Efficacy of an exoskeleton-based physical therapy program for non-ambulatory patients during subacute stroke rehabilitation: a randomized controlled trial.

BACKGROUND: Individuals requiring greater physical assistance to practice walking complete fewer steps in physical therapy during subacute stroke rehabilitation. Powered exoskeletons have been developed to allow repetitious overground gait training for individuals with lower limb weakness. The objective of this study was to determine the efficacy of exoskeleton-based physical therapy training during subacute rehabilitation for walking recovery in non-ambulatory patients with stroke. METHODS: An assessor-blinded randomized controlled trial was conducted at 3 inpatient rehabilitation hospitals. Patients with subacute stroke (< 3 months) who were unable to walk without substantial assistance (Functional Ambulation Category rating of 0 or 1) were randomly assigned to receive exoskeleton-based or standard physical therapy during rehabilitation, until discharge or a maximum of 8 weeks. The experimental protocol replaced 75% of standard physical therapy sessions with individualized exoskeleton-based sessions to increase standing and stepping repetition, with the possibility of weaning off the device. The primary outcome was walking ability, measured using the Functional Ambulation Category. Secondary outcomes were gait speed, distance walked on the 6-Minute Walk Test, days to achieve unassisted gait, lower extremity motor function (Fugl-Meyer Assessment), Berg Balance Scale, Patient Health Questionnaire, Montreal Cognitive Assessment, and 36-Item Short Form Survey, measured post-intervention and after 6 months. RESULTS: Thirty-six patients with stroke (mean 39 days post-stroke) were randomized (Exoskeleton = 19, Usual Care = 17). On intention-to-treat analysis, no significant between-group differences were found in the primary or secondary outcomes at post-intervention or after 6 months. Five participants randomized to the Exoskeleton group did not receive the protocol as planned and thus exploratory as-treated and per-protocol analyses were undertaken. The as-treated analysis found that those adhering to exoskeleton-based physical therapy regained independent walking earlier (p = 0.03) and had greater gait speed (p = 0.04) and 6MWT (p = 0.03) at 6 months; however, these differences were not significant in the per-protocol analysis. No serious adverse events were reported. CONCLUSIONS: This study found that exoskeleton-based physical therapy does not result in greater improvements in walking independence than standard care but can be safely administered at no detriment to patient outcomes. Clinical Trial Registration The Exoskeleton for post-Stroke Recovery of Ambulation (ExStRA) trial was registered at ClinicalTrials.gov (NCT02995265, first registered: December 16, 2016).

Internationally Acquired Severe Systemic Infections in Febrile Pediatric Travelers Presenting to the Emergency Department.

OBJECTIVES: Most children in the United States who visit the emergency department (ED) with fever have minor illnesses not requiring treatment or hospitalization. However, when a child has recently immigrated or traveled abroad, internationally acquired severe systemic infections (ISSIs) must be considered. We sought to describe children who have traveled internationally and present to the ED with a complaint of fever and to determine risk factors associated with ISSIs in these patients. METHODS: We conducted a retrospective study of children younger than 18 years who presented to 2 pediatric EDs in Bronx, NY (June 2007 to May 2017). Patients were included if they had both fever within 24 hours and international travel within 30 days. We compared groups using bivariate analyses and created a prediction model for ISSIs using multivariable logistic regression. RESULTS: Of the 353 children included, 44 (12%) had ISSI: 25 (57%), malaria; 6 (14%), dengue; and 13 (30%), bacteremia. Eight (18%) of those with ISSI presented with fever to another medical provider in the week prior but did not receive bloodwork. Four variables were independently associated with ISSIs: headache (odds ratio [OR], 21.7; 95% confidence interval [CI], 6.8-69.3), travel to Africa or Asia (OR, 18.8; 95% CI, 4.8-73.2), platelets of 150,000/µL or less (OR, 15.1; 95% CI, 4.7-48.6), and alanine aminotransferase level of 30 IU/L or greater (OR, 8.9; 95% CI, 3.1-25.3). CONCLUSIONS: Children who travel internationally and present with fever upon return are at substantial risk for developing ISSIs. The diagnosis of ISSIs is often overlooked, but certain risk factors have the potential to aid clinicians.

Higher Doses Improve Walking Recovery During Stroke Inpatient Rehabilitation.

