Fractional flow reserve, ratio of the instantaneous pressure in the wave free period and the coronary computed tomographic angiography

Los índices fisiológicos permiten calcular el impacto hemodinámico de las lesiones coronarias. En la actualidad, los índices fisiológicos intracoronarios más usados y que mejor evalúan la severidad funcional de dichas lesiones, son el flujo de reserva fraccional, y la relación de la presión instantánea en el periodo libre de ondas. La fórmula simplificada del flujo de reserva fraccional es la relación entre la presión media distal a la lesión y la presión aórtica media bajo un estímulo hiperémico con adenosina; el valor 0,8 es el punto de corte aceptado para definir que una lesión coronaria es relevante desde el punto de vista hemodinámico. Por su parte, el período libre de ondas se define como una relación entre la presión intracoronaria media distal y la presión aórtica media, durante un periodo diastólico que inicia luego del 25% de la diástole y que termina 5 milisegundos antes de finalizar ésta (periodo libre de ondas), lo que permite determinar esta relación sin necesidad de administrar agentes hiperémicos. La angiografía coronaria mediante tomografía computarizada, se ha posicionado como una alternativa no invasiva para la evaluación de la anatomía coronaria, y al presente, la adición de pruebas funcionales a este estudio, como lo son el flujo de reserva fraccional y la angiotomografía coronaria, proporciona información de la anatomía coronaria, y de forma complementaria, del impacto fisiológico de las lesiones coronarias.The physiological indices can help to calculate the haemodynamic impact of coronary lesions. The most currently most used physiological indices those that better evaluate the functional severity of these lesions, are the fractional flow reserve and relationship of the instantaneous pressure in the wave free period. The simplified formula of the fractional flow reserve is the ratio between the mean pressure distal to the lesion and the mean aortic pressure under hyperaemic stimulation with adenosine. A cut-off value of 0.8 is accepted in order to define that a coronary lesion is significant from a haemodynamic point of view. For its part, the wave free period is defined as a ratio between the distal mean intracoronary pressure and the mean aortic pressure, during a diastolic period that starts after 25% of the diastole and ends 5 milliseconds before this finishes (wave free period). This helps to determine this ratio without the need to administer hyperaemic agents. The coronary angiography using computed tomography, has been shown to be a non-invasive alternative for the evaluation of the coronary anatomy, and to the present one, the addition of function tests to this study, as are the fractional flow reserve and computed tomography angiograph, provide information on the coronary anatomy, and in a complementary manner, of the physiological impact of the coronary lesions

La interacción de procesos hidrológicos, químicos y microbiológicos en la formación de películas flotantes ricas en hierro en ambientes acuáticos de pH circumneutro

17 páginas.-- 3 figuras.-- 4 tablas.-- 53 referencias.-- Postprint (Versión editorial)[EN]: The direct contribution of microbial activity to the formation of iron-oxide minerals is difficult to prove in wetlands due to the high reactivity of solid iron phases with different compounds and the variety of redox processes that may occur at each oxic-anoxic boundary. Here, we propose an explanation for the formation of iron-oxide films in wetlands and groundwater seepage areas fed by sandy aquifers based on the interaction of hydrological, chemical and microbiological processes under circumneutral conditions. The presence of a floating iron-oxide film was found to create a boundary at the air-water interface that maintains a suboxic and slightly acidic environment below the film compared with the environments obtained in other free-film wetland areas. The water trapped below this film had an average pH of 6.1, was particularly poor in O2, HCO–3, Na+, Ca2+, Mg2+, K+, and Tot-S, and has high concentrations of Tot-P, Tot-Fe, NH+4 and Zn. The formation of a floating iron-oxide film was reproduced under anaerobic conditions after progressive enrichment through the incubation of natural sediment samples in the laboratory. Heterotrophic bacteria belonging to the genus Enterobacter were the dominant bacteria in the enrichments that resulted in the formation of a floating iron-oxide film. The X-ray diffraction patterns showed that the presence of two-line ferrihydrite was common to the iron-oxide films collected in both the natural environment and the laboratory cultures, whereas other iron-oxides (goethite and low-crystalline lepidocrocite) were observed only in the natural environment. This study highlights the role of ubiquitous bacteria, which are generally considered unimportant participants in iron-transformation processes in the environment, and the contribution of both biological and non-biological processes to iron oxidation in natural systems under circumneutral conditions.[ES]: En los humedales, es difícil probar que la actividad microbiana sea la responsable de la formación de óxido de hierro mineral debido, tanto a la gran reactividad del hierro en fase sólida con diferentes sustancias, como a la variedad de procesos redox que pueden ocurrir en cada interfase óxica-anóxica. El presente trabajo propone una explicación, basada en la interacción de procesos hidrológicos, químicos y microbiológicos en condiciones circumneutras, para explicar la formación de un film de óxido de hierro en humedales y manaderos donde aflora agua subterránea proveniente de acuíferos de arenas silíceas. Además, la presencia de un film de óxido de hierro que flota sobre la interfase agua-aire genera condiciones subóxicas y ligeramente ácidas en el agua que queda atrapada debajo, y que son muy distintas a otras zonas libres de film en el mismo humedal. Este agua atrapada bajo el film se caracterizó por presentar un pH medio de 6.1, una menor concentración de O2, HCO–3, Na+, Ca2+, Mg2+, K+, y S total, pero una mayor riqueza en P total, Fe total, NH+4 y Zn. La formación de un film flotante de óxido de hierro se reprodujo en el laboratorio, en condiciones anaeróbicas, tras el enriquecimiento progresivo de las muestras del sedimento natural que habían sido incubadas. En dichos enriquecimientos, donde se produjeron films flotantes de óxido de hierro, la bacteria dominante perteneció al género Enterobacter. Mediante difracción por rayos X, se encontró ferrihidrita con estructura en doble cadena, tanto en el film de muestras naturales como de cultivos de laboratorio. Además se encontraron otros tipos de óxidos minerales (goetita y lepidocrocita de pobre cristalización) sólo en las muestras naturales de film. El presente estudio muestra la relevancia de bacterias ubicuas, hasta ahora consideradas sin importancia en procesos naturales de transformación del hierro, y la participación tanto de procesos bióticos como abióticos en la oxidación del hierro en sistemas naturales sometidos a condiciones circumneutras.We are grateful to Han Golterman for his support and suggestions. We thank Lotte Fleskens and Christien van der Zwart for collaborating with the sediment collection and P-fractionation at the laboratory. This study was partially supported by the Spanish Ministry of Education and Science (CGL2004-03927-C02-01/BOS)Peer reviewe

