A male mouse model of WIN 55,212-2 self-administration to study cannabinoid addiction

We have established for the first time a mouse model of cannabinoid addiction using WIN 55,212-2 intravenous self-administration (0.0125 mg/kg/infusion) in C57Bl/6J mice. This model allows to evaluate the addiction criteria by grouping them into 1) persistence of response during a period of non-availability of the drug, 2) motivation for WIN 55,212-2 with a progressive ratio, and 3) compulsivity when the reward is associated with a punishment such as an electric foot-shock, in agreement with the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5). This model also allows to measure two parameters that have been related with the DSM-5 diagnostic criteria of craving, resistance to extinction and reinstatement, and two phenotypic traits suggested as predisposing factors, impulsivity and sensitivity to reward. We found that 35.6% of mice developed the criteria of cannabinoid addiction, allowing to differentiate between resilient and vulnerable mice. Therefore, we have established a novel and reliable model to study the neurobiological correlates underlying the resilience or vulnerability to develop cannabinoid addiction. This model included the chemogenetic inhibition of neuronal activity in the medial prefrontal cortex to the nucleus accumbens pathway to assess the neurobiological substrate of cannabinoid addiction. This model will shed light on the neurobiological substrate underlying cannabinoid addiction

The Effectiveness of Advanced Practice Nurses with Respect to Complex Chronic Wounds in the Management of Venous Ulcers

This study aims to evaluate the effectiveness of advanced practice nurses with respect to complex chronic wounds (APN-CCWs) in the care of patients with venous ulcers. A multicentric, quasi-experimental pre-post study was conducted without a control group in the sanitary management areas where the APN-CCW program is being piloted. The intervention consisted of a mass training of clinical nurses from the participating districts on the proper management of injuries and the use of compression therapy. The data were collected through a specifically constructed questionnaire with questions regarding descriptive variables of injuries and their treatment. A total of 643 professionals responded (response rate of 89.1%), attending to a total population of 707,814 inhabitants. An increase in multilayer bandage use by 15.67%, an increase in elastic bandage use by 13.24%, and a significant decrease in the referral of patients to consultation with hospital specialists was achieved, from 21.08% to 12.34%. The number of patients referred to the APNs was 13.25%, which implied a resolution rate of 94.08% of their injuries. In conclusion, the coordination by the APN-CCWs in patients with venous ulcers was effective in improving the continuity of care, in the optimization of resources, and in their care role

La competición espacial en Europa tras la Gran Recesión. Un análisis de las posiciones ideológicas ideales y reales en Italia, España y Francia

European party systems have experienced crucial changes over the last few decades. Key among these changes have been the electoral punishment of incumbent parties, the political activation of populist attitudes, and the emergence of new parties. These phenomena have been strongly conditioned by the intensity of the economic crisis experienced by European countries. The analyses we present here constitute a first attempt to comparatively examine the main characteristics of spatial and ideological party competition in Spain, France, and Italy after the Great Recession. Our analysis compares actual ideological positions (as perceived by all voters) to the ideal or optimal ideological party positions predicted by spatial competition models based on proximity and directional voting, always on the assumption that parties will choose those positions that allow them to maximize their vote shares. Our analysis aims at assessing the degree to which public attitudes connected to the Great Recession, in particular, government evaluations and populist attitudes, have affected ideological locations. Our results show that there are appreciable differences between the estimates inferred from models using crisis-related variables and those derived from models that did not include such variables. The analysis also shows that the estimates based on models using governmental performance evaluations and populist attitudes are slightly closer to the real positions of political parties. Finally, we also observe that differences in ideal estimates are larger in Spain and Italy, that is, in the two countries that suffered the most during the Great Recession.Los sistemas de partidos europeos han experimentado grandes cambios en las últimas décadas. Especialmente importantes en este sentido han sido el castigo electoral de los partidos gobernantes, la activación política de las actitudes populistas y la emergencia de nuevos partidos. Estos fenómenos han estado fuertemente condicionados por la intensidad de la crisis económica experimentada por los países europeos. Los análisis que se presentan aquí examinan las principales características de la competición ideológica y espacial después de la Gran Recesión en España, Francia e Italia. Nuestro análisis compara las posiciones ideológicas reales (percibidas por todos los votantes) con las posiciones ideales y óptimas predichas por modelos de competición espacial basados en voto de proximidad y direccional, siempre bajo la premisa de que los partidos elegirán aquellas posiciones que les permitan maximizar su porcentaje de votos. Nuestro análisis intenta estimar el grado en el que las actitudes públicas conectadas a la Gran Recesión, en particular la evaluación de los gobiernos y las actitudes populistas, han afectado a las posiciones ideológicas de los partidos. Nuestros resultados indican que hay diferencias apreciables entre las estimaciones derivadas de modelos que usan variables conectadas a la crisis y aquellas basadas en modelos que no usan tales variables. Asimismo, este análisis muestra que las estimaciones basadas en modelos que utilizan las evaluaciones de rendimiento gubernamental y las actitudes populistas están ligeramente más cercanas a las posiciones reales de los partidos políticos. Finalmente, nuestro análisis muestra que las diferencias en las estimaciones ideales entre los modelos que usan tales variables y los que no las usan son mayores en España e Italia, esto es, en los dos países que sufrieron más acusadamente la Gran Recesión

