Replicon particle vaccination induces non-neutralizing anti-nucleoprotein antibody-mediated control of Crimean-Congo hemorrhagic fever virus.

Crimean-Congo hemorrhagic fever virus (CCHFV) can cause severe human disease and is considered a WHO priority pathogen due to the lack of efficacious vaccines and antivirals. A CCHF virus replicon particle (VRP) has previously shown protective efficacy in a lethal Ifnar-/- mouse model when administered as a single dose at least 3 days prior to challenge. Here, we determine that non-specific immune responses are not sufficient to confer short-term protection, since Lassa virus VRP vaccination 3 days prior to CCHFV challenge was not protective. We also investigate how CCHF VRP vaccination confers protective efficacy by examining viral kinetics, histopathology, clinical analytes and immunity early after challenge (3 and 6 days post infection) and compare to unvaccinated controls. We characterize how these effects differ based on vaccination period and correspond to previously reported CCHF VRP-mediated protection. Vaccinating Ifnar-/- mice with CCHF VRP 28, 14, 7, or 3 days prior to challenge, all known to confer complete protection, significantly reduced CCHFV viral load, mucosal shedding, and markers of clinical disease, with greater reductions associated with longer vaccination periods. Interestingly, there were no significant differences in innate immune responses, T cell activation, or antibody titers after challenge between groups of mice vaccinated a week or more before challenge, but higher anti-NP antibody avidity and effector function (ADCD) were positively associated with longer vaccination periods. These findings support the importance of antibody-mediated responses in VRP vaccine-mediated protection against CCHFV infection.

The effect of post-acute rehabilitation setting on 90-day mobility after stroke: A difference-in-difference analysis.

Background: After discharged from the hospital for acute stroke, individuals typically receive rehabilitation in one of three settings: inpatient rehabilitation facilities (IRFs), skilled nursing facilities (SNFs), or home with community services (i.e., home health or outpatient clinics). The initial setting of post-acute care (i.e., discharge location) is related to mortality and hospital readmission; however, the impact of this setting on the change in functional mobility at 90-days after discharge is still poorly understood. The purpose of this work was to examine the impact of discharge location on the change in functional mobility between hospital discharge and 90-days post-discharge. Methods: In this retrospective cohort study, we used the electronic health record to identify individuals admitted to Johns Hopkins Medicine with an acute stroke and who had measurements of mobility [Activity Measure for Post Acute Care Basic Mobility (AM-PAC BM)] at discharge from the acute hospital and 90-days post-discharge. Individuals were grouped by discharge location (IRF=190 [40%], SNF=103 [22%], Home with community services=182 [(38%]). We compared the change in mobility from time of discharge to 90-days post-discharge in each group using a difference-in-differences analysis and controlling for demographics, clinical characteristics, and social determinants of health. Results: We included 475 individuals (age 64.4 [14.8] years; female: 248 [52.2%]). After adjusting for covariates, individuals who were discharged to an IRF had a significantly greater improvement in AM-PAC BM from time of discharge to 90-days post-discharge compared to individuals discharged to a SNF or home with community services (ß=-3.5 (1.4), p=0.01 and ß=-8.2 (1.3), p=<0.001, respectively). Conclusions: These findings suggest that the initial post-acute rehabilitation setting impacts the magnitude of functional recovery at 90-days after discharge from the acute hospital. These findings support the need for high-intensity rehabilitation and for policies that facilitate the delivery of high-intensity rehabilitation after stroke.

Medicare Advantage Patterns of Poststroke Discharge to an Inpatient Rehabilitation or Skilled Nursing Facility: A Consideration of Demographic, Functional, and Payer Factors.

