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Abstract We previously linked TSHZ3 haploinsufficiency to autism spectrum disorder (ASD) and showed that embryonic or postnatal Tshz3 deletion in mice results in behavioral traits relevant to the two core domains of ASD, namely social interaction deficits and repetitive behaviors. Here, we provide evidence that cortical projection neurons (CPNs) and striatal cholinergic interneurons (SCINs) are two main and complementary players in the TSHZ3-linked ASD syndrome. In the cerebral cortex, TSHZ3 is expressed in CPNs and in a proportion of GABAergic interneurons, but not in cholinergic interneurons or glial cells. In the striatum, TSHZ3 is expressed in all SCINs, while its expression is absent or partial in the other main brain cholinergic systems. We then characterized two new conditional knockout (cKO) models generated by crossing Tshz3 flox/flox with Emx1-Cre (Emx1-cKO) or Chat-Cre (Chat-cKO) mice to decipher the respective role of CPNs and SCINs. Emx1-cKO mice show altered excitatory synaptic transmission onto CPNs and impaired plasticity at corticostriatal synapses, with neither cortical neuron loss nor abnormal layer distribution. These animals present social interaction deficits but no repetitive patterns of behavior. Chat-cKO mice exhibit no loss of SCINs but changes in the electrophysiological properties of these interneurons, associated with repetitive patterns of behavior without social interaction deficits. Therefore, dysfunction in either CPNs or SCINs segregates with a distinct ASD behavioral trait. These findings provide novel insights onto the implication of the corticostriatal circuitry in ASD by revealing an unexpected neuronal dichotomy in the biological background of the two core behavioral domains of this disorder.

Summary: A variety of mechanosensory neurons are involved in touch, proprioception, and pain. Many molecular components of the mechanotransduction machinery subserving these sensory modalities remain to be discovered. Here, we combine recordings of mechanosensitive (MS) currents in mechanosensory neurons with single-cell RNA sequencing. Transcriptional profiles are mapped onto previously identified sensory neuron types to identify cell-type correlates between datasets. Correlation of current signatures with single-cell transcriptomes provides a one-to-one correspondence between mechanoelectric properties and transcriptomically defined neuronal populations. Moreover, a gene-expression differential comparison provides a set of candidate genes for mechanotransduction complexes. Piezo2 is expectedly found to be enriched in rapidly adapting MS current-expressing neurons, whereas Tmem120a and Tmem150c, thought to mediate slow-type MS currents, are uniformly expressed in all mechanosensory neuron subtypes. Further knockdown experiments disqualify them as mediating MS currents in sensory neurons. This dataset constitutes an open resource to explore further the cell-type-specific determinants of mechanosensory properties.

Alteration of cerebrospinal fluid (CSF) flow and cilia defects are clinically associated with idiopathic scoliosis. This study shows that transient receptor potential channel Pkd2l1 is required for mechanosensory function of neurons detecting CSF flow and normal spine curvature development in zebrafish.

Abstract Background The reporting quality of physical activity (PA) programs in randomized controlled trials (RCTs) for the management of juvenile idiopathic arthritis (JIA) remains unknown. This study aimed to assess and compare the reporting quality of PA programs in RCTs for the management of JIA using three difference standardized assessment tools, and to describe the elements that were similar and different between these tools. Methods A systematic search was conducted for moderate-to high-quality RCTs of PA programs in JIA, published up until January 2019. Two reviewers independently included 10 RCTs and scored the reporting quality of PA programs using the following tools: Consensus on Exercise Reporting Template (CERT) checklist, Consensus on Therapeutic Exercise Training (CONTENT) scale, and Template for Intervention Description and Replication (TIDieR) checklist. Results Results showed that reporting of PA programs in 10 moderate- to high-quality RCTs for JIA management remains incomplete. The average reporting quality (± standard deviation) for all RCTs combined was moderate for the three standardized assessment tools with 70.8 (±14.3)% for the TIDieR checklist, 53.2 (±20.2)% for the CERT checklist, and 70.0 (±18.9)% for the CONTENT scale. Despite some overlap, the three standardized assessment tools (TIDieR, CERT, CONTENT) included different elements resulting in different scores. All tools assess elements linked to PA programs (provider, location, timing, personalization and adherence), but the CERT checklist includes other essential elements (e.g., additional resources, motivational strategies, adverse events). Conclusions The lack of complete reporting of PA programs in RCTs for the management of JIA and the variation in scores and assessed elements among standardized assessment tools show the need to improve reporting. Using the most comprehensive standardized tool (i.e., the CERT) and providing accessible supplemental information on PA programs may improve the reporting quality of PA programs in RCTs and help reproduce PA programs in research and clinical practice.

