The effect of caffeine chewing gum on muscle performance and fatigue after severe-intensity exercise: isometric vs. dynamic assessments in trained cyclists.

This study investigated the effect of caffeinated chewing gum (GUMCAF) on muscle fatigue (isometric vs. dynamic) after severe-intensity cycling bouts. Fifteen trained male cyclists participated in four visits. Each visit involved two severe-intensity cycling bouts (Δ1 and Δ2) lasting 6 min, separated by a 5-min recovery period. Muscle fatigue was assessed by isometric maximal voluntary knee extension contraction (IMVC) with twitch interpolation technique and dynamically by 7 s all-out cycling sprints. Assessments were performed before GUMCAF (Pre-GUM) and after the cycling bouts (Post-Exercise). GUMCAF and placebo gum (GUMPLA) were administered in a randomized double-blind procedure with participants receiving each gum type (GUMCAF and GUMPLA) during two separate visits. The results showed no significant interaction between gum types and time for the isometric and dynamic measurements (p > 0.05). The percentage change in performance from Pre-GUM to Post-Exercise showed no significant difference between GUMCAF and GUMPLA for either the dynamic-derived TMAX (~ -17.8% and -15.1%, respectively; p = 0.551) or isometric IMVC (~ -12.3% and -17.7%, respectively; p = 0.091) measurements. Moderate to large correlations (r = 0.31-0.51) were found between changes in sprint maximal torque and maximal power output measurements and isometric force, for both gum conditions. GUMCAF was not effective in attenuating muscle force decline triggered by severe-intensity cycling exercises, as measured by both isometric and dynamic methods. The correlations between IMVC and cycling maximal torque and power output suggest caution when interpreting isometric force as a direct measure of fatigue during dynamic cycling exercises.

Tubular Aggregates as a Marker of Aging in Skeletal Muscle.

Tubular aggregates (TA) are skeletal muscle structures that arise from the progressive accumulation of sarcoplasmic reticulum proteins, mainly with aging. Muscle regeneration plays a role in TA formation. TA quantification may aid in the evaluation of muscle aging and genetic muscle degeneration. TA form over time, appears in aging in normal murine muscles. TA reduction in injured conditions may be due to the degeneration-regeneration process in muscles, with loss of damaged muscle fibers and formation of new fibers that do not present protein aggregation. These new regenerated fibers do not improve the function capacity of the aged muscle. Here, we present a methodology for labeling and identifying tubular aggregates in muscle fibers and also the standardization of its quantification.

Development of the Brazilian version of the Performance of Upper Limb scale for children and adolescents with Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is one of the most common and disabling childhood genetic diseases. The course of DMD involves progressive muscular degeneration and weakness, leading to functional decline. The Performance of the Upper Limb scale (PUL) is a specific instrument designed to assess the upper limb function of patients with DMD. OBJECTIVE: To adapt the PUL cross-culturally to Brazilian Portuguese (PUL-Br) and assess the convergent validity, structural validity, inter-rater reliability, and internal consistency for Brazilian patients with DMD METHODS: The cross-cultural adaptation involved six steps: translation to Brazilian Portuguese, Brazilian Portuguese translation synthesis, back-translation to English, back-translation synthesis, an expert committee review, and a pre-final version test (n = 12). The convergent validity of the PUL-Br was evaluated by examining its correlation to the Motor Function Measure scale (MFM) using 30 patients with DMD. Confirmatory factor analysis was conducted to assess structural validity. Intraclass correlation coefficient (ICC) verified the PUL-Br interrater reliability. Cronbach's alpha was calculated to verify internal consistency. RESULTS: The PUL was cross-culturally adapted to Brazilian Portuguese. A strong and positive correlation was found between the PUL-Br total score and the total score on the MFM (r = 0.83; 95% CI: 0.67, 0.91). The PUL-Br showed a satisfactory fit of the data to the three-factor model, excellent inter-rater reliability (ICC: 0.94), and good internal consistency (Cronbach's: 0.91). CONCLUSION: The PUL-Br is valid and reliable for assessing the upper limb function of Brazilian patients with DMD.

Combination of acute diabetic neuropathies following intensive glycaemic management.

