Deficient Muscle Research Articles

Evaluation of Lateral and Medial Parts of the Hamstring Muscle Fatigue Symmetry in Professional Footballers Cleared to Play After ACL Reconstruction

Objectives: Rupture of the anterior cruciate ligament (ACL) is a severe injury common in sports. It also has a high rate of re-injury. The aim of this work was to assess hamstring muscle fatigue in active football players after ACL reconstruction who were cleared to play and to determine symmetry between the lateral and medial hamstring muscles. Methods: In professional football players post ACL reconstruction (n = 25) and non-injured players (n = 26), the bioelectrical activity of the medial (biceps femoris—BF) and lateral (semimembranosus and semitendinosus—SEM) hamstring muscles was measured during 60 s of isometric contraction. The fatigue variables were calculated using the Continuous Wavelet Transform (CWT) tool. Results: The football players following ACL reconstruction demonstrated significant asymmetry in fatigue of the lateral and medial hamstring muscles, with greater fatigue in the SEM compared to the BF muscle. Moreover, in those after reconstruction, the changes are more pronounced, with higher muscle fatigue in both limbs (they have lower MDF than non-injured players) and more severe SEM muscle insufficiency (noted in both limbs but with greater intensity in the non-operated one). Conclusions: The higher SEM muscle fatigue observed in this study influenced the lateral-to-medial activation ratio within the hamstring muscle, which may be a probable cause of this muscle’s insufficiency in laterally stabilizing the knee in the frontal and transverse plane. Furthermore, the hamstring muscles after reconstruction were more fatigued in both limbs, which may be another risk factor for ACL graft rupture. Therefore, increased fatigue in specific hamstring muscles may indicate the direction in which knee stabilization is compromised due to ACL overload. A muscle that becomes fatigued and inefficient more quickly also becomes ineffective in performing its function sooner, which can lead to increased overloading forces acting on the ACL graft.

Nrf2 deficiency in muscle attenuates experimental autoimmune myositis-induced muscle weakness.

Idiopathic inflammatory myopathies (IIMs) are systemic autoimmune diseases characterised by muscle weakness. Although multiple physiological and pathological processes are associated with IIMs, T-lymphocyte infiltration into muscle plays a key role in the development and exacerbation of IIMs. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that regulates inflammatory responses; therefore, muscle Nrf2 may serve an important role in the development of IIMs. In this study, we demonstrated that experimental autoimmune myositis (EAM) causes loss of muscle mass and function in oxidative and glycolytic muscles in C57BL/6 mice. EAM increased CD4+ and CD8+ T-lymphocyte infiltration, as well as interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α) mRNA expression in oxidative soleus and glycolytic extensor digitorum longus muscles, along with elevated chemokine mRNA levels (i.e. CCL3, CCL5, CXCL9, CXCL10 and CXCL16). IFN-γ and TNF-α treatments increased the mRNA expression levels of these chemokines in C2C12 myotubes. EAM also increased phosphorylated Nrf2 at Ser40 in soleus and glycolytic white vastus lateralis muscle. Although the expression of several chemokines was affected by Nrf2 activation following tert-butylhydroquinone treatment or Keap1 knockdown, CCL5 mRNA expression significantly increased in C2C12 myotubes and mouse skeletal muscle. Moreover, muscle-specific Nrf2 knockout in mice attenuates EAM-induced loss of muscle mass and function, which was associated with the inhibition of CCL5 mRNA expression, CD8+ T-lymphocyte infiltration and IFN-γ mRNA expression. Collectively, these findings reveal that regulating Nrf2 activity is a promising therapeutic approach for treating IIM-mediated muscle weakness. KEY POINTS: Experimental autoimmune myositis (EAM) causes loss of muscle mass and function. Loss of muscle mass and function in EAM were associated with increased chemokine mRNA expression (i.e. CCL3, CCL5, CXCL9, CXCL10 and CXCL16), T-lymphocyte infiltration and inflammatory cytokine mRNA expression (i.e. IFN-γ and TNF-α) in the skeletal muscle. EAM activated Nrf2 in muscle and increased Nrf2 activity in vivo and in vitro increased CCL5 mRNA expression. Muscle-specific Nrf2 knockout in mice attenuated EAM-induced muscle weakness by inhibiting CCL5 mRNA expression, CD8+ T-lymphocyte migration and IFN-γ mRNA expression in muscles. These results provide further evidence for the potential therapeutic targeting of Nrf2 to mitigate EAM-induced muscle weakness.

