Functional activation of the p53 tumor suppressor in non-tumorigenic variants of the HeLa cervical carcinoma cell line

Thesis (Sc. D.)--Massachusetts Institute of Technology, Division of Toxicology, 1996.Includes bibliographical references (leaves 119-131).by Maria G. Athanassiou-papaefthymiou.Sc.D

Coxsackievirus and adenovirus receptor expression in human endometrial adenocarcinoma: possible clinical implications

The coxsackievirus and adenovirus receptor (CAR) is a crucial receptor for the entry of both coxsackie B viruses and adenoviruses into host cells. CAR expression on tumor cells was reported to be associated with their sensitivity to adenoviral infection, while it was considered as a surrogate marker for monitoring and/or predicting the outcome of adenovirus-mediated gene therapy. The aim of the present study was to evaluate the clinical significance of CAR expression in endometrial adenocarcinoma. CAR expression was assessed immunohistochemically in tumoral samples of 41 endometrial adenocarcinoma patients and was statistically analyzed in relation to various clinicopathological parameters, tumor proliferative capacity and patient survival. CAR positivity was noted in 23 out of 41 (56%) endometrial adenocarcinoma cases, while high CAR expression in 8 out of 23 (35%) positive ones. CAR intensity of immunostaining was classified as mild in 11 (48%), moderate in 10 (43%) and intense in 2 (9%) out of the 23 positive cases. CAR positivity was significantly associated with tumor histological grade (p = 0.036), as well differentiated tumors more frequently demonstrating no CAR expression. CAR staining intensity was significantly associated with tumor histological type (p = 0.016), as tumors possessing squamous elements presented more frequently intense CAR immunostaining. High CAR expression showed a trend to be correlated with increased tumor proliferative capacity (p = 0.057). Patients with tumors presenting moderate or intense CAR staining intensity were characterized by longer survival times than those with mild one; however, this difference did not reach statistical significance. These data reveal, for the first time, the expression of CAR in clinical material obtained from patients with endometrial adenocarcinoma in relation to important clinicopathological parameters for their management. As CAR appears to modulate the proliferation and characteristics of cancer cells, its expression could be considered of possible clinical importance for future (gene) therapy applications

Ofeleein i mi Vlaptin-Volume II: Immunity Following Infection or mRNA Vaccination, Drug Therapies and Non-Pharmacological Management at Post-Two Years SARS-CoV-2 Pandemic.

The persistence of the coronavirus disease 2019 (COVID-19) pandemic has triggered research into limiting transmission, morbidity and mortality, thus warranting a comprehensive approach to guide balanced healthcare policies with respect to people's physical and mental health. The mainstay priority during COVID-19 is to achieve widespread immunity, which could be established through natural contact or vaccination. Deep knowledge of the immune response combined with recent specific data indicates the potential inferiority of induced immunity against infection. Moreover, the prevention of transmission has been founded on general non-pharmacological measures of protection, albeit debate exists considering their efficacy and, among other issues, their socio-psychological burden. The second line of defense is engaged after infection and is supported by a plethora of studied agents, such as antibiotics, steroids and non-steroid anti-inflammatory drugs, antiviral medications and other biological agents that have been proposed, though variability in terms of benefits and adverse events has not allowed distinct solutions, albeit certain treatments might have a role in prevention and/or treatment of the disease. This narrative review summarizes the existing literature on the advantages and weaknesses of current COVID-19 management measures, thus underlining the necessity of acting based on the classical principle of "ofeleein i mi vlaptin", that is, to help or not to harm

Association between Helicobacter pylori Infection and Nasal Polyps: A Systematic Review and Meta-Analysis.

BACKGROUND Helicobacter pylori (H. pylori) has definite or possible associations with multiple local and distant manifestations. H. pylori has been isolated from multiple sites throughout the body, including the nose. Clinical non-randomized studies with H. pylori report discrepant data regarding the association between H. pylori infection and nasal polyps. The aim of this first systematic review and meta-analysis was the assessment of the strength of the association between H. pylori infection and incidence of nasal polyps. METHODS We performed an electronic search in the three major medical databases, namely PubMed, EMBASE and Cochrane, to extract and analyze data as per PRISMA guidelines. RESULTS Out of 57 articles, 12 studies were graded as good quality for analysis. Male-to-female ratio was 2:1, and age ranged between 17-78 years. The cumulative pooled rate of H. pylori infection in the nasal polyp group was 32.3% (controls 17.8%). The comparison between the two groups revealed a more significant incidence of H. pylori infection among the nasal polyp group (OR 4.12), though with high heterogeneity I$^{2}$ = 66%. Subgroup analysis demonstrated that in European studies, the prevalence of H. pylori infection among the nasal polyp group was significantly higher than in controls, yielding null heterogeneity. Subgroup analysis based on immunohistochemistry resulted in null heterogeneity with preserving a statistically significant difference in H. pylori infection prevalence between the groups. CONCLUSION The present study revealed a positive association between H. pylori infection and nasal polyps

