Naltrexone accelerated oral traumatic ulcer healing and downregulated TLR-4/NF-kB pathway in Wistar rats.

OBJECTIVE: To assess the effect of naltrexone on oral mucosal healing using a traumatic ulcer model DESIGN: Wistar rats (n = 112) received distilled water (control) or naltrexone (0.5, 10, or 50 mg/kg/day). Ulcers were induced on the buccal mucosa using a round skin biopsy punch (diameter 6 mm). Euthanasia was performed on days 1, 3, 7, and 14. Healing was assessed by ulcer area, histological scores, histomorphometric analysis (number of polymorphonuclears, mononuclears, and fibroblasts), and collagen percentage. Immunohistochemistry for TLR-2, TLR-4, NF-kB, and CD31 was evaluated. Nociceptive threshold was measured daily. RESULTS: The 50 mg/kg group showed reduced ulcer area on days 1 (p < 0.001), 3 (p < 0.05), and 14 (p < 0.01). In this group, there was, on day 14, an increase in the percentage of reepithelization (p = 0.043) and collagen (p < 0.05), an increase in connective tissue maturation (p = 0.016), and on day 7 an increase in fibroblasts (p < 0.001). The 10 mg/kg dose reduced the ulcer area on day 1 (p < 0.001). The 50 mg/kg group showed lower expression of TLR-4 (p < 0.001) on day 1, NF-kB on days 1 (p < 0.05) and 14 (p < 0.05), and CD31 on day 14 (p < 0.05). The 0.5 and 10 mg/kg doses reduced TLR-4 expression on day 1 (p < 0.05; p < 0.01, respectively). Nociceptive threshold increased in the 50 mg/kg group (p < 0.01). CONCLUSION: Naltrexone enhanced traumatic oral ulcer healing by reducing TLR-4/NF-kB signaling and promoting fibroblast proliferation and collagen deposition. Additionally, naltrexone reduced pain in rats.

Interleukin-17 plays a role in dental pulp inflammation mediated by zoledronic acid: a mechanism unrelated to the Th17 immune response?

OBJECTIVE: To evaluate the influence of RORγT inhibition by digoxin on inflammatory changes related to interleukin-17 (IL-17) in the pulp of rats treated with zoledronate (ZOL). METHODOLOGY: Forty male Wistar rats were divided into a negative control group (NCG) treated with saline solution, a positive control group (PCG) treated with ZOL (0.20 mg/kg), and three groups treated with ZOL and co-treated with digoxin 1, 2, or 4 mg/kg (DG1, 2, and 4). After four intravenous administrations of ZOL or saline solution in a 70-day protocol, the right molars were evaluated by histomorphometry (number of blood vessels, blood vessels/µm2, cells/µm2, total blood vessel area, and average blood vessel area) and immunohistochemistry (IL-17, TNF-α, IL-6, and TGF-ß). The Kruskal-Wallis/Dunn test was used for statistical analysis. RESULTS: PCG showed an increase in total blood vessel area (p=0.008) and average blood vessel area (p=0.014), and digoxin treatment reversed these changes. DG4 showed a reduction in blood vessels/µm2 (p<0.001). In PCG odontoblasts, there was an increase in IL-17 (p=0.002) and TNF-α (p=0.002) immunostaining, and in DG4, these changes were reversed. Odontoblasts in the digoxin-treated groups also showed an increase in IL-6 immunostaining (p<0.001) and a reduction in TGF-ß immunostaining (p=0.002), and all ZOL-treated groups showed an increase in IL-17 (p=0.011) and TNF-α (p=0.017) in non-odontoblasts cells. CONCLUSION: ZOL induces TNF-α- and IL-17-dependent vasodilation and ectasia, and the classical Th17 response activation pathway does not seem to participate in this process.

Mu and Kappa opioid receptor immunolabeling indicates the prognosis of oropharyngeal squamous cell carcinoma: A cross-sectional observational study.

