Cytokine Production but Lack of Proliferation in Peripheral Blood Mononuclear Cells from Chronic Chagas' Disease Cardiomyopathy Patients in Response to T. cruzi Ribosomal P Proteins

Background:Trypanosoma cruzi ribosomal P proteins, P2β and P0, induce high levels of antibodies in patients with chronic Chagas' disease Cardiomyopathy (CCC). It is well known that these antibodies alter the beating rate of cardiomyocytes and provoke apoptosis by their interaction with β1-adrenergic and M2-muscarinic cardiac receptors. Based on these findings, we decided to study the cellular immune response to these proteins in CCC patients compared to non-infected individuals.Methodology/Principal findings:We evaluated proliferation, presence of surface activation markers and cytokine production in peripheral blood mononuclear cells (PBMC) stimulated with P2β, the C-terminal portion of P0 (CP0) proteins and T. cruzi lysate from CCC patients predominantly infected with TcVI lineage. PBMC from CCC patients cultured with P2β or CP0 proteins, failed to proliferate and express CD25 and HLA-DR on T cell populations. However, multiplex cytokine assays showed that these antigens triggered higher secretion of IL-10, TNF-α and GM-CSF by PBMC as well as both CD4+ and CD8+ T cells subsets of CCC subjects. Upon T. cruzi lysate stimulation, PBMC from CCC patients not only proliferated but also became activated within the context of Th1 response. Interestingly, T. cruzi lysate was also able to induce the secretion of GM-CSF by CD4+ or CD8+ T cells.Conclusions/Significance:Our results showed that although the lack of PBMC proliferation in CCC patients in response to ribosomal P proteins, the detection of IL-10, TNF-α and GM-CSF suggests that specific T cells could have both immunoregulatory and pro-inflammatory potential, which might modulate the immune response in Chagas' disease. Furthermore, it was possible to demonstrate for the first time that GM-CSF was produced by PBMC of CCC patients in response not only to recombinant ribosomal P proteins but also to parasite lysate, suggesting the value of this cytokine to evaluate T cells responses in T. cruzi infection.Fil: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Atienza, Augusto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Perez Prados, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Buying, Alcinette. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Balouz, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Buscaglia, Carlos Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Santos, Radleigh. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Tasso, Laura Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Bonato, Ricardo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Chiale, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Pinilla, Clemencia. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Judkowski, Valeria A.. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Effect of the relative shift between the electron density and temperature pedestal position on the pedestal stability in JET-ILW and comparison with JET-C

The electron temperature and density pedestals tend to vary in their relative radial positions, as observed in DIII-D (Beurskens et al 2011 Phys. Plasmas 18 056120) and ASDEX Upgrade (Dunne et al 2017 Plasma Phys. Control. Fusion 59 14017). This so-called relative shift has an impact on the pedestal magnetohydrodynamic (MHD) stability and hence on the pedestal height (Osborne et al 2015 Nucl. Fusion 55 063018). The present work studies the effect of the relative shift on pedestal stability of JET ITER-like wall (JET-ILW) baseline low triangularity (\u3b4) unseeded plasmas, and similar JET-C discharges. As shown in this paper, the increase of the pedestal relative shift is correlated with the reduction of the normalized pressure gradient, therefore playing a strong role in pedestal stability. Furthermore, JET-ILW tends to have a larger relative shift compared to JET carbon wall (JET-C), suggesting a possible role of the plasma facing materials in affecting the density profile location. Experimental results are then compared with stability analysis performed in terms of the peeling-ballooning model and with pedestal predictive model EUROPED (Saarelma et al 2017 Plasma Phys. Control. Fusion). Stability analysis is consistent with the experimental findings, showing an improvement of the pedestal stability, when the relative shift is reduced. This has been ascribed mainly to the increase of the edge bootstrap current, and to minor effects related to the increase of the pedestal pressure gradient and narrowing of the pedestal pressure width. Pedestal predictive model EUROPED shows a qualitative agreement with experiment, especially for low values of the relative shift

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Obesity increases eosinophil activity in asthmatic children and adolescents

BACKGROUND: A clear relationship between asthma and obesity has been reported, but the mechanisms remain unclear. The aim of this study was to evaluate the influence of obesity on eosinophil activity (chemotaxis and adhesion) in asthmatic children and adolescents compared with cells from healthy volunteers. METHODS: Asthmatic obese (AO), asthmatic non-obese (ANO), non-asthmatic obese (NAO) and non-asthmatic non-obese (NANO) individuals were included in the present study. The chemotaxis of eosinophils after stimulation with eotaxin (300 ng/ml), platelet-activating factor (10 μM; PAF) and RANTES (100 ng/ml) was performed using a microchemotaxis chamber. The eosinophil peroxidase activity was measured to determine the adhesion activity of eosinophils cultivated on fibronectin-coated plates. The serum leptin, adiponectin, TNF-α and IgE levels were quantified using ELISA assays. RESULTS: The serum IgE levels and eosinophil counts were significantly higher in asthmatic (obese and non-obese) individuals compared with non-asthmatic individuals (obese and non-obese). Spontaneous eosinophil chemotaxis was greater in the AO group compared with either the ANO or NANO groups. The activation of eosinophils using eotaxin and PAF increased eosinophil chemotaxis in the AO group. RANTES treatment increased eosinophil chemotaxis in the NAO group compared with the NANO or ANO groups. The activation of eosinophils using eotaxin significantly increased eosinophil adhesion in the AO group compared with other groups. The serum leptin and TNF-α levels were higher in obese subjects (asthmatic and non-asthmatic), whereas the levels of adiponectin did not significantly differ among these groups. CONCLUSION: This study is the first to show increased eosinophilic activity (chemotaxis and adhesion) associated with high serum leptin and TNF-α levels in atopic asthmatic obese children and adolescents compared with non-obese healthy volunteers