Status and perspectives of hospital mortality in a public urban Hellenic hospital, based on a five-year review

<p>Abstract</p> <p>Background</p> <p>Analysis of hospital mortality helps to assess the standards of health-care delivery.</p> <p>Methods</p> <p>This is a retrospective cohort study evaluating the causes of deaths which occurred during the years 1995–1999 in a single hospital. The causes of death were classified according to the International Statistical Classification of Diseases (ICD-10).</p> <p>Results</p> <p>Of the 149,896 patients who were discharged the 5836 (3.4%) died. Males constituted 55% and females 45%. The median age was 75.1 years (1 day – 100 years).</p> <p>The seven most common ICD-10 chapters IX, II, IV, XI, XX, X, XIV included 92% of the total 5836 deaths.</p> <p>The most common contributors of non-neoplasmatic causes of death were cerebrovascular diseases (I60–I69) at 15.8%, ischemic heart disease (I20–I25) at 10.3%, cardiac failure (I50.0–I50.9) at 7.9%, diseases of the digestive system (K00–K93) at 6.7%, diabetes mellitus (E10–E14) at 6.6%, external causes of morbidity and mortality (V01–Y98) at 6.2%, renal failure (N17–N19) at 4.5%, influenza and pneumonia (J10–J18) at 4.1% and certain infectious and parasitic diseases (A00–B99) at 3.2%, accounting for 65.3% of the total 5836 deaths.</p> <p>Neoplasms (C00–D48) caused 17.7% (n = 1027) of the total 5836 deaths, with leading forms being the malignant neoplasms of bronchus and lung (C34) at 3.5% and the malignant neoplasms of large intestine (C18–21.2) at 1.5%. The highest death rates occurred in the intensive care unit (23.3%), general medicine (10.7%), cardiology (6.5%) and nephrology (5.5%).</p> <p>Key problems related to certification of death were identified. Nearly half of the deaths (49.3%: n = 2879) occurred by the completion of the third day, which indicates the time limits for investigation and treatment. On the other hand, 6% (n = 356) died between the 29^thand 262^nddays after admission.</p> <p>Inadequacies of the emergency care service, infection control, medical oncology, rehabilitation, chronic and terminal care facilities, as well as lack of regional targets for reducing mortality related to diabetes, recruitment of organ donors, provision for the aging population and lack of prevention programs were substantiated.</p> <p>Conclusion</p> <p>Several important issues were raised. Disease specific characteristics, as well as functional and infrastructural inadequacies were identified and provided evidence for defining priorities and strategies for improving the standards of care. Effective transformation can promise better prospects.</p

