Pseudoexfoliation syndrome: The critical role of the extracellular matrix in pathogenesis and treatment.

Pseudoexfoliation syndrome (PEXS) is an age-related condition manifesting mainly in ocular tissues. PEXS is manifested through excess aggregation of fibrillary extracellular material at the anterior part of the eye that consists of a plethora of biomolecules, such as different proteoglycans (PGs) and glycosaminoglycans. PEXS is often linked to increased intraocular pressure, and can also lead to pseudoexfoliation glaucoma with very poor prognosis. Various stimuli are known to affect PEXS, including oxidation stress (OS), UV radiation and osmotic pressure. OS, is prominently involved on the progression of the syndrome as it promotes fibrogenesis, possibly via the induction of transforming growth factor-ß (TGF-ß) and other biomolecular effectors. In addition, PEXS initiation is tightly connected with the dysregulation of extracellular matrix (ECM) homeostasis since aberrant expression of ECM molecules is linked to both the accumulation and low degradation of pseudoexfoliation material. This article aims at uncovering the crucial role of various ECM effectors such as lysyl oxidase-like proteins, matrix metalloproteinases, and TGF-ß1, as well as the biochemical pathways involved in the development and the progression of the PEXS.

p53 mutations in oral cavity carcinoma.

Head and neck squamous cell carcinoma (HNSCC) includes a variety of SCCs derived from the anatomic regions of the oral and nasal cavity and also of the pharynx and larynx. Oral cavity SCC (OCSCC) demonstrates an increasing rate due to viral -related (High Risk Human Papilloma Virus-HR HPV) persistent infection, cigarette smoking and alcohol consumption. Gross chromosomal alterations (polysomy, aneuploidy) and specific gene aberrations such as amplifications, deletions, point mutations combined or not with epigenetic ones (promoter methylations and miRNA deregulations) are responsible for the progressive transformation of normal squamous epithelia to the corresponding malignant. In the majority of OCSCC cases, critical genes, such as p53 are found to be inactivated, leading to an overactivated cell cycle correlated to carcinogenetic process. P53 (gene location: 17p13.1) is a suppressor gene acting as a key regulator of the cell's genomic stability, function and homeostasis. P53 aberrant overexpression is frequently observed in OCSCC tissues as a result of point mutation or deletion. In the current special article we explored the role of the p53 gene deregulation - especially focused on its mutation status - in OCSCCs.

mTOR deregulation in oral cavity squamous cell carcinoma.

Signal transduction pathways consist of a variety of inter- and intra-cellular molecules. They act as supporting mechanisms for cell survival and homeostasis. Among them, the phosphatidylinositol 3-kinase (PI3K)/tumor suppressor phosphatase and tensin homologue deleted on chromosome ten (PTEN)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway plays a crucial role in regulating normal cell growth based on growth factor receptors (GFRs) interaction, including epidermal GFR (type II-HER2) and insulin GFR (IGF). mTOR protein acts as a serine-threonine kinase that belongs to the PI3K-related kinase family. It mediates protein and lipid synthesis, mitochondrial metabolism, biogenesis, proliferation and also negatively regulates autophagy. Two distinct multiprotein complexes have been mainly identified and cloned: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). mTOR is deregulated predominantly due to mutations, deletions, loss of heterozygosity (LOH) or abnormal phosphorylation of the upstream molecules inside the current pathway. Pure mTOR mutations are very rare. Development of specific inhibitors at the basis of targeted therapeutic strategies such as rapamycin (rapalogs) is an evolution in handling patients with mTOR abnormal overactivity. In the current special article we explored the role of the gene deregulation leading to abnormal protein expression in oral cavity squamous cell carcinoma (SCC).

Topoisomerase I deregulation in laryngeal squamous cell carcinomas based on tissue microarray analysis.

