Exploring the role of the WNT5A rs566926 polymorphism and its interactions in non-syndromic orofacial cleft: a multicenter study in Brazil.

BACKGROUND: Associations between the WNT5A rs566926 variant and non-syndromic orofacial cleft (NSOC) have been reported in different populations. OBJECTIVE: This study aimed to investigate the role of the rs566926 single nucleotide polymorphism (SNP) in WNT5A and its interactions with SNPs in BMP4, FGFR1, GREM1, MMP2, and WNT3 in the occurrence of NSOC in a Brazilian population. METHODOLOGY: A case-control genetic association study was carried out involving participants from four regions of Brazil, totaling 801 patients with non-syndromic cleft lip with or without cleft palate (NSCL±P), 273 patients with cleft palate only (NSCPO), and 881 health volunteers without any congenital condition (control). Applying TaqMan allelic discrimination assays, we evaluated WNT5A rs566926 in an ancestry-structured multiple logistic regression analysis, considering sex and genomic ancestry as covariates. Interactions between rs566926 and variants in genes involved in the WNT5A signaling pathway (BMP4, FGFR1, GREM1, MMP2, and WNT3) were also explored. RESULTS: WNT5A rs566926 was significantly associated with an increased risk of NSCL±P, particularly due to a strong association with non-syndromic cleft lip only (NSCLO), in which the C allele increased the risk by 32% (OR: 1.32, 95% CI: 1.04-1.67, p=0.01). According to the proportions of European and African genomic ancestry, the association of rs566926 reached significant levels only in patients with European ancestry. Multiple interactions were detected between WNT5A rs566926 and BMP4 rs2071047, GREM1 rs16969681 and rs16969862, and FGFR1 rs7829058. CONCLUSION: The WNT5A rs566926 polymorphism was associated with NSCL±P, particularly in individuals with NSCLO and high European ancestry. Epistatic interactions involving WNT5A rs566926 and variants in BMP4, GREM1, and FGFR1 may contribute to the risk of NSCL±P in the Brazilian population.

Exploring the role of the WNT5A rs566926 polymorphism and its interactions in non-syndromic orofacial cleft: a multicenter study in Brazil

Abstract Associations between the WNT5A rs566926 variant and non-syndromic orofacial cleft (NSOC) have been reported in different populations. Objective This study aimed to investigate the role of the rs566926 single nucleotide polymorphism (SNP) in WNT5A and its interactions with SNPs in BMP4, FGFR1, GREM1, MMP2, and WNT3 in the occurrence of NSOC in a Brazilian population. Methodology A case-control genetic association study was carried out involving participants from four regions of Brazil, totaling 801 patients with non-syndromic cleft lip with or without cleft palate (NSCL±P), 273 patients with cleft palate only (NSCPO), and 881 health volunteers without any congenital condition (control). Applying TaqMan allelic discrimination assays, we evaluated WNT5A rs566926 in an ancestry-structured multiple logistic regression analysis, considering sex and genomic ancestry as covariates. Interactions between rs566926 and variants in genes involved in the WNT5A signaling pathway (BMP4, FGFR1, GREM1, MMP2, and WNT3) were also explored. Results WNT5A rs566926 was significantly associated with an increased risk of NSCL±P, particularly due to a strong association with non-syndromic cleft lip only (NSCLO), in which the C allele increased the risk by 32% (OR: 1.32, 95% CI: 1.04-1.67, p=0.01). According to the proportions of European and African genomic ancestry, the association of rs566926 reached significant levels only in patients with European ancestry. Multiple interactions were detected between WNT5A rs566926 and BMP4 rs2071047, GREM1 rs16969681 and rs16969862, and FGFR1 rs7829058. Conclusion The WNT5A rs566926 polymorphism was associated with NSCL±P, particularly in individuals with NSCLO and high European ancestry. Epistatic interactions involving WNT5A rs566926 and variants in BMP4, GREM1, and FGFR1 may contribute to the risk of NSCL±P in the Brazilian population.

Guanosine treatment prevents lipopolysaccharide-induced depressive-like behavior in mice.

Guanosine is a purinergic nucleoside that has been shown to have neuroprotective effects, mainly through its ability to modulate the glutamatergic system. An increase in pro-inflammatory cytokine levels triggers the activation of the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1), leading to glutamatergic excitotoxicity, which has important roles in the pathophysiology of depression. The aim of this study was to investigate the possible antidepressant-like effects and underlying mechanisms of action of guanosine against lipopolysaccharide (LPS)-induced depression in a mouse model. Mice were orally pre-treated with saline (0.9% NaCl), guanosine (8 or 16 mg/kg), or fluoxetine (30 mg/kg) for 7 days before LPS (0.5 mg/kg, intraperitoneal) injection. One day after LPS injection, mice were subjected to the forced swim test (FST), tail suspension test (TST), and open field test (OFT). After the behavioral tests, mice were euthanized and the levels of tumor necrosis factor-α (TNF-α), IDO-1, glutathione, and malondialdehyde in the hippocampus were measured. Pretreatment with guanosine was able to prevent LPS- induced depressive-like behaviors in the TST and FST. In the OFT, no locomotor changes were observed with any treatment. Both guanosine (8 and 16 mg/kg/day) and fluoxetine treatment prevented the LPS-induced increase in TNF-α and IDO expression and lipid peroxidation as well as decrease of reduced glutathione levels in the hippocampus. Taken together, our findings suggest that guanosine may have neuroprotective effects against LPS-induced depressive-like behavior through preventing oxidative stress and the expression of IDO-1 and TNF-α in the hippocampus.