While acute and monophasic diabetic neuropathy variants are considered relatively uncommon, diabetes mellitus affects over 6% of the global population, with more than 50% experiencing some form of diabetic neuropathy. Treatment-induced neuropathy of diabetes is an iatrogenic, transient neuropathy characterised by small fibre involvement precipitated by rapid glycaemic control. Diabetic lumbosacral radiculoplexus neuropathy is an asymmetric, predominantly motor neuropathy of the lower limbs, typically starting with localised leg pain. We present a 59-year-old man manifesting features of both conditions following a 12.5% decrease in glycated haemoglobin over 3 months.

Influence of ß2-adrenergic selective agonist formoterol on the motor unit of a mouse model of a congenital myasthenic syndrome with complete VAChT deletion.

Congenital Myasthenic Syndromes (CMS) are a set of genetic diseases that affect the neuromuscular transmission causing muscular weakness. The standard pharmacological treatment aims at ameliorating the myasthenic symptom by acetylcholinesterase inhibitors. Most patients respond well in the short and medium term, however, over time the beneficial effects rapidly fade, and the efficacy of the treatment diminishes. Increasing evidence shows that ß2-adrenergic agonists can be a suitable choice for the treatment of neuromuscular disorders, including CMS, as they promote beneficial effects in the neuromuscular system. The exact mechanism on which they rely is not completely understood, although patients and animal models respond well to the treatment, especially over extended periods. Here, we report the use of the long-lasting specific ß2-adrenergic agonist formoterol in a myasthenic mouse model (mnVAChT-KD), featuring deletion of VAChT (Vesicular Acetylcholine Transporter) specifically in the α-motoneurons. Our findings demonstrate that formoterol treatment (300 µg/kg/day; sc) for 30 days increased the neuromuscular junction area, induced skeletal muscle hypertrophy and altered fibre type composition in myasthenic mice. Interestingly, ß2-adrenergic agonists have shown efficacy even in the absence of ACh (acetylcholine). Our data provide important evidence supporting the potential of ß2-adrenergic agonists in treating neuromuscular disorders of pre-synaptic origin and characterized by disruptions in nerve-muscle communication, through a direct and beneficial action within the motor unit.

Quantifying Muscle Regeneration: Activated Muscle Satellite Cells and New Regenerated Myofibers in Chronic and Acute Degeneration Models.

Regeneration is a remarkable characteristic of the skeletal muscle. Triggered by common lesions, regeneration is stimulated resulting in muscle fiber repair and restoration of muscle homeostasis in normal muscle. In genetic dystrophic muscle, the cycle of degeneration/regeneration is an endless loop that leads to impaired regeneration and substitution of muscle fibers by connective and adipose tissue, causing muscle weakness. Identification and characterization of muscle regeneration steps can help discover potential therapy targets for muscle diseases and aging. Muscle regeneration markers such as the number of satellite cells in the muscle, the proportion of activated satellite cells, and the quantity of regenerating muscle fiber can be quantified using immunolabeling.Here we are presenting a quantitative method to measure muscle regeneration that can be applied to different proposals. To demonstrate the protocol applicability, we used models for acute and chronic muscle injuries. As model of acute degeneration, a wild-type C57BL6 mice with muscle injury induced by electroporation was used, and the muscle was analyzed after 5 and 10 days post-injury. DMDmdx mouse muscle was used as a model of chronic degeneration. The methodologies presented here are among the gold standard methodologies for muscle regeneration analysis and can be easily applied to any type of muscle regeneration study.

Randomized Clinical Trial of Electrostimulation Therapies as an Adjuvant for the Treatment of Temporomandibular Disorders.

We carried out a comparison of the neuromuscular and clinical effects produced by electrostimulation therapies, as an adjuvant to the use of occlusal splints (removable muscle relaxation apparatus) in patients with temporomandibular disorders In this simple randomized clinical trial, 91 patients were randomly divided into three groups. Group A (GA) received transcutaneous electrostimulation therapy and an occlusal splint, Group B (GB) received percutaneous electrostimulation therapy and an occlusal splint, and Group C (GC) received an occlusal splint. The neuromuscular activity, as well as the signs and symptoms of each patient, were evaluated every week throughout the treatment (T0 = baseline; T1 = 7 days; T2 = 14 days; T3 = 21 days; T4 = 28 days; and T5 = 35 days). Pain was measured with a visual analog scale, and neuromuscular electrical activity was determined by the root mean square of the masseter muscles through the use of a UNAM-CINVESTAV 1.2 electromyograph. Comparisons were made using ANOVA for repeated measures (p-value = 0.05). The comparison between the groups determined that muscle fatigue (p-value = 0.001), joint pain (p-value = 0.009), and muscle pain (p-value = 0.003) decreased to a greater extent, and in the short term for the group treated with transcutaneous electrostimulation therapy as an adjuvant to the use of the occlusal splint. The comparison between the groups determined that muscle fatigue (p-value = 0.001), joint pain (p-value = 0.009), and muscle pain (p-value = 0.003) decreased to a greater extent and in a shorter term in the GA (calculation therapy, transcutaneous electrostimulation) and GB (occlusal splint). Transcutaneous electrostimulation is a feasible and faster alternative that was accepted by most of the patients for treating temporomandibular disorders.

