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ABSTRACT Background: Williams-Beuren syndrome is a multisystemic disorder caused by a microdeletion of the 7q11.23 region. Although familial cases with autosomal dominant inheritance have been reported, the vast majority are sporadic. Objective: To investigate the main complaints and clinical findings of patients with Williams-Beuren syndrome. Methods: A total of 757 parents of patients registered in the Brazilian Association of Williams-Beuren Syndrome (ABSW) received a questionnaire via WhatsApp from March to July 2017. Results: In total, 229 parents answered the survey. Age of diagnosis ranged from 2 days to 34 years (median: 3 years). The main clinical findings reported by the parents were abdominal colic (83.3%), failure to thrive (71.5%), feeding difficulty in the first year (68.9%), otitis (56.6%), urinary tract infections (31.9%), precocious puberty (27.1%) and scoliosis (15.9%). Cardiac defects were present in 66% of patients, and the most frequent defect was supravalvular aortic stenosis (36%). Arterial hypertension was reported in 23%. Hypercalcemia was reported in 10.5% of patients, mainly during the first year of life. Hyperacusis and hypersociability were common complaints (both present in 89%). Other behavioral and neuropsychiatric symptoms reported by the parents included attention deficit (89%), anger crises (83%), excessive fear (66%), depression (64%), anxiety (67%) and hypersexuality (33%). The most common complaints were hypersensitivity to sounds, talkative personality, emotional dependence and learning difficulties. In 98.3%, the parents denied family history. Conclusions: Williams-Beuren syndrome requires close follow-up with different medical specialties due to their variable clinical comorbidities, including language and school learning difficulties, behavioral and psychiatric problems.

The need to determine risk factors for complex diseases continues to drive efforts to identify etiological factors of common conditions. Molecular tools have created new opportunities to identify risk factors that may act interactively. The goal of this work was to explore potential interactions between oral microbial species and common genetic variants. Ninety-two 6- to 19-year-old individuals recruited through the University of Pittsburgh Dental Registry and DNA Repository project that had oral microbiome and genotyping of 44 single nucleotide polymorphism (SNP) data available were studied. Over-representation of alleles between individuals with or without particular microorganisms was determined using chi-square or Fisher's exact tests. An alpha of 0.001, to account for multiple testing (0.05/44), was considered statistically significant. Associations were found between Candida albicans and enamelin rs3796704 (p = 0.0006), and Staphylococcus epidermidis and tuftelin rs3828054 (p = 0.001). Microbiota and their metabolites might predispose to oral disease when interacting with the host genetic variation and future studies should address their causal roles in oral disease.

Objective: To determine if there are differences in protein profiles in saliva depending if children of caries- free versus caries affected. Material and Methods: A cohort of 91 children with ages between 6 and 19 years, along clinical status of caries experience. Protein profiles in saliva were determined using electrophoresis and the calculation of the percentage of a specific band at a specific molecular weight in relationship to the total protein in that sample (% of total) using molecular weight standards. This quantification was repeated for each protein band across a range of molecular weights for each sample. Chi- square, Fisher’s exact, and Student t-tests were used to compare the distributions between caries-free and caries affected children (α=0.05). Results: Histatin was more likely to be non-detectable or reduced in caries-free children (OR=7.56; 95% CI 1.62-35.13) and these children had on average one less gel band detected by the assay we used. Conclusion: We have found differences in proteins between caries affected and caries-free children, suggesting that this line of investigation holds the promise of providing new tools for caries management.

