CRISPR editing demonstrates rs10490924 raised oxidative stress in iPSC-derived retinal cells from patients with ARMS2/HTRA1-related AMD.

Genome-wide association studies (GWAS) have identified genetic risk loci for age-related macular degeneration (AMD) on the chromosome 10q26 (Chr10) locus and are tightly linked: the A69S (G>T) rs10490924 single-nucleotide variant (SNV) and the AATAA-rich insertion-deletion (indel, del443/ins54), which are found in the age-related maculopathy susceptibility 2 (ARMS2) gene, and the G512A (G>A) rs11200638 SNV, which is found in the high-temperature requirement A serine peptidase 1 (HTRA1) promoter. The fourth variant is Y402H complement factor H (CFH), which directs CFH signaling. CRISPR manipulation of retinal pigment epithelium (RPE) cells may allow one to isolate the effects of the individual SNV and thus identify SNV-specific effects on cell phenotype. Clustered regularly interspaced short palindromic repeats (CRISPR) editing demonstrates that rs10490924 raised oxidative stress in induced pluripotent stem cell (iPSC)-derived retinal cells from patients with AMD. Sodium phenylbutyrate preferentially reverses the cell death caused by ARMS2 rs10490924 but not HTRA1 rs11200638. This study serves as a proof of concept for the use of patient-specific iPSCs for functional annotation of tightly linked GWAS to study the etiology of a late-onset disease phenotype. More importantly, we demonstrate that antioxidant administration may be useful for reducing reactive oxidative stress in AMD, a prevalent late-onset neurodegenerative disorder.

Long-term vitamin A supplementation in a preclinical mouse model for RhoD190N-associated retinitis pigmentosa.

Retinitis pigmentosa (RP) is caused by one of many possible gene mutations. The National Institutes of Health recommends high daily doses of vitamin A palmitate for RP patients. There is a critical knowledge gap surrounding the therapeutic applicability of vitamin A to patients with the different subtypes of the disease. Here, we present a case report of a patient with RP caused by a p.D190N mutation in Rhodopsin (RHO) associated with abnormally high quantitative autofluorescence values after long-term vitamin A supplementation. We investigated the effects of vitamin A treatment strategy on RP caused by the p.D190N mutation in RHO by exposing Rhodopsin p.D190N (RhoD190N/+) and wild-type (WT) mice to experimental vitamin A-supplemented and standard control diets. The patient's case suggests that the vitamin A treatment strategy should be further studied to determine its effect on RP caused by p.D190N mutation in RHO and other mutations. Our mouse experiments revealed that RhoD190N/+ mice on the vitamin A diet exhibited higher levels of autofluorescence and lipofuscin metabolites compared to WT mice on the same diet and isogenic controls on the standard control diet. Vitamin A supplementation diminished photoreceptor function in RhoD190N/+ mice while preserving cone response in WT mice. Our findings highlight the importance of more investigations into the efficacy of clinical treatments like vitamin A for patients with certain genetic subtypes of disease and of genotyping in the precision care of inherited retinal degenerations.

Arriba por la Vida Estudio: a randomized controlled trial promoting standing behavior to reduce sitting time among postmenopausal Latinas.

Postmenopausal Hispanic/Latina (N = 254) women with a body mass index (BMI) ≥ 25 kg/m2 were randomized to an intervention to reduce sitting time or a comparison condition for 12 weeks. The standing intervention group received three in-person health-counseling sessions, one home visit, and up to eight motivational interviewing calls. The heart healthy lifestyle comparison group (C) received an equal number of contact hours to discuss healthy aging. The primary outcome was 12-week change in sitting time measured via thigh-worn activPAL. Group differences in outcomes were analyzed using linear mixed-effects models. Participants had a mean age of 65 (6.5) years, preferred Spanish language (89%), BMI of 32.4 (4.8) kg/m2, and sat for an average of 540 (86) minutes/day. Significant between-group differences were observed in reductions of sitting time across the 12-week period [Mdifference (SE): C - 7.5 (9.1), SI - 71.0 (9.8), p < 0.01]. Results demonstrate that coaching models to reduce sitting are feasible and effective.

Effects of transcranial direct current stimulation alone and in combination with rehabilitation therapies on gait and balance among individuals with Parkinson's disease: a systematic review and meta-analysis.