Laminin-α2 chain deficiency in skeletal muscle causes dysregulation of multiple cellular mechanisms.

LAMA2, coding for the laminin-α2 chain, is a crucial ECM component, particularly abundant in skeletal muscle. Mutations in LAMA2 trigger the often-lethal LAMA2-congenital muscular dystrophy (LAMA2-CMD). Various phenotypes have been linked to LAMA2-CMD; nevertheless, the precise mechanisms that malfunction during disease onset in utero remain unknown. We generated Lama2-deficient C2C12 cells and found that Lama2-deficient myoblasts display proliferation, differentiation, and fusion defects, DNA damage, oxidative stress, and mitochondrial dysfunction. Moreover, fetal myoblasts isolated from the dy W mouse model of LAMA2-CMD display impaired differentiation and fusion in vitro. We also showed that disease onset during fetal development is characterized by a significant down-regulation of gene expression in muscle fibers, causing pronounced effects on cytoskeletal organization, muscle differentiation, and altered DNA repair and oxidative stress responses. Together, our findings provide unique insights into the critical importance of the laminin-α2 chain for muscle differentiation and muscle cell homeostasis.

527P Small molecule adenylosuccinic acid supports muscle metabolism in Adss1 deficient muscle phenotypes

527P Small molecule adenylosuccinic acid supports muscle metabolism in Adss1 deficient muscle phenotypes

Heme deficiency in skeletal muscle exacerbates sarcopenia and impairs autophagy by reducing AMPK signaling

Heme serves as a prosthetic group in hemoproteins, including subunits of the mammalian mitochondrial electron transfer chain. The first enzyme in vertebrate heme biosynthesis, 5-aminolevulinic acid synthase 1 (ALAS1), is ubiquitously expressed and essential for producing 5-aminolevulinic acid (ALA). We previously showed that Alas1 heterozygous mice at 20–35 weeks (aged-A1+/−s) manifested impaired glucose metabolism, mitochondrial malformation in skeletal muscle, and reduced exercise tolerance, potentially linked to autophagy dysfunction. In this study, we investigated autophagy in A1+/−s and a sarcopenic phenotype in A1+/−s at 75–95 weeks (senile-A1+/−s). Senile-A1+/−s exhibited significantly reduced body and gastrocnemius muscle weight, and muscle strength, indicating an accelerated sarcopenic phenotype. Decreases in total LC3 and LC3-II protein and Map1lc3a mRNA levels were observed in aged-A1+/−s under fasting conditions and in Alas1 knockdown myocyte-differentiated C2C12 cells (A1KD-C2C12s) cultured in high- or low-glucose medium. ALA treatment largely reversed these declines. Reduced AMP-activated protein kinase (AMPK) signaling was associated with decreased autophagy in aged-A1+/−s and A1KD-C2C12s. AMPK modulation using AICAR (activator) and dorsomorphin (inhibitor) affected LC3 protein levels in an AMPK-dependent manner. Our findings suggest that heme deficiency contributes to accelerated sarcopenia-like defects and reduced autophagy in skeletal muscle, primarily due to decreased AMPK signaling.

ATF4-dependent and independent mitokine secretion from OPA1 deficient skeletal muscle in mice is sexually dimorphic.

