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Catheter-associated urinary tract infections are the most common hospital-acquired infections and cause patient discomfort, increased morbidity, and prolonged stays, altogether posing a huge burden on healthcare services. Colonization occurs upon insertion, or later by ascending microbes from the rich periurethral flora, and is therefore virtually unavoidable by medical procedures. Importantly, the dwell time is a significant risk factor for bacteriuria because it gives biofilms time to develop and mature. This is why we engineer antibacterial and antibiofilm coating through ultrasound- and nanoparticle-assisted self-assembly on silicone surfaces and validate it thoroughly in vitro and in vivo. To this end, we combine bimetallic silver/gold nanoparticles, which exercise both biocidal and structural roles, with dopamine-modified gelatin in a facile and substrate-independent sonochemical coating process. The latter mussel-inspired bioadhesive potentiates the activity and durability of the coating while attenuating the intrinsic toxicity of silver. As a result, our approach effectively reduces biofilm formation in a hydrodynamic model of the human bladder and prevents bacteriuria in catheterized rabbits during a week of placement, outperforming conventional silicone catheters. These results substantiate the practical use of nanoparticle–biopolymer composites in combination with ultrasound for the antimicrobial functionalization of indwelling medical devices., Peer Reviewed, Postprint (published version)

Objective: To analyse if platelet responsiveness to aspirin (ASA) may be associated with a different ability of platelets to generate nitric oxide (NO). Patients/methods: Platelets were obtained from 50 patients with stable coronary ischemia and were divided into ASA-sensitive (n = 26) and ASA-resistant (n = 24) using a platelet functionality test (PFA-100). Results: ASA-sensitive platelets tended to release more NO (determined as nitrite + nitrate) than ASA-resistant platelets but it did not reach statistical significance. Protein expression of nitric oxide synthase 3 (NOS3) was higher in ASA-sensitive than in ASA-resistant platelets but there were no differences in the platelet expression of nitric oxide synthase 2 (NOS2) isoform. The highest NOS3 expression in ASA-sensitive platelets was independent of the presence of T-to-C mutation at nucleotide position -786 (T(-786) → C) in the NOS3-coding gene. However, platelet content of phosphorylated NOS3 at Serine (Ser)(1177), an active form of NOS3, was higher in ASA-sensitive than in ASA-resistant platelets. The level of platelet NOS3 Ser(1177) phosphorylation was positively associated with the closure time in the PFA-100 test. In vitro, collagen failed to stimulate the aggregation of ASA-sensitive platelets, determined by lumiaggregometry, and it was associated with a significant increase (p = 0.018) of NOS3 phosphorylation at Ser(1177). On the contrary, collagen stimulated the aggregation of ASA-resistant platelets but did not significantly modify the platelet content of phosphorylated NOS3 Ser(1177). During collagen stimulation the release of NO from ASA-sensitive platelets was significantly enhanced but it was not modified in ASA-resistant platelets. Conclusions: Functional platelet responsiveness to ASA was associated with the platelet content of phosphorylated NOS3 at Ser(1177)., Instituto de Salud Carlos III, Unión Europea, Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, TRUE, pub

The purpose of this study was to compare the effect of dual antiplatelet therapy [clopidogrel + aspirin (ASA)] with respect to ASA on the protein expression of platelets from controlled type-2 diabetic patients with stable coronary ischemia. Patients had been taking ASA (100 mg day) and they were randomized to receive (n = 29) or not (n = 28) 75 mg day clopidogrel for 12 ± 2 weeks in a blind form. Protein expression was analyzed by two-dimensional electrophoresis and mass spectrometry. The protein expression of a limited number of proteins such as actin-binding protein isotypes 2 and 5, lactate dehydrogenase, serotransferrin isotype 4, protein disulfide isomerase-A3 isotype 1, fibrinogen beta chain isotype 5, Ras-related protein Rab-7b isotypes 1 and 6, and immunoglobulin heavy chain was changed after dual antiplatelet therapy. Plasma level of platelet factor 4 (PF4), an in vivo marker of platelet activity, was not different between both groups. These changes suggest lower platelet reactivity after dual antiplatelet therapy in the studied patients. However, the variation in platelet proteome was lower than it would be initially expected, taking into account the apparent clinical beneficial effects of dual antiplatelet therapy. PF4 plasma level was not further decreased in the platelets treated for a longer time than 9-12 months with ASA + clopidogrel, as compared with ASA alone., Fondo de Investigacion de la Seguridad Social, Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, TRUE, pub

