Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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11 pages, 1760 KiB  
Case Report
An Intronic Heterozygous SYNE2 Splice Site Mutation: A Rare Cause for Myalgia and hyperCKemia?
by Theresa Paulus, Natalie Young, Emily Jessop, Carolin Berwanger, Christoph Stephan Clemen, Rolf Schröder, Rafal Ploski, Christian Hagel, Yorck Hellenbroich, Andreas Moser and Iakowos Karakesisoglou
Muscles 2024, 3(1), 100-109; https://doi.org/10.3390/muscles3010010 - 15 Mar 2024
Viewed by 797
Abstract
SYNE2 mutations have been associated with skeletal and cardiac muscle diseases, including Emery-Dreifuss muscular dystrophy (EDMD). Here, we present a 70-year-old male patient with muscle pain and elevated serum creatine kinase levels in whom whole-exome sequencing revealed a novel heterozygous SYNE2 splice site [...] Read more.
SYNE2 mutations have been associated with skeletal and cardiac muscle diseases, including Emery-Dreifuss muscular dystrophy (EDMD). Here, we present a 70-year-old male patient with muscle pain and elevated serum creatine kinase levels in whom whole-exome sequencing revealed a novel heterozygous SYNE2 splice site mutation (NM_182914.3:c.15306+2T>G). This mutation is likely to result in the loss of the donor splice site in intron 82. While a diagnostic muscle biopsy showed unspecific myopathological findings, immunofluorescence analyses of skeletal muscle and dermal cells derived from the patient showed nuclear shape alterations when compared to control cells. In addition, a significantly reduced nesprin-2 giant protein localisation to the nuclear envelope was observed in patient-derived dermal fibroblasts. Our findings imply that the novel heterozygous SYNE2 mutation results in a monoallelic splicing defect of nesprin-2, thereby leading to a rare cause of myalgia and hyperCKemia. Full article
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12 pages, 259 KiB  
Article
Age-Related Differences in Physical Fitness and Performance of an “Ability Test” among Firefighters
by Koulla Parpa and Marcos Michaelides
Muscles 2024, 3(1), 88-99; https://doi.org/10.3390/muscles3010009 - 7 Mar 2024
Cited by 1 | Viewed by 664
Abstract
This study’s primary objective was to examine the differences in body composition, abdominal strength, absolute and relative power, handgrip strength, one repetition maximum for squat and bench press, and the maximum count of push-up and sit-up repetitions executed within a minute across different [...] Read more.
This study’s primary objective was to examine the differences in body composition, abdominal strength, absolute and relative power, handgrip strength, one repetition maximum for squat and bench press, and the maximum count of push-up and sit-up repetitions executed within a minute across different age cohorts of firefighters. Furthermore, this study aimed to evaluate the age-related differences in firefighters’ completion times of six firefighting tasks. Eighty-four male volunteer firefighters (age 33.79 ± 6.97 years) were grouped into three age categories, 20–30 years, 31–40 years, and 41–50 years, and underwent the aforementioned evaluations. One-way analysis of variance (MANOVA) revealed that age exerts a statistically significant influence (p < 0.001) on body fat percentage, waist circumference, and waist-to-hip ratio. Furthermore, age significantly affected the overall time of the ability test (p < 0.001) and the duration required to accomplish each individual task (p < 0.001). Additionally, age significantly affected abdominal strength, relative power (as measured by the step test), and the maximum count of push-up and sit-up repetitions performed within a minute. These outcomes support earlier research indicating an age-associated decrement in physical fitness parameters among firefighters. It is recommended that firefighters prioritize maintaining strength and endurance of the abdominal muscles, upper body muscular endurance, and a healthy body weight. The emphasis on specific muscular groups is essential for improving task performance within this profession. Full article
17 pages, 1590 KiB  
Review
Clinical and Therapeutic Implications of BCAAs Metabolism during Chronic Liver Disease in Humans: Crosstalk between Skeletal Muscle and Liver
by Maria Camila Trillos-Almanza, Magnolia Martinez-Aguilar, Johanna C. Arroyave-Ospina, Frederike van Vilsteren, Hans Blokzijl and Han Moshage
Muscles 2024, 3(1), 71-87; https://doi.org/10.3390/muscles3010008 - 4 Mar 2024
Viewed by 1843
Abstract
This comprehensive review focuses on the dynamics of branched-chain amino acids (BCAAs) metabolism and its clinical implications in chronic liver disease, with emphasis on the emerging concept of muscle–liver crosstalk. BCAAs, indispensable for protein synthesis and metabolic pathways, undergo unique tissue-specific processing in [...] Read more.
