Neuromuscular Dysfunction Research Articles

Autophagy Impairment in Aging Motor Neurons

Neuromuscular dysfunction is common in old age. A hallmark of aging is the aggregation of damaged cytoplasmic structures, especially in post‐mitotic cells like motor neurons. Autophagy flux may be impaired as a result of deficits in the formation of double membrane autophagosomes, the fusion of autophagosomes with lysosomes, or lysosome‐based degradation. Our overarching hypothesis is that autophagy contributes to neuromuscular dysfunction in old age, and that this effect occurs in motor neurons. We evaluated changes in expression levels of core autophagy proteins necessary for the initiation (Beclin1) and elongation (LC3‐I, LC3‐II, ATG7 and ATG5‐ATG12 complex) phases of autophagsome formation, as well as lysosome degradation (assessed by p62 clearance), in adult male and female C57BL/6 mice at 6, 18, and 24 months of age (reflecting 100%, 90% and 75% survival, respectively). Protein expression was analyzed by Western blotting in the cervical spinal cord segments C2–C6. Expression of p62 was reduced in the cervical spinal cord of adult mice at 18 months compared to 24 months, suggesting increased clearance and autophagy flux at 18 months of age. There was no evidence of an effect of age on the expression of the other autophagy markers. In separate animals, immunohistochemical (IHC) analyses of the C2‐C6 segments was used to determine the relative expression of LC3 and p62 in gray and white matter regions. Across all age groups, LC3 and p62 immunoreactivity was evident in the gray matter with minimal expression in the white matter. The ratio of both LC3 and p62 in motor neurons vs. gray matter was compared using a mixed linear model with animal as a random effect. No effect of sex was evident. Increased expression of both LC3 and p62 was evident in choline acetyl transferase (ChAT)‐positive motor neurons (~2–3 fold) compared to the remainder of the gray matter. There was evidence of a difference in relative LC3 and p62 expression in motor neurons across age (F349,2 =12.5, p<0.001), with a significant increase by 24 months of age (p<0.005). Taken together, these findings suggest that 1) there is an aging effect on autophagy markers in the cervical spinal cord of mice; 2) an increase in autophagy by 18 months of age reflects an increase in autophagosome clearance (reduced p62 expression) not restricted to motor neurons; and, 3) increased motor neuron expression of both LC3 and p62 by 24 months of age reflect autophagsome accumulation and autophagy impairment in motor neurons. These findings are also is in accordance with previous reports suggesting a period of vulnerability between 18 and 24 months of age in mice, where autophagy may play a role in the development of age‐related neuromuscular dysfunction.Support or Funding InformationSupported by NIH R01 AG057052.

Compensatory Plasticity of Breathing in Patients with Neuromuscular Disease

Neuromuscular diseases are comprised of variable, often inherited conditions and characterized by muscular (e.g. Duchenne muscular dystrophy), neural (e.g. amyotrophic lateral sclerosis) or a mixed neuromuscular (e.g. Pompe disease) dysfunction. While individual neuromuscular disorders differ in the underlying mechanism and exhibit a unique disease presentation, the consistently leading cause of morbidity and mortality is respiratory failure. Loss of breathing function is literally a “life‐or‐death" issue for patients. Clinical management of breathing relies upon pulmonary function tests to estimate the degree of respiratory involvement in patients, but standard pulmonary function test results can be biased by learning, cognition, or poor effort. This presentation will discuss compensatory neuromuscular adaptations to preserve breathing in the face of worsening disease, including changes in neural drive, neuromuscular junction plasticity, and a greater reliance on less‐affected respiratory motor pools. Detection of these adaptations is needed for prescribing supportive therapies with greater precision and identifying clinically meaningful changes in response to treatments. Citing natural history studies from our team and others, this presentation will feature clinical approaches to objectively evaluate respiratory motor control and gain mechanistic insights into neuromuscular disease. The control of breathing will then be discussed in the context of clinical trials, with an emphasis on current and emerging treatments directed toward improvements in ventilation. Examples will highlight basic‐clinical collaborations that promote new therapeutic frontiers for patients with neuromuscular disease.Support or Funding InformationThis work is supported by National Institutes of Health awards R21 HD090752 and U01 HL121842.

