Enhancement of STroke REhabilitation with Levodopa (ESTREL): Rationale and design of a randomized placebo-controlled, double blind superiority trial.

RATIONALE: Novel therapeutic approaches are needed in stroke recovery. Whether pharmacological therapies are beneficial for enhancing stroke recovery is unclear. Dopamine is a neurotransmitter involved in motor learning, reward, and brain plasticity. Its prodrug levodopa is a promising agent for stroke recovery. AIM AND HYPOTHESIS: To investigate the hypothesis that levodopa, in addition to standardized rehabilitation therapy based on active task training, results in an enhancement of functional recovery in acute ischemic or hemorrhagic stroke patients compared to placebo. DESIGN: ESTREL (Enhancement of Stroke REhabilitation with Levodopa) is a randomized (ratio 1:1), multicenter, placebo-controlled, double-blind, parallel-group superiority trial. PARTICIPANTS: 610 participants (according to sample size calculation) with a clinically meaningful hemiparesis will be enrolled ⩽7 days after stroke onset. Key eligibility criteria include (i) in-hospital-rehabilitation required, (ii) capability to participate in rehabilitation, (iii) previous independence in daily living. INTERVENTION: Levodopa 100 mg/carbidopa 25 mg three times daily, administered for 5 weeks in addition to standardized rehabilitation. The study intervention will be initiated within 7 days after stroke onset. COMPARISON: Matching placebo plus standardized rehabilitation. OUTCOMES: The primary outcome is the between-group difference of the Fugl-Meyer-Motor Assessment (FMMA) total score measured 3 months after randomization. Secondary outcomes include patient-reported health and wellbeing (PROMIS 10 and 29), patient-reported assessment of improvement, Rivermead Mobility Index, modified Rankin Scale, National Institutes of Health Stroke Scale (NIHSS), and as measures of harm: mortality, recurrent stroke, and serious adverse events. CONCLUSION: The ESTREL trial will provide evidence of whether the use of Levodopa in addition to standardized rehabilitation in stroke patients leads to better functional recovery compared to rehabilitation alone.

Accuracy, concurrent validity, and test-retest reliability of pressure-based insoles for gait measurement in chronic stroke patients.

Introduction: Wearables are potentially valuable tools for understanding mobility behavior in individuals with neurological disorders and how it changes depending on health status, such as after rehabilitation. However, the accurate detection of gait events, which are crucial for the evaluation of gait performance and quality, is challenging due to highly individual-specific patterns that also vary greatly in movement and speed, especially after stroke. Therefore, the purpose of this study was to assess the accuracy, concurrent validity, and test-retest reliability of a commercially available insole system in the detection of gait events and the calculation of stance duration in individuals with chronic stroke. Methods: Pressure insole data were collected from 17 individuals with chronic stroke during two measurement blocks, each comprising three 10-min walking tests conducted in a clinical setting. The gait assessments were recorded with a video camera that served as a ground truth, and pressure insoles as an experimental system. We compared the number of gait events and stance durations between systems. Results and discussion: Over all 3,820 gait events, 90.86% were correctly identified by the insole system. Recall values ranged from 0.994 to 1, with a precision of 1 for all measurements. The F1 score ranged from 0.997 to 1. Excellent absolute agreement (Intraclass correlation coefficient, ICC = 0.874) was observed for the calculation of the stance duration, with a slightly longer stance duration recorded by the insole system (difference of -0.01 s). Bland-Altmann analysis indicated limits of agreement of 0.33 s that were robust to changes in walking speed. This consistency makes the system well-suited for individuals post-stroke. The test-retest reliability between measurement timepoints T1 and T2 was excellent (ICC = 0.928). The mean difference in stance duration between T1 and T2 was 0.03 s. We conclude that the insole system is valid for use in a clinical setting to quantitatively assess continuous walking in individuals with stroke.

Interrater reliability of the Fugl-Meyer Motor assessment in stroke patients: a quality management project within the ESTREL study.