This comprehensive review focuses on the dynamics of branched-chain amino acids (BCAAs) metabolism and its clinical implications in chronic liver disease, with emphasis on the emerging concept of muscle–liver crosstalk. BCAAs, indispensable for protein synthesis and metabolic pathways, undergo unique tissue-specific processing in skeletal muscle and liver. The liver, responsible for amino acid metabolism, plays a distinctive role in sensing BCAAs catabolism, influencing glucose regulation and contributing to the systemic metabolism of BCAAs. Within the context of chronic liver disease, compromised liver metabolism becomes evident through amino acid abnormalities, particularly in the decrease of the Fischer ratio (BCAAs/aromatic amino acids concentrations in plasma). This reduction becomes important in assessing the severity of liver dysfunction due to its associations with adverse outcomes, including increased mortality and complications related to the liver disease. BCAAs supplementation, as explored in this review, emerges as a promising avenue, displaying positive effects on skeletal muscle mass, strength, and overall nutritional status in cirrhosis management. Understanding this interplay offers insights into therapeutic strategies for chronic liver diseases, exploring the way for precision interventions in clinical practice. Full article
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11 pages, 1764 KiB  
Article
The Effects of Regional Muscle Strength and Mass on Standing Long Jump Performance
by Yuki Nakai, Yujiro Usumoto and Yasufumi Takeshita
Muscles 2024, 3(1), 60-70; https://doi.org/10.3390/muscles3010007 - 4 Mar 2024
Viewed by 1506
Abstract
Muscle strength and mass strongly influence performance. The role of the trunk, upper limbs, and lower limbs in a specific performance is important but unclear in terms of muscle strength, muscle mass, and the degree of influence of each part. Standing long jump [...] Read more.
Muscle strength and mass strongly influence performance. The role of the trunk, upper limbs, and lower limbs in a specific performance is important but unclear in terms of muscle strength, muscle mass, and the degree of influence of each part. Standing long jump is a performance that produces results by not only the muscles of the lower limbs working together but also the entire body, including the trunk and upper limbs. To determine the influence of muscle strength and the mass of each body part on standing long jump, 31 healthy young adults (18 males and 13 females) participated in this study. Abdominal trunk muscle strength, grip strength, and knee extension muscle strength were measured, each of which was defined as trunk, upper limb, and lower limb muscle strength. The trunk, upper limb, and lower limb muscle masses were measured using a body composition analyzer. Performance was measured using the standing long jump test (jumping power). Factors influencing standing long jump were examined. A multiple regression analysis revealed that trunk (β = 0.367, p = 0.006) and upper limb (β = 0.608, p < 0.001) muscle strength values were extracted for standing long jump (adjusted R2 = 0.574, p < 0.01). Trunk and upper limb muscle strength influence standing long jumps. Full article
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12 pages, 435 KiB  
Review
Sarcopenia and Pleural Mesothelioma: The Current Knowledge
by Nikolaos D. Karakousis, Konstantinos I. Gourgoulianis, Nikolaos Papanas and Ourania S. Kotsiou
Muscles 2024, 3(1), 48-59; https://doi.org/10.3390/muscles3010006 - 8 Feb 2024
Viewed by 1131
Abstract
Pleural mesothelioma (PM) is a tumor related to adverse prognosis. The PM WHO classification has mainly identified three major subtypes of PM which are epithelioid, biphasic, and sarcomatoid. Sarcopenia is a medical issue related to a reduction in muscle mass and strength. It [...] Read more.
