An international study of diversity in occupational therapy research- A bibliographic review of English research literature.

BACKGROUND: The cornerstone of a strong profession is the research that supports its knowledge base and practice. However, little is known about the range of international occupational therapy research. OBJECTIVE: To explore the range and diversity of the international occupational therapy research from published peer reviewed literature in English during the year 2018. METHODOLOGY: Limited to 2018, a review was conducted of sources from i) health-related search engines using search terms associated with occupational therapy practice, and ii) content pages of occupational therapy publications. Articles were excluded if they i) had no occupational therapy author, ii) were not peer reviewed, iii) not in English, and iv) did not include primary data collection (e.g., opinion pieces, position statements, study protocols). Of articles selected for analysis, data were extracted and synthesized according to the study's origin country, publishing research journal, the characteristics of the represented research, and its alignment with World Federation of Occupational Therapists research priorities. RESULTS: A total of 4,169 articles were retrieved from the search (i.e., 3,459 from health-related search engines and 710 through a manual search of occupational therapy journals). After exclusions, 2,345 articles were included for analysis. CONCLUSION: The review identified English published research was predominantly conducted in economically privileged countries. In addition, it revealed several research priorities that need further development such as evaluating the effectiveness of occupational therapy interventions.

A systematic review of video-modelling interventions for children and adolescents with attention-deficit hyperactivity disorder.

OBJECTIVE: To identify, appraise, and synthesise the evidence for video-modelling interventions for individuals with attention-deficit hyperactivity disorder (ADHD). METHOD: We searched four electronic databases. Two independent researchers screened abstracts and methodologically assessed data using the Kmet appraisal checklist. RESULTS: A total of 15 studies met the inclusion criteria (11 original studies and four follow-up studies). Of the 11 original studies, one was a randomised controlled trial, one was a controlled between-group comparative design, two were one group pre-test post-test studies, one was an experimental 2 × 2 factorial design, and six were single-case experimental design studies. Studies included 1-35 participants with ADHD aged 5-16 years. Three studies targeted behaviour, three targeted social play skills, two targeted social behaviour, one targeted social skills, one targeted goal orientation and friendship quality, targeted and one attention/comprehension of social behaviour. In four studies video-modelling was the whole intervention, with no other intervention components reported. Nine studies reported positive outcomes immediately after intervention, two studies reported mixed findings. All studies were found to have good or strong methodological quality. CONCLUSION: There is preliminary evidence to suggest video-modelling may be a promising intervention approach for targeting the social skills and behaviours of individuals with ADHD when used in conjunction with other intervention components. Future studies need to lower the risk of bias and use larger sample sizes before the efficacy of video-modelling interventions can be fully investigated.

Models of Governance of Disability Therapy Support Workers in Rural and Remote Settings: A Systematic Scoping Review.

The National Disability Insurance Scheme (NDIS) ushered in a transformative era in disability services in Australia, requiring new workforce models to meet evolving participant needs. Therapy Assistants are utilised to increase the capacity of therapy services in areas of workforce shortage. The governance arrangements required to support this emergent workforce have received limited attention in the literature. This review examined the key components and contextual factors of governance in rural settings, specifically focusing on therapy support workers under the guidance of allied health professionals in rural and remote areas. Guided by the social model of disability and the International Classification of Functioning, Disability and Health, a realist perspective was used to analyse 26 papers (after deduplication), mostly Australian and qualitative, with an emphasis on staff capabilities, training, and credentialling. Success measures were often vaguely defined, with most papers focusing on staff improvement and few focusing on client or organisational improvement. Consistent staffing, role clarity, community collaboration, and supportive leadership were identified as enabling contexts for successful governance of disability therapy support workers in rural areas. Investment in capability (soft skills) development, tailored training, competency assessment, credentialling, and supervision were identified as key activities that, when coupled with the identified enabling contexts, were likely to influence staff, client and organisational outcomes. Further research is warranted to explore long-term impacts of governance arrangements, educational program accountability, and activities targeted at enhancing staff capabilities.

DNA methylation profiles in individuals with rare, atypical 7q11.23 CNVs correlate with GTF2I and GTF2IRD1 copy number.

