Cytotoxicity-related Gene Expression and Chromatin Accessibility Define a Subset of CD4+ T Cells that Mark Progression to Type 1 Diabetes

Type 1 diabetes in children is heralded by a preclinical phase defined by circulating autoantibodies to pancreatic islet antigens. How islet autoimmunity is initiated and then progresses to clinical diabetes remains poorly understood. Only one study has reported gene expression in specific immune cells of at-risk children, associated with progression to islet autoimmunity. We analysed gene expression by RNAseq in CD4⁺ and CD8⁺ T cells, NK cells and B cells, and chromatin accessibility by ATACseq in CD4⁺ T cells, in five genetically at-risk children with islet autoantibodies who progressed to diabetes over a median of 3 years (‘Progressors’) compared to five children matched for sex, age and HLA-DR who had not progressed (‘Non-progressors). In Progressors, differentially expressed genes (DEGs) were largely confined to CD4⁺ T cells and enriched for cytotoxicity-related genes/pathways. Several top-ranked DEGs were validated in a semi-independent cohort of 13 Progressors and 11 Non-progressors. Flow cytometry confirmed progression was associated with expansion of CD4⁺cells with a cytotoxic phenotype. By ATAC-seq, progression was associated with reconfiguration of regulatory chromatin regions in CD4⁺cells, some linked to differentially expressed cytotoxicity-related genes. Our findings suggest that cytotoxic CD4⁺T cells play a role in promoting progression to type 1 diabetes.

Cytotoxicity-related Gene Expression and Chromatin Accessibility Define a Subset of CD4+ T Cells that Mark Progression to Type 1 Diabetes

Type 1 diabetes in children is heralded by a preclinical phase defined by circulating autoantibodies to pancreatic islet antigens. How islet autoimmunity is initiated and then progresses to clinical diabetes remains poorly understood. Only one study has reported gene expression in specific immune cells of at-risk children, associated with progression to islet autoimmunity. We analysed gene expression by RNAseq in CD4⁺ and CD8⁺ T cells, NK cells and B cells, and chromatin accessibility by ATACseq in CD4⁺ T cells, in five genetically at-risk children with islet autoantibodies who progressed to diabetes over a median of 3 years (‘Progressors’) compared to five children matched for sex, age and HLA-DR who had not progressed (‘Non-progressors). In Progressors, differentially expressed genes (DEGs) were largely confined to CD4⁺ T cells and enriched for cytotoxicity-related genes/pathways. Several top-ranked DEGs were validated in a semi-independent cohort of 13 Progressors and 11 Non-progressors. Flow cytometry confirmed progression was associated with expansion of CD4⁺cells with a cytotoxic phenotype. By ATAC-seq, progression was associated with reconfiguration of regulatory chromatin regions in CD4⁺cells, some linked to differentially expressed cytotoxicity-related genes. Our findings suggest that cytotoxic CD4⁺T cells play a role in promoting progression to type 1 diabetes.

Cytotoxicity-related gene expression and chromatin accessibility define a subset of CD4+ T cells that mark progression to type 1 diabetes

Type 1 diabetes in children is heralded by a preclinical phase defined by circulating autoantibodies to pancreatic islet antigens. How islet autoimmunity is initiated and then progresses to clinical diabetes remains poorly understood. Only one study has reported gene expression in specific immune cells of at-risk children, associated with progression to islet autoimmunity. We analysed gene expression by RNAseq in CD4+ and CD8+ T cells, NK cells and B cells, and chromatin accessibility by ATACseq in CD4+ T cells, in five genetically at-risk children with islet autoantibodies who progressed to diabetes over a median of 3 years (‘Progressors’) compared to five children matched for sex, age and HLA-DR who had not progressed (‘Non-progressors). In Progressors, differentially expressed genes (DEGs) were largely confined to CD4+ T cells and enriched for cytotoxicity-related genes/pathways. Several top-ranked DEGs were validated in a semi-independent cohort of 13 Progressors and 11 Non-progressors. Flow cytometry confirmed progression was associated with expansion of CD4+ cells with a cytotoxic phenotype. By ATAC-seq, progression was associated with reconfiguration of regulatory chromatin regions in CD4+ T cells, some linked to differentially expressed cytotoxicity-related genes. Our findings suggest that cytotoxic CD4+ T cells play a role in promoting progression to type 1 diabetes.