Pleural mesothelioma (PM) is a tumor related to adverse prognosis. The PM WHO classification has mainly identified three major subtypes of PM which are epithelioid, biphasic, and sarcomatoid. Sarcopenia is a medical issue related to a reduction in muscle mass and strength. It represents a major health issue globally because it is related to adverse effects such as hospitalization, increased length of stay, disability, increased morbidity and mortality and augmented health care expenditures. In this literature review, we attempted to examine the upcoming association between sarcopenia and PM. As recorded by the current literature, muscle loss in PM subjects was related to poorer survival and lower levels of activity. Subjects with PM had increased rates of pre-sarcopenia and malnutrition, while pre-sarcopenia was related to worse activity levels, and malnutrition was related to worse quality of life (QoL). Both tumor volume and sarcopenia were related to long-term mortality in surgically treated PM subjects, while sarcopenia was present both pre-operatively and post-operatively in these subjects. In addition, post-operative sarcopenic subjects showed a decreased 3-year overall survival (OS) in comparison with those who did not have sarcopenia, while pre-operative sarcopenia was importantly related to an increased rate of post-operative adverse outcomes. More studies are needed to validate these claims. Full article
(This article belongs to the Special Issue Sarcopenia: The Impact on Health and Disease)
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8 pages, 455 KiB  
Case Report
Eculizumab as Additional Rescue Therapy in Myasthenic Crisis
by Francesco Crescenzo, Mattia Zanoni, Laura Ferigo, Francesca Rossi, Matteo Grecò, Angelica Lupato, Alessandra Danese, Domenico Ajena and Michelangelo Turazzini
Muscles 2024, 3(1), 40-47; https://doi.org/10.3390/muscles3010005 - 7 Feb 2024
Viewed by 1003
Abstract
Eculizumab is a monoclonal antibody blocking the terminal complement protein C5. As demonstrated in the phase III randomized, placebo-controlled, REGAIN clinical trial, eculizumab is efficacious in acetylcholine receptor antibody (AChR-Ab)-positive refractory generalized myasthenia gravis (gMG) (Myasthenia Gravis Foundation of America—MGFA class II–IV). It [...] Read more.
Eculizumab is a monoclonal antibody blocking the terminal complement protein C5. As demonstrated in the phase III randomized, placebo-controlled, REGAIN clinical trial, eculizumab is efficacious in acetylcholine receptor antibody (AChR-Ab)-positive refractory generalized myasthenia gravis (gMG) (Myasthenia Gravis Foundation of America—MGFA class II–IV). It has not been studied in severe myasthenic exacerbation or myasthenic crisis (MGFA V). A 73-year-old man diagnosed with myasthenia gravis AChR-Ab positivity came to our observation for symptoms of bulbar and ocular weakness and unresponsiveness or intolerability to conventional immunosuppressive therapies (prednisone and azathioprine). Due to the recurrent clinical worsening with intubation over a short-term period, the patient was treated with eculizumab. After 15 days of eculizumab treatment, we observed a significant recovery of clinical condition. We discharged the patient to an outpatient regimen, where he is continuing with maintenance doses of eculizumab and slowly tapering steroid intake. The use of eculizumab in myasthenic crises is still anecdotal. Our case aims to provide eculizumab benefit for refractory severe gMG in a practical, real-world setting beyond the criteria of the REGAIN study. Further studies are needed to evaluate the efficacy and safety of eculizumab in myasthenic crises. Full article
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12 pages, 2452 KiB  
Article
Neuromuscular Rehabilitation of the Brachioradialis Muscle after Distal Radius Fracture in Two Professional Soccer Players Using Electromyographic Biofeedback
by Verónica Morales-Sánchez, Rafael E. Reigal, Verónica García-Morales, Antonio Hernández-Mendo and Coral Falcó
Muscles 2024, 3(1), 16-27; https://doi.org/10.3390/muscles3010003 - 23 Jan 2024
Viewed by 1600
Abstract
The use of electromyographic biofeedback (EMG-BF) in the rehabilitation of injuries has been widely referenced in the psychological literature. However, despite some pioneering work in the field of sports, its use in the rehabilitation of sports injuries has hardly been explored. A case [...] Read more.
