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IntroductionSialolithiasis remains a clinical problem with unclear etiopathogenesis, lack of prevention methods and only surgical treatment. Materials and MethodsAn ultrastructure examination of submandibular sialoliths obtained from patients with chronic sialolithiasis was conducted using a scanning electron microscope and X-ray photoelectron spectroscopy. ResultsBased on the results, we divided sialoliths into three types: calcified (CAL), organic/lipid (LIP) and mixed (MIX). The core structure of the CAL and MIX is very similar. The core of the LIP has a prevalence of organic components. The intermediate layers structure of the CAL is different from LIP and MIX. In LIP and MIX, the organic component begins to increase in intermediate layers rapidly. The structure of the superficial layers for all types of sialoliths is similar. ConclusionsWe introduced a new classification of the submandibular salivary gland stones. Based on the results, it can be said that sialoliths type CAL and LIP have their separate path of origin and development, while MIX is formed as CAL stone, and the further pathway of their growth passes as LIP stones. Organic components was much more than inorganic in all layers of salivary gland stones, which highly prevents their dissolution in the patients salivary gland duct.

Withdrawal statementThe authors have withdrawn their manuscript owing to because authors want to do further study about period2-mediated downregulation of ERK/MAPK phosphorylation in nasopharyngeal carcinoma. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

ObjectivePharyngocutaneous fistula (PCF) and salivary leaks are well known complications of head and neck surgery. The medical management of PCF has included the use of octreotide without a well-defined understanding of its therapeutic mechanism. We hypothesized that octreotide induces alterations in the saliva proteome and that these alterations may provide insight into the mechanism of action underlying improved PCF healing. We undertook an exploratory pilot study in healthy controls that involved collecting saliva before and after a subcutaneous injection of octreotide and performing proteomic analysis to determine the effects of octreotide. Materials and MethodsFour healthy adult participants provided saliva samples before and after subcutaneous injection of octreotide. A mass-spectrometry based workflow optimized for the quantitative proteomic analysis of biofluids was then employed to analyze changes in salivary protein abundance after octreotide administration. ResultsThere were 3,076 human, 332 S. mitis, 102 G. haemolyans and 42 G. adiacens protein groups quantified in saliva samples. A paired statistical analysis was performed using the generalized linear model (glm) function in edgeR. There were and [~]300 proteins that had a p<0.05 between the pre-and post-octreotide groups [~]50 proteins with an FDR-corrected p<0.05 between pre-and post-groups. These results were visualized using a volcano plot after filtering on proteins quantified by 2 more or unique precursors. Both human and bacterial proteins were among the proteins altered by octreotide treatment. Notably, four isoforms of the human cystatins, belonging to a family of cysteine proteases, that had significantly lower abundance after treatment. ConclusionThis pilot study demonstrated octreotide-induced downregulation of cystatins. By downregulation of cystatins in the saliva, there is decreased inhibition of cysteine proteases such as Cathepsin S. This results in increased cysteine protease activity that has been linked to enhanced angiogenic response, cell proliferation and migration that have resulted in improved wound healing. These insights provide first steps at furthering our understanding of octreotides effects on saliva and reports of improved PCF healing.

