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Introduction: Participating in family gatherings can provide enjoyment and quality time together as a family. However, being the primary carers, mothers of children with autism spectrum disorder may experience this phenomenon differently. The purpose of this study is to explore how available literature describes mothers' experiences of participation in family gatherings and social events with their children with autism spectrum disorder., Methods: A scoping review was used to explore available literature and identify studies describing mothers' experiences of family gatherings and social events with their children. A thematic synthesis was performed to analyse and synthesise the findings., Results: A total of 8 articles were included for review. The analysis of the included studies resulted in one central theme-Negative experiences despite strategies-and four analytical themes: Feeling fear, stress, and anxiety; Avoiding family gatherings; Enjoying less and becoming less confident; and Using strategies., Conclusion: These findings indicate that mothers of children with autism spectrum disorder experience difficulties during gatherings even when using strategies, hence limiting their participation., (© 2023 The Authors. Australian Occupational Therapy Journal published by John Wiley & Sons Australia, Ltd on behalf of Occupational Therapy Australia.)

How enhancers activate their distal target promoters remains incompletely understood. Here we dissect how CTCF-mediated loops facilitate and restrict such regulatory interactions. Using an allelic series of mouse mutants, we show that CTCF is neither required for the interaction of the Sox2 gene with distal enhancers, nor for its expression. Insertion of various combinations of CTCF motifs, between Sox2 and its distal enhancers, generated boundaries with varying degrees of insulation that directly correlated with reduced transcriptional output. However, in both epiblast and neural tissues, enhancer contacts and transcriptional induction could not be fully abolished, and insertions failed to disrupt implantation and neurogenesis. In contrast, Sox2 expression was undetectable in the anterior foregut of mutants carrying the strongest boundaries, and these animals fully phenocopied loss of SOX2 in this tissue. We propose that enhancer clusters with a high density of regulatory activity can better overcome physical barriers to maintain faithful gene expression and phenotypic robustness., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Occupational therapy (OT) enhances functional independence in the daily activities of people with disabilities and subsequently their quality of life. Research in OT generates evidence to provide safe and effective services to the disabled. However, OT research in India has been shown to have various methodological limitations. These methodological limitations are expected to impact the quality of OT research as well as the evidence derived from this research to inform decision-making in rehabilitation. The majority of the OT research is disseminated and promoted through the All India Occupational Therapists' Association's (AIOTA) annual national conference (ANC). Analyzing the abstracts, selected for the presentation at the ANC could help understand and strategically improve the quality of OT research in India., Objectives: To explore and describe the quality of OT research in India., Study Design: Descriptive analysis., Methods: Descriptive, nonsystematic review and analysis of the key methodological aspects of the conference abstracts submitted for the AIOTA ANC published in the Indian Journal of OT (IJOT) from 2017 to 2021 was carried out. Information related to the methodological aspects of the research abstracts was extracted using a data extraction form and the data were synthesized and reported descriptively., Results: About 218 abstracts had been selected for either poster or oral presentations in the AIOTA ANC. All the abstracts were included for the review. A total of 8055 participants were recruited for the studies conducted from 2017 to 2021. About 5757 (72%) of the participants were recruited for cross-sectional studies. Nearly 72 (33%) of the abstracts presented were related to cross-sectional studies, 52 (24%) were case studies and 66 (30%) were experimental studies. However, research designs implying highest level of evidence such as systematic reviews were only 4 (2%) and randomized controlled trials were only 9 (4%) with 297 participants. Notably, 203 (98%) of the all the studies evaluating effectiveness of interventions or aiming to investigate associations reported positive results with statistically significant improvements and associations., Conclusion: The review provides invaluable information related to the quality of OT research in India. It implies the need to improve the scientific rigor of the evidence generated in relation to OT research in India. This review also implies the need for a radical change and strengthening of OT research within OT education and professional practice in India. National and global OT associations need to prioritize good quality OT research by enhancing the research skills and competencies of OTs in India. This could help promote evidence-based OT science and develop the OT profession in the world's second-most populous country. In addition, it is also expected to encourage those OT researchers who have been striving to build OT research standards in India., Competing Interests: Conflicts of Interest There are no conflicts of interest.