BACKGROUND AND PURPOSE: We investigated the effect of higher therapeutic exercise doses on walking during inpatient rehabilitation, typically commencing 1 to 4 weeks poststroke. METHODS: This phase II, blinded-assessor, randomized controlled trial recruited from 6 Canadian inpatient rehabilitation units, between 2014 and 2018. Subjects (n=75; 25/group) were randomized into: control (usual care) physical therapy: typically, 1 hour, 5 days/week; Determining Optimal Post-Stroke Exercise (DOSE1): 1 hour, 5 days/week, more than double the intensity of Control (based on aerobic minutes and walking steps); and DOSE2: 2 hours, 5 days/week, more than quadruple the intensity of Control, each for 4 weeks duration. The primary outcome, walking endurance at completion of the 4-week intervention (post-evaluation), was compared across these groups using linear regression. Secondary outcomes at post-evaluation, and longitudinal outcomes at 6 and 12-month evaluations, were also analyzed. RESULTS: Both DOSE1 (mean change 61 m [95% CI, 9-113], P=0.02) and DOSE2 (mean change 58 m, 6-110, P=0.03) demonstrated greater walking endurance compared with Control at the post-evaluation. Significant improvements were also observed with DOSE2 in gait speed (5-m walk), and both DOSE groups in quality of life (EQ-5D-5 L) compared with Control. Longitudinal analyses revealed that improvements in walking endurance from the DOSE intervention were retained during the 1-year follow-up period over usual care. CONCLUSIONS: This study provides the first preliminary evidence that patients with stroke can improve their walking recovery and quality of life with higher doses of aerobic and stepping activity within a critical time period for neurological recovery. Furthermore, walking endurance benefits achieved from a 4-week intervention are retained over the first-year poststroke. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01915368.

Exoskeleton for post-stroke recovery of ambulation (ExStRA): study protocol for a mixed-methods study investigating the efficacy and acceptance of an exoskeleton-based physical therapy program during stroke inpatient rehabilitation.

BACKGROUND: The ability to walk is commonly reported as a top rehabilitation priority for individuals after a stroke. However, not all individuals with stroke are able to practice walking, especially those who require more assistance from their therapist to do so. Powered robotic exoskeletons are a new generation of robotic-assisted gait training devices, designed to assist lower extremity movement to allow repetitious overground walking practice. To date, minimal research has been conducted on the use of an exoskeleton for gait rehabilitation after stroke. The following research protocol aims to evaluate the efficacy and acceptability, and thus adoptability, of an exoskeleton-based gait rehabilitation program for individuals with stroke. METHODS: This research protocol describes a prospective, multi-center, mixed-methods study comprised of a randomized controlled trial and a nested qualitative study. Forty adults with subacute stroke will be recruited from three inpatient rehabilitation hospitals and randomized to receive either the exoskeleton-based gait rehabilitation program or usual physical therapy care. The primary outcome measure is the Functional Ambulation Category at post-intervention, and secondary outcomes include motor recovery, functional mobility, cognitive, and quality-of-life measures. Outcome data will be collected at baseline, post-intervention, and at 6 months. The qualitative component will explore the experience and acceptability of using a powered robotic exoskeleton for stroke rehabilitation from the point of view of individuals with stroke and physical therapists. Semi-structured interviews will be conducted with participants who receive the exoskeleton intervention, and with the therapists who provide the intervention. Qualitative data will be analyzed using interpretive description. DISCUSSION: This study will be the first mixed-methods study examining the adoptability of exoskeleton-based rehabilitation for individuals with stroke. It will provide valuable information regarding the efficacy of exoskeleton-based training for walking recovery and will shed light on how physical therapists and patients with stroke perceive the device. The findings will help guide the integration of robotic exoskeletons into clinical practice. TRIAL REGISTRATION: NCT02995265 (clinicaltrials.gov), Registered 16 December 2016.

Probing sulphur clusters in a microfluidic electrochemical cell with synchrotron-based photoionization mass spectrometry.

We present synchrotron-based mass spectrometry to probe products formed in a lithium sulphide electrolyte. In operando analysis was carried out at two different potentials in a vacuum compatible microfluidic electrochemical cell. Mass spectral observations show that the charged electrolyte formed sulphur clusters under dynamic conditions, demonstrating electrolyte electron shuttling.

