Airborne particulate matter PM2.5 from Mexico City affects the generation of reactive oxygen species by blood neutrophils from asthmatics: an in vitro approach

<p>Abstract</p> <p>Background</p> <p>The Mexico City Metropolitan Area is densely populated, and toxic air pollutants are generated and concentrated at a higher rate because of its geographic characteristics. It is well known that exposure to particulate matter, especially to fine and ultra-fine particles, enhances the risk of cardio-respiratory diseases, especially in populations susceptible to oxidative stress. The aim of this study was to evaluate the effect of fine particles on the respiratory burst of circulating neutrophils from asthmatic patients living in Mexico City.</p> <p>Methods</p> <p>In total, 6 subjects diagnosed with mild asthma and 11 healthy volunteers were asked to participate. Neutrophils were isolated from peripheral venous blood and incubated with fine particles, and the generation of reactive oxygen species was recorded by chemiluminescence. We also measured plasma lipoperoxidation susceptibility and plasma myeloperoxidase and paraoxonase activities by spectrophotometry.</p> <p>Results</p> <p>Asthmatic patients showed significantly lower plasma paraoxonase activity, higher susceptibility to plasma lipoperoxidation and an increase in myeloperoxidase activity that differed significantly from the control group. In the presence of fine particles, neutrophils from asthmatic patients showed an increased tendency to generate reactive oxygen species after stimulation with fine particles (PM_2.5).</p> <p>Conclusion</p> <p>These findings suggest that asthmatic patients have higher oxidation of plasmatic lipids due to reduced antioxidant defense. Furthermore, fine particles tended to increase the respiratory burst of blood human neutrophils from the asthmatic group.</p> <p>On the whole, increased myeloperoxidase activity and susceptibility to lipoperoxidation with a concomitant decrease in paraoxonase activity in asthmatic patients could favor lung infection and hence disrupt the control of asthmatic crises.</p

CFD modelling of particle matter dispersion in a real hot-spot

Urban air quality is one of the main environmental concerns. The interaction between atmosphere and buildings induces complex flows within the streets and squares. This fact joint with the traffic emissions produce a heterogeneous distribution of pollutants with high gradients of concentration. The main objective of this work is to obtain high resolution maps of particle matter concentration using a CFD model so as to analyze air quality and population exposure. This study is focused on a heavily trafficked roundabout in Madrid (Fernandez Ladreda square). To achieve this objective, CFD modelling coupled with detailed emissions of PM10 and PM2.5 and outputs from WRF meteorological mesoscale model is performed. Emissions from vehicle exhaust and particle resuspension are considered with a resolution of 5 m x 5 m. The simulated mesoscale vertical profiles of wind velocity and turbulent kinetic energy, previously checked with onsite meteorological measurements, are used as boundary conditions. The effects of urban vegetation are modelled and moreover, the CFD modelling is improved implementing vehicle induced turbulence as a source of turbulence on the roads. Modelling results are evaluated for several periods of summer and winter by using data from experimental campaigns carried out in this zone in the framework of the TECNAIRE research project

Influence of air pollutants on circulating inflammatory cells and microRNA expression in acute myocardial infarction.

Air pollutants increase the risk and mortality of myocardial infarction (MI). The aim of this study was to assess the inflammatory changes in circulating immune cells and microRNAs in MIs related to short-term exposure to air pollutants. We studied 192 patients with acute coronary syndromes and 57 controls with stable angina. For each patient, air pollution exposure in the 24-h before admission, was collected. All patients underwent systematic circulating inflammatory cell analyses. According to PM2.5 exposure, 31 patients were selected for microRNA analyses. STEMI patients exposed to PM2.5 showed a reduction of CD4+ regulatory T cells. Furthermore, in STEMI patients the exposure to PM2.5 was associated with an increase of miR-146a-5p and miR-423-3p. In STEMI and NSTEMI patients PM2.5 exposure was associated with an increase of miR-let-7f-5p. STEMI related to PM2.5 short-term exposure is associated with changes involving regulatory T cells, miR-146a-5p and miR-423-3p.This work was supported by Ministerio de Ciencia e Innovación [SAF2017-82886-R, to F.S.M] Proyecto de Investigación en Salud [PI21/01583 to H.F.]. Grant from the Sociedad Española de Cardiologia to F.A. Ministerio de Ciencia, Innovación y Universidades, Carlos III Institute of Health-Fondo de Investigación Sanitaria [PI19/00545 to P.M.] From the Comunidad de Madrid [S2017/BMD-3671-INFLAMUNE-CM] to FSM and PM. Tis research has been co-fnanced by Fondo Europeo de Desarrollo Regional (FEDER).S