Isolated nonsyndromic cleft palate: multicenter epidemiological study in the Brazil.

BACKGROUND: Nonsyndromic orofacial clefts (NSOC) are the craniofacial most common congenital malformations. There are evidences that the nonsyndromic cleft palate (NSCP) development differs from other NSOC. However, most of the publications treat NSCP without considering that information. Furthermore, few studies focus on NSCP. The aim of this study was to describe epidemiological findings of patients with isolated NSCP in Brazil. METHODS: In this cross-sectional multicenter study, four reference Centers for treatment in three different Brazilian states was investigated. Data were obtained from clinical records of patients, between November 2021 and June 2022. Researched variables were sociodemographic, clinical characteristics and pregnancy and family history. Pearson's chi-square and ANOVA One-way tests were used for associations. RESULTS: Majority were female (58.1%), white (60.7%) with incomplete NSCP (61.2%). There was an association between complete NSCP and a positive history of medical problems during pregnancy (p = 0.016; 27.9%; OR: 1.94; 1.12-3.35). Systemic alterations were perceived in 40.6% of the sample with odds ratio for development of the complete type (OR: 1.21; 0.74-1.97). Higher OR was visualized in medication use during pregnancy (OR: 1.35; 0.76-2.37) and positive family history of oral cleft (OR: 1.44; 0.80-2.55). Dental and surgical care was associated with higher age groups (p < 0.050). CONCLUSIONS: NSCP was most prevalent in white skin color female. Complete NSCP is associated with medical problems during pregnancy. Medication use during pregnancy and positive family history of oral cleft increase the chance of developing complete NSCP.

Ethnic Differences in the Brazilian Population Influence the Impact of BMP4 Genetic Variants on Susceptibility of Nonsyndromic Orofacial Clefts.

OBJECTIVE: The study evaluated the association of BMP4 tag-SNPs and SNP-SNP interactions involving genes active by BMP4 pathway during craniofacial development in the susceptibility of nonsyndromic orofacial clefts (NSOC) in the Brazilian population. DESIGN: Case-control study. SETTING: Brazilian Oral Cleft Group. PARTICIPANTS: The study included 881 healthy controls and 800 patients with different types of NSOC: 232 with cleft lip only (NSCLO), 568 with cleft lip and palate (NSCLP), and 274 with cleft palate only (NSCPO). INTERVENTIONS: The genomic DNA was genotyped with allelic discrimination assays for five BMP4 tag-SNPs (rs11623717, rs17563, rs2071047, rs2761887 and rs4898820), and analyzed their allelic and genotypic associations using multiple logistic regression. The interactions of these variants with genes involved in the BMP4 signaling pathway, including FGFR1, GREM1, NOG, VAX1 and the 4p16.2 locus, were explored. MAIN OUTCOME MEASURES: BMP4 variants in the NSOC risk. RESULTS: Although only nominal p values were identified when the whole sample was considered, subgroup analysis including the patients with high African genomic ancestry showed significant associations of rs2761887 with risk for nonsyndromic cleft lip with or without cleft palate (NSCL ± P)[(ORhom: 2.16; 95% CI: 1.21-3.85; p = 0.01) and (ORrec: 2.05; 95% CI: 1.21-3.47; p = 0.006)]. Thirteen significant SNP-SNP interactions involving BMP4 and the SNPs at FGFR1, GREM1, NOG and VAX1 and at locus 4p16.2 for increased risk of NSCL ± P were identified. CONCLUSIONS: Our results demonstrate an increased risk of NSCL ± P in Brazilian individuals with enrichment of African ancestry in the presence of the BMP4 rs2762887 polymorphism, and reveal relevant genetic contribution of SNP-SNP epistatic interactions involving BMP4 variants to NSCL ± P risk.

Oral manifestations in patients diagnosed with psoriasis: A systematic review.

AIMS: To identify the main types of oral lesions associated with psoriasis. METHODS AND RESULTS: It was a systematic review, based on a search performed in the PubMed/Medline, and Scielo databases, and an associated manual search. Descriptors were selected from DeCs/MeSH and the PICOS strategy (population, intervention, comparison, outcomes, and study design) was applied. Randomized clinical trials and retrospective and prospective studies published from 2000 to 2022 were included, according to the PRISMA parameters (Preferred Reporting Items for Systematic Reviews and Meta-Analysis), registered in the PROSPERO platform. The STROBE quality scale (Strengthening the Reporting of Observational studies in Epidemiology) was also used. One hundred fourteen articles were identified using the search strategy, and nine articles were found in the manual search. Of the sixty-six preselected articles, seven were included in the study. Although it was not possible to identify a specific oral lesion associated with psoriasis, there was a greater occurrence of geographic tongue, fissured tongue, and Candida sp. infection CONCLUSION: Evidence shows that although patients with psoriasis may exhibit lesions in the oral mucosa, they are not specific to this condition. Further epidemiological studies are needed to address the association of psoriasis with possible changes in the oral mucosa.