Abstract Background Leadership by point-of-care and senior managers is increasingly recognized as critical to the acceptance and use of research evidence in practice. The purpose of this systematic review was to identify the leadership behaviours of managers that are associated with research use by clinical staff in nursing and allied health professionals. Methods A mixed methods systematic review was performed. Eight electronic bibliographic databases were searched. Studies examining the association between leadership behaviours and nurses and allied health professionals’ use of research were eligible for inclusion. Studies were excluded if leadership could not be clearly attributed to someone in a management position. Two reviewers independently screened abstracts, reviewed full-text articles, extracted data and performed quality assessments. Narrative synthesis was conducted. Results The search yielded 7019 unique titles and abstracts after duplicates were removed. Three hundred five full-text articles were reviewed, and 31 studies reported in 34 articles were included. Methods used were qualitative (n = 19), cross-sectional survey (n = 9), and mixed methods (n = 3). All studies included nurses, and six also included allied health professionals. Twelve leadership behaviours were extracted from the data for point-of-care managers and ten for senior managers. Findings indicated that managers performed a diverse range of leadership behaviours that encompassed change-oriented, relation-oriented and task-oriented behaviours. The most commonly described behavior was support for the change, which involved demonstrating conceptual and operational commitment to research-based practices. Conclusions This systematic review adds to the growing body of evidence that indicates that manager-staff dyads are influential in translating research evidence into action. Findings also reveal that leadership for research use involves change and task-oriented behaviours that influence the environmental milieu and the organisational infrastructure that supports clinical care. While findings explain how managers enact leadership for research use, we now require robust methodological studies to determine which behaviours are effective in enabling research use with nurses and allied health professionals for high-quality evidence-based care. Trial registration PROSPERO CRD42014007660

Abstract Background The prevalence of hand osteoarthritis (HOA) has been reported to be higher amongst women over 50 years old (66%) compared to men of the same age (34%). Although exercise therapy has been shown effective in reducing symptoms and disability associated with HOA, adherence to treatment programs remains low. The primary objective of this RCT is to examine the effectiveness of a 12-week knitting program for morning stiffness (primary outcome) and pain relief (secondary outcome) 2 h post-wakening in females (aged 50 to 85 years old) with mild to moderate hand osteoarthritis (HOA). Methods/design A single-blind, two-arm randomized controlled trial (RCT) with a parallel group design will be used to reach this objective and compare results to a control group receiving an educational pamphlet on osteoarththritis (OA) designed by the Arthritis Society. The premise behind the knitting program is to use a meaningful occupation as the main component of an exercise program. The knitting program will include two components: 1) bi-weekly 20-min knitting sessions at a senior’s club and 2) 20-min home daily knitting sessions for the five remaining weekdays. Participants assigned to the control group will be encouraged to read the educational pamphlet and continue with usual routine. Pain, morning stiffness, hand function, self-efficacy and quality of life will be measured at baseline, six weeks, 12 weeks (end of program) with standardized tools. We hypothesize that participants in the knitting program will have significant improvements in all clinical outcomes compared to the control group. A published case study as well as the preliminary results of a feasibility study as examined through a 6-week pre-post study (n = 5 women with HOA) involving 20-min daily knitting morning sessions led to this proposed randomized controlled trial research protocol. This article describes the intervention, the empirical evidence to support it. Discussion This knitting RCT has the potential to enhance our understanding of the daily HOA symptoms control and exercise adherence, refine functional exercise recommendations in this prevalent disease, and reduce the burden of disability in older women. Trial Registration (ACTRN12617000843358) registered on 7/06/2017.

