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Abstract Dual cognitive-walking treadmill training (DTT), designed to replicate real-life walking conditions, has shown promise effect in individuals with Parkinson’s disease (PD). This study aims to compare the effects of DTT versus single treadmill training (STT) on cognitive and walking performance under both single and dual task conditions, as well as on fall, patients’ subjective feeling, and quality of life. Sixteen individuals with PD were randomly assigned to DTT or STT group and underwent 8 weeks of training. The DTT group received treadmill training with cognitive loads, while the STT group received treadmill training without cognitive load. Outcome measures included gait parameters (speed, step length) and cognitive performance (reaction time, accuracy, composite score) under both single and dual task conditions. Unified Parkinson’s Disease Rating Scale-part III (UPDRS-III), Falls Efficacy Scale (FES), Patient Global Impression of Change (PGIC), and Parkinson’s Disease Questionnaire (PDQ-39) were also measured. Both DTT and STT groups showed increased comfortable walking speed and step length. Only the DTT group demonstrated significant improvements in cognitive composite score under both single and dual task conditions, as well as UPDRS-III, FES, and PDQ-39(p

Abstract 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

BackgroundStroke is a leading cause of long-term disability among stroke survivors. Despite the availability of numerous stroke rehabilitative therapies, such as mirror therapy, bilateral arm training, and robot-assisted therapy, the recovery of motor function after stroke remains incomplete. Bilateral arm function is a key component in stroke patients to perform activities of daily living and to reflect their functional autonomy.ObjectiveThis clinimetric study investigated and compared the construct validity and responsiveness of 2 bimanual activity outcome measures, the Chedoke Arm and Hand Activity Inventory (CAHAI) and the ABILHAND Questionnaire, in individuals receiving stroke rehabilitation.MethodsThe present study is a secondary analysis following the framework of the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). Individuals with chronic stroke (N = 113) were recruited from outpatient rehabilitation settings. Participants received 18 to 20 sessions of robot-assisted therapy, mirror therapy, combined therapy, or conventional rehabilitation for 4 to 6 weeks. The CAHAI, ABILHAND Questionnaire, and a comparison instrument, the Motor Activity Log (MAL), were administered twice at a 4- to 6-week interval to all participants. ABILHAND scores, in logits, were converted from raw ordinal scores into a linear measure.ResultsThere was medium to large correlation of the CAHAI and the MAL (ρ = 0.60–0.62, p

Abstract Background Various neurocognitive tests have shown that cycling enhances cognitive performance compared to resting. Event-related potentials (ERPs) elicited by an oddball or flanker task have clarified the impact of dual-task cycling on perception and attention. In this study, we investigate the effect of cycling on cognitive recruitment during tasks that involve not only stimulus identification but also semantic processing and memory retention. Methods We recruited 24 healthy young adults (12 males, 12 females; mean age = 22.71, SD = 1.97 years) to perform three neurocognitive tasks (namely color-word matching, arithmetic calculation, and spatial working memory) at rest and while cycling, employing a within-subject design with rest/cycling counterbalancing. Results The reaction time on the spatial working memory task was faster while cycling than at rest at a level approaching statistical significance. The commission error percentage on the color–word matching task was significantly lower at rest than while cycling. Dual-task cycling while responding to neurocognitive tests elicited the following results: (a) a greater ERP P1 amplitude, delayed P3a latency, less negative N4, and less positivity in the late slow wave (LSW) during color-word matching; (b) a greater P1 amplitude during memory encoding and smaller posterior negativity during memory retention on the spatial working memory task; and (c) a smaller P3 amplitude, followed by a more negative N4 and less LSW positivity during arithmetic calculation. Conclusion The encoding of color-word and spatial information while cycling may have resulted in compensatory visual processing and attention allocation to cope with the additional cycling task load. The dual-task cycling and cognitive performance reduced the demands of semantic processing for color-word matching and the cognitive load associated with temporarily suspending spatial information. While dual-tasking may have required enhanced semantic processing to initiate mental arithmetic, a compensatory decrement was noted during arithmetic calculation. These significant neurocognitive findings demonstrate the effect of cycling on semantic-demand and memory retention-demand tasks.

