Androgen action on myogenesis throughout the lifespan; comparison with neurogenesis.

Androgens' pleiotropic actions in promoting sex differences present not only a challenge to providing a comprehensive account of their function, but also an opportunity to gain insights by comparing androgenic actions across organ systems. Although often overlooked by neuroscientists, skeletal muscle is another androgen-responsive organ system which shares with the nervous system properties of electrochemical excitability, behavioral relevance, and remarkable capacity for adaptive plasticity. Here we review androgenic regulation of mitogenic plasticity in skeletal muscle with the goal of identifying areas of interest to those researching androgenic mechanisms mediating sexual differentiation of neurogenesis. We use an organizational-activational framework to relate broad areas of similarity and difference between androgen effects on mitogenesis in muscle and brain throughout the lifespan, from early organogenesis, through pubertal organization, adult activation, and aging. The focus of the review is androgenic regulation of muscle-specific stem cells (satellite cells), which share with neural stem cells essential functions in development, plasticity, and repair, albeit with distinct, muscle-specific features. Also considered are areas of paracrine and endocrine interaction between androgen action on muscle and nervous system, including mediation of neural plasticity of innervating and distal neural populations by muscle-produced trophic factors.

Manual dexterity in school-age children measured by the Grooved Pegboard test: Evaluation of training effect and performance in dual-task.

Background: Manual dexterity is the ability to manipulate objects using the hands and fingers for a specific task. Although manual dexterity is widely investigated in the general and special population at all ages, numerous aspects still remain to be explored in children. The aim of this study was to assess the presence of the training effect of the execution of the Grooved Pegboard test (GPT) and to measure the performance of the GPT in dual-task (DT), i.e., during a motor task and a cognitive task. Methods: In this observational, cross-sectional study manual dexterity was assessed in children aged between 6 and 8. The procedure consisted of two phases: (1) the execution of five consecutive trials of the GPT to evaluate the training effect; (2) the execution of one trial of the GPT associated with a motor task (finger tapping test, GPT-FTT), and one trial of the GPT associated with a cognitive task (counting test, GPT-CT) to evaluate the performance in DT. Results: As for the training effect, a significant difference (p < 0.001) between the five trials of the GPT (i.e., GPT1, GPT2, GPT3, GPT4, GPT5) was detected. In particular, we found a significant difference between GPT1 and GPT3 (p < 0.05), GPT1 and GPT4 (p < 0.001), and GPT1 and GPT5 (p < 0.001), as well as between GPT2 and GPT4 (p < 0.001), and GPT2 and GPT5 (p < 0.001).As for the performance in DT, no differences between the best trial of the GPT (i.e., GPT5) and both the GPT-FTT and GPT-CT was found. Conclusion: Our findings suggest that the execution of the GPT in children has a training effect up to the third consecutive trial. Furthermore, the administration of the GPT in DT does not affect GPT performance.

Effects of Physical Activity Program on Body Composition, Physical Performance, and Neuromuscular Strategies during Walking in Older Adults with Sarcopenic Obesity: Randomized Controlled Trial.

The potential impact of a specific physical activity program on biomechanical gait parameters and neuromuscular strategies around the ankle joint in older adults with sarcopenic obesity (SO) remains largely unexplored. The objective of this study was to investigate the effectiveness of a 24-week posture, strengthening, and motricity (PSM) program on improving neuromuscular strategies and biomechanical gait parameters in older adults with SO. 40 participants were randomly assigned to either the trained group (TG) and the control group (CG). Only the TG received the PSM program. Standardized evaluations were performed before and after the intervention, including walking tests on an instrumented gait analysis treadmill to evaluate biomechanical gait parameters and EMG activity of ankle muscles. After the PSM program, TG exhibited an increase in comfortable walking speed (+80%, p < 0.001) and step length (+38%, p < 0.05). Moreover, TG demonstrated a reduction in CoP velocity (-26%, p < 0.01). These gait modifications were associated with decreased muscle activity during the different gait phases (p < 0.05). The PSM program effectively improved gait and neuromuscular capacities in older adults with SO. Notably, these results shed light on the remarkable trainability of neuromuscular capacities in older adults with SO, despite the adverse effects of aging and obesity.

Distinct patterning responses of wing and leg neuromuscular systems to different preaxial polydactylies.

