Therapeutic Advances and Challenges for the Management of HPV-Associated Oropharyngeal Cancer.

The use of conventional chemotherapy in conjunction with targeted and immunotherapy drugs has emerged as an option to limit the severity of side effects in patients diagnosed with head and neck cancer (HNC), particularly oropharyngeal cancer (OPC). OPC prevalence has increased exponentially in the past 30 years due to the prevalence of human papillomavirus (HPV) infection. This study reports a comprehensive review of clinical trials registered in public databases and reported in the literature (PubMed/Medline, Scopus, and ISI web of science databases). Of the 55 clinical trials identified, the majority (83.3%) were conducted after 2015, of which 77.7% were performed in the United States alone. Eight drugs have been approved by the FDA for HNC, including both generic and commercial forms: bleomycin sulfate, cetuximab (Erbitux), docetaxel (Taxotere), hydroxyurea (Hydrea), pembrolizumab (Keytruda), loqtorzi (Toripalimab-tpzi), methotrexate sodium (Trexall), and nivolumab (Opdivo). The most common drugs to treat HPV-associated OPC under these clinical trials and implemented as well for HPV-negative HNC include cisplatin, nivolumab, cetuximab, paclitaxel, pembrolizumab, 5-fluorouracil, and docetaxel. Few studies have highlighted the necessity for new drugs specifically tailored to patients with HPV-associated OPC, where molecular mechanisms and clinical prognosis are distinct from HPV-negative tumors. In this context, we identified most mutated genes found in HPV-associated OPC that can represent potential targets for drug development. These include TP53, PIK3CA, PTEN, NOTCH1, RB1, FAT1, FBXW7, HRAS, KRAS, and CDKN2A.

TeleCleft: Development and Evaluation of a Mobile Application for Monitoring Cleft Patients.

OBJECTIVE: Development and evaluation of a mobile application for remote monitoring and guidance of pediatric patients diagnosed with cleft lip and/or palate (CL ± P) and their caregivers. DESIGN: This is a pilot cross-sectional, applied, and quantitative study. SETTING: The study was conducted in two tertiary care treatment centers in Brazil. PARTICIPANTS: The participants included 20 caregivers and infants undergoing treatment with nasoalveolar molding (NAM) for CL ± P. INTERVENTIONS: The intervention involved using the TeleCleft mobile application for remote monitoring and guidance of caregivers and infants during NAM treatment. MAIN OUTCOME MEASURE(S): The main outcome measures included usability and satisfaction of users with the TeleCleft application. RESULTS: The results showed high usability and satisfaction ratings among users of the TeleCleft application. Most participants found remote monitoring to be effective and expressed positive opinions about its convenience and usefulness. CONCLUSION: TeleCleft could be a viable tool for remote monitoring and guidance, reducing the need for patients and caregivers to travel to treatment centers, which could potentially alleviate the burden of care faced by families during the journey of CL ± P treatment.

Antimicrobial effect and the mechanical and surface properties of a self-disinfecting and a chlorhexidine-incorporated Type IV dental stone.