Reducing Optic Atrophy 1 (OPA1) expression in skeletal muscle in male mice induces Activation Transcription Factor 4 (ATF4) and the integrated stress response (ISR). Additionally, skeletal muscle secretion of Fibroblast Growth Factor 21 (FGF21) is increased, which mediates metabolic adaptations including resistance to diet-induced obesity (DIO) and glucose intolerance in these mice. Although FGF21 induction in this model can be reversed with pharmacological attenuation of ER stress, it remains to be determined if ATF4 is responsible for FGF21 induction and its metabolic benefits in this model. We generated mice with homozygous floxed Opa1 and Atf4 alleles and a tamoxifen-inducible Cre transgene controlled by the human skeletal actin promoter to enable simultaneous depletion of OPA1 and ATF4 in skeletal muscle (mAO DKO). Mice were fed high fat (HFD) or control diet and evaluated for ISR activation, body mass, fat mass, glucose tolerance, insulin tolerance and circulating concentrations of FGF21 and growth differentiation factor 15 (GDF15). In mAO DKO mice, ATF4 induction is absent. Other indices of ISR activation, including XBP1s, ATF6, and CHOP were induced in mAO DKO males, but not in mOPA1 or mAO DKO females. Resistance to diet-induced obesity was not reversed in mAO DKO mice of both sexes. Circulating FGF21 and GDF15 illustrated sexually dimorphic patterns. Loss of OPA1 in skeletal muscle increases circulating FGF21 in mOPA1 males, but not in mOPA1 females. Additional loss of ATF4 decreased circulating FGF21 in mAO DKO male mice, but increased circulating FGF21 in female mAO DKO mice. Conversely, circulating GDF15 was increased in mAO DKO males and mOPA1 females, but not in mAO DKO females. Sex differences exist in the transcriptional outputs of the ISR following OPA deletion in skeletal muscle. Deletion of ATF4 in male and female OPA1 KO mice does not reverse the resistance to DIO. Induction of circulating FGF21 is ATF4 dependent in males, whereas induction of circulating GDF15 is ATF4 dependent in females. Elevated GDF15 in males and FGF21 in females could reflect activation by other transcriptional outputs of the ISR, that maintain mitokine-dependent metabolic protection in an ATF4-independent manner.

Urinary disorders in patients diagnosed with organic brain pathology

Introduction. This study is relevant due to the high prevalence of organic brain pathology and the negative influence of urination disorders on the quality of life.Objective. To analyse the impaired function of lower urinary tracts in patients with organic brain pathology.Materials & methods. We analysed 607 patients with severe organic brain pathology (105 had traumatic spinal cord injury (TSCI) and 457 had consequences of acute stroke (AS)). We performed clinical urological examinations. During the survey, attention was paid to the presence of urinary tract pathology at the examining time and anamnesis. Structural changes in the urinary tract were objectively assessed. We objectively assessed structural changes in urinary tracts including prostate adenoma in men, insufficiency of pelvic floor muscles in women and strictures of the urethra or ureters. The degree of the spastic syndrome was assessed with the Ashworth Scale. The neurourological examination included cystometry with the measurement of bladder volume and post-void residual urine. The cognitive status of the patients was assessed with the MMSE (Mini-Mental State Examination) questionnaire. The correlation analysis between the degree of spastic syndrome measured with the Ashworth Scale and urination disorders was performed with Spearman rank correlation.Results. All patients had neurogenic dysfunction of the lower urinary tract. A combination of bladder retention and emptying disorders was found in 62 men older than 45yo with benign prostate hyperplasia (10,2% of all cases). An impaired accumulation function in history was found in 45 women older than 45yo (7,4% of all observations). The level of spasticity was 3 or 4 points on the Ashworth Scale in patients with TSCI and 2 to 4 points in those with AS. The analysis of correlations between the degree of spasticity and urination disorders showed a moderate relationship (r = 0,4) in patients with TSCI and a medium relationship (r = 0.65) in patients with AS.Conclusion. Neurogenic dysfunction of the lower urinary tract accompanies patients with severe organic brain pathology throughout their life and requires adequate correction.

