength or functional task performance and hip cartilage defects, controlling for body mass index, age, testing site and cam morphology, incorporating sex-specific interaction terms. RESULTS: One hundred and eighty-two (37 women) sub-elite (soccer or Australian football) players with hip/groin pain (age 26 ± 7 years) were included. Greater hip extension strength was associated with higher cartilage total score (adjusted incidence rate ratio [aIRR] 1.01, 95%CI: 1.0 to 1.02, p = 0.013) and superolateral cartilage score (adjusted odds ratio (aOR) 1.03, 95% confidence interval (CI): 1.01 to 1.06, p < 0.01). In female sub-elite football players, greater hip external rotation strength was associated with lateral cartilage defects (aOR 1.61, 95%CI: 1.05 to 2.48, p = 0.03) and higher cartilage total score (aIRR 1.25, 95%CI: 1.01 to 1.66, p = 0.042). A one-repetition increase in one-leg rise performance was related to lower odds of superomedial cartilage defects (aOR 0.96, 95%CI: 0.94 to 0.99, p < 0.01). CONCLUSIONS: Overall, there were few associations between peak isometric hip muscle strength and overall hip cartilage defects. It is possible that other factors may have relevance in sub-elite football players. Additional studies are needed to support or refute our findings that higher one leg rise performance was associated with reduced superomedial cartilage defect severity and greater hip extension strength was related to higher cartilage defect severity scores.

Physical performance and sarcopenia assessment in patients with a recent fracture visiting the Fracture Liaison Service.

Impaired physical performance is associated with increased fracture risk. Performance on four physical functioning tests and prevalence of sarcopenia were assessed for 1789 fracture patients and compared to reference data. Performance was low on all tests, especially for patients with a hip, major or ≥ 1 prevalent vertebral fracture. PURPOSE INTRODUCTION: Impaired physical performance and sarcopenia are associated with increased fracture risk. This study aims to assess physical performance and the prevalence of sarcopenia in patients with a recent clinical fracture attending the Fracture Liaison Service (FLS) compared to population means. METHODS: In this cross-sectional study, chair stand test (CST), handgrip strength (HGS), timed-up-and-go (TUG), 6-min walking-test (6MWT), and sarcopenia (following EWGSOP2) were assessed. The proportion of patients with impaired/poor performance compared to reference data was calculated (Z-score: ≥ - 2SD to < - 1 (impaired) and < - 2 SD (poor)). Associations of fracture type, sex, age, and time since fracture with Z-scores were assessed using linear regression analyses. RESULTS: A total of 1789 consecutive FLS patients were included (median age (IQR): 66 (59-74), 70.7% females, 3.9 (± 1.6) months after fracture). The prevalence of impaired/poor performance for CST, HGS, TUG, and 6MWT was 39.2%, 30.4%, 21.9%, and 71.5%, respectively (expected proportion of 16%) and 2.8% had sarcopenia. Lower Z-scores (P < 0.001) were found for hip, major, and ≥ 1 prevalent vertebral fracture (VF) in CST (major: regression coefficient (B) (95%CI) = - 0.25 [- 0.34, - 0.16]; hip: B = - 0.32 [- 0.47, - 0.17], VF: B = - 0.22 [- 0.34, - 0.11]), TUG; (major: B = - 0.54 [- 0.75, - 0.33]; hip: B = - 1.72 [- 2.08, -1.35], VF: B = - 0.61 [- 0.88, - 0.57]), 6MWT (major: B = - 0.34 [- 0.47, - 0.21]; hip: B = - 0.99 [- 1,22, - 0.77], VF: B = - 0.36 [- 0.53, - 0.19]). CONCLUSIONS: Physical performance is significantly lower in FLS patients compared to healthy peers, especially in patients with hip, major or prevalent VF. These findings underline the need to assess and improve the physical performance of FLS patients, despite a low prevalence of sarcopenia.

Reductions in Motor Unit Firing are Associated with Clinically Meaningful Leg Extensor Weakness in Older Adults.

