Direct evidence that KLK4 is a hydroxyapatite-binding protein.

The protease kallikrein 4 (KLK4) plays a pivotal role during dental enamel formation by degrading the major enamel protein, amelogenin, prior to the final steps of enamel hardening. KLK4 dysfunction is known to cause some types of developmental defect in enamel but the mechanisms responsible for transient retention of KLK4 in semi-hardened enamel matrix remain unclear. To address contradictory reports about the affinity of KLK4 for enamel hydroxyapatite-like mineral, we used pure components in quasi-physiological conditions and found that KLK4 binds hydroxyapatite directly. Hypothesising KLK4 self-destructs once amelogenin is degraded, biochemical analyses revealed that KLK4 progressively lost activity, became aggregated, and autofragmented when incubated without substrate in both the presence and absence of reducer. However, with non-ionic detergent present as proxy substrate, KLK4 remained active and intact throughout. These findings prompt a new mechanistic model and line of enquiry into the role of KLK4 in enamel hardening and malformation.

Early-life sugar consumption and breastfeeding practices: a multicenter initiative in Latin America.

The aim of this multicenter study was to explore the early-life sugar consumption and dietary practices in Latin America as well as to investigate the association between breastfeeding duration and the age at which foods and beverages with added sugars are introduced. A cross-sectional study was conducted with 805 1- to 3-year-old children from 10 Latin American countries, as a complementary study to the Research Observatory for Dental Caries of the Latin American Region (OICAL). A Food Frequency Questionnaire previously tested in different countries was applied to children's mothers and data on breastfeeding and age at introduction of sugary foods and beverages was collected. Statistical analysis included the Kruskal-Wallis test and Poisson regression with robust variance, with the calculation of crude and adjusted mean ratios (MR) and 95% of confidence intervals (CI). The average age at introduction of sugary foods and beverages was 10.1 months (95%CI 9.7-10.4) and 9.6 (95%CI 9.2-9.9) months, respectively, with a significant variation between countries (p < 0.001). The average daily frequency of sugary foods-beverages was 3.3 times per day (95%CI 3.1-3.5) and varied significantly between countries (p = 0.004). Breastfeeding duration of over six months was associated with an increase in the age of introduction of sweet drinks (16%; MR 1.16; 95%CI 1.05-1.28) and foods (21%; MR 1.21; 95%CI 1.10-1.33). In conclusion, most children from vulnerable settings in Latin America start consuming sugary products in the first year of life and a high frequency of consumption was reported through early childhood. Additionally, breastfeeding contributes to a delay in the introduction of sugary products.

Impact on oral health-quality of life in infants: Multicenter study in Latin American countries.

To assess the impact of oral conditions on oral health-related quality of life (OHRQoL) in infants in ten Latin America countries (LAC). A cross-sectional study was conducted with 930 pairs of 1-to-3-year-old children/parents from 10 LAC, as a complementary study of the Research Observatory for Dental Caries of the Latin American Region. The scale ECOHIS, previously tested and valid in ten countries, was applied to parents/caregivers of children to measure OHRQoL. Statistical analysis included descriptive data analysis and one-way analysis of variance (ANOVA-One-Way) were performed to compare age groups with OHRQoL. Bootstrapping procedures (1000 re-samplings; 95%CI Bca) were performed. The mean scores of the 'Child Impact' section in the LAC was 4.0(±8.3), in the 'Family Impact' section was 2.0(±4.0), and in overall ECOHIS score was 6.0(±12.0). In the 'Child Impact' section, Argentina 10.0(+2.4) and Venezuela 17.8(±17.5) demonstrated mean scores higher than the LAC total data. In the 'Family Impact' section, the countries with higher mean scores were Argentina 4.9(±2.0), Ecuador 2.1(±3.1) and Venezuela 7.9(±7.8). In the overall ECOHIS score, Argentina 15.1 (±4.1) and Venezuela 25.7(±25.2) has higher mean scores than the values of LAC. There is an association between children's age and parents' report of impact on the OHRQoL (p<0.001). Three-year-olds had a higher mean when compared to one- and two-year-olds, both in the Impact on the Child and Impact on the Family (p<0.001) sections, as well as in the overall ECOHIS (p<0.001). In conclusion, there are differences in OHRQoL among Latin American countries, impacting older children more significantly.

