Contribution of Impaired Insulin Signaling to the Pathogenesis of Diabetic Cardiomyopathy

Diabetes; Diabetic cardiomyopathy; HeartDiabetis; Cardiomiopatia diabètica; CorDiabetes; Cardiomiopatía diabética; CorazónDiabetic cardiomyopathy (DCM) has emerged as a relevant cause of heart failure among the diabetic population. Defined as a cardiac dysfunction that develops in diabetic patients independently of other major cardiovascular risks factors, such as high blood pressure and coronary artery disease, the underlying cause of DCMremains to be unveiled. Several pathogenic factors, including glucose and lipid toxicity, mitochondrial dysfunction, increased oxidative stress, sustained activation of the renin-angiotensin system (RAS) or altered calcium homeostasis, have been shown to contribute to the structural and functional alterations that characterize diabetic hearts. However, all these pathogenic mechanisms appear to stem from the metabolic inflexibility imposed by insulin resistance or lack of insulin signaling. This results in absolute reliance on fatty acids for the synthesis of ATP and impairment of glucose oxidation. Glucose is then rerouted to other metabolic pathways, with harmful effects on cardiomyocyte function. Here, we discuss the role that impaired cardiac insulin signaling in diabetic or insulin-resistant individuals plays in the onset and progression of DCM.Supported by grants BFU2015-64462R from the Ministerio de Economía y Competitividad (MINECO/FEDER, UE) and HR17-00627 from La Caixa Foundation to J.A.V

Effects of Surface and Top Wind Shear on the Spatial Organization of Marine Stratocumulus-Topped Boundary Layers

The convective nature of Stratocumulus topped boundary layers (STBL) involves the motion of updrafts and downdrafts, driven by surface fluxes and radiative cooling, respectively. The balance between shear and buoyant forcings at the surface can determine the organization of updrafts between cellular and roll structures. We investigate the effect of varying shear at the surface and top of the STBL using Large Eddy Simulations, taking DYCOMS II RF01 as a base case. We focus on spatial identification of the following features: coherent updrafts and downdrafts, and observe how they are affected by varying shear. Stronger surface shear organizes the updrafts in rolls, causes less well-mixed thermodynamic profiles, and decreases cloud fraction and liquid water path (LWP). Stronger top shear also decreases cloud fraction and LWP more than surface shear, by thinning the cloud from the top. Features with stronger top than surface shear are associated with a net downward momentum transport and show early signs of decoupling. Classifying updrafts and downdrafts based on their vertical span and horizontal size confirms the dominance of tall objects spanning the whole STBL. Tall objects occupy 30% of the volume in the STBL, while short ones occupy less than 1%. For updraft and downdraft fluxes, these tall objects explain 65% of the vertical velocity variance and 83% of the buoyancy flux, on average. Stronger top shear also weakens the contribution of downdrafts to the turbulent fluxes and tilts the otherwise vertical development of updrafts

La figura de Yoshitsune en el katazuke Umewaka: un analisis del dispositivo estetico y coreografico del rol de kokata en el teatro Nō

Sin da subito l'indagine ha avuto l'esigenza di orientarsi in una cornice antropologica che contemplasse diversi esempi, individuati nelle teatralità asiatiche, nei quali l'infanzia si poneva come veicolo performativo. Fondamentale per giungere all'identificazione delle difficoltà tecniche sostenute da parte dell'attore fanciullo nonché indispensabile a definire il caso di studio e ridimensionarlo, nello specifico, alla teatralità classica giapponese. L'importanza degli elementi di natura orale, scritta e aurale sono stati identificati come paradigmatici nella dialettica di trasmissione del sapere attirare che nel caso specifico del teatro nō presuppongono compenenti indispensabili per la realizzazione dell'embodimente di tradizione da parte dell'attore in età adulta, lo shiteFrom the beginning, this research has developed an anthropological from that contemplates several example, individuated within the Asian performance. Meaningful to identify the technical difficulty that holds the child actor in order to define the case of study within a new dimension, specifically into the Japanese Classical theatricality. The importance of the orality, written and listening spheres have been identified as paradigmatic of the transmission epistemology dialectics of that will give a nuance for the understanding of embodiment trasdizion for the actor in adulthood, the master shit

Seguridad y Salud en el Trabajo una innovación constante

La Seguridad y Salud en el Trabajo es un tema que toma cada vez más importancia dentro de las organizaciones, por lo tanto,  hablar de innovación en este campo es elemento clave y diferenciador en las organizaciones, que puede contribuir a reducir el riesgo de accidentes y enfermedades laborales, así como aumentar la competitividad de la empresa y por ende mejorar su calidad de vida; la innovación puede incluir medidas organizativas hasta nuevos sistemas de control de los peligros, algunas estrategias de innovación están orientadas a Introducir nuevas tecnologías de seguridad.&nbsp

Clinical characteristics and outcome of Spanish patients with ANCA-associated vasculitides: Impact of the vasculitis type, ANCA specificity, and treatment on mortality and morbidity