PURPOSE: Topoisomerases (types: I/IIa-b/IIIa-b) represent a super-family of nucleic enzymes involved in the DNA replication, transcription, recombination, and also chromosome topological formation. Topoisomerase's I (Topo I- gene location: 20q12) aberrant expression is a frequent genetic event in a variety of solid malignancies. Topo I inhibition promotes cell death due to DNA damage and for this reason it is a target for specific targeted chemotherapy (camptothecin, topotecan, irinotecan). Our aim was to investigate the role of abnormal Topo I protein expression in laryngeal squamous cell carcinomas (LSCC) in which there are very limited data regarding the influence of the marker. METHODS: Using tissue microarray (TMA) technology, 50 formalin-fixed, paraffin-embedded primary laryngeal SCCs were cored and re-pembedded into one recipient block. Immunohistochemistry was performed using anti- Topo I antibody. Digital image analysis was also implemented for evaluating objectively the protein expression levels on the corresponding stained nuclei. RESULTS: Topo I protein overexpression (moderate to high staining intensity values) was observed in 32/50 (64%) tissue cores, whereas low expression rates were detected in 18/50 (36%) cases. Topo I overall expression was strongly associated with the differentiation grade of the examined tumors (p=0.021). No other statistical correlations were identified. CONCLUSIONS: Topo I overexpression is observed in a significant subset of LSCCs affecting the level of differentiation in them. Additional molecular studies focused on the mechanism of Topo I gene/protein deregulation (i.e. amplification, abnormal epigenetic promoter methylation, mRNA aberrant expression) are necessary discriminating the eligible patients for applying specific chemotherapeutic strategies based on anti-Topo I agents.

Novel molecular and metabolic aspects in osteosarcoma.

Osteosarcoma (OS) is the most frequent bone-forming malignancy in children and adolescents. Concerning its molecular landscape, there is no a direct relationship with a specific gene, but a combination of genetic events. A broad spectrum of activated oncogenes and downregulated suppressor genes has been already explored and considered crucial for its progressive pathogenesis. Mechanisms of gene deregulation include amplifications, point mutations, allelic losses and also epigenetic abnormalities such as aberrant promoter methylation. Although a significant progress in understanding the molecular nature of the OS has been achieved, its aggressive phenotype - characterized by high metastatic potential - remains unexplored. Novel targeted therapeutic strategies include monoclonal antibodies (mABs) and also tyrosine-kinase inhibitors (TKIs). Additionally, sophisticated and innovative diagnostic techniques, such as 18 fluorodeoxyglucose positron emission tomography plus CT (18F-FDG/PET/CT), provide critical data regarding its biological behavior. In the current paper, we present novel molecular and metabolic advances by analyzing OS genetic profile and biochemical microenvironment.

Non­Hodgkin's lymphomas of the lacrimal sac: Current insights and future directions (Review).

Non-Hodgkin's lymphoma (NHL) of the lacrimal sac is a rare, yet clinically significant entity within the spectrum of ocular malignancies. While primary lacrimal sac lymphoma is uncommon, it poses unique diagnostic and therapeutic challenges due to its anatomical location and potential for aggressive behavior. Despite advancements being made in the current understanding and treatment of NHL, research that specifically addresses the involvement of the lacrimal sac is currently lacking. Thus, the present review aimed to provide insight into the epidemiology, clinical presentation, diagnostic modalities, histopathological features, treatment strategies and prognosis of lacrimal sac NHL. Through a methodical analysis of previous literature, the present review highlights the diverse spectrum of NHL subtypes that affect the lacrimal sac, including diffuse large B-cell lymphoma, extranodal marginal zone lymphoma, mantle cell lymphoma and follicular lymphoma. Moreover, the present review discusses the role of advanced imaging techniques in accurate staging and treatment planning, including computed tomography (CT), magnetic resonance imaging and positron emission tomography-CT. The present review also discusses evolving treatment approaches, such as surgical intervention, chemotherapy, radiotherapy, immunotherapy, combinations of the aforementioned treatments and targeted therapy. In addition, the present review highlights the significance of multidisciplinary collaboration in attaining optimal outcomes for individuals with lacrimal sac NHL. The present review aimed to provide a basis for 'further investigations into novel treatment modalities and prognostic markers that may aid in guiding personalized management strategies, ultimately improving outcomes for patients with NHL.

Multiple Behavioral Risk Factors As Assets for Chronic Disease Prevention: Observations From Urban Primary Care Settings in Crete, Greece.