Introduction: The Fugl-Meyer Motor Assessment (FMMA) is recommended for evaluating stroke motor recovery in clinical practice and research. However, its widespread use requires refined reliability data, particularly across different health professions. We therefore investigated the interrater reliability of the FMMA scored by a physical therapist and a physician using video recordings of stroke patients. Methods: The FMMA videos of 50 individuals 3 months post stroke (28 females, mean age 71.64 years, median National Institutes of Health Stroke Scale score 3.00) participating in the ESTREL trial (Enhancement of Stroke Rehabilitation with Levodopa: a randomized placebo-controlled trial) were independently scored by two experienced assessors (i.e., a physical therapist and a physician) with specific training to ensure consistency. As primary endpoint, the interrater reliability was calculated for the total scores of the entire FMMA and the total scores of the FMMA for the upper and lower extremities using intraclass correlation coefficients (ICC). In addition, Spearman's rank order correlation coefficients (Spearman's rho) were calculated for the total score and subscale levels. Secondary endpoints included the FMMA item scores using percentage agreement, weighted Cohen's kappa coefficients, and Gwet's AC1/AC2 coefficients. Results: ICCs were 0.98 (95% confidence intervals (CI) 0.96-0.99) for the total scores of the entire FMMA, 0.98 (95% CI 0.96-0.99) for the total scores of the FMMA for the upper extremity, and 0.85 (95% CI 0.70-0.92) for the total scores of the FMMA for the lower extremity. Spearman's rho ranged from 0.61 to 0.94 for total and subscale scores. The interrater reliability at the item level of the FMMA showed (i) percentage agreement values with a median of 77% (range 44-100%), (ii) weighted Cohen's kappa coefficients with a median of 0.69 (range 0.00-0.98) and (iii) Gwet's AC1/AC2 coefficients with a median of 0.84 (range 0.42-0.98). Discussion and conclusion: The FMMA appears to be a highly reliable measuring instrument at the overall score level for assessors from different health professions. The FMMA total scores seem to be suitable for the quantitative measurement of stroke recovery in both clinical practice and research, although there is potential for improvement at the item level.

Telerehabilitation Following Stroke.

Stroke remains a major cause of disability. Intensive rehabilitation therapy can improve outcomes, but most patients receive limited doses. Telehealth methods can overcome obstacles to delivering intensive therapy and thereby address this unmet need. A specific example is reviewed in detail, focused on a telerehabilitation system that targets upper extremity motor deficits after stroke. Strengths of this system include provision of daily therapy associated with very high patient compliance, safety and feasibility in the inpatient or home setting, comparable efficacy to dose-matched therapy provided in-clinic, and a holistic approach that includes assessment, education, prevention, and activity-based therapy.

Cerebral blood flow velocity progressively decreases with increasing levels of verticalization in healthy adults. A cross-sectional study with an observational design.

Background: Autoregulation of the cerebral vasculature keeps brain perfusion stable over a range of systemic mean arterial pressures to ensure brain functioning, e.g., in different body positions. Verticalization, i.e., transfer from lying (0°) to upright (70°), which causes systemic blood pressure drop, would otherwise dramatically lower cerebral perfusion pressure inducing fainting. Understanding cerebral autoregulation is therefore a prerequisite to safe mobilization of patients in therapy. Aim: We measured the impact of verticalization on cerebral blood flow velocity (CBFV) and systemic blood pressure (BP), heart rate (HR) and oxygen saturation in healthy individuals. Methods: We measured CBFV in the middle cerebral artery (MCA) of the dominant hemisphere in 20 subjects using continuous transcranial doppler ultrasound (TCD). Subjects were verticalized at 0°, -5°, 15°, 30°, 45° and 70° for 3-5 min each, using a standardized Sara Combilizer chair. In addition, blood pressure, heart rate and oxygen saturation were continuously monitored. Results: We show that CBFV progressively decreases in the MCA with increasing degrees of verticalization. Systolic and diastolic BP, as well as HR, show a compensatory increase during verticalization. Conclusion: In healthy adults CBFV changes rapidly with changing levels of verticalization. The changes in the circulatory parameters are similar to results regarding classic orthostasis. Registration: ClinicalTrials.gov, identifier: NCT04573114.