The use of electromyographic biofeedback (EMG-BF) in the rehabilitation of injuries has been widely referenced in the psychological literature. However, despite some pioneering work in the field of sports, its use in the rehabilitation of sports injuries has hardly been explored. A case of two professional soccer players who each suffered a distal radius fracture is presented here. Parallel to the rehabilitation plan established by medical services, an intervention strategy using EMG-BF was established. An EMG-BF intervention was performed on the brachioradialis muscle with the aim of improving the voluntary control of its electromyographic activity. The study protocol was registered with the identifier NCT05376072. An ABA design was used. In each session, a pre- and postline was recorded to determine the EMG gain acquired at each point of the session. After six sessions, the intervention was terminated. One more follow-up session was performed. The results obtained indicated the efficacy of the intervention; a statistically significant increase in muscle activity in the brachioradialis muscle was observed. Full article
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13 pages, 1100 KiB  
Article
Sex-Related Differences of Weight Bearing and Non-Weight Bearing Muscle Properties
by Omid Nabavizadeh and Ashley A. Herda
Muscles 2023, 2(4), 400-412; https://doi.org/10.3390/muscles2040031 - 15 Dec 2023
Viewed by 1039
Abstract
This study evaluated muscle composition, quality, and strength of non-weight bearing and weight bearing muscles between males and females. Twenty-eight, healthy males (n = 14; mean ± SD; age = 25.1 ± 4.2 years; height = 181.9 ± 10.6 cm; weight = [...] Read more.
This study evaluated muscle composition, quality, and strength of non-weight bearing and weight bearing muscles between males and females. Twenty-eight, healthy males (n = 14; mean ± SD; age = 25.1 ± 4.2 years; height = 181.9 ± 10.6 cm; weight = 91.6 ± 17.2 kg) and females (n = 14; age = 25.0 ± 3.4 years; height = 165.9 ± 6.9 cm; weight = 66.0 ± 10.2 kg) underwent body composition assessment to estimate body fat (%BF) and total-body, arm, and leg fat-free mass (TFFM, ArmFFM, and LegFFM, respectively) and muscle composition via B-mode ultrasound to measure muscle cross-sectional area (mCSA), echo intensity (EI), and thickness (mT) of four muscles [rectus femoris (RF), vastus lateralis (VL), flexor digitorum superficialis (FDS), and flexor carpi radialis (FCR)]. Additionally, upper- [handgrip strength (HG)] and lower-body [leg extension (LE)] maximal strength were measured, recorded, and expressed relative to FFM to determine muscle quality (MQ) for the dominant arm and leg, respectively. Males had greater TFFM, ArmFFM, and LegFFM (p < 0.001), mCSA for RF, VL, FCR, and FDS (p < 0.001), and mT for RF, VL (p < 0.001–0.006). Females had greater EI for RF, VL, and FDS (p = 0.003–0.01). Negative correlations were identified between EI and MQ for all muscles in males and females, however, no significance was determined. Despite the sex differences in absolute strength and size, muscle quality (relative strength) was not different for the upper nor lower body. Full article
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15 pages, 2568 KiB  
Systematic Review
A Straightforward Approach to Analyze Skeletal Muscle MRI in Limb-Girdle Muscular Dystrophy for Differential Diagnosis: A Systematic Review
by Ryo Morishima and Benedikt Schoser
Muscles 2023, 2(4), 374-388; https://doi.org/10.3390/muscles2040029 - 8 Nov 2023
Cited by 3 | Viewed by 1498
Abstract
Skeletal muscle MRI studies in limb-girdle muscular dystrophy (LGMD) have increased over the past decades, improving the utility of MRI as a differential diagnostic tool. Nevertheless, the relative rarity of individual genotypes limits the scope of what each study can address, making it [...] Read more.