A Breakthrough in Understanding the Pathogenesis of Molar Hypomineralisation: The Mineralisation-Poisoning Model.

Popularly known as "chalky teeth", molar hypomineralisation (MH) affects over 1-in-5 children worldwide, triggering massive amounts of suffering from toothache and rapid decay. MH stems from childhood illness and so offers a medical-prevention avenue for improving oral and paediatric health. With a cross-sector translational research and education network (The D3 Group; thed3group.org) now highlighting this global health opportunity, aetiological understanding is urgently needed to enable better awareness, management and eventual prevention of MH. Causation and pathogenesis of "chalky enamel spots" (i.e., demarcated opacities, the defining pathology of MH) remain unclear despite 100 years of investigation. However, recent biochemical studies provided a pathomechanistic breakthrough by explaining several hallmarks of chalky opacities for the first time. This article outlines these findings in context of previous understanding and provides a working model for future investigations. The proposed pathomechanism, termed "mineralisation poisoning", involves localised exposure of immature enamel to serum albumin. Albumin binds to enamel-mineral crystals and blocks their growth, leading to chalky opacities with distinct borders. Being centred on extracellular fluid rather than enamel-forming cells as held by dogma, this localising pathomechanism invokes a new type of connection with childhood illness. These advances open a novel direction for research into pathogenesis and causation of MH, and offer prospects for better clinical management. Future research will require wide-ranging inputs that ideally should be coordinated through a worldwide translational network. We hope this breakthrough will ultimately lead to medical prevention of MH, prompting global health benefits including major reductions in childhood tooth decay.

Pathogenesis of Molar Hypomineralisation: Aged Albumin Demarcates Chalky Regions of Hypomineralised Enamel.

Molar hypomineralisation (MH) is becoming globally recognised as a significant public health problem linked to childhood tooth decay. However, with causation and pathogenesis unclear after 100 years of investigation, better pathological understanding is needed if MH is to become preventable. Our studies have implicated serum albumin in an extracellular pathomechanism for chalky enamel, opposing longheld dogma about systemic injury to enamel-forming cells. Hypothesising that chalky enamel arises through developmental exposure to serum albumin, this study used biochemical approaches to characterise demarcated opacities from 6-year molars. Addressing contradictory literature, normal enamel was found to completely lack albumin subject to removal of surface contamination. Querying surface permeability, intact opacities were found to lack salivary amylase, indicating that "enamel albumin" had become entrapped before tooth eruption. Thirdly, comparative profiling of chalky and hard-white enamel supported a dose-response relationship between albumin and clinical hardness of opacities. Moreover, albumin abundance delineated chalky enamel from white transitional enamel at opacity borders. Finally, addressing the corollary that enamel albumin had been entrapped for several years, clear signs of molecular ageing (oxidative aggregation and fragmentation) were identified. By establishing aged albumin as a biomarker for chalky enamel, these findings hold methodological, clinical, and aetiological significance. Foremost, direct inhibition of enamel-crystal growth by albumin (here termed "mineralisation poisoning") at last provides a cogent explanation for the clinical presentation of demarcated opacities. Together, these findings justify pursuit of an extracellular paradigm for the pathogenesis of MH and offer exciting new prospects for alleviating childhood tooth decay through medical prevention of MH.

Pathogenesis of Molar Hypomineralisation: Hypomineralised 6-Year Molars Contain Traces of Fetal Serum Albumin.

