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Head and neck squamous cell carcinomas (HNSCCs), a heterogeneous group of cancers that arise from the mucosal epithelia cells in the head and neck areas, present great challenges in diagnosis, treatment and prognosis due to their complex aetiology and various clinical manifestations. Several factors, including smoking, alcohol consumption, oncogenic genes, growth factors, Epstein‑Barr virus and human papillomavirus infections can contribute to HNSCC development. The unpredictable tumour microenvironment adds to the complexity of managing HNSCC. Despite significant advances in therapies, the prediction of outcome after treatment for patients with HNSCC remains poor, and the 5‑year overall survival rate is low due to late diagnosis. Early detection greatly increases the chances of successful treatment. The present review aimed to bring together the latest findings related to the molecular mechanisms of HNSCC carcinogenesis and progression. Comprehensive genomic, transcriptomic, metabolomic, microbiome and proteomic analyses allow researchers to identify important biological markers such as genetic alterations, gene expression signatures and protein markers that drive HNSCC tumours. These biomarkers associated with the stages of initiation, progression and metastasis of cancer are useful in the management of patients with cancer in order to improve their life expectancy and quality of life.

Due to the addictive qualities of tobacco products and the compulsive craving and dependence associated with their use, nicotine dependence continues to be a serious public health concern on a global scale. Despite awareness of the associated health risks, nicotine addiction contributes to numerous acute and chronic medical conditions, including cardiovascular disease, respiratory disorders and cancer. The nocturnal secretion of pineal melatonin, known as the 'hormone of darkness', influences circadian rhythms and is implicated in addiction‑related behaviors. Melatonin receptors are found throughout the brain, influencing dopaminergic neurotransmission and potentially attenuating nicotine‑seeking behavior. Additionally, the antioxidant properties of melatonin may mitigate oxidative stress from chronic nicotine exposure, reducing cellular damage and lowering the risk of nicotine‑related health issues. In addition to its effects on circadian rhythmicity, melatonin acting via specific neural receptors influences sleep and mood, and provides neuroprotection. Disruptions in melatonin signaling may contribute to sleep disturbances and mood disorders, highlighting the potential therapeutic role of melatonin in addiction and psychiatric conditions. Melatonin may influence neurotransmitter systems involved in addiction, such as the dopaminergic, glutamatergic, serotonergic and endogenous opioid systems. Preclinical studies suggest the potential of melatonin in modulating reward processing, attenuating drug‑induced hyperactivity and reducing opioid withdrawal symptoms. Chronotherapeutic approaches targeting circadian rhythms and melatonin signaling show promise in smoking cessation interventions. Melatonin supplementation during periods of heightened nicotine cravings may alleviate withdrawal symptoms and reduce the reinforcing effects of nicotine. Further research is required however, to examine the molecular mechanisms underlying the melatonin‑nicotine association and the optimization of therapeutic interventions. Challenges include variability in individual responses to melatonin, optimal dosing regimens and identifying biomarkers of treatment response. Understanding these complexities could lead to personalized treatment strategies and improve smoking cessation outcomes.

It is well known how the precise localization of glioblastoma multiforme (GBM) predicts the direction of tumor spread in the surrounding neuronal structures. The aim of the present review is to reveal the lateralization of GBM by evaluating the anatomical regions where it is frequently located as well as the main molecular alterations observed in different brain regions. According to the literature, the precise or most frequent lateralization of GBM has yet to be determined. However, it can be said that GBM is more frequently observed in the frontal lobe. Tractus and fascicles involved in GBM appear to be focused on the corticospinal tract, superior longitudinal I, II and III fascicles, arcuate fascicle long segment, frontal strait tract, and inferior fronto‑occipital fasciculus. Considering the anatomical features of GBM and its brain involvement, it is logical that the main brain regions involved are the frontal‑temporal‑parietal‑occipital lobes, respectively. Although tumor volumes are higher in the right hemisphere, it has been determined that the prognosis of patients diagnosed with cancer in the left hemisphere is worse, probably reflecting the anatomical distribution of some detrimental alterations such as TP53 mutations, PTEN loss, EGFR amplification, and MGMT promoter methylation. There are theories stating that the right hemisphere is less exposed to external influences in its development as it is responsible for the functions necessary for survival while tumors in the left hemisphere may be more aggressive. To shed light on specific anatomical and molecular features of GBM in different brain regions, the present review article is aimed at describing the main lateralization pathways as well as gene mutations or epigenetic modifications associated with the development of brain tumors.

Atypical pneumonia encompasses diverse pathogens, such as Chlamydia pneumoniae , Mycoplasma pneumoniae and Legionella species, which differ from typical bacterial pneumonia in their extrapulmonary manifestations. Clinical differentiation relies on systemic involvement rather than on standalone symptoms. Despite challenges in distinct diagnosis, syndromic approaches and weighted point systems aid in accurate presumptive diagnoses. Antibiotic treatment, often non-β-lactams due to the unique cell structures of atypical pathogens, targets intracellular processes. Macrolides, tetracyclines, quinolones and ketolides are effective due to their intracellular penetration, crucial for combating these intracellular pathogens. The prevalence of atypical pneumonia varies globally, with Europe, Asia/Africa and Latin America reporting detection rates between 20-28%. Streptococcus pneumoniae remains a primary cause of pneumonia; however, atypical pathogens contribute significantly to this disease, being more prevalent in outpatient settings and among young adults. Legionella stands out in severe hospitalized cases and is associated with higher mortality rates. Diagnosis proves challenging due to overlapping symptoms with other respiratory infections. Differentiation among pathogens, such as Chlamydia pneumoniae , Mycoplasma pneumoniae and Legionella relies on subtle clinical variations and imaging findings. Diagnostic methods include serological studies, cultures and polymerase chain reaction, each with limitations in sensitivity or specificity. Prognosis varies widely. Atypical pneumonia can progress to severe forms with fatal outcomes, causing multi-organ damage. Complications extend beyond the respiratory system, affecting the cardiovascular system, exacerbating conditions such as chronic obstructive pulmonary disease and asthma, and potentially linking to conditions such as lung cancer. Increasing antibiotic resistance poses a significant challenge, influencing treatment outcomes and prolonging illness duration., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © 2024 Georgakopoulou et al.)

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., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Diakou et al.)

Precision medicine in breast cancer is a revolutionary approach that customizes diagnosis and treatment based on individual and tumor characteristics, departing from the traditional one-size-fits-all approach. Breast cancer is diverse, with various subtypes driven by distinct genetic mutations. Understanding this diversity is crucial for tailored treatment strategies that target specific vulnerabilities in each tumor. Genetic testing, particularly for mutations in breast cancer gene (BRCA) DNA repair-associated genes, helps assess hereditary risks and influences treatment decisions. Molecular subtyping guides personalized treatments, such as hormonal therapies for receptor-positive tumors and human epidermal growth factor receptor 2 (HER2)-targeted treatments. Targeted therapies, including those for HER2-positive and hormone receptor-positive breast cancers, offer more effective and precise interventions. Immunotherapy, especially checkpoint inhibitors, shows promise, particularly in certain subtypes such as triple-negative breast cancer, with ongoing research aiming to broaden its effectiveness. Integration of big data and artificial intelligence enhances personalized treatment strategies, while liquid biopsies provide real-time insights into tumor dynamics, aiding in treatment monitoring and modification. Challenges persist, including accessibility and tumor complexity, but emerging technologies and precision prevention offer hope for improved outcomes. Ultimately, precision medicine aims to optimize treatment efficacy, minimize adverse effects and enhance the quality of life for patients with breast cancer., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © 2024 Papalexis et al.)