Comparison of spatiotemporal and angular parameters during shallow water walking in different immersion depths by older adults with and without Parkinson's disease.

BACKGROUND: People with Parkinson's Disease (PwPD) have motor symptoms that directly interfere on dry land walking performance. Despite the shallow water walking is a viable and beneficial physical intervention for PwPD, it lacks information on the comparison of the biomechanical responses of the shallow water walking by PwPD and age paired healthy individuals. RESEARCH QUESTION: Are there differences in the spatiotemporal and angular responses of shallow water walking by older adults with and without Parkinson's disease? METHODS: In this cross-sectional study, ten older adults (9 men/1 women) with Parkinson disease (PwPD group) and ten older adults (3 men/7 women) without Parkinson's disease (Older group) walked in shallow water at self-selected comfortable speed on pool floor in the immersion depths of waist and xiphoid levels. The 2D kinematic data from the sagittal plane was collected to calculate the walking speed, stride length, stride frequency, duty factor, walk ratio, lower limb joints' range of motion and peak angular speed RESULTS: Both groups reduced similarly the walking speed with the immersion depth increase. The speed decrease was achieved by a reducing both the stride frequency and stride length only in the PwPD. The PwPD had lower contact phase than Older in the waist depth, probably due to the reduced risk of fall in water immersion and to attenuate drag force effects. The total range of joint motion was similar between groups, while the peak angular speed of ankle and knee reduced in the deeper depth in both groups. SIGNIFICANCE: The present findings can help professionals of aquatic rehabilitation to choose the best depth for exercise programs, according to the treatment objectives. To our knowledge, this was the first study that analyzed spatiotemporal and angular variables during shallow water walking of PwPD at different depths and compared them with older people without Parkinson's disease.

Survival analysis of myasthenia gravis patients at a Referral Center in Pará, Brazil (2005-2020) / Análise de sobrevivência de pacientes com miastenia ravis em um Centro de Referência no Pará, Brasil (2005-2020)

Objective: To evaluate the profile and survival of patients diagnosed with Myasthenia Gravis, by reviewing medical records of neurological consultations at a referral service in the interior of Pará (Brazil), between 2005 and 2020. Methods: a historical, observational and retrospective cohort study. 36 participants were included. Survival analysis methods were used to identify prognostic factors for disease remission at the observation time of 36 months. The correlation between the variables and the death outcome was performed using the chi-square test. Results: Most patients were women (66.6%) and had the generalized form of the disease (86.1%). The most prevalent symptoms were: ophthalmoparesis (97.2%), fatigability (75%) and dysphagia (72.2%). Among the complications, 19.4% had myasthenic crisis. The dosage of antiacetylcholine receptor (AChR) antibody was positive in 58.3% and 69.4% underwent electroneuromyography, and 72% of them had electrodecrement. Most of the patients responded to the staggered standard treatment and achieved remission (83.3%), while 16.6% died. Survival analysis showed through Kaplan-Meier curves and Log-rank test that the variables related to poor control were male gender (p=0.01), thymus disease (p=0.02) and use of cyclosporine (p=0.02). The factors that influenced the death outcome were male gender, cyclosporine and thymectomy. Conclusion: The study showed that the evolution of people with Myasthenia Gravis over 15 years and the poor prognostic factors were equivalent to the international literature.

