Chronic psychosocial stress triggers microglial-/macrophage-induced inflammatory responses leading to neuronal dysfunction and depressive-related behavior.

Chronic environmental stress and traumatic social experiences induce maladaptive behavioral changes and is a risk factor for major depressive disorder (MDD) and various anxiety-related psychiatric disorders. Clinical studies and animal models of chronic stress have reported that symptom severity is correlated with innate immune responses and upregulation of neuroinflammatory cytokine signaling in brain areas implicated in mood regulation (mPFC; medial Prefrontal Cortex). Despite increasing evidence implicating impairments of neuroplasticity and synaptic signaling deficits into the pathophysiology of stress-related mental disorders, how microglia may modulate neuronal homeostasis in response to chronic stress has not been defined. Here, using the repeated social defeat stress (RSDS) mouse model we demonstrate that microglial-induced inflammatory responses are regulating neuronal plasticity associated with psychosocial stress. Specifically, we show that chronic stress induces a rapid activation and proliferation of microglia as well as macrophage infiltration in the mPFC, and these processes are spatially related to neuronal activation. Moreover, we report a significant association of microglial inflammatory responses with susceptibility or resilience to chronic stress. In addition, we find that exposure to chronic stress exacerbates phagocytosis of synaptic elements and deficits in neuronal plasticity. Importantly, by utilizing two different CSF1R inhibitors (the brain penetrant PLX5622 and the non-penetrant PLX73086) we highlight a crucial role for microglia (and secondarily macrophages) in catalyzing the pathological manifestations linked to psychosocial stress in the mPFC and the resulting behavioral deficits usually associated with depression.

Mature astrocytes as source for astrocyte repopulation after deletion in the medial prefrontal cortex: Implications for depression.

The adult brain retains a high repopulation capacity of astrocytes after deletion, and both mature astrocytes in the neocortex and neural stem cells in neurogenic regions possess the potential to generate astrocytes. However, the origin and the repopulation dynamics of the repopulating astrocytes after deletion remain largely unclear. The number of astrocytes is reduced in the medial prefrontal cortex (mPFC) of patients with depression, and selective elimination of mPFC astrocytes is sufficient to induce depression-like behaviors in rodents. However, whether astrocyte repopulation capacity is impaired in depression is unknown. In this study, we used different transgenic mouse lines to genetically label different cell types and demonstrated that in the mPFC of normal adult mice of both sexes, mature astrocytes were a major source of the repopulating astrocytes after acute deletion induced by an astrocyte-specific toxin, L-alpha-aminoadipic acid (L-AAA), and astrocyte regeneration was accomplished within two weeks accompanied by reversal of depression-like behaviors. Furthermore, re-ablation of mPFC astrocytes post repopulation led to reappearance of depression-like behaviors. In adult male mice subjected to 14-day chronic restraint stress, a well-validated mouse model of depression, the number of mPFC astrocytes was reduced; however, the ability of mPFC astrocytes to repopulate after L-AAA-induced deletion was largely unaltered. Our study highlights a potentially beneficial role for repopulating astrocytes in depression and provides novel therapeutic insights into enhancing local mature astrocyte generation in depression.

Chronic unpredictable stress induces autophagic death of adult hippocampal neural stem cells.

Chronic psychological stress is a critical factor for neurological complications like anxiety disorders, dementia, and depression. Our previous results show that chronic restraint stress causes cognitive deficits and mood dysregulation by inducing autophagic death of adult hippocampal neural stem cells (NSCs). However, it is unknown whether other models of psychological stress also induce autophagic death of adult hippocampal NSCs. Here, we show that chronic unpredictable stress (CUS) for 10 days impaired memory function and increased anxiety in mice. Immunohistochemical staining with SOX2 and KI67 revealed a significant reduction in the number of NSCs in the hippocampus following exposure to CUS. However, these deficits were prevented by NSC-specific, inducible conditional deletion of Atg7. These findings suggest that autophagic death of adult hippocampal NSCs is a critical pathogenic mechanism underlying stress-induced brain disorders.

Alpha-synuclein-induced stress sensitivity renders the Parkinson's disease brain susceptible to neurodegeneration.

A link between chronic stress and Parkinson's disease (PD) pathogenesis is emerging. Ample evidence demonstrates that the presynaptic neuronal protein alpha-synuclein (asyn) is closely tied to PD pathogenesis. However, it is not known whether stress system dysfunction is present in PD, if asyn is involved, and if, together, they contribute to neurodegeneration. To address these questions, we assess stress axis function in transgenic rats overexpressing full-length wildtype human asyn (asyn BAC rats) and perform multi-level stress and PD phenotyping following chronic corticosterone administration. Stress signaling, namely corticotropin-releasing factor, glucocorticoid and mineralocorticoid receptor gene expression, is also examined in post-mortem PD patient brains. Overexpression of human wildtype asyn leads to HPA axis dysregulation in rats, while chronic corticosterone administration significantly aggravates nigrostriatal degeneration, serine129 phosphorylated asyn (pS129) expression and neuroinflammation, leading to phenoconversion from a prodromal to an overt motor PD phenotype. Interestingly, chronic corticosterone in asyn BAC rats induces a robust, twofold increase in pS129 expression in the hypothalamus, the master regulator of the stress response, while the hippocampus, both a regulator and a target of the stress response, also demonstrates elevated pS129 asyn levels and altered markers of stress signalling. Finally, defective hippocampal stress signalling is mirrored in human PD brains and correlates with asyn expression levels. Taken together, our results link brain stress system dysregulation with asyn and provide evidence that elevated circulating glucocorticoids can contribute to asyn-induced neurodegeneration, ultimately triggering phenoconversion from prodromal to overt PD.