Skeletal muscle MRI studies in limb-girdle muscular dystrophy (LGMD) have increased over the past decades, improving the utility of MRI as a differential diagnostic tool. Nevertheless, the relative rarity of individual genotypes limits the scope of what each study can address, making it challenging to obtain a comprehensive overview of the MRI image of this splintered group. Furthermore, MRI studies have varied in their methods for assessing fat infiltration, which is essential in skeletal muscle MRI evaluation. It stayed problematic and impeded attempts to integrate multiple studies to cover the core MRI features of a distinct LGMD. In this study, we conducted a systematic review of LGMD in adults published until April 2023; 935 references were screened in PubMed and EMBASE, searches of the gray literature, and additional records were added during the screening process. Finally, 39 studies were included in our final analysis. We attempted to quantitatively synthesize the MRI data sets from the 39 individual studies. Finally, we illustrated ideal and simple MRI muscle involvement patterns of six representative LGMD genotypes. Our summary synthesis reveals a distinct distribution pattern of affected muscles by LGMD genotypes, which may be helpful for a quick first-tier differential diagnosis guiding genetic diagnostics. Full article
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13 pages, 796 KiB  
Article
Efficacy of Electromyographic Biofeedback in the Recovery of the Vastus Lateralis after Knee Injury: A Single-Group Case Study
by Verónica Morales-Sánchez, Rafael E. Reigal, Raul Antunes, Rui Matos, Antonio Hernández-Mendo and Diogo Monteiro
Muscles 2023, 2(4), 361-373; https://doi.org/10.3390/muscles2040028 - 7 Nov 2023
Cited by 1 | Viewed by 1098
Abstract
Electromyographic biofeedback (EMG-BF) is a technique that can contribute to the improvement of muscle tone and control in the rehabilitation process after injury. The aim of this research was to determine the effectiveness of EMG-BF in increasing the electromyographic activity of the vastus [...] Read more.
Electromyographic biofeedback (EMG-BF) is a technique that can contribute to the improvement of muscle tone and control in the rehabilitation process after injury. The aim of this research was to determine the effectiveness of EMG-BF in increasing the electromyographic activity of the vastus lateralis after knee injury. The sample consisted of four individuals who had undergone surgery or rehabilitation to resolve either a partial meniscal tear or a patellar tendon strain. The intervention consisted of a program of ten sessions of EMG-BF work. Twelve trials were performed in each session, in which participants were instructed to target the muscle tension produced by the vastus lateralis of the uninjured hemilateral limb. Of the twelve trials in each session, the first three and the last three were performed without feedback, and the intermediate six with feedback. The recording of muscle activity was performed using CY-351/2 Mioback equipment, which allowed the amplitude of the electromyographic signal to be evaluated. The results indicated that the sample analyzed reached greater amplitude during the biofeedback trials, both for the maximum (Z = −13.43, p < 0.001, Cohen’s d = 0.64, 95% CI (0.27, 1.01)) and mean (Z = −7.26, p < 0.001, Cohen’s d = 0.24, 95% CI (−0.12, 0.60)) values. The amplitude also increased throughout the ten sessions, both for the maximum (Z = −3.06, p < 0.01, Cohen’s d = 1.37, 95% CI (0.29, 2.45)) and mean (Z = −3.06, p < 0.01, Cohen’s d = 1.20, 95% CI (0.34, 2.08)) values. Thus, the results highlight the efficacy of this technique in improving muscle activity, suggesting that it is a useful therapeutic procedure in injury recovery. Full article
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15 pages, 1047 KiB  
Review
Advances and Prospects in Understanding Vertebrate Cardiac Conduction System, Pacemaker Cell, and Cardiac Muscle Development: Toward Novel Biological Therapies
by Ridwan Opeyemi Bello, Shannon Frew, Yusra Siddiqui and Rashid Minhas
Muscles 2023, 2(4), 338-352; https://doi.org/10.3390/muscles2040026 - 12 Oct 2023
Viewed by 1982
Abstract
The heart is composed of muscle cells called cardiomyocytes, including a specialized population named pacemaker cells that form the cardiac conduction system (CCS), which is responsible for generating the action potential dictating heart contractions. Failure of the CCS system leads to cardiac arrhythmias, [...] Read more.
