Recent publications
Background: Hyponatremia has been identified as a marker of disease severity in various inflammatory conditions. However, its role in predicting acute complicated appendicitis (ACA) in children remains under investigation. This study evaluated the association between preoperative hyponatremia and ACA in a pediatric population. Methods: A retrospective study was conducted on pediatric patients treated for acute appendicitis in two major pediatric centers in Greece. Patients were categorized into groups based on the presence of acute uncomplicated appendicitis (AUA) and acute complicated appendicitis (ACA). Preoperative laboratory parameters were analyzed to identify potential predictors of ACA. Results: This study included 491 pediatric patients, with a mean age of 10 years. ACA patients exhibited significantly lower Na levels compared to those with AUA (136 vs. 138 mmol/L, p < 0.001). Hyponatremia (<135 mmol/L) was present in 38.4% of ACA cases compared to 2.2% of AUA cases (p < 0.001), and was associated with a significantly increased risk of ACA (OR = 18.30, p < 0.001). A sodium threshold of 135 mmol/L also demonstrated a sensitivity of 48% and a specificity of 92.1% Conclusions: Hyponatremia is a strong and specific predictor of ACA in children. When combined with other inflammatory markers, it may enhance early risk stratification, aiding in timely surgical decision making.
Background/Objectives: The objective of the study was to explore the combined effect of polymorphisms in the platelet glycoproteins Ia (GpIa) and IIIa (GpIIIa), along with the platelet-endothelial cell adhesion molecule-1 (PECAM-1) and P-Selectin genes, on the risk of recurrent pregnancy loss. Methods: This study involved 162 women with primary unexplained recurrent miscarriages and 60 fertile controls who had at least one uncomplicated full-term pregnancy without experiencing fetal loss. All participants were of Greek origin and were genotyped for four single nucleotide polymorphisms (SNPs), GpIa-C807T, GpIIIa-PlA1/PlA2, PECAM-1-C373G, and P-Selectin-A37674C, using pyrosequencing. A genetic risk score (GRS) was calculated in two forms: one based on the number of SNPs (dominant model) and the other based on the number of polymorphic alleles (additive model), utilizing logistic regression and receiver operator characteristic (ROC) analyses. Results: A statistically significant increase in the risk of miscarriage was observed with the number of polymorphic genes, with an odds ratio (OR) of 2.2 (95% confidence interval [CI]: 1.5 to 3.2, p < 0.001) for each additional SNP. The ROC analysis revealed an area under the curve (AUC) of 0.689 (95% CI: 0.614 to 0.763, p < 0.001). The presence of two or more polymorphic genes demonstrated a sensitivity of 69.8% and specificity of 65%, with an OR = 4.3 (95% CI: 2.3 to 8.0, p < 0.001). The performance of the GRS improved in younger patients and those experiencing late miscarriages. An AUC = 0.839 (95% CI: 0.749 to 0.930, p < 0.001) and an OR = 7.0 (95% CI: 2.8 to 17.8, p < 0.001) per SNP were achieved for the age group < 30 years. For subjects with second trimester fetal loss, the GRS yielded an AUC = 0.742 (95% CI: 0.610 to 0.874, p = 0.002) and an OR = 3.6 (95%OR = 7.0, 95% CI: 2.8 to 17.8) per SNP. The allelic GRS produced similar or slightly diminished results. Conclusions: This study highlights the promising potential of a genetic risk score based on four SNPs in predicting unexplained recurrent miscarriages, particularly in younger individuals and in cases of late miscarriage. These findings contribute to a deeper understanding of the epidemiology of unexplained recurrent miscarriage, emphasizing the role of platelet thrombophilia.