AIM: This study aimed to assess the health profile of patient-attendees visiting primary healthcare (PHC) practice settings in the midst of the COVID-19 pandemic and to explore the relationships between multiple behavioral risk factors (MBRFs) and consultation-driven health information. Multiple behavioral risk factors involve a variety of unhealthy behaviors that are associated with an increased prevalence of non-communicable diseases (NCDs). SUBJECTS AND METHODS: The study design was based on a dataset analysis, afterward exploring the feasibility and diagnostic capacity of respiratory morbidity aspects from a study previously conducted. The study dataset contained information regarding socio-demographic characteristics, health habits, clinical information, and reported comorbidities from 183 primary care patient-attendees. A categorical regression analysis was performed, using as a numeric variable the multiple MBRFs (clustering of 0 to four factors) in order to examine relationships with the basic and clinical characteristics of the patient-attendees. RESULTS: Based on this secondary analysis, it was found that the prevalence of MBRFs is quite common among patient-attendees visiting urban PHC facilities. The prevalence of current smoking, sleep deprivation, increased body weight, and medium/high perceived stress levels were 33.9%, 52.5%, 83.1%, and 35.0%, respectively. An increased occurrence of MBRFs might be significantly predicted by the lower age of patient-attendees (b = -0.221, p = 0.05), by the absence of gray hair at an early age (b = -0.144, p = 0.042), by the physical discomfort during activities (b = 0.191, p = 0.017), or by the lower oxygen saturation (b = -0.184, p = 0.004). Diabetes mellitus (25.1%) was the most prevalent condition, followed by bronchial asthma (18.6%) and depression (15.8%). CONCLUSIONS: Lower age, absence of premature hair whitening, physical discomfort during activities, and lower oxygen saturation are linked with an increased occurrence of MBRFs, leading to a neglected way of living. Those factors could be used to alert researchers, policymakers, and PHC professionals to act accordingly in order to prevent or early diagnose NCDs.

Emerging roles of oxidative stress in the pathogenesis of pseudoexfoliation syndrome (Review).

Pseudoexfoliation syndrome (PEXS) is a systemic disease caused by defects in the extracellular matrix (ECM) remodelling process leading to the chronic deposition of extracellular, fibrillary, white flaky pseudoexfoliation material (PEXM) throughout the body. Specifically, PEXM deposits on the lens capsule cause open-angle glaucoma, cataracts and blindness in patients with PEXS. Several gene single nucleotide polymorphisms are linked to the development of PEXS in humans, including lysyl oxidase-like 1 gene, clusterin and fibulin-5. The exact reason for the PEXM generation and its resulting pathogenesis is not well understood. However, defective ECM remodelling and oxidative stress (OS) have been hypothesized as significant events leading to the PEXM. Specifically, the link between OS and PEXS has been well studied, although the investigation is still ongoing. The present review explored recent advances in various aspects of PEXS and the involvement of OS in the eye for PEXS development.

Antioxidant Defense and Pseudoexfoliation Syndrome: An Updated Review.

Oxidative stress (OS) affects the anterior ocular tissues, rendering them susceptible to several eye diseases. On the other hand, protection of the eye from harmful factors is achieved by unique defense mechanisms, including enzymatic and non-enzymatic antioxidants. The imbalance between oxidants and antioxidants could be the cause of pseudoexfoliation syndrome (PEXS), a condition of defective extracellular matrix (ECM) remodeling. A systematic English-language literature review was conducted from May 2022 to June 2022. The main antioxidant enzymes protecting the eye from reactive oxygen species (ROS) are superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), which catalyze the reduction of specific types of ROS. Similarly, non-enzymatic antioxidants such as vitamins A, E and C, carotenoids and glutathione (GSH) are involved in removing ROS from the cells. PEXS is a genetic disease, however, environmental and dietary factors also influence its development. Additionally, many OS products disrupting the ECM remodeling process and modifying the antioxidative defense status could lead to PEXS. This review discusses the antioxidative defense of the eye in association with PEXS, and the intricate link between OS and PEXS. Understanding the pathways of PEXS evolution, and developing new methods to reduce OS, are crucial to control and treat this disease. However, further studies are required to elucidate the molecular pathogenesis of PEXS.

Caspase 8 Expression Patterns in Meningiomas: A Tissue Microarray Digital Image Analysis.

BACKGROUND: Caspases (cysteine-aspartic proteases) represent a family of enzymes that critically influence cell homeostasis by being involved in inflammation and apoptosis mechanisms. Meningiomas demonstrate the most common intracranial primary central nervous system tumors in adults worldwide. AIM: Our purpose was to explore the role of caspase 8 expression in meningiomas' pathological features. MATERIALS AND METHODS: A total of 50 meningioma cases were included in the study, comprising a broad spectrum of histopathological sub-types. An immunohistochemistry assay was applied on tissue microarray cores followed by digital image analysis. RESULTS: Overexpression of caspase 8 protein was observed in 21/50 (42%) cases, whereas the rest of them (29/50, 58%) demonstrated moderate to low levels of the molecule. Caspase 8 overall expression was statistically significantly correlated to grade of the examined tumors and to mitotic index (p=0.001,p=0.002, respectively). CONCLUSIONS: Caspase 8 aberrant expression is observed in meningiomas associated with their differentiation grade and mitotic activity. Targeted therapeutic strategies focused on enhancing caspase 8 expression and also inducing the overall apoptotic activity should be a very promising approach in rationally handling sub-groups of meningioma patients.