Access and use of the oral health service in a reference center in oral cleft in the state of Bahia / Acesso e utilização de serviço de saúde bucal em centro de referência em fissura oral no estado da Bahia

ABSTRACT This study aimed to determine the access and utilization of dental services in a reference center for orofacial defects in the state of Bahia, Brazil. In an interview, a questionnaire was done about socio-demographic information, cleft type, specialized treatments, scheduling time and return of the consultation of 101 patients with nonsyndromic cleft lip with or without cleft palate and 101 healthy controls. In both groups the age was between 5 to 12 years old. It was observed that individuals with cleft had faster access to the dental service in relation to the control group and shorter scheduling time between the first consultation and their return. Different needs in the use of dental services were observed in the study groups with differences in relation to the specialties (p=0.000). The nonsyndromic cleft lip with or without cleft palate individuals showed socialization difficulties in the age group between 9 and 12 years and did not present difficulties in accessing primary dental care in specialized service. In conclusion, in this study NSCL±P individuals did not present difficulties in accessing the specialized dental center. To complement the comprehensive care, it is suggested the performance of educational activities of oral health, not yet fully implemented in this multidisciplinary treatment center.

RESUMO Esta pesquisa teve como objetivo determinar o acesso e a utilização de serviços odontológicos em centro de referência para pacientes com defeitos orofaciais no estado da Bahia, Brasil. Em entrevista um questionário foi preenchido sobre informações sociodemográficas, tipo de fissura, tipos de tratamentos especializados, tempo para agendamento e de retorno da consulta de 101 pacientes com fissura labial com ou sem fissura palatina não sindrômica e 101 indivíduos controles sem a malformação. Em ambos os grupos a faixa etária foi de 5 a 12 anos. Observou-se que indivíduos fissurados tiveram acesso mais rápido ao serviço odontológico em relação ao grupo controle e menor tempo de agendamento entre a primeira consulta e o retorno. Distintas necessidades na utilização de serviços odontológicos foram observadas nos grupos de estudo com diferenças em relação às especialidades (p=0,000). Indivíduos com fissura labial com ou sem fissura palatina não sindrômica mostraram dificuldades de socialização no grupo de faixa etária entre 9 e 12 anos e não tiveram dificuldades no acesso ao serviço odontológico especializado. Através desse estudo concluiu-se que os indivíduos fissurados não apresentaram dificuldades no acesso ao serviço especializado. Sugere-se a implementação de atividades educacionais básicas de saúde oral nesse centro de tratamento multidisciplinar.

Serum levels of vitamin A, selenium, and better dietary total antioxidant capacity are related to lower oxidative DNA damage: A cross-sectional study of individuals at cardiovascular risk.

The risk for cardiovascular diseases (CVR) has been associated with oxidative DNA damage, but the genetic and environmental factors involved in the antioxidant and DNA repair system contributing to this damage are unknown. The aim was to evaluate the levels of oxidative DNA damage in CVR subjects and how it is related with some genetic and nutritional factors. The cross-sectional study evaluated 136 individuals of both sexes, aged 20-59 years, with at least one cardiovascular risk factor. The global risk score was used to classify individuals at low, intermediate, and high cardiovascular risk. The dietary total antioxidant capacity (DTAC) was calculated using table with FRAP values. The oxidative DNA damage was verified by the comet assay. The variants null of Glutathione-S-transferases Mu1 and Theta 1(GSTM1 and GSTT1) and rs25487 of X-Ray Repair Cross Complementing Protein 1 (XRCC1) were analyzed by real-time PCR and PCR-RFLP, respectively. The oxidative DNA damage was higher in patients with intermediate/high CVR than in patients with low CVR (P=.01). Individuals with GSTT1/GSTM1 null genotypes or arg/gln+gln/gln genotypes of the XRCC1 (rs25487) gene showed similar levels of oxidative DNA damage compared wild genotype. Multivariate regression analysis demonstrated that oxidative DNA damage in individuals with CVR depends on serum levels of vitamin A, selenium, and DTAC independently of the other factors [F(6.110)=8.213; P<.001; R2=0.330]. These findings suggest that nutritional factors such as DTAC, vitamin A and selenium may have a protective effect against oxidative DNA damage in these individuals.

Oral Lichen Planus: Associations Between Histomorphometric Characteristics and White and Red Lesions.

Histomorphometry seems to provide more rigid quantitative elements for histological analysis and to bring less subjectivity to the diagnosis of oral lichen planus lesions (OLP). This study aimed to verify the association between white and red lesions and histomorphometric characteristics of OLP lesions. This retrospective cross-sectional study assessed 48 hematoxylin- and eosin-stained histological sections from incisional biopsies obtained from OLP cases. A single previously calibrated evaluator performed the light microscopy analyses to evaluate morphological and morphometric parameters. Analyses of associations among variables were performed using the Fisher's exact test. Morphometric variables were assessed using the Mann-Whitney non-parametric test. Comparisons among the three groups (age range) were performed using the Kruskal-Wallis test. In this study, 81.2% of the participants were women aged < 50 years. Keratosis, acanthosis, and inflammatory infiltrates were noted in 10.4, 10.4, and 37.5% of moderate/severe cases, respectively. Inflammatory infiltrate (52.1%), papillary projections (54.2%), saw teeth (12.5%), basal layer degeneration (39.6%), and Civatte bodies (68.8%) were also observed. There was no significant association between lesion type and clinicopathological variables (p > 0.05) or between lesion type and histological (p > 0.05) and morphometric variables (p > 0.05). Furthermore, the morphometric variables analyzed did not differ between white and red lesions (p > 0.05) or in their associations with clinicopathological variables (p > 0.05). The results of this investigation showed no associations between white and red OLP lesions and the histomorphometric characteristics evaluated.

Evaluation of genome-wide association signals for nonsyndromic cleft lip with or without cleft palate in a multiethnic Brazilian population.

