Muscles

The present study is the first research that analyzes the quality of life (QoL) of people affected by a dominant form of limb–girdle muscular dystrophy, specifically limb–girdle muscular dystrophy D2 (LGMD-D2). Additionally, clinical forms of the individual cases of the six affected patients are presented. This study also aims to explore the differences between patients’ reports and caregivers’ reports, and between LGMD-D2 and recessive forms of LGMD. The instruments used were as follows: sociodemographic data, GSGC, and INQoL instrument. The sample consisted of six people affected by LGMD-D2: three caregivers of three affected people, and three patients with recessive LGMD. They came from associations of affected people and a hospital in Padua. Those affected have multiple symptoms that lead to disability, which ultimately leads to dependence on the assistance. The present study shows that LGMD-D2 has a greater impact on activities of daily living, fatigue, muscle pain, and independence than other LGMD pathologies or other neuromuscular diseases. It also appears that age could influence QoL, and that muscle weakness is a very disabling symptom in this variant. In the current context of constantly developing research for new treatments, it is essential to analyze which aspects are most affected. Finally, caregivers can play an essential role in symptom reporting, as certain psychological adjustment mechanisms in the patient may be interfering with the objectivity of the report. Full article

Background: Falls risk assessment tools are used in hospital inpatient settings to identify patients at increased risk of falls to guide and target interventions for fall prevention. In 2022, Western Health, Melbourne, Australia, introduced a new falls risk assessment tool, the Western Health St. Thomas’ Risk Assessment Tool (WH-STRATIFY), which adapted The Northern Hospital’s risk tool (TNH-STRATIFY) by adding non-English speaking background and falls-risk medication domains to reflect patient demographics. WH-STRATIFY replaced Peninsula Health Risk Screening Tool (PH-FRAT) previously in use at Western Health. This study compared the predictive accuracy of the three falls risk assessment tools in an older inpatient high-risk population. Aims: To determine the predictive accuracy of three falls risk assessment tools (PH-FRAT, TNH-STRATIFY, and WH-STRATIFY) on admission to Geriatric Evaluation Management (GEM) units (subacute inpatient wards where the most frail and older patients rehabilitate under a multi-disciplinary team). Method: A retrospective observational study was conducted on four GEM units. Data was collected on 54 consecutive patients who fell during admission and 62 randomly sampled patients who did not fall between December 2020 and June 2021. Participants were scored against three falls risk assessment tools. The event rate Youden (Youden Index^ER) indices were calculated and compared using default and optimal cut points to determine which tool was most accurate for predicting falls. Results: Overall, all tools had low predictive accuracy for falls. Using default cut points to compare falls assessment tools, TNH-STRATIFY had the highest predictive accuracy (Youden Index^ER = 0.20, 95% confidence interval CI = 0.07, 0.34). The PH-FRAT (Youden Index^ER = 0.01 and 95% CI = −0.04, 0.05) and WH-STRATIFY (Youden Index^ER = 0.00 and 95% CI = −0.04, 0.03) were statistically equivalent and not predictive of falls compared to TNH-STRATIFY. When calculated optimal cut points were applied, predictive accuracy improved for PH-FRAT (Cut point 17, Youden Index^ER = 0.14 and 95% CI = 0.01, 0.29) and WH-STRATIFY (Cut point 7, Youden Index^ER = 0.18 and 95% CI = 0.00, 0.35). Conclusions: TNH-STRATIFY had the highest predictive accuracy for falls. The predictive accuracy of WH-STRATIFY improved and was significant when the calculated optimal cut point was applied. The optimal cut points of falls risk assessment tools should be determined and validated in different clinical settings to optimise local predictive accuracy, enabling targeted fall risk mitigation strategies and resource allocation. Full article

This study aimed to examine the chronic effect of a stair climbing–descending exercise (ST-EX) program on glycemic control in individuals with type 2 diabetes (T2D). Sixteen T2D participants were randomly divided into two groups and followed up over 12 weeks: they either performed regular ST-EX after meals at home (n = 8) or maintained their daily routine (CON; no training) (n = 8). The participants in the ST-EX group were instructed to perform a minimum of 12 sessions/week of ST-EX for more than three days/week. One session of ST-EX consisted of two repetitions of 3 min bouts of climbing to the second floor, followed by walking down to the first floor. Fourteen participants completed the study (seven for each group). The decrease in glycoalbumin levels was significantly greater in the ST-EX group (mean value: −1.0%) than in the CON group (+0.4%). Moreover, the knee extension force increased greatly in the ST-EX group (+0.2 Nm/kg) compared with that in the CON group (−0.1 Nm/kg), with no significant change in the skeletal muscle mass. Performing regular ST-EX after meals may be an effective strategy to improve glycemic control and lower-extremity muscle strength in individuals with T2D. Full article