Development of a Chronic Disease Management Program for Stroke Survivors Using Intervention Mapping: The Stroke Coach.

OBJECTIVE: To describe the systematic development of the Stroke Coach, a theory- and evidence-based intervention to improve control of lifestyle behavior risk factors in patients with stroke. DESIGN: Intervention development. SETTING: Community. PARTICIPANTS: Individuals who have had a stroke. INTERVENTIONS: We used intervention mapping to guide the development of the Stroke Coach. Intervention mapping is a systematic process used for intervention development and composed of steps that progress from the integration of theory and evidence to the organization of realistic strategies to facilitate the development of a practical intervention supported by empirical evidence. Social cognitive theory was the underlying premise for behavior change, whereas control theory methods were directed toward sustaining the changes to ensure long-term health benefits. Practical evidence-based strategies were linked to behavioral determinants to improve stroke risk factor control. MAIN OUTCOME MEASURES: Not applicable. RESULTS: The Stroke Coach is a patient-centered, community-based, telehealth intervention to promote healthy lifestyles after stroke. Over 6 months, participants receive seven 30- to 60-minute telephone sessions with a lifestyle coach who provides education, facilitates motivation for lifestyle modification, and empowers participants to self-management their stroke risk factors. Participants also receive a self-management manual and a self-monitoring kit. CONCLUSIONS: Through the use of intervention mapping, we developed a theoretically sound and evidence-grounded intervention to improve risk factor control in patients with stroke. If empirical evaluation of the Stroke Coach produces positive results, the next step will be to develop an implementation intervention to ensure successful uptake and delivery of the program in community and outpatient settings.

Computational design of a red fluorophore ligase for site-specific protein labeling in living cells.

Chemical fluorophores offer tremendous size and photophysical advantages over fluorescent proteins but are much more challenging to target to specific cellular proteins. Here, we used Rosetta-based computation to design a fluorophore ligase that accepts the red dye resorufin, starting from Escherichia coli lipoic acid ligase. X-ray crystallography showed that the design closely matched the experimental structure. Resorufin ligase catalyzed the site-specific and covalent attachment of resorufin to various cellular proteins genetically fused to a 13-aa recognition peptide in multiple mammalian cell lines and in primary cultured neurons. We used resorufin ligase to perform superresolution imaging of the intermediate filament protein vimentin by stimulated emission depletion and electron microscopies. This work illustrates the power of Rosetta for major redesign of enzyme specificity and introduces a tool for minimally invasive, highly specific imaging of cellular proteins by both conventional and superresolution microscopies.

Investigating the Telerehabilitation With Aims to Improve Lower Extremity Recovery Poststroke Program: A Feasibility Study.

OBJECTIVE: The purpose of this study was to examine the feasibility of a progressive virtual exercise and self-management intervention, the TeleRehabilitation with Aims to Improve Lower extremity recovery poststroke program (TRAIL), in individuals with stroke. METHODS: A single group pre-post study design was used. Thirty-two participants were recruited who were aged 19 years or older, had a stroke within 18 months of the beginning of the study, had hemiparesis of the lower extremity, and were able to tolerate 50 minutes of activity. Participants completed TRAIL, a synchronous exercise and self-management program delivered via videoconferencing. Participants received 8 telerehabilitation sessions over 4 weeks that were 60 to 90 minutes, with a trained physical therapist in a ≤2 to 1 participant-to-therapist ratio. Feasibility indicators in the areas of process (recruitment and retention rates, perceived satisfaction), resources (treatment fidelity and adherence, participant and assessor burden, therapist burden), management (equipment, processing time), and scientific indicators (safety, treatment response, treatment effect) were collected throughout the study using a priori criteria for success. The treatment effect was examined on the Timed "Up & Go" test, the virtual Fugl-Meyer Lower Extremity Assessment, the 30-Second Sit-to-Stand Test, the Functional Reach, the Tandem Stand, the Activities-Specific Balance Confidence Scale, the Stroke Impact Scale, and the Goal Attainment Scale. RESULTS: Forty-seven individuals were screened, of which 32 (78% male; median age of 64.5 years) were included for the study from 5 sites across Canada. Nine feasibility indicators met our study-specific threshold criteria for success: retention rate (0 dropouts), perceived satisfaction, treatment fidelity, adherence, therapist burden, equipment, and safety. In terms of treatment response and effect, improvements were observed in Timed "Up & Go" test (Cohen d = 0.57); Fugl-Meyer Lower Extremity Assessment (d = 0.76); 30-Second Sit-to-Stand Test (d = 0.89); and Goal Attainment Scale (d = 0.95). CONCLUSION: The delivery of TRAIL, a lower extremity stroke rehabilitation program using videoconferencing technology, is feasible and appears to have positive influences on mobility, lower extremity impairment, strength, and goal attainment. IMPACT: Community-based telerehabilitation programs, such as TRAIL, could extend the continuum of care during the transition back to community postdischarge or during global disruptions, such as Coronavirus Disease 2019 (COVID-19). Delivery of synchronous lower extremity rehabilitation via videoconferencing to community-dwelling stroke survivors is feasible.