Gastric cancer (GC) constitutes one of the most wide-ranging cancers, with brain metastasis (BM) being a markedly uncommon and unfavorable outcome. The present meta-analysis evaluated the relationship between no-surgical treatment vs. additional surgical BM resection on the patient's quality of life and potential survival using electronic databases, including PubMed (1980-April 2024), Medline (1980-April 2024), Cochrane Library, and EMBASE (1980-April 2024). After a literature search, six articles were included in the final study pool. The number of patients with BM and conservative treatment was 289 (80.05%) compared with those that underwent an additional surgical resection 72 (19.95%). The mean age was 59.2 years, and the males were 195 (73.8%) of 264 available from five studies. The findings of the present meta-analysis revealed that the curative effect of BM tumor resection on patients with GC undergoing additional treatment with stereotactic radiosurgery, whole-brain radiotherapy or chemotherapy was favorable for their survival., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © 2024 Fotakopoulos et al.)

The gut‑microbiota‑brain axis is a complex bidirectional communication system linking the gastrointestinal tract to the brain. Changes in the balance, composition and diversity of the gut‑microbiota (gut dysbiosis) have been found to be associated with the development of psychosis. Early‑life stress, along with various stressors encountered in different developmental phases, have been shown to be associated with the abnormal composition of the gut microbiota, leading to irregular immunological and neuroendocrine functions, which are potentially responsible for the occurrence of first‑episode psychosis (FEP). The aim of the present narrative review was to summarize the significant differences of the altered microbiome composition in patients suffering from FEP vs. healthy controls, and to discuss its effects on the occurrence and intensity of symptoms in FEP.

Chronic subdural hematoma (CSDH) is one of the most challenging realities in the neurosurgical world. The aim of the present study was to compare different surgical techniques, such as burr hole evacuation with subperiosteal drain or subdural drain and mini-craniotomy, and to review the diverse outcomes on the post-operative clinical state of patients. The present study was a retrospective cohort study with 122 patients with CSDH treated at a single center. The patients were separated into three groups according to the surgical technique used as follows: group 1, two burr holes with the placement of a subperiosteal drain; group 2, single burr hole per hematoma with the placement of an intradural drain; and group 3, mini-craniotomy. The duration of hospitalization, hematoma recurrence, complications, Glasgow coma scale at discharge and mortality were reported as outcome measures. A total of 3 patients succumbed following hematoma evacuation; of these 2 patients were from group 2 and 1 patient was from group 3. The patients from groups 1 and 3 exhibited a significantly lower odds ratio (OR) of hematoma recurrence than patients in group 2 (OR, 0.76; P<0.01; and OR, 0.8; P<0.01, respectively). The patients in group 1 exhibited a significantly lower probability of having a depressed level of consciousness on discharge (OR, 0.249; P=0.031). Group 2 was associated with a statistically significant prolongation of hospitalization. On the whole, the present study demonstrates that multiple burr hole hematoma evacuation with subperiosteal drain placement and mild suction is a very promising technique with very beneficial post-operative outcomes, such as zero mortality, a low CSDH recurrence risk, a reduced period of hospitalization and an improved post-operative quality of life., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © 2024 Chatzidakis et al.)

Mycoplasmas, the smallest self-replicating prokaryotes without a cell wall, are the most prevalent and extensively studied species in humans. They significantly contribute to chronic respiratory tract illnesses and pneumonia, with children and adolescents being particularly vulnerable. Mycoplasma pneumoniae ( M. pneumoniae ) infections typically tend to be self-limiting and mild but can progress to severe or even life-threatening conditions in certain individuals. Extrapulmonary effects often occur without pneumonia, and both intrapulmonary and extrapulmonary complications operate through separate pathological mechanisms. The indirect immune-mediated damage of the immune system, vascular blockages brought on by vasculitis or thrombosis and direct harm from invasion or locally induced inflammatory cytokines are potential causes of extrapulmonary manifestations due to M. pneumoniae . Proteins associated with adhesion serve as the primary factor crucial for the pathogenicity of M. pneumoniae , relying on a specialized polarized terminal attachment organelle. The type and density of these host receptors significantly impact the adhesion and movement of M. pneumoniae , subsequently influencing the pathogenic mechanism and infection outcomes. Adjacent proteins are crucial for the proper assembly of the attachment organelle, with variations in the genetic domains of P1, P40 and P90 surfaces contributing to the variability of clinical symptoms and offering new avenues for developing vaccines against M. pneumoniae infections. M. pneumoniae causes oxidative stress within respiratory tract epithelial cells by adhering to host cells and releasing hydrogen peroxide and superoxide radicals. This oxidative stress enhances the vulnerability of host cells to harm induced by oxygen molecules. The lack of superoxide dismutase and catalase of bacteria allows it to hinder the catalase activity of the host cell, leading to the reduced breakdown of peroxides. Lung macrophages play a significant role in managing M. pneumoniae infection, identifying it via Toll-like receptor 2 and initiating the myeloid differentiation primary response gene 88-nuclear factor κΒ signaling cascade. However, the precise mechanisms enabling M. pneumoniae to evade intracellular host defenses remain unknown, necessitating further exploration of the pathways involved in intracellular survival. The present comprehensive review delves into the pathogenesis of M. pneumoniae infection within the pulmonary system and into extrapulmonary areas, outlining its impact., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © 2024 Georgakopoulou et al.)

In the realm of respiratory illnesses, despite the immense costs and efforts invested in diagnosis and treatment, numerous patients with chronic respiratory conditions or malignancies do not respond well to existing therapies. Delayed diagnoses and inadequate treatments contribute to these challenges, along with adverse reactions or treatment limitations due to side-effects. However, recent advancements in understanding respiratory diseases have paved the way for personalized medical treatments, considering individual genetic, molecular and environmental factors. Precision medicine, which accommodates individual differences in disease susceptibility and response to treatments, aims to improve patient care by aligning medical research with tailored therapies. Innovative technologies, such as genomic sequencing and biomarker identification contribute to this approach, allowing for customized treatments and the identification of effective therapies. Additionally, the application of precision medicine in lung cancer treatment exemplifies the forefront of individualized care within respiratory medicine. Several studies have explored the role of precision medicine in managing respiratory infectious diseases, asthma and idiopathic pulmonary fibrosis, aiming to categorize diseases more accurately and design targeted therapies. The ultimate goal is to enhance treatment effectiveness, minimize adverse events, and shift towards a patient-centered approach to managing respiratory conditions. Despite limitations, precision medicine holds promise for improving patient outcomes and emphasizing personalized care in respiratory medicine., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Georgakopoulou et al.)

Intracranial cavernous malformations (CMs) are vascular lesions with a high bleeding rate. At present, the debate regarding their treatment is still ongoing. The present systematic review and meta-analysis aimed to evaluate the safety of surgery or radiosurgery (SRS) for the management of CMs and to determine their potential outcomes compared with conservative treatment. The present systematic review and meta-analysis investigated the relative articles involving the management of intracranial CMs, namely their natural history (conservative treatment) vs. surgical/SRS treatment through electronic databases until June, 2023. The collected variables included the first author's name, the study period covered, the year of publication, the total number of patients examined and their age, and the number of males. In total, six articles met the eligibility criteria. The total number of patients was 399 (157 in the surgery/SRS group and 242 in the conservative treatment group). The results revealed that surgical or SRS management is a safe procedure for CMs compared with conservative treatment. Notably, the use of hemosiderin in the pre-MRI, the free of seizures parameter and the neurological deficit parameters were associated with improved outcomes in the surgical or SRS group of patients., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © 2024 Fotakopoulos et al.)

The present article discusses the interconnectedness of coronavirus disease 2019 (COVID-19) and obesity as global health crises. The similarities between the two conditions are highlighted; these include shared risk factors and comorbidities, and the impact of obesity on the immune system. The present article also mentions the challenges faced in combating both pandemics, including misinformation and prejudice against obesity. It discusses the development of therapeutic medications and vaccines for COVID-19 and the potential of injectable incretin analogues for weight loss. Socioeconomic issues are also addressed, with obesity being more prevalent in lower socioeconomic groups and the cost of obesity treatments being a barrier for those in need. The present article emphasizes the need for comprehensive and sustainable solutions, including public health interventions, education, policy changes and equitable distribution of resources, to address both COVID-19 and obesity., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © 2024 Georgakopoulou et al.)

