AMPK regulates the maintenance and remodelling of the neuromuscular junction.

Objective: The molecular mechanisms underlying the maintenance and adaptability of the neuromuscular junction (NMJ) remain poorly understood. This study aimed to investigate the role of AMP-activated protein kinase (AMPK) as a key regulator of NMJ stability and plasticity.

Method: A comprehensive, multifaceted approach was employed, integrating genetic, physiological, and pharmacological methodologies to elucidate the role of skeletal muscle AMPK in modulating the neuromuscular synapse.

Low baseline ribosome-related gene expression and resistance training-induced declines in ribosome-related gene expression are associated with skeletal muscle hypertrophy in young men and women.

Ribosomes are essential cellular machinery for protein synthesis. It is hypothesised that ribosome content supports muscle growth and that individuals with more ribosomes have greater increases in muscle size following resistance training (RT). Aerobic conditioning (AC) also elicits distinct physiological adaptations; however, no measures of ribosome content following AC have been conducted.

CARM1 drives mitophagy and autophagy flux during fasting-induced skeletal muscle atrophy.

CARM1 (coactivator associated arginine methyltransferase 1) has recently emerged as a powerful regulator of skeletal muscle biology. However, the molecular mechanisms by which the methyltransferase remodels muscle remain to be fully understood. In this study, skeletal muscle-specific knockout (mKO) mice exhibited lower muscle mass with dysregulated macroautophagic/autophagic and atrophic signaling, including depressed AMP-activated protein kinase (AMPK) site-specific phosphorylation of ULK1 (unc-51 like autophagy activating kinase 1; Ser555) and FOXO3 (forkhead box O3; Ser588), as well as MTOR (mechanistic target of rapamycin kinase)-induced inhibition of ULK1 (Ser757), along with AKT/protein kinase B site-specific suppression of FOXO1 (Ser256) and FOXO3 (Ser253).

Sex-Specific Effect of CARM1 in Skeletal Muscle Adaptations to Exercise.

Purpose: The purpose of this study was to determine how the intersection of coactivator-associated arginine methyltransferase 1 (CARM1) and biological sex affects skeletal muscle adaptations to chronic physical activity.

Methods: Twelve-week-old female (F) and male (M) wild-type (WT) and CARM1 skeletal muscle-specific knockout (mKO) mice were randomly assigned to sedentary (SED) or voluntary wheel running (VWR) experimental groups. For 8 wk, the animals in the VWR cohort had volitional access to running wheels.

Impact of short-term, pharmacological CARM1 inhibition on skeletal muscle mass, function, and atrophy in mice.

Coactivator-associated arginine methyltransferase 1 (CARM1) catalyzes the methylation of arginine residues on target proteins critical for health and disease. The purpose of this study was to characterize the effects of short-term, pharmacological CARM1 inhibition on skeletal muscle size, function, and atrophy. Adult mice ( = 10 or 11/sex) were treated with either a CARM1 inhibitor (150 mg/kg EZM2302; EZM) or vehicle (Veh) via oral gavage for 11-13 days and muscle mass, function, and exercise capacity were assessed.

Fortetropin supplementation prevents the rise in circulating myostatin but not disuse-induced muscle atrophy in young men with limb immobilization: A randomized controlled trial.

Supplementation with Fortetropin® (FOR), a naturally occurring component from fertilized egg yolks, reduces circulating myostatin concentration. We hypothesized that FOR would mitigate muscle atrophy during immobilization. We examined the effect of FOR supplementation on muscle size and strength during 2-wk of single-leg immobilization and recovery.

AMPK is mitochondrial medicine for neuromuscular disorders.

Duchenne muscular dystrophy (DMD), myotonic dystrophy type 1 (DM1), and spinal muscular atrophy (SMA) are the most prevalent neuromuscular disorders (NMDs) in children and adults. Central to a healthy neuromuscular system are the processes that govern mitochondrial turnover and dynamics, which are regulated by AMP-activated protein kinase (AMPK). Here, we survey mitochondrial stresses that are common between, as well as unique to, DMD, DM1, and SMA, and which may serve as potential therapeutic targets to mitigate neuromuscular disease.

