108 research outputs found

    Neuro-axonal injury in COVID-19: the role of systemic inflammation and SARS-CoV-2 specific immune response

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    Background: In coronavirus disease-2019 (COVID-19) patients, there is increasing evidence of neuronal injury by the means of elevated serum neurofilament light chain (sNfL) levels. However, the role of systemic inflammation and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific immune response with regard to neuronal injury has not yet been investigated. Methods: In a prospective cohort study, we recruited patients with mild–moderate (n = 39) and severe (n = 14) COVID-19 and measured sNfL levels, cytokine concentrations, SARS-CoV-2-specific antibodies including neutralizing antibody titers, and cell-mediated immune responses at enrollment and at 28(±7) days. We explored the association of neuro-axonal injury as by the means of sNfL measurements with disease severity, cytokine levels, and virus-specific immune responses. Results: sNfL levels, as an indicator for neuronal injury, were higher at enrollment and increased during follow-up in severely ill patients, whereas during mild–moderate COVID-19, sNfL levels remained unchanged. Severe COVID-19 was associated with increased concentrations of cytokines assessed [interleukin (IL)-6, IL-8, interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α)], higher anti-spike IgG and anti-nucleocapsid IgG concentrations, and increased neutralizing antibody titers compared with mild–moderate disease. Patients with more severe disease had higher counts of defined SARS-CoV-2-specific T cells. Increases in sNfL concentrations from baseline to day 28(±7) positively correlated with anti-spike protein IgG antibody levels and with titers of neutralizing antibodies. Conclusion: Severe COVID-19 is associated with increased serum concentration of cytokines and subsequent neuronal injury as reflected by increased levels of sNfL. Patients with more severe disease developed higher neutralizing antibody titers and higher counts of SARS-CoV-2-specific T cells during the course of COVID-19 disease. Mounting a pronounced virus-specific humoral and cell-mediated immune response upon SARS-CoV-2 infection did not protect from neuro-axonal damage as by the means of sNfL levels

    A drift-kinetic Semi-Lagrangian 4D code for ion turbulence simulation

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    A new code is presented here, named Gyrokinetic SEmi-LAgragian (GYSELA) code, which solves 4D drift-kinetic equations for ion temperature gradient driven turbulence in a cylinder (r, theta, z). The code validation is performed with the slab ITG mode that only depends on the parallel velocity. This code uses a semi-Lagrangian numerical scheme, which exhibits good properties of energy conservation in non-linear regime as well as an accurate description of fine spatial scales. The code has been validated in the linear and non-linear regimes. The GYSELA code is found to be stable over long simulation times (more than 20 times the linear growth rate of the most unstable mode), including for cases with a high resolution mesh (delta r similar to 0.1 Larmor radius, delta z similar to 10 Larmor radius). (c) 2006 Elsevier Inc. All rights reserved

    Adjunctive Dexamethasone Affects the Expression of Genes Related to Inflammation, Neurogenesis and Apoptosis in Infant Rat Pneumococcal Meningitis

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    Streptococcus pneumoniae is the most common pathogen causing non-epidemic bacterial meningitis worldwide. The immune response and inflammatory processes contribute to the pathophysiology. Hence, the anti-inflammatory dexamethasone is advocated as adjuvant treatment although its clinical efficacy remains a question at issue. In experimental models of pneumococcal meningitis, dexamethasone increased neuronal damage in the dentate gyrus. Here, we investigated expressional changes in the hippocampus and cortex at 72 h after infection when dexamethasone was given to infant rats with pneumococcal meningitis. Nursing Wistar rats were intracisternally infected with Streptococcus pneumoniae to induce experimental meningitis or were sham-infected with pyrogen-free saline. Besides antibiotics, animals were either treated with dexamethasone or saline. Expressional changes were assessed by the use of GeneChip® Rat Exon 1.0 ST Arrays and quantitative real-time PCR. Protein levels of brain-derived neurotrophic factor, cytokines and chemokines were evaluated in immunoassays using Luminex xMAP® technology. In infected animals, 213 and 264 genes were significantly regulated by dexamethasone in the hippocampus and cortex respectively. Separately for the cortex and the hippocampus, Gene Ontology analysis identified clusters of biological processes which were assigned to the predefined categories “inflammation”, “growth”, “apoptosis” and others. Dexamethasone affected the expression of genes and protein levels of chemokines reflecting diminished activation of microglia. Dexamethasone-induced changes of genes related to apoptosis suggest the downregulation of the Akt-survival pathway and the induction of caspase-independent apoptosis. Signalling of pro-neurogenic pathways such as transforming growth factor pathway was reduced by dexamethasone resulting in a lack of pro-survival triggers. The anti-inflammatory properties of dexamethasone were observed on gene and protein level in experimental pneumococcal meningitis. Further dexamethasone-induced expressional changes reflect an increase of pro-apoptotic signals and a decrease of pro-neurogenic processes. The findings may help to identify potential mechanisms leading to apoptosis by dexamethasone in experimental pneumococcal meningitis

    Inventorying geological heritage in large territories : a methodological proposal applied to Brazil

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    An adequate management of geological heritage by national and regional authorities presupposes the existence of a solid geosites inventory. Unfortunately, this is not the case for many countries. Most often, there is no national inventory at all or the method and criteria used to assess geosites was not adequate. This paper makes an overview of the strengths and weaknesses of the most common procedures to produce a geosite inventory and proposes a methodology particularly adapted for large territories such as Brazil. Nevertheless, this methodological approach can be easily adapted to any other geographical or geological setting, promoting the characterization and conservation of the world's geological heritage.High Level Scholarship Programme of the European Union - Programme AlβanFundação para a Ciência e a Tecnologia (FCT)

    Inventory and quantitative assessment of geosites and geodiversity sites: a review

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    "Published online: 15 January 2015"The inventory and quantitative assessment of the most valuable occurrences of geodiversity are essential steps in any geoconservation strategy and in the establishment of priorities in site management. Despite the existence of many site inventories applied to different scales (countries, municipalities, parks, etc.), the criteria used for their selection are often unclear and poorly defined. This paper proposes a new approach to the concepts of geosite and geodiversity site and reviews the procedures used in the development of a systematic site inventory applied to different scales and values. Procedures to achieve a numerical evaluation of the value and degradation risk of sites are reviewed and new criteria are proposed. Finally, guidelines are presented, bearing in mind the preparation of effective geodiversity inventories, to support geoparks’ strategies. This paper aims to contribute to a better understanding and use of the above-mentioned concepts, which are essential for the implementation of geoconservation actions worldwide.The author thanks Diamantino Pereira, Flavia Lima, and Paulo Pereira for fruitful discussions and insights; Teresa Mota for the English revision; and the reviewers for significant improvements of the first submitted version. This paper results of the research done at the University of Minho and at the Geology Centre of the University of Porto, partially founded by the Foundation for Science and Technology (Portugal), strategic project with reference PEst-OE/CTE/UI0039/2014
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