STATEMENT OF PROBLEM: Stone casts are subject to contamination, but whether disinfectants incorporated into the stone are effective is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the antimicrobial activity and the mechanical and surface properties of self-disinfecting gypsum (SDG) and gypsum mixed with 2% chlorhexidine (GCHX). MATERIAL AND METHODS: Antimicrobial action was evaluated using the diffusion-disk technique on Streptococcus aureus and Candida albicans 1 hour and 24 hours after pouring the gypsum. The groups were SDG, GCHX, a positive control (PC) of gypsum mixed with distilled water, and a negative control (NC) of filter paper disk soaked with 2% chlorhexidine; n=8. Inhibition halos were measured using the ImageJ software program and statistically analyzed using the repeated measures mixed ANOVA with time×group interaction. Compressive strength (CS) in MPa and surface roughness (SR) in µm (parameters: Ra - roughness average; and Sa - 3-dimensional (3D) arithmetic mean of the surface profile) tests were performed to characterize the specimens (evaluated groups: SDG, GCHX, and PC; n=10). CS data were analyzed by a 2-way ANOVA with time×group interaction, and SR data by a 1-way ANOVA (α=.05). RESULTS: For S aureus, there were differences between GCHX and SDG at 1 hour and 24 hours (P<.05), but no significant differences were found for C albicans (P>.05). GCHX was better than PC, except for C albicans, and showed a reduction in CS when compared with PC and SDG (P<.05) at all time intervals. The SR of GCHX increased (Ra:1.76, Sa:2.08) when compared with PC (Ra:0.89, Sa:1.12) and SDG (Ra:1.03, Sa:1.35) (Ra: P<.004 and Sa: P<.001). CONCLUSIONS: The antimicrobial activity of GCHX against S aureus was better than that of SDG, but neither had an effect against C albicans. As for CS and SR, GCHX presented a decrease in properties when compared with PC and SDG but was within the American Dental Association #25 specification values.

Is there an association between rheumatoid arthritis and bone changes in the temporomandibular joint diagnosed by cone-beam computed tomography? A systematic review and meta-analysis.

OBJECTIVES: Evaluate the relation of rheumatoid arthritis (RA) and bone changes in the temporomandibular joint diagnosed by cone-beam computed tomography (CBCT). MATERIALS AND METHODS: This systematic review and meta-analysis were recorded in the PROSPERO database, using the CRD42020153246 protocol. The electronic searches were performed in the following databases: Pubmed, Scopus, Web of Science, Lilacs, Cochrane, and Open Grey. Cross-sectional studies that evaluated patients with RA with bone changes in the temporomandibular joint diagnosed by CBCT, without language restriction or publication date, were included. Meta-analysis was performed in Stata Software (StataCorp, TX, USA, version 12.0), using the metan, and a random effects model, and the risk of different bone alterations occurring in adults with and without arthritis was estimated using odds ratios (ORs) as a pooled measure of effect. Forest plots were used to present the isolated and the pooled effects (ORs and 95% CI). RESULTS: Six studies were used for qualitative synthesis and 2 studies for quantitative synthesis. All studies diagnosed higher prevalence changes in the bone structures of the TMJ of RA patients, described as erosion, flattening, sclerosis, and osteophytes. Meta-analysis showed that the chance of bone changes occurring in components of the TMJ is greater in individuals who have RA. CONCLUSION: There is an association between RA and bone changes in TMJ structures diagnosed through CBCT, as RA patients were more likely to have osteoarthritic changes in this joint. CLINICAL RELEVANCE: Understanding the existence of an association between bone alterations in TMJ and RA can assist in the management of patients.

Tobacco Use, Attitudes, Knowledge, and Perception About Smoking Cessation Counseling Among Brazilian Dental Students: a Cross-Sectional Study.

The aim of this study was to evaluate the prevalence of tobacco use, exposure to secondhand smoke, and knowledge and perception about smoking cessation counseling among dental students in Brazil. A cross-sectional study was performed at the School of Dentistry, Universidade Federal de Pernambuco, Brazil. The Global Health Professions Student Survey (GHPSS) research instrument was used. In the second half of 2017, students from the 5th to the 10th semester were recruited to answer the anonymous and self-administered survey in classrooms. The data were tabulated and analyzed, and information about the variables was presented using descriptive statistics. The association between the variables was determined through the Chi-square test and binary logistic regression. Two hundred and twenty-four students answered the survey. More than 40% of the students had tried cigarettes at least once and 8.9% were current smokers. About 28% of the participants reported having been exposed to secondhand smoke in their home and 57.1% in other environments. Most students recognized that they are role models for society and believed they should receive training in smoking cessation counseling. However, only 12.5% of the students reported having received some formal training in this subject. In conclusion, although dental students are aware of the harmful effects of tobacco, there is still a lack of training in smoking prevention and control among these future professionals.

