Effectiveness of Robotic Intervention on Improving Social Development and Participation of Children with Autism Spectrum Disorder - A Randomised Controlled Trial.

Evidence-based robotic intervention programmes for children with autism spectrum disorder (ASD) have been limited. As yet, there is insufficient evidence to inform therapists, teachers, and service providers on effectiveness of robotic intervention to enhance social development and participation of children with ASD in a real context. This study used a randomised controlled trial to test the efficacy of robotic intervention programmes in enhancing the social development and participation of children with ASD. 60 children with ASD were included. The participants were randomly assigned to the following groups: (1) robotic intervention programme (n = 20), (2) human-instructed programme (n = 20), and (3) control group (n = 20). Both the performance-based behavioural change in social communication and parent-reported change in social responsiveness were evaluated. The participants in the robotic intervention group demonstrated statistically significant changes in both the performance-based assessment and parent-reported change in social participation. Significant differences were found in the communication and reciprocal social interactions scores between the experimental group and the control and comparison groups in the performance-based assessment (p < 0.01). The effectiveness of robotic intervention programme to enhance the social communication and participation was confirmed. Future studies may also consider adding a maintenance phase to document how the effects of the intervention carry over to the participants over a longer period. (Clinical trial number: NCT04879303; Date of registration: 10 May 2021).

Building and Testing of a Conceptual Model to Describe and Measure the Health of People as Affected by Post-traumatic Stress Disorder During Social Unrest: A Confirmatory Factor Analysis and Structural Equation Modeling.

Background: Social unrest affects people's health and well-being. People's health-related needs during social unrest are concerns in both research and clinical practice. This study aimed to build and test a framework to describe and understand the health status and needs of people with post-traumatic stress disorder (PTSD) during social unrest. Methods: This study was a cross-sectional survey. A total of 460 people who had experienced post-traumatic distress as a result of the social unrest in 2019 and 2020 were included. A conceptual model comprised four essential areas, namely posttraumatic distress symptoms, participation restrictions, perceived stigma and functional disability, was built from literature. Part 1 validated four instruments that evaluate and define the factor structure of these four areas, In Part II, structural equation modeling was used to test and validate a combined model. Results: Factors underlying the four areas were defined. Analysis using structural equation modeling confirmed a best fit of the model. PTSD symptoms, perceived stigma and participation restriction during social unrest contributed significantly to functional disability; PTSD symptoms exerted a direct effect on participation restriction and perceived stigma; and the effect of PTSD symptoms on functional disability was mediated through its influence on perceived stigma during social unrest. Conclusions: A community-based inclusive approach is essential to understand the holistic needs of people with PTSD during social unrest. To improve health and well-being in addition to evaluating mental health impacts, considering interactions with the rapid change and stressful social environment is essential.

Effect of human library intervention on mental health literacy: a multigroup pretest-posttest study.

BACKGROUND: Mental health literacy (MHL) is an evolving concept encompassing knowledge of mental illness, help-seeking options, perceived stigma, and discrimination. This study aimed to test the effectiveness of a human library intervention at enhancing MHL. A human library intervention was adopted to enhance MHL in this study. The human library intervention aims to establish a positive framework and safe space for dialogue between readers and a 'human book'. It works to promote dialogue, reduce prejudice, and encourage understanding of people who are regarded as disadvantaged or in a minority group. METHODS: An experimental approach with a multigroup pretest-posttest design was adopted. Forty-five participants aged between 18 and 23 years were recruited and randomly assigned to the experimental group (human library intervention), comparison group (didactic teaching session), or control group (no intervention). Adapted vignette-based MHL scale scores were used as the outcome measures. The overall and subscale scores were included in the analysis. RESULTS: The human library intervention group showed a significant improvement in overall MHL compared with the other two groups. In a multivariate analysis of the variance in subscale scores, the intervention was shown to significantly reduce stigma and preferred social distance, but had no significant effect on knowledge acquisition. CONCLUSIONS: The human library intervention is effective at enhancing overall MHL and reducing stigma and preferred social distance. Further studies are suggested to further develop the MHL construct, human library interventions, and the MHL scales for consolidating evidence-based practice.