Coronavirus disease 2019 (COVID‑19), a systemic illness caused by severe acute respiratory distress syndrome 2 (SARS‑CoV‑2), has triggered a worldwide pandemic with symptoms ranging from asymptomatic to chronic, affecting practically every organ. Melatonin, an ancient antioxidant found in all living organisms, has been suggested as a safe and effective therapeutic option for the treatment of SARS‑CoV‑2 infection due to its good safety characteristics and broad‑spectrum antiviral medication properties. Melatonin is essential in various metabolic pathways and governs physiological processes, such as the sleep‑wake cycle and circadian rhythms. It exhibits oncostatic, anti‑inflammatory, antioxidant and anti‑aging properties, exhibiting promise for use in the treatment of numerous disorders, including COVID‑19. The preventive and therapeutic effects of melatonin have been widely explored in a number of conditions and have been well‑established in experimental ischemia/reperfusion investigations, particularly in coronary heart disease and stroke. Clinical research evaluating the use of melatonin in COVID‑19 has shown various improved outcomes, including reduced hospitalization durations; however, the trials are small. Melatonin can alleviate mitochondrial dysfunction in COVID‑19, improve immune cell function and provide antioxidant properties. However, its therapeutic potential remains underexplored due to funding limitations and thus further investigations are required.

The likelihood and severity of cognitive decline related to coronavirus disease 2019 (COVID-19) have been shown to be reflected by the severity of the infection and concomitant alterations in specific biomarkers. The present review discusses the role of microRNAs (miRNAs/miRs) as biomarkers in COVID-19 and the potential molecular mechanisms of cognitive dysfunction related to COVID-19. A systematic search of published articles was carried out from January 31, 2000 to December 31, 2022 using the PubMed, ProQuest, Science Direct and Google Scholar databases, combining the following terms: 'COVID-19' OR 'SARS-CoV-2' OR 'post-COVID-19 effects' OR 'cognitive decline' OR 'neurodegeneration' OR 'microRNAs'. The quality of the evidence was evaluated as high, moderate, low, or very low based on the GRADE rating. A total of 36 studies were identified which demonstrated reduced blood levels of miR-146a, miR-155, Let-7b, miR 31 and miR-21 in patients with COVID-19 in comparison with a healthy group. The overexpression of the Let-7b may result in the downregulation of BCL-2 during COVID-9 by adjusting the immune responses between chronic inflammatory disease, type 2 diabetes, COVID-19 and cognitive impairment. The reduced expression of miR-31 is associated with cognitive dysfunction and increased microcoagulability in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). miR-155 mediates synaptic dysfunction and the dysregulation of neurotransmitters due to acute inflammation, leading to brain atrophy and a subcortical cognitive profile. The downregulation of miR-21 in patients with COVID-19 aggravates systemic inflammation, mediating an uncontrollable immune response and the failure of T-cell function, provoking cognitive impairment in patients with SARS-CoV-2. On the whole, the present review indicates that dysregulated levels of miR-146a, miR-155, Let-7b, miR-31, and miR-21 in the blood of individuals with COVID-19 are associated with cognitive decline, the chronic activation of immune mechanisms, the cytokine storm, and the vicious cycle of damage and systemic inflammation., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © 2024 Bougea et al.)

Bruxism is a non-functional involuntary muscle activity that affects more than one-third of the population at some point in their lives. A number of factors have been found to be related to the etiopathogenesis of bruxism; therefore, the condition is considered multifactorial. The most commonly accepted factor is stress. Stress has long been considered to increase muscle tone and to reduce the pain threshold. Current evidence indicates that exposure to chronic stress, distress and allostatic load ignite neurological degeneration and the attenuation of critical neuronal pathways that are highly implicated in the orofacial involuntary muscle activity. The present review discusses the negative effects that chronic stress exerts on certain parts of the central nervous system and the mechanisms through which these changes are involved in the etiopathogenesis of bruxism. The extent of these morphological and functional changes on nerves and neuronal tracts provides valuable insight into the obstacles that need to be overcome in order to achieve successful treatment. Additionally, particular emphasis is given on the effects of bruxism on the central nervous system, particularly the activation of the hypothalamic-pituitary-adrenal axis, as this subsequently induces an increase in circulating corticosterone levels, also evidenced by increased levels of salivary cortisol, thereby transforming bruxism into a self-reinforcing loop., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © Pavlou et al.)

Patients with a history of endometriosis have an increased risk of developing various autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis and celiac disease. There is a potential association between endometriosis and an increased susceptibility for Sjögren's syndrome (SS). SS is a common chronic, inflammatory, systemic, autoimmune, multifactorial disease of complex pathology, with genetic, epigenetic and environmental factors contributing to the development of this condition. It occurs in 0.5‑1% of the population, is characterized by the presence of ocular dryness, lymphocytic infiltrations and contributes to neurological, gastrointestinal, vascular and dermatological manifestations. Endometriosis is an inflammatory, estrogen‑dependent, multifactorial, heterogeneous gynecological disease, affecting ≤10% of reproductive‑age women. It is characterized by the occurrence of endometrial tissue outside the uterine cavity, mainly in the pelvic cavity, and is associated with pelvic pain, dysmenorrhea, deep dyspareunia and either subfertility or infertility. It is still unclear whether SS appears as a secondary response to endometriosis, or it is developed due to any potential shared mechanisms of these conditions. The aim of the present review was to explore further the biological basis only of the co‑occurrence of these disorders but not their association at clinical basis, focusing on the analysis of the partially shared genetic background between endometriosis and SS, and the clarification of the possible similarities in the underlying pathogenetic mechanisms and the relevant molecular pathways.

Allicin is a thiosulphate molecule produced in garlic ( Allium sativum ) and has a wide range of biological actions and pharmaceutical applications. Its precursor molecule is the non-proteinogenic amino acid alliin (S-allylcysteine sulphoxide). The alliin biosynthetic pathway in garlic involves a group of enzymes, members of which are the γ-glutamyl-transpeptidase isoenzymes, Allium sativum γ-glutamyl-transpeptidase AsGGT1, AsGGT2 and AsGGT3, which catalyze the removal of the γ-glutamyl group from γ-glutamyl-S-allyl-L-cysteine to produce S-allyl-L-cysteine. This removal is followed by an S-oxygenation, which leads to the biosynthesis of alliin. The aim of the present study is to annotate previously discovered genes of garlic γ-glutamyl-transpeptidases, as well as a fourth candidate gene (AsGGT4) that has yet not been described. The annotation includes identifying the loci of the genes in the garlic genome, revealing the overall structure and conserved regions of these genes, and elucidating the evolutionary history of these enzymes through their phylogenetic analysis. The genomic structure of γ-glutamyl-transpeptidase genes is conserved; each gene consists of seven exons, and these genes are located on different chromosomes. AsGGT3 and AsGGT4 enzymes contain a signal peptide. To that end, the AsGGT3 protein sequence was corrected; four indel events occurring in AsGGT3 coding regions suggested that at least in the garlic variety Ershuizao, AsGGT3 may be a pseudogene. Finally, the use of protein structure prediction tools allowed the visualization of the tertiary structure of the candidate peptide., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © Baltzi et al.)