BACKGROUND: Opioids are the most effective drugs currently available for cancer pain management. The administration of morphine, in addition to its analgesic effect, can alter tumor development. OBJECTIVE: To characterize the immunoexpression of opioid receptors µ and κ in oropharyngeal squamous cell carcinoma, and correlate it with prognostic factors, proliferation markers, and cell death. MATERIALS AND METHODS: A retrospective, cross-sectional observational study was carried out with 50 patients diagnosed at Haroldo Juaçaba Hospital. Sociodemographic, clinicopathological, and overall survival data were collected, and excisional biopsies were taken for immunohistochemistry using tissue microarrays for opioid receptors µ and κ, Ki-67, and caspase-3. Immunolabeling was evaluated and correlated with other variables using Mann-Whitney, Kruskal-Wallis, Spearman correlation, log-rank (Mantel-Cox), and Cox regression tests. RESULTS: Immunoexpression of opioid receptors µ and κ, Ki-67, and caspase-3 was significantly higher in p16+ and p16- primary tumors and lymph node metastases than in surgical resection margins. The overall survival of patients with p16- tumors was 57.53 ± 8.43 months and that of patients with p16+ tumors was slightly higher at 75.92 ± 11.14 months. Multivariate analysis showed that the expression of opioid receptors µ and κ in the nucleus was directly associated with a lower and higher risk of death, respectively. CONCLUSION: We found increased expression of opioid receptors µ and κ in tumor tissues. The nuclear expression of opioid receptors µ and κ influences overall survival and may be a prognostic factor of oropharyngeal squamous cell carcinoma.

A simple and low-cost technic for immobilization of mandible during head and heck radiotherapy: a technical note.

Immobilization protocols for head and neck radiotherapy (HNR) are needed to reduce radiation dispersion in non-tumoral tissues and to reduce damage to noble structures; however, involuntary mandibular movements require additional adaptations of thermoplastic masks. PURPOSE: Our objective was to describe an easy and low-cost disposition to help thermoplastic masks immobilize the mandible during HNR. MATERIALS AND METHODS: We created Styrofoam models to stabilize the mandible which was used to make adaptation to the thermoplastic masks. The Styrofoam model was inserted into alginate to construct a mold and a self-curing acrylic resin was added into the mold. After the acrylic resin hardened, the dispositive mandibular immobilizer was removed from the alginate mold and adjusted with Maxicut and Minicut or other drills and sandpaper. The alginate mold can be used on the same day to create backup devices. RESULTS AND CONCLUSIONS: Our device was made in a simple way, has a low cost, and helps the thermoplastic masks to immobilize the mandible, leading to a more precise individualization of head and neck immobilization that can reduce unanticipated radiation scatter and improve radiation distribution.

Interleukin-17 plays a role in dental pulp inflammation mediated by zoledronic acid: a mechanism unrelated to the Th17 immune response?

Abstract Objective To evaluate the influence of RORγT inhibition by digoxin on inflammatory changes related to interleukin-17 (IL-17) in the pulp of rats treated with zoledronate (ZOL). Methodology Forty male Wistar rats were divided into a negative control group (NCG) treated with saline solution, a positive control group (PCG) treated with ZOL (0.20 mg/kg), and three groups treated with ZOL and co-treated with digoxin 1, 2, or 4 mg/kg (DG1, 2, and 4). After four intravenous administrations of ZOL or saline solution in a 70-day protocol, the right molars were evaluated by histomorphometry (number of blood vessels, blood vessels/µm2, cells/µm2, total blood vessel area, and average blood vessel area) and immunohistochemistry (IL-17, TNF-α, IL-6, and TGF-β). The Kruskal-Wallis/Dunn test was used for statistical analysis. Results PCG showed an increase in total blood vessel area (p=0.008) and average blood vessel area (p=0.014), and digoxin treatment reversed these changes. DG4 showed a reduction in blood vessels/µm2 (p<0.001). In PCG odontoblasts, there was an increase in IL-17 (p=0.002) and TNF-α (p=0.002) immunostaining, and in DG4, these changes were reversed. Odontoblasts in the digoxin-treated groups also showed an increase in IL-6 immunostaining (p<0.001) and a reduction in TGF-β immunostaining (p=0.002), and all ZOL-treated groups showed an increase in IL-17 (p=0.011) and TNF-α (p=0.017) in non-odontoblasts cells. Conclusion ZOL induces TNF-α- and IL-17-dependent vasodilation and ectasia, and the classical Th17 response activation pathway does not seem to participate in this process.

Development and professional validation of an App to support Oral Cancer Screening.