Expression of ALS-linked SOD1 Mutation in Motoneurons or Myotubes Induces Differential Effects on Neuromuscular Function In vitro

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that selectively affects upper and lower motoneurons. Dismantlement of the neuromuscular junction (NMJ) is an early pathological hallmark of the disease whose cellular origin remains still debated. We developed an in vitro NMJ model to investigate the differential contribution of motoneurons and muscle cells expressing ALS-causing mutation in the superoxide dismutase 1 (SOD1) to neuromuscular dysfunction. The primary co-culture system allows the formation of functional NMJs and fosters the expression of the ALS-sensitive fast fatigable type II-b myosin heavy chain (MHC) isoform. Expression of SOD1G93A in myotubes does not prevent the formation of a functional NMJ but leads to decreased contraction frequency and lowers the slow type I MHC isoform transcript levels. Expression of SOD1G93A in both motoneurons and myotubes or in motoneurons alone however alters the formation of a functional NMJ. Our results strongly suggest that motoneurons are a major factor involved in the process of NMJ dismantlement in an experimental model of ALS.

ICU nurses’ knowledge, attitude and behavior about ICU acquired weakness

Background and objective: Intensive care unit (ICU) acquired weakness (ICU-AW) is muscle weakness caused by neuromuscular dysfunction, which can cause muscle mass and muscle strength decline, and is one of the common complications of ICU. ICU-AW can affect patients' daily activities and long-term quality of life. We sought to understand the current knowledge, attitude and behavior of ICU nurses relative to ICU-AW, and analyze the factors influencing the knowledge, attitude and behavior.Methods: Design: A cross-sectional survey. A survey was conducted of 236 ICU nurses using a self-designed questionnaire.Results: The knowledge, attitude and behavior scores of ICU nurses were 17.05 ± 6.003, 17.47 ± 5.538 and 19.84 ± 5.100, respectively. Multivariate analysis showed that education level, previous exposure to ICU-AW and ICU-AW-related knowledge were the three factors affecting ICU nurses' knowledge of ICU-AW. Education level and previous exposure to ICU-AW were the two factors affecting attitude. Education level and ICU-AW-related knowledge were the factors influencing nurses’ behavior (p < .05).Conclusions: ICU nurses have a lower knowledge and attitude score on ICU-AW and a higher score on ICU-AW intervention practice. Relevance to clinical practice: ICU nurses need to acquire more theoretical knowledge and deepen their understanding of ICU-AW, so as to prevent the incidence of ICU-AW.

Colonic dysmotility associated with high-fat diet-induced obesity: Role of enteric glia.

The present study was designed to examine the role of enteric glial cells (EGCs) in colonic neuromuscular dysfunctions in a mouse model of high-fat diet (HFD)-induced obesity. C57BL/6J mice were fed with HFD or standard diet (SD) for 1, 2, or 8weeks. Colonic interleukin (IL)-1β, IL-6, and malondialdehyde (MDA) levels were measured. Expression of occludin in colonic tissues was examined by western blot. Substance P (SP), S100β, GFAP, and phosphorylated mitogen-activated protein kinase 1 (pERK) were assessed in whole mount specimens of colonic plexus by immunohistochemistry. Colonic tachykininergic contractions, elicited by electrical stimulation or exogenous SP, were recorded in the presence or absence of fluorocitrate (FC). To mimic exposure to HFD, cultured EGCs were incubated with palmitate (PA) and/or lipopolysaccharide (LPS). SP and IL-1β levels were assayed in the culture medium by ELISA. HFD mice displayed an increase in colonic IL-1β and MDA, and a reduction of occludin at week 2. These changes occurred to a greater extent at week 8. In vitro electrically evoked tachykininergic contractions were enhanced in HFD mice after 2 or 8weeks, and they were blunted by FC. Colonic IL-6 levels as well as substance P and S100β density in myenteric ganglia of HFD mice were increased at week 8, but not at week 1 or 2. In cultured EGCs, co-incubation with palmitate plus LPS led to a significant increase in both SP and IL-1β release. HFD-induced obesity is characterized by a hyperactivation of EGCs and is involved in the development of enteric motor disorders through an increase in tachykininergic activity and release of pro-inflammatory mediators.