Vascular Endothelial Growth Factor Expression Patterns in non- Human Papillomavirus - Related Pterygia: An Experimental Study on Cell Spot Arrays Digital Analysis.

PURPOSE: The role of angiogenic factors -such as vascular endothelial growth factor (VEGF) - in the development and progression of pterygia lesions remains under investigation. In the current study, we analyzed VEGF protein expression in a series of pterygia and normal conjunctiva epithelia. METHODS: Using a liquid-based cytology assay, thirty (n = 30) cell specimens were obtained by applying a smooth scraping on conjunctiva epithelia and fixed accordingly. None of them had a history of Human Papillomavirus (HPV) infection. Similarly, the same process was applied also in normal conjunctiva epithelia (n = 10; control group). We constructed five (n = 5) slides each containing eight (n = 8) cell spots. An immunocytochemistry (ICC) assay was implemented. Digital image analysis was also performed for evaluating objectively the corresponding immunostaining intensity levels. RESULTS: All the examined pterygia cell samples over-expressed the marker. High staining intensity levels were detected in 15/30 (50%), whereas the rest 15/30 (50%) demonstrated moderate expression. Overall VEGF expression was statistically significantly higher in pterygia compared to normal conjunctiva epithelia (p=.0001). Concerning the other parameters, VEGF protein expression did not associate with the gender of the patients (p = 0.518), the presence of a recurrent lesion (p = 0.311), the anatomical location (p = 0.191) or with their morphology (p = 0.316). Interestingly, the recurrent lesions demonstrated the highest levels of VEGF expression. CONCLUSIONS: VEGF overexpression is a frequent event in pterygia playing a potentially central molecular role in the progression of the lesion. Cell spot array analysis -based on liquid cytology- seems to be an innovative, easy-to-use technique for analyzing a broad variety of molecules in multiple specimens on the same slide by applying different ICC assays.

Fibroblast Growth Factor-2 (FGF-2) Expression in Pterygia Using Cell Spot Arrays.

Fibroblast growth factor (FGF) is a main regulator of cell differentiation, cell migration and angiogenesis in normal and abnormal conjunctiva epithelia, but specific mechanisms of its aberrant expression are yet to be investigated. In the present study, we investigated FGF-2 protein expression within several pterygia. Using a liquid-based cytology assay, we obtained cell specimens from pterygia and healthy tissues directly from patients. A combination of immunocytochemistry followed by digital image analysis showed significant overexpression of FGF-2 in all the examined pterygia. In 30/60 (50%) cases there were high levels of staining intensity, whereas in the remaining 30/60 (50%) cases there were moderate levels of expression. FGF-2 levels of the control group were significantly lower in comparison with the pterygia group. There was no significant correlation between FGF-2 levels and either sex or location of the pterygium. FGF-2 levels had a significant correlation with morphological characteristics of the pterygia. More specifically, FGF-2 levels were significantly higher in the pterygia with a fleshy morphology. Interestingly, recurrent lesions demonstrated high expression levels. An overexpression of FGF-2 has been observed frequently in pterygia, where it may play a crucial role in determining the lesion's progression. FGF-2 upregulation correlates with the morphology of pterygia and its tendency to recur. Cell spot analysis based on liquid-based cytology is a simple, yet effective, method for detecting a broad spectrum of protein markers and could be useful in analyzing potential pterygia patient samples.

c-FOS Expression Analysis in Pterygia Cell Spot Arrays.

BACKGROUND/AIM: Mechanisms of c-FOS activation in the onset and progression of pterygia remain under investigation. This study aimed to comparatively analyze c-FOS proto-oncogene expression levels in neoplastic pterygia and normal epithelia. MATERIALS AND METHODS: We used a liquid-based cytology assay on thirty (n=30) pterygia cell populations and normal epithelia (n=10) extracted by a smooth scraping of conjunctiva epithelia. Applying a cell spot-based technique, we constructed five (n=5) slides, each containing eight (n=8) cell spots. A modified immune-cytochemistry (ICC) assay for c-FOS protein was used. Additionally, digital image analysis was implemented to calculate c-FOS immunostaining intensity levels. RESULTS: High staining intensity levels of c-FOS were detected in 12/30 (40%), whereas the rest 18/30 (60%) demonstrated moderate expression. c-FOS levels were statistically significantly higher in the pterygia compared to control tissues (p=0.001). c-FOS levels in the pterygia were not associated with the sex of patients (p=0.678), the presence of recurrent lesion (p=0.390) or the location of the lesion (p=0.158). The levels of c-FOS, however, were marginally significantly affected by the morphology of the pterygia (p=0.005). More precisely, the c-FOS levels were significantly higher in pterygia with a fleshy morphology. CONCLUSION: c-FOS over-expression is observed frequently in pterygia. It seems to be critically involved in the molecular mechanism of the lesion by its over-expression affecting partially their morphological features. Cell spot liquid - based array analysis is an innovative, easy to implement technique for simultaneously evaluating a broad spectrum of molecules in multiple specimens on the same slide.

