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Migrants and refugees face elevated risks for mental health problems but have limited access to services. This study compared two strategies for training and supervising nonspecialists to deliver a scalable psychological intervention, Group Problem Management Plus (gPM+), in northern Colombia. Adult women who reported elevated psychological distress and functional impairment were randomized to receive gPM+ delivered by nonspecialists who received training and supervision by: 1) a psychologist ( specialized technical support ); or 2) a nonspecialist who had been trained as a trainer/supervisor ( nonspecialized technical support ). We examined effectiveness and implementation outcomes using a mixed-methods approach. Thirteen nonspecialists were trained as gPM+ facilitators and three were trained-as-trainers. We enrolled 128 women to participate in gPM+ across the two conditions. Intervention attendance was higher in the specialized technical support condition. The nonspecialized technical support condition demonstrated higher fidelity to gPM+ and lower cost of implementation. Other indicators of effectiveness, adoption and implementation were comparable between the two implementation strategies. These results suggest it is feasible to implement mental health interventions, like gPM+, using lower-resource, community-embedded task sharing models, while maintaining safety and fidelity. Further evidence from fully powered trials is needed to make definitive conclusions about the relative cost of these implementation strategies., Competing Interests: P.V. is a staff member of the United Nations. The views expressed in this manuscript are those of the authors and do not necessarily reflect the view of the United Nations. The remaining authors have no other competing interests to declare., (© The Author(s) 2024.)

Scholarly practice (SP) is considered a key competency of occupational therapy and physiotherapy. To date, the three sectors-education/research, practice, and policy/regulation-that support SP have been working relatively independently. The goals of this project were to (a) understand how representatives of the three sectors conceptualize SP; (b) define each sector's individual and collective roles in supporting SP; (c) identify factors influencing the enactment of SP and the specific needs of how best to support SP; and (d) co-develop goals and strategies to support SP across all sectors. We used interpretive description methodology. Consistent with an integrated knowledge translation approach, partners representing the three sectors across Canada recruited individuals from each sector, developed the content and questions for three focus groups, and collected and analyzed the data. Inspired by the Consolidated Framework for Implementation Research, we developed the questions for the second focus group. We analyzed the data using an inductive thematic analysis method. Thirty-nine participants from the three sectors participated. Themes related to participants' conceptualization of SP included (a) ongoing process, (b) reflective process, (c) broad concept, and (d) collective effort. Themes describing factors influencing and supporting SP were (a) recognition, (b) appropriate conceptualization, (c) social network, (d) accessibility to resources, and (e) forces outside of practitioners' effort. Goals to support SP included (a) further recognizing SP, (b) sustaining SP competency, and (c) ensuring access to information. SP requires collaborative and integrated intersectoral support and further recognition of its importance through the collaboration of multiple stakeholders., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Aim: To evaluate the effect of a parent-administered sensorimotor intervention (PASI) program on developmental outcomes of infants born preterm during their stay in the neonatal intensive care unit (NICU)., Method: A randomized clinical study was conducted with 94 infants (mean gestational age 31 weeks [SD 2.2 weeks]; 1658 g [SD 478 g]; 49 males, 45 females) initially enrolled and randomly assigned to an experimental or a control group. Infants in the experimental group received a PASI, consisting of tactile input to oral structures, trunk/limbs, and non-nutritive sucking for 15 minutes, once a day, for 10 days. Infants in the control group received standard care. Outcomes included attainment of complete oral feeds, occurrence of direct breastfeeding at hospital discharge, and motor function assessed using the Test of Infant Motor Performance (TIMP)., Results: A total of 80 infants completed the study. Infants in the experimental group achieved complete oral feeds sooner (11.9 [SD 4.3] vs 15.3 [SD 6.5] days, p = 0.013), and a greater number of them received direct breastfeeds (22 vs 12, p = 0.010) than controls. Infants in both groups had equivalent motor functions scores on the TIMP (46.9 [SD 4.8], 46.8 [SD 8.4], p = 0.961)., Interpretation: A PASI program may enhance an infant's oral feeding skills. These findings provide evidence to advocate for the institution of PASI in NICUs., (© 2024 Mac Keith Press.)

Background: Arthrogryposis multiplex congenita (AMC) is a group of rare musculoskeletal conditions that is associated with complex healthcare needs and long-term follow up. The literature reports significant direct, indirect, and psychosocial costs for caregivers of children with neuromuscular conditions. Due to mobility limitations and frequent hospital visits, caring for a child with AMC is complex. Other challenges experienced by caregivers include financial strain, job changes, changes in interpersonal relationships and abandonment. This study was aimed at exploring the lived experience of caregivers of children with AMC., Methods: The present study is part of a larger global mixed methods study. In the initial quantitative aspect of the study, caregivers (n = 158) of children and youths with AMC (aged 0-21 years) responded to a cost of care survey on an electronic platform. Of the 158 participants, 13 caregivers then further consented to participate in the qualitative aspect of the study in which a 60-min semi-structured, individual interview was conducted remotely. Open-ended questions were developed to gain a deeper understanding of the direct and indirect costs of care, their impact on the caregivers' lives and the quality of the care-giving experience. Interviews were transcribed, and a coding scheme was developed drawing from both the existing literature and the content of the interviews. A deductive and inductive thematic analysis was used to analyze the qualitative data using the NVivo® qualitative data analysis software., Results and Conclusion: Five themes describing the experiences of caregivers of children with AMC emerged from the analysis of the qualitative data: 1. Impact of the caregiving experience; 2. Cost of childcare; 3. Support system for care; 4. Managing and navigating care; 5. Supporting the child's growth and development. In addition to the results of the thematic analysis, specific recommendations shared by the caregivers included the need for support groups and provision of support to youths to prepare them for adolescence. These findings will inform resource allocation, policymaking, and support services for children with rare conditions, their caregivers and families., (© 2024. The Author(s).)

Identifying the aberrant expression of DUX4 in skeletal muscle as the cause of facioscapulohumeral dystrophy (FSHD) has led to rational therapeutic development and clinical trials. Several studies support the use of MRI characteristics and the expression of DUX4-regulated genes in muscle biopsies as biomarkers of FSHD disease activity and progression. We performed lower-extremity MRI and muscle biopsies in the mid-portion of the tibialis anterior (TA) muscles bilaterally in FSHD subjects and validated our prior reports of the strong association between MRI characteristics and expression of genes regulated by DUX4 and other gene categories associated with FSHD disease activity. We further show that measurements of normalized fat content in the entire TA muscle strongly predict molecular signatures in the mid-portion of the TA, indicating that regional biopsies can accurately measure progression in the whole muscle and providing a strong basis for inclusion of MRI and molecular biomarkers in clinical trial design. An unanticipated finding was the strong correlations of molecular signatures in the bilateral comparisons, including markers of B-cells and other immune cell populations, suggesting that a systemic immune cell infiltration of skeletal muscle might have a role in disease progression., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background. Performance-based outcome measures (PBOMs) are objective measures that assess physical capacity or performance in specific tasks or movements. Purpose. 1) to identify which PBOMs are most frequently reported to evaluate upper extremity (UE) function in pediatric rehabilitation 2) to determine the link between constructs of the ICF and meaningful concepts extracted from each identified PBOM. Methods. Pediatric UE PBOMs were searched in four databases. The selection of outcome measures included an initial title and abstract screening, followed by full-text review of the articles to be included based on identified selection criteria. Two reviewers were appointed to link the meaningful concepts identified in the outcome measures independently and a third reviewer was consulted in case of ambiguity to make a final decision. Findings. After the initial screening, 1786 full-text articles were reviewed, 1191 met the inclusion criteria, in which 77 outcome measures were identified and 32 were included in the linking process. From the included 32 outcome measures, 538 items were extracted and linked to the ICF. The most commonly cited measures included Assisting Hand Assessment, Jebsen-Taylor Hand Function Test, Melbourne Assessment of Unilateral Upper Limb. The Activity and Participation domain represented 364 codes followed by the Body Functions domain domain which represented 174 codes. Implications. A majority of the outcome measures identified were linked with the Mobility, Fine Hand Use of the ICF. Therefore, when selecting a PBOM, careful considerations need to be made regarding which concept of health is to be assessed.