Gut-brain barrier dysfunction bridge autistic-like behavior in mouse model of maternal separation stress: A behavioral, histopathological, and molecular study.

Autism spectrum disorder (ASD) is a fast-growing neurodevelopmental disorder throughout the world. Experiencing early life stresses (ELS) like maternal separation (MS) is associated with autistic-like behaviors. It has been proposed that disturbance in the gut-brain axis-mediated psychiatric disorders following MS. The role of disruption in the integrity of gut-brain barrier in ASD remains unclear. Addressing this knowledge gap, in this study we aimed to investigate role of the gut-brain barrier integrity in mediating autistic-like behaviors in mouse models of MS stress. To do this, mice neonates are separated daily from their mothers from postnatal day (PND) 2 to PND 14 for 3 hours. During PND58-60, behavioral tests related to autistic-like behaviors including three-chamber sociability, shuttle box, and resident-intruder tests were performed. Then, prefrontal cortex (PFC), hippocampus, and colon samples were dissected out for histopathological and molecular evaluations. Results showed that MS is associated with impaired sociability and social preference indexes, aggressive behaviors, and impaired passive avoidance memory. The gene expression of CLDN1 decreased in the colon, and the gene expression of CLDN5, CLDN12, and MMP9 increased in the PFC of the MS mice. MS is associated with decrease in the diameter of CA1 and CA3 areas of the hippocampus. In addition, MS led to histopathological changes in the colon. We concluded that, probably, disturbance in the gut-brain barrier integrities mediated the autistic-like behavior in MS stress in mice.

Chronic restraint stress induces depression-like behaviors and alterations in the afferent projections of medial prefrontal cortex from multiple brain regions in mice.

INTRODUCTION: The medial prefrontal cortex (mPFC) forms output pathways through projection neurons, inversely receiving adjacent and long-range inputs from other brain regions. However, how afferent neurons of mPFC are affected by chronic stress needs to be clarified. In this study, the effects of chronic restraint stress (CRS) on the distribution density of mPFC dendrites/dendritic spines and the projections from the cortex and subcortical brain regions to the mPFC were investigated. METHODS: In the present study, C57BL/6 J transgenic (Thy1-YFP-H) mice were subjected to CRS to establish an animal model of depression. The infralimbic (IL) of mPFC was selected as the injection site of retrograde AAV using stereotactic technique. The effects of CRS on dendrites/dendritic spines and afferent neurons of the mPFC IL were investigaed by quantitatively assessing the distribution density of green fluorescent (YFP) positive dendrites/dendritic spines and red fluorescent (retrograde AAV recombinant protein) positive neurons, respectively. RESULTS: The results revealed that retrograde tracing virus labeled neurons were widely distributed in ipsilateral and contralateral cingulate cortex (Cg1), second cingulate cortex (Cg2), prelimbic cortex (PrL), infralimbic cortex, medial orbital cortex (MO), and dorsal peduncular cortex (DP). The effects of CRS on the distribution density of mPFC red fluorescence positive neurons exhibited regional differences, ranging from rostral to caudal or from top to bottom. Simultaneously, CRS resulted a decrease in the distribution density of basal, proximal and distal dendrites, as well as an increase in the loss of dendritic spines of the distal dendrites in the IL of mPFC. Furthermore, varying degrees of red retrograde tracing virus fluorescence signals were observed in other cortices, amygdala, hippocampus, septum/basal forebrain, hypothalamus, thalamus, mesencephalon, and brainstem in both ipsilateral and contralateral brain. CRS significantly reduced the distribution density of red fluorescence positive neurons in other cortices, hippocampus, septum/basal forebrain, hypothalamus, and thalamus. Conversely, CRS significantly increased the distribution density of red fluorescence positive neurons in amygdala. CONCLUSION: Our results suggest a possible mechanism that CRS leads to disturbances in synaptic plasticity by affecting multiple inputs to the mPFC, which is characterized by a decrease in the distribution density of dendrites/dendritic spines in the IL of mPFC and a reduction in input neurons of multiple cortices to the IL of mPFC as well as an increase in input neurons of amygdala to the IL of mPFC, ultimately causing depression-like behaviors.

Pacientes hospitalizados con hiperglucemia de estrés: incidencia de diabetes y mortalidad al seguimiento / Hospitalized patients with stress hyperglycemia: incidence of diabetes and mortality on follow-up

Introducción: El objetivo fue estimar la incidencia de diabetes y explorar la mortalidad de pacientes hospitalizados durante el seguimiento posterior al alta, clasificados durante la misma según el comportamiento glucémico como hiperglucemia de estrés (HE) o normoglucemia (NG). Material y métodos: Cohorte retrospectiva de adultos no diabéticos con HE (>140mg/dl y HbA1c<6,5%) o NG (todos los valores de glucemia <=140mg/dl). Resultados: Se identificaron 3981 pacientes con NG y 884 con HE. Durante el período de observación (mediana de seguimiento de 1,83 años), hubo un total de 255 casos de diabetes y 831 muertes. La incidencia acumulada de diabetes al año fue de 1,59% (IC95%:1,23-2,06) en NG y 7,39% (IC95% 5,70-9,56) en HE. HE se asoció significativamente con la incidencia de diabetes (HR crudo 1,33; IC95% 1,13-1,73; p 0,025), incluso después del ajuste por edad y sexo (HR ajustado 1,38; IC95% 1,06-1,78; p 0,014). La incidencia de mortalidad al año fue 10,07% (IC95%:9,18-11,05) en NG y 13,24% (IC95%:11,17-15,65) en HE. El sub hazard ratio de desarrollar diabetes considerando la muerte como evento competitivo fue 1,41 (IC95% 1,29-1,53; p<0,001). Conclusiones: La HE es un factor de riesgo para desarrollar diabetes. No hubo diferencias de mortalidad en el seguimiento, pero la muerte parece comportarse como un evento competitivo al desarrollo de diabetes en esta población