BACKGROUND: Parkinson's disease (PD) is a neurogenerative disorder implicated in dysfunctions of motor functions, particularly gait and balance. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation offered as a potential adjuvant therapy for PD. This systematic review and meta-analysis were conducted to identify whether tDCS alone and combined with additional rehabilitation therapies improve gait and balance among individuals with PD. METHODS: We searched PubMed, Embase, Web of Science, and relevant databases for eligible studies from inception to December 2022. Studies with a comparative design investigating the effects of tDCS on motor functions, including gait and balance among individuals with PD, were included. A meta-analysis was performed for each outcome using a random effects model for subgroup analysis and pooling of overall effect sizes. RESULTS: A total of 23 studies were included in the meta-analysis. The pooled results revealed that tDCS has moderate overall effects on gait, measured by gait speed (standardized mean deviation [SMD] = 0.238; 95% confidence interval [CI] - 0.026 to 0.502); stride length (SMD = 0.318; 95% CI - 0.015 to 0.652); cadence (SMD = - 0.632; 95% CI - 0.932 to - 0.333); freezing of gait questionnaire scores (SMD = - 0.360; 95% CI - 0.692 to - 0.027); step length (SMD = 0.459; 95% CI - 0.031 to 0.949); walking time (SMD = - 0.253; 95% CI - 0.758 to 0.252); stride time (SMD = - 0.785; 95% CI: - 1.680 to 0.111); double support time (SMD = 1.139; 95% CI - 0.244 to 0.523); and balance, measured by timed up and go (TUG) test (SMD = - 0.294; 95% CI - 0.516 to - 0.073), Berg balance scale (BBS) scores (SMD = 0.406; 95% CI - 0.059 to 0.87), and dynamic gait index (SMD = 0.275; 95% CI - 0.349 to 0.898). For the subgroup analysis, gait and balance demonstrated moderate effect sizes. However, only cadence, stride time, and TUG indicated a significant difference between real and sham tDCS (P = 0.027, P = 0.002, and P = 0.023, respectively), whereas cadence and BBS (P < 0.01 and P = 0.045, respectively) significantly differed after real tDCS plus other therapies rather than after sham tDCS plus other therapies. CONCLUSIONS: Our results indicated that tDCS is significantly associated with gait and balance improvements among individuals with PD. The findings of this study provide more proof supporting the effectiveness of tDCS, encouraging tDCS to be utilized alone or in combination with other therapies in clinical practice for PD rehabilitation.

Myoelectric, Myo-Oxygenation, and Myotonometry Changes during Robot-Assisted Bilateral Arm Exercises with Varying Resistances.

Robot-assisted bilateral arm training has demonstrated its effectiveness in improving motor function in individuals post-stroke, showing significant enhancements with increased repetitions. However, prolonged training sessions may lead to both mental and muscle fatigue. We conducted two types of robot-assisted bimanual wrist exercises on 16 healthy adults, separated by one week: long-duration, low-resistance workouts and short-duration, high-resistance exercises. Various measures, including surface electromyograms, near-infrared spectroscopy, heart rate, and the Borg Rating of Perceived Exertion scale, were employed to assess fatigue levels and the impacts of exercise intensity. High-resistance exercise resulted in a more pronounced decline in electromyogram median frequency and recruited a greater amount of hemoglobin, indicating increased muscle fatigue and a higher metabolic demand to cope with the intensified workload. Additionally, high-resistance exercise led to increased sympathetic activation and a greater sense of exertion. Conversely, engaging in low-resistance exercises proved beneficial for reducing post-exercise muscle stiffness and enhancing muscle elasticity. Choosing a low-resistance setting for robot-assisted wrist movements offers advantages by alleviating mental and physiological loads. The reduced training intensity can be further optimized by enabling extended exercise periods while maintaining an approximate dosage compared to high-resistance exercises.

Deep Neural Network for the Detections of Fall and Physical Activities Using Foot Pressures and Inertial Sensing.

