DNA Methyltransferase Genes Are Associated with Oral Mucositis and Creatinine Levels in Oncopediatric Patients.

The aim of this study was to investigate the association of single-nucleotide polymorphisms (SNPs) and the DNA methylation profiles of the DNA methyltransferase (DNMT) gene family with oral mucositis in children and adolescents with hematologic malignancies treated with methotrexate (MTX®). The population was comprised of healthy and oncopediatric patients aged between 4 and 19 years. An evaluation of oral conditions was performed using the Oral Assessment Guide. Demographic, clinical, hematological, and biochemical data were obtained from medical records. Genomic DNA extracted from oral mucosal cells was used for the analysis of polymorphisms in DNMT1 (rs2228611), DNMT3A (rs7590760), and DNMT3B (rs6087990) using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique (n = 102) and for DNA methylation using the methylation-specific PCR (MSP) technique (n = 85). The allele and genotypic frequencies of SNPs did not reveal any differences between patients with or without oral mucositis. An increase in the methylation frequency for DNMT1 in patients recovered from mucositis was detected. The DNMT3A methylated profile associated with the CC genotype (SNP rs7590760) appeared to be connected to higher values of creatinine. In addition, the DNMT3B unmethylated profile associated with the CC genotype (SNP rs6087990) appeared to be connected with higher values of creatinine. We conclude that the DNMT1 methylation profile is associated with the post-mucositis period and that the genetic and epigenetic profiles of DNMT3A and DNMT3B are associated with creatinine levels.

Polymorphism but not methylation status in the vitamin D receptor gene contributes to oral mucositis in children.

OBJECTIVE: To investigate the relationship between the polymorphisms rs1544410 (BsmI), rs2228570 (FokI) and rs731236 (TaqI) and DNA methylation status in the VDR gene (vitamin D receptor) with oral mucositis (OM) in oncopaediatric patients treated with methotrexate (MTX®). METHODS: The population comprised healthy patients with haematological malignancies aged between 5 and 19 years. An evaluation of oral conditions was performed using the Oral Assessment Guide. Demographic, clinical, biochemical and haematological data were obtained from medical records. Genomic DNA from oral mucosal cells was used for the analysis of polymorphisms (n = 102) (PCR-restriction fragment length polymorphism) and DNA methylation (n = 81) (methylation-specific PCR). RESULTS: Males predominated (57.8%), and the mean age was 10.3 years (±4.7). OM affected 84.3% of patients, of which 53.1% developed severe oral mucositis (SOM). Patients with OM had lower platelet and leukocyte counts (p < 0.05). The G allele of rs1544410 (p = 0.040) and the CT genotype of rs2228570 polymorphisms were associated with SOM (p = 0.038). A partially methylated status in the VDR promoter was found in all patients. CONCLUSION: OM is associated with lower leukocyte and platelet counts. SOM is associated with the rs1544410 and rs2228570 polymorphisms. The methylation status of the VDR is not associated with inflammation or exposure to MTX®.

Genetic polymorphisms of genes involved in oxidative stress and inflammatory management in oncopediatric patients with chemo-induced oral mucositis.

OBJECTIVE: Oral mucositis (OM) is a painful inflammatory oral condition that affects children who undergo chemotherapy. Oxidative stress is a known OM mediator and pro-inflammatory cytokines contribute to the amplification of the immune response. To investigate the possible associations of rs4880 (superoxide dismutase 2, SOD2 47 C/T), rs7943316 (catalase, CAT -21 A/T), rs1800629 (tumor necrosis factor α, TNF- α -308 G/A), and rs1800795 (interleukin 6, IL-6 -174 G/C) polymorphisms with chemo-induced OM occurrence and severity in oncopediatric patients. METHODOLOGY: We conducted a single-center, observational cross-sectional study with sample collection of oral epithelial cells from 95 children and adolescents with hematological cancers who underwent chemotherapy, followed by genomic DNA extraction. Single-nucleotide polymorphisms (SNPs) were assessed with PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism). Demographic data and information concerning OM occurrence were obtained from dental charts of the multidisciplinary oral care team. Information on OM severity was obtained from appropriately-filled Oral Assessment Guide records. Descriptive and inferential statistics were conducted with Student's T test, chi-squared test, and Fisher's exact test, with p≤0.05. RESULTS: The mean age was 10 years-old and most patients were male individuals (57.89%). Female sex was considered a protective factor for OM occurrence (OR=4.83; CI=[1.14; 16.57]). The AA genotype for CAT was the most frequent amongst individuals with severe OM (p=0.04). The GA genotype for TNF- α was the most frequent amongst individuals without severe OM (p=0.03). For SOD2 and IL-6 , the most frequent genotypes were CT and GG respectively for all groups (p>0.05). CONCLUSION: The AA genotype for CAT -21 A/T was a tendency among the group with severe OM. Data on TNF- α -308 G/A were inconclusive. No associations were detected for SOD2 47 C/T and IL-6 -174 G/C polymorphisms in oncopediatric patients with chemo-induced oral mucositis.