Background Several mechanisms have been proposed to explain why some platelets have a reduced response to aspirin (ASA). Among them, it was reported an increased circulating level of vitamin-D-binding protein (DBP). In addition, nitric oxide (NO) released from mononuclear cells was involved in the antiplatelet effects of ASA. The aim was to analyse the relationship between platelet response to ASA and both NO generation and vitamin-D-binding protein content in mononuclear cells. Materials and methods Mononuclear cells were obtained from patients with stable coronary artery disease that were divided by a platelet functionality test (PFA-100) as ASA-sensitive (n = 23) and ASA resistant (n = 27). Results Both the release of NO (determined by nitrite + nitrate concentration) and the expression of endothelial-type NO synthase (eNOS) were higher in mononuclear cells from ASA sensitive as compared with those from ASA-resistant patients. There was a positive correlation between either the release of NO and the expression of eNOS protein in mononuclear cells with the ability of ASA to inhibit platelet activity. DBP content in mononuclear cells was higher in ASA resistant than in ASA sensitive. The level of DBP content in mononuclear cells was negatively associated with the ability of ASA to inhibit platelets. However, in vitro experiments suggested that there was no association between DBP and NO production by mononuclear cells. Conclusions Mononuclear cells from patients with platelets with lower responsiveness to ASA showed a reduced ability to produce NO., Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, FALSE, pub

Stroke patients have a high risk of vascular recurrence. Biomarkers related to vascular recurrence, however, remain to be identified. The aim of the study was to identify, through proteomic analysis, plasma biomarkers associated with vascular recurrence within one year after the first ischemic stroke. This is a substudy (n = 134) of a large prospective multicenter study of post-stroke patients with an ischemic stroke. Plasma samples were obtained at inclusion. Among the identified proteins, only plasma levels of desmoplakin I were associated with protection against a new vascular event (Odds ratio: 0.64; 95% CI: 0.46-0.89; p = 0.009) after adjustment for hypercholesterolemia, statins and previous atherothrombotic stroke subtype. A greater number of patients without vascular recurrence had been treated with statins within three months of the recent ischemic stroke. Only patients who had been taking statins for 3 months after the ischemic stroke and did not suffer vascular recurrence over a follow-up year, have higher levels of desmoplakin I at the time of inclusion (Odds ratio 0.49; 95% CI: 0.28-0.86; p = 0.013). Increased desmoplakin I levels, determined within 1-3 months of the first ischemic stroke, could be a biomarker for statin responsiveness against a new vascular event in post-ischemic stroke patients taking statins early (1-3 months) after the ischemic stroke., Brystol-Myers Squibb, Fondo de Investigaciones de la Seguridad Social, Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, TRUE, pub