How distal regulatory elements control gene transcription and chromatin topology is not clearly defined, yet these processes are closely linked in lineage specification during development. Through allele-specific genome editing and chromatin interaction analyses of the Sox2 locus in mouse embryonic stem cells, we found a striking disconnection between transcriptional control and chromatin architecture. We traced nearly all Sox2 transcriptional activation to a small number of key transcription factor binding sites, whose deletions have no effect on promoter-enhancer interaction frequencies or topological domain organization. Local chromatin architecture maintenance, including at the topologically associating domain (TAD) boundary downstream from the Sox2 enhancer, is widely distributed over multiple transcription factor-bound regions and maintained in a CTCF-independent manner. Furthermore, partial disruption of promoter-enhancer interactions by ectopic chromatin loop formation has no effect on Sox2 transcription. These findings indicate that many transcription factors are involved in modulating chromatin architecture independently of CTCF., (© 2022 Taylor et al.; Published by Cold Spring Harbor Laboratory Press.)

Background: Occupational therapists are considered an important workforce for the rehabilitation of persons with disabilities globally. However, in India, the profession is just beginning to gain recognition within the national and state-level systems for health care. One of the reasons for this could be the paucity of specific research related to the development of occupational therapy (OT) and its benefits to the health systems. Therefore, it is of immense public health importance to explore the priorities and gaps in OT research in India. A vast majority of the OT research in India is promoted and disseminated through the All-India Occupational Therapists Association (AIOTA) and its annual national conference (ANC)., Objectives: The objective of this study is to descriptively review the conference abstracts of the AIOTA ANC published in the Indian Journal of OT (IJOT), an official publication of the AIOTA, from 2017 to 2021., Study Design: The study design was a descriptive, nonsystematic review., Methods: Review of the abstracts selected for the AIOTA ANC published in the IJOT from 2017 to 2021. A data extraction form was developed and used to synthesize data related to the clinical and demographic characteristics of OT research in India., Results: The search yielded 218 abstracts. State-level trends indicated that close to 85% of the research submissions were from four states and no submissions from the northeastern states until 2020. Nearly 60% of the abstracts were clinical research with OT interventions. About 40% of these research abstracts were related to pediatrics, followed by neurology (17%), musculoskeletal (15%), mental health (10%), and ergonomics and assistive technology (8%). There were 1%-2% of research abstracts submitted related to coronavirus disease-2019 (COVID-19) and geriatrics. About 85% of the research abstracts were related to impairment (39%), activity limitation (26%), and social participation (22%)., Conclusion: This review highlights the need for diversifying the research in OT in India. This is particularly important in relation to expanding from selected states to pan-India research and development, especially in the northeastern states. Furthermore, the focus of OT research must move beyond impairments and approach disability from the biopsychosocial perspective. It is also very important to diversify the research in OT to areas that are of public health importance such as COVID-19, geriatrics, noncommunicable diseases, and rehabilitation in health systems. Priority setting for research in OT in India is an important implication of this review., Competing Interests: Conflicts of Interest There are no conflicts of interest.

Persons with Disabilities (PWD) experience unmet needs related to health, rehabilitation, education, livelihood, social participation, and empowerment, particularly those living in a resource-poor context such as in the Indian context. The same applies to Children with Disabilities (CWD) as well. Given the pandemic restrictions imposed by the government of India, the provision of therapeutic rehabilitation services for PWDs and CWDs has come to a deadlock. Therefore, the PWDs and the parents of CWDs are substantially impacted by the double contextual burden of demand and access to rehabilitation services in India. However, there has been some light at the end of this dark tunnel provided by the existing telecommunication strategies. Both parents/caregivers and rehabilitation service providers started to find a way out of this situation on their own in India by optimizing their skills and resources for telerehabilitation. However, adopting this strategy requires evidence. Hence a critical Strengths Weaknesses Opportunities and Threats (SWOT) analysis of the telerehabilitation strategy for empowering PWDs and CWDs in an Indian context is warranted and is of immense public health importance. A narrative review was conducted. Telerehabilitation has several strengths, weaknesses, opportunities, and threats. Telecommunication resources, Access to Rehabilitation services, Parent's and consumer acceptance, Service efficiency, and data documentation could be considered as strengths; Skills, Competencies, Opportunity cost, Resource intensiveness, Evidence for Effectiveness, Comprehensibility could be considered as weaknesses; Therapy innovations, Evidence generation, System strengthening and Capacity Building could be considered as opportunities; Patient Safety, Ethical Integrity, Data security, and Professional practice insecurity could be considered as potential Threats to Telerehabilitation. Telerehabilitation has considerable scope for providing meaningful therapeutic experience and hastens the process of rehabilitation of CWDs in the current context. The SWOT and its implications must be kept in mind to ensure that CWDs receive the best quality continuum of care in the present context with utmost ethical and evidence-based considerations. This could bridge the gaps in access to rehabilitation services with sustainable solutions than patchy temporary solutions that are not sustainable.