The heart is composed of muscle cells called cardiomyocytes, including a specialized population named pacemaker cells that form the cardiac conduction system (CCS), which is responsible for generating the action potential dictating heart contractions. Failure of the CCS system leads to cardiac arrhythmias, which require complicated therapies and often the surgical implantation of electrical pacemakers. However, recent research has focused on the development of novel therapies using biological pacemakers that aim to substitute electrical devices. While most signaling pathways and transcription factors involved in the development of the pacemaker cells are known, the upstream regulatory networks need to be predicted through computer-based databases, mathematical modeling, as well as the functional testing of the regulatory elements in vivo, indicating the need for further research. Here, we summarize the current knowledge about the vertebrate myocardial CCS system and the development of the pacemaker cells, as well as emphasize the areas of future research to clarify the regulation of muscle pacemaker cells and the ease of development of biological therapies. Full article
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18 pages, 5139 KiB  
Article
Degradative Signaling in ATG7-Deficient Skeletal Muscle Following Cardiotoxin Injury
by Fasih Ahmad Rahman, Troy Campbell, Darin Bloemberg, Sarah Chapman and Joe Quadrilatero
Muscles 2023, 2(3), 299-316; https://doi.org/10.3390/muscles2030023 - 15 Sep 2023
Viewed by 964
Abstract
Skeletal muscle is a complex tissue comprising multinucleated and post-mitotic cells (i.e., myofibers). Given this, skeletal muscle must maintain a fine balance between growth and degradative signals. A major system regulating the remodeling of skeletal muscle is autophagy, where cellular quality control is [...] Read more.
Skeletal muscle is a complex tissue comprising multinucleated and post-mitotic cells (i.e., myofibers). Given this, skeletal muscle must maintain a fine balance between growth and degradative signals. A major system regulating the remodeling of skeletal muscle is autophagy, where cellular quality control is mediated by the degradation of damaged cellular components. The accumulation of damaged cellular material can result in elevated apoptotic signaling, which is particularly relevant in skeletal muscle given its post-mitotic nature. Luckily, skeletal muscle possesses the unique ability to regenerate in response to injury. It is unknown whether a relationship between autophagy and apoptotic signaling exists in injured skeletal muscle and how autophagy deficiency influences myofiber apoptosis and regeneration. In the present study, we demonstrate that an initial inducible muscle-specific autophagy deficiency does not alter apoptotic signaling following cardiotoxin injury. This finding is presumably due to the re-establishment of ATG7 levels following injury, which may be attributed to the contribution of a functional Atg7 gene from satellite cells. Furthermore, the re-expression of ATG7 resulted in virtually identical regenerative potential. Overall, our data demonstrate that catastrophic injury may “reset” muscle gene expression via the incorporation of nuclei from satellite cells. Full article
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12 pages, 866 KiB  
Article
Limb–Girdle Muscular Dystrophy D2 TNPO3-Related: A Quality of Life Study
by Alicia Aurora Rodríguez, Imanol Amayra, Irune García and Corrado Angelini
Muscles 2023, 2(3), 274-285; https://doi.org/10.3390/muscles2030021 - 24 Jul 2023
Viewed by 1456
Abstract
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 [...] Read more.
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
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21 pages, 1009 KiB  
Article
Current Cut Points of Three Falls Risk Assessment Tools Are Inferior to Calculated Cut Points in Geriatric Evaluation and Management Units
by Vivian Lee, Linda Appiah-Kubi, Sara Vogrin, Jesse Zanker and Joanna Mitropoulos
Muscles 2023, 2(3), 250-270; https://doi.org/10.3390/muscles2030019 - 7 Jul 2023
Viewed by 1266
Abstract
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 [...] Read more.
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 IndexER) 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 IndexER = 0.20, 95% confidence interval CI = 0.07, 0.34). The PH-FRAT (Youden IndexER = 0.01 and 95% CI = −0.04, 0.05) and WH-STRATIFY (Youden IndexER = 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 IndexER = 0.14 and 95% CI = 0.01, 0.29) and WH-STRATIFY (Cut point 7, Youden IndexER = 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
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12 pages, 1021 KiB  
Article
The Chronic Effect of Stair Climbing–Descending Exercises after Meals on Glycemic Control in Individuals with Type 2 Diabetes: A Randomized Controlled Trial
by Hiroto Honda, Hiromi Fukutomi, Makoto Igaki, Shinichiro Tanaka, Tetsuo Takaishi and Tatsuya Hayashi
Muscles 2023, 2(2), 238-249; https://doi.org/10.3390/muscles2020018 - 15 Jun 2023
Viewed by 1557
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Recent Perspectives Regarding Muscle and Exercise Training)
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17 pages, 694 KiB  
Review
Heat Shock Proteins: Important Helpers for the Development, Maintenance and Regeneration of Skeletal Muscles
by Silvia Pomella, Matteo Cassandri, Francesco Antoniani, Samuele Crotti, Laura Mediani, Beatrice Silvestri, Margherita Medici, Rossella Rota, Alessandro Rosa and Serena Carra
Muscles 2023, 2(2), 187-203; https://doi.org/10.3390/muscles2020014 - 18 Apr 2023
Cited by 3 | Viewed by 2679
Abstract
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 [...] Read more.
