Preclinical discovery of duloxetine for the treatment of depression

Introduction: Affective disorders, including major depressive disorder (MDD), are among the most severely disabling mental disorders, and in many cases areIntroduction: Affective disorders, including major depressive disorder (MDD), are among the most severely disabling mental disorders, and in many cases are associated with poor treatment outcomes. From the emergence of the monoamine hypothesis of depression, the first-line treatment for MDD had mainly acted by inhibiting monoamine reuptake, and thereby increasing these levels in the synaptic cleft. However, in recent years, several newantidepressant drugs have appeared, including duloxetine, a dual serotonin (5-HT) and noradrenaline (NA) reuptake inhibitor recommended for the treatment of MDD. Areas covered: The article reviews and discusses the biochemical and functional profile of duloxetine splitting the review into acute and long-term treatment with this dual monoamine reuptake inhibitor. In addition, the authors summarize available preclinical behavioral research data, which have demonstrated among other effects, the antidepressant-like activity of duloxetine in several animal models. The authors focus on the most recent literature on synaptic neuroplasticity modulation of this antidepressant drug. Finally, the authors briefly mention other approved indications of duloxetine. Expert opinion: Duloxetine inhibits 5-HT and NA reuptake, effectively desensitizes various autoreceptors and promotes neuroplasticity. Clinically, duloxetine is an effective antidepressant that is well tolerated and has significant efficacy in the treatment of MDD. associated with poor treatment outcomes. From the emergence of the monoamine hypothesis of depression, the first-line treatment for MDD had mainly acted by inhibiting monoamine reuptake, and thereby increasing these levels in the synaptic cleft. However, in recent years, several new antidepressant drugs have appeared, including duloxetine, a dual serotonin (5-HT) and noradrenaline (NA) reuptake inhibitor recommended for the treatment of MDD

Assessing and forecasting the impacts of global change on Mediterranean rivers. The SCARCE Consolider project on Iberian basins

Introduction The Consolider-Ingenio 2010 project SCARCE, with the full title “Assessing and predicting effects on water quantity and quality in Iberian Rivers caused by global change” aims to examine and predict the relevance of global change on water availability, water quality, and ecosystem services in Mediterranean river basins of the Iberian Peninsula, as well as their socio-economic impacts. Starting in December 2009, it brought together a multidisciplinary team of 11 partner Spanish institutions, as well as the active involvement of water authorities, river basin managers, and other relevant agents as stakeholders. Methods The study areas are the Llobregat, Ebro, Jucar, and Guadalquivir river basins. These basins have been included in previous studies and projects, the majority of whom considered some of the aspects included in SCARCE but individually. Historical data will be used as a starting point of the project but also to obtain longer time series. The main added value of SCARCE project is the inclusion of scientific disciplines ranging from hydrology, geomorphology, ecology, chemistry, and ecotoxicology, to engineering, modeling, and economy, in an unprecedented effort in the Mediterranean area. The project performs data mining, field, and lab research as well as modeling and upscaling of the findings to apply them to the entire river basin. Results Scales ranging from the laboratory to river basins are addressed with the potential to help improve river basin management. The project emphasizes, thus, linking basic research and management practices in a single framework. In fact, one of the main objectives of SCARCE is to act as a bridge between the scientific and the management and to transform research results on management keys and tools for improving the River Basin Management Plans. Here, we outline the general structure of the project and the activities conducted within the ten Work Packages of SCARCE

Induction of the mitochondrial NDUFA4L2 protein by HIF-1α decreases oxygen consumption by inhibiting complex i activity

The fine regulation of mitochondrial function has proved to be an essential metabolic adaptation to fluctuations in oxygen availability. During hypoxia, cells activate an anaerobic switch that favors glycolysis and attenuates the mitochondrial activity. This switch involves the hypoxia-inducible transcription factor-1 (HIF-1). We have identified a HIF-1 target gene, the mitochondrial NDUFA4L2 (NADH dehydrogenase [ubiquinone] 1 alpha subcomplex, 4-like 2). Our results, obtained employing NDUFA4L2-silenced cells and NDUFA4L2 knockout murine embryonic fibroblasts, indicate that hypoxia-induced NDUFA4L2 attenuates mitochondrial oxygen consumption involving inhibition of Complex I activity, which limits the intracellular ROS production under low-oxygen conditions. Thus, reducing mitochondrial Complex I activity via NDUFA4L2 appears to be an essential element in the mitochondrial reprogramming induced by HIF-1This work was supported by Ministerio de Ciencia e Innovación (SAF 2007-06592, SAF2010-14851), Comunidad Autónoma de Madrid (SAL 2006/ 0311), Metoxia Project-Health (F2 2009-222741), and Recava Network (RD 06/0014/0031) to M.O.L.; PS09/00101 and CP07/00143 to A.M.-R.; PI060701, PS09/00116, and CP08/00204 to S.C.; BFU2008-03407/BMC to J.A.; SAF2009-08007 to J.A.E.; and CSD2007-00020 to A.M.-R. and J.A.E. The CNIC is supported by the Instituto de Salud Carlos III-MICINN and the Pro-CNIC Foundation. We are grateful to Mike Murphy (Mitochondrial Biology Unit, MRC, Cambridge, UK) for the gift of MitoQ. We also thank Stephen Y. Chan and Joseph Loscalzo (Harvard Medical School, Boston, MA) for providing us ISCU expression vector

La administración municipal y sus funcionarios. Resumen de la conferencia

El autor aboga por un funcionariado capacitado, bien remunerado y estable para el mejor funcionamiento de las instituciones locales

Documento de consenso multidisciplinar para la implantación del Proceso Asistencial Integrado Fibromialgia en el área hospitalaria dependiente del Hospital Universitario de Puerto Real

