Effects of computer-based cognitive training combined with physical training for older adults with cognitive impairment: A four-arm randomized controlled trial.

Objective: Combined physical (PHY) and cognitive (COG) training in sequential (SEQ) and simultaneous (SIMUL) sessions may delay the progression of cognitive impairment. To date, no study has directly compared in older adults with cognitive impairment the effects of COG training, PHY training, SEQ motor-cognitive training and SIMUL motor-cognitve training on specific indices of cognitive performance and activities of daily living (ADL). The purpose of this study was to determine whether SEQ and SIMUL motor-cognitive training can improve treatment outcomes compared with PHY or COG training alone. We also aimed to compare the effects of SEQ versus SIMUL motor-cognitive training on cognitive functions and instrumental ADL (IADL) in older adults with cognitive impairment. Methods: A cluster randomized controlled trial was conducted. Eighty older adults with cognitive impairment were randomly assigned to COG, PHY, SEQ or SIMUL training groups. The intervention consisted of 90-min training sessions, totaling 36 sessions. Outcome measures were the Montreal Cognitive Assessment, three subtests of the Wechsler Memory Scale (WMS) and the Lawton IADL scale. Results: Significant interaction effects between group and time were found in WMS-spatial span (p = 0.04) and WMS-word lists (p = 0.041). For WMS-spatial span, the SIMUL group showed outperformed the COG (p = 0.039), PHY (p = 0.010) and SEQ groups (p = 0.017). For WMS-word lists, the SEQ group improve more than COG (p = 0.013), PHY (p = 0.030) and SIMUL (p = 0.019) groups. No significant differences were found in IADL performance among four groups (p = 0.645). Conclusions: Our study showed SEQ and SIMUL motor-cognitive training led to more pronounced improvements in visuospatial working memory or verbal memory compared with isolated COG or PHY training for community-based older adults with cognitive impairment. For enhancing effects on IADL, we suggest the use of sensitive measurement tools and context-enriched cognitive training involving real-life task demands.

Indirect causal path from motor function to quality of life through daily use of the affected arm poststroke after task-specific training: a longitudinal mediation analysis.

PURPOSE: Task-specific training generally targets motor function, with the ultimate goal of improving quality of life (QoL). This study aimed to determine whether motor function indirectly affects QoL through daily use of the affected arm and activities of daily living (ADL) in patients with chronic stroke. METHODS: This was a retrospective cohort study of 155 patients who received training for 90-120 min/session, 3-5 sessions/week, for 4-6 weeks. The training involved specific mirror or robot-assisted therapy, followed by functional task practice for 15-30 min in each session. Patients were assessed before and after the intervention. RESULTS: At both pre-test and post-test, significant indirect effects of motor function on QoL through daily use of the affect arm and ADL were observed (ß = 0.087-0.124). When the change scores of the measures between the pre-test and post-test were used, significant mediating effects of daily arm use on the relationship between motor function and QoL were identified (ß = 0.094-0.103). CONCLUSIONS: Enhanced motor function after intervention may lead to an increase in arm use for daily activities and subsequently result in an improvement in QoL. These results highlight the critical role of daily arm use in task-specific training aimed at improving QoL.IMPLICATIONS FOR REHABILITATIONTask-specific training may improve motor function, daily arm use, activities of daily living, and quality of life in patients with mild-to-moderate arm hemiparesis.To improve quality of life in task-specific training, clinicians may work in sequence from motor function to daily arm use and then to activities of daily living.Emphasizing the use of the affected arm in daily life is critical to improve quality of life in task-specific training.

Rapid screening of novel tyrosinase inhibitory peptides from a pearl shell meat hydrolysate by molecular docking and the anti-melanin mechanism.