The tetrapod limb has long served as a paradigm to study vertebrate pattern formation and evolutionary diversification. The distal part of the limb, the so-called autopod, is of particular interest in this regard, given the numerous modifications in both its morphology and behavioral motor output. While the underlying alterations in skeletal form have received considerable attention, much less is known about the accompanying changes in the neuromuscular system. However, modifications in the skeleton need to be properly integrated with both muscle and nerve patterns, to result in a fully functional limb. This task is further complicated by the distinct embryonic origins of the three main tissue types involved-skeleton, muscles and nerves-and, accordingly, how they are patterned and connected with one another during development. To evaluate the degree of regulative crosstalk in this complex limb patterning process, here we analyze the developing limb neuromuscular system of Silkie breed chicken. These animals display a preaxial polydactyly, due to a polymorphism in the limb regulatory region of the Sonic Hedgehog gene. Using lightsheet microscopy and 3D-reconstructions, we investigate the neuromuscular patterns of extra digits in Silkie wings and legs, and compare our results to Retinoic Acid-induced polydactylies. Contrary to previous findings, Silkie autopod muscle patterns do not adjust to alterations in the underlying skeletal topology, while nerves show partial responsiveness. We discuss the implications of tissue-specific sensitivities to global limb patterning cues for our understanding of the evolution of novel forms and functions in the distal tetrapod limb.

Novel Organoruthenium(II) Complex C1 Selectively Inhibits Butyrylcholinesterase without Side Effects on Neuromuscular Transmission.

Enzyme butyrylcholinesterase (BChE) shows increased activity in some brain regions after progression of Alzheimer's disease and is therefore one of the therapeutic targets for symptomatic treatment of this neurodegenerative disorder. The organoruthenium(II) complex [(η6-p-cymene)Ru(II)(1-hydroxy-3-methoxypyridine-2(1H)-thionato)pta]PF6 (C1) was designed based on the results of our previous structure-activity studies. Inhibitory activity toward cholinesterase enzymes shows that this complex selectively, competitively, and reversibly inhibits horse serum BChE (hsBChE) with an IC50 value of 2.88 µM. When tested at supra-pharmacological concentrations (30, 60, 90, and 120 µM), C1 had no significant effect on the maximal amplitude of nerve-evoked and directly elicited single-twitch and tetanic contractions. At the highest tested concentration (120 µM), C1 had no effect on resting membrane potential, but significantly decreased the amplitude of miniature end-plate potentials (MEPP) without reducing their frequency. The same concentration of C1 had no effect on the amplitude of end-plate potentials (EPP), however it shortened the half-decay time of MEPPs and EPPs. The decrease in the amplitude of MEPPs and shortening of the half-decay time of MEPPs and EPPs suggest a possible weak inhibitory effect on muscle-type nicotinic acetylcholine receptors (nAChR). These combined results show that, when applied at supra-pharmacological concentrations up to 120 µM, C1 does not importantly affect the physiology of neuromuscular transmission and skeletal muscle contraction.

Transmission-selective muscle pathology induced by the active propagation of mutant huntingtin across the human neuromuscular synapse.

Neuron-to-neuron transmission of aggregation-prone, misfolded proteins may potentially explain the spatiotemporal accumulation of pathological lesions in the brains of patients with neurodegenerative protein-misfolding diseases (PMDs). However, little is known about protein transmission from the central nervous system to the periphery, or how this propagation contributes to PMD pathology. To deepen our understanding of these processes, we established two functional neuromuscular systems derived from human iPSCs. One was suitable for long-term high-throughput live-cell imaging and the other was adapted to a microfluidic system assuring that connectivity between motor neurons and muscle cells was restricted to the neuromuscular junction. We show that the Huntington's disease (HD)-associated mutant HTT exon 1 protein (mHTTEx1) is transmitted from neurons to muscle cells across the human neuromuscular junction. We found that transmission is an active and dynamic process that starts before aggregate formation and is regulated by synaptic activity. We further found that transmitted mHTTEx1 causes HD-relevant pathology at both molecular and functional levels in human muscle cells, even in the presence of the ubiquitous expression of mHTTEx1. In conclusion, we have uncovered a causal link between mHTTEx1 synaptic transmission and HD pathology, highlighting the therapeutic potential of blocking toxic protein transmission in PMDs.

Development of a high-throughput tailored imaging method in zebrafish to understand and treat neuromuscular diseases.