BackgroundOur aim was to investigate the relationship between caries experience and erosive tooth wear in adolescents.MethodsWe compared the Decayed, Missing, and Filled Teeth (dmft/DMFT) data of 795 adolescents to their erosive tooth wear scores using diet as a covariate and determined whether dental caries and erosive tooth wear scores are associated with each other, using linear regression analysis. Diet data and oral hygiene habits were collected using self-reported surveys and erosive tooth wear scores were previously collected. We also compared patients' genotypes and phenotypes and looked for an association between erosive tooth wear experience and different single nucleotide polymorphisms (SNPs). A Bonferroni correction was implemented to correct multiple comparisons. Two-group comparisons were made depending on the phenotype definitions implemented, and both chi-square and linear regression analyses were used to the test association between genetic variants and caries definitions. All covariates were included in each model.ResultsFor four SNPs (rs17159702, rs10246939, rs1800972, and rs1676303), there was an association between a spike in caries experience of DMFT 4 or more between two time points and increased frequency of fruit juice intake. A fifth SNP rs2860216 was shown to be a protective factor against a caries spike when associated with more frequent yogurt consumption. We did not find significant associations between our dental caries phenotypes or our demographic data and erosive tooth wear status in our linear regression.ConclusionsDental caries and erosive tooth wear are two diseases that differ in mechanism and heritability.

Certain patients, despite receiving proper treatment, still show higher failure rates of restorative dental treatments. The aim of this work was to test if MMP2 and MMP3 alleles are overrepresented in individuals with secondary caries. A total of 1,089 individuals from the University of Pittsburgh School of Dental Medicine Dental Registry and DNA Repository project were selected for this study. From this total, 341 individuals were selected for having a record of secondary caries in any type of restoration and were matched with 748 individuals by sex, age, ethnicity, and restorative work in the same teeth that did not fail. Genomic DNA extracted from saliva was used to obtain genotypes in five markers of MMP2 and MMP3 using TaqMan chemistry and end-point analysis. Chi-square was used to test if differences in allele and genotype distributions were statistically different at an alpha of 0.05. The less common allele and homozygote genotype of MMP2 rs9923304 were less commonly found among individuals with secondary caries. The less common allele of MMP2 rs2287074 was also less frequent among individuals with secondary caries. These results provide statistical evidence for the role of MMP2 in failure of restorations due to secondary caries. We can conclude that MMP2 variation impacts the risk of having secondary caries, independent of the restorative material.

Abstract Objectives Dental caries is a highly prevalent infectious disease that causes tooth decay. While no single bacterial species is causative of dental caries, the role of the oral microbiome in oral health and caries is gaining interest. The purpose of this study is to compare the major species present in whole saliva samples from caries‐free and caries‐active children using the IBIS Universal Biosensor. Material and Methods The abundant microbial species in ninety‐five whole saliva samples from caries‐free and caries‐active subjects were characterized using the IBIS Universal Biosensor. Results Twenty‐four genera and sixty‐five species were detected. Candida and Streptococcus were common across samples, and often the dominant genus. While we did not observe a strong association between the most abundant species and oral health, Bacteroides thetaiotaomicron and Rothia mucilaginosa were enriched in children with active caries; while, Staphylococcus epidermidis was enriched in caries‐free children. Conclusions These study trends observed suggest that microbial markers in saliva may serve as predictors of oral health and thus aid in diagnosis and treatments for prevention of caries. Consistent with competitive interactions, we also observed negative associations between Streptococcus pneumoniae and other streptococcal species, Staphylococcus aureus and S. epidermidis, Candida and Neisseria, and Saccharomyces and Streptococcus.

The goal of this study was to test if oral health outcomes are associated with the same genetic markers in Black and White individuals who did not have cancer. From a total of 6,100 subjects from the Dental Registry and DNA Repository project, 1,042 individuals who self-identified as White and 266 as Black without a history of cancer were included in this analysis. Genotyping data from IRE1—rs196929, RHEB—rs2374261 and rs1109089, AXIN2—rs2240308 and rs11867417, and RPTOR—rs4396582, present in cell regulatory pathways, were analyzed. We ran separate analyses in self-reported Black and White groups to reduce possible confounding effects of population stratification. Internal diagnostic codes from our dental registry were converted into Phecodes in order to run the analysis using the PheWAS package, installed in R Studio software. Periodontitis was associated with RHEB in both Black and White patients, with the minor allele increasing the likelihood of developing periodontitis in the White group and yielding a protective effect in the Black individuals. The presence of ulcers and gingivitis were associated with RPTOR and AXIN2, respectively, in the White group, but an association was not detected for the Black group. On the other hand, phenotypes such as dental fracture, diseases of the tongue, attrition, erosion, abrasion, fordyce granules, and torus and exostosis were uniquely associated with the Black group. Periodontitis associated with RHEB in both Black and White patients, and associations found in Black individuals may be the result of social disparities that lead to higher levels of stress, and these observed differences require further study.

