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

Estudio del comportamiento de mostazas de azufre pesadas frente a descontaminantes comerciales

Los objetivos de esta Tesis Doctoral han sido la evaluación de la eficacia de descontaminantes comerciales frente a mostazas de azufre pesadas, el desarrollo de métodos de tratamiento de muestras y análisis para evaluar la eficacia de los distintos descontaminantes mediante cromatografía de gases y la caracterización de los productos de degradación mayoritarios mediante espectrometría de masas.En todos los casos, las mostazas de azufre pesadas se han preparado y utilizado sin ulterior purificación con objeto de simular un escenario real. La presencia de productos secundarios en el medio descontaminante podría utilizarse como “señuelos o indicadores” (huella química) para casos de estudios forenses como consecuencia de un atentado y así poder identificar el origen del agresivo químico en base a la metodología de síntesis empleada. La pureza de las mostazas de azufre pesadas ha sido, en todos los casos, superior al 75%.Los datos experimentales obtenidos en esta memoria de tesis, permiten concluir que la eficacia del proceso de descontaminación depende de la naturaleza del descontaminante, (base orgánica o acuosa) y de la longitud de la cadena alifática de la mostaza de azufre pesada. La solubilidad de los agresivos de guerra química (CWA) en el medio descontaminante es un factor crítico para la eficacia del proceso de descontaminación. En todos los casos, los descontaminantes de base orgánica (DS2, GD5, GD6 y GDS2000) han sido más eficaces que los descontaminantes de base acuosa (RM21, RM31, RM3.

Estrategia docente para comprender la importancia de la química orgánica en la profesión farmacéutica

Memoria ID-060. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2018-2019

Aproximación a la medición de Revenue Management en destinos turísticos

Dada la gran importancia que tiene el turismo en la economía española, el presente trabajo se centra en la definición de indicadores de Revenue Management que permitan identificar los sectores que generan mayores ingresos y aquellos que conviene potenciar dentro del destino turístico. Todo ello con el fin de proponer mejoras para incrementar la rentabilidad a nivel de destino turístico mediante la medición y el análisis del indicador básico de Revenue Management. En este sentido, desde un punto de vista teórico, se ha explicado la ampliación del alcance del concepto de Revenue Management, centrándose en su aplicación en destinos turísticos. A continuación, se profundiza en la relevancia que tiene la gestión de destinos en la mejora de los ingresos de estos y se identifican los sectores en los que los turistas realizan un mayor gasto. Por último, se ha seleccionado un destino turístico concreto para medir a través del indicador el nivel de ingresos de sus sectores y subsectores.Due to the great importance of tourism in the Spanish economy, the current work focuses on the definition of Revenue Management indicators that allow to identify the sectors that generate higher incomes and those that should be promoted within the tourist destination. All this in order to propose improvements to increase the profitability of the tourist destination through the measurement and the analysis of the basic indicator of Revenue Management. In this way, from a theoretical point of view, the extension of the scope of the Revenue Management concept has been explained, focusing on its application in tourist destinations. Afterwards, the study reveals the relevance of destination management in improving its income level and the sectors in which tourists spend more money are identified. Finally, a specific tourist destination has been selected to measure the income level of its sectors and subsector

Coping Strategies against peer victimization: differences according to gender, grade, victimization status and perceived classroom social climate

The Sustainable Development Goals (SDGs) include 'Good Health andWell-being' (SDG3) and 'Quality Education' (SDG4). Nevertheless, many students cannot achieve these goals if they suffer peer victimization at their schools, and intervention programs to reduce it are necessary. These programs should consider the possible differences in the coping strategies preferred by students according to some personal (e.g., gender, grade, victimization status) and contextual (e.g., perceived classroom social climate) factors to be more effective. Therefore, the objective of this study was to analyze the possible differences in the coping strategies preferred by students (ask a friend for help, ask a teacher for help, ask parents for help, not ask anyone for help, fighting back, avoid the aggressor and ask the aggressor why) to handle situations of relational, physical and verbal peer victimization according to their gender, school grade, victimization status and perceived classroom social climate. The sample comprised 479 students (52.2% boys, 47.8% girls) aged from 9 to 14 years (M = 11.21, SD = 1.52). The results showed that girls chose the strategies of asking friends or adults for help and asking the aggressor why more than boys, while boys chose the strategies of fighting back and not ask anyone for help more than girls. The coping strategy of asking a teacher for help was preferred more by students of lower school grades and by students with a positive perception of the classroom climate. Victimized students preferred the strategy of not asking anyone for help. These results may be useful for developing more effective intervention programs. These programs should aim to enhance the teacher-student relationship in upper school grades, help victimized students to inform about peer aggression situations and improve perceived classroom social climate