Compassionate Ventilator Release in Patients With Neuromuscular Disease: A Two-Case Comparison

Dyspnea, the subjective sensation of breathlessness, is a distressing and potentially traumatic symptom. Dyspnea associated with mechanical ventilation may contribute to intensive care unit (ICU) associated post-traumatic stress disorder and impaired quality of life. Dyspnea is both difficult to alleviate and a cause of significant distress to patients, their loved ones, and care providers People living with neuromuscular disease, such as amyotrophic lateral sclerosis (ALS) or myasthenia gravis (MG), often rely on a ventilator at late stages of illness due to complications of progressive respiratory muscle weakness and paralysis. When unable to wean from the ventilator, conversations turn towards goals of care and release from the ventilator for comfort and end of life (EOL). Patients with and without neuromuscular disease have high risk for dyspnea at EOL upon ventilator liberation. Although limited recommendations have been published specific to patients with ALS, no guidelines currently exist for the terminal liberation from mechanical ventilation in patients experiencing respiratory muscle insufficiency from a neuromuscular disease. Further research on this topic is needed, including creation of a protocol for ventilator release in patients with neuromuscular disease. The following case reports detail the dissimilar EOL experiences of two patients with different forms of neuromuscular disease.

Dietary intervention rescues a bone porosity phenotype in a murine model of Neurofibromatosis Type 1 (NF1).

Neurofibromatosis type 1 (NF1) is a complex genetic disorder that affects a range of tissues including muscle and bone. Recent preclinical and clinical studies have shown that Nf1 deficiency in muscle causes metabolic changes resulting in intramyocellular lipid accumulation and muscle weakness. These can be subsequently rescued by dietary interventions aimed at modulating lipid availability and metabolism. It was speculated that the modified diet may rescue defects in cortical bone as NF1 deficiency has been reported to affect genes involved with lipid metabolism. Bone specimens were analyzed from wild type control mice as well as Nf1Prx1-/- (limb-targeted Nf1 knockout mice) fed standard chow versus a range of modified chows hypothesized to influence lipid metabolism. Mice were fed from 4 weeks to 12 weeks of age. MicroCT analysis was performed on the cortical bone to examine standard parameters (bone volume, tissue mineral density, cortical thickness) and specific porosity measures (closed pores corresponding to osteocyte lacunae, and larger open pores). Nf1Prx1-/- bones were found to have inferior bone properties to wild type bones, with a 4-fold increase in the porosity attributed to open pores. These measures were rescued by dietary interventions including a L-carnitine + medium-chain fatty acid supplemented chow previously shown to improve muscle histology function. Histological staining visualized these changes in bone porosity. These data support the concept that lipid metabolism may have a mechanistic impact on bone porosity and quality in NF1.

Antenatally detected megaurethra: A challenging prenatal diagnosis of Prune Belly syndrome

Prune Belly Syndrome (PBS) is a rare congenital disorder characterized by a triad of urinary tract dilatation, abdominal wall musculature deficiency and bilateral cryptorchidism. Here, we present a case report of a 31-year-old woman referred to our department for ultrasound examination at 22 weeks and 2 days of gestation due to fetal bladder dilation.

Skeletal muscle cystathionine γ-lyase deficiency promotes obesity and insulin resistance and results in hyperglycemia and skeletal muscle injury upon HFD in mice

