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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 ).

Abstract Time spent sitting is positively correlated with endothelial dysfunction and cardiovascular disease risk. The underlying molecular mechanisms are unknown. MicroRNAs contained in extracellular vesicles (EVs) reflect cell/tissue status and mediate intercellular communication. We explored the association between sitting patterns and microRNAs isolated from endothelial cell (EC)-derived EVs. Using extant actigraphy based sitting behavior data on a cohort of 518 postmenopausal overweight/obese women, we grouped the woman as Interrupted Sitters (IS; N = 18) or Super Sitters (SS; N = 53) if they were in the shortest or longest sitting pattern quartile, respectively. The cargo microRNA in EC-EVs from the IS and SS women were compared. MicroRNA data were weighted by age, physical functioning, MVPA, device wear days, device wear time, waist circumference, and body mass index. Screening of CVD-related microRNAs demonstrated that miR-199a-5p, let-7d-5p, miR-140-5p, miR-142-3p, miR-133b level were significantly elevated in SS compared to IS groups. Group differences in let-7d-5p, miR-133b, and miR-142-3p were validated in expanded groups. Pathway enrichment analyses show that mucin-type O-glycan biosynthesis and cardiomyocyte adrenergic signaling (P

Abstract Background EEGs are frequently employed to measure cerebral activations during physical exercise or in response to specific physical tasks. However, few studies have attempted to understand how exercise-state brain activity is modulated by exercise intensity. Methods Ten healthy subjects were recruited for sustained cycle ergometer exercises at low and high resistance, performed on two separate days a week apart. Exercise-state EEG spectral power and phase-locking values (PLV) are analyzed to assess brain activity modulated by exercise intensity. Results The high-resistance exercise produced significant changes in beta-band PLV from early to late pedal stages for electrode pairs F3-Cz, P3-Pz, and P3-P4, and in alpha-band PLV for P3-P4, as well as the significant change rate in alpha-band power for electrodes C3 and P3. On the contrary, the evidence for changes in brain activity during the low-resistance exercise was not found. Conclusion These results show that the cortical activation and cortico-cortical coupling are enhanced to take on more workload, maintaining high-resistance pedaling at the required speed, during the late stage of the exercise period.

Background: This study used novel human neurophysiologic models to investigate whether the mechanism of rate-sensitive H-reflex depression lies in the pre-synaptic or post-synaptic locus in humans. We hypothesized that pre-synaptic inhibition would suppress Ia afferents and H-reflexes without suppressing alpha motor neurons or motor evoked potentials (MEPs). In contrast, post-synaptic inhibition would suppress alpha motor neurons, thereby reducing H-reflexes and MEPs. Methods: We recruited 23 healthy adults with typical rate-sensitive H-reflex depression, 2 participants with acute sensory-impaired spinal cord injury (SCI) (to rule out influence of sensory stimulation on supra-spinal excitability), and an atypical cohort of 5 healthy adults without rate-sensitive depression. After a single electrical stimulation to the tibial nerve, we administered either a testing H-reflex or a testing MEP at 50–5000 ms intervals. Results: Testing MEPs were not diminished in healthy subjects with or without typical rate-sensitive H-reflex depression, or in subjects with sensory-impaired SCI. MEP responses were similar in healthy subjects with versus without rate-sensitive H-reflex depression. Conclusions: Results from these novel in vivo human models support a pre-synaptic locus of rate-sensitive H-reflex depression for the first time in humans. Spinal reflex excitability can be modulated separately from descending corticospinal influence. Each represents a potential target for neuromodulatory intervention. Keywords: H-reflex, Motor evoked potential, Pre-synaptic, Soleus, Spinal cord, Spinal cord injury

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.