Fall detection and physical activity (PA) classification are important health maintenance issues for the elderly and people with mobility dysfunctions. The literature review showed that most studies concerning fall detection and PA classification addressed these issues individually, and many were based on inertial sensing from the trunk and upper extremities. While shoes are common footwear in daily off-bed activities, most of the aforementioned studies did not focus much on shoe-based measurements. In this paper, we propose a novel footwear approach to detect falls and classify various types of PAs based on a convolutional neural network and recurrent neural network hybrid. The footwear-based detections using deep-learning technology were demonstrated to be efficient based on the data collected from 32 participants, each performing simulated falls and various types of PAs: fall detection with inertial measures had a higher F1-score than detection using foot pressures; the detections of dynamic PAs (jump, jog, walks) had higher F1-scores while using inertial measures, whereas the detections of static PAs (sit, stand) had higher F1-scores while using foot pressures; the combination of foot pressures and inertial measures was most efficient in detecting fall, static, and dynamic PAs.

CRIg+ Macrophages Prevent Gut Microbial DNA-Containing Extracellular Vesicle-Induced Tissue Inflammation and Insulin Resistance.

BACKGROUND & AIMS: Liver CRIg+ (complement receptor of the immunoglobulin superfamily) macrophages play a critical role in filtering bacteria and their products from circulation. Translocation of microbiota-derived products from an impaired gut barrier contributes to the development of obesity-associated tissue inflammation and insulin resistance. However, the critical role of CRIg+ macrophages in clearing microbiota-derived products from the bloodstream in the context of obesity is largely unknown. METHODS: We performed studies with CRIg-/-, C3-/-, cGAS-/-, and their wild-type littermate mice. The CRIg+ macrophage population and bacterial DNA abundance were examined in both mouse and human liver by either flow cytometric or immunohistochemistry analysis. Gut microbial DNA-containing extracellular vesicles (mEVs) were adoptively transferred into CRIg-/-, C3-/-, or wild-type mice, and tissue inflammation and insulin sensitivity were measured in these mice. After coculture with gut mEVs, cellular insulin responses and cGAS/STING-mediated inflammatory responses were evaluated. RESULTS: Gut mEVs can reach metabolic tissues in obesity. Liver CRIg+ macrophages efficiently clear mEVs from the bloodstream through a C3-dependent opsonization mechanism, whereas obesity elicits a marked reduction in the CRIg+ macrophage population. Depletion of CRIg+ cells results in the spread of mEVs into distant metabolic tissues, subsequently exacerbating tissue inflammation and metabolic disorders. Additionally, in vitro treatment of obese mEVs directly triggers inflammation and insulin resistance of insulin target cells. Depletion of microbial DNA blunts the pathogenic effects of intestinal EVs. Furthermore, the cGAS/STING pathway is crucial for microbial DNA-mediated inflammatory responses. CONCLUSIONS: Deficiency of CRIg+ macrophages and leakage of intestinal EVs containing microbial DNA contribute to the development of obesity-associated tissue inflammation and metabolic diseases.

Therapeutic perspectives of extracellular vesicles and extracellular microRNAs in atherosclerosis.

Extracellular signaling molecules, such as growth factors, cytokines, and hormones, regulate cell behaviors and fate through endocrine, paracrine, and autocrine actions and play essential roles in maintaining tissue homeostasis. MicroRNAs, an important class of posttranscriptional modulators, could stably present in extracellular space and body fluids and participate in intercellular communication in health and diseases. Indeed, recent studies demonstrated that microRNAs could be secreted through vesicular and non-vesicular routes, transported in body fluids, and then transmitted to recipient cells to regulate target gene expression and signaling events. Over the past decade, a great deal of effort has been made to investigate the functional roles of extracellular vesicles and extracellular microRNAs in pathological conditions. Emerging evidence suggests that altered levels of extracellular vesicles and extracellular microRNAs in body fluids, as part of the cellular responses to atherogenic factors, are associated with the development of atherosclerosis. This review article provides a brief overview of extracellular vesicles and perspectives of their applications as therapeutic tools for cardiovascular pathologies. In addition, we highlight the role of extracellular microRNAs in atherogenesis and offer a summary of circulating microRNAs in liquid biopsies associated with atherosclerosis.

Mechanogenetics for the remote and noninvasive control of cancer immunotherapy.