ABSTRACT Objectives The objective of this study was to investigate whether skeletal muscle cystathionine γ-lyase (CTH) contributes to high-fat diet (HFD)-induced metabolic disorders using skeletal muscle Cth knockout (CthΔskm ) mice. Methods The Cth Δskm mice and littermate Cth-floxed (Cthf/f ) mice were fed with either HFD or chow diet for 13 weeks. Metabolomics and transcriptome analysis were used to assess the impact of CTH deficiency in skeletal muscle. Results Metabolomics coupled with transcriptome showed that CthΔskm mice displayed impaired energy metabolism and some signaling pathways linked to insulin resistance (IR) in skeletal muscle although the mice had normal insulin sensitivity. HFD led to reduced CTH expression and impaired energy metabolism in skeletal muscle in Cthf/f mice. CTH deficiency and HFD had some common pathways enriched in the aspects of amino acid metabolism, carbon metabolism, and fatty acid metabolism. CthΔskm +HFD mice exhibited increased body weight gain, fasting blood glucose, plasma insulin, and IR, and reduced glucose transporter 4 and CD36 expression in skeletal muscle compared to Cthf/f +HFD mice. Impaired mitochondria and irregular arrangement in myofilament occurred in CthΔskm +HFD mice. Omics analysis showed differential pathways enriched between CthΔskm mice and Cthf/f mice upon HFD. More severity in impaired energy metabolism, reduced AMPK signaling, and increased oxidative stress and ferroptosis occurred in CthΔskm +HFD mice compared to Cthf/f +HFD mice. Discussion Our results indicate that skeletal muscle CTH expression dysregulation contributes to metabolism disorders upon HFD.

Dual-mobility bearings reduce instability but may not be the only answer in revision total hip arthroplasty for recurrent dislocation.

There is little information in the literature about the use of dual-mobility (DM) bearings in preventing re-dislocation in revision total hip arthroplasty (THA). The aim of this study was to compare the use of DM bearings, standard bearings, and constrained liners in revision THA for recurrent dislocation, and to identify risk factors for re-dislocation. We reviewed 86 consecutive revision THAs performed for dislocation between August 2012 and July 2019. A total of 38 revisions (44.2%) involved a DM bearing, while 39 (45.3%) and nine (10.5%) involved a standard bearing and a constrained liner, respectively. Rates of re-dislocation, re-revision for dislocation, and overall re-revision were compared. Radiographs were assessed for the positioning of the acetabular component, the restoration of the centre of rotation, leg length, and offset. Risk factors for re-dislocation were determined by Cox regression analysis. The modified Harris Hip Scores (mHHSs) were recorded. The mean age of the patients at the time of revision was 70 years (43 to 88); 54 were female (62.8%). The mean follow-up was 5.0 years (2.0 to 8.75). DM bearings were used significantly more frequently in elderly patients (p = 0.003) and in hips with abductor deficiency (p < 0.001). The re-dislocation rate was 13.2% for DM bearings compared with 17.9% for standard bearings, and 22.2% for constrained liners (p = 0.432). Re-revision-free survival for DM bearings was 84% (95% confidence interval (CI) 0.77 to 0.91) compared with 74% (95% CI 0.67 to 0.81) for standard articulations, and 67% (95% CI 0.51 to 0.82) for constrained liners (p = 0.361). Younger age (hazard ratio (HR) 0.92 (95% CI 0.85 to 0.99); p = 0.031), lower comorbidity (HR 0.44 (95% CI 0.20 to 0.95); p = 0.037), smaller heads (HR 0.80 (95% CI 0.64 to 0.99); p = 0.046), and retention of the acetabular component (HR 8.26 (95% CI 1.37 to 49.96); p = 0.022) were significantly associated with re-dislocation. All DM bearings which re-dislocated were in patients with abductor muscle deficiency (HR 48.34 (95% CI 0.03 to 7,737.98); p = 0.303). The radiological analysis did not reveal a significant relationship between restoration of the geometry of the hip and re-dislocation. The mean mHHSs significantly improved from 43 points (0 to 88) to 67 points (20 to 91; p < 0.001) at the final follow-up, with no differences between the types of bearing. We found that the use of DM bearings reduced the rates of re-dislocation and re-revision in revision THA for recurrent dislocation, but did not guarantee stability. Abductor deficiency is an important predictor of persistent instability.

Respiratory function in adult patients with spinal muscular atrophy treated with nusinersen - a monocenter observational study.

