Prenatal stress increases the obesogenic effects of a high-fat-sucrose diet in adult rats in a sex-specific manner

Stress during pregnancy can induce metabolic disorders in adult offspring. To analyze the possible differential response to a high-fat-sucrose (HFS) diet in offspring affected by prenatal stress (PNS) or not, pregnant Wistar rats (n = 11) were exposed to a chronic mild stress during the third week of gestation. The aim of this study was to model a chronic depressive-like state that develops over time in response to exposure of rats to a series of mild and unpredictable stressors. Control dams (n = 11) remained undisturbed. Adult offspring were fed chow or HFS diet (20% protein, 35% carbohydrate, 45% fat) for 10 weeks. Changes in adiposity, biochemical profile, and retroperitoneal adipose tissue gene expression by real-time polymerase chain reaction were analyzed. An interaction was observed between HFS and PNS concerning visceral adiposity, with higher fat mass in HFS-fed stressed rats, statistically significant only in females. HFS modified lipid profile and increased insulin resistance biomarkers, while PNS reduced insulin concentrations and the homeostasis model assessment index. HFS diet increased gene (mRNA) expression for leptin and apelin and decreased cyclin-dependent kinase inhibitor 1A and fatty acid synthase (Fasn), whereas PNS increased Fasn and stearoyl-CoA desaturase1. An interaction between diet and PNS was observed for adiponutrin (Adpn) and peroxisome proliferator-activated receptor-gamma coactivator1-alpha (Ppargc1a) gene expression: Adpn was increased by the PNS only in HFS-fed rats, whereas Ppargc1a was increased by the PNS only in chow-fed rats. From these results, it can be concluded that experience of maternal stress during intrauterine development can enhance predisposition to obesity induced by a HFS diet intak

Methyl donor supplementation in rats reverses the deleterious effect of maternal separation on depression-like behaviour

Adverse early life events are associated with altered stress responsiveness and metabolic disturbances in the adult life. Dietary methyl donor supplementation could be able to reverse the negative effects of maternal separation by affecting DNA methylation in the brain. In this study, maternal separation during lactation reduced body weight gain in the female adult offspring without affecting food intake, and altered total and HDL-cholesterol levels. Also, maternal separation induced a cognitive deficit as measured by NORT and an increase in the immobility time in the Porsolt forced swimming test, consistent with increased depression-like behaviour. An 18-week dietary supplementation with methyl donors (choline, betaine, folate and vitamin B12) from postnatal day 60 also reduced body weight without affecting food intake. Some of the deleterious effects induced by maternal separation, such as the abnormal levels of total and HDL-cholesterol, but especially the depression-like behaviour as measured by the Porsolt test, were reversed by methyl donor supplementation. Also, the administration of methyl donors increased total DNA methylation (measured by immunohistochemistry) and affected the expression of insulin receptor in the hippocampus of the adult offspring. However, no changes were observed in the DNA methylation status of insulin receptor and corticotropin-releasing hormone (CRH) promoter regions in the hypothalamus. In summary, methyl donor supplementation reversed some of the deleterious effects of an early life-induced model of depression in rats and altered the DNA methylation profile in the brain

Impact of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients: A nationwide study in Spain

Objective To assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain. Settings The initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied. Participants This was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020. Interventions An exploratory factorial analysis was performed to select the most relevant variables of the sample. Primary and secondary outcome measures Univariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection. Results Sixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/10 5 people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade =3 (OR 2.5) and preoperative GCS 3-8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test <72 hours preoperatively (OR 0.76), community COVID-19 incidence (cases/10 5 people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated. Conclusions Perioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/10 5 people/week) was a statistically independent predictor of mortality. Trial registration number CEIM 20/217

Efecto del estrés durante diferentes etapas del ciclo vital sobre el desarrollo de obesidad inducida por la dieta

