ENaC gene variants and their involvement in Covid­19 severity.

Epidemiological studies report the association of diverse cardiovascular conditions with coronavirus disease 2019 (COVID-19), but the causality has remained to be established. Specific genetic factors and the extent to which they can explain variation in susceptibility or severity are largely elusive. The present study aimed to evaluate the link between 32 cardio-metabolic traits and COVID-19. A total of 60 participants were enrolled, who were categorized into the following 4 groups: A control group with no COVID-19 or any other underlying pathologies, a group of patients with a certain form of dyslipidemia and predisposition to atherosclerotic disease, a COVID-19 group with mild or no symptoms and a COVID-19 group with severe symptomatology hospitalized at the Intensive Care Unit of Sotiria Hospital (Athens, Greece). Demographic, clinical and laboratory data were recorded and genetic material was isolated, followed by simultaneous analysis of the genes related to dyslipidemia using a custom-made next-generation sequencing panel. In the COVID-19 group with mild or absent symptoms, the variant c.112C>T:p.P38S was detected in the sodium channel epithelial 1 subunit α (SCNN1A) gene, with a major allele frequency (Maf) of <0.01. In the COVID-19 group with severe symptoms, the variant c.786G>A:p.T262T was detected in the SCNN1B gene, which encodes for the ß-subunit of the epithelial sodium channel ENaC, with a Maf <0.01. None of the two rare variants were detected in the control or dyslipidemia groups. In conclusion, the current study suggests that ENaC variants are likely associated with genetic susceptibility to COVID-19, supporting the rationale for the risk and protective genetic factors for the morbidity and mortality of COVID-19.

The Intersection of Artificial Intelligence and Precision Endocrinology.

Bioinformatics and artificial intelligence (AI) have emerged as transformative tools in modern medicine, revolutionising the landscape of medical diagnosis and treatment. Herein, we provide an overview of the synergistic relationship between bioinformatics and AI, elucidating their pivotal roles in deciphering complex biological data and advancing precision medicine and, in particular, endocrinology. We explore various applications of bioinformatics and AI in medical research, including genomic analysis, drug discovery, disease diagnosis, and personalised treatment strategies. Additionally, we discuss challenges and future directions in leveraging these technologies to enhance healthcare outcomes.

Multi­label classification of biomedical data.

Biomedical datasets constitute a rich source of information, containing multivariate data collected during medical practice. In spite of inherent challenges, such as missing or imbalanced data, these types of datasets are increasingly utilized as a basis for the construction of predictive machine-learning models. The prediction of disease outcomes and complications could inform the process of decision-making in the hospital setting and ensure the best possible patient management according to the patient's features. Multi-label classification algorithms, which are trained to assign a set of labels to input samples, can efficiently tackle outcome prediction tasks. Myocardial infarction (MI) represents a widespread health risk, accounting for a significant portion of heart disease-related mortality. Moreover, the danger of potential complications occurring in patients with MI during their period of hospitalization underlines the need for systems to efficiently assess the risks of patients with MI. In order to demonstrate the critical role of applying machine-learning methods in medical challenges, in the present study, a set of multi-label classifiers was evaluated on a public dataset of MI-related complications to predict the outcomes of hospitalized patients with MI, based on a set of input patient features. Such methods can be scaled through the use of larger datasets of patient records, along with fine-tuning for specific patient sub-groups or patient populations in specific regions, to increase the performance of these approaches. Overall, a prediction system based on classifiers trained on patient records may assist healthcare professionals in providing personalized care and efficient monitoring of high-risk patient subgroups.

Stress-Related Roles of Exosomes and Exosomal miRNAs in Common Neuropsychiatric Disorders.