The zebrafish (Danio rerio) is a vertebrate species offering multitude of advantages for the study of conserved biological systems in human and has considerably enriched our knowledge in developmental biology and physiology. Being equally important in medical research, the zebrafish has become a critical tool in the fields of diagnosis, gene discovery, disease modeling, and pharmacology-based therapy. Studies on the zebrafish neuromuscular system allowed for deciphering key molecular pathways in this tissue, and established it as a model of choice to study numerous motor neurons, neuromuscular junctions, and muscle diseases. Starting with the similarities of the zebrafish neuromuscular system with the human system, we review disease models associated with the neuromuscular system to focus on current methodologies employed to study them and outline their caveats. In particular, we put in perspective the necessity to develop standardized and high-resolution methodologies that are necessary to deepen our understanding of not only fundamental signaling pathways in a healthy tissue but also the changes leading to disease phenotype outbreaks, and offer templates for high-content screening strategies. While the development of high-throughput methodologies is underway for motility assays, there is no automated approach to quantify the key molecular cues of the neuromuscular junction. Here, we provide a novel high-throughput imaging methodology in the zebrafish that is standardized, highly resolutive, quantitative, and fit for drug screening. By providing a proof of concept for its robustness in identifying novel molecular players and therapeutic drugs in giant axonal neuropathy (GAN) disease, we foresee that this new tool could be useful for both fundamental and biomedical research.

Electrophysiological and functional signs of Guillain-Barré syndrome predicted by a multiscale neuromuscular computational model.

Objective.The diagnosis of nerve disorders in humans has relied heavily on the measurement of electrical signals from nerves or muscles in response to electrical stimuli applied at appropriate locations on the body surface. The present study investigated the demyelinating subtype of Guillain-Barré syndrome using multiscale computational model simulations to verify how demyelination of peripheral axons may affect plantar flexion torque as well as the ongoing electromyogram (EMG) during voluntary isometric or isotonic contractions.Approach.Changes in axonal conduction velocities, mimicking those found in patients with the disease at different stages, were imposed on a multiscale computational neuromusculoskeletal model to simulate subjects performing unipodal plantar flexion force and position tasks.Main results.The simulated results indicated changes in the torque signal during the early phase of the disease while performing isotonic tasks, as well as in torque variability after partial conduction block while performing both isometric and isotonic tasks. Our results also indicated changes in the root mean square values and in the power spectrum of the soleus EMG signal as well as changes in the synchronization index computed from the firing times of the active motor units. All these quantitative changes in functional indicators suggest that the adoption of such additional measurements, such as torques and ongoing EMG, could be used with advantage in the diagnosis and be relevant in providing extra information for the neurologist about the level of the disease.Significance.Our findings enrich the knowledge of the possible ways demyelination affects force generation and position control during plantarflexion. Moreover, this work extends computational neuroscience to computational neurology and shows the potential of biologically compatible neuromuscular computational models in providing relevant quantitative signs that may be useful for diagnosis in the clinic, complementing the tools traditionally used in neurological electrodiagnosis.

Membrane capacitance and characteristic frequency are associated with contractile properties of skeletal muscle.

The cell membrane capacitance (Cm) and characteristic frequencies (fc) of tissues can be obtained using segmental bioelectrical impedance spectroscopy (S-BIS). Higher Cm and lower fc are associated with a larger surface area of skeletal muscle fibers with T-tubules in the tissues. Muscle fiber membrane is one of the major physiological factors that influence surface electromyograms (EMGs) as well as the number of recruited motor units so that the amplitude of surface EMG may be correlated with Cm and fc. The aim of the current study was to examine the association of fc or Cm in the lower leg with contractile and neuromuscular properties in the plantar flexors. We analyzed data from 59 participants (29 women) aged 21-83 years. The Cm, fc, and intracellular water (ICW) in the lower leg were obtained using S-BIS. We measured electrical-evoked torque, maximal voluntary contraction (MVC) torque, and amplitude of EMG normalized by the M wave during MVC contraction. The high Cm group had a significantly lower fc and significantly higher MVC torque, estimated maximum torque, twitch torque, and root mean square (RMS) of EMG normalized by the M wave (EMG:M) in the musculus triceps surae compared to the low Cm group (P < 0.05). Cm was positively and fc was negatively correlated with the nRMS of EMG:M in the triceps surae (P < 0.05). S-BIS recordings can be used to detect changes in skeletal muscle membrane capacitance, which may provide insights into the number of T-tubules. The muscle capacitance measured with S-BIS can be predictive of muscle force generation.