Background: The current evidence for occupational therapy practice, teaching, and research is replicated and implemented significantly from high-income countries in India. Therefore, a systematic review and an evaluation of existing evidence for occupational therapy (OT) to reduce disabilities including impairments, activity limitations, and participation restriction in persons with disabilities (PWD) in India are warranted., Objectives: The objective of this review was to evaluate the effectiveness of OT interventions for reducing disabilities in PWD in India., Study Design: Systematic review., Methods: We searched the Cochrane CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, AMED, and Web of Science. A hand search was also carried out in selected Indian journals, OT-specific databases, and repositories, such as Indian Journal of Occupational Therapy , Indian Journal of Physiotherapy and Occupational Therapy , OT Seekers, World Federation of Occupational Therapy Bulletin, Asia Pacific Occupational Therapists Regional Group, and clinical trials registers. The search was restricted to published studies conducted in India during 2000-2021. We included randomized controlled trials (RCTs) of an occupational therapy intervention delivered by OTs for PWD, where the effects of the intervention were evaluated using any relevant disability outcome measure. Studies without access to full text were excluded. Two review authors independently completed screening, and one author reviewed the full text of the screened studies. Another pair of authors extracted data from included studies for prespecified disability outcomes, and two authors assessed the risk of bias in the included studies., Results: We identified seven RCTs of occupational therapy interventions for PWD in India with 305 participants in total. All seven studies were very different in terms of their objective, participants, comparison, and outcomes. Allocation concealment and blinding and risk of bias were high in five trials. All the trials reported impairment outcomes with a statistically significant difference between the experimental arm and the control arm in terms of their primary outcomes except one. Given the sample size and the risk of bias in each of the included trials, the effect size has to be understood and interpreted with utmost caution., Conclusion: Overall, this review establishes the paucity of evidence for occupational therapy for PWD in India. Building the capacity for rigorous and relevant scientific research in occupational therapy would enable bridging the gaps in evidence for occupational therapy in India., Competing Interests: Conflicts of Interest There are no conflicts of interest.

Transcriptional enhancers are critical for development and phenotype evolution and are often mutated in disease contexts; however, even in well-studied cell types, the sequence code conferring enhancer activity remains unknown. To examine the enhancer regulatory code for pluripotent stem cells, we identified genomic regions with conserved binding of multiple transcription factors in mouse and human embryonic stem cells (ESCs). Examination of these regions revealed that they contain on average 12.6 conserved transcription factor binding site (TFBS) sequences. Enriched TFBSs are a diverse repertoire of 70 different sequences representing the binding sequences of both known and novel ESC regulators. Using a diverse set of TFBSs from this repertoire was sufficient to construct short synthetic enhancers with activity comparable to native enhancers. Site-directed mutagenesis of conserved TFBSs in endogenous enhancers or TFBS deletion from synthetic sequences revealed a requirement for 10 or more different TFBSs. Furthermore, specific TFBSs, including the POU5F1:SOX2 comotif, are dispensable, despite cobinding the POU5F1 (also known as OCT4), SOX2, and NANOG master regulators of pluripotency. These findings reveal that a TFBS sequence diversity threshold overrides the need for optimized regulatory grammar and individual TFBSs that recruit specific master regulators., (© 2021 Singh et al.; Published by Cold Spring Harbor Laboratory Press.)

Enhancers are cis -regulatory sequences located distally to target genes. These sequences consolidate developmental and environmental cues to coordinate gene expression in a tissue-specific manner. Enhancer function and tissue specificity depend on the expressed set of transcription factors, which recognize binding sites and recruit cofactors that regulate local chromatin organization and gene transcription. Unlike other genomic elements, enhancers are challenging to identify because they function independently of orientation, are often distant from their promoters, have poorly defined boundaries, and display no reading frame. In addition, there are no defined genetic or epigenetic features that are unambiguously associated with enhancer activity. Over recent years there have been developments in both empirical assays and computational methods for enhancer prediction. We review genome-wide tools, CRISPR advancements, and high-throughput screening approaches that have improved our ability to both observe and manipulate enhancers in vitro at the level of primary genetic sequences, chromatin states, and spatial interactions. We also highlight contemporary animal models and their importance to enhancer validation. Together, these experimental systems and techniques complement one another and broaden our understanding of enhancer function in development, evolution, and disease.