Introduction: Artificial lighting at night (ALAN) leads to pervasive light pollution, affecting ecosystems and human health globally. Satellite assessments reveal widespread nocturnal illumination worldwide and research indicates adverse health effects. Environmental light pollution disrupts natural cycles, affecting the behavior and reproduction of various organisms. Aim/Method: In this narrative review we aimed to present research on the effects of ALAN on glucose metabolism and diabetes and hone on its recently reported association with gestational diabetes (GDM). Results: Conflicting data exist on the effects of melatonin’s administration vis-à-vis glycemia, with some studies suggesting beneficial outcomes for patients with type 2 diabetes mellitus and insomnia. Ambient light influences plasma glucose, with bright light increasing both fasting and postprandial glucose levels. Perinatal light exposure is linked to later-life health risks and prenatal exposure to ALAN is linked to fetal macrosomia. Analyzing European ALAN data in conjunction with epidemiological records for GDM reveals a notable probable association. Additionally, recent research from China (one case-control and two cohort studies) has shown that exposure to ALAN during pregnancy significantly increases the risk of GDM. Discussion/Conclusion: Despite progress, interdisciplinary research is needed to understand the impact of light pollution on health, especially regarding disrupted light-dark cycles and physiological functions relevant to conditions like GDM. At present, the simplest advice for all people and particularly for women who anticipate pregnancy, or for pregnant women, is to ensure a totally dark environment during sleep time.
Sleep disorders and the resultant sleep deprivation (SD) are very common nowadays, resulting in depressed mood, poor memory and concentration, and various important changes in health, performance and safety. They may provoke further impairment of the cell lining of the blood vessels, as acting as a risk factor for cardiovascular disease (CVD) onset and progression. SD may lead to low neuronal regaining and plasticity, drastically affecting brain function. Thus, SD is a known risk factor for mental, behavioral and developmental disorders. Due to the inflammatory and oxidative stressful nature of SD, immune response modulation and antioxidants could be another therapeutic approach, apart from the already known symptomatic treatment with sedatives. Additionally, many drugs approved for other indications and under investigation, have been revisited due to their wide array of pharmacological activities. This review summarizes the main aspects of SD pathology and SD interrelated comorbidities and presents direct and indirect antioxidant molecules and drugs with multi-targeting potential that could assist in the prevention or management of these factors. A number of research groups have investigated well-known antioxidant compounds with multi-targeting cores, combining structural characteristics with properties including antiinflammatory, metal chelatory, gene transcription and immune modulatory that may add towards the effective SD and its associated comorbidities treatment.
Morphogens, which are non-classical transcription factors, according to several studies, display a crucial role in tissue patterning, organ architecture establishment, and human disease pathogenesis. Recent advances have expanded the morphogen participation to a wide range of human diseases. There are many genetic syndromes caused by mutations of components of morphogen signaling pathways. The aberrant morphogen pathways also promote cancer cell maintenance, renewal, proliferation, and migration. On the other hand, exosomes and their application in the biomedical field are of evolving significance. The evidence that membrane structures participate in the creation of morphogenic gradience and biodistribution of morphogen components renders them attractive as new therapeutic tools. This intercellular morphogen transport is performed by cell-derived structures, mainly exosomes and cytonemes, and extracellular substances like heparan sulphate proteoglycans and lipoproteins. The interaction between morphogens and Extracellular Vesicles has been observed at first in the most studied insect, Drosophila, and afterwards analogous findings have been proved in vertebrates. This review presents the protagonists and mechanisms of lipid-modified morphogens (Hedgehog and Wnt/β-catenin) biodistribution.