The objective of this study was to develop and validate an App for identifying risk factors for oral cancer. To this end, we developed an App (OCS: Oral Cancer Screening) with predictors of Oral Cancer (OC) and algorithm assembly to estimate the risk of its development. METHODOLOGY: Simulated clinical cases were designed so that 40 professionals with expertise in oral diagnostics could validate the algorithm and test its usability (SUS: System Usability Score) and acceptability (TAM: Technology Acceptance Model). Cronbach's alpha coefficient, Friedman/Dunn tests, and Spearman correlation evaluated the SUS and TAM scales. ROC curve was plotted to estimate the cutoff point of the algorithm in suggesting a high risk for OCS of the simulated cases. Chi-square and Fisher's exact tests were additionally used (p<0.05, SPSS v20.0). RESULTS: Professionals with expertise in oral diagnosis had usability of 84.63±10.66 and acceptability of 84.75±10.62, which correlated positively (p<0.001, r=0.647). Acting in clinical areas of dentistry (p=0.034) and history of performing OC risk factor orientation (p=0.048) increased acceptability while acting in higher education increased usability (p=0.011). The cutoff point suggested by the App after validation of the simulated clinical cases showed high sensitivity of 84.8% and lower specificity of 58.4%. CONCLUSION: The OCS was effective and with adequate sensitivity, usability, and acceptability and may contribute to the detection of early oral lesions.

Development and professional validation of an App to support Oral Cancer Screening

Abstract The objective of this study was to develop and validate an App for identifying risk factors for oral cancer. To this end, we developed an App (OCS: Oral Cancer Screening) with predictors of Oral Cancer (OC) and algorithm assembly to estimate the risk of its development. Methodology: Simulated clinical cases were designed so that 40 professionals with expertise in oral diagnostics could validate the algorithm and test its usability (SUS: System Usability Score) and acceptability (TAM: Technology Acceptance Model). Cronbach's alpha coefficient, Friedman/Dunn tests, and Spearman correlation evaluated the SUS and TAM scales. ROC curve was plotted to estimate the cutoff point of the algorithm in suggesting a high risk for OCS of the simulated cases. Chi-square and Fisher's exact tests were additionally used (p<0.05, SPSS v20.0). Results: Professionals with expertise in oral diagnosis had usability of 84.63±10.66 and acceptability of 84.75±10.62, which correlated positively (p<0.001, r=0.647). Acting in clinical areas of dentistry (p=0.034) and history of performing OC risk factor orientation (p=0.048) increased acceptability while acting in higher education increased usability (p=0.011). The cutoff point suggested by the App after validation of the simulated clinical cases showed high sensitivity of 84.8% and lower specificity of 58.4%. Conclusion: The OCS was effective and with adequate sensitivity, usability, and acceptability and may contribute to the detection of early oral lesions.

Resumo O objetivo deste estudo foi desenvolver e validar um aplicativo para identificação de fatores de risco para câncer bucal. Para tanto, desenvolvemos um aplicativo (OCS: Oral Cancer Screening) com preditores de Câncer Oral (CO) e montagem de algoritmo para estimar o risco de seu desenvolvimento. Metodologia: Casos clínicos simulados foram projetados para que 40 profissionais com expertise em diagnóstico oral pudessem validar o algoritmo e testar sua usabilidade (SUS: System Usabilidade Score) e aceitabilidade (TAM: Technology Acceptance Model). O coeficiente alfa de Cronbach, os testes de Friedman/Dunn e a correlação de Spearman avaliaram as escalas SUS e TAM. A curva ROC foi traçada para estimar o ponto de corte do algoritmo ao sugerir um alto risco para OCS dos casos simulados. Os testes do qui-quadrado e exato de Fisher foram usados adicionalmente (p<0,05, SPSS v20.0). Resultados: Profissionais com expertise em diagnóstico oral tiveram usabilidade de 84,63±10,66 e aceitabilidade de 84,75±10,62, que se correlacionaram positivamente (p<0,001, r=0,647). Atuar em áreas clínicas da odontologia (p=0,034) e histórico de realização de CO orientação de fator de risco (p=0,048) aumentaram a aceitabilidade enquanto atuar no ensino superior aumentou a usabilidade (p=0,011). O ponto de corte sugerido pelo App após validação dos casos clínicos simulados apresentou alta sensibilidade de 84,8% e baixa especificidade de 58,4%. Conclusão: O OCS foi eficaz e com sensibilidade, usabilidade e aceitabilidade adequadas e pode contribuir para a detecção de lesões orais precoces.

Outcomes of Oral and Oropharyngeal Squamous Cell Carcinoma Related to Healthcare Coverage: A Retrospective Cohort Study in Brazil.

