Social networking website increases efficacy and engagement in a distance learning course about oral lesions.

PURPOSE: Distance learning appears to be an attractive approach to continuing education courses, but one barrier is maintaining learner engagement throughout the course. The primary aim of this research was to evaluate the operational efficacy of a private Facebook™ group (FG) in serving as a support mechanism for distance learning courses, and its impact on three fundamental dimensions: the attrition rates of participants who did not complete the course (commonly referred to as dropout rates), the rates of course completion and approval, and the overall performance of the participants. METHODS: The participants of this quasi-experimental study comprised 159 dental students and 565 dentists enrolled in an e-learning course on oral mucosal lesion diagnosis. Prior to the initiation of the course, all participants were provided with the option to join a private FG. Within this group, moderators shared motivational messages and provided reminders concerning deadlines. Moreover, participants had the opportunity to engage in interactive discussions pertaining to topics related to the course. The course itself followed a self-guided format, employing the flipped-classroom methodology, spanning a total of 50 instructional hours. In order to assess the effectiveness of the course, participants were presented with photographs illustrating 30 oral lesions and were asked to propose diagnostic hypotheses both before and after the educational intervention (pre-tests and post-tests). RESULTS: Dentists who participated in the FG exhibited a significantly lower rate of discontinuation. As for dental students, their involvement in the group was positively associated with better performance, as determined by the percentage of accurate diagnostic hypotheses (a minimum of 70% correct responses was required for their approval in the course). CONCLUSIONS: Facebook™ demonstrates promise as a supplementary pedagogical tool in distance education courses. The interactive nature of the platform has the potential to alleviate the inherent challenges of remote learning.

Propolis: A useful agent on psychiatric and neurological disorders? A focus on CAPE and pinocembrin components.

Propolis consists of a honeybee product, with a complex mix of substances that have been widely used in traditional medicine. Among several compounds present in propolis, caffeic acid phenethyl ester (CAPE), and pinocembrin emerge as two principal bioactive compounds, with benefits in a variety of body systems. In addition to its well-explored pharmacological properties, neuropharmacological activities have been poorly discussed. In an unprecedented way, the present review addresses the current finding on the promising therapeutic purposes of propolis, focusing on CAPE and pinocembrin, highlighting its use on neurological disturbance, as cerebral ischemia, neuroinflammation, convulsion, and cognitive impairment, as well as psychiatric disorders, such as anxiety and depression. In addition, we provide a critical analysis, discussion, and systematization of the molecular mechanisms which underlie these central nervous system effects. We hypothesize that the pleiotropic action of CAPE and pinocembrin, per se or associated with other substances present in propolis may result in the therapeutic activities reported. Inhibition of the pro-inflammatory cascade, antioxidant activity, and positive neurotrophic modulatory effects consist of the main molecular targets attributed to CAPE and pinocembrin in health benefits.

Photobiomodulation therapy drives massive epigenetic histone modifications, stem cells mobilization and accelerated epithelial healing.

Emerging evidence indicates the clinical benefits of photobiomodulation therapy (PBMT) in the management of skin and mucosal wounds. Here, we decided to explore the effects of different regiments of PBMT on epithelial cells and stem cells, and the potential implications over the epigenetic circuitry during healing. Scratch-wound migration, immunofluorescence (anti-acetyl-Histone H3, anti-acetyl-CBP/p300 and anti-BMI1), nuclear morphometry and western blotting (anti-Phospho-S6, anti-methyl-CpG binding domain protein 2 [MBD2]) were performed. Epithelial stem cells were identified by the aldehyde dehydrogenase enzymatic levels and sphere-forming assay. We observed that PBMT-induced accelerated epithelial migration and chromatin relaxation along with increased levels of histones acetylation, the transcription cofactors CBP/p300 and mammalian target of rapamycin. We further observed a reduction of the transcription repression-associated protein MBD2 and a reduced number of epithelial stem cells and spheres. In this study, we showed that PBMT could induce epigenetic modifications of epithelial cells and control stem cell fate, leading to an accelerated healing phenotype.

Continuing education activities improve dentists' self-efficacy to manage oral mucosal lesions and oral cancer.