An online method to monitor hand muscle tone during robot-assisted rehabilitation.

Introduction: Robot-assisted neurorehabilitation is becoming an established method to complement conventional therapy after stroke and provide intensive therapy regimes in unsupervised settings (e.g., home rehabilitation). Intensive therapies may temporarily contribute to increasing muscle tone and spasticity, especially in stroke patients presenting tone alterations. If sustained without supervision, such an increase in muscle tone could have negative effects (e.g., functional disability, pain). We propose an online perturbation-based method that monitors finger muscle tone during unsupervised robot-assisted hand therapy exercises. Methods: We used the ReHandyBot, a novel 2 degrees of freedom (DOF) haptic device to perform robot-assisted therapy exercises training hand grasping (i.e., flexion-extension of the fingers) and forearm pronosupination. The tone estimation method consisted of fast (150 ms) and slow (250 ms) 20 mm ramp-and-hold perturbations on the grasping DOF, which were applied during the exercises to stretch the finger flexors. The perturbation-induced peak force at the finger pads was used to compute tone. In this work, we evaluated the method performance in a stiffness identification experiment with springs (0.97 and 1.57 N/mm), which simulated the stiffness of a human hand, and in a pilot study with subjects with increased muscle tone after stroke and unimpaired, which performed one active sensorimotor exercise embedding the tone monitoring method. Results: The method accurately estimates forces with root mean square percentage errors of 3.8% and 11.3% for the soft and stiff spring, respectively. In the pilot study, six chronic ischemic stroke patients [141.8 (56.7) months after stroke, 64.3 (9.5) years old, expressed as mean (std)] and ten unimpaired subjects [59.9 (6.1) years old] were tested without adverse events. The average reaction force at the level of the fingertip during slow and fast perturbations in the exercise were respectively 10.7 (5.6) N and 13.7 (5.6) N for the patients and 5.8 (4.2) N and 6.8 (5.1) N for the unimpaired subjects. Discussion: The proposed method estimates reaction forces of physical springs accurately, and captures online increased reaction forces in persons with stroke compared to unimpaired subjects within unsupervised human-robot interactions. In the future, the identified range of muscle tone increase after stroke could be used to customize therapy for each subject and maintain safety during intensive robot-assisted rehabilitation.

Reliability and Validity of a Wearable Sensing System and Online Gait Analysis Report in Persons after Stroke.

The restoration of gait and mobility after stroke is an important and challenging therapy goal due to the complexity of the potentially impaired functions. As a result, precise and clinically feasible assessment methods are required for personalized gait rehabilitation after stroke. The aim of this study is to investigate the reliability and validity of a sensor-based gait analysis system in stroke survivors with different severities of gait deficits. For this purpose, 28 chronic stroke survivors (9 women, ages: 62.04 ± 11.68 years) with mild to moderate walking impairments performed a set of ambulatory assessments (3× 10MWT, 1× 6MWT per session) twice while being equipped with a sensor suit. The derived gait reports provided information about speed, step length, step width, swing and stance phases, as well as joint angles of the hip, knee, and ankle, which we analyzed for test-retest reliability and hypothesis testing. Further, test-retest reliability resulted in a mean ICC of 0.78 (range: 0.46-0.88) for walking 10 m and a mean ICC of 0.90 (range: 0.63-0.99) for walking 6 min. Additionally, all gait parameters showed moderate-to-strong correlations with clinical scales reflecting lower limb function. These results support the applicability of this sensor-based gait analysis system for individuals with stroke-related walking impairments.

A low-dimensional representation of arm movements and hand grip forces in post-stroke individuals.