3:09 PM Abstract No. 219 Feasibility of percutaneous gastrostomy tube placement in patients with neuromuscular dysfunction using only local anesthesia

3:09 PM Abstract No. 219 Feasibility of percutaneous gastrostomy tube placement in patients with neuromuscular dysfunction using only local anesthesia

Neuronal selectivity of botulinum neurotoxins

Botulinum neurotoxins (BoNTs) are highly potent toxins responsible for a severe disease, called botulism. They are also efficient therapeutic tools with an increasing number of indications ranging from neuromuscular dysfunction to hypersecretion syndrome, pain release, depression as well as cosmetic application. BoNTs are known to mainly target the motor-neurons terminals and to induce flaccid paralysis. BoNTs recognize a specific double receptor on neuronal cells consisting of gangliosides and synaptic vesicle protein, SV2 or synaptotagmin. Using cultured neuronal cells, BoNTs have been established blocking the release of a wide variety of neurotransmitters. However, BoNTs are more potent in motor-neurons than in the other neuronal cell types. In in vivo models, BoNT/A impairs the cholinergic neuronal transmission at the motor-neurons but also at neurons controlling secretions and smooth muscle neurons, and blocks several neuronal pathways including excitatory, inhibitory, and sensitive neurons. However, only a few reports investigated the neuronal selectivity of BoNTs in vivo. In the intestinal wall, BoNT/A and BoNT/B target mainly the cholinergic neurons and to a lower extent the other non-cholinergic neurons including serotonergic, glutamatergic, GABAergic, and VIP-neurons. The in vivo effects induced by BoNTs on the non-cholinergic neurons remain to be precisely investigated. We report here a literature review of the neuronal selectivity of BoNTs.

A cocktail of growth factors released from a heparin hyaluronic-acid hydrogel promotes the myogenic potential of human urine-derived stem cells in vivo

Traditional cell therapy technology relies on the maximum expansion of primary stem cells in vitro, through multiple passages and potential differentiation protocols, in order to generate the abundance of cells needed prior to transplantation in vivo. Implantation of in vitro over-expanded and pre-differentiated cells typically results in poor cell survival and reduced regeneration capacity for tissue repair in vivo. We hypothesized that implantation of primary stem cells, after a short time culture in vitro (passage number ≤p3), in combination with controlled release of relevant growth factors would improve in vivo cell viability, engraftment and tissue regeneration. The goal of this study was to determine whether the release of myogenic growth factors from a heparin-hyaluronic acid gel (hp-HA gel) could enhance in vivo cell survival, in-growth and myogenic differentiation of human urine-derived stem cells (USC) with a corresponding enhancement in graft vascularization, innervation and regenerative properties. Human USC were obtained from healthy adult donors (n = 6), expanded and then mixed with a hp-HA gel containing sets of growth factors known to enhance myogenesis (IGF1, HGF, PDGF-BB), neurogenesis (NGF, FGF) and angiogenesis (VEGF), or a cocktail with a combination of growth factors. Primary cultured USC (p3) mixed with the hp-HA gel and the various combinations of growth factors, were subcutaneously injected into athymic mice. In vivo cell survival, engraftment and functional differentiation within the host tissue were assessed. The implanted grafts containing USC and the growth factor cocktail showed the greatest number of surviving cells as well as increased numbers of cells that expressed myogenic and endothelial cell markers as compared to other groups 4 weeks after implantation. Moreover, the graft with USC and the growth factor cocktail showed increased numbers of blood vessels and infiltrating neurons. Thus, growth factors released in a controlled manner from an hp-HA gel containing USC efficiently improved in vivo cell survival and supported vascularization and myogenic differentiation within the grafts. This study provides evidence for the use of primary USC and growth factors in a hydrogel as a novel mode of cell therapy for the promotion of myogenic differentiation for the treatment of injured muscle tissue. Statement of significanceCell therapies are a promising treatment option for neuromuscular dysfunction disorders. However, major limitations in cell retention and engraftment after implantation remain a hindrance to the use of stem cell therapy for the treatment of muscle injuries or diseased tissues. Implanted long-term in vitro cultured cells tend to demonstrate low rates of survival and tissue engraftment, lessened paracrine effects, and poor homing and differentiation. Human USC are an easily obtainable stem cell source that possess stem cell characteristics such as a robust proliferative potential, paracrine effects on neighboring cells, and multi-potential differentiation. In this study, we demonstrated that a combination of primary human USC with a cocktail of growth factors combined in a hyaluronic gel was optimal for cell survival and engraftment, including myogenic differentiation potential of USC, angiogenesis and host nerve fiber recruitment in vivo. The present study also demonstrated that the use of primary urine derived stem cells at early passages, without in vitro pre-differentiation, implanted in a hyaluronic-heparin hydrogel containing a cocktail of growth factors, provided an alternative safe site-specific delivery method for cell therapy.