Intrauterine growth restriction (IUGR) is the second most common obstetric complication after preterm labor. Appropriate trophoblast differentiation and placental structure, growth and function are key for the maintenance of pregnancy and normal fetal growth, development and survival. Extravillous trophoblast cell proliferation, migration and invasion are regulated by molecules produced by the fetomaternal interface, including autocrine factors produced by the trophoblast, such as insulin-like growth factor (IGF)-1. The aim of the present study was to investigate expression patterns of IGF-1Ea isoform in IUGR placenta compared with appropriate for gestational age (AGA) pregnancies. Placental frozen tissues were collected from 13 AGA and 15 IUGR third trimester pregnancies for detection of IGF-1Ea mRNA expression using reverse transcription-quantitative PCR. Formalin-fixed paraffin-embedded samples from 15 AGA and 47 IUGR pregnancies were analyzed immunohistochemically for the identification and localization of the IGF-1Ea peptide and comparison of clinical and histopathological parameters. To the best of our knowledge, the present study is the first to show IGF-1Ea expression in third trimester human placenta. The results indicated that similar IGF-1Ea mRNA expression levels were present in placental specimens from both groups. Cytoplasmic IGF-1Ea expression was localized in the perivillous syncytiotrophoblast, extravillous trophoblast and endothelium of the villous and decidual vessels in both groups. No significant difference in the scores and intensity of IGF-1Ea expression in perivillous syncytiotrophoblasts were noted in the IUGR vs. AGA pregnancies. Most IUGR cases showed negative IGF-1Ea expression in the extravillous trophoblast, whereas AGA pregnancies showed predominantly positive immunostaining. A sex-specific expression pattern was noted in the extravillous trophoblast, with negative IGF-1Ea expression in the placentas of female IUGR cases. Additionally, positive immunostaining for IGF-1Ea peptide in fetal villous and maternal decidual vessels, was more frequently observed in the IUGR group compared with AGA. In conclusion, no difference in total IGF-1Ea mRNA placental expression was observed between IUGR and AGA pregnancies, likely due to heterogeneity of histological structures expressing this isoform. Negative IGF-1Ea immunohistological expression in the extravillous trophoblast from IUGR placentas, associated with histological changes of maternal malperfusion, may reflect the involvement of this isoform in defective placentation. The presence of IGF-1Ea peptide in the endothelium of the villous vessels in IUGR placentas may indicate a reactive autocrine regulation to compensate for malperfused villi in IUGR pregnancy by regulating angiogenesis and vasodilation. The observed sex differences in IGF-1Ea expression between IUGR and AGA placentas may indicate interactions between sex hormones and selective IGF-1 binding proteins in regulating IGF-1Ea synthesis; however, this requires further elucidation.
Historically, the transgender population has faced prejudice and discrimination within society. The purpose of diagnostic terms is to direct clinical care and facilitate insurance coverage. However, the existence of a medical diagnosis for gender nonconformity can exacerbate the stigmatization of transgender people with adverse consequences on their emotional health and social life. Whether transgenderism and gender dysphoria are indeed a psychopathological condition or even any kind of nosological entity is a contested issue. Many advocates of human rights, trans activists, social scientists, and clinicians support either the removal of gender incongruence from the list of mental disorders or at least its transfer to a separate category. Reforming the classification is an intermediate step toward depathologization and permits access to transgender-related care. Nonetheless, it partly preserves the stigma associated with abnormality and puts the availability of psychiatric care at risk. A more radical approach dictates that the classification of diseases serves exclusively medical purposes and must be dissociated from the respect for the legitimacy of one’s autonomy and dignity. In the long term, only a swing in societal values can detach stigma from mental and physical illnesses. Enhancing collective respect for life, human rights, and diversity is the best way to achieve cohesion and well-being among members of society. Health professionals can be pioneers of social change in this field.
Background
Early life infections (ELIs), encompassing both viral and bacterial types, occur within the first six months of life. Influenced by genetic host factors and environmental conditions, the relationship between ELIs and subsequent allergic manifestations, particularly cow's milk protein allergy (CMPA) and atopic dermatitis (AD), is complex and not fully understood.
Objective
The aim of the current study was to examine the potential interplay between nutrition, infections, and allergic manifestations in the first six months of life in infants with a family history of allergies, who were either exclusively breastfed (EBF) or fed a combination of breast milk and standard (SF) or partially hydrolyzed infant formula (pHF).
