HOXA1 3'UTR Methylation Is a Potential Prognostic Biomarker in Oral Squamous cell Carcinoma.

BACKGROUND: HOXA1 is a prognostic marker and a potential predictive biomarker for radioresistance in head and neck tumors. Its overexpression has been associated with promoter methylation and a worse prognosis in oral squamous cell carcinoma (OSCC) patients. However, opposite outcomes are also described. The effect of the methylation of this gene on different gene regions, other than the promoter, remains uncertain. We investigated the methylation profile at different genomic regions of HOXA1 in OSCC and correlated differentially methylated CpG sites with clinicopathological data. METHODS: The HOXA1 DNA methylation status was evaluated by analyzing data from The Cancer Genome Atlas and three Gene Expression Omnibus datasets. Significant differentially methylated CpG sites were considered with a |∆ß| ≥ 0.10 and a Bonferroni-corrected p-value < 0.01. Differentially methylated CpGs were validated by pyrosequencing using two independent cohorts of 15 and 47 OSCC patients, respectively. RESULTS: Compared to normal tissues, we found significantly higher DNA methylation levels in the 3'UTR region of HOXA1 in OSCC. Higher methylation levels in tumor samples were positively correlated with smoking habits and patients' overall survival. CONCLUSIONS: Our findings suggest that HOXA1 gene body methylation is a promising prognostic biomarker for OSCC with potential clinical applications in patient monitoring.

Convolutional neural network misclassification analysis in oral lesions: an error evaluation criterion by image characteristics.

OBJECTIVE: This retrospective study analyzed the errors generated by a convolutional neural network (CNN) when performing automated classification of oral lesions according to their clinical characteristics, seeking to identify patterns in systemic errors in the intermediate layers of the CNN. STUDY DESIGN: A cross-sectional analysis nested in a previous trial in which automated classification by a CNN model of elementary lesions from clinical images of oral lesions was performed. The resulting CNN classification errors formed the dataset for this study. A total of 116 real outputs were identified that diverged from the estimated outputs, representing 7.6% of the total images analyzed by the CNN. RESULTS: The discrepancies between the real and estimated outputs were associated with problems relating to image sharpness, resolution, and focus; human errors; and the impact of data augmentation. CONCLUSIONS: From qualitative analysis of errors in the process of automated classification of clinical images, it was possible to confirm the impact of image quality, as well as identify the strong impact of the data augmentation process. Knowledge of the factors that models evaluate to make decisions can increase confidence in the high classification potential of CNNs.

Knowledge of Brazilian dentists about bisphosphonate-associated osteonecrosis of the jaw / Conhecimento de dentistas brasileiros sobre a osteonecrose dos maxilares associada ao uso de bisfosfonatos

Osteonecrosis of the jaw associated with bisphosphonate use is a matter of utmost importance in clinical practice for the safe treatment of patients using this medication. Objective: The aim of this study was to evaluate the level of knowledge of dentists who carry out clinical practice about bisphosphonate-associated jaw osteonecrosis. Material and Methods: The methodology used in the present research consisted of a non-probability sampling approach for the selection of participants. To conduct the study, a questionnaire created on the Google Forms platform was sent via Direct on Instagram to the professionals who agreed to participate. The data were sent for analysis, using the frequency for each response, and the professionals were divided into subcategories according to their time of professional practice. Results: Participants were familiar with the purpose of the medication (65%) or had heard of it (34%); regarding the professionals' opinion on their knowledge and practice about bisphosphonate-related osteonecrosis a significant percentage (93.24%) responded positively regarding the existence of side effects resulting from the therapeutic use of bisphosphonates and 48.65% self-evaluated their level of knowledge on the subject as insufficient. Conclusion: The study reveals that almost all participating dentists have good knowledge about the effects caused by bisphosphonates, but some of them still do not feel specifically confident about the management and knowledge of jaw osteonecrosis (AU)

