Cardiovascular drugs inducing QT prolongation: facts and evidence

Acquired QT syndrome is mainly caused by the administration of drugs that prolong ventricular repolarization. On the other hand, the risk of drug-induced torsades de pointes is increased by numerous predisposing factors, such as genetic predisposition, female sex, hypokalemia and cardiac dysfunction. This adverse reaction is induced by different chemical compounds used for the treatment of a variety of pathologies, including arrhythmias. As it is known, antiarrhythmic agents and other cardiovascular drugs can prolong the QT interval, causing this adverse reaction. Of the 20 most commonly reported drugs, 10 were cardiovascular agents and these appeared in 348 of the reports (46%). Class Ia antiarrhythmic agents have frequently been linked to inducing arrhythmia, including torsades de pointes. Sotalol and amiodarone, class III antiarrhythmics, are known to prolong the QT interval by blocking IKr. Due to the severity of events caused by the therapeutic use of these drugs, in this work of revision the cardiovascular drugs that present this property and the factors and evidence will be mentioned.Fil: Taira, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; ArgentinaFil: Opezzo, Javier A. W.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; ArgentinaFil: Mayer, Marcos Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; ArgentinaFil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentin

Aceleración y estabilización: disparidad en la tendencia de obesidad en escolares de la provincia de La Pampa (Argentina) entre 1990 y 2016

Despite the efforts launched by several organizations to reduce obesity, only some developed countries show either a slowdown or a leveling off in obesity rate. In this study we evaluated trends in body mass index (BMI) and rates of overweight (OW) and obesity (OB) in schoolchildren, from 1990 to 2016, together with their socioeconomic distribution. Three cross-sectional surveys conducted in 1990, 2005/07 and 2015/16 in schoolchildren from Santa Rosa (La Pampa, Argentina) were compared. The International Obesity Task Force (IOTF) reference was used to calculate standard deviation scores of BMI and define OW and OB categories. The type of school (public or private) was used as a measure of socioeconomic status (SES). The association of dependent variables with survey year, sex, and SES was analyzed by linear (BMI) and logistic regression (OW, OB) models. Temporal changes in OW and OB rates were assessed by Chi-squared test for trend among proportions. BMI, OW, and OB increased significantly throughout the period 1990-2016, resulting in one third of children with excessive weight. From 2005/07 to 2015/16 significant increases were seen only in children attending public schools. Trends were similar among boys and girls. It is concluded that the weight status of this schoolchildren population shows a non-linear but continuous pattern of increase, developed over the last 25 years, with stabilization in those children of higher SES in the last decade. A pesar de los esfuerzos de diversos organismos para reducir la obesidad, sólo algunos países desarrollados muestran una desaceleración o estabilización de su prevalencia. Este trabajo presenta las tendencias en el índice de masa corporal (IMC) y las prevalencias de sobrepeso (SP) y obesidad (OB) ocurridas en escolares entre 1990 y 2016, y su distribución socioeconómica. Se compararon tres encuestas transversales realizadas en 1990, 2005/07 y 2015/16 en escolares primarios de Santa Rosa (La Pampa, Argentina). Para estandarizar los valores de IMC y definir las categorías SP y OB se empleó la referencia International Obesity Task Force (IOTF). El tipo de escuela se empleó como medida de nivel socioeconómico (NSE). Para analizar la asociación entre las variables dependientes con año de encuesta, sexo y NSE se aplicaron modelos de regresión lineal (IMC) y logística (SP, OB). El cambio temporal en las prevalencias de SP y OB se evaluó mediante Chi- cuadrado de tendencia entre proporciones. IMC, SP y OB incrementaron significativamente en el periodo 1990-2016, resultando en un tercio de la población con exceso de peso. Entre 2005/07 y 2015/16 sólo hubo incrementos significativos en niños que asistían a escuelas públicas. Las tendencias fueron similares en varones y niñas. Se concluye que el estatus de peso en esta población escolar muestra un patrón de aumento no lineal pero continuo en los últimos 25 años, con una estabilización en los sectores de mayor NSE durante la última década. &nbsp

Acceleration and stabilization: disparity in obesity trend in schoolchildren from La Pampa (Argentina) between 1990 and 2016