Background: Students with Intellectual Disability undergo frequent cognitive testing. Testing with this population is limited by insensitivity to relative strengths and weaknesses due to floor effects., Aim: The study explored the utility of deviation scores via four case studies as a supplement to educational decision-making., Methods: Four students with Intellectual Disability completed cognitive testing. Deviation scores were calculated using age dependent raw z-score transformations to determine deviation from the standardization sample norms., Results: The application of deviation scores highlighted true relative strengths and weaknesses for students with Intellectual Disability rather than documenting previously known deficits. The four cases studies illustrated where deviation scores could, or could not, add value above and beyond traditional scoring., Discussion: Deviation scores can supplement placement and service decisions for students. Practical and psychometric considerations are reviewed., Conclusion: The findings highlight the usefulness of deviation scores in providing meaningful information to school- and clinic-based practitioners., (© 2023 John Wiley & Sons Ltd.)

Worldwide, 200 million children experience disability, with the vast majority living in low- and middle-income countries. The United Nations Convention on the Rights of the Child (CRC) places great importance on the rights of all children for the opportunities for survival, growth, health, and development. A subsequent document, the UN Convention on the Rights of Persons with Disabilities (CRPD), identifies children with disabilities as rights bearers who should be considered in all policies and programming worldwide. Nigeria, in 1991 and 2010, ratified the CRC and the CRPD, respectively. Nonetheless, knowledge of the extent to which their disability and child-directed policies considers these two key conventions, in ensuring that children and children with disabilities have access to care within their right remains limited. This study examined the extent to which Nigeria's current disability and childhood policies have integrated the two child and disability related conventions from the UN. Using a structured search of databases and Nigerian federal and state government websites, we conducted a policy review to identify their disability and child-related disability policies. We also included the CRC and CRPD reports submitted by the Nigerian government to the United Nations Office of the High Commissioner for Human Rights (OHCHR) (2008 and 2010 cyclical year). A thematic analysis, based on the CRC and CRPD report, identified the following six themes: participation, support systems, awareness raising, factors associated with adherence to the CRC, laws and rights, and services. The review showed that the available Nigerian disability policies were federal, with some state policies which aligned with the CRC and CRPD. Also identified was the lack of disability policies specific to children and their families. We concluded that, to ensure proper inclusion of the rights of all children, including those with disabilities, in Nigeria there is a need for a more optimal uptake of recommendations of the CRC and CRPD as laid out by the UN.

Background: Upper extremity (UE) involvement is prevalent in 73% of individuals with arthrogryposis multiplex congenita (AMC), yet no AMC-specific outcome measure exists. When developing a measure specific to a population with a rare musculoskeletal condition, clinicians' and patients' perspectives and involvement is a crucial and necessary step. This study sought to determine the most clinically useful items for an outcome measure of UE function for children with AMC as defined by caregivers and clinicians., Methods: To ensure the perspectives and needs of caregivers of children with AMC and clinicians were considered in the development of the UE measure for AMC, a Nominal Group technique (NGT) with caregivers of children with AMC (phase 1) followed by a three-round survey with clinicians (phase 2) were carried out., Results: Phase 1: Eleven individuals participated in the nominal group technique and identified 32 items. The most important items were Picking up an object (n = 11), Eating (n = 10), Reaching mouth (n = 10), Getting out of bed (n = 10). Phase 2: Invitations to participate to an online survey was sent to 47 experts in the field of AMC, 20 participants completed round 1, 15 completed round 2 and 13 completed round 3. Throughout the survey, participants were asked about movement required to screen the UE, essential domains to be included in the measure, establishing a scoring guide and identifying tasks associated with joint motion and position., Conclusion: A preliminary version of an UE AMC-specific outcome measure was developed with the help of caregivers' perspectives and expert opinions., (© 2023. BioMed Central Ltd., part of Springer Nature.)

This paper proposes a framework for comprehensive, collaborative, and community-based care (C4) for accessible mental health services in low-resource settings. Because mental health conditions have many causes, this framework includes social, public health, wellness and clinical services. It accommodates integration of stand-alone mental health programs with health and non-health community-based services. It addresses gaps in previous models including lack of community-based psychotherapeutic and social services, difficulty in addressing comorbidity of mental and physical conditions, and how workers interact with respect to referral and coordination of care. The framework is based on task-shifting of services to non-specialized workers. While the framework draws on the World Health Organization's Mental Health Gap Action Program and other global mental health models, there are important differences. The C4 Framework delineates types of workers based on their skills. Separate workers focus on: basic psychoeducation and information sharing; community-level, evidence-based psychotherapeutic counseling; and primary medical care and more advanced, specialized mental health services for more severe or complex cases. This paper is intended for individuals, organizations and governments interested in implementing mental health services. The primary aim is to provide a framework for the provision of widely accessible mental health care and services., Competing Interests: Dr. Dan J Stein has received research grants and/or consultancy honoraria from Discovery Vitality, Johnson & Johnson, Kanna, Lundbeck, Orion, Sanofi, Servier, Takeda and Vistagen. The authors alone are responsible for the views expressed in this article and they do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated., (© The Author(s) 2023.)

Background: The purpose of this study was to develop and validate reliable computed tomography (CT) imaging criteria for the diagnosis of gastric band slippage., Material and Methods: We retrospectively evaluated 67 patients for gastric band slippage using CT. Of these, 14 had surgically proven gastric band slippage (study group), 22 had their gastric bands removed for reasons other than slippage (control group 1), and 31 did not require removal (control group 2). All of the studies were read independently by two radiologists in a blinded fashion. The "O" sign, phi angle, amount of inferior displacement from the esophageal hiatus, and gastric pouch size were used to create CT diagnostic criteria. Standard statistical methods were used., Results: There was good overall interobserver agreement for diagnosis of gastric band slippage using CT diagnostic criteria (kappa = 0.83). Agreement was excellent for the "O" sign (kappa = 0.93) and phi angle (intraclass correlation coefficient = 0.976). The "O" sign, inferior displacement from the hiatus >3.5 cm, and gastric pouch volume >55 cm 3 each had 100% positive predictive value. A phi angle <20° or >60° had the highest negative predictive value (NPV) (98%). Of all CT diagnostic criteria, enlarged gastric pouch size was most correlated with band slippage with an AUC of 0.991., Conclusion: All four imaging parameters were useful in evaluating for gastric band slippage on CT, with good interobserver agreement. Of these parameters, enlarged gastric pouch size was most correlated with slippage and abnormal phi angle had the highest NPV., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)

Background and Study Objectives: MHPSS is increasingly seen as a critical component to effective and responsible humanitarian programming. This review examines the extent to which MHPSS research generated since 2010 has contributed to the public health evidence base and how this has influenced and impacted programming and policy in humanitarian settings., Methods: This mixed-method study included a scoping literature review ( n = 50) and a consultation process with qualitative key informant interviews ( n = 19) and online survey responses ( n = 52) to identify the facilitating and inhibiting factors for the two areas of inquiry and to understand the broader context in which knowledge is generated and taken up. The interviews were thematically analysed and the survey responses were descriptively analysed., Results: The review identified a rapidly growing evidence base that has evaluated a range of MHPSS interventions. However, few studies examined long-term impacts of interventions, there was limited direct evidence on outcomes for children and adolescents and whole family approaches, and there were minimal replications of the same approach that could test efficacy across settings and population groups. A general shift was identified in the consultation process away from a focus on disorder towards the more positive aspects of wellbeing. However, there remained a mismatch in many studies included in the literature review, whereby the interventions were broad, community-based but the outcome measures used still focused on changes in symptoms of mental disorders., Conclusion: The evidence base for MHPSS has grown significantly over the last 10 years. However, several knowledge gaps remain, as does the divide between research and practice. Moving forward, MHPSS intervention research needs to be more responsive to the needs on the ground., (© The Author(s) 2022.)