BackgroundPresbycusis, also known as age-related hearing loss (ARHL), is the most frequent sensory disability affecting elderly adults worldwide.ARHL is typified by a bilateral, progressive, sensorineural hearing loss that is pronounced in high frequency. Conventional factors associated with ARHL include diabetes, hypertension, and family history of hereditary hearing loss. The severity of hearing impairment varies between individuals. The accurate causative molecular pathogenesis for ARHL is unknown, therefore the investigation of the underlying pathogenic mechanisms involved in ARHL is imperative for the development of effective therapeutic approaches. Epigenetics is the study of phenotypic changes caused by modification of genetic expression rather than alteration of DNA sequence. It is hypothesized that ARHL could result from unclarified epigenetic susceptibility, nevertheless, there is a shortage of information on the exact contribution of epigenetic modifications to ARHL. Here we present an investigation on the involvement of DNA methylation with Age-related hearing loss. ResultsIn the present study the Illumina Infinium(R) Methylation EPIC Beadchip has been used to identify regions with aberrant levels of methylation across genomes from ARHL patients. Hearing measurements were used to determine the audioprofiles. Clinical, audiometric patterns, DNA testing, and methylation pattern screening were undertaken. Our results demonstrate a strong correlation between patients hearing measurements and CpG sites methylation in ESPN and TNFRSF25. A Methylation Polymerase chain reaction (PCR) assay was used to confirm methylation levels at specific gene locus in ARHL patients. ConclusionAberrant DNA methylation and its impact on gene expression have been implicated in many biological processes. By interrogating methylation status across the genome at single-nucleotide resolution of hearing loss patients, our study can help establish the association between audiometric patterns and methylation status in age-related hearing loss patients.

IntroductionSARS-CoV-2 is a respiratory virus supposed to enter the organism through aerosol or fomite transmission to the nose, eyes and oropharynx. It is responsible for various clinical symptoms, including hyposmia and other neurological ones. Current literature suggests the olfactory mucosa as a port of entry to the CNS, but how the virus reaches the olfactory groove is still unknown. Because the first neurological symptoms of invasion (hyposmia) do not correspond to first signs of infection, the hypothesis of direct contact through airborne droplets during primary infection and therefore during inspiration is not plausible. The aim of this study is to evaluate if a secondary spread to the olfactory groove in a retrograde manner during expiration could be more probable. MethodsFour three-dimensional virtual models were obtained from actual CT scans and used to simulate expiratory droplets. The volume mesh consists of 25 million of cells, the simulated condition is a steady expiration, driving a flow rate of 270 ml/s, for a duration of 0.6 seconds. The droplet diameter is of 5 m. ResultsThe analysis of the simulations shows the virus to have a high probability to be deployed in the rhinopharynx, on the tail of medium and upper turbinates. The possibility for droplets to access the olfactory mucosa during the expiratory phase is lower than other nasal areas, but consistent. DiscussionThe data obtained from these simulations demonstrates the virus can be deployed in the olfactory groove during expiration. Even if the total amount in a single act is scarce, it must be considered it is repeated tens of thousands of times a day, and the source of contamination continuously acts on a timescale of several days. The present results also imply CNS penetration of SARS-CoV-2 through olfactory mucosa might be considered a complication and, consequently, prevention strategies should be considered in diseased patients.

Aim of studyThe present study aimed to evaluate anti-inflammatory and immunomodulating properties of BNO 1030 (Tonsilgon(R) N) and its direct effect on the indicators of the local immunity of oropharyngeal mucosa in patients with acute tonsillopharyngitis (TP) or exacerbation of chronic TP without evident systemic inflammatory syndrome. Materials and methodsA total of 60 adult patients with acute TP or exacerbation of chronic TP without severe systemic inflammatory syndrome were randomly divided into 2 groups: Group 1 L 30 patients took BNO 1030 (Tonsilgon(R) N), Group 2 L 30 patients took sage tablets according to the summary of product characteristics during 7 days. During 3 visits (day 1, day 3, day 7) symptoms and oropharyngeal mucosa condition were evaluated using a 10-point visual analogue scale (VAS). Local immunity parameters of oropharyngeal mucosa (cytokines: IL-1{beta}, IL-6, IL-8, IL-10, IL-17, TNF-, and lysozyme, lactoferrin, sIgA) were determined by ELISA and by real time polymerase chain reaction. ResultsReduction of the main symptoms was significantly faster under BNO 1030 therapy than under sage therapy. In BNO 1030 group reduction of clinical symptoms correlated with the onset of action and the local immunological parameters. During BNO 1030 treatment IL-1{beta}, IL-6, and IL-8 mRNA levels decreased below the levels in healthy controls, while, the immune factors lysozyme, lactoferrin and sIgA increased. Therapy with sage tablets did not affect local immunity parameters. ConclusionBoth treatment regimens resulted in elimination of clinical signs and mucosal pharyngeal barrier regeneration. In contrast to the sage tablets, BNO 1030 can also affect local mucosal immunity via regulating the balance of pro- and anti-inflammatory factors. Study highlightsO_LIThis study can answer the question regarding influence on main local immunity parameters of subjects with tonsillitis C_LIO_LIThe one of main task of this study is to evaluate what local immune parameters of oral cavity are most changeable C_LIO_LITonsilgon N usage is not decrease main local immunity parameters such as IL-1{beta}, IL-8, lysozyme and lactoferrin C_LIO_LIThis study evaluated the functional condition of mucosal immunity of oral cavity in subjects with tonsillopharingitis C_LI

