Disseminated intravascular coagulation phenotype is regulated by the TRPM7 channel during sepsis

BACKGROUND: Sepsis is an uncontrolled inflammatory response against a systemic infection that results in elevated mortality, mainly induced by bacterial products known as endotoxins, producing endotoxemia. Disseminated intravascular coagulation (DIC) is frequently observed in septic patients and is associated with organ failure and death. Sepsis activates endothelial cells (ECs), promoting a prothrombotic phenotype contributing to DIC. Ion channel mediated calcium permeability participates in coagulation. The transient reception potential melastatin 7 (TRPM7) non-selective divalent cation channel that also contains an α-kinase domain, which is permeable to divalent cations including Ca2+, regulates endotoxin-stimulated calcium permeability in ECs and is associated with increased mortality in septic patients. However, whether endothelial TRPM7 mediates endotoxemia-induced coagulation is not known. Therefore, our aim was to examine if TRPM7 mediates coagulation during endotoxemia. RESULTS: The results showed that TRPM7 regulated endotoxin-induced platelet and neutrophil adhesion to ECs, dependent on the TRPM7 ion channel activity and by the α-kinase function. Endotoxic animals showed that TRPM7 mediated neutrophil rolling on blood vessels and intravascular coagulation. TRPM7 mediated the increased expression of the adhesion proteins, von Willebrand factor (vWF), intercellular adhesion molecule 1 (ICAM-1), and P-selectin, which were also mediated by the TRPM7 α-kinase function. Notably, endotoxin-induced expression of vWF, ICAM-1 and P-selectin were required for endotoxin-induced platelet and neutrophil adhesion to ECs. Endotoxemic rats showed increased endothelial TRPM7 expression associated with a procoagulant phenotype, liver and kidney dysfunction, increased death events and an increased relative risk of death. Interestingly, circulating ECs (CECs) from septic shock patients (SSPs) showed increased TRPM7 expression associated with increased DIC scores and decreased survival times. Additionally, SSPs with a high expression of TRPM7 in CECs showed increased mortality and relative risk of death. Notably, CECs from SSPs showed significant results from the AUROC analyses for predicting mortality in SSPs that were better than the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) scores. CONCLUSIONS: Our study demonstrates that sepsis-induced DIC is mediated by TRPM7 in ECs. TRPM7 ion channel activity and α-kinase function are required by DIC-mediated sepsis-induced organ dysfunction and its expression are associated with increased mortality during sepsis. TRPM7 appears as a new prognostic biomarker to predict mortality associated to DIC in SSPs, and as a novel target for drug development against DIC during infectious inflammatory diseases.

Adaptación de una metodología de especificaciones en la calificación y retroalimentación en la enseñanza de cursos de ciencias básicas en una carrera de la salud para mejorar los aprendizajes y la motivación / Adaptation of a specifications gradings and feedback methodology for basic sciences courses teaching in a health science career to improving learning and motivation

Introducción: la enseñanza de cursos de ciencias básicas en carreras de la salud es un desafío por no estar directa e inmediatamente rela-cionada con el ámbito profesional. Por otra parte, las condiciones de estrés que ha impuesto el trabajo a distancia requiere de metodologías motivantes, y, que a su vez permitan una evaluación significativa. Objetivos: reportar las adaptaciones metodológicas y los resultados de una adaptación local de la metodología de especificaciones de las calificaciones y retroalimentación del trabajo. Métodos: se aplica una metodología de formación basada en la retroalimentación en el curso de Física para estudiantes de Tecnología Médica (N=106) durante un semestre. Las calificaciones promedio de los estudiantes fueron comparadas con las obtenidas en años anteriores. Para evaluar el desempeño docente se realizaron 2 encuestas a los estudiantes. El cumplimiento de los logros de aprendizaje se midió mediante auto-evaluación (escala likert 1 a 5) al inicio y término de cada uno de los cuatro capítulos. Resultados: las reprobaciones y eliminaciones de estudiantes en el curso fueron menores a años anteriores, siendo las notas significativamente mayores subiendo desde 4,89 a 6,29 (escala de 1 a 7, p<0,001). Los estudiantes se mostraron en un 95% satisfechos con el desempeño docente y finalmente, la auto-evaluación de logros de aprendizaje mostró un aumento promedio de 1 punto. Conclusiones: la metodología de evaluación basada en especificaciones adaptada a dos entregas y con evaluaciones en una escala no-binaria mejoró el rendimiento, los logros de los aprendizajes esperados y la motivación de los estudiantes.