Strenuous exercise involving eccentric muscle actions induces skeletal muscle damage resulting in delayed onset muscle soreness (DOMS). Antioxidant supplementation, such as astaxanthin (AX), may alleviate muscle injury following intense exercise. The purpose of this study was to investigate the effect of a four-week course of AX supplementation at 12 mg/day⁻¹ on subjective markers of DOMS, recovery, and performance after a bout of muscle damaging eccentric exercise. Nineteen resistance-trained men (mean ± SD: age, 22.6 ± 2.2 y) completed a between-group design with a four-week supplementation period of 12 mg/day⁻¹ of either AX or a placebo. Subjects completed four trials, with trials One and Three designed to induce muscle damage, consisting of a one repetition maximum test (1RM) for leg-press, followed by five sets of ten repetitions at 65% of 1RM. Trials Two and Four were performance trials, conducted 48 h later and consisting of repetitions to failure at 65%, 70%, and 75% of 1RM. Subjective markers of DOMS and recovery were collected at multiple timepoints post-trial for trials One and Three. Although performance was not affected (p > 0.05), AX supplementation significantly decreased subjective markers of DOMS (p = 0.01) compared to the placebo. The results demonstrated that AX may enhance recovery by reducing DOMS without detriment to performance in resistance-trained men. Full article

The aim of the study was to analyze muscle activation in the three positions of the deadlift (DL). Twenty male participants (33.4 ± 3.9 years; 42.2 ± 9.1 months of experience with DL; 91.0 ± 14.8 kg; and 1.78 ± 0.06 m) pulled a bar through isometric actions in three DL positions: lift-off, mid-pull, and lockout. Isometric strength, knee angle, and activation of the rectus femoris (RF), biceps femoris (BF), lateral gastrocnemius (GAL), and erector spinae (ERE) muscles were collected. The analysis of variance showed that the maximum isometric force presented differences between the positions (p = 0.001; η² = 0.973) considered large with higher values at the mid-pull position. Interactions were found between muscles and position (p = 0.001; η² = 0.527) considered large. The RF and ERE showed greater activation in the lift-off position, while in the mid-pull position, there was greater activation of the BF and GAL muscles. The DL positions produce different activations in the bi-articular and uni-articular muscles. The lift-off requires more activation from the RF and ERE positions. The mid-pull position, despite generating greater force, presented greater activations in the BF and GAL. The ERE showed higher activations as the external torque was greater. Full article

Exercise-induced muscle injury and the subsequent release of Damage-Associated Molecular Patterns (DAMP) result in soreness and inflammation. Dietary supplements may accelerate the rate of recovery by supporting resolution of inflammation. The purpose of this study was to determine if methylsulfonylmethane (MSM) supplementation (30 d prior to exercise and during recovery) altered mRNA expression in LPS-exposed blood leukocytes after a bout of downhill running. Exercise consisted of 60 min of downhill running (−15% grade). Blood (baseline, pre-exercise, 4, 24, 48, and 72 h post-exercise) was diluted (1:10) and combined with LPS (20 µg/mL) for 24 h. Total RNA was isolated from leukocytes and analyzed for 574 immune-associated mRNA (Nanostring nCounter; ROSALIND.BIO). Data were expressed as log2 fold change from baseline for each condition (MSM and placebo). Compared to placebo, MSM supplementation was associated with an improved inflammation response (15 mRNA) and viral immune response (2 mRNA). The largest number of changes were found at 4 and 24 h post-exercise. The key finding in the present study is that MSM supplementation can improve inflammation management and the innate immune response after exercise. Full article

The skeletal muscle is a highly plastic tissue that shows a remarkable adaptive capacity in response to acute and resistance exercise, and modifies its composition to adapt to use and disuse, a process referred to as muscle plasticity. Heat shock proteins (HSPs), a class of evolutionarily conserved molecular chaperones, have been implicated in the regulation of skeletal muscle plasticity. Here, we summarize key findings supporting the notion that HSPs are important components required to maintain skeletal muscle integrity and functionality. HSPs participate in the transcriptional program required for myogenesis and are activated following muscle exercise and injury. Their dysfunction, either as a consequence of improper expression or genetic mutations, contributes to muscle atrophy and leads to the development of myopathies and peripheral motor neuropathies. Denervation/reinnervation and repeated rounds of nerve degeneration/regeneration have been observed in motor neuropathies, suggesting that an imbalance in HSP expression and function may impair the repair of the neuromuscular junctions. Boosting HSP activity may help preventing muscle atrophy by promoting muscle differentiation and helping the repair of NMJs. Boosting HSP function may also help to combat the development of rhabdomyosarcoma (RMS), a highly aggressive type of pediatric soft tissue sarcoma whose cells have skeletal muscle features but are unable to fully differentiate into skeletal muscle cells. Full article