Introduction: an integrated healthcare process for fibromyalgia -Proceso Asistencial Integrado (PAI) Fibro-mialgia- was published in 2005 in Andalusia to provide healthcare professionals with a valid protocol for the management of patients with this disease. In 2009 a decision was made to write a document allowing PAI to be adapted to the healthcare area served by Hospital Universitario de Puerto Real in order to facilitate its implementation. Objective: to develop a consensus document on the implementation of PAI Fibromialgia in the healthcare area served by Hospital Universitario de Puerto Real by representatives of the major healthcare specialties involved in the diagnosis and treatment of this condition, as well as representatives of patient associations. Method: the document published by Junta de Andalucía on the PAI Fibromialgia project, and the new aspects of this disease in the current medical literature were all reviewed in an attempt to adjust this process within the actual practice of healthcare centers served by Hospital Universitario de Puerto Real. Some common consensus techniques were used (nominal group and brainstorming). Conclusion: the PAI Fibromialgia paper edited by Junta de Andalucía is a document that, while relevant, cannot be implemented as such within the actual practice of healthcare centers served by Hospital Universitario de Puerto Real. Based on this paper a process implementation document was developed with the aid and consensus of in-hospital specialized care and primary care specialists, as well as fibromyalgia patient associations. This document is now allowing the gradual implementation of PAI Fibromialgia in the healthcare area served by Hospital Universitario de Puerto Real.Introducción: en el año 2005 se publicó en Andalucía el Proceso Asistencial Integrado (PAI) Fibromialgia para dotar de un protocolo válido de actuación a los profesionales sanitarios ante los pacientes con esta patología. En el año 2009 se decidió realizar un documento que permitiera la adaptación del PAI al Área Sanitaria del Hospital Universitario Puerto Real para facilitar su implantación. Objetivo: desarrollar un documento de consenso sobre la implantación del PAI Fibromialgia en el Área Sanitaria del Hospital Universitario Puerto Real realizado por representantes de las principales especialidades sanitarias que intervienen en el diagnóstico y tratamiento de dicha patología, así como representantes de las asociaciones de pacientes. Método: se revisó el documento de la Junta de Andalucía sobre el PAI Fibromialgia y los nuevos aspectos sobre dicha patología en la literatura médica actual, intentando adaptarlos a la realidad asistencial de los centros sanitarios dependientes del Hospital Universitario Puerto Real. Se emplearon algunas de las técnicas habituales para realizar consensos (grupo nominal y brainstorming). Conclusión: el PAI Fibromialgia editado por la Junta de Andalucía es un documento que, aunque importante, no se puede implementar como tal en la realidad asistencial de los centros sanitarios dependientes del Hospital Universitario Puerto Real. Tomando dicho documento como base se creó un documento de implantación del proceso, para ello se contó con la participación y consenso de Especialistas de Atención Especializada Hospitalaria y Atención Primaria así como de las Asociaciones de Pacientes con Fibromialgia. Este documento está permitiendo la implementación progresiva del PAI Fibromialgia en el Área Sanitaria del Hospital Universitario Puerto Real

Homenaje a Andrés Bello : 27-01-1966

José María Souvirón. Julián Echavarri Elorza. Óscar Godoy. Andrés Rojas. Luis Íñigo. Miguel ArtecheJosé María Souvirón dedica unas palabras a Chile -- Min. 02.12: El embajador de Chile Julián Echavarri Elorza habla sobre la personalidad y la vida de Andrés Bello -- Min. 9.14: Óscar Godoy ofrece una conferencia "La idea de filosofía de Andrés Bello" -- Min. 31.31: Andrés Rojas trata el tema de Bello y la Universidad de Chile -- Min. 47.20: Luis Íñigo presenta la poesía de Bello -- 1 Hora 09 Min.: Miguel Arteche da lectura de un fragmento de la poesía de Bello Alocución a la poesí

Cueva de El Cierro (Fresnu, Ribadesella, Asturias, Spain): Summary of data from the excavations in three different areas of the archaeological site

RESUMEN: En este artículo se hace una puesta al día sobre la información disponible relativa a las excavaciones arqueológicas efectuadas en la Cueva de El Cierro. Está focalizado en las intervenciones llevadas a cabo con posterioridad a la primera excavación en el yacimiento, realizada por el profesor Francisco Jordá Cerdá en 1959, tanto las efectuadas por este investigador y por Alejandro Gómez Fuentes entre 1976 y 1979, como las llevadas a cabo a partir del año 2014. Además de las excavaciones realizadas en el perfil estratigráfico de las excavaciones antiguas, a partir de este año se investigan otras dos zonas de la cueva, la entrada este (depresión cerrada exterior) y la entrada sur de la cavidad. Se publican los datos relativos a los restos cerámicos, de aves y de peces de las diferentes intervenciones, se hace hincapié en las llevadas a cabo en la entrada este y se publican dos fechas radiocarbónicas nuevas.ABSTRACT: This paper updates the available information about the archaeological excavations in El Cierro cave. It concentrates on the excavations following the first fieldwork in the cave, by Professor Francisco Jordá in 1959. Thus, the excavations performed by that researcher and Alejandro Gómez Fuentes from 1976 to 1979 and those carried out since 2014 are described. In addition to excavations in the stratigraphic section left by the old excavations, two other areas in the cave have been investigated: The Eastern Entrance (outer enclosed depression) and the Southern Entrance. Information is provided about the ceramic, fish and bird remains found in the fieldwork, the work in the Eastern Entrance is highlighted, and two new radiocarbon dates are presented.Este artículo ha sido realizado en el marco de los proyectos PALEONTHEMOVE (PID2020-114462GB-I00) y CantabricOIS2 (PID2020-115192GB-I00), Ministerio de Ciencia e Innovación, Gobierno de España