Introduction: The study objective was to estimate during post-discharge follow-up the incidence of diabetes and to ascertain mortality in hospitalized patients, classified during follow-up as having stress hyperglycemia (SH) or normoglycemia (NG) based on blood glucose levels. Material and methods: A retrospective cohort of non-diabetic adults with SH (> 140mg/dl and HbA1c <6.5%) or NG (all blood glucose values ≤ 140mg/dl) was used. Results: There were 3981 patients with NG and 884 with SH. During the observation period (median follow-up of 1.83 years), there were 255 cases of diabetes and 831 deaths. The cumulative incidence of diabetes per year was 1.59% (95% CI: 1.23-2.06) in patients with NG and 7.39% (95% CI: 5.70-9.56) in those with SH. SH was significantly associated to diabetes (crude HR 1.33, 95% CI: 1.13-1.73, p .025), even after adjusting for age and sex (adjusted HR 1.38, 95% CI 1.06-1.78, p .014). The mortality rate at one year was 10.07% (95% CI: 9.18-11.05) in NG patients and 13.24% (95% CI: 11.17-15.65) in SH patients. The sub-hazard ratio of developing diabetes considering death as a competitive event was 1.41 (95% CI 1.29-1.53, p <.001). Conclusions: SH is a risk factor for diabetes. There were no differences in mortality during follow-up, but death appears to be a competitive event in development of diabetes in this population

Immediate and late effects of chronic stress in the testes of prepubertal and adult rats / 亚洲男科学杂志(英文版)

The objective of this study was to investigate the effects of chronic stress on the testes of prepubertal and adult rats and to evaluate whether any alterations could be reversed when stress induction is ended. Seventy-six male rats were assigned to eight groups depending on the type of treatment (control or stressed), the age at which stress was initiated (prepubertal or adult), and the time of evaluation (immediate or late). Stress stimuli were applied for 6 weeks. Stressed prepubertal and adult rats evaluated immediately after the last stress stimulus were included in SP-I and SA-I groups, respectively. The late prepubertal (SP-L) and adult (SA-L) groups of stressed rats were evaluated 6 weeks after the last stress stimulus. Age-matched rats were used as controls (CP-I, CA-I, CP-L, and CA-L groups). Application of stress stimuli to rats in the SP-I group resulted in body weight and seminiferous tubule diameter reduction. The rats in the SA-I group also showed several functional (testosterone level and sperm parameter) and morphological (testicular weight and seminiferous tubule diameter) reductions. The rats in the SP-L group showed increased body weight and intertubular compartment volumetric and absolute densities and reduced tubular compartment volumetric density. The rats in the SA-L group presented only reduced sperm viability. Stress stimuli promoted changes in the rats in all the study groups. The testes of the adult rats were the most affected by chronic stress. However, the stressed adult rats recovered well from the testicular alterations.

Predicting onset and maintenance of men's eating disorders / Predictores de inicio y desarrollo de patología alimentaria en hombres

Background/Objective: Eating disorders (EDs) represent serious yet understudied mental health issues, particularly amongst young adult men attending colleges, who are at the average age of onset. Despite this and recent evidence that in young adult men the core ED symptoms are prevalent and remain relatively stable over the college period, little is known about factors associated with both the onset and maintenance of diagnosable EDs in this population. This work sought to address these research gaps. Method: Logistic regression analyses were conducted using data from an on-going longitudinal study of eating and mental health issues to examine the influence of theoretically relevant factors in predicting the onset and maintenance of men's (DSM-5) EDs at 4-year follow-up (N=2,507). Results: Body dissatisfaction, self-objectification, appearance-ideal internalization, dieting, and negative affectivity were all predictors of ED onset and maintenance. Self-objectification was the largest contributor to both ED onset and maintenance. Conclusions: The findings highlight potentially similar psychosocial foci for prevention and treatment efforts. Implications for improving existing preventive and treatment approaches are discussed (AU)

Antecedentes/Objetivo: Los trastornos de la conducta alimentaria (TCAs) representan graves, aunque poco estudiados, problemas de salud mental en las universidades, especialmente en hombres jóvenes, quienes se encuentran en la edad media de inicio. A pesar de la evidencia de que en hombres adultos jóvenes los principales síntomas de TCA son frecuentes y se mantienen relativamente estables durante el período universitario, poco se sabe sobre los factores asociados con la aparición y el mantenimiento de los TCAs en esta población. Este trabajo trata de abordar estas lagunas de investigación. Método: Se realizaron análisis de regresión logística utilizando datos de un estudio longitudinal en curso sobre alimentación y salud mental para examinar la influencia de factores teóricamente relevantes para predecir la aparición y el mantenimiento de los TCAs (DSM-5) en hombres durante 4 años de seguimiento (N=2.507). Resultados: La insatisfacción corporal, la auto-objetivación, la internalización de la apariencia ideal, las dietas, y la afectividad negativa fueron predictores de inicio y mantenimiento de TCA. La auto-objetivación fue el mayor contribuyente a la aparición y mantenimiento de TCA. Conclusiones: Los resultados destacan focos similares para su prevención y tratamiento. Se discuten las implicaciones para mejorar los enfoques preventivos y de tratamiento existentes (AU)

Evolución del estrés familiar en niños con trastorno por déficit de atención con hiperactividad / Evolution of stress in families of children with attention deficit hyperactivity disorder