Applying forecasting Revenue Management techniques to enrolment management in a university centre

Revenue Management methodology is shown to be an innovative application for fixed capacity firms or service entities which require a management system that supports pricing and inventory decision-making. The present research study takes one of the elements of this philosophy – demand forecasting and estimation - as a theoretical basis and applies it to the case study. The aim is to obtain the predicted demand of enrolments in each academic year. This will support the improvement and optimisation of the operations related to capacity management in a university centr

Modelling intervals of minimum/maximum temperatures in the Iberian Peninsula

In this paper, we propose to model intervals of minimum/maximum temperatures observed at a given location by fitting unobserved component models to bivariate systems of center and log-range temperatures. In doing so, the center and logrange temperature are decomposed into potentially stochastic trends, seasonal and transitory components. We contribute to the debate on whether the trend and seasonal components are better represented by stochastic or deterministic components. The methodology is implemented to intervals of minimum/maximum temperatures observed monthly in four locations in the Iberian Peninsula, namely, Barcelona, Coruña, Madrid and Seville. We show that, at each location, the center temperature can be represented by a smooth integrated random walk with time-varying slope while the log-range seems to be better represented by a stochastic level. We also show that center and log-range temperature are unrelated. The methodology is then extended to model simultaneously minimum/maximum temperatures observed at several locations. We fit a multi-level dynamic factor model to extract potential commonalities among center (log-range) temperature while also allowing for heterogeneity in different areas. The model is fitted to intervals of minimum/maximum temperatures observed at a large number of locations in the Iberian Peninsula.Financial Supportfrom\laCaixa"Foundation,grantLCF/PR/SR20/52550012-Climate change and economic challenges for the Spanish society, is gratefully acknowledged. The third author also acknowledges financial support from the Spanish Government grant PID2019-108079GBC21/AIE/10.13039/501100011033 (MINECO/FEDER).The suppor tof Jouni Helske with some of the codes used in this paper is also gratefully acknowledged. We are also grateful to participants at the 69th International Symposium of Forecasters (July, 2022),Rome-Waseda Time Series Symposium (October, 2022) and 16th International Conference, Computational and Financial Econometrics (December, 2022).Any remaining errors are obviously our responsibility

Actividades lúdicas para el aprendizaje de la matemática en los estudiantes de educación básica regular

La presente investigación tiene como propósito describir cómo las actividades lúdicas mejoran el aprendizaje de matemática en los estudiantes de la educación básica regular; la metodología estuvo basada en la revisión sistemática de artículos científicos de enfoque cuantitativo. La población estuvo conformada 66 manuscritos, de los cuales se tomó una muestra de 18 pertenecientes a revistas indexadas en las bases de datos de Scopus, EBSCO, Scielo, Dialnet, Redalyc, entre otras, las que fueron seleccionados a partir del protocolo Prisma. El instrumento utilizado fue el registro de datos electrónico. Los resultados muestran como a través de las actividades lúdicas los estudiantes logran aprender matemática de manera significativa pariendo desde su entorno más cercano favoreciendo la resolución de problemas de su vida cotidiana. Dichos hallazgos, se registraron en tablas múltiples. Por ello, es pertinente aprovechar dicha metodología en las clases de los diferentes niveles de la educación básica regular

Las técnicas de estudio y el aprendizaje en los estudiantes de cuarto de secundaria de una institución educativa pública.

La presente investigación recaba información para dar respuesta a la interrogante: ¿Cuál es la relación existente entre las técnicas de estudio y el aprendizaje en los en los estudiantes de cuarto año de secundaria de una institución educativa pública, el estudio en mención tuvo el enfoque cuantitativo, es del tipo sustantivo o de base, con diseño descriptivo correlacional. La muestra se conformó con 60 estudiantes. Los instrumentos que posibilitaron recabar la información respectiva fueron: cuestionario de técnicas de estudio y cuestionario del aprendizaje para estudiantes. El diseño estadístico contempló estadísticos descriptivos e inferenciales. Las conclusiones a las que se arribó, fueron las siguientes: Existe relación significativa entre las técnicas de estudio, en su dimensión espacio y ambiente de estudio, planificación del tiempo de estudio, método de estudio y motivación pór el estudio; y el aprendizaje en los estudiantes de cuarto año de secundaria de una institución educativa pública.Universidad Nacional de Educación Enrique Guzmán y Valle.Tesi