Characterizing post-stroke impairments in the sensorimotor control of arm and hand is essential to better understand altered mechanisms of movement generation. Herein, we used a decomposition algorithm to characterize impairments in end-effector velocity and hand grip force data collected from an instrumented functional task in 83 healthy control and 27 chronic post-stroke individuals with mild-to-moderate impairments. According to kinematic and kinetic raw data, post-stroke individuals showed reduced functional performance during all task phases. After applying the decomposition algorithm, we observed that the behavioural data from healthy controls relies on a low-dimensional representation and demonstrated that this representation is mostly preserved post-stroke. Further, it emerged that reduced functional performance post-stroke correlates to an abnormal variance distribution of the behavioural representation, except when reducing hand grip forces. This suggests that the behavioural repertoire in these post-stroke individuals is mostly preserved, thereby pointing towards therapeutic strategies that optimize movement quality and the reduction of grip forces to improve performance of daily life activities post-stroke.

Characterization of stroke-related upper limb motor impairments across various upper limb activities by use of kinematic core set measures.

BACKGROUND: Upper limb kinematic assessments provide quantifiable information on qualitative movement behavior and limitations after stroke. A comprehensive characterization of spatiotemporal kinematics of stroke subjects during upper limb daily living activities is lacking. Herein, kinematic expressions were investigated with respect to different movement types and impairment levels for the entire task as well as for motion subphases. METHOD: Chronic stroke subjects with upper limb movement impairments and healthy subjects performed a set of daily living activities including gesture and grasp movements. Kinematic measures of trunk displacement, shoulder flexion/extension, shoulder abduction/adduction, elbow flexion/extension, forearm pronation/supination, wrist flexion/extension, movement time, hand peak velocity, number of velocity peaks (NVP), and spectral arc length (SPARC) were extracted for the whole movement as well as the subphases of reaching distally and proximally. The effects of the factors gesture versus grasp movements, and the impairment level on the kinematics of the whole task were tested. Similarities considering the metrics expressions and relations were investigated for the subphases of reaching proximally and distally between tasks and subgroups. RESULTS: Data of 26 stroke and 5 healthy subjects were included. Gesture and grasp movements were differently expressed across subjects. Gestures were performed with larger shoulder motions besides higher peak velocity. Grasp movements were expressed by larger trunk, forearm, and wrist motions. Trunk displacement, movement time, and NVP increased and shoulder flexion/extension decreased significantly with increased impairment level. Across tasks, phases of reaching distally were comparable in terms of trunk displacement, shoulder motions and peak velocity, while reaching proximally showed comparable expressions in trunk motions. Consistent metric relations during reaching distally were found between shoulder flexion/extension, elbow flexion/extension, peak velocity, and between movement time, NVP, and SPARC. Reaching proximally revealed reproducible correlations between forearm pronation/supination and wrist flexion/extension, movement time and NVP. CONCLUSION: Spatiotemporal differences between gestures versus grasp movements and between different impairment levels were confirmed. The consistencies of metric expressions during movement subphases across tasks can be useful for linking kinematic assessment standards and daily living measures in future research and performing task and study comparisons. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03135093. Registered 26 April 2017, https://clinicaltrials.gov/ct2/show/NCT03135093 .

Changes in Stroke Rehabilitation during the Sars-Cov-2 Shutdown in Switzerland.

INTRODUCTION: Many stroke survivors require continuous outpatient rehabilitation therapy to maintain or improve their neurological functioning, independ-ence, and quality of life. In Switzerland and many other countries, the shutdown to contain SARS-CoV-2 infections led to mobility restrictions and a decrease in therapy delivery. This study investigated the impact of the COVID-19 shutdown on stroke survivors' access to therapy, physical activity, functioning and mood. METHODS: A prospective observational cohort study in stroke subjects. At 4 time-points (before, during, after the shutdown, and at 3-month follow-up), the amount of therapy, physical activities, motor func-tion, anxiety, and depression were assessed. RESULTS: Thirty-six community-dwelling stroke subjects (median 70 years of age, 10 months post--stroke) were enrolled. Therapy reductions related to the shutdown were reported in 72% of subjects. This decrease was associated with significantly extended sedentary time and minimal deterioration in physical activity during the shutdown. Both parameters improved between reopening and 3-month follow-up. Depressive symptoms increased slightly during the observation period. Patients more frequently report-ed on self-directed training during shutdown. CONCLUSION: The COVID-19 shutdown had measurable immediate, but no persistent, effects on post--stroke outcomes, except for depression. Importantly, a 2-month reduction in therapy may trigger improvements when therapy is fully re-initiated thereafter.