TWEAK promotes peritoneal inflammation

Peritoneal dialysis (PD) is complicated by peritonitis episodes that cause loss of mesothelium and eventually sclerosing peritonitis. An improved understanding of the molecular contributors to peritoneal injury and defense may increase the therapeutic armamentarium to optimize peritoneal defenses while minimizing peritoneal injury. There is no information on the expression and function of the cytokine TWEAK and its receptor Fn14 during peritoneal injury. Fn14 expression and soluble TWEAK levels were measured in human PD peritoneal effluent cells or fluids with or without peritonitis. Fn14 expression was also analyzed in peritoneal biopsies from PD patients. Actions of intraperitoneal TWEAK were studied in mice in vivo. sTWEAK levels were increased in peritoneal effluent in PD peritonitis. Effluent sTWEAK levels correlated with the number of peritoneal macrophages (r = 0.491, p = 0.002). Potential TWEAK targets that express the receptor Fn14 include mesothelial cells and macrophages, as demonstrated by flow cytometry of peritoneal effluents and by analysis of peritoneal biopsies. Peritoneal biopsy Fn14 correlated with mesothelial injury, fibrosis and inflammation, suggesting a potential deleterious effect of TWEAK/Fn14. In this regard, intraperitoneal TWEAK administration to mice promoted peritoneal inflammation characterized by increased peritoneal effluent MCP-1, Fn14 and Gr1+ macrophages, increased mesothelial Fn14, MCP-1 and CCL21 expression and submesothelial tissue macrophage recruitment. Taken together these data suggest that the TWEAK/Fn14 system may promote inflammation and tissue injury during peritonitis and PD.This work was supported by FIS PS09/00447, PI08/1564, PI10/00234, MS12/03262, FEDER funds ISCIII-RETIC REDinREN/RD06/0016, RD12/0021, Comunidad de Madrid (Fibroteam S2010/BMD-2321, S2010/BMD-2378). Programa Intensificación Actividad Investigadora (ISCIII/Agencia Laı´n-Entralgo/CM) to AO, Programa Estabilizacio´n Investigadores to LB-C, Miguel Servet to ABS, Sara Borrell to BS, MDSN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Methylation regulation of Antiviral host factors, Interferon Stimulated Genes (ISGs) and T-cell responses associated with natural HIV control

GWAS, immune analyses and biomarker screenings have identified host factors associated within vivoHIV-1 control. However, there is a gap in the knowledge about the mechanisms that regulate the expression of such host factors. Here, we aimed to assess DNA methylation impact on host genome in natural HIV-1 control. To this end, whole DNA methylome in 70 untreated HIV-1 infected individuals with either high (>50,000 HIV-1-RNA copies/ml, n = 29) or low (<10,000 HIV-1-RNA copies/ml, n = 41) plasma viral load (pVL) levels were compared and identified 2,649 differentially methylated positions (DMPs). Of these, a classification random forest model selected 55 DMPs that correlated with virologic (pVL and proviral levels) and HIV-1 specific adaptive immunity parameters (IFNg-T cell responses and neutralizing antibodies capacity). Then, cluster and functional analyses identified two DMP clusters: cluster 1 contained hypo-methylated genes involved in antiviral and interferon response (e.g.PARP9,MX1, andUSP18) in individuals with high viral loads while in cluster 2, genes related to T follicular helper cell (Tfh) commitment (e.g.CXCR5andTCF7) were hyper-methylated in the same group of individuals with uncontrolled infection. For selected genes, mRNA levels negatively correlated with DNA methylation, confirming an epigenetic regulation of gene expression. Further, these gene expression signatures were also confirmed in early and chronic stages of infection, including untreated, cART treated and elite controllers HIV-1 infected individuals (n = 37). These data provide the first evidence that host genes critically involved in immune control of the virus are under methylation regulation in HIV-1 infection. These insights may offer new opportunities to identify novel mechanisms ofin vivovirus control and may prove crucial for the development of future therapeutic interventions aimed at HIV-1 cure. Author summary The infection with the human immunodeficiency virus (HIV), as for other viral infections, induce global DNA Methylation changes in the host genome. Herein, we identified for first time the methylation impact on host genome in untreated HIV-1 infection with different degrees ofin vivovirus control. Specifically, we observed that individuals with a better HIV-1 control showed a hypermethylation of genes associated with antiviral and interferon pathways and the hypomethylation of genes associated with the differentiation process of T follicular helper cells. Interestingly, these epigenetic imprints in host genome were strongly correlated with virus content and HIV-specific T cell responses. Therefore, we propose DNA Methylation as the regulation mechanism of host genes involved in immune HIV-1 control that could interfere in the efficacy of cure strategies. We also highlight the importance of DNA Methylation to regulate immune responses not only in HIV-1 but also in chronic infections or other pathologic situations associated with a sustained activation of the immune system

