1,721,014 research outputs found
Role of intestinal permeability in patients at risk of cardiovascular diseases
Full text linkIntroduction: Platelet toll-like receptor 4 (TLR4) is overexpressed in patients with atrial fibrillation (AF) and myocardial infarction (MI), but its activation and potential trigger are not understood.
Methods: Serum levels of lipopolysaccharide (LPS) and platelet aggregation (PA) to collagen alone or in combination with a TLR4 inhibitor (TLR4i) were studied ex vivo in platelets from 50 patients with AF, 50 with MI and 50 controls matched for age, sex and atherosclerotic risk factors. The TIR domain-containing platelet adaptor protein (TIRAP) and the TIRAP-MyD88 interaction were investigated by Western blot and co-immunoprecipitation, respectively. In addition, the role of LPS in patients and its association with markers of gut permeability (zonulin), platelet aggregation, oxidative stress (sNOX2-dp, H2O2) and endothelial dysfunction (NO bioavailability, ET-1) were evaluated ex vivo by enzyme-linked immunosorbent or colorimetric assays. Furthermore, two different in vitro experiments were performed: 1) to test whether LPS induces activation of TLR4 pathway by evaluation of platelet TIR domain-containing adaptor protein (TIRAP) and TIRAP-MyD88 interaction, investigated by western blot and co-immunoprecipitation, respectively. 2) to test, on human intestinal mucosa cell line (Caco-2), whether LPS treatment induces direct damage to tight junction proteins (occludin) by Western blot analysis and co-immunoprecipitation and indirect damage by oxidative stress production.
Results: Serum LPS was significantly higher in both patient groups, AF an MI, compared to controls. Collagen-stimulated platelets from AF and MI pre-treated with TLR4i showed a significant decrease in PA compared to collagen-stimulated platelets. The ex vivo study showed that TIRAP phosphorylation and TIRAP-MyD88 immunocomplex formation were higher in both patient groups compared to controls. Also, serum zonulin, a biomarker of impaired gut barrier function, was significantly higher in both patient groups, AF an MI, compared to controls and positively correlated with serum LPS levels.
The in vitro studies showed that: 1) LPS, at concentrations similar to those found in AF and MI patients circulation, dose-dependently activated TLR4 pathway as highlighted by an increase of TIRAP phosphorylation, TIRAP-MyD88 immunocomplex formation and platelet response to the agonist, all these effect were attenuated by TLR4i. 2) the stimulation with LPS of Caco-2 cells was able to induce an increase in oxidative stress and damage to TJs proteins, reducing NOX2 activation and the expression of occluding, respectively.
Conclusion: The study proves that platelet TLR4 is activated in the AF and MI patient groups, suggesting circulating LPS as a potential trigger for platelet aggregation and intestinal barrier damage
Gut barrier dysfunction and endotoxemia in heart failure: A dangerous connubium?
No full text: Heart failure (HF) is a leading cause of death worldwide despite recent advances in pharmacological treatments. Gut microbiota dysbiosis and gut barrier dysfunction with consequent bacterial translocation and increased blood endotoxemia has gained much attention as one of the key pathogenetic mechanisms contributing to increased mortality of patients at risk or with cardiovascular disease. Indeed, increased blood levels of lipopolysaccharide (LPS), a glycolipid of outer membrane of gut gram-negative bacteria, have been detected in patients with diabetes, obesity and nonalcoholic fatty liver disease or in patients with established coronary disease such as myocardial infarction or atrial fibrillation, suggesting endotoxemia as aggravating factor via systemic inflammation and eventually vascular damage. Upon interaction with its receptor Toll-like receptor 4 (TLR4) LPS may, in fact, act at different cellular levels so eliciting formation of proinflammatory cytokines or exerting a procoagulant activity. Increasing body of evidence pointed to endotoxemia as factor potentially deteriorating the clinical course of patients with HF, that, in fact, is associated with gut dysbiosis-derived changes of gut barrier functionality and eventually bacteria or bacterial product translocation into systemic circulation. The aim of this review is to summarize current experimental and clinical evidence on the mechanisms linking gut dysbiosis-related endotoxemia with HF, its potential negative impact with HF progression, and the therapeutic strategies that can counteract endotoxemia
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Benchmarks for environmental impact of housing in Europe: Definition of archetypes and LCA of the residential building stock
Full text linkThis study describes the results of Life Cycle Assessment (LCA) applied to 24 statistically-based dwelling archetypes, representative of the EU housing stock in 2010. The aim is to quantify the average environmental impacts related to housing in Europe and to define reference values (baseline scenario) for policies development. The average environmental impacts have been calculated taking into consideration the number of dwellings (clustered per typology, year of construction and climate zone) related to each representative model. System boundaries include production, construction, use (energy and water consumption), maintenance/replacement, and end-of-life phases of each dwelling. The environmental life cycle impact assessment was carried out using the ILCD method. EU average annual environmental impact per person, per dwelling, and per m2 were calculated. Results show that the average life cycle greenhouse gases emissions related to housing per person per year are 2.62 t CO2eq and related to a representative dwelling per year are of 6.36 t CO2eq. The use phase (energy and water consumption) is the most relevant one, followed by the production and the maintenance/replacement phases. Single-family houses are responsible for the highest share of impacts related to housing in Europe. The same type of building has different impacts in different climatic zones, due to the differences in the need for space heating. In general, electricity use and space heating are the activities that contribute more to the overall impacts. The final results could be used as a baseline scenario for testing eco-innovation scenarios and setting targets toward impact reduction
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