Exploring the experiences of an exercise-based telerehabilitation program among Canadian community-dwelling adults with stroke.

PURPOSE: Telerehabilitation is emerging as a means for delivering stroke rehabilitation to address unmet lower extremity rehabilitation needs. However, there is currently limited and low-quality evidence supporting the use telerehabilitation interventions for lower extremity recovery after stroke. Thus, we developed an exercise-based telerehabilitation program (TRAIL) for safe and effective promotion of lower extremity function after stroke. This study reports on the qualitative findings from the feasibility study of the TRAIL program. METHODS: An interpretive description methodology and inductive thematic analysis approach were undertaken. One-on-one semi-structured interviews were conducted on a subset of participants who completed the TRAIL feasibility study. Participants were recruited via email and enrolled into the study based on pre-determined purposeful sampling strategies. RESULTS: Ten participants (6 men, 4 women) completed a semi-structured interview. Two main themes emerged: (i) TRAIL ingredients for success and (ii) telerehabilitation is a viable option for stroke rehabilitation. CONCLUSION: Exercise-based telerehabilitation appears to be well-received by men and women post-stroke when social support, professional guidance, and program resources are offered. TRAIL may also prolong the continuum of care that individuals receive once they are discharged back into the community, and contribute to improvements in mobility, lower extremity strength and balance.

Exercise-based telerehabilitation for individuals with stroke can be delivered safely when clinicians are trained, and social support and program resources are available.Exercise-based telerehabilitation may be viable and accessible for men and women with stroke to extend the opportunity for rehabilitation services within the first year post-event.Synchronously delivered telerehabilitation programs using user-friendly videoconference software is recommended for optimal participant satisfaction.

Blood pressure trajectory of inpatient stroke rehabilitation patients from the Determining Optimal Post-Stroke Exercise (DOSE) trial over the first 12 months post-stroke.

Background: High blood pressure (BP) is the primary risk factor for recurrent strokes. Despite established clinical guidelines, some stroke survivors exhibit uncontrolled BP over the first 12 months post-stroke. Furthermore, research on BP trajectories in stroke survivors admitted to inpatient rehabilitation hospitals is limited. Exercise is recommended to reduce BP after stroke. However, the effect of high repetition gait training at aerobic intensities (>40% heart rate reserve; HRR) during inpatient rehabilitation on BP is unclear. We aimed to determine the effect of an aerobic gait training intervention on BP trajectory over the first 12 months post-stroke. Methods: This is a secondary analysis of the Determining Optimal Post-Stroke Exercise (DOSE) trial. Participants with stroke admitted to inpatient rehabilitation hospitals were recruited and randomized to usual care (n = 24), DOSE1 (n = 25; >2,000 steps, 40-60% HRR for >30 min/session, 20 sessions over 4 weeks), or DOSE2 (n = 25; additional DOSE1 session/day) groups. Resting BP [systolic (SBP) and diastolic (DBP)] was measured at baseline (inpatient rehabilitation admission), post-intervention (near inpatient discharge), 6- and 12-month post-stroke. Linear mixed-effects models were used to examine the effects of group and time (weeks post-stroke) on SBP, DBP and hypertension (≥140/90 mmHg; ≥130/80 mmHg, if diabetic), controlling for age, stroke type, and baseline history of hypertension. Results: No effect of intervention group on SBP, DBP, or hypertension was observed. BP increased from baseline to 12-month post-stroke for SBP (from [mean ± standard deviation] 121.8 ± 15.0 to 131.8 ± 17.8 mmHg) and for DBP (74.4 ± 9.8 to 78.5 ± 10.1 mmHg). The proportion of hypertensive participants increased from 20.8% (n = 15/72) to 32.8% (n = 19/58). These increases in BP were statistically significant: an effect [estimation (95%CI), value of p] of time was observed on SBP [0.19 (0.12-0.26) mmHg/week, p < 0.001], DBP [0.09 (0.05-0.14) mmHg/week, p < 0.001], and hypertension [OR (95%CI): 1.03 (1.01-1.05), p = 0.010]. A baseline history of hypertension was associated with higher SBP by 13.45 (8.73-18.17) mmHg, higher DBP by 5.57 (2.02-9.12) mmHg, and 42.22 (6.60-270.08) times the odds of being hypertensive at each timepoint, compared to those without. Conclusion: Blood pressure increased after inpatient rehabilitation over the first 12 months post-stroke, especially among those with a history of hypertension. The 4-week aerobic gait training intervention did not influence this trajectory.