We investigated the differences in prognosis according to the type of healthcare coverage of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). This study included 875 medical records. Patients covered by the publicly funded Unified Health System (SUS) had a low educational level, with advanced T stage and delayed treatment initiation. Multivariate analyses revealed an association between T stage (p = .035) and poor prognosis in oral squamous cell carcinoma, and age (p = .029) in oropharyngeal squamous cell carcinoma. Surgical treatment (p = .036) and marital status (p = .015) were considered predictors of better prognosis in OOSCC. Exclusive SUS-dependency can be considered an indirect prognostic factor for OOSCC.

Prognostic factors and overall survival in a 15-year followup of patients with malignant salivary gland tumors: a retrospective analysis of 193 patients / Fatores prognósticos e sobrevida global em um seguimento de 15 anos de pacientes com tumores malignos da glândula salivar: uma análise retrospectiva de 193 pacientes

Abstract Introduction Malignant tumors of the salivary glands are uncommon pathological entities, representing less than 5% of head and neck neoplasms. The prognosis of patients with malignant tumors of the salivary glands is highly variable and certain clinical factors can significantly influence overall survival. Objective To analyze the clinicopathologic and sociodemographic characteristics that influence survival in patients with malignant tumors of the salivary glands Methods This retrospective study analyzed sex, age, race, education level, tumor location, tumor size, lymph node involvement, distant metastasis, margin status, treatment type, marital status, method of health care access and 15-year overall survival in 193 patients with malignant tumors of the salivary glands. The X², log-rank Mantel-Cox, multinomial regression and Cox logistic regression tests were used (SPSS 20.0,p < 0.05). Results The most common histological types were adenocarcinoma (32.1%), adenoid cystic carcinoma (31.1%) and mucoepidermoid carcinoma (18.7%). The 15-year overall survival rate was 67.4%, with a mean of 116 ± 6 months. The univariate analysis revealed that male sex (p = 0.026), age > 50 years (p = 0.001), referral origin from the public health system (p = 0.011), T stage (p = 0.007), M stage (p < 0.001), clinical stage (p < 0.001), compromised surgical margins (p = 0.013), and chemotherapy (p < 0.001) were associated with a poor prognosis. Multivariate analyses also showed that age > 50 years was independently associated with a poor prognosis (p = 0.016). The level of education was the only factor more prevalent in older patients (p = 0.011). Conclusion Patients with malignant tumors of the salivary glands older than 50 years have a worse prognosis and an independent association with a low education level.

Resumo Introdução Os tumores malignos das glândulas salivares são entidades patológicas incomuns, representam menos de 5% das neoplasias de cabeça e pescoço. O prognóstico dos pacientes com tumores malignos das glândulas salivares é altamente variável e alguns fatores clínicos podem influenciar significativamente a sobrevida global. Objetivo Analisar as características clinicopatológicas e sociodemográficas que influenciam a sobrevida em pacientes com tumores malignos das glândulas salivares. Método Este estudo retrospectivo analisou sexo, idade, etnia, nível de escolaridade, localização do tumor, tamanho do tumor, envolvimento linfonodal, metástase distante, margens, tipo de tratamento, estado civil, método de acesso à assistência médica e sobrevida global em 15 anos de 193 pacientes com tumores malignos das glândulas salivares. Foram usados os testes X2, log-rank Mantel-Cox, regressão multinomial e regressão logística de Cox (SPSS 20.0, p < 0,05). Resultados Os tipos histológicos mais comuns foram adenocarcinoma (32,1%), carcinoma adenoide cístico (31,1%) e carcinoma mucoepidermoide (18,7%). A taxa de sobrevida global em 15 anos foi de 67,4%, com média de 116 ± 6 meses. A análise univariada revelou que sexo masculino (p = 0,026), idade > 50 anos (p = 0,001), origem de referência do sistema público de saúde (p = 0,011), estádio T (p = 0,007), estádio M (p < 0,001)), estágio clínico (p < 0,001), margens cirúrgicas comprometidas (p = 0,013) e quimioterapia (p < 0,001) foram associados a um prognóstico ruim. As análises multivariadas também mostraram que a idade > 50 anos foi associada independentemente a um prognóstico ruim (p = 0,016). O nível de escolaridade foi o único fator mais prevalente em pacientes idosos (p = 0,011). Conclusão Pacientes com tumores malignos das glândulas salivares acima de 50 anos apresentam pior prognóstico e associação independente com baixo nível de escolaridade.

Photodynamic therapy and photobiomodulation therapy in zoledronic acid-induced osteonecrosis in rats.

