Fructose metabolism as a common evolutionary pathway of survival associated with climate change, food shortage and droughts.

Mass extinctions occur frequently in natural history. While studies of animals that became extinct can be informative, it is the survivors that provide clues for mechanisms of adaptation when conditions are adverse. Here, we describe a survival pathway used by many species as a means for providing adequate fuel and water, while also providing protection from a decrease in oxygen availability. Fructose, whether supplied in the diet (primarily fruits and honey), or endogenously (via activation of the polyol pathway), preferentially shifts the organism towards the storing of fuel (fat, glycogen) that can be used to provide energy and water at a later date. Fructose causes sodium retention and raises blood pressure and likely helped survival in the setting of dehydration or salt deprivation. By shifting energy production from the mitochondria to glycolysis, fructose reduced oxygen demands to aid survival in situations where oxygen availability is low. The actions of fructose are driven in part by vasopressin and the generation of uric acid. Twice in history, mutations occurred during periods of mass extinction that enhanced the activity of fructose to generate fat, with the first being a mutation in vitamin C metabolism during the Cretaceous-Paleogene extinction (65 million years ago) and the second being a mutation in uricase that occurred during the Middle Miocene disruption (12-14 million years ago). Today, the excessive intake of fructose due to the availability of refined sugar and high-fructose corn syrup is driving 'burden of life style' diseases, including obesity, diabetes and high blood pressure.

High prevalence of Pneumocystis jirovecii pneumonia among Mozambican children <5 years of age admitted to hospital with clinical severe pneumonia.

We aimed to describe Pneumocystis jirovecii pneumonia (PCP) prevalence and features in children from sub-Saharan Africa and to investigate PCP-associated risk factors. During 2006-2007 we used molecular methods to test children younger than 5 years old admitted with severe pneumonia to a hospital in southern Mozambique for Pneumocystis infection. We recruited 834 children. PCP prevalence was 6.8% and HIV prevalence was 25.7%. The in-hospital and delayed mortality were significantly higher among children with PCP (20.8% vs. 10.2%, p 0.021, and 11.5% vs. 3.6%, p 0.044, respectively). Clinical features were mostly overlapping between the two groups. Independent risk factors for PCP were age less than a year (odds ratio (OR) 6.34, 95% confidence interval (CI) 1.86-21.65), HIV infection (OR 2.99, 95% CI 1.16-7.70), grunting (OR 2.64, 95% CI 1.04-6.73) and digital clubbing (OR 10.75, 95% CI 1.21-95.56). PCP is a common and life-threatening cause of severe pneumonia in Mozambican children. Mother-to-child HIV transmission prevention should be strengthened. Better diagnostic tools are needed.

Mechanisms by Which Dehydration May Lead to Chronic Kidney Disease.

Dehydration, a condition that characterizes excessive loss of body water, is well known to be associated with acute renal dysfunction; however, it has largely been considered reversible and to be associated with no long-term effects on the kidney. Recently, an epidemic of chronic kidney disease has emerged in Central America in which the major risk factor seems to be recurrent heat-associated dehydration. This has led to studies investigating whether recurrent dehydration may lead to permanent kidney damage. Three major potential mechanisms have been identified, including the effects of vasopressin on the kidney, the activation of the aldose reductase-fructokinase pathway, and the effects of chronic hyperuricemia. The discovery of these pathways has also led to the recognition that mild dehydration may be a risk factor in progression of all types of chronic kidney diseases. Furthermore, there is some evidence that increasing hydration, particularly with water, may actually prevent CKD. Thus, a whole new area of investigation is developing that focuses on the role of water and osmolarity and their influence on kidney function and health.

Biomarcadores para el despistaje de enfermedades infecciosas: una revolución diagnóstica para los países pobres / Biomarkers for the screening of pediatric infectious diseases: a true diagnostic revolution for the developing world

El personal clínico que trabaja en países en desarrollose enfrenta cada día al diagnóstico ytratamiento de niños enfermos. Malaria, neumonía y diarreason lasenfermedades infecciosas másimportantes en los países con recursos limitados entérminos de morbilidad ymortalidadinfantil. La escasez deherramientas diagnósticaspara determinar su etiologíaen estos medios es un problema frecuente, y por lo tanto es difícil orientar el manejo clínico, incluyendola prescripción demedicamentos para estas patologías. Por otro lado, los síntomas demalaria, de algunas infecciones bacterianasy de infeccionesviralesson a menudo compartidos y difíciles de distinguir en ausencia de apoyo diagnóstico. El reconocimiento erróneode estas enfermedadespuede aumentarlamorbimortalidadpediátrica, así como los niveles de resistenciaa fármacos antimaláricosy antibióticos. Es importante, por tanto, desarrollarnuevasherramientas diagnósticas paraenfermedadesinfecciosasque se puedan utilizarincluso en las zonas más rurales de países con recursos limitados. Las pruebas de diagnóstico rápido demalaria son un buen ejemplo de estas herramientas de diagnóstico precoz, asequibles, accesibles, de resultado casi inmediato y con alto impacto en el diagnóstico de una de las enfermedades que más mortalidad causan en el mundo en desarrollo. La implementación de pruebas de diagnóstico rápido similares para otras enfermedades infecciosas, significaría sin duda un gran avance en el diagnóstico y manejo de las infecciones pediátricas, suponiendo un paso adelante en la disminución de la inaceptablemente alta mortalidad infantil que todavía afecta a estos países (AU)