Background: Compared with other health areas, the mental health impacts of climate change have received less research attention. The literature on climate change and mental health is growing rapidly but is characterised by several limitations and research gaps. In a field where the need for designing evidence-based adaptation strategies is urgent, and research gaps are vast, implementing a broad, all-encompassing research agenda will require some strategic focus., Methods: We followed a structured approach to prioritise future climate change and mental health research. We consulted with experts working across mental health and climate change, both within and outside of research and working in high, middle, and low-income countries, to garner consensus about the future research priorities for mental health and climate change. Experts were identified based on whether they had published work on climate change and mental health, worked in governmental and non-governmental organisations on climate change and mental health, and from the professional networks of the authors who have been active in the mental health and climate change space., Results: Twenty-two experts participated from across low- and middle-income countries (n = 4) and high-income countries (n = 18). Our process identified ten key priorities for progressing research on mental health and climate change., Conclusion: While climate change is considered the biggest threat to global mental health in the coming century, tackling this threat could be the most significant opportunity to shape our mental health for centuries to come because of health co-benefits of transitioning to more sustainable ways of living. Research on the impacts of climate change on mental health and mental health-related systems will assist decision-makers to develop robust evidence-based mitigation and adaptation policies and plans with the potential for broad benefits to society and the environment., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background : Internationally deployed humanitarian aid (HA) workers are routinely confronted with potentially traumatic stressors. However, it remains unknown whether HA deployment and related traumatic stress are associated with long-term changes in hypothalamic-pituitary-adrenal (HPA) axis function. Therefore, we investigated whether cortisol awakening response (CAR) decreased upon deployment and whether this was moderated by previous and recent trauma exposure and parallel changes in symptom severity and perceived social support. Methods : In this prospective study, n = 86 HA workers (68% females) completed questionnaires regarding trauma exposure, posttraumatic stress disorder (PTSD), anxiety and depressive symptoms and perceived social support, as well as salivary cortisol assessments at awakening and 30 minutes post-awakening at before, early and 3-6 months post-deployment. Results : Linear mixed models showed significantly decreased CAR ( b(SE)  = -.036(.011), p = .002) and awakening cortisol over time ( b(SE)  = -.007(.003), p = .014). The extent of awakening cortisol change was significantly moderated by interactions between previous and recent trauma exposure. Also, a steeper awakening cortisol decrease was significantly associated with higher mean anxiety and PTSD symptoms across assessments. No significant effects were found for social support. Conclusions : We observed attenuated CAR and awakening cortisol upon HA deployment, with a dose-response effect between trauma exposure before and during the recent deployment on awakening cortisol. Awakening cortisol change was associated with PTSD and anxiety symptom levels across assessments. Our findings support the need for organizational awareness that work-related exposures may have long-lasting biological effects. Further research assessing symptoms and biological measures in parallel is needed to translate current findings into guidelines on the individual level., Competing Interests: No potential conflict of interest was reported by the authors., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Arthrogryposis multiplex congenita is a term used to describe congenital contractures in at least two body parts with an overall prevalence of 1 in 3000 live births. It is often caused by lack of fetal movement in utero and presents as contractures of varying severity, which may affect the upper and lower extremities, the spine and jaw. Currently, no practice recommendations exist to inform best clinical practice for arthrogryposis multiplex congenita. Purpose: To identify the needs surrounding rehabilitation as experienced by youth with arthrogryposis multiplex congenita, caregivers, and clinicians and to propose solutions to develop family- and client-centred rehabilitation recommendations. Materials and methods: A modified experience-based co-design methodology was used where qualitative interviews were conducted with key stakeholders. Results: Twenty-seven participants completed the interviews and demographic information was collected where early-active rehabilitation began at birth in most cases and became less frequent through adolescence. Three overarching themes were determined for each stakeholder group. Conclusions: All participants reported that early-active rehabilitation is beneficial as it helps determine future treatments. Transition times and participation need to be at the center of interventions to ensure that the needs of youth with arthrogryposis multiplex congenita are being met. The development a condition-specific outcome-measure and rehabilitation practice recommendations will assist clinicians in addressing the needs of youth with arthrogryposis multiplex congenita.Implications for rehabilitationArthrogryposis multiplex congenita presents in at least two different areas of the body as multiple congenital contractures of varying severity which may affect the upper and lower extremities, spine and jaw.Youth with arthrogryposis multiplex congenita identified participation as an essential component of their life, however caregivers and clinicians did not emphasize this need.Gathering information from different stakeholders is important to ensure varying needs are addressed.Rehabilitation was reported to be beneficial from early childhood to late adolescence by youth, caregivers, and clinicians.Frequency of rehabilitation diminished over time, emphasizing the need for continued follow-up into adolescence.

Objectives: To develop expert-informed content regarding the early motor attributes of cerebral palsy (CP) that should prompt physician referral for diagnostic assessment of CP, as well as concurrent referral recommendations. This content will be used in the creation of knowledge translation (KT) tools for primary care practitioners and parents., Methods: Two nominal group processes were conducted with relevant stakeholders, representing Canadian ' content experts ' and ' knowledge-users' , using an integrated KT approach., Results: Six attributes were identified that should prompt referral for diagnosis. If the child demonstrates: Early handedness <12 months; stiffness or tightness in the legs between 6 and 12 months; persistent fisting of the hands >4 months; persistent head-lag >4 months; inability to sit without support >9 months; any asymmetry in posture or movement. Five referral recommendations were agreed upon: Motor intervention specialist (physical therapy and/or occupational therapy) for ALL; speech-language pathology IF there is a communication delay; audiology IF there is parental or healthcare professional concern regarding a communication delay; functional vision specialist (e.g., optometrist or occupational therapist) IF there is a vision concern (e.g., not fixating, following, or tracking); feeding specialist (e.g., occupational therapist, speech-language pathologist) IF there are feeding difficulties (e.g., poor sucking, poor swallowing, choking, and/or not gaining weight)., Conclusion: Rigorous consensus methods provided the initial evidence necessary to inform the content of tools to assist primary care providers in the early detection of CP. Results will be validated through a Delphi process with international experts, and user-friendly formats of this KT tool will be developed collaboratively with stakeholders., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: To establish international expert recommendations on clinical features to prompt referral for diagnostic assessment of cerebral palsy (CP)., Method: An online Delphi survey was conducted with international experts in early identification and intervention for children with CP, to validate the results obtained in two previous consensus groups with Canadian content experts and knowledge users. We sent two rounds of questionnaires by e-mail. Participants rated their agreement using a 4-point Likert scale, along with optional open-ended questions for additional feedback. Additionally, a panel of experts and knowledge-users reviewed the results of each round and determined the content of subsequent surveys., Results: Overall, there was high-level of agreement on: (1) six clinical features that should prompt referral for diagnosis; (2) two 'warning sign' features that warrant monitoring rather than immediate referral for diagnosis; and (3) five referral recommendations to other healthcare professionals to occur simultaneously with referral for diagnosis., Interpretation: There was high agreement among international experts, suggesting that the features and referral recommendations proposed for primary care physicians for early detection of CP were broadly generalizable. These results will inform the content of educational tools to improve the early detection of CP in the primary care context., What This Paper Adds: International experts provide strong agreement on clinical features to detect cerebral palsy. Consensus on clinical 'warning signs' to monitor over time. Referral recommendations from primary care to specialized health services are identified., (© 2019 Mac Keith Press.)