The molecular stimuli that trigger a parosmic response have been identified. Parosmia is a debilitating disease in which familiar smells become distorted and unpleasant. Often a result of post infectious smell loss, incidences are increasing as the number of COVID-19 cases escalates worldwide. Little is understood of its pathophysiology, but the prevailing hypothesis for the underlying mechanism is a mis-wiring of olfactory sensory neurons. We identified 15 different molecular triggers in coffee using GC-Olfactometry as a relatively rapid screening tool for assessment of both quantitative olfactory loss and parosmia. This provides evidence for peripheral causation, but places constraints on the mis-wiring theory.

IntroductionHead and neck cancers (HNC) treatments often cause a metallic taste (MT), adversely affecting patients quality of life. This study aims to investigate the lipoperoxidation hypothesis of MT by examining salivary malondialdehyde (MDA) levels, a marker of oxidative stress, in HNC patients undergoing treatment. MethodsThis prospective cohort study included 44 newly diagnosed HNC patients. Saliva samples were collected before, during and up to one year after the HNC treatment. Analyses including MDA and other markers were performed. Additionally, a bovine lactoferrin mouthwash was evaluated for its efficacy in alleviating MT. ResultsOut of the 44 patients, 12 (27.2%) reported MT, primarily during treatment phases. Salivary MDA levels significantly increased during radiotherapy, peaking mid-treatment, before declining post-treatment. Despite this fluctuation, no significant relationship was found between MDA levels and MT. Bovine lactoferrin mouthwash alleviated MT at least partially in 63.2% of the occurrences. Other salivary markers such as protein concentration, antioxidant properties, catalase activity, and superoxide dismutase activity showed no significant link to MT. DiscussionThe increase in MDA levels during radiotherapy indicated heightened oxidative stress. However, the lack of a significant association between MDA and MT suggests other factors may contribute to MT development. The partial efficacy of lactoferrin mouthwash highlighted a potential benefits. Future research should explore other mechanisms, such as the role of oral microbiota, to better understand and manage MT in HNC patients.

ObjectiveTo determine the prevalence of olfactory dysfunctions, mainly, anosmia and to identify its associated factors in patients with COVID-19 infection. Study designA hospital-based prospective observational cohort study SettingA COVID dedicated hospital, Square Hospitals Ltd., Dhaka, Bangladesh. MethodsWe collected patients information including laboratory-confirmed COVID-19 test results. We used Pearson Chi-square test and logistic regression model to assess the associations between demographic and clinical characteristics and olfactory outcomes. ResultsOut of 600 COVID-19 positive patients, 38.7% were diagnosed with olfactory dysfunction. Our analyses showed that patients age, smoking status, cough, dyspnea, sore throat, asthenia, and nausea or vomiting were significantly associated with the anosmia. We observed the risk of developing anosmia was greater in younger patients than in older patients, and this risk decreased as age increased [odds ratio (OR) range for different age groups: 1.26 to 1.08]. Smoking patients were 1.73 times more likely to experience anosmia than non-smoking patients [OR=1.73, 95% confidence interval (CI) = 1.01-2.98]. In addition, patients complained asthenia had a significantly double risk of developing the anosmia [OR = 1.96, CI = 1.23-3.06]. ConclusionsOur study shows that about 39% of patients diagnosed with olfactory dysfunction. Patients age, smoking status, and asthenia are significantly positively associated with the anosmia. Since anosmia can be a significant marker for the diagnosis of COVID-19, we suggest regular screening of olfactory dysfunction in patients with early symptoms of COVID-19, particularly younger patients, smoker, and complained asthenia.