A osteonecrose dos maxilares associada ao uso de bisfosfonatos é um assunto de suma importância na prática clínica para o atendimento seguro dos pacientes que fazem uso terapêutico do medicamento. Objetivo: O objetivo deste trabalho foi avaliar o nível de conhecimento de cirurgiões dentistas que realizam atendimento clínico acerca da osteonecrose dos maxilares associada ao uso dos bisfosfonatos. Material e Métodos: A metodologia utilizada na presente pesquisa consistiu em uma abordagem de amostragem não probabilística para a seleção dos participantes. Para conduzir o estudo, enviamos um questionário criado na plataforma Google Forms via Direct no Instagram para os profissionais que concordaram em participar. Os dados foram enviados para análise, usando a frequência para cada resposta, sendo que os profissionais foram divididos em subcategorias por tempo de formação. Resultados: Os participantes estavam familiarizados com a finalidade do medicamento (65%) ou já haviam ouvido falar deles (34%); em relação à opinião dos profissionais sobre seu conhecimento e prática acerca da osteonecrose relacionada aos bisfosfonatos, observou-se que 48,65% autoavaliaram seu nível de conhecimento sobre o assunto como insuficiente e uma parcela expressiva (93,24%) respondeu positivamente em relação à existência de efeitos colaterais decorrentes ao uso terapêutico dos bisfosfonatos. Conclusão: O estudo revela que quase todos os dentistas participantes possuem um bom conhecimento acerca dos efeitos causados pelos bisfosfonatos, mas que parte deles ainda não se sentem seguros especificamente em relação ao manejo e conhecimento da osteonecrose dos maxilares (AU)

Evaluation of remote teaching in master programs in the Oral Pathology and Oral Medicine during the COVID-19 pandemic. Brazilian multicentric study

Background: With the COVID-19 pandemic, there was a need to adopt online teaching methods in a generalized and sudden way, a situation that led to unprecedented changes in the routine of post-graduate students and research development. This study aimed to analyze the evaluation of remote teaching by graduates of master's degrees and advisors in master's programs in the Oral Pathology and Oral Medicine who needed to adapt to a remote teaching methodology in the pandemic. Material and Methods: This quantitative study evaluated the remote teaching in the perception of master's graduates and advisors from postgraduate programs in Oral Pathology and Oral Medicine. Data were collected through an online Google forms® questionnaire. Results: Participated in the study 14 master graduates and 14 master's advisors. Master graduates evaluated that the professors had a good performance (p=0.001), that the duration of the classes was adequate (p=0.015), that the interaction with professors was satisfactory (p=0.007), that they had good interaction with the advisor (p=0.001), that they were satisfied with the remote guidance process (p=0.038) and that face-to-face practical activities were missed (p=0.002). Master's advisors reported satisfaction with remote teaching, good adaptation (p=0.018) and motivation for remote teaching (p=0.016), they evaluated that students were cooperative in activities (p=0.019) and that face-to-face practical activities were missed (p=0.002). Conclusions: Despite the difficulties, remote teaching proved to be an effective alternative to face-to-face teaching. (AU)

Preliminary Findings on the Salivary Metabolome of Hookah and Cigarette Smokers.

The aim of the study was to evaluate the salivary metabolomic profile of patients who habitually smoke hookah and cigarettes. The groups consisted of 33 regular and exclusive hookah smokers, 26 regular and exclusive cigarette smokers, and 30 nonsmokers. Unstimulated whole saliva was collected for the measurement of salivary metabolites by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). The MetaboAnalyst software was used for statistical analysis and evaluation of biomarkers. 11 smoking salivary biomarkers were identified using the area under receiving-operator curver criterion and threshold of 0.9. Xylitol and octadecanol were higher in cigarette smokers compared to controls; arabitol and maltose were higher in controls compared to cigarette smokers; octadecanol and tyramine were higher in hookah smokers compared to controls; phenylalanine was higher in controls compared to hookah smokers; and fructose, isocitric acid, glucuronic acid, tryptamine, maltose, tyramine, and 3-hydroxyisolvaleric acid were higher in hookah smokers compared to cigarettes smokers. Conclusions: The evaluation of the salivary metabolome of hookah smokers, showing separation between the groups, especially between the control versus hookah groups and cigarette versus hookah groups, and it seems to demonstrate that the use of hookah tobacco is more damaging to health.

Hidden colon adenocarcinoma diagnosed from mouth metastasis: case report and literature review.