TeleRehabilitation with Aims to Improve Lower extremity recovery in community-dwelling individuals who have had a stroke: protocol for a multisite, parallel group, assessor-blinded, randomised attention-controlled trial.

INTRODUCTION: Telerehabilitation is an accessible service delivery model that may support innovative lower extremity rehabilitation programmes that extend the stroke recovery continuum into the community. Unfortunately, there is limited evidence on the provision of exercises for lower extremity recovery after stroke delivered using telerehabilitation. In response, we developed the TeleRehabilitation with Aims to Improve Lower extremity recovery poststroke (TRAIL) programme, a 4-week progressive exercise and self-management intervention delivered synchronously using video-conferencing technology. Our primary hypothesis is that individual within 1-year poststroke who participate in TRAIL will experience significantly greater improvements in functional mobility than individuals in an attention-controlled education programme (EDUCATION). METHODS AND ANALYSIS: In this multisite, parallel group, assessor-blinded randomised attention-controlled trial, 96 community-living stroke survivors within 1-year poststroke will be recruited from five sites (Vancouver, Winnipeg, Toronto, London and Halifax, Canada) from the CanStroke Recovery Trials Platform which is a network of Canadian hospital sites that are affiliated with academic institutions to facilitate participant recruitment and quality trial practices. Participants will be randomised on a 1:1 basis to TRAIL or EDUCATION. Participants randomised to TRAIL will receive eight telerehabilitation sessions where they will perform exercises and receive self-management support to improve lower extremity recovery from a TRAIL physical therapist. The primary outcome will be measured using the Timed Up and Go. Secondary outcomes include lower extremity muscle strength, functional balance, motor impairment, balance self-efficacy, health-related quality of life and health service use for our economic evaluation. Measurements will be taken at baseline, immediately after the intervention, 3-month and 6-month postintervention. ETHICS AND DISSEMINATION: Ethics approval for this research has been obtained by all participating sites. All study participants will provide their informed consent prior to enrolling them in the study. Findings from this trial will be disseminated in peer-reviewed journals and presentations at international scientific meetings. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT04908241.

Higher intensity walking improves global cognition during inpatient rehabilitation: a secondary analysis of a randomized control trial.

Cognitive deficits are common poststroke. Cognitive rehabilitation is typically used to improve cognitive deficits. It is unknown whether higher doses of exercise to promote motor recovery influence cognitive outcomes. Our recent trial, Determining Optimal Post-Stroke Exercise (DOSE), shows more than double the steps and aerobic minutes can be achieved during inpatient rehabilitation versus usual care, and translates to improved long-term walking outcomes. Thus, the secondary analysis aim was to determine the effect of the DOSE protocol on cognitive outcomes over 1-year poststroke. The DOSE protocol progressively increased step number and aerobic minutes during inpatient stroke rehabilitation over 20 sessions. The Montreal Cognitive Assessment (MoCA), Digit Symbol Substitution Test (DSST), and Trail Making Test B were completed at baseline, post-intervention, and 6- and 12-months poststroke, administered using standardized guidelines. Using the DOSE data, we used mixed-effect spline regression to model participants' trajectories of cognitive recovery, controlling for relevant covariates. Participants (Usual Care n = 25, DOSE n = 50) were 56.7(11.7) years old, and 27(10) days post stroke. For the MoCA, there were statistically significant Group × Trajectory(p = 0.019), and Group × ΔTrajectory (p = 0.018) interactions with a substantial clinically meaningful difference, from +5.44 points/month improvement of the DOSE group compared to +1.59 points/month improvement with Usual Care during the 4-week intervention. The DSST and Trails B improved over time but were not different between groups. Taking advantage of this early difference may lend support to continued efforts to increase intensity, during and after discharge from inpatient rehabilitation, to improve cognition. Clinical trial registration: www.clinicaltrials.gov, NCT01915368.