OBJECTIVES: This cross-sectional study aims to evaluate whether Continuing Education Activities (CEA) influence dentists' behaviour in relation to oral lesions. The secondary aim is to assess the association between dentists' perception of learning adequacy and self-efficacy for oral mucosal lesion management. METHODS: A self-administered online questionnaire was conducted on dentists working at the public health system of Rio Grande do Sul State, Brazil. The questionnaire included questions pertaining to perception of adequacy for oral diagnosis classes upon graduation, participation in oral cancer CEA and self-efficacy in managing oral mucosal lesions. RESULTS: 221 dentists from 91 municipalities answered the questionnaire. Most participants were female (71.5%) with a mean age of 38.3 years. Perception of learning as adequate during undergraduate coursework was associated with self-efficacy to diagnose, biopsy, and treat oral mucosal lesions (P < .05, Chi-squared test). However, 83.3% of dentists considered the time devoted to these topics prior to graduation insufficient. The frequency of oral lesion detection was related to self-efficacy to treat oral lesions and detecting oral cancer (P < .05, Chi-squared test). Among dentists who detected oral lesions frequently, 88.9% had attended CEA, whereas 11.1% of them had never attended these activities. CONCLUSIONS: CEA may improve awareness and efficacy of primary healthcare professional's detection of oral cancer.

TrkB-Targeted Therapy for Mucoepidermoid Carcinoma.

The brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase B (TrkB) pathway was previously associated with key oncogenic outcomes in a number of adenocarcinomas. The aim of our study was to determine the role of this pathway in mucoepidermoid carcinoma (MEC). Three MEC cell lines (UM-HMC-2, H253 and H292) were exposed to Cisplatin, the TrkB inhibitor, ANA-12 and a combination of these drugs. Ultrastructural changes were assessed through transmission electron microscopy; scratch and Transwell assays were used to assess migration and invasion; and a clonogenic assay and spheroid-forming assay allowed assessment of survival and percentage of cancer stem cells (CSC). Changes in cell ultrastructure demonstrated Cisplatin cytotoxicity, while the effects of ANA-12 were less pronounced. Both drugs, used individually and in combination, delayed MEC cell migration, invasion and survival. ANA-12 significantly reduced the number of CSC, but the Cisplatin effect was greater, almost eliminating this cell population in all MEC cell lines. Interestingly, the spheroid forming capacity recovered, following the combination therapy, as compared to Cisplatin alone. Our studies allowed us to conclude that the TrkB inhibition, efficiently impaired MEC cell migration, invasion and survival in vitro, however, the decrease in CSC number, following the combined treatment of ANA-12 and Cisplatin, was less than that seen with Cisplatin alone; this represents a limiting factor.

Head and neck cancer patient-derived xenograft models - A systematic review.

BACKGROUND: Patient-derived xenograft (PDX) involve the direct surgical transfer of fresh human tumor samples to immunodeficient mice. This systematic review aimed to identify publications of head and neck cancer PDX (HNC-PDX) models, describing the main methodological characteristics and outcomes. METHODS: An electronic search was undertaken in four databases, including publications having used HNC-PDX. Data were analyzed descriptively. RESULTS: 63 articles were yielded. The nude mouse was one most commonly animal model used (38.8 %), and squamous cell carcinoma accounted for the majority of HNC-PDX (80.6 %). Tumors were mostly implanted in the flank (86.3 %), and the latency period ranged from 30 to 401 days. The successful rate ranged from 17 % to 100 %. Different drugs and pathways were identified. CONCLUSION: HNC-PDX appears to significantly recapitulate the morphology of the original HNC and represents a valuable method in translational research for the assessment of the in vivo effect of novel therapies for HNC.

Photobiomodulation therapy improves human dental pulp stem cell viability and migration in vitro associated to upregulation of histone acetylation.

This in vitro study evaluated the role of photobiomodulation therapy (PBMT) on viability and migration of human dental pulp stem cells (hDPSCs) and its association to epigenetic mechanisms such as histone acetylation. The hDPSCs were characterized and assigned into control and PBMT groups. For the PBMT, five laser irradiations at 6-h intervals were performed using a continuous-wave InGaAlP diode laser. Viability (MTT), migration (scratch), and histone acetylation H3 (H3K9ac immunofluorescence) were evaluated immediately after the last irradiation. PBMT significantly increased the viability (P = 0.004). Also, PBMT group showed significantly increased migration of cells in the wound compared to the control in 6 h (P = 0.002), 12 h (P = 0.014) and 18 h (P = 0.083) being faster than the control, which only finished the process at 24 h. PBMT induced epigenetic modifications in hDPSC due to increased histone acetylation (P = 0.001). PBMT increased viability and migration of hDPSCs, which are related with the upregulation of histone acetylation and could be considered a promising adjuvant therapy for regenerative endodontic treatment.

Prognostic value of CRTC1-MAML2 translocation in salivary mucoepidermoid carcinoma: Systematic review and meta-analysis.