Objetivo: Avaliar o perfil e a sobrevida de pacientes com diagnóstico de Miastenia Gravis, por meio da revisão de prontuários de consultas neurológicas em um serviço de referência no interior do Pará (Brasil), entre 2005 e 2020. Métodos: estudo de coorte histórico, observacional e retrospectivo. 36 participantes foram incluídos. Métodos de análise de sobrevivência foram utilizados para identificar fatores prognósticos para remissão da doença no período de observação de 36 meses. A correlação entre as variáveis e o desfecho de óbito foi realizada por meio do teste qui-quadrado. Resultados: A maioria dos pacientes eram mulheres (66,6%) e apresentavam a forma generalizada da doença (86,1%). Os sintomas mais prevalentes foram: oftalmoparesia (97,2%), fadiga (75%) e disfagia (72,2%). Dentre as complicações, 19,4% tiveram crise miastênica. A dosagem do anticorpo anti-receptor de acetilcolina (AChR) foi positiva em 58,3% e 69,4% realizaram eletroneuromiografia, sendo que 72% deles apresentaram eletrodecremento. A maioria dos pacientes respondeu ao tratamento padrão escalonado e obteve remissão (83,3%), enquanto 16,6% morreram. A análise de sobrevivência mostrou através de curvas de Kaplan-Meier e teste Log-rank que as variáveis relacionadas ao mau controle foram sexo masculino (p=0,01), doença do timo (p=0,02) e uso de ciclosporina (p=0,02). Os fatores que influenciaram no desfecho óbito foram sexo masculino, ciclosporina e timectomia. Conclusão: O estudo mostrou que a evolução das pessoas com Miastenia Gravis ao longo de 15 anos e os fatores de mau prognóstico foram equivalentes à literatura internacional.

Reabilitação fisioterapêutica em pacientes com síndrome da pessoa rígida: revisão integrativa / Physiotherapy rehabilitation in patients with stiff person syndrome: integrative review

Introdução: A Síndrome da Pessoa Rígida é uma doença neuroimunológica rara do sistema nervoso central caracterizada por espasmos dolorosos e rigidez progressiva que envolvem os músculos proximais dos membros e axiais do tronco. A forma clássica tem início insidioso com piora gradual ao longo do tempo e muitas vezes leva à incapacidade permanente. Objetivo: Analisar os estudos publicados na literatura científica que utilizaram a reabilitação fisioterapêutica como proposta de tratamento dos sintomas motores na Síndrome da Pessoa Rígida. Método: Trata-se de uma revisão integrativa da literatura realizada no período de julho a dezembro de 2022 nas bases de dados PubMed, SciELO, LILACS e BVS. Resultados: Foram encontrados 12 artigos publicados entre o período de 2002 a 2021, que discorriam sobre o tratamento fisioterapêutico nesta população. O número escasso de estudos se dá pela raridade da patologia que dificulta a realização de ensaios clínicos robustos. Os artigos selecionados eram relatos de casos de um ou mais indivíduos, com enfoque nas intervenções realizadas de acordo com cada queixa funcional apresentada, sendo estas a dor, fraqueza muscular, hipomobilidade articular, rigidez, instabilidade postural, alterações na marcha e limitações nas atividades de vida diária. Conclusão: A reabilitação fisioterapêutica faz parte do tratamento sintomatológico e tem como finalidade, auxiliar na manutenção da funcionalidade e qualidade de vida, minimizando as repercussões motoras que são desencadeadas pela síndrome.

Introduction: Stiff Person Syndrome is a rare neuroimmunological disease of the central nervous system characterized by painful spasms and progressive rigidity involving the proximal muscles of the limbs and axial muscles of the trunk. The classic form has an insidious onset with gradual worsening over time and often leads to permanent disability. Objective: To analyze the studies published in the scientific literature that used hysiotherapeutic rehabilitation as a proposal for treating motor symptoms in Stiff Person Syndrome. Method: This is an integrative review of the literature carried out from July to December 2022 in the PubMed, SciELO, LILACS and VHL databases. Results: 12 articles published between 2002 and 2021 were found, which discussed physiotherapeutic treatment in this population. The scarce number of studies is due to the rarity of the pathology, which makes it difficult to carry out robust clinical trials. The selected articles were case reports of one or more individuals, focusing on interventions carried out according to each functional complaint presented, these being pain, muscle weakness, joint hypomobility, stiffness, postural instability, changes in gait and limitations in walking activities. daily life. Conclusion: Physiotherapy rehabilitation is part of symptomatological treatment and aims to help maintain functionality and quality of life, minimizing the motor repercussions that are triggered by the syndrome.