Pearls are an edible and medicinal resource with whitening activity and nutritional value in China. In the previous study, we found that the pearl shell meat hydrolysate showed dual activities of antioxidation and tyrosinase inhibition, which were similar to the activities of pearls. In this research, a pearl shell meat hydrolysate was isolated, identified and screened by molecular docking, and three peptides FLF, SPSSS and WLL with high tyrosinase inhibitory activities were obtained. The results indicated that FLF, SPSSS and WLL could effectively inhibit tyrosinase activities and the inhibition rates (1.0 mg mL-1) were 54.32%, 65.26% and 57.50%, respectively. The results of a zebrafish whitening experiment showed that the tyrosinase activities of zebrafish treated with FLF, SPSSS and WLL decreased by 75.41%, 62.87% and 64.99% (p < 0.05), respectively, and the melanin content decreased by 37.34%, 38.52% and 40.39% (p < 0.05), respectively. In a B16F10 cell whitening experiment, compared with a control group, FLF, SPSSS and WLL also showed a significant whitening effect, the tyrosinase activities decreased by 84.08%, 79.08% and 77.45% (p < 0.05), respectively, and the melanin content decreased by 42.23%, 34.37% and 34.02% (p < 0.05), respectively. Moreover, the active peptides could act on three signal pathways including Wnt/ß-catenin, MAPK and MC1R/α-MSH and significantly downregulated the expressions of the signaling factors WNT4, MITF, ß-catenin, ERK, JNK, TRP1 and TRP2 (p < 0.05). The results demonstrated that the whitening active peptides were edible natural antioxidants, tyrosinase inhibitors and skin anti-melanin agents, which could be added to functional foods as food ingredients.

Identification and functional analysis of three novel osteogenic peptides isolated from tilapia scale collagen hydrolysate.

On the basis of our previous study that 133 peptides were identified from the tilapia scale peptide-calcium chelate, the potential osteogenic peptide monomers through the calcium-binding properties of peptides and molecular docking were screened, and the osteogenic activity and active mechanism of the peptides were further researched in this study. Three highly osteogenic peptides GPAGPHGPVG (844.4191 Da), APDPFRMY (995.4534 Da), and TPERYY (827.3813 Da) were screened. Molecular docking showed that the three osteogenic peptides had the same interaction sites in the epidermal growth factor receptor (EGFR), namely ARG 285, GLN 8, GLY 317, THR 406, and HIS 409. Compared to the blank control group, within 50 µg/mL of GPAGPHGPVG, APDPFRMY, and TPERYY increased the proliferation of MC3T3-E1 cells by changing the cell proportion in the S and G2/M phases, and the alkaline phosphatase (ALP) activity of MC3T3-E1 cells treated with 50 µg/mL of the three active peptides increased by 25%, 37%, and 56%, respectively. The three active peptides at 10 µg/mL concentration significantly promoted the mineralization of osteoblasts, and the mineralized calcium nodules increased by 166%, 161%, and 111%, respectively. TPERYY significantly increased the expression of osteogenic genes (osteocalcin (OCN), type I collagen (Col I α) and transcription factor (OSX)). Moreover, TPERYY significantly increased the mRNA and protein expression of ß-catenin to 1.39 and 2.6 times of the blank control group, respectively, while decreased the mRNA and protein expression of glycogen synthesis kinase (GSK3ß) to 1.6 and 2.3 times of the blank control group, respectively. This study provides a theoretical basis for using GPAGPHGPVG, APDPFRMY, and TPERYY peptides as functional foods to prevent osteoporosis.

Preparation, characterization, and osteogenic activity mechanism of casein phosphopeptide-calcium chelate.

Casein phosphopeptides (CPPs) are good at calcium-binding and intestinal calcium absorption, but there are few studies on the osteogenic activity of CPPs. In this study, the preparation of casein phosphopeptide calcium chelate (CPP-Ca) was optimized on the basis of previous studies, and its peptide-calcium chelating activity was characterized. Subsequently, the effects of CPP-Ca on the proliferation, differentiation, and mineralization of MC3T3-E1 cells were studied, and the differentiation mechanism of CPP-Ca on MC3T3-E1 cells was further elucidated by RNA sequencing (RNA-seq). The results showed that the calcium chelation rate of CPPs was 23.37%, and the calcium content of CPP-Ca reached 2.64 × 105 mg/kg. The test results of Ultraviolet-Visible absorption spectroscopy (UV) and Fourier transform infrared spectroscopy (FTIR) indicated that carboxyl oxygen and amino nitrogen atoms of CPPs might be chelated with calcium during the chelation. Compared with the control group, the proliferation of MC3T3-E1 cells treated with 250 µg/mL of CPP-Ca increased by 21.65%, 26.43%, and 28.43% at 24, 48, and 72 h, respectively, and the alkaline phosphatase (ALP) activity and mineralized calcium nodules of MC3T3-E1 cells were notably increased by 55% and 72%. RNA-seq results showed that 321 differentially expressed genes (DEGs) were found in MC3T3-E1 cells treated with CPP-Ca, including 121 upregulated and 200 downregulated genes. Gene ontology (GO) revealed that the DEGs mainly played important roles in the regulation of cellular components. The enrichment of the Kyoto Encyclopedia of Genes and Genomes Database (KEGG) pathway indicated that the AMPK, PI3K-Akt, MAPK, and Wnt signaling pathways were involved in the differentiation of MC3T3-E1 cells. The results of a quantitative real-time PCR (qRT-PCR) showed that compared with the blank control group, the mRNA expressions of Apolipoprotein D (APOD), Osteoglycin (OGN), and Insulin-like growth factor (IGF1) were significantly increased by 2.6, 2.0 and 3.0 times, respectively, while the mRNA levels of NOTUM, WIF1, and LRP4 notably decreased to 2.3, 2.1, and 4.2 times, respectively, which were consistent both in GO functional and KEGG enrichment pathway analysis. This study provided a theoretical basis for CPP-Ca as a nutritional additive in the treatment and prevention of osteoporosis.