The presence of the CRTC1-MAML2 translocation has been described in mucoepidermoid carcinoma (MEC) as a predictor of better survival rates. However, the real prognostic value of the translocation has been debated due to recent controversial findings. The aim of this study was to perform a systematic review to understand the prognostic potential of the CRTC1-MAML2 translocation in MEC. An electronic search was carried out using the MEDLINE/PubMed, EMBASE and Scopus databases. Articles that assessed the association between the CRTC1-MAML2 translocation and survival of MEC patients were selected for the systematic review. Ten published articles were included in the qualitative synthesis. The prevalence of the translocation varied from 33.7% to 69.7%. Seven studies observed a significant association between the presence of the CRTC1-MAML2 translocation and a favourable clinical outcome, which could improve disease-free, disease-specific or overall survival. Five studies were included in the quantitative synthesis. Fixed-effects model confirmed that translocation-positive patients have a decreased risk of death (combined odds ratio 0.08, 95% confidence interval - 0.03-0.23, P < .00001). The detection of the CRTC1-MAML2 translocation appears to be useful as a prognostic factor in MEC. However, the level of evidence is not as high as it could be once important limitations were found in the published studies.

Interference with the bromodomain epigenome readers drives p21 expression and tumor senescence.

Head and neck cancer (HNSCC) are one of the most common solid malignancies of the world, being responsible for over 350,000 deaths every year. Much of the complications in managing and treating HNSCC advent from the complex genetic and epigenetic landscape of the disease. Emerging information has shown promising results in targeting BRD4, an epigenetic regulator bromodomain that functions as a scaffold for transcription factors at promoters and super-enhancers. Here we show that by disrupting the interaction between BRD4 and histones using the bromodomain inhibitor JQ1, HNSCC cells undergo cell growth arrest followed by cellular senescence. Mechanistically, JQ1 negatively impacted the phosphorylation levels of SIRT1 along with the acetylation levels of mutant p53 (active). In vivo administration of JQ1 resulted in disruption of HNSCC growth along with the activation of cellular senescence, observed by the accumulation of DNA double-strand breaks, p16ink4, accumulation of senescence-associated beta-galactosidase, and loss of phosphorylated Sirt1ser47. Furthermore, we also demonstrate that JQ1 was efficient in reducing the population of cancer stem cells from HNSCC xenografts.

Matrix stiffness mechanically conditions EMT and migratory behavior of oral squamous cell carcinoma.

Tumors are composed of heterogeneous phenotypes, each having different sensitivities to the microenvironment. One microenvironment characteristic - matrix stiffness - helps to regulate malignant transformation and invasion in mammary tumors, but its influence on oral squamous cell carcinoma (OSCC) is unclear. We observed that, on stiff matrices, a highly invasive OSCC cell line (SCC25) comprising a low E-cad to N-cad ratio (InvH/E:NL; SCC25) had increased migration velocity and decreased adhesion strength compared to a less invasive OSCC cell line (Cal27) with high E-cad to N-cad ratio (InvL/E:NH; Cal27). However, InvL/E:NH cells acquire a mesenchymal signature and begin to migrate faster when exposed to prolonged time on a stiff niche, suggesting that cells can be mechanically conditioned. Owing to increased focal adhesion assembly, InvL/E:NH cells migrated faster, which could be reduced when increasing integrin affinity with high divalent cation concentrations. Mirroring these data in human patients, we observed that collagen organization, an indicator of matrix stiffness, was increased with advanced disease and correlated with early recurrence. Consistent with epithelial tumors, our data suggest that OSCC cells are mechanically sensitive and that their contribution to tumor progression is mediated in part by this sensitivity.This article has an associated First Person interview with the first author of the paper.

A multicentre study of 268 cases of calcifying odontogenic cysts and a literature review.

OBJECTIVES: To investigate the frequency of calcifying odontogenic cysts (COCs) that have been submitted for microscopic examination from representative geographic regions of Brazil and to compare it with literature data. MATERIALS AND METHODS: A retrospective study was conducted on biopsies obtained from 1953 to 2016 at 10 Brazilian oral and maxillofacial pathology centres. A total of 198,350 biopsy specimens were analysed. Demographic data and histopathological diagnosis were evaluated descriptively and statistically. In addition, a literature review of case series was carried out in four electronic databases. RESULTS: A total of 268 cases of COC were surveyed, representing 0.1% of the oral lesions at the centres studied. Female patients in their second decade of life and the maxilla were more affected. The mean lesion size of symptomatic individuals was larger than that of cases without symptoms (p = 0.026). The literature review showed a higher frequency in Asia and Europe, mainly affecting men in the third decade of life. CONCLUSIONS: COC is a rare lesion. Novel data on the clinicopathological features of 268 cases have been added to the literature. Data regarding gender and age of the Brazilian patients reported herein contrast with findings of case series and retrospective studies reported elsewhere.