ObjectivesThe molecular basis and mechanisms of Juvenile Nasopharyngeal Angiofibromas (JNA) pathogenesis are still unknown. Despite being a rare and benign neoplasm, JNA is a locally aggressive and potentially destructive neoplasm among head and neck tumors, typically diagnosed in young males. The advancement of genome technologies and analytical tools has provided an unparalleled opportunity to explore the intricacy of JNA. The present study provides the first evidence of the involvement of chromosome Y genes in JNA. MethodsThirteen JNA patients at an advanced disease stage and 5 age-matched male controls were registered for this study. Whole-exome sequencing (WES) analysis was conducted followed by functional analysis to understand the molecular mechanism of the JNA. ResultsWES analysis revealed a high prevalence of mutations in 14 genes within the protein-coding, Male-Specific Region of the Y-chromosome of young males (mean age: 13.8 {+/-} 2.4) with JNA. These mutations, occurring at 28 distinct positions, were characterized as moderate to high impact and were prevalent in 9 JNA patients but not in the control group. The most frequently mutated genes were USP9Y and UTY, followed by KDM5D, DDX3Y and TSPY4. The expression of USP9Y, UTY and DDX3Y was found to be co-modulated, implying their coordinated regulation as a complex. Furthermore, somatic mutations were detected in genes previously linked to JNA. ConclusionThe wide array of genetic and somatic mutations identified in JNA provides novel insight into JNA pathophysiology.

Maes et al. (2008) published the first paper demonstrating that major depressive disorder (MDD) is accompanied by abnormalities in the microbiota-gut-brain axis, as evidenced by elevated serum IgM/IgA to lipopolysaccharides (LPS) of Gram-negative bacteria, such as Morganella morganii and Klebsiella Pneumoniae. The latter aberrations, which point to increased gut permeability (leaky gut), are linked to activated neuro-immune and oxidative pathways in MDD. To delineate the profile and composition of the gut microbiome in Thai patients with MDD, we examined fecal samples of 32 MDD patients and 37 controls using 16S rDNA sequencing and analyzed -(Chao and Shannon indices) and {beta}-diversity (Bray-Curtis dissimilarity) and conducted Linear discriminant analysis (LDA) Effect Size (LEfSe) analysis. Neither -nor {beta}-diversity differed significantly between MDD and controls. Rhodospirillaceae, Hungatella, Clostridium bolteae, Hungatella hathewayi, and Clostridium propionicum were significantly enriched in MDD, while Gracillibacteraceae family, Lutispora, and Ruminococcus genus, Ruminococcus callidus, Desulfovibrio piger, Coprococcus comes, and Gemmiger, were enriched in controls. Contradictory results have been reported for all these taxa, with the exception of Ruminococcus which is depleted in 6 different MDD studies (one study showed increased abundance), many medical disorders that show comorbidities with MDD, and animal MDD models. Our results may suggest a specific profile of compositional gut dysbiosis in Thai MDD patients with increases in some pathobionts and depletion of some beneficial microbiota. The results suggest that depletion of Ruminococcus may be a more universal biomarker of MDD that maybe contributes to increased enteral LPS load, LPS translocation, and gut-brain axis abnormalities.

Autoimmune inner ear disease (AIED) is a rare cause of sensorineural hearing loss, typically characterized by progressive bilateral hearing loss and vestibular symptoms. Diagnosing AIED is challenging due to the lack of specific biomarkers and its overlapping clinical features with other causes of hearing loss. This scoping review examines the recent advancements in the diagnostic approaches for AIED from 2020 to 2024, focusing on studies indexed in SCI, MEDLINE, and INSPEC. The review highlights progress in laboratory tests, imaging techniques, and genetic assessments, and discusses the implications of these advances in improving early diagnosis and treatment outcomes.

