Behavioral and Endocrine Consequences of Simultaneous Exposure to Two Different Stressors in Rats: Interaction or Independence?

Although behavioral and endocrine consequences of acute exposure to stressors have been extensively studied, little is known about how simultaneous exposure to two different stressors interacts to induce short- and long-term effects. In the present experiment we studied this interaction in adult male rats exposed to cat fur odor (impregnated cloth) or immobilization on boards either separately or simultaneously. We reasoned that exposure to the odor of a potential predator while immobilized, may potentiate its negative consequences as compared to exposure to only one of the stressors. Exposure to cat odor elicited the expected reduction of activity and avoidance of the area where the impregnated cloth was located. The endocrine response (plasma levels of ACTH and corticosterone, as a measure of the hypothalamic-pituitary-adrenal axis, HPA) was markedly greater after immobilization than after cat fur odor and no additive effects were found by simultaneous exposure to both stressors. Cat odor, but not immobilization, increased anxiety-like behavior as evaluated in the elevated plus-maze 7 days after the stressors, with no evidence of enhanced HPA activation. In addition, cat odor exposure resulted in long-lasting (8 days later) fear conditioning to the box containing a clean cloth, which was reflected by hypoactivity, avoidance of the cloth area and enhanced HPA activation. All these effects were similarly observed in rats exposed simultaneously to cat odor and immobilization. In rats only exposed to immobilization, only some weak behavioral signs of fear conditioning were found, but HPA activation in response to the context paired to immobilization was enhanced to the same extent as in cat odor-exposed animals, supporting a certain degree of endocrine conditioning. The present results did not reveal important behavioral interactions between the two stressors when animals experienced both simultaneously, whereas some interactions were found regarding HPA activation. Theoretical implications are discussed

The ATENción Plena en Enfermedad de Alzheimer (ATENEA-Mindfulness in Alzheimer's Disease) Program for Caregivers : Study Protocol for a Randomized Controlled Trial

A person affected by Alzheimer's disease (AD) gradually loses the ability to perform activities of daily living and becomes dependent on caregivers, thereby having a negative impact on the caregivers' quality of life. There is evidence that suggests that interventions aimed at caregivers, such as mindfulness, may be effective at reducing this burden and emotional issues, such as depression and anxiety, and improving their quality of life. However, there is a lack of consistency in the findings and conclusions remain tentative. In addition, as neuropsychiatric symptoms (NPSs) of AD are major determinants of the caregiver's burden, these interventions should examine the relationship between these symptoms and caregiver outcomes. Importantly, to improve the design of therapeutic interventions for caregivers and complement the treatment of AD, aspects related to occupational performance and the participation of people with AD and their caregivers should also be considered. Therefore, this study will aim to examine first, the effects of a mindfulness-based program designed for caregivers on NPSs of AD and caregivers' anxiety and depression; second, the effects of this program on patients' functional capacity, cognitive performance, executive functions, and quality of life, and on caregivers' burden, quality of life, occupational balance, executive functions, psychological wellbeing, and self-compassion. We believe that the findings of this study will have significant implications for future healthcare strategies focused on improving the quality of life and wellbeing of caregivers

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Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Mar Menor: una laguna singular y sensible. Evaluación científica de su estado.