Experiencia en la transición de adolescentes con enfermedad neuromuscular en el Hospital Garrahan / Experience in the transition of adolescents with neuromuscular disease at Garrahan Hospital

El desarrollo de nuevos abordajes terapéuticos ha generado un aumento en la esperanza de vida de los pacientes con enfermedades neuromusculares (ENM). Se trata de un grupo de enfermedades heterogéneas desde la clínica y los posibles tratamientos. La transición en los pacientes con ENM, implica un gran desafío por presentar niveles intelectuales dentro de rangos promedio, compromisos motor, respiratorio y cardiológico progresivos que resulta en aumento de la dependencia física conforme aumenta la necesidad de autonomía emocional del adolescente. La descripción de transiciones exitosas en ENM incluye intervenciones psicosociales individuales o grupales con un enfoque multidimensional e interdisciplinario, que contemple la participación de la familia para reducir la ansiedad y la preocupación sobre sus hijos. En el Hospital Garrahan los pacientes con ENM son atendidos dentro del Programa de Atención, Docencia e Investigación de Pacientes con Enfermedad Neuromuscular desde 2008. En este trabajo nos proponemos describir la experiencia en transición pre y post pandemia, de los adolescentes con ENM en seguimiento en el Hospital de Pediatría Garrahan (AU)

The development of new care and therapeutic approaches has generated an increase in the life expectancy of patients with neuromuscular diseases (NMD), a group of heterogeneous diseases from a clinical point of view. The transition in patients with MND involves a great challenge due to progressive motor, respiratory and cardiological compromises that result in an increase in physical dependence as the adolescent needs emotional autonomy. The description of successful transitions in patients with MND includes individual and psychosocial interventions with a multidimensional and interdisciplinary approach with family participation. Since 2008, we developed a Care, Teaching and Research Program for Patients with NMD Disease at the Garrahan Hospital. The objective of this work is to describe the pre- and post-pandemic transition experience of adolescents with NMD follow-up in our hospital (AU)

Cuidados respiratorios en pacientes con atrofia muscular espinal para evitar el fallo ventilatorio agudo y la traqueostomía: revisión literaria y recomendaciones consensuadas / Respiratory care in patients with spinal muscular atrophy to avoid acute ventilatory failure and tracheostomy: literature review and consensus recommendations

La atrofia muscular espinal (AME) 5q es una de las enfermedades neuromusculares de mayor incidencia en la infancia. Sin embargo, la prevalencia de AME tipo 1, su forma más severa de presentación, es menor debido a muertes prematuras evitables antes de los dos años por insuficiencia ventilatoria subtratada. La irrupción de nuevos tratamientos modificadores de la enfermedad pueden cambiar dramáticamente este pronóstico y es una oportunidad para actualizar el manejo respiratorio, a través de cuidados estandarizados básicos, preferentemente no invasivos, abordando la debilidad de los músculos respiratorios, la insuficiencia tusígena y ventilatoria, con un enfoque preventivo. La siguiente revisión literaria entrega estrategias para evitar la intubación y la traqueostomía usando soporte ventilatorio no invasivo (SVN), reclutamiento de volumen pulmonar (RVP) y facilitación de la tos. Se analizan en detalle los protocolos de extubación en niños con AME tipo 1.

Spinal muscular atrophy (SMA) 5q is one of the neuromuscular diseases with the highest incidence in childhood. Nevertheless, the prevalence of its most severe form SMA1 is lower due to premature preventable deaths before two years of age related to ventilatory insufficiency undertreated. The emergence of new disease-modifying treatments can dramatically change this prognosis and is an opportunity to update respiratory management, through basic standardized care, mostly non-invasive, addressing respiratory muscles pump weakness, cough and ventilatory insufficiency with a preventive approach. This literature review provides consensus recommendations for strategies to avoid intubation and tracheostomy using noninvasive ventilatory support (NVS), lung volume recruitment (LVR), and cough facilitation. Extubation protocols in children with SMA type 1 are analyzed in detail.

Short-term treatment with Uncaria tomentosa aggravates the injury phenotype in mdx mice

