Dopamine D4 receptor counteracts morphine-induced changes in M opioid receptor signaling in the striosomes of the rat caudate putamen.

Morphine is one of the most potent analgesic drugs used to relieve moderate to severe pain. After long-term use of morphine, neuroadaptive changes in the brain promotes tolerance, which result in a reduced sensitivity to most of its effects with attenuation of analgesic efficacy, and dependence, revealed by drug craving and physical or psychological manifestations of drug withdrawal. The mu opioid receptor (MOR) is critical, not only in mediating morphine analgesia, but also in addictive behaviors by the induction of a strong rewarding effect. We have previously shown that dopamine D4 receptor (D4R) stimulation counteracts morphine-induced activation of dopaminergic nigrostriatal pathway and accumulation of Fos family transcription factors in the caudate putamen (CPu). In the present work, we have studied the effect of D4R activation on MOR changes induced by morphine in the rat CPu on a continuous drug treatment paradigm, by analyzing MOR protein level, pharmacological profile, and functional coupling to G proteins. Furthermore, using conditioned place preference and withdrawal syndrome test, we have investigated the role of D4R activation on morphine-related behavioural effects. MOR immunoreactivity, agonist binding density and its coupling to G proteins are up-regulated in the striosomes by continuous morphine treatment. Interestingly, co-treatment of morphine with the dopamine D4 receptor (D4R) agonist PD168,077 fully counteracts these adaptive changes in MOR, in spite of the fact that continuous PD168,077 treatment increases the [3H]DAMGO Bmax values to the same degree as seen after continuous morphine treatment. In addition, the administration of the D4R agonist counteracts the rewarding effects of morphine, as well as the development of physical dependence. The present results give support for the existence of antagonistic functional D4R-MOR receptor-receptor interactions in the adaptive changes occurring in MOR of striosomes on continuous administration of morphine and preventing morphine-related behaviour.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Dopamine D4 receptor activation counteracts nigrostriatal pathway activation by morphine: relevance in drug addiction.

Morphine induces dopamine release in the caudate putamen (CPu), which promotes stereotyped behavior and habit learning for drug-seeking and –taking. Nigrostriatal pathway stimulation by morphine is due to a removal of tonic inhibition arising from SNr GABA interneurons on SNc dopaminergic neurons through the mu opioid receptor (MOR). Long-term morphine exposure produces a series of adaptations in SNc dopamine neurons, which affect neuron excitability and dopamine output to CPu. We have previously shown that dopamine D4 receptor (D4R) stimulation counteracts acute and chronic morphine-induced accumulation of several transcription factors in the CPu (Gago et al., 2011 Brain Res.). Since D4R is expressed in the SNr (Rivera et al., Brain Res. 2003), we postulate that a functional D4R-MOR interaction at the midbrain level could exists. We have investigated the role of D4R in the morphine-induced nigroestriatal dopamine metabolism in the rat brain using biochemical and immunohistochemical techniques. We also have studied the influence of D4R on morphine-induced morphological changes in SNc dopamine neurons using both immunohistochemical and image analysis techniques. Finally, we examined a possible underlying mechanism of the D4R-MOR interaction at the SN level using in vitro quantitative receptor autoradiography. We have found that D4R activation restores dopamine metabolism in the nigroestriatal pathway after acute morphine treatment and prevents morphine-induced rise of tyroxine hydroxylase and dopamine transporter. Rats receiving a continuous treatment of morphine (6 days) showed SNc dopamine neurons with smaller size and higher circularity index compared with the controls animals. These morphine-induced morphological adaptatives changes were prevented when a D4R agonist (PD168,077) was administered at the same time with morphine. Autoradiographic studies demonstrated that the D4R agonist reduce the affinity of MOR. The present study provides evidence for the existence of a fully blocking effect of the D4R on the activation of dopaminergic nigroestriatal pathway by morphine.Financiación: P09-CVI- 4702 (Proyecto de Excelencia de la Junta de Andalucía

El teletrabajo y su influencia en la calidad de vida laboral en la empresa ASILORZA S.A.C., en el año 2021