OBJECTIVE: The purpose of this study was to determine the factors influencing the discharge to an inpatient rehabilitation facility (IRF) or a skilled nursing facility (SNF) of people poststroke with Medicare Advantage plans. METHODS: A retrospective cohort study was conducted with data from naviHealth, a company that manages postacute care discharge placement on behalf of Medicare Advantage organizations. The dependent variable was discharge destination (IRF or SNF). Variables included age, sex, prior living setting, functional status (Activity Measure for Post-Acute Care [AM-PAC]), acute hospital length of stay, comorbidities, and payers (health plans). Analysis estimated relative risk (RR) of discharge to SNF, while controlling for regional variation. RESULTS: Individuals discharged to an SNF were older (RR = 1.17), women (RR = 1.05), lived at home alone or in assisted living (RR = 1.13 and 1.39, respectively), had comorbidities impacting their function "some" or "severely" (RR = 1.43 and 1.81, respectively), and had a length of stay greater than 5 days (RR = 1.16). Individuals with better AM-PAC Basic Mobility (RR = 0.95) went to an IRF, and individuals with better Daily Activity (RR = 1.01) scores went to an SNF. There was a substantial, significant variation in discharge of individuals to SNF by payer group (RR range = 1.12-1.92). CONCLUSIONS: The results of this study show that individuals poststroke are more likely to be discharged to an SNF than to an IRF. This study did not find a different discharge decision-making picture for those with Medicare Advantage plans than previously described for other insurance programs. IMPACT: Medicare Advantage payers have varied patterns in discharge placement to an IRF or SNF for patients poststroke.

Label-free in vitro assays predict the potency of anti-disialoganglioside chimeric antigen receptor T-cell products.

BACKGROUND AIMS: Chimeric antigen receptor (CAR) T cells have demonstrated remarkable efficacy against hematological malignancies; however, they have not experienced the same success against solid tumors such as glioblastoma (GBM). There is a growing need for high-throughput functional screening platforms to measure CAR T-cell potency against solid tumor cells. METHODS: We used real-time, label-free cellular impedance sensing to evaluate the potency of anti-disialoganglioside (GD2) targeting CAR T-cell products against GD2+ patient-derived GBM stem cells over a period of 2 days and 7 days in vitro. We compared CAR T products using two different modes of gene transfer: retroviral transduction and virus-free CRISPR-editing. Endpoint flow cytometry, cytokine analysis and metabolomics data were acquired and integrated to create a predictive model of CAR T-cell potency. RESULTS: Results indicated faster cytolysis by virus-free CRISPR-edited CAR T cells compared with retrovirally transduced CAR T cells, accompanied by increased inflammatory cytokine release, CD8+ CAR T-cell presence in co-culture conditions and CAR T-cell infiltration into three-dimensional GBM spheroids. Computational modeling identified increased tumor necrosis factor α concentrations with decreased glutamine, lactate and formate as being most predictive of short-term (2 days) and long-term (7 days) CAR T cell potency against GBM stem cells. CONCLUSIONS: These studies establish impedance sensing as a high-throughput, label-free assay for preclinical potency testing of CAR T cells against solid tumors.

Investigating the effects of cyclic topology on the performance of a plastic degrading enzyme for polyethylene terephthalate degradation.

Agitation is a commonly encountered stress for enzymes during all stages of production and application, but investigations that aim to improve their tolerance using topological engineering have yet to be reported. Here, the plastic-degrading enzyme IsPETase was cyclized in a range of topologies including a cyclic monomer, cyclic dimer and catenane using SpyTag/SpyCatcher technologies, and their tolerance towards different stresses including mechanical agitation was investigated. The cyclic dimer and catenane topologies were less susceptible to agitation-induced inactivation resulting in enhancement of polyethylene terephthalate (PET) degradation. While contrary to conventional belief, cyclic topologies did not improve tolerance of IsPETase towards heat or proteolytic treatment, the close proximity of active sites in the dimeric and catenane variants was found to enhance PET conversion into small soluble products. Together, these findings illustrate that it is worthwhile to explore the topology engineering of enzymes used in heterogeneous catalysis as it improves factors that are often overlooked in homogeneous catalysis studies.