Acute, next-generation AMPK activation initiates a disease-resistant gene expression program in dystrophic skeletal muscle.

Duchenne muscular dystrophy (DMD) is a life-limiting neuromuscular disorder characterized by muscle weakness and wasting. Previous proof-of-concept studies demonstrate that the dystrophic phenotype can be mitigated with the pharmacological stimulation of AMP-activated protein kinase (AMPK). However, first-generation AMPK activators have failed to translate from bench to bedside due to either their lack of potency or toxic, off-target effects.

A single dose of exercise stimulates skeletal muscle mitochondrial plasticity in myotonic dystrophy type 1.

Aim: Myotonic dystrophy type 1 (DM1) is the second most common muscular dystrophy after Duchenne and is the most prevalent muscular dystrophy in adults. DM1 patients that participate in aerobic exercise training experience several physiological benefits concomitant with improved muscle mitochondrial function without alterations in typical DM1-specific disease mechanisms, which suggests that correcting organelle health is key to ameliorate the DM1 pathology. However, our understanding of the molecular mechanisms of mitochondrial turnover and dynamics in DM1 skeletal muscle is lacking.

The CARM1 transcriptome and arginine methylproteome mediate skeletal muscle integrative biology.

Objective: Coactivator-associated arginine methyltransferase 1 (CARM1) catalyzes the methylation of arginine residues on target proteins to regulate critical processes in health and disease. A mechanistic understanding of the role(s) of CARM1 in skeletal muscle biology is only gradually emerging. The purpose of this study was to elucidate the function of CARM1 in regulating the maintenance and plasticity of skeletal muscle.

Aerobic exercise elicits clinical adaptations in myotonic dystrophy type 1 patients independently of pathophysiological changes.

BackgroundMyotonic dystrophy type 1 (DM1) is a complex life-limiting neuromuscular disorder characterized by severe skeletal muscle atrophy, weakness, and cardiorespiratory defects. Exercised DM1 mice exhibit numerous physiological benefits that are underpinned by reduced CUG foci and improved alternative splicing. However, the efficacy of physical activity in patients is unknown.

CARM1 Regulates AMPK Signaling in Skeletal Muscle.

Coactivator-associated arginine methyltransferase 1 (CARM1) is an emerging mediator of skeletal muscle plasticity. We employed genetic, physiologic, and pharmacologic approaches to determine whether CARM1 regulates the master neuromuscular phenotypic modifier AMP-activated protein kinase (AMPK). CARM1 skeletal muscle-specific knockout (mKO) mice displayed reduced muscle mass and dysregulated autophagic and atrophic processes downstream of AMPK.

Recent insights into neuromuscular junction biology in Duchenne muscular dystrophy: Impacts, challenges, and opportunities.

Duchenne muscular dystrophy (DMD) is the most common and relentless form of muscular dystrophy. The pleiotropic effects of dystrophin deficiency include remarkable impacts on neuromuscular junction (NMJ) structure and function. Some of these alterations contribute to the severe muscle wasting and weakness that distinguish DMD, while others attempt to compensate for them.

Mechanisms of exercise-induced survival motor neuron expression in the skeletal muscle of spinal muscular atrophy-like mice.

Key Points: Spinal muscular atrophy (SMA) is a health- and life-limiting neuromuscular disorder caused by a deficiency in survival motor neuron (SMN) protein. While historically considered a motor neuron disease, current understanding of SMA emphasizes its systemic nature, which requires addressing affected peripheral tissues such as skeletal muscle in particular. Chronic physical activity is beneficial for SMA patients, but the cellular and molecular mechanisms of exercise biology are largely undefined in SMA.

Exercise biology of neuromuscular disorders.

