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1.
Hormones (Athens) ; 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38311659

ABSTRACT

Premature ovarian failure (POF) defines the occurrence of ovarian failure prior to the age of 40. It occurs in one out of 100 women but is very rare before age 20 (1:10,000). Maturity-onset diabetes of the young (MODY), caused by mutations in the HNF1A gene, is also a rare disorder; all types of MODY account for 1-2% of adult diabetic cases. These two rare nosologic entities coexisted in an adolescent girl evaluated for delayed puberty. Although this combination could represent a chance association, an interrelation might exist. We examined HNF1A expression in human fetal and adult ovaries by immunohistochemistry using a polyclonal HNF1A antibody. HNF1A protein was expressed in both the fetal and adult human ovaries. Based on these findings, we hypothesize that HNF1A participates in ovarian organogenesis and/or function and that mutations in the HNF1A gene might represent another molecular defect causing POF, possibly in combination with other genetic factors. The study underlines the importance of rare clinical paradigms in leading the way to elucidation of the pathogenetic mechanisms of rare diseases.

2.
Neuroimage ; 236: 118011, 2021 08 01.
Article in English | MEDLINE | ID: mdl-33852941

ABSTRACT

The hippocampus is a highly plastic brain structure supporting functions central to human cognition. Morphological changes in the hippocampus have been implicated in development, aging, as well as in a broad range of neurological and psychiatric disorders. A growing body of research suggests that hippocampal plasticity is closely linked to the actions of brain-derived neurotrophic factor (BDNF). However, evidence on the relationship between hippocampal volume (HCV) and peripheral BDNF levels is scarce and limited to elderly and patient populations. Further, despite evidence that BDNF expression differs throughout the hippocampus and is implicated in adult neurogenesis specifically in the dentate gyrus, no study has so far related peripheral BDNF levels to the volumes of individual hippocampal subfields. Besides its clinical implications, BDNF-facilitated hippocampal plasticity plays an important role in regulating cognitive and affective processes. In the current registered report, we investigated how serum BDNF (sBDNF) levels relate to volumes of the hippocampal formation and its subfields in a large sample of healthy adults (N = 279, 160 f) with a broad age range (20-55 years, mean 40.5) recruited in the context of the ReSource Project. We related HCV to basal sBDNF and, in a subsample (n = 103, 57 f), to acute stress-reactive change in sBDNF. We further tested the role of age as a moderator of both associations. Contrary to our hypotheses, neither basal sBDNF levels nor stress-reactive sBDNF change were associated with total HCV or volume of the dentate gyrus/cornu ammonis 4 (DG/CA4) subfield. We also found no evidence for a moderating effect of age on any of these associations. Our null results provide a first point of reference on the relationship between sBDNF and HCV in healthy mid-age, in contrast to patient or aging populations. We suggest that sBDNF levels have limited predictive value for morphological differences of the hippocampal structure when notable challenge to its neuronal integrity or to neurotrophic capacity is absent.


Subject(s)
Brain-Derived Neurotrophic Factor/blood , Hippocampus/anatomy & histology , Adult , Dentate Gyrus/anatomy & histology , Dentate Gyrus/diagnostic imaging , Female , Hippocampus/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Young Adult
3.
Neuropsychopharmacology ; 44(10): 1797-1804, 2019 09.
Article in English | MEDLINE | ID: mdl-30991416

ABSTRACT

Brain-derived neurotrophic factor (BDNF) is an essential facilitator of neuronal plasticity. By counteracting the adverse effects of excessive stress-induced glucocorticoid signaling, BDNF has been implicated as a resilience factor to psychopathology caused by chronic stress. Insights into the effects of acute stress on peripheral BDNF levels in humans are inconclusive. The short-term interplay between BDNF and cortisol in response to acute psychosocial stress remains unexplored. Furthermore, it is unknown whether mental training that is effective at reducing cortisol reactivity can also influence BDNF during acute stress. In the current study, we investigated serum BDNF levels during an acute psychosocial stress paradigm, the Trier Social Stress Test (TSST), in 301 healthy participants (178 women, mean age = 40.65) recruited as part of the ReSource Project, a large-scale mental training study consisting of three distinct 3-month training modules. Using a cross-sectional study design, we first examined the relationship between BDNF and salivary cortisol in a control group with no mental training. Subsequent analyses focused on differences in BDNF stress levels between control and mental training groups. We show that serum BDNF is indeed stress-sensitive, characterized by a significant post-stress increase and subsequent decline to recovery. While respective increases in BDNF and cortisol were not associated, we found two indications for an antagonistic relationship. Higher BDNF peaks after stress were associated with steeper cortisol recovery. On the other hand, the magnitude of the cortisol stress response was linked to steeper BDNF recovery after stress. BDNF levels were not modulated by any of the mental training modules. Providing novel evidence for the dynamics of BDNF and cortisol during acute stress, our findings may further inform research on the physiological mechanisms involved in stress chronification and the associated health risks.