Bone mineral density and bone indices in male adolescents

There has been an increased incidence of osteoporosis and fractures in children and adolescents during the last few decades. Fractures during growth represent a common and neglected public health problem as more attention has been given to determining and minimizing the risk of fracturing later in the life and less attention has been directed toward determining risk factors for fractures sustained during growth. Studying the bone mineral density and the determinants of fracture risk in healthy children and adolescents is important not only because they are associated with significant consequences, that is, cost, hospitalization, developmental sequelae, time off school and activity-restricted days, but also because low bone density in this age group may be a sign of impaired bone health and persistent skeletal fragility.The aim of this study was to record bone mineral density and indices of bone metabolism in otherwise healthy Greek male adolescents, assessing possible associations between potential risk factors for fractures and their occurrence.A total of 63 male adolescents participated in the study, 21 males with a history of at least one fracture and 42 healthy male controls. Each participant was assessed for physical and pubertal status, hormonal profile, bone mineral density, bone turnover indices, and dietary habits.There was a statistically significant positive correlation between insulin-like growth factor-1, testosterone, position flexibility and bone mineral density. An increase in CTX, tP1NP and OPG was proved to reduce bone mineral density. The lower bone mineral density-z scores and increasing testosterone and serum collagen type 1 CTXinked C-telopeptide levels were related to fracture risk, whereas increased insulin-like growth factor-1, soluble receptor activator of nuclear factor kappa-B (factor-κB) ligand, and soluble receptor activator of nuclear factors-κB ligand/osteoprotegerin levels were protective for fractures.The findings indicate a potential ‘added value’ of hormonal parameters and bone markers to bone mineral density for evaluating fracture risk in healthy male adolescents. An increased awareness of the problem of osteoporosis in men is needed at all levels in the community, so that research efforts are increased and fractures are prevented.Τις τελευταίες δεκαετίες, παρατηρείται αυξημένη επίπτωση της οστεοπόρωσης και των καταγμάτων σε παιδιά και εφήβους. Τα κατάγματα στη διάρκεια της ανάπτυξης αποτελούν ένα κοινό αλλά παραμελημένο δημόσιο πρόβλημα υγείας, καθώς το βάρος έχει δοθεί στο να καθοριστούν και να περιοριστούν οι παράγοντες κινδύνου στη διάρκεια της ενήλικης ζωής, ενώ περιορισμένη προσοχή δίνεται στο να καθοριστούν οι παράγοντες κινδύνου για κάταγμα, που ξεκινούν στην εφηβεία. Είναι σημαντικό να μελετηθεί η οστική πυκνότητα και οι παράγοντες κινδύνου για κάταγμα σε υγιή παιδιά και εφήβους, όχι μόνο γιατί σχετίζονται με σοβαρές συνέπειες , όπως κόστος, νοσηλεία, καθυστέρηση ανάπτυξης, ώρες εκτός σχολείου και μέρες με περιορισμό της δραστηριότητας, αλλά ταυτόχρονα, επειδή η χαμηλή οστική πυκνότητα σε αυτή την ηλικιακή ομάδα αποτελεί ένδειξη διαταραγμένης οστικής υγείας και επίμονης σκελετικής ευθραυστότητας. Σκοπός της παρούσας μελέτης ήταν να καταγράψει την οστική πυκνότητα και τους δείκτες οστικού μεταβολισμού σε υγιείς άρρενες εφήβους και να εκτιμήσει πιθανές συσχετίσεις μεταξύ παραγόντων κινδύνου για κάταγμα, καθώς και την επίπτωσή τους.Στη μελέτη έλαβαν μέρος 63 άρρενες έφηβοι, 21 με ιστορικό κατάγματος και 42 υγιείς έφηβοι χωρίς ιστορικό κατάγματος. Ο κάθε έφηβος εκτιμήθηκε για τη φυσική του κατάσταση, το στάδιο εφηβείας του, το ορμονικό του προφίλ, την οστική πυκνότητα, τους δείκτες οστικού μεταβολισμού και τις διαιτητικές του συνήθειες.Παρατηρήθηκε στατιστικά σημαντική θετική συσχέτιση μεταξύ οστικής πυκνότητας και των παραμέτρων IGF-1, τεστοστερόνης και της ευκαμψίας από την εδραία θέση. Αύξηση των δεικτών CTX, tP1NP και OPG οδήγησε σε μείωση της οστικής πυκνότητας. Χαμηλά z-scores στην οστική πυκνότητα και αυξημένη τεστοστερόνη και αυξημένα επίπεδα CTX σχετίστηκαν με αυξημένο κίνδυνο κατάγματος, ενώ αυξημένα επίπεδα IGF-1, sRANKL και sRANKL/OPG αποδείχθηκαν προστατευτικά για εμφάνιση καταγμάτων.Τα ευρήματα της μελέτης μας υποδεικνύουν μια ‘προστιθέμενη αξία’ του ορμονικού προφίλ και των δεικτών οστικού μεταβολισμού στην οστική πυκνότητα, ώστε να εκτιμηθεί πληρέστερα ο καταγματικός κίνδυνος σε υγιείς άρρενες εφήβους. Κρίνεται αναγκαία η αυξημένη επαγρύπνηση της κοινωνίας σε όλα τα επίπεδα σχετικά με το πρόβλημα της οστεοπόρωσης στους άνδρες, έτσι ώστε να αυξηθούν οι ερευνητικές προσπάθειες και να προληφθούν τα κατάγματα

COVID-19 mRNA Vaccine Effectiveness against Elderly Frail People

The frail, elderly population is often characterized by poor immunogenicity post COVID-19 mRNA vaccination. “Inflame-ageing” and “immune-senescence” are pathogenetic mechanisms that might explain this phenomenon. Complex interplay with cytokines and microbiota is also implicated in this inflammatory cascade. The abovementioned population, although very important from immunologic perspective, has barely been included in the mRNA vaccination clinical trials

COVID-19 mRNA Vaccine Effectiveness against Elderly Frail People

The frail, elderly population is often characterized by poor immunogenicity post COVID-19 mRNA vaccination. &ldquo;Inflame-ageing&rdquo; and &ldquo;immune-senescence&rdquo; are pathogenetic mechanisms that might explain this phenomenon. Complex interplay with cytokines and microbiota is also implicated in this inflammatory cascade. The abovementioned population, although very important from immunologic perspective, has barely been included in the mRNA vaccination clinical trials