Mild stress conditions during laboratory culture promote the proliferation of mutations that negatively affect Sigma B activity in Listeria monocytogenes

In Listeria monocytogenes, the full details of how stress signals are integrated into the σB regulatory pathway are not yet available. To help shed light on this question, we investigated a collection of transposon mutants that were predicted to have compromised activity of the alternative sigma factor B (σB). These mutants were tested for acid tolerance, a trait that is known to be under σB regulation, and they were found to display increased acid sensitivity, similar to a mutant lacking σB (ΔsigB). The transposon insertions were confirmed by whole-genome sequencing, but in each case, the strains were also found to carry a frameshift mutation in the sigB operon. The changes were predicted to result in premature stop codons, with negative consequences for σB activation, independently of the transposon location. Reduced σB activation in these mutants was confirmed. Growth measurements under conditions similar to those used during the construction of the transposon library revealed that the frameshifted sigB operon alleles conferred a growth advantage at higher temperatures, during late exponential phase. Mixed-culture experiments at 42°C demonstrated that the loss of σB activity allowed mutants to take over a population of parental bacteria. Together, our results suggest that mutations affecting σB activity can arise during laboratory culture because of the growth advantage conferred by these mutations under mild stress conditions. The data highlight the significant cost of stress protection in this foodborne pathogen and emphasize the need for whole-genome sequence analysis of newly constructed strains to confirm the expected genotype.This project has received funding from the European Union’s Horizon 2020 research-and-innovation program under Marie Skłodowska-Curie grant agreement no. 721456. Jialun Wu was funded by the Department of Agriculture, Food and the Marine (17/F/244)

Characterization of Plasmodium vivax Proteins in Plasma-Derived Exosomes From Malaria-Infected Liver-Chimeric Humanized Mice

Exosomes are extracellular vesicles of endocytic origin containing molecular signatures implying the cell of origin; thus, they offer a unique opportunity to discover biomarkers of disease. Plasmodium vivax, responsible for more than half of all malaria cases outside Africa, is a major obstacle in the goal of malaria elimination due to the presence of dormant liver stages (hypnozoites), which after the initial infection may reactivate to cause disease. Hypnozoite infection is asymptomatic and there are currently no diagnostic tools to detect their presence. The human liver-chimeric (FRG huHep) mouse is a robust P. vivax infection model for exo-erythrocytic development of liver stages, including hypnozoites. We studied the proteome of plasma-derived exosomes isolated from P. vivax infected FRG huHep mice with the objective of identifying liver-stage expressed parasite proteins indicative of infection. Proteomic analysis of these exosomes showed the presence of 290 and 234 proteins from mouse and human origin, respectively, including canonical exosomal markers. Human proteins include proteins previously detected in liver-derived exosomes, highlighting the potential of this chimeric mouse model to study plasma exosomes derived unequivocally from human hepatocytes. Noticeably, we identified 17 parasite proteins including enzymes, surface proteins, components of the endocytic pathway and translation machinery, as well as uncharacterized proteins. Western blot analysis validated the presence of human arginase-I and an uncharacterized P. vivax protein in plasma-derived exosomes. This study represents a proof-of-principle that plasma-derived exosomes from P. vivax infected FRG-huHep mice contain human hepatocyte and P. vivax proteins with the potential to unveil biological features of liver infection and identify biomarkers of hypnozoite infection

On cytoadhesion of Plasmodium vivax: raison d'etre?