Subject(s)
Affect , Attention , Brain-Derived Neurotrophic Factor/metabolism , Hydrocortisone/metabolism , Metacognition , Social Behavior , Stress, Psychological/metabolism , Adult , Cross-Sectional Studies , Empathy , Female , Humans , Interoception , Male , Meditation , Middle Aged , Mindfulness , Motivation , Saliva/chemistry , Stress, Psychological/psychology , Young Adult
4.
BJOG ; 126(8): 984-995, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30786138

ABSTRACT

OBJECTIVE: To assess the separate and combined associations of maternal pre-pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact. DESIGN: Individual participant data meta-analysis of 39 cohorts. SETTING: Europe, North America, and Oceania. POPULATION: 265 270 births. METHODS: Information on maternal pre-pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used. MAIN OUTCOME MEASURES: Gestational hypertension, pre-eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth. RESULTS: Higher maternal pre-pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31- 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain. CONCLUSIONS: Maternal pre-pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre-pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity. TWEETABLE ABSTRACT: Promoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.


Subject(s)
Body Mass Index , Gestational Weight Gain/physiology , Overweight/complications , Pregnancy Complications/etiology , Adult , Australia/epidemiology , Birth Weight , Cohort Studies , Europe/epidemiology , Female , Gestational Age , Humans , Infant, Newborn , North America/epidemiology , Odds Ratio , Pregnancy , Pregnancy Complications/epidemiology , Risk Factors
6.
Eur J Nutr ; 57(3): 1147-1155, 2018 Apr.
Article in English | MEDLINE | ID: mdl-28349252

ABSTRACT

PURPOSE: The aim of the present study was to report for the first time the prevalence of hypertension and its phenotypes in obese children and in children with central obesity in a large sample of Greek children. METHODS: A regionally representative sample of 2263 schoolchildren (50.3% boys) (9-13 years) having full data on blood pressure assessment, physical examination, anthropometric, and physical activity participated in a cross-sectional study in Greece. RESULTS: Prevalence of stage 1 and 2 hypertension, of isolated systolic hypertension (ISH) and of combined systolic or diastolic hypertension, was significantly higher for obese children and children on the 3rd tertile of waist circumference in the total sample, as well as in each gender separately. ISH was the most prevalent phenotype reaching 24.3% in obese children and 17.5% in children on the highest tertile of waist circumference. Obese children and children on the highest tertile of waist circumference had 6.31 times and 3.94 times, respectively, higher likelihood to have abnormal systolic or diastolic blood pressure (SBP or DBP) than their normal-weight counterparts. CONCLUSIONS: Prevalence of hypertension and especially ISH in obese children and in children with central obesity in Greece are among the highest reported in Europe. Future public health initiatives should aim to prevent or tackle several underlying factors related to childhood hypertension, focusing primarily on children with excess body weight.


Subject(s)
Child Nutritional Physiological Phenomena , Hypertension/etiology , Obesity, Abdominal/physiopathology , Overweight/physiopathology , Pediatric Obesity/physiopathology , Prehypertension/etiology , Adolescent , Adolescent Nutritional Physiological Phenomena , Body Mass Index , Child , Cross-Sectional Studies , Female , Greece/epidemiology , Humans , Hypertension/diagnosis , Hypertension/epidemiology , Hypertension/physiopathology , Male , Mass Screening , Prehypertension/diagnosis , Prehypertension/epidemiology , Prehypertension/physiopathology , Prevalence , Risk , Severity of Illness Index , Thinness/physiopathology , Waist Circumference
8.
Cancer Causes Control ; 28(6): 599-624, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28401353