Features of phosphorus-calcium metabolism in children with neurogenic disorders of urination

THE AIM: To study the characteristics of phosphorus-calcium metabolism in patients with neurogenic disorders of urination, taking into account the severity of the manifestations of connective tissue dysplasia. PATIENTS AND METHODS. The study included 90 children, including 60 children with neuro-muscular dysfunction of the bladder (NMDB) and 30 children with enuresis from the age of 5 to 15 years. The diagnosis was established based on a comprehensive examination and according to industry standards. Connective tissue dysplasia was diagnosed in children with the detection of 6 or more small external or visceral manifestations involving 3 or more organs from different systems. Assessment of the severity (severity) of connective tissue dysplasia was carried out according to the point system proposed by T.I. Kadurina et al. Each group was divided into subgroups depending on the severity of the manifestations of connective tissue dysplasia. The determination of the level of calcium and phosphorus in the blood and urine, as well as the calculation of the calcium-creatinine coefficient followed by a comparison of the results in these groups and subgroups. To assess the significance of differences, the Mann-Whitney test was calculated, p <0.05 was considered significant. RESULTS. he level of calcium and phosphorus in the urine was slightly higher in children with enuresis, especially in the morning portion of urine, where the concentration of calcium was 26% higher than in patients with NMDB. At the same time, the value of calcium /creatinine coefficient was significantly higher in the group of patients with enuresis and was 2 times higher than the normative indicators, which indicates the importance of hypercalciuria in the development of enuresis. СONCLUSION. According to the obtained data, the severity of calciuria, determined by the value of the calcium-creatinine coefficient, is significantly higher in patients with enuresis than with NMDB.

Amplification of Snake Venom Toxicity by Endogenous Signaling Pathways.

The active components of snake venoms encompass a complex and variable mixture of proteins that produce a diverse, but largely stereotypical, range of pharmacologic effects and toxicities. Venom protein diversity and host susceptibilities determine the relative contributions of five main pathologies: neuromuscular dysfunction, inflammation, coagulopathy, cell/organ injury, and disruption of homeostatic mechanisms of normal physiology. In this review, we describe how snakebite is not only a condition mediated directly by venom, but by the amplification of signals dysregulating inflammation, coagulation, neurotransmission, and cell survival. Although venom proteins are diverse, the majority of important pathologic events following envenoming follow from a small group of enzyme-like activities and the actions of small toxic peptides. This review focuses on two of the most important enzymatic activities: snake venom phospholipases (svPLA2) and snake venom metalloproteases (svMP). These two enzyme classes are adept at enabling venom to recruit homologous endogenous signaling systems with sufficient magnitude and duration to produce and amplify cell injury beyond what would be expected from the direct impact of a whole venom dose. This magnification produces many of the most acutely important consequences of envenoming as well as chronic sequelae. Snake venom PLA2s and MPs enzymes recruit prey analogs of similar activity. The transduction mechanisms that recruit endogenous responses include arachidonic acid, intracellular calcium, cytokines, bioactive peptides, and possibly dimerization of venom and prey protein homologs. Despite years of investigation, the precise mechanism of svPLA2-induced neuromuscular paralysis remains incomplete. Based on recent studies, paralysis results from a self-amplifying cycle of endogenous PLA2 activation, arachidonic acid, increases in intracellular Ca2+ and nicotinic receptor deactivation. When prolonged, synaptic suppression supports the degeneration of the synapse. Interaction between endothelium-damaging MPs, sPLA2s and hyaluronidases enhance venom spread, accentuating venom-induced neurotoxicity, inflammation, coagulopathy and tissue injury. Improving snakebite treatment requires new tools to understand direct and indirect effects of envenoming. Homologous PLA2 and MP activities in both venoms and prey/snakebite victim provide molecular targets for non-antibody, small molecule agents for dissecting mechanisms of venom toxicity. Importantly, these tools enable the separation of venom-specific and prey-specific pathological responses to venom.