Molar Hypomineralisation (MH) is gaining cross-sector attention as a global health problem, making deeper enquiry into its prevention a research priority. However, causation and pathogenesis of MH remain unclear despite 100 years of investigation into "chalky" dental enamel. Contradicting aetiological dogma involving disrupted enamel-forming cells (ameloblasts), our earlier biochemical analysis of chalky enamel opacities implicated extracellular serum albumin in enamel hypomineralisation. This study sought evidence that the albumin found in chalky enamel reflected causal events during enamel development rather than later association with pre-existing enamel porosity. Hypothesising that blood-derived albumin infiltrates immature enamel and directly blocks its hardening, we developed a "molecular timestamping" method that quantifies the adult and fetal isoforms of serum albumin ratiometrically. Applying this novel approach to 6-year molars, both isoforms of albumin were detectable in 6 of 8 chalky opacities examined (corresponding to 4 of 5 cases), indicating developmental acquisition during early infancy. Addressing protein survival, in vitro analysis showed that, like adult albumin, the fetal isoform (alpha-fetoprotein) bound hydroxyapatite avidly and was resistant to kallikrein-4, the pivotal protease involved in enamel hardening. These results shift primary attention from ameloblast injury and indicate instead that an extracellular mechanism involving localised exposure of immature enamel to serum albumin constitutes the crux of MH pathogenesis. Together, our pathomechanistic findings plus the biomarker approach for onset timing open a new direction for aetiological investigations into the medical prevention of MH.

Early-life sugar consumption and breastfeeding practices: a multicenter initiative in Latin America

Abstract The aim of this multicenter study was to explore the early-life sugar consumption and dietary practices in Latin America as well as to investigate the association between breastfeeding duration and the age at which foods and beverages with added sugars are introduced. A cross-sectional study was conducted with 805 1- to 3-year-old children from 10 Latin American countries, as a complementary study to the Research Observatory for Dental Caries of the Latin American Region (OICAL). A Food Frequency Questionnaire previously tested in different countries was applied to children's mothers and data on breastfeeding and age at introduction of sugary foods and beverages was collected. Statistical analysis included the Kruskal-Wallis test and Poisson regression with robust variance, with the calculation of crude and adjusted mean ratios (MR) and 95% of confidence intervals (CI). The average age at introduction of sugary foods and beverages was 10.1 months (95%CI 9.7-10.4) and 9.6 (95%CI 9.2-9.9) months, respectively, with a significant variation between countries (p < 0.001). The average daily frequency of sugary foods-beverages was 3.3 times per day (95%CI 3.1-3.5) and varied significantly between countries (p = 0.004). Breastfeeding duration of over six months was associated with an increase in the age of introduction of sweet drinks (16%; MR 1.16; 95%CI 1.05-1.28) and foods (21%; MR 1.21; 95%CI 1.10-1.33). In conclusion, most children from vulnerable settings in Latin America start consuming sugary products in the first year of life and a high frequency of consumption was reported through early childhood. Additionally, breastfeeding contributes to a delay in the introduction of sugary products.

Molar Hypomineralisation: A Call to Arms for Enamel Researchers.

Developmental dental defects (DDDs, hereafter "D3s") hold significance for scientists and practitioners from both medicine and dentistry. Although, attention has classically dwelt on three other D3s (amelogenesis imperfecta, dental fluorosis, and enamel hypoplasia), dental interest has recently swung toward Molar Hypomineralisation (MH), a prevalent condition characterised by well-delineated ("demarcated") opacities in enamel. MH imposes a significant burden on global health and has potential to become medically preventable, being linked to infantile illness. Yet even in medico-dental research communities there is only narrow awareness of this childhood problem and its link to tooth decay, and of allied research opportunities. Major knowledge gaps exist at population, case and tooth levels and salient information from enamel researchers has sometimes been omitted from clinically-oriented conclusions. From our perspective, a cross-sector translational approach is required to address these complex inadequacies effectively, with the ultimate aim of prevention. Drawing on experience with a translational research network spanning Australia and New Zealand (The D3 Group; www.thed3group.org), we firstly depict MH as a silent public health problem that is generally more concerning than the three classical D3s. Second, we argue that diverse research inputs are needed to undertake a multi-faceted attack on this problem, and outline demarcated opacities as the central research target. Third, we suggest that, given past victories studying other dental conditions, enamel researchers stand to make crucial contributions to the understanding and prevention of MH. Finally, to focus geographically diverse research interests onto this nascent field, further internationalisation of The D3 Group is warranted.

