Muscle-Specific Tyrosine Kinase-Associated Myasthenia Gravis: A Neuromuscular Surprise

Myasthenia gravis is a neuromuscular autoimmune disease that results in skeletal muscle weakness that worsens after periods of activity and improves after rest. Myasthenia gravis means “grave (serious), muscle weakness.” Although not completely curable, it can be managed well with a relatively high quality of life and expectancy. In myasthenia gravis, antibodies against the acetylcholine receptors at the neuromuscular junction interfere with regular muscular contraction. Although most commonly caused by antibodies to the acetylcholine receptor, antibodies against MuSK (muscle-specific kinase) protein can also weaken transmission at the neuromuscular junction. Muscle-specific tyrosine kinase myasthenia gravis (MuSK-Ab MG) is a rare subtype of myasthenia gravis with distinct pathogenesis and unique clinical features. Diagnosis can be challenging due to its atypical presentation as compared to seropositive myasthenia gravis. It responds inconsistently to steroids, but plasma exchange and immunosuppressive therapies have shown promising results. We report a case of a 49-year-old female who presented with acute hypoxic respiratory failure. Our patient experienced progressive, undiagnosed MuSK-Ab MG for years without a diagnosis.

Simple and efficient differentiation of human iPSCs into contractible skeletal muscles for muscular disease modeling

Pathophysiological analysis and drug discovery targeting human diseases require disease models that suitably recapitulate patients pathology. Disease-specific human induced pluripotent stem cells (hiPSCs) can potentially recapitulate disease pathology more accurately than existing disease models when differentiated into affected cell types. Thus, successful modeling of muscular diseases requires efficient differentiation of hiPSCs into skeletal muscles. hiPSCs transduced with doxycycline-inducible MYOD1 (MYOD1-hiPSCs) have been widely used; however, they require time- and labor-consuming clonal selection procedures, and clonal variations must be overcome. Moreover, their functionality to exhibit muscular contraction has never been reported. Here, we demonstrated that bulk MYOD1-hiPSCs established with puromycin selection, but not with G418 selection, showed high differentiation efficiency, generating more than 80% Myogenin (MyoG)+ and Myosin heavy chain (MHC)+ muscle cells within seven days. Interestingly, bulk MYOD1-hiPSCs exhibited average differentiation properties compared with those of clonally established MYOD1-hiPSCs, suggesting that the bulk method may minimize the effects of clonal variations. Finally, three-dimensional muscle tissues were fabricated from bulk MYOD1-hiPSCs, which exhibited contractile force upon electrical pulse stimulation, indicating their functionality. Together, the findings indicate that our bulk differentiation requires less time and labor than existing methods, efficiently generates contractible skeletal muscles, and facilitates the generation of muscular disease models.

Comparative Analysis of Intellectual Methods for Muscular Contraction Interpretation for Gesture Interface Implementation

The paper considers comparative analysis results of the machine learning methods used for the gesture recognition based on the surface single-channel electromyography (sEMG) data. The data were processed using multilayer perceptron, support vector machine, decision tree ensemble (Random Forest) and logistic regression for the chosen four gesture types. The conclusion was derived on the analysis efficiency of these methods using commonly recommended accuracy metrics.

Acupuncture E_cacy Study Using Electromyographic Signals

Acupuncture is a centuries-old therapeutic technique. However, because of the large number of complicating circumstances, it has been difficult to clearly prove the treatment's therapeutic effectiveness.As a result, acupuncture has failed to acquire acceptance in the mainstream clinical sector. An electromyography (EMG) sensor was built and used to test the efficacy of acupuncture in alleviating muscular stiffness in this study. Electrodes, differential and inverting amplifiers, filters, and a full-wave rectifier made up the EMG circuit. The output of the circuit was sent to a microcontroller for analog-to-digital transformation in order to perform data acquisition. Acupuncture was used to treat four participants who had muscular dysfunction in various regions of their bodies in our case study. Before and after the therapy, EMG signals at the damaged regions were recorded. The findings revealed that the therapy had no immediate conceivable impact on the patients, since the levels of muscular contraction before and after the treatment were comparable. When the EMG signals were measured 30 minutes after the therapy, signs of muscular alleviation were found. This shows that acupuncture does supply patients with beneficial medicine, although slowly. The act of placing the highly conducting needles into the acupuncture sites, we believe, is similar to connecting a parallel wire to a circuit, resulting in a short-circuited route at the meridian. It permits the meridian's polarized in- ner energy, or qi, to pass through. The equilibrium in qi regulation can therefore be restored by unclogging the ow of qi.The repair process is relatively slow, and the treatment impact may not be immediately apparent, because the consti- tutive qualities at the acupuncture points where the needles are pricked may not alter quickly.