Spain; ANCA; VasculitidesEspanya; ANCA; VasculitisEspaña; ANCA; VasculitisThe aim of this study was to describe the clinical characteristics of ANCA-associated vasculitides (AAV) at presentation, in a wide cohort of Spanish patients, and to analyze the impact of the vasculitis type, ANCA specificity, prognostic factors, and treatments administered at diagnosis, in the outcome.A total of 450 patients diagnosed between January 1990 and January 2014 in 20 Hospitals from Spain were included. Altogether, 40.9% had granulomatosis with polyangiitis (GPA), 37.1% microscopic polyangiitis (MPA), and 22% eosinophilic granulomatosis with polyangiitis (EGPA). The mean age at diagnosis was 55.6 ± 17.3 years, patients with MPA being significantly older (P < 0.001). Fever, arthralgia, weight loss, respiratory, and ear-nose-throat (ENT) symptoms, were the most common at disease onset. ANCAs tested positive in 86.4% of cases: 36.2% C-ANCA-PR3 and 50.2% P-ANCA-MPO. P-ANCA-MPO was significantly associated with an increased risk for renal disease (OR 2.6, P < 0.001) and alveolar hemorrhage (OR 2, P = 0.010), while C-ANCA-PR3 was significantly associated with an increased risk for ENT (OR 3.4, P < 0.001) and ocular involvement (OR 2.3, P = 0.002). All patients received corticosteroids (CS) and 74.9% cyclophosphamide (CYC). The median follow-up was 82 months (IQR 100.4). Over this period 39.9% of patients suffered bacterial infections and 14.6% opportunistic infections, both being most prevalent in patients with high-cumulated doses of CYC and CS (P < 0.001). Relapses were recorded in 36.4% of cases with a mean rate of 2.5 ± 2.3, and were more frequent in patients with C-ANCA-PR3 (P = 0.012). The initial disease severity was significantly associated with mortality but not with the occurrence of relapses. One hundred twenty-nine (28.7%) patients (74 MPA, 41 GPA, 14 EGPA) died. The mean survival was 58 months (IQR 105) and was significantly lower for patients with MPA (P < 0.001). Factors independently related to death were renal involvement (P = 0.010), cardiac failure (P = 0.029) and age over 65 years old (P < 0.001) at disease onset, and bacterial infections (P < 0.001). An improved outcome with significant decrease in mortality and treatment-related morbidity was observed in patients diagnosed after 2000, and was related to the implementation of less toxic regimens adapted to the disease activity and stage, and a drastic reduction in the cumulated CYC and CS dose

Nutritional intra-amniotic therapy increases survival in a rabbit model of fetal growth restriction

Objective To evaluate the perinatal effects of a prenatal therapy based on intra-amniotic nutritional supplementation in a rabbit model of intrauterine growth restriction (IUGR). Methods IUGR was surgically induced in pregnant rabbits at gestational day 25 by ligating 40-50% of uteroplacental vessels of each gestational sac. At the same time, modified-parenteral nutrition solution (containing glucose, amino acids and electrolytes) was injected into the amniotic sac of nearly half of the IUGR fetuses (IUGR-T group n = 106), whereas sham injections were performed in the rest of fetuses (IUGR group n = 118). A control group without IUGR induction but sham injection was also included (n = 115). Five days after the ligation procedure, a cesarean section was performed to evaluate fetal cardiac function, survival and birth weight. Results Survival was significantly improved in the IUGR fetuses that were treated with intra-amniotic nutritional supplementation as compared to non-treated IUGR animals (survival rate: controls 71% vs. IUGR 44% p = 0.003 and IUGR-T 63% vs. IUGR 44% p = 0.02), whereas, birth weight (controls mean 43g ± SD 9 vs. IUGR 36g ± SD 9 vs. IUGR-T 35g ± SD 8, p = 0.001) and fetal cardiac function were similar among the IUGR groups. Conclusion Intra-amniotic injection of a modified-parenteral nutrient solution appears to be a promising therapy for reducing mortality among IUGR. These results provide an opportunity to develop new intra-amniotic nutritional strategies to reach the fetus by bypassing the placental insufficienc

Gene therapy with Angiotensin-(1-9) preserves left ventricular systolic function after myocardial infarction