Cinnamaldehyde is a biologically active compound for the disinfection of removable denture: blinded randomized crossover clinical study.

BACKGROUND: Fungal infections associated with the use of dentures, like denture stomatitis, are difficult to prevent and treat. This in situ study aimed to investigate the efficacy of cinnamaldehyde for the disinfection of complete removable dentures, and the effect on the physical and mechanical properties (Vickers microhardness, color, and surface roughness) of the acrylic resin. METHODS: Acrylic resin disks were inserted into the dentures of a probabilistic sample of 33 complete denture users, that used cinnamaldehyde (27 µg/mL) and 0.5% sodium hypochlorite solutions in a 20 min/7-days protocol of dentures immersion in each solution, with a wash-out period of 7 days, to constitute a crossover-study. The disks were analyzed before and after the immersion, for the presence of microorganisms (CFU/mL) and by scanning electron microscope (SEM). Also, the surface roughness (Ra) and Vickers microhardness were measured, and color parameters were analyzed using the National Bureau of Standards (NBS) method. Data was analyzed by Wilcoxon and Friedman (microbiological evaluation), paired t-test (color and roughness) and independent t-test (Vickers hardness) (α = 0.05). RESULTS: A significant reduction (P < 0.05) in the number of microorganisms was observed for each species (total microorganisms, Streptococcus mutans, and Candida spp.), with no significant differences (P > 0.05) between hypochlorite and cinnamaldehyde. There was an increase in the roughness and a decrease in the hardness of the test specimens, with no difference between the two disinfectant substances (P > 0.05). Both hypochlorite and cinnamaldehyde also caused changes in color, considered as "perceptible" by the NBS classification, but with no significant difference between disinfectant substances (P < 0.05), and under the clinically acceptable limit (ΔE ≤ 3.7). CONCLUSION: The 27 µg/mL cinnamaldehyde solution was effective against all evaluated microorganisms and caused minor alterations in hardness, surface roughness, and color parameters, with no clinical relevance.

Antifungal activity and Shore A hardness of a tissue conditioner incorporated with terpinen-4-ol and cinnamaldehyde.

PURPOSE: This study investigated the anti-Candida activity and the Shore A hardness of a tissue conditioner (Softone™) modified by incorporation of terpinen-4-ol and cinnamaldehyde. MATERIAL AND METHODS: Agar diffusion, microdilution, and mechanism of action methods were performed to determine to evaluate the antifungal activity of phytoconstituents. Then, phytoconstituents in varying concentrations were incorporated into the tissue conditioner. The anti-Candida effect of the modified conditioner was evaluated through agar punch well and biofilm formation methods. Shore A hardness of the experimental liners was evaluated after baseline, 24 h, 48 h, 4 days, and 7 days immersion on artificial saliva. RESULTS: The phytoconstituents incorporated into Softone showed completely inhibited fungal growth in concentrations of 20-40% and did not present significant antifungal activity until their concentrations where higher than 5%. There were differences between non-modified Softone and M5, M10, C10, and T10% (p < 0.05). The groups containing 10-40% of cinnamaldehyde incorporated into Softone were able to completely inhibit the biofilm. Concentrations below 40% of terpinen-4-ol showed unsatisfactory biofilm inhibition. The T40% and C40% groups presented the lowest Shore A hardness values. Hardness values from groups T40% at 7 days (p = 0.476); C40% at 4 days (p = 0.058); and T20% (p = 0.058), C20% (p = 0.205), T30% (p = 0.154), and C30% (p = 0.874) after 48 h did not differ from the control group. CONCLUSIONS: Cinnamaldehyde incorporated into Softone inhibited Candida biofilm formation at concentrations of 10-40%, being more effective than terpinen-4-ol modification despite of halo inhibition observed by both products. CLINICAL RELEVANCE: All modifications showed a very similar pattern of hardness being useful for clinical practice.

In vitro effect of S. mutans biofilm on fluoride/MDPB-containing adhesive system bonded to caries-affected primary dentin.

