Spectrum of activity testing for therapeutics against all four dengue virus serotypes in AG129 mouse models: Proof-of-concept studies with the adenosine nucleoside inhibitor NITD-008.

Dengue is a mosquito-borne disease of global public health importance caused by four genetically and serologically related viruses (DENV-1 to DENV-4). Efforts to develop effective vaccines and therapeutics for dengue have been slowed by the paucity of preclinical models that mimic human disease. DENV-2 models in interferon receptor deficient AG129 mice were an important advance but only allowed testing against a single DENV serotype. We have developed complementary AG129 mouse models of severe disseminated dengue infection using strains of the other three DENV serotypes. Here we used the adenosine nucleoside inhibitor NITD-008 to show that these models provide the ability to perform comparative preclinical efficacy testing of candidate antivirals in vivo against the full-spectrum of DENV serotypes. Although NITD-008 was effective in modulating disease caused by all DENV serotypes, the variability in protection among DENV serotypes was greater than expected from differences in activity in in vitro testing studies emphasizing the need to undertake spectrum of activity testing to help in prioritization of candidate compounds for further development.

Factores de riesgo asociados al desarrollo de la tuberculosis extrapulmonar en pacientes de la Red de Salud del municipio de Choloma, Cortés, Honduras de 2014 al 2016 / Risk factors associated with the development of extrapulmonary tuberculosis in patients of the Health Network of the municipality of Choloma, Cortés, Honduras from 2014 to 2016

OBJETIVO: Analizar los factores de riesgo asociados al desarrollo de la tuberculosis extrapulmonar en pacientes de la Red de Salud del municipio de Choloma, Cortés, Honduras de 2014 al 2016. METODOLOGÍA: Se realizó un muestreo aleatorio de 1:4 al universo, la muestra estuvo formada por 54 casos de tuberculosis extrapulmonar y 162 controles de tuberculosis pulmonar extraídos de los libros de control de seguimiento de casos de tuberculosis. RESULTADOS: Se compararon los casos de tuberculosis extrapulmonar con los controles de tuberculosis pulmonar; el Sexo el valor de p 0.936, OR de 0.975 y el IC (95%) 0.521- 1.824; las Medias para las edades fue para tuberculosis extrapulmonar de 29.80 años y para la tuberculosis pulmonar de 40.38 años, su valor de p 0.001; para la HTA el valor de p 0.412, OR de 1.338 con un IC (95%) 1.237-1.446; para la DM el valor de p 0.737, OR de 1.509 y su IC (95%) 0.134-16.986; en relación al VIH su valor de p fue 0.016, con OR 3.348 y su IC (95%) 1.191-9.414; para el Esquema de tratamiento el valor de p 0.033; la variable Nuevos para tuberculosis su valor de p 0.037 con OR de 6.625 con IC (95%) 0.863-50.856; las Recaídas en relación al diagnóstico de tuberculosis su valor de p 0.037, OR de 0.0151 su IC (95%) 0.20-1.159, los Abandonos del tratamiento de tuberculosis el valor de p 0.412, OR de 3.038 y el IC (95%) 0.187-49.415. CONCLUSIONES: Se concluyó que, como factores de riesgo, la edad joven, VIH positivo, recibir tratamiento primario y ser clasificado como paciente Nuevo para tuberculosis. El sexo, antecedentes de HTA y DM o ser clasificado como paciente que abandonó el tratamiento para tuberculosis no se consideraron factores de riesgo; ser clasificado como paciente con Recaída para tuberculosis se consideró como un factor protector para el desarrollo de la tuberculosis extrapulmonar en la población de Choloma

Prevalencia del síndrome de burn out en los profesionales sanitarios del centro de salud Luis Alonso Suazo, de junio a septiembre del 2015, Tegucigalpa, Honduras

