Nicky Kilpatrick

Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence

Pierre Robin sequence (PRS) is an important subgroup of cleft palate. We report several lines of evidence for the existence of a 17q24 locus underlying PRS, including linkage analysis results, a clustering of translocation breakpoints 1.06–1.23 Mb upstream of SOX9, and microdeletions both ∼1.5 Mb centromeric and ∼1.5 Mb telomeric of SOX9. We have also identified a heterozygous point mutation in an evolutionarily conserved region of DNA with in vitro and in vivo features of a developmental enhancer. This enhancer is centromeric to the breakpoint cluster and maps within one of the microdeletion regions. The mutation abrogates the in vitro enhancer function and alters binding of the transcription factor MSX1 as compared to the wild-type sequence. In the developing mouse mandible, the 3-Mb region bounded by the microdeletions shows a regionally specific chromatin decompaction in cells expressing Sox9. Some cases of PRS may thus result from developmental misexpression of SOX9 due to disruption of very-long-range cis-regulatory elements.

Micro-mechanical characterisation of the properties of primary tooth dentine

OBJECTIVES Understanding the mechanical properties of dentine is of importance as adhesive restorative materials mainly achieve their bonding to the tooth structure through dentine. The current study measures the hardness and modulus of elasticity of primary molar dentine using an Ultra-Micro-Indentation System (UMIS), which allows the dentine to remain hydrated and thus is assumed to be closer to the in vivo conditions. METHODS Eight sound primary molar teeth were axially sectioned, embedded in resin and fine polished. Two linear arrays of indentations were done on coronal dentine, from the pulp wall to dentino-enamel junction (DEJ) parallel to the tubule direction under a force load of 25mN. RESULTS The mean hardness and elastic modulus of the dentine nearest the pulp wall was 0.52+/-0.24 and 11.59+/-3.95GPa, respectively, which was significantly lower than those of dentine in the middle area, which was 0.85+/-0.19 and 17.06+/-3.09GPa, respectively, and the dentine nearest DEJ, which was 0.91+/-0.15 and 16.33+/-3.83GPa, respectively. There is a statistically significant linear correlation between the hardness and modulus of elasticity. CONCLUSIONS The hardness and modulus of elasticity of dentine decreases with decreasing distance from the pulp. This is of importance to clinicians because an extension of cavity preparation towards the pulp may lead to less mechanical support for a restoration.

Body mass index and dental caries in children and adolescents: a systematic review of literature published 2004 to 2011

The objectiveThe authors undertook an updated systematic review of the relationship between body mass index and dental caries in children and adolescents.MethodThe authors searched Medline, ISI, Cochrane, Scopus, Global Health and CINAHL databases and conducted lateral searches from reference lists for papers published from 2004 to 2011, inclusive. All empirical papers that tested associations between body mass index and dental caries in child and adolescent populations (aged 0 to 18 years) were included.ResultsDental caries is associated with both high and low body mass index.ConclusionA non-linear association between body mass index and dental caries may account for inconsistent findings in previous research. We recommend future research investigate the nature of the association between body mass index and dental caries in samples that include a full range of body mass index scores, and explore how factors such as socioeconomic status mediate the association between body mass index and dental caries.

Characterisation of tribochemically assisted bonding of composite resin to porcelain and metal

OBJECTIVE The fracture of bonded ceramic to metal restorations remains a problem in clinical dental practice. The use of resin based composites to repair such fractures is generally unsatisfactory. Tribochemical technology creates a surface layer of small silica particles fused to the surface substrate. Such a layer potentially improves adhesion of resin to both alloy and porcelain. Adhesion between two substrates is traditionally studied using shear or tensile bond strength tests. However, the highest stress at bond failure may not represent the real bonding characteristics correctly. An alternative method is to describe the bonding characteristics by determining the strain energy release rate for a given interface. This study compares the bonding characteristics of a resin to gold/porcelain interface using a tribochemical coating process with those of a control group using simple gritblasting. METHODS Pre-cracked specimens were subjected to load-unload cycles using a simple four point bending test and the resultant strain energy release rates were calculated. RESULTS Tribochemically pretreating the porcelain resulted in a significant increase in the resultant strain energy release rate from 42.72+/-3.65J/m(2) for the controls to 61.35+/-6.26J/m(2). Likewise there was a significant improvement in the strain energy release rate for the gold/composite interface from 27.31+/-3.00J/m(2) to 42.13+/-4.83J/m(2). CONCLUSIONS Tribochemical technology offers significant potential advantages for clinical dental practice.