Proteasome inhibitor bortezomib is an anticancer agent approved for treatment of multiple myeloma and mantle cell lymphoma. However, its application in other types of cancer, primarily in solid tumors, is limited due to poor pharmacokinetics, inefficient tissue penetration, low stability and frequent adverse effects. In the present study, a novel micellar nano-scaled delivery system was manufactured, composed of amphiphilic poly(N-vinylpyrrolidone) nanoparticles loaded with bortezomib. Similar nanoparticles loaded with prothionamide, a drug without anticancer effect, were used as control. The size and zeta potential of the obtained polymeric micelles were measured by dynamic light scattering. Bortezomib-loaded micelles exhibited significant cytotoxic activity in vitro in monolayer tumor cell cultures (IC 50 ~6.5 µg/ml) and in 3D multicellular tumor spheroids (IC 50 ~8.5 µg/ml) of human glioblastoma cell lines U87 and T98G. Additionally, the toxic effects in vivo were studied in zebrafish Danio rerio embryos, with an estimated 50% lethal concentration of 0.1 mg/ml. Considering that bortezomib and other molecules from the class of proteasome inhibitors are potent antitumor agents, nanodelivery approach can help reduce adverse effects and expand the range of its applications for treatment of various oncological diseases., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Yagolovich et al.)

The coronavirus disease (COVID-19) pandemic has already affected millions of individuals, with increasing numbers of survivors. These data suggest that the pulmonary sequelae of the infection may have an effect on a wide range of individuals. The aim of the present study was to evaluate pulmonary function in patients hospitalized due to COVID-19 three months after hospital discharge. A total of 116 patients, 34 females and 82 males, with a mean age of 57.77±11.45 years, who were hospitalized due to COVID-19, underwent pulmonary function testing three months after their hospital discharge. Of these, 83 (71.6%) patients were hospitalized in the period of alpha variant predominance, 16 (13.8%) in the period of delta variant predominance and 17 (14.6%) in the omicron variant predominance period. The mean value of diffusion capacity for carbon monoxide (DLCO)% predicted (pred) was statistically higher in patients affected by the omicron variant (P=0.028). Abnormal values (<80% pred) of DLCO and total lung capacity (TLC) were observed in 28.4 and 20.7% of the patients, respectively. Active smoking was an independent predictor of abnormal values of forced expiratory volume in 1 sec % pred and TLC% pred [P=0.038; odds ratio (OR): 8.574, confidence interval (CI) 1.124-65.424 and P=0.004, OR: 14.733, CI 2.323-93.429, respectively], age was an independent predictor of abnormal values of forced vital capacity % pred and DLCO% pred (P=0.027, OR: 1.124, CI 1.014-1.246 and P=0.011, OR:1.054, CI 1.012-1.098, respectively); and female sex was an independent predictor of abnormal values of DLCO% pred (P=0.009, OR: 1.124, CI 1.014-1.246). Α significant percentage of hospitalized patients due to COVID-19 pneumonia will develop abnormal pulmonary function, regardless of the SARS-CoV-2 variant., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © Georgakopoulou et al.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) represented a global public health crisis and the most significant pandemic in modern times. Transmission characteristics, and the lack of effective antiviral treatment protocol and protective vaccines, pushed healthcare systems, particularly intensive care units (ICUs), to their limits and led to extreme quarantine measures to control the pandemic. It was evident from an early stage that patient stratification approaches needed to be developed to better predict disease progression. In the present study, the predictive value of clinical and blood biomarkers for the outcomes of patients with COVID-19 hospitalized in the ICU were investigated, taking age and sex into consideration. The present study analyzed blood samples from 3,050 patients with COVID-19 hospitalized in the ICU. The analysis revealed that the levels of procalcitonin, N-terminal pro-B-type natriuretic peptide, D-dimer, ferritin, liver enzymes, C-reactive protein and lactate dehydrogenase were increased and were associated with disease progression, resulting in a prolonged hospitalization period and severe COVID-19 related complications. Additionally, significant age and sex disparities among these biomarkers were documented and discussed in specific cases. On the whole, the results of the present study suggest a potential association of the demographic characteristics and blood biomarkers with prolonged hospitalization in the ICU and the mortality of patients with COVID-19., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © Genc et al.)

The application of decompressive craniectomy (DC) is thoroughly documented in the management of brain edema, particularly following traumatic brain injury. However, an increasing amount of concern is developing among the universal medical community as regards the application of DC in the treatment of other causes of brain edema, such as subarachnoid hemorrhage, cerebral hemorrhage, sinus thrombosis and encephalitis. Managing stroke continues to remain challenging, and demands the aggressive and intensive consulting of a number of medical specialties. Middle cerebral artery (MCA) infarcts, which consist of 1-10% of all supratentorial infarcts, are often associated with mass effects, and high mortality and morbidity rates. Over the past three decades, a number of neurosurgical medical centers have reported their experience with the application of DC in the treatment of malignant MCA infarction with varying results. In addition, over the past decade, major efforts have been dedicated to multicenter randomized clinical trials. The present study reviews the pertinent literature to outline the use of DC in the management of malignant MCA infarction. The PubMed database was systematically searched for the following terms: 'Malignant cerebral infarction', 'surgery for stroke', 'DC for cerebral infarction', and all their combinations. Case reports were excluded from the review. The articles were categorized into a number of groups; the majority of these were human clinical studies, with a few animal experimental clinical studies. The surgical technique involved was DC, or hemicraniectomy. Other aspects that were included in the selection of articles were methodological characteristics and the number of patients. The multicenter randomized trials were promising. The mortality rate has unanimously decreased. As for the functional outcome, different scales were employed; the Glasgow Outcome Scale Extended was not sufficient; the Modified Rankin Scale and Bathel index, as well as other scales, were applied. Other aspects considered were demographics, statistics and the very interesting radiological ones. There is no doubt that DC decreases mortality rates, as shown in all clinical trials. Functional outcome appears to be the goal standard in modern-era neurosurgery, and quality of life should be further discussed among the medical community and with patient consent., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © Fotakopoulos et al.)

The objective of the present review was to summarize the molecular mechanisms associated with the effects of the vitamins A, C, E and K, and group B vitamins on bone and their potential roles in the development of osteoporosis. Epidemiological findings have demonstrated an association between vitamin deficiency and a higher risk of developing osteoporosis; vitamins are positively related to bone health upon their intake at the physiological range. Excessive vitamin intake can also adversely affect bone formation, as clearly demonstrated for vitamin A. Vitamins E (tocopherols and tocotrienols), K2 (menaquinones 4 and 7) and C have also been shown to promote osteoblast development through bone morphogenetic protein (BMP)/Smad and Wnt/β‑catenin signaling, as well as the TGFβ/Smad pathway (α‑tocopherol). Vitamin A metabolite (all‑trans retinoic acid) exerts both inhibitory and stimulatory effects on BMP‑ and Wnt/β‑catenin‑mediated osteogenesis at the nanomolar and micromolar range, respectively. Certain vitamins significantly reduce receptor activator of nuclear factor kappa‑B ligand (RANKL) production and RANKL/RANK signaling, while increasing the level of osteoprotegerin (OPG), thus reducing the RANKL/OPG ratio and exerting anti‑osteoclastogenic effects. Ascorbic acid can both promote and inhibit RANKL signaling, being essential for osteoclastogenesis. Vitamin K2 has also been shown to prevent vascular calcification by activating matrix Gla protein through its carboxylation. Therefore, the maintenance of a physiological intake of vitamins should be considered as a nutritional strategy for the prevention of osteoporosis.

Telomeres are major contributors to cell fate and aging through their involvement in cell cycle arrest and senescence. The accelerated attrition of telomeres is associated with aging‑related diseases, and agents able to maintain telomere length (TL) through telomerase activation may serve as potential treatment strategies. The aim of the present study was to assess the potency of a novel telomerase activator on TL and telomerase activity in vivo . The administration of a nutraceutical formulation containing Centella asiatica extract, vitamin C, zinc and vitamin D3 in 18‑month‑old rats for a period of 3 months reduced the telomere shortening rate at the lower supplement dose and increased mean the TL at the higher dose, compared to pre‑treatment levels. TL was determined using the Q‑FISH method in peripheral blood mononuclear cells collected from the tail vein of the rats and cultured with RPMI‑1640 medium. In both cases, TLs were significantly longer compared to the untreated controls (P≤0.001). In addition, telomerase activity was increased in the peripheral blood mononuclear cells of both treatment groups. On the whole, the present study demonstrates that the nutraceutical formulation can maintain or even increase TL and telomerase activity in middle‑aged rats, indicating a potential role of this formula in the prevention and treatment of aging‑related diseases.

