Publications

Milk is a biological fluid with a dynamic composition of micronutrients and bioactive molecules that serves as a vital nutrient source for infants. Milk composition is affected by multiple factors, including genetics, geographical location, environmental conditions, lactation phase, and maternal nutrition, and plays a key role in dictating its microbiome. This study addresses a less-explored aspect, comparing the microbial communities in human breast milk with those in mature milk from species that are used for milk consumption. Since mature animal milk is used as a supplement for both the infant (formula) and the child/adolescent, our main aim was to identify shared microbial communities in colostrum and mature human milk. Using 16S rRNA metagenomic sequencing, we focused on characterizing the milk microbiota in the Northern Greek population by identifying shared microbial communities across samples and comparing the relative abundance of prevalent genera. We analyzed ten human milk samples (from five mothers), with five collected three days postpartum (colostrum) and five collected thirty to forty days postpartum (mature milk) from corresponding mothers. To perform an interspecies comparison of human milk microbiota, we analyzed five goat and five bovine milk samples from a local dairy industry, collected fifty to seventy days after birth. Alpha diversity analysis indicated moderate diversity and stability in bovine milk, high richness in goat milk, and constrained diversity in breast milk. Beta diversity analysis revealed significant distinctions among mammalian species, emphasizing both presence/absence and abundance-based clustering. Despite noticeable differences, shared microbial components underscore fundamental aspects across all mammalian species, highlighting the presence of a core microbiota predominantly comprising the Proteobacteria, Firmicutes, and Actinobacteriota phyla. At the genus level, Acinetobacter, Gemella, and Sphingobium exhibit significant higher abundance in human milk compared to bovine and goat milk, while Pseudomonas and Atopostipes are more prevalent in animal milk. Our comparative analysis revealed differences and commonalities in the microbial communities of various mammalian milks and unraveled the existence of a common fundamental milk core microbiome. We thus revealed both species-specific and conserved microbial communities in human, bovine, and goat milk. The existence of a common core microbiome with conserved differences between colostrum and mature human milk underscores fundamental similarities in the microbiota of milk across mammalian species, which could offer valuable implications for optimizing the nutritional quality and safety of dairy products as well as supplements for infant health.

During blastocyst implantation, the maternal endometrial response to the invading semi-allograft has characteristics of an acute, aseptic inflammatory response. However, once implanted, the embryo suppresses this response and prevents rejection. Simultaneously, the mother's immune system prevents a graft VS. host reaction deriving from the fetal immune system. We have shown that embryonic trophoblast and maternal decidua cells, i.e., cells located in the interface between the fetal placenta and the maternal endometrium, produce corticotropin-releasing hormone (CRH) and express Fas ligand. CRH may play a crucial role in the implantation and the anti-rejection process that protects the fetus from the maternal immune system, primarily by killing activated T cells through the Fas-FasL interaction. In experimental animals, type 1 CRH receptor (CRH-R1) blockade by antalarmin, a specific type 1 CRH receptor antagonist, decreased implantation sites by approximately 70%. CRH is also involved in controlled trophoblast invasion, by downregulating the synthesis of the carcinoembryonic antigen-related cell adhesion molecule 1 by extravillous trophoblast cells. IN VITRO findings showed that CRH-R1 blockade by antalarmin increased trophoblast invasion by approximately 60%. Defective uterine CRH/CRH-R1 system during early pregnancy may be implicated in the pathophysiology of recurrent miscarriage, placenta accreta, and preeclampsia.

Endocrine dysfunction may cause psychiatric symptoms and, vice versa, psychiatric diseases may lead to endocrine alterations. The adrenal as the end organ of both the hypothalamic-pituitary-adrenocortical and sympatho-adrenal axes is subject to the functional changes of the stress system. Thus, increased adrenal gland weight was observed previously in victims of violent suicide. This study was designed to analyze the morphological and morphodynamic changes of adrenals from suicide victims. We investigated 30 adrenals obtained from 15 suicide victims using immunohistochemistry and a computerized video system. In addition, apoptosis and cell proliferation were analyzed. We found a significant enlargement of the adrenal cortex to 158.8% (SD = 29.8%, p < 0.01) that was restricted to the two inner zones only (zona reticularis, 161.6 ± 35.3%; zonafasciculata, 186.4 ± 34.4%). This increase in adrenocortical size correlated with a decrease in the number of apoptotic cells within the zona fasciculata. In conclusion, these results clearly demonstrate chronic structural adrenal changes in suicide victims. The adrenal gland mirrors the functional changes of the stress system which leaves an imprint on the morphology of the gland.