BACKGROUND: We report an unusual case of metastatic colon adenocarcinoma to the maxilla as an initial clinical sign of the disease, this being the second case reported in the palate. In addition, we show an extensive review of the literature, with clinical cases of adenocarcinoma with metastasis to the mouth. CASE PRESENTATION: An 80-year-old man complained of "swelling on the palate" with a 3-week evolution time. He reported suffering from constipation and high blood pressure. The intraoral examination revealed a pedunculated, red, and painless nodule on the maxillary gingiva. Under the diagnostic hypotheses of squamous cell carcinoma and malignant neoplasm of the salivary gland, an incisional biopsy was performed. Microscopically, the columnar epithelium was observed forming papillary areas, neoplastic cells with prominent nucleoli, hyperchromatic nuclei, atypical mitotic figures, and mucous cells, being positive for CK 20, suggesting the provisional diagnosis of metastatic adenocarcinoma, probably of gastrointestinal origin. The patient was submitted to endoscopy and colonoscopy exams, and a lesion in the sigmoid region of the colon was observed. After a colon biopsy, a moderately differentiated adenocarcinoma was confirmed, establishing the final diagnosis of metastatic neoplasia of colon adenocarcinoma to the oral lesion. The literature review revealed 45 clinical cases of colon adenocarcinoma with metastasis to the oral cavity. To the best of our knowledge, it is the second case on the palate. CONCLUSIONS: Colon adenocarcinoma with metastasis to the oral cavity is rare but should be included in the differential diagnosis of neoplasms of the oral cavity, even when there are no known primary tumors in some cases, and this may be the first indication of the presence of a tumor.

The Effect of Nicotine Lozenge Over Teeth Bleaching During Cigarette's Addiction Treatment

The aim of this study was to evaluate the effect of nicotine lozenge on teeth staining with/without bleaching in animal model study. A total of 15 Wistar rats were exposed in an acrylic container to 10 cigarettes smoke three times a day for 8 minutes per time, and sacrificed after 60 days. A total of 30 incisor teeth were treated (n=10) as the following: Group-1: in-office bleaching, at-home bleaching and immersion in artificial saliva; group-2: in-office bleaching, at - home bleaching and immersion in nicotine lozenge solution and in artificial saliva; group-3: immersion in nicotine lozenge solution and in artificial. The specimens of all groups were photographed using a stereomicroscope at T1) immediately after the extraction and before any treatment; T2) after one month of the treatment; and T3) after two months of the treatment. Four equidistant points of each specimen were analyzed using CMYK shade guide. The data were analyzed one-way ANOVA test followed by Tukey test for multiple comparisons with (a ≤ 0.05). In group-1, there was a significant difference of the color saturation of specimens between T1 and T2, and between T1 and T3 readings (P<0.0001). In group-2, there was a significant difference of the color saturation of specimens between T1 and T2, between T2 and T3 readings (P<0.0001). In group-3, there was a significant difference of the color saturation of specimens between T1 and T2, and between T1 and T3 readings (P<0.0001). The usage of nicotine lozenge promotes teeth lighting with/without bleaching.

El objetivo de este estudio fue evaluar el efecto de comprimidos de nicotina sobre la tinción de los dientes con/sin blanqueamiento en un estudio de modelo animal. Un total de 15 ratas Wistar fueron expuestas en un recipiente acrílico al humo de 10 cigarrillos tres veces al día durante 8 minutos por vez, y sacrificadas después de 60 días. Se trataron un total de 30 dientes incisivos (n=10) de la siguiente manera: Grupo-1: blanqueamiento en consultorio, blanqueamiento en casa e inmersión en saliva artificial; grupo-2: blanqueamiento en consultorio, blanqueamiento en casa e inmersión en solución de comprimidos de nicotina y en saliva artificial; grupo-3: inmersión en solución de nicotina en comprimidos y en artificial. Los especímenes de todos los grupos fueron fotografiados utilizando un microscopio estereoscópico en T1) inmediatamente después de la extracción y antes de cualquier tratamiento; T2) después de un mes del tratamiento; y T3) a los dos meses del tratamiento. Se analizaron cuatro puntos equidistantes de cada espécimen utilizando la guía de colores CMYK. Los datos se analizaron con la prueba ANOVA unidireccional seguida de la prueba de Tukey para comparaciones múltiples con (a ≤ 0,05). En el grupo 1, hubo una diferencia significativa de la saturación de color de las muestras entre T1 y T2, y entre las lecturas T1 y T3 (P<0,0001). En el grupo 2, hubo una diferencia significativa de la saturación de color de las muestras entre T1 y T2, entre las lecturas de T2 y T3 (P<0.0001). En el grupo 3, hubo unadiferencia significativa de la saturación de color de las muestras entre T1 y T2, y entre las lecturas T1 y T3 (P<0,0001). El uso de comprimidos de nicotina promueve la iluminación de los dientes con/sin blanqueamiento.

