Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy.

We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic (P/LP) variants and 58 of 327 (17.7%) as having variants of uncertain significance. Multiple classes of P/LP variants included single-nucleotide variants (SNVs)/indels (6.7%), copy number variations (3.4%) and mitochondrial mutations (1.5%). The COL4A1 gene had the most P/LP SNVs. We also analyzed two pediatric control cohorts (n = 203 trios and n = 89 sib-pair families) to provide a baseline for de novo mutation rates and genetic burden analyses, the latter of which demonstrated associations between de novo deleterious variants and genes related to the nervous system. An enrichment analysis revealed previously undescribed plausible candidate CP genes (SMOC1, KDM5B, BCL11A and CYP51A1). A multifactorial CP risk profile and substantial presence of P/LP variants combine to support WGS in the diagnostic work-up across all CP and related phenotypes.

Quick, Effective Screening Tasks Identify Children With Medical Conditions or Disabilities Needing Physical Literacy Support.

PURPOSE: This study evaluated screening tasks able to identify children with medical conditions or disabilities who may benefit from physical literacy. METHOD: Children completed ≤20 screening tasks during their clinic visit and then the Canadian Assessment of Physical Literacy (2nd edition) at a separate visit. Total Canadian Assessment of Physical Literacy scores <30th percentile were categorized as potentially needing physical literacy support. Receiver operator characteristic curves identified assessment cut points with 80% sensitivity and 40% specificity relative to total physical literacy scores. RESULTS: 223 children (97 girls; 10.1 [2.6] y) participated. Physical activity adequacy, predilection, and physical competence achieved ≥80% sensitivity and ≥40% specificity in both data sets. Adequacy ≤ 6.5 had 86% to 100% sensitivity and 48% to 49% specificity. Daily screen time >4.9 hours combined with Adequacy ≤6.15 had 88% to 10% sensitivity and 53% to 56% specificity. CONCLUSIONS: Activity adequacy, alone or with screen time, most effectively identified children likely to benefit from physical literacy support. Adequacy and screen time questionnaires are suitable for clinical use. Similar results regardless of diagnosis suggest physical competence deficits are not primary determinants of active lifestyles. Research to enhance screening specificity is required.

Tone management: An environmental scan of current management practices across Canada.

BACKGROUND: Currently, there are no standardized approaches to care or evaluation for tone dysfunction in Canada. The study authors hypothesize that there is significant practice variation across the country. This environmental scan is aimed to describe the current practice for management of paediatric patients with hypertonia across Canada. METHODS: A web-based survey was developed by the authors with a multi-disciplinary approach and sent to representative paediatric rehabilitation sites in each province in Canada. Disciplines at the rehabilitation sites surveyed included all or some of the following disciplines: physiatry, neurology, neurosurgery, plastic surgery, orthopaedic surgery, physiotherapy and occupational therapy. All statistical analyses were performed using the R statistical software version 4.0. Fifteen rehabilitation sites were contacted, and 12 sites were used for the final analysis. RESULTS: Cerebral palsy was found to be the most common diagnosis for tone dysfunction, with 58% of sites diagnosing greater than 20 new patients per year. In 67% of sites, patients were seen within a formal multidisciplinary clinic to manage hypertonia. All 12 sites utilized oral baclofen and gabapentin, and 92% of sites utilized trihexyphenidyl. Botulinum toxin injections were offered at 50% of sites. Upper and lower extremity surgical procedures were offered in 83% of the sites. CONCLUSION: The information gained from this study provides some insight into the current practice across Canada for children with hypertonia. This study may assist in the development of a national, standardized strategy to tone management, potentially facilitating more equitable access to care for patients.

Effectiveness of extended postpartum inpatient monitoring for hypertensive disorders of pregnancy to reduce the risk of readmission for preeclampsia with severe features.