Although coronavirus disease 2019 (COVID-19)-induced changes in laboratory parameters in patients upon admission have been well-documented, information on their temporal changes is limited. The present study describes the laboratory trends and the effect of dexamethasone treatment on these parameters, in patients with COVID-19 in the intensive care unit (ICU). Routine laboratory parameters, namely white blood cell (WBC), neutrophil, lymphocyte and platelet (PLT) counts, fibrinogen, C-reactive protein (CRP), lactate dehydrogenase (LDH) and albumin concentrations, were recorded upon admission to the ICU and, thereafter, on days 3, 5, 10, 15 and 21; these values were compared between survivors and non-survivors, as well as between those who were treated with dexamethasone and those who were not. Among the 733 patients in the ICU, (mean age, 65±13 years; 68% males; ICU mortality rate 45%; 76% of patients treated with dexamethasone), the WBC and neutrophil counts were persistently high in all patients, without significant differences over the first 15 days. Initially, low lymphocyte counts exhibited increasing trends, but remained higher in survivors compared to non-survivors (P=0.01). The neutrophil-to-lymphocyte ratio (NLR) was persistently elevated in all patients, although it was significantly higher in non-survivors compared to survivors (P < 0.001). The PLT count was initially increased in all patients, although it was significantly decreased in non-survivors over time. The fibrinogen and LDH values remained similarly elevated in all patients. However, the increased levels of CRP, which did not differ between patients upon admission, further increased in non-survivors compared to survivors after day 10 (P=0.001). Declining trends in albumin levels over time, overall, with a significant decrease in non-survivors compared to survivors, were observed. Dexamethasone treatment significantly affected the temporal progression of fibrinogen and CRP in survivors and that of NLR in non-survivors. On the whole, the present study demonstrates that patients in the ICU with COVID-19 present persistently abnormal laboratory findings and significant differences in laboratory trends of NLR, CRP, PLT and albumin, but not in WBC and neutrophil count, and fibrinogen and LDH levels, between survivors and non-survivors. The temporal progression of fibrinogen, CRP and NLR is affected by dexamethasone treatment., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © Kokkoris et al.)

Coronavirus disease 2019 (COVID-19) is characterized by poor outcomes and a high mortality rate, particularly among elderly patients. Since the beginning of the pandemic, an older age has been recognized as a critical risk factor for disease severity, with increasing mortality rates in each decade of life. This phenomenon may be a consequence of a poor previous health status, with a higher prevalence of pre-existing comorbidities and a higher degree of frailty. The majority of studies on the outcomes and risk factors of elderly patients refer to the first waves of the pandemic and the predictors of in-hospital mortality in these patients. The aim of the present study was to provide a detailed description of the clinical characteristics and management of a cohort of elderly patients (≥65 years of age) who were hospitalized with COVID-19-related pneumonia in all phases of the pandemic, presenting their outcomes, and investigating predictors of in-hospital and out-of-hospital mortality over a period of 1 year in this particularly vulnerable population. A total of 1,124 elderly patients (603 males, 53.7%) with a mean age of 78.51±7.42 years and a median Charlson comorbidity index (CCI) of 5 were included in the study. Of these patients, 104 (9.3%) were hospitalized during the period of prevalence of the original strain Wuhan, 385 (34.3%) were hospitalized during the period of prevalence of the Alpha variant, 221 (19.7%) were hospitalized during the period of prevalence of the Delta variant, and 414 (36.8%) were hospitalized during the period of prevalence of the Omicron variant. Overall, the in-hospital mortality rate was 33.4% (375 patients), and the 1-year mortality rate was 44.7% (502 patients). The majority of patients had not been vaccinated or had not completed full vaccination against severe acute respiratory syndrome coronavirus-2 (843 patients, 75%), given the period of infection. Age, immature granulocytes, lactate dehydrogenase (LDH) levels, ferritin levels, chest X-ray score, as well as the absence of full vaccination, cough and fatigue, were statistically significantly and independently associated with in-hospital mortality, while age, LDH levels, ferritin levels, alanine aminotransferase levels, CCI, chest X-ray score, the absence of cough and fatigue, and a history of dementia were statistically significantly and independently associated with 1-year mortality. On the whole, the present study demonstrates that both the in-hospital mortality and 1-year mortality rates of elderly patients hospitalized due to COVID-19-related pneumonia are high., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © Georgakopoulou et al.)

Stress is a state of disrupted homeostasis, triggered by intrinsic or extrinsic factors, the stressors, which are counteracted by various physiological and behavioural adaptive responses. Stress has been linked to cancer development and incidence for decades; however, epidemiological studies and clinical trials have yielded contradictory results. The present review discusses the effects of stress on cancer development and the various underlying mechanisms. Animal studies have revealed a clear link between stress and cancer progression, revealing molecular, cellular and endocrine processes that are implicated in these effects. Thus, stress hormones, their receptor systems and their intracellular molecular pathways mediate the effects of stress on cancer initiation, progression and the development of metastases. The mechanisms linking stress and cancer progression can either be indirect, mediated by changes in the cancer microenvironment or immune system dysregulation, or direct, through the binding of neuroendocrine stress‑related signalling molecules to cancer cell receptors. Stress affects numerous anti‑ and pro‑cancer immune system components, including host resistance to metastasis, tumour retention and/or immune suppression. Chronic psychological stress through the elevation of catecholamine levels may increase cancer cell death resistance. On the whole, stress is linked to cancer development and incidence, with psychological stressors playing a crucial role. Animal studies have revealed a better link than human ones, with stress‑related hormones influencing tumour development, migration, invasion and cell proliferation. Randomized controlled trials are required to further evaluate the long‑term cancer outcomes of stress and its management.

Stress has been well-documented to have a significant role in the etiopathogenesis of bruxism. Activation of the hypothalamic-pituitary-adrenal axis (HPA) and subsequent release of corticosteroids lead to increased muscle activity. Neurological studies have demonstrated that chronic stress exposure induces neurodegeneration of important neuronal structures and destabilization of the mesocortical dopaminergic pathway. These disruptions impair the abilities to counteract the overactivity of the HPA axis and disinhibit involuntary muscle activity, while at the same time, there is activation of the amygdala. Recent evidence shows that overactivation of the amygdala under stressful stimuli causes rhythmic jaw muscle activity by over activating the mesencephalic and motor trigeminal nuclei. The present review aimed to discuss the negative effects of certain vitamin and mineral deficiencies, such as vitamin D, magnesium, and omega-3 fatty acids, on the central nervous system. It provides evidence on how such insufficiencies may increase stress sensitivity and neuromuscular excitability and thereby reduce the ability to effectively respond to the overactivation of the sympathetic nervous system, and also how stress can in turn lead to these insufficiencies. Finally, the positive effects of individualized supplementation are discussed in the context of diminishing anxiety and oxidative stress, neuroprotection and in the reversal of neurodegeneration, and also in alleviating/reducing neuromuscular symptoms., Competing Interests: IAP, MA and VZ declare that they have no competing interests. DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision for this article., (Copyright: © Pavlou et al.)

