Attitudes of Employees in Unaccompanied Children's Shelters and Work-Related Stress During the COVID-19 Pandemic.

Data related to the stress of employees in shelters for unaccompanied minors are scarce, especially when considering the escalation of the refugee issue. This study analyzed aspects of this issue as it was carried out in child protection organizations in Greece, which is a country where a huge number of immigrants and refugees pass through and thousands of professionals are employed in this field.More specifically, the aim of this study was to examine the stress (general, perceived, work-related) and burnout symptoms of a specific group of employees exposed to the COVID-19 quarantine restrictions, employees at the 'front line' of care in shelters that host unaccompanied minors and teenagers.The study was carried out from March 2020 to December 2021, when social restrictions and other preventive measures were imposed. The study sample was recruited from non-governmental organizations and shelters for unaccompanied minors, in the urban area of the center of Athens, i.e. the International Organization for Migration, The Home Project, Arsis, Iliachtida, and Zeuxis. The sample consisted of employees at the 'front line' of care in shelters that hosted unaccompanied minors and teenagers. Participants were professionals whose duty was to deal with and respond to the needs of children and adolescents within the shelters they lived in. Participants completed the following questionaires before and after the pandemic restrictions: the Job Stress Measure (JSM), the Maslach Burnout Inventory (MBI), the Perceived Stress Scale (PSS), the Stress in General Scale (SiGS) and a questionnaire of 11-items regarding COVID-19, focusing on the professionals' perceived stress, working conditions, working demands and the impact of COVID-19 on all the aforementioned.The study sample consisted of 50 employees (40 females, 10 males; mean age ± SD 31.46 ± 7.91 years) in hostels for unaccompanied minors. A statistically significant difference was found only in SiGS, with increased stress after COVID-19 (p = 0.001). In terms of sex, significant differences were found at baseline in PSS and Emotional Exhaustion (p = 0.036 and p = 0.028, respectively) (females revealed higher levels than males). Age and educational level were factors that interacted with the increased levels in SiGS after COVID-19 (p = 0.015 and p = 0.006, respectively). Moreover, significant differences were found at baseline in PSS (p = 0.004), with higher levels observed in employees with higher education. Workers who did not work remotely had lower levels in Personal Accomplishment after COVID-19 compared to employees who worked remotely (p = 0.050). Interestingly, the JSM showed a tendency for decreased stress levels after the implementation of the quarantine, suggesting that the employees' work-related stress remained approximately at the same levels. On the other hand, perceived stress increased as the job demands remained the same, while social and personal outlet was in appeasement.The necessity for more research to be held among health professionals is evident and is also imperative to carry out interventional studies to manage stress and thus, provide better mental health services to unaccompanied minors. There is also need for further research in similar populations of professionals outside the urban context of Athens, i.e. in the Greek islands near the sea borders, where the refugees' entries are higher in number and more frequent.

Perceived Changes in Emotions, Worries and Everyday Behaviors in Children and Adolescents Aged 5-18 Years with Type 1 Diabetes during the COVID-19 Pandemic.

The COVID-19 pandemic and the consequent restrictive measures may be related to increased stress and anxiety and to changes in daily behaviors. Children with type 1 diabetes (T1D) are a vulnerable group due to their difficulties in achieving glycemic control and to their medical and psychological comorbidities. The purpose of the current study was to the investigate the changes on emotional and behavioral parameters in children with T1D due to the Coronavirus crisis. A total of 152 children and adolescents, aged 5−18, were studied: 114 (62 boys) with T1D and 38 (19 boys) healthy volunteers (HV) (controls). The study was performed at the Diabetes Center, Aghia Sofia Children's Hospital, during the first national lockdown in Greece. The CRISIS questionnaire was completed by parents/caregivers. The data were collected in May 2020 and referred to two time-points: three months prior (before the pandemic), and the past two weeks. During the lockdown, it was observed significant aggravation in the "Emotion/Worries (EW)" symptoms in both groups (logEW-before vs. logEW-during the crisis, T1D: 2.66 ± 0.23 vs. 3.00 ± 0.21, p < 0.001 and HV: 2.62 ± 0.16 vs. 2.83 ± 0.18, p < 0.001). Deterioration of "ΕW" was recorded for 93.0% of those with T1D and 92.1% of the HV. "EW" during the lockdown were affected by: previous psychological condition, COVID-related concerns, and "Life Changes due to the COVID-19 crisis in the past two weeks (LC)". Deterioration was observed in the "daily behaviors" and "use of digital media" for all of the children. The crisis and the associated restrictions negatively affected both the lifestyle parameters and the behavioral and emotional variables of the children with T1D.