INTRODUCTION: Uncaria tomentosa (Willd. ex Roem. & Schult.) DC. (Rubiaceae) or UT is a medicinal plant with antiviral, antimutagenic, anti-inflammatory and antioxidant properties. Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by mutations in the dystrophin gene; this deficiency leads to sarcolemma instability, inflammation, muscle degeneration and fibrosis. OBJECTIVE: Considering the importance of inflammation to dystrophy progression and the anti-inflammatory activity of UT, in the present study we evaluated whether oral administration of UT extract would ameliorate dystrophy in the mdx mice, a DMD model. METHODS: Eight-week-old male mdx mice were submitted to 200 mg/kg body weight daily UT oral administration for 6 weeks. General histopathology was analysed, and muscle tumor necrosis factor α, transforming growth factor-ß, myostatin and osteopontin transcript levels were assessed. The ability of mice to sustain limb tension to oppose their gravitational force was measured. Data were analysed with the unpaired Student's t-test. RESULTS: Morphologically, both untreated and UT-treated animals exhibited internalised nuclei, increased endomysial connective tissue and variations in muscle fibre diameters. Body weight and muscle strength were significantly reduced in the UT-treated animals. Blood creatine kinase was higher in UT-treated compared to untreated animals. In tibialis anterior, myostatin, transcript was more highly expressed in the UT-treated while in the diaphragm muscle, transforming growth factor-ß transcripts were less expressed in the UT-treated. CONCLUSION: While previous studies identified anti-inflammatory, antiproliferative and anticarcinogenic UT effects, the extract indicates worsening of dystrophic muscles phenotype after short-term treatment in mdx mice.

Ladder-based resistance training with the progression of training load altered the tibial nerve ultrastructure and muscle fiber area without altering the morphology of the postsynaptic compartment.

Scientific evidence regarding the effect of different ladder-based resistance training (LRT) protocols on the morphology of the neuromuscular system is scarce. Therefore, the present study aimed to compare the morphological response induced by different LRT protocols in the ultrastructure of the tibial nerve and morphology of the motor endplate and muscle fibers of the soleus and plantaris muscles of young adult Wistar rats. Rats were divided into groups: sedentary control (control, n = 9), a predetermined number of climbs and progressive submaximal intensity (fixed, n = 9), high-intensity and high-volume pyramidal system with a predetermined number of climbs (Pyramid, n = 9) and lrt with a high-intensity pyramidal system to exhaustion (failure, n = 9). myelinated fibers and myelin sheath thickness were statistically larger in pyramid, fixed, and failure. myelinated axons were statistically larger in pyramid than in control. schwann cell nuclei were statistically larger in pyramid, fixed, and failure. microtubules and neurofilaments were greater in pyramid than in control. morphological analysis of the postsynaptic component of the plantar and soleus muscles did not indicate any significant difference. for plantaris, the type i myofibers were statistically larger in the pyramid and fixed compared to control. the pyramid, fixed, and failure groups for type ii myofibers had larger csa than control. for soleus, the type i myofibers were statistically larger in the pyramid than in control. pyramid and fixed had larger csa for type ii myofibers than control and failure. the pyramid and fixed groups showed greater mass progression delta than the failure. We concluded that the LRT protocols with greater volume and progression of accumulated mass elicit more significant changes in the ultrastructure of the tibial nerve and muscle hypertrophy without endplate changes.

The Cloning and Characterization of a Three-Finger Toxin Homolog (NXH8) from the Coralsnake Micrurus corallinus That Interacts with Skeletal Muscle Nicotinic Acetylcholine Receptors.

Coralsnakes (Micrurus spp.) are the only elapids found throughout the Americas. They are recognized for their highly neurotoxic venom, which is comprised of a wide variety of toxins, including the stable, low-mass toxins known as three-finger toxins (3FTx). Due to difficulties in venom extraction and availability, research on coralsnake venoms is still very limited when compared to that of other Elapidae snakes like cobras, kraits, and mambas. In this study, two previously described 3FTx from the venom of M. corallinus, NXH1 (3SOC1_MICCO), and NXH8 (3NO48_MICCO) were characterized. Using in silico, in vitro, and ex vivo experiments, the biological activities of these toxins were predicted and evaluated. The results showed that only NXH8 was capable of binding to skeletal muscle cells and modulating the activity of nAChRs in nerve-diaphragm preparations. These effects were antagonized by anti-rNXH8 or antielapidic sera. Sequence analysis revealed that the NXH1 toxin possesses eight cysteine residues and four disulfide bonds, while the NXH8 toxin has a primary structure similar to that of non-conventional 3FTx, with an additional disulfide bond on the first loop. These findings add more information related to the structural diversity present within the 3FTx class, while expanding our understanding of the mechanisms of the toxicity of this coralsnake venom and opening new perspectives for developing more effective therapeutic interventions.

Quantitative ultrasonography reveals skeletal muscle abnormalities in carriers of DMD pathogenic variants.