Introducción: El objetivo del estudio fue analizar la evolución del estrés en las familias de niños o adolescentes que comienzan tratamiento psicofarmacológico, tras ser diagnosticados de un trastorno por déficit de atención con hiperactividad (TDAH), y la capacidad de detección de este cambio mediante el cuestionario Family Strain Index (FSI). Metodología: Cuarenta y ocho especialistas en psiquiatría infanto-juvenil o neuropediatría incluyeron 429 familias de niños diagnosticados de TDAH, representadas por el padre, la madre o el tutor del niño. En la visita basal, a los 2 y 4 meses, se evaluó la intensidad de los síntomas del TDAH mediante la escala de Conners abreviada, y el estrés familiar mediante el cuestionario FSI. Resultados: Se observó: a) mejoría en la puntuación global del FSI y en todas sus dimensiones (p<0,001); b) mejoría en la intensidad de los síntomas de hiperactividad (Conners, p<0,0001);c) una buena concordancia entre las 2 escalas, a los 2 meses (R-intraclase 0,825, p<0,0001) y a los 4 meses de seguimiento (R-intraclase 0,784, p<0,0001). El 97,9% de los niños (420) recibieron tratamiento con metilfenidato de liberación modificada. Conclusiones: Se observó una correlación significativa entre la evolución positiva de los síntomas de los niños con TDAH y la reducción del estrés familiar evaluado mediante el cuestionario FSI, tras la instauración del tratamiento psicofarmacológico. Este estudio demostró una gran sensibilidad al cambio de la situación clínica de los pacientes con TDAH evaluado a través del estrés producido sobre sus familias. Se recomienda el uso de este cuestionario como medida indirecta de la repercusión del trastorno sobre el entorno del niño con TDAH en términos de estrés familiar (AU)

Introduction. The objective of this study was to assess the evolution of stress in families of children and adolescents who start psychopharmacological treatment after being diagnosed with attention deficit hyperactivity disorder (ADHD), and the ability to detect this change using the FSI (Family Strain Index) questionnaire. Methodology: Forty eight (48) specialists in child-adolescent psychiatry or neuropediatrics included 429 families of children diagnosed with ADHD, represented by the father, mother or guardian of the child. In the baseline visit, and at two and four months, the intensity of the symptoms of ADHD was evaluated using the abbreviated Conners scale, and family stress was evaluated using the FSI questionnaire. Results: The following was observed: a) an improvement in the overall FSI score and in all its dimensions (P<.001); b) an improvement in the intensity of the symptoms of hyperactivity (Conners, P<.0001); c) good agreement between these two scales at two months (R-intraclass 0.825, P<.0001) and at four months of follow-up (R-intraclass 0.784, P<.0001). Ninety seven point nine percent (97.9%) of the children or adolescents (420) received treatment with modified-release methylphenidate. Conclusions: There was a significant relationship between the positive evolution of symptoms in children with ADHD and the reduction of family stress, as evaluated by the FSI questionnaire, after starting psychopharmacological treatment. This study showed a great sensitivity to change in the clinical situation of patients with ADHD, evaluated through the stress it produces on its families. It is recommended to use this questionnaire as an indirect measurement of the repercussions of the disorder on the environment of the child with ADHD in terms of family stress (AU)

Conocimientos sobre estrés, salud y creencias de control para la Atención Primaria de Salud / Knowledge of stress, health and control belief for primary health care

Se realizó una revisión sobre la relación del estrés, salud y creencias de control para la Atención Primaria de Salud, resaltando que el estrés es una condición que de no abordarse adecuadamente sus síntomas producen una serie de trastornos en el individuo, repercutiendo en la salud de este, pudiendo crearse diversos problemas como conflictos, insatisfacciones y dificultad en su desenvolvimiento social. Es decir, el estrés se nos presenta como un fenómeno que representa un modo particular de relación del hombre con el entorno, que tiene diferentes grados que se distinguen por la intensidad de las vivencias emocionales presentes, su carácter placentero/displacentero; la magnitud de la estimulación que el sujeto recibe de manera pasiva; o por conllevar una respuesta fisiológica, más o menos específica y que de acuerdo a las creencias de control, son los recursos internos y externos con que cuentan los sujetos para afrontarlo y que de ser adecuados atenuarían los daños a la salud. Este último aspecto nos motivó, por su gran valor, a la actualización en el tema para el equipo básico de salud, donde a partir de su comprensión permitirá el desarrollo de estrategias de intervención que logren atenuar sus efectos sobre la salud de los individuos y familia(AU)

A review was held on the relationship of stress, health and control beliefs in Primary Health Care, highlighting that stress is a condition requiring adequately addressing since its symptoms produce a series of disturbances in the individual, affecting health, creating problems such as conflicts, dissatisfaction, and difficulty in social development. This disease is presented as a phenomenon that represents a particular type of relationship between man and the environment. It has different degrees that are distinguished by the intensity of emotional experiences present, for its pleasant/unpleasant character; the magnitude of stimulation the subject passively receives; or physiological result, more or less specific answer according to the control beliefs that are both internal and external resources available individual have to cope with it. If appropriate, the harm to health lessens. This motivated updating on the theme for the basic health team to develop intervention strategies based on their understanding and to allow mitigating its effects on the health of individuals and families(AU)

Estrés y resiliencia como factores relacionados a la hipertensión arterial sistémica / Stress and resilience as factors related to hypertension

La hipertensión arterial (HTA) constituye uno de los principales factores de riesgo para el desarrollo de enfermedad cardiovascular (ECV), cada vez en aumento a nivel mundial. Su etiología incluye múltiples factores que deben ser conocidos y abordados para disminuir el impacto que esta patología genera en la sociedad. Estos factores van desde los no modificables como la carga genética, hasta aquellos relacionados con los estilos de vida; es allí donde el estrés, la reactividad aumentada al mismo y la escasa adaptación a las situaciones estresantes (conductas no resilientes) deben ser conocidas y abordadas para tratar de forma completa este padecimiento.