PURPOSE: To evaluate the effect of storage in S. mutans culture or water on the durability of fluoride and MDPB-containing adhesive system on artificial caries-affected primary dentin. METHODS: Dentin flat surfaces of primary molars were submitted to artificial caries development using S. mutans biofilm. CAPD cavities were restored with Adper Scotchbond Multi-Purpose (SBM) or Clearfil Protect Bond (CPB) and they were serially sectioned into sticks (1 mm2 cross-sectional area) and stored in S. mutans biofilm for 3 days, in deionized water for 3 months and afterwards subjected to microtensile bond strength (µTBS) test. A control group was submitted to immediate TBS testing. Two-way ANOVA and Tukey's tests were used. Failure sites were observed by SEM and classified as cohesive (dentin or resin) and adhesive failures. RESULTS: The control group showed the highest µTBS values (MPa) for both SBM (25.2 ± 8.5) and CPB (15.6 ± 6.1) adhesive systems. A significant decrease in µTBS values after S. mutans biofilm and water storage was observed for SBM (18.7 ± 5.7 and 17.4 ± 4.1, respectively) and CPB (13.9 ± 5.2 and 13.7 ± 4.8, respectively), but no difference was found between them. The highest percentage of adhesive failure was observed for all groups. However, cohesive failure in dentin was observed in a higher percentage for SBM than CP.

Digital resources in the monitoring of patients with cleft lip and palate: protocol for a scoping review.

INTRODUCTION: Cleft lip and/or palate (CL+/-P) is a congenital malformation affecting the lip and palate, requiring long-term treatment due to potential associated complications. For this reason, it is important for the patient to be continuously monitored and followed for health promotion and prevention, as well as improving the quality of life. The aim of this scoping review protocol is to identify and map the available evidence regarding the application of digital resources and technologies in the monitoring and follow-up of patients with CL+/-P. METHODS AND ANALYSIS: This scoping review protocol follows the guidelines recommended by the Joanna Briggs Institute Manual, employing the PCC acronym (Patient/Concept/Context). Searches will be conducted, in May 2024, of PubMed, Web of Science, Scopus, Latin American and Caribbean Health Sciences Literature, ScienceDirect, as well as grey literature indexed in ProQuest Open Access Dissertations & Theses and Google Scholar. The review will consider all types of published studies, including grey literature, in English, Portuguese and Spanish languages, and will consider studies regardless of publication date. Exclusions will apply to studies that do not address the use of digital resources and technologies in CL+/-P monitoring and follow-up. ETHICS AND DISSEMINATION: As this is a scoping review, no ethics committee approval is required. After completion, the plan is to publish results in scientific journals on craniofacial malformations. STUDY REGISTRATION: Open Science Framework, DOI:10.17605/OSF.IO/Y6AG8.

Detection of cytokeratins in ghost cells of calcifying cystic odontogenic tumor indicates an altered keratinization and hair follicle differentiation for their development.

Calcifying cystic odontogenic tumors (CCOTs) are benign cystic lesions of odontogenic origin characterized by an ameloblastoma-like epithelium and the presence of a group of cells named ghost cells. The pattern of cytokeratin (Ck) expression on these lesions remains unclear and needs to be clarified. To this end, the expression of Ck6, Ck13, Ck14, Ck18, and Ck19 in the epithelium lining of 7 cases of CCOTs was evaluated by immunohistochemistry. For this, the epithelium lining was divided into 3 distinct regions: basal layer, suprabasal layer, and the compartment composed of ghost cells. In this study, 6 cases (85.7%) were classified as type 1 and 1 (14.3%) as type 4. All cases were negative for Ck13 and Ck18, despite the epithelial layer, as well as in the ghost cells. Ck6 was only positive in the ghost cells. Positivity for Ck14 and Ck19 was found in the basal and suprabasal layers, including the ghost cells. The results showing positivity for Ck14 and Ck19 in all of the analyzed cases reinforce CCOT as being of odontogenic origin, and the restricted expression of Ck6 in the ghost cells may be indicative that these cells suffer an altered differentiation into hair follicles in CCOTs.