Weakness, one of the key characteristics of sarcopenia, is a significant risk factor for functional limitations and disability in older adults. It has long been suspected that reductions in motor unit firing rates (MUFRs) are one of the mechanistic causes of age-related weakness. However, prior work has not investigated the extent to which MUFR is associated with clinically meaningful weakness in older adults. Forty-three community-dwelling older adults (mean: 75.4 ± 7.4 years; 46.5% female) and 24 young adults (mean: 22.0 ± 1.8 years; 58.3% female) performed torque matching tasks at varying submaximal intensities with their non-dominant leg extensors. Decomposed surface electromyographic recordings were used to quantify MUFRs from the vastus lateralis muscle. Computational modeling was subsequently used to independently predict how slowed MUFRs would negatively impact strength in older adults. Bivariate correlations between MUFRs and indices of lean mass, voluntary activation, and physical function/mobility were also assessed in older adults. Weak older adults (n = 14) exhibited an approximate 1.5 and 3 Hz reduction in MUFR relative to non-weak older adults (n = 29) at 50% and 80% MVC, respectively. Older adults also exhibited an approximate 3 Hz reduction in MUFR relative to young adults at 80% MVC only. Our model predicted that a 3 Hz reduction in MUFR results in a strength decrement of 11-26%. Additionally, significant correlations were found between slower MUFRs and poorer neuromuscular quality, voluntary activation, chair rise time performance, and stair climb power (r's = 0.31 to 0.43). These findings provide evidence that slowed MUFRs are mechanistically linked with clinically meaningful leg extensor weakness in older adults.

Prevalence of Sarcopenia and Its Defining Components in Non-alcoholic Fatty Liver Disease Varies According to the Method of Assessment and Adjustment: Findings from the UK Biobank.

Sarcopenia may increase non-alcoholic fatty liver disease (NAFLD) risk, but prevalence likely varies with different diagnostic criteria. This study examined the prevalence of sarcopenia and its defining components in adults with and without NAFLD and whether it varied by the method of muscle mass assessment [bioelectrical impedance (BIA) versus dual-energy X-ray absorptiometry (DXA)] and adjustment (height2 versus BMI). Adults (n = 7266) in the UK Biobank study (45-79 years) with and without NAFLD diagnosed by MRI, were included. Sarcopenia was defined by the 2018 European Working Group on Sarcopenia in Older People definition, with low appendicular skeletal muscle mass (ASM) assessed by BIA and DXA and adjusted for height2 or BMI. Overall, 21% of participants had NAFLD and the sex-specific prevalence of low muscle strength (3.6-7.2%) and sarcopenia (0.1-1.4%) did not differ by NAFLD status. However, NAFLD was associated with 74% (males) and 370% (females) higher prevalence of low ASM when adjusted for BMI but an 82% (males) to 89% (females) lower prevalence when adjusted for height2 (all P < 0.05). The prevalence of impaired physical function was 40% (males, P = 0.08) to 123% (females, P < 0.001) higher in NAFLD. In middle-aged and older adults, NAFLD was not associated with a higher prevalence of low muscle strength or sarcopenia but was associated with an increased risk of impaired physical function and low muscle mass when adjusted for BMI. These findings support the use of adiposity-based adjustments when assessing low muscle mass and the assessment of physical function in NAFLD.

Post-activation potentiation after isometric contractions is strongly related to contraction intensity despite the similar torque-time integral.

Post-activation potentiation (PAP) is defined as an enhanced contractile response of a muscle following its own contractile activity and is influenced by the intensity and duration of the conditioning contraction. The aim of this study was to determine if the combination of intensity and duration, that is, torque-time integral (TTI) is a determinant of PAP amplitude. We compared PAP amplitude following low-to-maximal voluntary conditioning contraction intensities with and without similar TTI in the knee extensors. Twelve healthy males completed two experimental sessions. Femoral nerve stimulation was applied to evoke single twitches on the relaxed quadriceps before and after isometric conditioning contractions of knee extensors. In one session, participants performed conditioning contractions without similar TTI (6 s at 100, 80, 60, 40 and 20% maximal voluntary contraction (MVC)), while they performed conditioning contractions with similar TTI in the other session (6 s at 100%, 7.5 s at 80%, 10 s at 60%, 15 s at 40%, and 30 s at 20% MVC). In both sessions, PAP amplitude was related to conditioning contraction intensity. The higher the conditioning contraction intensity with or without similar TTI, the higher PAP. Significant correlations were found (i) between PAP and conditioning contraction intensity with (r2 = 0.70; P < 0.001) or without similar TTI (r2 = 0.64; P < 0.001), and (ii) between PAP with and without similar TTI (r2 = 0.82; P < 0.001). The results provide evidence that TTI has a minor influence on PAP in the knee extensors. This suggests that to optimize the effect of PAP, it is more relevant to control the intensity of the contraction rather than the TTI.