Is the Activity Measure for Postacute Care "6-Clicks" Tool Associated With Discharge Destination Postacute Stroke?

Objective: To investigate the association of poststroke physical function, measured within 24 hours prior to discharge from the acute care hospital using Activity Measure for Postacute Care (AM-PAC) Inpatient "6-Clicks" scores and discharge destination (home vs facility and inpatient rehabilitation facility [IRF] vs skilled nursing facility [SNF]). Design: Retrospective cross-sectional cohort study. Setting: Acute care, University Hospital. Participants: Individuals post acute ischemic stroke, N=721, 51.3% male, mean age 63.6±16.4 years. Interventions: Not applicable. Main Outcome Measures: AM-PAC "6-Clicks" 3 domains: basic mobility, daily activity, and applied cognition. Results: AM-PAC basic mobility and daily activity were significant predictors of discharge. Those in the home discharge group had AM-PAC basic mobility mean t scale score of 48.5 compared with a score of 34.8 for individuals sent to a facility and daily activity score of 47.2 compared with 32.7 for individuals sent to a facility. The AM-PAC variables accounted for an additional 24% of the variance in the discharge destination, with basic mobility and daily activity accounting for most of the variance.The AM-PAC scores were not statistically different and were not able to discriminate between placement in an IRF vs SNF. The mean basic mobility t scale score for individuals going to an IRF was 34.9 compared with 34.6 for those going to an SNF. The daily activity score for IRF was 32.8 compared with 32.6 for SNF. The AM-PAC accounted for no additional variance in discharge destination to an IRF or SNF. Conclusions: The AM-PAC Inpatient "6-Clicks" 3 domains are able to distinguish individuals with stroke being discharged to home from postacute care (PAC) but not for differentiating between PAC facilities (IRF vs SNF) in this cohort of individuals post stroke.

Personalized practice dosages may improve motor learning in older adults compared to "standard of care" practice dosages: A randomized controlled trial.

Standard dosages of motor practice in clinical physical rehabilitation are insufficient to optimize motor learning, particularly for older patients who often learn at a slower rate than younger patients. Personalized practice dosing (i.e., practicing a task to or beyond one's plateau in performance) may provide a clinically feasible method for determining a dose of practice that is both standardized and individualized, and may improve motor learning. The purpose of this study was to investigate whether personalized practice dosages [practice to plateau (PtP) and overpractice (OVP)] improve retention and transfer of a motor task, compared to low dose [LD] practice that mimics standard clinical dosages. In this pilot randomized controlled trial (NCT02898701, ClinicalTrials.gov), community-dwelling older adults (n = 41, 25 female, mean age 68.9 years) with a range of balance ability performed a standing serial reaction time task in which they stepped to specific targets. Presented stimuli included random sequences and a blinded repeating sequence. Participants were randomly assigned to one of three groups: LD (n = 15, 6 practice trials equaling 144 steps), PtP (n = 14, practice until reaching an estimated personal plateau in performance), or OVP (n = 12, practice 100% more trials after reaching an estimated plateau in performance). Measures of task-specific learning (i.e., faster speed on retention tests) and transfer of learning were performed after 2-4 days of no practice. Learning of the random sequence was greater for the OVP group compared to the LD group (p = 0.020). The OVP (p = 0.004) and PtP (p = 0.010) groups learned the repeated sequence more than the LD group, although the number of practice trials across groups more strongly predicted learning (p = 0.020) than did group assignment (OVP vs. PtP, p = 0.270). No group effect was observed for transfer, although significant transfer was observed in this study as a whole (p < 0.001). Overall, high and personalized dosages of postural training were well-tolerated by older adults, suggesting that this approach is clinically feasible. Practicing well-beyond standard dosages also improved motor learning. Further research should determine the clinical benefit of this personalized approach, and if one of the personalized approaches (PtP vs. OVP) is more beneficial than the other for older patients.