Unlocking the secrets of saliva: the promising potential of salivary biomarkers for evaluating crack use / Desvendando os segredos da saliva: o potencial promissor dos biomarcadores salivares para avaliar o uso de crack

The forthcoming letter will encompass the following highlights: Crack cocaine use involves smoking a highly addictive form of cocaine, which is a significant concern in Brazil, particularly in urban areas. This addiction is linked to various health problems, including cardiovascular issues, sexually transmitted infections (STIs) like AIDS and syphilis, tuberculosis, and a notable increase in mortality, largely due to violent causes. Furthermore, crack cocaine users are particularly vulnerable to dental caries, gingival inflammation, oral mucosa lesions, and xerostomia (AU)

A próxima carta incluirá os seguintes destaques: O uso de crack envolve fumar uma forma altamente viciante da cocaína, o que é uma preocupação significativa no Brasil, especialmente em áreas urbanas. Esta dependência está ligada a vários problemas de saúde, incluindo problemas cardiovasculares, infecções sexualmente transmissíveis (IST), como a AIDS e a sífilis, a tuberculose e um aumento notável da mortalidade, devido, em grande parte, a causas violentas. Além disso, os usuários de crack são particularmente vulneráveis a cáries dentárias, inflamação gengival, lesões na mucosa oral e xerostomia (AU)

The Fagerström and AUDIT Tests as Probable Screening Tools in Oral Cancer and Their Correlation with CYP1A1, GSTM1, GSTP1, and GSTT1 Gene Expression.

BACKGROUND: Cancer is currently a major public health problem worldwide, with a marked increase of about 70% in the number of expected diagnosed cases over the next two decades. The amount of tobacco and alcohol consumed is calculated based on the subjective information provided by the user. Tobacco exposure can be assessed using the Fagerström Test for Cigarette Dependence (FTCD) and alcohol consumption by the Alcohol Use Disorder Identification Test (AUDIT). MATERIALS AND METHODS: Forty-eight subjects answered the Fagerström, and AUDIT tests and we studied them as likely screening tools for oral cancer and their correlation with the expression of CYP1A1, GSTM1, GSTP1, and GSTT1 genes by the RT-qPCR method. RESULTS: There were significant differences in the AUDIT score and CYP1A1 expression between cancer and control groups. Participants in advanced stages, whether due to tumor size or regional metastasis, showed significant differences in the duration of tobacco use, FTCD, AUDIT score, and CYP1A1 expression when compared to patients in early stages. Among subjects without cancer, we found a significant correlation between participant age and GSTP1 expression. Furthermore, the expression of GSTP1 was significantly correlated with the number of cigarettes smoked per day, duration of tobacco use, and FTCD. CONCLUSIONS: Questionnaires designed to evaluate the degree of tobacco and alcohol exposure and dependence combined with gene expression tests can be useful to assess the risk of developing oral cancer. Furthermore, raising the awareness of individuals regarding their degree of dependence and encouraging them to participate in cessation programs are important educational measures for the prevention of tobacco-related malignancies.

Micro-Fourier-transform infrared reflectance spectroscopy as tool for probing IgG glycosylation in COVID-19 patients.

