Avoidable blindness and value based healthcare: More value with a population approach

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Dual Effect of Beta-Amyloid on α7 and α4β2 Nicotinic Receptors Controlling the Release of Glutamate, Aspartate and GABA in Rat Hippocampus

BACKGROUND: We previously showed that beta-amyloid (Aβ), a peptide considered as relevant to Alzheimer's Disease, is able to act as a neuromodulator affecting neurotransmitter release in absence of evident sign of neurotoxicity in two different rat brain areas. In this paper we focused on the hippocampus, a brain area which is sensitive to Alzheimer's Disease pathology, evaluating the effect of Aβ (at different concentrations) on the neurotransmitter release stimulated by the activation of pre-synaptic cholinergic nicotinic receptors (nAChRs, α4β2 and α7 subtypes). Particularly, we focused on some neurotransmitters that are usually involved in learning and memory: glutamate, aspartate and GABA. METHODOLOGY/FINDINGS: WE USED A DUAL APPROACH: in vivo experiments (microdialysis technique on freely moving rats) in parallel to in vitro experiments (isolated nerve endings derived from rat hippocampus). Both in vivo and in vitro the administration of nicotine stimulated an overflow of aspartate, glutamate and GABA. This effect was greatly inhibited by the highest concentrations of Aβ considered (10 µM in vivo and 100 nM in vitro). In vivo administration of 100 nM Aβ (the lowest concentration considered) potentiated the GABA overflow evoked by nicotine. All these effects were specific for Aβ and for nicotinic secretory stimuli. The in vitro administration of either choline or 5-Iodo-A-85380 dihydrochloride (α7 and α4β2 nAChRs selective agonists, respectively) elicited the hippocampal release of aspartate, glutamate, and GABA. High Aβ concentrations (100 nM) inhibited the overflow of all three neurotransmitters evoked by both choline and 5-Iodo-A-85380 dihydrochloride. On the contrary, low Aβ concentrations (1 nM and 100 pM) selectively acted on α7 subtypes potentiating the choline-induced release of both aspartate and glutamate, but not the one of GABA. CONCLUSIONS/SIGNIFICANCE: The results reinforce the concept that Aβ has relevant neuromodulatory effects, which may span from facilitation to inhibition of stimulated release depending upon the concentration used

Metabotropic glutamate receptor 5 as a potential target for smoking cessation

Rationale Most habitual smokers find it difficult to quit smoking because they are dependent upon the nicotine present in tobacco smoke. Tobacco dependence is commonly treated pharmacologically using nicotine replacement therapy or drugs, such as varenicline, that target the nicotinic receptor. Relapse rates, however, remain high and there remains a need to develop novel non-nicotinic pharmacotherapies for the dependence that are more effective than existing treatments. Objective The purpose of this paper is to review the evidence from preclinical and clinical studies that drugs that antagonise the metabotropic glutamate receptor 5 (mGluR5) in the brain are likely to be efficacious as treatments for tobacco dependence. Results Imaging studies reveal that chronic exposure to tobacco smoke reduces the density of mGluR5s in human brain. Preclinical results demonstrate that negative allosteric modulators (NAMs) at mGluR5 attenuate both nicotine self-administration and the reinstatement of responding evoked by exposure to conditioned cues paired with nicotine delivery. They also attenuate the effects of nicotine on brain dopamine pathways implicated in addiction. Conclusions Although mGluR5 NAMs attenuate most of the key facets of nicotine dependence they potentiate the symptoms of nicotine withdrawal. This may limit their value as smoking cessation aids. The NAMs that have been employed most widely in preclinical studies of nicotine dependence have too many \u201coff target\u201d effects to be used clinically. However newer mGluR5 NAMs have been developed for clinical use in other indications. Future studies will determine if these agents can also be used effectively and safely to treat tobacco dependence