U-Limb: A multi-modal, multi-center database on arm motion control in healthy and post-stroke conditions.

BACKGROUND: Shedding light on the neuroscientific mechanisms of human upper limb motor control, in both healthy and disease conditions (e.g., after a stroke), can help to devise effective tools for a quantitative evaluation of the impaired conditions, and to properly inform the rehabilitative process. Furthermore, the design and control of mechatronic devices can also benefit from such neuroscientific outcomes, with important implications for assistive and rehabilitation robotics and advanced human-machine interaction. To reach these goals, we believe that an exhaustive data collection on human behavior is a mandatory step. For this reason, we release U-Limb, a large, multi-modal, multi-center data collection on human upper limb movements, with the aim of fostering trans-disciplinary cross-fertilization. CONTRIBUTION: This collection of signals consists of data from 91 able-bodied and 65 post-stroke participants and is organized at 3 levels: (i) upper limb daily living activities, during which kinematic and physiological signals (electromyography, electro-encephalography, and electrocardiography) were recorded; (ii) force-kinematic behavior during precise manipulation tasks with a haptic device; and (iii) brain activity during hand control using functional magnetic resonance imaging.

Comparing a Novel Neuroanimation Experience to Conventional Therapy for High-Dose Intensive Upper-Limb Training in Subacute Stroke: The SMARTS2 Randomized Trial.

BACKGROUND: Evidence from animal studies suggests that greater reductions in poststroke motor impairment can be attained with significantly higher doses and intensities of therapy focused on movement quality. These studies also indicate a dose-timing interaction, with more pronounced effects if high-intensity therapy is delivered in the acute/subacute, rather than chronic, poststroke period. OBJECTIVE: To compare 2 approaches of delivering high-intensity, high-dose upper-limb therapy in patients with subacute stroke: a novel exploratory neuroanimation therapy (NAT) and modified conventional occupational therapy (COT). METHODS: A total of 24 patients were randomized to NAT or COT and underwent 30 sessions of 60 minutes time-on-task in addition to standard care. The primary outcome was the Fugl-Meyer Upper Extremity motor score (FM-UE). Secondary outcomes included Action Research Arm Test (ARAT), grip strength, Stroke Impact Scale hand domain, and upper-limb kinematics. Outcomes were assessed at baseline, and days 3, 90, and 180 posttraining. Both groups were compared to a matched historical cohort (HC), which received only 30 minutes of upper-limb therapy per day. RESULTS: There were no significant between-group differences in FM-UE change or any of the secondary outcomes at any timepoint. Both high-dose groups showed greater recovery on the ARAT (7.3 ± 2.9 points; P = .011) but not the FM-UE (1.4 ± 2.6 points; P = .564) when compared with the HC. CONCLUSIONS: Neuroanimation may offer a new, enjoyable, efficient, and scalable way to deliver high-dose and intensive upper-limb therapy.

Quantifying Pathological Synergies in the Upper Extremity of Stroke Subjects With the Use of Inertial Measurement Units: A Pilot Study.