Facilitating learning of community-based rehabilitation through problem-based learning in higher education.

BACKGROUND: The quality of community-based rehabilitation (CBR) personnel is one of the key factors that contributes to the success of CBR programs. Integrating knowledge and practical skills in various stages of the learning process is essential in community-based rehabilitation. Problem-based learning (PBL) is a pedagogical strategy that uses real-world situations as the basis for developing knowledge and problem-solving skills. Through PBL, learners are guided and facilitated in assuming active problem-solving roles in real-world situations. This study developed and tested a framework and a PBL protocol for use in teaching community-based rehabilitation (CBR) in higher education. METHODS: Part I of this study focused on the development of a framework and a protocol for PBL. An initial framework for the development of this protocol was formed based on a review of relevant literature. Concrete guidelines were delineated to describe the application, process, and delivery of teaching and learning. PBL was implemented in three CBR related courses. Students were facilitated to learn CBR in passing various stages of PBL through a self-directed learning process. The cumulative efforts of each group were compiled, recorded, and displayed using e-portfolios. In Part II, the processes and outcomes of using this new learning mode were evaluated using a case study approach to examine the protocol's efficacy. Focus group interviews, a questionnaire, and a detailed examination of the e-portfolios were administered for evaluation. RESULTS: One hundred thirty-three students from three CBR related courses were recruited. PBL was regarded as an effective, realistic and practical method that enables critical thinking in CBR. Practicality was addressed by covering context-related materials with the use of real cases or examples. Participants were actively engaged in the learning process and their CBR competence was enhanced. CONCLUSIONS: Through the new protocol, the students were equipped with active learning, critical thinking, and problem-solving skills that should facilitate success in CBR.

Daily Vaginal Swabs and Mobile Phone Sex Report for Assessing HIV Virion Exposure Prospectively Among a Cohort of Young Sexually Active Women in South Africa (HVTN 915).

BACKGROUND: Measurements of HIV exposure could help identify subpopulations at highest risk of acquisition and improve the design of HIV prevention efficacy trials and public health interventions. The HVTN 915 study evaluated the feasibility of self-administered vaginal swabs for detection of HIV virions to assess exposure. METHODS: Fifty 18- to 25-year-old sexually active HIV-seronegative women using contraception were enrolled in Soweto, South Africa. Participants self-administered daily vaginal swabs and answered sexual behavior questions through mobile phone for 90 days. Clinician-administered vaginal swabs, behavioral questionnaires, HIV diagnostic testing, and counseling were performed at 8 clinic visits. Glycogen concentrations assessed adherence to swabbing. Y-chromosome DNA (Yc-DNA) assessed the accuracy of reported condom use. HIV exposure was measured by virion polymerase chain reaction in swabs from 41 women who reported unprotected vaginal sex during follow-up. RESULTS: Glycogen was detected in 315/336 (93.8%) participant-collected and in all clinician-collected swabs. Approximately 20/39 daily swabs (51.3%) linked to mobile reports of unprotected sex tested positive for Yc-DNA, whereas 10/187 swabs collected after 3 days of abstinence or protected sex (5.3%) had detectable Yc-DNA. No participant became HIV infected during the study; yet, exposure to HIV was detected by nucleic acids in 2 vaginal swabs from 1 participant, collected less than 1 hour after coitus. CONCLUSION: There was high adherence to daily vaginal swabbing. Daily mobile surveys had accurate reporting of unprotected sex. Detection of HIV in self-collected vaginal swabs from an uninfected participant demonstrated it was possible to measure HIV exposure, but the detection rate was lower than expected.

Identifying evidence to define community-based rehabilitation practice in China using a case study approach with multiple embedded case study design.