It has been reported that patients diagnosed with COVID-19 become critically ill primarily around the time of activation of the adaptive immune response. However the role of antibodies in the worsening of disease is not obvious. Higher titers of anti-spike immunoglobulin IgG1 associated with low fucosylation of the antibody Fc tail have been associated to excessive inflammatory response. In contrast it has been also reported that NP-, S-, RBD- specific IgA, IgG, and IgM are not associated with SARS-CoV-2 viral load, indicating that there is no obvious correlation between antibody response and viral antigen detection. In the present work the micro-Fourier-transform infrared reflectance spectroscopy (micro-FTIR) was employed to investigate blood serum samples of healthy and COVID-19-ill (mild or oligosymptomatic) individuals (82 healthcare workers volunteers in "Instituto de Infectologia Emilio Ribas", São Paulo, Brazil). The molecular-level-sensitive, multiplexing quantitative and qualitative FTIR data probed on 1 µL of dried biofluid was compared to signal-to-cutoff index of chemiluminescent immunoassays CLIA and ELISA (IgG antibodies against SARS-CoV-2). Our main result indicated that 1702-1785 [Formula: see text] spectral window (carbonyl C=O vibration) is a spectral marker of the degree of IgG glycosylation, allowing to probe distinctive sub-populations of COVID-19 patients, depending on their degree of severity. The specificity was 87.5 % while the detection rate of true positive was 100%. The computed area under the receiver operating curve was equivalent to CLIA, ELISA and other ATR-FTIR methods ([Formula: see text]). In summary, overall discrimination of healthy and COVID-19 individuals and severity prediction as well could be potentially implemented using micro-FTIR reflectance spectroscopy on blood serum samples. Considering the minimal and reagent-free sample preparation procedures combined to fast (few minutes) outcome of FTIR we can state that this technology is suitable for fast screening of immune response of individuals with COVID-19. It would be an important tool in prospective studies, helping investigate the physiology of the asymptomatic, oligosymptomatic, or severe individuals and measure the extension of infection dissemination in patients.

MALDI-TOF mass spectrometry of saliva samples as a prognostic tool for COVID-19.

BACKGROUND: The SARS-CoV-2 infections are still imposing a great public health challenge despite the recent developments in vaccines and therapy. Searching for diagnostic and prognostic methods that are fast, low-cost and accurate are essential for disease control and patient recovery. The MALDI-TOF mass spectrometry technique is rapid, low cost and accurate when compared to other MS methods, thus its use is already reported in the literature for various applications, including microorganism identification, diagnosis and prognosis of diseases. METHODS: Here we developed a prognostic method for COVID-19 using the proteomic profile of saliva samples submitted to MALDI-TOF and machine learning algorithms to train models for COVID-19 severity assessment. RESULTS: We achieved an accuracy of 88.5%, specificity of 85% and sensitivity of 91.5% for classification between mild/moderate and severe conditions. When we tested the model performance in an independent dataset, we achieved an accuracy, sensitivity and specificity of 67.18, 52.17 and 75.60% respectively. CONCLUSION: Saliva is already reported to have high inter-sample variation; however, our results demonstrates that this approach has the potential to be a prognostic method for COVID-19. Additionally, the technology used is already available in several clinics, facilitating the implementation of the method. Further investigation using a larger dataset is necessary to consolidate the technique.

Finding the combination of multiple biomarkers to diagnose oral squamous cell carcinoma - A data mining approach.

Data mining has proven to be a reliable method to analyze and discover useful knowledge about various diseases, including cancer research. In particular, data mining and machine learning algorithms to study oral squamous cell carcinoma (OSCC), the most common form of oral cancer, is a new area of research. This malignant neoplasm can be studied using saliva samples. Saliva is an important biofluid that must be used to verify potential biomarkers associated with oral cancer. In this study, first, we provide an overview of OSSC diagnoses based on machine learning and salivary metabolites. To our knowledge, this is the first study to apply advanced data mining techniques to diagnose OSCC. Then, we give new results of classification and feature selection algorithms used to identify potential salivary biomarkers of OSCC. To accomplish this task, we used the filter feature selection random forest importance algorithm and a wrapper methodology to evaluate the importance of metabolites obtained from gas chromatography mass-spectrometry (GC-MS) in the context of differentiation of OSCC and the control group. Salivary samples (n = 68) were collected for the control group, and the OSCC group were from patients matched for gender, age, and smoking habit. The classification process occurred based on Random Forest (RF) classification algorithm along with 10-cross validation. The results showed that glucuronic acid, maleic acid, and batyl alcohol can classify the samples with an area under the curve (AUC) of 0.91 versus an AUC of 0.76 using all 51 metabolites analyzed. The methodology used in this study can assist healthcare professionals and be adopted to discover diagnostic biomarkers for other diseases.