Telehealth in oral medicine: A cross-sectional evaluation based on a mobile application.

BACKGROUND: Teledentistry is considered a good tool in the diagnostic process. In oral medicine, there is a low number of trained professionals and dentists have difficulty in diagnosing and treating oral lesions. OBJECTIVE: We aimed to perform a cross-sectional evaluation based on the mobile application for oral diagnosis using a mobile application in a Brazilian State. METHODS: This is a retrospective, cross-sectional, observational study of the data of the "Telehealth in Stomatology in Paraíba" carried out between May 2021 and November 2022. RESULTS: The app has a team of 16 consultants (Ph.D. professors, postgraduate students, residents, and dentists). In addition, there are 289 registered professionals, with a mean age of 33.7 years, predominantly female (70.2%), working in primary care (79.2%), and general practitioners (42.6%). Regarding the cases, the app has 194 cases, and reactive lesions are the most suggested hypotheses reported by dentists (24.5%) and consultants (22.3%). We had an overall concordance rate of 64.1%. CONCLUSION: The application is easily accessible and has an assistance network that helps with early diagnosis. In addition, it has good coverage with users in more than 50% of the cities in the state. Thus, applications that provide specialized care to distant areas are important for better public health.

Oral Lymphatic Malformations: A 21-Year Retrospective Study in a Single Institution.

Introduction. Oral lymphatic malformations are uncommon lesions. This study assessed the clinicopathological and sociodemographic features of oral lymphatic malformations in a Brazilian oral pathology service. Methods. Between 2000 and 2021, all oral lymphatic malformations diagnosed in a single oral pathology service were selected for the study. Clinical data, such as age, sex, site of the lesion, clinical presentation, diagnosis clinical, and the type of biopsy were recorded from the patient's clinical charts. Results. From 7554 oral lesions, 17 (0.22%) were oral lymphatic malformations. This lesion similarly affected both sexes, and the mean age of the patients was 16.5 years. The tongue was the most common site (n = 13; 76%). The mean size of the lesions was 17 mm. Oral lymphatic malformations were asymptomatic for 29% of the patients. Clinically, most lesions appeared as a reddish, sessile nodule, with a pebbly surface. In addition, the clinical and histopathological diagnoses agreed for most lesions (n = 11; 64%). The type of biopsy performed was excisional in 41% of lesions. Conclusions. In summary, oral lymphatic malformations present a low prevalence among the oral lesions diagnosed in an oral pathology service. Moreover, they affect equally both sexes, especially young patients, and usually appear as an asymptomatic or symptomatic nodular swelling on the tongue.

Implications and Emerging Therapeutic Avenues of Inflammatory Response in HPV+ Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinomas (HNSCC) are a heterogeneous group of malignancies which have shown exponential incidence in the last two decades especially due to human papillomavirus (HPV) infection. The HPV family comprises more than 100 types of viruses with HPV16 and HPV18 being the most prevalent strains in HNSCC. Literature data reveal that the mutation profile as well as the response to chemotherapy and radiotherapy are distinct among HPV+ versus HPV-negative tumors. Furthermore, the presence of the virus induces activation of an immune response, in particular the recruitment of specific antiviral T lymphocytes to tumor sites. These T cells when activated produce soluble factors including cytokines and chemokines capable of modifying the local immune tumor microenvironment and impact on tumor response to the treatment. In this comprehensive review we investigated current knowledge on how the presence of an HPV can modify the inflammatory response systemically and within the tumor microenvironment's immunological responses, thereby impacting on disease prognosis and survival. We highlighted the research gaps and emerging approaches necessary to discover novel immunotherapeutic targets for HPV-associated HNSCC.

Impact of COVID-19 on dental practice and anxiety among increased risk group dentists: A cross-sectional study.