Background: To investigate the effect and dose-response of functional electrical stimulation cycling (FES-cycling) training on spasticity in the individuals with spinal cord injury (SCI).Method: Five electronic databases [PubMed, Scopus, Medline (Proquest), Embase, and Cochrane Central Register of Controlled Trials (CENTRAL)] were searched before September 2021. The human trials and studies of English language were only included. Two authors independently reviewed and extracted the searched studies. The primary outcome measure was spasticity assessed by Modified Ashworth Scale or Ashworth Scale for lower limbs. The secondary outcome measures were walking abilities, such as 6 Min Walk Test (6MWT), Timed Up and Go (TUG), and lower limbs muscle strength (LEMS). A subgroup analysis was performed to investigate the efficacious threshold number of training sessions. A meta-regression analysis was used to examine the linear relationship between the training sessions and the effect on spasticity.Results: A total of 764 studies were identified. After screening, 12 selected studies were used for the qualitative synthesis, in which eight of them were quantitatively analyzed. Eight studies included ninety-nine subjects in total with SCI (male: female = 83:16). The time since injury was from less than 4 weeks to 17 years. The age ranged from 20 to 67 years. American Spinal Injury Association (ASIA) impairment level of the number of participants was 59 for ASIA A, 11 for ASIA B, 18 for ASIA C, and 11 for ASIA D. There were 43 subjects with tetraplegia and 56 subjects with paraplegia. Spasticity decreased significantly (95% CI = − 1.538 to − 0.182, p = 0.013) in favor of FES-cycling training. The walking ability and LEMS also improved significantly in favor of FES-cycling training. The subgroup analysis showed that spasticity decreased significantly only in more than 20 training sessions (95% CI = − 1.749 to − 0.149, p = 0.020). The meta-regression analysis showed training sessions and spasticity were not significantly associated (coefficient = − 0.0025, SE = 0.0129, p = 0.849, R2 analog = 0.37).Conclusion: Functional electrical stimulation-cycling training can improve spasticity, walking ability, and the strength of the lower limbs in the individuals with SCI. The number of training sessions is not linearly related to the decrease of spasticity. Twenty sessions of FES-cycling training are required to obtain the efficacy to decrease spasticity.

Background: Stroke survivors can remain impaired in body functions, activity, and participation. A novel rehabilitation regimen is required to obtain scientific evidence and to help clinicians determine effective interventions for stroke. Mirror therapy (MT) and bilateral upper limb training (BULT) are based on the tenet of bilateral movement practice; however, the additional effect of bilateral robotic priming combined with these two therapies is unclear.Objectives: This study examined the effects of two hybrid therapies, robotic priming combined with MT and robotic priming combined with BULT, in stroke survivors.Methodology: The study randomized 31 participants to groups that received robotic priming combined with MT (n = 15) or robotic priming combined with BULT (n = 16). Outcome measures included the Fugl–Meyer Assessment (FMA), the revised Nottingham Sensory Assessment (rNSA), the Chedoke Arm and Hand Activity Inventory (CAHAI), and accelerometer data.Results: Both groups showed statistically significant within-group improvements in most outcome measures. Significant between-group differences and medium-to-large effect sizes were found in favor of the group that received robotic priming combined with MT based on the FMA distal part subscale scores, FMA total scores, and accelerometer data.Conclusion: Robotic priming combined with MT may have beneficial effects for patients in the improvements of overall and distal arm motor impairment as well as affected arm use in real life. Additional follow-up, a larger sample size, and consideration of the effect of lesion location or different levels of cognitive impairment are warranted to validate our findings in future studies.Clinical trial registration:www.ClinicalTrials.gov, identifier NCT03773653.

Leg cycling is one of the most common modes of exercise used in athletics and rehabilitation. This study used a novel cycling setting to elucidate the mechanisms, central vs. peripheral fatigue induced by different resistance with equivalent works (watt∗min). Twelve male adults received low and relatively high resistance cycling fatigue tests until exhausted (RPE > 18) in 2 weeks. The maximal voluntary contraction, voluntary activation level, and twitch forces were measured immediately before and after cycling to calculate General (GFI), central (CFI), and peripheral (PFI) fatigue indices of knee extensors, respectively. The results showed that the CFI (high: 92.26 ± 8.67%, low: 78.32 ± 11.77%, p = 0.004) and PFI (high: 73.76 ± 17.32%, low: 89.63 ± 11.01%, p < 0.017) were specific to the resistance of fatigue protocol. The GFI is influenced by the resistance of cycling to support the equivalent dosage. This study concluded that the mechanism of fatigue would be influenced by the resistance of fatigue protocol although the total works had been controlled.

