Bone morphogenic protein-4 availability in the cardiac microenvironment controls inflammation and fibrosis in autoimmune myocarditis

Myocarditis is an inflammatory heart disease that leads to loss of cardiomyocytes and frequently precipitates fibrotic remodeling of the myocardium, culminating in heart failure. However, the molecular mechanisms underlying immune cell control and maintenance of tissue integrity in the inflamed cardiac microenvironment remain elusive. In this study, we found that bone morphogenic protein-4 (BMP4) gradients maintain cardiac tissue homeostasis by single-cell transcriptomics analyses of inflamed murine and human myocardial tissues. Cardiac BMP pathway dysregulation was reflected by reduced BMP4 serum concentration in patients with myocarditis. Restoration of BMP signaling by antibody-mediated neutralization of the BMP inhibitors gremlin-1 and gremlin-2 ameliorated T cell-induced myocardial inflammation in mice. Moreover, progression to inflammatory cardiomyopathy was blocked through the reduction of fibrotic remodeling and preservation of cardiomyocyte integrity. These results unveil the BMP4–gremlin axis as a druggable pathway for the treatment of myocardial inflammation, limiting the severe sequelae of cardiac fibrosis and heart failure

Mechanisms for a nutrient-conserving carbon pump in a seasonally stratified, temperate continental shelf sea

Continental shelf seas may have a significant role in oceanic uptake and storage of carbon dioxide (CO2) from the atmosphere, through a ‘continental shelf pump’ mechanism. The northwest European continental shelf, in particular the Celtic Sea (50°N 8°W), was the target of extensive biogeochemical sampling from March 2014 to September 2015, as part of the UK Shelf Sea Biogeochemistry research programme (UK-SSB). Here, we use the UK-SSB carbonate chemistry and macronutrient measurements to investigate the biogeochemical seasonality in this temperate, seasonally stratified system. Following the onset of stratification, near-surface biological primary production during spring and summer removed dissolved inorganic carbon and nutrients, and a fraction of the sinking particulate organic matter was subsequently remineralised beneath the thermocline. Water column inventories of these variables throughout 1.5 seasonal cycles, corrected for air-sea CO2 exchange and sedimentary denitrification and anammox, isolated the combined effect of net community production (NCP) and remineralisation on the inorganic macronutrient inventories. Overall inorganic inventory changes suggested that a significant fraction (>50%) of the annual NCP of around 3 mol-C m–2 yr–1 appeared to be stored within a long-lived organic matter (OM) pool with a lifetime of several months or more. Moreover, transfers into and out of this pool appeared not to be in steady state over the one full seasonal cycle sampled. Accumulation of such a long-lived and potentially C-rich OM pool is suggested to be at least partially responsible for the estimated net air-to-sea CO2 flux of ∼1.3 mol-C m–2 yr–1 at our study site, while providing a mechanism through which a nutrient-conserving continental shelf pump for CO2 could potentially operate in this and other similar regions

Protection by Anti-β-Glucan Antibodies Is Associated with Restricted β-1,3 Glucan Binding Specificity and Inhibition of Fungal Growth and Adherence

Anti-β-glucan antibodies elicited by a laminarin-conjugate vaccine confer cross-protection to mice challenged with major fungal pathogens such as Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans. To gain insights into protective β-glucan epitope(s) and protection mechanisms, we studied two anti-β-glucan monoclonal antibodies (mAb) with identical complementarity-determining regions but different isotypes (mAb 2G8, IgG2b and mAb 1E12, IgM). C. albicans, the most relevant fungal pathogen for humans, was used as a model

The relationship between social welfare policy and multidimensional well-being : an analysis using the South African Child Support Grant

Socio-historical context and ideology are often overlooked in analyses of how social welfare policy is used to promote well-being. This paper uses the South African Child Support Grant (CSG) to illuminate how a policy may enhance or hinder well-being, not only for individuals but also for a society. Forged through a combination of the inherited apartheid state's architecture, the redistributive ideology of the ruling African National Congress, social development theory and the constraints of economic globalisation, the CSG has produced paradoxically positive material well-being outcomes for many poor South Africans and possibly reproduced problematic subjective and relational forms of well-being nationally. Analysing how the grant, as a social policy, is historically and ideologically situated illuminates some of the constraints imposed upon a twenty-first century democratic developmental state as it tries to find its way in a global market, redistribute wealth, satisfy different constituencies and promote individual and collective well-being. Grants are a necessary but insufficient strategy for a twenty-first century democratic developmental state like South Africa.http://muse.jhu.edu/journals/transformationhj2021Educational PsychologySociolog

Abstract Number ‐ 205: Impact of Automated Neuroimaging Triage Platform on Time Metrics at a Thrombectomy Capable Stroke Center

