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Introduction: Lynch syndrome (LS) is an inherited cancer predisposition syndrome characterized by a high risk of colorectal and extracolonic tumors. Germline pathogenic variants (GPV) in the PMS2 gene are associated with <15% of all cases. The PMS2CL pseudogene presents high homology with PMS2, challenging molecular diagnosis by next-generation sequencing (NGS). Due to the high methodological complexity required to distinguish variants between PMS2 and PMS2CL, most laboratories do not clearly report the origin of this molecular finding. Objective: The aim of this study was to confirm the GPVs detected by NGS in regions of high homology segments of the PMS2 gene in a Brazilian sample. Methods: An orthogonal and gold standard long-range PCR (LR-PCR) methodology to separate variants detected in the PMS2 gene from those detected in the pseudogene. Results: A total of 74 samples with a PMS2 GPV detected by NGS in exons with high homology with PMS2CL pseudogene were evaluated. The most common was NM_000535.6:c.2182_2184delinsG, which was previously described as deleterious mutation in a study of African-American patients with LS and has been widely reported by laboratories as a pathogenic variant associated with the LS phenotype. Of all GPVs identified, only 6.8% were confirmed by LR-PCR. Conversely, more than 90% of GPV were not confirmed after LR-PCR, and the diagnosis of LS was ruled out by molecular mechanisms associated with PMS2. Conclusion: In conclusion, the use of LR-PCR was demonstrated to be a reliable approach for accurate molecular analysis of PMS2 variants in segments with high homology with PMS2CL. We highlight that our laboratory is a pioneer in routine diagnostic complementation of the PMS2 gene in Brazil, directly contributing to a more assertive molecular diagnosis and adequate genetic counseling for these patients and their families.
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PURPOSE: This study aims to conduct a thorough analysis, both quantitative and qualitative, of bibliometric parameters related to preemptive analgesia (PA) in oral surgical procedures (OSP). METHODS: Research trends on PA in OSP using ibuprofen were reviewed through bibliometric analysis of 68 journal articles published from 1991 to 2022 in the Web of Science database. Bibliometric indicators were applied to analyze the journal article data, including the annual distribution of publications and literature growth, document types, citation indicators to measure qualitative research performance, and keyword mapping to identify research trends. The results were imported into RStudio, and the Bibliometrix package was used to prepare and analyze the metadata. RESULTS: The 68 included articles received a total of 900 citations, ranging from 1 source to 72 citations with some fluctuations. The papers on PA in OSP using ibuprofen had an average of 16.85 citations per paper. These publications were originated from 25 countries, with the highest contributions from Brazil (n = 17), the USA (n = 13), and Turkey (n = 8). The top five major contributing journals were the International Journal of Oral and Maxillofacial Surgery, Journal of Oral and Maxillofacial Surgery, Journal of Cranio-Maxillo-Facial Surgery, Journal of Periodontology, and Acta Odontologica Scandinavica, representing more than half of all selected papers. CONCLUSION: Papers focused on PA in OSP received numerous citations. The citation per article correlated with the number of publications at the affiliation, author, country, and journal levels. However, there is still a scarcity of studies in this field.
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Bibliometria , Ibuprofeno , Procedimentos Cirúrgicos Bucais , Ibuprofeno/uso terapêutico , Humanos , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico , Analgesia/métodos , Analgésicos não Narcóticos/uso terapêuticoRESUMO
The mandibular interforaminal region has been considered safe for surgical procedures; nevertheless, the risk of injury to neurovascular structures, such as the mental foramen (MF) and its related structures (anterior loop [AL] and lingual foramina [LF]) should not be overlooked. The study aimed to evaluate the relative risk of injury to these structures during surgical procedures in the anterior region of the mandible based on cone-beam computed tomography (CBCT) scans. A retrospective cross-sectional and observational study was performed on 250 CBCTs from adults (18-69 years) with dentate jaws. Linear measurements of the MF, AL, and LF were evaluated to estimate the risk of injury to these structures during chin-related surgical procedures. The most frequent distance between the base of the mandible (BM) and MF was 8 mm (30.2%). In addition, 20.4% of the CTs had 6 mm from the vestibular cortical bone to the LF. The commonly found measurement from LF to the apex of the nearest tooth was 7 mm (24.0%); 64.2% of the CTs showed a 2-mm distance between the most distal point of the dental implant site to the most anterior point of the AL. Safety distances for genioplasty techniques (MF to mandible base > 6 mm, 96.6% [CI 95%, 95.0%-98.2%]) were observed. Considering the 5-mm cut-off point between the lower limit of a hypothetical bone graft and the chin, 65.4% (CI 95%, 58.9%-71.9%) of CTs were within this distance. Regarding the safety margin of 8 mm, 85.6% (CI 95%, 80.8%-90.4%) were up to this value. This study found safety margins for genioplasty and chin bone grafting surgical techniques that adopt a 5-mm cut-off point. Further similar studies assessing other surgical methods and employing larger samples from different geographical origins may contribute to this field of investigation.