BACKGROUND: This study investigated the effect of antimicrobial photodynamic therapy (PDT), using methylene blue (MBO) and photobiomodulation therapy (PT), on the alveolar bone of rats submitted to bisphosphonate-induced osteonecrosis of the maxillaries (OMB) model using zoledronic acid (ZA). METHODS: Sixty rats divided into six groups were used: SALINE, PDT, ZA, ZA+PDT, ZA+PT, and ZA+MBO. Three weekly administrations (Days 0, 7, and 14) of ZA 0.20 mg/kg or saline solution were performed. After one month (Day 42), the exodontia of the left lower first molars were performed. An additional dose of ZA was administered at Day 49. PDT was performed on days 42, 45, 49, and 54. One month after exodontia (Day 70), the animals were euthanized to obtain samples for imaging and microscopic analysis. ANOVA/Bonferroni tests were used for statistical analysis. RESULTS: The ZA+PDT group showed a significantly lower percentage of apoptotic osteocytes than the ZA group (p < 0.001). The ZA+MBO, ZA+PT, and PDT groups significantly reduced the number of mononuclear cells compared to the ZA group (p < 0.001). The ZA+PT and ZA+PDT groups showed a significant reduction in the number of CD 68+ (p < 0.001) and CD3+ (p = 0.002) cells compared to the ZA group. The number of cells expressing INF-y had a significant reduction in the groups co-treated with PT and PDT compared to the ZA group (p < 0.001). CONCLUSIONS: We conclude that PDT and PT attenuated the severity of OMB and the inflammatory process due to a reduction of macrophages, T lymphocytes, and cytokines that stimulate the activity of these cells.

Sociodemographic factors affect the quality of life and burden of caregivers in special care in dentistry.

AIMS: To analyze the epidemiological profile and quality of life (QoL) of patients with special needs and overload their caregivers. METHODS AND RESULTS: Health-related QoL was assessed in a quantitative, observational, cross-sectional study of prospective characteristics using the WHOQOL-BREF and ZARIT-22 questionnaires. This study included 122 patients were included; they were divided into patients without caregiver assistance (n = 63) who answered WHOQOL-BREF, 49 caregivers (n = 49) who responded to ZARIT-22, and 10 patients were secondarily caregivers of their parents and answered the ZARIT-22 + WHOQOL-BREF questionnaires. The WHOQOL-BREF general score was 71.94 ± 10.58, and patients born in urban areas and married had positive correlations (p < .05) with the QoL scores in the physical and social domains. ZARIT-22 scores showed an average of 58.63 ± 14.07. Data cross-checking revealed that patients of white races (p = .030) and who lived in urban regions (p = .003) generated less overload to caregivers. CONCLUSION: In the WHOQOL-BREF analysis, family income was a factor with direct impact, and all caregivers referred to moderate-to-high overload, with an increase in prevalence as far away from the service the patient resides.

Photobiomodulation Reduces Pain-Related Symptoms Without Interfering in the Efficacy of In-Office Tooth Bleaching: A Systematic Review and Meta-Analysis of Placebo-Controlled Clinical Trials.

Objective: This systematic review aimed to determine whether the use of photobiomodulation (PBM) with low-level laser therapy prevents tooth sensitivity induced by in-office tooth bleaching with hydrogen. Methods: Placebo-controlled clinical trials were included to evaluate the efficacy of PBM with low-level laser therapy in the prevention of tooth sensitivity after in-office tooth bleaching. Searches were conducted on the Medline database via PubMed, Scopus, Web of Science, EBSCO, SciELO, LILACS, Cochrane, DOSS, and Google Scholar until July 2020, and fixed-effects meta-analysis was performed for tooth sensitivity [standardized mean differences (MDs)] and color changes (MDs). Results: Five studies were included in this systematic review and meta-analysis, with a total of 288 patients, 123 patients in the PBM group and 165 patients in the placebo group. In the meta-analysis, despite high heterogeneity, PBM significantly reduced the tooth sensitivity after the first [p < 0.001; Cohen's d = -0.32, 95% confidence interval (CI) = -0.46 to -0.18], second (p < 0.001; Cohen's d = -0.30, 95% CI = -0.46 to -0.15), and third (p < 0.001; Cohen's d = -0.82, 95% CI = -1.06 to -0.58) sessions of in-office tooth bleaching, without impairing the ΔE (p = 0.300). Conclusions: The results of this systematic review and meta-analysis suggest that PBM significantly prevents pain-related symptoms after the first three weekly sessions of in-office tooth bleaching with hydrogen.

Prognostic factors and overall survival in a 15-year followup of patients with malignant salivary gland tumors: a retrospective analysis of 193 patients.