Methylation regulation of Antiviral host factors, Interferon Stimulated Genes (ISGs) and T-cell responses associated with natural HIV control

GWAS, immune analyses and biomarker screenings have identified host factors associated with in vivo HIV-1 control. However, there is a gap in the knowledge about the mechanisms that regulate the expression of such host factors. Here, we aimed to assess DNA methylation impact on host genome in natural HIV-1 control. To this end, whole DNA methylome in 70 untreated HIV-1 infected individuals with either high (>50,000 HIV-1-RNA copies/ml, n = 29) or low (<10,000 HIV-1-RNA copies/ml, n = 41) plasma viral load (pVL) levels were compared and identified 2,649 differentially methylated positions (DMPs). Of these, a classification random forest model selected 55 DMPs that correlated with virologic (pVL and proviral levels) and HIV-1 specific adaptive immunity parameters (IFNg-T cell responses and neutralizing antibodies capacity). Then, cluster and functional analyses identified two DMP clusters: cluster 1 contained hypo-methylated genes involved in antiviral and interferon response (e.g. PARP9, MX1, and USP18) in individuals with high viral loads while in cluster 2, genes related to T follicular helper cell (Tfh) commitment (e.g. CXCR5 and TCF7) were hyper-methylated in the same group of individuals with uncontrolled infection. For selected genes, mRNA levels negatively correlated with DNA methylation, confirming an epigenetic regulation of gene expression. Further, these gene expression signatures were also confirmed in early and chronic stages of infection, including untreated, cART treated and elite controllers HIV-1 infected individuals (n = 37). These data provide the first evidence that host genes critically involved in immune control of the virus are under methylation regulation in HIV-1 infection. These insights may offer new opportunities to identify novel mechanisms of in vivo virus control and may prove crucial for the development of future therapeutic interventions aimed at HIV-1 cure

Improving the earthquake resilience of primary schools in the border regions of neighbouring countries

This work summarises the strategy adopted in the European research project PERSISTAH. It aims to increase the resilience of the population, focusing on the existing primary schools in the Algarve (Portugal) and Huelva (Spain) regions. Software was developed to assess the seismic safety of these schools, considering different earthquake scenarios. Seismic retrofitting measures were studied and numerically tested. Some of them were also implemented in the retrofitting activities of two case study schools (one in each country). It was found that the adopted ground motion prediction equations (GMPEs) considerably affect the results obtained with the software, especially for offshore earthquake scenarios. Furthermore, the results show that the masonry buildings would be the most damaged school typologies for all the scenarios considered. Additionally, a set of guidelines was created to support the school community and the technicians related to the construction industry. The goal of these documents is to increase the seismic resilience of the population. Different activities were carried out to train schoolteachers in seismic safety based on the guidelines produced, obtaining positive feedback from them.info:eu-repo/semantics/publishedVersio

Occupational history and human spatial organization in northwestern Patagonia: insights from Cueva Yagui (northern Neuquén province, Argentina)