La presente investigación tuvo como objetivo general determinar la influencia del teletrabajo en la calidad de vida laboral en la empresa Asilorza S.A.C., en el año 2021. La investigación fue de método cuantitativo, de diseño no experimental, de tipo transversal y correlacional-causal. Se utilizó una muestra censal compuesta por 38 tele trabajadores. Asimismo, para medir ambas variables se aplicó como instrumento el cuestionario, sometidos a la confiabilidad y validez, conformado por 26 ítems para teletrabajo y 29 ítems para calidad de vida laboral, medidos en una escala de Likert. Respecto al procesamiento de los datos, se utilizó el sistema SPSS versión 20 para la estadística descriptica y para la estadística inferencial se utilizó la prueba rho de Spearman para datos no paramétricos; mediante el cual se encontró que el coeficiente de correlación de la variable teletrabajo y la variable calidad de vida laboral es correlación positiva considerable de 0,768, lo cual indica que el teletrabajo influye de forma significativa (Sig.<0.05) en la calidad de vida laboral, por consiguiente se acepta la hipótesis general planteada en que existe una influencia significativa del Teletrabajo en la Calidad de vida laboral en la empresa Asilorza S.A.C., en el año 2021

Historical palaeohydrology and landscape resilience of a Mediterranean rambla (Castellon, NE Spain): Floods and people.

This paper provides a new methodological approach to analyse secular patterns of flooding (magnitude and frequency) from sedimentary evidence (palaeofloods), taking into account changes in channel geometry, and their links to historical environmental changes and the inherent social and demographic evolution within the catchment. A case study analysis was focused in Rambla de la Viuda (drainage area of 1500 km2) whose stream flow is related to extreme rainfalls. A 500 years sedimentary archive was reconstructed from eight stratigraphic profiles comprising continuous sequences of slackwater flood deposits interbedded with episodic colluvial and edaphic horizons. Discharge estimates associated to sedimentary flood evidences were obtained from one-dimensional hydraulic modelling. The stratigraphic units were sampled to characterise their geochemical and paleobotanical (phytoliths) contents. Palaeoflood chronology was obtained from radiocarbon and luminescence (OSL) dating, supported by documentary data (written historical documents). A high frequency and high magnitude palaeoflood period took place during the 15th-middle 16th century, which seem to correlate in time with general wetter conditions. Three short-term environment stability conditions (land use and climatic) also made possible the development of three paleosols. The lowest flood magnitude and discharges in the sedimentary record was found between the mid-17th to mid-18th centuries, under prevailing drier environmental conditions. Episodic high magnitude flooding took place at late 18th century, correlating in time with palaeovegetation and geochemical evidences of important changes on land use (deforestation and grazing). Poorer developed soils were found at upper stratigraphic sequences (19th century) characterised by thick units of colluvium deposits, usually culminating sequences of short-lived continuous slackwater flood units. Despite of the potential human influence (land-use) on soil hydrology, the longterm behaviour of high magnitude floods (>1000 m3 s-1) has been stationary over the last 500 years

Extreme Floods in Small Mediterranean Catchments: Long-Term Response to Climate Variability and Change

Climate change implies changes in the frequency and magnitude of flood events. The influence of climate variability on flooding was evaluated by an analysis of sedimentary (palaeofloods) and documentary archives. A 500-year palaeoflood record at Montlleó River (657 km2 in catchment area), eastern Spain, revealed up to 31 palaeofloods with a range of discharges of 20–950 m3 s−1, and with at least five floods exceeding 740–950 m3 s−1. This information contrasts with the available gauged flood registers (since year 1971) with an annual maximum daily discharge of 129 m3 s−1. Our palaeoflood dataset indicates flood cluster episodes at (1) 1570–1620, (2) 1775–1795, (3) 1850–1890, and (4) 1920–1969. Flood rich periods 1 and 3 corresponded to cooler than usual (about 0.3 °C and 0.2 °C) climate oscillations, whereas 2 and 4 were characterised by higher inter-annual climatic variability (floods and droughts). This high inter-annual rainfall variability increased over the last 150 years, leading to a reduction of annual maximum flow. Flood quantiles (>50 years) calculated from palaeoflood+gauged data showed 30%–40% higher peak discharges than those using only instrumental records, whereas when increasing the catchment area (1500 km2) the discharge estimation variance decreased to ~15%. The results reflect the higher sensitivity of small catchments to changes on flood magnitude and frequency due to climate variability whereas a larger catchment buffers the response due to the limited extent of convective storms. Our findings show that extended flood records provide robust knowledge about hazardous flooding that can assist in the prioritization of low-regret actions for flood-risk adaptation to climate change

