Impact of Ubiquitination Signaling Pathway Modifications on Oral Carcinoma.

Among intra-cellular homeostasis mechanisms, ubiquitination plays a critical role in protein metabolism regulation by degrading proteins via activating a broad spectrum of ubiquitin chains. In fact, ubiquitination and sumoylation signaling pathways are characterized by increased complexity regarding the molecules and their interactions. The Ubiquitin-Proteasome System (Ub-PS) recognizes and targets a broad spectrum of protein substrates. Ubiquitin conjugation modifies each substrate protein determining its biochemical fate (degradation). A major functional activity of Ub-PS is autophagy mechanism regulation. Interestingly, Ub-PS promotes all stages of bulk autophagy (initiation, execution, and termination). Autophagy is a crucial catabolic process that provides protein degradation and for this reason the interaction with Ub-PS is crucial. Furthermore, ubiquitination controls and regulates specific types of protein targets. Ub-PS is also involved in oxidative cellular stress and DNA damage response. Additionally, the functional role of Ub-PS in ribosome machinery regulation seems to be crucial. Concerning carcinogenesis, Ub-PS is involved in malignant disease development and progression by negatively affecting the corresponding TGF-B-, MEEK/MAPK/ERK-JNK- dependent signaling pathways. In the current review article, we describe the role of Ub-PS biochemical modifications and alterations in oral squamous cell carcinoma (OSCC).

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.

Impact of Ribosome Activity on SARS-CoV-2 LNP - Based mRNA Vaccines.

Coronavirus-related Severe Acute Respiratory Syndrome-2 (SARS-CoV-2) initially was detected in Wuhan, Hubei, China. Since early 2021, World Health Organization (WHO) has declared Coronavirus Disease 2019 (COVID-19) a pandemic due to rapidly transformed to a globally massive catastrophic viral infection. In order to confront this emergency situation, many pharmaceutical companies focused on the design and development of efficient vaccines that are considered necessary for providing a level of normalization in totally affected human social-economical activity worldwide. A variety of vaccine types are under development, validation or even some of them have already completed these stages, initially approved as conditional marketing authorisation by Food and Drug Administration (FDA), European Medicines Agency (EMA), and other national health authorities for commercial purposes (in vivo use in general population), accelerating their production and distribution process. Innovative nucleoside-modified viral messenger RNA (v-mRNA)-based vaccines encapsulated within nanoparticles-specifically lipid ones (LNPs)-are now well recognized. Although this is a promising genetic engineering topic in the field of nanopharmacogenomics or targeted nucleic vaccines, there are limited but continuously enriched in vivo data in depth of time regarding their safety, efficacy, and immune response. In the current paper we expand the limited published data in the field of ribosome machinery and SARS-CoV-2 mRNA fragment vaccines interaction by describing their functional specialization and modifications. Additionally, alterations in post-transcriptional/translational molecules and mechanisms that could potentially affect the interaction between target cells and vaccines are also presented. Understanding these mechanisms is a crucial step for the next generation v-mRNA vaccines development.

Expression of vimentin (VIM) and metastasis-associated 1 (MTA1) protein in laryngeal squamous cell carcinoma are associated with prognostic outcome of patients.

PURPOSE: Laryngeal squamous cell carcinoma (LSCC), a common type of head and neck cancer, is associated with high rates of metastasis and recurrence. In this study, we investigated the potential combinatorial prognostic value of NOTCH1, Vimentin (VIM), and Metastasis-associated 1 (MTA1) protein in LSCC, using immunohistochemistry. MATERIALS AND METHODS: Tissue specimens from 69 patients with LSCC were immunohistochemically evaluated for the protein expression of NOTCH1, VIM, and MTA1. Then, biostatistical analysis was performed, in order to assess the prognostic value of the expression of each one of these proteins. RESULTS: NOTCH1 expression status was not a significant prognosticator in LSCC, as shown in Kaplan-Meier survival analysis. On the contrary, both VIM and MTA1 seem to have an important prognostic potential, independently of TNM staging and histological grade of the tumor. In fact, positive VIM expression was shown to predict patients' relapse and poor outcome regarding patients' overall survival, in contrast with MTA1, the positive expression of which predicts higher disease-free survival (DFS) and overall survival (OS) rates in LSCC. CONCLUSIONS: VIM and MTA1 constitute potential tumor biomarkers in LSCC and could be integrated into a multiparametric prognostic model. Undoubtedly, their prognostic value needs further validation in larger cohorts of LSCC patients.

Translation and validation of the dizziness handicap inventory in Greek language.

OBJECTIVE: The aim of the study was to test the reliability and validity of the Dizziness Handicap Inventory in the Greek language (DHI). DESIGN: This study was performed in a university tertiary centre. Internal consistency was estimated using Cronbach's alpha for the DHI, physical (DHI-P), functional (DHI-F) and emotional (DHI-E) subscale scores. Correlation between DHI (total and subscales) and the SOT (sensory organisation test) as well as correlation between the DHI and FGA (functional gait assessment) was tested using Spearman's correlation coefficient. Test-retest reliability was tested using ICC (Intraclass Correlation Coefficient). SAMPLE SIZE: Ninety (90) patients were included in the study. RESULTS: Internal consistency was excellent for the total score and very good for the physical functional and emotional subscale scores. No statistically significant correlation was found between SOT and DHI. There was a moderate correlation between FGA and total DHI scores (r = -0.472; p < 0.0001) and poor to moderate between FGA and DHI subscale scores (DHI-E r1 = -0.342; p1 = 0.001, DHI-F r2 = -0.448 p2 < 0.0001, DHI-P r3 = -0.472 p3 < 0.0001). Test-retest reliability was excellent. CONCLUSION: Greek version of DHI is recommended as a valid measure for patients with vestibular disorders.