Impact on oral health-quality of life in infants: Multicenter study in Latin American countries

Abstract To assess the impact of oral conditions on oral health-related quality of life (OHRQoL) in infants in ten Latin America countries (LAC). A cross-sectional study was conducted with 930 pairs of 1-to-3-year-old children/parents from 10 LAC, as a complementary study of the Research Observatory for Dental Caries of the Latin American Region. The scale ECOHIS, previously tested and valid in ten countries, was applied to parents/caregivers of children to measure OHRQoL. Statistical analysis included descriptive data analysis and one-way analysis of variance (ANOVA-One-Way) were performed to compare age groups with OHRQoL. Bootstrapping procedures (1000 re-samplings; 95%CI Bca) were performed. The mean scores of the 'Child Impact' section in the LAC was 4.0(±8.3), in the 'Family Impact' section was 2.0(±4.0), and in overall ECOHIS score was 6.0(±12.0). In the 'Child Impact' section, Argentina 10.0(+2.4) and Venezuela 17.8(±17.5) demonstrated mean scores higher than the LAC total data. In the 'Family Impact' section, the countries with higher mean scores were Argentina 4.9(±2.0), Ecuador 2.1(±3.1) and Venezuela 7.9(±7.8). In the overall ECOHIS score, Argentina 15.1 (±4.1) and Venezuela 25.7(±25.2) has higher mean scores than the values of LAC. There is an association between children's age and parents' report of impact on the OHRQoL (p<0.001). Three-year-olds had a higher mean when compared to one- and two-year-olds, both in the Impact on the Child and Impact on the Family (p<0.001) sections, as well as in the overall ECOHIS (p<0.001). In conclusion, there are differences in OHRQoL among Latin American countries, impacting older children more significantly.

Resumo Avaliar o impacto das condições bucais na qualidade de vida relacionada à saúde bucal (QVRSB) em crianças de dez países da América Latina (AL). Foi realizado um estudo transversal com 930 pares de crianças/pais de 1 a 3 anos de 10 países da AL, como estudo complementar do Research Observatory for Dental Caries of the Latin American Region. A escala ECOHIS, previamente testada e validada em dez países, foi aplicada a pais/cuidadores de crianças para mensurar a QVRSB. A análise estatística incluiu análise descritiva de dados e análise de variância unidirecional (ANOVA-One-Way) para comparar grupos etários com QVRSB. Procedimentos de bootstrapping (1000 reamostragens; 95%IC Bca) foram realizados. A pontuação média da seção 'Impacto na Criança' na AL foi 4,0 (±8,3), na seção 'Impacto na Família' foi 2,0 (±4,0) e no escore total do ECOHIS foi 6,0 (±12,0). Na seção 'Impacto na Criança', Argentina 10,0(+2,4) e Venezuela 17,8(±17,5) demonstraram pontuações médias superiores aos dados totais da AL. Na seção 'Impacto na Família', os países com pontuações médias mais altas foram Argentina 4,9(±2,0), Equador 2,1(±3,1) e Venezuela 7,9(±7,8). No escore total do ECOHIS, Argentina 15,1 (±4,1) e Venezuela 25,7(±25,2) apresentaram escores médios superiores aos valores de AL. Houve associação entre a idade das crianças e o relato dos pais de impacto na QVRSB (p<0,001). As crianças de três anos tiveram média maior quando comparadas às de um e dois anos, tanto nas seções 'Impacto na Criança' e 'Impacto na Família' (p<0,001), quanto no escore total ECOHIS (p<0,001). Em conclusão, houveram diferenças na QVRSB entre os países da América Latina, impactando de forma mais significativa as crianças mais velhas.