Methods
The Allergy Reduction Trial (ART) is a multicenter, randomized controlled trial involving 551 participants. From birth, these participants were divided into three groups: Exclusive Breastfeeding (EBF), Partially Hydrolyzed Formula (pHF), and Standard Formula (SF). ELIs, defined as viral and bacterial infections occurring during the first 6 months, and outcomes (AD, CMPA) were recorded through questionnaires (i.e., SCORAD and CоMiSS) and clinical assessments.
Results
The relative risk (RR) for CMPA in infants with ELIs was 0.20 (95% CI: 0.07–0.58), highlighting a protective effect of ELIs against CMPA development. Notably, the incidence of CMPA was significantly lower in infants who experienced ELIs compared to those without (3% vs. 13.4%, p = 0.001), with no cases of CMPA observed at 6 months in exclusively breastfed (EBF) infants with ELIs. For AD, a trend was observed where the incidence was lower in infants with ELIs who were fed with pHF at 6.5%, compared to those fed with SF at 18.2% (p = 0.092), suggesting a potential protective effect of ELIs in the pHF group against AD development.
Conclusion
The study highlights a potential protective role of ELIs in reducing the risk of CMPA, particularly in EBF infants. Furthermore, it suggests a trend towards lower AD incidence in infants fed with pHF, highlighting the complex interplay between early microbial exposures, feeding practices, and immune development. Further research is warranted to unravel this challenging relationship and appropriately inform early life allergy prevention strategies
Introduction: The seasonality of human births has been studied globally for over two centuries, revealing diverse patterns across populations shaped by intricate interactions involving both biological and socio-cultural factors. This study offers a thorough examination of national birth data in Greece spanning from 1956 to 2022, aiming to elucidate long-term trends and changes in seasonal birth patterns.
Materials and methods: Data on live births in Greece were categorized by month based on national registries, and the analysis of birth seasonality was conducted annually. The Edwards method was utilized to evaluate birth seasonality by calculating the peak angle (PA), which identifies the center of the seasonal birth distribution. Additionally, the peak-to-low ratio (PLR) was computed for each year to serve as an indicator of the amplitude of birth seasonality. To investigate trends and temporal changes, joinpoint regression analysis was employed, specifically focusing on the annual percentage change (APC) within defined segments, along with a 95% confidence interval (95% CI).
Results: A total of 8,144,465 live births were recorded between 1956 and 2022. Birth seasonality was statistically significant for all examined years. The results revealed a progressive shift in the concentration of births to the second half of the year, transitioning from a peak in January and February to two significant major peaks in July and September. Additionally, in the last two decades, the lowest birth rates were observed in spring, particularly in April, as well as in December. The PA shifted significantly over time, moving from mid-January in 1956 to late August in 2022, with an APC of 39.6 (95% CI: 17.4 to 99.7) during 1956-1960 and 7.5 (95% CI: 2.2 to 11.3) during 1960-1975. Between 1975 and 2022, the trend continued at a lower stable rate (APC = 1.0, 95% CI: 0.2 to 1.5). The PLR, after a brief upward trend during 1956-1960 (APC = 6.0, 95% CI: 3.1 to 11.3), exhibited a statistically significant decline in seasonal amplitude from 1960 to 1992 (1960-1964: APC = -5.5, 95% CI: -8.6 to -2.4, 1964-1992: APC = -0.4, 95% CI: -0.8 to -0.2), and relatively stabilized during the last thirty years (1992-2022).
Conclusions: This study highlights significant changes in birth seasonality in Greece, marked by a shift in the distribution of births toward the second half of the year and a transition from peaks in births during January and February to two major surges in July and September. These trends reflect evolving reproductive behaviors in the Greek population and hold important implications for reproductive and perinatal healthcare in the country.