Exosomes, natural nanovesicles that contain a cargo of biologically active molecules such as lipids, proteins, and nucleic acids, are released from cells to the extracellular environment. They then act as autocrine, paracrine, or endocrine mediators of communication between cells by delivering their cargo into recipient cells and causing downstream effects. Exosomes are greatly enriched in miRNAs, which are small non-coding RNAs that act both as cytoplasmic post-transcriptional repression agents, modulating the translation of mRNAs into proteins, as well as nuclear transcriptional gene activators. Neuronal exosomal miRNAs have important physiologic functions in the central nervous system (CNS), including cell-to-cell communication, synaptic plasticity, and neurogenesis, as well as modulating stress and inflammatory responses. Stress-induced changes in exosomal functions include effects on neurogenesis and neuroinflammation, which can lead to the appearance of various neuropsychiatric disorders such as schizophrenia, major depression, bipolar disorder, and Alzheimer's and Huntington's diseases. The current knowledge regarding the roles of exosomes in the pathophysiology of common mental disorders is discussed in this review.

Analysis of Human Milk Microbiota in Northern Greece by Comparative 16S rRNA Sequencing vs. Local Dairy Animals.

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.

Milk exosomes and a new way of communication between mother and child.

Extracellular vesicles are a heterogeneous group of lipid-bound vesicles released by cells into the extracellular space. EVs are an important mediator of intercellular communications and carry a wide variety of molecules that exert a biological function, such as lipids, nucleic acids, proteins, ions, and adenosine triphosphate (ATP). Extracellular vesicles are classified into microvesicles, exosomes, and apoptotic bodies depending on their biogenesis and size. Exosomes are spherical lipid-bilayer vesicles with a diameter of about 40 to 100 nm. Exosomes originate from intracellular endosomal compartments, while microvesicles originated directly from a cell's plasma membrane and apoptotic bodies originate from cells undergoing apoptosis and are released via outward blebbing and fragmentation of the plasma membrane. Specifically, exosomes have garnered great attention since they display great potential as both biomarkers and carriers of therapeutic molecules.

Exosomal Epigenetics.

Epigenetics is the study of heritable changes in gene expression that occur without changes to the underlying DNA sequence. Epigenetic modifications can include DNA methylation, histone modifications, and non-coding RNAs, among others. These modifications can influence the expression of genes by altering the way DNA is packaged and accessed by transcriptional machinery, thereby affecting cellular function and behavior. Epigenetic modifications can be influenced by a variety of factors, including environmental exposures, lifestyle factors, and aging, whilst abnormal epigenetic modifications have been implicated in a range of diseases, including cancer, neurodegenerative disorders, and cardiovascular disease. The study of epigenetics has the potential to provide new insights into the mechanisms of disease and could lead to the development of new diagnostic and therapeutic strategies. Exosomes can transfer epigenetic information to recipient cells, thereby influencing various physiological and pathological processes, and the identification of specific epigenetic modifications that are associated with a particular disease could lead to the development of targeted therapies that restore normal gene expression patterns. In recent years, the emerging role of exosomal epigenetics in human breast milk, highlighting its significance in infant nutrition and immune development. Milk exosomes are shown to carry epigenetic regulators, including miRNAs and long non-coding RNAs, which can modulate gene expression in recipient cells. These epigenetic modifications mediated by milk exosomal RNAs have implications for the development of the gastrointestinal tract, immune system, and metabolic processes in infants.

Fingerprinting Breast Milk; insights into Milk Exosomics.

Breast milk, often referred to as "liquid gold," is a complex biofluid that provides essential nutrients, immune factors, and developmental cues for newborns. Recent advancements in the field of exosome research have shed light on the critical role of exosomes in breast milk. Exosomes are nanosized vesicles that carry bioactive molecules, including proteins, lipids, nucleic acids, and miRNAs. These tiny messengers play a vital role in intercellular communication and are now being recognized as key players in infant health and development. This paper explores the emerging field of milk exosomics, emphasizing the potential of exosome fingerprinting to uncover valuable insights into the composition and function of breast milk. By deciphering the exosomal cargo, we can gain a deeper understanding of how breast milk influences neonatal health and may even pave the way for personalized nutrition strategies.