Influence of nicotine dependence, current smoking status and gender on CYP1A1, CYP1B1 and CYP2A6 expression in oral squamous cell carcinoma / Influência da dependência nicotínica, parâmetros de consumo de tabaco e gênero na expressão de CYP1A1, CYP1B1 e CYP2A6 em carcinoma de células escamosas oral

Objective: Tobacco smoke is composed of cancer-causing chemicals referred to as carcinogens. These carcinogens are metabolized by the enzymes of the cytochrome P450 (CYP) family. Our objective was to evaluate the correlation of tobacco consumption parameters with CYP1A1, CYP1B1 and CYP2A6 expression using qRT-PCR in samples of oral squamous cell carcinoma (OSCC). Material and Methods: The sample was divided into 2 groups: Cancer (36 subjects) and non-Cancer (12 subjects). The smokers' participants (36) were evaluated regarding their Nicotine dependence (ND) was assessed by the Fagerström test for cigarette dependence (FTCD). Questions regarding tobacco consumption like the number of cigarettes/day (CPD), duration of use, and pack-years were also evaluated. The Mann-Whitney and Spearman correlation tests were used at a significance level of 5%. Results: 48 participants were included, 32 men (66.7%), 36 smokers (75%) and 27 smokers with OSCC (56.3%). Samples of OSCC expressed more CYP1A1, CYP1B1, and CYP2A6. Especially, the CYP1B1 gene was significantly expressed in OSCC samples, regardless gender or tobacco use. No women expressed CYP2A6, as well as, non-smokers did not express the CYP1A1 and CYP2A6 genes. CYP1A1 gene was higher among men (P = 0.021). Conclusion: Lack of exposure to tobacco may justify the absence of CYP1A1 and CYP2A6 expression in non-smokers. The CYP1B1 gene was significantly expressed in the cancer presence despite gender or tobacco use. The assessment of ND and quantification of tobacco consumption are important instruments in monitoring smokers with benign oral lesions and, especially, in the presence of cancer.(AU)

Objetivo: A fumaça do tabaco é composta de substâncias químicas cancerígenas conhecidas como carcinógenos. Esses carcinógenos são metabolizados pelas enzimas da família do citocromo P450 (CYP). Nosso objetivo foi avaliar a correlação dos parâmetros do consumo de tabaco com a expressão de CYP1A1, CYP1B1 e CYP2A6 por qRT-PCR em amostras de carcinoma de células escamosas bucal (CCEB). Material e Métodos: A amostra foi dividida em 2 grupos: Câncer (36 indivíduos) e sem Câncer (12 indivíduos). Os participantes fumantes (36) foram avaliados quanto à dependência nicotínica (DN) pelo teste de Fagerström para dependência de cigarro (TFDC). Questões relacionadas ao consumo de tabaco como número de cigarros / dia (CPD), tempo de uso e anos-maço também foram avaliadas. Os testes de correlação de Mann-Whitney e Spearman foram utilizados com nível de significância de 5%. Resultados: foram incluídos 48 participantes, 32 homens (66,7%), 36 fumantes (75%) e 27 fumantes com CCEB (56,3%). Amostras de CCEB expressaram mais CYP1A1, CYP1B1 e CYP2A6. Especialmente, o gene CYP1B1 foi significativamente expresso em amostras de CCEB, apesar do sexo ou uso de tabaco. Nenhuma mulher expressou CYP2A6, assim como, não fumantes não expressaram os genes CYP1A1 e CYP2A6. O gene CYP1A1 foi maior entre os homens (P = 0,021). Conclusão: A falta de exposição pode justificar a ausência da expressão dos genes CYP1A1 e CYP2A6 entre não fumantes. O gene CYP1B1 foi significativamente expresso na presença de câncer, independentemente do sexo ou do uso de tabaco. A avaliação da DN e a quantificação do consumo de tabaco são importantes instrumentos no acompanhamento de fumantes com lesões bucais benignas e, principalmente, na presença de câncer (AU)