Machine learning predicts clinically significant health related quality of life improvement after sensorimotor rehabilitation interventions in chronic stroke.

Health related quality of life (HRQOL) reflects individuals perceived of wellness in health domains and is often deteriorated after stroke. Precise prediction of HRQOL changes after rehabilitation interventions is critical for optimizing stroke rehabilitation efficiency and efficacy. Machine learning (ML) has become a promising outcome prediction approach because of its high accuracy and easiness to use. Incorporating ML models into rehabilitation practice may facilitate efficient and accurate clinical decision making. Therefore, this study aimed to determine if ML algorithms could accurately predict clinically significant HRQOL improvements after stroke sensorimotor rehabilitation interventions and identify important predictors. Five ML algorithms including the random forest (RF), k-nearest neighbors (KNN), artificial neural network, support vector machine and logistic regression were used. Datasets from 132 people with chronic stroke were included. The Stroke Impact Scale was used for assessing multi-dimensional and global self-perceived HRQOL. Potential predictors included personal characteristics and baseline cognitive/motor/sensory/functional/HRQOL attributes. Data were divided into training and test sets. Tenfold cross-validation procedure with the training data set was used for developing models. The test set was used for determining model performance. Results revealed that RF was effective at predicting multidimensional HRQOL (accuracy: 85%; area under the receiver operating characteristic curve, AUC-ROC: 0.86) and global perceived recovery (accuracy: 80%; AUC-ROC: 0.75), and KNN was effective at predicting global perceived recovery (accuracy: 82.5%; AUC-ROC: 0.76). Age/gender, baseline HRQOL, wrist/hand muscle function, arm movement efficiency and sensory function were identified as crucial predictors. Our study indicated that RF and KNN outperformed the other three models on predicting HRQOL recovery after sensorimotor rehabilitation in stroke patients and could be considered for future clinical application.

Baseline Global Cognitive Function Affects Cognitive and Functional Outcomes of Combined Physical and Cognitive Training Among Older Adults With Cognitive Decline.

IMPORTANCE: Baseline global cognitive function may affect cognitive and functional outcomes during combined physical and cognitive training; however, how it influences the effects of combined training remains uncertain. OBJECTIVE: To determine the impact of baseline global cognitive function on cognitive and functional outcomes after combined physical and cognitive training among older adults with cognitive decline. DESIGN: Observational. SETTING: Local communities and senior centers. PARTICIPANTS: Older adults with mild cognitive decline (MCD; n = 51) and moderate to severe cognitive decline (MSCD; n = 40). INTERVENTION: Participants received 45 to 55 min of physical exercise training followed by 45 to 55 min of cognitive training in one session per week for 12 wk. Outcomes and Measures: Montreal Cognitive Assessment (MoCA), Lawton-Brody Instrumental Activities of Daily Living Scale (Lawton-Brody IADL), Word Recall Test (WRT), Stroop Color and Word Test (SCWT), Digital Symbol Substitution Test (DSST), and Trail Making Test (TMT) scores were assessed and compared between the MCD and MSCD groups. RESULTS: Significant interaction effects were found for the WRT, SCWT, MoCA, and Lawton-Brody IADL. WRT and SCWT scores significantly improved in the MCD group, whereas MoCA and Lawton-Brody IADL scores significantly improved in the MSCD group. DSST scores increased among all participants, but TMT scores improved only in the MCD group. CONCLUSIONS AND RELEVANCE: Older adults' baseline global cognitive function affected cognitive and instrumental activities of daily living (IADL) outcomes regarding combined training. High-level cognitive function, including inhibition and shifting abilities and working memory capacity, improved among older adults with MCD, whereas general cognitive function and IADLs improved among older adults with MSCD. What This Article Adds: Findings revealed domain-specific changes with respect to baseline cognitive function, which may help to refine current combined training protocols and facilitate development of personalized combined training programs for older adults with cognitive impairments.