OBJECTIVE: To evaluate previous nonsyndromic cleft lip with or without cleft palate (NSCL±P) associated signals in 4p16.2, 8p11.23, 12q13.13, 12q13.2 and 17q21.32 in a multiethnic Brazilian cohort. DESIGN: The single nucleotide polymorphisms (SNPs) rs34246903 in 4p16.2, rs13317 in 8p11.23 (FGFR1, fibroblast growth factor receptor 1), rs3741442 in 12q13.13, rs705704 in 12q13.2 and rs4968247 in 17q21.32 were genotyped with TaqMan allelic discrimination assays in a case-control sample including 801 NSCL±P patients [233 nonsyndromic cleft lip (NSCLO) and 568 nonsyndromic cleft lip and palate (NSCLP)] and 881 healthy controls. Multiple logistic regression analyses, considering sex and genomic ancestry as covariates, were conducted, and the p value was adjusted with Bonferroni multiple correction testing (p ≤ 0.01). RESULTS: Although several associations were identified, those that resisted the multiple correction testing involved the alleles and genotypes of rs34246903 and rs13317. The NSCLO group had a lower frequency of the minor C allele of rs34246903 compared to controls, giving an odds ratio (OR) of 0.74 [95% confidence interval (CI): 0.59-0.93, p = 0.01]. The rs34246903 CC genotype (homozygous) and the recessive model revealed significant protective associations with NSCLO, yielding ORs of 0.50 (95% CI: 0.29-0.85, p = 0.005) and 0.55 (95% CI: 0.33-0.93, p = 0.01) respectively. The presence of C variant allele of rs13317 (OR: 0.81, 95% CI: 0.69-0.96, p = 0.01) as well the TC genotype (OR: 0.77, 95% CI: 0.62-0.94, p = 0.01) and the dominant model (OR: 0.77, 95% CI: 0.63-0.94, p = 0.009) showed significant associations with reduced risk of NSCL±P. CONCLUSION: Our study is the first to support the association of rs34246903 (4p16.2) with NSCLO and rs13317 within FGFR1 with NSCL±P in the highly admixed Brazilian population. Further studies are needed to determine the functionality of those SNPs or to identify the causal markers in linkage disequilibrium with those susceptibility markers.

Perfil técnico-científico de egressos de um Mestrado Profissional em Odontologia: estudo de corte transversal / Technical-scientific profile of graduates from a Professional Master's degree course in Dentistry: a cross-sectional study

Atualmente tem havido uma crescente demanda por mestrados profissionais. Contudo, o impacto desta modalidade de pós-graduação stricto sensuna sociedade ainda tem sido pouco avaliado.O presente estudo objetivou caracterizar o perfil dos egressos de um mestrado profissional em Odontologia de uma instituição de ensino superior privada, acerca da sua inserção no mercado de trabalho, qualificação e produção técnico-científica.Tratou-se deum estudo retrospectivo, de corte transversal, decaráter censitário. Foram utilizadas como estratégias de busca dos egressosasredes sociais, número de telefones fixo e móvel, e-mail pessoal e institucional. Para coleta de dados foi utilizado um questionário semiestruturado elaborado pelos pesquisadores, nos formatos físico e eletrônicoqueforam organizados em uma tabelaunidimensional de frequência, a partir da qual foram identificados os seus respectivos percentuais. Foi constatado que 71,8% dos egressos responderamaos questionários enviados.A maioria dos egressos conseguiu se inserir no mercado de trabalho de forma destacada, pois 62,1% destes ingressaramem atividades relacionadas à docência. Cerca de86,5% publicarama sua pesquisa sob a forma de artigo científico, além das produções técnicas destacadas,como apresentações de trabalho em congressos, entrevistas, textos informativos em websites e cursos ministrados. Constatou-se aparticipaçãoem atividades do setor público e privado, com percentuais de 43,2% e 56,8%, respectivamente.Conclui-se que o perfil dos egressos do mestrado profissional em Odontologiaavaliado neste estudo foi caracterizado por ampla participação em atividades relacionadas à docência, assim como em pesquisas e trabalhos técnicos, com participação significativa nos setores público e privado. Essa modalidade de pós-graduação propiciouao egresso uma formação tecnicamente qualificada, caracterizando-se como uma prática avançada e transformadora (AU).

Nowadays there's a growing demand for professionals master's degrees course. However, the impact of this stricto sensu postgraduate studies modality in society has been lowly evaluated. This study aims to characterize the profile of students who graduate from a professional master's degree course from a private higher education institution, through their entry in labor market, qualification and technical-scientific production. This is a retrospective cross-sectional census study. Social media, phone and cellphone numbers and personal and institutional emails were used as research strategies of those students who graduated the program. A semi-structured questionnaire was created by the researchers of this study, available in both online and offline versions, to collect data and it was organized in a one-dimensional frequency table, where the following percentage rates were identified. It was found that 71,8% of the graduates responded to the form sent to them. Most of them managed to entry the labor market in an outstanding way, because 62,1% of those joined activities related to teaching. Around 86,5% of them published their researches as scientific manuscripts, beside their outstanding technical production, such as conference presentations, interviews, online informative texts and courses taught. The participation in public and private sectors activities was found in 43,2% and 56,8% of them, respectively. It is concluded that the profile of the students who finish the professional master's degree course in Odontology evaluated in this study is characterized for significant participation in activities related to teaching, such as technical researches and work, with significant participation in the public and private sectors. This modality of postgraduate course provided to the graduates a technically qualified training, characterized as an advanced and transforming practice (AU).