New photobiomodulation protocol prevents oral mucositis in hematopoietic stem cell transplantation recipients-a retrospective study.

Oral mucositis (OM) is an adverse side effect among hematopoietic stem cell transplantation (HSCT) recipients. The objective of this retrospective study was to evaluate the preventive effect of photobiomodulation (PBM) applied three times per week versus seven times per week in patients undergoing HSCT. The risk factors related to the incidence and severity of OM were also assessed. This was a retrospective study that evaluated 99 HSCT recipients who received different PBM protocols. Group I received three sessions per week, and group II received daily treatment. PBM was applied using a continuous-wave diode laser (InGaAlP; MM Optics, São Carlos, SP, Brazil) at a wavelength of 660 nm (visible-red) and a total radiant energy of 0.24 J per point. The baseline disease, type of transplant, type of conditioning, prophylaxis against graft-versus-host disease, OM grade, absolute leukocyte and platelet counts, and levels of liver and renal function markers were collected from medical records. The patients' age ranged from 13 to 71 years (mean/SD, 40.54 ± 16.45). No significant difference was observed between groups I and II regarding sex, age, ethnic, diagnosis, donor type, and conditioning treatment. Both PBM protocols were equally efficient in preventing OM (p = 0.34, ANOVA). Independent of the PBM protocol used, patients who received allogeneic transplant (p < 0.01-Fischer's exact test), total body irradiation (TBI-12Gy) (p = 0.01-chi-square test), busulfan + cyclophosphamide (p < 0.01-chi-square test), or methotrexate-containing regimens (p < 0.01-Fischer's exact test) demonstrated higher OM incidence and severity. Myelosuppression (p < 0.01-Mann-Whitney test) and impaired renal function (p = 0.02-Mann-Whitney test) were also considered risk factors for OM. Based on this retrospective data, PBM was effective in preventing OM in patients undergoing HSCT even when it was applied three times a week. A prospective study might be necessary to confirm these findings.

Hypoacetylation of acetyl-histone H3 (H3K9ac) as marker of poor prognosis in oral cancer.

AIMS: Epigenetics refers to changes in cell characteristics that occur independently of modifications to the DNA sequence. Oral carcinogenesis is influenced by modifications in epigenetic mechanisms, including changes in histones, which are proteins that support chromatin remodelling for the dynamic regulation of gene expression and silencing. The dysregulation of histone acetylation can lead to the uncontrolled activity of different genes, thereby triggering events associated with malignant transformation. The aim of this study was to analyse the expression of acetyl-histone H3 at lys9 (H3K9ac) in oral leucoplakia (OL) and oral squamous cell carcinoma (OSCC) in addition to its association with cell proliferation, epithelial-mesenchymal transition (EMT) and clinical-pathological findings. METHODS AND RESULTS: Samples of normal oral mucosa (NOM), OL and OSCC were submitted to immunohistochemical analysis using anti-H3K9ac, Ki67 and vimentin. Slides were submitted to quantitative analysis regarding the percentage of positive cells. OSCC presented less expression of H3K9ac in comparison to OL (P < 0.01), whereas Ki67 and vimentin levels increased from OL to OSCC (P < 0.001 and P = 0.03, respectively). OSCC patients with poor prognosis had less H3K9ac expression (P = 0.04). The Kaplan-Meier cumulative survival curves also revealed lower survival rates in patients with less H3K9ac expression (P < 0.01). CONCLUSIONS: The present findings suggest that changes in H3K9ac occur during the process of oral carcinogenesis along with an increase in cell proliferation and EMT. The results demonstrate that H3K9ac may be a useful novel prognostic marker for OSCC.

Teledentistry: A Tool to Promote Continuing Education Actions on Oral Medicine for Primary Healthcare Professionals.