BackgroundChemosensory disorders (including smell, taste and chemesthesis) are among the established symptoms of COVID-19 infection; however, new data indicate that the changes in chemosensory sensation caused by COVID-19 may differ among populations and COVID-19 variants. To date, few studies have focused on the influence of the SARS-CoV-2 Omicron variant on qualitative changes and quantitative reductions in chemosensory function in China. MethodologyWe conducted a cross sectional study of patients with COVID-19 caused by the Omicron variant, to investigate the prevalence of chemosensory disorders and chemosensory function before and during infection, using an online questionnaire. ResultsA total of 1245 patients with COVID-19 completed the survey. The prevalence rates of smell, taste, and chemesthesis disorders were 69.2%, 67.7%, and 31.4%, respectively. Our data indicate that sex, age, smoking, and COVID-19-related symptoms, such as lack of appetite, dyspnea, and fatigue, may be associated with chemosensory disorders during COVID-19. ConclusionsSelf-rating of chemosensory function revealed that patients experienced a general decline in smell, taste, and chemesthesis function. Further longitudinal research studies are needed to generate additional data based on objective assessment and investigate the factors influencing chemosensory function in COVID-19.

IntroductionCommon diseases are influenced by a variety of factors that can enhance one persons susceptibility to developing a specific condition. Complex traits have been investigated in several biological levels. One that reflects the high interconnectivity and interaction of genes, proteins and transcription factors is the transcriptome. In this study, we disclose the protocol for a systematic review and meta-analysis aiming at summarizing the available evidence regarding transcriptomic gene expression levels of peripheral blood samples comparing subjects with psychiatric, neurological and other common disorders to healthy controls. Methods and analysisThe investigation of the transcriptomic levels in the peripheral blood enables the unique opportunity to unravel the etiology of common diseases in patients ex-vivo. However, the experimental results should be minimally consistent across studies for them to be considered as the best approximation of the true effect. In order to test this, we will systematically identify all transcriptome studies that compared subjects with common disorders to their respective control samples. We will apply meta-analyses to assess the overall differentially expressed genes throughout the studies of each condition. Ethics and disseminationThe data that will be used to conduct this study are available online and have already been published following their own ethical laws. Therefore this study requires no further ethical approval. The results of this study will be published in leading peer-reviewed journals of the area and also presented at relevant national and international conferences. Strengths and limitations of this study We present a new and systematically centered method to assess the overall effect of transcriptomic levels in the blood of subjects with common conditions. Meta-analyses are a robust statistical method to assess effect sizes across studies. The analysis is limited by the availability of studies, as well as their quality and comprehensiveness. Subgroup and meta-regression analyses will be also limited by the amount and quality of sample characterization variables made available by original studies.

The clinical diagnosis of major depressive disorder (MDD), a heterogeneous disorder, still depends on subjective information in terms of various symptoms regarding mood. Detecting extracellular vesicles (EVs) in blood may result in finding a diagnostic biomarker that reflects the depressive stage of patients with MDD. Here, we report the results on the glycosylation pattern of enriched plasma EVs from patients with MDD and age-matched healthy subjects. In this cohort, the levels of Triticum vulgaris (wheat germ) agglutinin (WGA), N-acetyl glucosamine (GlcNAc) and N-acetylneuraminic acid (Neu5Ac, sialic acid) - binding lectin, were significantly decreased in patients with MDD in depressive state compared to healthy subjects (area under the curve (AUC): 0.87 (95% confidence interval (CI) 0.76 - 0.97)) and in remission state (AUC: 0.88 (95% CI 0.72 - 1.00)). Furthermore, proteome analysis revealed that the von Willebrand factor (vWF) was a significant factor recognized by WGA. WGA-binding vWF antigen differentiated patients with MDD versus healthy subjects (AUC: 0.92 (95% CI 0.82 - 1.00)) and the same patients with MDD in depressive versus remission state (AUC: 0.98 (95% CI 0.93 - 1.00)). In this study, the change patterns in the glycoproteins contained in plasma EVs support the usability of testing to identify patients who are at increased risk of depression during antidepressant treatment.