The goal of the present work was to revisit published data to test if genetic variation in interferon regulatory factor 6 (IRF6) is associated with children born with cleft lip with or without cleft palate (CL/P) for cases with positive history of maternal smoking. From the 573 individuals originally studied, this reanalysis focused on 57 who had a positive history of maternal smoking during pregnancy (39 born with CL/P and 18 born without CL/P). Seven IRF6 markers (rs4844880, rs2235371, rs2013162, ra861019, rs2073487, rs642961, and rs658860) were tested for over-transmission of alleles and an alpha of 0.05 was considered statistically significant. All individuals born with CL/P were homozygous for the wild type allele of rs2235371 in comparison to just two individuals born without clefts (p = 0.0000001). For rs861019, individuals born with CL/P were more likely to have the variant allele (p = 0.006). A similar trend was seen for rs642961 (p = 0.09). The results suggest that statistical evidence of over-representation of IRF6 alleles in individuals born with CL/P may be unveiled only when maternal smoking during pregnancy is used as the inclusion criterion in the analysis.

Molar incisor hypomineralization (MIH) is an enamel condition characterized by lesions ranging in color from white to brown which present rapid caries progression, and mainly affects permanent first molars and incisors. These enamel defects usually occur when there are disturbances during the mineralization or maturation stage of amelogenesis. Both genetic and environmental factors have been suggested to play roles in MIH's development, but no conclusive risk factors have shown the source of the disease. During head and neck development, the interferon regulatory factor 6 (IRF6) gene is involved in the structure formation of the oral and maxillofacial regions, and the transforming growth factor alpha (TGFA) is an essential cell regulator, acting during proliferation, differentiation, migration and apoptosis. In this present study, it was hypothesized that these genes interact and contribute to predisposition of MIH. Environmental factors affecting children that were 3 years of age or older were also hypothesized to play a role in the disease etiology. Those factors included respiratory issues, malnutrition, food intolerance, infection of any sort and medication intake. A total of 1,065 salivary samples from four different cohorts were obtained, and DNA was extracted from each sample and genotyped for nine different single nucleotide polymorphisms. Association tests and logistic regression implemented in PLINK were used for analyses. A potential interaction between TGFA rs930655 with all markers tested in the cohort from Turkey was identified. These interactions were not identified in the remaining cohorts. Associations (p