Kinematic descriptions of upper limb function using simulated tasks in activities of daily living after stroke.

Assessment of upper limb function poststroke is critical for clinical management and determining the efficacy of interventions. We designed a unilateral upper limb task to simulate activities of daily living to examine how chronic stroke survivors manage reaching, grasping and handling skills simultaneously to perform the functional task using kinematic analysis. The aim of the study was to compare the motor strategies for performing a functional task between paretic and nonparetic arms. Sixteen chronic stroke survivors were instructed to control an ergonomic spoon to transfer liquid from a large bowl to a small bowl using paretic or nonparetic arm. Kinematic data were recorded using a Vicon motion capture system. Outcome measures included movement duration, relative timing, path length, joint excursions, and trial-to-trial variability. Results showed that movement duration, spoon path length, and trunk path length increased significantly when participants used paretic arm to perform the task. Participants tended to reduce shoulder and elbow excursions, and increase trunk excursions to perform the task with paretic arm and altered the relative timing of the task. Although participants used different motor strategies to perform the task with their paretic arms, we did not find the significant differences in trial-to trial variability of joint excursions between paretic and nonparetic arms. The results revealed differences in temporal and spatial aspects of motor strategies between paretic and nonparetic arms. Clinicians should explore the underlying causes of pathological movement patterns and facilitate preferred movement patterns of paretic arm.

Predicting clinically significant motor function improvement after contemporary task-oriented interventions using machine learning approaches.

BACKGROUND: Accurate prediction of motor recovery after stroke is critical for treatment decisions and planning. Machine learning has been proposed to be a promising technique for outcome prediction because of its high accuracy and ability to process large volumes of data. It has been used to predict acute stroke recovery; however, whether machine learning would be effective for predicting rehabilitation outcomes in chronic stroke patients for common contemporary task-oriented interventions remains largely unexplored. This study aimed to determine the accuracy and performance of machine learning to predict clinically significant motor function improvements after contemporary task-oriented intervention in chronic stroke patients and identify important predictors for building machine learning prediction models. METHODS: This study was a secondary analysis of data using two common machine learning approaches, which were the k-nearest neighbor (KNN) and artificial neural network (ANN). Chronic stroke patients (N = 239) that received 30 h of task-oriented training including the constraint-induced movement therapy, bilateral arm training, robot-assisted therapy and mirror therapy were included. The Fugl-Meyer assessment scale (FMA) was the main outcome. Potential predictors include age, gender, side of lesion, time since stroke, baseline functional status, motor function and quality of life. We divided the data set into a training set and a test set and used the cross-validation procedure to construct machine learning models based on the training set. After the models were built, we used the test data set to evaluate the accuracy and prediction performance of the models. RESULTS: Three important predictors were identified, which were time since stroke, baseline functional independence measure (FIM) and baseline FMA scores. Models for predicting motor function improvements were accurate. The prediction accuracy of the KNN model was 85.42% and area under the receiver operating characteristic curve (AUC-ROC) was 0.89. The prediction accuracy of the ANN model was 81.25% and the AUC-ROC was 0.77. CONCLUSIONS: Incorporating machine learning into clinical outcome prediction using three key predictors including time since stroke, baseline functional and motor ability may help clinicians/therapists to identify patients that are most likely to benefit from contemporary task-oriented interventions. The KNN and ANN models may be potentially useful for predicting clinically significant motor recovery in chronic stroke.

Test-retest reliability and minimal detectable change of the Contextual Memory Test in older adults with and without mild cognitive impairment.