BACKGROUND: Preeclampsia is an obstetrical disorder, which complicates 3% to 6% of pregnancies and contributes to 21.6% of readmissions in the postpartum period. The optimal strategy for inpatient monitoring of blood pressures to minimize readmissions for postpartum patients with hypertensive disorders is not known. We hypothesized that extended monitoring of postpartum patients with hypertensive disorders of pregnancy for at least 36 hours after the last blood pressure that was ≥150/100 mm Hg would result in decreased readmission rates for preeclampsia with severe features compared with those who were not observed by these blood pressure goals. OBJECTIVE: This study aimed to evaluate whether extended inpatient monitoring of postpartum patients with hypertensive disorders of pregnancy for at least 36 hours after their last blood pressure that was ≥150/100 mm Hg would improve readmission rates for preeclampsia with severe features within 6 weeks of delivery. STUDY DESIGN: This was a retrospective cohort study in patients with a singleton pregnancy and a diagnosis of a hypertensive disorder of pregnancy at their delivery admission or at any point during pregnancy who delivered 1 year before and 1 year after the implementation of extended inpatient monitoring of postpartum hypertension. The primary outcome was readmission for preeclampsia with severe features within 6 weeks of delivery. The secondary outcomes were length of stay during first admission, number of readmissions for any indication, intensive care unit admission, postpartum day at readmission, median systolic blood pressure in the 24-hour period before discharge, median diastolic blood pressure in the 24-hour period before discharge, intravenous antihypertensive medication required during first admission, and intravenous antihypertensive medication required during second admission. Univariable analysis was performed for the association between baseline maternal characteristics and the primary outcome. Multivariable analysis was performed, adjusting for baseline maternal characteristic differences between exposure groups. RESULTS: A total of 567 patients met the inclusion criteria of which 248 patients delivered before and 319 delivered after the implementation of extended monitoring. For baseline characteristics, the extended monitoring group had a significantly higher proportion of patients who were non-Hispanic Black and Hispanic, more diagnoses of hypertensive disorders and/or diabetes mellitus at the time of admission for delivery, a difference in the distribution of hypertensive diagnoses at the time of discharge from the first admission, and fewer discharged patients from their first admission on labetalol than the preintervention group. In a univariable analysis of the primary outcome, there was a significantly increased risk of readmission for preeclampsia with severe features in the extended monitoring group (62.5% vs 96.2% of total readmissions; P=.004). In multivariable analysis, patients in the extended monitoring group were more likely to be readmitted for preeclampsia with severe features than patients in the preintervention group (adjusted odds ratio, 3.45; 95% confidence interval, 1.03-11.5; P=.044). CONCLUSION: Extended monitoring with a strict blood pressure goal of <150/<100 mm Hg did not decrease readmissions for preeclampsia with severe features in patients with a previous diagnosis of a hypertensive disorder of pregnancy.

A Meta-Analysis and Systematic Review of Community-Based Intimate Partner Violence Interventions in India.

Intimate partner violence (IPV) in India remains an entrenched and prevalent public health issue. Despite ample evidence of the widespread problem of IPV in India and associated mental and physical morbidities, far less is known about intervention models to reduce IPV in India. The aims of this meta-analysis and systematic review are to assess the effectiveness of community-based interventions to reduce IPV in India and to provide a narrative synthesis of these intervention approaches. A total of 9 databases were searched to identify peer-reviewed, English-language articles published between January 2000 and September 2022. The search identified 10 studies that met study inclusion criteria, including 3 randomized control trials, 4 quasi-experimental, 2 pre/post, and 1 time-series evaluation. Eight studies were included in the meta-analysis. There was notable variation in the interventions and approaches employed to reduce IPV and varying measurement of IPV outcomes. The results of the meta-analysis show that participating in community-based IPV interventions produced a significant reduction in IPV among women. When considering different types of IPV, study participants were less likely to report physical and psychological IPV victimization. In addition, participants were also less likely to report approving of IPV after participating in community-based IPV interventions. Community-based interventions and research addressing IPV are still evolving in India. Missing descriptions of theoretical frameworks, sampling, intervention design, and inadequately reported effectiveness of intervention (both quantitative and qualitative reporting) need to be addressed. Moreover, long-term evaluations of the pilot interventions are needed to provide a clear picture of the long-term effectiveness, sustainability, and replicability of the community-based IPV interventions. The findings have implications for researchers, practitioners (community health workers, clinicians, and social workers), and policymakers keen on IPV reduction in India and globally.

