14 research outputs found

    Differential IL-1β secretion by monocyte subsets is regulated by Hsp27 through modulating mRNA stability.

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    Monocytes play a central role in regulating inflammation in response to infection or injury, and during auto-inflammatory diseases. Human blood contains classical, intermediate and non-classical monocyte subsets that each express characteristic patterns of cell surface CD16 and CD14; each subset also has specific functional properties, but the mechanisms underlying many of their distinctive features are undefined. Of particular interest is how monocyte subsets regulate secretion of the apical pro-inflammatory cytokine IL-1β, which is central to the initiation of immune responses but is also implicated in the pathology of various auto-immune/auto-inflammatory conditions. Here we show that primary human non-classical monocytes, exposed to LPS or LPS + BzATP (3'-O-(4-benzoyl)benzyl-ATP, a P2X7R agonist), produce approx. 80% less IL-1β than intermediate or classical monocytes. Despite their low CD14 expression, LPS-sensing, caspase-1 activation and P2X7R activity were comparable in non-classical monocytes to other subsets: their diminished ability to produce IL-1β instead arose from 50% increased IL-1β mRNA decay rates, mediated by Hsp27. These findings identify the Hsp27 pathway as a novel therapeutic target for the management of conditions featuring dysregulated IL-1β production, and represent an advancement in understanding of both physiological inflammatory responses and the pathogenesis of inflammatory diseases involving monocyte-derived IL-1β

    Gaia Early Data Release 3: Structure and properties of the Magellanic Clouds

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    We compare the Gaia DR2 and Gaia EDR3 performances in the study of the Magellanic Clouds and show the clear improvements in precision and accuracy in the new release. We also show that the systematics still present in the data make the determination of the 3D geometry of the LMC a difficult endeavour; this is at the very limit of the usefulness of the Gaia EDR3 astrometry, but it may become feasible with the use of additional external data. We derive radial and tangential velocity maps and global profiles for the LMC for the several subsamples we defined. To our knowledge, this is the first time that the two planar components of the ordered and random motions are derived for multiple stellar evolutionary phases in a galactic disc outside the Milky Way, showing the differences between younger and older phases. We also analyse the spatial structure and motions in the central region, the bar, and the disc, providing new insights into features and kinematics. Finally, we show that the Gaia EDR3 data allows clearly resolving the Magellanic Bridge, and we trace the density and velocity flow of the stars from the SMC towards the LMC not only globally, but also separately for young and evolved populations. This allows us to confirm an evolved population in the Bridge that is slightly shift from the younger population. Additionally, we were able to study the outskirts of both Magellanic Clouds, in which we detected some well-known features and indications of new ones

    European Society of Cardiology: Cardiovascular Disease Statistics 2019

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    Aims The 2019 report from the European Society of Cardiology (ESC) Atlas provides a contemporary analysis of cardiovascular disease (CVD) statistics across 56 member countries, with particular emphasis on international inequalities in disease burden and healthcare delivery together with estimates of progress towards meeting 2025 World Health Organization (WHO) non-communicable disease targets. Methods and results In this report, contemporary CVD statistics are presented for member countries of the ESC. The statistics are drawn from the ESC Atlas which is a repository of CVD data from a variety of sources including the WHO, the Institute for Health Metrics and Evaluation, and the World Bank. The Atlas also includes novel ESC sponsored data on human and capital infrastructure and cardiovascular healthcare delivery obtained by annual survey of the national societies of ESC member countries. Across ESC member countries, the prevalence of obesity (body mass index ≥30 kg/m2) and diabetes has increased two- to three-fold during the last 30 years making the WHO 2025 target to halt rises in these risk factors unlikely to be achieved. More encouraging have been variable declines in hypertension, smoking, and alcohol consumption but on current trends only the reduction in smoking from 28% to 21% during the last 20 years appears sufficient for the WHO target to be achieved. The median age-standardized prevalence of major risk factors was higher in middle-income compared with high-income ESC member countries for hypertension {23.8% [interquartile range (IQR) 22.5–23.1%] vs. 15.7% (IQR 14.5–21.1%)}, diabetes [7.7% (IQR 7.1–10.1%) vs. 5.6% (IQR 4.8–7.0%)], and among males smoking [43.8% (IQR 37.4–48.0%) vs. 26.0% (IQR 20.9–31.7%)] although among females smoking was less common in middle-income countries [8.7% (IQR 3.0–10.8) vs. 16.7% (IQR 13.9–19.7%)]. There were associated inequalities in disease burden with disability-adjusted life years per 100 000 people due to CVD over three times as high in middle-income [7160 (IQR 5655–8115)] compared with high-income [2235 (IQR 1896–3602)] countries. Cardiovascular disease mortality was also higher in middle-income countries where it accounted for a greater proportion of potential years of life lost compared with high-income countries in both females (43% vs. 28%) and males (39% vs. 28%). Despite the inequalities in disease burden across ESC member countries, survey data from the National Cardiac Societies of the ESC showed that middle-income member countries remain severely under-resourced compared with high-income countries in terms of cardiological person-power and technological infrastructure. Under-resourcing in middle-income countries is associated with a severe procedural deficit compared with high-income countries in terms of coronary intervention, device implantation and cardiac surgical procedures. Conclusion A seemingly inexorable rise in the prevalence of obesity and diabetes currently provides the greatest challenge to achieving further reductions in CVD burden across ESC member countries. Additional challenges are provided by inequalities in disease burden that now require intensification of policy initiatives in order to reduce population risk and prioritize cardiovascular healthcare delivery, particularly in the middle-income countries of the ESC where need is greatest

