Publications

Sleep apnea and associated daytime sleepiness and fatigue are common manifestations of mainly obese middle-aged men. The onset of sleep apnea peaks in middle age, and its morbid and mortal sequelae include complications from accidents and cardiovascular events. The pathophysiology of sleep apnea remains obscure. The purpose of this study was to test three separate, albeit closely related, hypotheses. 1) Does sleep apnea contribute to the previously reported changes of plasma cytokine (tumor necrosis factor-α and interleukin-6) and leptin levels independently of obesity? 2) Among obese patients, is it generalized or visceral obesity that predisposes to sleep apnea? 3) Is apnea a factor independent from obesity in the development of insulin resistance? Obese middle-aged men with sleep apnea were first compared with nonapneic age- and body mass index (BMI)-matched obese and age-matched lean men. All subjects were monitored in the sleep laboratory for 4 consecutive nights. We obtained simultaneous indexes of sleep, sleep stages, and sleep apnea, including apnea/hypopnea index and percent minimum oxygen saturation. The sleep apneic men had higher plasma concentrations of the adipose tissue-derived hormone, leptin, and of the inflammatory, fatigue-causing, and insulin resistance-producing cytokines tumor necrosis factor-α and interleukin-6 than nonapneic obese men, who had intermediate values, or lean men, who had the lowest values. Because these findings suggested that sleep apneics might have a higher degree of insulin resistance than the BMI-matched controls, we studied groups of sleep-apneic obese and age- and BMI-matched nonapneic controls in whom we obtained computed tomographic scan measures of total, sc, and visceral abdominal fat, and additional biochemical indexes of insulin resistance, including fasting plasma glucose and insulin. The sleep apnea patients had a significantly greater amount of visceral fat compared to obese controls (<0.05) and indexes of sleep disordered breathing were positively correlated with visceral fat, but not with BMI or total or sc fat. Furthermore, the biochemical data confirmed a higher degree of insulin resistance in the group of apneics than in BMI-matched nonapneic controls. We conclude that there is a strong independent association among sleep apnea, visceral obesity, insulin resistance and hypercytokinemia, which may contribute to the pathological manifestations and somatic sequelae of this condition.

Thalassemia Major (TM) is a hereditary disease caused by defective globin synthesis. Because of the significant increase in life expectancy, these patients suffer from various health conditions, including endocrinopathies and low bone mineral density. Aim: The aim of the present study was to evaluate the fracture incidence regarding the markers of bone metabolism, bone mineral density and treatment of osteoporosis as well as treatment of comorbidities. Methods: Sixty-four patients with TM (32 men and 32 women) participated in a cross-sectional study design. The patients were recruited from “Aghia Sofia” Children’s Hospital and evaluated using dual-energy X-ray absorptiometry (DXA) of the lumbar spine and femoral neck and with markers of bone remodeling including receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), C-terminal telopeptide (CTX), and sclerostin. Results: The statistical analysis of markers of bone metabolism in relation to fractures revealed no statistical significance. However, statistical analysis of bone mineral density and markers of bone metabolism in relation to fractures was also not significant. Conclusions: In TM patients, fractures are not related to bone mineral density. Maybe some other conditions are the cause, haemosidirosis, drugs, comorbid conditions.

recently sent a letter to the editor 1 raising issues of reliability and validity of our study "Stress management and in Vitro Fertilization (IVF): A pilot randomized controlled trial". 2 Their comments focused on the default of the registration, the absence of any mention of case dropout, the ambiguity in the details of IVF treatment and the lack of specific figures on the background of the participants.However, the principles of CONSORT 2010 cannot be applied to Pilot Randomized and Feasibility Trials, only to Randomized Trials (RTs) or Randomized Controlled Trials (RCTs).Similarly, the CONSORT Extension 2016 suggested some principles for Pilot and Feasibility Trials, but again it does not directly apply to internal pilot studies, non-randomized pilot and feasibility studies, or phase II studies. 3,4Many international journals do not require registration for Pilot and Feasibility Trials, but only for RTs or RCTs, 5 granted that clinical trial registration is not an indicator of low risk of bias. 6hanks to the useful comments by Komiya et al, our article 2 now includes online "Supplementary Materials" in which we clarify all their points one by one.Specifically, the Material and Method section of Supplementary Materials includes details for the Registration, the Flow Chart and the IVF Treatment, and the Results section includes details for the Background of the Participants.Thus, we believe that the level of reliability and validity of the study can be now examined and ensured.