BACKGROUND: Stroke is one of the main causes of disability in the world, causing loss of motor function on mainly one side of the body. A proper assessment of motor function is required to help to direct and evaluate therapy. Assessment is currently performed by therapists using observer-based standardized clinical assessment protocols. Sensor-based technologies can be used to objectively quantify the presence and severity of motor impairments in stroke patients. METHODS: In this work, a minimally obstructive distributed inertial sensing system, intended to measure kinematics of the upper extremity, was developed and tested in a pilot study, where 10 chronic stroke subjects performed the arm-related tasks from the Fugl-Meyer Assessment protocol with the affected and non-affected side. RESULTS: The pilot study showed that the developed distributed measurement system was adequately sensitive to show significant differences in stroke subjects' arm postures between the affected and non-affected side. The presence of pathological synergies can be analysed using the measured joint angles of the upper limb segments, that describe the movement patterns of the subject. CONCLUSION: Features measured by the system vary from the assessed FMA-UE sub-score showing its potential to provide more detailed clinical information.

Technology-aided assessment of functionally relevant sensorimotor impairments in arm and hand of post-stroke individuals.

BACKGROUND: Assessing arm and hand sensorimotor impairments that are functionally relevant is essential to optimize the impact of neurorehabilitation interventions. Technology-aided assessments should provide a sensitive and objective characterization of upper limb impairments, but often provide arm weight support and neglect the importance of the hand, thereby questioning their functional relevance. The Virtual Peg Insertion Test (VPIT) addresses these limitations by quantifying arm and hand movements as well as grip forces during a goal-directed manipulation task requiring active lifting of the upper limb against gravity. The aim of this work was to evaluate the ability of the VPIT metrics to characterize arm and hand sensorimotor impairments that are relevant for performing functional tasks. METHODS: Arm and hand sensorimotor impairments were systematically characterized in 30 chronic stroke patients using conventional clinical scales and the VPIT. For the latter, ten previously established kinematic and kinetic core metrics were extracted. The validity and robustness of these metrics was investigated by analyzing their clinimetric properties (test-retest reliability, measurement error, learning effects, concurrent validity). RESULTS: Twenty-three of the participants, the ones with mild to moderate sensorimotor impairments and without strong cognitive deficits, were able to successfully complete the VPIT protocol (duration 16.6 min). The VPIT metrics detected impairments in arm and hand in 90.0% of the participants, and were sensitive to increased muscle tone and pathological joint coupling. Most importantly, significant moderate to high correlations between conventional scales of activity limitations and the VPIT metrics were found, thereby indicating their functional relevance when grasping and transporting objects, and when performing dexterous finger manipulations. Lastly, the robustness of three out of the ten VPIT core metrics in post-stroke individuals was confirmed. CONCLUSIONS: This work provides evidence that technology-aided assessments requiring goal-directed manipulations without arm weight support can provide an objective, robust, and clinically feasible way to assess functionally relevant sensorimotor impairments in arm and hand in chronic post-stroke individuals with mild to moderate deficits. This allows for a better identification of impairments with high functional relevance and can contribute to optimizing the functional benefits of neurorehabilitation interventions.

Assessment of Upper Limb Movement Impairments after Stroke Using Wearable Inertial Sensing.

Precise and objective assessments of upper limb movement quality after strokes in functional task conditions are an important prerequisite to improve understanding of the pathophysiology of movement deficits and to prove the effectiveness of interventions. Herein, a wearable inertial sensing system was used to capture movements from the fingers to the trunk in 10 chronic stroke subjects when performing reach-to-grasp activities with the affected and non-affected upper limb. It was investigated whether the factors, tested arm, object weight, and target height, affect the expressions of range of motion in trunk compensation and flexion-extension of the elbow, wrist, and finger during object displacement. The relationship between these metrics and clinically measured impairment was explored. Nine subjects were included in the analysis, as one had to be excluded due to defective data. The tested arm and target height showed strong effects on all metrics, while an increased object weight showed effects on trunk compensation. High inter- and intrasubject variability was found in all metrics without clear relationships to clinical measures. Relating all metrics to each other resulted in significant negative correlations between trunk compensation and elbow flexion-extension in the affected arm. The findings support the clinical usability of sensor-based motion analysis.

A data-driven framework for selecting and validating digital health metrics: use-case in neurological sensorimotor impairments.

