Combined Effects of Early Life Stress and Prolonged Exposure to Western Diet on Emotional Responses and Gut Microbiota.

BACKGROUND: Exposure to early life stress (ELS) and maternal consumption of a high-fat and high-sugar diet can have detrimental effects on adult emotional responses. The microbiota and gut-brain axis have been proposed as playing a mediating role in the regulation of stress and emotion. METHOD: Young male rats were exposed to maternal separation (MS) together with maternal and postnatal consumption of a HFS diet (45%kcal saturated fat, 17%kcal sucrose). Anxiety-like behaviour was evaluated using an elevated zero-maze, and depression-like behaviour using the forced-swim and sucrose preference tests. Microbiota composition and derived metabolites were also analysed in faecal samples using a gas chromatograph and mass spectrometry. RESULTS: Combined exposure to MS and lifelong consumption of a HFS diet partially reversed the abnormal anxiety-like and depression-like behaviours in early adulthood caused by each adverse factor alone. Diet composition had a greater negative impact than ELS exposure on the gut microbiota, and both environmental factors interacted with microbiota composition partially counteracting their negative effects. CONCLUSIONS: The effects of exposure to early life stress and a HFS diet independently are partially reversed after the combination of both factors. These results suggest that ELS and diet interact to modulate adult stress response and gut microbiota.

A shift to a standard diet after exposure to a high-fat, high-sucrose diet from gestation to weaning restores brain metabolism and behavioral flexibility in adult rats.

Prolonged consumption of diets high in saturated fat and sugar has been related to obesity and overweight, which in turn are linked to cognitive impairment in both humans and rodents. This has become a current issue, especially in children and adolescents, because these stages are crucial to neurodevelopmental processes and programming of adult behavior. To evaluate the effects of gestational and early exposure to an obesogenic diet, three groups with different dietary patterns were established: high-fat and high-sucrose diet (HFS), standard diet (SD), and a dietary shift from a high-fat, high-sucrose diet to a standard diet after weaning (R). Spatial learning and behavioral flexibility in adult male and female Wistar rats were evaluated using the Morris water maze (MWM) at PND 60. Furthermore, regional brain oxidative metabolism was assessed in the prefrontal cortex and the hippocampus. Contrary to our hypothesis, the HFS diet groups showed similar performance on the spatial learning task as the other groups, although they showed impaired cognitive flexibility. The HFS group had increased brain metabolic capacity compared to that of animals fed the standard diet. Shifting from the HFS diet to the SD diet after weaning restored the brain metabolic capacity in both sexes to levels similar to those observed in animals fed the SD diet. In addition, animals in the R group performed similarly to those fed the SD diet in the Morris water maze in both tasks. However, dietary shift from HFS diet to standard diet after weaning had only moderate sex-dependent effects on body weight and fat distribution. In conclusion, switching from an HFS diet to a balanced diet after weaning would have beneficial effects on behavioral flexibility and brain metabolism, without significant sex differences.

Combined Effects of Early Life Stress and Prolonged Exposure to Western Diet on Emotional Responses and Gut Microbiota / Efectos Combinados del Estrés Vital Temprano y la Exposición Prolongada a la Dieta Occidental Sobre las Respuestas Emocionales y la Microbiota Intestinal

Background: Exposure to early life stress (ELS) and maternal consumption of a high-fat and high-sugar diet can have detrimental effects on adult emotional responses. The microbiota and gut-brain axis have been proposed as playing a mediating role in the regulation of stress and emotion. Method: Young male rats were exposed to maternal separation (MS) together with maternal and postnatal consumption of a HFS diet (45%kcal saturated fat, 17%kcal sucrose). Anxiety-like behaviour was evaluated using an elevated zero-maze, and depression-like behaviour using the forced-swim and sucrose preference tests. Microbiota composition and derived metabolites were also analysed in faecal samples using a gas chromatograph and mass spectrometry. Results: Combined exposure to MS and lifelong consumption of a HFS diet partially reversed the abnormal anxiety-like and depression-like behaviours in early adulthood caused by each adverse factor alone. Diet composition had a greater negative impact than ELS exposure on the gut microbiota, and both environmental factors interacted with microbiota composition partially counteracting their negative effects. Conclusions: The effects of exposure to early life stress and a HFS diet independently are partially reversed after the combination of both factors. These results suggest that ELS and diet interact to modulate adult stress response and gut microbiota.(AU)