Aim: To explore what is currently known regarding participation among children and youth with arthrogryposis multiplex congenita (AMC) using empirical studies, gray literature, and YouTube videos. The secondary objectives included identifying activity types, outcome measures used, interventions provided, and barriers and facilitators to participation., Method: Empirical studies and gray literature were searched through electronic databases and videos were searched on YouTube. Articles and videos pertaining to participation and youth with AMC were included by two reviewers. Data regarding activity types, location, outcomes measures, interventions, and barriers and facilitators to participation was extracted. Data was critically appraised using specific evaluation criteria., Result: Eleven empirical studies, six gray literature articles and 71 videos met the inclusion criteria. The most common activity types reported in the empirical studies and YouTube videos were active-physical, social, and skill-based activities. Outcome measures included evaluations and questionnaires, none of which were designed to address participation. Interventions did not target participation although the environments could affect participation., Conclusion: The paucity of research indicates a need for future studies of participation in this population. Interventions should target participation and address environmental barriers. Videos provide insight for clinicians, youth, and families to help promote participation in the natural environment.

Inhibitors of the enzyme xanthine oxidase (XO) with radical scavenging properties hold promise as novel agents against reperfusion injuries after ischemic events. By suppressing the formation of damaging reactive oxygen species (ROS) by XO or scavenging ROS from other sources, these compounds may prevent a buildup of ROS in the aftermath of a heart attack or stroke. To combine these two properties in a single molecule, we synthesized and characterized the non-purine XO inhibitor caffeic acid phenethylester (CAPE) and 19 derivatives using a convenient microwave-assisted Knoevenagel condensation protocol. Varying systematically the number and positions of the hydroxyl groups at the two phenyl rings, we derived structure-activity relationships based on experimentally determined XO inhibition data. Molecular docking suggested that critical enzyme/inhibitor interactions involved π-π interactions between the phenolic inhibitor ring and Tyr914, hydrogen bonds between inhibitor hydroxyl groups and Glu802, and hydrophobic interactions between the CAPE phenyl ring and non-polar residues located at the entrance of the binding site. To effectively scavenge the stable radical DPPH, two hydroxyl groups in 1,2- or 1,4-position at the phenyl ring were required. Among all compounds tested, E-phenyl 3-(3,4-dihydroxyphenyl)acrylate, a CAPE analog without the ethyl tether, showed the most promising properties., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Facioscapulohumeral muscular dystrophy (FSHD) is a common, dominantly inherited disease caused by the epigenetic de-repression of the DUX4 gene, a transcription factor normally repressed in skeletal muscle. As targeted therapies are now possible in FSHD, a better understanding of the relationship between DUX4 activity, muscle pathology and muscle magnetic resonance imaging (MRI) changes is crucial both to understand disease mechanisms and for the design of future clinical trials. Here, we performed MRIs of the lower extremities in 36 individuals with FSHD, followed by needle muscle biopsies in safely accessible muscles. We examined the correlation between MRI characteristics, muscle pathology and expression of DUX4 target genes. Results show that the presence of elevated MRI short tau inversion recovery signal has substantial predictive value in identifying muscles with active disease as determined by histopathology and DUX4 target gene expression. In addition, DUX4 target gene expression was detected only in FSHD-affected muscles and not in control muscles. These results support the use of MRI to identify FSHD muscles most likely to have active disease and higher levels of DUX4 target gene expression and might be useful in early phase therapeutic trials to demonstrate target engagement in therapies aiming to suppress DUX4 expression.

Rehabilitation specialists are an integral part of the team in the neonatal intensive care unit (NICU). New approaches to rehabilitation practice in the NICU have evolved over the past decade that aim to promote child health and development., Aims: The aim of this study was to describe the current roles of the occupational therapist (OT), physical therapist (PT) and speech-language pathologist (SLP) in Canadian NICUs as compared to the roles documented in an earlier national survey conducted 15 years ago., Methods: A telephone survey was conducted across Canadian NICUs and each telephone interview was recorded by a research assistant. In total, 42 questionnaires were completed across 25 health care institutions., Results: Eighty percent of the PT, 93.7% of OT and 50% of SLP provided direct services to neonates in the NICU. The results demonstrated that the therapists were involved with case discussion (85.7%), decision-making (97.6%), referrals to other services (97.6%) and discharge planning (97.6%). Splinting (87.5%) and feeding (100%) were most often carried out by OT, whereas chest physiotherapy (65%) and range of motion (100%) were predominantly provided by PT. Changes in the role of rehabilitation specialists over the last decade predominantly included enhanced collaboration with the NICU team, more frequent use of standardized outcome measures and use of interventions supported by evidence., Conclusion: In comparison with results of the previous survey of rehabilitation practices in Canadian NICUs, rehabilitation specialists now have more dedicated time in the NICU and more frequently use standardized measures and apply interventions that are supported by recent scientific studies.

In humans, a copy of the DUX4 retrogene is located in each unit of the D4Z4 macrosatellite repeat that normally comprises 8-100 units. The D4Z4 repeat has heterochromatic features and does not express DUX4 in somatic cells. Individuals with facioscapulohumeral muscular dystrophy (FSHD) have a partial failure of somatic DUX4 repression resulting in the presence of DUX4 protein in sporadic muscle nuclei. Somatic DUX4 derepression is caused by contraction of the D4Z4 repeat to 1-10 units (FSHD1) or by heterozygous mutations in genes responsible for maintaining the D4Z4 chromatin structure in a repressive state (FSHD2). One of the FSHD2 genes is the structural maintenance of chromosomes hinge domain 1 (SMCHD1) gene. SMCHD1 mutations have also been identified in FSHD1; patients carrying a contracted D4Z4 repeat and a SMCHD1 mutation are more severely affected than relatives with only a contracted repeat or a SMCHD1 mutation. To evaluate the modifier role of SMCHD1, we crossbred mice carrying a contracted D4Z4 repeat (D4Z4-2.5 mice) with mice that are haploinsufficient for Smchd1 (Smchd1MommeD1 mice). D4Z4-2.5/Smchd1MommeD1 mice presented with a significantly reduced body weight and developed skin lesions. The same skin lesions, albeit in a milder form, were also observed in D4Z4-2.5 mice, suggesting that reduced Smchd1 levels aggravate disease in the D4Z4-2.5 mouse model. Our study emphasizes the evolutionary conservation of the SMCHD1-dependent epigenetic regulation of the D4Z4 repeat array and further suggests that the D4Z4-2.5/Smchd1MommeD1 mouse model may be used to unravel the function of DUX4 in non-muscle tissues like the skin., (© The Author(s) 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Facioscapulohumeral muscular dystrophy is caused by incomplete repression of the transcription factor DUX4 in skeletal muscle as a consequence of D4Z4 macrosatellite repeat contraction in chromosome 4q35 (FSHD1) or variants in genes encoding D4Z4 chromatin repressors (FSHD2). A clinical hallmark of FSHD is variability in onset and progression suggesting the presence of disease modifiers. A well-known cis modifier is the polymorphic DUX4 polyadenylation signal (PAS) that defines FSHD permissive alleles: D4Z4 chromatin relaxation on non-permissive alleles which lack the DUX4-PAS cannot cause disease in the absence of stable DUX4 mRNA. We have explored the nature and relevance of a common variant of the major FSHD haplotype 4A161, which is defined by 1.6 kb size difference of the most distal D4Z4 repeat unit. While the short variant (4A161S) has been extensively studied, we demonstrate that the long variant (4A161L) is relatively common in the European population, is capable of expressing DUX4, but that DUX4 mRNA processing differs from 4A161S. While we do not find evidence for a difference in disease severity between FSHD carriers of an 4A161S or 4A161L allele, our study does uncover biallelic DUX4 expression in FSHD2 patients. Compared to control individuals, we observed an increased frequency of FSHD2 patients homozygous for disease permissive alleles, and who are thus capable of biallelic DUX4 expression, while SMCHD1 variant carriers with only one permissive allele were significantly more often asymptomatic. This suggests that biallelic DUX4 expression lowers the threshold for disease presentation and is a modifier for disease severity in FSHD2.