Implementation of increased physical therapy intensity for improving walking after stroke: Walk 'n watch protocol for a multisite stepped-wedge cluster-randomized controlled trial.

RATIONALE: Clinical practice guidelines support structured, progressive protocols for improving walking after stroke. Yet, practice is slow to change, evidenced by the little amount of walking activity in stroke rehabilitation units. Our recent study (n = 75) found that a structured, progressive protocol integrated with typical daily physical therapy improved walking and quality-of-life measures over usual care. Research therapists progressed the intensity of exercise by using heart rate and step counters worn by the participants with stroke during therapy. To have the greatest impact, our next step is to undertake an implementation trial to change practice across stroke units where we enable the entire unit to use the protocol as part of standard of care. AIMS: What is the effect of introducing structured, progressive exercise (termed the Walk 'n Watch protocol) to the standard of care on the primary outcome of walking in adult participants with stroke over the hospital inpatient rehabilitation period? Secondary outcomes will be evaluated and include quality of life. METHODS AND SAMPLE SIZE ESTIMATES: This national, multisite clinical trial will randomize 12 sites using a stepped-wedge design where each site will be randomized to deliver Usual Care initially for 4, 8, 12, or 16 months (three sites for each duration). Then, each site will switch to the Walk 'n Watch phase for the remaining duration of a total 20-month enrolment period. Each participant will be exposed to either Usual Care or Walk 'n Watch. The trial will enroll a total of 195 participants with stroke to achieve a power of 80% with a Type I error rate of 5%, allowing for 20% dropout. Participants will be medically stable adults post-stroke and able to take five steps with a maximum physical assistance from one therapist. The Walk 'n Watch protocol focuses on completing a minimum of 30 min of weight-bearing, walking-related activities (at the physical therapists' discretion) that progressively increase in intensity informed by activity trackers measuring heart rate and step number. STUDY OUTCOME(S): The primary outcome will be the change in walking endurance, measured by the 6-Minute Walk Test, from baseline (T1) to 4 weeks (T2). This change will be compared across Usual Care and Walk 'n Watch phases using a linear mixed-effects model. Additional physical, cognitive, and quality of life outcomes will be measured at T1, T2, and 12 months post-stroke (T3) by a blinded assessor. DISCUSSION: The implementation of stepped-wedge cluster-randomized trial enables the protocol to be tested under real-world conditions, involving all clinicians on the unit. It will result in all sites and all clinicians on the unit to gain expertise in protocol delivery. Hence, a deliberate outcome of the trial is facilitating changes in best practice to improve outcomes for participants with stroke in the trial and for the many participants with stroke admitted after the trial ends.

Fluorophore targeting to cellular proteins via enzyme-mediated azide ligation and strain-promoted cycloaddition.

Methods for targeting of small molecules to cellular proteins can allow imaging with fluorophores that are smaller, brighter, and more photostable than fluorescent proteins. Previously, we reported targeting of the blue fluorophore coumarin to cellular proteins fused to a 13-amino acid recognition sequence (LAP), catalyzed by a mutant of the Escherichia coli enzyme lipoic acid ligase (LplA). Here, we extend LplA-based labeling to green- and red-emitting fluorophores by employing a two-step targeting scheme. First, we found that the W37I mutant of LplA catalyzes site-specific ligation of 10-azidodecanoic acid to LAP in cells, in nearly quantitative yield after 30 min. Second, we evaluated a panel of five different cyclooctyne structures and found that fluorophore conjugates to aza-dibenzocyclooctyne (ADIBO) gave the highest and most specific derivatization of azide-conjugated LAP in cells. However, for targeting of hydrophobic fluorophores such as ATTO 647N, the hydrophobicity of ADIBO was detrimental, and superior targeting was achieved by conjugation to the less hydrophobic monofluorinated cyclooctyne (MOFO). Our optimized two-step enzymatic/chemical labeling scheme was used to tag and image a variety of LAP fusion proteins in multiple mammalian cell lines with diverse fluorophores including fluorescein, rhodamine, Alexa Fluor 568, ATTO 647N, and ATTO 655.