Pediatric cancer and its treatment may have an impact on the neurocognitive functions of childhood cancer survivors (CCS). The aim of the present meta‑analysis was to compare the intelligence quotient (IQ) scores between CCS of acute lymphoblastic leukemia (ALL) and controls. A comprehensive electronic search identified original research articles that reported scores of the Wechsler Intelligence Scale (WISC; WISC‑III, WISC‑IV and WISC‑R) for children and adolescents, aged 6‑16 years at evaluation, survivors of ALL and healthy controls. The included CCS had completed anticancer treatment and were in remission at the time of assessment. A total of 16 studies were included in the meta‑analysis, out of 128 extracted studies, and involved a total of 1,676 children and adolescents: 991 CCS (ALL) and 685 healthy controls. Among the studies, a random effects model revealed a moderate estimate of effect size [standardized mean difference (SMD), ‑0.78; 95% CI, ‑1.05 to ‑0.50], indicating that the WISC scores for total IQ were significantly lower in the CCS than in the controls. The mean total IQ range was 85.2‑107.2 in the CCS and 88.4‑114.1 in the controls. The difference in the mean total IQ between controls and CCS ranged from ‑13.8 to 20.6. As regards the WISC scores for verbal IQ, 11 studies were included. A random effects model revealed a moderate estimate of effect size (SMD, ‑0.71; 95% CI, ‑1.05 to ‑0.38), indicating that the WISC scores for verbal IQ were significantly lower in the CCS than in the controls. Among the 9 studies that had available data for performance IQ scores, a fixed effect model revealed a moderate estimate of effect size (SMD, ‑0.80; 95% CI, ‑1.09 to ‑0.52), indicating that the WISC scores for performance IQ were significantly lower in the CCS than in the controls. As the survival rates of children and adolescents with ALL are steadily increasing, regular, lifelong follow‑up for neurocognitive late effects is imperative in order to improve their education and employment prospects and overall, their quality of life.

Previous studies have showed that perceived stress (PS) in patients with multiple sclerosis (MS) constitutes an important factor for disease onset, relapse, symptomatology and psychological adjustment.Objectives:The aim of this pilot cross-sectional study was to examine the role of self-esteem in PS, after controlling for sociodemographical characteristics, depression and personality in MS patients.Methods:Sixty-six relapsing-remitting MS patients (66.67% females, mean age of 40 ± 11.1 years old, mean duration of disease 133.6 ± 128.8 months) were studied. Perceived stress, self-esteem, depression and personality type were assessed using self-administered questionnaires. Hierarchical multivariate regression modelling was used.Results:Higher education and depression and lower self-esteem were independently and significantly associated with increased PS, accounting for 40.5% of its variance. Univariate analyses revealed that low extroversion and openness and higher neurotism were associated with higher PS, although no significant after adjusting for other factors.Discussion:Although our findings need further confirmation, psychological interventions targetting self-esteem are strongly encouraged.

Obesity and cardiovascular disease (CVD) often co-exist, but the pathophysiologic mechanisms that link the two are not fully understood. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is involved in the modification of lipids within atheromatous plaques. Recently, circulating Lp-PLA2 was found to be predictive of thromboembolic episodes in adults, independently of a variety of other potential risk factors, including markers of inflammation, renal function, and hemodynamic stress. However, the function of this lipase and its importance as a biomarker in childhood obesity is much less studied. The aim of the study was to study Lp-PLA2, a non-traditional risk factor of CVD, in obese children.Sixty-seven lean [39 boys and 28 girls, mean body mass index (BMI) z-score -0.2±0.8] and 66 obese (32 boys and 34 girls, mean BMI z-score 4.4±1.2) age-matched (p=0.251) children, aged 6-12 years, were studied. BMI z-score was calculated based on the Greek BMI growth curves, and children were categorized as obese according to the Cole criteria. All children underwent physical examination and a fasting morning blood sample was obtained for glucose, insulin, lipid profile, and Lp-PLA2 assessment. Plasma concentrations of Lp-PLA2 were determined by a commercially available Lp-PLA2 enzyme-linked immunosorbent assay kit (PLAC Test), while other measurements were performed using standard methods.Plasma Lp-PLA2 levels were significantly higher in obese children (322.5±77.8 ng/mL) compared with normal-weight ones (278.0±64.4 ng/mL, p<0.001). Lp-PLA2 concentrations were significantly correlated with the BMI z-score (p=0.004). Receiver operating characteristic analysis on Lp-PLA2 values resulted in significant areas under the curve (AUC) for distinguishing between obese and normal-weight groups of children (AUC, 0.726; p<0.001).We found significantly higher Lp-PLA2 levels in obese children than lean controls. Interestingly, they all had levels >200 ng/mL, which are considered to correlate with atherosclerosis and a high thromboembolic risk in adults. The positive correlation of Lp-PLA2 with BMI suggests that Lp-PLA2 might be the link between obesity and increased cardiovascular risk, which can be elevated even at a very young age. Measurement of Lp-PLA2 in plasma could therefore represent a further biomarker for assessing increased CVD risk in obese children and adolescents.