Population structure in diverse pepper (Capsicum spp.) accessions.

BACKGROUND: Peppers, bell and chile, are a culturally and economically important worldwide. Domesticated Capsicum spp. are distributed globally and represent a complex of valuable genetic resources. OBJECTIVES: Explore population structure and diversity in a collection of 467 peppers representing eight species, spanning the spectrum from highly domesticated to wild using 22,916 SNP markers distributed across the twelve chromosomes of pepper. RESULTS: These species contained varied levels of genetic diversity, which also varied across chromosomes; the species also differ in the size of genetic bottlenecks they have experienced. We found that levels of diversity negatively correlate to levels of domestication, with the more diverse being the least domesticated.

A randomized, cross-over trial comparing the effect of innovative robotic gait training and functional clinical therapy in children with cerebral palsy; a protocol to test feasibility.

PURPOSE: Robotic gait training is relatively new in the world of pediatric rehabilitation. Preliminary feasibility studies and case reports include stationary robot-assisted treadmill training. Mobile robotic gait trainers hold greater promise for intensive practice-based therapy within hospitals, schools, rehabilitation centers, and at-home therapy as they enable participation and social integration while practicing high-quality gait patterns. MATERIALS AND METHODS: This paper (clinical trials registry number: NCT05378243) provides a detailed description of a mixed-method cross-over trial design with a broad set of outcome measures. Ultimately the goal is to establish the feasibility of this design which includes the collection of qualitative data regarding patient, family, and therapist experience and quantitative data regarding gait efficiency and quality, impact on tone, individualized goal achievement and bone strength.

Synergistic Protection against Secondary Pneumococcal Infection by Human Monoclonal Antibodies Targeting Distinct Epitopes.

Streptococcus pneumoniae persists as a leading cause of bacterial pneumonia despite the widespread use of polysaccharide-based vaccines. The limited serotype coverage of current vaccines has led to increased incidence of nonvaccine serotypes, as well as an increase in antibiotic resistance among these serotypes. Pneumococcal infection often follows a primary viral infection such as influenza virus, which hinders host defense and results in bacterial spread to the lungs. We previously isolated human monoclonal Abs (mAbs) against the conserved surface Ag pneumococcal histidine triad protein D (PhtD), and we demonstrated that mAbs to this Ag are protective against lethal pneumococcal challenge prophylactically and therapeutically. In this study, we elucidated the mechanism of protection of a protective anti-pneumococcal human mAb, PhtD3, which is mediated by the presence of complement and macrophages in a mouse model of pneumococcal infection. Treatment with mAb PhtD3 reduced blood and lung bacterial burden in mice, and mAb PhtD3 is able to bind to bacteria in the presence of the capsular polysaccharide, indicating exposure of surface PhtD on encapsulated bacteria. In a mouse model of secondary pneumococcal infection, protection mediated by mAb PhtD3 and another mAb targeting a different epitope, PhtD7, was reduced; however, robust protection was restored by combining mAb PhtD3 with mAb PhtD7, indicating a synergistic effect. Overall, these studies provide new insights into anti-pneumococcal mAb protection and demonstrate, to our knowledge, for the first time, that mAbs to pneumococcal surface proteins can protect against secondary pneumococcal infection in the mouse model.

Parent-therapist partnership to ELEVATE gross motor function in children with perinatal stroke: protocol for a mixed methods randomized controlled trial.