ALK Protein Expression Patterns in Squamous Cell Carcinoma of the Oral Cavity.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is characterized by a broad spectrum of genomic imbalances, including gross chromosomal (polysomy/aneuploidy) ones as well as specific gene alterations. Aberrant expression of anaplastic lymphoma kinase (ALK) seems to be a useful molecular marker for discriminating patients based on genetic signatures in a variety of solid malignancies, such as lung carcinoma. Our aim was to analyze ALK protein expression patterns in a series of OSCCs. MATERIALS AND METHODS: Fifty (n=50) OSCC tissue sections were analyzed by implementing an ALK-based immunohistochemistry protocol. Digital image analysis was performed for measuring the corresponding protein expression levels. RESULTS: ALK overexpression was observed in 14/50 (28%) OSCC tissue sections, whereas the rest 36/50 (72%) demonstrated low expression levels. ALK expression was negatively associated with grade (p=0.027) and stage (p=0.0028) of the examined cases. CONCLUSION: Abnormal ALK expression in subsets of patients with OSCC seems to be related to an aggressive phenotype (advanced stage/progressive dedifferentiation). ALK protein overexpression may be used as a significant marker for applying targeted therapeutic regimens.

From delta to Omicron: S1-RBD/S2 mutation/deletion equilibrium in SARS-CoV-2 defined variants.

Coronavirus-related Severe Acute Respiratory Syndrome (SARS-CoV) in 2002/2003, Middle-East Respiratory Syndrome (MERS-CoV) in 2012/2013, and especially the current 2019/2021 Severe Acute Respiratory Syndrome-2 (SARS-CoV-2) affected negatively the national health systems' endurance worldwide. SARS-Cov-2 virus belongs to lineage b of beta-CoVs demonstrating a strong phylogenetic similarity with BatCoVRaTG13 type. Spike (S) glycoprotein projections -consisting of two subunits S1/S2- provide a unique crown-like formation (corona) on virion's surface. Concerning their functional role, S1 represents the main receptor-binding domain (RBD), whereas S2 is involved in the virus-cell membrane fusion mechanism. On Nov 26th 2021, WHO designated the new SARS-CoV-2 strain - named Omicron, from letter ''όµÎ¹κρον'' in the Greek alphabet - as a variant of concern (B.1.1529 variant). Potentially this new variant is associated with high transmissibility leading to elevated infectivity and probably increased re-infection rates. Its impact on morbidity/mortality remains under investigation. In the current paper, analyzing and comparing the alterations of SARS-CoV-2 S RNA sequences in the defined variants (Alpha to Omicron), we observed some interesting findings regarding the S1-RBD/S2 mutation/deletion equilibrium that maybe affect and modify its activity.

Key Matrix Remodeling Enzymes: Functions and Targeting in Cancer.

Tissue functionality and integrity demand continuous changes in distribution of major components in the extracellular matrices (ECMs) under normal conditions aiming tissue homeostasis. Major matrix degrading proteolytic enzymes are matrix metalloproteinases (MMPs), plasminogen activators, atypical proteases such as intracellular cathepsins and glycolytic enzymes including heparanase and hyaluronidases. Matrix proteases evoke epithelial-to-mesenchymal transition (EMT) and regulate ECM turnover under normal procedures as well as cancer cell phenotype, motility, invasion, autophagy, angiogenesis and exosome formation through vital signaling cascades. ECM remodeling is also achieved by glycolytic enzymes that are essential for cancer cell survival, proliferation and tumor progression. In this article, the types of major matrix remodeling enzymes, their effects in cancer initiation, propagation and progression as well as their pharmacological targeting and ongoing clinical trials are presented and critically discussed.