BACKGROUND: This study examined community-based rehabilitation (CBR) practice in China on the basis of the development of an evaluation system using current evidence in a real context. METHODS: A multiple embedded case study design was used to interpret both quantitative and qualitative data. In Part 1, a thematic analysis was conducted to identify the different levels of evidence available in CBR programs in China. Identified themes were then associated with the literature to form a system to code, categorise, and rank the obtained evidence. In Part 2, CBR practice was examined in 12 CBR programs by using the developed evaluation system with the CBR matrix and CBR framework. RESULTS: Six themes under three categorised levels of evidence for demonstrating quality of practice were found. An evaluation system of program practice, based on existing standards to define levels of evidence, was created and used with the CBR matrix and CBR framework to evaluate the quality of practice in 12 CBR programs. The results of a within-case analysis revealed the strengths and areas for improvement in each program. An across-case analysis by using identified correlations revealed the characteristics of CBR practice in China, as demonstrated in the interaction of core CBR components. The content elements of CBR programs were significantly correlated with health outcomes, social development, education, and empowerment. Empowerment was significantly correlated with participant governance and community ownership. CONCLUSION: The proposed evaluation system, as developed in a real context, is feasible for monitoring and identifying the strengths of and areas for improvement in CBR programs. This study described the characteristics and interaction of different CBR components in CBR practice in China and is pertinent for enhancing the evidence-based practices and quality of CBR programs in China.

Validation of two scales for measuring participation and perceived stigma in Chinese community-based rehabilitation programs.

BACKGROUND: The World Health Organization has asserted the importance of enhancing participation of people with disabilities within the International Classification of Functioning, Disability and Health framework. Participation is regarded as a vital outcome in community-based rehabilitation. The actualization of the right to participate is limited by social stigma and discrimination. To date, there is no validated instrument for use in Chinese communities to measure participation restriction or self-perceived stigma. This study aimed to translate and validate the Participation Scale and the Explanatory Model Interview Catalogue (EMIC) Stigma Scale for use in Chinese communities with people with physical disabilities. METHODS: The Chinese versions of the Participation Scale and the EMIC stigma scale were administered to 264 adults with physical disabilities. The two scales were examined separately. The reliability analysis was studied in conjunction with the construct validity. Reliability analysis was conducted to assess the internal consistency and item-total correlation. Exploratory factor analysis was conducted to investigate the latent patterns of relationships among variables. A Rasch model analysis was conducted to test the dimensionality, internal validity, item hierarchy, and scoring category structure of the two scales. RESULTS: Both the Participation Scale and the EMIC stigma scale were confirmed to have good internal consistency and high item-total correlation. Exploratory factor analysis revealed the factor structure of the two scales, which demonstrated the fitting of a pattern of variables within the studied construct. The Participation Scale was found to be multidimensional, whereas the EMIC stigma scale was confirmed to be unidimensional. The item hierarchies of the Participation Scale and the EMIC stigma scale were discussed and were regarded as compatible with the cultural characteristics of Chinese communities. CONCLUSION: The Chinese versions of the Participation Scale and the EMIC stigma scale were thoroughly tested in this study to demonstrate their robustness and feasibility in measuring the participation restriction and perceived stigma of people with physical disabilities in Chinese communities. This is crucial as it provides valid measurements to enable comprehensive understanding and assessment of the participation and stigma among people with physical disabilities in Chinese communities.

DataPackageR: Reproducible data preprocessing, standardization and sharing using R/Bioconductor for collaborative data analysis.