INTRODUCTION/AIMS: Carriers of DMD pathogenic variants may become symptomatic and develop muscle-related manifestations. Despite that, few studies have attempted to characterize changes in the muscles of these carriers using imaging tools, particularly muscle ultrasound (MUS). The aim of this study was to compare lower limb MUS findings in carriers of DMD pathogenic variants (cDMD) vs healthy controls. METHODS: Twenty-eight women (15 cDMD and 13 controls) underwent clinical evaluation and MUS. We collected information about muscle-related symptoms and assessed muscle strength. MUS was performed by a single physician (blind to the genetic status of subjects). The following muscles were assessed: rectus femoris, sartorius, tibialis anterior, and medial gastrocnemius. For each site, we computed data on muscle thickness, cross-sectional area, sound attenuation index, and elastography. Between-group comparisons were assessed using nonparametric tests and p-values <.05 were deemed significant. RESULTS: None of the subjects had objective muscle weakness, but exercise intolerance/fatigue was reported by four cDMDs and only one control. Regarding MUS, sound attenuation indices were significantly higher among carriers for all muscles tested. Longitudinal and axial deep echo intensities for the rectus femoris and tibialis anterior were also higher in the cDMD group compared with controls. No significant between-group differences were noted for elastography values, muscle area, or mean echo intensities. DISCUSSION: cDMD have skeletal muscle abnormalities that can be detected using quantitative MUS. Further studies are needed to determine whether such abnormalities are related to muscle symptoms in these patients.

Guillain-Barré syndrome and checkpoint inhibitor therapy: insights from pharmacovigilance data.

Background There are increasing reports of cases of Guillain-Barré syndrome (GBS), as an adverse event of an immune checkpoint inhibitor (ICI) but postmarket data on the incidence of this remains scarce. This study sought to conduct a comprehensive review of GBS events arising as a secondary outcome of ICI treatments in real-world patients, using the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods Data covering the period from the third quarter of 2003 to the second quarter of 2023 were extracted from the FAERS database. GBS cases (associated with the usage of avelumab, atezolizumab, ipilimumab, nivolumab and pembrolizumab) were subjected to disproportionality analysis to detect potential signals. Results A total of 2208 reports of GBS were identified within the FAERS database, with 242 of these cases (10.9%) being associated with ICIs. All five drugs exhibited a disproportionality in the reporting of adverse events, with the highest observed for avelumab (reporting OR, ROR: 29.8), followed by atezolizumab (ROR: 17.0), ipilimumab (ROR: 16.0), pembrolizumab (ROR: 11.9) and nivolumab (ROR: 8.2). Conclusion These checkpoint inhibitors are associated with a statistically significant disproportionate number of reports of GBS as an adverse event, with avelumab being the ICI with the highest association. The present pharmacovigilance study serves as a valuable tool, offering a more comprehensive and nuanced perspective on GBS associated with ICIs. This study contributes to a deeper comprehension of this rare adverse drug effect.

Clinical and Genetic Aspects of Juvenile Amyotrophic Lateral Sclerosis: A Promising Era Emerges.

Juvenile Amyotrophic Lateral Sclerosis is a genetically heterogeneous neurodegenerative disorder, which is frequently misdiagnosed due to low clinical suspicion and little knowledge about disease characteristics. More than 20 different genetic loci have been associated with both sporadic and familial juvenile Amyotrophic Lateral Sclerosis. Currently, almost 40% of cases have an identifiable monogenic basis; type 6, associated with FUS gene variants, is the most prevalent globally. Despite several upper motor neuron-dominant forms being generally associated with long-standing motor symptoms and slowly progressive course, certain subtypes with lower motor neuron-dominant features and early bulbar compromise lead to rapidly progressive motor handicap. For some monogenic forms, there is a well-established genotypic-phenotypic correlation. There are no specific biochemical and neuroimaging biomarkers for the diagnosis of juvenile Amyotrophic Lateral Sclerosis. There are several inherited neurodegenerative and neurometabolic disorders which can lead to the signs of motor neuron impairment. This review emphasizes the importance of high clinical suspicion, assessment, and proper diagnostic work-up for juvenile Amyotrophic Lateral Sclerosis.

Does Grappling Combat Sports Experience Influence Exercise Tolerance of Handgrip Muscles in the Severe-Intensity Domain?