A Prospective, Longitudinal Study of Feeding Skills in a Cohort of Babies With Cleft Conditions

Objective: To examine the natural history of feeding skills in babies with clefts and identify risk factors and predictors of poor feeding. Participants: Sixty-two babies with clefts were examined at 2 weeks, 3 months, and 14 months of age. Main Outcome Measures: Feeding ability, oral motor function, and feeding efficiency were assessed. Univariate analyses were used to determine whether oral motor function and sequelae varied according to feeding ability or cleft condition. Multivariable logistic regressions were used to determine risk factors for poor feeding. Results: Poor feeding skills were detected in one third of newborns. The prevalence of poor feeding reduced to 19% at 3 months of age and 15% at 14 months of age. Oral motor dysfunction and sequelae (particularly nasal regurgitation) were more commonly observed in babies with poor feeding skills irrespective of comorbidity. The main risk factor for poor feeding was a diagnosis of syndrome or Pierre Robin sequence (PRS). At 2 weeks of age, babies with syndrome or PRS were 15 times more likely to have poor feeding skills than their nonsyndromic counterparts. When syndrome or PRS was controlled for, babies with cleft palate and cleft lip and palate were equally likely to have poor feeding skills. Parental report of feeding efficiency was predictive of poor feeding in young babies. Conclusions: Poor feeding skills are relatively common in newborns with cleft palate and cleft lip and palate. Treatment for feeding problems may be needed beyond the first year of life, especially for babies born with PRS or a syndrome.

Sucking performance of babies with cleft conditions

Objective: To describe the sucking performance of bottle-fed babies with cleft conditions. Participants: Forty 2-week-old-babies with cleft lip (CL; n = 8), cleft palate (CP; n = 22), and cleft lip and palate (CLP; n = 10) were examined. Methods: Suction, compression, and other sucking parameters were measured during bottle-feeding and compared to determine if they varied with cleft condition or feeding ability. Results: All babies with CL and one with CLP demonstrated suction. Thirteen of 22 babies with CP demonstrated suction but only three maintained regular pressure changes over time. Between-group differences in the amplitude of suction and compression were associated with cleft condition. Cleft lip participants demonstrated the greatest amplitude of suction followed by those with CP and CLP. Cleft lip and CP participants generated similar amplitudes of compression. This was greater than their counterparts with CLP. Good feeders (n = 15) generated high levels of suction, while satisfactory (n = 15) and poor feeders (n = 10) did not generate any during bottle-feeding. Conclusion: Between-group differences in intra-oral pressures were confirmed when babies were examined by cleft condition. Babies with smaller clefts (i.e., CL or minor soft palate clefts) were more likely to generate normal levels of suction and compression compared to their counterparts with larger clefts. Since good feeders were more likely to have smaller clefts it was not surprising that they demonstrated higher suction pressures than babies with satisfactory or poor feeding ability. Compression values were not significantly different across the feeding ability groups. These data may inform feeding management strategies.

Surface Integrity Governs the Proteome of Hypomineralized Enamel

Growing interest in the treatment and prevention of Molar/Incisor Hypomineralization (MIH) warrants investigation into the protein composition of hypomineralized enamel. Hypothesizing abnormality akin to amelogenesis imperfecta, we profiled proteins in hypomineralized enamel from human permanent first molars using a biochemical approach. Hypomineralized enamel was found to have from 3- to 15-fold higher protein content than normal, but a near-normal level of residual amelogenins. This distinguished MIH from hypomaturation defects with high residual amelogenins (amelogenesis imperfecta, fluorosis) and so typified it as a hypocalcification defect. Second, hypomineralized enamel was found to have accumulated various proteins from oral fluid and blood, with differential incorporation depending on integrity of the enamel surface. Pathogenically, these results point to a pre-eruptive disturbance of mineralization involving albumin and, in cases with post-eruptive breakdown, subsequent protein adsorption on the exposed hydroxyapatite matrix. These insights into the pathogenesis and properties of hypomineralized enamel hold significance for prevention and treatment of MIH.