Digital health metrics promise to advance the understanding of impaired body functions, for example in neurological disorders. However, their clinical integration is challenged by an insufficient validation of the many existing and often abstract metrics. Here, we propose a data-driven framework to select and validate a clinically relevant core set of digital health metrics extracted from a technology-aided assessment. As an exemplary use-case, the framework is applied to the Virtual Peg Insertion Test (VPIT), a technology-aided assessment of upper limb sensorimotor impairments. The framework builds on a use-case-specific pathophysiological motivation of metrics, models demographic confounds, and evaluates the most important clinimetric properties (discriminant validity, structural validity, reliability, measurement error, learning effects). Applied to 77 metrics of the VPIT collected from 120 neurologically intact and 89 affected individuals, the framework allowed selecting 10 clinically relevant core metrics. These assessed the severity of multiple sensorimotor impairments in a valid, reliable, and informative manner. These metrics provided added clinical value by detecting impairments in neurological subjects that did not show any deficits according to conventional scales, and by covering sensorimotor impairments of the arm and hand with a single assessment. The proposed framework provides a transparent, step-by-step selection procedure based on clinically relevant evidence. This creates an interesting alternative to established selection algorithms that optimize mathematical loss functions and are not always intuitive to retrace. This could help addressing the insufficient clinical integration of digital health metrics. For the VPIT, it allowed establishing validated core metrics, paving the way for their integration into neurorehabilitation trials.

Measures of Interjoint Coordination Post-stroke Across Different Upper Limb Movement Tasks.

Background: Deficits in interjoint coordination, such as the inability to move out of synergy, are frequent symptoms in stroke subjects with upper limb impairments that hinder them from regaining normal motor function. Kinematic measurements allow a fine-grained assessment of movement pathologies, thereby complementing clinical scales, like the Fugl-Meyer Motor Assessment of the Upper Extremity (FMMA-UE). The study goal was to investigate the effects of the performed task, the tested arm, the dominant affected hand, upper limb function, and age on spatiotemporal parameters of the elbow, shoulder, and trunk. The construct validity of the metrics was examined by relating them with each other, the FMMA-UE, and its arm section. Methods: This is a cross-sectional observational study including chronic stroke patients with mild to moderate upper limb motor impairment. Kinematic measurements were taken using a wearable sensor suit while performing four movements with both upper limbs: (1) isolated shoulder flexion, (2) pointing, (3) reach-to-grasp a glass, and (4) key insertion. The kinematic parameters included the joint ranges of shoulder abduction/adduction, shoulder flexion/extension, and elbow flexion/extension; trunk displacement; shoulder-elbow correlation coefficient; median slope; and curve efficiency. The effects of the task and tested arm on the metrics were investigated using a mixed-model analysis. The validity of metrics compared to clinically measured interjoint coordination (FMMA-UE) was done by correlation analysis. Results: Twenty-six subjects were included in the analysis. The movement task and tested arm showed significant effects (p < 0.05) on all kinematic parameters. Hand dominance resulted in significant effects on shoulder flexion/extension and curve efficiency. The level of upper limb function showed influences on curve efficiency and the factor age on median slope. Relations with the FMMA-UE revealed the strongest and significant correlation for curve efficiency (r = 0.75), followed by shoulder flexion/extension (r = 0.68), elbow flexion/extension (r = 0.53), and shoulder abduction/adduction (r = 0.49). Curve efficiency additionally correlated significantly with the arm subsection, focusing on synergistic control (r = 0.59). Conclusion: The kinematic parameters of the upper limb after stroke were influenced largely by the task. These results underpin the necessity to assess different relevant functional movements close to real-world conditions rather than relying solely on clinical measures. Study Registration: clinicaltrials.gov, identifier NCT03135093 and BASEC-ID 2016-02075.

Insect Meal as Alternative Protein Source Exerts Pronounced Lipid-Lowering Effects in Hyperlipidemic Obese Zucker Rats.