Combining the AM-PAC "6-Clicks" and the Morse Fall Scale to Predict Individuals at Risk for Falls in an Inpatient Rehabilitation Hospital.

OBJECTIVE: To determine the effect of adding the Activity Measure for Post-Acute Care (AM-PAC) Inpatient '6-Clicks' Short Forms to the Morse Fall Scale (MFS) to assess fall risk. Falls that occur in a rehabilitation hospital result in increased morbidity and mortality, increased cost, and negatively affect reimbursement. Identifying individuals at high risk for falls would enable targeted fall prevention strategies and facilitate appropriate resource allocation to address this critical patient safety issue. DESIGN: We used a retrospective observational design and repeated k-fold cross-validation (10 repeats and 10 folds) of logistic regression models with falls regressed onto: MFS alone, AM-PAC basic mobility and applied cognitive scales alone, and MFS and AM-PAC combined. SETTING: Inpatient rehabilitation hospital. PARTICIPANTS: After exclusions, 2007 patients from an inpatient setting (N=2007; 131 experienced a fall). Primary diagnoses included 602 individuals with stroke (30%), 502 with brain injury (25%), 321 with spinal cord injury (16%), and 582 with other diagnoses (29%). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Experience of a fall during inpatient stay. RESULTS: The MFS at admission was associated with falls (area under the curve [AUC], 0.64). Above and beyond the MFS, AM-PAC applied cognitive and basic mobility at admission were also significantly associated with falls (combined model AUC, 0.70). Although MFS and applied cognition showed linear associations, there was evidence for a nonlinear association with AM-PAC basic mobility. CONCLUSIONS: The AM-PAC basic mobility and AM-PAC applied cognitive scales showed associations with falls above and beyond the MFS. More work is needed to validate model predictions in an independent sample with truly longitudinal data; prediction accuracy would also need to be substantially improved. However, the current data do suggest that the AM-PAC has the potential to reduce the burden of fall management by focusing resources on a smaller cohort of patients identified as having a high fall risk.

Approaches for peptide and protein cyclisation.

The cyclisation of polypeptides can play a crucial role in exerting biological functions, maintaining stability under harsh conditions and conferring proteolytic resistance, as demonstrated both in nature and in the laboratory. To date, various approaches have been reported for polypeptide cyclisation. These approaches range from the direct linkage of N- and C- termini to the connection of amino acid side chains, which can be applied both in reaction vessels and in living systems. In this review, we categorise the cyclisation approaches into chemical methods (e.g. direct backbone cyclisation, native chemical ligation, aldehyde-based ligations, bioorthogonal reactions, disulphide formation), enzymatic methods (e.g. subtiligase variants, sortases, asparaginyl endopeptidases, transglutaminases, non-ribosomal peptide synthetases) and protein tags (e.g. inteins, engineered protein domains for isopeptide bond formation). The features of each approach and the considerations for selecting an appropriate method of cyclisation are discussed.

I Want to Row Across the Atlantic. But You Have Amyotrophic Lateral Sclerosis!

ABSTRACT: We describe an individual with slowly progressive amyotrophic lateral sclerosis who decided to enter the Talisker Whisky Atlantic Challenge, a rowing event across the Atlantic Ocean, and completes it in 51 days in a 5-man boat.

The feasibility and efficacy of a serial reaction time task that measures motor learning of anticipatory stepping.