BACKGROUND: There is increasing evidence for early, active rehabilitation to enhance motor function following early brain injury. This is clear for interventions targeting the upper extremity, whereas passive treatment approaches for the lower extremity persist. The purpose of this trial is to evaluate the effectiveness of early, intensive rehabilitation targeting the lower extremity and delivered in a parent-therapist partnership model for children with perinatal stroke. METHODS: We describe a protocol for a waitlist-control, single-blind, mixed methods effectiveness randomized controlled trial, with an embedded qualitative study using interpretative description. Participants are children with perinatal stroke aged eight months to three years with signs of hemiparesis. Participants will be randomly allocated to an immediate ELEVATE (Engaging the Lower Extremity Via Active Therapy Early) intervention group, or a waitlist-control group, who will receive usual care for six months. The ELEVATE intervention involves one hour of training four days per week for 12 weeks, with a pediatric therapist and a parent or guardian each delivering two sessions per week. The intervention targets the affected lower extremity by progressively challenging the child while standing and walking. The primary outcome measure is the Gross Motor Function Measure-66. Secondary outcomes include the Pediatric Quality of Life Inventory™, Young Children's Participation and Environment Measure, and an instrumented measure of spasticity. A cost-effectiveness analysis and qualitative component will explore benefit to costs ratios and parents' perspectives of early, intensive rehabilitation, and their role as a partner in the rehabilitation, respectively. DISCUSSION: This study has the potential to change current rehabilitation for young children with perinatal stroke if the ELEVATE intervention is effective. The parent interviews will provide further insight into benefits and challenges of a partnership model of rehabilitation. The mixed methods design will enable optimization for transfer of this collaborative approach into physical therapy practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT03672864 . Registered 17 September 2018.

Prioritizing a Research Agenda of Transitional Care Interventions for Childhood-Onset Disabilities.

Transitional care interventions have the potential to optimize continuity of care, improve health outcomes and enhance quality of life for adolescents and young adults living with chronic childhood-onset disabilities, including neurodevelopmental disorders, as they transition to adult health and social care services. The paucity of research in this area poses challenges in identifying and implementing interventions for research, evaluation and implementation. The purpose of this project was to advance this research agenda by identifying the transitional care interventions from the scientific literature and prioritize interventions for study. A modified-Delphi approach involving two rounds of online surveys followed by a face-to-face consensus meeting with knowledge users, researchers and clinician experts in transitional care (n = 19) was used. A subsequent virtual meeting concluded the formulation of next steps. Experts rated 16 categories of interventions, derived from a systematic review, on importance, impact, and feasibility. Seven of the 16 interventions categories received a mean score rating of ≥7 (out of 10) on all three rating categories. Participants then rank ordered the reduced list of seven interventions in order of priority and the top four ranked interventions advanced for further discussion at a consensus meeting. Using the Template for Intervention Description and Replication (TIDieR) checklist as a guide, the participants identified that a study of a peer system navigator was worthy of future evaluation. This study highlighted that transitional care interventions are complex and multifaceted. However, the presence of a peer to support system navigation, advocacy and individual and family education was considered the most ideal intervention addressing the current gap in care. Future research, which aims to engage patients and families in a co-design approach, is recommended to further develop this intervention.

Characterization of physical literacy in children with chronic medical conditions compared with healthy controls: a cross-sectional study.

To determine the physical literacy, defined as the capability for a physically active lifestyle, of children with medical conditions compared with healthy peers, this multicenter cross-sectional study recruited children with medical conditions from cardiology, neurology (including concussion), rheumatology, mental health, respirology, oncology, hematology, and rehabilitation (including cerebral palsy) clinics. Participants aged 8-12 years (N = 130; mean age: 10.0 ± 1.44 years; 44% female) were randomly matched to 3 healthy peers from a normative database, based on age, gender, and month of testing. Total physical literacy was assessed by the Canadian Assessment of Physical Literacy, a validated assessment of physical literacy measuring physical competence, daily behaviour, knowledge/understanding, and motivation/confidence. Total physical literacy mean scores (/100) did not differ (t(498) = -0.67; p = 0.44) between participants (61.0 ± 14.2) and matched healthy peers (62.0 ± 10.7). Children with medical conditions had lower mean physical competence scores (/30; -6.5 [-7.44 to -5.51]; p < 0.001) but higher mean motivation/confidence scores (/30; 2.6 [1.67 to 3.63]; p < 0.001). Mean daily behaviour and knowledge/understanding scores did not differ from matches (/30; 1.8 [0.26 to 3.33]; p = 0.02;/10; -0.04 [-0.38 to 0.30]; p = 0.81; respectively). Children with medical conditions are motivated to be physically active but demonstrate impaired movement skills and fitness, suggesting the need for targeted interventions to improve their physical competence. Novelty: Physical literacy in children with diverse chronic medical conditions is similar to healthy peers. Children with medical conditions have lower physical competence than healthy peers, but higher motivation and confidence. Physical competence (motor skill, fitness) interventions, rather than motivation or education, are needed for these youth.