THC exposure during adolescence increases impulsivity-like behavior in adulthood in a WIN 55,212-2 self-administration mouse model

Cannabis addiction is a chronically relapsing disorder lacking effective treatment. Regular cannabis consumption typically begins during adolescence, and this early cannabinoid exposure may increase the risk for drug addiction in adulthood. This study investigates the development of cannabis addiction-like behavior in adult mice after adolescent exposure to the main psychoactive component of cannabis, Δ 9 -tetrahydrocannabinol (THC). Adolescent male mice were exposed to 5 mg/kg of THC from postnatal days 37 to 57. Operant self-administration sessions of WIN 55,212-2 (12.5 μg/kg/infusion) were conducted for 10 days. Mice were tested for three addiction-like criteria (persistence of response, motivation, and compulsivity), two parameters related to craving (resistance to extinction and drug-seeking behavior), and two phenotypic vulnerability traits related to substance use disorders (impulsivity and reward sensitivity). Additionally, qPCR assays were performed to detect differentially expressed genes in medial prefrontal cortex (mPFC), nucleus accumbens (NAc), dorsal striatum, and hippocampus (HPC) of "addicted" and "non-addicted" mice. Adolescent THC exposure did not modify WIN 55,212-2 reinforcement nor the development of cannabis addiction-like behavior. Inversely, THC pre-exposed mice displayed impulsive-like behavior in adulthood, which was more pronounced in mice that developed the addiction-like criteria. Moreover, downregulated drd2 and adora2a gene expression in NAc and HPC was revealed in THC pre-exposed mice, as well as a downregulation of drd2 expression in mPFC of vehicle pre-treated mice that developed addiction-like behaviors. These findings suggest that adolescent THC exposure may promote impulsivity-like behavior in adulthood, associated with downregulated drd2 and adora2a expression in NAc and HPC

Biomecánica de riesgo disergonómico y su aporte en la aparición de trastornos músculo-esqueléticos en los estibadores de la empresa Ejecutores y Consultores Bencaingenieros E. I. R. L, Arequipa 2018