BACKGROUND: The ability to detect one's own memory capacity and develop strategies based on daily contexts is important for daily activities. The Contextual Memory Test (CMT) assesses self-awareness, self-efficacy, self-perception/evaluation of performance, recall, and strategy use that are associated with daily contexts, and could be a potentially suitable measurement for assessing memory and meta-memory in older adults with and without cognitive impairment. Nevertheless, the test-retest reliability and minimal detectable change (MDC) remain unknown in these individuals. OBJECTIVE: The purpose of this study was to examine test-retest reliability and calculate MDC of the CMT in healthy older adults and those with mild cognitive impairment (MCI). METHODS: Eighty-three participants completed the CMT twice with a one-month interval. Test-retest reliability was examined using intraclass correlation coefficient (ICC) in all seven domains of the CMT and the recognition subtest. The standard error of measurement (SEM) and MDC were calculated. The Bland-Altman analysis was performed to evaluate the degree of agreement between measurements. RESULTS: The ICC of five domains (self-awareness, self-perception/evaluation of performance, immediate/delayed/total recall) and the recognition subtest were good to excellent (ICC = 0.63-0.94) in healthy and MCI participants and the MDC% were less than 30% The ICC of the other two domains (self-efficacy and total strategy use, TSS) were low (ICC = 0.07-0.59) and the MDC% exceeded 30%. The Bland-Altman analysis showed generally better performance in the 2nd than the 1st measurement in most CMT domains. CONCLUSIONS: Our results revealed sufficient test-retest reliability and acceptable MDC in most CMT domains in healthy and MCI participants. Only the self-efficacy and TSS domains demonstrated low ICC and large MDC. Possible practice effects were found between repeated measurements. Clinicians should be cautious when evaluating self-efficacy and strategy use using the CMT in older adults. Further improvements are needed for these two domains.

Timing-dependent effects of transcranial direct current stimulation with mirror therapy on daily function and motor control in chronic stroke: a randomized controlled pilot study.

BACKGROUND: The timing of transcranial direct current stimulation (tDCS) with neurorehabilitation interventions may affect its modulatory effects. Motor function has been reported to be modulated by the timing of tDCS; however, whether the timing of tDCS would also affect restoration of daily function and upper extremity motor control with neurorehabilitation in stroke patients remains largely unexplored. Mirror therapy (MT) is a potentially effective neurorehabilitation approach for improving paretic arm function in stroke patients. This study aimed to determine whether the timing of tDCS with MT would influence treatment effects on daily function, motor function and motor control in individuals with chronic stroke. METHODS: This study was a double-blinded randomized controlled trial. Twenty-eight individuals with chronic stroke received one of the following three interventions: (1) sequentially combined tDCS with MT (SEQ), (2) concurrently combined tDCS with MT (CON), and (3) sham tDCS with MT (SHAM). Participants received interventions for 90 min/day, 5 days/week for 4 weeks. Daily function was assessed using the Nottingham Extended Activities of Daily Living Scale. Upper extremity motor function was assessed using the Fugl-Meyer Assessment Scale. Upper extremity motor control was evaluated using movement kinematic assessments. RESULTS: There were significant differences in daily function between the three groups. The SEQ group had greater improvement in daily function than the CON and SHAM groups. Kinematic analyses showed that movement time of the paretic hand significantly reduced in the SEQ group after interventions. All three groups had significant improvement in motor function from pre-intervention to post-intervention. CONCLUSION: The timing of tDCS with MT may influence restoration of daily function and movement efficiency of the paretic hand in chronic stroke patients. Sequentially applying tDCS prior to MT seems to be advantageous for enhancing daily function and hand movement control, and may be considered as a potentially useful strategy in future clinical application. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02827864 . Registered on 29th June, 2016.

Three Newly Isolated Calcium-Chelating Peptides from Tilapia Bone Collagen Hydrolysate Enhance Calcium Absorption Activity in Intestinal Caco-2 Cells.

