A multilevel intervention to increase physical activity and improve healthy eating and physical literacy among young children (ages 3-5) attending early childcare centres: the Healthy Start-Départ Santé cluster randomised controlled trial study protocol

Abstract: Background: Childhood obesity is a growing concern for public health. Given a majority of children in many countries spend approximately 30 h per week in early childcare centers, this environment represents a promising setting for implementing strategies to foster healthy behaviours for preventing and controlling childhood obesity. Healthy Start-Départ Santé was designed to promote physical activity, physical literacy, and healthy eating among preschoolers. The objectives of this study are to assess the effectiveness of the Healthy Start-Départ Santé intervention in improving physical activity levels, physical literacy, and healthy eating among preschoolers attending early childcare centers. Methods/Design: This study follows a cluster randomized controlled trial design in which the childcare centers are randomly assigned to receive the intervention or serve as usual care controls. The Healthy Start-Départ Santé intervention is comprised of interlinked components aiming to enable families and educators to integrate physical activity and healthy eating in the daily lives of young children by influencing factors at the intrapersonal, interpersonal, organizational, community, physical environment and policy levels. The intervention period, spanning 6-8 months, is preceded and followed by data collections. Participants are recruited from 61 childcare centers in two Canadian provinces, New Brunswick and Saskatchewan. Centers eligible for this study have to prepare and provide meals for lunch and have at least 20 children between the ages of 3 and 5. Centers are excluded if they have previously received a physical activity or nutrition promoting intervention. Eligible centers are stratified by province, geographical location (urban or rural) and language (English or French), then recruited and randomized using a one to one protocol for each stratum. Data collection is ongoing. The primary study outcomes are assessed using accelerometers (physical activity levels), the Test of Gross Motor Development-II (physical literacy), and digital photography-assisted weighted plate waste (food intake). Discussion: The multifaceted approach of Healthy Start-Départ Santé positions it well to improve the physical literacy and both dietary and physical activity behaviors of children attending early childcare centers. The results of this study will be of relevance given the overwhelming prevalence of overweight and obesity in children worldwide. Trial registration: NCT02375490 (ClinicalTrials.gov registry)

Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases

Microglial activation plays central roles in neuroinflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18 kDa Translocator Protein (TSPO) is widely used for localising inflammation in vivo, but its quantitative interpretation remains uncertain. We show that TSPO expression increases in activated microglia in mouse brain disease models but does not change in a non-human primate disease model or in common neurodegenerative and neuroinflammatory human diseases. We describe genetic divergence in the TSPO gene promoter, consistent with the hypothesis that the increase in TSPO expression in activated myeloid cells depends on the transcription factor AP1 and is unique to a subset of rodent species within the Muroidea superfamily. Finally, we identify LCP2 and TFEC as potential markers of microglial activation in humans. These data emphasise that TSPO expression in human myeloid cells is related to different phenomena than in mice, and that TSPO-PET signals in humans reflect the density of inflammatory cells rather than activation state.Published versionThe authors thank the UK MS Society for financial support (grant number: C008-16.1). DRO was funded by an MRC Clinician Scientist Award (MR/N008219/1). P.M.M. acknowledges generous support from Edmond J Safra Foundation and Lily Safra, the NIHR Senior Investigator programme and the UK Dementia Research Institute which receives its funding from DRI Ltd., funded by the UK Medical Research Council, Alzheimer’s Society, and Alzheimer’s Research UK. P.M.M. and D.R.O. thank the Imperial College Healthcare Trust-NIHR Biomedical Research Centre for infrastructure support and the Medical Research Council for support of TSPO studies (MR/N016343/1). E.A. was supported by the ALS Stichting (grant “The Dutch ALS Tissue Bank”). P.M. and B.B.T. are funded by the Swiss National Science Foundation (projects 320030_184713 and 310030_212322, respectively). S.T. was supported by an “Early Postdoc.Mobility” scholarship (P2GEP3_191446) from the Swiss National Science Foundation, a “Clinical Medicine Plus” scholarship from the Prof Dr. Max Cloëtta Foundation (Zurich, Switzerland), from the Jean et Madeleine Vachoux Foundation (Geneva, Switzerland) and from the University Hospitals of Geneva. This work was funded by NIH grants U01AG061356 (De Jager/Bennett), RF1AG057473 (De Jager/Bennett), and U01AG046152 (De Jager/Bennett) as part of the AMP-AD consortium, as well as NIH grants R01AG066831 (Menon) and U01AG072572 (De Jager/St George-Hyslop)

The impact of digital health technologies on tuberculosis treatment : a systematic review