BACKGROUND: Motor learning has been investigated using various paradigms, including serial reaction time tasks (SRTT) that examine upper extremity reaching and pointing while seated. Few studies have used a stepping SRTT, which could offer additional insights into motor learning involving postural demands. For a task to measure motor learning, naïve participants must demonstrate a) improved performance with task practice, and b) a dose-response relationship to learning the task. RESEARCH QUESTION: Is a stepping SRTT feasible and efficacious for measuring motor learning? METHODS: In this prospective study, 20 participants stood on an instrumented mat and were presented with stimuli on a computer screen. They stepped to the corresponding positions on the mat as quickly as possible. Presented stimuli included random sequences and a blinded imbedded repeating sequence. Three days after completing the randomly assigned practice dose [high dose group (n = 10) performed 4320 steps; low dose group (n = 10) performed 144 steps], a retention test of 72 steps was performed. Feasibility was measured as the proportion of participants who completed the assigned practice dose without adverse events. Efficacy was measured as within-group performance improvement on the random sequences and on the repeating sequence (paired t-tests), as well as a dose-response relationship to learning both types of sequences (independent t-tests). RESULTS: All participants (mean age 26.8 years) completed all practice sessions without adverse events, indicating feasibility. High dose practice resulted in performance improvement while low dose did not; a dose-response relationship was found, with high dose practice resulting in greater learning of the task than low dose practice, indicating efficacy. SIGNIFICANCE: This stepping SRTT is a feasible and efficacious way to measure motor learning, which could provide critical insights into anticipatory stepping, postural control, and fall risk. Future research is needed to determine feasibility, efficacy, and optimal practice dosages for older and impaired populations.

Omega-3 index and blood pressure responses to eating foods naturally enriched with omega-3 polyunsaturated fatty acids: a randomized controlled trial.

Diets low in seafood omega-3 polyunsaturated fatty acids (PUFAs) are very prevalent. Such diets have recently been ranked as the sixth most important dietary risk factor-1.5 million deaths and 33 million disability-adjusted life-years worldwide are attributable to this deficiency. Wild oily fish stocks are insufficient to feed the world's population, and levels of eicosapentaenoic acid and docosahexaenoic acid (DHA) in farmed fish have more than halved in the last 20 years. Here we report on a double-blinded, controlled trial, where 161 healthy normotensive adults were randomly allocated to eat at least three portions/week of omega-3-PUFA enriched (or control) chicken-meat, and to eat at least three omega-3-PUFA enriched (or control) eggs/week, for 6 months. We show that regular consumption of omega-3-PUFA enriched chicken-meat and eggs significantly increased the primary outcome, the red cell omega-3 index (mean difference [98.75% confidence interval] from the group that ate both control foods, 1.7% [0.7, 2.6]). Numbers of subjects with a very high-risk omega-3 index (index < 4%) were more than halved amongst the group that ate both enriched foods. Furthermore, eating the enriched foods resulted in clinically relevant reductions in diastolic blood pressure (- 3.1 mmHg [- 5.8, - 0.3]). We conclude that chicken-meat and eggs, naturally enriched with algae-sourced omega-3-PUFAs, may serve as alternative dietary sources of these essential micronutrients. Unlike many lifestyle interventions, long-term population health benefits do not depend on willingness of individuals to make long-lasting difficult dietary changes, but on the availability of a range of commonly eaten, relatively inexpensive, omega-3-PUFA enriched foods.

Daily acute intermittent hypoxia to improve walking function in persons with subacute spinal cord injury: a randomized clinical trial study protocol.