Background: Teaching basic science courses in health careers is a challenge because these courses are not directly linked to professional practice. On the other hand, the stressful conditions imposed by distance work require motivating methodologies and a meaningful evaluation. Objectives: To report the methodological adaptations and the results of a local adaptation of the specifications grading and feedback methodology. Methods: A training methodology based on feedback is applied in the Physics course for Medical Technology students (N = 106) during one semester. We compared the students' average grades to those obtained in previous years with the same topics. To evaluate the teaching performance, we conducted two student surveys. We measure compliance with learning achievements by self-assessment (Likert scale 1 to 5) at the beginning and end of each of the four chapters. Results: Failures and eliminations of students in the course were lower than previous years, with significantly higher grades from 4.89 to 6.29 (p <0.001). The students were 95% satisfied with the teaching performance, and finally, the self-evaluation of learning achievements showed an average increase of 1 point. Conclusion: The evaluation methodology based on specifications adapted to two deliveries and evaluations on a non-binary scale improved the performance, expected learning achievements, and students' motivation.

Susceptibilidad de la larva de aedes aegypti a bacillus thuringiensis var israelensis en Tegucigalpa, Honduras / Susceptibility of the larva de Aedes aegypti to bacillus thuringiensis var israelensis in Tegucigalpa, Honduras

Introducción: El dengue es la enfermedad viral transmitida por mosquitos con la propagación más rápida en el mundo. En Honduras constituye un importante problema de salud pública debido a su alta incidencia. Bacillus thuringiensis var israelensis (Bti) es un agente de control biológico aplicado en el control de vectores, se ha utilizado recientemente como parte de la estrategia contra el Aedes aegypti en Honduras. El presente estudio tiene como objetivo evaluar la susceptibilidad de la larva de Ae. aegypti a Bti en Tegucigalpa, Honduras para el año 2014. Métodos: Una muestra de 960 larvas de Ae. aegypti se recogieron de recipientes de almacenamiento en viviendas de las colonias La Cañada y Nueva Suyapa, ubicados en Tegucigalpa, Honduras. Los bioensayos se realizaron de acuerdo con las directrices emitidas por la Organización Mundial de la Salud y la Red Latinoamericana de Control de Vectores. Se llevaron a cabo 12 bioensayos por cada concentración estudiada. Se utilizaron cuatro concentraciones de Bti: 0,5 mg/L, 1 mg/L, 2,5 mg/L y 5 mg/L. La mortalidad se registró a las 24 h. Resultados: Se encontraron valores de mortalidad larvaria de 98.734 % para la dosis de 0.5 mg/L; 99.375 % para 1 mg/L; 100 % para 2,5 mg/L y 100 % para 5 mg/l. Conclusiones: Bti ha probado ser efectivo contra las larvas de Ae. aegytpi, se recomienda su evaluación sistemática y de manera periódica para mejorar su aplicación y posible desarrollo de resistencia...(AU)

Perfil de resistencia a antibióticos de serotipos de Salmonella spp. aislados de carne de res molida en la Ciudad de México / Antibiotic of resistence profile of Salmonella spp. serotypes isolated from retail beef in Mexico City