Background: Facioscapulohumeral dystrophy (FSHD) is a progressive muscle disease caused by mutations that lead to epigenetic derepression and inappropriate transcription of the double homeobox 4 (DUX4) gene in skeletal muscle. Drugs that enhance the repression of DUX4 and prevent its expression in skeletal muscle cells therefore represent candidate therapies for FSHD., Methods: We screened an aggregated chemical library enriched for compounds with epigenetic activities and the Pharmakon 1600 library composed of compounds that have reached clinical testing to identify molecules that decrease DUX4 expression as monitored by the levels of DUX4 target genes in FSHD patient-derived skeletal muscle cell cultures., Results: Our screens identified several classes of molecules that include inhibitors of the bromodomain and extra-terminal (BET) family of proteins and agonists of the beta-2 adrenergic receptor. Further studies showed that compounds from these two classes suppress the expression of DUX4 messenger RNA (mRNA) by blocking the activity of bromodomain-containing protein 4 (BRD4) or by increasing cyclic adenosine monophosphate (cAMP) levels, respectively., Conclusions: These data uncover pathways involved in the regulation of DUX4 expression in somatic cells, provide potential candidate classes of compounds for FSHD therapeutic development, and create an important opportunity for mechanistic studies that may uncover additional therapeutic targets.

Background: Research in emergencies is needed to understand the prevalence of mental health and psychosocial problems and strengthen the evidence base for interventions. All research - including operational needs assessments, programme monitoring and evaluation, and formal academic research - must be conducted ethically. While there is broad consensus on fundamental principles codified in research ethics guidelines, these do not address the ethical specificities of conducting mental health and psychosocial support (MHPSS) research with adults in emergencies. To address this gap, this paper presents a review of multidisciplinary literature to identify specific ethical principles applicable to MHPSS research in emergencies., Discussion: Fifty-nine sources meeting the literature review inclusion criteria were analysed following a thematic synthesis approach. There was consensus on the relevance of universal ethical research principles to MHPSS research in emergencies, including norms of participant informed consent and protection; ensuring benefit arises from research participation; researcher neutrality, accountability, and safety; and the duty to ensure research is well designed and accounts for contextual factors in emergency settings. We go onto discuss unresolved issues by highlighting six current debates relating to the application of ethics in emergency settings: (1) what constitutes fair benefits?; (2) how should informed consent be operationalised?; (3) is there a role for decision making capacity assessments?; (4) how do risk management approaches impact upon the construction of ethical research?; (5) how can ethical reflection best be achieved?, and (6) are ethical review boards sufficiently representative and equipped to judge the ethical and scientific merit of emergency MHPSS research? Underlying these debates is a systemic tension between procedural ethics and ethics in practice. In summary, underpinning the literature is a desire to ensure the protection of participants exposed to emergencies and in need of evidence-based MHPSS. However, there is a lack of agreement on how to contextualise guidelines and procedures to effectively maximise the perspectives of researchers, participants and ethical review boards. This is a tension that the field must address to strengthen ethical MHPSS research in emergencies.

Aims: To describe the focus of therapy practices in occupational and physical therapy for school-aged children with cerebral palsy, and better understand whether it is congruent with recommended practices., Methods: A Canada-wide Web-based survey was completed by 62 occupational and 61 physical therapists to identify problems, assessments, and treatment interventions for two case-based scenarios. Data were coded using the International Classification of Functioning, Disability and Health (ICF) definitions for "body functions and structure," "activity and participation," and "environment.", Results: Physical therapists, in comparison to occupational therapists, were more likely to select interventions classed in the "body functions and structure" category (34-42% and 18-20%, respectively). Both professions focused on "activity and participation" (34-61%) when identifying problems, assessing, and intervening; attention, however, was mainly directed towards task-oriented activities such as activities of daily living and mobility. Participation in leisure or community-based activities received less attention (2-15%). The environment received limited attention for problems and assessments (4-25%), though it was an important focus of intervention (19-37%)., Conclusions: While body functions and structure are well-addressed, other ICF elements, specifically participation, are poorly integrated into practice. The emerging focus on the environment in therapy intervention, by modifying the context rather than changing aspects of the child, is consistent with current approaches and evidence. Knowledge translation implementation initiatives are recommended to bridge identified gaps.

Facioscapulohumeral dystrophy (FSHD) is caused by the mis-expression of the double-homeodomain transcription factor DUX4 in skeletal muscle cells. Many different cell culture models have been developed to study the pathophysiology of FSHD, frequently based on endogenous expression of DUX4 in FSHD cells or by mis-expression of DUX4 in control human muscle cells. Although results generated using each model are generally consistent, differences have also been reported, making it unclear which model(s) faithfully recapitulate DUX4 and FSHD biology. In this study, we systematically compared RNA-seq data generated from three different models of FSHD—lentiviral-based DUX4 expression in myoblasts, doxycycline-inducible DUX4 in myoblasts, and differentiated human FSHD myocytes expressing endogenous DUX4—and show that the DUX4-associated gene expression signatures of each dataset are highly correlated (Pearson’s correlation coefficient, r ∼ 0.75-0.85). The few robust differences were attributable to different states of cell differentiation and other differences in experimental design. Our study describes a model system for inducible DUX4 expression that enables reproducible and synchronized experiments and validates the fidelity and FSHD relevance of multiple distinct models of DUX4 expression.