Hypertension is one of the most important risk factors in developing cardiovascular disease (CVD), and it continues to increase on a global level. Its ethiology includes multiple factors that should be known and addressed in order to lessen the impact that this pathology has on society. These factors go from non-modifiable like genetics to those related with lifestyle; stress, increased reactivity and poor adaptation to stressful situations (not resilient behaviors) are related to the last one and have to be known and addressed comprehensively to treat this condition.

Efectos de las experiencias adversas temprana y tardía en las características morfométricas y estereológicas de la glándula suprarrenal de ratas Sprague Dawley sometidas a estrés durante su vida adulta / Effects of early and late adverse experiences in morphometric and stereological characteristics of the adrenal gland of Sprague Dawley rats subjected to stress during adulthood

La ruptura temprana del vínculo materno y el aislamiento social son variables que están involucradas con los comportamientos social y emocional y también con el aumento de la ansiedad, especialmente en situaciones estresantes. Sin embargo, no se dispone de investigaciones que expliquen los cambios morfológicos de la glándula suprarrenal (GSR). Por lo anterior, el objetivo de este trabajo fue conocer experimentalmente, a través del modelo de alteración del vínculo social temprano madre-cría y alteración del vínculo social tardío por aislamiento, el efecto sobre las características morfométricas y estereológicas de la GSR, en ratas de la cepa Sprague Dawley sometidas a estrés crónico intermitente en la vida adulta. Utilizamos 35 ratas hembras recién nacidas, distribuidas en grupos de 7, en condiciones de lactancia y alimentación estandarizadas. Los grupos experimentales fueron expuestos a experiencias adversas temprana (E1), tardía (E2), temprana-tardía (E3) y posteriormente, sometidas a estrés crónico intermitente en la adultez. Se aisló la GSR izquierda de cada animal determinando características morfométricas y parámetros estereológicos. El peso absoluto fue mayor en los grupos control C2 y grupo experimental (E1). El número de células por mm3, el porcentaje de tejido glandular y la densidad de superficie en la zona fascicular de la GSR fue menor en el grupo E3. Las características estereológicas de la GRS en ratas, no sólo pueden ser afectadas por la exposición al estrés en la adultez, sino que también las experiencias adversas temprana y/o tardía juegan un rol importante en los cambios de los parámetros morfológicos cuantitativos observados en esta glándula.

The early break in maternal bonding and social isolation are variables involved with social and emotional behaviors and also with increased anxiety, especially in stressful situations. However, there is no research to explain the morphological changes of the adrenal gland (GSR). Therefore, our objective was to experimentally study through alteration model of social ties and early mother-cub bond alteration belated social isolation, the effect on the morphometric and stereological characteristics of the GSR in rats of the Sprague Dawley subjected to intermittent chronic stress in adulthood. We used 35 newborn female rats, divided into groups of 7 under lactating and standardized feeding conditions. The experimental groups were exposed to adverse experiences early (E1), late (E2), and early/late (E3) and subsequently, subject to intermittent chronic stress in adulthood. Left GSR was isolated from each animal determining morphometric characteristics and stereological parameters. The absolute weight was higher in control group C2 and the experimental group E1. In the group E3 number of cells per mm3, the percentage of glandular tissue and density of the surface in the fascicular area of the GSR was lower. Stereological characteristics of the GRS in rats, not only can be affected by exposure to stress in adulthood, but also early and / or late adverse experiences play an important role in the changes of quantitative morphological parameters observed in this gland.

Relógio circadiano em eucariotos fotossintetizantes (Archaeplastida) e adaptação ao estresse / Circadian clock in photosynthetic eukaryotes (Archaeplastida) and stress adaptation

Relógios endógenos controlam grande parte de processos biológicos através de osciladores bioquímicos que coordenam a sinalização de pistas ambientais até vias metabólicas, permitindo a percepção do tempo e adaptação a mudanças rítmicas. Comportamentos cíclicos diários foram primordialmente descritos em plantas e, mais recentemente, têm fornecido informações valiosas sobre os ciclos de retroalimentação da transcrição e tradução de genes que controlam estes osciladores. O florescimento é um exemplo bem conhecido da importância da percepção do comprimento do dia através do relógio, processo intimamente regulado por fotorreceptores e pelos genes centrais e periféricos do relógio biológico. Em organismos multicelulares há uma combinação específica de genes mais expressa em cada tecido, podendo ter funções, fases e períodos diferentes, o que aumenta a complexidade desse mecanismo. Devido a isso, tem-se buscado modelos alternativos mais simples dentro dos eucariotos fotossintetizantes relacionados às plantas terrestres. Modelos simplificados facilitam, por exemplo, a avaliação da combinação de fatores que induzem o estresse e como o relógio biológico se altera, permitindo a antecipação de mudanças ambientais e sincronização da fisiologia com o meio ambiente. Neste trabalho, verificou-se como o relógio circadiano se ajusta ao estresse em 3 diferentes modelos: Gracilaria tenuistipitata (Rhodophyta), Ostreococcus tauri (Chlorophyta) e Saccharum sp (Embryophyta). Para isso, estabeleceu-se em G. tenuistipitata métodos para avaliação de crescimento e da fluorescência da clorofila de modo automático, comprovando da existência de ritmos circadianos. Além disso, após padronização de genes de referência para normalização das RT-qPCRs, o gene TRX ficou superexpresso durante a primeira hora após o déficit hídrico. Já em O. tauri, onde os genes centrais do relógio são conhecidos, mudanças na expressão de LOV-HK e TOC1 estão relacionadas com maior crescimento em baixa e alta temperatura, respectivamente. Uma combinação específica de luz, temperatura e salinidade pode ser um importante indutor de eflorescências que reflete mudanças transcricionais no oscilador central, o que pode ser comparado às florescências de plantas terrestres. Já em Saccharum sp tolerante à seca, ritmos de fotossíntese e de expressão de CCA1 sofrem mudanças de fase em suas oscilações e transcritos de HVA-22 e DRP são significativamente mais expressos sob dessecação. Em suma, o estresse em Saccharum sp reseta o relógio, aumentando o período de oscilação da fotossíntese. Em O. tauri induz maior crescimento, mantendo as características do relógio. Não foi possível avaliar o efeito do estresse no relógio de G. tenuistipitata, mas ferramentas foram desenvolvidas visando este objetivo. Estudos de respostas do relógio podem fornecer informações valiosas para o entendimento da reprodução e crescimento de organismos com elevado potencial de aplicações biotecnológicas