Neuromuscular disorders (NMDs) are chronic conditions that affect the neuromuscular system. Many NMDs currently have no cure; however, as more effective therapies become available for NMD patients, these individuals will exhibit improved health and/or prolonged lifespans. As a result, persons with NMDs will likely desire to engage in a more diverse variety of activities of daily living, including increased physical activity or exercise.

The Role of AMPK in Neuromuscular Biology and Disease.

AMP-activated protein kinase (AMPK) is a primary regulator of cellular metabolism. Recent studies have revealed that AMPK also mediates the maintenance and plasticity of α-motoneurons, the neuromuscular junction, and skeletal muscle. Furthermore, AMPK stimulation by either genetic, pharmacological, or physiological approaches elicits beneficial phenotypic remodeling in neuromuscular disorders (NMDs).

Protein arginine methyltransferase expression and activity during myogenesis.

Despite the emerging importance of protein arginine methyltransferases (PRMTs) in regulating skeletal muscle plasticity, PRMT biology during muscle development is complex and not completely understood. Therefore, our purpose was to investigate PRMT1, -4, and -5 expression and function in skeletal muscle cells during the phenotypic remodeling elicited by myogenesis. CC muscle cell maturation, assessed during the myoblast (MB) stage, and during days 1, 3, 5, and 7 of differentiation, was employed as an model of myogenesis.

Comparison of early outcome of Weil osteotomy and distal metatarsal mini-invasive osteotomy for lesser toe metatarsalgia.

Purpose: To compare the 6-month outcome of Weil osteotomy with distal metatarsal mini-invasive osteotomy (DMMO) in 33 patients with lesser toe metatarsalgia.

Methods: Records of 33 patients who underwent Weil osteotomy (n=20, 41 toes) or DMMO (n=13, 22 toes) for lesser toe metatarsalgia by a single surgeon were reviewed. 25 of them had a concurrent procedure on the 1st toe.

Radiofrequency microtenotomy is as effective as plantar fasciotomy in the treatment of recalcitrant plantar fasciitis.

Background: Radiofrequency microtenotomy (RM) is effective for treating plantar fasciitis. No studies have compared it to the plantar fasciotomy (PF). We hypothesized that RM is equally effective and provides no additional benefit when performed with PF.

Endoscopic Plantar Fasciotomy Improves Early Postoperative Results: A Retrospective Comparison of Outcomes After Endoscopic Versus Open Plantar Fasciotomy.

Plantar fasciotomy is offered to patients with recalcitrant plantar fasciitis. Few studies have characterized the functional outcomes over time for the endoscopic approach compared with the open approach. We hypothesized that patients undergoing endoscopic surgery will have better postoperative functional outcomes early in the postoperative period but equivalent long-term outcomes compared with patients undergoing open surgery.

Tibiotalocalcaneal arthrodesis in a Singaporean hospital.

Purpose: To report 18 patients who underwent tibiotalocalcaneal arthrodesis using a retrograde intramedullary nail or cannulated screws.

Methods: 10 men and 8 women (19 ankles) aged 36 to 70 (mean, 52) years underwent tibiotalocalcaneal arthrodesis using a retrograde intramedullary nail (n=13) or cannulated screws (n=6). Indications for arthrodesis were severe cavovarus deformity secondary to polio or charcot-marie-tooth disease (n=7), severe osteoarthritis in the ankle and subtalar joints (n=6), Charcot joint deformity (n=3), failed fusion procedures (n=2), and foot drop secondary to T12 tumour surgery (n=1).

Total ankle replacement for rheumatoid arthritis of the ankle.

Rheumatoid arthritis is an autoimmune disease that may affect multiple joints, both small and large, and leads to numerous complications. The standard surgical treatment for a rheumatoid arthritic ankle has been an arthrodesis. The ideal candidate for an ankle replacement in a rheumatoid patient is one who is moderately active, has a well-aligned ankle and heel, and a fair range of motion in the ankle joint.