BACKGROUND: Difficulties in diagnosis of oral mucosal lesions are a significant cause of delayed oral cancer diagnosis, and this difficulty may be due to gaps in knowledge. This study evaluated the diagnostic skills of primary healthcare professionals regarding oral cancer and presented them with an e-learning course. MATERIALS AND METHODS: Forty-seven primary healthcare professionals (32 dentists and 15 nondentists) enrolled in a 24-h course on oral medicine delivered through an e-learning platform. A test, based on 33 clinical images of oral lesions, was used to evaluate the diagnostic skills of participants. The participants were requested to classify each lesion as benign, potentially malignant, or malignant as well as to inform their clinical impression. Three specialists also took the test as the gold standard. RESULTS: Twenty-seven participants completed the test. Nondentists and dentists showed a comparable sensitivity of 68.8 ± 11.1 and 63.7 ± 15.8, respectively. Specialists performed somewhat better; however, the difference was not statistically significant (81.0% ± 4.1%, p = 0.16). Dentists and specialists (70.0% ± 16.6% and 95.5% ± 3.1%, respectively) showed higher specificity than nondentists (39.3 ± 20.6, p < 0.01). Nondentists had a higher number of unanswered questions (p < 0.01) for classification and clinical impression (50.0% ±45.1% and 72.0% ± 25.0%, respectively) than dentists (5.7% ±11.9% and 19.8% ± 20%, respectively). Both dentists and nondentists had low attendance in the course (44.57% ± 37.38% and 26.53% ± 26.53%, respectively, p = 0.26). To the best of our knowledge, this is the first study to assess the diagnostic skills of public health workers belonging to different professional categories. CONCLUSION: Both dentists and nondentists have a fairly good capacity for discriminating the nature of oral lesions. Early squamous cell carcinoma is the most challenging situation and remains an issue to be addressed.

Immunohistochemical Study of TGF-ß1 in Oral Leukoplakia and Oral Squamous Cell Carcinoma: Correlations Between Clinicopathologic Factors and Overall Survival.

The aim of the present study was to analyze transforming growth factor ß1 (TGF-ß1) expression in cases of leukoplakia and oral squamous cell carcinoma (OSCC) and to correlate these expression profiles with proliferative labeling index, clinicopathologic factors, and clinical outcome. Clinical data for 24 cases of leukoplakia and 87 cases of OSCC were retrieved from medical records. OSCC tissues were included into tissue microarray blocks and sections of normal mucosa, leukoplakia, and OSCC tissue microarray's were prepared on slides. Immunohistochemistry was used to detect expression of TGF-ß1 and Ki67. The expression of TGF-ß1 and Ki67 were significantly increased from normal mucosa, through leukoplakia to OSCC. High expression of TGF-ß1 correlated with an increase in proliferative labeling index. No association between TGF-ß1 expression and the clinicopathologic factors examined was observed. Expression of TGF-ß1 also did not associate with clinical outcome in either of groups. Our results suggest that changes in TGF-ß1 are associated with the progression of oral carcinogenesis.

Semaphorins and neuropilins expression in salivary gland tumors.

BACKGROUND: Salivary gland tumors (SGT) account for 3-10% of all head and neck neoplasms, and little is known about their angiogenic properties. Despite semaphorins and neuropilins have been demonstrated to be prognostic determinants in many human cancers, they remain to be investigated in SGT. Therefore, the objective of this study was to analyze the clinical significance of the expression of class 3 semaphorins A (Sema3A) and B (Sema3B) and neuropilins-1 (Np-1) and neuropilins-2 (Np-2), in SGT. METHODS: Two hundred and forty-eight SGT were organized in tissue microarray paraffin blocks and expression of CD34, Sema3A, Sema3B, Np-1, and Np-2 was determined through immunohistochemistry. The immunoreactions were quantified using digital algorithms and the results correlated with clinicopathological parameters. RESULTS: Malignant tumors had an increased vascular density than their benign counterparts and their increased vascular area significantly correlated with recurrences (P < 0.05). Patients older than 40 years and the presence of recurrences determined an inferior survival rate (P = 0.0057 and P = 0.0303, respectively). In normal salivary glands, Np-1 and Np-2 expression was restricted to ductal cells, whereas Sema3A and Sema3B were positive in the serous acinar compartment. Tumors were positive for all markers and the co-expression of Np-1/Np-2 significantly correlated with the presence of paresthesia and advanced stages of the tumors (P = 0.01 and P = 0.04, respectively). CONCLUSION: Sema3A, Sema3B, Np-1, and Np-2 may be involved in the pathogenesis of SGT, but their expression did not present a statistically significant prognostic potential in this study.

Gingival Cysts of Adults: Retrospective Analysis from Two Centers in South Brazil and a Review of the Literature.

Gingival cysts of adults are rare developmental cysts, with an incidence of 0.3% among all odontogenic cysts. They are benign, well-defined nodules located on the attached gingiva with a fluid-filled appearance. The aim of the present study was to perform an analysis of gingival cysts in adults diagnosed at an oral pathology laboratory and a hospital pathology service in order to determine the frequency of occurrence of this lesion, and to perform a literature review to correlate the present findings with those described in the literature. This study emphasizes the low frequency of gingival cysts in adults and the importance of gathering clinical, radiographic and histopathological information to define the final diagnosis.