Endogenous clocks control a large range of biological processes through biochemical oscillators that coordinate the signaling of environmental cues to metabolic pathways, allowing the perception of time and adjust to rhythmic changes. Cyclical daily behaviors were first noticed in plants and, more recently, revealed information about the transcriptional-translational feedback loops of genes that control these oscillators. Flowering is a well-known process where the perception of day length by the clock is intimately regulated by photoreceptors and by the central and peripheric genes of the biological clock. Multicellular organisms have a tissue-specific combination of expressed clock genes that may have different phase and period, increasing the complexity of this mechanism. Due to this reason, alternative models have been proposed for land plants-related photosynthetic eukaryotes. New models can simplify, for example, which combination of factors induce stress and how the biological clock is altered, allowing the anticipation of environmental changes and synchronization of physiology and environmental factors. This work aimed to verify how the biological clock adjusts to different kinds of stresses in 3 species: Gracilaria tenuistipitata (Rhodophyta), Ostreococcus tauri (Chlorophyta) and Saccharum sp (Embryophyta). Automated measurement techniques for growth rate and photosynthesis were stablished for the red alga. This alga also showed, after establishment of reference genes for RT-qPCRs normalization, an overexpression of TRX during the first hour under water deficit. In O. tauri, where the central clock genes are known, changes in LOV-HK and TOC1 gene expression are related to a higher growth rate under low and high temperatures, respectively. Besides, a specific combination of light, temperature and salinity can be an important trigger of seasonal blooms that causes important transcriptional changes at the central oscillator, what is similar to land plants. In Saccharum sp tolerant to drought, photosynthesis rhythms and CCA1 expression change their phase under simulated water deficit and drought responsive transcripts like HVA-22 and DRP are significantly up-regulated. In short, stress resets the clock in Saccharum sp, increasing the period of photosynthesis oscillation. In O.tauri, it induces a higher growth, keeping clock features. It was not possible to verify clock responses to stress in G.tenuistipitata, but methods to do so were stablished. The biological clock responses to stress can provide invaluable information for the better understanding about the growth and reproduction of organisms with a high biotechnological potential

Abfracciones: lesiones cervicales no cariosas en cuña, su relación con el estrés / Abfractions: non-carious cervical in wedge, its relationship with stress

La abfracción es una lesión por pérdida del tejido duro en la unión amelo cementaría del diente en vestibular o lingual, acompañada generalmente de sensibilidad. El estrés emocional, la acción de fuerzas excéntricas generadas por interferencias oclusales, el bruxismo, pueden ser considerados factores predisponentes; por ello se planteó un estudio observacional descriptivo con componente analítico, el objetivo fue determinar la prevalencia de abfracciones, para luego asociarlas con el estrés emocional en 110 pacientes de 15 a 59 años en edad en la Facultad de Odontología de la Universidad Nacional de Asunción y una clínica privada en el año 2008. Para determinar el nivel de estrés emocional se utilizó un cuestionario, Maslach Burnout Inventory, valorado en una escala de alto/moderado, leve y bajo, se utilizó la inspección clínica y el sondeo para diagnosticar la abfracción. Se encontró una prevalencia de abfracción de 44%, de los cuales el 49% correspondió al sexo masculino. El diente más afectado fue el primer premolar inferior izquierdo (9,9%). El 100% de los pacientes presentaban estrés y hubo asociación estadísticamente significativa entre la abfracción y el bruxismo 0,004 p<0,005(F), también con el estado civil de los pacientes 0,001 p<0,005(F) entre los que prevalecían los casados 59%. Un alto porcentaje de pacientes presentaban abfracciones y estrés, pero no hubo asociación estadísticamente significativa p=0,3(F).

Abfraction is a lesion due to hard tissue loss at the cementoenamel junction either on buccal or lingual surface of a tooth, generally accompanied by sensitivity. Emotional estrés, eccentric forces generated by occlusal interferences, bruxism can be considered as predisposing factors, therefore an observational descriptive study with an analytic component was set out in order to determine the prevalence of abfractions and to relate them to emotional estrés in 110 patients ages 15 - 59 at the Facultad de Odontología de la Universidad Nacional de Asunción as well as at a private clinic in 2008. In order to determine emotional estrés, a questionnaire by Maslach Burnout Inventory was used, ranging from high, moderate, mild and low. Clinical checkup and probing were the means to diagnose abfraction. A prevalence of 44% was found, 49% of which were males. The most affected tooth was lower left first premolar (9.9%). 100% presented estrés and there was statistically significant relationship between abfraction and bruxism 0,004 p<0,005(F), also regarding marital status, there was more prevalence among married patients (59%). A high percentage of patients presented both abfraction and estrés, but there was no statistically significant association p=0,3(F).