While cell-based immunotherapy, especially chimeric antigen receptor (CAR)-expressing T cells, is becoming a paradigm-shifting therapeutic approach for cancer treatment, there is a lack of general methods to remotely and noninvasively regulate genetics in live mammalian cells and animals for cancer immunotherapy within confined local tissue space. To address this limitation, we have identified a mechanically sensitive Piezo1 ion channel (mechanosensor) that is activatable by ultrasound stimulation and integrated it with engineered genetic circuits (genetic transducer) in live HEK293T cells to convert the ultrasound-activated Piezo1 into transcriptional activities. We have further engineered the Jurkat T-cell line and primary T cells (peripheral blood mononuclear cells) to remotely sense the ultrasound wave and transduce it into transcriptional activation for the CAR expression to recognize and eradicate target tumor cells. This approach is modular and can be extended for remote-controlled activation of different cell types with high spatiotemporal precision for therapeutic applications.

Extracellular MicroRNA-92a Mediates Endothelial Cell-Macrophage Communication.

OBJECTIVE: Understanding message delivery among vascular cells is essential for deciphering the intercellular communications in cardiovascular diseases. MicroRNA (miR)-92a is enriched in endothelial cells (ECs) and circulation under atheroprone conditions. Macrophages are the primary immune cells in atherosclerotic lesions that modulate lesion development. Therefore, we hypothesize that, in response to atheroprone stimuli, ECs export miR-92a to macrophages to regulate their functions and enhance atherosclerotic progression. Approach and Results: We investigated the macrophage functions that are regulated by EC miR-92a under atheroprone microenvironments. We first determined the distributions of functional extracellular miR-92a by fractionating the intravesicular and extravesicular compartments from endothelial conditioned media and mice serum. The results indicate that extracellular vesicles are the primary vehicles for EC miR-92a transportation. Overexpression of miR-92a in ECs enhanced the proinflammatory responses and low-density lipoprotein uptake, while impaired the migration, of cocultured macrophage. Opposite effects were found in macrophages cocultured with ECs with miR-92a knockdown. Further analyses demonstrated that intravesicular miR-92a suppressed the expression of target gene KLF4 (Krüppel-like factor 4) in macrophages, suggesting a mechanism by which intravesicular miR-92a regulates recipient cell functions. Indeed, the overexpression of KLF4 rescued the EC miR-92a-induced macrophage atheroprone phenotypes. Furthermore, an inverse correlation of intravesicular miR-92a in blood serum and KLF4 expression in lesions was observed in atherosclerotic animals, indicating the potential function of extracellular miR-92a in regulating vascular diseases. CONCLUSIONS: EC miR-92a can be transported to macrophages through extracellular vesicles to regulate KLF4 levels, thus leading to the atheroprone phenotypes of macrophage and, hence, atherosclerotic lesion formation.

Alternating Modulation of Subthalamic Nucleus Beta Oscillations during Stepping.

Gait disturbances in Parkinson's disease are commonly refractory to current treatment options and majorly impair patient's quality of life. Auditory cues facilitate gait and prevent motor blocks. We investigated how neural dynamics in the human subthalamic nucleus of Parkinsons's disease patients (14 male, 2 female) vary during stepping and whether rhythmic auditory cues enhance the observed modulation. Oscillations in the beta band were suppressed after ipsilateral heel strikes, when the contralateral foot had to be raised, and reappeared after contralateral heel strikes, when the contralateral foot rested on the floor. The timing of this 20-30 Hz beta modulation was clearly distinct between the left and right subthalamic nucleus, and was alternating within each stepping cycle. This modulation was similar, whether stepping movements were made while sitting, standing, or during gait, confirming the utility of the stepping in place paradigm. During stepping in place, beta modulation increased with auditory cues that assisted patients in timing their steps more regularly. Our results suggest a link between the degree of power modulation within high beta frequency bands and stepping performance. These findings raise the possibility that alternating deep brain stimulation patterns may be superior to constant stimulation for improving parkinsonian gait.SIGNIFICANCE STATEMENT Gait disturbances in Parkinson's disease majorly reduce patients' quality of life and are often refractory to current treatment options. We investigated how neural activity in the subthalamic nucleus of patients who received deep brain stimulation surgery covaries with the stepping cycle. 20-30 Hz beta activity was modulated relative to each step, alternating between the left and right STN. The stepping performance of patients improved when auditory cues were provided, which went along with enhanced beta modulation. This raises the possibility that alternating stimulation patterns may also enhance beta modulation and may be more beneficial for gait control than continuous stimulation, which needs to be tested in future studies.

Subthalamic nucleus oscillations correlate with vulnerability to freezing of gait in patients with Parkinson's disease.