Neurodevelopmental profiles of children with unilateral cerebral palsy associated with middle cerebral artery and periventricular venous infarctions.

AIM: To compare the neurodevelopment of children with unilateral cerebral palsy (CP) with middle cerebral artery (MCA) and periventricular venous infarctions (PVIs). METHOD: In this cross-sectional study, children with unilateral CP completed a neurological exam, unimanual Quality of Upper Extremity Skills Test, hand usage questionnaires, and IQ test. Neuroimaging was obtained from health records. RESULTS: Two hundred and forty-five participants with unilateral CP had neuroimaging (151 [61.9%] male, ages 2-18y, median=7y 6mo, interquartile range [IQR]=6y 7mo, with 93.6% in Gross Motor Function Classification System level I/II and 78.8% in Manual Ability Classification System level I/II). Ninety-seven (39.6%) had MCA injuries and 106 (43.3%) had periventricular white matter injuries, of which 48 (45.3%) were PVIs. Median Quality of Upper Extremity Skills Test for the MCA group was 49.2 (IQR=55.8), PVI 79.9 (IQR=23.6) (Mann-Whitney U=988.50, p<0.001). Bimanual hand usage (Children's Hand-use Experience Questionnaire) (Mann-Whitney U=425, p<0.001) and light touch (odds ratio=9.12, 95% confidence interval 1.28-400.76, Fisher's exact test p=0.017) were lower in the MCA compared to the PVI group. Full-scale IQ median centile score for the MCA group was 18.0 (IQR=35.5) and 50.0 (IQR=30.0) for the PVI group (Mann-Whitney U=382, p<0.001). INTERPRETATION: Children with unilateral CP and MCA injuries demonstrated lower hand function and usage, decreased light touch, and lower IQs compared to the PVI group. This study aids in defining rehabilitation needs informed by brain injury patterns.

Mindfulness-based interventions for children and adolescents across all settings: a scoping review protocol.

BACKGROUND AND PURPOSE: Although mindfulness-based interventions (MBIs) are becoming increasingly popular, the application of MBIs with children and adolescents is still in its infancy. Mapping the existing literature is necessary to help guide pediatric mindfulness interventions. Our purpose is to synthesize the evidence of reported MBIs for children and adolescents with and without physical, mental, and cognitive disorders. Accordingly, we aim to identify trends and gaps in the literature, so that we can provide direction to researchers who seek to advance the evidence base for using MBIs in pediatric populations. METHODS: Our search strategy will be conducted following Arksey and O'Malley's methodological framework. It will include a comprehensive search of published studies in 7 databases, gray literature, conference proceedings, and citations of selected articles. Two independent reviewers will evaluate all abstracts and full articles that have a pediatric sample (children 2-17 years), use MBIs to promote development or to remediate underlying disorders, and are written in English or French. We will identify the definitions and concepts from MBIs, categorize accepted studies according to etiology and rehabilitation type, describe intervention methodology, and report outcomes of selected studies. DISCUSSION: Our review will provide a comprehensive overview of the pediatric mindfulness intervention literature to date, involving a range of mental, cognitive, and physical outcomes for healthy children and adolescents and for those with a variety of disorders in clinical and institutional settings. We will disseminate results to mindfulness practitioners and provide guidance to future pediatric researchers in their development and application of mindfulness interventions, thereby contributing to the scientific understanding of mindfulness for the ultimate betterment of child and adolescent well-being and life-long functioning. SYSTEMATIC REVIEW REGISTRATION: PROSPERO does not accept scoping review protocols.

Transitional Care Interventions for Youth With Disabilities: A Systematic Review.