La creciente prevalencia de la obesidad no puede ser atribuible únicamente a factores genéticos o a una mala nutrición como pueden ser las dietas altas en grasa, sino también al estilo de vida y a factores ambientales adversos. Dentro del estilo de vida, la sociedad actual se caracteriza por tener un ritmo acelerado, lo que produce una elevación de la tasa de estrés en la población. Este aumento paralelo tanto de las tasas de obesidad como del estrés, hace necesario el estudio de la interacción entre estos dos factores. Por este motivo, el objetivo general de este estudio es analizar en ratas adultas el posible efecto del estrés sufrido en diferentes etapas de la vida sobre el desarrollo de obesidad asociado a la ingesta de dietas hipercalóricas. Para alcanzar este objetivo general, se propuso inducir un estrés crónico durante la época adulta y durante dos etapas importantes en el desarrollo de las ratas (etapa prenatal y etapa postnatal) con los siguientes objetivos específicos: a) Analizar el efecto de un estrés crónico moderado en ratas adultas sobre los cambios fenotípicos, bioquímicos y hormonales, así como alteraciones en la expresión de genes relacionados con la obesidad y el metabolismo de los glucocorticoides en el tejido adiposo blanco inducidos por la ingesta de una dieta hipercalórica rica en grasa. b) Estudiar los cambios provocados por la separación materna durante la lactancia sobre los cambios fenotípicos, bioquímicos y hormonales, así como alteraciones en la expresión de genes relacionados con la obesidad y el metabolismo de los glucocorticoides en el tejido adiposo blanco inducidos por la ingesta de una dieta hipercalórica rica en grasa y azúcares en la época adulta. c) Determinar el efecto de un estrés crónico moderado durante la última semana del desarrollo embrionario en los cambios fenotípicos, bioquímicos y hormonales, así como alteraciones en la expresión de genes relacionados con la obesidad y el metabolismo de los glucocorticoides en el tejido adiposo blanco inducidos por la ingesta de una dieta hipercalórica rica en grasa y azúcares en la época adulta. d) Analizar el efecto de un estrés crónico moderado durante la última semana del desarrollo embrionario en la expresión de genes relacionados con la obesidad y el metabolismo de los glucocorticoides en el hipotálamo, así como en los cambios del patrón de metilación de los promotores de genes relacionados con la obesidad, inducidos por la ingesta de una dieta rica en grasa y azúcares en la época adulta

Efecto del estrés durante diferentes etapas del ciclo vital sobre el desarrollo de obesidad inducida por la dieta

La creciente prevalencia de la obesidad no puede ser atribuible únicamente a factores genéticos o a una mala nutrición como pueden ser las dietas altas en grasa, sino también al estilo de vida y a factores ambientales adversos. Dentro del estilo de vida, la sociedad actual se caracteriza por tener un ritmo acelerado, lo que produce una elevación de la tasa de estrés en la población. Este aumento paralelo tanto de las tasas de obesidad como del estrés, hace necesario el estudio de la interacción entre estos dos factores. Por este motivo, el objetivo general de este estudio es analizar en ratas adultas el posible efecto del estrés sufrido en diferentes etapas de la vida sobre el desarrollo de obesidad asociado a la ingesta de dietas hipercalóricas. Para alcanzar este objetivo general, se propuso inducir un estrés crónico durante la época adulta y durante dos etapas importantes en el desarrollo de las ratas (etapa prenatal y etapa postnatal) con los siguientes objetivos específicos: a) Analizar el efecto de un estrés crónico moderado en ratas adultas sobre los cambios fenotípicos, bioquímicos y hormonales, así como alteraciones en la expresión de genes relacionados con la obesidad y el metabolismo de los glucocorticoides en el tejido adiposo blanco inducidos por la ingesta de una dieta hipercalórica rica en grasa. b) Estudiar los cambios provocados por la separación materna durante la lactancia sobre los cambios fenotípicos, bioquímicos y hormonales, así como alteraciones en la expresión de genes relacionados con la obesidad y el metabolismo de los glucocorticoides en el tejido adiposo blanco inducidos por la ingesta de una dieta hipercalórica rica en grasa y azúcares en la época adulta. c) Determinar el efecto de un estrés crónico moderado durante la última semana del desarrollo embrionario en los cambios fenotípicos, bioquímicos y hormonales, así como alteraciones en la expresión de genes relacionados con la obesidad y el metabolismo de los glucocorticoides en el tejido adiposo blanco inducidos por la ingesta de una dieta hipercalórica rica en grasa y azúcares en la época adulta. d) Analizar el efecto de un estrés crónico moderado durante la última semana del desarrollo embrionario en la expresión de genes relacionados con la obesidad y el metabolismo de los glucocorticoides en el hipotálamo, así como en los cambios del patrón de metilación de los promotores de genes relacionados con la obesidad, inducidos por la ingesta de una dieta rica en grasa y azúcares en la época adulta

Postnatal maternal separation modifies the response to an obesogenic diet in adulthood in rats