ABSTRACT

PURPOSE: History of fetal loss including miscarriage and stillbirth has been inconsistently associated with childhood (0-14 years) leukemia in subsequent offspring. A quantitative synthesis of the inconclusive literature by leukemia subtype was therefore conducted. METHODS: Eligible studies (N = 32) were identified through the screening of over 3500 publications. Random-effects meta-analyses were conducted on the association of miscarriage/stillbirth history with overall (AL; 18,868 cases/35,685 controls), acute lymphoblastic (ALL; 16,150 cases/38,655 controls), and myeloid (AML; 3042 cases/32,997 controls) leukemia. Sensitivity and subgroup analyses by age and ALL subtype, as well as meta-regression were undertaken. RESULTS: Fetal loss history was associated with increased AL risk [Odds Ratio (OR) 1.10, 95% Confidence Intervals (CI) 1.04-1.18]. The positive association was seen for ALL (OR 1.12, 95%CI 1.05-1.19) and for AML (OR 1.13, 95%CI 0.91-1.41); for the latter the OR increased in sensitivity analyses. Notably, stillbirth history was significantly linked to ALL risk (OR 1.33, 95%CI 1.02-1.74), but not AML. By contrast, the association of ALL and AML with previous miscarriage reached marginal significance. The association of miscarriage history was strongest in infant ALL (OR 2.34, 95%CI 1.19-4.60). CONCLUSIONS: In this meta-analysis involving >50,000 children, we found noteworthy associations by indices of fetal loss, age at diagnosis, and leukemia type; namely, of stillbirth with ALL and miscarriage history with infant ALL. Elucidation of plausible underlying mechanisms may provide insight into leukemia pathogenesis and indicate monitoring interventions prior to and during pregnancy.


Subject(s)
Abortion, Spontaneous , Leukemia, Myeloid, Acute/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/etiology , Stillbirth , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Pregnancy , Risk Factors
9.
Mol Psychiatry ; 22(5): 640-646, 2017 05.
Article in English | MEDLINE | ID: mdl-28289275

ABSTRACT

Psychosocial stress triggers a set of behavioral, neural, hormonal, and molecular responses that can be a driving force for survival when adaptive and time-limited, but may also contribute to a host of disease states if dysregulated or chronic. The beneficial or detrimental effects of stress are largely mediated by the hypothalamic-pituitary axis, a highly conserved neurohormonal cascade that culminates in systemic secretion of glucocorticoids. Glucocorticoids activate the glucocorticoid receptor, a ubiquitous nuclear receptor that not only causes widespread changes in transcriptional programs, but also induces lasting epigenetic modifications in many target tissues. While the epigenome remains sensitive to stressors throughout life, we propose two key principles that may govern the epigenetics of stress and glucocorticoids along the lifespan: first, the presence of distinct life periods, during which the epigenome shows heightened plasticity to stress exposure, such as in early development and at advanced age; and, second, the potential of stress-induced epigenetic changes to accumulate throughout life both in select chromatin regions and at the genome-wide level. These principles have important clinical and translational implications, and they show striking parallels with the existence of sensitive developmental periods and the cumulative impact of stressful experiences on the development of stress-related phenotypes. We hope that this conceptual mechanistic framework will stimulate fruitful research that aims at unraveling the molecular pathways through which our life stories sculpt genomic function to contribute to complex behavioral and somatic phenotypes.


Subject(s)
Glucocorticoids/metabolism , Stress, Psychological/genetics , Stress, Psychological/metabolism , Animals , Epigenesis, Genetic , Humans , Receptors, Glucocorticoid/metabolism , Signal Transduction
10.
Article in English | MEDLINE | ID: mdl-27679978