Insufficiency of respiratory muscles is the most important reason for mortality in the natural history of SMA. Thus, improvement or stabilization of respiratory function by disease-modifying therapies (DMT) is a very important issue. We examined respiratory function using forced vital capacity (FVC) in 42 adult SMA patients (2 SMA type 1, 15 SMA type 2, 24 SMA type 3, 1 SMA type 4, median age 37 years, range 17-61 years) treated with nusinersen for a median of 22.1 months (range 2.1 to 46.7 months). Change in FVC was assessed using mixed effects linear regression models. Baseline FVC differed significantly between SMA type 1 (4.0, 8.0%), 2 (median 22.0%, IQR 18.0-44.0), 3 (median 81.0%, IQR 67.0-90.8) and, respectively, type 4 (84.0%) patients reflecting the heterogeneity of respiratory impairment based on the SMA type in adulthood (p < 0.0001). FVC remained stable during follow-up (mean -0.047, 95% CI -0.115 to 0.020, p = 0.17); however, subgroup analysis showed an increase in FVC of type 2 patients (mean 0.144, 95% CI 0.086 to 0.202, p < 0.0001) and a decrease in FVC of type 3/4 patients (-0.142, 95% CI -0.239 to -0.044, p = 0.005). The observed improvement in FVC in patients with SMA type 2 can be seen as a therapeutic response differing from the progressive decline typically seen in the spontaneous course. For SMA type 3/4 patients approaching normal spirometry at baseline, FVC may only be of limited use as an outcome parameter due to ceiling effects.

Anatomy and Deficiency of the Deltoid Muscle: A Review of Literature.

The deltoid muscle is impacted by common injuries and clinical procedures. This study aims to summarize the anatomy, injuries, and clinical considerations involving the deltoid muscle. A literature search was performed using PubMed and Google Scholar using keywords that focused on the deltoid muscle in the shoulder. Primary research articles and appropriate summary articles were selected for review. Reduced deltoid muscle function can be caused by axillary nerve injury, rupture of the deltoid itself, or iatrogenic damage to the muscle. The deltoid muscle has an intimate relationship with the axillary nerve and neighboring rotator cuff muscles. Injury to these nearby structures may be masked by compensating deltoid strength. Examination maneuvers in clinic such as the Akimbo Test should be used to isolate the deltoid muscle to determine if the presenting weakness is from the deltoid itself or from other surrounding injury. Additionally, prior to performing clinical procedures, it is important to be cognitive of the injuries that can occur. For example, incisions that extend distally from the acromion should not extend beyond 5-7 cm as this is the common location of the axillary nerve and vaccine administration should take measures to avoid misplaced injections to avoid unnecessary trauma. Deficiency of the deltoid muscle can be debilitating to patients and it is best clinical practice be aware of the anatomy, various causes, tests, and avoidance measures to help diagnose, restore or preserve normal functioning.

Multitissue transcriptomics demonstrates the systemic physiology of methionine deficiency in broiler chickens

Methionine (Met) supplementation is common practice in broilers to support nutrition, yet there are gaps in the understanding of its role in systemic physiology. Furthermore, several different Met sources are available that may have different physiological effects. This study evaluated the mode of action of Met deficiency (no Met-supplementation) and supplementation (0.25% DL- or L-Met, 0.41% liquid methionine hydroxy analog-free acid (MHA-FA)), and of Met source (DL-, L- or MHA-FA) in broiler chickens, via host transcriptomics. Biological pathway activation modeling was performed to predict the likely phenotypic effects of differentially expressed genes (DEGs) in tissue samples from the jejunum, liver and breast obtained at 10, 21 and 34/35 d of age from three experiments in a combined analysis. Animal performance data showed that Met deficiency reduced BW, daily BW gain, daily feed intake, and breast yield, and increased feed conversion ratio in all experiments (P < 0.05). Effects of Met deficiency on gene expression were least evident in the jejunum and most evident in the liver and breast, as evidenced by the number of DEG and activated pathways. Activated pathways suggested Met deficiency was associated with inhibited protein turnover, gut barrier integrity, and adaptive immunity functions in the jejunum, that predicted reduced breast yield. There was an interaction with age; in Met-deficient birds, there were 333 DEGs in the jejunum of starter vs finisher birds suggesting young birds were more sensitive to Met deficiency than older birds. In the liver, Met deficiency activated pathways associated with lipid turnover, amino acid metabolism, oxidative stress, and the immune system, whereas in breast, it activated pathways involved in metabolic regulation, hemostasis, the neuronal system, and oxidative stress, again predicting a negative impact on breast yield. In the starter phase, supplementation with DL-Met compared to MHA-FA inhibited gamma-aminobutyric acid activity and oxidative stress in breast tissue. When data from all tissues were integrated, increased expression of a liver gene (ENSGALG00000042797) was found to be correlated with the expression of several genes that best explained variation due to the Met deficiency in jejunum and breast muscle. Some of these genes were involved in anti-oxidant systems. Overall, the findings indicate that impaired growth performance due to Met deficiency results from an array of tissue-specific molecular mechanisms in which oxidative stress plays a key systemic role. Young birds are more sensitive to Met-deficiency and DL-Met was a preferential source of Met than L- or MHA-FA during the starter phase.

