Publications

The proinflammatory cytokines, TNFα and IL-6, are elevated in obstructive sleep apnea (OSA) and have been proposed as mediators of excessive daytime sleepiness in humans. We tested the effects of etanercept, a medication that neutralizes TNFα and is approved by the FDA for the treatment of rheumatoid arthritis, in eight obese male apneics. These patients participated in a pilot, placebo-controlled, double-blind study during which nighttime polysomnography, multiple sleep latency test, and fasting blood glucose and plasma levels of IL-6, C-reactive protein, insulin, and adiponectin were obtained. There was a significant and marked decrease in sleepiness by etanercept, which increased sleep latency during the multiple sleep latency test by 3.1 ± 1.0 min (P < 0.05) compared with placebo. Also, the number of apneas/hypopneas per hour was reduced significantly by the drug compared with placebo (52.8 ± 9.1 vs. 44.3 ± 10.3; adjusted difference, −8.4 ± 2.3; P < 0.05). Furthermore, IL-6 levels were significantly decreased after etanercept administration compared with placebo (3.8 ± 0.9 vs. 1.9 ± 0.4 pg/ml; adjusted difference, −1.9 ± 0.5; P < 0.01). However, no differences were observed in etanercept vs. placebo in the levels of fasting blood glucose and plasma C-reactive protein, insulin, and adiponectin. We conclude that neutralizing TNFα activity is associated with a significant reduction of objective sleepiness in obese patients with OSA. This effect, which is about 3-fold higher than the reported effects of continuous positive airway pressure on objective sleepiness in patients with OSA (0.9 vs. 3.1 min), suggests that proinflammatory cytokines contribute to the pathogenesis of OSA/sleepiness.

A bstract : Increased oxidation of carbohydrates and free fatty acids is a well‐known phenomenon during cold stress. Nevertheless, sources of the fuels used have not been fully clarified as yet. Thus, the aim of our study was to evaluate the effect of acute cold exposure on lipid and carbohydrate metabolism in human subcutaneous adipose tissue and to identify the possible regulatory mechanisms involved. Ten volunteers were exposed for 30 min to an ambient temperature of 4°C. Interstitial metabolism was assessed with the aid of the microdialysis technique. Lipolysis intensity was evaluated from changes of glycerol concentration in plasma and in dialysate. Cold exposure induced a significant increase of glycerol concentration both in plasma (by 199 ± 16%, p &lt; 0.01 ) and in dialysate (by 308 ± 58%, p &lt; 0.001 ). No changes in glucose concentration were found whether in plasma or in the dialysate. Ethanol concentration in dialysate increased (148 ± 15%, p &lt; 0.01 ), indicating a slower blood flow in the subcutaneous region. Plasma concentrations of various gluco‐ and/or lipid‐regulatory hormones remained unaffected by the cold exposure, except for norepinephrine, which rose about threefold (309 ± 41%, p &lt; 0.001 ). The data indicate an important role for subcutaneous adipose tissue in mobilization of free fatty acids during cold exposure. This process seems to be regulated by the sympathetic nervous system, whereas hormones involved in the regulation of lipid metabolism, such as epinephrine, insulin, cortisol, and growth hormone, may play a less significant role—at least under the conditions studied.

We examined the effectiveness of a computerised decision-support tool (DST), designed for paediatric healthcare professionals, as a means to tackle childhood obesity. A randomised controlled trial was conducted with 65 families of 6⁻12-year old overweight or obese children. Paediatricians, paediatric endocrinologists and a dietitian in two children's hospitals implemented the intervention. The intervention group (IG) received personalised meal plans and lifestyle optimisation recommendations via the DST, while families in the control group (CG) received general recommendations. After three months of intervention, the IG had a significant change in dietary fibre and sucrose intake by 4.1 and -4.6 g/day, respectively. In addition, the IG significantly reduced consumption of sweets (i.e., chocolates and cakes) and salty snacks (i.e., potato chips) by -0.1 and -0.3 portions/day, respectively. Furthermore, the CG had a significant increase of body weight and waist circumference by 1.4 kg and 2.1 cm, respectively, while Body Mass Index (BMI) decreased only in the IG by -0.4 kg/m². However, the aforementioned findings did not differ significantly between study groups. In conclusion, these findings indicate the dynamics of the DST in supporting paediatric healthcare professionals to improve the effectiveness of care in modifying obesity-related behaviours. Further research is needed to confirm these findings.