Inspiratory muscle endurance is similarly reduced in the early and late stages of chronic Chagas heart disease.

OBJECTIVE: Inspiratory muscle strength (IMS) appears to be reduced in subjects with chronic Chagas heart disease (CHD), especially in the presence of heart failure (HF). However, only one study about IMS and inspiratory muscle endurance (IME) in those with CHD without heart failure is available. This study aimed to compare IMS and IME in subjects with CHD in the presence and absence of HF. METHODS: This is a cross-sectional study in which 30 CHD adult patients were divided into CHD-CC group (initial phase of CHD, without HF; n = 15) and CHD-HF group (advanced phase of CHD, with HF; n = 15). We assessed IMS by maximum inspiratory pressure (MIP) and IME by incremental (Pthmax) and constant load (TLim) tests. Reduced IMS and IME were considered by predicted MIP values <70% and Pthmax/MIP <75%, respectively. RESULTS: Inspiratory muscle weakness (IMW) was more frequent in CHD-HF than in CHD-CC (46.7% vs. 13.3%; p = 0.05), and both groups had high frequencies of reduced IME (93.3% CHD-CC vs. 100.0% CHD-HF; p = 0.95). Age-adjusted logistic regression analysis using HF as a dependent variable showed that HF was associated with an increased chance of IMW compared with the CHD-CC group (OR = 7.47; p = 0.03; 95% CI 1.20-46.19). CONCLUSION: This study suggests that, in patients with CHD, HF is associated with IMW, and that reduction of IME is already present in the initial phase, similar to the advanced phase with HF.

Feasibility of virtual reality and comparison of its effectiveness to biofeedback in children with Duchenne and Becker muscular dystrophies.

INTRODUCTION/AIMS: The utilization of virtual reality (VR) and biofeedback training, while effective in diverse populations, remains limited in the treatment of Duchenne and Becker muscular dystrophies (D/BMD). This study aimed to determine the feasibility of VR in children with D/BMD and compare the effectiveness of VR and biofeedback in children with D/BMD. METHODS: The study included 25 children with D/BMD. Eight children in the control group participated in a routine follow-up rehabilitation program, while the remaining children were randomly assigned to the VR (n = 9) and biofeedback (n = 8) groups for a 12-week intervention. The following evaluations were performed before, during (week 6), and after treatment: Muscle pain and cramps, laboratory studies, muscle strength, timed performance, function (Motor Function Measurement Scale-32, Vignos, and Brooke Scales), and balance (Pediatric Functional Reach Test and Balance Master System). Motivation for rehabilitation was determined. RESULTS: The median ages were 9.00 (VR), 8.75 (biofeedback), and 7.00 (control) years. The study found no significant differences between groups in pretreatment assessments for most measures, except for tandem step width (p < .05). VR and biofeedback interventions significantly improved various aspects (pain intensity, cramp frequency, cramp severity, muscle strength, timed performance, functional level, and balance) in children with D/BMD (p < .05), while the conventional rehabilitation program maintained patients' current status without any changes. The study found VR and biofeedback equally effective, with VR maintaining children's motivation for rehabilitation longer (p < .05). DISCUSSION: The study showed that both VR and biofeedback appear to be effective for rehabilitation this population, but additional, larger studies are needed.

Quantitative multi-parameter assessment of age- and gender-related variation of back extensor muscles in healthy adults using Dixon MR imaging.