Brazilian Multiethnic Association Study of Genetic Variant Interactions among FOS, CASP8, MMP2 and CRISPLD2 in the Risk of Nonsyndromic Cleft Lip with or without Cleft Palate.

Associations of CRISPLD2 (cysteine-rich secretory protein LCCL domain containing 2) and genes belonging to its activation pathway, including FOS (Fos proto-oncogene), CASP8 (caspase 8) and MMP2 (matrix metalloproteinase 2), with nonsyndromic orofacial cleft risk, have been reported, but the results are yet unclear. The aim of this study was to evaluate single nucleotide polymorphisms (SNPs) in FOS, CASP8 and MMP2 and to determine their SNP-SNP interactions with CRISPLD2 variants in the risk of nonsyndromic cleft lip with or without cleft palate (NSCL±P) in the Brazilian population. The SNPs rs1046117 (FOS), rs3769825 (CASP8) and rs243836 (MMP2) were genotyped using TaqMan allelic discrimination assays in a case-control sample containing 801 NSCL±P patients (233 nonsyndromic cleft lip only (NSCLO) and 568 nonsyndromic cleft lip and palate (NSCLP)) and 881 healthy controls via logistic regression analysis adjusted for the effects of sex and genomic ancestry proportions with a multiple comparison p value set at ≤0.01. SNP-SNP interactions with rs1546124, rs8061351, rs2326398 and rs4783099 in CRISPLD2 were performed with the model-based multifactor dimensionality reduction test complemented with a 1000 permutation-based strategy. Although the association between FOS rs1046117 and risk of NSCL±P reached only nominal p values, NSCLO risk was significantly higher in carriers of the FOS rs1046117 C allele (OR: 1.28, 95% CI: 1.10-1.64, p = 0.004), TC heterozygous genotype (OR: 1.59, 95% CI: 1.16-2.18, p = 0.003), and in the dominant model (OR: 1.50, 95% CI: 1.10-2.02, p = 0.007). Individually, no significant associations between cleft risk and the SNPs in CASP8 and MMP2 were observed. SNP-SNP interactions involving CRISPLD2 variants and rs1046117 (FOS), rs3769825 (CASP8) and rs243836 (MMP2) yielded several significant p values, mostly driven by FOS rs1046117 and CASP8 rs3769825 in NSCL±P, FOS rs1046117 in NSCLO and CRISPLD2 rs8061351 in NSCLP. Our study is the first in the Brazilian population to reveal the association of FOS rs1046117 with NSCLO risk, and to support that CRISPLD2, CASP8, FOS and MMP2 interactions may be related to the pathogenesis of this common craniofacial malformation.

Identification of Novel Variants in Cleft Palate-Associated Genes in Brazilian Patients With Non-syndromic Cleft Palate Only.

The identification of genetic risk factors for non-syndromic oral clefts is of great importance for better understanding the biological processes related to this heterogeneous and complex group of diseases. Herein we applied whole-exome sequencing to identify potential variants related to non-syndromic cleft palate only (NSCPO) in the multiethnic Brazilian population. Thirty NSCPO samples and 30 sex- and genetic ancestry-matched healthy controls were pooled (3 pools with 10 samples for each group) and subjected to whole-exome sequencing. After filtering, the functional affects, individually and through interactions, of the selected variants and genes were assessed by bioinformatic analyses. As a group, 399 variants in 216 genes related to palatogenesis/cleft palate, corresponding to 6.43%, were exclusively identified in the NSCPO pools. Among those genes are 99 associated with syndromes displaying cleft palate in their clinical spectrum and 92 previously related to cleft lip palate. The most significantly biological processes and pathways overrepresented in the NSCPO-identified genes were associated with the folic acid metabolism, highlighting the interaction between LDL receptor-related protein 6 (LRP6) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) that interconnect two large networks. This study yields novel data on characterization of specific variants and complex processes and pathways related to NSCPO, including many variants in genes of the folate/homocysteine pathway, and confirms that variants in genes related to syndromic cleft palate and cleft lip-palate may cause NSCPO.

Impacto da terapia nutricional em pacientes com câncer de cabeça e pescoço com desnutrição: uma revisão sistemática / Impact of nutritional therapy in patients with head and neck cancer with malnutrition: systematic review

Introdução: o câncer de cabeça e pescoço (CCP) ocupa o 5º lugar entre as neoplasias mais prevalentes no Brasil. Por acometer regiões que estão relacionadas diretamente à alimentação, os efeitos secundários ao tratamento provoca diminuição da ingesta alimentar, que favorece perda de peso acelerada e desnutrição. A terapia nutricional (TN) contribui para a minimização desses efeitos, pois visa à manutenção ou recuperação do estado nutricional. Objetivo: avaliar o impacto da TN em pacientes com CCP com desnutrição, e na minimização dos efeitos colaterais advindos do tratamento antineoplásico. Metodologia: trata-se uma revisão sistemática, utilizando-se as bases de dados eletrônicas Lilacs, Medline, Pubmed, periódicos CAPES e Scielo, através dos descritores: "nutritional therapy", "head and neck neoplasms" e "malnutrition". Os critérios de inclusão estabelecidos foram ensaios clínicos randomizados, escritos em inglês e publicados entre os anos de 2013 e 2018; participantes dos estudos deveriam apresentar idade superior a 19 anos e submetidos a qualquer tipo e fase de tratamento oncológico. Resultados: observou-se um total de 755 indivíduos com CCP que participaram dos seis ensaios clínicos selecionados. Os estudos avaliaram o impacto nutricional no uso de suplementos alimentares e na eficácia da terapia enteral. Destes, apenas quatro constataram diferença em relação a intervenção nutricional (p<0,05) e dois não relataram resultados significativos (p>0,05). O acompanhamento nutricional mostra-se necessário para reduzir os riscos de piora do estado nutricional e da qualidade de vida. Conclusão: a TN oral ou enteral podem ser implementadas, para garantir a melhora da condição nutricional e de saúde do paciente com CCP.