In this study, we used reversed-phase high performance liquid chromatography (LC) to isolate three novel peptides with calcium-chelating capacity from tilapia bone collagen hydrolysate. Using LC-tandem mass spectrometry, we determined the amino acid sequences to be GPAGPHGPVG, FDHIVY, and YQEPVIAPKL. We then synthesized the three peptides and verified their calcium-chelating activity. Results showed that the calcium-chelating activity of GPAGPHGPVG, FDHIVY, and YQEPVIAPKL reached 18.80 ± 0.49, 35.73 ± 0.74, and 28.4 ± 0.94 mg/g, respectively. We next investigated how each peptide enhanced intestinal calcium absorption using Caco-2 cell monolayers. Compared with the control group, GPAGPHGPVG, FDHIVY, and YQEPVIAPKL potently enhanced calcium transport within 30 min by 89 ± 9, 202 ± 12, and 130 ± 7%, respectively. Results suggest that these peptides isolated from tilapia bone hydrolysate can be used as dietary supplements to increase calcium absorption.

Predictors of Clinically Important Changes in Actual and Perceived Functional Arm Use of the Affected Upper Limb After Rehabilitative Therapy in Chronic Stroke.

OBJECTIVE: To identify the predictors of minimal clinically important changes in actual and perceived functional arm use of the affected upper limb after rehabilitative therapy. DESIGN: Retrospective, observational cohort study. SETTING: Outpatient rehabilitation settings. PARTICIPANTS: A cohort of 94 patients with chronic stroke. INTERVENTIONS: Patients received robot-assisted therapy, mirror therapy, or combined therapy for 4 weeks. MAIN OUTCOME MEASURES: The primary outcome measures, assessed pre- and post intervention, included actual functional arm use measured by an accelerometer and perceived functional arm use measured by the Motor Activity Log (MAL). Candidate predictors included age, sex, time after stroke, side of stroke, and scores on the Fugl-Meyer Assessment, Modified Ashworth Scale, Medical Research Council scale, Wolf Motor Function Test, MAL (quality of movement), and Nottingham Extended Activities of Daily Living. RESULTS: Being male (odds ratio [OR], 3.17; 95% CI, 1.13-8.87) and having a higher than median Medical Research Council score (OR, 2.68; 95% CI, 1.12-6.41) significantly predicted minimal clinically important changes assessed by an accelerometer. Fugl-Meyer Assessment scores (odds ratio, 1.06; 95% CI, 1.02-1.11) were a significant predictor of achieving clinically important changes in MAL amount of use. Wolf Motor Function Test (quality) scores (OR, 3.05; 95% CI, 1.38-6.77) could predict clinically important improvements in MAL quality of movement. CONCLUSIONS: Predictors of clinically important changes in the use of the affected upper limb after robot-assisted therapy, mirror therapy, or combined therapy in patients with chronic stroke for 4 weeks differ for actual vs perceived use. Further studies are recommended to validate these findings in a larger sample.

The purification, identification and bioactivity study of a novel calcium-binding peptide from casein hydrolysate.

In this study, a novel calcium-binding peptide from casein hydrolysate was purified using reversed-phase high performance liquid chromatography and sequenced by high-performance liquid chromatography-mass spectrometry (MS)/MS. The amino acid sequence of the calcium-binding peptide was identified as VLPVPQK (N- to C-terminal, MW = 779.4960 Da). The calcium binding characteristics of VLPVPQK were further investigated using UV absorption spectroscopy, zeta potential and isothermal titration calorimetry (ITC). The results showed that VLPVPQK has a strong calcium binding activity (129.46 mg g-1), 312% higher than that of 3-hour enzymatic hydrolysates. VLPVPQK could chelate calcium with a 1 : 3 stoichiometry, causing a decrease in the positive charge of the peptide-Ca2+ complex. Furthermore, VLPVPQK could effectively enhance calcium transport and absorption in a concentration-dependent manner in Caco-2 cell monolayers, suggesting that VLPVPQK has the potential to be developed as a nutraceutical additive.

Not all brain regions are created equal for improving bimanual coordination in individuals with chronic stroke.