Effect of Endurance Training with Royal Jelly on CRP Gene Expression in Muscle Tissue of Rats with Alzheimer ’s Disease

Background: Studies have shown that Alzheimer’s disease (AD) causes neuromuscular dysfunction by damaging different parts of the central nervous system and inflammation that can increase C-reactive protein (CRP) levels. Nevertheless, the beneficial effects of endurance training (ET) and royal jelly (RJ) on inflammation and reduction of CRP are not fully elucidated. Objectives: The aim of this research was to investigate the effect of ET with RJ on gene expression of CRP in muscle tissues of rats with AD. Methods: In this experimental study, 24 rats with AD (8 mg/kg trimethyltin injection) were randomly divided into four groups of 1-ET, 2-ET + [RJ (100 mg/kg)], 3-RJ and 4-control. Also, six healthy rats were placed in the healthy control group to investigate the effects of AD induction on CRP gene expression. Endurance training groups performed endurance training with a speed of 15 - 20 m/min, 5 sessions per week for eight weeks. Results: Our findings showed ET and RJ significantly decreased CRP gene expression in muscle tissues of rats with AD (P = 0.001) as well as the interaction of ET and RJ was significant in reducing CRP gene expression in muscle tissues of rats with AD (P = 0.001). Conclusions: It appears that ET and RJ have interactive effects on the reduction of CRP in muscle tissues of rats with AD.

Inhibition of TrkB kinase activity impairs transdiaphragmatic pressure generation.

Signaling via the tropomyosin-related kinase receptor subtype B (TrkB) regulates neuromuscular transmission, and inhibition of TrkB kinase activity by 1NMPP1 in TrkBF616A mice worsens neuromuscular transmission failure (NMTF). We hypothesized that acute inhibition of TrkB kinase activity will impair the ability of the diaphragm muscle to produce maximal transdiaphragmatic pressure (Pdi) without impacting the ability to generate forces associated with ventilation, consistent with the greater susceptibility to NMTF in motor units responsible for higher-force nonventilatory behaviors. Adult male and female TrkBF616A mice were injected with 1NMPP1 (n = 8) or vehicle (DMSO; n = 8) 1 h before Pdi measurements during eupneic breathing, hypoxia/hypercapnia (10% O2/5% CO2), tracheal occlusion, spontaneous deep breaths ("sighs") and during maximal activation elicited by bilateral phrenic nerve stimulation. In the vehicle-treated group, Pdi increased from ~10 cmH2O during eupnea and hypoxia/hypercapnia, to ~35 cmH2O during sighs and tracheal occlusion, and to ~65 cm H2O during maximal stimulation. There was no effect of acute 1NMPP1 treatment on Pdi generated during most behaviors, except during maximal stimulation (~30% reduction; P < 0.05). This reduction in maximal Pdi is generally similar to the worsening of NMTF previously reported with TrkB kinase inhibition in rodents. Accordingly, impaired TrkB signaling limits the range of motor behaviors accomplished by the diaphragm muscle and may contribute to neuromuscular dysfunction, primarily by impacting fatigable, higher force-generating motor units.NEW & NOTEWORTHY TrkB signaling plays an important role in maintaining neuromuscular function in the diaphragm muscle and may be necessary to accomplish the various motor behaviors ranging from ventilation to expulsive, behaviors requiring near-maximal forces. This study shows that inhibition of TrkB kinase activity impairs maximal pressure generation by the diaphragm muscle, but the ability to generate the lower pressures required for ventilatory behaviors is not impacted.