Sentimentos vivenciados por mulheres infectadas pelo hpv ao saberem do diagnóstico da doença / Feelings of women infected by hpv after receiving the diagnosis / Sentimientos vividos por mujeres infectadas por el vph al saber del diagnóstico de la enfermedad

O Papilomavírus humano (HPV) é um vírus sexualmente transmissível com potencialidade carcinogênica para acérvice uterina, o que torna a infecção de mulheres pelo HPV um problema de Saúde Pública. Neste estudoutilizou-se a abordagem qualitativa segundo o referencial da Fenomenologia existencial de Martin Heidegger,com o objetivo de apreender os sentimentos vivenciados por mulheres infectadas pelo HPV ao saberem dodiagnóstico da doença. Os sujeitos foram 14 mulheres que tinham recebido o diagnóstico de HPV. A questãonorteadora foi: Como é para você estar com HPV? Conte-me a sua experiência desde que soube do diagnósticoaté hoje. Os sentimentos desvelados pelas mulheres infectadas foram: sofrimento, desespero, frustração, culpa,preocupação, vergonha e medo. O desvelamento destes sentimentos possibilitou uma melhor compreensão doprocesso vivenciado por estas mulheres ao receberem o diagnóstico da doença e o significado que permeia avivência de estar com o HPV. Mostrou-se a necessidade de que os profissionais da área da saúde avancem noque se refere ao cuidado com as mulheres infectadas pelo HPV, superando o trabalho restrito à racionalidade das ciências biomédicas. É preciso ser-com-o-outro e redescobrir a profundidade do ser em sua vida cotidiana, para assim intervir com qualidade nas ações de saúde.

The human papillomavirus (HPV) is a virus, transmitted through sexual contact, with potential to becomecarcinogenic for the uterine cervix, making the infected women a problem for the public health. This research hada qualitative focus, with reference to the Existential phenomenology by Martin Heidegger, with the intention ofunderstanding the feelings of women infected by HPV, after getting the positive test results. Were subjected tothis research 14 women HPV positive. We based our research on these questions: What does HPV positive meanfor you? Tell me the experience that you had since you knew you were infected until today. The feelings mentioned by the women were: suffering, desperation, frustration, guilt, preoccupation, embarrassment and fear. Knowing these feelings made possible to better understand the process that these infected women went throughafter the diagnosis, and the meaning of what is to live with HPV. The results showed that health professionalsshould make some improvements as for the care to women infected by HPV, going beyond the services restrictedto the rationality of biomedical sciences. It showed to be necessary be-with-the-other and rediscover the depth ofthe human beings role in their daily life, in order to intervene with quality in health care.

El Virus del Papiloma humano (VPH) es un virus sexualmente transmisible con potencialidad cancerígena para elcérvix uterino, que hace de la infección femenina para el VPH un problema de la salud pública. En este estudiose utilizó el abordaje cualitativo según el referencial de la Fenomenología existencial de Martin Heidegger, con elobjetivo de aprehender los sentimientos vividos por mujeres infectadas por el VPH al saber del diagnóstico de laenfermedad. Los sujetos fueron catorce mujeres que habían recibido el diagnóstico de VPH. La preguntaorientadora fue: ¿Cómo es para usted estar con VPH? Cuénteme su experiencia desde que supo del diagnóstico hasta hoy. Los sentimientos revelados por las mujeres infectadas fueron: sufrimiento, desesperación, frustración, culpa, preocupación, vergüenza y miedo. El descubrimiento de estos sentimientos posibilitó una mejor comprensión del proceso vivido por estas mujeres después de recibir el diagnóstico de la enfermedad y elsignificado que sobreviene la vivencia de estar con el VPH. Se mostró la necesidad de que los profesionales delárea de la salud avancen en lo que se refiere al cuidado con las mujeres infectadas por el VPH, sobrepasando eltrabajo restricto a la racionalidad de las ciencias biomédicas. Es necesario ser-con-el-otro y redescubrir laprofundidad del ser en su vida cotidiana, para así intervenir con calidad en las acciones de salud.

Discusión del trabajo. "Nuestra profesión vital, de Fred Busch / No disponible

No disponible

La "Escala de estrés percibido": estudio psicométrico sin restricciones en población no clínica y adictos a sustancias en tratamiento / The Perceived Stress Scale: an unrestricted approach to its psychometric properties in non-clinical population and treated substance-addicts

La "Escala de estrés percibido" (EEP) es uno de los autoinformes más utilizados en la actualidad para estimar el grado en que las personas sienten que controlan las circunstancias de la vida o se ven desbordadas por ellas. Se realizó un análisis factorial exploratorio sin restricciones sobre una muestra de participantes de población general (n= 1023) y un análisis confirmatorio en una muestra clínica de personas con adicción a drogas en tratamiento (n= 542). De las tres versiones de la EEP (14, 10 y 4 ítems), la de 10 ítems es la que presenta mejores propiedades psicométricas en ambas muestras. Los sujetos clínicos mostraron mayores niveles de estrés percibido, asociados con estrategias de afrontamiento pasivas (evitación) y con más sintomatología comportamental de origen prefrontal en la vida cotidiana. La EEP-10 presenta suficientes garantías psicométricas para su utilización tanto en población general como aplicada a muestras clínicas, permitiendo estimar una variable crucial en el estudio de aspectos relacionados con el estrés, como la disfunción prefrontal y las estrategias que se utilizan ante dificultades de la vida