Creación de un Currículo de Competencias en Cariología para Estudiantes de Pregrado de Odontología en Chile / Development of a Competency-based Curriculum in Cariology for Undergraduate Dental Students in Chile

RESUMEN: Objetivo: Creación de un currículo de competencias mínimas en Cariología, para la formación de los Cirujano-Dentistas egresados de las escuelas de Odontología de Chile. Metodologías: A partir de una reunión de académicos de las Universidades de Talca y de Chile (año 2011), se elaboró una propuesta de currículo inicial, basado en los dominios propuestos por la Unión Europea (Schulte AG y cols). Durante el año 2016, dicha propuesta fue analizada mediante diálogos digitales y grupos de trabajo, con la participación del 96% de las Escuelas de Odontología existentes en el país, que concluyeron en un documento intermedio. Este documento fue analizado, discutido y perfeccionado durante el Taller para el Desarrollo de un Currículo de Competencias Mínimas en Cariología para las Escuelas de Odontología Chilenas (22/Mayo/2017, Talca, organizado por la Universidad de Talca y la Universidad de Chile) con la asistencia de representantes del 96% de las escuelas dentales chilenas, Ministerio de Salud de Chile, Colegio de Cirujano-Dentistas de Chile y con la asesoría de los profesores de Cariología Dres. Margherita Fontana y Carlos González-Cabezas (Universidad de Michigan, Ann Arbor, EEUU). Cada grupo de trabajo revisó el documento y envió nuevos comentarios, los que fueron incorporados en el documento final por una comisión asesora. Resultados: El documento del Currículo en Cariología se organizó en 5 Dominios: 1. Conocimientos base; 2. Determinación de Riesgo, diagnóstico de caries y detección de lesiones de caries; 3. Toma de decisiones y manejo preventivo no operatorio; 4. Toma de decisiones y manejo operatorio y 5. Cariología basada en la evidencia, en la práctica clínica y de salud pública. Se consensuaron las definiciones operacionales, las competencias principales y las sub-competencias para cada uno de los dominios. Las sub-competencias fueron clasificadas en tres niveles: A: Ser competente en; B: Tener conocimientos sobre y C: Estar familiarizado con. El documento final fue enviado a todos los participantes del taller para su aprobación y difusión en cada una de las instituciones involucradas. Conclusiones: Se logró, por medio de consenso, la construcción del Currículo de Competencias mínimas en Cariología para estudiantes de pregrado de Odontología en las universidades chilenas.

ABSTRACT: Objective: Development of a minimum set of competencies in Cariology that every dentist graduated from a Dental School in Chile must have. Methodology: Starting from a meeting of scholars from the Universities of Talca and Chile (year 2011), an initial proposal for a curriculum was developed, based on the domains proposed by the European Cariology Curriculum (Schulte, et al, 2011). During 2016, this proposal was discussed through online dialogues and working groups, with the participation of 95.2% of the Chilean dental schools, which resulted in an intermediate document. This document was analyzed, discussed and refined during the Workshop for the Development of a Curriculum of Minimum Competencies in Cariology for Chilean Dental Schools (May 22, 2017, Talca, organized by the Universities of Talca and Chile) with the attendance of representatives from 95.2% of the Chilean dental schools, the Chilean Ministry of Health, Chilean College od Dentists and with the assistance of the professors of Cariology Margherita Fontana and Carlos González-Cabezas (University of Michigan, Ann Arbor, USA). Each working group revised the document and provided feedback, which was incorporated in the final document by an advisory committee, elected on the day of the workshop, including the authors of the present article. Results: The Cariology Curriculum was organized in 5 Domains: 1. Basic knowledge; 2. Risk assessment, caries diagnosis and caries lesion detection; 3. Decision-making and non-operative preventive treatment; 4. Decision making and operative treatment; and 5. Evidence-based, clinical and public health practice. Operational definitions, main competencies and sub-competencies for each domain were agreed. Sub-competencies were classified into three levels: A: Be competent in; B: Have knowledge about, and C: Be familiar with. The final document was sent to all the participants of the workshop for dissemination in each of the institutions involved. Conclusions: The development of the Competency-based Curriculum in Cariology for undergraduate dental students at Chilean universities was achieved through consensus.