A pesar de los esfuerzos de diversos organismos para reducir la obesidad, sólo algunos países desarrollados muestran una desaceleración o estabilización de su prevalencia. Este trabajo presenta las tendencias en el índice de masa corporal (IMC) y las prevalencias de sobrepeso (SP) y obesidad (OB) ocurridas en escolares entre 1990 y 2016, y su distribución socioeconómica. Se compararon tres encuestas transversales realizadas en 1990, 2005/07 y 2015/16 en escolares primarios de Santa Rosa (La Pampa, Argentina). Para estandarizar los valores de IMC y definir las categorías SP y OB se empleó la referencia International Obesity Task Force (IOTF). El tipo de escuela se empleó como medida de nivel socioeconómico (NSE). Para analizar la asociación entre las variables dependientes con año de encuesta, sexo y NSE se aplicaron modelos de regresión lineal (IMC) y logística (SP, OB). El cambio temporal en las prevalencias de SP y OB se evaluó mediante Chi- cuadrado de tendencia entre proporciones. IMC, SP y OB incrementaron significativamente en el periodo 1990-2016, resultando en un tercio de la población con exceso de peso. Entre 2005/07 y 2015/16 sólo hubo incrementos significativos en niños que asistían a escuelas públicas. Las tendencias fueron similares en varones y niñas. Se concluye que el estatus de peso en esta población escolar muestra un patrón de aumento no lineal pero continuo en los últimos 25 años, con una estabilización en los sectores de mayor NSE durante la última década.Asociación de Antropología Biológica de la República Argentin

Planning a collection of virtual patients to train clinical reasoning: a blueprint representative of the European population

Background: Virtual patients (VPs) are a suitable method for students to train their clinical reasoning abilities. We describe a process of developing a blueprint for a diverse and realistic VP collection (prior to VP creation) that facilitates deliberate practice of clinical reasoning and meets educational requirements of medical schools. Methods: An international and interdisciplinary partnership of five European countries developed a blueprint for a collection of 200 VPs in four steps: (1) Defining the criteria (e.g., key symptoms, age, sex) and categorizing them into disease-, patient-, encounter- and learner-related, (2) Identifying data sources for assessing the representativeness of the collection, (3) Populating the blueprint, and (4) Refining and reaching consensus. Results: The blueprint is publicly available and covers 29 key symptoms and 176 final diagnoses including the most prevalent medical conditions in Europe. Moreover, our analyses showed that the blueprint appears to be representative of the European population. Conclusions: The development of the blueprint required a stepwise approach, which can be replicated for the creation of other VP or case collections. We consider the blueprint an appropriate starting point for the actual creation of the VPs, but constant updating and refining is needed

The composition and functional protein subsystems of the human nasal microbiome in granulomatosis with polyangiitis: a pilot study

Abstract: Background: Ear, nose and throat involvement in granulomatosis with polyangiitis (GPA) is frequently the initial disease manifestation. Previous investigations have observed a higher prevalence of Staphylococcus aureus in patients with GPA, and chronic nasal carriage has been linked with an increased risk of disease relapse. In this cross-sectional study, we investigated changes in the nasal microbiota including a detailed analysis of Staphylococcus spp. by shotgun metagenomics in patients with active and inactive granulomatosis with polyangiitis (GPA). Shotgun metagenomic sequence data were also used to identify protein-encoding genes within the SEED database, and the abundance of proteins then correlated with the presence of bacterial species on an annotated heatmap. Results: The presence of S. aureus in the nose as assessed by culture was more frequently detected in patients with active GPA (66.7%) compared with inactive GPA (34.1%). Beta diversity analysis of nasal microbiota by bacterial 16S rRNA profiling revealed a different composition between GPA patients and healthy controls (P = 0.039). Beta diversity analysis of shotgun metagenomic sequence data for Staphylococcus spp. revealed a different composition between active GPA patients and healthy controls and disease controls (P = 0.0007 and P = 0.0023, respectively), and between healthy controls and inactive GPA patients and household controls (P = 0.0168 and P = 0.0168, respectively). Patients with active GPA had a higher abundance of S. aureus, mirroring the culture data, while healthy controls had a higher abundance of S. epidermidis. Staphylococcus pseudintermedius, generally assumed to be a pathogen of cats and dogs, showed an abundance of 13% among the Staphylococcus spp. in our cohort. During long-term follow-up of patients with inactive GPA at baseline, a higher S. aureus abundance was not associated with an increased relapse risk. Functional analyses identified ten SEED protein subsystems that differed between the groups. Most significant associations were related to chorismate synthesis and involved in the vitamin B12 pathway. Conclusion: Our data revealed a distinct dysbiosis of the nasal microbiota in GPA patients compared with disease and healthy controls. Metagenomic sequencing demonstrated that this dysbiosis in active GPA patients is manifested by increased abundance of S. aureus and a depletion of S. epidermidis, further demonstrating the antagonist relationships between these species. SEED functional protein subsystem analysis identified an association between the unique bacterial nasal microbiota clusters seen mainly in GPA patients and an elevated abundance of genes associated with chorismate synthesis and vitamin B12 pathways. Further studies are required to further elucidate the relationship between the biosynthesis genes and the associated bacterial species