BACKGROUND: Angiotensin-(1-9) [Ang-(1-9)] is a novel peptide of the counter-regulatory axis of the renin angiotensin system previously demonstrated to have therapeutic potential in hypertensive cardiomyopathy when administered via osmotic minipump in mice. Here, we investigate whether gene transfer of Ang-(1-9) is cardioprotective in a murine model of myocardial infarction (MI). OBJECTIVES: To evaluate effects of Ang-(1-9) gene therapy on myocardial structural and functional remodeling post infarction. METHODS: C57BL/6 mice underwent permanent left anterior descending coronary artery ligation and cardiac function was assessed using echocardiography for 8 weeks followed by a terminal measurement of left ventricular (LV) pressure-volume loops. Ang-(1-9) was delivered by adeno-associated viral vector via single tail vein injection immediately following induction of MI. Direct effects of Ang-(1-9) on cardiomyocyte excitation–contraction coupling and cardiac contraction were evaluated in isolated mouse and human cardiomyocytes and in an ex vivo Langendorff perfused whole heart model. RESULTS: Gene delivery of Ang-(1-9) significantly reduced sudden cardiac death post-MI. Pressure–volume measurements revealed complete restoration of end systolic pressure, ejection fraction, end systolic volume and the end diastolic pressure–volume relationship by Ang-(1-9) treatment. Stroke volume and cardiac output were significantly increased versus sham. Histological analysis revealed only mild effects on cardiac hypertrophy and fibrosis, but a significant increase in scar thickness. Direct assessment of Ang-(1-9) on isolated cardiomyocytes demonstrated a positive inotropic effect via increasing calcium transient amplitude and increasing contractility. Ang-(1-9) increased contraction in the Langendorff model through a protein kinase A-dependent mechanism. CONCLUSIONS: Our novel findings show that Ang-(1-9) gene therapy preserves LV systolic function post-MI, restoring cardiac function. Furthermore, Ang-(1-9) has a direct effect on cardiomyocyte 3 calcium handling through a protein kinase A-dependent mechanism. These data highlight Ang-(1-9) gene therapy as a potential new strategy in the context of MI

Cross-talk between the RcsCDB and RstAB systems to control STM1485 gene expression in Salmonella Typhimurium during acid-resistance response

Bacterial survive and respond to adverse changes in the environment by regulating gene transcription through two-component regulatory systems. In Salmonella Typhimurium the STM1485 gene expression is induced under low pH (4.5) during replication inside the epithelial host cell, but it is not involved in sensing or resisting to this condition. Since the RcsCDB system is activated under acidic conditions, we investigated whether this system is able to modulate STM1485 expression. We demonstrated that acid-induced activation of the RcsB represses STM1485 transcription by directly binding to the promoter. Under the same condition, the RstA regulator activates the expression of this gene. Physiologically, we observed that RcsB-dependent repression is required for the survival of bacteria when they are exposed to pancreatic fluids. We hypothesized that STM1485 plays an important role in Salmonella adaptation to pH changes, during transition in the gastrointestinal tract. We suggest that bacteria surviving the gastrointestinal environment invade the epithelial cells, where they can remain in vacuoles. In this new environment, acidity and magnesium starvation activate the expression of the RstA regulator in a PhoPQ-dependent manner, which in turn induces STM1485 expression. These levels of STM1485 allow increased bacterial replication within vacuoles to continue the course of infection.Fil: Torrez Lamberti, Monica Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Biológica; ArgentinaFil: Farizano, Juan Vicente. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Biológica; ArgentinaFil: Lopez, Fabian Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Biológica; Argentina. Universidad Nacional de Chilecito; ArgentinaFil: Martinez Zamora, Martin Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Biológica; ArgentinaFil: Pescaretti, María de Las Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Biológica; ArgentinaFil: Táquez Delgado, Mónica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Biológica; Argentin

Modelamiento del consumo y demanda de pomaceas: el caso de la ciudad de Talca

294 p.Esta investigación consiste en un estudio exploratorio del Consumo Interno y Demanda de Pomáceas en la ciudad de Talca. El trabajo considera un análisis de los consumidores talquinos, realizado a través de dos herramientas de recopilación de datos, una encuesta y un panel, las que fueron usadas para lo siguiente: a) La encuesta, sirvió para estudiar a los consumidores en cuanto a preferencias, lugares y frecuencias de compra, modos de consumo. Se utilizó para determinar las variables principales que inciden en la demanda y el consumo. b) La segunda herramienta fue un panel experimental de consumidores, donde registraban diariamente las cantidades compradas de cada pomácea, el precio de compra, la cantidad consumida y las formas de consumo; durante un mes. Los datos del panel se usaron para nivelar las variables m6s importantes, en una función de demanda que explica el comportamiento del consumidor talquino en relación a la toma de decisiones de compra de pomáceas. El modelo estimado consideró los siguientes predictores: la cantidad consumida del bien es función del precio del bien, del ingreso, del precio de otros bienes. Los gustos, que también afectan la demanda, se suponen dados o constantes por lo breve del periodo. Resumiendo los resultados obtenidos: 1) Las variables que poseen una influencia mayor en la decisión de compra de pomáceas son: el precio, la época del año, el precio de otras frutas, el ingreso, la disponibilidad de otras frutas, el término de la compra anterior, y el aspecto general de la fruta. La importancia de cada una de estas variables, cambia según el estrato socio-econ6mico. 2) En términos generales se observó que, los consumidores tienen un "comportamiento racional" en cuanto a la valoración de la variable precio como variable fundamental en la decisión de compra. Pero predominan influencias socio-económicas. 3) La elasticidad precio de la demanda cambia por estrato socio-económico. Para la manzana roja la función de demanda es elástica al precio en los estratos "C2C3" y "DE", siendo inelástica en el estrato ABC1. En el caso de la manzana verde y la pera la situación es igual para el estrato bajo y alto, en cambio en el grupo medio resulta una función de demanda inelástica, pero en menor medida que en el estrato alto. Las elasticidades ingreso estimadas, indican que las pomáceas son un bien normal para el estrato bajo, e inferior para el estrato alto y medio