P093 Crosstalk between Toll-like receptor 4 and enteric serotonergic pathways in a mouse model of dinitrobenzene sulfonic acid-induced colitis

Abstract Background Changes in serotonin (5-HT) levels, anomalies in serotonergic and cholinergic machinery and altered Toll-like receptor 4 (TLR4) expression have been shown in IBD in patients and related animal models. Thus, we aimed to assess the crosstalk of enteric serotonergic system and TLR4 signalling in a mouse model of dinitrobenzene sulfonic acid (DNBS)-induced colitis. Methods Male C57/Bl6 (WT) and TLR4−/− mice (9 ± 2 weeks old; N = 10 mice) were presensitised with 1% dinitrobenzene sulfonic acid (DNBS), and after 1 week was intrarectally instilled with 2.5% DNBS. Small intestine inflammation was measured by disease activity index and histological analysis. Changes in ileal muscle tension were isometrically recorded following: (1) cumulative addition of carbachol (CCh; 0.1–100 µM); (2) electric field stimulation (EFS, 0–40 Hz); (3) 60 mM KCl; (4) 30 μM 5-HT addition with or without 0.1 μM ondansetron (5-HT3R antagonist). Immunofluorescence distribution of the neuronal HuC/D and nNOS and glial GFAP markers were determined in longitudinal-muscle-myenteric plexus whole mounts (LMMPs) by confocal microscopy. Results In WT mice, DNBS treatment altered receptor and not-receptor mediated responses (+120% of Emax to CCh and +103% of contraction to KCl, respectively; p &amp;lt; 0.001, N = 5 mice/group) together with an altered cholinergic neurotransmission (−50% at 10 Hz; p &amp;lt; 0.01, N = 5 mice/group) and 2-fold increase to 30 μM 5-HT-mediated response (p &amp;lt; 0.001, N = 5 mice/group). After DNBS treatment TLR4−/− mice showed a significant increase in excitatory-mediated response (+98% of Emax to CCh; +80% of contraction to KCl; +120% at 10 Hz; p &amp;lt; 0.001, N = 5 mice/group) together with a significant reduction of 30 μM 5-HT-mediated response (−50%, p &amp;lt; 0.001, N = 5 mice/group). These changes were associated to a significant decrease of the total number of HuC/D+ neurons (−44% and −19% for WT DNBS and TLR4 DNBS mice, respectively) together with a 1.3-fold increase in S100b immunofluorescence in WT mice after DNBS treatment. Conclusion These findings not only suggest an important role of TLR4 in small intestine neuromuscular dysfunction during colitis but also provide novel information on the potential benefits of targeting TLR4 in various gut disorders that exhibit aberrant cholinergic and 5-HT signalling.

Respiratory complications in Cerebral Palsy: physiopathological consequences and clinical manifestations

Cerebral palsy (CP) is a condition that can occur at any time during brain development. Although its etiology is multifactorial, CP is usually linked to brain injury or infections during prenatal, perinatal, neonatal or early childhood period. The disability associated with CP varies from mild to severe, and may include involuntary movements, poor coordination, maintaining balance problems and the difficulty of performing voluntary movements. Although this condition (brain impairment) does not directly cause pulmonary complications, neuromuscular dysfunctions do so. In fact, aspiration and ineffective coughing could interfere with normal airway clearance, impair respiratory function, and worsen lung damage, resulting in increased mucus production and reduced secretions elimination. This consequent alteration of the pulmonary defense system increases the susceptibility to serious, progressive lung diseases. Physiotherapy is an essential component in the management of respiratory complications associated with severe CP. For optimal results, however, it is important customized treatment for every patient. This mini non-ystematic review would highlight the possible complications and the possible interventions for reduce them.

Analysis of Immunoexpression of Synaptic Proteins in Neuromuscular Junctions of Symptomatic and Presymptomatic mSOD1 Transgenic Mice with Model of Amyotrophic Lateral Sclerosis

Dysfunction of neuromuscular synapses is one of the earliest and most important events in the pathogenesis of amyotrophic lateral sclerosis (ALS). The present study was aimed to investigate the abundance of major synaptic proteins (synaptophysin, SNAP-25, synapsin I, nicotinic acetylcholine receptors) in the neuromuscular synapses of the diaphragm of mSOD1 transgenic mice with ALS model. Even in the presymptomatic stage of pathology, significant decrease of SNAP-25 and synapsin I abundance was found in neuromuscular synapses of mSOD1 mice, which can underlie synaptic dysfunctions described in previous studies. In the symptomatic mSOD1 mice, the immunoexpression of all studied presynaptic proteins was markedly decreased, as well as decrease in the degree of co-localization of the areas of expression of synaptophysin, and nicotinic acetylcholine receptors was shown. Thus, the molecular aspects of neuromuscular synapses dysfunction in different stages of modeled ALS in mSOD1 mice were described, which expands our understanding of the mechanisms of the ALS pathogenesis.