Cleft lip with or without cleft palate (CLP) is considered the most frequent congenital malformations of the head and neck, with cleft individuals exhibiting more chances of presenting abnormalities such as developmental defects of enamel (DDE). Matrix metallopeptidase 2 (MMP2) is a membrane-bound protein with collagen-degrading ability and has important roles in tooth formation and mineralization. The aim of this study was to evaluate the frequency, location, severity and extent of DDE found in the maxillary incisors for groups of individuals born with CLP, as well as understanding their relationship with the cleft side. Besides, this study addresses the hypothesis that DDE can be influenced by variation in the MMP2 genes (rs9923304). Individual samples, clinical history, intraoral photographs and panoramic radiographs were obtained from 233 patients under treatment at the Cleft Lip and Palate Service of the University Hospital Lauro Wanderley at the Federal University of Paraíba. Digital images were examined by the same evaluator using the Classification of Defects According to the Modified DDE Index, and then loaded into the Image Tool software, where two measurements were made: total area of the buccal surface (SA) and the area of the DDE (DA), obtaining the percentage of the surface area affected (%SAD) (ICC = 0.99). Genomic DNA was extracted from saliva samples from 124 participants. Genotyping was carried out using TaqMan chemistry for one marker in MMP2 (rs9923304). Statistical analyses were performed by The Jamovi Project software. The Shapiro-Wilk test was applied, followed by the Student's t-test and the Mann-Whitney test. Chi-square and Fisher's exact tests, and odds ratio (OR) with 95% confidence interval (CI) calculations were used to determine Hardy-Weinberg equilibrium and statistically significant differences with an alpha of 0.05. No significant differences in the prevalence and extent of enamel defects were found between male and female individuals born with CLP (p = 0.058256). The frequency of individuals presenting teeth with DDE, in relation to the cleft and non-cleft side, was statistically different (p 7.151> 10.942). However, the averages of %SAD were similar (p = 0.18). The highest means of the %SAD were found in individuals with bilateral cleft lip with or without cleft palate (BCLP) when compared to individuals with unilateral cleft lip with or without cleft palate (UCLP), for the teeth inside (IA) and outside the cleft area (OA) (p

Abstract Background Oral hygiene instruction is an intervention widely practiced but increased knowledge about oral health does not necessarily dramatically impact oral disease prevalence in populations. We aimed to measure plaque and bleeding in periodontal patients over time to determine patterns of patient response to oral hygiene instructions. Methods Longitudinal plaque and bleeding index data were evaluated in 227 periodontal patients to determine the impact of oral hygiene instructions. Over multiple visits, we determined relative plaque accumulation and gingival bleeding for each patient. Subsequently, we grouped them in three types of oral hygiene status in response to initial instructions, using the longitudinal data over the period they were treated and followed for their periodontal needs. These patterns of oral hygiene based on the plaque and gingival bleeding indexes were evaluated based on age, sex, ethnic background, interleukin 1 alpha and beta genotypes, diabetes status, smoking habits, and other concomitant diseases. Chi-square and Fisher’s exact tests were used to determine if any differences between these variables were statistically significant with alpha set at 0.05. Results Three patterns in response to oral hygiene instructions emerged. Plaque and gingival bleeding indexes improved, worsened, or fluctuated over time in the periodontal patients studied. Out of all the confounders considered, only ethnic background showed statistically significant differences. White individuals more often than other ethnic groups fluctuated in regards to oral hygiene quality after instructions. Conclusions There are different responses to professional oral hygiene instructions. These responses may be related to ethnicity.

The purpose of this study was to test two 8-year-old identical twins with ectodermal dysplasia (ED) and their unaffected parents for the presence of mutations in the EDA gene with the hypothesis that they might be carrying a de novo mutation in EDA and potentially eligible for recombinant EDA therapy. DNA was extracted using saliva samples obtained from the identical twin girls and both parents. PCR products of Ectodyplasin A (EDA), Ectodysplasin Receptor (EDAR), Ectodysplasin Receptor Associated Death Domain (EDARADD), and Connexin-30 (GJB6) were sequenced by the Sanger method and the results analyzed using a reference sequence. Exons and exon-intron boundaries of EDA, EDAR, EDARADD, and GJB6 were sequenced in both parents and the affected identical twin pair. No mutations were detected in EDA or GJB6. Genetic variants located in the intron of EDAR were found but determined to be non-contributory to the twins’ ED. A microsatellite polymorphism was detected in all four subjects in exon 4 of the EDARADD gene but determined not to be causal to the ED. There was a silent mutation detected in exon 6 of the EDARADD gene of both the daughters and their unaffected mother but also unlikely to be the cause of ED. These results suggest that ED of the subjects is caused by a de novo mutation in a gene not studied here. It is likely these subjects and their future offspring would not benefit from the development of recombinant EDA replacement therapy.