An early-life adverse environment has been implicated in the susceptibility to different diseases in adulthood, such as mental disorders, diabetes and obesity. We analyzed the effects of a high-fat sucrose (HFS) diet for 35 days in adult female rats that had experienced 180 minutes daily of maternal separation (MS) during lactancy. Changes in the obesity phenotype, biochemical profile, levels of glucocorticoid metabolism biomarkers, and the expression of different obesity- and glucocorticoid-metabolism-related genes were analyzed in periovaric adipose tissue. HFS intake increased body weight, adiposity and serum leptin levels, whereas MS decreased fat pad masses but only in rats fed an HFS diet. MS reduced insulin resistance markers but only in chow-fed rats. Corticosterone and estradiol serum levels did not change in this experimental model. A multiple gene expression analysis revealed that the expression of adiponutrin (Adpn) was increased owing to MS, and an interaction between HFS diet intake and MS was observed in the mRNA levels of leptin (Lep) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (Ppargc1a). These results revealed that early-life stress affects the response to an HFS diet later in life, and that this response can lead to phenotype and transcriptomic changes

Prenatal stress increases the obesogenic effects of a high-fat-sucrose diet in adult rats in a sex-specific manner

Stress during pregnancy can induce metabolic disorders in adult offspring. To analyze the possible differential response to a high-fat-sucrose (HFS) diet in offspring affected by prenatal stress (PNS) or not, pregnant Wistar rats (n = 11) were exposed to a chronic mild stress during the third week of gestation. The aim of this study was to model a chronic depressive-like state that develops over time in response to exposure of rats to a series of mild and unpredictable stressors. Control dams (n = 11) remained undisturbed. Adult offspring were fed chow or HFS diet (20% protein, 35% carbohydrate, 45% fat) for 10 weeks. Changes in adiposity, biochemical profile, and retroperitoneal adipose tissue gene expression by real-time polymerase chain reaction were analyzed. An interaction was observed between HFS and PNS concerning visceral adiposity, with higher fat mass in HFS-fed stressed rats, statistically significant only in females. HFS modified lipid profile and increased insulin resistance biomarkers, while PNS reduced insulin concentrations and the homeostasis model assessment index. HFS diet increased gene (mRNA) expression for leptin and apelin and decreased cyclin-dependent kinase inhibitor 1A and fatty acid synthase (Fasn), whereas PNS increased Fasn and stearoyl-CoA desaturase1. An interaction between diet and PNS was observed for adiponutrin (Adpn) and peroxisome proliferator-activated receptor-gamma coactivator1-alpha (Ppargc1a) gene expression: Adpn was increased by the PNS only in HFS-fed rats, whereas Ppargc1a was increased by the PNS only in chow-fed rats. From these results, it can be concluded that experience of maternal stress during intrauterine development can enhance predisposition to obesity induced by a HFS diet intak

Patients awaiting surgery for neurosurgical diseases during the first wave of the COVID-19 pandemic in Spain: a multicentre cohort study.

The large number of infected patients requiring mechanical ventilation has led to the postponement of scheduled neurosurgical procedures during the first wave of the COVID-19 pandemic. The aims of this study were to investigate the factors that influence the decision to postpone scheduled neurosurgical procedures and to evaluate the effect of the restriction in scheduled surgery adopted to deal with the first outbreak of the COVID-19 pandemic in Spain on the outcome of patients awaiting surgery. This was an observational retrospective study. A tertiary-level multicentre study of neurosurgery activity between 1 March and 30 June 2020. A total of 680 patients awaiting any scheduled neurosurgical procedure were enrolled. 470 patients (69.1%) were awaiting surgery because of spine degenerative disease, 86 patients (12.6%) due to functional disorders, 58 patients (8.5%) due to brain or spine tumours, 25 patients (3.7%) due to cerebrospinal fluid (CSF) disorders and 17 patients (2.5%) due to cerebrovascular disease. The primary outcome was mortality due to any reason and any deterioration of the specific neurosurgical condition. Second, we analysed the rate of confirmed SARS-CoV-2 infection. More than one-quarter of patients experienced clinical or radiological deterioration. The rate of worsening was higher among patients with functional (39.5%) or CSF disorders (40%). Two patients died (0.4%) during the waiting period, both because of a concurrent disease. We performed a multivariate logistic regression analysis to determine independent covariates associated with maintaining the surgical indication. We found that community SARS-CoV-2 incidence (OR=1.011, p Patients awaiting neurosurgery experienced significant collateral damage even when they were considered for scheduled procedures