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
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45 pages, 3108 KiB  
Review
The Role of Mitochondria in Mediation of Skeletal Muscle Repair
by Stephen E. Alway, Hector G. Paez and Christopher R. Pitzer
Muscles 2023, 2(2), 119-163; https://doi.org/10.3390/muscles2020011 - 24 Mar 2023
Cited by 5 | Viewed by 8973
Abstract
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 [...] Read more.
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 article belongs to the Special Issue State-of-the-Art Skeletal Muscle Research in USA)
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11 pages, 3978 KiB  
Article
Both Acute and Consecutive Days of Formoterol Stimulation Influence Myogenic, Mitochondrial, and myomiR Gene Expression in Human Skeletal Muscle Cells
by Ryan A. Gordon, Emily L. Zumbro, Gena D. Guerin, Matthew L. Sokoloski, Vic Ben-Ezra, Christopher S. Brower, Rhett B. Rigby and Anthony A. Duplanty
Muscles 2023, 2(1), 86-96; https://doi.org/10.3390/muscles2010008 - 22 Feb 2023
Viewed by 1780
Abstract
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 [...] Read more.
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
(This article belongs to the Topic Molecular Mechanisms of Exercise and Healthspan)
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24 pages, 8501 KiB  
Article
Pathological Sequelae Associated with Skeletal Muscle Atrophy and Histopathology in G93A*SOD1 Mice
by Richa Aishwarya, Chowdhury S. Abdullah, Naznin Sultana Remex, Sadia Nitu, Brandon Hartman, Judy King, Mohammad Alfrad Nobel Bhuiyan, Oren Rom, Sumitra Miriyala, Manikandan Panchatcharam, A. Wayne Orr, Christopher G. Kevil and Md. Shenuarin Bhuiyan
Muscles 2023, 2(1), 51-74; https://doi.org/10.3390/muscles2010006 - 2 Feb 2023
Cited by 1 | Viewed by 4236
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Feature Papers in Muscles)
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14 pages, 2471 KiB  
Article
The MRL Mitochondrial Genome Decreases Murine Muscular Dystrophy Severity
by Jenan Holley-Cuthrell, Aqsa Iqbal and Ahlke Heydemann
Muscles 2023, 2(1), 37-50; https://doi.org/10.3390/muscles2010005 - 16 Jan 2023
Viewed by 1906
Abstract
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 [...] Read more.
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+/–NucDMito%M and Sgcg+/–NucMMito%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
(This article belongs to the Special Issue State-of-the-Art Skeletal Muscle Research in USA)
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22 pages, 8111 KiB  
Review
Myokines in Appetite Control and Energy Balance
by Andrew Grannell, Alexander Kokkinos and Carel W. le Roux
Muscles 2022, 1(1), 26-47; https://doi.org/10.3390/muscles1010003 - 30 Jan 2022
Cited by 9 | Viewed by 7755
Abstract
Efficacy of obesity treatments varies between individuals, highlighting the presence of responders and non-responders. Whilst exercise alone or exercise combined with diet leads to underwhelming weight loss for most, there exist super responders losing significant weight. Furthermore, in response to weight loss, the [...] Read more.
Efficacy of obesity treatments varies between individuals, highlighting the presence of responders and non-responders. Whilst exercise alone or exercise combined with diet leads to underwhelming weight loss for most, there exist super responders losing significant weight. Furthermore, in response to weight loss, the majority but not all patients tend to regain weight. Within the biopsychosocial model, biology as a determinant of response has been underappreciated. The understanding of the role that organs beyond adipose tissue and the gastrointestinal tract play in appetite control and body weight regulation has developed in recent years. The aim of this review is to highlight potential myokines that may be important in appetite physiology and overall energy balance. A number of attractive targets are described that warrant further investigation. A deeper understanding of how these myokines may drive feeding behaviours has the potential to improve measures to prevent and treat obesity through a precision medicine approach. Full article
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