Publications

The Migraine Disability Assessment (MIDAS) Questionnaire is a reliable and valid instrument for migraine-related disability. Such a tool is needed to quantify migraine-related disability in the Greek population.This validation study aims to assess the test-retest reliability, internal consistency, item discriminant and convergent validity of the Greek translation of the MIDAS.Adults diagnosed with migraine completed the MIDAS Questionnaire on two occasions 3 weeks apart to assess reliability, and completed the RAND-36 to assess validity.Participants (n = 152) had a median MIDAS score of 24 and mostly severe disability (58% were grade IV). The test-retest reliability analysis (N = 59) revealed excellent reliability for the total score. Internal consistency was α = 0.71 for initial and α = 0.82 for retest completion. For item discriminant validity, the correlations between each question and the total score were significant, with high correlations for questions 2-5 (range 0.67 ≤ r ≤ 0.79; p < 0.01). For convergent validity, there was significant negative correlation between the total score and all RAND-36 subscales except for 'emotional wellbeing'. The negative correlation indicates that patients with a lower degree of disability according to their MIDAS score tended to have better wellbeing. Psychometric properties are comparable with those of other published validation studies of the MIDAS and the original. Findings on question 1 show that missing work/school days may be closely related with increased affect issues.The Greek version of the MIDAS Questionnaire has good reliability and validity. This study allowed for cross-cultural comparability of research findings.

Transition from childhood to adolescence is known to bring about many changes in the lifestyle and psycho-emotional state of adolescents. One of the major lifestyle factors that affect adolescents' physical and mental health is sleep. The aim of this study was to validate the Adolescent Sleep Hygiene Scale (ASHS), a tool that measures sleep hygiene, in an adolescent sample living in Greece. The study's sample consisted of 146 Greek adolescents aged 12-18 years. The Adolescent Stress Questionnaire was used for convergent validity and correlation with adolescents' stress. The pilot and the main study demonstrated sufficient internal consistency. Exploratory Factor Analysis showed an adequate adaptation of the original ASHS questionnaire to the Greek adolescents. The findings of this study support the use of ASHS as a reliable and valid tool for evaluating sleep-facilitating and sleep-inhibiting practices of Greek adolescents.

Interest is great in the new molecular concepts that explain, at the level of signal transduction, the process of reprogramming. Usually, transcription factors with developmental importance are used, but these approaches give limited information on the signaling networks involved, which could reveal new therapeutic opportunities. Recent findings involving reprogramming by genetic means and soluble factors with well-studied downstream signaling mechanisms, including signal transducer and activator of transcription 3 (STAT3) and hairy and enhancer of split 3 (Hes3), shed new light into the molecular mechanisms that might be involved. We examine the appropriateness of common culture systems and their ability to reveal unusual (noncanonical) signal transduction pathways that actually operate in vivo. We then discuss such novel pathways and their importance in various plastic cell types, culminating in their emerging roles in reprogramming mechanisms. We also discuss a number of reprogramming paradigms (mouse induced pluripotent stem cells, direct conversion to neural stem cells, and in vivo conversion of acinar cells to β-like cells). Specifically for acinar-to-β-cell reprogramming paradigms, we discuss the common view of the underlying mechanism (involving the Janus kinase-STAT pathway that leads to STAT3-tyrosine phosphorylation) and present alternative interpretations that implicate STAT3-serine phosphorylation alone or serine and tyrosine phosphorylation occurring in sequential order. The implications for drug design and therapy are important given that different phosphorylation sites on STAT3 intercept different signaling pathways. We introduce a new molecular perspective in the field of reprogramming with broad implications in basic, biotechnological, and translational research. Reprogramming is a powerful approach to change cell identity, with implications in both basic and applied biology. Most efforts involve the forced expression of key transcription factors, but recently, success has been reported with manipulating signal transduction pathways that might intercept them. It is important to start connecting the function of the classic reprogramming genes to signaling pathways that also mediate reprogramming, unifying the sciences of signal transduction, stem cell biology, and epigenetics. Neural stem cell studies have revealed the operation of noncanonical signaling pathways that are now appreciated to also operate during reprogramming, offering new mechanistic explanations.

In vitro fertilisation (IVF) has been widely used during the last decades. Recent studies demonstrated some alterations in IVF children's metabolic profile compared with controls. The recently reported lipocalins retinol-binding protein 4 (RBP-4) and neutrophil gelatinase-associated lipocalin (NGAL), as well as visfatin, which are associated with glucose intolerance and could help in the early detection of metabolic abnormalities, have not been studied in IVF children as yet. We studied the lipocalins RBP-4 and NGAL as well as visfatin in children born after IVF.A total of 100 children born after IVF (47 boys) and 60 controls born after normal conception (30 boys), aged 4-14 year, were studied cross-sectionally. All children had a physical examination, their fasting glucose, insulin, lipid profile, RBP-4, NGAL, and visfatin were determined and their homoeostasis model assessment (HOMA) index was calculated.Children born after IVF had significantly higher RBP-4 (P = 0·009) and NGAL (P = 0·028) levels than controls. When divided by gender, RBP-4 remained higher in IVF girls (P = 0·002), whereas NGAL was higher in IVF boys (P = 0·021). Linear regression analysis had revealed that the differences are attributed to the IVF procedure per se.In our study, IVF children had significantly higher RBP-4 and NGAL levels than controls, suggesting early metabolic derangements that could be attributed to an epigenetic phenomenon. These results are in accordance with our earlier findings of higher blood pressure and triglycerides in IVF children than controls. Further prospective studies in IVF children will determine the natural course of their metabolic profile.