Williams-Beuren syndrome (WBS) and 7q11.23 duplication syndrome (Dup7) are rare neurodevelopmental disorders caused by deletion and duplication of a 1.5 Mb region that includes at least five genes with a known role in epigenetic regulation. We have shown that CNV of this chromosome segment causes dose-dependent, genome-wide changes in DNA methylation, but the specific genes driving these changes are unknown. We measured genome-wide whole blood DNA methylation in six participants with atypical CNV of 7q11.23 (three with deletions and three with duplications) using the Illumina HumanMethylation450k array and compared their profiles with those from groups of individuals with classic WBS or classic Dup7 and with typically developing (TD) controls. Across the top 1000 most variable positions we found that only the atypical rearrangements that changed the copy number of GTF2IRD1 and/or GTF2I (coding for the TFII-IRD1 and TFII-I proteins) clustered with their respective syndromic cohorts. This finding was supported by results from hierarchical clustering across a selection of differentially methylated CpGs, in addition to pyrosequencing validation. These findings suggest that CNV of the GTF2I genes at the telomeric end of the 7q11.23 interval is a key contributor to the large changes in DNA methylation that are seen in blood DNA from our WBS and Dup7 cohorts, compared to TD controls. Our findings suggest that members of the TFII-I protein family are involved in epigenetic processes that alter DNA methylation on a genome-wide level.

Rare and low frequency genomic variants impacting neuronal functions modify the Dup7q11.23 phenotype.

BACKGROUND: 7q11.23 duplication (Dup7) is one of the most frequent recurrent copy number variants (CNVs) in individuals with autism spectrum disorder (ASD), but based on gold-standard assessments, only 19% of Dup7 carriers have ASD, suggesting that additional genetic factors are necessary to manifest the ASD phenotype. To assess the contribution of additional genetic variants to the Dup7 phenotype, we conducted whole-genome sequencing analysis of 20 Dup7 carriers: nine with ASD (Dup7-ASD) and 11 without ASD (Dup7-non-ASD). RESULTS: We identified three rare variants of potential clinical relevance for ASD: a 1q21.1 microdeletion (Dup7-non-ASD) and two deletions which disrupted IMMP2L (one Dup7-ASD, one Dup7-non-ASD). There were no significant differences in gene-set or pathway variant burden between the Dup7-ASD and Dup7-non-ASD groups. However, overall intellectual ability negatively correlated with the number of rare loss-of-function variants present in nervous system development and membrane component pathways, and adaptive behaviour standard scores negatively correlated with the number of low-frequency likely-damaging missense variants found in genes expressed in the prenatal human brain. ASD severity positively correlated with the number of low frequency loss-of-function variants impacting genes expressed at low levels in the brain, and genes with a low level of intolerance. CONCLUSIONS: Our study suggests that in the presence of the same pathogenic Dup7 variant, rare and low frequency genetic variants act additively to contribute to components of the overall Dup7 phenotype.

Transcription Factor 2I Regulates Neuronal Development via TRPC3 in 7q11.23 Disorder Models.

Williams syndrome (WS) and 7q11.23 duplication syndrome (Dup7q11.23) are neurodevelopmental disorders caused by the deletion and duplication, respectively, of ~ 25 protein-coding genes on chromosome 7q11.23. The general transcription factor 2I (GTF2I, protein TFII-I) is one of these proteins and has been implicated in the neurodevelopmental phenotypes of WS and Dup7q11.23. Here, we investigated the effect of copy number alterations in Gtf2i on neuronal maturation and intracellular calcium entry mechanisms known to be associated with this process. Mice with a single copy of Gtf2i (Gtf2i+/Del) had increased axonal outgrowth and increased TRPC3-mediated calcium entry upon carbachol stimulation. In contrast, mice with 3 copies of Gtf2i (Gtf2i+/Dup) had decreases in axon outgrowth and in TRPC3-mediated calcium entry. The underlying mechanism was that TFII-I did not affect TRPC3 protein expression, while it regulated TRPC3 membrane translocation. Together, our results provide novel functional insight into the cellular mechanisms that underlie neuronal maturation in the context of the 7q11.23 disorders.

The common inversion of the Williams-Beuren syndrome region at 7q11.23 does not cause clinical symptoms.