We describe two cases of myofibrillar myopathies, due to different gene mutations. The first was a girl with cardiomyopathy and sensory axonal neuropathy that underwent cardiac transplantation at 15 years and suffers from rotatory scoliosis due to BAG3 mutation. The second is a male patient, with evident limb-girdle weakness since age 3. Two muscle biopsies were performed at ages 3 and 15, with muscle MRI, and LDB3 gene sequence analysis also carried out. Muscle biopsies revealed the presence of dystrophic changes in the first biopsy and myopathic abnormalities in the second, and the MRI images of the lower limbs showed an asymmetrical involvement in the thigh of quadriceps muscles and in the calf of gastrocnemius muscles. The patient was responsive to treatment with an intermittent steroid regimen and muscle-strengthening exercises. Considerations on both muscle–bone interaction and psychological and socioeconomic conditions are carried out for both cases. Full article

Limb-girdle muscular dystrophies (LGMDs) represent a group of muscle diseases due to monogenic mutations encoding muscle proteins that are defective for heterozygous and homozygous mutations prevalent in certain regions. Advances in knowledge of their pathophysiology have shed light on these rare diseases, which were, until recently, difficult to diagnose. This paper has described the process of diagnosis in autosomal recessive limb-girdle dystrophy that in Tunisia are due to the c.521del mutation in gamma-sarcoglycanopathy and to ethnically specific mutations in other countries such as Italy. The epidemiology, pathophysiology clinical features, and the main socioeconomic needs as well as research progress are discussed. We discuss an Italian case for its psychosocial impact and socioeconomic consideration and compare this case with Tunisian patients. Full article

Musculoskeletal health is directly linked to independence and longevity, but disease and aging impairs muscle mass and health. Complete repair after a pathological or physiological muscle injury is critical for maintaining muscle function, yet muscle repair is compromised after disuse, or in conditions such as metabolic diseases, cancer, and aging. Regeneration of damaged tissue is critically dependent upon achieving the optimal function of satellite cells (muscle stem cells, MSCs). MSC remodeling in muscle repair is highly dependent upon its microenvironment, and metabolic health of MSCs, which is dependent on the functional capacity of their mitochondria. Muscle repair is energy demanding and mitochondria provide the primary source for energy production during regeneration. However, disease and aging induce mitochondrial dysfunction, which limits energy production during muscle regeneration. Nevertheless, the role of mitochondria in muscle repair likely extends beyond the production of ATP and mitochondria could provide potentially important regulatory signaling to MSCs during repair from injury. The scope of current research in muscle regeneration extends from molecules to exosomes, largely with the goal of understanding ways to improve MSC function. This review focuses on the role of mitochondria in skeletal muscle myogenesis/regeneration and repair. A therapeutic strategy for improving muscle mitochondrial number and health will be discussed as a means for enhancing muscle regeneration. Highlights: (a). Mitochondrial dysfunction limits muscle regeneration; (b). Muscle stem cell (MSC) function can be modulated by mitochondria; (c). Enhancing mitochondria in MSCs may provide a strategy for improving muscle regeneration after an injury. Full article

This study examines the relationships between ultrasonography measurements of skeletal muscle size and echo intensity (EI) with muscle strength and local muscle endurance in a habitually resistance-trained population. Twenty young, healthy participants underwent imaging of the biceps brachii in the sagittal and transverse planes and with the extended field of view (EFOV) technique. Linear regression was used to examine measures of muscle thickness (MT), muscle cross-sectional area (mCSA), EI, and corrected EI (cEI) in each scanning plane for their associations with strength (1RM biceps curl) and local muscle endurance (4x failure @ 50%1RM). The strongest predictor of 1RM strength and local muscle endurance was sagittal MT (adj. R² = 0.682) and sagittal cEI (adj. R² = 0.449), respectively. Strength and transverse MT (R² = 0.661) and the EFOV mCSA (R² = 0.643) demonstrated a positive relationship. Local muscle endurance and cEI in the transverse plane (R² = 0.265) and the EFOV scan (R² = 0.309) demonstrated a negative relationship. No associations were shown with uncorrected EI. While each scanning plane supports the muscle size-strength and echogenicity-endurance relationships, sagittal plane imaging demonstrated the strongest associations with muscle fitness. These findings provide important methodological insights regarding ultrasound imaging and muscle fitness relationships. Full article