Dream Recall/Affect and the Hypothalamic-Pituitary-Adrenal Axis.

In this concise review, we present an overview of research on dream recall/affect and of the hypothalamic-pituitary-adrenal (HPA) axis, discussing caveats regarding the action of hormones of the HPA axis (mainly cortisol and its free form, cortisol-binding globulin and glucocorticoid receptors). We present results of studies regarding dream recall/affect and the HPA axis under physiological (such as waking) or pathological conditions (such as in Cushing's syndrome or stressful situations). Finally, we try to integrate the effect of the current COVID-19 situation with dream recall/affect vis-à-vis the HPA axis.

Preterm Birth as a Risk Factor for Metabolic Syndrome and Cardiovascular Disease in Adult Life: A Systematic Review and Meta-Analysis.

OBJECTIVE: To determine if preterm birth is associated with components of the metabolic syndrome in adult life. STUDY DESIGN: A structured literature search was performed using PubMed. All comparative studies reported metabolic and cardiovascular outcomes in adults (≥18 years of age) born preterm (<37 weeks of gestation) compared with adults born at term (37-42 weeks of gestation) and published through March 2018 were included. The major outcomes assessed were body mass index, waist circumference, waist-to-hip ratio, fat mass, systolic blood pressure (SBP), diastolic blood pressure (DBP), 24-hour SBP, 24-hour DBP, endothelium-dependent brachial artery flow-mediated dilation, carotid intima-media thickness, pulse wave velocity, fasting glucose and insulin, Homeostasis Model Assessment-Estimated Insulin Resistance Index, and lipid profiles. Quality appraisal was performed using a modified version of the Newcastle-Ottawa scale. A meta-analysis was performed for comparable studies which reported sufficient data. RESULTS: Forty-three studies were included, including a combined total of 18 295 preterm and 294 063 term-born adults. Prematurity was associated with significantly higher fat mass (P = .03), SBP (P < .0001), DBP (P < .0001), 24-hour SBP (P < .001), and 24-hour DBP (P < .001). Furthermore, preterm-born adults presented higher values of fasting glucose (P = .01), insulin (P = .002), Homeostasis Model Assessment-Estimated Insulin Resistance Index (P = .05), and total cholesterol levels (P = .05) in comparison with adults born at term, in random effect models. No statistically significant difference was found between preterm and term-born adults for the other outcomes studied. CONCLUSIONS: Preterm birth is strongly associated with a number of components of the metabolic syndrome and cardiovascular disease in adult life.

Psychological vulnerability to stress in carriers of congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