Effect of dentifrices with different pH and fluoride concentrations on fluoride levels in biofilm and nails: an RCT.

PURPOSE: to evaluate the effect of dentifrice pH and fluoride concentration ([F]) on fluoride uptake on the biofilm and nails of children from a non-fluoridated area. METHODS: two hundred and twenty-eight two- to four-year-old children were randomly allocated into 3 groups according to the type of dentifrice: G1: 1100 µg F/g, pH 4.5 (n = 76); G2: 750 µg F/g, pH 4.5 (n = 74); and G3: 1100 µg F/g, pH 7.0 (n = 78). Nails were collected at 4, 8, and 12 months after starting dentifrice use and biofilm was collected 5 and 60 minutes after toothbrushing. The concentrations of F in nails and biofilm were analyzed by HMDS facilitated diffusion. Data were analyzed by Kruskal-Wallis/Mann-Whitney's test and the comparison between biofilm collection times was done using Wilcoxon test (p £ 0.05). RESULTS: a significant reduction of [F] in biofilm was observed 60 minutes after toothbrushing, regardless of the dentifrice used. However, 5 minutes after toothbrushing, G1 had a significantly higher [F] compared to G2 and G3, and 60 minutes after toothbrushing, [F] was significantly higher for G1 and G2 compared to G3. G1 and G3 had significantly higher [F] in the nails compared to G2. CONCLUSION: a lower dentifrice concentration is a relevant factor for the reduction of excessive fluoride intake. The use of a low-F acidified dentifrice combines the reduction of fluoride uptake with caries prevention by leading to greater incorporation of F into the biofilm over time.

Effect of dentifrices with different pH and fluoride concentrations on fluoride levels in biofilm and nails: an RCT

Abstract: Purpose: to evaluate the effect of dentifrice pH and fluoride concentration ([F]) on fluoride uptake on the biofilm and nails of children from a non-fluoridated area. Methods: two hundred and twenty-eight two- to four-year-old children were randomly allocated into 3 groups according to the type of dentifrice: G1: 1100 μg F/g, pH 4.5 (n = 76); G2: 750 μg F/g, pH 4.5 (n = 74); and G3: 1100 μg F/g, pH 7.0 (n = 78). Nails were collected at 4, 8, and 12 months after starting dentifrice use and biofilm was collected 5 and 60 minutes after toothbrushing. The concentrations of F in nails and biofilm were analyzed by HMDS facilitated diffusion. Data were analyzed by Kruskal-Wallis/Mann-Whitney's test and the comparison between biofilm collection times was done using Wilcoxon test (p £ 0.05). Results: a significant reduction of [F] in biofilm was observed 60 minutes after toothbrushing, regardless of the dentifrice used. However, 5 minutes after toothbrushing, G1 had a significantly higher [F] compared to G2 and G3, and 60 minutes after toothbrushing, [F] was significantly higher for G1 and G2 compared to G3. G1 and G3 had significantly higher [F] in the nails compared to G2. Conclusion: a lower dentifrice concentration is a relevant factor for the reduction of excessive fluoride intake. The use of a low-F acidified dentifrice combines the reduction of fluoride uptake with caries prevention by leading to greater incorporation of F into the biofilm over time.