The Perceived Stress Scale (PSS) is currently one of the most used selfreports to estimate the extent to which people feel that they control the challenges of life or are overwhelmed by them. An unrestricted exploratory factor analysis over a sample of participants from the general population (n= 1023) and a confirmatory analysis in a clinical sample of drug addicts in treatment (n= 542) were performed. From the three versions (14, 10 and 4 items), the results suggest that the 10-item version is the one has better psychometric fit indicators in both samples. Addicted people showed higher levels of perceived stress in all age groups, which was associated with passive coping strategies (avoidance) and higher levels of prefrontal behavioral symptoms in everyday life. In conclusion, the 10-item version of the PSS presents enough psychometric properties for its use in estimating the perceived stress, applied both to general population and clinical samples. Its use allows to estimate a crucial variable in the study of stress-related conditions such as prefrontal dysfunction and strategies that the people used to cope with the difficulties of life

Proyecto ES3: intentando la cuantificación y medida del nivel de estrés / Project ES3: attempting to quantify and measure the level of stress

Introducción. La Organización Mundial de la Salud ha calificado al estrés de ‘epidemia mundial’, debido a su cada vez mayor incidencia en la salud. El trabajo que se presenta en este artículo representa un intento de cuantificar objetivamente el nivel de estrés. Objetivo. La metodología desarrollada tiene como objetivo medir cuán lejos o cuán cerca se encuentra un sujeto de una situación considerada médica y socialmente como ‘normal’. Sujetos y métodos. Se ha realizado un estudio bibliográfico de la fisiopatología del estrés y sus métodos de estudio, en experimentación animal y en humanos. Se han puesto en marcha nueve estudios prospectivos observacionales con distintas tipologías de sujetos y estresores que cubren las diferentes tipologías de estrés. Resultados. Como resultado del estudio bibliográfico, se han identificado las distintas tipologías de estrés, los indicadores que describen resultados significativos, los tests psicométricos y los ‘agentes estresantes’ bien documentados. Este material ha permitido diseñar la metodología general y el detalle de los nueve ensayos clínicos. Los resultados preliminares obtenidos en algunos de los estudios han servido para validar los indicadores, así como la eficacia de las técnicas utilizadas experimentalmente para disminuir el estrés o para producirlo. Conclusiones. Los resultados preliminares obtenidos en los ensayos experimentales muestran que se está en el camino correcto hacia la definición y validación de marcadores multivariable para la cuantificación de los niveles de estrés, y sugieren que la metodología puede ser aplicada de forma similar al estudio de trastornos mentales (AU)

Introduction. The WHO has qualified stress as a ‘world epidemic’ due to its increasingly greater incidence on health. The work described in this paper represents an attempt to objectively quantify the level of stress. Aim. The aim of the method developed here is to measure how close or how far a subject is from a situation that can be considered ‘normal’ in medical and social terms. Subjects and methods. The literature on the pathophysiology of stress and its methods of study in experiments on both animals and humans was reviewed. Nine prospective observational studies were undertaken with different types of subjects and stressors covering the different types of stress. Results. The results of the literature review made it possible to identify the different types of stress, the indicators that yield significant results, the psychometric tests and the well-documented ‘stressors’. This material was then used to design the general method and the details of the nine clinical trials. The preliminary results obtained in some of the studies were used to validate the indicators as well as the efficacy of the techniques used experimentally to diminish stress or to produce it. Conclusions. The early results obtained in the experimental trials show that we are on the right path towards defining and validating multivariable markers for quantifying levels of stress and also suggest that the method can be applied in a similar way to the study of mental disorders (AU)

Trabalho, adoecimento e histórias de vida em trabalhadoras da indústria calçadista / Work, sickness and life histories of workers in the shoe industry

Os portadores de Lesões por Esforços Repetitivos (LER/DORT), além das queixas de dores osteomusculares, manifestam sofrimento psíquico relacionado ao adoecimento. Nesta investigação, buscou-se, por meio do método das Histórias de Vida, compreender como se constituíram as relações sociais de trabalho e os processos de adoecimento de trabalhadoras portadoras de LER/DORT, oriundas da indústria calçadista do Rio Grande do Sul, atendidas no Ambulatório de Doenças do Trabalho do Hospital de Clínicas de Porto Alegre. Realizaram-se entrevistas individuais abertas, que foram transcritas e analisadas. As recorrências e as singularidades presentes nos depoimentos originaram cinco categorias temáticas: trabalho infantil; baixa escolaridade e início da trajetória de trabalho na indústria calçadista; relação de prazer e sofrimento com o trabalho; marcas do trabalho no corpo; e afastamento do trabalho e sofrimento. As histórias destas trabalhadoras apontaram para as vivências de culpa, fracasso e exclusão, por não mais poderem desempenhar o que lhes é socialmente esperado: o trabalho.

The bearers of Lesions for Repetitive Efforts (LER/DORT), besides the complaints of musculoskeletal pains, they manifest psychic suffering related to the illness. In this investigation, it was looked for, through the methodology of the Histories of Life, to understand as the social relationships were constituted, of work and the processes of ilness of workers bearers of LER/DORT, originating from of the shoes industry of Rio Grande do Sul, assisted at the Hospital de Clínicas de Porto Alegre. They took place open individual interviews that were transcribed and analyzed. The appeals and the present singularities in the depositions originated five thematic categories: child work; low education and beginning in the shoes industry; pleasure relationship and suffering with the work; marks of the work in the body and removal of the work and suffering. These workers' histories appeared for the fault existences, failure and exclusion for no more work.