Objectives: To compare image quality and diagnostic accuracy for the detection of liver lesions of virtual unenhanced (VU) images based on third-generation dual-source dual- energy computed tomography (DECT) compared to conventional unenhanced (CU) images., Methods: Thirty patients underwent triphasic abdominal CT consisting of single-energy CU (120kV, 147 ref.mAs) and dual-energy CT arterial and portal-venous phase acquisitions (100/Sn150kV, 180/90 ref.mAs). VU images were generated from arterial (AVU) and portal venous (PVU) phases. CU, AVU and PVU datasets were reconstructed. Quantitative image quality analysis was performed and two abdominal radiologists independently analyzed all datasets to evaluate image quality and identify liver lesions. Radiation dose was recorded and potential radiation dose reduction was estimated., Results: Image quality was rated diagnostic in 100% of the VU datasets. The mean subjective image quality of the CU datasets was higher than that of VU images (p<0.0001). No significant difference was observed in the mean attenuation values of the liver parenchyma (p>0.99) and hypoattenuating liver lesions (p≥0.21) between CU, AVU and PVU. However, a significant reduction in the attenuation values of calcified lesions (p<0.0001), metallic clips (p<0.0001) and gallstones (p≤0.047) was observed in the AVU and PVU images compared with CU images. A total of 122 liver lesions were found in 25 patients. VU images were more sensitive than CU images for detection of small hypoattenuating liver lesions (≤1cm). However, CU images were more sensitive than VU for calcified liver lesions. The mean radiation dose reduction achievable by avoiding the unenhanced acquisition was 32.9%±1.1% (p<0.01)., Conclusions: Third-generation DSCT VU images of the liver provide diagnostic image quality and improve small (≤1cm) liver lesion detection; however calcified liver lesions can be missed due to complete subtraction., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Perfluorocarbon droplets that are capable of an ultrasound-mediated phase transition have applications in diagnostic and therapeutic ultrasound. Techniques to modify the droplet size distribution are of interest because of the size-dependent acoustic response of the droplets. Differential centrifugation has been used to isolate specific sizes of microbubbles. In this work, differential centrifugation was employed to isolate droplets with diameters between 1 and 3 μm and 2 and 5 μm from an initially polydisperse distribution. Further, an empirical model was developed for predicting the droplet size distribution following differential centrifugation and to facilitate the selection of centrifugation parameters for obtaining desired size distributions.

Background: Teachers' occupational role and performance can be undermined when working with students with disruptive classroom behaviours., Purpose: This pilot study aimed to explore the impact of school-based occupational therapy intervention on teachers' classroom management self-efficacy and perceived performance/satisfaction in their management of students with disruptive behaviours., Method: This pilot study used a multiple-case replication study design. A cohort of regular classroom elementary school teachers (n = 11) participated in a 1-day workshop on sensorimotor strategies for supporting student self-regulation followed by eight individual sessions of Occupational Performance Coaching (OPC). Measurement tools were the Canadian Occupational Performance Measure, Goal Attainment Scaling (GAS), and Teachers' Self-Efficacy Scale-Classroom Management., Findings: Improvement in teachers' perception of performance, satisfaction, and classroom management was seen. GAS showed clinically significant improvement. Improvements were sustained at 7 weeks follow-up., Implications: Preliminary results support the use of sensorimotor education combined with OPC to enable teachers' occupational performance., (© CAOT 2016.)

In this study, we evaluated the abilities of a series of chalcones to inhibit the activity of the enzyme xanthine oxidase (XO) and to scavenge radicals. 20 mono- and polyhydroxylated chalcone derivatives were synthesized by Claisen-Schmidt condensation reactions and then tested for inhibitory potency against XO, a known generator of reactive oxygen species (ROS). In parallel, the ability of the synthesized chalcones to scavenge a stable radical was determined. Structure-activity relationship analysis in conjunction with molecular docking indicated that the most active XO inhibitors carried a minimum of three hydroxyl groups. Moreover, the most effective radical scavengers had two neighboring hydroxyl groups on at least one of the two phenyl rings. Since it has been proposed previously that XO inhibition and radical scavenging could be useful properties for reduction of ROS-levels in tissue, we determined the chalcones' effects to rescue neurons subjected to ROS-induced stress created by the addition of β-amyloid peptide. Best protection was provided by chalcones that combined good inhibitory potency with high radical scavenging ability in a single molecule, an observation that points to a potential therapeutic value of this compound class., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Despite the growing interest in understanding the psycho-social impact of rare genetic diseases, few studies examine this concept and even fewer seek to obtain feedback from families who have lived the experience. The aim of this project was to involve families of children living with osteogenesis imperfecta (OI) in the development of a tool to assess the impact of OI on the lives of patients and their families., Methods: This project used an integrated knowledge translation approach in which knowledge users (clinicians and people living with OI and their families) were consulted throughout the four steps of development, that is: content mapping, item generation, tool appraisal and pre-testing of the questionnaires. The International Classification of Functioning and Health was used as a framework for content mapping. Based on a scoping review we selected two validated tools to use as a basis for developing the questionnaire. The final parent self-report version measured six domains: experience of diagnosis; use of health services; use of social and psychological support services; expectations about tertiary specialized centers; and socio-demographic information., Results: A total of 27 out of 40 families receiving care at the Shriners Hospital for Children-Canada and invited to participate in the pre-test returned the completed questionnaires. In more than two-thirds of families (69%; n = 18) OI was suspected either at or within the first 3 months after birth. Up to 46% of families consulted between 3 and 5 doctors (46%; n = 12) prior to final diagnosis. The use of services by families varied from 0 to 16 consultations, 0 to 9 exploratory examinations and 1 to 10 types of allied health services. In the 12 months prior to the study, fewer than a quarter of children had been admitted, for treatment, for hospital stays of longer than 8 hours or to an emergency department (24% and 9% respectively). Only 29% of parents received psychological support., Conclusion: This joint development process generated a tool, with good psychometric properties, that provides unique insight into the experiences of patients and families with OI, the psycho-social impact of the illness, and their service needs and expectations.

Psychological First Aid (PFA) is the recommended immediate psychosocial response during crises. As PFA is now widely implemented in crises worldwide, there are increasing calls to evaluate its effectiveness. World Vision used PFA as a fundamental component of their emergency response following the 2014 conflict in Gaza. Anecdotal reports from Gaza suggest a range of benefits for those who received PFA. Though not intending to undertake rigorous research, World Vision explored learnings about PFA in Gaza through Focus Group Discussions with PFA providers, Gazan women, men and children and a Key Informant Interview with a PFA trainer. The qualitative analyses aimed to determine if PFA helped individuals to feel safe, calm, connected to social supports, hopeful and efficacious - factors suggested by the disaster literature to promote coping and recovery (Hobfoll et al., 2007). Results show positive psychosocial benefits for children, women and men receiving PFA, confirming that PFA contributed to: safety, reduced distress, ability to engage in calming practices and to support each other, and a greater sense of control and hopefulness irrespective of their adverse circumstances. The data shows that PFA formed an important part of a continuum of care to meet psychosocial needs in Gaza and served as a gateway for addressing additional psychosocial support needs. A "whole-of-family" approach to PFA showed particularly strong impacts and strengthened relationships. Of note, the findings from World Vision's implementation of PFA in Gaza suggests that future PFA research go beyond a narrow focus on clinical outcomes, to a wider examination of psychosocial, familial and community-based outcomes.