Smoking is a leading cause of preventable death. The effect of tobacco is even more contundent in people with mental illness and, in general, cigarette smoking addiction is influenced by genetic factors. The opioid system is involved in the mesolimbic reward system, which is of great importance in addictive behaviors, such as smoking and is influenced by genes such as the OPRM1. The aim of this study was to evaluate if selecting a comparison group that include light smokers versus people that never smoked impacts the results of genetic association studies. In addition, to evaluate the genetic association in different groups of smokers by analyzing independent covariates such as mental illness and clinical dental data. All subjects were participants of the Dental Registry and DNA Repository project. Genotyping was carried out using TaqMan chemistry for two markers in OPRM1 (rs553202 and rs7755635). Logistic regression analyses were performed as implemented in PLINK. The established value for alpha was 5%, and the Hardy-Weinberg equilibrium was evaluated by the chi-square test with one degree of freedom for each marker. 1,897 patients were included, which were allocated to eight distinct groups, according to the frequency and quantity of cigarettes smoked and mental illness status. There was no significant association between the two markers in OPRM1 and smoking. When mental illness and dental clinical data (tooth loss, dental caries, and periodontitis) were used as covariates, there were associations between heavy smoking and OPRM1, when non-smokers were used as comparison. We did not have diet or microbiome data to consider for these dental analyses and suggest that these kinds of data should be always incorporated in the future. Significant results were found only when the covariables mental illness and oral clinical data were added to the analysis.

Composite resins for posterior tooth restorations have become a viable alternative to dental amalgam. Failures sometimes cannot be easily explained, and we hypothesize that a genetic component may influence longevity of restorations. We aimed to determine if there is any evidence for a difference in the performance of amalgams versus composite resin in extensive posterior restorations. We also aimed to determine if risk factors such as age, sex, smoking tobacco, alcohol drinking, diabetes status, and periodontal health status may have a role in the failures of extensive anterior composite restorations. Finally, we investigated if genetic variation in matrix metalloproteinases that are present in the mineralized dentin is associated with failure of composite resin. The data used to perform this research were obtained from the Dental Registry and DNA Repository project after screening 4,856 patients. All restorations were evaluated at times of 1, 2, and 5 years after the restoration placement. 6,266 amalgam and 2,010 composite restorations were analyzed in a total of 807 patients in a period of approximately 10 years (period corresponding to the database existence). An additional 443 extensive direct composite resin restorations in anterior teeth were also studied. Failure rates of amalgam and composite restorations are similar, and by the end of 5 years, composites outperformed amalgams slightly. Failures of anterior composite restorations occurred more often in males who smoked tobacco (p = 0.05), despite a similar number of females and males that smoked tobacco in the sample (116 individuals smoked tobacco, 54 females and 62 males). Alcohol drinking increased failure rate within 2 years (p = 0.03). We found a statistically significant association between matrix metalloproteinase 2 rs9923304 and failure of composite restorations (p = 0.007). Composite resins can replace amalgam restorations. Smoking tobacco and drinking alcohol will increase the chance of restoration failure.

Este estudo apresenta reflexões acerca dos conceitos de cidadania e democracia no contexto das Conferências Nacionais de Saúde - CNS tendo como fonte de referência seus relatórios finais e a série histórica 8ª CNS a 14ª CNS. As variáveis elencadas foram a cidadania e a democracia, buscando-se perscrutar referências explícitas e/ou implícitas aos referidos termos. Por meio de análise documental buscou-se identificar em que momentos, que atores sociais ou ramo da saúde estes termos foram de forma mais recorrente referidos. Percebe-se a contribuição histórica das CNS, sendo o SUS seu grande legado, assim como a extrema relevância nas discussões deflagradas em seus contextos imputada aos termos cidadania e democracia sendo o controle social/participação social o espaço mais profícuo a estas discussões.