Introduction Rapid detection and appropriate triage of large vessel occlusion (LVO) strokes, upon arrival to a hospital system, is key to achieving better outcomes after endovascular thrombectomy (EVT) mediated recanalization of LVO strokes . Automated neuroimaging analyses has the potential to streamline intra‐ hospital workflow. We aim to study the change in vital intra‐hospital time metrics before and after adoption of an automated neuroimaging triage platform (ANTP). Methods We performed a retrospective analysis of prospectively collected data at our EVT capable stroke center between April 2019 and November 2021. IschemaView’s Rapid software was adopted in October 2020 for triage of stroke patients. Patients treated before were our control cohort and patients treated after were our intervention cohort. Confirmed LVO strokes presenting to our center within 24 hours of stroke onset were included. Results A total of 305 patients were included‐ control (n = 150) and intervention cohort (n = 155). Age (70±15 vs 72 ±15,p = .40), NIHSS score (13 ±8 vs 14 ±7, p = .24), and last‐known‐well to arrival (392 ±464 vs 376 ±427 min, p = .38) were comparable between the two groups. Time from arrival to non‐contrast CT head was also comparable between the two groups (150 ±712 vs 161 ±794, p = .89). Time from non‐contrast CT head to decision to EVT (36 ±54 vs 22 ±58, p = .06) and time from non‐contrast CT to groin puncture (41 ±61 vs 61 ±65, p = .01) were shorter in the intervention cohort compared to control cohort. Length of stay and discharge mRS score were similar between the two cohorts. Conclusions Automated neuroimaging triage platform has the potential to improve workflow by decreasing time from non‐contrast CT to EVT decision and groin puncture. Further studies are required to study impact on patient outcomes

Rate of Return to Military Active Duty After Single and 2-Level Anterior Cervical Discectomy and Fusion: A 4-Year Retrospective Review.

BACKGROUND: Over the years of rigorous of military service, military personnel may experience cervical spondylosis and radiculopathy. Given the frequency of this occurrence, the capacity to return to unrestricted full duty in the military after anterior cervical discectomy and fusion (ACDF) is worthy of analysis. OBJECTIVE: To identify the rate of return to full, unrestricted active duty after single and 2-level anterior cervical discectomy, and fusion surgery in military personnel. METHODS: A retrospective chart review was performed at a tertiary care military treatment facility for all active duty personnel who underwent a single or 2-level ACDF over a 4-yr period. Patient and procedural data were collected to include single or 2-level fusion, indication for surgery, fusion level, tobacco use, age, and military rank. Fischer\u27s Exact and Wilcoxon Rank Sum tests were used to identify statistically significant differences in the rate of return to active duty. RESULTS: A total of 132 anterior cervical discectomy and fusions were analyzed. One hundred sixteen patients (88%) were able to return to unrestricted full active duty, while the remaining 16 required separation from the military for continued pain or disability. The return to active duty rate was significantly higher in service members with a rank of E7 or above (99%) than those E6 and below (73%). There was a strong association between the presence of a pseudoarthrosis and the capacity to return to full duty (P = .013). CONCLUSION: Both single and 2-level ACDFs have high overall success with an 88% rate of return to full duty

Pour une sociologie du racisme. L'experience europeenne

Available from INIST (FR), Document Supply Service, under shelf-number : AR 16543 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEMinistere de la Recherche et de l'Espace (MRE), 75 - Paris (France)FRFranc

Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial

Background: We undertook a randomised, double-blinded, placebo-controlled, crossover trial to test whether intake of artificial food colour and additives (AFCA) affected childhood behaviour.Methods: 153 3-year-old and 144 8/9-year-old children were included in the study. The challenge drink contained sodium benzoate and one of two AFCA mixes (A or B) or a placebo mix. The main outcome measure was a global hyperactivity aggregate (GHA), based on aggregated z-scores of observed behaviours and ratings by teachers and parents, plus, for 8/9-year-old children, a computerised test of attention. This clinical trial is registered with Current Controlled Trials (registration number ISRCTN74481308). Analysis was per protocol.Findings: 16 3-year-old children and 14 8/9-year-old children did not complete the study, for reasons unrelated to childhood behaviour. Mix A had a significantly adverse effect compared with placebo in GHA for all 3-year-old children (effect size 0.20 [95% CI 0.01–0.39], p=0.044) but not mix B versus placebo. This result persisted when analysis was restricted to 3-year-old children who consumed more than 85% of juice and had no missing data (0.32 [0.05–0.60], p=0.02). 8/9-year-old children showed a significantly adverse effect when given mix A (0.12 [0.02–0.23], p=0.023) or mix B (0.17 [0.07–0.28], p=0.001) when analysis was restricted to those children consuming at least 85% of drinks with no missing data.Interpretation: Artificial colours or a sodium benzoate preservative (or both) in the diet result in increased hyperactivity in 3-year-old and 8/9-year-old children in the general population