Degenerative cervical myelopathy (DCM) is a common aging condition caused by spinal cord compression. Individuals with DCM often presented with residual balance and functional impairments postoperatively. Perturbation-based balance training (PBT) has been shown to have positive effects on populations with neurological disorders but has yet to be investigated in DCM. The objective of this study was therefore to evaluate the effects of PBT on balance and functional performance in postoperative individuals with DCM. Fifteen postoperative individuals with DCM (DCM group) and 14 healthy adults (healthy control group) were recruited. The DCM group received a 4-weeks PBT using a perturbation treadmill. The outcome measures included mean velocity of center of pressure (COP) during quiet standing; center of mass (COM) variance and reaction time to balance perturbation during standing with forward and backward perturbation; gait speed during level ground walking; Timed Up and Go Test (TUG) and disability questionnaire scores including Visual Analog Scale, Neck Disability Index, and Lower Extremity Function of Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire. The assessments were conducted pre- and post-training postoperatively for the DCM group but only once for the healthy control group. Significant improvements were observed in the mean velocity of COP, COM variance, reaction time, gait speed, and TUG in the DCM group. Disability questionnaire scores were not significantly different after training in DCM group. For between-group comparisons, significant differences that were observed pre-training were not observed post-training. The 4-weeks PBT is a potential rehabilitation strategy for addressing balance and functional impairment in postoperative individuals with DCM. In addition, the post-training performance in the DCM group exhibited trends comparable to those of age-matched healthy controls. Furthermore, the training regimens offer a practical reference for future studies on populations with balance disorders. Future studies complemented with neurophysiological assessments could reveal more information of the underlying mechanisms of PBT.

Background Sedentary behavior is pervasive, especially in older adults, and is associated with cardiometabolic disease and mortality. Relationships between cardiometabolic biomarkers and sitting time are unexplored in older women, as are possible ethnic differences. Methods and Results Ethnic differences in sitting behavior and associations with cardiometabolic risk were explored in overweight/obese postmenopausal women (n=518; mean±SD age 63±6 years; mean body mass index 31.4±4.8 kg/m2). Accelerometer data were processed using validated machine‐learned algorithms to measure total daily sitting time and mean sitting bout duration (an indicator of sitting behavior pattern). Multivariable linear regression was used to compare sitting among Hispanic women (n=102) and non‐Hispanic women (n=416) and tested associations with cardiometabolic risk biomarkers. Hispanic women sat, on average, 50.3 minutes less/day than non‐Hispanic women (P

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.

Abstract 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

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.

Wheat noodles incorporated with isomaltodextrin were assessed in relation to physicochemical properties (color), microstructure features, biochemical composition (fiber profile), cooking properties, textural attributes, and sensory evaluations during different storage temperatures (25, 4, −20 °C) and periods (0, 3, 6, 9, 12, 15, 18, 21, 24 months). Meanwhile, an accelerated study was also carried out at 40 °C storage conditions for 12 months to evaluate the fiber profile changes. Under different conditions, the overall quality of both raw and cooked noodle samples depended slightly on both the type and amount of added fiber isomaltodextrin, resistant starch (RS), insoluble high-molecular-weight dietary fiber (IHMWDF), and soluble high-molecular-weight dietary fiber (SHMWDF). However, this significantly changed for the fiber profile under 40 °C of storage for 12 months. Cooking quality, fiber profile, and color parameter did not differ by storage at −20 °C after 24 months than at 0 months, and noodles only slightly differed in texture and sensory characteristics. On sensory analysis, noodle samples were acceptable by panelists, with an acceptability score >5. In short, storage temperature is one of the most important factors in preserving food stability and retail properties. Isomaltodextrin noodles samples should be stored at low temperature to preserve the product functionality.