Gait disorders are a fundamental challenge in Parkinson’s disease (PD). The use of laser-light visual cues emitted from shoes has demonstrated effective in improving freezing of gait within less restrictive environments. However, the effectiveness of shoes-based laser-light cueing may vary among individuals with PD who have different types of impairments. We introduced an innovative laser-light visual shoes system capable of producing alternating visual cues for the left and right feet through one-side cueing at a time, while simultaneously recording foot inertial data and foot pressures. The effects of this visual cueing system on gait patterns were assessed in individuals with PD, both those with well-gait and those with worse-gait. Our device successfully quantified gait characteristics, including the asymmetry in the center of pressure trajectory, in individuals with PD. Furthermore, visual cueing prolonged stride times and increased the percentage of stance phase, while concurrently reducing stride length in PD individuals with well-gait. Conversely, in PD individuals with worse-gait, visual cueing resulted in a decreased freeze index and a reduction in the proportion of intervals prone to freezing episodes. The effects of visual cueing varied between PD individuals with well-gait and those with worse-gait. Visual cueing slowed down gait in the well-gait group while it appeared to mitigate freezing episodes in worse-gait group. Future researches, including enhancements to extend the projection distance of visual cues and clinical assessments conducted in real-world settings, will help establish the clinical utility of our proposed visual cueing system.

Abstract Iron accumulation causes cell death and disrupts tissue functions, which necessitates chelation therapy to reduce iron overload. However, clinical utilization of deferoxamine (DFO), an iron chelator, has been documented to give rise to systemic adverse effects, including ocular toxicity. This study provided the pathogenic and molecular basis for DFO‐related retinopathy and identified retinal pigment epithelium (RPE) as the target tissue in DFO‐related retinopathy. Our modeling demonstrated the susceptibility of RPE to DFO compared with the neuroretina. Intriguingly, we established upregulation of hypoxia inducible factor (HIF) 2α and mitochondrial deficit as the most prominent pathogenesis underlying the RPE atrophy. Moreover, suppressing hyperactivity of HIF2α and preserving mitochondrial dysfunction by α‐ketoglutarate (AKG) protects the RPE against lesions both in vitro and in vivo. This supported our observation that AKG supplementation alleviates visual impairment in a patient undergoing DFO‐chelation therapy. Overall, our study established a significant role of iron deficiency in initiating DFO‐related RPE atrophy. Inhibiting HIF2α and rescuing mitochondrial function by AKG protect RPE cells and can potentially ameliorate patients' visual function.

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.

Background: Continuous passive motion device (CPM) provides repetitive movement over extended periods of time for those who have low functional ability. The purpose of this research was to evaluate the effects of a four-week program of continuous passive motion of the ankle joint on the changes in soleus hypertonia in individuals with cerebral palsy who suffered from life-long hypertonia. Methods: A single group, repeated-measures study was conducted. Eight individuals (7 males and 1 female with a mean age of 21.8 ± 8.5 years) with spastic cerebral palsy underwent bilateral ankle CPM for 1 h a day, 5 days a week, for 4 weeks. The outcome measures included the Modified Ashworth Scale (MAS) score, passive range of motion (PROM) of the ankle, the ratio of maximum H reflex to maximum soleus M-response (H/M ratio), and post-activation depression (PAD). All outcomes were measured before and after the intervention. A paired t-test was used to examine treatment effects pre-versus post-intervention. Results: Paired t-tests showed that the CPM program significantly decreased the MAS score (p = 0.006), decreased the maximum H/M ratio (p=0.001), improved PAD (p = 0.003, p = 0.040, and p = 0.032 at 0.2 Hz, 1 Hz, and 2 Hz, respectively), and increased the passive ankle range of motion (p = 0.049). Conclusion: Ankle CPM not only reduced soleus hypertonia but also improved the PROM in individuals with cerebral palsy. The results of this study show ankle CPM to be an effective intervention for individuals with cerebral palsy.