Este libro recopila las aportaciones que equipos de investigación de la Universidad de Murcia, Universidad Politécnica de Cartagena, Instituto Geológico-Minero de España, Universidad de Alicante, el Instituto Español de Oceanografía y otros organismos hicieron en las Jornadas Científicas del Mar Menor, celebradas en diciembre de 2014.La información recogida en este libro se estructura en dos grandes bloques, uno de Biología y Ecología del Mar Menor (capítulos 1 al 8) y otro de Condiciones fisicoquímicas e impacto de actividades humanas en la laguna (capítulos 9 al 14). El primer bloque resume buena parte de los estudios ecológicos realizados en el Mar Menor, que han servido para mejorar su conocimiento y también para cambiar antiguas asunciones sobre la naturaleza y el funcionamiento de estos ecosistemas lagunares (Capítulo 1). El segundo capítulo muestra que esta laguna alberga en zonas someras de su perímetro hábitats fundamentales para mantener y conservar tanto especies migratorias como residentes, que es necesario conocer para paliar el impacto de las actividades humanas que les afectan. En este sentido la reducción de la carga de nutrientes y contaminantes orgánicos e inorgánicos que fluyen hacia el Mar Menor puede ayudar a preservar la laguna en mejores condiciones, bien sea tratando las escorrentías (plantas de tratamiento, humedales artificiales u otras técnicas) y recuperar este agua para uso agrícola o evitar su descarga en la laguna (Capítulo 3). Estas actuaciones serán clave para la conservación de especies emblemáticas como el caballito de mar (Capítulo 4) y reducir el impacto de las proliferaciones masivas de medusas que se producen en la laguna desde 1993 (Capítulo 5). En este mismo sentido los cambios acaecidos en la laguna han favorecido la incursión de invertebrados marinos alóctonos (Capítulo 6) y han afectado a la respuesta de la dinámica poblacional de las aves acuáticas a distintas escalas (Capítulo 7). Para completar este bloque se ofrece una perspectiva histórica de la importancia que ha tenido la investigación sobre acuicultura realizada en esta laguna, que ha servido de base para su gran desarrollo actual (Capítulo 8). El segundo bloque se inicia con una evaluación del origen y evolución del Mar Menor desde el punto de vista geológico, y evidencia su vulnerabilidad ante el deterioro que puede sufrir la desaparición de la barrera de cierre y/o su colmatación (Capítulo 9). En el Capítulo 10 se describe la relevancia que tiene la interacción de los acuíferos del Campo de Cartagena con la laguna, que se produce no sólo a nivel superficial sino también subterráneo. Esta interacción permite el acceso de nutrientes a la laguna, a pesar de la cierta capacidad de depuración de los humedales que le circundan, y también de metales traza por los aportes de residuos mineros (Capítulo 11). De hecho los metales traza están presentes en los sedimentos de la laguna, y su distribución se ha caracterizado en la columna sedimentaria relacionándola con la granulometría y el contenido de materia orgánica del sedimento (Capítulo 12). Posteriormente se describe la entrada de diversos contaminantes orgánicos, incluyendo pesticidas y fármacos a través de la rambla del Albujón, y su distribución estacional en agua y sedimento de la laguna (Capítulo 13). Este segundo bloque finaliza con el Capítulo 14 en el que se describe la bioacumulación de hidrocarburos aromáticos policíclicos, pesticidas y fármacos en moluscos y peces del Mar Menor, así como los efectos biológicos que la carga contaminante que accede a través de la rambla del Albujón produce en los organismos que allí habitan. El libro concluye con un breve epílogo redactado por los editores de este libro

Mar Menor: una laguna singular y sensible. Evaluación científica de su estado.

Este libro recopila las aportaciones que equipos de investigación de la Universidad de Murcia, Universidad Politécnica de Cartagena, Instituto Geológico-Minero de España, Universidad de Alicante, el Instituto Español de Oceanografía y otros organismos hicieron en las Jornadas Científicas del Mar Menor, celebradas en diciembre de 2014.La información recogida en este libro se estructura en dos grandes bloques, uno de Biología y Ecología del Mar Menor (capítulos 1 al 8) y otro de Condiciones fisicoquímicas e impacto de actividades humanas en la laguna (capítulos 9 al 14). El primer bloque resume buena parte de los estudios ecológicos realizados en el Mar Menor, que han servido para mejorar su conocimiento y también para cambiar antiguas asunciones sobre la naturaleza y el funcionamiento de estos ecosistemas lagunares (Capítulo 1). El segundo capítulo muestra que esta laguna alberga en zonas someras de su perímetro hábitats fundamentales para mantener y conservar tanto especies migratorias como residentes, que es necesario conocer para paliar el impacto de las actividades humanas que les afectan. En este sentido la reducción de la carga de nutrientes y contaminantes orgánicos e inorgánicos que fluyen hacia el Mar Menor puede ayudar a preservar la laguna en mejores condiciones, bien sea tratando las escorrentías (plantas de tratamiento, humedales artificiales u otras técnicas) y recuperar este agua para uso agrícola o evitar su descarga en la laguna (Capítulo 3). Estas actuaciones serán clave para la conservación de especies emblemáticas como el caballito de mar (Capítulo 4) y reducir el impacto de las proliferaciones masivas de medusas que se producen en la laguna desde 1993 (Capítulo 5). En este mismo sentido los cambios acaecidos en la laguna han favorecido la incursión de invertebrados marinos alóctonos (Capítulo 6) y han afectado a la respuesta de la dinámica poblacional de las aves acuáticas a distintas escalas (Capítulo 7). Para completar este bloque se ofrece una perspectiva histórica de la importancia que ha tenido la investigación sobre acuicultura realizada en esta laguna, que ha servido de base para su gran desarrollo actual (Capítulo 8). El segundo bloque se inicia con una evaluación del origen y evolución del Mar Menor desde el punto de vista geológico, y evidencia su vulnerabilidad ante el deterioro que puede sufrir la desaparición de la barrera de cierre y/o su colmatación (Capítulo 9). En el Capítulo 10 se describe la relevancia que tiene la interacción de los acuíferos del Campo de Cartagena con la laguna, que se produce no sólo a nivel superficial sino también subterráneo. Esta interacción permite el acceso de nutrientes a la laguna, a pesar de la cierta capacidad de depuración de los humedales que le circundan, y también de metales traza por los aportes de residuos mineros (Capítulo 11). De hecho los metales traza están presentes en los sedimentos de la laguna, y su distribución se ha caracterizado en la columna sedimentaria relacionándola con la granulometría y el contenido de materia orgánica del sedimento (Capítulo 12). Posteriormente se describe la entrada de diversos contaminantes orgánicos, incluyendo pesticidas y fármacos a través de la rambla del Albujón, y su distribución estacional en agua y sedimento de la laguna (Capítulo 13). Este segundo bloque finaliza con el Capítulo 14 en el que se describe la bioacumulación de hidrocarburos aromáticos policíclicos, pesticidas y fármacos en moluscos y peces del Mar Menor, así como los efectos biológicos que la carga contaminante que accede a través de la rambla del Albujón produce en los organismos que allí habitan. El libro concluye con un breve epílogo redactado por los editores de este libro.Versión del edito