OBJECTIVE: Carriers of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) demonstrate increased secretion of cortisol precursors following ACTH stimulation, suggestive of impaired cortisol production and compensatory increases in hypothalamic corticotropin-releasing hormone (CRH) secretion. Both cortisol and CRH have behavioral effects, and hypothalamic CRH hypersecretion has been associated with chronic states of anxiety and depression. We performed an endocrinologic and psychological evaluation in carriers of 21-OHD and matched control subjects. DESIGN: We recruited 29 parents of children with classic CAH (14 males, 15 females; age (mean±SD): 41.8±5.7 yr), and hence 21-OHD carriers, and 13 normal subjects (5 males, 8 females; age: 43.8±6.1 yr). All subjects underwent a formal ovine (o) CRH stimulation test with measurement of ACTH, cortisol, 17-hydroxyprogesterone (17-OHP) and androstenedione concentrations, which was preceded by determination of 24-hour urinary free cortisol (UFC) excretion. Psychometric assessment was performed by administering the State-Anxiety (STAI 1) and Trait-Anxiety (STAI 2) Inventory, Beck Depression Inventory, Symptom Checklist-90R and Temperament and Character Inventory. RESULTS: Carriers of 21-OHD had significantly higher 17-OHP concentrations following oCRH stimulation and higher STAI 1 (47.6±5.6 vs. 43.3±5.4, P=0.023) scores than control subjects. Mean 24-hour UFC concentrations were positively correlated with paranoid ideation (r=0.435; P=0.023) and psychoticism (r=0.454; P=0.017). Stepwise multiple linear regression analysis revealed that the single independent predictor of STAI 1 was peak stimulated 17-OHP concentrations (ß: 0.055, SE: 0.023, R2: 0.290, P=0.031). CONCLUSIONS: Carriers of 21-OHD may be predisposed to the development of anxiety disorders.

Milestones in CRH Research.

The Corticotropin-releasing Hormone (CRH) mammalian family members include CRH, urocortin I, Stresscopin (SCP) and Stresscopin-related peptide (SRP), along with the CRH receptors type 1 (CRHR1) and type 2 (CRHR2), and CRH-binding protein (CRH-BP). These family members differ in their tissue distribution and pharmacology. Several studies have provided evidence supporting an important role of this family in the regulation of the neuroendocrine and behavioral responses to stress. Regulation of the relative contribution of CRH and its homologs and the two CRH receptors in brain CRH pathways may be essential in coordinating physiologic responses to stress. The development of disorders related to heightened stress sensitivity and dysregulation of stress-coping mechanisms appears to involve regulatory mechanisms of the CRH family members. Therapeutic agents that target CRH family members may offer a new approach to the treatment of these disorders. The purpose of this review is to summarize the most significant discoveries related to CRH over time.

Laparoscopic vs. open abdominal surgery in male pigs: marked differences in cortisol and catecholamine response depending on the size of surgical incision.

OBJECTIVE: Minimally invasive operations, such as laparoscopic cholecystectomy and adrenalectomy, result in a more rapid recovery of normal function, less physiological disturbances and less stress to the organism than similar open operations. The purpose of this study was to determine the stress response associated with minimally invasive abdominal surgery compared to conventional small or large incision laparotomy. METHODS: We compared the responses of the stress hormones cortisol and the catecholamines adrenaline and noradrenaline to elective conventional and laparoscopic cholecystectomy and unilateral adrenalectomy in male pigs. Blood samples were taken from all animals at the same time, one day before surgery, at the beginning of the operation, every 15 minutes during surgery and on the first postoperative morning. RESULTS: Plasma adrenaline and noradrenaline concentrations were significantly lower in both cholecystectomies (p<0.05) and adrenalectomies (p<0.01) during laparoscopic than during open surgery. Plasma cortisol levels were significantly lower in laparoscopic than in open adrenalectomies both during surgery and on postoperative day one (p<0.05), while no major differences in cortisol levels were observed between laparoscopic and open cholecystectomies. Thus, the stress-related benefit of laparoscopic surgery depended on the size of the surgical incision in the conventional operation. CONCLUSION: Laparoscopic surgery was associated with less surgical stress than open surgery and this difference was accentuated as the surgical abdominal wall trauma increased.

Prednisolone exerts late mitogenic and biphasic effects on resistant acute lymphoblastic leukemia cells: Relation to early gene expression.

