Effects of Hyperkinetic,a β Subunit of Shaker Voltage-Dependent K+ Channels,on the Oxidation State of Presynaptic Nerve Terminals

The Drosophila Hyperkinetic (Hk) gene encodes a β subunit of Shaker (Sh) K⁺ channels and shows high sequence homology to aldoketoreductase. Hk mutations are known to modify the voltage dependence and kinetics of Sh currents, which are also influenced by the oxidative state of the N-terminus region of the Sh channel, as demonstrated in heterologous expression experiments in frog oocytes. However, an in vivo role of Hk in cellular reduction/oxidation (redox) has not been demonstrated. By using a fluorescent indicator of reactive oxygen species (ROS), dihydrorhodamine-123 (DHR), we show that the presynaptic nerve terminal of larval motor axons is metabolically active, with more rapid accumulation of ROS in comparison with muscle cells. In Hk terminals, DHR fluorescence was greatly enhanced, indicating increased ROS levels. This observation implicates a role of the Hk β subunit in redox regulation in presynaptic terminals. This phenomenon was paralleled by the expected effects of the mutations affecting glutathione S-transferase S1 as well as applying H₂O₂ to wild-type synaptic terminals. Thus, our results also establish DHR as a useful tool for detecting ROS levels in the Drosophila neuromuscular junction.     

Multiple Selectin Blockade With a Small-Molecule Selectin Inhibitor Does Not Affect Survival After a Second Inflammatory Challenge With Nonlethal LPS

The effects of anti-adhesion molecule antibodies on the blockade of leukocyte-endothelial interactions have the potential of decreasing survival through possibly increased infection vulnerability. The aim of this study was to determine the effect of a small-molecule selectin inhibitor (TBC-1269) on both liver response and survival to a nonlethal lipopolysaccharide (LPS) challenge after hemorrhagic shock. Ninety-six Sprague-Dawley rats were subjected to a model of uncontrolled hemorrhagic shock. Six groups of animals were included in this study ( n = 16 per group): sham/saline, sham/LPS, shock/saline, shock/LPS, shock/TBC1269, and shock/TBC-1269/LPS. Experimental design consisted of the development of hemorrhagick shock (3 mL/100 g) in a 15-min period, tail amputation and drug administration at 30 min, and subsequent resuscitation to maintain mean arterial pressure at 70mm Hg. A septic challenge was produced with 0.1 mg/kg of LPS ( Escherichia coli type 78H4086; Sigma Chemical, St. Louis, MO) given intravenously via penile vein at 20 h. Liver injury tests (alanine aminotransferase, ALT), liver myeloperoxidase, liver histology, and 21-day survival were evaluated. Statistical analysis included the Bartlett test for equality of variance, a two-way analysis of variance (ANOVA), and overall followed by pairwise log-rank test for survival. Significant improvements in liver function and histology were observed in animals treated with TBC-1269 with or without a nonlethal septic challenge. Neutrophil infiltration, as evidenced by liver myeloperoxidase (MPO) was significantly decreased in animals treated with TBC-1269 alone and those having LPS administration after TBC-1269 treatment. We conclude that TBC-1269, multisectin blocker, was effective in reducing liver damage even with the addition of a second inflammatory insult as the nonlethal LPS challenge used in this study.     

Improved postural control in response to a 4-week balance training with partially unloaded bodyweight

Balance training (BT) is successfully implemented in therapy as a countermeasure against postural dysfunctions. However, patients suffering from motor impairments may not be able to perform balance rehabilitation with full body load. The purpose of this study was to investigate whether partial unloading leads to the same functional and neuromuscular adaptations. The impact on postural control of a 4-week BT intervention has been compared between full and partial body load.32 subjects were randomly assigned to a CON (conventional BT) or a PART group (partially unloaded BT). BT comprised balance exercises addressing dynamic stabilization in mono- and bipedal stance. Before and after training, centre of pressure (COP) displacement and electromyographic activity of selected muscles were monitored during different balance tasks. Co-contraction index (CCI) of soleus (SOL)/tibialis (TA) was calculated. SOL H-reflexes were elicited to evaluate changes in the excitability of the spinal reflex circuitry.Adaptations in response to the training were in a similar extent for both groups: (i) after the intervention, the COP displacement was reduced (P < 0.05). This reduction was accompanied by (ii) a decreased CCI of SOL/TA (P < 0.05) and (iii) a decrease in H-reflex amplitude (P < 0.05).BT under partial unloading led to reduced COP displacements comparable to conventional BT indicating improved balance control. Moreover, decreased co-contraction of antagonistic muscles and reduced spinal excitability of the SOL motoneuron pool point towards changed postural control strategies generally observed after full body load training. Thus, BT considering partial unloading is an appropriate alternative for patients unable to conduct BT under full body load.     

Skeletal muscle ultrasound

Abstract

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Muscle ultrasound is a convenient technique to visualize normal and pathological muscle tissue as it is non-invasive and real-time. Neuromuscular disorders give rise to structural muscle changes that can be visualized with ultrasound: atrophy can be objectified by measuring muscle thickness, while infiltration of fat and fibrous tissue increases muscle echo intensity, i.e. the muscles become whiter on the ultrasound image. Muscle echo intensity needs to be quantified to correct for age-related increase in echo intensity and differences between individual muscles. This can be done by gray scale analysis, a method that can be easily applied in daily clinical practice. Using this technique, it is possible to detect neuromuscular disorders with predictive values of 90%. Only in young children and metabolic myopathies the sensitivity is lower. Ultrasound is a dynamic technique and therefore capable of visualizing normal and pathological muscle movements. Fasciculations can easily be differentiated from other muscle movements. Ultrasound appeared to be even more sensitive in detecting fasciculations compared to Electromyography (EMG) and clinical observations, because it can visualize a large muscle area and deeper located muscles. With improving resolution and frame rate it has recently become clear that also smaller scale spontaneous muscle activity such as fibrillations can be detected by ultrasound. This opens the way to a broader use of muscle ultrasound in the diagnosis of peripheral nerve and muscle disorders.     