BACKGROUND: Restoring community walking remains a highly valued goal for persons recovering from traumatic incomplete spinal cord injury (SCI). Recently, studies report that brief episodes of low-oxygen breathing (acute intermittent hypoxia, AIH) may serve as an effective plasticity-inducing primer that enhances the effects of walking therapy in persons with chronic (> 1 year) SCI. More persistent walking recovery may occur following repetitive (weeks) AIH treatment involving persons with more acute SCI, but this possibility remains unknown. Here we present our clinical trial protocol, designed to examine the distinct influences of repetitive AIH, with and without walking practice, on walking recovery in persons with sub-acute SCI (< 12 months) SCI. Our overarching hypothesis is that daily exposure (10 sessions, 2 weeks) to AIH will enhance walking recovery in ambulatory and non-ambulatory persons with subacute (< 12 months) SCI, presumably by harnessing endogenous mechanisms of plasticity that occur soon after injury. METHODS: To test our hypothesis, we are conducting a randomized, placebo-controlled clinical trial on 85 study participants who we stratify into two groups according to walking ability; those unable to walk (non-ambulatory group) and those able to walk (ambulatory group). The non-ambulatory group receives either daily AIH (15, 90s episodes at 10.0% O2 with 60s intervals at 20.9% O2) or daily SHAM (15, 90s episodes at 20.9% O2 with 60s intervals at 20.9% O2) intervention. The ambulatory group receives either 60-min walking practice (WALK), daily AIH + WALK, or daily SHAM+WALK intervention. Our primary outcome measures assess overground walking speed (10-Meter Walk Test), endurance (6-Minute Walk Test), and balance (Timed Up & Go Test). For safety, we also measure levels of pain, spasticity, systemic hypertension, and autonomic dysreflexia. We record outcome measures at baseline, days 5 and 10, and follow-ups at 1 week, 1 month, 6 months, and 12 months post-treatment. DISCUSSION: The goal of this clinical trial is to reveal the extent to which daily AIH, alone or in combination with task-specific walking practice, safely promotes persistent recovery of walking in persons with traumatic, subacute SCI. Outcomes from this study may provide new insight into ways to enhance walking recovery in persons with SCI. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02632422 . Registered 16 December 2015.

Comparison of driving capacity among patients with amyotrophic lateral sclerosis and healthy controls using the lane change task.

OBJECTIVE: Compare driving capacity of individuals with Amyotrophic Lateral Sclerosis (ALS) and healthy controls (HC) using a driving simulation program. METHODS: A prospective study was performed on individuals with ALS who reported they were still driving, and a group of HCs. Demographic data included age and gender. Assessment included cognitive assessments (Montreal cognitive assessment [MoCA] and ALS Cognitive Behavioral Scale [ALS-CBS]); gait speed (m/s); ALS Functional Rating Scale-revised total score (ALSFRS-R); and simulated driving assessment (Lane Change Task [LCT]). The LCT is a simple assessment tool which simulates the visual, cognitive, and motor demands of driving to detect at-risk drivers and uses distractions (secondary tasks) to quantify the performance loss on the primary task (lane changes). RESULTS: Twenty-eight individuals with ALS (22 males, mean age 64 years) and 20 HCs (7 males, mean age 59 years) were studied. Individuals with mild to moderate ALS (ALSFRS-R mean 36.2) were older, had mild cognitive difficulty (MoCA 24 vs 27; ALS-CBS 14.19 [SD 3.85]) and mobility decline (gait speed 1.1 vs 1.4 m/s) compared to HC. Driving assessment using the LCT found no differences in baseline scores or during motor, cognitive, or visually distracting conditions. CONCLUSIONS: Individuals with ALS with mild to moderate disease progression, with cognitive and motor weakness still demonstrate similar driving capacity to HCs using a driving simulation task. Driving assessment needs to be expanded longitudinally and perhaps with more robust measures to more precisely identify types of driving challenges that lead to cessation of driving in individuals with ALS.

Novel method for action potential measurements from intact cardiac monolayers with multiwell microelectrode array technology.

The cardiac action potential (AP) is vital for understanding healthy and diseased cardiac biology and drug safety testing. However, techniques for high throughput cardiac AP measurements have been limited. Here, we introduce a novel technique for reliably increasing the coupling of cardiomyocyte syncytium to planar multiwell microelectrode arrays, resulting in a stable, label-free local extracellular action potential (LEAP). We characterized the reliability and stability of LEAP, its relationship to the field potential, and its efficacy for quantifying AP morphology of human induced pluripotent stem cell derived and primary rodent cardiomyocytes. Rise time, action potential duration, beat period, and triangulation were used to quantify compound responses and AP morphology changes induced by genetic modification. LEAP is the first high throughput, non-invasive, label-free, stable method to capture AP morphology from an intact cardiomyocyte syncytium. LEAP can accelerate our understanding of stem cell models, while improving the automation and accuracy of drug testing.