Endoscopic Submucosal Dissection (ESD) is a technique developed in Japan for "en bloc" resection of larger superficial neoplasms of the gastrointestinal tract as an alternative to the traditional Endoscopic Mucosal Resection (EMR), with removal of the lesion in multiple fragments ("piecemeal"). ESD offers a lower recurrence rate and allows a more accurate histopathological examination. This procedure is however considered technically difficult and therefore requires an adequate learning curve, it is time consuming with more discomfort for the patient, it has a higher complication rate, it is more expensive. To overcome these disadvantages, in the Western countries a hybrid technique called Circumferential Submucosal Incision - Endoscopic Mucosal Resection (CSI-EMR) has been developed and is especially employed for colonic lesions. This article analyzes retrospectively the results obtained in a single centre by a single operator in the treatment of 23 patients (12 men and 11 women, average age 65,6 years), all suffering from superficial, larger than ≥ 20 mm colorectal neoplasms: 9 were treated with ESD for rectal lesions and 14 were treated with CSI-EMR for colonic lesions. Findings show a technical success rate of 66,6% for ESD and 78,5% for CSI-EM, and a 0% recurrence rate during follow-up, 4,3% bleeding and 13% perforation complications. The histology of the removed lesions showed 13 (56,5%) low grade dysplasia adenomas, 8 (34,7%) high grade dysplasia adenomas, one grade 1 sigmoid colon adenocarcinoma infiltrating the submucosal layer without lymphovascular invasion, with free margins (R0), treated conservatively, and one grade 1 cecum adenocarcinoma, infiltrating the submucosal layer, with lymphovascular invasion and involved excision margin, treated surgically with no residual neoplastic disease in the surgical specimen. These data are in line with the most significant ones in literature, except for the higher complication rate, which the authors ascribe to the "learning curve" and the smaller number of treated patients.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by the aberrant expression of the DUX4 transcription factor in skeletal muscle. The DUX4 retrogene is encoded in the D4Z4 macrosatellite repeat array, and smaller array size or a mutation in the SMCHD1 gene results in inefficient epigenetic repression of DUX4 in skeletal muscle, causing FSHD1 and FSHD2, respectively. Previously we showed that the entire D4Z4 repeat is bi-directionally transcribed with the generation of small si- or miRNA-like fragments and suggested that these might suppress DUX4 expression through the endogenous RNAi pathway. Here we show that exogenous siRNA targeting the region upstream of the DUX4 transcription start site suppressed DUX4 mRNA expression and increased both H3K9 methylation and AGO2 recruitment. In contrast, similarly targeted MOE-gapmer antisense oligonucleotides that degrade RNA but do not engage the RNAi pathway did not repress DUX4 expression. In addition, knockdown of DICER or AGO2 using either siRNA or MOE-gapmer chemistries resulted in the induction of DUX4 expression in control muscle cells that normally do not express DUX4, indicating that the endogenous RNAi pathway is necessary to maintain repression of DUX4 in control muscle cells. Together these data demonstrate a role of the endogenous RNAi pathway in repeat-mediated epigenetic repression of the D4Z4 macrosatellite repeat, and show that enhancing the activity of this pathway by supplying exogenous siRNA oligonucleotides represents a potential therapeutic approach to silencing DUX4 in FSHD., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Children with ADHD often present with handwriting difficulties. However, the extent to which motor and attention skills influence performance in this group has not yet been explored. The objective of this study was to examine the factors associated with change in handwriting performance., Method: This study examines the factors associated with change in handwriting performance of 49 children newly diagnosed with ADHD (mean age = 8.4 [SD=1.3] years) prior to and 3 months following use of a stimulant medication., Results: Handwriting legibility and speed improved significantly at follow-up evaluation. However, most of the children with legibility difficulties at baseline continued to demonstrate difficulties when evaluated 3 months after initiation of medication. Change in handwriting legibility was best determined by improvements in visual-motor integration skills (β = 0.07-0.10; p < .001), while the change in speed did not appear to be consistently related to a single factor., Conclusion: Handwriting difficulties are common in children with ADHD, and medication alone is not sufficient to resolve these challenges., (© 2012 SAGE Publications.)

Facioscapulohumeral muscular dystrophy (FSHD) is a muscular dystrophy caused by inefficient epigenetic repression of the D4Z4 macrosatellite array and somatic expression of the DUX4 retrogene. DUX4 is a double homeobox transcription factor that is normally expressed in the testis and causes apoptosis and FSHD when misexpressed in skeletal muscle. The mechanism(s) of DUX4 toxicity in muscle is incompletely understood. We report that DUX4-triggered proteolytic degradation of UPF1, a central component of the nonsense-mediated decay (NMD) machinery, is associated with profound NMD inhibition, resulting in global accumulation of RNAs normally degraded as NMD substrates. DUX4 mRNA is itself degraded by NMD, such that inhibition of NMD by DUX4 protein stabilizes DUX4 mRNA through a double-negative feedback loop in FSHD muscle cells. This feedback loop illustrates an unexpected mode of autoregulatory behavior of a transcription factor, is consistent with 'bursts' of DUX4 expression in FSHD muscle, and has implications for FSHD pathogenesis.

The health-related quality of life of school-aged children with high-functioning autism is poorly understood. The objectives of this study were to compare the health-related quality of life of children with high-functioning autism to that of typically developing peers and to compare child-self and parent-proxy reports of health-related quality of life of children. A cross-sectional study of children with high-functioning autism (n = 30) and peers (n = 31) was conducted using the Pediatric Quality of Life Inventory 4.0 Generic Core Scales. Children with high-functioning autism had significantly poorer health-related quality of life than peers whether reported by themselves (p < .001) or their parents (p < .001), although disagreement (intra-class coefficient = -.075) between children and parental scores suggested variance in points of view. This study specifically investigated health-related quality of life in children with high-functioning autism as compared to a sample of peers, from the child's perspective. It strengthens earlier findings that children with high-functioning autism experience poorer health-related quality of life than those without this disorder and points to the importance of clinicians working with families to identify areas in a child's life that promote or hinder their sense of well-being., (© The Author(s) 2013.)

This study investigates occupational therapy for early communication in children with autism spectrum disorders (ASD). The research explored the role of occupational therapists in supporting children with ASD to become better communicators by considering their inter-professional collaboration with speech-language pathologists. Convenience samples of 21 clinical occupational therapists and speech-language pathologists were recruited to participate in semi-structured audio-recorded focus groups, using a qualitative design. Distinct views included a child-centred focus from speech-language pathologists, whereas occupational therapists spoke of the child through societal viewpoints, which later pointed to occupational therapists' proficiency in enabling skill generalization in ASD. An equal partnership was consistently reported between these clinicians, who identified the same objectives, shared strategies, joint treatments, and ongoing collaboration as the four main facilitators to inter-professional collaboration when treating children with ASD. Three unique roles of occupational therapy comprised developing non-verbal and verbal communication pre-requisites, adapting the setting, educating-partnering-advocating for the child, and providing occupation-based intervention. These three themes meshed with the discipline-specific occupational therapy domains represented in the Person-Environment-Occupation framework. When working in inter-professional collaboration, speech-language pathologists and occupational therapists agree that occupational therapy is indispensable to early intervention in enabling communication in ASD.

