Functional screening of selective mitochondrial inhibitors of Plasmodium.

Phenotypic screening has produced most of the new chemical entities currently in clinical development for malaria, plus many lead compounds active against Plasmodium falciparum asexual stages. However, lack of knowledge about the mode of action of these compounds delays and may even hamper their future development. Identifying the mode of action of the inhibitors greatly helps to prioritise compounds for further development as novel antimalarials. Here we describe a whole-cell method to detect inhibitors of the mitochondrial electron transport chain, using oxygen consumption as high throughput readout in 384-well plate format. The usefulness of the method has been confirmed with the Tres Cantos Antimalarial Compound Set (TCAMS). The assay identified 124 respiratory inhibitors in TCAMS, seven of which were novel anti-plasmodial chemical structures never before described as mitochondrial inhibitors.

[Outbreak of gastroenteritis caused by Norwalk virus at a senior citizens assisted living facility in Granada, Spain]. / Brote de gastroenteritis por virus Norwalk en una residencia de ancianos de Granada.

BACKGROUND: The outbreaks of acute gastroenteritis caused by a virus are currently one of the health problems having the greatest impact on those living in senior citizen facilities. The objective of this study is that of investigating the causes of the start and contagion of an outbreak of acute gastroenteritis caused by a Norwalk-Like virus. METHOD: At a senior citizen living facility with 141 residents and 71 employees exposed, the relations between the disease in question and different independent variables: personal traits, features of location, date of onset of symptoms, clinical pattern of the disease and causal factors (food and drinking water intake). A descriptive study, a contingency table and a hypothesis ?2 test, design of cases and controls with the calculation of the unprocessed and subsequently adjusted Odds Ratio (IC 95%) were carried out using logic regression. RESULTS: No significant differences were found in the personal trait and features of location variables. The attack rate among the residents was 30.1%, being 21.12% among the employees. In the adjusted Odds Ratio calculation, solely the whipped cream mousse showed causal relationship values (adjusted Odds Ratio = 4.66; IC-95% 1.15-18.91; p = 0.031). Ten patient stool samples were sent for analysis, no disease-causing bacteria having been detected, Norwalk-Like virus however having been isolated in three samples. CONCLUSIONS: The whipped cream mousse having been found to possibly have been responsible for the outbreak is a first involving Norwalk virus, but this result is subject to limitations, such as the possible bias of classification due to failing to recall having eaten foods. Even so, this is an element to be taken into account in the control of acute viral gastroenteritis.

Brote de gastroenteritis por virus norwalk en unaresidencia de ancianos de Granada / Outbreak of gastroenteritis caused by norwalk virus at a senior citizen assisted living facility in Granada, Spain

Fundamento: Los brotes de gastroenteritis aguda de origen vírico son actualmente uno de los problemas de salud que más están afectando a las personas residentes en instituciones de la tercera edad. El objetivo del estudio es investigar las causas del origen y transmisión de un brote de gastroenteritis aguda por virus NorwalLike. Método: En una residencia de ancianos con 141 residentes y 71 trabajadores expuestos, se investigó la relación entre un brote de gastroenteritis aguda y distintas variables: características personales, de lugar, fecha de inicio de los síntomas, clínica de la enfermedad y factores causales (alimentos y agua de consumo). Se realizó un estudio descriptivo, tabla de contingencia y test de hipótesis 2, diseño de casos y controles con el calculo de Odds Ratio cruda y posteriormente ajustada (IC al 95 por ciento) utilizando regresión logística. Resultados: No se observaron diferencias significativas en las variables de características personales y de lugar. La tasa de ataque en los residentes fue del 30,1 por ciento y en trabajadores fue del 21,12 por ciento. En el calculo de la Odds Ratio ajustada sólo tuvo valores de relación causal la mousse de nata (Odds Ratio ajustada=4,66; IC-95 por ciento 1,1518,91; p=0,031). Se remitieron 10 muestras de heces de enfermos para su análisis, no detectándose ninguna bacteria patógena, pero si se aisló en 3 de ellas virus Norwal-Like. Conclusiones: El hallazgo de la mousse de nata como posible responsable del brote supone una primicia en la presencia de virus Norwalk, pero este resultado está sujeto a limitaciones, como el posible sesgo de clasificación por no recuerdo de consumo de alimentos. Aún así, supone un elemento a tener en cuenta en el control de gastroenteritis agudas por virus (AU)

Background: The outbreaks of acute gastroenteritis caused by a virus are currently one of the health problems having the greatest impact on those living in senior citizen facilities. The objective of this study is that of investigating the causes of the start and contagion of an outbreak of acute gastroenteritis caused by a Norwalk-Like virus. Method: At a senior citizen living facility with 141 residents and 71 employees exposed, the relations between the disease in question and different independent variables: personal traits, features of location, date of onset of symptoms, clinical pattern of the disease and causal factors (food and drinking water intake). A descriptive study, a contingency table and a hypothesis ?2 test, design of cases and controls with the calculation of the unprocessed and subsequently adjusted Odds Ratio (IC 95%) were carried out using logic regression. Results: No significant differences were found in the personal trait and features of location variables. The attack rate among the residents was 30.1%, being 21.12% among the employees. In the adjusted Odds Ratio calculation, solely the whipped cream mousse showed causal relationship values (adjusted Odds Ratio = 4.66; IC-95% 1.15-18.91; p=0.031). Ten patient stool samples were sent for analysis, no disease-causing bacteria having been detected, Norwalk-Like virus however having been isolated in three samples. Conclusions: The whipped cream mousse having been found to possibly have been responsible for the outbreak is a first involving Norwalk virus, but this result is subject to limitations, such as the possible bias of classification due to failing to recall having eaten foods. Even so, this is an element to be taken into account in the control of acute viral gastroenteritis (AU)