Oropharyngeal and laryngeal but not oral cancers are strongly associated with high-risk human papillomavirus in 172 Greek patients.

A strong and consistent association has been reported between human papillomavirus (HPV) infection and oropharyngeal cancer, whereas a similar link has not yet been clarified in oral and laryngeal cancer. The purpose of this study was to investigate the association between HPV infection and head and neck squamous cell carcinoma (HNSCC) in Greek patients. Cytological or tissue specimens from 172 cases patients with HNSCC and cytological specimens from 91 control subjects were analyzed for HPV DNA detection and genotyping using a microarray-based assay. Multivariate logistic regression was used to estimate odds ratios (ORs) for the association between the presence of HPV infection and HNSCC for each of the tumor site, after adjustment for potential confounders. The adjusted ORs for positivity to high-risk HPV infection for oropharyngeal and laryngeal cancer were 20.3 (95% CI: 1.7-250.1) and 22.8 (95% CI: 2.5-206.2), respectively. High-risk HPV infection was not significantly associated with oral cancer. HPV infection was independently associated with poorly differentiated tumors (OR = 2.8; 95% CI: 1.1-7.5). Our results suggest a strong association of high-risk HPV infection with oropharyngeal and laryngeal cancer. J. Med. Virol. 89:170-176, 2017. © 2016 Wiley Periodicals, Inc.

Extensive laryngeal infiltration from a neglected papillary thyroid carcinoma: A case report.

Papillary carcinoma of the thyroid is the commonest type of thyroid cancer. Laryngeal infiltration from papillary thyroid carcinoma is extremely rare, with only a few cases of partial invasion described in the literature. We present a very unusual case of complete infiltration of both thyroid and cricoid cartilages from a neglected papillary thyroid carcinoma in a 59-year-old male. This sequel resulted from refusal of the patient to undergo treatment when initially diagnosed. An invasion to such an extent has not been described in the literature before, and in this case warranted a total laryngectomy followed by radioactive iodine. Prompt management of papillary carcinomas is crucial for avoiding such complications. Future guidelines should include management options for the patients who deny treatment initially.

Complications of cochlear implantation in adults.

OBJECTIVES: We describe our experience of intraoperative and postoperative complications of cochlear implantation in an adult population. METHODS: Between April 1986 and June 2010, the senior author (A.S.) performed 449 cochlear implantations in two different institutions. Of these, 212 implantations were in adults. The operative techniques were similar in all cases. RESULTS: Complications were observed in 12 of the 212 adult cases (5.7%), of which 10 were major (4.7%) and 2 minor (1%). In 7 cases, reimplantation was necessitated by device failure (6 cases; 2.8%) or device extrusion (1 case; 0.5%). In 2 elderly patients (1%), a minor dural injury with a cerebrospinal fluid leak was controlled during the operation with temporalis fascia grafting. In 1 patient (0.5%), a subdural hematoma was observed after bipolar cauterization of a prominent diploic vein. In 2 subjects (1%), a wound infection was noted soon after implantation and was treated successfully on an outpatient basis. CONCLUSIONS: Cochlear implantation is generally a safe procedure. The most common complication was device failure. Although complications in this adult population were rather uncommon, some of them were serious, and an immediate intervention was necessary for a successful outcome.

Use of Glasgow Benefit Inventory (GBI) in Meniere's disease managed with intratympanic dexamethasone perfusion: Quality of life assessment.

OBJECTIVE: To evaluate patients' quality of life following intratympanic dexamethasone perfusion in management of Meniere's disease (MD). METHODS: This is a retrospective study in a tertiary referral center that uses the Glasgow Benefit Inventory (GBI). Intratympanic perfusion of 24mg/ml of dexamethasone was administered after failure to respond to previous management with diuretics and low-salt diet. GBI questionnaires were collected and analyzed in a 12 months follow-up of participating patients. RESULTS: Thirty patients (20 women and 10 men, aged 28-85 years) with MD underwent intratympanic dexamethasone perfusion and were assessed with the assistance of GBI questionnaire. Follow-up ranged from 12 to 48 months (mean 30 months). Audiometric results were also available in all of them. In the short term (4 weeks post-perfusion) 6 patients demonstrated a greater than 10dB improvement in PTA, and 6 patients had an increase in SDS of at least 15%, while in the long-term (12 months post-perfusion) the number of patients in the respective groups decreased to 5 and 2. With regards to the GBI responses, 9 patients (50%) expressed an overall benefit, while 6 (33%) expressed no benefit and 3 patients (17%) complained of negative effect after the intervention. CONCLUSION: The mean GBI score indicates substantial improvement in patients' overall quality of life following intratympanic dexamethasone perfusion, which was also confirmed by the audiometric results.