Abstract Background Children and adolescents with Juvenile Idiopathic Arthritis (JIA) typically have reduced physical activity level and impaired aerobic and anaerobic exercise capacity when compared to their non-JIA counterparts. Low intensity exercise regimens appear to be safe in children with JIA and may results in improvements in overall physical function. Poor adherence to paediatric rheumatology treatment may lead to negative clinical outcomes and possibly increased disease activity. This includes symptoms such as pain, fatigue, quality of life, longer term outcomes including joint damage, as well as increase of healthcare associated costs. Low adherence to medications such as methotrexate and biological-drugs remains a significant issue for paediatric rheumatologists, with alarming reports that less than half of the children with JIA are compliant to drug-therapy. Main body The recent advances in interactive technology resulting in a variety of wearable user-friendly smart devices may become a key solution to address important questions in JIA clinical management. Fully understanding the impact that arthritis and treatment complications have upon individual children and their families has long been a challenge for clinicians. Modern interactive technologies can be customised and accessed directly in the hands or wrists of children with JIA. These secured networks could be accessible ‘live’ at anytime and anywhere by the child, parents and clinicians. Multidisciplinary teams in paediatric rheumatology may benefit from adopting these technologies to better understand domains such as patient biological parameters, symptoms progression, adherence to drug-therapy, quality of life, and participation in physical activities. Most importantly the use of smart devices technologies may also facilitate more timely clinical decisions, improve self-management and parents awareness in the progression of their child’s disease. Paediatric rheumatology research could also benefit from the use of these smart devices, as they would allow real-time access to meaningful data to thoroughly understand the disease-patterns of JIA, such as pain and physical activity outcomes. Data collection that typically occurs once every 1 or 3 months in the clinical setting could instead be gathered every week, day, minute or virtually live online. Arguably, few limitations in wearing such interactive technologies still exist and require further developments. Conclusion Finally, by embracing and adapting these new and now highly accessible interactive technologies, clinical management and research in paediatric rheumatology may be greatly advanced.

Evidence suggests physical activity (PA) is beneficial for people diagnosed with cancer. Clinical practice guidelines provide specific recommendations based on available research and are useful in informing evidence-based practice and guiding future research. Little is known on the extent and quality of guidelines on PA targeted to the cancer population. The objectives of this systematic review were to: 1) identify recent clinical practice guidelines including PA or exercise recommendations for people with cancer and 2) critically appraise the methodological quality of the included guidelines. A systematic search of four electronic databases (MEDLINE, EMBASE, CINAHL and PEDro) and supplementary sources was conducted. Two reviewers independently scanned articles and selected guidelines for inclusion according to the following criteria: published in English, developed or updated in previous five years (January 2012-June 2017), published in peer-reviewed scientific journals, including ≥1 specific recommendation on PA or exercise, and relevant to adults diagnosed with cancer. Subsequently, two trained assessors independently appraised the included guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool. Average scores for six domains (scope and purpose; stakeholder involvement; rigour of development; clarity of presentation; applicability; and editorial independence) and overall quality were calculated. From the literature search, we identified 29 articles, representing 20 sets of guidelines meeting the selection criteria. The guidelines were applicable to the following cancer populations: general (n = 9), breast (n = 5), lung (n = 2), colorectal (n = 1), head and neck (n = 1), myeloma (n = 1) and prostate (n = 1). The guidelines were generally of moderate methodological quality (mean AGREE II overall quality score: 4.6/7, range 2.5-6). The area of lowest quality was in the domain of applicability (mean AGREE II quality domain score: 40%), whereas the strongest domains were related to scope and purpose (81%) and clarity of presentation (77%). Although there are limitations in the primary research informing the recommendations, guidelines of acceptable quality exist to direct stakeholders on targeted PA recommendations for a range of cancer populations. Improvement is needed in the applicability of guidelines to enhance their relevance and clinical use. Health professionals can play an important role in supporting people with cancer throughout the disease trajectory and benefit from access to well-developed and appropriate materials to interpret research knowledge on effective rehabilitation strategies, including PA.

BackgroundThe Cochrane risk of bias (CROB) tool and Physiotherapy Evidence Database (PEDro) scale are used to evaluate risk of bias of randomized controlled trials. We assessed the level of agreement between the instruments.MethodsWe searched the Cochrane Library to identify trials included in systematic reviews evaluating physical therapy interventions. For trials that met our inclusion criteria (primary reference in Cochrane review, review used CROB (2008 version), indexed in PEDro), CROB items were extracted from the reviews and PEDro items and total score were downloaded from PEDro. Kappa statistics were used to determine the agreement between CROB and PEDro scale items that evaluate similar constructs (e.g., randomization). The total PEDro score was compared to the CROB summary score (% of items met) using an Intraclass Correlation Coefficient. Sensitivity analyses explored the impact of the CROB "unclear" category and variants of CROB blinding items. Kappa statistics were used to determine agreement between different thresholds for "acceptable" risk of bias between CROB and PEDro scale summary scores.ResultsWe included 1442 trials from 108 Cochrane reviews. Agreement was "moderate" for three of the six CROB and PEDro scale items that evaluate similar constructs (allocation concealment, participant blinding, assessor blinding; Kappa = 0.479-0.582). Agreement between the summary scores was "poor" (Intraclass Correlation Coefficient = 0.285). Agreement was highest when the CROB "unclear" category was collapsed with "high" and when participant, personnel and assessor blinding were evaluated separately in CROB. Agreement for different thresholds for "acceptable" risk of bias between CROB and PEDro summary scores was, at best, "fair".ConclusionThere was moderate agreement for half of the PEDro and CROB items that evaluate similar constructs. Interpretation of the CROB "unclear" category and variants of the CROB blinding items substantially influenced agreement. Either instrument can be used to quantify risk of bias, but they can't be used interchangeably.

