Pathological changes in oral epithelium and the expression of SARS-CoV-2 entry receptors, ACE2 and furin.

BACKGROUND: Expression of angiotensin-converting enzyme (ACE)-2 and co-factors like furin, play key-roles in entry of SARS-CoV-2 into host cells. Furin is also involved in oral carcinogenesis. We investigated their expression in oral pre-malignant/malignant epithelial pathologies to evaluate whether ACE2 and furin expression might increase susceptibility of patients with these lesions for SARS-CoV-2 infection. METHODS: Study included normal oral mucosa (N = 14), epithelial hyperplasia-mild dysplasia (N = 27), moderate-to-severe dysplasia (N = 24), squamous cell carcinoma (SCC, N = 34) and oral lichen planus (N = 51). Evaluation of ACE2/furin membranous/membranous-cytoplasmic immunohistochemical expression was divided by epithelial thirds (basal/middle/upper), on a 5-tier scale (0, 1-weak, 1.5 -weak-to-moderate, 2-moderate, 3-strong). Total score per case was the sum of all epithelial thirds, and the mean staining score per group was calculated. Real time-polymerase chain reaction was performed for ACE2-RNA. Statistical differences were analyzed by One-way ANOVA, significance at p<0.05. RESULTS: All oral mucosa samples were negative for ACE2 immuno-expression and its transcripts. Overall, furin expression was weakly present with total mean expression being higher in moderate-to-severe dysplasia and hyperplasia-mild dysplasia than in normal epithelium (p = 0.01, each) and SCC (p = 0.008, p = 0.009, respectively). CONCLUSIONS: Oral mucosa, normal or with epithelial pathologies lacked ACE2 expression. Furin was weak and mainly expressed in dysplastic lesions. Thus, patients with epithelial pathologies do not seem to be at higher risk for SARS-CoV-2 infection. Overall, results show that oral mucosae do not seem to be a major site of SARS-CoV-2 entry and these were discussed vis-à-vis a comprehensive analysis of the literature.

The prevalence of bruxism and oral parafunction activities among Israeli juveniles with autism spectrum disorder: A preliminary study during the COVID-19 pandemic.

OBJECTIVE: To evaluate the prevalence of oral habits, bruxism, and Temporomandibular Disorders (TMD) injuvenileswithautisticspectrumdisorder(ASD). METHODS: Data included 165 juveniles diagnosed with ASD, allocated to younger group aged 6 21 (n=86) and older group aged 13-21 (n=79). RESULTS: Sleep bruxism was reported by 26.7% in the younger group and by 5% in the older group. Awake bruxism was reported by 22% and 17.7%, respectively. Oral habits were reported by 43% of all participants, with similar rate in both groups. TMD related p ain was low in both groups (6.3% and 7% respectively). The influence of the COVID 19 pandemic on oral parafunction was moderate in the younger group (17.4%) and mild in the older group (8.6%), influence on bruxism was mild in both groups (5.8% and 2.5%, respectively). CONCLUSION: The prevalence of bruxism and oral parafunctions was similar to the reported in the literature for the general population.

The effect of post-COVID-19 on gustatory and olfactory function: A preliminary case-controlled study.

AIMS: The aim of the study was to analyze objective and subjective olfactory/gustatory function in post-COVID-19 infection (PCI). MATERIALS AND METHODS: Patients with past PCR-confirmed COVID-19 infection and persistent olfactory/gustatory complaints were investigated. Olfactory threshold and identification, gustatory detection, identification, and magnitude scaling were tested. RESULTS: A total of 42 PCI subjects were compared to 41 age- and gender-matched controls with no COVID-19 history. All PCI tested had mild COVID-19 disease. Mean interval between COVID-19 confirmations to testing was 7.4 ± 3.1 months. PCI subjects complained of combined dysfunction in 85.7%, isolated olfactory or gustatory dysfunction in 7.1% each. Combined complaints were significantly higher in PCI (p < 0.001). Objective testing showed significantly higher prevalence of dysfunction in PCI versus controls for hyposmia (73.8%, 12.2%), anosmia (11.9%, 0%), odor identification (68.5%, 83.0%), hypogeusia (23% and 2.4%, respectively), and impaired magnitude scaling, (p < 0.05). All PCI subjects with hypogeusia had abnormal gustatory magnitude scaling. CONCLUSIONS: While most PCI subjects complained of combined gustatory and olfactory dysfunction, objective testing showed in the majority an isolated single sense dysfunction, with a low level of agreement between subjective and objective findings. Abnormal objective results for all olfactory and gustatory functions tested may suggest a central rather than peripheral mechanism, although concomitant mechanisms cannot be excluded.

Hyposalivation Affecting Womens' Voice.