Tobacco smoke exposure remains a significant public health concern, particularly for lactating women and their infants. Despite widespread awareness of the harms of smoking during pregnancy, many women continue to smoke postpartum, directly impacting lactation success and infant health. Studies have shown that nicotine, the primary component of tobacco smoke, inhibits prolactin production and the milk ejection reflex, resulting in a decreased milk supply and poor breastfeeding outcomes. Additionally, the presence of harmful chemicals in tobacco smoke, such as cadmium and lead, can accumulate in breast milk, exposing infants to toxic substances with potential long-term health implications. Maternity professionals play a crucial role in supporting smoking cessation efforts among postpartum women, providing evidence-based counseling, resources, and referrals to cessation programs. This review aims to provide an update for maternity professionals on the effects of tobacco smoke exposure on lactation and breastfeeding outcomes. In this review, we will explore the physiological mechanisms through which tobacco smoke components can interfere with lactation. Furthermore, we will discuss the challenges faced by lactating women who smoke, including increased risk of mastitis, reduced breastfeeding duration, and impaired infant growth and development. Finally, we will highlight emerging research on novel interventions to reduce the adverse effects of tobacco smoke exposure on lactation, including pharmacological treatments and behavioral interventions tailored to postpartum women.
Introduction/Aim: Central sensitivity to thyroid hormones refers to the responsiveness of the hypothalamic–pituitary–thyroid (HPT) axis to changes in circulating free thyroxine (fT4). Although dose–response relationships between thyroid hormones per se and urinary iodine (UI) levels have been observed, central sensitivity to thyroid hormones in relation to UI remains unexplored. The aim of the present study was to evaluate central sensitivity to thyroid hormones (by means of the Thyroid Feedback Quantile-based Index [TFQI], which is a calculated measure, based on TSH and fT4, that estimates central sensitivity to thyroid hormones) in pregnancy and to assess whether it differs according to gestational age and/or iodine intake. Materials and Methods: One thousand, one hundred and two blood and urine samples were collected from pregnant women (with a mean age ± SD of 30.4 ± 4.6 years) during singleton pregnancies; women with known/diagnosed thyroid disease were excluded. Specifically, TSH and fT4, anti-thyroid peroxidase antibodies and UI were measured in each trimester and at two months postpartum, while the TFQI was calculated for all the study samples. After the elimination of outliers, statistical analysis was conducted with analysis of variance (ANOVA) for the variables versus time period, while Pearson’s correlation was used to assess the TFQI versus UI. Results: The mean TFQI index ranged from −0.060 (second trimester) to −0.053 (two months postpartum), while the corresponding UI was 137 and 165 μg/L, respectively. The TFQI-UI correlation was marginally negative (Pearson r: −0.323, p: 0.04) and significantly positive (r: +0.368, p: 0.050) for UI values over 250 μg/L, in the first and the second trimesters of pregnancy, respectively. Discussion: The TFQI is a new index reflecting central sensitivity to thyroid hormones. A lower TFQI indicates higher sensitivity to thyroid hormones. In our sample, the TFQI was mainly positively related to iodine intake in the second trimester of pregnancy (following the critical period of organogenesis). Thus, the observed changes in the TFQI may reflect the different ways of the central action of thyroid hormones, according to the phase of pregnancy. These results have the potential to enhance our comprehension of the changes in the HPT axis’ function via variations in central sensitivity to thyroid hormones and its interplay with nutritional iodine status during pregnancy.
Transgender persons need to regularly interact with health services and practitioners for both gender-transition purposes and routine care. Communication between clinicians and patients is a key element of health care. However, barriers to communication with transgender people in the health care context are usual. They typically include a lack of willingness among health staff to care for trans patients, an adherence to cisnormativity and misgendering by clinicians, and the existence of a displeasing climate during the interaction. Miscommunication generates a series of adverse consequences, including the avoidance of health care by patients and the social marginalization of transgender people. The implementation of novel health policies and organizational restructuring are important steps to create a safe environment for the trans population within health systems. Modification of administrative procedures as well as training and advice for health practitioners are also necessary to facilitate communication with trans people and improve health outcomes among this underprivileged population. The establishment of a society with equal rights among its members and a life without discriminations is the ultimate goal.
