606 research outputs found

    CO17 107. Experiencia inicial con la prótesis de válvula aórtica sin sutura 3f-enable de segunda generación

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    ObjetivosLa válvula aórtica ATS-3F-Enable™ representa una nueva generación con pericardio equino, stent de nitinol autoexpandible e implantación sin suturas. Evaluamos la técnica de implantación, la seguridad y efectividad de la válvula así como los resultados al año de implantación.Material y métodosAnálisis de resultados en una serie de 27 pacientes consecutivos con estenosis de válvula aórtica y reemplazamiento aislado de la válvula por una ATS-3F-Enable™ entre agosto de 2007 y febrero de 2009. La edad media fue 75,7±6,6 años. Diecisiete mujeres (63%). EuroSCORE mediano: 8, y medio: 7,1±1,7.ResultadosEl tamaño medio de válvula implantada fue de 23mm (franja: 19-27mm). La media de tiempo de clampaje aórtico fue de 39,8±15min (franja: 29-103min). La media de tiempo de circulación extracorpórea fue de 58,6±20min (franja: 41-127). La media de tiempo de hospitalización fue de 11 días (7-22). No hubo mortalidad durante la intervención. Al alta, los gradientes de presión transvalvular medio y alto con ecocardiografía fueron de 11,6 y 18,5mmHg, respectivamente. Dos pacientes presentaron una fuga paravalvular moderada y un paciente fue reoperado a causa de una fuga paravalvular grave. Se requirió la implantación de marcapasos en cinco pacientes (18,5%). El seguimiento al cabo de 1 año fue del 100% y la supervivencia fue del 86%.ConclusionesLa prótesis aórtica ATS-3F-Enable™ puede ser implantada con seguridad y presenta resultados hemodinámicos favorables. El stent autoexpandible y la técnica sin sutura permite una implantación rápida, sin embargo, no tan rápida como esperado. Acumulación de experiencia y algunas modificaciones en el diseño de la prótesis podrán ayudar a perfeccionar la técnica

    Antimicrobial residue assessment in 5, 357 commercialized meat samples from the Spain-France cross-border area: A new approach for effective monitoring

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    Although antimicrobials are valuable allies in animal production, their extended use has led to unexpected threats associated with the emergence and propagation of antimicrobial resistance. Moreover, when withdrawal periods in food-producing animals are not observed, antimicrobial residues can access the food chain, causing direct toxicity, allergies, and/or intestinal microbiota dysbiosis in consumers. Given that Spain and France are the largest meat producers in the EU and also count among the top consumers of meat, our study''s aim was to investigate the presence of antimicrobials in commercialized meat purchased in the Spain-France cross-border area (POCTEFA region). 5, 357 meat samples were collected from different animal species and a variety of different retailer types in Spain (Zaragoza, Bilbao, and Logroño) as well as in France (Toulouse and Perpignan). Meat samples were analysed by a screening method (Explorer®+QuinoScan®), yielding 194 positive samples, which were further evaluated by UPLC-QTOF (Ultra Performance Liquid Chromatography-Quadrupole Time of Flight) for confirmation. Chromatographic analyses found antimicrobial residues in 30 samples, although only 5 of them (0.093% of initial samples) were non-compliant according to the current legislation. Further studies suggested that this mismatch between screening and confirmatory analyses might be due to the presence of biologically active metabolites derived from degradation of antimicrobials that were not identified by the targeted UPLC-QTOF method, but which might play a decisive role in the inhibition of the biological Explorer® test. Although chromatographic techniques detect the marker compounds determined by European and national regulations, and although they are the methods selected for official control of antimicrobials in food, certain unknown metabolites might escape their monitoring. This thus suggests that biological tests are the most adequate ones in terms of ideal consumer health protection

    Field-adapted sampling of whole blood to determine the levels of amodiaquine and its metabolite in children with uncomplicated malaria treated with amodiaquine plus artesunate combination