ABSTRACT

BACKGROUND: Functional gastrointestinal disorders (FGIDs) are a common, diverse group of disorders of unknown etiology, resulting in significant socieconomic burden. In this study, we aimed to assess the prevalence of FGIDs in children aged 6-18 years and examine their association with various demographic and socioeconomic parameters. METHODS: This was a school-based, cross-sectional study approved by the relevant government authorities. Informed consent was obtained by the legal representatives of all children who participated. Diagnoses of FGIDs were based on the Greek official translation of the ROME-III questionnaire. Demographic and socioeconomic information were also collected. KEY RESULTS: A total of 1588 children (51.8% females, mean age: 12.9±2.8 years) were included. The overall prevalence of any-FGID was 23.1% (95% CI: 21.1-25.2). The most common FGIDs were functional constipation, n=231 (13.9%), abdominal migraine, n=84 (5.6%), aerophagia, n=58 (3.5%), and irritable bowel syndrome, n=48 (3.0%). Multiple logistic regression analysis on the probability of any-FGID identified physical exercise, TV-exposure, victimization, gender, parental educational level, number of children at home and number of adults at home as significant covariates for any-FGID in the final model. CONCLUSIONS AND INFERENCES: FGIDs affect approximately 1 in 4 school-aged children in Greece. The following characteristics are associated with a higher probability of any-FGID: female gender, living in a non-nuclear household, victimization, lower parental education level, infrequent physical activity, and high television exposure.


Subject(s)
Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/epidemiology , Surveys and Questionnaires , Adolescent , Child , Cross-Sectional Studies , Female , Gastrointestinal Diseases/physiopathology , Greece/epidemiology , Humans , Male , Risk Factors
11.
Psychiatriki ; 27(2): 89-97, 2016.
Article in Greek | MEDLINE | ID: mdl-27467029

ABSTRACT

Compassion is closely related with human's survival as a mammal and has been developed through evolution for pain reduction, for forming affiliative bonds and alliances with non kin in order to increase protection and cope with external threats. Compassion seems to influence people's ability to deal with life's adverse situations such as stress and it is linked with lower psychopathology and greater wellbeing. Compassion is closely related to empathy and altruism and it is defined as the recognition of the pain of the self or others' that is accompanied with the will to take action in order to relieve the person from pain. Its main features are kindness instead of self-judgment and indifference, the recognition of common humanity instead of the feeling of separation and mindfulness when facing adverse conditions instead of over-identification with one's pain or disengagement with the pain of others. According to the biopsychosocial approach, stress can be defined by three dimensions such as the cause or stressful factors that can be major life events or daily hassles, the perception of stress that is manifested through cognitive, emotional and behavioural reactions and the physiological response for achieving homeostasis. The purpose of the present study was to investigate the role of compassion for self and others in the occurrence of stressful events and levels of perceived stress in students. Participants were 280 undergraduate students from two Greek universities. Results indicated that students who had experienced a greater amount of stressful events during the past year reported having higher levels of perceived stress and that higher self-compassion was correlated with less perceived stress. Moreover, the adverse effect of stressful events on perceived stress was partially explained by the mediating role of self-compassion. Students who reported more stressful events showed higher compassion for others in opposition to compassion towards themselves but compassion for others was not significantly correlated with perceived stress. Since compassion is not considered being a fixed personality trait but it is seen as a capacity that can be developed by appropriate training it was suggested that enhancing self-compassion's stress buffering properties can be useful for dealing with stressful events and reducing stress responses. Moeover, it was suggested that it is interesting to explore the relationship between compassion for others and positive characteristics such as sense of coherence, quality of life and social support that may enhance stress resilience indirectly. The above findings imply that it is important to investigate further the role of compassion in coping with stress in qualitative, longitudinal studies as well as randomized control trials. Compassion may be an alternative mechanism for coping with stressful events and stress, other than fight or flight that has been shaped by evolution.


Subject(s)
Adaptation, Psychological/physiology , Emotional Intelligence , Empathy , Quality of Life , Resilience, Psychological , Stress, Psychological , Adolescent , Adult , Female , Humans , Male , Psychophysiology , Social Support , Stress, Psychological/diagnosis , Stress, Psychological/physiopathology , Stress, Psychological/psychology , Students/psychology
12.
J Endocrinol Invest ; 39(10): 1125-30, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27312860