Plasticity and structural alterations of mitochondria and sarcoplasmic organelles in muscles of mice deficient in α-dystrobrevin, a component of the dystrophin-glycoprotein complex.

The dystrophin-glycoprotein complex (DGC) plays a crucial role in maintaining the structural integrity of the plasma membrane and the neuromuscular junction. In this study, we investigated the impact of the deficiency of α-dystrobrevin (αdbn), a component of the DGC, on the homeostasis of intracellular organelles, specifically mitochondria and the sarcoplasmic reticulum (SR). In αdbn deficient muscles, we observed a significant increase in the membrane-bound ATP synthase complex levels, a marker for mitochondria in oxidative muscle fiber types compared to wild-type. Furthermore, examination of muscle fibers deficient in αdbn using electron microscopy revealed profound alterations in the organization of mitochondria and the SR within certain myofibrils of muscle fibers. This included the formation of hyper-branched intermyofibrillar mitochondria with extended connections, an extensive network spanning several myofibrils, and a substantial increase in the number/density of subsarcolemmal mitochondria. Concurrently, in some cases, we observed significant structural alterations in mitochondria, such as cristae loss, fragmentation, swelling, and the formation of vacuoles and inclusions within the mitochondrial matrix cristae. Muscles deficient in αdbn also displayed notable alterations in the morphology of the SR, along with the formation of distinct anomalous concentric SR structures known as whorls. These whorls were prevalent in αdbn-deficient mice but were absent in wild-type muscles. These results suggest a crucial role of the DGC αdbn in regulating intracellular organelles, particularly mitochondria and the SR, within muscle cells. The remodeling of the SR and the formation of whorls may represent a novel mechanism of the unfolded protein response (UPR) in muscle cells.

Reciprocal communication between FAPs and muscle cells via distinct extracellular vesicle miRNAs in muscle regeneration.

Muscle regeneration is a complex process relying on precise teamwork between multiple cell types, including muscle stem cells (MuSCs) and fibroadipogenic progenitors (FAPs). FAPs are also the main source of intramuscular adipose tissue (IMAT). Muscles without FAPs exhibit decreased IMAT infiltration but also deficient muscle regeneration, indicating the importance of FAPs in the repair process. Here, we demonstrate the presence of bidirectional crosstalk between FAPs and MuSCs via their secretion of extracellular vesicles (EVs) containing distinct clusters of miRNAs that is crucial for normal muscle regeneration. Thus, after acute muscle injury, there is activation of FAPs leading to a transient rise in IMAT. These FAPs also release EVs enriched with a selected group of miRNAs, a number of which come from an imprinted region on chromosome 12. The most abundant of these is miR-127-3p, which targets the sphingosine-1-phosphate receptor S1pr3 and activates myogenesis. Indeed, intramuscular injection of EVs from immortalized FAPs speeds regeneration of injured muscle. In late stages of muscle repair, in a feedback loop, MuSCs and their derived myoblasts/myotubes secrete EVs enriched in miR-206-3p and miR-27a/b-3p. The miRNAs repress FAP adipogenesis, allowing full muscle regeneration. Together, the reciprocal communication between FAPs and muscle cells via miRNAs in their secreted EVs plays a critical role in limiting IMAT infiltration while stimulating muscle regeneration, hence providing an important mechanism for skeletal muscle repair and homeostasis.