Valoración geriátrica y factores pronósticos de mortalidad en la neumonía del anciano

Estudi de la relació entre les variables incloses a la valoració geriàtrica integral amb mortalitat als pacients ancians ingressats amb el diagnòstic de pneumònia extrahospitalària. Es va estudiar la situació funcional prèvia (índex de Barthel (IBp) i índex de Lawton), la situació funcional a l'ingrés (índex de barthel (IBi)) i pèrdua funcional [(IBp-IBi/IBp) x 100], situació cognitiva (test de Pfeiffer), comorbilitat (índex de Charlson), estat nutricional (determinació de proteïnes i albúmina) així com la presència prèvia a l'ingrés de les síndromes geriàtriques d'immobilitat, úlceres per pressió (UPP) i deteriorament cognitiu i l'aparició durant l'ingrés d'immobilitat, UPP i síndrome confusional aguda.Estudio de la relación entre las variables incluidas en la valoración geriátrica integral con mortalidad, en pacientes ancianos ingresados con diagnostico de neumonía extrahospitalaria. Se estudió la situación funcional previa (índice de Barthel (IBp) e índice de Lawton), situación funcional al ingreso (índice de Barthel (IBi) y pérdida funcional [(IBp-IBi/IBp) x 100]), función cognitiva (test de Pfeiffer), comorbilidad (índice de Charlson), estado nutricional (determinación de proteínas y albúmina), así como la presencia al ingreso de los síndromes geriátricos: inmovilidad, ulceras por presión (UPP) y deterioro cognitivo, así como la aparición durante el ingreso de inmovilidad, UPP y síndrome confusional agudo

Extreme Floods in Small Mediterranean Catchments: Long-Term Response to Climate Variability and Change

: Climate change implies changes in the frequency and magnitude of flood events. The influence of climate variability on flooding was evaluated by an analysis of sedimentary (palaeofloods) and documentary archives. A 500-year palaeoflood record at Montlleó River (657 km2 in catchment area), eastern Spain, revealed up to 31 palaeofloods with a range of discharges of 20-950 m3 s −1 , and with at least five floods exceeding 740-950 m3 s −1 . This information contrasts with the available gauged flood registers (since year 1971) with an annual maximum daily discharge of 129 m3 s −1 . Our palaeoflood dataset indicates flood cluster episodes at (1) 1570-1620, (2) 1775-1795, (3) 1850-1890, and (4) 1920-1969. Flood rich periods 1 and 3 corresponded to cooler than usual (about 0.3 ◦C and 0.2 ◦C) climate oscillations, whereas 2 and 4 were characterised by higher inter-annual climatic variability (floods and droughts). This high inter-annual rainfall variability increased over the last 150 years, leading to a reduction of annual maximum flow. Flood quantiles (>50 years) calculated from palaeoflood+gauged data showed 30%-40% higher peak discharges than those using only instrumental records, whereas when increasing the catchment area (1500 km2 ) the discharge estimation variance decreased to ~15%. The results reflect the higher sensitivity of small catchments to changes on flood magnitude and frequency due to climate variability whereas a larger catchment buffers the response due to the limited extent of convective storms. Our findings show that extended flood records provide robust knowledge about hazardous flooding that can assist in the prioritization of low-regret actions for flood-risk adaptation to climate change

El consentimiento, como nueva causa de exclusión de la antijuridicidad en las relaciones sexuales entre adolescentes menores de 14 y mayores de 12 años