Telomeres are the ends of chromosomes that protect them from DNA damage. There is evidence to suggest that telomere shortening appears with advanced age. Since aging is a significant risk factor for developing age-related complications, it is plausible that telomere shortening may be involved in the development of osteoporosis. The present review summarizes the potential of telomere shortening as a biomarker for detecting the onset of osteoporosis. For the purposes of the present review, the following scientific databases were searched for relevant articles: PubMed/NCBI, Cochrane Library of Systematic Reviews, Scopus, Embase and Google Scholar. The present review includes randomized and non-randomized controlled studies and case series involving humans, irrespective of the time of their publication. In six out of the 11 included studies providing data on humans, there was at least a weak association between telomere length and osteoporosis, with the remaining studies exhibiting no such association. As a result, telomere shortening may be used as a biomarker or as part of a panel of biomarkers for tracking the onset and progression of osteoporosis., Competing Interests: DAS is the editor-in-chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision for this article. The other authors declare that they have no competing interests., (Copyright: © Kakridonis et al.)

Gout is a chronic disease frequently associated with lifestyle; its prevalence is increasing in Western societies, as well as in the Middle East. Apart from its partial genetic features, diet accounts for 12% of the causality of the disease, while purine-rich foods contribute decisively to its development and evaluation. The influential Persian physician of the medieval ages, Abu Bakr Muhammad Ibn Zakariya al-Razi (or by his Latin name Rhazes; 860-925 AD), wrote a short book (20 chapters) entitled ' Treatise on gout '. Rhazes adopted the Hippocratic humoralism, and suggested that the disease results from metabolic excess in the peripheral blood, presenting sex dimorphism and age-dependence. His therapeutic guidelines include a diet prescribed by a physician, the use of laxatives and emetics, counter-balancing excess or deficiency of bile or phlegm and analgesics, bloodletting, foot and steam baths, as well as salves and poultices as preventive measures. He appends differential dietary restrictions/suggestions for phlegmatic or choleric patients: Small rations and intake of good quality foods low in purine by 20% for phlegmatic and 28% for choleric patients, as well as the restriction of foods high in purine by 27% for phlegmatic and 22% for the choleric patients. Finally, the acidic to alkaloid food intake ratio suggested is 2/5 for choleric and 3/7 for phlegmatic patients. His suggested foods and drugs are vitamin C and B-rich complexes, thereby inhibiting the accumulation of tophi., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Geronikolou et al.)

Cervical myelopathy is a well-described medulla spinalis syndrome characterized by sensory disorders, such as pain, numbness, or paresthesia in the limbs, and motor disorders, such as muscle weakness, gait difficulties, spasticity, or hyperreflexia. If left untreated, cervical myelopathy can significantly affect the quality of life of patients, while in severe cases, it can cause disability or even quadriplegia. Cervical myelopathy is the final stage of spinal cord insult and can result from transgene dysplasias of the spinal cord, and acute or chronic injuries. Spondylosis is a common, multifactor cause of cervical myelopathy and affects various elements of the spine. The development of spondylotic changes in the spine is gradual during the patient's life and the symptoms are presented at a late stage, when significant damage has already been inflicted on the spinal cord. Spondylosis is widely considered a condition affecting the middle aged and elderly. Given the fact that the population is gradually becoming older, in the near future, clinicians may have to face an increased number of patients with spondylotic myelopathy., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © Fotakopoulos et al.)

In the context of coronavirus disease 2019 (COVID-19), laboratory medicine has played a crucial role in both diagnosis and severity assessment. Although the importance of baseline laboratory findings has been extensively reported, data regarding their evolution over the clinical course are limited. The aim of the present narrative review was to provide the dynamic changes of the routine laboratory variables reported in patients with severe COVID-19 over the course of their critical illness. A search was made of the literature for articles providing data on the time-course of routine laboratory tests in patients with severe COVID-19 during their stay in the intensive care unit (ICU). White blood cell, neutrophil and lymphocyte counts, neutrophil to lymphocyte ratio, platelet counts, as well as D-dimer, fibrinogen, C-reactive protein, lactate dehydrogenase and serum albumin levels were selected as disease characteristics and routine laboratory parameters. A total of 25 research articles reporting dynamic trends in the aforementioned laboratory parameters over the clinical course of severe COVID-19 were identified. During the follow-up period provided by each study, the majority of the laboratory values remained persistently abnormal in both survivors and non-survivors. Furthermore, in the majority of studies, the temporal trends of laboratory values distinctly differentiated patients between survivors and non-survivors. In conclusion, there are distinct temporal trends in selected routine laboratory parameters between survivors and non-survivors with severe COVID-19 admitted to the ICU, indicating their importance in the prognosis of clinical outcome., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Kokkoris et al.)

The present review article presents the key messages of the 8th Workshop on Paediatric Virology organised virtually by the Institute of Paediatric Virology based on the island of Euboea in Greece. The major topics covered during the workshop were the following: i) New advances in antiviral agents and vaccines against cytomegalovirus; ii) hantavirus nephropathy in children; iii) human rhinovirus infections in children requiring paediatric intensive care; iv) complications and management of human adenovirus infections; v) challenges of post‑coronavirus disease 2019 (COVID‑19) syndrome in children and adolescents; and vi) foetal magnetic resonance imaging in viral infections involving the central nervous system. The COVID‑19 era requires a more intensive, strategic, global scientific effort in the clinic and in the laboratory, focusing on the diagnosis, management and prevention of viral infections in neonates and children.

Meningitis/ventriculitis (MV) is an illness which can occur as a complication following neurosurgical procedures. Devices such as an external ventricular drain (EVD) are also related to considerable complications, such as infections. The present study examined the risk factors associated with central nervous system (CNS) infections associated with the external ventricle drainage system. The present retrospective study included all patients hospitalized between April, 2011 and August, 2018 who had been receiving therapy with EVD for developed hydrocephalus. A total of 48 out of 65 patients were classified into two groups as follows: Patients without MV (group A) and patients who developed MV (group B). The durations of hospital stay and intensive care unit (ICU) stay were significantly lower in group A (32.4±24 and 21.1±11 days, respectively) compared to group B (54.7±37 and 42±24 days, respectively) (P=0.027 and P=0.001, respectively). The Acute Physiological and Chronic Health Evaluation II (APACHE II) score and EVD distance from the wound exit side to the burr hole were significantly lower in the survivors compared to the non-survivors (17.5±6 and 15.4±4 vs. 22.5±6 and 39.8±38, respectively). Receiver operating characteristic analysis revealed that the APACHE II score with an area under the curve [(AUC) of 0.677, P=0.044, and 95% confidence interval (CI) of (0.516-0.839)] and a cut-off value of 14 could predict mortality with a sensitivity of 100% and a specificity of 71%; the EVD distance from the wound exit side from the burr hole with an AUC of 0.694 (P=0.028), 95% CI of 0.521-0.866 and a cut-off value of 11.5 mm could predict mortality with a sensitivity of 88% and a specificity of 83%. On the whole, the present study demonstrates that the EVD-related distance from the wound exit side of the burr hole can predict poor outcomes due to CNS infections in patients undergoing neurosurgery., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Gatos et al.)

Remdesivir, a viral RNA polymerase inhibitor, has constituted a key component of therapeutic regimens against the pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Originally approved for administration in hospitalized patients, remdesivir leads to improved outcomes in patients with moderate to severe coronavirus disease 2019 (COVID-19). After proving to be effective in hospitalized patients, its use gained approval in early-stage disease for symptomatic outpatients who are at a high risk of progression to severe disease. The present study is a real-life prospective cohort study involving 143 elderly non-hospitalized patients with SARS-CoV-2 (≥65 years of age) who attended the emergency department of the authors' hospital seeking care for COVID-19 symptoms appearing within the prior 7 days. Eligible patients received intravenous remdesivir at a dose of 200 mg on the first day and 100 mg on days 2 and 3. The efficacy endpoints were set as the need for COVID-19-related hospitalization and all-cause mortality in the following 28 days. A total of 143 patients participated in the study. Of these patients, 118 (82.5%) patients were vaccinated with at least two doses. All patients enrolled completed the 3-day course, with a total of 6 out of 143 patients (4.2%) having a COVID-19-related hospitalization by day 28, and 5 patients (3.5%) succumbing to the disease within the study period. In the univariate Cox regression analysis, the neutrophil-to-lymphocyte ratio and haematological malignancy were identified as predictors of progression to severe disease, and albumin levels, the C-reactive protein-to-albumin ratio (CAR) and haematological malignancy were identified as predictors of 28-day mortality. On the whole, the findings of the present study demonstrated that among the elderly outpatients, a 3-day course of intravenous remdesivir was associated with favourable outcomes., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © Georgakopoulou et al.)