Control strategies modeling for robotic exoskeletons facilitating sit-to-stand transitions in geriatric and lower limb impaired

With the growing global aging population, there's been an amplified societal emphasis on preserving the health of the elderly and enhancing their quality of life. In this scenario, robotic exoskeletons have emerged as a cutting-edge solution to assist the elderly and those with lower limb muscle deficiencies in Sit-to-Stand (STS) exercises. These exoskeletons adopt two main approaches: full assistance for those with entirely weakened lower limbs and partial assistance for those with some remaining muscle strength. This article introduces two modeling methods and concepts for these control strategies, aligning with the full and partial assistance directions, respectively. Both approaches hinge on the Lagrange equation as their foundational structure, integrating distinct kinematic designs to form their individual dynamic models. Based on this, the models are further adapted to address the specific risks associated with STS activities as per each strategy. Research outcomes highlight that by assessing the wearer's EMG signal, the partial assistance strategy considerably mitigates the lower limb muscle strength required for STS under conditions such as low-speed, medium-speed, sitback-like, and step-like. This not only improves balance but also augments the likelihood of successful STS execution, consequently diminishing fall incidents.

Not So Rare: Diseases Based on Mutant Proteins Controlling Endoplasmic Reticulum-Mitochondria Contact (MERC) Tethering.

Mitochondria-endoplasmic reticulum contacts (MERCs), also called endoplasmic reticulum (ER)-mitochondria contact sites (ERMCS), are the membrane domains, where these two organelles exchange lipids, Ca2+ ions, and reactive oxygen species. This crosstalk is a major determinant of cell metabolism, since it allows the ER to control mitochondrial oxidative phosphorylation and the Krebs cycle, while conversely, it allows the mitochondria to provide sufficient ATP to control ER proteostasis. MERC metabolic signaling is under the control of tethers and a multitude of regulatory proteins. Many of these proteins have recently been discovered to give rise to rare diseases if their genes are mutated. Surprisingly, these diseases share important hallmarks and cause neurological defects, sometimes paired with, or replaced by skeletal muscle deficiency. Typical symptoms include developmental delay, intellectual disability, facial dysmorphism and ophthalmologic defects. Seizures, epilepsy, deafness, ataxia, or peripheral neuropathy can also occur upon mutation of a MERC protein. Given that most MERC tethers and regulatory proteins have secondary functions, some MERC protein-based diseases do not fit into this categorization. Typically, however, the proteins affected in those diseases have dominant functions unrelated to their roles in MERCs tethering or their regulation. We are discussing avenues to pharmacologically target genetic diseases leading to MERC defects, based on our novel insight that MERC defects lead to common characteristics in rare diseases. These shared characteristics of MERCs disorders raise the hope that they may allow for similar treatment options.

Nutritional considerations for people living with a Fontan circulation: a narrative review.

The population of people living with a Fontan circulation are highly heterogenous, including both children and adults, who have complex health issues and comorbidities associated with their unique physiology throughout life. Research focused on nutritional considerations and interventions in the Fontan population is extremely limited beyond childhood. This review article discusses the current literature examining nutritional considerations in the setting of Fontan physiology and provides an overview of the available evidence to support nutritional management strategies and future research directions. Protein-losing enteropathy, growth deficits, bone mineral loss, and malabsorption are well-recognised nutritional concerns within this population, but increased adiposity, altered glucose metabolism, and skeletal muscle deficiency are also more recently identified issues. Emergencing evidence suggets that abnormal body composition is associated with poor circulatory function and health outcomes. Many nutrition-related issues, including the impact of congenital heart disease on nutritional status, factors contributing to altered body composition and comorbidities, as well as the role of the microbiome and metabolomics, remain poodly understood.