Freezing of gait (FOG) is a disabling clinical phenomenon often found in patients with advanced Parkinson's disease (PD). FOG impairs motor function, causes falls and leads to loss of independence. Whereas dual tasking that distracts patients' attention precipitates FOG, auditory or visual cues ameliorate this phenomenon. The pathophysiology of FOG remains unclear. Previous studies suggest that the basal ganglia are involved in the generation of FOG. Investigation of the modulation of neuronal activities within basal ganglia structures during walking is warranted. To this end, we recorded local field potentials (LFP) from the subthalamic nucleus (STN) while PD patients performed single-task gait (ST) or walked while dual-tasking (DT). An index of FOG (iFOG) derived from trunk accelerometry was used as an objective measure to differentiate FOG-vulnerable gait from normal gait. Two spectral activities recorded from the STN region were associated with vulnerability to freezing. Greater LFP power in the low beta (15-21 Hz) and theta (5-8 Hz) bands were noted during periods of vulnerable gait in both ST and DT states. Whereas the elevation of low beta activities was distributed across STN, the increase in theta activity was focal and found in ventral STN and/or substantia nigra (SNr) in ST. The results demonstrate that low beta and theta band oscillations within the STN area occur during gait susceptible to freezing in PD. They also add to the evidence that narrow band ~18 Hz activity may be linked to FOG.

Unilateral vs Bilateral Hybrid Approaches for Upper Limb Rehabilitation in Chronic Stroke: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effects of unilateral hybrid therapy (UHT) and bilateral hybrid therapy (BHT) compared with robot-assisted therapy (RT) alone in patients with chronic stroke. DESIGN: A single-blind, randomized controlled trial. SETTING: Four hospitals. PARTICIPANTS: Outpatients with chronic stroke and mild to moderate motor impairment (N=44). INTERVENTION: UHT combined unilateral RT (URT) and modified constraint-induced therapy. BHT combined bilateral RT (BRT) and bilateral arm training. The RT group received URT and BRT. The intervention frequency for the 3 groups was 90 min/d 3 d/wk for 6 weeks. MAIN OUTCOME MEASURES: Fugl-Meyer Assessment (FMA, divided into the proximal and distal subscale) and Stroke Impact Scale (SIS) version 3.0 scores before, immediately after, and 3 months after treatment and Wolf Motor Function Test (WMFT) and Nottingham Extended Activities of Daily Living (NEADL) scale scores before and immediately after treatment. RESULTS: The results favored BHT over UHT on the FMA total score and distal score at the posttest (P=.03 and .04) and follow-up (P=.01 and .047) assessment and BHT over RT on the follow-up FMA distal scores (P=.03). At the posttest assessment, the WMFT and SIS scores of the 3 groups improved significantly without between-group differences, and the RT group showed significantly greater improvement in the mobility domain of NEADL compared with the BHT group (P<.01). CONCLUSIONS: BHT was more effective for improving upper extremity motor function, particularly distal motor function at follow-up, and individuals in the RT group demonstrated improved functional ambulation post intervention.

Fatigue and Muscle Strength Involving Walking Speed in Parkinson's Disease: Insights for Developing Rehabilitation Strategy for PD.

Background. Problems with gait in Parkinson's disease (PD) are a challenge in neurorehabilitation, partly because the mechanisms causing the walking disability are unclear. Weakness and fatigue, which may significantly influence gait, are commonly reported by patients with PD. Hence, the aim of this study was to investigate the association between weakness and fatigue and walking ability in patients with PD. Methods. We recruited 25 patients with idiopathic PD and 25 age-matched healthy adults. The maximum voluntary contraction (MVC), twitch force, and voluntary activation levels were measured before and after a knee fatigue exercise. General fatigue, central fatigue, and peripheral fatigue were quantified by exercise-induced changes in MVC, twitch force, and activation level. In addition, subjective fatigue was measured using the Multidimensional Fatigue Inventory (MFI) and Fatigue Severity Scale (FSS). Results. The patients with PD had lower activation levels, more central fatigue, and more subjective fatigue than the healthy controls. There were no significant differences in twitch force or peripheral fatigue index between the two groups. The reduction in walking speed was related to the loss of peripheral strength and PD itself. Conclusion. Fatigue and weakness of central origin were related to PD, while peripheral strength was important for walking ability. The results suggest that rehabilitation programs for PD should focus on improving both central and peripheral components of force.