Successful performance in grappling combat sports (GCS) can be influenced by the fighter's capacity to sustain high-intensity contractions of the handgrip muscles during combat. This study investigated the influence of GCS experience on the critical torque (CT), impulse above CT (W'), tolerance, and neuromuscular fatigue development during severe-intensity handgrip exercise by comparing fighters and untrained individuals. Eleven GCS fighters and twelve untrained individuals participated in three experimental sessions for handgrip muscles: (1) familiarization with the experimental procedures and strength assessment; (2) an all-out test to determine CT and W'; and (3) intermittent exercise performed in the severe-intensity domain (CT + 15%) until task failure. No significant differences were found in CT and neuromuscular fatigue between groups (p > 0.05). However, GCS fighters showed greater W' (GCS fighters 2238.8 ± 581.2 N·m·s vs. untrained 1670.4 ± 680.6 N·m·s, p < 0.05) and exercise tolerance (GCS fighters 8.38 ± 2.93 min vs. untrained 5.36 ± 1.42 min, p < 0.05) than untrained individuals. These results suggest that long-term GCS sports training can promote increased tolerance to severe-intensity handgrip exercise and improved W' without changes in CT or the magnitude of neuromuscular fatigue.

Efficiency of pulsed electromagnetic field and neuromuscular electrical stimulation on painful shoulder following stroke / Eficiência do campo eletromagnético pulsado e da estimulação elétrica neuromuscular em ombro doloroso após acidente vascular cerebral

INTRODUCTION: Shoulder pain after stroke, a complication with a prevalence of up to 16­84% usually occurs after 2­3 months and leads to patients withdrawing from rehabilitation programs, staying in the hospital longer, having less limb function and having a great negative impact on their quality of life. The aim of the present study was to determine the effect of PEMF and NMES in reducing shoulder pain in patients with stroke. MATERIAL AND METHODS: A prospective, randomized controlled trial included 51 patients with shoulder pain following stroke. The patients were randomly assigned to three groups (17 people in each group): Pulsed Electromagnetic Field (PEMF), Neuromuscular Electrical Stimulation (NMES) and Control group. The outcome measures were Visual Analogue Scale (VAS), Modified Ashworth Scale (MAS) and Fugl Meyer Assessment­Upper Extremity (FMA-UE), Active and Passive Range of Motion (AROM/PROM) assessed at the baseline, six weeks into the intervention, and one week into the follow-up. RESULTS: VAS score for pain showed a mean change of 1.60, 1.60 and 4.94 in PEMF, NMES, and control respectively after 20 sessions. It showed pain was significantly improved in all the groups (p<0.001), but the effectiveness of the PEMF and NMES groups was superior to the control group. CONCLUSION: The current literature showed that PEMF & NMES are effective in improving post-stroke shoulder pain, spasticity, range of motion and motor function and a novel method for stroke patients undergoing rehabilitation.

INTRODUÇÃO: Dor no ombro após acidente vascular cerebral com prevalência de 16­84% geralmente ocorre após 2­3 meses e pode resultar na suspensão de programas de reabilitação, internações hospitalares mais longas e redução da função dos membros, prejudicando qualidade de vida dos pacientes com AVC. O objetivo do presente estudo foi determinar o efeito da PEMF e da EENM na redução da dor no ombro em pacientes com acidente vascular cerebral. MATERIAL E MÉTODOS: Um estudo prospectivo, randomizado e controlado incluiu 51 pacientes com dor no ombro pós-AVC. Os pacientes foram divididos aleatoriamente em três grupos (17 pessoas em cada grupo): grupo Campo Eletromagnético Pulsado (PEMF), grupo Estimulação Elétrica Neuromuscular (EENM) e grupo Controle. As medidas de resultados foram na Escala Visual Analógica (VAS), Escala de Ashworth Modificada (MAS) e Avaliação de Fugl Meyer ­ Extremidade Superior (FMA-UE), Amplitude de Movimento (AROM/PROM) foram avaliadas no início do estudo, após seis semanas de tratamento, e após um acompanhamento semanal. RESULTADOS: A pontuação VAS para dor mostrada uma alteração média de 1,60, 1,60 e 4,94 na PEMF, EENM e Controle, respectivamente, após 20 sessões. Mostrou melhora significativa entre os três grupos (p<0,001), mas a eficácia do grupo PEMF e EENM foi superior ao grupo Controle. CONCLUSÃO: O presente estudo mostrou que PEMF e EENM são eficazes na melhora da dor no ombro pós-AVC, espasticidade, amplitude de movimento e função motora e um novo método para pacientes com AVC em reabilitação. Nossas descobertas indicam que a eficácia da EENM é claramente superior à do PEMF na manutenção da analgesia a longo prazo.