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    <p>Abstract</p> <p>Background</p> <p>Artemisinin combination therapy (ACT) has been widely adopted as first-line treatment for uncomplicated falciparum malaria. In Uganda, amodiaquine plus artesunate (AQ+AS), is the alternative first-line regimen to Coartem<sup>® </sup>(artemether + lumefantrine) for the treatment of uncomplicated falciparum malaria. Currently, there are few field-adapted analytical techniques for monitoring amodiaquine utilization in patients. This study evaluates the field applicability of a new method to determine amodiaquine and its metabolite concentrations in whole blood dried on filter paper.</p> <p>Methods</p> <p>Twelve patients aged between 1.5 to 8 years with uncomplicated malaria received three standard oral doses of AQ+AS. Filter paper blood samples were collected before drug intake and at six different time points over 28 days period. A new field-adapted sampling procedure and liquid chromatographic method was used for quantitative determination of amodiaquine and its metabolite in whole blood.</p> <p>Results</p> <p>The sampling procedure was successively applied in the field. Amodiaquine could be quantified for at least three days and the metabolite up to 28 days. All parasites in all the 12 patients cleared within the first three days of treatment and no adverse drug effects were observed.</p> <p>Conclusion</p> <p>The methodology is suitable for field studies. The possibility to determine the concentration of the active metabolite of amodiaquine up to 28 days suggested that the method is sensitive enough to monitor amodiaquine utilization in patients. Amodiaquine plus artesunate seems effective for treatment of falciparum malaria.</p

    Drosha drives the formation of DNA:RNA hybrids around DNA break sites to facilitate DNA repair

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    The error-free and efficient repair of DNA double-stranded breaks (DSBs) is extremely important for cell survival. RNA has been implicated in the resolution of DNA damage but the mechanism remains poorly understood. Here, we show that miRNA biogenesis enzymes, Drosha and Dicer, control the recruitment of repair factors from multiple pathways to sites of damage. Depletion of Drosha significantly reduces DNA repair by both homologous recombination (HR) and non-homologous end joining (NHEJ). Drosha is required within minutes of break induction, suggesting a central and early role for RNA processing in DNA repair. Sequencing of DNA:RNA hybrids reveals RNA invasion around DNA break sites in a Drosha-dependent manner. Removal of the RNA component of these structures results in impaired repair. These results show how RNA can be a direct and critical mediator of DNA damage repair in human cells

    A genome-wide IR-induced RAD51 foci RNAi screen identifies CDC73 involved in chromatin remodeling for DNA repair

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    To identify new regulators of homologous recombination repair, we carried out a genome-wide short-interfering RNA screen combined with ionizing irradiation using RAD51 foci formation as readout. All candidates were confirmed by independent short-interfering RNAs and validated in secondary assays like recombination repair activity and RPA foci formation. Network analysis of the top modifiers identified gene clusters involved in recombination repair as well as components of the ribosome, the proteasome and the spliceosome, which are known to be required for effective DNA repair. We identified and characterized the RNA polymerase II-associated protein CDC73/Parafibromin as a new player in recombination repair and show that it is critical for genomic stability. CDC73 interacts with components of the SCF/Cullin and INO80/NuA4 chromatin-remodeling complexes to promote Histone ubiquitination. Our findings indicate that CDC73 is involved in local chromatin decondensation at sites of DNA damage to promote DNA repair. This function of CDC73 is related to but independent of its role in transcriptional elongation

    A genome-wide screening uncovers the role of CCAR2 as an antagonist of DNA end resection

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    There are two major and alternative pathways to repair DNA double-strand breaks: non-homologous end-joining and homologous recombination. Here we identify and characterize novel factors involved in choosing between these pathways; in this study we took advantage of the SeeSaw Reporter, in which the repair of double-strand breaks by homology-independent or -dependent mechanisms is distinguished by the accumulation of green or red fluorescence, respectively. Using a genome-wide human esiRNA (endoribonuclease- prepared siRNA) library, we isolate genes that control the recombination/endjoining ratio. Here we report that two distinct sets of genes are involved in the control of the balance between NHEJ and HR: those that are required to facilitate recombination and those that favour NHEJ. This last category includes CCAR2/DBC1, which we show inhibits recombination by limiting the initiation and the extent of DNA end resection, thereby acting as an antagonist of CtIP

    Consistent patterns of common species across tropical tree communities

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    Trees structure the Earth's most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations1−6^{1-6} in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth's 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories7^{7}, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world's most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees
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