Modified glass ionomer and orthodontic band: an interim alternative for the treatment of molar incisor hypomineralization: a case report

Introduction: Molar incisor hypomineralization (MIH) is a developmental condition resulting in defects in the enamel characterized by demarcated opacities mainly affecting first permanent molars and occasionally permanent incisors in 1 of every 6 children worldwide. Affected molars have greater susceptibility to post eruptive breakdown, extensive caries and, in severe cases, are difficult to restore. When the MIH-affected molar presents severe crown destruction, it is necessary to perform an intermediate restoration to preserve the remaining dental structure in order to maintain occlusion, proper hygiene and periodontal health. The case of an 11-year-old patient with severe MIH is reported. The patient had extensive crown destruction by caries in tooth 1.6 without clinical or radiographic signs of pulp pathology. After an initial preventive intervention, enamel without dentin support and carious dentin were removed from tooth 1.6. Subsequently, crown restoration was performed with resin-modified glass ionomer, followed by the cementation of an orthodontic band. After 18 months of follow-up, the patient reported no pain or discomfort. The restoration was preserved intact, maintaining occlusal functionality, pulp and gingival health. Conclusion: The interim treatment, cementing an orthodontic band over a tooth restored with glass ionomer seems to favor retention and compressive strength, keeping the MIH-affected molar asymptomatic for at least 18 months. Further studies evaluating this treatment option in similar clinical situations are recommended.

Características de la oclusión dentaria en niños de 4 y 5 años / Characteristic of the occlusion in 4 and 5 years children

Se realizó un estudio observacional, descriptivo y transversal de los 86 niños de 4 y 5 años de edad, pertenecientes al quinto y sexto años de vida del Círculo Infantil Ana de Quesada de Santiago de Cuba, de octubre del 2015 a marzo del 2016, a fin de caracterizarles en cuanto a la oclusión dentaria. En la serie se obtuvo que al menos 17,4 por ciento de los niños examinados presentaban alteración en la oclusión permanente respecto a la relación de los molares temporales, con más frecuencia del sobrepase de media corona (31,4 por ciento) y menos reiteración de la oclusión de los dientes de borde a borde (con solo 9 niños). Por último, pudo concluirse que 46,6 por cientode los párvulos presentó una oclusión anómala

An observational, descriptive and cross-sectional study of the 86 4 and 5 years old children, belonging to the fifth and sixth years from Ana de Quesada child day care center in Santiago de Cuba was carried out from October, 2015 to March, 2016, in order to characterize them as for their occlusions. In the series it was obtained that at least 17,4 percent of the examined children presented changes in the permanent occlusion regarding the relationship of the temporary molars, with more frequency of the overbite of half crown (31,4 percent) and less reiteration of the occlusion of border to border teeth (just in 9 children). Lastly, it could be concluded that 46,6 percent of the children presented an anomalous occlusion

Inyección de sustancias esclerosantes vasculares en el manejo de lesiones vasculares orbitarias / Injection of vascular sclerosing agent in the treatment of orbital vascular lesions

Objetivo: Evaluar el efecto de la inyección de espuma de polidocanol como sustancia esclerosante vascular en la reducción del tamaño de hemangiomas y linfangiomas orbitarios. Material y Métodos: Estudios prospectivo intervencional de 2 casos con diagnóstico de hemangioma capilar, 7 casos de linfangioma de la región orbitaria y 1 malformación vascular superficial preseptal, que recibieron una o más inyecciones de polidocanol intralesional. Se evaluaron el tipo de tumor, disminución de su tamaño, variación de ptosis palpebral, proptosis y presencia de complicaciones con el procedimiento. Resultados: Se realizaron 4,5 inyecciones promedio con una dosificación final de 0,6 cc al 0,5 por ciento de polidocanol. El seguimiento promedio fue 16,2 meses. Todos los pacientes redujeron el tamaño de la lesión significativamente. La principal complicación fue dolor postinyección. Conclusiones: El uso de inyecciones de polidocanol en el tratamiento de hemangiomas capilares y linfangiomas orbitarios sería una alternativa novedosa y efectiva para reducir el tamaño de las lesiones sin mayores complicaciones.