Introduction: head and neck cancer (HNC) ranks 5th among the most prevalent cancers in Brazil. By affecting regions that are directly related to food, the side effects of treatment may cause decreased food intak with weight loss and malnutrition. Nutritional therapy (NT) contributes to minimization this, as it aims to maintain or recover nutritional status. Aim: evaluate the impact of nutritional therapy in patients with HNC with malnutrition, and minimizing side effects from antineoplastic treatment. Methodology ­ A systematic review was carried out using Lilacs, Medline, Pubmed, periodicals CAPES and Scielo, through the descriptors: "nutritional therapy", "head and neck neoplasms" and "malnutrition". The inclusion criteria were randomized clinical trials, in English and published between 2013 and 2018. Participants in the studies should be over the age of 19 years, submitted to any type and stage of cancer treatment. Results: a total of 755 individuals with CCP who participated in the six selected clinical trials were observed. The studies evaluated the nutritional impact of dietary supplement use and the efficacy of enteral therapy. Of these, only four found a difference in relation to nutritional intervention (p <0.05) and two did not report significant results (p> 0.05). Depending on staging of the disease, only nutritional counseling is not enough to prevent weight loss. Nutritional monitoring is necessary to reduce the risks of worsening nutritional status and quality of life. Conclusions: oral or enteral NT can be implemented to ensure the improvement of the nutritional and health condition of the patient with CCP.

Adherence of head and neck cancer patients to laser photobiomodulation in a public health service: Pilot study.

OBJECTIVE: The aim of this study was to evaluate the adherence of patients with head and neck cancer who underwent radiotherapy or radio-chemotherapy combined to the preventive laser photobiomodulation protocol in a public health service. MATERIALS AND METHODS: This was a cross-sectional study, whose population sample included patients with malignant head and neck neoplasms. Thirty head and neck cancer patients undergoing cancer treatment, were examined and interviewed through a record of signs and symptoms of oral mucositis (OM) and adherence to the preventive laser photobiomodulation protocol, that began in the first session of radiotherapy, and included the laser application three times a week during the 3-week period. The collected data were documented, and the descriptive and inferential statistics were performed with a significance level of p < 0.05. RESULTS: It was observed that 66.6% of patients developed OM. There was a predominance of degrees I and II, with 36.8% and 31.6%, respectively. A total of fifteen patients (50%) missed one or more laser photobiomodulation sessions. A positive association was found between patients who missed at least two laser photobiomodulation sessions with the development of OM degrees III (p < 0.05). CONCLUSIONS: There was moderate adherence of patients with head and neck cancer to the laser photobiomodulation protocol and the development of more severe degrees of OM was related to individuals that didn't attend scheduled sessions.

A retrospective study on the oral health of patients in the intesive care unit / Um estudo retrospectivo sobre a condição bucal de pacientes em unidade de terapia intensiva

Introduction: the oral condition of patients in the Intensive Care Unit (ICU) is extremely important for clinical status monitoring, as lesions in the oral mucosa may imply complications and worsening of the health status of these patients. A higher probability of adherence, colonization, and bacterial infection in the oral cavity of patients in the ICU has also been reported. The poor oral hygiene conditions of these patients may be related to the reduction of salivary flow and difficulties in maintaining oral hygiene in a hospital environment, which rarely employs dentists on staff. Objective: to analyze the dental condition of patients admitted to the ICU of Roberto Santos General Hospital, Salvador, Bahia, Brazil. Methodology: a total of 73 patients were evaluated through an oral examination performed with a wooden spatula and sterile gauze under natural light, and data were collected and analyzed. Results: The most commom oral lesions were tongue-coating (41%) and ulcerations in the oral mucosa caused by trauma or dehydration (19.1%). The occurrence of pseudomembranous candidiasis (8.2%), dehydration of the lips and mucosa (26%), and angular cheilitis (9.5%) was additionally recorded. It was observed that 31.5% patients had more than 10 days of hospitalization and of these, 26% presented pseudomembranous candidiasis. This clinical condition was not seen in patients with a shorter hospital stay. Conclusions: this study suggest a possible association between the length of stay of these patients and the clinical conditions presented. Thus, the results of this study may guide preventive and curative measures implemented by dental surgeons who may, in the future, be part of the multidisciplinary team of professionals working in the hospital environment, especially in ICUs.