OBJECTIVE: The now standard cortical stimulation approach of inhibiting contralesional primary motor cortex (cM1) disrupts bimanual coordination while facilitating ipsilesional M1 (iM1) fails to enhance paretic arm function, in severely impaired individuals. We propose an alternative target, enhancing contralesional dorsal premotor cortex (cPMd) to improve bimanual coordination and compare its effects to iM1. METHODS: Fourteen participants with stroke received 5-Hz repetitive transcranial magnetic stimulation (rTMS) on cPMd or iM1 in a repeated cross-over design. Bimanual force/neuromuscular coordination and cortical excitability were assessed. We also examined the relationship of baseline motor function/interhemispheric inhibition (IHI) to participant's responses to each stimulation target. RESULTS: We identified two patterns of responses. Participants with more severe impairment and weaker IHI improved bimanual force/neuromuscular coordination, ipsilesional activations and reduced IHI after cPMd-rTMS; whereas, those with milder impairment and stronger IHI improved only after iM1-rTMS. CONCLUSIONS: Cortical stimulation protocols could be tailored to the types of tasks and to individuals' severity of impairment. Facilitation of cPMd may improve bimanual coordination especially for individuals with limited arm/hand function. SIGNIFICANCE: Our study is the first to identify cortical stimulation strategies for improving bimanual coordination for individuals with different level of severity of stroke.

Isolation and identification of iron-chelating peptides from casein hydrolysates.

Iron deficiency is a common nutritional disorder worldwide. Peptides derived from protein hydrolysates have recently attracted interest as novel iron chelators due to their superiority in terms of increasing solubility, bioavailability, absorption and stability. The aim of this study was to isolate and identify iron-chelating peptides from casein hydrolysates. Casein was hydrolyzed (trypsin, 3 h) and subsequently isolated using ultrafiltration and RP-HPLC. Four iron-chelating casein hydrolysate peptides, named CHP-1, CHP-2, CHP-3 and CHP-4, were identified by LC-MS/MS, and their amino acid sequences were Glu-Asp-Val-Pro-Ser-Glu-Arg (EDVPSER), His-Lys-Glu-Met-Pro-Phe-Pro-Lys (HKEMPFPK), Asn-Met-Ala-Ile-Asn-Pro-Ser-Lys (NMAINPSK) and Ala-Val-Pro-Tyr-Pro-Gln-Arg (AVPYPQR), with molecular weights of 830.6120 Da, 1012.5280 Da, 873.4440 Da and 829.4570 Da, respectively. The artificially synthesized peptides of CHP-1, CHP-2, CHP-3 and CHP-4 were verified, and their iron-chelating rates were 11.14%, 8.02%, 7.57% and 59.76%, respectively. These results suggested that the isolated iron-chelating peptides might serve as potential iron supplements and be used as food additives and functional foods.

Anti-fatigue and anti-oxidant activities of oyster (Ostrea rivularis) hydrolysate prepared by compound protease.

Oyster, which is rich in protein and widely used as a marine traditional Chinese medicine, was believed to have good curative effects in health care and on chronic diseases. This study was designed to evaluate the anti-fatigue and anti-oxidant effects of oyster hydrolysate. Oyster meat (OM) was hydrolyzed with a complex protease, and oyster hydrolysate (OH) was separated by a 6 kDa ultrafiltration membrane into two fractions, OH-I (<6 kDa) and OH-II (≥6 kDa). The anti-fatigue effects of OM, OH, OH-I and OH-II groups were first investigated, and then the antioxidant activities of OH-I and OH-II were further analyzed. Anti-fatigue experimental results showed that OH-I displayed the strongest activity among the four groups. Compared to the control group, OH-I significantly prolonged swimming time (67.79%), increased the content of muscle glycogen (45.65%) and liver glycogen (49.01%), and reduced the content of blood urea nitrogen (BUN) (18.44%) (P < 0.05). Meanwhile, OH-I showed excellent chemical and cellular antioxidant activities, especially when the concentration increased; its antioxidant activity was significantly better than that of OH-II (P < 0.05). Results of an amino acid analysis showed that OH-I was rich in branched-chain amino acids (10.84 g per 100 g), Glu (8.63 g per 100 g), Tau (1.68 g per 100 g), Asp (5.02 g per 100 g) and Arg (3.61 g per 100 g), which were expected to contribute to its antioxidant and anti-fatigue activities.

Neural motor control differs between bimanual common-goal vs. bimanual dual-goal tasks.

