Publications

Pharmacologic doses of glucocorticoids are administered to patients with adrenal insufficiency during operative procedures to prevent hemodynamic instability, cardiovascular collapse, and death. Since these supraphysiologic doses might not be necessary and might have adverse effects, we examined the effects of different doses of glucocorticoids on hemodynamic adaptation during surgical stress in adrenalectomized primates. Sham-adrenalectomized placebo-treated animals served as controls. Adrenalectomized monkeys were maintained for 4 mo on physiologic glucocorticoid and mineralocorticoid replacement. The adrenalectomized monkeys were then stratified into three groups receiving, respectively, subphysiological (one-tenth the normal cortisol production rate), physiological, or supraphysiological (10 times the normal cortisol production rate) cortisol (hydrocortisone) treatment. 4 d later a cholecystectomy was performed. The intraoperative hemodynamic and metabolic parameters, perioperative survival rates, and postoperative wound healing were compared. The subphysiologically treated group was hemodynamically unstable before, during, and after surgery and had a significantly higher mortality rate than control. In this group, arterial blood pressure was low, and the cardiac index, systemic vascular resistance index, and left ventricular stroke work index were all reduced, suggesting decreased cardiac contractility and blood vessel tone. In contrast, the physiologically replaced group was indistinguishable from either supraphysiologically treated animals or sham-operated controls. All groups had similar metabolic profiles and normal wound healing. These findings suggest that the permissive actions of physiologic glucocorticoid replacement are both necessary and sufficient for primates to tolerate surgical stress. Supraphysiological glucocorticoid treatment has no apparent advantage during this form of stress in the primate.

Child and adolescent obesity constitute one of the greatest contemporary public health menaces. The enduring disproportion between calorie intake and energy consumption, determined by a complex interaction of genetic, epigenetic, and environmental factors, finally leads to the development of overweight and obesity. Child and adolescent overweight/obesity promotes smoldering systemic inflammation (“para-inflammation”) and increases the likelihood of later metabolic and cardiovascular complications, including metabolic syndrome and its components, which progressively deteriorate during adulthood. Exosomes are endosome-derived extracellular vesicles that are secreted by a variety of cells, are naturally taken-up by target cells, and may be involved in many physiological and pathological processes. Over the last decade, intensive research has been conducted regarding the special role of exosomes and the non-coding (nc) RNAs they contain (primarily micro (mi) RNAs, long (l) non-coding RNAs, messenger (m) RNAs and other molecules) in inter-cellular communications. Through their action as communication mediators, exosomes may contribute to the pathogenesis of obesity and associated disorders. There is increasing evidence that exosomal miRNAs and lncRNAs are involved in pivotal processes of adipocyte biology and that, possibly, play important roles in gene regulation linked to human obesity. This review aims to improve our understanding of the roles of exosomes and their cargo in the development of obesity and related metabolic and inflammatory disorders. We examined their potential roles in adipose tissue physiology and reviewed the scarce data regarding the altered patterns of circulating miRNAs and lncRNAs observed in obese children and adolescents, compared them to the equivalent, more abundant existing findings of adult studies, and speculated on their proposed mechanisms of action. Exosomal miRNAs and lncRNAs could be applied as cardiometabolic risk biomarkers, useful in the early diagnosis and prevention of obesity. Furthermore, the targeting of crucial circulating exosomal cargo to tissues involved in the pathogenesis and maintenance of obesity could provide a novel therapeutic approach to this devastating and management-resistant pandemic.

Classic congenital adrenal hyperplasia (CAH) is associated with impaired function of the adrenal cortex and medulla leading to decreased production of cortisol and epinephrine. As a result, the normal exercise-induced rise in blood glucose is markedly blunted in such individuals. We examined whether an extra dose of hydrocortisone, similar to that given during other forms of physical stress such as intercurrent illness, would normalize blood glucose levels during exercise in patients with CAH. We studied hormonal, metabolic, and cardiorespiratory parameters in response to a standardized high-intensity exercise protocol in nine adolescent patients with classic CAH. Patients were assigned to receive either an additional morning dose of hydrocortisone or placebo, in addition to their usual glucocorticoid and mineralocorticoid replacement in a randomized, double-blind, crossover design 1 h before exercising. Although plasma cortisol levels approximately doubled after administration of the additional hydrocortisone dose compared with the usual single dose, fasting and exercise-induced blood glucose levels did not differ. In addition, no differences were observed in the serum concentrations of the glucose-modulating hormones epinephrine, insulin, glucagon, and GH and of the metabolic parameters lactate and free fatty acids. Although maximal heart rate was slightly higher after stress dosing (193 +/- 3 vs. 191 +/- 3 beats/min, mean +/- sem, P < 0.05), this did not affect exercise performance or perceived exertion. We conclude that patients with classic CAH do not benefit from additional hydrocortisone during short-term, high-intensity exercise. Although this has not been tested with long-term exercise, a high degree of caution should be used when considering the frequent use of additional hydrocortisone administration with exercise, given the adverse side effects of glucocorticoid excess.

Seismic fragility curves provide the probability of exceedance of a given damage state, should different levels of ground motion intensity be experienced at the site where the structure, or component, is located. Such curves are often derived via multiple nonlinear response history analyses (NLRHA) using sets of “suitable” ground motions that, in line with the best practice, should be consistent with the seismic hazard at the site. Based on the selected sets of records, one can estimate fragility functions that are often assumed to follow a lognormal distribution defined by two parameters, i.e., the logarithmic mean (µ) and the logarithmic standard deviation (β). Our focus is on estimating them using a state-of-the-art approach that involves hazard-consistent record selection via Conditional Spectrum and multiple stripe analysis. However, this approach usually requires many NLRHAs, with high computational costs, especially for the complex structural models typical of the nuclear industry. This study investigates the optimal number of ground motions and intensity levels required to keep the computational burden acceptable without compromising accuracy. To do so, we adopt a Bayesian framework with Markov chain Monte Carlo simulation and Metropolis–Hasting sampling. Our findings show that this approach effectively helps analysts best allocate computational resources while ensuring acceptable accuracy in estimating the probability of reaching or exceeding the considered damage states.

