Transcriptomic atlas and interaction networks of brain cells in mouse CNS demyelination and remyelination

Demyelination is a hallmark of multiple sclerosis, leukoencephalopathies, cerebral vasculopathies, and several neurodegenerative diseases. The cuprizone mouse model is widely used to simulate demyelination and remyelination occurring in these diseases. Here, we present a high-resolution single-nucleus RNA sequencing (snRNA-seq) analysis of gene expression changes across all brain cells in this model. We define demyelination-associated oligodendrocytes (DOLs) and remyelination-associated MAF

Addressing Risks of Lead in Water and Soil: Using Citizen Science and a Unique Partnership with Faith Organizations

One of the most widespread environmental health hazards in the United States remains exposure to the harmful neurotoxin lead. So much lead remains in the urban environment that it is not unusual to find neighborhoods where more than 10% of children exhibit harmful levels of lead, compared to the national average of about 1%. To overcome this challenge, a partnership between IUPUI researchers and faith organizations in Indianapolis is taking aim at the risk of household lead contamination by providing residents the tools they need to protect against it. The community-driven science aspect of this project is intentional—not only will the individuals who participate benefit directly, but the resulting data will also play a role in keeping communities safer more broadly

BRITAIN, THE TWO WORLD WARS, AND THE PROBLEM OF NARRATIVE

AbstractThe concept of coming to terms with the past originated in post-1945 West Germany but such historical therapy is evident in all the belligerent countries. In that process, the two world wars are intricately connected, each seen refractively through the prism of the other. This article focuses on Britain whose national obsession with the two world wars is particularly acute. The first and second sections suggest that British public discourse has been able to construct a satisfying narrative of 1939–45 but not of 1914–18, meaning a narrative that has both a clear beginning, middle, and end and also a stark moral meaning. Viable narratives draw on the events themselves, the words used to conceptualize them, and the interpretations of 'instant' histories and memoirs. The third section argues that the elevation of 1939–45 in national discourse as our ‘finest hour’ (Churchill) has aggravated the problematic nature of 1914–18 for the British. In the wake of Brexit, the last section argues that Britain – unlike France and Germany – has found it difficult to move on from the era of the two world wars by locating these conflicts in a more positive narrative of the twentieth century as the eventual triumph of European integration.</jats:p

Tolerance of uncertainty: A systematic review of health and healthcare-related outcomes.

BACKGROUND: Uncertainty tolerance (UT) is thought to be a characteristic of individuals that influences various outcomes related to health, healthcare, and healthcare education. We undertook a systematic literature review to evaluate the state of the evidence on UT and its relationship to these outcomes. METHODS: We conducted electronic and bibliographic searches to identify relevant studies examining associations between UT and health, healthcare, or healthcare education outcomes. We used standardized tools to assess methodological quality and analyzed the major findings of existing studies, which we organized and classified by theme. RESULTS: Searches yielded 542 potentially relevant articles, of which 67 met inclusion criteria. Existing studies were heterogeneous in focus, setting, and measurement approach, were largely cross-sectional in design, and overall methodological quality was low. UT was associated with various trainee-centered, provider-centered, and patient-centered outcomes which were cognitive, emotional, and behavioral in nature. UT was most consistently associated with emotional well-being. CONCLUSIONS: Uncertainty tolerance is associated with several important trainee-, provider-, and patient-centered outcomes in healthcare and healthcare education. However, low methodological quality, study design limitations, and heterogeneity in the measurement of UT limit strong inferences about its effects, and addressing these problems is a critical need for future research

Tolerance of uncertainty: A systematic review of health and healthcare-related outcomes

Background: Uncertainty tolerance (UT) is thought to be a characteristic of individuals that influences various outcomes related to health, healthcare, and healthcare education. We undertook a systematic literature review to evaluate the state of the evidence on UT and its relationship to these outcomes. Methods: We conducted electronic and bibliographic searches to identify relevant studies examining associations between UT and health, healthcare, or healthcare education outcomes. We used standardized tools to assess methodological quality and analyzed the major findings of existing studies, which we organized and classified by theme. Results: Searches yielded 542 potentially relevant articles, of which 67 met inclusion criteria. Existing studies were heterogeneous in focus, setting, and measurement approach, were largely cross-sectional in design, and overall methodological quality was low. UT was associated with various trainee-centered, provider-centered, and patient-centered outcomes which were cognitive, emotional, and behavioral in nature. UT was most consistently associated with emotional well-being. Conclusions: Uncertainty tolerance is associated with several important trainee-, provider-, and patient-centered outcomes in healthcare and healthcare education. However, low methodological quality, study design limitations, and heterogeneity in the measurement of UT limit strong inferences about its effects, and addressing these problems is a critical need for future research