Perfluorooctane sulfonic acid (PFOS) exposures interfere with behaviors and transcription of genes on nervous and muscle system in zebrafish embryos.

Perfluorooctane sulfonic acid (PFOS) has been widely detected in environment and organisms. PFOS has been identified as the driving agent for the behavioral changes of zebrafish larvae, while the underlying molecular mechanism remains unclear. In this study, zebrafish embryos/larvae were exposed to 0, 0.04, 0.1, 0.4 and 1 µM PFOS for 166 h. The locomotor behaviors and the mRNA transcription of genes in neuromuscular system were detected. Exposure to PFOS did not affect the hatching/death rates and body length, but increased the heart beat rates and frequency of spontaneous tail coiling. Locomotor behavior in zebrafish larvae of 0.4 and 1 µM PFOS groups were increased in the light condition. Additionally, the levels of acetylcholine (Ach) in 0.4 µM PFOS group and dopamine (DA) in 0.1, 0.4 and 1 µM PFOS groups were found to be significantly increased. The expression of genes related to the synthesis and decomposition of ACh，the synthesis and receptor of DA, and fosab was increased in the different PFOS treatment groups, while the expression of all the other genes of the neuromuscular system were significantly reduced. The findings of this investigation demonstrated that PFOS exposure may alter the locomotor behavior of zebrafish through disrupting the expressions of genes in neuromuscular system. The disturbed process of neurotransmitter transmission and muscle contraction caused by PFOS may be the dominant mechanism of hyperactivity in zebrafish.

Collagen VI ablation in zebrafish causes neuromuscular defects during developmental and adult stages.

Collagen VI (COL6) is an extracellular matrix protein exerting multiple functions in different tissues. In humans, mutations of COL6 genes cause rare inherited congenital disorders, primarily affecting skeletal muscles and collectively known as COL6-related myopathies, for which no cure is available yet. In order to get insights into the pathogenic mechanisms underlying COL6-related diseases, diverse animal models were produced. However, the roles exerted by COL6 during embryogenesis remain largely unknown. Here, we generated the first zebrafish COL6 knockout line through CRISPR/Cas9 site-specific mutagenesis of the col6a1 gene. Phenotypic characterization during embryonic and larval development revealed that lack of COL6 leads to neuromuscular defects and motor dysfunctions, together with distinctive alterations in the three-dimensional architecture of craniofacial cartilages. These phenotypic features were maintained in adult col6a1 null fish, which displayed defective muscle organization and impaired swimming capabilities. Moreover, col6a1 null fish showed autophagy defects and organelle abnormalities at both embryonic and adult stages, thus recapitulating the main features of patients affected by COL6-related myopathies. Mechanistically, lack of COL6 led to increased BMP signaling, and direct inhibition of BMP activity ameliorated the locomotor activity of col6a1 null embryos. Finally, treatment with salbutamol, a  ß2-adrenergic receptor agonist, elicited a significant amelioration of the neuromuscular and motility defects of col6a1 null fish embryos. Altogether, these findings indicate that this newly generated zebrafish col6a1 null line is a valuable in vivo tool to model COL6-related myopathies and suitable for drug screenings aimed at addressing the quest for effective therapeutic strategies for these disorders.

The impact of local therapies for breast cancer on shoulder muscle health and function.

Advances in breast cancer treatment have improved patient survival but have also created complications, such as shoulder morbidity, impacting the patient's quality of life. Local therapies for breast cancer influence shoulder muscle health through changes to the muscular microenvironment, macroscopic muscle morphology, and neuromuscular function. Our findings suggest both surgery and radiation therapy compromise the healthy functioning of shoulder musculature. Mastectomy and post-mastectomy breast reconstruction directly affect shoulder function through muscle morphology and neuromuscular function alterations. Radiation therapy damages satellite cells and myocytes, causing cell death both during treatment and years after recovery. This damage creates an environment limited in its ability to prevent atrophy. However, research to date is limited to a small number of analyses with small experimental populations and a lack of control for covariates. Future research to uncover the pathophysiological mechanisms underlying shoulder morbidity after breast cancer treatment must integrate measures of shoulder muscle health and shoulder function.