ABSTRACT

BACKGROUND: The significance of vitamin D deficiency in the incidence of bone fractures in children has been under investigated. Here, we aimed to associate serum 25-hydroxyvitamin D levels and fractures in Saudi children. MATERIALS AND METHODS: This cross-sectional study was conducted in 1022 Saudi children without fracture history [476 boys (age 14.56 ± 1.81, BMI 22.38 ± 5.81) and 546 girls (age 13.57 ± 1.67, BMI 22.24 ± 4.94)] and 234 Saudi children with a history of fracture [148 boys (age 14.25 ± 1.39, BMI 22.66 ± 6.08) and 86 girls (age 13.76 ± 1.35, BMI 21.33 ± 1.35)]. Anthropometric and fasting serum biochemical data were collected. Serum 25-hydroxyvitamin D level was assessed using electrochemiluminescence. RESULTS: Mean circulating 25-hydroxyvitamin (25OH) D level in subjects with a history of fracture was significantly lower in both boys (p < 0.01) and girls (p < 0.01) than those without, however both groups had low mean 25(OH)D levels. Furthermore, age was positively associated with 25-hydroxyvitamin D in boys (p < 0.05) and negatively in girls (p < 0.05) with a history of fracture. CONCLUSION: In conclusion, vitamin D levels were significantly lower in children with a history of bone fractures in both boys and girls than those without such a history; even in the absence of fracture history, vitamin D status correction is warranted in the general Saudi pediatric population.


Subject(s)
Biomarkers/blood , Fractures, Bone/complications , Vitamin D Deficiency/diagnosis , Vitamin D/analogs & derivatives , Adolescent , Anthropometry , Case-Control Studies , Child , Cross-Sectional Studies , Female , Humans , Male , Saudi Arabia/epidemiology , Vitamin D/blood , Vitamin D Deficiency/blood , Vitamin D Deficiency/epidemiology
13.
Mol Endocrinol ; 30(1): 62-76, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26554443

ABSTRACT

We demonstrate 2 novel mutations of the LHCGR, each homozygous, in a 46,XY patient with severe Leydig cell hypoplasia. One is a mutation in the signal peptide (p.Gln18_Leu19ins9; referred to here as SP) that results in an alteration of the coding sequence of the N terminus of the mature mutant receptor. The other mutation (p.G71R) is also within the ectodomain. Similar to many other inactivating mutations, the cell surface expression of recombinant human LHR(SP,G71R) is greatly reduced due to intracellular retention. However, we made the unusual discovery that the intrinsic efficacy for agonist-stimulated cAMP in the reduced numbers of receptors on the cell surface was greatly increased relative to the same low number of cell surface wild-type receptor. Remarkably, this appears to be a general attribute of misfolding mutations in the ectodomains, but not serpentine domains, of the gonadotropin receptors. These findings suggest that there must be a common, shared mechanism by which disparate mutations in the ectodomain that cause misfolding and therefore reduced cell surface expression concomitantly confer increased agonist efficacy to those receptor mutants on the cell surface. Our data further suggest that, due to their increased agonist efficacy, extremely small changes in cell surface expression of misfolded ectodomain mutants cause larger than expected alterations in the cellular response to agonist. Therefore, for inactivating LHCGR mutations causing ectodomain misfolding, the numbers of cell surface mutant receptors on fetal Leydig cells of 46,XY individuals exert a more exquisite effect on the relative severity of the clinical phenotypes than already appreciated.


Subject(s)
Leydig Cells/metabolism , Mutation , Puberty, Delayed/metabolism , Receptors, LH/metabolism , Adolescent , Female , Humans , Male , Protein Folding , Puberty, Delayed/genetics , Receptors, LH/genetics , Signal Transduction
14.
J Hum Hypertens ; 30(6): 397-403, 2016 06.
Article in English | MEDLINE | ID: mdl-26424102

ABSTRACT

Current hypertension guidelines advocate strategies encouraging healthy lifestyle behaviours. So far, there is a paucity of studies for the efficacy of such multifaceted programmes. The aim of this study is to investigate the efficacy of an 8-week health-promotion programme for lowering blood pressure (BP) in prehypertensive and hypertensive patients in the community. This was a quasi-experimental study using wait-list controls of 548 patients. The intervention group was administered with an 8-week health-promotion intervention. Measurements included home BP, smoking, body mass index (BMI), perceived stress, depression, anxiety and Health Locus of Control. After adjusting for confounders, the intervention group had a significant reduction in both systolic BP (SBP; mean -2.62 mm Hg, 95% confidence interval (CI): -1.29 to -3.96) and diastolic BP (DBP; mean -1.0, 95% CI: -0.93 to -1.9) compared with controls. In all, 14.9% of patients in the intervention group had >10 mm Hg reduction in SBP vs 4.4% in the control group (P<0.001, numbers needed to treat (NNT)=10). With regards to DBP, 21.7% of patients in the intervention group had >5 mm Hg reduction vs 12.5% in the control group (P=0.01, NNT=11). In terms of effect size, moderate-to-large improvements of BMI, perceived stress, anxiety, depression, external and chance Health Locus of Control were recorded. Changes in SBP and DBP were attributed to BMI and depressive symptom reductions, respectively. Comprehensive non-pharmaceutical programmes for BP management are strongly encouraged. Their long-term benefits on cardiovascular morbidity and mortality remain to be established by future research.