Brazilian network of COVID-19 during pregnancy (REBRACO: A multicentre study protocol)

Introduction The aim of this study was to evaluate the clinical, epidemiological and laboratory aspects of SARS-CoV-2 infection during pregnancy and postpartum in 16 maternity hospitals. Methods and analysis A prospective multicentre study, with five axes. First, the prevalence of SARS-CoV-2 infection among women admitted for childbirth will be described in a cross-sectional study. Second, maternal and perinatal outcomes will be assessed in a prospective cohort study including pregnant or postpartum women with suspected COVID-19. Third, a cohort of positive COVID-19 cases with sampling of a variety of biological material. Histopathological and viral analysis of biological maternal and neonatal samples will be performed, and the assessment of nutritional variables to evaluate the association between vitamin D and severity of infection. Fourth, a monitoring and evaluation committee to collect relevant healthcare information and plan actions in centres facing the pandemic. Furthermore, qualitative studies will be performed to study pregnant women, their families and health professionals. Fifth, an ecological study will monitor the number of live births, stillbirths and other outcomes to explore any trend among the periods before, during and after the pandemic. Data will systematically be collected in an electronic platform following standardised operational procedures. For quantitative study components, an appropriate statistical approach will be used for each analysis. For qualitative data, in-depth interviews recorded in audio will be transcribed, checking the text obtained with the recording. Subsequently, thematic analysis with the aid of the NVivo programme will be performed. Ethics and dissemination Ethical approval was obtained (letters of approval numbers 4.047.168, 4.179.679 and 4.083.988). All women will be fully informed to sign the consent form before enrolment in the study. Findings will be disseminated through peer-reviewed journals and scientific conferences.School of Medical Sciences. Department of Obstetrics and Gynaecology State University of Campinas Faculty of Medical SciencesDepartment of Obstetrics and Gynaecology State University of Campinas Faculty of Medical SciencesDepartment of Obstetrics and Gynecology State University of Campinas Faculty of Medical SciencesObstetrics and Gineacology State University of Campinas Faculty of Medical SciencesObstetrics and Gyneacology State University of Campinas Faculty of Medical SciencesDepartment of Obstetrics and Gynecology Faculdade de Medicina de JundiaiDepartment of Obstetrics and Gynecology Universidade Federal Do Rio Grande Do SulDepartment of Obstetrics and Gynecology Unimed Belo HorizonteDepartment of Obstetrics and Gynecology Sociedade de Assistencia A Maternidade Escola Assis ChateaubriandDepartment of Obstetrics and Gynecology UNIFESPDepartment of Obstetrics and Gynecology Hospital Moinhos de VentoDepartment of Obstetrics and Gynecology UFSCarDepartment of Obstetrics and Gynecology State University of CampinasDepartment of Obstetrics and Gynecology UFMGDepartment of Obstetrics Instituto Fernandes FigueiraDepartment of Obstetrics and Gynecology UNESP Campus de BotucatuUniversity of PernambucoObstetrics and Gyneacology Salvador UniversitySanta Casa de Misericordia Do Para BelemDepartment of Obstetrics and Gynecology UNESP Campus de Botucat

Brazilian network of COVID-19 during pregnancy (REBRACO: a multicentre study protocol)

IntroductionThe aim of this study was to evaluate the clinical, epidemiological and laboratory aspects of SARS-CoV-2 infection during pregnancy and postpartum in 16 maternity hospitals.Methods and analysisA prospective multicentre study, with five axes. First, the prevalence of SARS-CoV-2 infection among women admitted for childbirth will be described in a cross-sectional study. Second, maternal and perinatal outcomes will be assessed in a prospective cohort study including pregnant or postpartum women with suspected COVID-19. Third, a cohort of positive COVID-19 cases with sampling of a variety of biological material. Histopathological and viral analysis of biological maternal and neonatal samples will be performed, and the assessment of nutritional variables to evaluate the association between vitamin D and severity of infection. Fourth, a monitoring and evaluation committee to collect relevant healthcare information and plan actions in centres facing the pandemic. Furthermore, qualitative studies will be performed to study pregnant women, their families and health professionals. Fifth, an ecological study will monitor the number of live births, stillbirths and other outcomes to explore any trend among the periods before, during and after the pandemic. Data will systematically be collected in an electronic platform following standardised operational procedures. For quantitative study components, an appropriate statistical approach will be used for each analysis. For qualitative data, in-depth interviews recorded in audio will be transcribed, checking the text obtained with the recording. Subsequently, thematic analysis with the aid of the NVivo programme will be performed.Ethics and disseminationEthical approval was obtained (letters of approval numbers 4.047.168, 4.179.679 and 4.083.988). All women will be fully informed to sign the consent form before enrolment in the study. Findings will be disseminated through peer-reviewed journals and scientific conferences.</jats:sec