The present work studied the relationship between the concept of unlawfulness in relation to consensual sexual relations between adolescents older than twelve and younger than 14 years old, in the context of the criminal type of rape and its sanction in the Organic Integral Penal Code. The research was developed under a qualitative approach, with the use of inductive-deductive, historical-logical, analytical-synthetic, and comparative methods, as well as the techniques of file and bibliographic review. It was theoretically justified that consensual sexual relations between peers over twelve years of age and under fourteen years of age do not constitute a crime, and therefore should not be punished. In addition, a reform of Ecuador's Organic Integral Penal Code is needed to regulate this issue.El presente trabajo estudió la relación entre el concepto de la antijuridicidad frente a las relaciones sexuales consentidas de adolescentes pares mayores de 12 y menores de 14 años, en el contexto del tipo penal de violación y su sanción en el Código Orgánico Integral Penal de Ecuador. La investigación se desarrolló bajo un enfoque cualitativo, con la utilización de los métodos inductivo-deductivo, histórico-lógico, analítico-sintético y comparativo, así como las técnicas de fichaje y revisión bibliográfica. Se justificó teóricamente que las relaciones sexuales consentidas entre pares mayores de doce años y menores de catorce años no constituyen un delito, por lo que no deben ser sancionadas. Adicionalmente, se necesita una reforma al Código Orgánico Integral Penal de Ecuador que regule este particular.&nbsp

Conception Of The Subject In The School From The Perspective Of Six Teachers Assigned To A School With Inclusive Trend Located In The City Of Santiago De Cali

RESUMEN El siguiente trabajo investigativo tuvo como finalidad describir la concepción del sujeto en la escuela desde la mirada de 6 docentes adscritos a una institución educativa con tendencia inclusiva ubicada en la ciudad de Santiago de Cali. Es una investigación de tipo descriptivo con un diseño No experimental-transversal y para dar cumplimiento al objetivo general se seleccionó como recurso metodológico la aplicación de un cuestionario de 121 preguntas abiertas que dan cuenta del sujeto en la escuela desde las políticas, culturas y prácticas inclusivas extraídas de la Guía para la Evaluación y la Mejora de la Educación Inclusiva2 desarrollada por Booth y Ainscow (2000) a 6 docentes de una institución educativa con tendencia inclusiva. La recolección de la información se efectuó a partir de un trabajo de campo y la presentación de los resultados fue a manera de relato. Igualmente se caracterizó la concepción del sujeto en la escuela frente a la perspectiva conductual, normal/anormal de Foucault y Touraine. Conclusiones: Se evidencia la tendencia hacia una concepción ideal de sujeto “touriano” al que se le reconocen múltiples factores diferenciales a nivel familiar, económico, físico y cognitivo y cultural; sin embargo tal concepción ideal es confrontada a manera de antítesis por la concepción de un sujeto normal/anormal buscando una homologación o normalización del sujeto hacia una “media escolar”. Tal contraposición influye para que la escuela inclusiva siga tornándose conductual o clásica haciendo tabula rasa de esas diferencias, promoviendo una integración del sujeto diverso en la escuela pero no una movilización realmente inclusiva. ABSTRACT The following research work aimed to describe the conception of the subject in the school from the eyes of 6 teachers assigned to a school with inclusive trend located in the city of Santiago de Cali. It is a descriptive research design with experimental not cross. To comply with the general objective was selected as a methodological implementation of an open questionnaire of 121 questions that reflect the subject in the school from the political, cultural and inclusive practices learned from the Guidelines for the Evaluation and Improvement of Inclusive Education developed by Booth and Ainscow (2000) to 6 teachers assigned to a school with inclusive trend. The data collection was done from field work and presentation of the results was by way of narrative. Also characterized the conception of the subject in school compared to the behavioral perspective, normal/ abnormal Foucault and Touraine. Conclusions: We found a trend towards an ideal conception of subject “touriano” that are attributed to multiple factors at the household level differentials, economic, physical, cognitive and cultural, but this ideal conception is confronted by way of antithesis to the conception of a subject normal / abnormal seeking approval or normalization of the subject to a "middle-school." Such influences opposed to becoming an inclusive school follow classical behavior or making “tabula rasa” of these differences to promote an integration of different subjects in school but not a truly inclusive movement