Subject(s)
Health Behavior , Health Promotion/methods , Healthy Lifestyle , Hypertension/therapy , Prehypertension/therapy , Risk Reduction Behavior , Self Care/methods , Stress, Psychological/therapy , Adolescent , Adult , Aged , Female , Greece , Humans , Hypertension/diagnosis , Hypertension/physiopathology , Hypertension/psychology , Male , Middle Aged , Prehypertension/diagnosis , Prehypertension/physiopathology , Prehypertension/psychology , Risk Factors , Stress, Psychological/diagnosis , Stress, Psychological/physiopathology , Stress, Psychological/psychology , Time Factors , Treatment Outcome , Young Adult
15.
Mol Psychiatry ; 21(2): 277-89, 2016 Feb.
Article in English | MEDLINE | ID: mdl-25849320

ABSTRACT

Psychotropic medications target glycogen synthase kinase 3ß (GSK3ß), but the functional integration with other factors relevant for drug efficacy is poorly understood. We discovered that the suggested psychiatric risk factor FK506 binding protein 51 (FKBP51) increases phosphorylation of GSK3ß at serine 9 (pGSK3ß(S9)). FKBP51 associates with GSK3ß mainly through its FK1 domain; furthermore, it also changes GSK3ß's heterocomplex assembly by associating with the phosphatase PP2A and the kinase cyclin-dependent kinase 5. FKBP51 acts through GSK3ß on the downstream targets Tau, ß-catenin and T-cell factor/lymphoid enhancing factor (TCF/LEF). Lithium and the antidepressant (AD) paroxetine (PAR) functionally synergize with FKBP51, as revealed by reporter gene and protein association analyses. Deletion of FKBP51 blunted the PAR- or lithium-induced increase in pGSK3ß(S9) in cells and mice and attenuated the behavioral effects of lithium treatment. Clinical improvement in depressive patients was predicted by baseline GSK3ß pathway activity and by pGSK3ß(S9) reactivity to ex vivo treatment of peripheral blood mononuclear lymphocytes with lithium or PAR. In sum, FKBP51-directed GSK3ß activity contributes to the action of psychotropic medications. Components of the FKBP51-GSK3ß pathway may be useful as biomarkers predicting AD response and as targets for the development of novel ADs.


Subject(s)
Glycogen Synthase Kinase 3/metabolism , Tacrolimus Binding Proteins/genetics , Adult , Animals , Antidepressive Agents/pharmacology , Biomarkers/blood , Cell Culture Techniques , Cell Line , Cyclin-Dependent Kinase 5 , Female , Glycogen Synthase Kinase 3 beta , HEK293 Cells , Humans , Leukocytes, Mononuclear/metabolism , Lithium , Male , Mice , Middle Aged , Phosphorylation/drug effects , Psychotropic Drugs/pharmacology , Signal Transduction/drug effects , Tacrolimus Binding Proteins/metabolism , beta Catenin/metabolism
16.
Clin Endocrinol (Oxf) ; 82(4): 543-9, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25041270