A TMEM63A Nonsense Heterozygous Variant Linked to Infantile Transient Hypomyelinating Leukodystrophy Type 19?

Infantile onset transient hypomyelination (IOTH) is a rare form of leukodystrophy that is associated with transient motor impairment and delayed central nervous system myelination. Here, we report a case of a new mutation in the transmembrane protein 63A (TMEM63A) gene identified using Whole-Exome Sequencing (WES) in an 8.5-year-old boy with clinical symptoms similar to IOTH. The patient exhibited a mild developmental delay, including hypotonia and delayed motor milestones, as well as some notable phenotypic characteristics, such as macrocephaly and macrosomia. Despite the absence of early neuroimaging, genetic testing revealed a paternally inherited variant in TMEM63A (NM_14698.3:c.220A>T;p:(Arg74*)), potentially linked to infantile transient hypomyelinating leukodystrophy type 19. Our findings in this study and the patient's favorable clinical course underscore the potential for successful myelination even with delayed initiation and may contribute to a better understanding of the genotype-phenotype correlation in IOTH, emphasizing the importance of genetic analysis in unresolved developmental delay cases and providing critical insights for accurate diagnosis, prognosis and potential therapeutic strategies in rare leukodystrophies.

SNP and Structural Study of the Notch Superfamily Provides Insights and Novel Pharmacological Targets against the CADASIL Syndrome and Neurodegenerative Diseases.

The evolutionary conserved Notch signaling pathway functions as a mediator of direct cell-cell communication between neighboring cells during development. Notch plays a crucial role in various fundamental biological processes in a wide range of tissues. Accordingly, the aberrant signaling of this pathway underlies multiple genetic pathologies such as developmental syndromes, congenital disorders, neurodegenerative diseases, and cancer. Over the last two decades, significant data have shown that the Notch signaling pathway displays a significant function in the mature brains of vertebrates and invertebrates beyond neuronal development and specification during embryonic development. Neuronal connection, synaptic plasticity, learning, and memory appear to be regulated by this pathway. Specific mutations in human Notch family proteins have been linked to several neurodegenerative diseases including Alzheimer's disease, CADASIL, and ischemic injury. Neurodegenerative diseases are incurable disorders of the central nervous system that cause the progressive degeneration and/or death of brain nerve cells, affecting both mental function and movement (ataxia). There is currently a lot of study being conducted to better understand the molecular mechanisms by which Notch plays an essential role in the mature brain. In this study, an in silico analysis of polymorphisms and mutations in human Notch family members that lead to neurodegenerative diseases was performed in order to investigate the correlations among Notch family proteins and neurodegenerative diseases. Particular emphasis was placed on the study of mutations in the Notch3 protein and the structure analysis of the mutant Notch3 protein that leads to the manifestation of the CADASIL syndrome in order to spot possible conserved mutations and interpret the effect of these mutations in the Notch3 protein structure. Conserved mutations of cysteine residues may be candidate pharmacological targets for the potential therapy of CADASIL syndrome.

Unraveling Desmin's Head Domain Structure and Function.

Understanding the structure and function of intermediate filaments (IFs) is necessary in order to explain why more than 70 related IF genes have evolved in vertebrates while maintaining such dramatically tissue-specific expression. Desmin is a member of the large multigene family of IF proteins and is specifically expressed in myocytes. In an effort to elucidate its muscle-specific behavior, we have used a yeast two-hybrid system in order to identify desmin's head binding partners. We described a mitochondrial and a lysosomal protein, NADH ubiquinone oxidoreductase core subunit S2 (NDUFS2), and saposin D, respectively, as direct desmin binding partners. In silico analysis indicated that both interactions at the atomic level occur in a very similar way, by the formation of a three-helix bundle with hydrophobic interactions in the interdomain space and hydrogen bonds at R16 and S32 of the desmin head domain. The interactions, confirmed also by GST pull-down assays, indicating the necessity of the desmin head domain and, furthermore, point out its role in function of mitochondria and lysosomes, organelles which are disrupted in myopathies due to desmin head domain mutations.