Is Going Beyond Rasch Analysis Necessary to Assess the Construct Validity of a Motor Function Scale?

Objective

To examine whether a Rasch analysis is sufficient to establish the construct validity of the Motor Function Measure (MFM) and discuss whether weighting the MFM item scores would improve the MFM construct validity.

神经肌肉电刺激治疗脑卒中后吞咽障碍临床疗效的Meta分析

目的 评价神经肌肉电刺激治疗脑卒中后吞咽障碍的疗效,为临床治疗和进一步研究提供参考依据。 方法 计算机检索Cochrane library、Pubmed、Embase、CINAHL、Pro Quest、Psyc ARTICLES、中国知网数据库、中国生物医学文献数据库、维普中文科技期刊全文数据库、万方数据库中有关神经肌肉电刺激治疗脑卒中后吞咽障碍临床疗效的随机对照试验文献,同时筛检纳入文献的参考文献,检索时限为建库至2017年7月30日。由2名研究员按照纳入和排除标准筛选文献、评价质量、提取资料和合并数据,采用RevMan 5.3版软件对文献进行Meta分析。 结果 共纳入11篇随机对照试验文献,共计576例患者。Meta分析结果表明,在有效性上,神经肌肉电刺激联合吞咽训练的疗效优于单纯的吞咽训练,差异具有统计学意义(P<0.01),但并不能缩短咽传递时间(P>0.05);在安全性上,神经肌肉电刺激联合吞咽训练可降低发生误吸的风险,差异具有统计学意义(P<0.01);且神经肌肉电刺激联合吞咽训练可改善生活质量（P<0.01）。 结论 神经肌肉电刺激联合吞咽训练可改善脑卒中后吞咽障碍患者的吞咽功能和生活质量,并降低发生误吸的风险,且目前尚无证据表明神经肌肉电刺激联合吞咽训练可缩短咽传递时间。     

The effect of acute alloxan diabetes on the sensitivity of the rat skeletal neuromuscular junction to drugs

Summary Preparations from alloxan diabetic rats showed a reduced sensitivity to the neuromuscular blocking action of (+)-tubocurarine but no alteration in sensitivity to the deplolarizing neuromuscular blocking drug decamethonium. Physostigmine was less effective in augmenting twitch height in preparations from alloxan diabetic rats and such preparations had a significantly lowered total cholinesterase activity compared with control preparations. An additional observation was a reduction in the effectiveness of the pre-junctionally active agent β-bungarotoxin in producing neuromuscular blockade in physostigmine-treated preparations from alloxan diabetic rats. All the changes produced by alloxan administration were prevented by treatment with insulin.     

Athletes with an ACL reconstruction show a different neuromuscular response to environmental challenges compared to uninjured athletes

BackgroundEvidence suggests that neuromuscular alterations in patients with an anterior cruciate ligament reconstruction (ACLR) are rooted in neurocognitive and proprioceptive deficits. The aim of this study was to assess neuromuscular control of athletes with ACLR under increased cognitive and environmental challenges.Research questionDo athletes with ACLR show a different neuromuscular response to cognitive and environmental challenges relative to controls?MethodsCross-sectional study. Twenty athletes who had an ACLR (age: 23.7 ± 4.3 years, 14 males, time post-surgery: 258.6 ± 54 days) and twenty uninjured controls (age: 21.4 ± 1.5 years, 14 males) performed a stepping down-task in four environmental conditions: no additional challenges, while performing a cognitive dual-task, while undergoing an unpredictable support surface perturbation, and with the cognitive dual-task and unpredictable perturbation combined. Muscle activations of the vastus medialis (VM), vastus lateralis, hamstrings medialis (HM), hamstrings lateralis (HL), gastrocnemius medialis, gastrocnemius lateralis (GL) and gluteus medius were recorded with surface EMG. A three-way ANOVA with main effects for group, dual-task and perturbation was used to compare muscle activations.ResultsAthletes with ACLR show larger HM (ES = 0.45) and HL activation (ES = 1.32) and lower VM activation (ES = 0.72), compared to controls.Athletes with ACLR show a significantly smaller increase in VM (ES = 0.69), VL (ES = 0.53) and GL activation (ES = 0.52) between perturbed and unperturbed tasks compared to controls. Furthermore, under cognitive loading a significantly larger decrease in HM activation (ES = 0.40) and (medial) co-contraction (ES = 0.75) was found in athletes with ACLR compared to controls.SignificanceAthletes with ACLR show an altered neuromuscular response which might represent an arthrogenic muscle response. They show less additional adaptation to perturbed tasks compared to controls, potentially as result of altered proprioceptive input. Furthermore a larger influence of increased cognitive loading on the neuromuscular control was found in athletes with ACLR, indicating that also neurocognitive limitations may contribute to altered neuromuscular control.