The acute effects of action observation on muscle strength/weakness and corticospinal excitability in older adults.

Muscle weakness is a critical problem facing many older adults. Interventions targeting nervous system plasticity may show promise in enhancing strength. The purpose of this study was to examine the acute effects of action observation on muscular strength characteristics and corticospinal excitability in older adults. Isometric wrist flexion strength characteristics and corticospinal excitability of the first dorsal interosseous (FDI) were measured in 14 older adults (mean age = 73 years) in response to observation of (1) STRONG contractions of the hand/wrist, (2) WEAK contractions of the hand/wrist, and (3) a CONTROL condition. Results from repeated measures analyses of variance (ANOVAs) indicated that rate of torque development at 200 ms (RTD200) significantly decreased from PRE to POST observation for CONTROL and WEAK, but not STRONG. No other ANOVAs were significant. However, effect sizes indicated that maximal voluntary contraction (MVC) peak torque showed moderate declines following WEAK (d = - 0.571) and CONTROL (d = - 0.636), but not STRONG (d = 0.024). Similarly, rate of torque development at 30 (RTD30), 50 (RTD50), and 200 (RTD200) ms showed large declines from PRE to POST after WEAK and CONTROL, but small changes following STRONG. FDI motor-evoked potential (MEP) amplitude tended to increase over time, but these results were variable. There was a pronounced effect from PRE to 8MIN (d = 0.954) during all conditions. Action observation of strong contractions may exert a preservatory effect on muscular strength. More work is needed to determine whether this is modulated by increased corticospinal excitability. The study was prospectively registered (ClinicalTrials.gov Identifier: NCT03946709).

Optogenetic tools for manipulation of cyclic nucleotides functionally coupled to cyclic nucleotide-gated channels.

BACKGROUND AND PURPOSE: The cyclic nucleotides cAMP and cGMP are ubiquitous second messengers regulating numerous biological processes. Malfunctional cNMP signalling is linked to diseases and thus is an important target in pharmaceutical research. The existing optogenetic toolbox in Caenorhabditis elegans is restricted to soluble adenylyl cyclases, the membrane-bound Blastocladiella emersonii CyclOp and hyperpolarizing rhodopsins; yet missing are membrane-bound photoactivatable adenylyl cyclases and hyperpolarizers based on K+ currents. EXPERIMENTAL APPROACH: For the characterization of photoactivatable nucleotidyl cyclases, we expressed the proteins alone or in combination with cyclic nucleotide-gated channels in muscle cells and cholinergic motor neurons. To investigate the extent of optogenetic cNMP production and the ability of the systems to depolarize or hyperpolarize cells, we performed behavioural analyses, measured cNMP content in vitro, and compared in vivo expression levels. KEY RESULTS: We implemented Catenaria CyclOp as a new tool for cGMP production, allowing fine-control of cGMP levels. We established photoactivatable membrane-bound adenylyl cyclases, based on mutated versions ("A-2x") of Blastocladiella and Catenaria ("Be," "Ca") CyclOp, as N-terminal YFP fusions, enabling more efficient and specific cAMP signalling compared to soluble bPAC, despite lower overall cAMP production. For hyperpolarization of excitable cells by two-component optogenetics, we introduced the cAMP-gated K+ -channel SthK from Spirochaeta thermophila and combined it with bPAC, BeCyclOp(A-2x), or YFP-BeCyclOp(A-2x). As an alternative, we implemented the B. emersonii cGMP-gated K+ -channel BeCNG1 together with BeCyclOp. CONCLUSION AND IMPLICATIONS: We established a comprehensive suite of optogenetic tools for cNMP manipulation, applicable in many cell types, including sensory neurons, and for potent hyperpolarization. LINKED ARTICLES: This article is part of a themed issue on cGMP Signalling in Cell Growth and Survival. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.11/issuetoc.