Anticipatory postural adjustment (APA) existed before a self-induced perturbation is an important motor control skill for balance and gait initiation, but cannot be easily monitored. During proactive balance test, a self-initiated weight shifting is produced. This might be an optimal paradigm for APA measurement. The purpose of this study was to investigate if APAs existed in the proactive balance test which consists of quantifiable weight shifting. The feature and reliability of the APAs were also evaluated. We firstly built a proactive balance test program on the commercially available Wii balance board. The program could generate adjustable target direction and distance for guiding subjects performing quantifiable weight shifting. The center of pressure (COP) was recorded and analyzed for balance-related variables (path length, path time, and direction error) and APA-related variables (APA time, APA distance, and APA correction). The results showed that APAs could be detected in every testing trial. Adequate to good reliability in both balance and APA-related variables were found. This study proved the feasibility of quantifying APA during proactive balance tests and its feasibility for clinical- and home-based measurements.

Fatigue is a common symptom in the general population and has a substantial effect on individuals' quality of life. The Multidimensional Fatigue Inventory (MFI) has been widely used to quantify the impact of fatigue, but no Traditional Chinese translation has yet been validated. The goal of this study was to translate the MFI from English into Traditional Chinese ('the MFI-TC') and subsequently to examine its validity and reliability.The study recruited a convenience sample of 123 people from various age groups in Taiwan. The MFI was examined using a two-step process: (1) translation and back-translation of the instrument; and (2) examination of construct validity, convergent validity, internal consistency, test-retest reliability, and measurement error. The validity and reliability of the MFI-TC were assessed by factor analysis, Spearman rho correlation coefficient, Cronbach's alpha coefficient, intraclass correlation coefficient (ICC), minimal detectable change (MDC), and Bland-Altman analysis. All participants completed the Short-Form-36 Health Survey Taiwan Form (SF-36-T) and the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) concurrently to test the convergent validity of the MFI-TC. Test-retest reliability was assessed by readministration of the MFI-TC after a 1-week interval.Factor analysis confirmed the four dimensions of fatigue: general/physical fatigue, reduced activity, reduced motivation, and mental fatigue. A four-factor model was extracted, combining general fatigue and physical fatigue as one factor. The results demonstrated moderate convergent validity when correlating fatigue (MFI-TC) with quality of life (SF-36-T) and sleep disturbances (PSQI) (Spearman's rho = 0.68 and 0.47, respectively). Cronbach's alpha for the MFI-TC total scale and subscales ranged from 0.73 (mental fatigue subscale) to 0.92 (MFI-TC total scale). ICCs ranged from 0.85 (reduced motivation) to 0.94 (MFI-TC total scale), and the MDC ranged from 2.33 points (mental fatigue) to 9.5 points (MFI-TC total scale). The Bland-Altman analyses showed no significant systematic bias between the repeated assessments.The results support the use of the Traditional Chinese version of the MFI as a comprehensive instrument for measuring specific aspects of fatigue. Clinicians and researchers should consider interpreting general fatigue and physical fatigue as one subscale when measuring fatigue in Traditional Chinese-speaking populations.

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.

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.

The aim of this study was to examine the change of the intermuscular cross-correlation and coherence of the rectus femoris (RF), vastus medialis (VM) and vastus lateralis (VL) during exhausting stepping exercise. Eleven healthy adults repeated the stepping exercise up to their individual endurance limits (RPE score reached 20), and the cross-correlation and coherence were assessed by surface electromyography (EMG) recordings. The coefficient and time lag of cross-correlation and the coherence areas in the alpha (8–12 Hz), beta (15–30 Hz), gamma (30–60 Hz) and high-gamma (60–150 Hz) bands among the three muscle pairs (RF-VM, RF-VL and VM-VL) were calculated. As muscle fatigue, RF-VM and VM-VL showed increases of coefficients and the shortening of time lags. RF-VM and RF-VL showed increases of beta-band coherence in the ascent and descent phases, respectively. The increased intermuscular cross-correlation and beta-band coherence may be a compensatory strategy for maintaining the coordination of knee synergistic muscles during fatigue due to the fatigue-related disturbance of the corticospinal transmission. Therefore, the intermuscular cross-correlation and beta-band coherence may be a potential index for assessing muscle fatigue and monitoring the central control of motor function during dynamic fatiguing exercise.