Glioblastoma multiforme (GBM) is the most frequent and malignant primary central nervous system tumor in adults. The gold-standard management of GBM includes post-operative radiotherapy (RT) with concurrent and secondary temozolomide (TMZ) treatment. The present meta-analysis study examined the efficacy of the early administration of bevacizumab prior to standard RT plus TMZ in managing patients with GBM and unfavorable prognostic factors. Between 1983 and 2020, the present study looked for comparative articles involving standard RT plus TMZ and RT/TMZ combined with bevacizumab treatment in patients with GBM. The primary outcomes involved in this study include progression-free survival and overall survival. The present study suggested that bevacizumab administration plus standard RT/TMZ (BEV group) treatment was associated with increased survival of patients with GBM compared with those treated with standard RT/TMZ (CG/Control group) treatment only., Competing Interests: The authors declare that they have no competing interests. DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article., (Copyright: © Aravantinou-Fatorou et al.)

Patients undergoing intracranial meningioma removal have been reported to have an increased risk of venous thromboembolism (VTE). The present study aimed to study meningioma operations and ascertain rates of postoperative VTE more closely and to find out the associated parameters with VTE-related morbidity and mortality in meningioma patients following resection. This meta-analysis included articles involving meningiomas surgery and postoperative VTE [thromboembolic complications: deep venous thrombosis (DVT) and pulmonary embolism (PE)] published in full-text form between January 1980 and January 2021). Collected variables included: First author name, study period covered, publication year, total number of patients and age, number of males, surgical duration, body mass index (BMI), tumor location, proliferation marker for human tumor cells Ki-67 and VTE-related morbidity and mortality. After the initial search and applying all exclusion and inclusion criteria, five articles were left in the final article pool. The total number of patients was 6,505 who underwent surgery for meningiomas and 299 (4.5%) revealed postoperative VTE. The final results showed no potentially significant difference between the total sample and the postoperative VTE group in tumor location and proliferation marker Ki-67 for human cells. By contrast, the results of the analysis for surgical duration and BMI showed a statistically significant difference. Patients who had experienced open surgery for meningiomas were associated with postoperative VTE. Furthermore, surgical duration and BMI were statistically significant VTE-related parameters in patients who underwent meningioma surgery, showing an association with VTE-related morbidity and mortality., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors have no competing interests., (Copyright: © Georgakopoulou et al.)

Intracranial aneurysm (IA) is a common cerebrovascular disease with a high risk of rupture. At present, the mechanisms underlying the formation and rupture of IAs is not clinically clear. MicroRNAs (miRNAs/miRs) are involved in the development of IAs. The present study aimed to determine the efficacy of circulating miRNA-126 (miR-126) levels as potential biomarkers for predicting aneurysmal ruptures. The present study searched comparative articles involving circulating miR-126 levels and intracranial aneurysms through electronic databases from 1980 to February, 2023. Collected variables included the first author's name, covered study period, publication year, total number of patients and age, and number of males. We collected information about the expression levels of circulating miR-126 in serum. Three articles met the eligibility criteria. The total number of patients was 379 [226 with IA rupture and 153 with non-rupture or/+ controls (healthy)]. The circulating miR-126 can be used as a biomarker for predicting aneurysmal rupture. Interestingly, an aneurysmal size >10 mm was associated with an IA rupture., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © Mathioudakis et al.)

Patients with Parkinson's disease (PD) and coronavirus disease 2019 (COVID-19)-associated pneumonia present, according to the literature, high mortality rates due to the nature of the disease, advanced age, and underlying diseases. Most available studies, however, refer to the first waves of the pandemic. The aim of the present study was to investigate the clinical characteristics and outcomes of elderly patients (≥65 years old) with PD hospitalized with COVID-19-associated pneumonia during the period of prevalence of various severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, as well as to determine possible prognostic factors for poor outcomes. During the period from February 15, 2021, to July 15, 2022, 1,144 elderly patients with COVID-19 pneumonia were hospitalized. Age, sex, Charlson comorbidity index, vaccination status against SARS-CoV-2, and admission laboratory parameters were recorded for all patients. A total of 36 (3.1%) patients with PD were hospitalized due to COVID-19-associated pneumonia (18 males, 50%). The mean age of the patients was 82.72±8.18 years. In total, 8 patients (22.2%) were hospitalized during the period of alpha variant predominance, 3 patients (8.3%) during the period of delta variant predominance, and 25 patients (69.4%) during the omicron variant predominance period. Of note, 16 patients (44.4%) were vaccinated with at least two doses. In addition, 17 (47.2%) patients succumbed to the disease. Between the patients who survived and those who succumbed, a statistically significant difference was only found in the mean value of albumin (37.48±6.02 vs. 31.97±5.34 g/l, P=0.019). In particular, as shown by receiver operating characteristic curve analysis, albumin exhibited a satisfactory predictive ability for mortality (area under the curve, 0.780; P=0.013) with an albumin value ≤37.7 g/l being able to predict mortality with 85.7% sensitivity and 54.8% specificity. Overall, the findings of the present study indicate that mortality among elderly patients with PD hospitalized with COVID-19-associated pneumonia was high in all phases of the pandemic. A low albumin value, not only as an indicator of the immune status, but also of the nutritional status, is a predictor of adverse outcomes., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Georgakopoulou et al.)

The mortality of elderly patients with dementia hospitalized with coronavirus disease 2019 (COVID-19)-associated pneumonia is high. The mortality rate of these patients continues to be high following their discharge. However, data on the outcomes of these patients in all phases of the pandemic are limited. The aim of the present study was to examine the clinical characteristics and the in-hospital and 90-day mortality rates of elderly patients with dementia hospitalized due to COVID-19-associated pneumonia during all phases of the pandemic. During the time period between February 15, 2021 to July 15, 2022, 105 elderly patients (≥65 years old) with dementia of various etiologies were hospitalized due to COVID-19-associated pneumonia. The patient characteristics and in-hospital outcomes within 90 days of admission were recorded. The mean age of the patients was 84.03±7.61 years and 60 (57.1%) patients were females. A total of 52 (49.5%) patients were hospitalized during the omicron variant period, 27 (25.7%) were fully vaccinated (three doses) and 38 (36.2%) patients succumbed during their hospitalization. In total, 52 (49.5%) patients succumbed within the first 90 days of admission. According to the univariate regression analysis, the omicron variant [hazard ratio (HR), 2.126; 95% confidence interval (CI), 1.073-4.213; P=0.031] and the absence of full vaccination (HR, 6.231; 95% CI, 1.500-25.87; P=0.012) were associated with a higher in-hospital mortality. In the multivariate regression analysis, only the absence of complete vaccination was an independent predictor of mortality (HR, 5.182; 95% CI, 1.205-22.28; P=0.027). According to the univariate regression analysis, age (HR, 1.045; 95% CI, 1.006-1.085; P=0.023) and the lack of complete vaccination (HR, 3.254; 95% CI, 1.294-8.181; P=0.012) were associated with 90-day mortality; in addition, by multivariate regression analysis, age (HR, 1.047; 95% CI, 1.007-1.048; P=0.021) and the absence of full vaccination (HR, 3.286; 95% CI, 1.307-8.265; P=0.011) exhibited an independent association with the 90-day mortality rate. Based on the findings presented herein, the in-hospital and 90-day mortality rates of elderly patients with dementia and COVID-19-associated pneumonia is high. An older age and the lack of complete vaccination are independently associated with poor outcomes., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © Georgakopoulou et al.)