Background
This study aims to investigate the correlation between the rising preterm birth rate (PBR) in Greece from 1991 to 2022 and the incidence of multiple births.
Methodology
Official data on live births in Greece from 1991 to 2022 were sourced from the Hellenic Statistical Authority. The PBR, defined as the number of live births occurring at <37 gestational weeks, and the multiple birth rate (MBR), representing live births from multifetal gestations, were calculated per 100 total live births. The relationship between the PBR and the MBR was evaluated using the non-parametric Spearman’s rank correlation coefficient (rho). This association was confirmed through linear regression models, with MBR as the independent variable and PBR as the dependent variable, calculating the beta coefficient (β) and the coefficient of determination (R-squared).
Results
A very strong direct positive correlation was identified between PBR and MBR throughout the study period, with a Spearman’s rho of 0.950 (p < 0.001). This conclusion was further supported by the linear regression model, which yielded a β coefficient of 3.32 (95% confidence interval = 2.78 to 3.86, p < 0.001). The R-squared was 0.838, indicating that the change in MBR explained 83.8% of the rise in PBR. The strongest correlations were observed for moderate PBR (32-33 weeks) with a rho of 0.962 (p < 0.001) and late PBR (34-36 weeks) with a rho of 0.940 (p < 0.001). During the period of a steep increase in prematurity rates in the country (1991-2011), an almost perfect correlation between PBR and MBR (rho = 0.987, p < 0.001) was noted. However, in recent years (2011-2022), characterized by a marginal increase in PBR, this association diminished, with a rho of 0.655 (p = 0.021).
Conclusions
This analysis revealed a strong positive correlation between the PBR and MBR in Greece from 1991 to 2022, underscoring the significant impact of multiple pregnancies on the substantial increase in preterm births within the Greek population.
Insulin-like Growth Factor-1 (IGF-1) is a crucial mitogenic factor with important functions in the mammary gland, mainly through its interaction with the IGF-1 receptor (IGF-1R). This interaction activates a complex signaling network that promotes cell proliferation, epithelial to mesenchymal transition (EMT) and inhibits apoptosis. Despite extensive research, the precise molecular pathways and intracellular mechanisms activated by IGF-1, in cancer, remain poorly understood. Recent evidence highlights the essential roles of IGF-1 and its isoforms in breast cancer (BC) development, progression, and metastasis. The peptides that define the IGF-1 isoforms—IGF-1Ea, IGF-1Eb, and IGF-1Ec—act as key points of convergence for various signaling pathways that influence the growth, metastasis and survival of BC cells. The aim of this review is to provide a detailed exami-nation of the role of the mature IGF-1 and its isoforms in BC biology and their potential use as possible therapeutical targets.
Hypertensive disorders of pregnancy affect approximately 5% to 10% of pregnant women. Eclampsia is a serious hypertensive disorder that is primarily characterized by the onset of grand mal seizure activity in the absence of other causative conditions. While eclampsia is diagnosed clinically, laboratory tests are recommended to assess for complications. Treatment strategies for eclampsia focus on controlling seizures and managing hypertension. Acute care during a seizure is critical because of the need for immediate medical interventions, including the management of the airway, breathing, and circulation, as well as ensuring the safety of the patient during convulsions. Magnesium sulfate is the preferred anticonvulsant drug. Care must be taken during administration to prevent magnesium toxicity. Antihypertensive drugs used in eclampsia include labetalol, hydralazine and nifedipine. The definitive treatment of eclampsia is delivery. Close monitoring of both mother and fetus is important to identify any indications for delivery. The timing and mode of delivery depend on obstetric indications, the severity of eclampsia, the gestational age of the fetus, and the overall clinical status of the patient. Neuraxial anesthesia is the anesthesia of choice for conscious, seizure-free, and with stable vital signs women undergoing cesarean section.
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