Genetic polymorphisms of genes involved in oxidative stress and inflammatory management in oncopediatric patients with chemo-induced oral mucositis

Abstract Oral mucositis (OM) is a painful inflammatory oral condition that affects children who undergo chemotherapy. Oxidative stress is a known OM mediator and pro-inflammatory cytokines contribute to the amplification of the immune response. Objective: To investigate the possible associations of rs4880 (superoxide dismutase 2, SOD2 47 C/T), rs7943316 (catalase, CAT −21 A/T), rs1800629 (tumor necrosis factor α, TNF- α −308 G/A), and rs1800795 (interleukin 6, IL-6 −174 G/C) polymorphisms with chemo-induced OM occurrence and severity in oncopediatric patients. Methodology: We conducted a single-center, observational cross-sectional study with sample collection of oral epithelial cells from 95 children and adolescents with hematological cancers who underwent chemotherapy, followed by genomic DNA extraction. Single-nucleotide polymorphisms (SNPs) were assessed with PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism). Demographic data and information concerning OM occurrence were obtained from dental charts of the multidisciplinary oral care team. Information on OM severity was obtained from appropriately-filled Oral Assessment Guide records. Descriptive and inferential statistics were conducted with Student's T test, chi-squared test, and Fisher's exact test, with p≤0.05. Results: The mean age was 10 years-old and most patients were male individuals (57.89%). Female sex was considered a protective factor for OM occurrence (OR=4.83; CI=[1.14; 16.57]). The AA genotype for CAT was the most frequent amongst individuals with severe OM (p=0.04). The GA genotype for TNF- α was the most frequent amongst individuals without severe OM (p=0.03). For SOD2 and IL-6 , the most frequent genotypes were CT and GG respectively for all groups (p>0.05). Conclusion: The AA genotype for CAT −21 A/T was a tendency among the group with severe OM. Data on TNF- α −308 G/A were inconclusive. No associations were detected for SOD2 47 C/T and IL-6 −174 G/C polymorphisms in oncopediatric patients with chemo-induced oral mucositis.

Impact of COVID-19 on Oral Healthcare for Oncopediatric Patients: The Setting in a Reference Hospital in Northeast Brazil

Abstract Objective: To describe the impact of the COVID-19 pandemic on dental care provided to pediatric cancer patients assisted in a referral hospital. Material and Methods: This is an observational, retrospective study based on secondary data extracted from worksheets of dental procedures for patients aged between 0 and 19 years assisted in the pediatric oncology sector of a hospital in João Pessoa, PB, Brazil. Dental procedures performed by the interdisciplinary team of researchers from August 2018 to February 2020 (19 months prior to the pandemic) and from April 2020 to October 2021 (19 months during the pandemic) were totaled and compared. A descriptive analysis of the data was performed. Results: There was a reduction of 80.2% in dental interventions implemented in the sector during the pandemic, with the number of procedures decreasing from 6,210 (the period before the pandemic) to 1,229 (during the pandemic). Most procedures in both periods were performed for patients assisted in beds, for whom there was a reduction of care provided for 81.2% from 5,275 to 994 procedures. Dental procedures in the outpatient clinic decreased by 74.9%, from 935 to 235. Conclusion: The COVID-19 pandemic negatively impacted dental care provided to pediatric oncology patients by restricting dental procedures to emergency demands, compromising performance prevention and health promotion actions.

ABCG2 polymorphism, age and leukocyte count may contribute to oral mucositis in oncopediatric patients.

The study investigated the relationship between genetic polymorphisms and the development of oral mucositis in pediatric patients undergoing chemotherapy involving methotrexate. A longitudinal study was conducted with 64 patients, and oral mucositis was evaluated by the modified Oral Assessment Guide, which aims to diagnose and classify oral mucositis. Epithelial cells were obtained by mouthwash and DNA was extracted. The polymorphisms MTHFR (rs1801133), DNMT3B (rs2424913), ABCC2 (rs717620), ABCG2 (rs2231137) and ABCG2 (rs2231142) were analyzed by PCR-RFLP method. Demographic, hematological and biochemical data were collected from medical records. Statistical analysis was performed using the SPSS software adopting a p-value of 0.05. Male sex predominated (56.2%), and the mean age was 10.8 years (± 4.9). Oral mucositis affected 65.6% of the patients, of which 61.9% developed the severe form of the disease. For the ABCG2 gene (rs2231142), the rare A allele and CA genotype were more frequent in individuals with mucositis (p= 0.02; RR = 0.60; CI = 0.387 - 0.813). The severity of the disease was mainly observed in younger patients (median = 9 years; p=0.02). Patients with severe oral mucositis presented lower leukocytes count (median = 2.150 mm3) compared to patients with the mild/moderate form (median = 4.200 mm3; p=0.03). Female patients and each 10,000-platelet increase were protective factors against the onset of oral mucositis (p=0.02). It is concluded that rs2231142 polymorphism increases the likelihood of oral mucositis and younger patients and patients with low leukocytes counts are more likely to develop severe form.