Abstract Mental disorders are strongly connected with several psychiatric conditions including depression, bipolar disorder, schizophrenia, eating disorder and suicides. There are many biological conditions and pathways that define these complicated illnesses. For example, eating disorders are complex mental health conditions that require the intervention of geneticists, psychiatrists and medical experts in order to alleviate their symptoms. A patient with suicidal ideation should first be identified and consequently monitored by a similar team of specialists. Both genetics and epigenetics can shed light on eating disorders and suicides as they are found in the main core of such investigations. In the present study, an analysis has been performed on two specific members of the GPCR family towards drawing conclusions regarding their functionality and implementation in mental disorders. Specifically, evolutionary and structural studies on the adrenoceptor alpha 2b (ADRA2B) and the 5-hydroxytryptamine receptor 1A (HTR1A) have been carried out. Both receptors are classified in the biogenic amine receptors sub-cluster of the GPCRs and have been connected in many studies with mental diseases and malnutrition conditions. The major goal of this study is the investigation of conserved motifs among biogenic amine receptors that play an important role in this family signaling pathway, through an updated evolutionary analysis and the correlation of this information with the structural features of the HTR1A and ADRA2B. Furthermore, structural comparison of ADRA2B, HTR1A, and other members of GPCRs related with mental disorders is performed.

The objective of this study was to determine whether measurements of human CRH in the inferior petrosal sinuses could distinguish patients with Cushing's syndrome from those with pseudo-Cushing states or normal physiology. Twenty-five patients with Cushing's disease, 17 patients with the syndrome of ectopic ACTH, 7 patients with Cushing's syndrome of adrenal origin, 6 patients with pseudo-Cushing states, and 11 volunteers believed to have normal hypothalamic-pituitary-adrenal axes were studied. Basal plasma human CRH and ACTH were measured at two time points in the petrosal sinuses and in a peripheral vein. Most subjects were studied after the administration of intravenous diazepam or midazolam and fentanyl, but because of the known inhibitory effects of such sedation on CRH secretion, 2 normal volunteers and 3 patients with pseudo-Cushing states were studied without sedation. Human CRH levels were near or below the detection limit of the assay in all subjects. Although the normal volunteers and patients with pseudo-Cushing states who were studied without sedation had significantly greater inferior petrosal sinus ACTH levels than those who received sedation, there were no differences in measured human CRH levels for any of the groups. We conclude that inferior petrosal sinus human CRH levels are not easily measured in the inferior petrosal sinuses and cannot be used to determine whether individual patients may have hypersecretion of CRH causing their ACTH secretion.

Emotional eating is the tendency to regulate negative emotions (such as stress, depression and anxiety) through increased or unhealthy food intake. Emotion management, such as stress management could be an appropriate approach to prevent or control maladaptive eating behavior among children.This is a controlled pragmatic trial, testing the effects of Pythagorean Self Awareness Intervention (PSAI), a cognitive stress management program in a primary school setting. The eligibility criterion was being a 4th grade active pupil. Participants were randomly assigned to either the intervention group (n = 23) or the control group (n = 22). Self-report measures were used for the evaluation of various variables at the beginning and the end of the 8-week monitoring period. Descriptive and inferential statistic methods were used for the statistical analysis.At the end of the 8-week period pupils in the intervention group experienced statistically significant reduction in stress (SIC, p < 0.001), anxiety (STAIC-trait anxiety, p = 0.019, STAIC-state anxiety, p = 0.006), guilt (p < 0.001) and emotional eating (EES-C, p < 0.001) and an increase in Mediterranean diet quality (KIDMED, p = 0.001) and pride (p < 0.001). No statistically significant differences between the two groups were recorded regarding depression symptoms (CDI, p = 0.551) and shame (p = 0.120).PSAI had positive effects on a sample of primary school attendants' emotional eating and psychological state.

Abstract Background Stress is defined as a state of threatened or perceived as threatened homeostasis. A broad spectrum of extrinsic or intrinsic, real or perceived stressful stimuli, called ‘stressors’, activates a highly conserved system, the ‘stress system’, which adjusts homeostasis through central and peripheral neuroendocrine responses. Inadequate, excessive or prolonged adaptive responses to stress may underlie the pathogenesis of several disease states prevalent in modern societies. The development and severity of these conditions primarily depend on the genetic vulnerability of the individual, the exposure to adverse environmental factors and the timing of the stressful event(s), given that prenatal life, infancy, childhood and adolescence are critical periods characterized by increased vulnerability to stressors. Materials and methods We conducted a systematic review of original articles and reviews published in MEDLINE from 1975 through June 2016. The search terms were ‘childhood stress’, ‘pediatric stress’, ‘stress and disorders’ and ‘stress management’. Results In this review, we discuss the historical and neuroendocrine aspects of stress, and we present representative examples of paediatric stress system disorders, such as early‐life adversity, obesity and bullying. We also discuss the adverse impact of a socio‐economic crisis on childhood health. The tremendous progress of epigenetics has enabled us to have a deeper understanding of the molecular mechanisms underlying paediatric stress‐related disorders. Conclusions The need for early successful stress management techniques to decrease the incidence of paediatric stress‐related diseases, as well as to prevent the development of several pathologic conditions in adolescence and adulthood, is imperative.