What can we know from pituitary-adrenal hormones about the nature and consequences of exposure to emotional stressors?

Exposure to stress induces profound physiological and behavioral changes in the organisms and some of these changes may be important regarding stressinduced pathologies and animal models of psychiatric diseases. Consequences of stress are dependent on the duration of exposure to stressors (acute, chronic), but also of certain characteristics such as intensity, controllability, and predictability. If some biological variables were able to reflect these characteristics, they could be used to predict negative consequences of stress. Among the myriad of physiological changes caused by stress, only a restricted number of variables appears to reflect the intensity of the situation, mainly plasma levels of ACTH and adrenaline. Peripheral hypothalamic-pituitary-adrenal (HPA) hormones (ACTH and corticosterone) are also able to reflect fear conditioning. In contrast, the activation of the HPA axis is not consistently related to anxiety as evaluated by classical tests such as the elevated plus-maze. Similarly, there is no consistent evidence about the sensitivity of the HPA axis to psychological variables such as controllability and predictability, despite the fact that: (a) lack of control over aversive stimuli can induce behavioral alterations not seen in animals which exert control, and (b) animals showed clear preference for predictable versus unpredictable stressful situations. New studies are needed to re-evaluate the relationship between the HPA axis and psychological stress characteristics using ACTH instead of corticosterone and taking advantages of our current knowledge about the regulation of this important stress system. © Springer Science+Business Media, LLC 2012

Behavioral and endocrine consequences of simultaneous exposure to two different stressors in rats : interaction or independence?

Although behavioral and endocrine consequences of acute exposure to stressors have been extensively studied, little is known about how simultaneous exposure to two different stressors interacts to induce short- and long-term effects. In the present experiment we studied this interaction in adult male rats exposed to cat fur odor (impregnated cloth) or immobilization on boards either separately or simultaneously. We reasoned that exposure to the odor of a potential predator while immobilized, may potentiate its negative consequences as compared to exposure to only one of the stressors. Exposure to cat odor elicited the expected reduction of activity and avoidance of the area where the impregnated cloth was located. The endocrine response (plasma levels of ACTH and corticosterone, as a measure of the hypothalamic-pituitary-adrenal axis, HPA) was markedly greater after immobilization than after cat fur odor and no additive effects were found by simultaneous exposure to both stressors. Cat odor, but not immobilization, increased anxiety-like behavior as evaluated in the elevated plus-maze 7 days after the stressors, with no evidence of enhanced HPA activation. In addition, cat odor exposure resulted in long-lasting (8 days later) fear conditioning to the box containing a clean cloth, which was reflected by hypoactivity, avoidance of the cloth area and enhanced HPA activation. All these effects were similarly observed in rats exposed simultaneously to cat odor and immobilization. In rats only exposed to immobilization, only some weak behavioral signs of fear conditioning were found, but HPA activation in response to the context paired to immobilization was enhanced to the same extent as in cat odor-exposed animals, supporting a certain degree of endocrine conditioning. The present results did not reveal important behavioral interactions between the two stressors when animals experienced both simultaneously, whereas some interactions were found regarding HPA activation. Theoretical implications are discussed