Percepção de crianças sobre a prática odontológica / Children's perception of dental practice

Objetivou-se conhecer a percepção de crianças sobre a prática odontológica por meio de desenhos à mão livre e de um questionário sobre a sua experiência odontológica prévia. Trata-se de um estudo observacional transversal, com análise de dados quantitativa e descritiva, realizado com 266 crianças de 7 a 12 anos de escolas públicas e privadas da cidade de Piancó (PB) e seus responsáveis. Os dados foram analisados por meio de estatística descritiva e inferencial (Exato de Fisher e Qui-quadrado de Pearson) operados pelo programa SPSS v. 20.0., adotando nível de significância de 5%. Observou-se que 69,2% das crianças já tinham ido ao dentista e 65,0% tinha recebido trata mento preventivo. A impressão positiva do cirurgião-dentista foi expressa por 63,2% das crianças, que ainda o classificaram como uma pessoa amistosa (92,3%). Das crianças avaliadas, 89,1% receberam orientações sobre os procedimentos odontológicos realizados anteriormente, das quais, 86,9% compreenderam as orientações prévias ao tratamento. Houve associação entre ser de escola pública e possuir renda familiar igual ou inferior a um salário mínimo (p<0,001), bem como entre a impressão geral do desenho e o entendimento das explicações prévias ao tratamento (p=0,046). Conclui-se neste estudo que a imagem do profissional está intimamente relacionada com a comunicação que ele desenvolve com o paciente, havendo necessidade de qualificação continuada ao profissional que atenda ao público infantil... (AU)

The aims were to get to know the children's perception of dental practice through freehand drawings and a questionnaire about their previous dental experience. This is a cross-sectional observational study, with quantitative and descriptive data analysis, carried out with 266 children aged 7 to 12 years from public and private schools in the city of Piancó (PB) and their parents. The data were analyzed using descriptive and inferential statistics (Fisher's Exact and Pearson's Chi-square) operated by the SPSS v. 20.0., Adopting a significance level of 5%. It was observed that 69.2% of the children had already gone to the dentist and 65.0% had received preventive treatment. The positive impression of the dentist was expressed by 63.2% of the children, who still classified him as a friendly person (92.3%). Of the children evaluated, 89.1% received guidance on the dental procedures performed previously, of which, 86.9% understood the guidelines prior to treatment. There was an association between being from a public school and having a family income equal to or less than a minimum wage (p <0.001), as well as between the general impression of the draw ing and the understanding of the explanations prior to treatment (p = 0.046). It is concluded in the study that the image of the professional is closely related to the communication that he develops with the pa tient, with the need for continued qualification to the professional that serves the child audience... (AU)

ABCG2 polymorphism, age and leukocyte count may contribute to oral mucositis in oncopediatric patients

Abstract The study investigated the relationship between genetic polymorphisms and the development of oral mucositis in pediatric patients undergoing chemotherapy involving methotrexate. A longitudinal study was conducted with 64 patients, and oral mucositis was evaluated by the modified Oral Assessment Guide, which aims to diagnose and classify oral mucositis. Epithelial cells were obtained by mouthwash and DNA was extracted. The polymorphisms MTHFR (rs1801133), DNMT3B (rs2424913), ABCC2 (rs717620), ABCG2 (rs2231137) and ABCG2 (rs2231142) were analyzed by PCR-RFLP method. Demographic, hematological and biochemical data were collected from medical records. Statistical analysis was performed using the SPSS software adopting a p-value of 0.05. Male sex predominated (56.2%), and the mean age was 10.8 years (± 4.9). Oral mucositis affected 65.6% of the patients, of which 61.9% developed the severe form of the disease. For the ABCG2 gene (rs2231142), the rare A allele and CA genotype were more frequent in individuals with mucositis (p= 0.02; RR = 0.60; CI = 0.387 - 0.813). The severity of the disease was mainly observed in younger patients (median = 9 years; p=0.02). Patients with severe oral mucositis presented lower leukocytes count (median = 2.150 mm3) compared to patients with the mild/moderate form (median = 4.200 mm3; p=0.03). Female patients and each 10,000-platelet increase were protective factors against the onset of oral mucositis (p=0.02). It is concluded that rs2231142 polymorphism increases the likelihood of oral mucositis and younger patients and patients with low leukocytes counts are more likely to develop severe form.