Digital technologies are increasingly harnessed to support treatment of persons with tuberculosis (TB). Since in-person directly observed treatment (DOT) can be resource intensive and challenging to implement, these technologies may have the potential to improve adherence and clinical outcomes. We reviewed the effect of these technologies on TB treatment adherence and patient outcomes. We searched several bibliographical databases for studies reporting the effect of digital interventions, including short message service (SMS), video-observed therapy (VOT) and medication monitors (MMs), to support treatment for active TB. Only studies with a control group and which reported effect estimates were included. Four trials showed no statistically significant effect on treatment completion when SMS was added to standard care. Two observational studies of VOT reported comparable treatment completion rates when compared with in-person DOT. MMs increased the probability of cure (RR 2.3, 95% CI 1.6-3.4) in one observational study, and one trial reported a statistically significant reduction in missed treatment doses relative to standard care (adjusted means ratio 0.58, 95% CI 0.42-0.79). Evidence of the effect of digital technologies to improve TB care remains limited. More studies of better quality are needed to determine how such technologies can enhance programme performance

CMB-S4

We describe the stage 4 cosmic microwave background ground-based experiment CMB-S4

Tracing the transformation of hematopoietic stem cells into leukemic cells using single-cell multi-omics

Cancer is a leading cause of death worldwide. While most cells have a limited lifespan, cancer stem cells can self-renew indefinitely and are thought to drive disease initiation, progression, and relapse. A major challenge in the development of chemotherapies is the necessity to specifically target these cancer-driving stem cells while sparing their healthy counterparts, which are phenotypically very similar. While non-genetic heterogeneity and the presence of stem cell hierarchies have significant clinical implications, the genetic het-erogeneity that contributes to a cancer’s ability to resist drug treatment represents a major obstacle in devising effective therapeutics. Using acute myeloid leukemia as a model system, we investigate the transformation of healthy hematopoietic stem cells into cancer stem cells. By combining single-cell transcriptomics and mutation-based lineage tracing, we single out the putative cancer "cells-of-origin" and pinpoint the mutations that precede and drive oncogenic transformation. We first apply single-cell transcriptomics to classify blood cells according to their differentiation state and cell type. Then using mutations detected in RNA, we identify healthy, pre-leukemic, and leukemic clones to create maps of their evolutionary trajectories and elucidate the patterns in clonal structure underlying leukemia. Taken together, we characterize blood cancer stem cells with high transcriptomic resolution. We further demonstrate the ability to detect clonal mitochondrial and nuclear mutations in single cells, allowing for the computational delineation of the order in which mutations arose, the assignment of cells to clones, and the discovery of novel clones. This approach also identifies differentiation blocks and unique gene-expression profiles present in leukemic stem cells. These achievements highlight the utility of single-cell sequencing technologies in answering fundamental questions in the field of cancer biology and beyond

Gut barrier defects, intestinal immune hyperactivation and enhanced lipid catabolism drive lethality in NGLY1-deficient Drosophila

Abstract Intestinal barrier dysfunction leads to inflammation and associated metabolic changes. However, the relative impact of gut bacteria versus non-bacterial insults on animal health in the context of barrier dysfunction is not well understood. Here, we establish that loss of Drosophila N-glycanase 1 (Pngl) in a specific intestinal cell type leads to gut barrier defects, causing starvation and JNK overactivation. These abnormalities, along with loss of Pngl in enterocytes and fat body, result in Foxo overactivation, leading to hyperactive innate immune response and lipid catabolism and thereby contributing to lethality. Germ-free rearing of Pngl mutants rescued their developmental delay but not lethality. However, raising Pngl mutants on isocaloric, fat-rich diets partially rescued lethality. Our data indicate that Pngl functions in Drosophila larvae to establish the gut barrier, and that the lethality caused by loss of Pngl is primarily mediated through non-bacterial induction of immune and metabolic abnormalities

Conservative Constraints on Early Cosmology: an illustration of the Monte Python cosmological parameter inference code

International audienceModels for the latest stages of the cosmological evolution rely on a lesssolid theoretical and observational ground than the description of earlierstages like BBN and recombination. As suggested in a previous work byVonlanthen et al., it is possible to tweak the analysis of CMB data in such wayto avoid making assumptions on the late evolution, and obtain robustconstraints on "early cosmology parameters". We extend this method in order tomarginalise the results over CMB lensing contamination, and present updatedresults based on recent CMB data. Our constraints on the minimal earlycosmology model are weaker than in a standard LCDM analysis, but do notconflict with this model. Besides, we obtain conservative bounds on theeffective neutrino number and neutrino mass, showing no hints for extrarelativistic degrees of freedom, and proving in a robust way that neutrinosexperienced their non-relativistic transition after the time of photondecoupling. This analysis is also an occasion to describe the main features ofthe new parameter inference code Monte Python, that we release together withthis paper. Monte Python is a user-friendly alternative to other public codeslike CosmoMC, interfaced with the Boltzmann code class