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)It is generally accepted that Plasmodium vivax, the most widely distributed human malaria parasite, causes mild disease and that this species does not sequester in the deep capillaries of internal organs. Recent evidence, however, has demonstrated that there is severe disease, sometimes resulting in death, exclusively associated with P. vivax and that P. vivax-infected reticulocytes are able to cytoadhere in vitro to different endothelial cells and placental cryosections. Here, we review the scarce and preliminary data on cytoadherence in P. vivax, reinforcing the importance of this phenomenon in this species and highlighting the avenues that it opens for our understanding of the pathology of this neglected human malaria parasite.10617984Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CELLEX FoundationMICINNFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Highlights of the São Paulo ISEV workshop on extracellular vesicles in cross-kingdom communication

In the past years, extracellular vesicles (EVs) have become an important field of research since EVs have been found to play a central role in biological processes. In pathogens, EVs are involved in several events during the host–pathogen interaction, including invasion, immunomodulation, and pathology as well as parasite–parasite communication. In this report, we summarised the role of EVs in infections caused by viruses, bacteria, fungi, protozoa, and helminths based on the talks and discussions carried out during the International Society for Extracellular Vesicles (ISEV) workshop held in São Paulo (November, 2016), Brazil, entitled Cross-organism Communication by Extracellular Vesicles: Hosts, Microbes and Parasites. © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.11Ysciescopu

Salmonella enterica Serovar Typhimurium Lacking hfq Gene Confers Protective Immunity against Murine Typhoid

Salmonella enterica is an important enteric pathogen and its various serovars are involved in causing both systemic and intestinal diseases in humans and domestic animals. The emergence of multidrug-resistant strains of Salmonella leading to increased morbidity and mortality has further complicated its management. Live attenuated vaccines have been proven superior over killed or subunit vaccines due to their ability to induce protective immunity. Of the various strategies used for the generation of live attenuated vaccine strains, focus has gradually shifted towards manipulation of virulence regulator genes. Hfq is a RNA chaperon which mediates the binding of small RNAs to the mRNA and assists in post-transcriptional gene regulation in bacteria. In this study, we evaluated the efficacy of the Salmonella Typhimurium Δhfq strain as a candidate for live oral vaccine in murine model of typhoid fever. Salmonella hfq deletion mutant is highly attenuated in cell culture and animal model implying a significant role of Hfq in bacterial virulence. Oral immunization with the Salmonella hfq deletion mutant efficiently protects mice against subsequent oral challenge with virulent strain of Salmonella Typhimurium. Moreover, protection was induced upon both multiple as well as single dose of immunizations. The vaccine strain appears to be safe for use in pregnant mice and the protection is mediated by the increase in the number of CD4+ T lymphocytes upon vaccination. The levels of serum IgG and secretory-IgA in intestinal washes specific to lipopolysaccharide and outer membrane protein were significantly increased upon vaccination. Furthermore, hfq deletion mutant showed enhanced antigen presentation by dendritic cells compared to the wild type strain. Taken together, the studies in murine immunization model suggest that the Salmonella hfq deletion mutant can be a novel live oral vaccine candidate

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Gene Expression Profiles of Chicken Embryo Fibroblasts in Response to Salmonella Enteritidis Infection

The response of chicken to non-typhoidal Salmonella infection is becoming well characterised but the role of particular cell types in this response is still far from being understood. Therefore, in this study we characterised the response of chicken embryo fibroblasts (CEFs) to infection with two different S. Enteritidis strains by microarray analysis. The expression of chicken genes identified as significantly up- or down-regulated (≥3-fold) by microarray analysis was verified by real-time PCR followed by functional classification of the genes and prediction of interactions between the proteins using Gene Ontology and STRING Database. Finally the expression of the newly identified genes was tested in HD11 macrophages and in vivo in chickens. Altogether 19 genes were induced in CEFs after S. Enteritidis infection. Twelve of them were also induced in HD11 macrophages and thirteen in the caecum of orally infected chickens. The majority of these genes were assigned different functions in the immune response, however five of them (LOC101750351, K123, BU460569, MOBKL2C and G0S2) have not been associated with the response of chicken to Salmonella infection so far. K123 and G0S2 were the only 'non-immune' genes inducible by S. Enteritidis in fibroblasts, HD11 macrophages and in the caecum after oral infection. The function of K123 is unknown but G0S2 is involved in lipid metabolism and in β-oxidation of fatty acids in mitochondria