Background: This study sought to investigate whether different physical function tests (objective measures of physical performance) may identify a low physical resilience in breast cancer survivors (BCS). Methods: This analytical cross-sectional study evaluated 146 BCS and 69 age-matched women without breast cancer history. The different times after the end of treatment were used as criteria for group division. Participants were divided into four groups: control (CT: n = 69–women without breast cancer history); <1.0 years after the end of treatment (<1 YAT: n = 60); 1–3.9 years after the end of treatment (1–3.9 YAT: n = 45); and ≥4 years after the end of treatment (>4 YAT: n = 41). Physical function was evaluated by 4 m walk test (4-MWT), five-times-sit-to-stand test (FTSST), timed up and go test (TUG), and short physical performance battery (SPPB). Age, menopausal status, smoking, number of medications, level of physical activity, body mass index, and muscle strength were used as confounding variables in ANCOVA. Results: All groups that underwent cancer treatment (<1 YAT, 1–3.9 YAT and ≥4 YAT) had lower physical performance (p < 0.001) identified by 4 MWT, TUG, and FTSST when compared to the CT group. For the SPPB, the <1 YAT and ≥4 YAT groups had lower performance (p = 0.005) when compared to the CT. Conclusions: The different physical function tests can be used to identify a low physical resilience in BCS. Full article

Skeletal muscle physiology is regulated by microRNA that are localized within skeletal muscle (myomiRs). This study investigated how the expression of myomiRs and genes regulating skeletal muscle mass and myogenesis are influenced in response to acute and consecutive days of exercise-related signaling using the exercise mimetic, formoterol, in vitro. Human skeletal muscle cells were proliferated and differentiated for 6 days. Experimental conditions included: (a) control, (b) acute formoterol stimulation (AFS), and (c) consecutive days of formoterol stimulation (CFS). For AFS, myotubes were treated with 30 nM of formoterol for three hours on day 6 of differentiation, and this was immediately followed by RNA extraction. For CFS, myotubes were treated with 30 nM of formoterol for three hours on two or three consecutive days, with RNA extracted immediately following the final three-hour formoterol treatment. We observed increased myomiR expression for both AFS and CFS. AFS appeared to promote myogenesis, but this effect was lost with CFS. Additionally, we observed increased expression of genes involved in metabolism, mitochondrial biogenesis, and muscle protein degradation in response to AFS. myomiR and gene expression appear to be sensitive to acute and long-term exercise-related stimuli, and this likely contributes to the regulation of skeletal muscle mass. Full article

The diagnosis of primary mitochondrial myopathy is often delayed by years due to non-specific clinical symptoms as well as variable testing of mitochondrial disorders. The aim of this review is to summarize and discuss the collective findings and novel insights regarding the diagnosing, testing, and clinical presentation of primary mitochondrial myopathy (PMM). PMM results from a disruption of the oxidative phosphorylation (OXPHOS) chain in mitochondria due to mutations in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). Although there are many named syndromes caused by mitochondrial mutations, this review will focus on PMM, which are mitochondrial disorders mainly affecting, but not limited to, the skeletal muscle. Clinical presentation may include muscle weakness, exercise intolerance, myalgia, and rhabdomyolysis. Although skeletal muscle and respiratory function are most frequently affected due to their high energy demand, multisystem dysfunction may also occur, which may lead to the inclusion of mitochondrial myopathies on the differential. Currently, there are no effective disease-modifying treatments, and treatment programs typically only focus on managing the symptomatic manifestations of the disease. Although the field has a large unmet need regarding treatment options, diagnostic pathways are better understood and can help shorten the diagnostic journey to aid in disease management and clinical trial enrollment. Full article