Developmental and genetic perspectives on Pierre Robin sequence

Pierre Robin sequence (PRS) is a craniofacial anomaly comprising mandibular hypoplasia, cleft secondary palate and glossoptosis leading to life‐threatening obstructive apnea and feeding difficulties during the neonatal period. The respiratory issues require careful management and in severe cases may require extended stays in neonatal intensive care units and surgical intervention such as lengthening the lower jaw or tracheotomy to relieve airway obstruction. These feeding and respiratory complications frequently continue well into childhood, affecting not only growth and development but also impacting on long term educational attainment. The diagnosis of PRS depends on readily recognizable clinical features but the phenotypic similarity of many PRS individuals conceals considerable etiological heterogeneity. Defects in the growth of the mandible sit at the core of PRS and the natural history of PRS can be classified into two major streams: primary defects of mandibular outgrowth and elongation and issues that are external to the mandibular skeleton but that secondarily impact on its growth. These altered developmental trajectories appear to be driven by a range of influences including defects in cartilage growth, neuromuscular function and fetal constraint. Various genetic and cytogenetic associations have been made with PRS and the diversity of these associations highlights the fact that there are numerous ways to arrive at this common phenotypic endpoint.

Molar incisor hypomineralization: a survey of members of the Australian and New Zealand Society of Paediatric Dentistry

BACKGROUND Worldwide, molar incisor hypomineralization (MIH) affects a substantial number of children and impacts greatly on treatment need and dental anxiety, yet there is little information regarding its prevalence, aetiology, presentation and management. The aims of this survey were to assess awareness and perceptions of the Australian paediatric dental community concerning MIH, and to describe current treatment strategies. METHODS A questionnaire, based upon a previous European study, was sent to all Australian members of the Australian and New Zealand Society of Paediatric Dentistry. The questionnaire sought information on clinical experience of MIH, knowledge of prevalence, aetiology and contemporary management strategies for MIH. RESULTS One hundred and thirty useable responses were received (58.8 per cent response rate) of which 36 were paediatric dentists, 6 paediatric dentistry postgraduate students, 59 general dentists, 14 dental therapists and 14 specialists in other fields. Most (98.5 per cent) respondents were familiar with MIH and encountered it in their practice. The majority (73.1 per cent) estimated that MIH occurred in between 5 to 25 per cent of their clinical practice and almost all (96.9 per cent) considered it to be a clinical problem. Only 16.9 per cent of respondents were aware of existing prevalence data and 96.9 per cent valued investigating the prevalence of MIH. No consensus existed regarding the aetiology of MIH or its restorative management. Paediatric dentists used preformed crowns significantly more than non-specialists, however glass ionomer cements were popular with all groups. CONCLUSIONS MIH is a well recognized and widely encountered clinical condition. MIH presents several clinical problems and is worthy of further investigation. Currently, no consistent clinical management strategies are utilized.

Etiology of molar incisor hypomineralization – A systematic review

OBJECTIVES Molar incisor hypomineralization (MIH) is a common developmental dental defect of permanent teeth, which can increase the risk of dental caries, infection and hospitalization. The etiology is currently unclear although prenatal or early childhood health factors are suspected. The aim of this systematic review was to assess the strength of evidence linking etiological factors with MIH. METHODS A systematic search was conducted using the Medline and Embase electronic databases for studies investigating environmental etiological factors of MIH. Two reviewers assessed the eligibility of studies. The level of evidence and bias was determined for all eligible studies according to Australian National Health and Medical Research Council guidelines for systematic reviews of etiology and the Newcastle-Ottawa Scale. RESULTS From a total of 2254 studies identified through electronic and hand searching, 28 were eligible for inclusion. Twenty-five of these investigated MIH and three investigated a related condition in primary teeth, hypomineralized second primary molars (HSPM), and these were analysed separately. A limited number of studies reported significant associations between MIH and pre- and perinatal factors such as maternal illness and medication use in pregnancy, prematurity and birth complications. Early childhood illness was implicated as an etiological factor in MIH in several studies, in particular fever, asthma and pneumonia. The studies investigating HSPM revealed an association with maternal alcohol consumption, infantile fever and ethnicity. However, the validity of these findings is impaired by study design, lack of adjustment for confounders, lack of detail and consistency of exposures investigated and poor reporting. CONCLUSIONS Childhood illness is likely to be associated with MIH. Further prospective studies of the etiology of MIH/HSPM are needed.