Resistance or sensitivity to glucocorticoids is considered to be of crucial importance for disease prognosis in childhood acute lymphoblastic leukemia. Prednisolone exerted a delayed biphasic effect on the resistant CCRF-CEM leukemic cell line, necrotic at low doses and apoptotic at higher doses. At low doses, prednisolone exerted a pre-dominant mitogenic effect despite its induction on total cell death, while at higher doses, prednisolone's mitogenic and cell death effects were counterbalanced. Early gene microarray analysis revealed notable differences in 40 genes. The mitogenic/biphasic effects of prednisolone are of clinical importance in the case of resistant leukemic cells. This approach might lead to the identification of gene candidates for future molecular drug targets in combination therapy with glucocorticoids, along with early markers for glucocorticoid resistance.

Reproductive corticotropin releasing hormone, implantation, and fetal immunotolerance.

The fundamental process of implantation involves a series of steps leading to effective cross-talk between invasive trophoblast cells and the maternal endometrium. The molecular interactions at the embryo-maternal interface during the time of blastocyst adhesion and subsequent invasion are not fully understood. Embryonic trophoblast and maternal decidual cells produce corticotropin-releasing hormone (CRH) and express Fas ligand (FasL), a proapoptotic cytokine. Fas and its ligand are pivotal in the regulation of immune tolerance. Trophoblast and decidual CRH play crucial roles in implantation, as well as in the anti-rejection process that protects the fetus from the maternal immune system, primarily by killing activated T cells through Fas-FasL interaction. The potential use of CRH antagonists is presently under intense investigation. CRH antagonists have been used experimentally to elucidate the role of CRH in blastocyst implantation and invasion, early fetal immunotolerance, and premature labor.

Peripheral corticotropin-releasing hormone is produced in the immune and reproductive systems: actions, potential roles and clinical implications.

Corticotropin-releasing hormone (CRH), the principal regulator of the hypothalamic-pituitary-adrenal axis, has been identified in various organ systems, including the immune and the female and male reproductive systems. CRH-like immunoreactivity has been reported in peripheral inflammatory sites and in a number of reproductive organs, including the ovaries, endometrial glands, decidualized endometrial stroma, placenta, decidua, and the testes. Therefore, "immune" and "reproductive" CRH are forms of "tissue" CRH; i.e., CRH found in peripheral tissues. Immune CRH plays a direct immunomodulatory role as an autocrine/paracrine mediator of inflammation. Immune CRH participates in several experimental inflammations and, in humans, in inflamed tissues from patients with autoimmune and inflammatory diseases. One of the early effects of immune CRH is the degranulation of mast cells and the release of histamine and several inflammatory cytokines. Reproductive CRH is regulating reproductive functions with an inflammatory component, such as ovulation, luteolysis, decidualization, implantation, and early maternal tolerance. Placental CRH participates in the physiology of pregnancy and the onset of labor. Circulating placental CRH is responsible for the physiologic hypercortisolism of the latter half of pregnancy. Postpartum, this hypercortisolism is followed by a transient adrenal suppression, which may explain the blues/depression and increased autoimmune phenomena observed during this period.

Intracrine modulation of gene expression by intracellular generation of active glucocorticoids.

Glucocorticoids (GC) by either up-regulating or down-regulating the expression of genes influence cellular processes in every tissue and organ of the body. The enzyme 11beta-hydroxysteroid dehydrogenase Type-1 (11beta-HSD-1) confers bioactivity upon the inactive GC cortisone (E) and prednisone (P) by converting them to cortisol (F) and prednisolone (L), respectively. We sought to investigate whether gene expression modulation by GC is under the regulation of an intracrine mechanism that determines the intracellular concentration of active GC. Human cell lines were transiently and stably co-transfected with an expression construct for 11beta-HSD-1 and a GC-responsive reporter gene and incubated with active and inactive GC. Whereas in cells that were not transfected with the expression construct for 11beta-HSD-1 inactive GC had no transcriptional activity, in both transiently and stably transfected cells E and P demonstrated a dose-dependent transcriptional activity. This transcriptional potency of both inactive GC was effectively abolished by carbenoxolone, an 11beta-HSD-1 inhibitor, and was directly related to the concentration of transfected 11beta-HSD-1. We conclude that gene expression modulation by GC is under a decisive influence of target cell 11beta-HSD-1 that modulates the intracellular concentration of active GC. The intracrine mechanism is an under-appreciated aspect of GC activity that could be a potential target for future therapies aimed at modulating GC effects at the cellular level.