El propósito de la presente investigación fue establecer la prevalencia delsíndrome de Burn out en el personal profesional sanitario del centro de salud LuisAlonso Suazo en Tegucigalpa, Honduras en el período de junio a septiembre del2015.La población estudiada fue de 42 profesionales sanitarios cuyos datos fueronobtenidos a través de dos cuestionarios anónimos y de auto llenado, uno sobre lascaracterísticas sociodemográficas y el cuestionario Internacional Maslach Burnout Inventory (MBI), instrumento internacionalmente utilizado y validado para elestudio de esta patología.Se concluyó que la prevalencia del síndrome de Burn out fue de 21 profesionalessanitarios afectados representando el 50% en otras palabras la mitad de lamuestra estudiada del personal profesional sanitario del centro de salud LuisAlonso Suazo se correlaciona con la reportada en la literatura revisada, afectandomayormente a las mujeres casadas entre 40 a 44 años, se determinó que la otramitad de la muestra estudiada no reportó presencia del síndrome reportando 50%.La esfera más afectada fue el cansancio emocional con 62% seguido de ladespersonalización con 38% finalmente la realización personal presentó el 14% dela muestra estudiada.En relación con los niveles del síndrome de Burn out se presentó en primer lugarel nivel moderado representando el 36% seguido del nivel alto en un 9% en últimolugar el nivel bajo con el 5% de los afectados por el síndrome.

Hemodynamic effects of anthrax toxins in the rabbit model and the cardiac pathology induced by lethal toxin.

Anthrax lethal toxin (LeTx) and edema toxin (EdTx) have been shown to alter hemodynamics in the rodent model, while LeTx primarily is reported to induce extensive tissue pathology. However, the rodent model has limitations when used for comparison to higher organisms such as humans. The rabbit model, on the other hand, has gained recognition as a useful model for studying anthrax infection and its pathophysiological effects. In this study, we assessed the hemodynamic effects of lethal toxin (LeTx) and edema toxin (EdTx) in the rabbit model using physiologically relevant amounts of the toxins. Moreover, we further examine the pathological effects of LeTx on cardiac tissue. We intravenously injected Dutch-belted rabbits with either low-dose and high-dose recombinant LeTx or a single dose of EdTx. The animals' heart rate and mean arterial pressure were continuously monitored via telemetry until either 48 or 72 h post-challenge. Additional animals challenged with LeTx were used for cardiac troponin I (cTnI) quantitation, cardiac histopathology, and echocardiography. LeTx depressed heart rate at the lower dose and mean arterial pressure (MAP) at the higher dose. EdTx, on the other hand, temporarily intensified heart rate while lowering MAP. Both doses of LeTx caused cardiac pathology with the higher dose having a more profound effect. Lastly, left-ventricular dilation due to LeTx was not apparent at the given time-points. Our study demonstrates the hemodynamic effects of anthrax toxins, as well as the pathological effects of LeTx on the heart in the rabbit model, and it provides further evidence for the toxins' direct impact on the heart.

Telemetric left ventricular monitoring using wireless telemetry in the rabbit model.

BACKGROUND: Heart failure is a critical condition that affects many people and often results from left ventricular dysfunction. Numerous studies investigating this condition have been performed using various model systems. To do so, investigators must be able to accurately measure myocardial performance in order to determine the degree of left ventricular function. In this model development study, we employ a wireless telemetry system purchased from Data Sciences International to continuously assess left ventricular function in the rabbit model. FINDINGS: We surgically implanted pressure-sensitive catheters fitted to wireless radio-transmitters into the left ventricle of Dutch-belted rabbits. Following recovery of the animals, we continuously recorded indices of cardiac contractility and ventricular relaxation at baseline for a given time period. The telemetry system allowed us to continuously record baseline left ventricular parameters for the entire recording period. During this time, the animals were unrestrained and fully conscious. The values we recorded are similar to those obtained using other reported methods. CONCLUSIONS: The wireless telemetry system can continuously measure left ventricular pressure, cardiac contractility, and cardiac relaxation in the rabbit model. These results, which were obtained just as baseline levels, substantiate the need for further validation in this model system of left ventricular assessment.