Knowledge Resources Management and Sharing in the TENCompetence Project

One of the most relevant activities in the EU TENCompetence project is directed at the development of models and tools to stimulate the sharing and management of knowledge resources. Knowledge resources are the containers that store the explicit knowledge for sharing purposes. Examples are learning objects, articles, books, software programs, informal messages, etc. From the technical perspective the main outcome of this part of the research in TENCompetence is to develop an infrastructure suitable to provide users with functionalities for the creation, storage in distributed, federated digital repositories, search, support, retrieval, packaging, reuse, sharing and quality rating of knowledge resources. Moreover, in order to guarantee a high degree of interoperability, each knowledge resource must be both packaged according to existing specifications (e.g. IMS-CP and SCORM) and uniquely identifiable using worldwide unique identifiers and metadata descriptors (e.g. LOM or Dublin Core format). This paper is an overview on the objectives, issues and potential technical solutions identified in the initial phase of the project

Water quality regulation from the perspective of engineering and environmental economics

Resumen: Debido a su importancia para la vida humana y a la magnitud del despliegue necesario tanto para su disposición como para su cuidado, el control de la calidad del agua se ha transformado en las últimas décadas en unas de las áreas más prominentes de la ingeniería ambiental y de la economía ambiental. Una estrategia implementada por países que cuentan con una importante experiencia en este tipo de políticas ambientales consiste en recurrir a incentivos económicos, con el fin de sumar a los distintos agentes contaminadores al proceso mismo de reducción de la contaminación. En este trabajo analizamos los posibles resultados de este tipo de regulación, aplicada a calidad del agua en el curso de un río sobre el cual se producen vertidos de diversas fuentes, mediante la implementación de un modelo de control de la contaminación y a su correspondiente simulación computacional. Se plantea un problema de optimización sobre un modelo de simulación de mercado basado en agentes de descargas de efluentes (puntuales y no puntuales), desarrollado en Estados Unidos de América (USA) y que puede ser aplicable en muchos aspectos, con su correspondiente adaptación, a nuestro país.Abstract: Due to its importance for human life and the magnitude of the deployment necessary both for its disposal and for its care, the control of water quality has in recent decades become one of the most prominent areas of environmental engineering and environmental economics A strategy implemented by countries that have significant experience in this type of environmental policies is to resort to economic incentives, in order to include the different pollutants to the process of pollution reduction. In this work we analyze the possible results of this type of regulation, applied to water quality in the course of a river on which spills from various sources occur, through the implementation of a pollution control model and its corresponding computational simulation. An optimization problem arises on a market simulation model based on effluent discharge agents (punctual and non-punctual), developed in the United States of America (USA) and which can be applicable in many aspects, with their corresponding adaptation, to our country

W-band Atmospheric Radiowave Propagation - A Challenge for Satellite TLC Systems

This contribution is aimed at presenting the scenario of the expected atmospheric impairments suffered by a radio link operating in the W band, as derived by the present theoretical and experimental knowledge. The contributions to signal fade due to gases, clouds, scintillation and rain (with emphasis also on the impact of the hydrometeor size distribution), as well as the melting layer characteristics and the depolarization of the electromagnetic waves are discussed. The main objective is to assess the constraints to face in the design of a satellite TLC system operating in the W band

Redes neuronales artificiales aplicadas al análisis de datos en ingeniería ambiental e impacto ambiental

Resumen: Se realiza una revisión sobre los antecedentes de las Redes Neuronales Artificiales (RNA) como método de análisis de bases de datos medioambientales, aplicado en las diversas áreas de la Ingeniería Ambiental en general y de Impacto Ambiental en particular. Se describe como ejemplo, la aplicación de RNA en los algoritmos de inversión de datos obtenidos por sensado remoto satelital, para la medición de variables geofísicasAbstract: A review of the history of Artificial Neural Networks (ANN) as a method of analysis of environmental data, applied to different areas of Environmental Engineering in general, and Environmental Impact in particular is presented. As an example, ANN applications dealing with the satellital remote measurements of geophysical variables are described