Context: Interindividual variations in glucocorticoid sensitivity have been associated with manifestations of cortisol excess or deficiency and may be partly explained by polymorphisms in the human glucocorticoid receptor (hGR) gene. We studied a 43-yr-old female, who presented with manifestations consistent with tissue-selective glucocorticoid hypersensitivity. We detected a novel, single, heterozygous nucleotide (G → C) substitution at position 1201 (exon 2) of the hGR gene, which resulted in aspartic acid to histidine substitution at amino acid position 401 in the amino-terminal domain of the hGRα. We investigated the molecular mechanisms of action of the natural mutant receptor hGRαD401H. Methods-Results: Compared with the wild-type hGRα, the mutant receptor hGRαD401H demonstrated a 2.4-fold increase in its ability to transactivate the glucocorticoid-inducible mouse mammary tumor virus promoter in response to dexamethasone but had similar affinity for the ligand (dissociation constant = 6.2 ± 0.6 vs. 6.1 ± 0.6 nm) and time to nuclear translocation (14.75 ± 0.25 vs. 14.25 ± 1.13 min). The mutant receptor hGRαD401H did not exert a dominant positive or negative effect upon the wild-type receptor, it preserved its ability to bind to glucocorticoid response elements, and displayed a normal interaction with the glucocorticoid receptor-interacting protein 1 coactivator. Conclusions: The mutant receptor hGRαD401H enhances the transcriptional activity of glucocorticoid-responsive genes. The presence of the D401H mutation may predispose subjects to obesity, hypertension, and other manifestations of the metabolic syndrome.

Reports in adults and children have correlated history of wheezing or asthma with the presence of obstructive sleep-disordered breathing but the mechanism of this epidemiologic association is unknown. The goal of the present study was to examine whether tonsillar hypertophy can explain this association.Children were recruited from the Emergency Department and the Pediatric Pulmonology Clinic. History of wheezing requiring treatment (explanatory variable) and snoring > or = 1 night/week (outcome) were recorded and presence of tonsillar hypertrophy (outcome) was assessed.Four hundred forty-two children were recruited (mean age: 7.6 + or - 3.6 years) and 210 of them had history of wheezing. History of wheezing was significantly associated with the presence of tonsillar hypertrophy and snoring even after adjustment for age, gender, obesity, and passive smoking [odds ratio (95% confidence interval): 2.23 (1.37-3.63); P = 0.001 and 1.73 (1.12-2.67); P = 0.013, respectively]. When only children with tonsillar hypertrophy were considered (n = 92), history of wheezing was significantly related to the presence of snoring, whereas in subjects without tonsillar hypertrophy (n = 350) wheezing did not affect snoring [odds ratio: 2.76 (1.10-6.93); P = 0.031 and 1.49 (0.92-2.43); P = 0.107, respectively].Children with history of wheezing have more frequently tonsillar hypertrophy than those without wheezing. Tonsillar hypertrophy may mediate at least in part the reported association between asthma and obstructive sleep-disordered breathing in childhood.

Telomere length, an indicator of ageing and longevity, has been correlated with several biomarkers of cardiometabolic disease in both Arab children and adults. It is not known, however, whether or not telomere length is a highly conserved inheritable trait in this homogeneous cohort, where age-related diseases are highly prevalent. As such, the aim of this study was to address the inheritability of telomere length in Saudi families and the impact of cardiometabolic disease biomarkers on telomere length. A total of 119 randomly selected Saudi families (123 adults and 131 children) were included in this cross-sectional study. Anthropometrics were obtained and fasting blood samples were taken for routine analyses of fasting glucose and lipid profile. Leukocyte telomere length was determined using quantitative real time PCR. Telomere length was highly heritable as assessed by a parent-offspring regression [h2 = 0.64 (p = 0.0006)]. Telomere length was modestly associated with BMI (R2 0.07; p-value 0.0087), total cholesterol (R2 0.08; p-value 0.0033), and LDL-cholesterol (R2 0.15; p-value 3 x 10-5) after adjustments for gender, age and age within generation. The high heritability of telomere length in Arab families, and the associations of telomere length with various cardiometabolic parameters suggest heritable genetic fetal and/or epigenetic influences on the early predisposition of Arab children to age-related diseases and accelerated ageing.