The inflammatory foreign body response (FBR) following cochlear implantation (CI) can negatively impact CI outcomes, including increased electrode impedances. This study aims to investigate the long-term efficacy of dexamethasone eluting cochlear implant and locally delivered dexamethasone, a potent anti-inflammatory glucocorticoid on the intracochlear FBR and electrical impedance post-implantation in a murine model and human subjects. The left ears of CX3CR1+/GFP Thy1+/YFP (macrophage-neuron dual reporter) mice were implanted with dexamethasone-eluting cochlear implants (Dex-CI) or standard implant (Standard-CI) while the right ear served as unoperated control. Another group of dual reporter mice was implanted with a standard CI electrode array followed by injection of dexamethasone in the middle ear to mimic current clinical practice (Dex-local). Mouse implants were electrically stimulated with serial measurement of electrical impedance. Human subjects were implanted with either standard or Dex-CI followed by serial impedance measurements. Dex-CI reduced electrical impedance in the murine model and human subjects and inflammatory FBR in the murine model for an extended period. Dex-local in the murine model is ineffective for long-term reduction of FBR and electrode impedance. Our data suggest that dexamethasone eluting arrays are more effective than the current clinical practice of locally applied dexamethasone in reducing FBR and electrical impedance.

Objective: Chronic rhinosinusitis (CRS) impacts an estimated 5% to 15% of people worldwide, incurring significant economic healthcare burden. There is a urgent need for the discovery of predictive biomarkers to improve treatment strategies and outcomes for CRS patients. Study design: Cohort study of CRS patients and healthy controls using blood samples. Setting: Out-patient clinics. Methods: Whole blood samples were collected for flow cytometric analysis. Mechanistic studies involved the transfection of human primary T cells and Jurkat cells. Results: Our analysis began with a 63-69 year-old female patient diagnosed with refractory CRS. Despite undergoing multiple surgeries, she continually faced sinus infections. Whole exome sequencing pinpointed a heterozygous IL-12Rb1 mutation situated in the linker region adjacent to the cytokine binding domain. When subjected to IL-12 stimulation, the patients CD4 T-cells exhibited diminished STAT4 phosphorylation. However, computer modeling or T-cell lines harboring the same IL-12 receptor mutation did not corroborate the hypothesis that IL-12Rb could be responsible for the reduced phosphorylation of STAT4 by IL-12 stimulation. Upon expanding our investigation to a broader CRS patient group using the pSTAT4 assay, we discerned a subset of refractory CRS patients with abnormally low STAT4 phosphorylation. The deficiency showed improvement both in-vitro and in-vivo after exposure to Latilactobacillus sakei (aka Lactobacillus sakei), an effect at least partially dependent on IL-12. Conclusion: In refractory CRS patients, an identified STAT4 defect correlates with poor clinical outcomes after sinus surgery, which can be therapeutically targeted by Latilactobacillus sakei treatment. Prospective double-blind placebo-controlled trials are needed to validate our findings.

BackgroundThis study aimed to examine the neurotrophic factors secreted from brain in depression by analyzing astrocyte-derived extracellular vesicles (ADEVs) isolated from plasma, and to explore the causal relationship between the expression of neurotrophic factors in the brain and depression. MethodsA total of 40 patients with treatment-resistant depression (TRD) and 35 matched healthy controls (HCs) were recruited at baseline, and 34 TRD patients completed the post-electroconvulsive therapy (ECT) visits. The concentrations of five neurotrophic factors in ADEVs were measured. A correlation analysis was performed between neurotrophic factors in ADEVs and neurogenesis marker doublecortin (DCX) in neuron-derived extracellular vesicles (NDEVs). Subsequently, Mendelian randomization (MR) study and cell experiments were conducted. ResultsOur findings revealed a decrease in the level of epidermal growth factor (EGF) in ADEVs among TRD patients, with an increase observed post-ECT. The corrected area under the curve for EGF were larger than those for other neurotrophic factors: 0.99 (95% CI: 0.98-1.00). MR suggested that decreased expression levels of the EGF gene in the cortex constitute a risk factor for depression. We observed a positive correlation between the levels of EGF in ADEVs and DCX in NDEVs. Subsequently, cell experiments suggested that EGF can activate EGF receptor (EGFR) to trigger the PI3K-Akt pathway, participating in the promotion of DCX. ConclusionsThis study provides the in vivo evidences supporting that a reduction in EGF levels in the central nervous system could potentially contribute to depression and serve as a biomarker for it. Additionally, the EGF/EGFR signaling pathway may be involved in regulating early neurogenesis traits in depression.

