Two forms of short-interval intracortical inhibition in human motor cortex

BackgroundPulses of transcranial magnetic stimulation (TMS) with a predominantly anterior-posterior (AP) or posterior-anterior (PA) current direction over the primary motor cortex appear to activate distinct excitatory inputs to corticospinal neurons. In contrast, very few reports have examined whether the inhibitory neurons responsible for short-interval intracortical inhibition (SICI) are sensitive to TMS current direction.ObjectivesTo investigate whether SICI evaluated with AP and PA conditioning stimuli (CS_PA and CS_AP) activate different inhibitory pathways. SICI was always assessed using a PA-oriented test stimulus (TS_PA).MethodsUsing two superimposed TMS coils, CS_PA and CS_AP were applied at interstimulus intervals (ISI) of 1–5 ms before a TS_PA, and at a range of different intensities. Using a triple stimulation design, we then tested whether SICI at ISI of 3 ms using opposite directions of CS (SICI_CSPA3 and SICI_CSAP3) interacted differently with three other forms of inhibition, including SICI at ISI of 2 ms (SICI_CSPA2), cerebellum-motor cortex inhibition (CBI 5 ms) and short-latency afferent inhibition (SAI 22 ms). Finally, we compared the effect of tonic and phasic voluntary contraction on SICI_CSPA3 and SICI_CSAP3.ResultsCS_AP produced little SICI at ISIs = 1 and 2 ms. However, at ISI = 3 ms, both CS_AP and CS_PA were equally effective at the same percent of maximum stimulator output. Despite this apparent similarity, combining SICI_CSPA3 or SICI_CSAP3 with other forms of inhibition led to quite different results: SICI_CSPA3 interacted in complex ways with CBI, SAI and SICI_CSPA2, whereas the effect of SICI_CSAP3 appeared to be quite independent of them. Although SICI_CSPA and SICI_CSAP were both reduced by the same amount during voluntary tonic contraction compared with rest, in a simple reaction time task SICI_CSAP was disinhibited much earlier following the imperative signal than SICI_CSPA.ConclusionsSICI_CSPA appears to activate a different inhibitory pathway to that activated by SICI_CSAP. The difference is behaviourally relevant since the pathways are controlled differently during volitional contraction. The results may explain some previous pathological data and open the possibility of testing whether these pathways are differentially recruited in a range of tasks.     

Thalamic deep brain stimulation for Tourette Syndrome: A naturalistic trial with brief randomized,double-blinded sham-controlled periods

BackgroundThere is still a lack of controlled studies to prove efficacy of thalamic deep brain stimulation for Tourette's Syndrome.ObjectivesIn this controlled trial, we investigated the course of tic severity, comorbidities and quality of life during thalamic stimulation and whether changes in tic severity can be assigned to ongoing compared to sham stimulation.MethodsWe included eight adult patients with medically refractory Tourette's syndrome. Bilateral electrodes were implanted in the centromedian-parafascicular-complex and the nucleus ventro-oralis internus. Tic severity, quality of life and comorbidities were assessed before surgery as well as six and twelve months after. Short randomized, double-blinded sham-controlled crossover sequences with either active or sham stimulation were implemented at both six- and twelve-months’ assessments. The primary outcome measurement was the difference in the Yale Global Tic Severity Scale tic score between active and sham stimulation. Adverse events were systematically surveyed for all patients to evaluate safety.ResultsActive stimulation resulted in significantly higher tic reductions than sham stimulation (F = 79.5; p = 0.001). Overall quality of life and comorbidities improved significantly in the open-label-phase. Over the course of the trial two severe adverse events occurred that were resolved without sequelae.ConclusionOur results provide evidence that thalamic stimulation is effective in improving tic severity and overall quality of life. Crucially, the reduction of tic severity was primarily driven by active stimulation. Further research may focus on improving stimulation protocols and refining patient selection to improve efficacy and safety of deep brain stimulation for Tourette's Syndrome.     

Difference in background factors between responders to gabapentin enacarbil treatment and responders to placebo: pooled analyses of two randomized,double-blind,placebo-controlled studies in Japanese patients with restless legs syndrome