Morphological and binding properties of interleukin-6 on thin ZnO films grown on (100) silicon substrates for biosensor applications.

To develop effective protein immobilization technology with minimal amounts of protein for high sensitivity surface acoustic wave biosensors, we determined the binding properties, and morphological characteristics of human interleukin-6 (IL-6), a pro-inflammatory cytokine, on the surface of ZnO, and SiO(2) films grown onto (100) Si substrates, for the first time. Interleukin-6 was immobilized in the range of 0.276-10 pg/ml on the surface of ZnO and SiO(2), and visualized at each stage, while protein-protein interactions were measured with the antigen/antibody immunoassay of solid-phase ELISA, which we modified for these types of substrates. A relative mass value was determined in each case. ELISA detected upward of 1 and 6 ng/ml of protein applied on ZnO and SiO(2), respectively. It is concluded that the more reactive ZnO surface is a new and more effective template for protein immobilization.

The human glucocorticoid receptor (GR) isoform {beta} differentially suppresses GR{alpha}-induced transactivation stimulated by synthetic glucocorticoids.

The beta-isoform of human glucocorticoid receptor beta (hGRbeta) acts as a natural dominant negative inhibitor of hGRalpha-induced transactivation of glucocorticoid-responsive genes. We determined hGRbeta ability to suppress hGRalpha transactivation that was induced by commonly used synthetic glucocorticoids. HepG2/C3A cells were transiently cotransfected with GR cDNA and a glucocorticoid-responsive promoter, luciferase (MMTV-luc). Transfected cells were incubated for 16 h with glucocorticoid and luciferase. For each compound, a dose-response curve was constructed, and half-maximal effective concentrations and maximal transcriptional activities were compared. hGRbeta, at a 1:1 ratio to hGRalpha, differentially suppressed hGRalpha-induced maximal transcriptional activity stimulated by triamcinolone, dexamethasone, hydrocortisone, and betamethasone (by 96, 68, 62, and 49%, respectively) but not by methylprednisolone. The suppressive effect of hGRbeta on hGRalpha-induced transactivation was stronger at lower concentrations of all tested glucocorticoids, whereas it was blunted at higher concentrations. We conclude that the potency of the dominant negative effect of hGRbeta on hGRalpha-induced transactivation depends on both the type and the dose of the synthetic glucocorticoids in use. These results may provide helpful information concerning the selection of synthetic glucocorticoids for treatment of pathological conditions in which hGRbeta modulates the sensitivity of tissues to glucocorticoids.

Reproductive functions of corticotropin-releasing hormone. Research and potential clinical utility of antalarmins (CRH receptor type 1 antagonists).

BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis exerts a complex, mostly inhibitory, effect on the female reproductive system. In addition, the principal regulator of this axis, the hypothalamic neuropeptide corticotropin-releasing hormone (CRH) and its receptors have been identified in most female reproductive tissues, including the ovary, uterus, and placenta. Furthermore, CRH is secreted in peripheral inflammatory sites where it exerts strong inflammatory actions. Antalarmins (CRH receptor type 1 antagonists) have been used to elucidate the roles of CRH in stress, inflammation and reproduction. METHOD OF STUDY: We review existing data on the effects of CRH in the female reproductive system. RESULTS: Ovarian CRH participates in female sex steroid production, follicular maturation, ovulation and luteolysis. Uterine CRH participates in decidualization, implantation, and early maternal tolerance. Placental CRH participates in the physiology of pregnancy and the onset of parturition. Circulating placental CRH is secreted mostly during the latter half of pregnancy and is responsible for the concurrently increasing physiologic hypercortisolism of this period. After labor and delivery, this hypercortisolism is ensued by a transient suppression of hypothalamic CRH secretion, which may explain the postpartum blues and depression and the increased autoimmune manifestations depression of period, the postpartum period. CONCLUSIONS: These data show that CRH is present in female reproductive tissues, and is regulating key reproductive functions with an inflammatory component, such as ovulation, luteolysis, implantation, and parturition.