Se presenta un nuevo corpus de información arqueológica y cronológica producto de la excavación del sitio Cueva Yagui (norte del Neuquén, noroeste de Patagonia, Argentina), cuya secuencia ocupacional humana se inicia hace al menos 8.500 años calendáricos. Un análisis crono-estratigráfico preliminar permitió distinguir dos pulsos diacrónicos en su historia ocupacional, vinculados al Holoceno medio y tardío, y asociados con diferentes tasas de descarte de materiales (líticos, cerámicos, faunísticos, botánicos) y de producción de arte rupestre. Los resultados sugieren que el sitio y su entorno fueron ocupados en forma comparativamente más intensa que otros sectores adyacentes con propiedades disímiles, desempeñando un rol clave para la articulación estratégica de diferentes ambientes y recursos característicos de los paisajes andino-patagónicos. Esta nueva información permite ampliar la profundidad temporal respecto del rolcentral que, durante el Holoceno, ocuparon los espacios altitudinales intermedios para la organización espacial humana en relación con la estructura biogeográfica del paisaje del norte de Neuquén.A new corpus of archaeological and chronological information is presented as a result of the excavation of Cueva Yagui site (northern Neuquén, northwestern Patagonia, Argentina), with an occupational sequence beginning at least at 8,500 calendar years ago. A preliminary chrono-stratigraphic analysis allowed to distinguish two diachronic pulses in the occupational history, respectively linked to the middle and late Holocene, and associated with different material discard rates (lithic, ceramic, faunal, botanical) and rock art production. The results obtained suggest that the site and its surroundings were occupied more intensively than adjacent sectors with contrasting biogeographic properties, thus playing a key role in the strategic articulation of different environments and resources typical of Andean-Patagonian landscapes. This new information allows expanding the temporal depth regarding the central role that intermediate altitudinal spaces played for human spatial organization in relation to the biogeographic structure of the landscape of northern Neuquén during the Holocene.Fil: Romero Villanueva Badin, Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Secretaría de Cultura de la Nación. Dirección Nacional de Cultura y Museos. Instituto Nacional de Antropología y Pensamiento Latinoamericano; ArgentinaFil: Rughini, Agustina Ayelén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Multidisciplinario de Historia y Ciencias Humanas; ArgentinaFil: Paiva, Jimena María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; ArgentinaFil: Garvey, Raven. University Of Michigan. Department Of Anthopology; Estados UnidosFil: Brera, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; ArgentinaFil: Sanchez, María Clara del Cielo. Universidad Nacional de Cuyo. Facultad de Ciencias Aplicadas a la Industria; ArgentinaFil: Borrazzo, Karen Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Multidisciplinario de Historia y Ciencias Humanas; ArgentinaFil: Frigolé, Cecilia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; ArgentinaFil: Gasco, Alejandra Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; ArgentinaFil: Llano, Carina Lourdes. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Aplicadas a la Industria; ArgentinaFil: Fernandez Blanco, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Diversidad Cultural y Procesos de Cambio. Universidad Nacional de Río Negro. Instituto de Investigaciones en Diversidad Cultural y Procesos de Cambio; ArgentinaFil: Magliolo, Ruth. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Departamento de Ciencias Antropológicas; ArgentinaFil: Barberena, Ramiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; Argentin

Tocilizumab in refractory Caucasian Takayasu's arteritis: a multicenter study of 54 patients and literature review

Objective: To assess the efficacy and safety of tocilizumab (TCZ) in Caucasian patients with refractory Takayasu's arteritis (TAK) in clinical practice. Methods: A multicenter study of Caucasian patients with refractory TAK who received TCZ. The outcome variables were remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A comparative study between patients who received TCZ as monotherapy (TCZMONO) and combined with conventional disease modifying anti-rheumatic drugs (cDMARDs) (TCZCOMBO) was performed. Results: The study comprised 54 patients (46 women/8 men) with a median [interquartile range (IQR)] age of 42.0 (32.5-50.5) years. TCZ was started after a median (IQR) of 12.0 (3.0-31.5) months since TAK diagnosis. Remission was achieved in 12/54 (22.2%), 19/49 (38.8%), 23/44 (52.3%), and 27/36 (75%) patients at 1, 3, 6, and 12 months, respectively. The prednisone dose was reduced from 30.0 mg/day (12.5-50.0) to 5.0 (0.0-5.6) mg/day at 12 months. An improvement in imaging findings was reported in 28 (73.7%) patients after a median (IQR) of 9.0 (6.0-14.0) months. Twenty-three (42.6%) patients were on TCZMONO and 31 (57.4%) on TCZCOMBO: MTX (n = 28), cyclosporine A (n = 2), azathioprine (n = 1). Patients on TCZCOMBO were younger [38.0 (27.0-46.0) versus 45.0 (38.0-57.0)] years; difference (diff) [95% confidence interval (CI) = -7.0 (-17.9, -0.56] with a trend to longer TAK duration [21.0 (6.0-38.0) versus 6.0 (1.0-23.0)] months; diff 95% CI = 15 (-8.9, 35.5), and higher c-reactive protein [2.4 (0.7-5.6) versus 1.3 (0.3-3.3)] mg/dl; diff 95% CI = 1.1 (-0.26, 2.99). Despite these differences, similar outcomes were observed in both groups (log rank p = 0.862). Relevant adverse events were reported in six (11.1%) patients, but only three developed severe events that required TCZ withdrawal. Conclusion: TCZ in monotherapy, or combined with cDMARDs, is effective and safe in patients with refractory TAK of Caucasian origin.Funding: This work was partially supported by RETICS Programs, RD08/0075 (RIER), RD12/0009/0013 and RD16/0012 from “Instituto de Salud Carlos III” (ISCIII) (Spain)