ObjectiveRestless legs syndrome (RLS) is a sensorimotor disorder that is characterized by uncomfortable and unpleasant sensations mainly in the legs. Two placebo-controlled studies (Phase II/III and post-marketing) in Japanese patients with RLS failed to demonstrate the efficacy of gabapentin enacarbil (GE) 600 mg in the change from baseline in International Restless Legs Syndrome Rating Scale (IRLS) score at the end of the treatment period. The high response to placebo is thought to be a possible reason why the post-marketing study failed. The objectives of these post hoc analyses were to determine potential predictive factors associated with improvement in IRLS score with GE treatment and to identify subgroups with higher placebo responses.MethodsWe combined data from the two Japanese studies and analyzed change from baseline in IRLS score in the pooled population and subgroups defined by several patient characteristics. Moreover, we calculated the variable importance of each factor and performed predictive enrichment analysis to identify an enrichable subpopulation with greater improvement by GE treatment.ResultsThe post hoc analyses suggested that higher baseline IRLS score (≥21) and higher body mass index (≥25 kg/m²) were associated with higher placebo responses. On the other hand, positive family history of RLS, prior use of dopaminergic receptor agonists, and higher baseline ferritin level (≥50 ng/mL) were associated with higher responses to GE.ConclusionsOur results suggest that patients with typical idiopathic RLS characteristics, including positive family history and no low ferritin level, would be expected to derive the greatest benefits from GE treatment.     

Dry eyes in patients with diabetes mellitus

Dry eyes may be caused by impairment in the tear production or excessive tear evaporation and are associated with photophobia, red eyes, vision impairment, local pain and pruritus. It has been described that patients with Diabetes Mellitus (DM) may have a higher prevalence of dry eyes than normal population.This is a case control study of 120 patients with Diabetes Mellitus (DM) and 120 paired controls aiming to compare their prevalence of dry eyes (by the Schirmer test) and its severity (measured by OSDI or Ocular Surface Disease Index) as well as their association with diseases’ clinical variables.We found that 38.3% of DM patients had dry eyes, a prevalence that was higher than controls (p = 0.02). At univariate analysis, they were found to be more common in older individuals (p = 0.001) with type 2 diabetes (p = 0.001) and in those using metformin (p = 0.001). A multivariate linear regression showed that metformin use was the only independent variable associated with dry eyes. When patients with dry eyes with and without DM were compared, no differences in the symptom’s intensity were found.     

杨继国教授运用“气至而有效”理论治疗面瘫后遗症经验总结＊

目的 介绍杨继国教授运用“气至而有效”理论治疗面瘫后遗症的经验，为临床治疗提供参考。方法 详细将杨继国教授治疗此病的临床经验记录于本文，除了运用临床治疗本病的常规针刺方法以外，特别注重“气至而有效”理论的运用，通过循经远取合谷穴，运用“钻木取火”法和引导患者“以意领气”，激发经气，使气至而有效，同时配合艾灸及TDP神灯照射，多法联用。结果 本文结合一典型案例说明本法在临床使用过程中取得了满意的疗效。结论 杨继国教授治疗面瘫后遗症重视“气至而有效”理论的运用，提示针刺取效的关键在于“气至”，手法运用和医患治神则是“气至”的关键，临床疗效显著，其治疗经验值得临床参考和借鉴。     

加快伦理审查效率实践及策略探讨＊

本文根据临床试验研究者、申办方在提交项目伦理申请材料及伦理审查过程中，希望加快伦理审查效率的实际需求，探讨了在临床试验项目，尤其是多中心临床研究项目的伦理审查过程中，加快伦理审查效率的关键环节，分享了本院伦理审查过程中创新的、适合中医院实际情况的改革策略。具体包括统一各中心伦理递交审查材料清单、简化便捷伦理审查流程，通过电子化系统管理伦理受理、送审、审查、决定传达及归档的全过程，逐步建立合理有效的伦理审查工作程序，完善各中心伦理委员会的沟通交流机制，不断优化伦理委员会办公室的工作流程，逐步提高临床研究项目伦理审查的整体效率，更加全面系统的保护受试者的权益及安全。同时，本文也分享了本院伦理委员会通过接受中心伦理审查，科学性审查前置，重视伦理申请材料的形式审查，加强伦理委员会的主审制、预审制，注重伦理会议审查的要点，依托于电子化信息系统等具体实际方式，逐步提高我院伦理委员会的审查效率和伦理审查的质量。     

医学院校体质弱势群体体医融合教学模式研究

《"健康中国2030"规划纲要》作为引领中国体育治理能力和治理体系的现代化国策,将"体医融合"上升至解决当前中国健康问题的重要战略地位,为全民健身和全民健康的深度融合的战略行动计划实施指明了方向。同时,也为"体育+医学"元素融入大学传统公共体育教育环节提供了全新的视角。文章运用文献资料法、逻辑分析法、访谈法、问卷调查等研究方法对医药类高校公共体育保健康复课程的实施现状进行一系列的调查研究,对医学院校体质弱势群体学生的体育保健康复课程建设发展困境进行深入分析,初步提出针对医学院校的"体医融合"混合式体育保健康复课程教育模式的构想,以期通过体医融合教学干预策略改善高校大学生体质弱势群体身体及心理的健康状况,为全国同类院校体育保健课的发展实现真正意义上的突破。