OBJECTIVES: Investigate sex differences in age-related back extensor muscle degeneration using Dixon MRI and analyze the relationship between quantitative muscle parameters and back muscle strength in healthy adults. METHODS: 105 healthy subjects underwent lumbar Dixon MRI. Fat fraction (FF), cross-sectional area (CSA), functional CSA (FCSA), and relative FCSA (RFCSA) of multifidus muscle (MF) and erector spinae (ES) were quantified. Back extension muscle strength was measured using an external fixation dynamometer. ANOVA with post hoc Tukey correction was used for age group comparisons. Partial and Spearman's correlation analyzed relationships between age, muscle parameters, and muscle strength. RESULTS: MF and ES FF significantly increased with age in both genders (r = 0.55-0.85; p < 0.001). Muscle FF increased prominently for females (40-49 years, MF and 50-59 years, ES) and males (60-73 years, MF and ES). In females, total ES FCSA and RFCSA (r = - 0.42, - 0.37; p < 0.01) correlated with age. While in males, all MF and ES muscle size parameters, except total MF CSA, correlated with age (r = - 0.30 to - 0.58; p < 0.05). Back extension muscle strength correlated with mean FF, total CSA, and total FCAS for MF and ES individually (p < 0.001). The combined MF + ES FCSA correlation coefficient (r = 0.63) was higher than FF (r = - 0.51) and CSA (r = 0.59) (p < 0.001). CONCLUSIONS: Age-related back extensor muscle degeneration varies by muscle type and sex. FCSA has the highest association with back muscle strength compared to FF and CSA. CLINICAL RELEVANCE STATEMENT: The investigation of sex differences in age-related back extensor muscle degeneration utilizing Dixon imaging may hold significant implications for evaluating spine health and enabling earlier intervention. Muscles' FCSA could contribute to acquiring additional evidence for reflecting muscle function change. KEY POINTS: • The multifidus muscle (MF) and erector spinae (ES) fat fraction (FF) increased with age at all lumbar disc levels in females and males. • Age-related changes in muscle morphological quantitative parameters of healthy adults were specific by muscle type and gender. • The muscle functional cross-sectional area (FCSA) measured by Dixon imaging may better monitor back extensor muscle strength changes than muscle FF and cross-sectional area (CSA).

Higher dietary methyl donor micronutrient consumption is associated with higher muscle strength in adults: a cross-sectional study.

Methyl donor micronutrients might affect muscle strength via DNA methylation. We aimed to evaluate the combined relationship of dietary methyl donor micronutrients containing betaine, choline, methionine, vitamin B12, vitamin B6 and folate on muscle strength. This cross-sectional study was conducted on 267 subjects including 113 men and 154 women. Dietary intake of micronutrients was assessed utilising a validated 168-item semi-quantitative FFQ, and methyl donor micronutrient score (MDMS) was calculated. The muscle strength of the participants was measured using a digital handgrip dynamometer. The association was determined using linear regression analysis. The mean age of participants was 36·8 ± 13·2 years. After taking into account potential confounding variables, there was no significant association between dietary methyl donor micronutrient score (MDMS) and the mean left-hand muscle strength (ß: 0·07, se: 0·05, P = 0·07); however, the changes were significant in the mean right-hand muscle strength (ß: 0·09, se: 0·04, P = 0·03). There was also a significant positive relationship between mean muscle strength and methyl donors' intake after fully adjusting for potential confounders (ß: 0·08, se: 0·04, P = 0·04). In conclusion, our findings revealed that higher dietary methyl donor micronutrient consumption is associated with enhanced muscle strength. As a result, advice on a higher intake of methyl donor-rich foods including grains, nuts, dairy products and seafood might be recommended by dietitians as a general guideline to adhere to. Additional prospective studies are needed to confirm the findings.

H2OAthletes study protocol: effects of hydration changes on neuromuscular function in athletes.

We aim to understand the effects of hydration changes on athletes' neuromuscular performance, on body water compartments, fat-free mass hydration and hydration biomarkers and to test the effects of the intervention on the response of acute dehydration in the hydration indexes. The H2OAthletes study (clinicaltrials.gov ID: NCT05380089) is a randomised controlled trial in thirty-eight national/international athletes of both sexes with low total water intake (WI) (i.e. < 35·0 ml/kg/d). In the intervention, participants will be randomly assigned to the control (CG, n 19) or experimental group (EG, n 19). During the 4-day intervention, WI will be maintained in the CG and increased in the EG (i.e. > 45·0 ml/kg/d). Exercise-induced dehydration protocols with thermal stress will be performed before and after the intervention. Neuromuscular performance (knee extension/flexion with electromyography and handgrip), hydration indexes (serum, urine and saliva osmolality), body water compartments and water flux (dilution techniques, body composition (four-compartment model) and biochemical parameters (vasopressin and Na) will be evaluated. This trial will provide novel evidence about the effects of hydration changes on neuromuscular function and hydration status in athletes with low WI, providing useful information for athletes and sports-related professionals aiming to improve athletic performance.