La investigación tiene por objetivo realizar el Análisis Biomecánico de riesgo disergonómico en los estibadores de la empresa Bencaingenieros E. I. R. L. La investigación es de tipo no experimental de diseño correccional. Para el desarrollo del análisis se utilizó el instrumento de análisis biomecánico estático coplanar isométrico de Chaffin. Para levantar la información se utilizó la muestra compuesta por 18 trabajadores destacados en la actividad de estiba de rocas ornamentales. Se aplicó dicho instrumento para determinar el nivel de riesgos disergonómicos en relación a los esfuerzos físicos realizados en determinadas posturas y niveles repetitivos específicos. Los datos recolectados en campo se han ingresado en una matriz de Excel para luego ser analizados por el software de Ergonautas BIO-MEC con la finalidad procesar los datos mediante cálculos físico - mecánicos y obtener los resultados del nivel de riesgo disergonómicos por el esfuerzo realizado por articulación durante el movimiento realizado por trabajos de estiba. Para conocer los procesos de la actividad se ha hecho un seguimiento desde la cantera hasta la zona de corte y disposición por el cliente, registrando de manera fotográfica la forma como realizan sus tareas. La interpretación de los resultados, se ha realizado según niveles de valoración del método que analiza los niveles de esfuerzo, carga máximos recomendables por articulación y su relación con la aparición de trastornos musculo esqueléticos.The research aims to perform the Biomechanical Analysis of disergonomic risks in the dockers of the company BENCAINGENIEROS SAC. The research is a non-experimental type of correctional design. The Chaffin isometric coplanar static biomechanical analysis instrument was used for the analysis. To collect the information, the sample composed of 18 outstanding workers in the activity of stowage of ornamental rocks was used. This instrument was applied to determine the level of disergonomic risks in relation to the physical efforts made in certain positions and specific repetitive levels. The data collected in the field have been entered into an Excel matrix and then analyzed by the BIO-MEC Ergonauts software in order to process the data through physical-mechanical calculations and obtain the results of the level of disergonomic risk due to the effort made by articulation during the movement performed by stowage works. To know the processes of the activity, a follow-up has been carried out from the quarry to the cutting area and disposition by the client, recording in a photographic way the way they perform their tasks. The interpretation of the results has been carried out according to levels of assessment of the method that analyzes the levels of effort, maximum recommended load per joint and its relationship with the appearance of skeletal muscle disorders.TesisCampus Arequip

Corrections in numerical methodology to evaluate plasticity induced crack closure along the thickness.

Uncorrected ProofThe influence of the three-dimensional effects of the distribution of the stress intensity factor in the numerical calculation of plasticity-induced crack closure is analysed in this paper. The usual methodology assumes a constant distribution of K along the thickness to obtain the effective stress intensity factor of the crack. This assumption should not be transposed to models that intend to observe phenomena in the crack front vicinity, where 3-D effects are a key aspect in the results. Through numerical simulations of both fracture and fatigue of through thickness straight cracks (CT specimen in mode I), the local opening and closure moment of each crack node is obtained and compared with previous one. Corrections are proposed for numerical methodology to obtain K⁠op and K⁠cl distribution along the thicknessJunta de Andalucía, Proyectos de Excelencia grant reference TEP-324

Numerical modelling of three-dimensional fatigue crack closure: mesh refinement.

Accepted ManuscriptFatigue crack closure has been studied by means of the finite element method for a long time. Most work has been performed considering bi-dimensional models where the numerical methodology has been developed. A great number of bi-dimensional studies analyses different numerical parameters and optimise them. Three-dimensional models have extended lately. Nevertheless, the methodology employed was taken from the one developed for bi-dimensional cases. The current computational capabilities allow a comprehensive three-dimensional study of the influence of the different modelling parameters in a similar way to those studies carried out with bi-dimensional models. In particular, one of the key issues is related to the element size, which has a huge influence on crack opening and closure values. In the present work, a CT aluminium specimen has been modelled threedimensionally and several calculations have been made in order to evaluate the influence of the mesh size around the crack front. The numerical accuracy is analysed in terms of crack closure and opening values. Classical bi-dimensional recommendations are updated. A similar linear relationship has been identified and a minimum mesh recommendation of 60 divisions of the Dugdale’s plastic zone size is made.Ministerio de Economía y Competitividad de España MAT2016-76951-C2-2-P

Analysis of the Mechanical Properties of the Human Tympanic Membrane and Its Influence on the Dynamic Behaviour of the Human Hearing System

The difficulty to estimate the mechanical properties of the tympanic membrane (TM) is a limitation to understand the sound transmission mechanism. In this paper, based on finite element calculations, the sensitivity of the human hearing system to these properties is evaluated. The parameters that define the bending stiffness properties of the membrane have been studied, specifically two key parameters: Young’s modulus of the tympanic membrane and the thickness of the eardrum. Additionally, it has been completed with the evaluation of the presence of an initial prestrain inside the TM. Modal analysis is used to study the qualitative characteristics of the TM comparing with vibration patterns obtained by holography. Higher-order modes are shown as a tool to identify these properties. The results show that different combinations of elastic properties and prestrain provide similar responses. The presence of prestrain at the membrane adds more uncertainty, and it is pointed out as a source for the lack of agreement of some previous TM elastic modulus estimations