Abnormal Gait and Neuromuscular Dysfunction Analysis in Patients with Lumbar Disc Herniation

Abstract The lumbar disc herniation (LDH) has become one of the most common orthopedic diseases. But the effects of LDH on the gait and neuromuscular activities have not been well understood. The purpose of this study was to examine the biomechanical and neuromuscular characteristics in LDH during walking. Sixteen patients with LDH and seven healthy subjects participated in the experiment. All the subjects were required to walk straight along a 5-meters line drawn on the ground at their usual speed. During walking, gait kinematic signals and surface electromyography (sEMG) signals were recorded simultaneously. Seven gait parameters (step length, stride length, step width, cadence, double support phase, single support phase and speed) were extracted for gait assessment. Root mean square (RMS) and median frequency (MDF) of the sEMG signals were extracted for evaluation of neuromuscular function. The bivariate correlation analysis was applied to examine the correlation between gait and muscle activation parameters. The patients with LDH showed decreased cadence, increased muscular activation and increased correlation between single support phase and muscle activation. The LDH can result in slower steps and increased muscle activation, indicating decreased gait flexibility and increased energy consumption in patients with LDH during walking. This study sheds light on the abnormal gait and neuromuscular dysfunction in the LDH patients. The methodology developed in this study may facilitate functional evaluation of LDH.

Putative Otobius megnini -associated clinical signs in horses in South Africa (2012–2018)

Otobius megnini has been associated with certain clinical conditions in horses in both California and Mexico. A number of cases similar to those described previously have been identified by the author in South Africa. This case report summarises these cases to demonstrate that the clinical condition occurs readily in South Africa and may be increasing in occurrence. The disease has minimal coverage in the literature making it more likely that a veterinarian, unfamiliar with the disease, will miss the diagnosis. The author would like to make veterinarians aware of this as a potential differential diagnosis. This study is a retrospective review of clinical data. Clinical records of patients with similar clinical signs and treatment were reviewed and grouped together as relevant cases for this case report. Ten cases of O. megnini associated neuromuscular dysfunction are reported, suggesting a link between the occurrence of the tick and the clinical condition. Clinical signs include third eyelid prolapse, localised muscle fasciculations, elevated heart rate and limb stamping. Serum chemistry changes commonly show increased aspartate aminotransferase and creatine kinase enzymes activities. The occurrence of the ticks within South Africa and the increasing number of cases presented demonstrate the need for more investigation into the pathophysiology of this condition.

Colonic dysmotility and inflammation associated with high fat diet-induced obesity: role of the enteric glia

AbstractIntroductionEnteric glial cells (EGCs) contribute to the regulation of bowel motility, and have been implicated in the onset and development of several digestive disorders. However, the involvement of EGCs in obesity-related intestinal dysmotility is unknown. Accordingly, this study examined the role of EGCs in colonic neuromuscular dysfunctions in a mouse model of diet-induced obesity.Materials and MethodsC57BL/6 male mice (n = 6 per group) were fed with standard diet (SD) or high fat diet (HFD) for 8 weeks. Body and epididymal fat weight, and blood fasting glucose levels were evaluated the day before sacrifice. Colonic longitudinal muscle strips were set up in organ baths with Krebs solution and connected to isometric transducers. The effects of fluorocitrate (FC, gliotoxin) were tested on contractile responses mediated by NK1 tachykininergic receptors upon application of electrical stimuli (0.5 ms, 28 V, 10 Hz) [incubation with atropine, guanethidine, L-NAME, GR159897 and SB218795 (NK2 and NK3 antagonists, respectively)] or exogenous substance P (SP). Colonic levels of interleukin (IL)-1β, IL-6, malondialdehyde (MDA) and occludin (a tight junction protein involved the maintenance of mucosal barrier) were measured. Cultured rat EGCs were exposed to palmitate and lipopolysaccharide (LPS), either alone or in combination, to mimic the exposure to HFD. IL-1β and SP levels were then assessed in cell supernatants, while toll-like receptor 4 (TLR4) expression was evaluated in cell lysates.ResultsHFD-mice displayed increments of body weight, epididymal fat weight and blood glucose levels. In in vitro experiments, electrically induced colonic tachykininergic contractions were enhanced in HFD mice, as compared with SD animals. No differences were observed when comparing contractions to exogenous SP. The increase in electrically evoked tachykininergic contractions was blunted upon incubation with the gliotoxin FC. Exogenous SP-induced contractions were not affected by FC. HFD mice displayed an increase in colonic IL-1β, IL-6 and MDA levels and a reduced occludin expression, as compared with SD mice. Exposure of EGCs to palmitate, alone or in combination with LPS, resulted in a significant increase in TLR4 expression, while LPS alone was without effects. The combination of palmitate and LPS increased significantly IL-1β and SP levels in cell supernatants, while single treatments were without effects.DiscussionHFD is characterized by colonic dysmotility along with bowel inflammation, oxidative stress, and an impairment of mucosal barrier integrity. In this setting, the hyperactivation of EGCs, likely via TLR4, appears to contribute to inflammation and colonic tachykininergic motor dysfunctions.