Weight loss/weight control is a major concern in prevention of cardiovascular disease and the realm of health promotion. The primary aim of this study was to investigate the effect of neuromuscular electrical stimulation (NMES) at different intensities on energy expenditure (oxygen and calories) in healthy adults. The secondary aim was to develop a generalized linear regression (GEE) model to predict the increase of energy expenditure facilitated by NMES and identify factors (NMES stimulation intensity level, age, body mass index, weight, body fat percentage, waist/hip ratio, and gender) associated with this NMES-induced increase of energy expenditure. Forty sedentary healthy adults (18 males and 22 females) participated. NMES was given at the following stimulation intensities for 10 minutes each: sensory level (E1), motor threshold (E2), and maximal intensity comfortably tolerated (E3). Cardiopulmonary gas exchange was evaluated during rest, NMES, and recovery stage. The results revealed that NMES at E2 and E3 significantly increased energy expenditure and the energy expenditure at recovery stage was still significantly higher than baseline. The GEE model demonstrated that a linear dose-response relationship existed between the stimulation intensity and the increase of energy expenditure. No subject’s demographic or anthropometric characteristics tested were significantly associated with the increase of energy expenditure. This study suggested NMES may be used to serve as an additional intervention for weight loss programs. Future studies to develop electrical stimulators or stimulation electrodes to maximize the comfort of NMES are recommended.

Hypotension is frequently reported during hemodialysis. This study aimed to examine the effect of the intermittent pneumatic circulator on blood pressure during hemodialysis. Sixteen subjects with chronic hemodialysis were recruited. Each subject randomly received two test conditions on separate days, hemodialysis with and without the circulator. The circulator was applied to the subject on lower extremities during 0.5–1 hr, 1.5–2 hr, 2.5–3 hr, and 3.5–4 hr of hemodialysis. Systolic and diastolic blood pressures (SBP and DBP) and heart rate (HR) were analyzed at pre-dialysis, 1 hr, 2 hr, and 3 hr of hemodialysis. Stroke volume (SV) and cardiac output (CO) were evaluated between 2.5 and 3.0 hr of hemodialysis. Blood chemicals (sodium, calcium, potassium, and phosphorous) and Kt/V before and after each hemodialysis session were analyzed. The number of episodes of hypotension was also recorded. The circulator intervention significantly improved SBP and DBP across all time points (P = 0.002 for SBP; P = 0.002 for DBP). The frequency of hypotension was significantly decreased (P = 0.028). SV and CO were significantly improved with the circulator intervention (P = 0.017 for SV; P = 0.026 for CO) and no statistical significances were found on blood chemicals or Kt/V analyses. The results suggested that the circulator intervention helps stabilize blood pressure and appears to be a practical treatment. Future studies are suggested to develop new circulator innovations with sensor feedback systems to enhance safety and maximize treatment efficiency.

Interpolated twitch technique (ITT) is a non-invasive method for assessing the completeness of muscle activation in clinical settings. Voluntary activation level (VA), measured by ITT and estimated by a conventional linear model, was reported to have a non-linear relationship with true voluntary contraction force at higher activation levels. The relationship needs to be further clarified for the correct use by clinicians and researchers. This study was to established a modified voluntary activation (modified VA) and define a valid range by fitting a non-linear logistic growth model. Eight healthy male adults participated in this study. Each subject performed three sets of voluntary isometric ankle plantar flexions at 20, 40, 60, 80 and 100% maximal voluntary contraction (MVC) with real-time feedback on a computer screen. A supramaximal electrical stimulation was applied on tibia nerve at rest and during contractions. The estimated VA was calculated for each contraction. The relationship between the estimated VA and the actual voluntary contraction force was fitted by a logistic growth model. The result showed that according to the upper and lower limit points of the logistic curve, the valid range was between the 95.16% and 10.55% MVC. The modified VA estimated by this logistic growth model demonstrated less error than the conventional model. This study provided a transfer function for the voluntary activation level and defined the valid range which would provide useful information in clinical applications.