Resumo O presente estudo investigou a relação entre cinco polimorfismos genéticos e o desenvolvimento de mucosite oral em pacientes pediátricos recebendo quimioterapia com metrotexato. O estudo longitudinal foi conduzido com 64 pacientes e a mucosite oral avaliada pelo Oral Assessment Guide modificado, que tem como objetivo diagnosticar e classificar a mucosite oral. Células epiteliais bucais foram obtidas por bochecho e o DNA foi extraído. Os polimorfismos MTHFR (rs1801133), DNMT3B (rs2424913), ABCC2 (rs717620), ABCG2 (rs2231137) e ABCG2 (rs2231142), foram analisados pela técnica de PCR-RFLP. Dados demográficos, hematológicos e bioquímicos foram coletados a partir de registros médicos. Análise estatística foi realizada utilizando o software SPSS adotando um valor de p=0,05. Observou-se que, o sexo masculino foi predominante (56,2%), e a idade média foi de 10,8 anos (± 4.9). A mucosite oral acometeu 65,6% dos pacientes, dos quais, 61,9% desenvolveram a forma grave da doença. Para o gene ABCG2 (rs2231142), o alelo raro A e o genótipo CA foram mais frequentes em indivíduos com mucosite (p= 0.02; RR = 0.60; CI = 0.387 - 0.813). A gravidade da doença foi observada principalmente em pacientes mais jovens (mediana = 9 anos; p=0.02). Além disso, os pacientes com mucosite oral grave apresentaram menor contagem de leucócitos (mediana = 2150 mm3) em comparação aos pacientes com a forma leve/moderada (mediana = 4200 mm3; p=0.03). Pacientes do sexo feminino e aumento a cada 10.000 plaquetas foram fatores de proteção contra o aparecimento de mucosite oral (p=0.02). Concluiu-se que a presença do polimorfismo rs2231142 aumenta o risco de o paciente desenvolver a mucosite oral, bem como pacientes mais jovens e menor contagem de leucócitos contribui com a severidade.

miR-9-1 gene methylation and DNMT3B (rs2424913) polymorphism may contribute to periodontitis.

BACKGROUND: Genetic and epigenetic changes have been associated with periodontitis in various genes; however, little is known about genes involved in epigenetic mechanisms and in oxidative stress. OBJECTIVE: This study aims to investigate the association of polymorphisms C677T in MTHFR (rs1801133) and -149C→T in DNMT3B (rs2424913), as well as the methylation profiles of MTHFR, miR-9-1, miR-9-3, SOD1, and CAT with periodontitis. The association between polymorphisms and DNA methylation profiles was also analyzed. METHODOLOGY: The population studied was composed of 100 nonsmokers of both sexes, divided into healthy and periodontitis groups. Genomic DNA was extracted from the epithelial buccal cells, which were collected through a mouthwash. Polymorphism analysis was performed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while methylation-specific PCR (MSP) or combined bisulfite restriction analysis techniques were applied for methylation analysis. RESULTS: For DNMT3B, the T allele and the TT genotype were detected more frequently in the periodontitis group, as well as the methylated profile on the miR-9-1 promoter region. There was also a tendency towards promoter region methylation on the CAT sequence of individuals with periodontal disease. CONCLUSION: The polymorphism -149C→T in DNMT3B (rs2424913) and the methylated profile of the miR-9-1 promoter region are associated with periodontitis.

miR-9-1 gene methylation and DNMT3B (rs2424913) polymorphism may contribute to periodontitis