CONTEXT: Transition from the pediatric to the adult health care system is a complex process that should include medical, psychosocial, educational, recreational, and vocational considerations. OBJECTIVE: In this systematic review, we aim to synthesize the evidence on transitional care interventions (TCIs) to improve the quality of life (QoL) for adolescents and young adults with childhood-onset disabilities, including neurodevelopmental disorders. DATA SOURCES: Four electronic databases (Medline, Embase, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature) were searched. STUDY SELECTION: In the included studies, researchers examined TCIs for adolescents and young adults (12-24 years of age) with childhood-onset disabilities. Studies were experimental, quasi-experimental, and observational studies published in the last 26 years. DATA EXTRACTION: Two reviewers independently completed study screening, data extraction, and risk-of-bias assessment. RESULTS: Fifty-two studies were included. Five studies reported on QoL, but statistically significant improvements were noted in only 1 of these studies. Significant improvements were also found in secondary outcomes including disability-related knowledge and transitional readiness. TCIs targeted patients, families and/or caregivers, and health care providers and exhibited great heterogeneity in their characteristics and components. LIMITATIONS: Inconsistent reporting on interventions between studies hindered synthesis of the relationships between specific intervention characteristics and outcomes. CONCLUSIONS: Although there is limited evidence on the impact of TCIs on the QoL for youth with childhood-onset disabilities, there is indication that they can be effective in improving patient and provider outcomes. The initiation of transition-focused care at an early age may contribute to improved long-term health outcomes in this population.

A National Spinal Muscular Atrophy Registry for Real-World Evidence.

BACKGROUND: Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population. METHODS: The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials. RESULTS: The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner. CONCLUSION: Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.

Placental endothelin-converting enzyme-1 is decreased in preeclampsia.

Endothelin-converting enzyme-1(ECE-1) is a key regulatory enzyme in the processing of endothelin-1 (ET-1). We quantified and localized ECE-1 in normal and preeclamptic placentas. Normal (n=6) and preeclamptic (n=6) placentas were serially sectioned for immunofluorescence (IF). Cell type specific markers identified endothelial, trophoblast, macrophage, smooth muscle, and fibroblast cells. Quantitative analyses were performed by western blot and ELISA. IF identified ECE-1 expression within the stroma and villous space. Cellular localization of ECE-1 was limited to endothelial membranes. There was significantly less ECE-1 in preeclamptic placentas, suggesting ECE-1 is important for proper regulation of ET-1 within the placenta.

Development of a robotic walker for individuals with cerebral palsy.

Objective: This study describes the first use of a robotic walker in youth and young adults with cerebral palsy (CP) Gross Motor Function Classification (GMFCS) IV.Methods: Semi-structured interviews were conducted before and after each robotic walker trial. Interviews were recorded, then transcribed and subjected to thematic analysis.Results: Five participants (4 male, 13-22 years of age) with quadriplegia secondary to CP were recruited. Four individuals with mixed tone quadriplegia GMFCS IV were able to independently walk with the device. One individual with significant dyskinesia was unable to utilize the device. The assessment team included two physiotherapists, an occupational therapist, a physiatrist and three engineers. Major themes related to physical and social impacts were identified. Some physical advantages include the ability to walk hands-free and promotion of physical fitness. Examples of physical barriers include limited harness design and large device size. Social advantages include increased independence and peer engagement. Finally, a social disadvantage identified was limited use on uneven terrains.Discussion: Suggestions for modifications for identified challenges and disadvantages include decreasing the size of the robotic walker, more harness designs, decreasing the force required to take an initial step, adding a joy stick for user control and creating a more versatile base that can be used on different terrains such as ice or baseball fields.Conclusion: Robotics holds great hope for individuals with CP where mobility options are limited. Physical and social advantages are evident. Recommendations for future improvement and studies of use in exercise and participation are provided.IMPLICATIONS FOR REHABILITATIONAs youth and young adults with cerebral palsy age, options for mobilization can become limited with challenges in placing them in a walking device due to size and numerous other physical limitations.A robotic walker with a built-in mechanical lift is available for individuals with cerebral palsy.This study was able to gather important information and recommendations to tailor a new robotic walker prototype specifically for individuals with cerebral palsy.

The Impact of Fetal Anomalies on Contemporary Labor Patterns.