BACKGROUND: The likelihood of infection with SARS-COV-2 (COVID-19) in the dental office is considered high. OBJECTIVES: Assessing the impact of the COVID-19 on dental practices and anxiety levels in risk group Brazilian dentists. METHODS: A cross-sectional study was performed using an online questionnaire. The data obtained were analyzed using the IBM SPSS 25.0 software (Pearson's Chi-square association test, multivariate logistic regression, and Poisson multiple regression), with subsequent calculation of the odds ratio at a 95% confidence interval, with a significance level of 5%. RESULTS: Responses of 578 dentists distributed in all regions of Brazil were collected. Most of the dentists were female, with an average age of 35. Of the participants, 23.4% were part of the increased risk group for COVID-19. The professionals who belonged to the increased risk group had a greater chance of not feeling prepared to perform consultations (OR = 1.67) and were not performing any procedures during the pandemic (OR = 2.03). Belonging to the increased risk group did not influence anxiety levels among the dentists. The factors associated with increased anxiety were being female, being younger, working in the southeastern region of the country, being afraid of contracting COVID-19 while working, and being concerned for one's professional future. CONCLUSIONS: The pandemic has had a negative impact on the professional practice of individuals at risk, but the level of anxiety was like professionals who were not part of the increased risk group for COVID-19.

Evaluation of the economic impact of COVID-19 on Brazilian private dental clinics: A cross-sectional study.

BACKGROUND: The changes in dental care in the face of the COVID-19 pandemic resulted in the need for greater financial investment by dentists in biosafety measures and increase in the costs of dental consultations. OBJECTIVE: To evaluate the economic impact of the COVID-19 pandemic on dental practices in private clinics in Brazil. METHODS: A cross-sectional study was carried out, using an online questionnaire indexed in Google Forms, and distributed among dentists. The data obtained were analyzed using the IBM SPSS 25.0 software, evaluating the factors associated with strong or very strong impact on the participants' income and the factors that motivated the dentists to look for a credit line. Multiple logistic regression models were constructed to identify the associated factors. Variables with p < 0.05 were considered statistically significant. RESULTS: Most participants were female, with a median age of 35 years. Dentists who are most concerned about their professional future (OR = 3.134; 95% CI: 1.804-5.445), who have longer office hours (OR = 2.056; 95% CI: 1.198-3.529), who had the greatest impact on the flow of patients (OR = 16.358; 95% CI: 9.408-28.443) and in need of investing in infrastructure (OR = 1.756; 95% CI: 1.014-3.041), had the greatest impact on monthly earnings. CONCLUSIONS: The pandemic and the new biosafety recommendations for care during this period had a negative impact on the income of Brazilian dental offices and increased the chance of seeking credit to alleviate the financial deficit.

No association between periodontal disease and GHQ-12 in a Brazilian Police population.

OBJECTIVES: We attempt to investigate a possible association between periodontal disease (PD) and mental disorders (MD) in a population of Brazilian Police. STUDY METHOD: From a total study population consisting of 803 policemen, 345 police officers were obtained by a sample calculation using the finite population correction who were randomly selected in Montes Claros, Minas Gerais, Brazil. Patients who had been prescribed steroids or those diagnosed with diabetes and cardiovascular diseases were excluded from this study. The General Health Questionnaire (GHQ-12) was used to assess mental disorders. Odds ratios (ORs) for periodontal diseases severity and their respective 95% confidence intervals (CIs) were estimated. The risk of advanced scores in Clinical Attachment Level (CAL) and Community Periodontal Index (CPI) were estimated using Poisson Regression analyses. RESULTS: Only smoking and age were associated with severity in CAL and CPI index. No relation between MD and PD was observed even in different positions within the police department. CONCLUSIONS: It was not observed relation between GHQ-12 and the incidence of Periodontal Disease in a Brazilian Police population. Classical factors like age and smoking, however, were associated with CAL and CPI index higher scores in this population.