The MothersBabies Study: analysing the preconception microbiome to determine risk of adverse maternal-child health outcomes

The microbiome has been recognised as a key determinant of health, and it is now accepted that the development of a person’s microbiome begins well before birth and has the ability to exert effects on the health of the next generation, with preconception health conditions and lifestyle choices playing significant contributors. The MothersBabies Study hypothesises there are microbiome signatures and early life exposures that contribute or predict adverse pregnancy outcomes (GDM, pre-eclampsia, excessive gestational weight gain, perinatal mood disorders) and postnatal long-term health outcomes for both mother and child. It is a longitudinal cohort study of 2000 mother-infant pairs commencing from preconception followed through to two years postpartum. Assessments of stool, vaginal, oral, blood, urine and skin microbiomes using a multiomic approach (metagenomics, metabolomics, host genomics) is undertaken, as well as anthropometric, metabolic, dietary and cognitive parameter assessments. This will determine the association between multi-site microbiomes and preconception risk to determine if the microbiome can successfully categorise maternal-health risk prior to conception. The microbiome is examined for two years postpartum, to determine if these preconception and pregnancy exposures impact on the growth and development of the child. The study aims to determine microbiome biomarkers that can be used to identify and manage risk, and construct predictive computational models that incorporate novel microbiome signatures and traditional preconception metadata for use in future preconception clinical care. By the conclusion, we expect to know what microbes influence future development of adverse pregnancy and postnatal outcomes for both mother and child. Early stratification of risk in the preconception phase will ensure women can be adequately managed, therefore shifting current maternal-child health practice towards prevention of disease. It will also provide the foundation for future interventional trials to manipulate the microbiome towards a low-risk state in the preconception period. This ongoing research will determine feasibility of preconception screening clinics coordinated by trained health professionals, ensuring high quality, comprehensive preconception care so that everyone can make informed decisions about what influences maternal health and child development

Polysaccharide Capsules Equip the Human Symbiont Bacteroides thetaiotaomicron to Modulate Immune Responses to a Dominant Antigen in the Intestine

Bacteria express multiple diverse capsular polysaccharides (CPSs) for protection against environmental and host factors, including the host immune system. Using a mouse TCR transgenic CD4+ T cell, BθOM, that is specific for B. thetaiotaomicron and a complete set of single CPS-expressing B. thetaiotaomicron strains, we ask whether CPSs can modify the immune responses to specific bacterial Ags. Acapsular B. thetaiotaomicron, which lacks all B. thetaiotaomicron CPSs, stimulated BθOM T cells more strongly than wild-type B. thetaiotaomicron Despite similar levels of BθOM Ag expression, many single CPS-expressing B. thetaiotaomicron strains were antistimulatory and weakly activated BθOM T cells, but a few strains were prostimulatory and strongly activated BθOM T cells just as well or better than an acapsular strain. B. thetaiotaomicron strains that expressed an antistimulatory CPS blocked Ag delivery to the immune system, which could be rescued by Fc receptor-dependent Ab opsonization. All single CPS-expressing B. thetaiotaomicron strains stimulated the innate immune system to skew toward M1 macrophages and release inflammatory cytokines in an MyD88-dependent manner, with antistimulatory CPS activating the innate immune system in a weaker manner than prostimulatory CPS. The expression of antistimulatory versus prostimulatory CPSs on outer membrane vesicles also regulated immune responses. Moreover, antistimulatory and prostimulatory single CPS-expressing B. thetaiotaomicron strains regulated the activation of Ag-specific and polyclonal T cells as well as clearance of dominant Ag in vivo. These studies establish that the immune responses to specific bacterial Ags can be modulated by a diverse set of CPSs