The notoriety of parasitic nematode survival is directly related to chronic pathogenicity, which is evident in human lymphatic filariasis. It is a disease of poverty which causes severe disability affecting more than 120 million people worldwide. These nematodes down-regulate host immune system through a myriad of strategies that includes secretion of antioxidant and detoxification enzymes like glutathione-S-transferases (GSTs). Earlier studies have shown Wuchereria bancrofti GST to be a potential therapeutic target. Parasite GSTs catalyse the conjugation of glutathione to xenobiotic and other endogenous electrophiles and are essential for their long-term survival in lymph tissues. Hence, the crystal structure of WbGST along with its cofactor GSH at 2.3 Å resolution was determined. Structural comparisons against host GST reveal distinct differences in the substrate binding sites. The parasite xenobiotic binding site is more substrate/solvent accessible. The structure also suggests the presence of putative non-catalytic binding sites that may permit sequestration of endogenous and exogenous ligands. The structure of WbGST also provides a case for the role of the π-cation interaction in stabilizing catalytic Tyr compared to stabilization interactions described for other GSTs. Hence, the obtained information regarding crucial differences in the active sites will support future design of parasite specific inhibitors. Further, the study also evaluates the inhibition of WbGST and its variants by antifilarial diethylcarbamazine through kinetic assays., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Transcriptional enhancers are critical for maintaining cell-type-specific gene expression and driving cell fate changes during development. Highly transcribed genes are often associated with a cluster of individual enhancers such as those found in locus control regions. Recently, these have been termed stretch enhancers or super-enhancers, which have been predicted to regulate critical cell identity genes. We employed a CRISPR/Cas9-mediated deletion approach to study the function of several enhancer clusters (ECs) and isolated enhancers in mouse embryonic stem (ES) cells. Our results reveal that the effect of deleting ECs, also classified as ES cell super-enhancers, is highly variable, resulting in target gene expression reductions ranging from 12% to as much as 92%. Partial deletions of these ECs which removed only one enhancer or a subcluster of enhancers revealed partially redundant control of the regulated gene by multiple enhancers within the larger cluster. Many highly transcribed genes in ES cells are not associated with a super-enhancer; furthermore, super-enhancer predictions ignore 81% of the potentially active regulatory elements predicted by cobinding of five or more pluripotency-associated transcription factors. Deletion of these additional enhancer regions revealed their robust regulatory role in gene transcription. In addition, select super-enhancers and enhancers were identified that regulated clusters of paralogous genes. We conclude that, whereas robust transcriptional output can be achieved by an isolated enhancer, clusters of enhancers acting on a common target gene act in a partially redundant manner to fine tune transcriptional output of their target genes., (© 2017 Moorthy et al.; Published by Cold Spring Harbor Laboratory Press.)

Enhancers control cell identity by regulating tissue-specific gene expression in a position and orientation independent manner. These enhancers are often located distally from the regulated gene in intergenic regions or even within the body of another gene. The position independent nature of enhancer activity makes it difficult to match enhancers with the genes they regulate. Deletion of an enhancer region provides direct evidence for enhancer activity and is the gold standard to reveal an enhancer's role in endogenous gene transcription. Conventional homologous recombination based deletion methods have been surpassed by recent advances in genome editing technology which enable rapid and precisely located changes to the genomes of numerous model organisms. CRISPR/Cas9 mediated genome editing can be used to manipulate the genome in many cell types and organisms rapidly and cost effectively, due to the ease with which Cas9 can be targeted to the genome by a guide RNA from a bespoke expression plasmid. Homozygous deletion of essential gene regulatory elements might lead to lethality or alter cellular phenotype whereas monoallelic deletion of transcriptional enhancers allows for the study of cis-regulation of gene expression without this confounding issue. Presented here is a protocol for CRISPR/Cas9 mediated deletion in F1 mouse embryonic stem (ES) cells (Mus musculus(129) x Mus castaneus). Monoallelic deletion, screening and expression analysis is facilitated by single nucleotide polymorphisms (SNP) between the two alleles which occur on average every 125 bp in these cells.

Dynamic structural properties of chromatin play an essential role in defining cell identity and function. Transcription factors and chromatin modifiers establish and maintain cell states through alteration of DNA accessibility and histone modifications. This activity is focused at both gene-proximal promoter regions and distally located regulatory elements. In the three-dimensional space of the nucleus, distal elements are localized in close physical proximity to the gene-proximal regulatory sequences through the formation of chromatin loops. These looping features in the genome are highly dynamic as embryonic stem cells differentiate and commit to specific lineages, and throughout reprogramming as differentiated cells reacquire pluripotency. Identifying these functional distal regulatory regions in the genome provides insight into the regulatory processes governing early mammalian development and guidance for improving the protocols that generate induced pluripotent cells.