INTRODUCTION: Malignant tumors of the salivary glands are uncommon pathological entities, representing less than 5% of head and neck neoplasms. The prognosis of patients with malignant tumors of the salivary glands is highly variable and certain clinical factors can significantly influence overall survival. OBJECTIVE: To analyze the clinicopathologic and sociodemographic characteristics that influence survival in patients with malignant tumors of the salivary glands METHODS: This retrospective study analyzed sex, age, race, education level, tumor location, tumor size, lymph node involvement, distant metastasis, margin status, treatment type, marital status, method of health care access and 15-year overall survival in 193 patients with malignant tumors of the salivary glands. The X², log-rank Mantel-Cox, multinomial regression and Cox logistic regression tests were used (SPSS 20.0,p < 0.05). RESULTS: The most common histological types were adenocarcinoma (32.1%), adenoid cystic carcinoma (31.1%) and mucoepidermoid carcinoma (18.7%). The 15-year overall survival rate was 67.4%, with a mean of 116±6 months. The univariate analysis revealed that male sex (p = 0.026), age > 50 years (p=0.001), referral origin from the public health system (p=0.011), T stage (p= 0.007), M stage (p< 0.001), clinical stage (p< 0.001), compromised surgical margins (p= 0.013), and chemotherapy (p< 0.001) were associated with a poor prognosis. Multivariate analyses also showed that age > 50 years was independently associated with a poor prognosis (p= 0.016). The level of education was the only factor more prevalent in older patients (p= 0.011). CONCLUSION: Patients with malignant tumors of the salivary glands older than 50 years have a worse prognosis and an independent association with a low education level.

Distance education in dentistry in Brazil: a critical STROBE-based analysis.

The COVID-19 pandemic has forced dentistry schools (DSs) to adapt their teaching techniques to digital platforms. Therefore, we aimed to evaluate distance classes in the Brazilian DS curriculum. After an online search of higher education institutions (HEIs) with DS on the e-Ministry of Education (MEC) platform, we included institutions with at least one graduated class to extract the age/localization of the DS, funding, number of authorized seats, MEC-grade, ENADE-score, and workload. HEIs' webpages were consulted to identify the curriculum, subjects offered in the distance education (DE) format, extracurricular programs, scientific events, postgraduate programs, and institutional YouTube channels. Chi-square/Fisher's tests plus binary logistic regression were performed (SPSS 20.0, p < 0.05). Of the 241 DSs evaluated, 82 (34.0%) offered distance classes, and a high prevalence was observed in the southeast region (p <0.001) and private HEIs (p = 0.001). HEIs with distance classes had lower ENADE scores (p = 0.004), lower workload (p = 0.007), and higher workload for optional subjects (p = 0.016), doctoral programs (p = 0.041), specialization courses (p = 0.017), and institutional YouTube channels (p < 0.001). Southern dental schools (p < 0.001), lower workload (p = 0.022), optional subjects (p = 0.033), and institutional YouTube channels (p = 0.005) were independently associated with distance classes. In one-third of the Brazilian DSs, distance classes and institutional YouTube channels were strongly associated variables. The association of distance learning with lower workload and low academic performance draws attention to the need for regulatory bodies for controlling the quality of DE.

Prognostic factors on surgically and non-surgically treated oral squamous cell carcinoma: Advances in survival in fifteen years of follow up.

BACKGROUND: Retrospectively to evaluate the influence of radiochemotherapy (RCT) in the treatment of surgically and non-surgically treated Oral Squamous Cell Carcinoma (OSCC). MATERIAL AND METHODS: We analysed 934 patients treated in Hospital Haroldo Juaçaba (2000-2014; 15 years of study) by extraction of data type of cancer, localization of tumour, sex, age, race, education level, risk factors (smoking and alcohol use), year of diagnosis, TNM stage, therapeutic approach, health system used (public or private) and overall survival (OS). Surgically and non-surgically treated OSCC were compared by chi-square and Fisher's exact tests, and their prognostic factors were analysed by log-rank Mantel-Cox plus Cox regression tests (SPSS 20.0, p<0.05). RESULTS: Non-surgically treated OSCC patients had a lower OS than surgically treated OSCC patients (p<0.001), but an increase in OS was shown in both groups. Although the 2010-2014 period (p=0.003), education level (p=0.032), tongue/mouth floor/palate localization (p=0.023) and TNM stage (p<0.05) were important in non-surgically treated OSCC OS, the major prognostic factors were node metastasis (p=0.003) and non-use of RCT (p=0.039) (multivariate analysis). In surgically treated OSCC patients, higher OS was shown in the 2010-2014 period (p<0.001), females (p=0.012), non-drinkers (p=0.011), non-smokers (p=0.009) and those with lower TNM stage (p<0.05), but the major prognostic factor was the 2010-2014 period (p=0.004) (multivariate analysis), which was directly associated with an increase in RCT indication (p<0.001). CONCLUSIONS: The increase in RCT improved the OS in this large cohort of surgically and non-surgically treated OSCC patients. Key words:Mouth neoplasms, neck, radiotherapy, drug therapy, combination.