Indications of younger age at menarche in Greek adolescents but with no relation to body mass index.

PURPOSE: This study aimed to present recent trends in the pubertal timing of a Greek female sample. METHODS: Data were collected retrospectively from medical records of healthy females aged 6-18 years who attended a tertiary Adolescent Friendly Health Center over a 5-year period (2016-2020) and included gestational age, birth anthropometrics, and age of thelarche and/or pubarche and/or menarche, along with corresponding anthropometric, hormonal, and biochemical measurements. RESULTS: Data from 298 girls' medical records were included in the analysis. Median age at menarche, thelarche, and pubarche was 12, 9, and 9 years, respectively. The mean interval between pubertal onset and menarche was 1.99 years. The mean body mass index (BMI) at menarche and thelarche was 20.99 kg/m2 and 18.90 kg/m2, respectively. The mean weight at menarche was 49.6 kg, whereas the mean height difference between thelarche and menarche was 19.17 cm. Among participants, 6.3% had premature menarche, while 24.0% had premature thelarche. Birth weight was moderately correlated with BMI at thelarche/pubarche (rs=0.334, p = 0.005). Birth weight and BMI at thelarche/pubarche were not predictive of premature menarche or premature thelarche. Median (interquartile range, IQR) levels at menarche vs. thelarche were significantly higher for insulin-like growth factor-1 [358.00 (140.50) vs. 176.00 (55.00) ng/ml], follicle stimulation hormone [5.65 (3.14) vs. 3.10 (4.23) mIU/ml], testosterone [25.50 (31.00) vs. 13.00 (21.00) ng/dl], dehydroepiandrosterone sulfate [117.00 (112.50) vs. 46.40 (51.90) µg/dl], and insulin [17.40 (15.05) vs. 8.47 (4.97) µIU/ml]. CONCLUSION: The timing of pubertal stages in the Greek female sample studied followed the recent international downward trends. Younger age at menarche was not related to BMI.

Use of in silico approaches, synthesis and profiling of Pan-filovirus GP-1,2 preprotein specific antibodies.

Intermolecular interactions of protein-protein complexes play a principal role in the process of discovering new substances used in the diagnosis and treatment of many diseases. Among such complexes of proteins, we have to mention antibodies; they interact with specific antigens of two genera of single-stranded RNA viruses belonging to the family Filoviridae-Ebolavirus and Marburgvirus; both cause rare but fatal viral hemorrhagic fever in Africa, with pandemic potential. In this research, we conduct studies aimed at the design and evaluation of antibodies targeting the filovirus glycoprotein precursor GP-1,2 to develop potential targets for the pan-filovirus easy-to-use rapid diagnostic tests. The in silico research using the available 3D structure of the natural antibody-antigen complex was carried out to determine the stability of individual protein segments in the process of its formation and maintenance. The computed free binding energy of the complex and its decomposition for all amino acids allowed us to define the residues that play an essential role in the structure and indicated the spots where potential antibodies can be improved. Following that, the study involved targeting six epitopes of the filovirus GP1,2 with two polyclonal antibodies (pABs) and 14 monoclonal antibodies (mABs). The evaluation conducted using Enzyme Immunoassays tested 62 different sandwich combinations of monoclonal antibodies (mAbs), identifying 10 combinations that successfully captured the recombinant GP1,2 (rGP). Among these combinations, the sandwich option (3G2G12* - (rGP) - 2D8F11) exhibited the highest propensity for capturing the rGP antigen.

Pythagorean Self-Awareness Intervention Promoted Healthy Dietary Patterns, Controlled Body Mass Index, and Reduced Self-Reported Stress Levels of Primary School Children: Α One-Arm Pilot Study.