Antecedentes: El estrés temprano (ET) y el consumo materno de una dieta alta en grasas y azúcares (HFS) pueden tener efectos perjudiciales sobre las respuestas emocionales en la adultez. La microbiota y el eje intestino-cerebro podrían mediar la regulación del estrés y las emociones. Método: Ratas macho jóvenes se expusieron a separación materna (SM) y a consumo materno y postnatal de una dieta HFS (45%kcal grasa saturada, 17%kcal sacarosa). Se evaluó el comportamiento ansioso mediante el laberinto cero elevado y el comportamiento depresivo mediante natación forzada y preferencia por sacarosa. Se analizó la microbiota en heces empleando cromatografía de gas y espectrometría de masas. Resultados: La exposición combinada a la SM y el consumo de una dieta HFS revirtió parcialmente la ansiedad y depresión en adultos causadas independientemente por cada factor adverso. La dieta influyó negativamente más que la exposición a ET en la microbiota y ambos factores modificaron su composición contrarrestando parcialmente sus efectos negativos. Conclusiones: Los efectos del ET y una dieta HFS por independiente varían con respecto a los efectos de la combinación de ambos factores, sugiriendo que el ET y la dieta interactúan modulando en el adulto la respuesta al estrés y la microbiota intestinal.(AU)

Evaluating Rural Health Disparities in Colombia: Identifying Barriers and Strategies to Advancing Refugee Health.

Health disparities within rural communities, notably those affecting migrant and refugee populations, are well-documented. Refugees often grapple with high disease burdens and mortality rates due to limited access to primary healthcare and their vulnerable socio-economic and political situations. This issue is particularly acute in the rural areas around Medellin, Colombia, where the refugee influx exacerbates the existing public health challenges. Studies highlight a substantial gap between community needs and public health policies, resulting in inadequate healthcare access. Our study, utilizing the Delphi technique, aimed to identify common barriers and strategies to enhance rural healthcare for refugees. Through consensus-building with community leaders, we identified six primary barriers to healthcare access and five barriers to healthcare quality. Community leaders endorsed five strategies to address the access barriers and eight strategies to improve healthcare quality. This research provides valuable insights for optimizing resource allocation and designing effective support programs for these vulnerable populations.

Sexual dimorphism in spatial learning and brain metabolism after exposure to a western diet and early life stress in rats.

Prolonged daily intake of Western-type diet rich in saturated fats and sugars, and exposure to early life stress have been independently linked to impaired neurodevelopment and behaviour in animal models. However, sex-specific effects of both environmental factors combined on spatial learning and memory, behavioural flexibility, and brain oxidative capacity have still not been addressed. The current study aimed to evaluate the impact of maternal and postnatal exposure to a high-fat and high-sugar diet (HFS), and exposure to early life stress by maternal separation in adult male and female Wistar rats. For this purpose, spatial learning and memory and behavioural flexibility were evaluated in the Morris water maze, and regional brain oxidative capacity and oxidative stress levels were measured in the hippocampus and medial prefrontal cortex. Spatial memory, regional brain oxidative metabolism, and levels of oxidative stress differed between females and males, suggesting sexual dimorphism in the effects of a HFS diet and early life stress. Males fed the HFS diet performed better than all other experimental groups independently of early life stress exposure. However, behavioural flexibility evaluated in the spatial reversal leaning task was impaired in males fed the HFS diet. In addition, exposure to maternal separation or the HFS diet increased the metabolic capacity of the prefrontal cortex and dorsal hippocampus in males and females. Levels of oxidative stress measured in the latter brain regions were also increased in groups fed the HFS diet, but maternal separation seemed to dampen regional brain oxidative stress levels. Therefore, these results suggest a compensatory effect resulting from the interaction between prolonged exposure to a HFS diet and early life stress.

Aproximación al coste de enfermedades profesionales atendidas en siete hospitales en España / Approximation to the cost of occupational diseases treated in seven hospitals in Spain

Objetivo: Estimar el coste hospitalario de una muestra de casos atendidos en siete hospitales del Sistema Nacional de Salud de diferentes ciudades españolas. Método: Estudio basado en 78 casos de enfermedad profesional reconocida por la Seguridad Social, atendidos en centros hospitalarios de Badalona, Barcelona, Ferrol, Gijón, Girona, Madrid y Vigo entre 2017 y 2019. Resultados: La actividad asistencial generada en estos hospitales para atender estos procesos supuso un coste total para el Sistema Nacional de Salud de 282.927 €. Conclusiones: Urge mejorar la coordinación entre los dos sistemas públicos de salud: la asistencia sanitaria de la Seguridad Social y el Sistema Nacional de Salud. (AU)

Objective: To estimate the hospital cost of a sample of cases treated in seven hospitals of the National Health System in several Spanish cities. Method: Study based on 78 cases of occupational disease recognized by the social security, and previously treated in hospitals in Badalona, Barcelona, Ferrol, Gijón, Girona, Madrid and Vigo between 2017 and 2019. Results: The healthcare activity generated by these hospitals to attend these processes involved a total cost of 282,927€. Conclusions: It is urgent to improve the coordination between the two public health systems, the social security health care system and the National Health System. (AU)

Early-life stress induces emotional and molecular alterations in female mice that are partially reversed by cannabidiol.