Cancer is considered the most important clinical, social and economic issue regarding cause‑specific disability‑adjusted life years among all human pathologies. Exogenous, endogenous and individual factors, including genetic predisposition, participate in cancer triggering. Telomeres are specific DNA structures positioned at the end of chromosomes and consist of repetitive nucleotide sequences, which, together with shelterin proteins, facilitate the maintenance of chromosome stability, while protecting them from genomic erosion. Even though the connection between telomere status and carcinogenesis has been identified, the absence of a universal or even a cancer‑specific trend renders consent even more complex. It is indicative that both short and long telomere lengths have been associated with a high risk of cancer incidence. When evaluating risk associations between cancer and telomere length, a disparity appears to emerge. Even though shorter telomeres have been adopted as a marker of poorer health status and an older biological age, longer telomeres due to increased cell growth potential are associated with the acquirement of cancer‑initiating somatic mutations. Therefore, the present review aimed to comprehensively present the multifaceted pattern of telomere length and cancer incidence association.

The relationship between trauma and psychosis is complex and multifaceted, with evidence suggesting that trauma can be both a risk factor for the development of psychosis and a consequence of psychotic experiences. The present review aimed to provide an overview of the current state of knowledge on the relationship between trauma and psychosis, including historical and conceptual considerations, as well as epidemiological evidence. The potential explanation of the link between trauma and psychosis is provided through available models and similarities in their neurobiological associations. Overall, the research confirms the relationship between trauma and psychosis, and suggests that individuals with a co-occurring history of trauma and psychosis may have increased symptom severity and worse functional outcomes compared with individuals with psychosis alone. Future research should focus on elucidating the underlying causal pathways between trauma exposure and psychosis in order to inform effective treatment approaches aiming to prevent the intensification of psychotic symptoms and processes., Competing Interests: IG, SG, MS and ER declare that they have no competing interests. DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article., (Copyright: © Giannopoulou et al.)

Patients with acute ischemic stroke (AIS) presenting mild symptoms with a low National Institutes of Health Stroke Scale (NIHSS) score ≤8 and also found to have an intracranial large vessel occlusion (LVO) undergo endovascular thrombolysis (ET) or medical management alone. The current study aimed to evaluate the safety and effectiveness of medical management vs. ET therapy among patients with mild AIS symptoms (NIHSS score ≤8) accompanied by LVO. The present meta-analysis included articles involving mild AIS, LVO, thrombectomy/ET and medical management alone published in full-text form (from 1980 to 2022). Collected variables included: First author name, covered study period, publication year, the total number of patients and age, number of males, presence of diabetes mellitus, hypertension, atrial fibrillation, prior ischemic stroke, location, NIHSS of admission, modified Rankin scale, bleeding, morbidity and mortality. After the initial search and applying all exclusion and inclusion criteria, eight articles were left in the final article pool. The total number of patients who underwent ET was 569, compared with 1097 with medical management for LVO strokes with minimal symptoms. The findings of the present meta-analysis study point out that ET management may be associated with a high risk of bleeding and mortality in patients with LVO presenting with mild symptoms (NIHSS score ≤8)., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article., (Copyright: © Anagnostopoulos et al.)

With the onset of the coronavirus disease 2019 (COVID-19) pandemic, numerous countries imposed strict lockdown measures and travel bans, resulting in the closure of hotels. Over time, the opening of hotel units was gradually allowed, and new strict regulations and protocols were issued to ensure the hygiene and safety of swimming pools in the era of COVID-19. The present study aimed to evaluate the implementation of strict health COVID-19-related protocols in hotel units during the 2020 summer tourist season concerning microbiological hygiene and physicochemical parameters of water, and to compare the data with those from the 2019 tourist season. For this reason, 591 water samples from 62 swimming pools were analyzed, of which 381 samples were for the 2019 tourist season and 210 samples were for the 2020 tourist season. To examine the presence of Legionella spp , 132 additional samples were taken from 14 pools, of which 49 in 2019 and 83 in 2020. In 2019, 2.89% (11/381) of the samples were out of legislative limits (0/250 mg/l) regarding the presence of Escherichia coli ( E. coli ), 9.45% (36/381) were out of acceptable limits (0/250 mg/l) regarding the presence of Pseudomonas aeruginosa ( P. aeruginosa ) and 8.92% (34/381) had residual chlorine levels <0.4 mg/l. In 2020, 1.43% (3/210) of the samples were out of the legislative limits as regards the presence of E. coli , 7.14% (15/210) were out of acceptable limits regarding the presence of P. aeruginosa and 3.33% (7/210) of the samples measured residual chlorine levels <0.4 mg/l. The risk ratio (RR) in relation to the presence of E. coli due to incorrect compliance with the requirements for residual chlorine was calculated for 2019 at 8.50, while in 2020 it was calculated at 14.50 (P=0.008). The RR of the presence of P. aeruginosa due to inappropriate residual chlorine requirements was calculated in 2019 at 2.04 (P=0.0814), while in 2020 it was calculated at 2.07 (P=0.44). According to the microbiological hygiene and physicochemical parameters of the water samples studied, there was a significant improvement due to the strict protocols for the swimming pools in the summer season of 2020 compared to the tourist season of 2019, namely 72.72% ( E. coli ), 58.33% ( P. aeruginosa ), 79.41% (of residual chlorine <0.4 mg/l) in the three main parameters studied. Finally, an increased colonization by Legionella spp. detected in the internal networks of the hotels due to the non-operation of the hotels during the lockdown, the improper disinfection and stagnant water in the internal water supply networks. Specifically, in 2019, 95.92% (47/49) of the samples tested negative and 4.08% (2/49) tested positive (≥50 CFU/l) for Legionella spp. , compared to 2020 where 91.57% (76/83) of the samples tested negative and 8.43% (7/83) tested positive., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2023 Papadakis et al.)

Vaccination against hepatitis B virus (HBV) remains the most effective strategy against HBV infection in humans. The present review summarized the optimal vaccination strategies against HBV in childhood. The following points are discussed: i) When and how the first HBV vaccines were developed; ii) the dosages, schedules and injection routes that are used for HBV vaccination; iii) the contraindications for HBV vaccination in the general paediatric population; iv) the challenges with the use of multivalent vaccines; v) the long-term immunogenicity and duration of protection against HBV; vi) the use of selective HBV vaccination and the hepatitis B immune globulin strategy in HBV-exposed infants; and vii) the effectiveness of the current HBV vaccination schemes. The present review is based on a Paediatric Virology Study Group (PVSG) webinar performed in the context of the 8th Workshop on Paediatric Virology., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. AK is a member of the Academic Board of the Institute of Paediatric Virology. INM and DAS are co-founders of the Institute of Paediatric Virology., (Copyright: © Κramvis et al.)

The gut microbiota plays a key role in maintaining health and regulating the host's immune response. The use of probiotics and concomitant vitamins can increase mucus secretion by improving the intestinal microbial population and prevent the breakdown of tight junction proteins by reducing lipopolysaccharide concentration. Changes in the intestinal microbiome mass affect multiple metabolic and physiological functions. Studies on how this microbiome mass and the regulation in the gastrointestinal tract are affected by probiotic supplements and vitamin combinations have attracted attention. The current study evaluated vitamins K and E and probiotic combinations effects on Escherichia coli and Staphylococcus aureus . Minimal inhibition concentrations of vitamins and probiotics were determined. In addition, inhibition zone diameters, antioxidant activities and immunohistochemical evaluation of the cell for DNA damage were performed to evaluate the effects of vitamins and probiotics. At the specified dose intervals, L. acidophilus and vitamin combinations inhibit the growth of Escherichia coli and Staphylococcus aureus . It could thus contribute positively to biological functions by exerting immune system‑strengthening activities.