Effect of EMG-triggered neuromuscular electrical stimulation with bilateral arm training on hemiplegic shoulder pain and arm function after stroke: a randomized controlled trial.

BACKGROUND: Hemiplegic shoulder pain is a frequent complication after stroke, leading to limited use of the affected arm. Neuromuscular electrical stimulation (NMES) and transcutaneous electrical nerve stimulation (TENS) are two widely used interventions to reduce pain, but the comparative efficacy of these two modalities remains uncertain. The purpose of this research was to compare the immediate and retained effects of EMG-triggered NMES and TENS, both in combination with bilateral arm training, on hemiplegic shoulder pain and arm function of stroke patients. METHODS: A single-blind, randomized controlled trial was conducted at two medical centers. Thirty-eight patients (25 males and 13 females, 60.75 ± 10.84 years old, post stroke duration 32.68 ± 53.07 months) who had experienced a stroke more than 3 months ago at the time of recruitment and hemiplegic shoulder pain were randomized to EMG-triggered NMES or TENS. Both groups received electrical stimulation followed by bilateral arm training 3 times a week for 4 weeks. The primary outcome measures included a vertical Numerical Rating Scale supplemented with a Faces Rating Scale, and the short form of the Brief Pain Inventory. The secondary outcome measures were the upper-limb subscale of the Fugl-Meyer Assessment, and pain-free passive shoulder range of motion. All outcomes were measured pretreatment, post-treatment, and at 1-month after post-treatment. Two-way mixed repeated measures ANOVAs were used to examine treatment effects. RESULTS: Compared to TENS with bilateral arm training, the EMG-triggered NMES with bilateral arm training was associated with lower pain intensity during active and passive shoulder movement (P =0.007, P =0.008), lower worst pain intensity (P = 0.003), and greater pain-free passive shoulder abduction (P =0.001) and internal rotation (P =0.004) at follow-up. Both groups improved in pain at rest (P =0.02), pain interference with daily activities, the Fugl-Meyer Assessment, and pain-free passive shoulder flexion and external rotation post-treatment (P < 0.001) and maintained the improvement at follow-up (P < 0.001), except for resting pain (P =0.08). CONCLUSIONS: EMG-triggered NMES with bilateral arm training exhibited greater immediate and retained effects than TENS with bilateral arm training with respect to pain and shoulder impairment for chronic and subacute stroke patients with hemiplegic shoulder pain. TRIAL REGISTRATION: NCT01913509 .

The antalgic effects of non-invasive physical modalities on central post-stroke pain: a systematic review.

[Purpose] This study systematically reviewed the antalgic effects of non-invasive physical modalities (NIPMs) on central post-stroke pain (CPSP). [Subjects and Methods] Clinical studies were sought on September 2015 in 10 electronic databases, including Medline and Scopus. The searching strings were "central pain and stroke" and "treatment, and physical or non-pharmacological". The inclusion and exclusion criteria were set for screening the clinical articles by two reviewers. Pain scores on visual analog scale in an article were used as the outcome measure for resulting judgment. The NIPMs intervention summarized from the eligible articles was rated from Levels A to C according to Evidence Classification Scheme for Therapeutic Interventions. [Results] Over 1200 articles were identified in the initial searches and 85 studies were retrieved. Sixteen studies were eligible and judged. Caloric vestibular stimulation (n=3), heterotopic noxious conditioning stimulation (n=1), and transcutaneous electrical stimulation (n=1) were rated below Level C. Transcranial direct current stimulation (TDCS; n=2) and transcranial magnetic stimulation (TMS; n=9) were rated as Level B. [Conclusion] The findings suggest that TMS and TDCS were better than other treatments for CPSP relief but the studies were of insufficient quality.

Cycling regimen induces spinal circuitry plasticity and improves leg muscle coordination in individuals with spinocerebellar ataxia.