Gender is considered as a pivotal determinant of mental health. Indeed, several psychiatric disorders such as anxiety and depression are more common and persistent in women than in men. In the past two decades, impaired brain energy metabolism has been highlighted as a risk factor for the development of these psychiatric disorders. However, comprehensive behavioural and neurobiological studies in brain regions relevant to anxiety and depression symptomatology are scarce. In the present study, we summarize findings describing cannabidiol effects on anxiety and depression in maternally separated female mice as a well-established rodent model of early-life stress associated with many mental disorders. Our results indicate that cannabidiol could prevent anxiolytic- and depressive-related behaviour in early-life stressed female mice. Additionally, maternal separation with early weaning (MSEW) caused long-term changes in brain oxidative metabolism in both nucleus accumbens and amygdalar complex measured by cytochrome c oxidase quantitative histochemistry. However, cannabidiol treatment could not revert brain oxidative metabolism impairment. Moreover, we identified hyperphosphorylation of mTOR and ERK 1/2 proteins in the amygdala but not in the striatum, that could also reflect altered brain intracellular signalling related with to bioenergetic impairment. Altogether, our study supports the hypothesis that MSEW induces profound long-lasting molecular changes in mTOR signalling and brain energy metabolism related to depressive-like and anxiety-like behaviours in female mice, which were partially ameliorated by CBD administration.

[Approximation to the cost of occupational diseases treated in seven hospitals in Spain]. / Aproximación al coste de enfermedades profesionales atendidas en siete hospitales en España.

OBJECTIVE: To estimate the hospital cost of a sample of cases treated in seven hospitals of the National Health System in several Spanish cities. METHOD: Study based on 78 cases of occupational disease recognized by the social security, and previously treated in hospitals in Badalona, Barcelona, Ferrol, Gijón, Girona, Madrid and Vigo between 2017 and 2019. RESULTS: The healthcare activity generated by these hospitals to attend these processes involved a total cost of 282,927€. CONCLUSIONS: It is urgent to improve the coordination between the two public health systems, the social security health care system and the National Health System.

Identificación y reconocimiento de enfermedades profesionales en siete hospitales públicos de España / Identification and recognition of occupational diseases in seven public hospitals in Spain

Antecedentes: La infra-notificación y reconocimiento de enfermedad profesional (EP) es un problema secular en España y demás países europeos. El proyecto de Carga de la Enfermedad Profesional en España (CEPS) pretende contribuir a resolver este problema. Objetivo: Describir el proceso de identificación y reconocimiento de EP en siete hospitales españoles entre 2017 y 2019. Material y Métodos: En los siete hospitales que participan en el estudio se creó una unidad de patología laboral (UPL) la cual estimulaba en los servicios asistenciales la identificación de posibles EP atendidas en el hospital. Los pacientes confirmados por la UPL fueron acompañados en el proceso de reconocimiento. Resultados: En este periodo fueron derivados 308 casos, y en 154 (62%) se confirmó la sospecha EP. De éstos, 78 (65%) han sido reconocidos. La tasa de confirmación (casos confirmados/ derivados) varió según hospitales (de un 25% en el Badalona Serveis Assistencials a un 100% en el Hospital Universitario Fundación Jiménez Díaz) y grupos de diagnósticos (de un 13% para trastornos musculoesqueléticos a un 100% para patologías varias). La tasa de reconocimiento (casos confirmados/casos reconocidos) varió según centro, diagnóstico, sexo y edad, siendo más alta en mujeres, con ≥ 55 años y diagnosticados con patologías varias (oculares, infecciosas, mentales, entre otras). Conclusión: Las UPL contribuyen significativamente en el proceso de identificación y reconocimiento de EP, lo que los pacientes posiblemente no hubieran obtenido de otra forma (AU)