ABSTRACT

BACKGROUND: Nonclassical congenital adrenal hyperplasia (NC-CAH) is caused by mutations of the CYP21A2 gene. The clinical manifestations and hormonal derangements of NC-CAH are quite variable. OBJECTIVES: (i) To define the phenotype and its relation to genotype according to gender and age and (ii) to evaluate the validity of currently applied hormonal criteria for establishing the diagnosis of NC-CAH. PATIENTS AND METHODS: The clinical, hormonal and molecular data of 280 subjects (235 female) with NC-CAH and a median age of 17·6 years were analysed. CYP21A2 genotyping was performed in all subjects. RESULTS: The majority of females aged less than 8 years presented with premature pubarche (88·3%), while those older than 8 presented with a polycystic ovary-like phenotype (63·2%). A total of 7·7% of the females and 51·1% of the males were asymptomatic at the time of diagnosis. In the total group, 50·4% of the subjects were compound heterozygotes for one classical (C) and one nonclassical (NC) mutation, while 46% of the alleles studied carried the p.V281L mutation. Basal 17OHP values were below 6 nm (2 ng/ml) in 2·1% of the subjects with NC-CAH, but none had peak 17OHP values post-ACTH lower than 30 nm (10 ng/ml). CONCLUSIONS: NC-CAH has a variable phenotype depending on the age, gender and the presence of a classical mutation. A peak cut-off value of 17OHP post-ACTH lower than 30 nm excludes the diagnosis of NC-CAH, whereas basal 17OHP <6 nm may represent a false-negative result. A significant number of patients harboured a classical mutation, a finding which requires genotyping of the partner for genetic counselling.


Subject(s)
Adrenal Hyperplasia, Congenital/genetics , Mutation , Steroid 21-Hydroxylase/genetics , Adolescent , Adult , Aged , Alleles , Child , Child, Preschool , Female , Genotype , Heterozygote , Humans , Infant , Male , Middle Aged , Phenotype , Polycystic Ovary Syndrome/physiopathology , Young Adult
17.
J Public Health (Oxf) ; 37(1): 70-7, 2015 Mar.
Article in English | MEDLINE | ID: mdl-24297780

ABSTRACT

BACKGROUND: Several important socio-behavioral public health problems that either peak or start during the second decade of life contribute to young people's mortality. The aim of this study was to explore patterns, rates, trends and regional variations of external-cause (due to environmental events/circumstances) mortality among young people aged 10-24 years in Greece, over the decade 2000-09. METHODS: Data were electronically derived from the database of the Hellenic Statistical Authority to study general and specific mortality rates by major causes of death. RESULTS: Road traffic crashes (RTCs), illicit drug use and suicide accounted for 65.8, 14.7 and 4.8%, of total external-cause mortality, respectively. Mortality rates (deaths per 100 000) did not exhibit intra-country variability, were higher in young adults than in adolescents, in males than in females and decreased by 39%, from 33.6 in 2000 to 20.4 in 2009 (P < 0.001), due to declines in mortality from RTCs (from 21.3 to 14.3; P = 0.001), substance abuse (from 5.1 to 2.1; P = 0.003) and suicides (from 2.0 to 0.9; P = 0.003). CONCLUSIONS: External causes of young people's mortality were mainly psychosocial and behavioral in origin. Despite improvement over the decade, young people in Greece still have unmet health-care needs and may further benefit from a multipronged public health approach through improved youth-friendly health services.


Subject(s)
Accidents, Traffic/trends , Cause of Death/trends , Drug-Seeking Behavior/trends , Mortality/trends , Suicide/trends , Accidents, Traffic/history , Adolescent , Adolescent Behavior , Adult , Child , Female , Forecasting , Greece , History, 21st Century , Humans , Male , Sex Factors , Substance-Related Disorders/mortality , Suicide/history , Young Adult
18.
J Hum Nutr Diet ; 28 Suppl 2: 50-8, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24303926

ABSTRACT

BACKGROUND: The Healthy Lifestyle-Diet Index (HLD-index), previously developed to assess the degree of adherence to dietary and lifestyle guidelines for primary schoolchildren, was revised according to updated recommendations. Τhe association of the revised HLD-index (R-HLD-index) with obesity and iron deficiency (ID) was also examined. METHODS: A representative sample of 2660 primary schoolchildren from Greece (9-13 years old) participating in the 'Healthy Growth Study' was examined. Twelve components related to dietary and lifestyle patterns were used to develop the R-HLD-index. Scores from 0 up to 4 were assigned to each one of these components, giving a total score ranging from 0 to 48. The associations between the R-HLD-index, obesity and ID were examined via logistic regression analysis. RESULTS: The total score of the R-HLD-index calculated for each one of the study participants was found to range between 2 and 32 units, with higher scores being indicative of a healthier lifestyle and better diet quality. After adjusting for potential confounders, logistic regression analysis showed that an increase in the R-HLD-index score by one unit was associated with 6% lower odds for obesity. However, no significant association was observed between the R-HLD-index score and ID. CONCLUSIONS: The R-HLD-index may be a useful tool for public health policy makers and healthcare professionals when assessing diet quality and lifestyle patterns of primary schoolchildren. Identification of children with lower scores in the R-HLD-index and its individual components could guide tailored made interventions targeting specific children and behaviors.