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Tomografia Computadorizada de Feixe Cônico , Mandíbula , Humanos , Adulto , Pessoa de Meia-Idade , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Mandíbula/anatomia & histologia , Estudos Transversais , Adolescente , Idoso , Estudos Retrospectivos , Adulto Jovem , Masculino , Feminino , Forame Mentual/diagnóstico por imagem , Forame Mentual/anatomia & histologia , Medição de Risco , Queixo/anatomia & histologia , Queixo/diagnóstico por imagemRESUMO
This cross-sectional study evaluated the association between salivary immunoglobulins, plaque index, and gingival index in Brazilian children with and without type 1 diabetes mellitus (DM1). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for the reporting of observational studies was followed. The DM1 group had 38 children, and an equal number of volunteers matched by sex and age were recruited as controls. Clinical examination was performed for plaque index and gingival index determination. Non-stimulated whole saliva was collected. Concentrations of IgA, IgG, and IgM were determined by ELISA test. Data were tested by the Kolmogorov-Smirnov, Mann-Whitney, and Spearman tests and a multiple linear regression model (p<0.05) was performed. Gingival index was higher in the Control (DM1: 0.16±0.17; Control: 0.24±0.23, p=0.040). In DM1, there was a correlation between IgA and age (rho=0.371, p=0.024), IgM and IgG (rho=0.459, p=0.007), and IgM and gingival index (rho=0.394, p=0.014). In DM1, multiple linear regression showed that age (p=0.041; ß=0.363), gingival index (p=0.041; ß=0.398), and plaque index (p=0.008; ß=-0.506) were good predictors of IgA levels in saliva. Thus, IgA was the only researched immunoglobulin that was directly associated with plaque and gingival indices in Brazilian children with DM1, but not in control subjects.
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Índice de Placa Dentária , Diabetes Mellitus Tipo 1 , Imunoglobulina A , Índice Periodontal , Saliva , Humanos , Diabetes Mellitus Tipo 1/imunologia , Masculino , Feminino , Saliva/química , Saliva/imunologia , Estudos Transversais , Criança , Brasil/epidemiologia , Estudos de Casos e Controles , Imunoglobulina A/análise , Imunoglobulina G/análise , Estatísticas não Paramétricas , Imunoglobulina M/análise , Valores de Referência , Ensaio de Imunoadsorção Enzimática , Adolescente , Modelos Lineares , Fatores Etários , Imunoglobulinas/análiseRESUMO
Background: To evaluate the influence of chemotherapy on the prevalence of trismus in irradiated head and neck cancer patients. Material and Methods: This systematic review guided by PRISMA-2020 and registered in PROSPERO (CRD42021255377) screened 963 articles in 7 scientific-databases (PubMed, Lilacs, Livivo, Scopus, Embase, Web of Science, EBSCO) and 3 grey-literature databases (Open Grey, Google Scholar, ProQuest) and eight articles were included for qualitative synthesis, meta-analysis (combined odds ratio, inverse variance method plus random effects), heterogeneity analysis (I² and Tau²), one-of-out evaluation and publication bias analysis (Eggs' and Begg's tests) (RevMan®, p<0.05). The Newcastle-Ottawa Quality Assessment Scale Cohort Studies was used to assess the risk of bias (RoB). The classification assessment, development, and recommendations (GRADE) approach was used to assess the certainty of evidence. Results: The eight articles evaluated 1474 patients treated with chemoradiotherapy and 858 patients treated with radiotherapy. Five articles had low RoB, and three had high RoB. Chemoradiotherapy significantly (p=0.0003) increased the prevalence of trismus (OR=2.55, 95% CI = 1.53-4.23) compared to radiotherapy, with significant (p=0.010) but low heterogeneity (I²=59%;Tau²=0.29). There was no significant risk of publication bias, one-out analysis showed no significant difference between studies, and GRADE showed a moderate level of evidence. Trismus was directly associated to worse quality of life. Conclusions: The incidence of trismus increases when chemotherapy is combined with radiotherapy for head and neck cancer, which negatively impacts the quality of life. Key words:Radiotherapy, Chemoradiotherapy, Head and Neck Neoplasms, Trismus, Quality of Life.