A microfluidic electrochemical cell for studying the corrosion of uranium dioxide (UO2).

We have developed a specialized microfluidic electrochemical cell that enables in situ investigation of the electrochemical corrosion of microgram quantities of redox active solids. The advantage of downscaling is the reduction of hazards, waste, expense, and greatly expanding data collection for hazardous materials, including radioactive samples. Cyclic voltammetry was used to monitor the oxidation-reduction cycle of minute quantities of micron-size uraninite (UO2) particles, from the formation of hexavalent uranium (U(vi)), U3O7 and reduction to UO2+x . Reaction progress was also studied in situ with scanning electron microscopy. The electrochemical measurements matched those obtained at the bulk-scale and were consistent with ex situ characterization of the run products by X-ray photoelectron spectroscopy, scanning transmission electron microscopy, and atomic force microscopy; thus, demonstrating the utility of the microfluidic approach for studying radioactive materials.

Telehealth coaching to improve self-management for secondary prevention after stroke: A randomized controlled trial of Stroke Coach.

BACKGROUND: Stroke Coach is a lifestyle coaching telehealth program to improve self-management of stroke risk factors. AIMS: To examine the efficacy of Stroke Coach on lifestyle behavior and risk factor control among community-living stroke survivors within one-year post stroke. METHODS: Participants were randomized to Stroke Coach or an attention control Memory Training group. Lifestyle behavior was measured using the Health Promoting Lifestyle Profile II. Secondary outcomes included specific behavioral and cardiometabolic risk factors, health-related quality of life (HRQoL), cognitive status, and depressive symptoms. Measurements were taken at baseline, post-intervention (6 months), and retention (12 month). Linear mixed-effects models were used to test the study hypotheses (p < 0.05). All analyses were intention-to-treat. RESULTS: The mean age of the Stroke Coach (n = 64) and Memory Training (n = 62) groups was 67.2 and 69.1 years, respectively. The majority of participants (n = 100) had mild stroke (modified Rankin Scale = 1 or 2), were active, with controlled blood pressure (mean = 129/79 mmHg) at baseline. At post-intervention, there were no significant differences in lifestyle (b = -2.87; 95%CI - 8.03 to 2.29; p = 0.28). Glucose control, as measured by HbA1c (b = 0.17; 95%CI 0.17 to 0.32; p = 0.03), and HRQoL, measured using SF-36 Physical Component Summary (b = -3.05; 95%CI -5.88 to -0.21; p = 0.04), were significantly improved in Stroke Coach compared to Memory Training, and the improvements were maintained at retention. CONCLUSION: Stroke Coach did not improve lifestyle behavior; however, there were improvements to HbA1c and HRQoL among community-living stroke survivors with mild stroke-related disability. (ClinicalTrials.gov identifier: NCT02207023).

Step Number and Aerobic Minute Exercise Prescription and Progression in Stroke: A Roadmap.

BACKGROUND: While higher therapeutic intensity improves motor recovery after stroke, translating findings from successful studies is challenging without clear exercise intensity targets. We show in the DOSE trial1 more than double the steps and aerobic minutes within a session can be achieved compared with usual care and translates to improved long-term walking outcomes. OBJECTIVE: We modeled data from this successful higher intensity multi-site RCT to develop targets for prescribing and progressing exercise for varying levels of walking impairment after stroke. METHODS: In twenty-five individuals in inpatient rehabilitation, twenty sessions were monitored for a total of 500 one-hour physical therapy sessions. For the 500 sessions, step number and aerobic minute progression were modeled using linear mixed effects regression. Using formulas from the linear mixed effects regression, targets were calculated. RESULTS: The model for step number included session number and baseline walking speed, and for aerobic minutes, session number and age. For steps, there was an increase of 73 steps per session. With baseline walking speed, for every 0.1 m/s increase, a corresponding increase of 302 steps was predicted. For aerobic minutes, there was an increase of .56 minutes of aerobic activity (ie, 34 seconds) per session. For every year increase in age, a decrease of .39 minutes (ie, 23 seconds) was predicted. CONCLUSIONS: Using data associated with better walking outcomes, we provide step number and aerobic minute targets that future studies can cross-validate. As walking speed and age are collected at admission, these models allow for uptake of routine measurement of therapeutic intensity.Registration: www.clinicaltrials.gov; NCT01915368.