Facioscapulohumeral dystrophy (FSHD) is caused by decreased epigenetic repression of the D4Z4 macrosatellite array and recent studies have shown that this results in the expression of low levels of the DUX4 mRNA in skeletal muscle. Several other mechanisms have been suggested for FSHD pathophysiology and it remains unknown whether DUX4 expression can account for most of the molecular changes seen in FSHD. Since DUX4 is a transcription factor, we used RNA-seq to measure gene expression in muscle cells transduced with DUX4, and in muscle cells and biopsies from control and FSHD individuals. We show that DUX4 target gene expression is the major molecular signature in FSHD muscle together with a gene expression signature consistent with an immune cell infiltration. In addition, one unaffected individual without a known FSHD-causing mutation showed the expression of DUX4 target genes. This individual has a sibling with FSHD and also without a known FSHD-causing mutation, suggesting the presence of an unidentified modifier locus for DUX4 expression and FSHD. These findings demonstrate that the expression of DUX4 accounts for the majority of the gene expression changes in FSHD skeletal muscle together with an immune cell infiltration., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues. Facioscapulohumeral muscular dystrophy (FSHD) is caused by mutations that decrease the epigenetic repression of DUX4 in somatic tissues and result in mis-expression of this transcription factor in skeletal muscle. DUX4 binds sites in the human genome that contain a double-homeobox sequence motif, including sites in unique regions of the genome as well as many sites in repetitive elements. Using ChIP-seq and RNA-seq on myoblasts transduced with DUX4 we show that DUX4 binds and activates transcription of mammalian apparent LTR-retrotransposons (MaLRs), endogenous retrovirus (ERVL and ERVK) elements, and pericentromeric satellite HSATII sequences. Some DUX4-activated MaLR and ERV elements create novel promoters for genes, long non-coding RNAs, and antisense transcripts. Many of these novel transcripts are expressed in FSHD muscle cells but not control cells, and thus might contribute to FSHD pathology. For example, HEY1, a repressor of myogenesis, is activated by DUX4 through a MaLR promoter. DUX4-bound motifs, including those in repetitive elements, show evolutionary conservation and some repeat-initiated transcripts are expressed in healthy testis, the normal expression site of DUX4, but more rarely in other somatic tissues. Testis expression patterns are known to have evolved rapidly in mammals, but the mechanisms behind this rapid change have not yet been identified: our results suggest that mobilization of MaLR and ERV elements during mammalian evolution altered germline gene expression patterns through transcriptional activation by DUX4. Our findings demonstrate a role for DUX4 and repetitive elements in mammalian germline evolution and in FSHD muscular dystrophy., Competing Interests: The authors have declared that no competing interests exist.

Neonatal intensive care unit (NICU) light and noise may be stressful to preterm infants. This research evaluated the physiological stability of 54 infants born at 28- to 32-weeks' gestational age while wearing eye goggles and earmuffs for a 4-hour period in the NICU. Infants were recruited from four NICUs of university-affiliated hospitals and randomized to the intervention-control or control-intervention sequences. Heart rate (HR), heart rate variability (HRV), and oxygen saturation (O2 sat) were collected using the SomtéTM device. Confounding variables such as position and handling were assessed by videotaping infants during the study periods. Results indicated that infants had more stress responses while wearing eye goggles and earmuffs since maximum HR was found to be significantly higher and high-frequency power of HRV significantly lower during the intervention as compared with the control period. Therefore, this intervention is not recommended for the clinical practice.

Facioscapulohumeral dystrophy (FSHD) is a progressive muscular dystrophy caused by decreased epigenetic repression of the D4Z4 macrosatellite repeats and ectopic expression of DUX4, a retrogene encoding a germline transcription factor encoded in each repeat. Unaffected individuals generally have more than 10 repeats arrayed in the subtelomeric region of chromosome 4, whereas the most common form of FSHD (FSHD1) is caused by a contraction of the array to fewer than 10 repeats, associated with decreased epigenetic repression and variegated expression of DUX4 in skeletal muscle. We have generated transgenic mice carrying D4Z4 arrays from an FSHD1 allele and from a control allele. These mice recapitulate important epigenetic and DUX4 expression attributes seen in patients and controls, respectively, including high DUX4 expression levels in the germline, (incomplete) epigenetic repression in somatic tissue, and FSHD-specific variegated DUX4 expression in sporadic muscle nuclei associated with D4Z4 chromatin relaxation. In addition we show that DUX4 is able to activate similar functional gene groups in mouse muscle cells as it does in human muscle cells. These transgenic mice therefore represent a valuable animal model for FSHD and will be a useful resource to study the molecular mechanisms underlying FSHD and to test new therapeutic intervention strategies., Competing Interests: The authors have declared that no competing interests exist.

The psychometric properties of assessments must be established for specific populations. The psychometric properties of the Children's Assessment of Participation and Enjoyment/Preference for Activities of Children have been studied only in a sample of children with physical disability. We conducted a study to determine the appropriateness of drawing inferences from this assessment for children with high-functioning autism (HFA). The content validity and test-retest reliability (r > .7) were both found to be adequate for this population. Parents' agreement with most of their children's self-ratings on this assessment provided an estimate of interrater reliability. We also ascertained the feasibility of gathering recreational participation information from children with HFA and found that adaptations to facilitate the self-completion of the tool should be made available. The study findings support the use of this tool to assess recreational participation among children with HFA., (Copyright © 2013 by the American Occupational Therapy Association, Inc.)

The recreation of children with High Functioning Autism (HFA) is not well understood. The objective of this cross-sectional study was to compare the recreational engagement of children with HFA and their typically developing peers. Children with HFA (n = 30) and peers (n = 31) were similar on key characteristics that may impact recreation except those related to the HFA attributes. Children with HFA differed from peers in terms of diversity (p = .002), social aspects (p = .006) and locations (p < .001) of recreation. The two groups were not statistically different in personal intensity (p = .684), enjoyment (p = .239) or preferences (p = .788) of recreation. A recreational profile was developed to benefit parents and clinicians in supporting the recreation of these children.

Motor difficulties are common in children with Attention Deficit Hyperactivity Disorder (ADHD). Although preliminary evidence has suggested that methylphenidate can improve the motor skills in children with ADHD and Developmental Coordination Disorder (DCD), the effect of stimulant medication on motor performance in children newly diagnosed with ADHD with or without motor impairment remains unclear. A cohort study of 49 medication-naïve children (39 male; mean age 8.4±1.3 years) with ADHD was conducted. Children were evaluated using the Movement Assessment Battery for Children and the developmental test of visual motor integration at diagnosis and again three months following daily treatment with a stimulant medication. Motor difficulties were highly present at baseline (73.5%) but resolved in a subset after treatment with stimulant medication, suggesting that their motor difficulties may be attributed in part to their attentional problems. Nevertheless, motor impairment persisted in 55.1% of the sample. The severity of the behavioural symptoms was significantly associated with balance skills in children without motor impairments (r(2)=0.30, p<0.01) and with visual motor integration skills in children with persisting motor difficulties (r(2)=0.27, p<0.01). Attentional difficulties negatively affect the motor skills of children with ADHD. Following the use of stimulant medication, an important subset continued to demonstrate motor difficulties. The improvement in behaviour was insufficient to resolve motor problems and these children should therefore be targeted for rehabilitation services., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Transplantation of myogenic stem cells possesses great potential for long-term repair of dystrophic muscle. In murine-to-murine transplantation experiments, CXCR4 expression marks a population of adult murine satellite cells with robust engraftment potential in mdx mice, and CXCR4-positive murine muscle-derived SP cells home more effectively to dystrophic muscle after intra-arterial delivery in mdx5cv mice. Together, these data suggest that CXCR4 plays an important role in donor cell engraftment. Therefore, we sought to translate these results to a clinically relevant canine-to-canine allogeneic transplant model for Duchenne muscular dystrophy (DMD) and determine if CXCR4 is important for donor cell engraftment., Methods: In this study, we used a canine-to-murine xenotransplantation model to quantitatively compare canine muscle cell engraftment, and test the most effective cell population and modulating factor in a canine model of DMD using allogeneic transplantation experiments., Results: We show that CXCR4 expressing cells are important for donor muscle cell engraftment, yet FACS sorted CXCR4-positive cells display decreased engraftment efficiency. However, diprotin A, a positive modulator of CXCR4-SDF-1 binding, significantly enhanced engraftment and stimulated sustained proliferation of donor cells in vivo. Furthermore, the canine-to-murine xenotransplantation model accurately predicted results in canine-to-canine muscle cell transplantation., Conclusions: Therefore, these results establish the efficacy of diprotin A in stimulating muscle cell engraftment, and highlight the pre-clinical utility of a xenotransplantation model in assessing the relative efficacy of muscle stem cell populations.