Enhancement of antibody-dependent cellular cytotoxicity of cetuximab by a chimeric protein encompassing interleukin-15

Enhancement of antibody-dependent cellular cytotoxicity (ADCC) may potentiate the antitumor efficacy of tumor-targeted monoclonal antibodies. Increasing the numbers and antitumor activity of NK cells is a promising strategy to maximize the ADCC of standard-of-care tumor-targeted antibodies. For this purpose, we have preclinically tested a recombinant chimeric protein encompassing the sushi domain of the IL15Rα, IL-15, and apolipoprotein A-I (Sushi-IL15-Apo) as produced in CHO cells. The size-exclusion purified monomeric fraction of this chimeric protein was stable and retained the IL-15 and the sushi domain bioactivity as measured by CTLL-2 and Mo-7e cell proliferation and STAT5 phosphorylation in freshly isolated human NK and CD8+ T cells. On cell cultures, Sushi-IL15-Apo increases NK cell proliferation and survival as well as spontaneous and antibody-mediated cytotoxicity. Scavenger receptor class B type I (SR-B1) is the receptor for ApoA-I and is expressed on the surface of tumor cells. SR-B1 can adsorb the chimeric protein on tumor cells and can transpresent IL-15 to NK and CD8+ T cells. A transient NK-humanized murine model was developed to test the increase of ADCC attained by the chimeric protein in vivo. The EGFR+ human colon cancer cell line HT-29 was intraperitoneally inoculated in immune-deficient Rag2-/-γc-/- mice that were reconstituted with freshly isolated PBMCs and treated with the anti-EGFR mAb cetuximab. The combination of the Sushi-IL15-Apo protein and cetuximab reduced the number of remaining tumor cells in the peritoneal cavity and delayed tumor engraftment in the peritoneum. Furthermore, Sushi-IL15-Apo increased the anti-tumor effect of a murine anti-EGFR mAb in Rag1-/- mice bearing subcutaneous MC38 colon cancer transfected to express EGFR. Thus, Sushi-IL15-Apo is a potent tool to increase the number and the activation of NK cells to promote the ADCC activity of antibodies targeting tumor antigens

Socialización escolar : procesos, experiencias y trayectos

En los artículos que forman parte de este libro se despliega un conjunto de temas, problemas y debates que, en un primer momento, se hicieron presentes entre el equipo coordinador del libro y que luego fueron compartidos con los investigadores miembros del Grupo de Trabajo "Juventudes, Infancias: Políticas, Culturas e Instituciones Sociales" (GT) del Consejo Latinoamericano de Ciencias Sociales (CLACSO). En tal sentido, el propósito de la compilación consiste en aportar a la actualización de un área o campo que, desde sus inicios, fue y es pensado por las ciencias sociales: la escuela y los sistemas educativos. Sin embargo, en los últimos años, el campo de estudios sobre la escuela se ha diversificado y especializado, encontrando nuevos objetos de estudio y ampliando los ya existentes, al tiempo que los temas y problemas educativos se hablan y debaten por toda la sociedad

Copernicus Marine Service Ocean State Report

This is the final version. Available from Taylor & Francis via the DOI in this record