Design and objective: This paper describes the protocol for a three-arm, single-blind, parallel design randomized controlled trial (RCT) to investigate the perceived usability of Facebook to share information from an evidence-based arthritis self-management program with patients compared with email or an educational website after two weeks. Study population Three-hundred and twenty-seven arthritis health professionals (i.e., nurses or physical/occupational therapists) registered with their regulatory body in Canada, currently practicing clinically defined as spending a minimum of 50% of their time (working week) in direct arthritis patient care. Interventions The proposed RCT will include three information and communication technology (ICT) intervention groups: Facebook, email, and an educational website. Outcome measures The primary outcome will be perceived usefulness by health professionals of using the ICT intervention to share information with their patients according to the technology acceptance model 2 (TAM2) questionnaire at two weeks post-intervention. Secondary outcomes will include other usability domains of the TAM2 questionnaire (i.e., perceived ease of use, result demonstrability, output quality, job relevance, image, voluntariness, subjective norm, and intention to use) at two weeks, three months, and six months post-intervention. Analysis: An analysis of variance will be conducted to compare TAM2 questionnaire scores of the Facebook group with the email and educational website groups.

Objective The objective of this systematic review was to summarize the evidence pertaining to the use of social media by health professionals to facilitate chronic disease self-management with their patients. Methods A systematic approach was used to retrieve and extract relevant data. A total of 5163 citations were identified, of which seven unique studies met criteria for inclusion; one was a randomized controlled trial, two were prospective cohort studies, and four were qualitative studies. The following social media platforms were evaluated: discussion forums (6 studies) and collaborative project (1 study). Results The available evidence suggests that health professionals perceived discussion forums and collaborative projects to be useful social media platforms to facilitate chronic disease self-management with patients. No relevant evidence was found regarding the use of other social media platforms. Most studies indicated positive findings regarding health professionals’ intention to use discussion forums, while the one study that used a collaborative project also indicated positive findings with its perceived ease of use as health professionals felt that it was useful to facilitate chronic disease self-management with patients. Mixed findings were seen in regards to health professionals’ perceived ease of use of discussion forums. The most common barrier to using social media platforms was the lack of time in health professionals’ schedules. Conclusions Discussion forums and collaborative projects appear to be promising resources for health professionals to assist their patients in self-managing their chronic conditions; however, further research comparing various social media platforms is needed.

Objective The objective of this study was to determine the feasibility of Facebook as a dissemination strategy for the People Getting a Grip on Arthritis self-management program by arthritis health professionals to their patients. Methods The feasibility study comprised a single arm, pre-post design that included a convenience sample of 78 arthritis health professionals across Canada. Assessments were performed at baseline, two-weeks post-intervention, and at three-months follow-up using online questionnaires. The primary outcome measure was change in perceived usability of Facebook as a dissemination strategy for the People Getting a Grip on Arthritis program with patients at two-weeks post-intervention using an instrument based on an extended version of the Technology Acceptance Model 2. Comparisons with baseline were assessed using t -test analyses. Results Statistically significant improvements from baseline were seen for all items of the Technology Acceptance Model 2 domains: perceived ease of use (four items), intention to use (two items) and output quality (two items) domains. Variable results were seen for the job relevance , perceived usefulness , voluntariness , and result demonstrability domains of the Technology Acceptance Model 2. There were no statistically significant improvements for the subjective norm and image domains. Conclusions Facebook may provide arthritis health professionals with an additional option of how to best share evidence-based information to allow their patients to successfully self-manage their arthritis.