Introdução: a condição oral de pacientes internados em Unidade de Terapia Intensiva (UTI) é de extrema importância na evolução do quadro clínico desta população, já que lesões na mucosa oral podem implicar em complicações e agravo do estado de saúde destes indivíduos. Tem sido relatado também maior probabilidade de aderência, colonização e infecção bacteriana na cavidade oral de pacientes que se encontram em leitos de UTI. As condições precárias de higiene oral que estes pacientes normalmente apresentam podem estar relacionadas à redução do fluxo salivar e às dificuldades de higienização oral inerentes ao ambiente hospitalar, o qual geralmente não conta com cirurgiões-dentistas integrando a equipe de profissionais da instituição. Objetivo: a presente pesquisa visou analisar a condição odontológica de pacientes internados na Unidade de Terapia Intensiva do Hospital Geral Roberto Santos. Metodologia: setenta e três foram avaliados através de um exame bucal, realizado com espátula de madeira e gaze estéril sob a iluminação de luz natural e seus dados foram coletados e analisados. Resultados: as lesões orais mais comuns foram saburra lingual (41%) e ulcerações na mucosa oral provocadas por trauma ou ressecamento (19,1%). A ocorrência de candidíase pseudomembranosa (8,2%), lábios e mucosas desidratados (26%) e queilite angular foi adicionalmente registrada. Foi observado que dos 31,5% dos pacientes com mais de 10 dias de internação, 26% apresentaram candidíase pseudomembranosa. Essa condição clínica não foi observada em pacientes com menor tempo de internação. Conclusão: o presente estudo sugere uma possível associação entre o tempo de internação destes pacientes e as condições clínicas apresentadas. Desta forma, a descrição dos resultados desta investigação pode contribuir para nortear os cuidados preventivos e curativos a serem adotados por cirurgiões-dentistas que futuramente integrem a equipe multidisciplinar de profissionais que atuam no ambiente hospitalar, em especial, nas unidades de terapia intensiva.

Evaluation of preventive laser photobiomodulation in patients with head and neck cancer undergoing radiochemotherapy: Laser in patients with head and neck cancer.

AIMS: This study aimed to evaluate the effect of laser photobiomodulation in the prevention of oral mucositis (OM), salivary hypofunction and referred pain in patients with head and neck cancer. METHODS AND RESULTS: This randomized clinical study divided patients into two groups: the laser group (LG, n = 30) and the control group (CG, n = 24). The LG (InGaAlP, 660 nm, 86.7 mW, 2 J/cm2 ) participated in the preventive protocol, while the CG underwent a simulated procedure without light emission. The degree of OM, salivary flow, and referred pain were evaluated at five different periods of radiotherapy. Both groups showed a significant increase in the degree of OM (P < .01). Regarding OM, salivary flow, and oral pain, there were no significant differences between the groups. CONCLUSIONS: The laser photobiomodulation protocol used in this study was not effective in preventing radiochemotherapy-induced OM, salivary hypofunction, and referred pain in patients with head and neck cancer. Notably, although the development of OM did not differ significantly according to the use of laser therapy, the severity of oral mucositis was reduced in patients who underwent laser therapy compared to that in patients who did not.

Exploring GRHL3 polymorphisms and SNP-SNP interactions in the risk of non-syndromic oral clefts in the Brazilian population.

OBJECTIVE: To investigate the association of single-nucleotide polymorphisms (SNP) in grainyhead-like 3 (GRHL3) and to verify its possible interactions with others genes responsible for craniofacial development in the risk of non-syndromic oral cleft (NSOC). METHODS: Applying TaqMan allelic discrimination assays, we evaluated GRHL3 SNPs (rs10903078, rs41268753, and rs4648975) in an ancestry-structured case-control sample composed of 1,127 Brazilian participants [272 non-syndromic cleft palate only (NSCPO), 242 non-syndromic cleft lip only (NSCLO), 319 non-syndromic cleft lip and palate (NSCLP), and 294 healthy controls]. Additionally, SNP-SNP interactions of GRHL3 and previously reported variants in FAM49A, FOXE1, NTN1, and VAX1 were verified in non-syndromic cleft lip with or without cleft palate (NSCL ± P). To eliminate false-positive associations, Bonferroni correction or 1,000 permutation method was applied. RESULTS: The multiple logistic regression analysis showed that the CC genotype of rs10903078 (p = .03) and the haplotype C-C formed by the SNPs rs10903078 and rs41268753 (p = .04) were associated with NSCLO, but the p-values did not withstand Bonferroni correction. However, SNP-SNP test revealed significant interactions between GRHL3 SNPs and FAM49A (rs7552), FOXE1 (rs3758249), VAX1 (rs7078160 and rs751231), and NTN1 (rs9891446). CONCLUSIONS: Our results confirm the importance of GRHL3 and its interactions with previously NSOC-associated genes, including FAM49A, FOXE1, NTN1, and VAX1, in the pathogenesis of NSOC in the Brazilian population.

Evaluation of the Impact of Oral Hygiene and Chamomile Tea in the Development of Oral Mucositis: Pilot Study / Avaliação do Impacto da Higiene Oral Associada ao Uso do Chá de Camomila no Desenvolvimento de Mucosite Oral: Estudo-Piloto / Evaluación del Impacto de la Higiene Oral y el Té de Manzanilla en el Desarrollo de la Mucositis Oral: Estudio Piloto

Introduction: The oral mucositis (OM) represents a frequent inflammatory condition in cancer patients, and poor oral hygiene has been related as a predisposing factor for its onset. Chamomile tea has been studied as an adjunctive therapy in the management of OM due to its analgesic and anti-inflammatory properties. Objective: The objective of this study was to evaluate the influence of chamomile tea associated with a rigorous oral hygiene in the OM prevention. Method: Randomized pilot clinical study, with 35 patients assigned to two groups. The case-group underwent oral hygiene control associated with the use of chamomile tea before starting the first cycle of chemotherapy, while the control group, there were no previous guidelines and prescriptions. Data about sociodemographic characteristics, the type of neoplasm and the chemotherapy scheme proposed were collected. The variables OM, salivary flow and pain associated to the oral cavity were evaluated, and statistical analysis was performed with significance level p <0.05. Results: It was observed that the majority of the patients had a mean age of 50 years, breast (57%) was the most prevalent tumor site and cyclophosphamide (52%), the most frequently used drug In this sample, no statistically significant result was observed in the two groups for OM, salivary flow and pain variables (p> 0.05). Conclusion: These data suggest that the use of chamomile tea and the accuracy of oral hygiene were not sufficient to prevent OM.