A central tenet of reproducible research is that scientific results are published along with the underlying data and software code necessary to reproduce and verify the findings. A host of tools and software have been released that facilitate such work-flows and scientific journals have increasingly demanded that code and primary data be made available with publications. There has been little practical advice on implementing reproducible research work-flows for large 'omics' or systems biology data sets used by teams of analysts working in collaboration. In such instances it is important to ensure all analysts use the same version of a data set for their analyses. Yet, instantiating relational databases and standard operating procedures can be unwieldy, with high "startup" costs and poor adherence to procedures when they deviate substantially from an analyst's usual work-flow. Ideally a reproducible research work-flow should fit naturally into an individual's existing work-flow, with minimal disruption. Here, we provide an overview of how we have leveraged popular open source tools, including Bioconductor, Rmarkdown, git version control, R, and specifically R's package system combined with a new tool DataPackageR, to implement a lightweight reproducible research work-flow for preprocessing large data sets, suitable for sharing among small-to-medium sized teams of computational scientists. Our primary contribution is the DataPackageR tool, which decouples time-consuming data processing from data analysis while leaving a traceable record of how raw data is processed into analysis-ready data sets. The software ensures packaged data objects are properly documented and performs checksum verification of these along with basic package version management, and importantly, leaves a record of data processing code in the form of package vignettes. Our group has implemented this work-flow to manage, analyze and report on pre-clinical immunological trial data from multi-center, multi-assay studies for the past three years.

Outcomes and impact of community-based rehabilitation programmes in Chinese communities.

PURPOSE: To identify the most common and most valued outcomes of community-based rehabilitation (CBR) in Chinese communities and to map these to the CBR evaluation framework. METHOD: A multiple, embedded case study design was used. Four CBR programmes in China met the criteria for inclusion and participated. Data collection, via participant "story telling", followed the procedures of the most significant change technique (MSC) over a period for five months. Content analysis with thematic coding was used to detect the common significant changes described in "top-rated" stories and in the entire pool of stories. Meta-analysis using the CBR framework was carried out to enrich the understanding of programme outcomes. RESULTS: A total of 101 stories were collected in the two rounds of story collection from the four programmes. Aggregated results demonstrated that, across all programmes, 78.21% of stories focused on changes in people with disabilities, 9.9% described aspects of programme development, 8.91% reported on outcomes related to CBR workers, and only 2.97% were focused on advocacy. When mapped against the elements of the CBR framework the MSCs among these four programmes were (1) psychosocial changes, (2) increased family participation and (3) improved physical functioning. CONCLUSIONS: CBR practice in Chinese communities remains orientated towards an approach of functional rehabilitation rather than community-based inclusive development. Implications for rehabilitation Community-based rehabilitation is a strategy for community-based inclusive development. Commonly reported significant outcomes of community-based rehabilitation programmes in China focus on changes in psychosocial and physical status of people with disabilities and family participation. Community-based rehabilitation in China continues to focus on traditional rehabilitation. New efforts and directions are needed to also include goals of equity and community inclusion. Further efforts to promote the use of CBR guideline with the goal of facilitating inclusion and equal participation are strongly recommended.

The Outcomes and Impact of a Post-Earthquake Rehabilitation Program in China: A Qualitative Study.

This study evaluated the outcomes and impact of a post-earthquake rehabilitation program in Sichuan, China. A case-study approach was adopted to conduct an in-depth examination of the program. The results show that the program effectively enhanced the functional outcomes of earthquake survivors. However, the empowerment of earthquake survivors with disabilities requires further consideration, and the local community's ownership of the program must also be addressed. A combination of institution- and community-based approaches was advocated in developing the post-earthquake rehabilitation program to enhance its impact on the local community.

Constitutive MAP kinase activation in hematopoietic stem cells induces a myeloproliferative disorder.

Myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPNs) are a group of myeloid neoplasms in which abnormal activation of the Ras signaling pathway is commonly observed. The PI3K/Akt pathway is a known target of Ras; however, activation of the PI3K/Akt pathway has been shown to lead to neoplastic transformation of not only myeloid but also lymphoid cells, suggesting that pathways other than the PI3K/Akt pathway should play a central role in pathogenesis of Ras-mediated MDS/MPN. The MEK/ERK pathway is another downstream target of Ras, which is involved in regulation of cell survival and proliferation. However, the role of the MEK/ERK pathway in the pathogenesis of MDS/MPN remains unclear. Here, we show that introduction of a constitutively activated form of MEK into hematopoietic stem cells (HSCs) causes hematopoietic neoplasms that are limited to MDS/MPNs, despite the multipotent differentiation potential of HSCs. Active MEK-mediated MDS/MPNs are lethal, but are not considered a frank leukemia because it cannot be transplanted into naïve animals. However, transplantation of MDS/MPNs co-expressing active MEK and an anti-apoptotic molecule, Bcl-2, results in T-cell acute lymphocytic leukemia (T-ALL), suggesting that longevity of cells may impact transplantability and alter disease phenotype. Our results clearly demonstrate the proto-oncogenic property of the MEK/ERK pathway in hematopoietic cells, which manifest in MDS/MPN development.

Role of Ras/Raf/MEK/ERK signaling in physiological hematopoiesis and leukemia development.

Recent research on hematological malignancies has shown that malignant cells often co-opt physiological pathways to promote their growth and development. Bone marrow homeostasis requires a fine balance between cellular differentiation and self-renewal; cell survival and apoptosis; and cellular proliferation and senescence. The Ras/Raf/MEK/ERK pathway has been shown to be important in regulating these biological functions. Moreover, the Ras/Raf/MEK/ERK pathway has been estimated to be mutated in 30% of all cancers, thus making it the focus of many scientific studies which have lead to a deeper understanding of cancer development and help to elucidate potential weaknesses that can be targeted by pharmacological agents [1]. In this review, we specifically focus on the role of this pathway in physiological hematopoiesis and how augmentation of the pathway may lead to hematopoietic malignancies. We also discuss the challenges and success of targeting this pathway.

A framework for evaluating community-based rehabilitation programmes in Chinese communities.

PURPOSE: The primary aim of this study was to develop an evaluation framework that could effectively describe the quality of community-based rehabilitation (CBR) practice in Chinese communities. METHOD: This study adopted a case study approach to build and validate a CBR evaluation framework. Core elements of CBR programmes were defined from the literature to form an Initial Framework. Domains and elements of the Initial Framework were then verified with examples of CBR programmes cited in published articles. The revised framework was then further tested for relevance and appropriateness in the real life context through testing in five Chinese CBR programmes. RESULTS: A final framework for evaluating CBR programmes was developed. It consists of 5 domains, 25 categorised core elements and 72 indicators. CONCLUSION: A comprehensive CBR evaluation framework was built and initially verified with domains, elements and indicators, and is ready for use in Chinese CBR settings.

When East meets Wests: community-based rehabilitation in Chinese communities.

PURPOSE: Community-based rehabilitation (CBR) has been practiced in mainland China for over three decades. This study reviews the development of CBR and describes its practice in Chinese communities in order to discuss current controversies within CBR practice internationally and in the Chinese context. METHOD: Review of literature. Development of CBR, its principles and controversies internationally and in the Eastern world is reviewed. CBR practice in Chinese communities is examined. RESULTS: Shifting ideology and practices mean many different activities are labelled CBR. Variation across contexts has led to many controversies, specifically: the lack of evidence to support practice; ownership of programs; conceptual differences surrounding autonomy and participation and cultural issues. Contemporary Chinese cultural values and Chinese CBR are shaped by traditional peasant culture, traditional Chinese philosophy and socialist ideology. CONCLUSION: The review indicates that Western CBR concepts and philosophy cannot be directly applied to the Chinese context. An appropriate model or framework is needed to fit the unique Chinese cultural context and to guide practice in Chinese communities.

HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells.