Characteristics of enamel may influence or modulate individual susceptibility to caries and erosion. These characteristics are defined during development, which is under strict genetic control, but can easily be modified in many ways by environmental factors. In the symposium, translational aspects of embryology, biochemistry, and genetics of amelogenesis were presented. The symposium provided unique insight into how basic sciences integrate with clinically relevant problems. The need for improved understanding of risks at the individual level, taking into consideration both environmental exposures and genetic background, was presented. The symposium was divided into four stepwise and interconnected topics as follows: 1) The Many Faces of Enamel Development; 2) Enamel Pathogenesis: Biochemistry Lessons; 3) Environmental Factors on Enamel Formation; and, 4) Genetic Variation in Enamel Formation Genes.

Este artigo aborda a Política Nacional de Atenção Integral às Pessoas com Doenças Raras. Objetivou-se analisar as características e preceitos normativos da referida Política a partir dos elementos percebidos como essenciais na construção e dinâmica de gestão de uma política de saúde. Para subsidiar as análises foram recrutados ainda a Portaria nº 981, textos normativos de Políticas Concorrentes e arcabouços teóricos pertinentes às Doenças Raras, Políticas Públicas e Advocacia em Saúde, sendo estes três eixos o Marco Conceitual deste estudo. Utilizou-se como metodologia a análise documental e o levantamento da literatura pertinente aos eixos elencados. Conclui-se que embora a Política Nacional de Atenção Integral às Pessoas com Doenças Raras contemple em suas diretrizes ações com vias a corrigir as lacunas dos serviços de saúde especializados por meio de incentivos e adequações profissionais, tanto o diagnóstico como a terapêutica requerem a efetivação das diretrizes que já orientam o Sistema Único de Saúde – SUS: universalidade, integralidade, equidade e descentralização. Destaca-se ainda que embora tenham sido observados os elementos objetivos e subjetivos essenciais na construção de uma política de saúde, é de fundamental importância que haja o espírito colaborativo de outras instâncias da gestão pública, assim como dos profissionais de saúde.

Introduction: Although rotary instrumentation has been widely studied in permanent dentition, it is a rather new field of study concerning primary teeth. Purpose: We aimed to evaluate apical displacement and time needed for instrumentation of root canals of primary molars by manual and rotary techniques. Materials and Methods: Root canals of 144 extracted first and second primary maxillary molars were randomly divided into 2 groups: I- manual instrumentation (K-files); II- rotary instrumentation (K3 Rotary System®). The canals were radiographed with pathfinding files in place, prepared by both techniques, and instrumentation time was recorded. After preparation, root canals were radiographed again with pathfinding files in place. To analyze the degree of apical displacement, digital images were superimposed using the Adobe Photoshop® software. Results: Mean apical displacement (0.70 mm) in the manual instrumentation group was not statistically different from that in the rotary instrumentation group (0.79 mm). However, mean time for root canal preparation was significantly shorter using the rotary system (128.0 s) than using the manual system (174.0 s) (p

A cidade de Belém no Pará passou por ampla reforma urbana no período de 1890-1911. Dentre os sujeitos que participaram deste processo de modernização da cidade, estão o Intendente Antônio Lemos e o engenheiro Francisco Bolonha. Neste artigo apresento uma visão geral sobre esta modernização e analiso como as concessões feitas por Lemos ao engenheiro Bolonha, além de contribuir para a modernização da cidade, provocou tensões no seio da politica local, contribuindo para que ocorresse o fim da chamada “era lemos”. Pretendo, também, compreender sob que matrizes teóricas a urbanização da cidade de Belém se assentou e como os ideários do progresso, presentes no recém-proclamado Regime Republicano, foram recebidos e aplicados nesta urbanização. Para esta análise foram utilizados sete volumes dos Relatórios de Intendência Municipal, publicados entre 1897 e 1908 e diversos artigos publicados nos jornais locais, O Estado do Pará, A Província do Pará, Folha do Norte e O Jornal.