Stress is common in childhood and an important factor that affects behavior later in adulthood. The aim of this study was to assess the effects of the Pythagorean Self-Awareness Intervention (PSAI), a holistic "cognitive reconstruction" technique to assess primary school children's stress levels, adherence to the Mediterranean diet, and body mass index. Secondary outcome measures included relations with peers, sleep, and hair cortisol concentrations. This one-arm pilot study took place in a primary school, from February to June 2019. Participants were 32 pupils attending the second grade of primary school who received the 8-week PSAI to adopt healthy behaviors and lifestyle. Self-report measures were applied for the evaluation of various variables at the beginning and the end of the eight-week intervention. There were statistically significant reductions in stress levels (p = 0.00), nightmares' frequency (p = 0.00), body mass index (p = 0.03), and bully scale (p = 0.00), and improvement in Mediterranean diet quality (p = 0.00). Hair cortisol concentrations increased (p = 0.02). The social scale significantly increased. Bedtime remained the same after the intervention. This pilot trial showed that the PSAI promoted healthy dietary patterns, controlled children's body mass index, and reduced their self-reported stress levels. Further research on the implementation of this holistic program on children is suggested, in well-powered randomized controlled trials.

The Effect of Pythagorean Self-Awareness Intervention on Stress and Mental Health Characteristics of Civil Servants in Crete, Greece.

Evidence is limited regarding the effects of holistic programs on work-related stress, anxiety, and depressive symptomatology. This study aimed to evaluate the effects of the Pythagorean Self-Awareness Intervention (PSAI) on stress and mental health characteristics of civil servants in Crete, Greece. This was a single arm interventional study with PSAI outcome evaluation. Validated, self-reported scales were used to assess stress and mental health characteristics (PSS, DASS, UCLA, RSE, and STAXI). Hair samples were obtained to measure cortisol concentrations as a biological stress marker. Paired-samples t-test or Wilcoxon tests were used to evaluate pre- and post-intervention measures. Overall, 48 civil servants (56.3% women, mean age 51 years) participated in the study. Statistically significant reductions were observed in all self-reported stress scales (p < 0.05). Although hair cortisol decreased, this difference was not statistically significant (p = 0.109). Statistically significant improvements were also observed on depressive symptomatology (p < 0.001), self-esteem (p < 0.001), loneliness (p < 0.001), self-efficacy (p = 0.002), and anger (p = 0.017). The PSAI appeared beneficial with respect to all self-reported outcomes. Larger studies including control groups and further follow-up evaluations are needed to ascertain these findings.

Validation of the Greek Version of the State Shame and Guilt Scale (SSGS).

Both shame and guilt are self-conscious negative emotions claiming self-representations and self-awareness. Growing evidence indicates that these pessimistic emotions are associated to stress and stress-related disorders. The aim of this study was to translate and investigate the validity and reliability of the State Shame and Guilt Scale (SSGS) in a Greek adult population sample. A total of 181 adults (63% women) participated in the study. To validate the SSGS, correlations with the Depression Anxiety Stress Scales (DASS) and the Perceived Stress Scale (PSS) were also examined. Exploratory factor analysis was used to examine the factors of the Greek version of the SSGS. In addition, for greater validity, comparisons were made according to sex, marital status and level of education. The reliability assessment revealed that the index of internal consistency (Cronbach's alpha) was above the acceptable margin (0.7) for the three subscales (shame; 0.717, guilt; 0.770, pride; 0.874). The Greek version of the 15-item State Shame and Guilt Scale (SSGS) demonstrated good psychometric properties and could be proven useful for the assessment of shame, guilt, and pride.

Post-traumatic Stress Disorder as a Risk Factor for the Development of Risky Behavior Among Adolescent Offenders: A Systematic Review.