Cost variation analysis of different brands of oral anti-epileptic drugs available in India

Background: Epilepsy is a group of neurological disorders, characterized by seizures, loss of consciousness, muscular contraction. Prevalence of epilepsy in India is about 1%. High medical care cost should be cause of concern for policy makers and service providers. Hence, a study was planned to analyse cost ratio and percentage cost variations of oral antiepileptic drugs available in India.Methods: An analytical study with maximum and minimum price of 10 tablets/capsules and syrup of one bottle of available strength of each drug was noted in Indian Rupee, using “Current Index of Medical Specialties” July to October 2020; “Drug Today” July To October 2020 volume-1 and “Indian Drug Review” 2020 volume-26 issue 6. Percentage cost variation and cost ratio for individual drugs was compared.Results: Significant cost variations were found in different brands of same drug. Among established oral antiepileptic drugs, Divalproex sodium 250 mg has highest cost ratio 16.071 and 1507.14% price variation and Clonazepam 0.25 mg with cost ratio 16.005 and 1500.55% price variation. Diazepam 2 mg has lowest cost ratio 1.024 and 2.43% price variation. Among newer oral antiepileptic drugs, Levetiracetam 500 mg has highest cost ratio 66.389 and 6538.93% price variation; least is Oxcarbazepine 450 mg with cost ratio 1.317 and 31.75% price variation.Conclusions: Epilepsy has long course of treatment. Increased adherence to treatment is achieved by switching to cost-effective therapy and by making Pharmacoeconomics an integral part of Undergraduate and Postgraduate Curriculum.

Contraction-dependent intracortical inhibition supports gravity-efficient motor control

Efficient control of voluntary movements along the gravity axis requires adapted shifts in muscular contraction modes. In daily life, rising the arm up involves shortening (i.e., concentric) contractions of arm flexors, while the reverse movement can rely on lengthening (i.e., eccentric) contractions of the same muscles with the help of gravity force. Although this muscular-control mode is universal, the neuromuscular mechanisms that subserve the control of such gravity-oriented movements remain unknown. In this study, we designed two neurophysiological experiments that allowed tracking modulations of cortical, spinal, and muscular outputs of arm flexors while healthy humans carried out vertical pointing movements. In conditions where upward and downward movements revealed kinematic features reminiscent of optimal motor commands (i.e., directional asymmetries), we report fine contraction-dependent modulations of the corticospinal output. The overall corticospinal excitability dropped during lengthening contractions (downward movements) compared with shortening contractions (upward movements). Specifically, we did not observe any change in spinal motoneuron responsiveness from cervicomedullary stimulations but a specific increase in intracortical inhibition during lengthening vs. shortening contractions. We discuss these fine contraction-dependent modulations of the supraspinal motor output in the light of feedforward mechanisms that may support gravity-tuned motor control. Generally, these results shed a new perspective on the neural policy that optimize movement control along the gravity axis.

Targeted neuromodulation of pelvic floor nerves in aging and multiparous rabbits improves continence

Pelvic floor muscle stretch injury during pregnancy and birth is associated with the incidence of stress urinary incontinence (SUI), a condition that affects 30–60% of the female population and is characterized by involuntary urine leakage during physical activity, further exacerbated by aging. Aging and multiparous rabbits suffer pelvic nerve and muscle damage, resulting in alterations in pelvic floor muscular contraction and low urethral pressure, resembling SUI. However, the extent of nerve injury is not fully understood. Here, we used electron microscopy analysis of pelvic and perineal nerves in multiparous rabbits to describe the extent of stretch nerve injury based on axon count, axon size, myelin-to-axon ratio, and elliptical ratio. Compared to young nulliparous controls, mid-age multiparous animals showed an increase in the density of unmyelinated axons and in myelin thickness in both nerves, albeit more significant in the bulbospongiosus nerve. This revealed a partial but sustained damage to these nerves, and the presence of some regenerated axons. Additionally, we tested whether electrical stimulation of the bulbospongiosus nerve would induce muscle contraction and urethral closure. Using a miniature wireless stimulator implanted on this perineal nerve in young nulliparous and middle age multiparous female rabbits, we confirmed that these partially damaged nerves can be acutely depolarized, either at low (2–5 Hz) or medium (10–20 Hz) frequencies, to induce a proportional increase in urethral pressure. Evaluation of micturition volume in the mid-age multiparous animals after perineal nerve stimulation, effectively reversed a baseline deficit, increasing it 2-fold (p = 0.02). These results support the notion that selective neuromodulation of pelvic floor muscles might serve as a potential treatment for SUI.