Associations and effects of omega-3 polyunsaturated fatty acids on cognitive function and mood in healthy adults: a protocol for a systematic review of observational and interventional studies.

INTRODUCTION: The association between long-chain omega-3 polyunsaturated fatty acids (PUFAs), brain health, cognitive function and mood has been the subject of intensive research. Marine-derived omega-3 PUFAs, such as docosahexaenoic acid and eicosapentaenoic acid, are highly concentrated in neuronal membranes and affect brain function. Many studies have found that consumption of omega-3 PUFAs is associated with lower risk of cognitive or mood dysfunction. However, other studies have demonstrated no beneficial effects. There appears to be inconsistent findings from both epidemiological and randomised controlled trial (RCT) studies. The aim of this review is to compile the previous literature and establish the efficacy of omega-3 PUFAs in enhancing cognitive performance and mood in healthy adults. METHODS AND ANALYSIS: Prospective cohort studies, RCTs, controlled clinical trials, controlled before and after studies, interrupted time series with a minimum of 3 months duration will be eligible for inclusion. Studies on healthy adults over the age of 18, where the intervention/exposure of interest is omega-3 PUFAs will be included. The outcomes of interest are cognition and mood. Studies will be eligible for inclusion if they measure changes in cognitive function or mood, or the risk of developing cognitive or mood disorders using validated tools and assessments. Relevant search terms and keywords will be used to generate a systematic search in Cochrane Library, MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Scopus and the grey literature. Two independent reviewers will screen studies for eligibility. Risk of bias in cohort and non-randomised studies will be assessed using the ROBINS-I tool. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials will be used for RCTs. If there are sufficient data, a meta-analysis will be conducted. ETHICS AND DISSEMINATION: This systematic review does not involve primary data collection and therefore formal ethical approval is not required. Results will be disseminated through peer reviewed publications, conference presentations and the popular press. PROSPERO REGISTRATION NUMBER: CRD42018080800.

Stepping Activity in Children With Congenital Myotonic Dystrophy.

PURPOSE: The purpose of this study was to investigate the physical activity levels in children with congenital myotonic dystrophy (CDM), and to examine whether patient clinical and functional characteristics correlated to physical activity. METHODS: Twenty-five children with CDM were assessed on functional measures, clinical measures, and physical activity levels. RESULTS: Results support that children with CDM spend the majority of their time inactive. There was a negative correlation between inactivity and cytosine-thymine-guanine repeats, suggesting increased inactivity with increased CDM severity. Age, body mass index, and lean muscle mass may be factors influencing activity levels. CONCLUSIONS: Children in this study received one-third the recommended steps per day. The number of steps per day is not correlated with clinical measures.

Modified dynamic gait index and limits of stability in myotonic dystrophy type 1.

INTRODUCTION: The purpose of this study was to describe and compare the performance of balance and walking tests in relation to self-reported fall history in adults with myotonic dystrophy type 1 (DM1). METHODS: Twenty-two (13 male) participants with DM1 completed, a 6-month fall history questionnaire, the modified Dynamic Gait Index (mDGI), limits of stability (LoS) testing, and 10-m walking tests. RESULTS: Mean (SD) falls in 6 months was 3.7 (3.1), and 19 (86%) participants reported at least 1 fall. Significant differences in mDGI scores (P = 0.006) and 10-m fast walking gait velocity (P = 0.02) were found between those who had been classified as "fallers" and those who had been classified as "nonfallers." Significant correlations were found between mDGI scores and 10-m walking time. DISCUSSION: Falls are common in DM1, and the mDGI may have potential to distinguish fallers from nonfallers, whereas the LoS failed to detect such impairment. Future studies should further explore use of the mDGI in DM1. Muscle Nerve 58: 694-699, 2018.