Subject(s)
Diet/standards , Feeding Behavior , Health Behavior , Iron Deficiencies , Life Style , Nutrition Policy , Obesity/etiology , Adolescent , Body Mass Index , Child , Female , Greece , Growth , Health , Humans , Logistic Models , Male , Schools
19.
Andrologia ; 46(9): 1022-31, 2014.
Article in English | MEDLINE | ID: mdl-25436273

ABSTRACT

Young people often experience excessive stress that definitely undermines their sexual life and leads them to adopt risky sexual behaviours. As such, the design and application of a stress management programme in this particular age group is, undoubtedly, a crucial matter. In this parallel randomised controlled trial, 60 psychology students of the Panteion University of Athens, aged 18­20, were randomly assigned to undergo either an 8-week stress management programme (n = 30; diaphragmatic breathing­progressive muscle relaxation and guided imagery, twice a day) or not (n = 30). Self-reported validated measures were used to evaluate stress, stressful life events, health locus of control, general health status, sexual behaviours, sexual desire, satisfaction from sexual life and interpersonal relationships. Between-group analyses revealed statistically significant differences in internal health locus of control and general health evaluation. Within the intervention group analyses showed reductions in BMI, stress, the 'chance' subscale of multidimensional health locus of control (MHLC) and greater satisfaction from sexual life. No other significant change was reported. We deem that our results should encourage relevant future studies.


Subject(s)
Health Promotion/methods , Reproductive Health , Stress, Psychological/therapy , Adolescent , Female , Humans , Male , Patient Satisfaction , Pilot Projects , Relaxation Therapy , Stress, Psychological/prevention & control , Young Adult
20.
Eur J Clin Nutr ; 68(3): 344-9, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24424081

ABSTRACT

BACKGROUND/OBJECTIVES: Although diet, physical activity (PA), sedentary behavior and sleep deprivation are factors that have been individually associated with insulin resistance (IR) in childhood, the combined effect of these lifestyle behaviors has not been examined yet. The current study aimed to examine the association of lifestyle patterns with IR, combining all these indices, in children. SUBJECTS/METHODS: Socio-economic, demographic, anthropometric (body weight, height and waist circumference), biochemical (plasma glucose and serum insulin), clinical (pubertal stage) and lifestyle (dietary intake, PA level and sleeping habits) data were collected from a representative sample of 2026 children (50.1% girls) aged 9-13 years in Greece. Homeostasis model assessment (HOMA-IR) was calculated, and principal component analysis was used to identify lifestyle patterns, combining all these lifestyle indices. RESULTS: In multivariable regression analyses, the lifestyle pattern characterized by more screen time, shorter sleep duration and higher consumption of sugared beverages was positively associated with HOMA-IR (ß=0.043; P=0.040), whereas the pattern characterized by more time spent on moderate-to-vigorous PA (MVPA) and more frequent eating occasions was inversely associated with HOMA-IR (ß=-0.061; P=0.003). In logistic regression analyses, children with 72.2 min/day of MVPA and 5.05 eating occasions/day and children with 141.8 min/day of MVPA and 5.22 eating occasions/day were less likely of being insulin resistant based on HOMA-IR, compared with children with 20.0 min/day of MVPA and 4.09 eating occasions/day. CONCLUSIONS: A lifestyle pattern of >72 min of MVPA and 5 eating occasions/day was associated with reduced likelihood of IR in children.


Subject(s)
Insulin Resistance/physiology , Life Style , Sleep Deprivation/physiopathology , Adolescent , Blood Glucose/metabolism , Body Height , Body Mass Index , Body Weight , Child , Cross-Sectional Studies , Demography , Diet , Energy Intake , Feeding Behavior , Female , Greece , Health Behavior , Humans , Logistic Models , Male , Meals , Motor Activity , Multivariate Analysis , Principal Component Analysis , Sedentary Behavior , Sleep/physiology , Socioeconomic Factors , Waist Circumference
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