Coordinating bimanual movements is essential for everyday activities. Two common types of bimanual tasks are common goal, where two arms share a united goal, and dual goal, which involves independent goals for each arm. Here, we examine how the neural control mechanisms differ between these two types of bimanual tasks. Ten non-disabled individuals performed isometric force tasks of the elbow at 10% of their maximal voluntary force in both bimanual common and dual goals as well as unimanual conditions. Using transcranial magnetic stimulation, we concurrently examined the intracortical inhibitory modulation (short-interval intracortical inhibition, SICI) as well as the interlimb coordination strategies utilized between common- vs. dual-goal tasks. Results showed a reduction of SICI in both hemispheres during dual-goal compared to common-goal tasks (dominant hemisphere: P = 0.04, non-dominant hemisphere: P = 0.03) and unimanual tasks (dominant hemisphere: P = 0.001, non-dominant hemisphere: P = 0.001). For the common-goal task, a reduction of SICI was only seen in the dominant hemisphere compared to unimanual tasks (P = 0.03). Behaviorally, two interlimb coordination patterns were identified. For the common-goal task, both arms were organized into a cooperative "give and take" movement pattern. Control of the non-dominant arm affected stabilization of bimanual force (R2 = 0.74, P = 0.001). In contrast, for the dual-goal task, both arms were coupled together in a positive fashion and neither arm affected stabilization of bimanual force (R2 = 0.31, P = 0.1). The finding that intracortical inhibition and interlimb coordination patterns were different based on the goal conceptualization of bimanual tasks has implications for future research.

Posture-related modulations in motor cortical excitability of the proximal and distal arm muscles.

The effect of postural orientation on the motor corticospinal excitability (MCE) of proximal and distal upper extremity (UE) muscles was investigated. In a crossover design, recruitment curves (RCs), short interval cortical inhibition (SICI) and intracortical facilitation (ICF) of resting anterior deltoid (AD) and first dorsal interosseus (FDI) was assessed in two postures: sitting and standing. Six healthy adults without contraindications to transcranial magnetic stimulation (TMS) participated in the study. TMS was applied over the motor cortical representation of FDI and AD at intensities ranging from 90% to 200% of resting motor threshold (RMT) in increments of 10%. SICI and ICF were assessed for each muscle using a conditioning stimulus (80% RMT) preceding a test stimulus (120% RMT) with an interstimulus interval of 2 ms and 15 ms, respectively. For AD, but not FDI, there was a significant and consistent increase in RC slope during standing compared to sitting. For FDI, there was no difference in ICF and SICI between sitting and standing. However, for AD, while there was no difference in ICF between the two postures, there was a clear trend for SICI to decrease (p=0.06) in standing compared to sitting. These results indicate that postural change from sitting to standing, affects the MCE of proximal but not distal muscles. While this indicates the role of proximal UE muscles in postural control, it also implies that rehabilitation protocols for enhancing proximal arm motor function may be advantaged if administered in a standing posture.

Effects of robot-assisted upper limb rehabilitation on daily function and real-world arm activity in patients with chronic stroke: a randomized controlled trial.

OBJECTIVE: To compare the outcome of robot-assisted therapy with dose-matched active control therapy by using accelerometers to study functional recovery in chronic stroke patients. DESIGN: Prospective, randomized, controlled trial. SETTING: Stroke units in three medical centres. SUBJECTS: Twenty patients post stroke for a mean of 22 months. INTERVENTION: Robot-assisted therapy (n = 10) or dose-matched active control therapy (n = 10). All patients received either of these two therapies for 90-105 minutes each day, 5 days per week, for four weeks. MAIN MEASURES: Outcome measures included arm activity ratio (the ratio of mean activity between the impaired and unimpaired arm) and scores on the Fugl-Meyer Assessment Scale, Functional Independence Measure, Motor Activity Log and ABILHAND questionnaire. RESULTS: The robot-assisted therapy group significantly increased motor function, hemiplegic arm activity and bilateral arm coordination (Fugl-Meyer Assessment Scale: 51.20 ± 8.82, P = 0.002; mean arm activity ratio: 0.76 ± 0.10, P = 0.026; ABILHAND questionnaire: 1.24 ± 0.28, P = 0.043) compared with the dose-matched active control group (Fugl-Meyer Assessment Scale: 40.90 ± 13.14; mean arm movement ratio: 0.69 ± 0.11; ABILHAND questionnaire: 0.95 ± 0.43). CONCLUSIONS: Symmetrical and bilateral robotic practice, combined with functional task training, can significantly improve motor function, arm activity, and self-perceived bilateral arm ability in patients late after stroke.