BACKGROUND: Specific dietary proteins exert strong health-related effects compared with casein. OBJECTIVE: Herein, the hypothesis was tested using screening and conventional biochemical and molecular biological techniques that protein-rich insect meal compared with casein influences metabolic health in hyperlipidemic rats. METHODS: A 4-wk feeding trial with male, 8-wk-old homozygous obese Zucker rats (n = 36) and male, 8-wk-old heterozygous lean Zucker rats (n = 12) was performed. Obese rats were randomly divided into 3 obese groups (OC, OI50, and OI100) of 12 rats each and lean rats served as a lean control group (LC). LC and OC were fed a control diet with 20% casein as protein source, whereas in OI50 and OI100 50% and 100% of the casein, respectively, was replaced isonitrogenously by insect meal from Tenebrio molitor L. All data were analyzed by 1-factor ANOVA, except transcriptomic data which were analyzed by groupwise comparisons with the OC group. RESULTS: Transcript profiling revealed a coordinated inhibition by -17% to -521% and -37% to -859% of genes involved in fatty acid, triacylglycerol (TG), and cholesterol biosynthesis in the livers of OI100 and OI50, respectively, compared with OC (P < 0.05). Enzyme activities of fatty acid synthase, glucose-6 phosphate dehydrogenase, and 3-hydroxy-3-methylglutaryl-coenzyme-A reductase in the liver were 100-150% greater in OC compared with LC, but reduced by 50-60% in OI100 compared with OC (P < 0.05), to the same level as in LC. Liver and plasma concentrations of TG and cholesterol were 250-1000%, 30-800%, and 40-600% higher in OC, OI50, and OI100, respectively, than in LC (P < 0.05), but 40-60% and 20-60% lower in OI100 and OI50, respectively, than in group OC (P < 0.05). Plasma and liver concentrations of homocysteine were 20-30% lower in group OI100 than in group OC (P < 0.05). CONCLUSION: Insect meal exerts pronounced lipid-lowering effects in hyperlipidemic rats and, thus, might be useful for hyperlipidemic individuals.

Systematic Review on Kinematic Assessments of Upper Limb Movements After Stroke.

Background and Purpose- Assessing upper limb movements poststroke is crucial to monitor and understand sensorimotor recovery. Kinematic assessments are expected to enable a sensitive quantification of movement quality and distinguish between restitution and compensation. The nature and practice of these assessments are highly variable and used without knowledge of their clinimetric properties. This presents a challenge when interpreting and comparing results. The purpose of this review was to summarize the state of the art regarding kinematic upper limb assessments poststroke with respect to the assessment task, measurement system, and performance metrics with their clinimetric properties. Subsequently, we aimed to provide evidence-based recommendations for future applications of upper limb kinematics in stroke recovery research. Methods- A systematic search was conducted in PubMed, Embase, CINAHL, and IEEE Xplore. Studies investigating clinimetric properties of applied metrics were assessed for risk of bias using the Consensus-Based Standards for the Selection of Health Measurement Instruments checklist. The quality of evidence for metrics was determined according to the Grading of Recommendations Assessment, Development, and Evaluation approach. Results- A total of 225 studies (N=6197) using 151 different kinematic metrics were identified and allocated to 5 task and 3 measurement system groups. Thirty studies investigated clinimetrics of 62 metrics: reliability (n=8), measurement error (n=5), convergent validity (n=22), and responsiveness (n=2). The metrics task/movement time, number of movement onsets, number of movement ends, path length ratio, peak velocity, number of velocity peaks, trunk displacement, and shoulder flexion/extension received a sufficient evaluation for one clinimetric property. Conclusions- Studies on kinematic assessments of upper limb sensorimotor function are poorly standardized and rarely investigate clinimetrics in an unbiased manner. Based on the available evidence, recommendations on the assessment task, measurement system, and performance metrics were made with the goal to increase standardization. Further high-quality studies evaluating clinimetric properties are needed to validate kinematic assessments, with the long-term goal to elucidate upper limb sensorimotor recovery poststroke. Clinical Trial Registration- URL: https://www.crd.york.ac.uk/prospero/ . Unique identifier: CRD42017064279.