Rate of perceived exertion (RPE) is a clinically convenient indicator for monitoring exercise intensity in cardiopulmonary rehabilitation. It might not be sensitive enough for clinicians to determine the patients’ physiological status because its association with the cardiovascular system and local muscle factors is unknown. This study used the electromyographic sensor to detect the local muscle fatigue and stabilization of patella, and analyzed the relationship between various local muscle and cardiovascular factors and the increase of RPE during stepping exercise, a common exercise program provided in cardiopulmonary rehabilitation. Ten healthy adults (4 males and 6 females) participated in this study. Each subject used their right bare foot to step up onto a 23-cm-high step at a constant speed until the RPE score reached 20. The RPE, heart rate (HR), and surface EMG of the rectus femoris (RF), vastus medialis, and vastus lateralis were recorded at 1-minute intervals during the stepping exercise. The generalized estimating equations (GEE) analysis indicated that the increase in RPE significantly correlated with the increase in HR, and decrease in median frequency (MF) of the EMG power spectrum of the RF. Experimental results suggest that the increase in RPE during stepping exercise was influenced by the cardiovascular status, localized muscle fatigue in the lower extremities. The weighting of the local muscle factors was more than half of the weighting of the cardiovascular factor.

This study was designed: (1) to test the reliability of surface electromyography (sEMG) recording of the diaphragm and external intercostals contractions response to cervical magnetic stimulation (CMS), (2) to examine the amount and the types of inspiratory muscle fatigue that developed after maximum voluntary ventilation (MVV) maneuvers.Ten male college students without physical disability (22.1±2.0 years old) participated in the study and each completed a control (quiet breathing) trial and a fatigue (MVV maneuvers) trial sequentially. In the quiet breathing trial, the subjects maintained quiet breathing for five minutes. The subjects performed five maximal static inspiratory efforts and received five CMS before and after the quiet breathing. In the MVV trial, subjects performed five maximal inspiratory efforts and received five CMS before, immediately after, and ten minutes after two sets of MVV maneuvers performed five minutes apart. Maximal inspiratory pressure (PImax), sEMG of diaphragm and external intercostals during maximal static inspiratory efforts and during CMS were recorded. In the quiet breathing trial, high intraclass correlation coefficients (ICC=0.95-0.99) were observed in all the variables. In the MVV trial, the PImax, the EMG amplitude and the median power frequency during maximal static inspiratory efforts significantly decreased in both the diaphragm and the external intercostals immediately after the MVV maneuvers Sensors 2008, 8 2175 (P < 0.05) and remained decreased in the diaphragm but not in the external intercostals after ten minutes of recovery. MVV maneuvers induced no EMG changes during CMS in either the diaphragm or the external intercostals (P > 0.05). It is concluded that the sEMG recordings of the diaphragm during maximal static inspiratory efforts and in response to CMS allow reproducible sequential assessment of diaphragm contractility. MVV maneuvers resulted in inspiratory muscles fatigue, possibly central fatigue.

In this study, we defined a new parameter, referred to as the cardiac stress index (CSI), using a nonlinear detrended fluctuation analysis (DFA) of heart rate (HR). Our study aimed to incorporate the CSI into a cycling based fatigue monitoring system developed in our previous work so the muscle fatigue and cardiac stress can be both continuously and quantitatively assessed for subjects undergoing the cycling exercise. By collecting electrocardiogram (ECG) signals, the DFA scaling exponent α was evaluated on the RR time series extracted from a windowed ECG segment. We then obtained the running estimate of α by shifting a one-minute window by a step of 20 seconds so the CSI, defined as the percentage of all the less-than-one α values, can be synchronously updated every 20 seconds. Since the rating of perceived exertion (RPE) scale is considered as a convenient index which is commonly used to monitor subjective perceived exercise intensity, we then related the Borg RPE scale value to the CSI in order to investigate and quantitatively characterize the relationship between exercise-induced fatigue and cardiac stress. Twenty-two young healthy participants were recruited in our study. Each participant was asked to maintain a fixed pedaling speed at a constant load during the cycling exercise. Experimental results showed that a decrease in DFA scaling exponent α or an increase in CSI was observed during the exercise. In addition, the Borg RPE scale and CSI were positively correlated, suggesting that the factors due to cardiac stress might also contribute to fatigue state during physical exercise. Since the CSI can effectively quantify the cardiac stress status during physical exercise, our system may be used in sports medicine, or used by cardiologists who carried out stress tests for monitoring heart condition in patients with heart diseases.

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.)