BackgroundRecent surge of olfactory dysfunction in patients who were referred to ENT clinics and concurrent COVID-19epidemic in Iran motivated us to evaluate anosmic/hyposmic patients to find any relation between these two events. MethodsThis is a cross-sectional study with an online checklist on voluntary cases in all provinces of Iran between the 12th and 17th March, 2020. Cases was defined as self-reported anosmia/hyposmia in responders fewer than 4 weeks later (from start the of COVID-19 epidemic in Iran). Variables consist of clinical presentations, related past medical history, family history of recent respiratory tract infection and hospitalization. ResultsIn this study 10069 participants aged 32.5{+/-}8.6 (7-78) years, 71.13% female and 81.68% non-smoker completed online checklist. They reported 10.55% a history of a trip out of home town and 1.1% hospitalization due to respiratory problems recently. From family members 12.17% had a history of severe respiratory disease in recent days and 48.23% had anosmia/hyposmia. Correlation between the number of olfactory disorder and reported COVID-19 patients in all 31 provinces till 16th March 2020 was highly significant (Spearman correlation coefficient=0.87, p-Value<0.001). The onset of anosmia was sudden in 76.24% and till the time of filling the questionnaire in 60.90% of patients decreased sense of smell was constant. Also 83.38 of this patients had decreased taste sensation in association with anosmia. ConclusionsIt seems that we have a surge in outbreak of olfactory dysfunction happened in Iran during the COVID-19 epidemic. The exact mechanism of anosmia/hyposmia in COVID-19 patients needs further investigations.

Oral tongue squamous cell carcinoma (OTSCC) have an increasing incidence in young patients and many have an aggressive course of disease. The molecular mechanisms for this increase are unknown and biologic markers to identify high risk patients are lacking. In an unbiased data screening for differential protein expression of younger ([&le;]45 years) and older (>45 years) OTSCC patients in The Cancer Genome Atlas (TCGA) cohort (n=98) we identified Protein kinase C alpha (PRKCA), to be significantly more frequently overexpressed in younger versus older patients (p=0.0001). These results were experimentally validated and confirmed in an independent Austrian OTSCC patient sample (n=34) by immunohistochemistry (p=0.0026). PRKCA upregulation was associated with negative anamnesis for alcohol consumption (p=0.009) and tobacco smoking (p=0.02). Univariate and multivariate analysis of overall survival (OS) and disease-free survival (DFS) showed a significantly worse prognosis in patients with tumors overexpressing PRKCA regarding OS (univariate p= 0.04, multivariate p< 0.01). In the young subgroup both OS and DFS were significantly decreased in PRKCA positive patients (both p< 0.001). TCGA messenger RNA enrichment analysis showed 24 mRNAs with significant differential expression in PRKCA positive OTSCC (all p[&le;] 0.05 after Benjamini-Hochberg correction). Our findings suggest the potential existence of a distinct molecular subtype of alcohol and tobacco negative, high risk OTSCC in a significant proportion of early onset individuals. Our findings warrant validation in additional OTSCC patient cohorts. Further analysis of the molecular PRKCA interactome may decipher the underlying mechanisms of carcinogenesis and clinicopathological behavior of PRKCA overexpressing OTSCC.