Probiotics for the treatment of depression and anxiety: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND & AIM: Probiotics in the gut have been suggested to have a beneficial effect on anxiety response and depressive disorder. Hence we conducted a systematic review and meta-analysis to summarize the effects of probiotics associated with or without pharmacological or psychological therapies in patients with depressive and/or anxiety symptoms or disorders. METHODS: We conducted searches of MEDLINE, EMBASE, CENTRAL, PsycINFO, CINAHL, ProQuest, LILACS, and Web of Science up to February 2020 to identify randomized controlled trials (RCTs) investigating the efficacy of probiotics associated with or without pharmacological or psychological therapies for patient-important outcomes including relief of depressive, anxiety and stress symptoms, cognitive functions, adverse events and quality of life. We used the GRADE approach to rate the overall certainty of the evidence by outcome. The protocol of the systematic review was registered with PROPSERO and published under the number CRD4202016329. RESULTS: 16 RCTs including 1,125 patients proved eligible. Results suggested a significant improvement in using Beck Depression Index (MD, -3.20 [95% CI, -5.91 to -0.49], p = 0.02; I2 = 21%, p = 0.28) for depression symptoms and State-Trait Anxiety Inventory (STAI) (MD, -6.88 [95% CI, -12.35 to -1.41], p = 0.01; I2 = 24%, p = 0.25) for anxiety with overall certainty in evidence rated as moderate and low, respectively. However, Depression Scale (DASS-Depression) (MD, 2.01 [95% CI, -0.80 to 4.82], p = 0.16; I2 = 0%, p = 0.62), Montgomery-Asberg Depression Rating Scale (MADRAS) (MD, -2,41 [95% CI, -10,55 to 5,72], p = 0,56; I2 = 87%, p = 0,006), Anxiety scale (DASS-Anxiety) (MD, 0.49 [95% CI, -4.05 to 5.02], p = 0.83; I2 = 74%, p = 0.05), and Stress Scale (DASS-Stress) (MD, 0.84 [95% CI, -2.64 to 4.33], p = 0.64; I2 = 34%, p = 0.22) showed no significant decrease in the relief of depression, anxiety and stress symptoms of probiotics compared to placebo with overall certainty in evidence rated as very low for all outcomes. We also found no differences in the Beck Anxiety Index (BAI) (MD, -3.21 [95% CI, -6.50 to 0.08], p = 0.06; I2 = 0%, p = 0.88) with overall certainty in evidence rated as low. Results suggested a non-statistically significantly effect of probiotics in the adverse events outcomes. CONCLUSIONS: The current review suggests that probiotics may improve symptoms of depression and anxiety in clinical patients. However, given the limitations in the included studies, RCTs with long-term follow-up and large sample sizes are needed.

Identification of Possible Salivary Metabolic Biomarkers and Altered Metabolic Pathways in South American Patients Diagnosed with Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) represents 90% of oral malignant neoplasms. The search for specific biomarkers for OSCC is a very active field of research contributing to establishing early diagnostic methods and unraveling underlying pathogenic mechanisms. In this work we investigated the salivary metabolites and the metabolic pathways of OSCC aiming find possible biomarkers. Salivary metabolites samples from 27 OSCC patients and 41 control individuals were compared through a gas chromatography coupled to a mass spectrometer (GC-MS) technique. Our results allowed identification of pathways of the malate-aspartate shuttle, the beta-alanine metabolism, and the Warburg effect. The possible salivary biomarkers were identified using the area under receiver-operating curve (AUC) criterion. Twenty-four metabolites were identified with AUC > 0.8. Using the threshold of AUC = 0.9 we find malic acid, maltose, protocatechuic acid, lactose, 2-ketoadipic, and catechol metabolites expressed. We notice that this is the first report of salivary metabolome in South American oral cancer patients, to the best of our knowledge. Our findings regarding these metabolic changes are important in discovering salivary biomarkers of OSCC patients. However, additional work needs to be performed considering larger populations to validate our results.