Infection with human immunodeficiency virus 1 (HIV-1) results in the dissemination of virus to gut-associated lymphoid tissue. Subsequently, HIV-1 mediates massive depletion of gut CD4+ T cells, which contributes to HIV-1-induced immune dysfunction. The migration of lymphocytes to gut-associated lymphoid tissue is mediated by integrin alpha4beta7. We demonstrate here that the HIV-1 envelope protein gp120 bound to an activated form of alpha4beta7. This interaction was mediated by a tripeptide in the V2 loop of gp120, a peptide motif that mimics structures presented by the natural ligands of alpha4beta7. On CD4+ T cells, engagement of alpha4beta7 by gp120 resulted in rapid activation of LFA-1, the central integrin involved in the establishment of virological synapses, which facilitate efficient cell-to-cell spreading of HIV-1.

R5 and X4 HIV envelopes induce distinct gene expression profiles in primary peripheral blood mononuclear cells.

HIV envelope binds to and signals through its primary cellular receptor, CD4, and through a coreceptor, either CC chemokine receptor 5 (CCR5) or CXC chemokine receptor 4 (CXCR4). Here, we evaluate the response of peripheral blood mononuclear cells to a panel of genetically diverse R5 and X4 envelope proteins. Modulation of gene expression was evaluated by using oligonucleotide microarrays. Activation of transcription factors was evaluated by using an array of oligonucleotides encoding transcription factor binding sites. Responses were strongly influenced by coreceptor specificity. Treatment of cells from CCR5delta32 homozygous donors with glycoprotein (gp)120 derived from an R5 virus demonstrated that the majority of responses elicited by R5 envelopes required engagement of CCR5. R5 envelopes, to a greater extent than X4 envelopes, induced the expression of genes belonging to mitogen-activated protein kinase signal transduction pathways and genes regulating the cell cycle. A number of genes induced by R5, but not X4, envelopes were also up-regulated in the resting CD4+ T cell population of HIV-infected individuals. These results suggest that R5 envelope facilitates replication of HIV in the pool of resting CD4+ T cells. Additionally, signaling by R5 gp120 may facilitate the transmission of R5 viruses by inducing a permissive environment for HIV replication.

HIV-1 gp120 induces NFAT nuclear translocation in resting CD4+ T-cells.

The replication of human immunodeficiency virus (HIV) in CD4+ T-cells is strongly dependent upon the state of activation of infected cells. Infection of sub-optimally activated cells is believed to play a critical role in both the transmission of virus and the persistence of CD4+ T-cell reservoirs. There is accumulating evidence that HIV can modulate signal-transduction pathways in a manner that may facilitate replication in such cells. We previously demonstrated that HIV gp120 induces virus replication in resting CD4+ T cells isolated from HIV-infected individuals. Here, we show that in resting CD4+ T-cells, gp120 activates NFATs and induces their translocation into the nucleus. The HIV LTR encodes NFAT recognition sites, and NFATs may play a critical role in promoting viral replication in sub-optimally activated cells. These observations provide insight into a potential mechanism by which HIV is able to establish infection in resting cells, which may have implications for both transmission of HIV and the persistence of viral reservoirs.

Targeted lysis of HIV-infected cells by natural killer cells armed and triggered by a recombinant immunoglobulin fusion protein: implications for immunotherapy.

Natural killer (NK) cells play an important role in both innate and adaptive antiviral immune responses. The adaptive response typically requires that virus-specific antibodies decorate infected cells which then direct NK cell lysis through a CD16 mediated process termed antibody-dependent cellular cytotoxicity (ADCC). In this report, we employ a highly polymerized chimeric IgG1/IgA immunoglobulin (Ig) fusion protein that, by virtue of its capacity to extensively crosslink CD16, activates NK cells while directing the lysis of infected target cells. We employ HIV as a model system, and demonstrate that freshly isolated NK cells preloaded with an HIV gp120-specific chimeric IgG1/IgA fusion protein efficiently lyse HIV-infected target cells at picomolar concentrations. NK cells pre-armed in this manner retain the capacity to kill targets over an extended period of time. This strategy may have application to other disease states including various viral infections and cancers.