Williams-Beuren syndrome (WBS) is caused by a approximately 1.5 million base pair deletion at 7q11.23. A common inversion of the region, WBSinv-1, exists as a polymorphism but was also found in individuals with WBS-like features but no deletion, suggesting it could cause clinical symptoms. We performed a full clinical, developmental and genetic assessment of two previously reported individuals with clinical symptoms and WBSinv-1 but no 7q11.23 deletion. We also examined expression of genes at 7q11.23 in individuals in the general population who have WBSinv-1. We show that individuals with clinical symptoms and WBSinv-1 do not show significant clinical or psychological overlap with individuals with WBS. In addition, a 1.3 Mb duplication of part of the velocardiofacial syndrome region on chromosome 22q11.2 was found in one participant with WBSinv-1 and clinical symptoms. We also demonstrate that individuals with WBSinv-1 show normal expression of genes from the WBS region. These results suggest that WBSinv-1 does not cause clinical symptoms and we advise caution when diagnosing individuals with atypical presentation of rare syndromes. Whole genome analysis may reveal previously unidentified copy number variants that could contribute to syndromic features.

Cigarette smoke exposure during pregnancy alters fetomaternal cell trafficking leading to retention of microchimeric cells in the maternal lung.

Cigarette smoke exposure causes chronic oxidative lung damage. During pregnancy, fetal microchimeric cells traffic to the mother. Their numbers are increased at the site of acute injury. We hypothesized that milder chronic diffuse smoke injury would attract fetal cells to maternal lungs. We used a green-fluorescent-protein (GFP) mouse model to study the effects of cigarette smoke exposure on fetomaternal cell trafficking. Wild-type female mice were exposed to cigarette smoke for about 4 weeks and bred with homozygote GFP males. Cigarette smoke exposure continued until lungs were harvested and analyzed. Exposure to cigarette smoke led to macrophage accumulation in the maternal lung and significantly lower fetal weights. Cigarette smoke exposure influenced fetomaternal cell trafficking. It was associated with retention of GFP-positive fetal cells in the maternal lung and a significant reduction of fetal cells in maternal livers at gestational day 18, when fetomaternal cell trafficking peaks in the mouse model. Cells quickly clear postpartum, leaving only a few, difficult to detect, persisting microchimeric cells behind. In our study, we confirmed the postpartum clearance of cells in the maternal lungs, with no significant difference in both groups. We conclude that in the mouse model, cigarette smoke exposure during pregnancy leads to a retention of fetal microchimeric cells in the maternal lung, the site of injury. Further studies will be needed to elucidate the effect of cigarette smoke exposure on the phenotypic characteristics and function of these fetal microchimeric cells, and confirm its course in cigarette smoke exposure in humans.

2,3,7,8-Tetrachlorodibenzo-p-dioxin induces suppressor of cytokine signaling 2 in murine B cells.

The B cell, a major component of humoral immunity, is a sensitive target for the immunotoxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), possibly by rendering cells less responsive to antigenic or mitogenic stimulation. Potential mechanisms of TCDD action on B cells were examined in murine B cell lymphoma cells (CH12.LX) treated with 3 nM TCDD or dimethyl sulfoxide vehicle using sequence-verified cDNA microarrays. One transcript that was significantly induced by TCDD was suppressor of cytokine signaling 2 (Socs2). Changes in Socs2 mRNA levels paralleled that of Cyp1a1 with a maximal 3-fold induction observed at 4 h, as determined by quantitative real-time polymerase chain reaction. Socs2 induction seems B cell-specific, because no induction was observed in TCDD-responsive mouse hepatoma cells or human breast cancer cells. TCDD-mediated induction of Socs2 mRNA was dose-dependent and exhibited the characteristic structure-activity relationships observed for the aryl hydrocarbon receptor (AhR) ligands 3,3',4,4',5-pentachlorobiphenyl (PCB-126), indolo[3,2-b]-carbazole, and beta-naphthoflavone. Experiments with cycloheximide and AhR-deficient B cells indicated that Socs2 mRNA induction is a primary effect that is AhR-dependent. Western blot analysis confirmed that Socs2 and Cyp1a1 protein levels were also induced in CH12.LX cells. Promoter analysis revealed the presence of four dioxin-response elements within 1000 base pairs upstream of the Socs2 transcriptional start site, and a reporter gene regulated by the Socs2 promoter was inducible by TCDD. Promoter activity was also dependent on a functional AhR signaling pathway. These results indicate that Socs2 is a primary TCDD-inducible gene that may represent a novel mechanism by which TCDD elicits its immunosuppressive effects.