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BACKGROUND: To evaluate the presence of myofibroblasts (MFs) in the development of lip carcinogenesis, through the correlation of clinical, histomorphometric and immunohistochemical parameters, in actinic cheilitis (ACs) and lower lip squamous cell carcinomas (LLSCCs). METHODS: Samples of ACs, LLSCCs, and control group (CG) were prepared by tissue microarray (TMA) for immunohistochemical TGF-ß, α-SMA, and Ki-67 and histochemical hematoxylin and eosin, picrosirius red, and verhoeff van gieson reactions. Clinical and microscopic data were associated using the Mann-Whitney, Kruskal-Wallis/Dunn, and Spearman correlation tests (SPSS, p < 0.05). RESULTS: ACs showed higher number of α-SMA+ MFs when compared to CG (p = 0.034), and these cells were associated with the vertical expansion of solar elastosis (SE) itself (p = 0.027). Areas of SE had lower deposits of collagen (p < 0.001), immunostaining for TGF-ß (p < 0.001), and higher density of elastic fibers (p < 0.05) when compared to areas without SE. A positive correlation was observed between high-risk epithelial dysplasia (ED) and the proximity of SE to the dysplastic epithelium (p = 0.027). LLSCCs showed a higher number of α-SMA+ MFs about CG (p = 0.034), as well as a reduction in the deposition of total collagen (p = 0.009) in relation to ACs and CG. There was also a negative correlation between the amount of α-SMA+ cells and the accumulation of total collagen (p = 0.041). Collagen and elastic density loss was higher in larger tumors (p = 0.045) with nodal invasion (p = 0.047). CONCLUSIONS: Our findings show the possible role of MFs, collagen fibers, and elastosis areas in the lip carcinogenesis process.
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Carcinoma de Células Escamosas , Queilite , Matriz Extracelular , Neoplasias Labiais , Miofibroblastos , Humanos , Queilite/patologia , Queilite/metabolismo , Neoplasias Labiais/patologia , Neoplasias Labiais/metabolismo , Miofibroblastos/patologia , Carcinoma de Células Escamosas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Matriz Extracelular/patologia , Idoso , Fator de Crescimento Transformador beta , Adulto , Actinas , Imuno-Histoquímica , Antígeno Ki-67 , Colágeno , Tecido Elástico/patologiaRESUMO
This is the first study to analyze the anti-inflammatory and antinociceptive effect of withanicandrin, isolated from Datura Ferox leaves, and the possible mechanism of action involved in adult zebrafish (ZFa). To this end, the animals were treated intraperitoneally (i. p.) with withanicandrin (4; 20 and 40â mg/kg; 20â µL) and subjected to locomotor activity and acute toxicity. Nociception tests were also carried out with chemical agents, in addition to tests to evaluate inflammatory processes induced by κ-Carrageenan 1.5 % and a Molecular Docking study. As a result, withanicandrin reduced nociceptive behavior by capsaicin at a dose of 40â mg/kg and by acid saline at doses of 4 and 40â mg/kg, through neuromodulation of TRPV1 channels and ASICs, identified through blocking the antinociceptive effect of withanicandrin by the antagonists capsazepine and naloxone. Furthermore, withanicandrin caused an anti-inflammatory effect through the reduction of abdominal edema, absence of leukocyte infiltrate in the liver tissue and reduction of ROS in thel liver tissue and presented better affinity energy compared to control morphine (TRPV1) and ibuprofen (COX-1 and COX-2).
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Analgésicos , Peixe-Zebra , Animais , Analgésicos/farmacologia , Analgésicos/química , Analgésicos/isolamento & purificação , Canais Iônicos Sensíveis a Ácido/metabolismo , Simulação de Acoplamento Molecular , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Carragenina , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/metabolismo , Edema/tratamento farmacológico , Edema/induzido quimicamente , Folhas de Planta/química , Estrutura MolecularRESUMO
OBJECTIVE: To evaluate the role of induced nitric oxide synthase (iNOS) in nociception/orofacial discomfort in rats submitted to tooth whitening with hydrogen peroxide (H2O2). DESIGN: Wistar rats were divided into three groups (n = 24/group): a sham group not submitted to whitening treatment, a saline group submitted to whitening treatment, and a test group submitted to whitening treatment and blockade of iNOS with aminoguanidine 50 mg/kg/day. After 24 and 48 h, and 7 days, the animals were euthanized to collect trigeminal ganglia and maxillae to histomorphometric analysis (size of neuronal bodies and percentage of pulp area filled by vessels) and behavior/nociception (Grimace scales, scratching and biting counting, weight loss and nociception assay). ANOVA-1- or - 2-way tests were used (p < 0.05, GraphPadPrism 5.0). RESULTS: The aminoguanidine-treated group showed a reduction in nociceptive threshold in the masseteric region (p < 0.001), Grimace scale scores (p < 0.001), number of scratching (p = 0.011) and body mass loss (p = 0.007). After 24 and 48 h of tooth bleaching, the saline group showed a significant increase in the mean area of the blood vessels (p = 0.020) and iNOS immunostaining in odontoblasts (p = 0.002) and non-odontoblasts cells (p = 0.025). Aminoguanidine reversed both increases. Tooth bleaching reduced the mean area of neuronal bodies, and aminoguanidine significantly reversed it (p = 0.019), but an increase in GFAP immunostaining in neuronal bodies did not reduce after seven-days or after aminoguanidine treatment (p = 0.003). CONCLUSION: iNOS blockage by aminoguanidine plays an important role in nociception and orofacial discomfort by control of inflammation in dental pulp after tooth bleaching with hydrogen peroxide (H2O2) 35%.