Aberrant enteric neuromuscular system and dysbiosis in amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis is a neuromuscular disease characterized by the progressive death of motor neurons and muscle atrophy. The gastrointestinal symptoms in ALS patients were largely ignored or underestimated. The relationship between the enteric neuromuscular system and microbiome in ALS progression is unknown. We performed longitudinal studies on the enteric neuron system (ENS) and microbiome in the ALS human-SOD1G93A (Superoxide Dismutase 1) transgenic mice. We treated age-matched wild-type and ALS mice with butyrate or antibiotics to investigate the microbiome and neuromuscular functions. We examined intestinal mobility, microbiome, an ENS marker GFAP (Glial Fibrillary Acidic Protein), a smooth muscle marker (SMMHC, Smooth Muscle Myosin Heavy Chain), and human colonoids. The distribution of human-G93A-SOD1 protein was tested as an indicator of ALS progression. At 2-month-old before ALS onset, SOD1G93A mice had significantly lower intestinal mobility, decreased grip strength, and reduced time in the rotarod. We observed increased GFAP and decreased SMMHC expression. These changes correlated with consistent increased aggregation of mutated SOD1G93A in the colon, small intestine, and spinal cord. Butyrate or antibiotics treated SOD1G93A mice had a significantly longer latency to fall in the rotarod test, reduced SOD1G93A aggregation, and enhanced enteric neuromuscular function. Feces from 2-month-old SOD1G93A mice significantly enhanced SOD1G93A aggregation in human colonoids transfected with a SOD1G93A-GFP plasmid. Longitudinal studies of microbiome data further showed the altered bacterial community related to autoimmunity (e.g., Clostridium sp. ASF502, Lachnospiraceae bacterium A4), inflammation (e.g., Enterohabdus Muris,), and metabolism (e.g., Desulfovibrio fairfieldensis) at 1- and 2-month-old SOD1G93A mice, suggesting the early microbial contribution to the pathological changes. We have demonstrated a novel link between the microbiome, hSOD1G93A aggregation, and intestinal mobility. Dysbiosis occurred at the early stage of the ALS mice before observed mutated-SOD1 aggregation and dysfunction of ENS. Manipulating the microbiome improves the muscle performance of SOD1G93A mice. We provide insights into the fundamentals of intestinal neuromuscular function and microbiome in ALS.

Beneficial effects of dietary supplementation with green tea catechins and cocoa flavanols on aging-related regressive changes in the mouse neuromuscular system.

Besides skeletal muscle wasting, sarcopenia entails morphological and molecular changes in distinct components of the neuromuscular system, including spinal cord motoneurons (MNs) and neuromuscular junctions (NMJs); moreover, noticeable microgliosis has also been observed around aged MNs. Here we examined the impact of two flavonoid-enriched diets containing either green tea extract (GTE) catechins or cocoa flavanols on age-associated regressive changes in the neuromuscular system of C57BL/6J mice. Compared to control mice, GTE- and cocoa-supplementation significantly improved the survival rate of mice, reduced the proportion of fibers with lipofuscin aggregates and central nuclei, and increased the density of satellite cells in skeletal muscles. Additionally, both supplements significantly augmented the number of innervated NMJs and their degree of maturity compared to controls. GTE, but not cocoa, prominently increased the density of VAChT and VGluT2 afferent synapses on MNs, which were lost in control aged spinal cords; conversely, cocoa, but not GTE, significantly augmented the proportion of VGluT1 afferent synapses on aged MNs. Moreover, GTE, but not cocoa, reduced aging-associated microgliosis and increased the proportion of neuroprotective microglial phenotypes. Our data indicate that certain plant flavonoids may be beneficial in the nutritional management of age-related deterioration of the neuromuscular system.

A COVID-19 Rehabilitation Prospective Surveillance Model for Use by Physiotherapists.

The long-term sequelae of coronavirus disease 2019 (COVID-19) are only now beginning to be defined, but it is already known that the disease can have direct and indirect impacts mainly on the cardiorespiratory and neuromuscular systems and may affect mental health. A role for rehabilitation professionals from all disciplines in addressing COVID-19 sequelae is recognised, but it is essential that patient assessment be systematic if health complications are to be identified and treated and, if possible, prevented. The aim is to present a COVID-19 prospective surveillance model based on sensitive and easily used assessment tools, which is urgently required. Following the Oxford Centre for Evidence-Based Medicine Level of Evidence Tool, an expert team in cardiorespiratory, neuromuscular and mental health worked via telemeetings to establish a model that provides guidelines to rehabilitation professionals working with patients who require rehabilitation after suffering from COVID-19. A COVID-19 prospective surveillance model is proposed for use by rehabilitation professionals and includes both face-to-face and telematic monitoring components. This model should facilitate the early identification and management of long-term COVID-19 sequelae, thus responding to an arising need.