Analysis of the Immunoexpression of Opioid Receptors and their Correlation with Markers of Angiogenesis, Cell Proliferation and Apoptosis in Breast Cancer.

OBJECTIVE: Breast cancer is a disease of great concern. The prognosis of this tumor is related to its staging. Opioids are widely used to minimize pain in oncology clinics; however, the relationship between the administration of opioids and their effects on tumor cells has yet to be elucidated. Therefore, this study aimed to evaluate the immunoexpression of mu- (µ) and kappa- (κ) opioid receptors and their correlation with markers of angiogenesis, cell proliferation, and apoptosis in biopsies of breast tumors. METHODS: Demographic data, tumor characteristics, opioid use, and prognostic factors were collected from medical records. After the selection of the excisional biopsies, immunohistochemistry was performed for µ- and κ-opioid receptors, vascular endothelial growth factor (VEGF), Ki-67, and TUNEL. RESULTS: A significant predominance of Ki-67 and µ-opioid receptor immunoexpression in the lymph nodes was observed in patients administered opioid medications. The luminal A subtype showed higher apoptosis levels (TUNEL) compared to the luminal B subtype. Patients with T4 tumor who had recurrence demonstrated a reduced expression of κ-opioid receptors at the lymph node location. Correlation analyses between the µ and κ opioid markers, VEGF, Ki-67, and TUNEL showed that these findings are likely involved in the same mechanisms the cancer of T4 stage breast cancer. CONCLUSION: The κ-opioid receptor has a lower immunoexpression in nodal tumor metastasis with recurrence, whereas the µ-opioid receptor is directly related to expression of TUNEL-positive cells  in tumors and indirectly to Ki-67 in nodal metastasis. Neither of the two receptors was expressed in the primary tumor or nodal metastasis in relation to VEGF.

Mismatch Repair Proteins in Oropharyngeal Squamous Cell Carcinoma: A Retrospective Observational Study.

Cases of oropharyngeal squamous cell carcinoma are on the rise and the disease now ranks as the most common human papillomavirus-related cancer. Although risk factors have been extensively discussed in the literature, the role of the DNA mismatch repair system remains unanswered. To evaluate the impact of the DNA mismatch repair (MMR) protein immunostaining on the tumor progression and prognosis of oropharyngeal squamous cell carcinoma (OPSCC). This retrospective observational study comprised 50 cases of OPSCC. Immunohistochemistry for MSH2, MSH6, PMS2, MLH1, Ki67, p16 and caspase-3 was performed. The expression of these proteins was assessed in surgical resection margins, primary tumor (PT), and lymph node metastasis (LNM) of p16+ and p16- OPSCC. Clinical-pathological involvement in immunostaining was evaluated with Kruskal-Wallis/Dunn or Mann-Whitney test, Wilcoxon test and Spearman's correlation. Overall survival (OS) was analyzed with Log-Rank Mantel-Cox and Cox regression. MSH6 and caspase-3 showed high expression in PT (p16+ and p16 -) and in LNM (p16+ and p16-), and high levels of MSH2 were found in LNM (p16+ and p16 -). An imbalance in MutSα also was observed. PMS2 and caspase-3 expression was associated with poor survival in p16- OPSCC and, in multivariate analysis, MSH2, MSH6 and MLH1 had the poorest prognostic impact in p16+ OPSCC. MMR protein immunostaining is involved in OPSCC progression, dissemination and prognosis. The overexpression of MMR proteins as a response to increased DNA mismatch caused by cell proliferation and MSH2, MSH6 and MLH1 proteins might constitute a prognostic marker in p16+ OPSCC.