MLH1, MSH2, MRE11, and XRCC1 in Oral Leukoplakia and Oral Squamous Cell Carcinoma.

BACKGROUND: DNA damage is accumulated in the cells over time as the result of both exogenous and endogenous factors. The objective of this study was to analyze the immunohistochemical expression of the repair proteins in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Paraffin blocks were selected from the archives of the Laboratory of Hospital Clinico Universitario de Santiago de Compostela, Spain. The sample was composed of 16 cases of OL without dysplasia, 14 cases of OL with dysplasia, and 15 cases of OSCC. The patients' clinical data were collected and immunohistochemical analysis was performed for MLH1, MSH2, MRE11, and XRCC1. The data were submitted to the χ2 and the Kruskal-Wallis (P≤0.05) tests. RESULTS: MSH2 was overexpressed in OSCC (P=0.020) and was positive in 100% of patients with OL with dysplasia or OSCC (P=0.019). Positivity for MLH1 was significantly associated with comorbidity (P=0.040), especially in patients who presented with 2 or more pathologies (P=0.028). XRCC1 positivity was also associated with comorbidity (P=0.039). No significant associations were found for the MRE11A expression. Although the simultaneous positivity for the 4 markers was observed in presence of comorbidities (P=0.006). CONCLUSIONS: This study supports the effect of the overexpression of MSH2 protein in samples of OL with dysplasia and OSCC, most notably in patients who present with comorbidities and negativity for OL without dysplasia.

Intraosseous neurilemoma of the mandible with unusual multilocular presentation: a case report.

This case report describes an intraosseous neurilemoma, observed radiographically as a multilocular lesion, in a 12-year-old patient. Physical examination revealed facial asymmetry, swelling on the right side of the mandibular body, and bone expansion in the region of the base of the buccal sulcus. Panoramic radiography revealed a multilocular radiolucency on the right side of the mandibular body in the periapical region extending from the distal region of the first premolar root to the second molar and adjacent to the third molar. Evaluation of a radiograph obtained 3 years earlier for an orthodontic assessment revealed that the lesion was present, appearing as a unilocular radiolucency near the root of the mandibular right first molar. An incisional biopsy of the multilocular lesion was performed, and Antoni A and Antoni B histologic patterns were identified by microscopic analysis. Immunohistochemical analysis was conducted, and neoplastic cells stained positive for the S-100 protein. The patient underwent conservative surgical excision of the lesion, and no recurrence was observed during 7 years of clinical follow-up. Based on analysis of the present case and previous cases reported in the literature, intraosseous neurilemoma, especially its multilocular variant, is an uncommon neoplasm. In the present case, evaluation of the lesion when it was first radiographically detectable, prior to orthodontic treatment, would have permitted a more limited surgical approach for the excision of a small intraosseous lesion.

E-cig might cause cell damage of oral mucosa.

OBJECTIVE: The aim of this study was to investigate cytogenetic and cytotoxic damage through the evaluation of micronuclei (MN) and metanuclear anomalies in the oral mucosa of electronic cigarette (e-cig) users. STUDY DESIGN: The patients were recruited into 4 groups: e-cig users, smokers, former smokers, and nonsmokers (control). The samples were collected by means of exfoliative cytology of the lateral region of the tongue and the floor of the mouth. The smears obtained were fixed and stained by the Feulgen method for investigation of MN and metanuclear anomalies. RESULTS: A significant difference was observed for MN frequency only between the smoker and control groups. As for metanuclear anomalies, significant differences were observed: karyolysis between: smokers and control, e-cig and control, as well as former smokers; karyorrhexis: between smoker and control; binucleation: between e-cig and former smoker, as well as control; broken eggs: between e-cig and all other groups; nuclear bud: between e-cig and former smokers, as well as control. CONCLUSIONS: E-cig and alcohol users presented genotoxicity and cytotoxicity in the oral mucosa cells. The use of e-cigs and alcohol by former smokers can cause more damage to the cells of the oral mucosa compared to those who have not used e-cigs.