Neuromuscular compensation strategies adopted at the shoulder following bilateral subpectoral implant breast reconstruction.

Immediate two-stage subpectoral implant breast reconstruction after mastectomy requires the surgical disinsertion of the sternocostal fiber region of the pectoralis major (PM). The disinsertion of the PM would need increased contributions from intact shoulder musculature to generate shoulder torques. This study aimed to identify neuromuscular compensation strategies adopted by subpectoral implant breast reconstruction patients using novel muscle synergy analyses. Fourteen patients treated bilaterally with subpectoral implant breast reconstruction (>2.5 years post-reconstruction) were compared to ten healthy controls. Surface electromyography was obtained from sixteen shoulder muscles as participants generated eight three-dimensional (3D) shoulder torques in five two-dimensional arm postures bilaterally. Non-negative matrix factorization revealed the muscle synergies utilized by each experimental group on the dominant and non-dominant limbs, and the normalized similarity index assessed group differences in overall synergy structure. Bilateral subpectoral implant patients exhibited similar shoulder strength to healthy controls on the dominant and non-dominant arms. Our results suggest that 3D shoulder torque is driven by three shoulder muscle synergies in both healthy participants and subpectoral implant patients. Two out of three synergies were more similar than is expected by chance between the groups on the non-dominant arm, whereas only one synergy is more similar than is expected by chance on the dominant arm. While bilateral shoulder strength is maintained following bilateral subpectoral implant breast reconstruction, a closer analysis of the muscle synergy patterns underlying 3D shoulder torque generation reveals that subpectoral implant patients adopt compensatory neuromuscular strategies only with the dominant arm.

Pain during and after COVID-19 in Germany and worldwide: a narrative review of current knowledge.

Pain is a common symptom accompanying the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Nonspecific discomfort such as sore throat and body ache are frequent. Parainfectious pain such as headache, myalgia, or neuropathic pain has also been reported. The latter seems to be associated with an autoimmune response or an affection of the peripheral neuromuscular system or the central nervous system because of the viral infection. Furthermore, chronic pain can be a complication of intensive care unit treatment due to COVID-19 itself (such as intensive care-acquired weakness) or of secondary diseases associated with the SARS-CoV-2 infection, including Guillain-Barré syndrome, polyneuritis, critical illness polyneuropathy, or central pain following cerebrovascular events. Data on long-lasting painful symptoms after clinically manifest COVID-19 and their consequences are lacking. In addition, preexisting chronic pain may be exacerbated by limited and disrupted health care and the psychological burden of the COVID-19 pandemic. Medical providers should be vigilant on pain during and after COVID-19.

Impact of sedentarism due to the COVID-19 home confinement on neuromuscular, cardiovascular and metabolic health: Physiological and pathophysiological implications and recommendations for physical and nutritional countermeasures.

The COVID-19 pandemic is an unprecedented health crisis as entire populations have been asked to self-isolate and live in home-confinement for several weeks to months, which in itself represents a physiological challenge with significant health risks. This paper describes the impact of sedentarism on the human body at the level of the muscular, cardiovascular, metabolic, endocrine and nervous systems and is based on evidence from several models of inactivity, including bed rest, unilateral limb suspension, and step-reduction. Data form these studies show that muscle wasting occurs rapidly, being detectable within two days of inactivity. This loss of muscle mass is associated with fibre denervation, neuromuscular junction damage and upregulation of protein breakdown, but is mostly explained by the suppression of muscle protein synthesis. Inactivity also affects glucose homeostasis as just few days of step reduction or bed rest, reduce insulin sensitivity, principally in muscle. Additionally, aerobic capacity is impaired at all levels of the O2 cascade, from the cardiovascular system, including peripheral circulation, to skeletal muscle oxidative function. Positive energy balance during physical inactivity is associated with fat deposition, associated with systemic inflammation and activation of antioxidant defences, exacerbating muscle loss. Importantly, these deleterious effects of inactivity can be diminished by routine exercise practice, but the exercise dose-response relationship is currently unknown. Nevertheless, low to medium-intensity high volume resistive exercise, easily implementable in home-settings, will have positive effects, particularly if combined with a 15-25% reduction in daily energy intake. This combined regimen seems ideal for preserving neuromuscular, metabolic and cardiovascular health.