Multiple symmetric lipomatosis (Madelung's disease) with symptoms and signs of hypertension, lipodystrophy, and dyspnea: A case report and literature review.

Madelung's disease generally refers to a benign symmetrical lipomatosis of the neck, but its presentation can vary. It is treated surgically and different approaches can be implemented. In cases of a threatened airway, a tracheostomy can be performed.

Short-term effect of non-preserved cationic oil-in-water ophthalmic emulsion on tear meniscus parameters of healthy individuals in a prospective, controlled pilot study.

Background: This study investigated the effect of instilling a single drop of non-preserved cationic oil-in- water ophthalmic emulsion (Cationorm®) on the lower (LTM) and upper tear meniscus (UTM) parameters of normal eyes. Methods: In this prospective, single-center, non-randomized, controlled pilot study, optical coherence tomography was used to estimate the UTM and LTM height, depth, and cross-sectional area in participants without a history of dry eye disease. In the right eye (study eye), we instilled one drop of Cationorm® in the lower conjunctival sac. Scans of the tear menisci were acquired at baseline, before the instillation, and at 5, 15, and 30 min thereafter. Control scans of the left eye (control eye) were obtained at the same timepoints. The tear meniscus parameters of the study eye were compared with the control eye at each timepoint. Results: Twenty subjects (11 male and 9 female; mean [standard deviation] of age: 37.8 [10.9] years) were included in the study. Compared to the control eye, instillation of a single drop of Cationorm® resulted in significantly higher LTM parameter values and a higher UTM cross-sectional area up to 30 min after instillation (all P < 0.05). The UTM height and depth were significantly greater in the study eye than in the control eye up to 5 min (P < 0.001 and 0.007, respectively) and 15-min (P = 0.045, and 0.002, respectively) after Cationorm® instillation. In the study eye, Cationorm® resulted in a significant increase in LTM parameter values up to 30 min post-instillation (all P < 0.001). The UTM height was significantly greater up to 15 min post-instillation than at baseline. The UTM depth and area increased significantly from baseline to 5 min after instillation (P = 0.043, and 0.002, respectively). Conclusions: Cationorm® seems to have a prolonged residence time on the ocular surface of healthy subjects as indicated by LTM parameters and to a lesser extent by UTM parameters.

COVID-19 pandemic and reasons to prioritize the needs of the health care system to ensure its sustainability: A scoping review from January to October 2020 (Review).

The worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led the World Health Organization to characterize the pandemic as a public health emergency of international concern. National health care systems in countries during the initial surge of the pandemic were unable to handle the sanitarian crisis that had emerged. Thus, the prevention and control of future global health emergencies must be a priority. The present scoping review aimed to retrieve articles that summarize the current experience on issues related to historical knowledge, and epidemiology, clinical features and overall burden of SARS-CoV-2 on health care services. In summary, a comprehensive overview of the information that has been learnt during this period is presented in the current review. Furthermore, taking into account the global experience, the need for planning cohesive and functional health services before similar pandemic events occur in the future is highlighted. The next public health issue should be prevented rather than treated. In spite of the vaccination benefits, a number of sporadic cases of SARS-CoV-2infections will persist. Information collected remains relevant for appraising how similar threats can be faced in the future. Overall, collaborative health care plans need to be rethought to increase preparedness.

Mutational landscape in Uveal Melanoma.

Gross chromosomal and specific gene alterations are genetic aspects that are involved in rise, progression, and metastatic expansion of malignances. Concerning Uveal melanoma (UM), a variety of chromosome and gene functional and numerical imbalances in crucial molecular pathways such as cell cycle regulation, signaling transduction, apoptosis or angiogenesis have been identified and explained. UM is the most common primary ocular malignancy demonstrating increased rates, especially in middle-aged white (Caucasian) populations. Chronic exposure to ultraviolet rays/sunlight, race, gender (males), or some familial hereditary syndrome in sub-groups of patients are major factors correlated to increased risk for UM rise and progression. Specific genetic signatures at the level of chromosomal instability (CI) or at the gene mutations status characterize sub-groups of patients affecting the biological behaviour of the tumour leading to aggressive phenotypes (advanced stage-distant metastases, poor response, and survival rates). Sporadic or hereditary mediated mutations in genes including BAP1, EIF1AX, GNA11, GNAQ CHEK2, PALB2, SMARCE1, MBD4, MSH6 and MLH1. In the current molecular review, we present specific mutations -as a landscape- that are implicated in UM genetic substrate and create a variety of genetic signatures in the corresponding patients.