Abstract Background Combining robotic therapy (RT) with task-oriented therapy is an emerging strategy to facilitate motor relearning in stroke rehabilitation. This study protocol will compare novel rehabilitation regimens that use bilateral RT as a priming technique to augment two task-oriented therapies: mirror therapy (MT) and bilateral arm training (BAT) with a control intervention: RT combined with impairment-oriented training (IOT). Methods This single-blind, randomized, comparative efficacy study will involve 96 participants with chronic stroke. Participants will be randomized into bilateral RT+MT, bilateral RT+BAT, and bilateral RT+IOT groups and receive 18 intervention sessions (90 min/day, 3 d/week for 6 weeks). The outcomes will include the Fugl-Meyer Assessment, Stroke Impact Scale version 3.0, Medical Research Council scale, Revised Nottingham Sensory Assessment, ABILHAND Questionnaire, and accelerometer and will be assessed at baseline, after treatment, and at the 3-month follow-up. Analysis of covariance and the chi-square automatic interaction detector method will be used to examine the comparative efficacy and predictors of outcome, respectively, after bilateral RT+MT, bilateral RT+BAT, and bilateral RT+IOT. Discussion The findings are expected to contribute to the research and development of robotic devices, to update the evidence-based protocols in postacute stroke care programs, and to investigate the use of accelerometers for monitoring activity level in real-life situations, which may in turn promote home-based practice by the patients and their caregivers. Directions for further studies and empirical implications for clinical practice will be further discussed in upper-extremity rehabilitation after stroke. Trial registration This trial was registered December 12, 2018, at www.clinicaltrials.gov ( NCT03773653 ).

The strength of lower extremity is important for individuals to maintain balance and ambulation functions. The previous studies showed that individuals with Parkinson’s disease suffered from fatigue and strength loss of central origin. The purpose of this study was to investigate the effect of lower extremities’ cycling training on different components of force and fatigue in individuals with Parkinson’s disease. Twenty-four individuals (13 males, 11 females, mean age: 60.58 ± 8.21 years) diagnosed with idiopathic Parkinson’s disease were randomized into training and control groups. The maximum voluntary contraction (MVC) force, voluntary activation level (VA), and twitch force of knee extensors were measured using a custom-made system with surface electrical stimulation. The general, central, and peripheral fatigue indexes (GFI, CFI, and PFI) were calculated after a fatiguing cycling protocol. Subjects received 8 weeks of low resistance cycling training (training group) or self-stretching (control group) programs. Results showed that MVC, VA, and twitch force improved (p < 0.05) only in the training group. Compared to the baseline, central fatigue significantly improved in the training group, whereas peripheral fatigue showed no significant difference in two groups. The cycling training was beneficial for individuals with Parkinson’s disease not only in muscle strengthening but also in central fatigue alleviation. Further in-depth investigation is required to confirm the effect of training and its mechanism on central fatigue.

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.

The edible leaves of the mulberry (Morus alba L.) plant are used worldwide. They contain abundant polyphenolic compounds with strong anticancer properties. We previously revealed that apoptosis was mediated in p53-negative Hep3B cells, and mulberry leaf polyphenol extract (MLPE) induced autophagy in p53-transfected Hep3B cells. However, how this autophagy is induced by p53 in human hepatoma HepG2 (p53 wild type) cells remains unclear. In the current study, MLPE induced autophagy, as demonstrated by enhanced acidic vesicular organelle staining, by upregulating beclin-1, increasing LC3-II conversion, and phosphorylating AMPK. In HepG2 cells, these processes were associated with p53. Western blot also revealed phosphatidylinositol-3 kinase (PI3K), p-AKT, and fatty acid synthase (FASN) suppression in MLPE-treated cells. Moreover, treatment with the p53 inhibitor pifithrin-α (PFT-α) inhibited autophagy and increased apoptotic response in MLPE-treated HepG2 cells. PFT-α treatment also reversed MLPE-induced PI3K, p-AKT, and FASN suppression. Thus, co-treatment with MLPE and PFT-α significantly increased caspase-3, caspase-8, and cytochrome c release, indicating that p53 deficiency caused the apoptosis. In addition, rutin, a bioactive polyphenol in MLPE, may affect autophagy in HepG2 cells. This study demonstrates that MLPE is a potential anticancer agent targeting autophagy and apoptosis in cells with p53 status. Moreover, this work provides insight into the mechanism of p53 action in MLPE-induced cytotoxicity in hepatocellular carcinoma.