Distance education in dentistry in Brazil: a critical STROBE-based analysis

Abstract The COVID-19 pandemic has forced dentistry schools (DSs) to adapt their teaching techniques to digital platforms. Therefore, we aimed to evaluate distance classes in the Brazilian DS curriculum. After an online search of higher education institutions (HEIs) with DS on the e-Ministry of Education (MEC) platform, we included institutions with at least one graduated class to extract the age/localization of the DS, funding, number of authorized seats, MEC-grade, ENADE-score, and workload. HEIs' webpages were consulted to identify the curriculum, subjects offered in the distance education (DE) format, extracurricular programs, scientific events, postgraduate programs, and institutional YouTube channels. Chi-square/Fisher's tests plus binary logistic regression were performed (SPSS 20.0, p < 0.05). Of the 241 DSs evaluated, 82 (34.0%) offered distance classes, and a high prevalence was observed in the southeast region (p <0.001) and private HEIs (p = 0.001). HEIs with distance classes had lower ENADE scores (p = 0.004), lower workload (p = 0.007), and higher workload for optional subjects (p = 0.016), doctoral programs (p = 0.041), specialization courses (p = 0.017), and institutional YouTube channels (p < 0.001). Southern dental schools (p < 0.001), lower workload (p = 0.022), optional subjects (p = 0.033), and institutional YouTube channels (p = 0.005) were independently associated with distance classes. In one-third of the Brazilian DSs, distance classes and institutional YouTube channels were strongly associated variables. The association of distance learning with lower workload and low academic performance draws attention to the need for regulatory bodies for controlling the quality of DE.

Photobiomodulation and antimicrobial photodynamic therapy as adjunct in the treatment and prevention of osteoradionecrosis of the jaws: A case report.

CASE REPORT: We report on a patient with a history of radiotherapy to the head and neck region exhibiting necrotic bone exposure associated with fistula and purulent exudation in the mandible, with the diagnosis of stage 3 osteoradionecrosis, in addition to a periapical cyst in the maxillary anterior region and multiple root remnants. An antibiotic coverage protocol with amoxicillin and metronidazole was prescribed for subsequent necrotic bone removal. The surgical procedure was performed along with the aPDT using methylene blue and red light, followed by coaptation of the edges of the surgical wound and the healing protocol with LLLT. The extraction of non-rehabilitated teeth was performed two per session using antibiotic coverage, aPDT, and LLLT and mouthwash with 0.12 % chlorhexidine was prescribed until the complete closure of the surgical wound was achieved. Additionally, two aPDT sessions and four LLLT protocols were performed for complete healing of the surgical sites. Extra and intraoral examinations and panoramic and periapical radiographs were performed. No emergence or recurrence of osteonecrosis was observed after 12 months of follow-up.

Abatacept treatment impairs the cell migration and wound healing of oral ulcers in rats: Role of interleukin (IL)-1ß, -6 and -10 and CD8/CD30 cells: Influence of abatacept treatment on oral wound healing: Experimental model on rats.

The present study aimed to evaluate the healing process of ulcers in the jugal mucosa of Wistar rats treated with abatacept. The rats were randomly assigned to four groups: saline-treated control (0.3 mL/kg) abatacept-treated groups at dosages of 3.2, 8.0 and 20.0 mg/kg/week. After two weeks of subcutaneous (SC) administration, ulcers were introduced into the left jugal mucosa with an 8-mm diameter punch. SC administration was continued until euthanasia (after 1, 3, 7, 14 and 21 days of ulceration), and ulcers were clinically measured and animals weighed. Histological slides were evaluated (healing scores and polymorphonuclear, mononuclear, vessel, and fibroblast/myofibroblast counts). We also performed collagenesis analysis (Picrosirius Red) and immunohistochemistry (induced nitric oxide synthase (iNOS), interleukin (IL)-1beta (1ß), -6, -10, plus the analysis of CD8 and CD30). The experiment was repeated to perform a vascular permeability assay. ANOVA 1-way or 2-way/Bonferroni and Kruskal-Wallis/Dunn tests were used for statistical analysis (GraphPad Prism 5.0®, p < 0.05). Abatacept treatment reduced the ulcer diameter and the numbers of polymorphonuclear and mononuclear cells; reduced the CD8+/CD30+ ratio and vascular permeability; and increased collagenesis and IL-10 expression at the beginning of the protocol. At the highest dose, there was a delay in repair and vascular proliferation; a reduction in the number of fibroblasts/myofibroblasts; and prolongation of iNOS, IL- and IL- expression. We conclude that abatacept accelerates the healing of oral ulcers by reducing the migration of inflammatory cells, but overdose of abatacept leads to delayed repair and prolongation of proinflammatory cytokine expression.