El nombre d’usuaris de lents de contacte (LC) augmenta cada any, i amb això les infeccions oculars associades al seu ús. La queratitis infecciosa és una causa important de pèrdua de visió i és comunament causada per bacteris. Actualment existeixen LC amb capacitat antibacteriana que ajuden a prevenir la queratitis bacteriana sense utilitzar antibiòtics, però és necessari desenvolupar materials més avançats per evitar també la toxicitat que poden generar i respectar la humectabilitat i les propietats òptiques de les LC. Els nanogels (NGs) són hidrogels nanomètrics, amb propietats més avançades; amb ells, es pot recobrir la superfície de les LC per conferir-lis les propietats desitjades. La goma aràbiga és un hidrocol·loide natural altament soluble en aigua i està carregat negativament. El clorur de polidialildimetilamoni (PDDA) és un polímer catiònic sintètic que té una gran activitat antimicrobiana. La rutina és un glucòsid flavonoide natural amb una alta activitat antioxidant que també té propietats antimicrobianes. L’objectiu general d’aquest estudi és produir un NG híbrid biocompatible a base de aquests tres compostos per realitzar recobriments de LC, proporcionant-lis propietats antimicrobianes, antibiofilm, antioxidants, biocompatibles i humectants per poder controlar i disminuir les infeccions bacterianes associades a l’ús de LC, mentre s’assegura el confort de l’usuari. Aquest treball es compon d'una part predominantment pràctica on s'han dut a terme diversos experiments de diferents disciplines. S'ha optimitzat la síntesi de nanogels mitjançant interaccions electroestàtiques i la caracterització dels mateixos mitjançant diferents tècniques, confirmant la correcta formació dels nanogels i demostrant les excel·lents propietats que posseeixen com: efecte antimicrobià, activitat antioxidant, escassa citotoxicitat… Finalment s'han recobert mostres de silicona simulant el recobriment sobre lents de contacte i s'han caracteritzat les mostres de silicones recoberte, El número de usuarios de lentes de contacto (LC) aumenta cada año, y con ello, las infecciones oculares asociadas a su uso. La queratitis infecciosa es una causa importante de pérdida de visión y es comúnmente causada por bacterias. Actualmente existen LC con capacidad antibacteriana que ayudan a prevenir la queratitis bacteriana sin utilizar antibióticos, pero es necesario desarrollar materiales más avanzados para evitar también la toxicidad que pueden generar y respetar la humectabilidad y las propiedades ópticas de las LC. Los nanogeles (NGs) son hidrogeles nanométricos, con propiedades más avanzadas; con ellos, se puede recubrir la superficie de las LC para conferirles las propiedades deseadas. La goma arábiga es un hidrocoloide natural altamente soluble en agua y está cargado negativamente. El cloruro de polidialildimetilamonio (PDDA) es un polímero catiónico sintético que tiene una gran actividad antimicrobiana. La rutina es un glucósido flavonoide natural con una alta actividad antioxidante que también tiene propiedades antimicrobianas. El objetivo general de este estudio es producir un NG híbrido biocompatible a base de estos tres compuestos para realizar recubrimientos de LC, proporcionándoles propiedades antimicrobianas, antibiofilm, antioxidantes, biocompatibles y humectantes para poder controlar y disminuir las infecciones bacterianas asociadas al uso de LC, mientras se asegura el confort del usuario. Este trabajo se compone de una parte predominantemente práctica en la que se han llevado a cabo varios experimentos de diferentes disciplinas. Se ha optimizado la síntesis de nanogeles mediante interacciones electroestáticas y la caracterización de los mismos mediante diferentes técnicas, confirmando la correcta formación de los nanogeles y demostrando las excelentes propiedades que poseen como: efecto antimicrobiano, actividad antioxidante, escasa citotoxicidad… Finalmente se han recubierto muestras de silicona simulando el recubrimiento sobre lentes de co, The contact lens (CL) wearer number grows every year, alongside with ocular infections associated with CL use. Infectious keratitis is an important cause of vision loss and is commonly caused by bacteria. Currently there are CL that show antibacterial activity and help prevent bacterial keratitis without using any antibiotics, but it is necessary to develop more advanced materials in order to prevent also the toxicity they can generate and respect the wettability and optical properties of CL. Nanogels (NGs) are nanometric hydrogels with more advanced properties; CL surface can be coated with them and provided with desired properties. Arabic gum is a highly water-soluble natural hydrocolloid and it is negatively charged. Poly(diallyldimethylammonium) chloride (PDDA) is a cationic synthetic polymer that has a high antimicrobial activity. Rutin is a natural flavonoid glucoside with a high antioxidant activity that also has antimicrobial properties. The general objective of this study is to produce a hybrid biocompatible NG based on these three compounds to perform CL coatings, providing them with antimicrobial, antibiofilm, antioxidant, biocompatible and moisturizing properties in order to control and decrease bacterial infections associated to CL use, and at the same time ensure wearer comfort. This work consists of a predominantly practical part in which several experiments from different disciplines have been carried out. The synthesis of nanogels has been optimized through electrostatic interactions and their characterization through different techniques, confirming the correct formation of the nanogels and demonstrating the excellent properties they have, such as: antimicrobial effect, antioxidant activity, low cytotoxicity... Finally, silicone samples have been coated simulating the coating on contact lenses and the coated silicone samples have been characterized, confirming the presence and stability of the coating material on the surface. These preliminary resu

Es realitzarà l'estudi de la implantació d'un sistema de protecció integral contra les descàrregues electroatmosferiques sobre una planta fotovoltaica ja construïda i que manca d'aquest sistema de protecció., Se realizará el estudio de la implantación de un sistema de protección integral contra las descargas electroatmosféricas sobre una planta fotovoltaica ya construida y que carece de dicho sistema de protección.

The article arises from the reading and listening of a poet who is dedicated to teaching theology. It is based on specific verses of today’s authors, and aims to be a fieldwork for a dialogue around the unfathomable and living mystery we call «God». A mystery that is a presence, if not plentiful, yet constant in the youngest poets. The section of contemporary Spanish poetry it addresses is that of authors whose literary career has consolidated since 2000, most of them born in the seventies, eighties and nineties., El artículo nace de la lectura y escucha de un poeta que se dedica a la enseñanza de la teología. Parte de versos concretos de autores de hoy, y quiere ser trabajo de campo de cara a un diálogo en torno al inabarcable y vivo misterio que llamamos «Dios». Un misterio que es presencia, si no abundante, sí constante en los poetas más jóvenes. El tramo de la poesía española contemporánea que aborda el estudio es el de autores españoles cuya trayectoria literaria se ha ido consolidando a partir del año 2000, la mayoría de ellos nacidos en las décadas de los setenta, ochenta y noventa.