Amyotrophic lateral sclerosis (ALS) is a complex systemic disease that primarily involves motor neuron dysfunction and skeletal muscle atrophy. One commonly used mouse model to study ALS was generated by transgenic expression of a mutant form of human superoxide dismutase 1 (SOD1) gene harboring a single amino acid substitution of glycine to alanine at codon 93 (G93A*SOD1). Although mutant-SOD1 is ubiquitously expressed in G93A*SOD1 mice, a detailed analysis of the skeletal muscle expression pattern of the mutant protein and the resultant muscle pathology were never performed. Using different skeletal muscles isolated from G93A*SOD1 mice, we extensively characterized the pathological sequelae of histological, molecular, ultrastructural, and biochemical alterations. Muscle atrophy in G93A*SOD1 mice was associated with increased and differential expression of mutant-SOD1 across myofibers and increased MuRF1 protein level. In addition, high collagen deposition and myopathic changes sections accompanied the reduced muscle strength in the G93A*SOD1 mice. Furthermore, all the muscles in G93A*SOD1 mice showed altered protein levels associated with different signaling pathways, including inflammation, mitochondrial membrane transport, mitochondrial lipid uptake, and antioxidant enzymes. In addition, the mutant-SOD1 protein was found in the mitochondrial fraction in the muscles from G93A*SOD1 mice, which was accompanied by vacuolized and abnormal mitochondria, altered OXPHOS and PDH complex protein levels, and defects in mitochondrial respiration. Overall, we reported the pathological sequelae observed in the skeletal muscles of G93A*SOD1 mice resulting from the whole-body mutant-SOD1 protein expression. Full article

It is well known that muscular dystrophy disease severity is controlled by genetic modifiers. The expectation is that by identifying these modifiers, we can illuminate additional therapeutic targets with which to combat the disease. To this end we have been investigating the MRL mouse strain, which is highly resistant to muscular dystrophy-mediated fibrosis. The MRL mouse strain contains two mitochondrial-encoded, naturally occurring heteroplasmies: T3900C in tRNA-Met, and variable adenine insertions at 9821 in tRNA-Arg. Heteroplasmies are mitochondrial mutations that are variably present in a cell’s mitochondria. Therefore, MRL cells can contain 0 to 100% of each mitochondrial mutation. We have chosen the severely affected ϒ-sarcoglycan (Sgcg–/–) deficient mice on the DBA2/J background as our muscular dystrophy model to demonstrate the effects of these mitochondrial heteroplasmies on disease severity. Mice from the (Sgcg–/–) DBA2/J (D) and wildtype MRL (M) strains were crossed for more than 10 generations to establish two separate, pure breeding mouse lines: Sgcg+/–Nuc^DMito^%M and Sgcg+/–Nuc^MMito^%M. The Sgcg–/– mice from these separate lines were analyzed at 8 weeks old for membrane permeability, hydroxyproline content, pAMPK content, fibronectin content, and percentage of each heteroplasmy. We have identified that the MRL mitochondrial mutation T3900C confers a portion of the fibrosis resistance identified in the MRL mouse strain. These results have been extended to significantly correlate increased MRL mitochondria with increased pAMPK and decreased muscular dystrophy fibrosis. The beneficial mechanisms controlled by the MRL mitochondria will be discussed. We are establishing metabolic aspects of muscular dystrophy pathogenesis. These metabolic pathways will now be investigated for therapeutic targets. Full article

We have previously shown that hypothermia leads to an increase in the synaptic modulating effects of ATP but not of adenosine in several different animal skeletal muscles. In this paper, we studied the effect of ATP on the amplitude–time parameters of single and tetanic contractions of rats’ isolated fast (1) and slow (2) muscles at different temperatures. We found that when muscles were stimulated by the electrical field (0.1 Hz, 0.5 ms, 10 V), with a decrease in the bath temperature from 37 °C to 14 °C (3), there was an increase in the half-relaxation time of the slow muscle (m. soleus), but not of the fast muscle (m. EDL). Similar effects were observed using a carbachol-induced contraction technique, which suggests the postsynaptic (4) nature of the expansion of the contractile response of the slow muscle induced by ATP (5). To confirm the postsynaptic nature of the observed phenomenon, experiments were performed at a high calcium level (7.2 mM), in which the presynaptic effects of ATP were shown to be offset. We found that the hypercalcium condition did not significantly change the effects of ATP on the measured parameters in both muscles. To record muscle tetanic contractions, we gradually increased the frequency of electrical impulses with the increment of 2.5 Hz to achieve the fusion frequencies of 12.5 Hz for m. soleus and 17.5 Hz for m. EDL at normal temperatures. ATP (100 μM) did not change the fusion frequency for both muscles at a normal temperature but decreased this parameter for the slow muscle to 5 Hz at 14 °C without affecting that for the fast muscle. We conclude that ATP potentiates a hypothermia-induced increase in the half-relaxation time of the contraction of rats’ slow, but not fast, skeletal muscles by acting on postsynaptic P2 receptors (6). Full article