Health workers in rural facilities in Africa are confronted every day with the diagnosis and treatment of sick children with infectious diseases. Malaria, pneumonia and diarrhea are among the most important infectious diseases in developing countries in terms of morbidity and mortality burden in children. However, there is a scarcity of diagnostic tools to determine the etiologic origin of these infections in health facilities in rural Africa, and therefore guide clinical management including the prescription of anti-malarials and/or antibiotics. Clinical presentations of malaria, bacterial infections and viral infections often overlap, particularly in children. Misdiagnosis of malaria, bacterial infections and viral infections may increase the morbidity and mortality among children, as well as boost resistance levels to antimalarial drugs and antibiotics. As a result, there is a need to develop new diagnostic tools for infectious diseases that can be used for diagnosis of such highly prevalent conditions in the developing world. Malaria rapid diagnostic tests are a good example of these new diagnostic tools, affordable, accessible and with a high-impact on the diagnosis of one of the diseases causing more deaths in the developing world. Widespread implementation of tools similar to the RDTs for other infectious diseases, and particularly those of bacterial origin, will surely result in improvements in the recognition and management of life-threatening childhood infections, and in a reduction of their intolerable burden (AU)

Fat storage syndrome in Pacific peoples: a combination of environment and genetics?

Pacific people (especially Micronesian and Polynesian) have some of the highest rates of obesity and diabetes in the world that largely developed since the introduction of western culture and diet. Recent studies suggest that much of the risk relates to the excessive intake of sugar (sucrose) and carbohydrates, leading to a type of fat storage syndrome (metabolic syndrome). Here we discuss some of the environmental. genetic and epigenetic reasons why this group might be especially prone to developing obesity and diabetes compared to other ethnic groups. Indirect evidence suggests that the higher endogenous uric acid levels in the Polynesian-Micronesian population may represent a predisposing factor for the development of obesity and diabetes in the context of Western diets and lifestyles. Pacific people may be an ideal group to study the role of "thrifty genes" in the pathogenesis of the current obesity epidemic.

La malaria en el mundo en 2010: ¿qué hay de nuevo acerca de esta vieja enfermedad? / Malaria in the world in 2010: What’s new about this old scourge?

El paludismo se mantiene en 2010 como uno de los grandes problemas de salud pública a nivel global. Endémico en 108 países del mundo, causa a día de hoy 250 millones de episodios clínicos y 863 000 muertes anuales, principalmente en el continente africano. El incremento en la última década de los fondos internacionales destinados a financiar actividades de control del paludismo ha condicionado un despliegue sin precedentes de herramientas de control disponibles. Así, millones de redes mosquiteras han sido distribuidas entre las poblaciones más vulnerables de África, y nuevos fármacos más potentes y eficaces han reemplazado en todos los países endémicos a los que habían quedado obsoletos. Como resultado de estos esfuerzos, y por primera vez en muchos años, estamos asistiendo a un cambio en las tendencias epidemiológicas de esta enfermedad, con una disminución de su incidencia global y, como consecuencia, una reducción de su morbimortalidad asociada. Estos progresos han espoleado a la comunidad científica a replantear de nuevo la posibilidad de erradicar esta enfermedad a nivel global. Sin embargo, y a pesar del optimismo imperante, este objetivo será imposible sin la aparición de herramientas de control nuevas y más eficaces, y no parece realista plantearlo a corto plazo. Estos esfuerzos deberán acompañarse de una agenda científica de investigación que sirva a la vez de guía para el diseño de nuevas intervenciones, pero también de mecanismo de monitorización de los progresos obtenidos. Para que el paludismo sea erradicado, también será necesario mantener un compromiso a largo plazo acompañado en paralelo de grandes esfuerzos para reforzar los frágiles sistemas de salud existentes en los países donde la enfermedad es un problema. Este artículo intentará revisar el estado actual del paludismo, en el nuevo contexto de los esfuerzos por su eliminación global (AU)

Malaria remains in 2010 a major global public health problem. The disease is endemic in 108 countries around the world, causing up to 250 million clinical episodes and 863,000 deaths annually, mainly in Africa. In the last decade, the increase of international funding available to finance malaria control activities has conditioned an unprecedented uptake of the different control tools available. Thus, millions of mosquito nets have been distributed among the most vulnerable populations in Africa, and new more potent and effective drugs have replaced those that had become obsolete in most endemic countries. As a result of these efforts, and for the first time in many years, we are witnessing a change in the epidemiology of this disease, with a decrease in its overall impact, and consequently a reduction in its associated morbidity and mortality. These developments have encouraged the scientific community to reconsider the possibility of eradicating the disease globally. However, despite the prevailing optimism, this goal will be impossible without the development of new and more effective control tools, and does not seem realistic to envisage them in the short-term. These efforts must be accompanied by a scientific research agenda that will serve both as a guideline for the design of new interventions, and also as a mechanism for monitoring the progress made. If malaria is to be eradicated, long-term commitments will be necessary, in parallel with greater efforts to strengthen the fragile health systems in countries where the disease is a problem. This article reviews the malaria situation in the light of the current efforts for its global elimination (AU)