OBJECTIVES: To compare the reciprocal control of agonist and antagonist muscles in individuals with and without spinocerebellar ataxia (SCA) and to evaluate the effect of a 4-week leg cycling regimen on functional coordination and reciprocal control of agonist and antagonist muscles in patients with SCA. DESIGN: Randomized controlled trial with repeated measures. SETTING: Research laboratory in a general hospital. PARTICIPANTS: Individuals with SCA (n=20) and without SCA (n=20). INTERVENTIONS: A single 15-minute session of leg cycling and a 4-week cycling regimen. MAIN OUTCOME MEASURES: Individuals with SCA (n=20) and without SCA (n=20) underwent disynaptic reciprocal inhibition and D1 inhibition tests of the soleus muscles before and after a single 15-minute cycling session. Individuals with SCA were randomly assigned to either participate in 4 weeks of cycling training (n=10) or to receive no training (n=10). The disynaptic reciprocal inhibition and D1 inhibition and International Cooperative Ataxia Rating Scale (ICARS) scores were evaluated in both groups after 4 weeks. RESULTS: Individuals with SCA showed abnormally strong resting values of disynaptic reciprocal inhibition and D1 inhibition (P<.001) and impaired inhibition modulation capacity after a single 15-minute session of cycling (P<.001). The inhibition modulation capacity was restored (P<.001), and the ICARS scores improved significantly (pre: 13.5±9.81, post: 11.3±8.74; P=.046) after 4 weeks of cycling training. CONCLUSIONS: A 4-week cycling regimen can normalize the modulation of reciprocal inhibition and functional performance in individuals with SCA. These findings are applicable to the coordination training of patients.

Restoration of Central Programmed Movement Pattern by Temporal Electrical Stimulation-Assisted Training in Patients with Spinal Cerebellar Atrophy.

Disrupted triphasic electromyography (EMG) patterns of agonist and antagonist muscle pairs during fast goal-directed movements have been found in patients with hypermetria. Since peripheral electrical stimulation (ES) and motor training may modulate motor cortical excitability through plasticity mechanisms, we aimed to investigate whether temporal ES-assisted movement training could influence premovement cortical excitability and alleviate hypermetria in patients with spinal cerebellar ataxia (SCA). The EMG of the agonist extensor carpi radialis muscle and antagonist flexor carpi radialis muscle, premovement motor evoked potentials (MEPs) of the flexor carpi radialis muscle, and the constant and variable errors of movements were assessed before and after 4 weeks of ES-assisted fast goal-directed wrist extension training in the training group and of general health education in the control group. After training, the premovement MEPs of the antagonist muscle were facilitated at 50 ms before the onset of movement. In addition, the EMG onset latency of the antagonist muscle shifted earlier and the constant error decreased significantly. In summary, temporal ES-assisted training alleviated hypermetria by restoring antagonist premovement and temporal triphasic EMG patterns in SCA patients. This technique may be applied to treat hypermetria in cerebellar disorders. (This trial is registered with NCT01983670.).

A turn-on indole-based sensor for hydrogen sulfate ion.

A simple indole-based receptor 1 was prepared by a simple Schiff-base reaction of 1H-indole-3-carbaldehyde with ethane 1,2-diamine and its fluoroionophoric properties toward anions were investigated. Indole-based receptor 1 acts as a selective turn-on fluorescent sensor for HSO4(-) in methanol among a series of tested anions. Fluorescence spectroscopy, ultraviolet and nuclear magnetic resonance imaging support that the HSO4(-) indeed interacted with imine nitrogen and the proton of nitrogen in indole ring.

A real-time fatigue monitoring and analysis system for lower extremity muscles with cycling movement.

A real-time muscle fatigue monitoring system was developed to quantitatively detect the muscle fatigue of subjects during cycling movement, where a fatigue progression measure (FPM) was built-in. During the cycling movement, the electromyogram (EMG) signals of the vastus lateralis and gastrocnemius muscles in one leg as well as cycling speed are synchronously measured in a real-time fashion. In addition, the heart rate (HR) and the Borg rating of perceived exertion scale value are recorded per minute. Using the EMG signals, the electrical activity and median frequency (MF) are calculated per cycle. Moreover, the updated FPM, based on the percentage of reduced MF counts during cycling movement, is calculated to measure the onset time and the progressive process of muscle fatigue. To demonstrate the performance of our system, five young healthy subjects were recruited. Each subject was asked to maintain a fixed speed of 60 RPM, as best he/she could, under a constant load during the pedaling. When the speed reached 20 RPM or the HR reached the maximal training HR, the experiment was then terminated immediately. The experimental results show that the proposed system may provide an on-line fatigue monitoring and analysis for the lower extremity muscles during cycling movement.