Association between nut consumption and low muscle strength among Korean adults.

Nuts are an important component of a healthy diet, but little has been known about their effects on muscle health. Therefore, this study examined the association between nut consumption and low muscle strength among Korean adults. This cross-sectional analysis was conducted using single 24-h recall and handgrip strength data from 3962 younger adults 19-39 years, 6921 middle-aged adults 40-64 years and 3961 older adults ≥65 years participated in the seventh cycle (2016-2018) of the Korea National Health and Nutrition Examination Survey. Low muscle strength was defined as handgrip strength <28 kg for men and <18 kg for women. Sex-specific OR were obtained for younger, middle-aged and older adults using multivariable logistic regression analyses. About one in four Korean adults were consuming nuts (using a culinary definition) with peanut being the most frequently consumed type. After adjustment for age, BMI, total energy intake, household income, alcohol consumption, smoking, resistance exercise, medical history and dietary protein intake, nut consumption was associated with the lower risk of low muscle strength among older adults ≥65 years (men: OR 0·55, 95 % CI (0·38, 0·79); women: OR 0·69, 95 % CI (0·51, 0·93)); however, this association was not observed among younger adults 19-39 years or middle-aged adults 40-64 years. Our results suggest that consuming nuts might be beneficial in lowering the risk of low muscle strength among Korean older adults.

Physical capacity in children and adolescents with newly diagnosed cancer: A systematic review and meta-analysis.

OBJECTIVE: To review the body of evidence on cardiorespiratory fitness, muscle strength, and physical performance in children with newly diagnosed cancer, five databases (MEDLINE, Embase, CINAHL, CENTRAL, and Web of Science) were searched on December 19, 2022. METHODS: Thirteen studies, embodying 594 participants within 1 month of cancer diagnosis and 3674 healthy controls were included. Eighteen different outcomes on cardiorespiratory fitness (n = 2), muscle strength (n = 5), physical performance (n = 10), and adverse events (n = 1) were analyzed. RESULTS: Fifteen out of 17 outcomes on physical capacity showed severe impairments compared with healthy controls. Where possible, random-effects meta-analysis was conducted to synthesize the results. No adverse events were reported related to testing. CONCLUSION: Children with cancer have impaired cardiorespiratory fitness, muscle strength, and physical performance within the first month after diagnosis. However, the evidence is based on a small number of studies with large clinical heterogeneity, limiting the certainty of evidence.

Physical functioning in adolescents with perinatal HIV.

Perinatal HIV impacts on growth and development in childhood, with physical impairments such as growth limitations, decreased physical activity, reduced exercise tolerance and cardiopulmonary dysfunction continuing into adolescence. There is limited data on other physical functioning domains in perinatally HIV-infected adolescents (PHIVA) thus the aim of this study was to establish the physical sequelae of perinatal HIV in adolescents. This South African cross-sectional study compared PHIVA with HIV-negative adolescents, assessing anthropometry, muscle strength, endurance and motor performance. All ethical considerations were adhered to. The study included 147 PHIVA and 102 HIV-negative adolescents, aged 10-16 years. The majority (87.1%) of PHIVA were virally suppressed however, they still showed significant deficits in height (p < 0.001), weight (p < 0.001) and BMI (p = 0.004). Both groups performed poorly in muscle strength and endurance but did not differ significantly. In motor performance, the PHIVA scored significantly lower for manual dexterity and balance, with significantly more PHIVA with motor difficulty. A regression analysis showed that viral suppression predicted muscle strength (p = 0.032) and age positively predicted endurance (p = 0.044) and negatively predicated aiming and catching (p = 0.009). In conclusion, PHIVA face growth deficits and challenges with motor performance, especially with manual dexterity and balance.