The objectives of this review are to: 1) appraise the methodological quality of clinical practice guidelines (CPGs) in juvenile idiopathic arthritis (JIA) providing pharmacological and/or non-pharmacological intervention recommendations, and 2) summarize the recommendations provided by the included CPGs and compare them where possible.A systematic search was performed. Three trained appraisers independently evaluated the methodological quality of the CPGs using a validated and reliable instrument, the Appraisal of Guidelines in Research and Evaluation II. Six domains were considered: 1) score and purpose; 2) stakeholder involvement; 3) rigor of development; 4) clarity of presentation; 5) applicability; and 6) editorial independence. The domains consist of a total of 23 items each scored on a 7-point scale. High quality CPGs were identified if they had a domain score above 60% in rigor of development, and two other domains.Of the three included CPGs, the Royal Australian College of General Practitioners (RACGP) and American College of Rheumatology (ACR) CPGs were considered to be of high quality, but the German Society for Pediatric Rheumatology was of lower quality. Domains one to four had high domain scores across the guidelines (mean (standard deviation)): 72.76 (13.80); 66.67 (9.81); 64.67 (7.77); and 87.00 (9.64), respectively. Lower scores were obtained for applicability (14.00 (5.57)) and editorial independence (43.44 (7.02)). Recommendations varied across CPGs due to differences in context, target audience (general practitioners, rheumatologists, and other multidisciplinary healthcare professionals) and patients' disease presentations. Despite this variability, progression of pharmacological treatment did not conflict between CPGs. Recommendations for non-pharmacological interventions were vague and the interventions considered varied between CPGs.Overall, recommendations were based on a paucity of evidence and weak study designs. Further research is needed on interventions in JIA, as well as higher quality CPGs to facilitate implementation of the best evidence-based recommendations in clinical practice.

Clinical practice CPGs (CPGs) have been developed to summarize evidence related to the management of osteoarthritis (OA). CPGs facilitate uptake of evidence-based knowledge by consumers, health professionals, health administrators and policy makers. The objectives of the present review were: 1) to assess the quality of the CPGs on non-pharmacological management of OA; using a standardized and validated instrument--the Appraisal of Guidelines Research and Evaluation (AGREE II) tool--by three pairs of trained appraisers; and 2) to summarize the recommendations based on only high-quality existing CPGs. Scientific literature databases from 2001 to 2013 were systematically searched for the state of evidence, with 17 CPGs for OA being identified. Most CPGs effectively addressed only a minority of AGREE II domains. Scope and purpose was effectively addressed in 10 CPGs on the management of OA, stakeholder involvement in 12 CPGs, rigour of development in 10 CPGs, clarity/presentation in 17 CPGs, editorial independence in 2 CPGs, and applicability in none of the OA CPGs. The overall quality of the included CPGs, according to the 7-point AGREE II scoring system, is 4.8 ± 0.41 for OA. Therapeutic exercises, patient education, transcutaneous electrical nerve stimulation, acupuncture, orthoses and insoles, heat and cryotherapy, patellar tapping, and weight control are commonly recommended for the non-pharmacological management of OA by the high-quality CPGs. The general clinical management recommendations tended to be similar among high-quality CPGs, although interventions addressed varied. Non-pharmacological management interventions were superficially addressed in more than half of the selected CPGs. For CPGs to be standardized uniform creators should use the AGREE II criteria when developing CPGs. Innovative and effective methods of CPG implementation to users are needed to ultimately enhance the quality of life of arthritic individuals.

Clinical practice guidelines (CPGs) have been developed to summarize evidence about the management of rheumatoid arthritis (RA) and facilitate the uptake of evidence-based knowledge by consumers, health professionals, health administrators and policy makers. The objectives of this review was to assess the quality of CPGS on non-pharmacological management of RA with a standardized and validated instrument--the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool and summarize the key recommendations from these CPGs. Scientific literature databases from 2001 to 2013 were systematically searched and a total of 13 CPGs for RA was identified. Only a minority of AGREE II domains were effectively addressed by the CPGS. Scope and purpose was effectively addressed in 10 out of 13 CPGs, stakeholder involvement in 11 CPGs, rigor of development in 6 CPGs, clarity/presentation in 9 CPGs, editorial independence in 1 CPGs, and applicability in none of the CPGs. The overall quality of the included CPGs according to the 7-point AGREE II scoring system was 4.8 ± 1.04. Patient education/self-management, aerobic, dynamic and stretching exercises were the commonly recommended for the non-pharmacological management of RA by the high-quality CPGs. The general clinical management recommendations tended to be similar among high-quality CPGs. Non-pharmacological management interventions were superficially addressed in more than half of the selected CPGs. CPGs creators should use the AGREE II criteria when developing guidelines. Innovative and effective methods of CPGs implementation to users are needed to ultimately enhance the quality of life of arthritic individuals. In addition, it was difficult to establish between strongly recommended, recommended and weakly recommended, as there is no consensus between the strength of the recommendations between the appraised CPGs.