Background: Under-reporting and recognition of occupational disease (OD) is a secular problem in Spain and other European countries. The burden of occupational disease in Spain project (CEPS) aims to contribute. Objective: To describe the process of identification and recognition of OD in seven Spanish between 2017 and 2020. Material and Methods: In the seven hospitals that participate in the study an occupational pathology unit (OPU) was created. The OPU encouraged the healthcare services to identify possible OD treated in the hospital. The patients confirmed by the OPU were accompanied in the recognition process. Results: 308 cases were referred in this period and 154 OD was confirmed (62%). Of these, 78 have been recognized (65%). The confirmation rate (confirmed/ referred cases) varied according to hospitals (from 25% at the Badalona Serveis Assistencials to 100% at the Hospital Universitario Fundación Jiménez Díaz) and diagnosis groups (from 13% for musculoskeletal disorders to 100% for various pathologies). The recognition rate (confirmed/ recognized cases) varied according to hospitals, diagnosis, sex and age, being higher in women, aged ≥ 55 years and diagnosed with various pathologies (ocular, infectious, mental, among others). Conclusion: OPU contribute significantly in the process of identification and recognition of OD, which the patients might not have obtained otherwise (AU)

Versatility of Protocols for Resistance Training and Assessment using Static and Dynamic Ladders in Animal Models.

Resistance training is a physical exercise model with profound benefits for health throughout life. The use of resistance exercise animal models is a way to gain insight into the underlying molecular mechanisms that orchestrate these adaptations. The aim of this article is to describe exercise models and training protocols designed for strength training and evaluation of resistance in animal models and provide examples. In this article, strength training and resistance evaluation are based on ladder climbing activity, using static and dynamic ladders. These devices allow a variety of training models as well as provide precise control of the main variables which determine resistance exercise: volume, load, velocity, and frequency. Furthermore, unlike resistance exercise in humans, this is a forced exercise. Thus, aversive stimuli must be avoided in this intervention to preserve animal welfare. Prior to implementation, a detailed design is necessary, along with an acclimatization and learning period. Acclimatization to training devices, such as ladders, weights, and clinical tape, as well as to the manipulations required, is necessary to avoid exercise rejection and to minimize stress. At the same time, the animals are taught to climb up the ladder, not down, to the resting area on the top of the ladder. Resistance evaluation can characterize physical strength and permit adjusting and quantifying the training load and the response to training. Furthermore, different types of strength can be evaluated. Regarding training programs, with appropriate design and device use, they can be sufficiently versatile to modulate different types of strength. Furthermore, they should be flexible enough to be modified depending on the adaptive and behavioral response of the animals or the presence of injuries. In conclusion, resistance training and assessment using ladders and weights are versatile methods in animal research.

Western Diet: Implications for Brain Function and Behavior.

The Western diet (WD) pattern characterized by high daily intake of saturated fats and refined carbohydrates often leads to obesity and overweight, and it has been linked to cognitive impairment and emotional disorders in both animal models and humans. This dietary pattern alters the composition of gut microbiota, influencing brain function by different mechanisms involving the gut-brain axis. In addition, long-term exposure to highly palatable foods typical of WD could induce addictive-like eating behaviors and hypothalamic-pituitary-adrenal (HPA) axis dysregulation associated with chronic stress, anxiety, and depression. In turn, chronic stress modulates eating behavior, and it could have detrimental effects on different brain regions such as the hippocampus, hypothalamus, amygdala, and several cortical regions. Moreover, obesity and overweight induce neuroinflammation, causing neuronal dysfunction. In this review, we summarize the current scientific evidence about the mechanisms and factors relating WD consumption with altered brain function and behavior. Possible therapeutic interventions and limitations are also discussed, aiming to tackle and prevent this current pandemic.

Sex-Specific Effects of Early Life Stress on Brain Mitochondrial Function, Monoamine Levels and Neuroinflammation.

Sex differences have been reported in the susceptibility to early life stress and its neurobiological correlates in humans and experimental animals. However, most of the current research with animal models of early stress has been performed mainly in males. In the present study, prolonged maternal separation (MS) paradigm was applied as an animal model to resemble the effects of adverse early experiences in male and female rats. Regional brain mitochondrial function, monoaminergic activity, and neuroinflammation were evaluated as adults. Mitochondrial energy metabolism was greatly decreased in MS females as compared with MS males in the prefrontal cortex, dorsal hippocampus, and the nucleus accumbens shell. In addition, MS males had lower serotonin levels and increased serotonin turnover in the prefrontal cortex and the hippocampus. However, MS females showed increased dopamine turnover in the prefrontal cortex and increased norepinephrine turnover in the striatum, but decreased dopamine turnover in the hippocampus. Sex differences were also found for pro-inflammatory cytokine levels, with increased levels of TNF-α and IL-6 in the prefrontal cortex and hippocampus of MS males, and increased IL-6 levels in the striatum of MS females. These results evidence the complex sex- and brain region-specific long-term consequences of early life stress.