Osteosarcopenic obesity was recently described as a variant phenotype of obesity, mainly observed in old age. This nested case-control study was performed to detect the differences in body composition between young, healthy overweight/obese and healthy lean populations of both genders. Our null hypothesis was that except for the fat mass, there would be absence of body composition differences, namely skeletal muscle and bone masses, between the groups.We used an advanced bio-impedance device to determine the body composition and measured circulating CRP (hsCRP) and diurnal salivary cortisol concentrations, as indices of inflammation and chronic stress, respectively. Overall, 2551 subjects aged 18-21 years participated in the study.The healthy lean group included 1072 participants [900 males (84%) and 172 females (16%)], and the healthy overweight/obese group included 1479 participants [74 males (5%) and 1405 females (95%)]. Healthy overweight/obese participants presented with an increased fat mass (P < 0·001), as expected, but lower muscle (P < 0·001) and bone (P < 0·001) masses than lean controls. These findings were accompanied by increased extracellular water compartments, circulating hsCRP levels and evening salivary cortisol concentrations in the healthy overweight/obese group.Our study suggests that 'osteosarcopenic' elements exist even in very young populations. These may represent a 'precursor' or forme fruste of the osteosarcopenic obesity phenotype in young healthy overweight/obese subjects, who may progressively develop osteosarcopenia in its full form at an older age. Our study highlights the significance of body composition analysis in medical practice, improving prevention and alleviating later health-related economic burden.

RNA modifications have recently become the focus of attention due to their extensive regulatory effects in a vast array of cellular networks and signaling pathways. Just as epigenetics is responsible for the imprinting of environmental conditions on a genetic level, epitranscriptomics follows the same principle at the RNA level, but in a more dynamic and sensitive manner. Nevertheless, its impact in the field of cardiovascular disease (CVD) remains largely unexplored. CVD and its associated pathologies remain the leading cause of death in Western populations due to the limited regenerative capacity of the heart. As such, maintenance of cardiac homeostasis is paramount for its physiological function and its capacity to respond to environmental stimuli. In this context, epitranscriptomic modifications offer a novel and promising therapeutic avenue, based on the fine‑tuning of regulatory cascades, necessary for cardiac function. This review aimed to provide an overview of the most recent findings of key epitranscriptomic modifications in both coding and non‑coding RNAs. Additionally, the methods used for their detection and important associations with genetic variations in the context of CVD were summarized. Current knowledge on cardiac epitranscriptomics, albeit limited still, indicates that the impact of epitranscriptomic editing in the heart, in both physiological and pathological conditions, holds untapped potential for the development of novel targeted therapeutic approaches in a dynamic manner.

Resistance to glucocorticoid therapy has been observed in patients with autoimmune/inflammatory diseases and may be related to the inflammatory process itself. The aim of this study was to examine the ability of tumor necrosis factor α (TNFα, a proinflammatory cytokine) and interleukin (IL)-10 (an anti-inflammatory cytokine) to differentially regulate the sensitivity of human monocytes/macrophages to glucocorticoids. To accomplish this, we first analyzed the pattern of TNFα and IL-10 inhibition by dexamethasone in LPS-stimulated whole-blood cell cultures. Second, we studied the modulation of the sensitivity of these cells to dexamethasone by preincubation with TNFα or IL-10 and measurement of LPS-stimulated IL-6 secretion. In addition, we evaluated the effect of dexamethasone on phorbol-myristate-acetate-stimulated IL-1 receptor antagonist secretion by the human monocytic cell line U937. Finally, we investigated whether the modulation of corticosensitivity in TNFα- and IL-10-pretreated U937 cells was related to a change of the glucocorticoid receptor concentration and affinity. Dexamethasone had different effects on LPS-induced TNFα and IL-10 secretion; whereas it suppressed TNFα in a dose-dependent fashion, its effect on IL-10 secretion was biphasic, producing stimulation at lower, and inhibition at higher doses. The concentration of LPS employed influenced the effect of dexamethasone on IL-10 secretion (P < 0.001). Pretreatment with TNFα diminished, and with IL-10 improved, the ability of dexamethasone to suppress IL-6 secretion in whole-blood cell cultures (P < 0.01 for both) and to enhance IL-1 receptor antagonist secretion by U937 cells (P < 0.05 for both). TNFα decreased (P < 0.001), while IL-10 increased (P < 0.001), the concentration of dexamethasone binding sites in these cells, with no discernible effect on their binding affinity. We conclude that glucocorticoids differentially modulate TNFα and IL-10 secretion by human monocytes in a LPS dose-dependent fashion and that the sensitivity of these cells to glucocorticoids is altered by TNFα or IL-10 pretreatment; TNFα blocks their effects, whereas IL-10 acts synergistically with glucocorticoids. This is accompanied by opposite glucocorticoid receptor changes, respectively opposing and favoring glucocorticoid actions. This study suggests that the pattern of pro-/antiinflammatory cytokine secretion may alter the response of patients to glucocorticoid therapy.