    Descending Aorta Diastolic Retrograde Flow Assessment for Aortic Regurgitation Quantification

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    Background: Diastolic retrograde flow in the descending aorta has been associated to the severity of aortic regurgitation; however,most of the parameters related to flow velocity are not validated with a reference imaging technique.Objective: The aim of this study was to assess the usefulness of diastolic retrograde flow in the descending thoracic aorta and theabdominal aorta in the quantification of aortic regurgitation using magnetic resonance imaging as reference.Methods: Forty consecutive patients were included in a prospective echocardiography and magnetic resonance study. The followingparameters were analyzed by pulsed-wave Doppler: a) velocity-time integral of the diastolic retrograde flow and b) peak end-diastolicvelocity of the regurgitant flow, both in the thoracic aorta, and c) holodiastolic flow reversal in the abdominal aorta. The cardiacmagnetic resonance protocol included phase contrast sequences to calculate the regurgitant fraction. Values ≥30% were consideredas severe aortic regurgitation.Results: Eleven patients (30%) presented a regurgitant fraction ≥30%. The velocity-time integral of diastolic retrograde flow demonstratedthe best diagnostic accuracy to detect severe aortic regurgitation: AUC=0.87, p15cm showed 91% sensitivity and 86% specificity to detect severe aortic regurgitation. Holodiastolicflow reversal in the abdominal aorta demonstrated excellent specificity (100%) but low sensitivity (50%) to detect severeaortic regurgitation.Conclusions: Diastolic retrograde flow assessment in the thoracic aorta allows an accurate diagnosis of severe aortic regurgitation.Holodiastolic flow reversal demonstrated good specificity but low sensitivity.RESUMEN Introducción El flujo diastólico retrogrado en la aorta descendente ha sido relacionado con la severidad de la insuficiencia aortica (IAO) pero sin una adecuada validación. Objetivos Valorar la utilidad del flujo retrogrado diastólico en la  aorta torácica descendente  y aorta abdominal en la cuantificación de la IAo utilizando como referencia la resonancia magnética (RM). Métodos Cuarenta pacientes consecutivos fueron incluidos en un estudio prospectivo de ecocardiográfia y RM. Los parámetros analizados por Doppler pulsado fueron en aorta torácica: a) la integral velocidad tiempo del flujo retrogrado diastólico (IVT-FRD), b) la velocidad máxima telediastólica del flujo regurgitante, y en aorta abdominal: c) el flujo holodiastólico reverso. El protocolo de RM incluyo  secuencias de contraste de fase para calcular la fracción regurgitante (FR). Valores  ≥30% fueron diagnósticados de IAO severa. Resultados Once pacientes (30%) tenían una FR ≥30%. Todos los parámetros  de flujo en la aorta toraco-abdominal mostraron correlación significativa con la FR obtenida por RM.  IVT-FRD demostró la mayor precisión en el diagnóstico de  IAo severa: AUC=0,87, P 15 cm demostró una sensibilidad = 91% y una especificidad= 86% para detectar IAO severa. El flujo pandiastólico reverso en aorta abdominal mostró  una excelente especifificidad (100%) para el diagnóstico de IAO severa, aunque con baja sensibilidad (50%). Conclusiones La valoración del flujo retrogrado diastólico en aorta torácica descendente permite un adecuado diagnóstico de la insuficiencia aórtica severa.  El flujo holodiastólico reverso aunque es poco sensible muestra una alta especificidad

    Genetic association study of coronary collateral circulation in patients with coronary artery disease using 22 single nucleotide polymorphisms corresponding to 10 genes involved in postischemic neovascularization.

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    BACKGROUND:/nCollateral growth in patients with coronary artery disease (CAD) is highly heterogeneous. Although multiple factors are thought to play a role in collateral development, the contribution of genetic factors to coronary collateral circulation (CCC) is largely unknown. The goal of this study was to assess whether functional single nucleotide polymorphisms (SNPs) in genes involved in vascular growth are associated with CCC. METHODS: 677 consecutive CAD patients were enrolled in the study and their CCC was assessed by the Rentrop method. 22 SNPs corresponding to 10 genes involved in postischemic neovascularization were genotyped and multivariate logistic regression models were adjusted using clinically relevant variables to estimate odds ratios and used to examine associations of allelic variants, genotypes and haplotypes with CCC. RESULTS: Statistical analysis showed that the HIF1A rs11549465 and rs2057482; VEGFA rs2010963, rs1570360, rs699947, rs3025039 and rs833061; KDR rs1870377, rs2305948 and rs2071559; CCL2 rs1024611, rs1024610, rs2857657 and rs2857654; NOS3 rs1799983; ICAM1 rs5498 and rs3093030; TGFB1 rs1800469; CD53 rs6679497; POSTN rs3829365 and rs1028728; and LGALS2 rs7291467 polymorphisms, as well as their haplotype combinations, were not associated with CCC (p < 0.05). CONCLUSIONS:/nWe could not validate in our cohort the association of the NOS3 rs1799983, HIF1A rs11549465, VEGFA rs2010963 and rs699947, and LGALS2 s7291467 variants with CCC reported by other authors. A validated SNP-based genome-wide association study is required to identify polymorphisms influencing CCC

    Mémoire du sol, espace des hommes

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