The purpose of this research study was to obtain greater insight into the associations of post-traumatic stress disorder (PTSD) and trauma-exposed experiences with the development of offending behavior in adolescents. Using the PubMed and Scopus databases, we performed a systematic review of recent cross-sectional studies between 2016 and 2022, investigating the associations of PTSD and trauma with the social and mental behavior of adolescents. Fifty-three articles were initially identified. Due to duplication, eight articles were excluded, leaving 45 remaining articles. In addition, 34 articles were excluded due to year of publication, review, abstract, or irrelevant title. Seven articles were included in this systematic review after excluding the remaining due to different study types or samples. Included studies primarily examined the associations of PTSD symptomatology and expression of externalizing symptoms with risky behavior and the commission of a crime. The strongest outcomes were increased levels of violent behavior, violent delinquency, and total risk in correlation with PTSD symptoms, emotional numbing, use of drugs, and in some cases maltreatment. The results of the systematic review suggest that PTSD symptoms and risky behavior, which can be also fueled by maltreatment activities in the family circle, are associated with criminal behavior. Future research is needed to confirm these findings.

Burnout in General Surgeons. A Systematic Review.

Occupational burnout is particularly widespread amongst surgical professionals. During the past 10 years, both the awareness and the ability to reliably measure and classify "burnout" in medical professionals have increased. The purpose of this systematic review was to summarize the current evidence on the burnout levels of general surgeons. Online searches were carried out using the scientific search engines PubMed, Embase, Cinahl, and Google scholar, from 2010 to 2020, before the COVID-19 pandemic. Articles that met the inclusion criteria were critically evaluated using the critical appraisal skills programme (CASP) tool. Five studies pertaining to 669 subjects were included in this review. As expected, "burnout syndrome" was mainly due to the exhaustive and demanding conditions of working life and was strongly observed in general surgeons. The incidence of the burnout syndrome increased with their years of service, compromised their quality of life, and had detrimental effects on their mental and physical health. Personal achievements and emotional satisfaction were protective for the occurrence of the syndrome. We conclude that valid recognition and prevention of the burnout syndrome are necessary. Further research is needed to manage this phenomenon within the healthcare settings and the surgical departments.

Mindfulness and Academic Performance of College and University Students: A Systematic Review.

Higher education's expectations place demands on students' attainment, leading them to experience stress and anxiety, which negatively affect their academic improvement and life satisfaction. The aim of this systematic review was to investigate (a) if mindfulness as an inner ability is related to academic attainment, through dependent variables, including compassion, engagement, stress or anxiety state, depression, self-efficacy, mindfulness's facets (non-reactivity, acting with awareness) and (b) if mindfulness-based interventions positively affect the academic performance of college and university students. The systematic review was conducted in accordance with the PRISMA statement. PubMed, Web of Science, and Cochrane Library Wiley were screened to identify studies published relevant to the topic. In total, 568 papers were retrieved in the initial search. Five papers met the eligibility criteria and were included in the systematic review: a randomized controlled trial, a non-randomized controlled trial, a quasi-experimental study, a quantitative exploratory pilot study, and a longitudinal randomized controlled study. Most interventional studies revealed a non-significant direct effect of practicing mindfulness technique on academic attainment. Further research, especially randomized controlled trials are necessary to clarify the effect of mindfulness on academic performance of college and university students.

How Does Meditation Affect the Default Mode Network: A Systematic Review.

This article provides a systematic review of studies evaluating the effect of meditation on the Default Mode Network (DMN). The review was conducted according to PRISMA guidelines. A literature search of PubMed, Scopus, and Embase was conducted up to June 2020. Search terms included default mode network or DMN and meditation.A total of 306 articles were identified, of which 16 controlled trials with a total of 853 experienced (in Mindfulness, Samatha, Raja Yoga, Transcendental Meditation, Vipassana, Insight meditation Theravada tradition) and non-experienced mediators were finally included in this systematic review. The results showed that meditative interventions affect the operation of DMN and there are differences in functional connectivity between networks. Further research should be undertaken to establish meditation as an effective intervention strategy for well-being.