Detecting Neuromuscular Disorders Using EMG Signals Based on TQWT Features

Neuromuscular disorders are characterized by abnormal functioning of muscles and nerves that communicate with the brain, resulting in muscle weakness and ultimately damage to nervous control, for instance amyotrophic lateral sclerosis (ALS) and myopathy (MYO). Diagnosis of these disorders is frequently done by examining ALS, MYO and normal electromyography (EMG) signals. In the present work, an efficient technique that involves wavelet transform using tunable-Q dynamics (TQWT) is proposed in order to identify disorders related to the neuromuscular domain of EMG signals. The EMG signal is decomposed by the TQWT technique into sub-bands, and these sub-bands are used to determine spectral features including spectral flatness, spectral stretch and spectral decrease, and statistical features including kurtosis, mean absolute deviation, and interquartile range. The extracted features are used as inputs into extreme learning machine classifiers in order to identify and analyze EMG signals associated with neuromuscular dysfunction. The results achieved with this technique illustrate a much better classification with regard to neuromuscular disturbance in electromyogram signals when compared with previous methods.

The effects of transcutaneous electrostimulation in patients in the intensive care unit

INTRODUCTION: Acquired muscle weakness in prolonged hospitalizations is common in approximately 50 -80% of hospitalized patients where all present electrophysiological evidence of neuromuscular dysfunction. Mobilization and early rehabilitation have been shown to improve functional results and quality of life and in this context, neuromuscular electrical stimulation (NMS) has positive evidences aiding in the preservation of protein synthesis and in the prevention of muscle atrophy during the immobilization period. OBJECTIVE: To analyze the benefits of electrostimulation in patients in the intensive care unit. METHODOLOGY: To carry out this review a search was performed in the following databases: SciELO, Medline, Lilacs, PEDro, PubMed and Cochrane, in the period from June to December 2018. 106 articles were found and 99 were excluded because they were not in accordance with our descriptors. In the end, 7 articles fit the criteria for the final analysis. The studies were selected first by the title, abstracts and methodologies. The criteria for inclusion of the studies were: comparator (es): NMS parameters used, muscle strength and therapy time per session, individuals over 18 years old, male and female, requiring invasive mechanical ventilation for more than 24 hours. Studies: Clinical trials, cross-sectional cohort, longitudinal cohort with this theme. No case studies, Systematic review articles, congress summaries on the subject, studies outside the chosen time interval, and other early mobilization techniques were selected. RESULTS: The total number of participants included in the studies was 594 adults, 323 in experimental groups and 271 in control groups, and all studies investigated the effects of NMS in critical patients. The studies were in adults with diverse diagnoses, there was great variability between the NMS protocols, number and time of session performed.CONCLUSION: The NMS has significant results in the increase of muscle strength, Improves functional independence, shortens hospital admission time, shortens time for invasive mechanical ventilation and lower levels of sedation. However, there is still a need for further studies with a better described methodology to actually investigate more accurately about the isolated effect of NMS in critical patients.