Uterine and embryonic trophoblast CRH promotes implantation and maintenance of early pregnancy.

Epithelial cells of human endometrium and differentiated endometrial stromal cells express the corticotropin-releasing hormone (CRH) gene. CRH is also produced by the human placental cytotrophoblast. Endometrial and placental CRH is under the endocrine control of gonadal steroids as well as under an autocrine/paracrine regulation by prostanoids and interleukins. Human endometrium, myometrium and placenta also express the relevant receptors. Invasive trophoblasts promote apoptosis of activated Fas-expressing human T lymphocytes, an effect potentiated by CRH and inhibited by the CRH type 1 antagonist, antalarmin. Female rats treated with antalarmin during the first 6 days of gestation had a dose-dependent decrease of implantation sites and live embryos, and significantly decreased endometrial FasL expression. Our data suggest important physiological roles of endometrial and placental CRH in the regulation of decidualization, blastocyst implantation, and early maternal tolerance.

Modulation of 11 beta-hydroxysteroid dehydrogenase type 1 in mature human subcutaneous adipocytes by hypothalamic messengers.

Glucocorticoids are regulated at the prereceptor level by 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), which interconverts inactive cortisone and active cortisol. In a previous study, we noted that patients with hypothalamic obesity had an increased ratio of cortisol/cortisone metabolites, suggesting enhanced 11 beta-HSD-1 activity. In this in vitro study, we tested the hypothesis that adipose 11 beta-HSD-1 is regulated by the hypothalamus via circulating hormones, sympathetic nervous system innervation, and/or cytokines. Preadipocytes were retrieved from sc fat from healthy nonobese individuals and differentiated in vitro to mature adipocytes. Cells were incubated with several potential effectors, and the activity of 11 beta-HSD-1 was assayed by measuring conversion of added 500 nM cortisone to cortisol. Expression of 11 beta-HSD-1 mRNA was determined by real-time PCR, whereas lipolytic effects were determined by measuring glycerol concentration in the culture medium. CRH down-regulated 11 beta-HSD-1 activity with maximal effect at 10(-9)M (65 +/- 10% of control; P < 0.001) and caused a reduction in lipolysis. Likewise, ACTH down-regulated 11 beta-HSD-1 activity with maximal effect at 10(-9) M (65 +/- 20%; P < 0.05) and reduced medium glycerol. Neither CRH nor ACTH affected 11 beta-HSD-1 mRNA expression. TNF alpha up-regulated 11 beta-HSD-1 activity maximally at 0.6 x 10(-9) M (140 +/- 20%; P < 0.001); the same cytokine increased 11 beta-HSD-1 mRNA levels to 3-fold of control (P < 0.05) and increased medium glycerol levels to 165 +/- 14% of control (P < 0.01). IL-1 beta also up-regulated 11 beta-HSD-1 activity maximally at 0.6 x 10(-9) M (160 +/- 33%; P < 0.001) and caused an increase in glycerol levels (159 +/- 11% of control; P < 0.001). Of the adrenergic agonists, salbutamol up-regulated 11 beta-HSD-1 activity maximally at 10(-7) M (162 +/- 46%; P < 0.02), and clonidine down-regulated it at 10(-7) M (82 +/- 15%; P < 0.005). We conclude that possible distinct hypothalamic mediators regulating adipose tissue 11 beta-HSD-1 might include down-regulation of 11 beta-HSD-1 activity by CRH, ACTH, and alpha 2 sympathetic stimulation, and up-regulation of the enzyme by beta 2 sympathetic stimulation and by the cytokines TNFalpha and IL-1 beta.