Abstract Genetic and epigenetic changes have been associated with periodontitis in various genes; however, little is known about genes involved in epigenetic mechanisms and in oxidative stress. Objective: This study aims to investigate the association of polymorphisms C677T in MTHFR (rs1801133) and −149C→T in DNMT3B (rs2424913), as well as the methylation profiles of MTHFR, miR-9-1, miR-9-3, SOD1, and CAT with periodontitis. The association between polymorphisms and DNA methylation profiles was also analyzed. Methodology: The population studied was composed of 100 nonsmokers of both sexes, divided into healthy and periodontitis groups. Genomic DNA was extracted from the epithelial buccal cells, which were collected through a mouthwash. Polymorphism analysis was performed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while methylation-specific PCR (MSP) or combined bisulfite restriction analysis techniques were applied for methylation analysis. Results: For DNMT3B, the T allele and the TT genotype were detected more frequently in the periodontitis group, as well as the methylated profile on the miR-9-1 promoter region. There was also a tendency towards promoter region methylation on the CAT sequence of individuals with periodontal disease. Conclusion: The polymorphism −149C→T in DNMT3B (rs2424913) and the methylated profile of the miR-9-1 promoter region are associated with periodontitis.

Anxiety of parents and children in dental care / Ansiedade dos pais e crianças no tratamento odontológico

ABSTRACT Objective: To verify the prevalence and association of parents' and children's anxiety concerning socioeconomic variables and child's behavior during dental care. Methods: This was a quantitative, observational, transversal and descriptive study. Data collection was performed through a questionnaire aiming at sociodemographic data and dental experience as well as Venham Picture Test, Corah Dental Anxiety Scales and Frankl Anxiety Scale. Data were analyzed using descriptive and inferential statistics (Chi-square and Fisher's exact test), α = 0.05. Results: The sample consisted of 7 to 9 year- old children (57.9%.), of whom 72.6% were submitted to invasive procedures. The prevalence of anxiety among children was 43.2% (n = 41). Regarding parents / guardians, the prevalence of anxiety was 88.4% (n = 84). A significant association was found between the dental appointment experience and the child's anxiety (p = 0.050) using the VPT. A significant association between anxiety and the type of dental procedure (p = 0.017) as well as the child's experience (p = 0.000) using the Frankl scale. Conclusion: There was no association between anxiety and socioeconomic variables. In the variables related to dental experiences, a significant association was found between the experience of the dental appointment and the anxiety of the child using the VPT scale. An association between anxiety and the type of procedure was observed, as well as dental appointment experience, using Frankl scale.

RESUMO Objetivo: Verificar a prevalência e a associação da ansiedade dos pais e filhos entre as variáveis socioeconômicas frente ao comportamento da criança durante o atendimento odontológico. Métodos: Este estudo foi caracterizado como quantitativo, observacional, transversal e descritivo. Para a coleta de dados, utilizou-se um questionário sobre dados sociodemográficos e experiência dentária, Escalas de Teste de Imagem de Venham, Escalas de Ansiedade Odontológica de Corah e Escala de Ansiedade de Frankl. Os dados foram analisados utilizando estatística descritiva e inferencial (Qui-quadrado e Teste exato de Fisher), α=0.05. Resultados: A maioria das crianças pertencia à faixa etária de 7 a 9 anos, 57,9%. Destas, 72,6% foram submetidos a procedimentos invasivos. A prevalência de ansiedade das crianças foi de 43,2% (n=41). Quanto aos pais/responsáveis, a prevalência de ansiedade foi de 88,4% (n=84). Foi verificada associação significativa entre experiência da consulta e ansiedade da criança (p= 0,050) utilizando a escala VTP. E foi verificada associação significativa entre a ansiedade e o tipo de procedimento (p= 0,017) e a experiência da criança (p=0,000) utilizando a escala de Frankl. Conclusão: Não houve associação entre ansiedade e as variáveis socioeconômicas. Nas variáveis relacionadas as experiências odontológicas, foi verificada associação significativa entre a experiência da consulta e a ansiedade da criança utilizando a escala VTP. Na escala de Frankl foi observada associação entre ansiedade e o tipo de procedimento, e experiência da consulta.