Introdução: A mucosite oral (MO) representa uma condição inflamatória frequente em pacientes oncológicos e uma higiene oral insatisfatória tem sido relacionada como fator predisponente para o seu surgimento. O chá de camomila vem sendo estudado como terapia adjuvante no manejo da MO em razão das suas propriedades analgésicas e anti-inflamatórias. Objetivo: Avaliar a influência do chá de camomila associada a uma rigorosa higiene oral na prevenção de MO. Método: Trata-se de um estudo-piloto clínico randomizado, no qual 35 pacientes foram alocados em dois grupos. O grupo-caso foi submetido ao controle de higiene oral associado ao uso do chá de camomila antes de iniciar o primeiro ciclo de quimioterapia; no grupo-controle, não houve orientações e prescrições prévias. Foram coletados dados referentes às características sociodemográficas, à neoplasia em questão e ao tipo de tratamento quimioterápico proposto. Foram avaliadas as variáveis MO, fluxo salivar e dor associada à cavidade oral, e realizada análise estatística com nível de significância p<0,05. Resultados: Observou-se que a maioria dos pacientes apresentava-se na quinta década de vida, a localização do tumor mais prevalente foi a mama (57%) e a droga mais utilizada por esses pacientes foi a ciclosfamida (52%). Nesta amostra, não foi observado resultado estatisticamente significativo entre os grupos, no que diz respeito às variáveis MO, fluxo salivar e dor (p>0,05). Conclusão: Os dados sugerem que o uso do chá de camomila e o rigor na higiene oral não foram suficientes para a prevenção da MO.

Introducción: La mucositis oral (MO) representa una afección inflamatoria frecuente en pacientes con cáncer, y la mala higiene bucal se ha relacionado como un factor predisponente para su aparición. El té de manzanilla se ha estudiado como una terapia adyuvante en el tratamiento de la OM debido a sus propiedades analgésicas y antiinflamatorias. Objetivo: El objetivo de este estudio fue evaluar la influencia del té de manzannilla asociado con una hygiene oral rigurosa en la prevención de la MO. Método: Fue un estudio clínico piloto aleatorizado, en el que treinta y cinco pacientes fueron asignados en dos grupos. El grupo de casos se sometió a un control de higiene oral asociado con el uso de té de manzanilla antes de comenzar el primer ciclo de quimioterapia, mientras que en el grupo de control, no había pautas ni recetas previas. Se recopilaron datos sobre las características sociodemográficas, el tipo de neoplasia y el esquema de quimioterapia propuesto. Se evaluaron las variables MO, flujo salival y dolor asociado a la cavidad oral, y se realizó un análisis estadístico con nivel de significancia p<0,05. Resultados: Se observó que la mayoría de los pacientes tenían una edad media de 50 años, el sitio del tumor más prevalente era la mama (57%) y el fármaco utilizado con mayor frecuencia era la ciclofamida (52%). En esta muestra, no se observaron resultados estadísticamente significativos entre los grupos con respecto a las variables MO, flujo salival y dolor (p>0,05). Conclusión: Estos datos sugieren que el uso de té de manzanilla y la precisión de la higiene oral no fueron suficientes para prevenir la MO.

Protein restriction in early life increases intracellular calcium and insulin secretion, but does not alter expression of SNARE proteins during pregnancy.

NEW FINDINGS: What is the central question of this study? Does protein restriction in early life modify glucose-induced insulin secretion by altering [Ca2+ ]i and the expression of SNARE proteins in pancreatic islets from pregnant rats? What is the main finding and its importance? Protein restriction in early life increased the first phase of glucose-induced insulin secretion and [Ca2+ ]i without altering the expression of SNARE proteins during pregnancy. This finding contributes to our understanding of the mechanisms of altered insulin secretion and might provide new perspectives for the development of therapeutic tools for gestational diabetes. ABSTRACT: We investigated the kinetics of glucose-induced insulin secretion and their relationship with [Ca2+ ]i and the expression of protein from exocytotic machinery in islets from recovered pregnant and long-term protein-deficient pregnant rats. Isolated islets were evaluated from control-fed pregnant (CP), protein-deficient pregnant (DP), control-fed non-pregnant (CNP) and protein-deficient non-pregnant (DNP) female adult rats, and from protein-deficient pregnant (RP) and non-pregnant (RNP) rats that were recovered after weaning. The insulin responses to glucose during the first phase of secretion were higher in RP than in CP groups, and both were higher than in the DP group. Islets from RP rats displayed a rapid increase in insulin release (first phase), followed by a plateau that was maintained thereafter. The [Ca2+ ]i in islets from the protein-deficient groups was lower than in the control groups, and both were lower than in the RP and RNP groups. SNAP-25 was increased in islets from pregnant rats independently of their nutritional status, and the syntaxin-1A content was reduced in islets from the RP rats compared with the RNP rats. The VAMP2 content was similar among the groups. Thus, protein restriction during intrauterine life and lactation increased insulin secretion during pregnancy, attributable, in part, to increased [Ca2+ ]i , and independent of an alteration of expression of SNARE proteins.