OBJECTIVE: To compare labor patterns in pregnancies affected by fetal anomalies to low-risk singletons. STUDY DESIGN: Labor data from the Consortium on Safe Labor, a multicenter retrospective study from 19 U.S. hospitals, including 98,674 low-risk singletons compared with 6,343 pregnancies with fetal anomalies were analyzed. Repeated-measures analysis constructed mean labor curves by parity, gestational age, and presence of fetal anomaly in women who reached full dilation. Interval-censored regression analysis adjusted for covariables was used to determine the median traverse times for labor progression. RESULTS: Labor curves for all groups indicated slower labor progress for patients with fetal anomalies. The most significant trends in median traverse times were observed in the preterm nulliparous and term multiparous groups. The median traverse times from 4 cm to complete dilation in the preterm nulliparous control versus anomaly groups were 5.0 and 5.4 hours (p < 0.0001). CONCLUSION: Labor proceeds at a slower rate in pregnancies affected by anomalies.

Sensitivity, specificity, and reliability of the Get Active Questionnaire for identifying children with medically necessary special considerations for physical activity.

Physical activity is promoted for optimal health but may carry risks for children who require medically necessary activity restrictions. The sensitivity, specificity, and reliability of the Get Active Questionnaire (GAQ) for identifying children needing special considerations during physical activity was evaluated among parents of 207 children aged 3 to 14 years (97 (47%) female, mean age of 8.4 ± 3.7 years). GAQ responses were compared with reports obtained directly from the treating physician (n = 192/207) and information in the medical chart (clinic notes/physician letter, n = 111/207). Parent GAQ responses (either "No to all questions" or "Yes to 1 or more questions") agreed with physician (κ = 0.16, p = 0.003) and medical record (κ = 0.15, p = 0.003) reports regarding the need for special consideration during physical activity (Yes/No). Sensitivity was 71% (20/28) and specificity was 59% (96/164), with few false-negative responses. The GAQ was most effective for rheumatology and cardiology patients. False positives were 29% to 46%, except among chronic pain (80%) and rehabilitation (75%) patients. Test-retest reliability was moderate (Cronbach's α = 0.70) among 57 parents who repeated the GAQ 1 week later. The GAQ effectively identified children not requiring physical activity restrictions and those with medical conditions similar to those of concern among adults. Additional questions from a qualified exercise professional, as recommended for a "Yes" response on the GAQ, should reduce the false-positive burden. Indicating the timeframe of reference for each question and including an option to describe other special considerations (e.g., medication, supervision) are recommended.

Repression of Mcl-1 expression by the CDC7/CDK9 inhibitor PHA-767491 overcomes bone marrow stroma-mediated drug resistance in AML.

Acute myeloid leukaemia (AML) is an aggressive cancer with 50-75% of patients relapsing even after successful chemotherapy. The role of the bone marrow microenvironment (BMM) in protecting AML cells from chemotherapeutics and causing consequent relapse is increasingly recognised. However the role that the anti-apoptotic Bcl-2 proteins play as effectors of BMM-mediated drug resistance are less understood. Here we show that bone marrow mesenchymal stromal cells (BMSC) provide resistance to AML cells against BH3-mimetics, cytarabine and daunorubicin, but this is not mediated by Bcl-2 and/or Bcl-XL as previously thought. Instead, BMSCs induced Mcl-1 expression over Bcl-2 and/or Bcl-XL in AML cells and inhibition of Mcl-1 with a small-molecule inhibitor, A1210477, or repressing its expression with the CDC7/CDK9 dual-inhibitor, PHA-767491 restored sensitivity to BH3-mimetics. Furthermore, combined inhibition of Bcl-2/Bcl-XL and Mcl-1 could revert BMSC-mediated resistance against cytarabine + daunorubicin. Importantly, the CD34+/CD38- leukemic stem cell-encompassing population was equally sensitive to the combination of PHA-767491 and ABT-737. These results indicate that Bcl-2/Bcl-XL and Mcl-1 act in a redundant fashion as effectors of BMM-mediated AML drug resistance and highlight the potential of Mcl-1-repression to revert BMM-mediated drug resistance in the leukemic stem cell population, thus, prevent disease relapse and ultimately improve patient survival.