52 research outputs found

    Profiling Early Lung Immune Responses in the Mouse Model of Tuberculosis

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    Tuberculosis (TB) is caused by the intracellular bacteria Mycobacterium tuberculosis, and kills more than 1.5 million people every year worldwide. Immunity to TB is associated with the accumulation of IFNγ-producing T helper cell type 1 (Th1) in the lungs, activation of M.tuberculosis-infected macrophages and control of bacterial growth. However, very little is known regarding the early immune responses that mediate accumulation of activated Th1 cells in the M.tuberculosis-infected lungs. To define the induction of early immune mediators in the M.tuberculosis-infected lung, we performed mRNA profiling studies and characterized immune cells in M.tuberculosis-infected lungs at early stages of infection in the mouse model. Our data show that induction of mRNAs involved in the recognition of pathogens, expression of inflammatory cytokines, activation of APCs and generation of Th1 responses occurs between day 15 and day 21 post infection. The induction of these mRNAs coincides with cellular accumulation of Th1 cells and activation of myeloid cells in M.tuberculosis-infected lungs. Strikingly, we show the induction of mRNAs associated with Gr1+ cells, namely neutrophils and inflammatory monocytes, takes place on day 12 and coincides with cellular accumulation of Gr1+ cells in M.tuberculosis-infected lungs. Interestingly, in vivo depletion of Gr1+ neutrophils between days 10–15 results in decreased accumulation of Th1 cells on day 21 in M.tuberculosis-infected lungs without impacting overall protective outcomes. These data suggest that the recruitment of Gr1+ neutrophils is an early event that leads to production of chemokines that regulate the accumulation of Th1 cells in the M.tuberculosis-infected lungs

    CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

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    Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

    Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

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    The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

    Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

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    Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

    Verticillium wilt of olive: a case study to implement an integrated strategy to control a soil-borne pathogen

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    La democracia y los ciudadanos

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    Cayo Marcio, Coriolano, el legendario general romano que venció a los volscos y ayudó a expulsar al último de los tarquinos, fue condenado por el pueblo al destierro perpetuo, con todo y los servicios que había prestado a la república. Se hizo acreedor a esta condena, en especial, por ser partidario de los patricios y no mostrarse condescendiente con la plebe. Coriolano, nieto del también épico Numa Pompilio, segundo rey de Roma, consideraba humillante, para un patricio como él, la naciente institución romana que obligaba a los patricios a obtener los sufragios de la plebe para ser nombrados cónsules; por esa razón, y a pesar de que aspiraba a dicho cargo, prefirió renunciar a sus pretensiones antes que inclinarse frente a la multitud, lo cual no sólo le cerró el camino a la magistratura sino que lo condujo al destierro

    Clinical and Imaging Outcomes of Plantar Fasciotomy Using Microdebrider Coblation Wand

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    Background: A plantar fasciotomy using a microdebrider coblation wand may be an effective treatment for treating chronic plantar fasciitis. The objective of this prospective study was to determine the success rate of performing a plantar fasciotomy using a microdebrider coblation wand to treat plantar fasciitis and determine utility of ultrasonographic imaging to evaluate for recovery after treatment. Methods: Patients with plantar fasciitis treated with a plantar fasciotomy using a microdebrider coblation wand were prospectively followed for 1 year. Outcome measures included numeric rating scale (NRS) for pain, Foot and Ankle Disability Index (FADI), the Foot and Ankle Ability Measure for activities of daily living (FAAMA) and for sports (FAAMS), and plantar fascia thickness evaluated with ultrasonographic imaging. Results: Forty patients were included. Average patient age was 53.4 ± 9.9 years. Average symptom duration prior to the procedure was 20 ± 26 months. Five patients dropped out of the study at various points, most due to the COVID quarantine. The mean preoperative NRS score was 4.7 and at 3 and 6 months postprocedure was ≤2. At 1 year, the outcomes were all improved compared to the preoperative status: NRS 0.7±1.3 ( P < .001), FADI 107±16 ( P < .001), FAAMA 95%±10% ( P < .001), FAAMS 84%±19% ( P < .001), and plantar fascia thickness 6.8 ± 1.2 mm ( P = .014). Furthermore, 86% of patients had clinically successful outcome in pain, defined as NRS score ≤ 2 (95% CI 0, 2), and 91% of patients had a clinically successful outcome in their function, defined as having an FAAMA score ≥75%. There were no complications at the operative site either during or after the procedure. Conclusion: In this study of 40 patients followed prospectively, we found percutaneous plantar fasciotomy using a microdebrider coblation wand to be an effective treatment for plantar fasciitis, with a low incidence of complications. Ultrasonographic imaging may help evaluate for interval healing. Level of Evidence: Level IV, prospective case series
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