Below Average Cognitive Ability—An under Researched Risk Factor for Emotional-Behavioural Difficulties in Childhood

Children with below average cognitive ability represent a substantial yet under-researched population for whom cognitive and social demands, which increase in complexity year by year, may pose significant challenges. This observational study examines the longitudinal relationship between early cognitive ability and emotional-behavioral difficulties (EBDs) between the age of three and nine. Participants include 7134 children from the population-based cohort study growing up in Ireland. Cognitive ability was measured at age three using the Picture Similarities Scale. A t-score one to two standard deviations below the mean was defined as below average cognitive ability (n = 767). EBDs were measured using the Strengths and Difficulties Questionnaire (SDQ) at three, five, and nine years of age. Generalized linear mixed models and logistic regression were used to examine the relationship. Below average cognitive ability was an independent predictor of higher longitudinal SDQ scores. After adjustment, children with below average cognitive ability were 1.39 times more likely (AOR 1.39, 95% CI 1.17–1.66, p < 0.001) to experience a clinically significant EBD between the ages of three to nine years. This study demonstrates the increased risk of EBDs for children with below average cognitive ability. A scalable method of early identification of at-risk children should be a research priority for public health, enabling early intervention for cognitive and adaptive outcomes.

The New European Political Arithmetic of Inequalities in Education: A History of the Present

The article describes the emergence and development of positive epistemology and quantification tools in the dynamics of inequalities in education. It contributes to a history of the present at a time when datafication and experimentalism are reappearing in educational policies to justify the reduction of inequalities across international surveys and randomised controlled trials. This socio‐history of metrics also sheds light on transformations about relationships historically established between the welfare state and education that have shaped the representation of inequalities and social programs in education. The use of large‐scale surveys and controlled experiments in social and educational policies developed in the 1920s and 30s, even if their methods and techniques have become more sophisticated due to statistical progress. However, statistical reasoning is today no less persuasive in justifying the measurement of student skills and various forms of state intervention for “at‐risk” children and youth. With the rise of international organisations, notably the European Commission, demographic issues related to school population and the reduction of inequalities have shifted. It is less a question of selecting the most talented or gifted among working‐class students than of investing in human capital from early childhood to improve the education systems’ performance and competitiveness for the lifelong learning economy and European social investment strategy. This article attempts to illustrate this new arithmetic of inequalities in education at the European level.

Prevalence of Iodine Deficiency among School Children from New Settlement in Kyrgyzstan

This study assesses the status of iodine deficiency among at risk-children and adolescents living in migrant settlements in the Kyrgyz Republic. Children aged 7–15 years from two regional primary schools in the new settlement regions were screened for cognitive and behavioural signs of iodine deficiency using questionnaires. The functional state of the thyroid gland was assessed using ultrasonography and blood tests. Out of 1058 schoolchildren, 15.8% showed signs of iodine deficiency. Female children aged 10–12 years showed a higher prevalence of iodine deficiency. The families of schoolchildren reported limited use of seafood and iodised salt. Children in the migrant regions were at risk of iodine deficiency disorder. Among children, clinical manifestations of iodine deficiency were observed as negative hormonal levels or the presence of goitre. Further investigation on standardised screening instruments for iodine deficiency and the relationship among multilevel analyses are warranted.

STATE POLICY OF SOCIAL PROTECTION OF CHILDREN AS A SOCIAL SAFETY FACTOR: HISTORICAL EXPERIENCE OF EUROPEAN COUNTRIES FROM THE 17th to 21th CENTURIES.

The historical aspect of the development of state social policy of social protection of children in Europe from the 17th to 21th centuries is considered in the article. The purpose of the article is to highlight the peculiarities of the historical development of the state policy of social protection of children in European countries of the 17th to 21th centuries and learning from the experience of social protection of children in the context of Ukraine's European integration. The regulatory framework of the system of social protection of children in Ukraine has been studied. The statistic on different categories of children in need of social protection by the state is analyzed. The structure of the system of social protection of children in Ukraine is considered. The research methodology is based on the principle of priority of universal human values. As part of the tools of the proposed work the theoretical one is the analysis and generalization of scientific sources, educational and methodological publications on the theme and synthesis, as well as comparison and generalization of data. Based on the analysis of materials on the peculiarities of social protection in the UK, Germany, France, Sweden and Norway, it was determined that the social protection of children in Europe is characterized by assistance to them in providing conditions for the realization of their rights and freedoms. Equally important is the setting up of various charitable institutions, schools, penal colonies that help children change, as well as the emergence of social services that protect the rights and interests of children. The authors suggest that in the course of the studying the history of the issue of state policy of children’s social protection, there is an opportunity for analogies, the implementation of already proven steps on the path of democratization of national social protection policy. The researchers see the prospects for further research in the study of global innovative forms of social protection and support for at-risk children.

Back to school with asthma in 2021

September is a peak time for asthma exacerbations in school-aged children. Heather Henry looks at the role of the general practice nurse in reducing this risk Each September marks a peak in asthma exacerbations in children returning to school for the autumn term. Children and families face the challenges of disturbed asthma management regimes, seasonal infections and asthma triggers. This year presents an additional challenge, coming as it does during a global pandemic, with primary care at breaking point. This article presents a pragmatic approach to prioritising the most at-risk children.