Prevalence of Walking Limitation After Acute Stroke and Its Impact on Discharge to Home.

OBJECTIVE: The purpose of this study was to provide contemporary estimates of the prevalence of lower extremity motor impairment and walking limitation after first-ever stroke and to characterize the predictive nature of early walking ability for being discharged home after acute hospitalization. METHODS: In this cohort study, data were collected from a metropolitan acute care hospital in Canada at admission for 487 adults with first-ever acute ischemic or hemorrhagic stroke. Lower extremity motor impairment and walking limitation were measured using the National Institutes of Health Stroke Scale and AlphaFIM, respectively. Parallel multivariable logistic regression models were built to predict discharge home after acute hospitalization compared with further hospitalization. RESULTS: For patients surviving a first-ever stroke, 44.1% presented with some degree of lower extremity motor impairment and 46.0% were unable to walk. In a multivariable model built around a binary classification of walking (Nagelkerke R2 = 0.41), those with any ability to walk at admission (with or without therapist assistance) had 9.48 times greater odds of being discharged home (odds ratio = 9.48, 95% CI = 6.11-14.92) than those who were unable. In a parallel multivariable model built around an ordinal classification of walking (Nagelkerke R2 = 0.49), patients had 2.07 times greater odds (odds ratio = 2.07, 95% CI = 1.82-2.38) of being discharged home for each increment on a 6-point walking scale (total dependence to complete independence) assessed at acute admission. CONCLUSION: Approximately one-half of patients with first-ever stroke present with lower extremity weakness and walking limitation. Early walking ability is a significant predictor of returning home after acute hospitalization, independent of stroke severity. Discharge planning may be facilitated early after stroke with the familiar assessment of walking ability. IMPACT: An early assessment of walking function within days of stroke admission can help to streamline discharge planning. LAY SUMMARY: Nearly one-half of all individuals who experience a first-time stroke have walking difficulty when they arrive at the hospital. The severity of the walking limitation can predict whether a patient will eventually be discharged home or go on to further hospitalization.

Patients' and therapists' experience and perception of exoskeleton-based physiotherapy during subacute stroke rehabilitation: a qualitative analysis.

PURPOSE: To explore the experience and acceptability of an exoskeleton-based physiotherapy program for non-ambulatory patients during subacute stroke rehabilitation from the perspective of patients and therapists. MATERIALS AND METHODS: This was a qualitative descriptive study using semi-structured interviews and thematic analysis. Fourteen patients with stroke who participated in the experimental arm of a randomized controlled trial investigating the efficacy of exoskeleton-based physiotherapy were recruited. Six physiotherapists who provided the intervention were also recruited. RESULTS: Three themes were identified relating to the experience and acceptability of an exoskeleton-based physiotherapy program: (1) A matter of getting into the swing of things depicted the initial and ongoing learning process of using an exoskeleton; (2) More of a positive experience than anything else described the participants' mostly favorable attitude toward exoskeleton-based gait training; and (3) The best step forward captured participant-identified recommendations and considerations for the future integration of exoskeleton training into stroke rehabilitation. CONCLUSIONS: Patients with stroke were even more optimistic than therapists toward the experience and benefits of exoskeleton-based gait training during subacute stroke rehabilitation. Future clinical practice should consider the balance between actual and perceived benefits, as well as the potential barriers to integrating an exoskeleton into stroke rehabilitation.IMPLICATIONS FOR REHABILITATIONPowered robotic exoskeletons can be used to provide higher duration and more repetitious walking practice for non-ambulatory patients with stroke.Patients with stroke view exoskeleton-based physiotherapy highly favorably, attributing greater opportunity and benefit to using the device during subacute rehabilitation.Physiotherapists should consider learning challenges, patient characteristics, and implementation barriers when integrating exoskeleton-based training within a treatment program.