OBJECTIVES: Balanced hydration is crucial for optimal physiological function, whereas hypohydration may cause adverse effects. Like many other organs, the larynx is negatively affected by hypohydration, potentially affecting voice production. Therefore, the purpose of this study was to examine voice properties in women diagnosed with dry-mouth. METHODS: Twenty-four women diagnosed with hyposalivation and 24 age-matched controls were recruited. All participants underwent three sialometry tests for quantifying oral-dryness. These tests were conducted in three conditions: after 2-hour fasting, after gustatory salivary stimulation and after drinking water. After each sialometry, participants were recorded while producing the vowels /a/ and /i/, and during a standardized reading task. A basic set of acoustic measures was extracted from these recordings. Self-evaluation of voice was performed using the VHI-10 questionnaire; and listeners' perception of the voice was performed by five professional judges who rated the recordings perceptually, using the GRBAS scale. RESULTS: Significant group differences were found in fundamental frequency and jitter, but not in shimmer and noise-to-harmonic ratio (corrected P < 0.05). The participants in the hyposalivation group exhibited higher scores on the VHI-10 questionnaire compared to the control group (P = 0.002), and the judges perceptually rated their voices higher on the Grade and Roughness scales (0.03 ≤ P ≤ 0.04). In contrast with the significant group differences, no significant differences were found between the three study conditions. CONCLUSIONS: Women suffering from oral-dryness were shown to exhibit degradation in voice quality, evident in both acoustic, perceptual and self-evaluation measures. However, in this paradigm, short-term superficial hydration was not shown to elicit a significant improvement in voice properties. These findings highlight the importance of consistent oral-hydration for voice, especially among people suffering from hyposalivation.

Unexpected Candidal Hyphae in Oral Mucosa Lesions-A Clinico-Pathological Study.

Background: Oral mucosal biopsies might harbor candidal hyphae (CH) in the absence of any clinical signs or symptoms. Aim: To assess oral mucosa biopsies for the frequency of unexpected CH and characterize their clinico-pathological features. Materials and Methods: All biopsy reports (2004−2019) were searched using CH/candida/candidiasis as key words. Cases with clinical diagnosis of oral candidiasis (OC) were excluded. Demographic data, health status, smoking habits, clinical features and diagnoses were collected. Statistical analysis included the chi-square test; significance was set at p < 0.05. Results: Of all the biopsies, 100 (1.05%) reported microscopical evidence of CH without typical clinical signs/symptoms of OC. Fifteen cases were from healthy, non-smoking patients. CH was common on buccal mucosa (38%) and lateral tongue (23%). The tip of tongue (OR = 54.5, 95% CI 9.02−329.4, p < 0.001) and lateral tongue (OR = 3.83, 95% CI 2.4−6.09, p < 0.001) were more likely to harbor CH-positive lesions. CH-positive lesions were diagnosed as epithelial hyperplasia (55%) and exophytic reactive lesions (30%). No correlation was found between CH and the grade of epithelial dysplasia. Conclusions: Microscopic evidence of CH embedded into oral epithelium without typical signs/symptoms of OC is rare, especially in healthy, non-smokers. Since CH was occasionally found in oral sites prone to local trauma and in association with reactive lesions, in absence of host co-morbidities, the contribution of local mechanical forces to CH embedment cannot be ruled out.

Oral adverse reactions associated with etoricoxib, a common pain medication.

BACKGROUND AND OVERVIEW: There have been reports of cutaneous adverse reactions to etoricoxib, a frequently used anti-inflammatory and antipain medication. In this report, the authors describe the first series of patients with adverse reactions to etoricoxib restricted to the oral mucosa. CASE DESCRIPTION: The series comprised 7 men and 4 women, aged 25 through 81 years, 10 of whom had only oral lesions, 1 with mucocutaneous involvement. Lesions were erosive and aphthouslike or erythema multiformelike. In most of the cases, bilateral involvement of the palate was reported. Lips, tongue, and buccal mucosa were also involved. All lesions resolved after drug discontinuation. In 6 patients, repeated use resulted in recurrence of signs and symptoms similar to the first attack. CONCLUSIONS AND PRACTICAL IMPLICATIONS: The dental and medical community should be aware of the oral adverse effects of etoricoxib, recognize them in time, recommend drug-use cessation, and warn patients against repeated use.

The effect of desalivation on the malignant transformation of the tongue epithelium and associated stromal myofibroblasts in a rat 4-nitroquinoline 1-oxide-induced carcinogenesis model.

The aim of our study was to analyse desalivated rat tongue epithelium for histopathological changes, proliferating cell nuclear antigen (PCNA), and epithelium-associated stromal myofibroblasts [SMF; alpha-smooth muscle actin (alphaSMA)] following 0.001% 4-nitroquinoline 1-oxide (4NQO) administration in drinking water. Results were compared with those of identically treated but salivated specimens. 4NQO was administered for 7, 14, 22 and 28 weeks. Tongue length was divided into anterior, middle and posterior 'thirds'. The histopathological changes per 'third' were scored as normal epithelium, hyperplasia, dysplasia, carcinoma-in-situ, and superficial and invasive carcinoma. The PCNA and alphaSMA stains were assessed by a point-counting method. At all time points, the histopathological changes in the anterior and middle thirds were higher in the desalivated than in the salivated group (P < 0.05) but almost identical in the posterior third (P > 0.05). PCNA scores were significantly lower in the desalivated vs. the salivated group at almost all time points and tongue thirds (P < 0.05). SMF were usually scarce in both groups, but there was a significant surge in the posterior third at 28 weeks: the score in the desalivated group was only about one-half that of the salivated group (P < 0.05). The absence of saliva seems to promote malignant transformation of the tongue epithelium in the early stages. PCNA cannot be regarded as a marker of proliferation and probably contributes to this process by other mechanisms. Emergence of SMF seems to be highly dependent on growth factors from saliva in addition to factors from cancerous cells.