Alzheimer's disease (AD) is a neurodegenerative disorder that has a significant association with age. Despite its increasing incidence in the population, the etiology of the disease remains poorly understood, and there are currently no effective treatments readily available. The main genes that are associated with AD are the amyloid precursor protein, presenilin‑1 and presenilin‑2, as well as the apolipoprotein E gene. In addition to genetic factors, a wide range of environmental and lifestyle factors are equally characterized as risk factors for the development of AD, while non‑coding RNAs (ncRNAs) and other epigenetic mechanisms play a key role in their detrimental effects. Multiple types of ncRNAs, such as microRNAs, circular RNAs, Piwi‑interacting RNAs and long non‑coding RNAs are being increasingly implicated in AD. Alterations in ncRNAs can be detected in cerebrospinal fluid, as well in as the brain, highlighting these as promising biomarkers for the detection and treatment of AD. Developments in high‑throughput technologies have led to the so‑called 'omics' era, which involves the collection of big data and information at both molecular and protein levels, while combining the development of novel computational and statistical tools capable of analyzing and filtering such data. The present review discusses the role of ncRNAs and their use as biomarkers for AD, and summarizes the findings from the application of omics technologies in AD.

In the first 2 years of the pandemic, from late 2019 to late 2021, several studies were conducted to determine the experience of children during the continuous lockdowns, school closures and isolation from their friends, teachers or relatives. The studies conducted included children being raised in childcare facilities and children being raised in their own homes, in various parts of the world. Numerous children worldwide, in addition to the stress and difficulties experienced by adults and minors during these years of the coronavirus disease 2019 (COVID-2019) pandemic, have experienced physical, psychological and sexual abuse. The available data indicate that the number of children presenting to hospitals with injuries from abuse has increased, despite the fact that there was a decrease in the number of reports of child abuse during the lockdowns. The financial difficulties that a number of families have faced, and continue to face, comprise the most prominent risk factor for child neglect. Additionally, a marked decrease has also been noted in the provision of care to children in care homes as regards quality. This has been mainly due to a reduction in the number of employees, either as they themselves or someone they cared for became infected with COVID-19, or as the employees and care givers suffered from exhaustion brought on by the very difficult working conditions and very strict measures taken during this period of the pandemic.

The purpose of this study was to examine the effects of an 8-week stress management intervention to enhance resilience and coping techniques and decrease stress in adolescent students. Teenagers, 11 to 17 years old, recruited from two tertiary Adolescent Medicine Centers of the National and Kapodistrian University of Athens, Greece, were randomly assigned into two groups: the stress management group (n=24) and the control group (n=25). Resilience, stress, anxiety, everyday use of social media, school performance and cognitive skills were measured in adolescents of both groups, pre- and post-intervention. Post-intervention, the stress management group had significantly higher resilience scores and school performance self-evaluation scores, lower scores of stress, anxiety and everyday use of social media and better cognitive skills than the control group. Regarding cognitive skills, the stress management group significantly improved the speed of information processing and memory. Adolescents following stress management experienced significantly reduced stress from interacting with teachers/parents, from peer pressure, from school/leisure conflict as well as compulsive behaviours. With respect to resilience, the intervention improved adolescents’ individual skills and resources, relationships with primary caregivers, and environmental factors that facilitated the sense of belonging. Future studies of large adolescent samples are required to evaluate the long-term benefits of stress management techniques on adolescents' health and resilience, as well as the need of continued support to preserve these benefits throughout transition to adulthood.

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.(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.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.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).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.