Resumen: Objetivo: Determinar el serotipo y perfil de resistencia a antibióticos de cepas de Salmonella spp. presentes en la carne de res que se expende en la capital mexicana. Material y métodos: Se analizaron 100 muestras de carne molida. Se aisló el patógeno por métodos convencionales y se confirmó por PCR (gen InvA, 284 pb). El perfil de resistencia a antibióticos se determinó por el método de Kirby-Bauer y la serotipificación por el esquema de Kauffman-White. Resultados: Se detectaron los serotipos Lomita (6), Derby (4), Senftenberg (2), Javiana y Cannsttat (1). Se observó alta resistencia a ampicilina (18/19), carbenicilina (16/19), tetraciclina (13/19) y trimetoprim-sulfametoxasol (13/19). Cinco cepas fueron no tipificables y 14 mostraron multirresistencia. Conclusiones: La carne de res que se vende en el principal centro de consumo del país está contaminada con serotipos de Salmonella spp. relevantes para la salud pública. Una importante proporción de éstos es resistente a múltiples antibióticos.

Abstract: Objective: To determine the serotype and antibiotic resistance profile of Salmonella spp. isolated from retail ground beef in Mexico City. Materials and methods: A total of 100 samples of ground beef were analyzed. The pathogen was isolated by conventional methods and confirmed by PCR (invA gene, 284 bp).The antibiotic resistance profile was determined by the Kirby-Bauer method while serotyping was performed according to the Kauffman-White scheme. Results: We isolated a total of 19 strains of Lomita (6), Derby (4), Senftenberg (2), Javiana and Cannsttat (1) and undetermined (5) serotypes. The strains showed a high resistance rate to ampicillin (18/19), carbenicillin (16/19), tetracyclin (13/19), and trimethoprim-sulfamethoxazole (13/19). Multidrug resistance was observed in 14 isolates. Conclusions: Several Salmonella spp. serotypes of public health significance are circulating in ground beef sold in the major Mexican city. Some of these strains are multi-drug resistance.

Non-selective cation channels and oxidative stress-induced cell swelling

Necrosis is considered as a non-specific form of cell death that induces tissue inflammation and is preceded by cell swelling. This increase in cell volume has been ascribed mainly to defective outward pumping of Na+ caused by metabolic depletion and/or to increased Na+ influx via membrane transporters. A specific mechanism of swelling and necrosis driven by the influx of Na+ through nonselective cation channels has been recently proposed (Barros et al., 2001a). We have characterized further the properties of the nonselective cation channel (NSCC) in HTC cells. The NSCC shows a conductance of approximately 18 pS, is equally permeable to Na+ and K+, impermeant to Ca2+, requires high intracellular Ca2+ as well as low intracellular ATP for activation and is inhibited by flufenamic acid. Hydrogen peroxide induced a significant increase in cell volume that was dependent on external Na+. We propose that the NSCC, which is ubiquitous though largely inactive in healthy cells, becomes activated under severe oxidative stress. The ensuing Na+ influx initiates via positive feedback a series of metabolic and electrolytic disturbances, resulting in cell death by necrosis

Colgajo musculocutáneo de platisma: procedimiento alternativo de la cirugía reconstructiva de cabeza y cuello / Myocutaneous platysma flap: alternative in soft tissues reconstructions of head and neck surgery

Se analiza la viabilidad del colgajo musculocutáneo de platisma como alternativa en la reconstrucción de partes blandas, post resecciones oncológicas de boca y orofaringe y como coberturas por defectos cutáneos de cabeza y cuello. Con tal fin se realizaron 29 colgajos para reconstruir la cavidad oral en 21 oportunidades, la orofaringe en 4 y como cobertura en otras 4. Se presentaron 8 complicaciones menores, 2 dehiscencias parciales, 2 epidermolisis de menos del 25 por ciento y 4 de más del 50 por ciento. En 3 casos -10,34 por ciento- hubo necrosis total del colgajo. Se destaca como ventaja la proximidad al lugar de la resección, su delgadez, ausencia de pelos, el no requerimiento de aparatología especializada, el reducido tiempo operativo y los excelentes resultados cosméticos y funcionales. No se aconseja realizarlo en cuellos irradiados, de escaso panículo adiposo, previamente operados, o cuando se requiera un vaciamiento radical de cuello.