Acute effects of plyometric warm-up with different box heights on sprint and agility performance in national-level field hockey athletes

BACKGROUND: Postactivation potentiation (PAP) is an acute and temporary enhancement of muscular performance resulting from previous muscular contraction. Extensive research exists examining the PAP effect after a heavy resistance exercise but there is limited research examining the PAP effect after a plyometric stimulus to the pre-competition practices (e.g., warm-up) of well-trained athletes. OBJECTIVE: The purpose of this study was to investigate the acute effects of plyometric warm-up with different box heights on sprint and agility performance in national-level field hockey athletes at recovery time of immediately, 5 minutes and 10 minutes. METHODS: In a randomized crossover design, ten male national-level field hockey athletes performed 30-m sprint (with 10-m split) and agility test at baseline, immediately (∼ 15 sec), 5 minutes and 10 minutes after a high-intensity plyometric warm-up (HIPW), a low-intensity plyometric warm-up (LIPW) and a control trial (CT). RESULTS: Mean 10-m sprint times, 30-m sprint times and agility times were similar between trials at baseline (p> 0.05). Significant trial x time interactions (p⩽ 0.05) were observed for 10-m sprint time, 30-m sprint time and agility time. 10-m sprint times were significantly decreased after HIPW at all time-points and LIPW at immediately time-point, relative to baseline (p⩽ 0.05). HIPW 10-m sprint times were faster at all time-points and LIPW sprint time was faster at 10 minutes when compared with CT (p⩽ 0.05). Thirty-meter sprint times were significantly decreased after HIPW and LIPW at all time-points, relative to baseline (p⩽ 0.05). HIPW 30-m sprint times at all time-points and LIPW at both the 5 and 10 minute time-points were faster than CT (p⩽ 0.05). Agility times were significantly decreased after HIPW at all time-points and LIPW at both the immediately and 5 minutes time-points, relative to baseline (p⩽ 0.05). HIPW and LIPW agility times were faster than CT, at all time-points (p⩽ 0.05). CONCLUSIONS: Both HIPW and LIPW may be effective in enhancing the pre-training or pre-competition practices in off-season for national-level field hockey athletes. However, the individualization of HIPW is highly recommended in order to maintain PAP effects for 10-m sprint times, 30-m sprint times and agility times throughout the 10 minutes when compared to LIPW.

Wearable nanocomposite kinesiology tape for distributed muscle engagement monitoring

Sports coaches help athletes develop and improve their skills by assessing their ability to perform motion primitives that make up functional sports tasks. Sports coaching today is mostly done visually, which demands constant attention and can be imprecise. While sensors like electronic textiles and surface electromyography can measure muscle engagement, they are susceptible to movement artifacts and noise due to surface electrode issues. Therefore, the work reported here focuses on our development of self-adhesive, fabric-based sensors that can be directly affixed onto skin for monitoring skin-strains and distributed muscular engagement during functional movements. The vision is that these sensors can be readily used by sports coaches and individuals to better assess motion primitives and the execution of sports tasks. The approach integrates piezoresistive graphene nanosheet thin films with kinesiology tape (K-Tape). Because every location of the film is responsive to strains, electrodes can also be judiciously placed along the nanocomposite for distributed strain sensing. Nanocomposite or “Smart K-Tape” sensors were fabricated, and electromechanical tests were conducted to characterize their tensile, compressive, and cyclic sensing properties. Upon confirming their linearity, repeatability, stability, and high sensitivity, individuals wore Smart K-Tape sensors over different muscle groups as they performed prescribed exercise and stretching movements. The Smart K-Tapes outputted unique waveforms that revealed the speed and duration of muscular engagement through movement sequences. Furthermore, the region of muscular contraction could also be localized using each Smart K-Tape as a distributed strain sensor, which demonstrated promise as a convenient and quantitative motion primitive assessment tool relevant for sports coaching and athletic skills development.