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1.  Prenatal Exposure to Antiepileptic Drugs and Dental Agenesis 
PLoS ONE  2014;9(1):e84420.
Objective
The aim of the study was to investigate the association between prenatal exposure to AEDs and the risk of dental agenesis and to differentiate between the possible effects of the different drugs used.
Methods
Data on 214 exposed and 255 unexposed children, aged 12–18 years, were extracted from the Prescription Database of the Central Denmark Region and North Denmark Region and the Danish Medical Birth Registry. The children's dental charts were examined for the presence of dental agenesis.
Results
Overall, children exposed to AED in utero had an increased risk of developing dental agenesis, but as a group, the difference was not significant (OR = 1.7; [95% CI: 0.8–3.6]). The risk of developing dental agenesis was three-fold increased (OR = 3.1; [95% CI: 1.3–7.4]) in children exposed to valproate in mono- or in poly-therapy with other AEDs than carbamazepine or oxcarbazepine. The risk was further increased (OR = 11.2; [95% CI: 2.4–51.9]) in children exposed to valproate and carbamazepine or oxcarbazepine in combination.
Conclusions
The present study shows that dental agenesis is a potential congenital abnormality that is related to prenatal exposure to valproate, and dental agenesis may be considered a sensitive marker for the teratogenicity of valproate.
doi:10.1371/journal.pone.0084420
PMCID: PMC3885552  PMID: 24416231
2.  Cytolethal Distending Toxin in Isolates of Aggregatibacter actinomycetemcomitans from Ghanaian Adolescents and Association with Serotype and Disease Progression 
PLoS ONE  2013;8(6):e65781.
Background and Objectives
The cytolethal distending toxin (Cdt) is a highly conserved exotoxin that are produced by a number of Gram negative bacteria, including Aggregatibacter actinomycetemcomitans, and affects mammalian cells by inhibiting cell division and causing apoptosis. A complete cdt-operon is present in the majority of A. actinomycetemcomitans, but the proportion of isolates that lack cdt-encoding genes (A, B and C) varies according to the population studied. The objectives of this study were to examine serotype, Cdt-genotype, and Cdt-activity in isolates of A. actinomycetemcomitans collected from an adolescent West African population and to examine the association between the carrier status of A. actinomycetemcomitans and the progression of attachment loss (AL).
Materials and Methods
A total of 249 A. actinomycetemcomitans isolates from 200 Ghanaian adolescents were examined for serotype and cdt-genotype by PCR. The activity of the Cdt-toxin was examined by DNA-staining of exposed cultured cells and documented with flow cytometry. The periodontal status of the participants was examined at baseline and at a two-year follow-up.
Results
Presence of all three cdt-encoding genes was detected in 79% of the examined A. actinomycetemcomitans isolates. All these isolates showed a substantial Cdt-activity. The two different cdt-genotypes (with and without presence of all three cdt-encoding genes) showed a serotype-dependent distribution pattern. Presence of A. actinomycetemcomitans was significantly associated with progression of AL (OR = 5.126; 95% CI = [2.994–8.779], p<0.001).
Conclusion
A. actinomycetemcomitans isolated from the Ghanaian adolescents showed a distribution of serotype and cdt-genotype in line with results based on other previously studied populations. Presence of A. actinomycetemcomitans was significantly associated with disease progression, in particular the b serotype, whereas the association with disease progression was not particularly related to cdt-genotype, and Cdt-activity.
doi:10.1371/journal.pone.0065781
PMCID: PMC3683020  PMID: 23922633
3.  Developmental Enamel Defects in Children Prenatally Exposed to Anti-Epileptic Drugs 
PLoS ONE  2013;8(3):e58213.
Objective
Some anti-epileptic drugs (AED) have well-known teratogenic effects. The aim of the present study was to elucidate the effect of prenatal exposure to AED and the risk of enamel defects in the primary and permanent dentition.
Methods
A total of 38 exposed and 129 non-exposed children, 6–10 years of age, were recruited from the Aarhus Birth Cohort and the Department of Neurology, Viborg Regional Hospital, Denmark. Medication during pregnancy was confirmed by the Danish Prescription Database. All children had their teeth examined and outcomes in terms of enamel opacities and enamel hypoplasia were recorded.
Results
Children prenatally exposed to AED have an increased prevalence of enamel hypoplasia (11% vs. 4%, odds ratio (OR) = 3.6 [95% confidence interval (CI): 0.9 to 15.4]), diffuse opacities (18% vs. 7%, OR = 3.0; [95% CI: 1.0 to 8.7, p<0.05]), and numerous (>3) white opacities (18% vs. 10%, OR = 2.2; [95% CI: 0.8 to 6.1]) in the primary dentition. In the permanent dentition, an increased risk of numerous (>3) white opacities (34% vs. 12%, OR = 3.3; [95% CI: 1.3 to 8.4]) was found.
Conclusions
The present study shows that children prenatally exposed to AED have an increased risk of developing numerous teeth with white opacities in their primary and permanent dentition. In addition, they also have an increased risk of developing diffuse opacities and enamel hypoplasia in their primary teeth.
doi:10.1371/journal.pone.0058213
PMCID: PMC3592922  PMID: 23520494
4.  Interactions of extracts from selected chewing stick sources with Aggregatibacter actinomycetemcomitans 
BMC Research Notes  2012;5:203.
Background
Aggregatibacter actinomycetemcomitans produces a leukotoxin that activates a pro-inflammatory death of human monocytes/macrophages. A specific clone of this bacterium (JP2) has a 530-base pair deletion in the leukotoxin promoter gene and significantly enhanced expression of leukotoxin. This specific clone of A. actinomycetemcomitans is common in some African populations and has a strong association with periodontal attachment loss in adolescents in these populations. Chewing sticks of plant origin are commonly used as oral hygiene tool in Africa, but their role as a therapeutic agent in periodontal disease is poorly investigated.
Results
Ethanol extracts were made from 7 common plants used as chewing sticks in West-Africa. None of the tested extracts inhibited growth of A. actinomycetemcomitans. However, extracts from Psidium guajava (Guava) completely neutralized the cell death and pro-inflammatory response of human leukocytes induced by the leukotoxin. None of the six other tested chewing stick extracts showed this effect.
Conclusions
The discovery that extracts from Guava efficiently neutralizes A. actinomycetemcomitans leukotoxicity might lead to novel therapeutic agents and strategies for prevention and treatment of aggressive forms of periodontitis induced by infections with the highly leukotoxic JP2 clone of this bacterium.
doi:10.1186/1756-0500-5-203
PMCID: PMC3393612  PMID: 22537711
5.  Development of Danish version of child oral-health-related quality of life questionnaires (CPQ8–10 and CPQ11–14) 
BMC Oral Health  2009;9:11.
Background
The Child Perceptions Questionnaire (CPQ) is a self-reported questionnaire developed to measure oral health-related quality of life in children. The CPQ aims to improve the description of children's oral health, while taking into consideration the importance of psychological aspects in the concept of health. The CPQ exists in two versions: the CPQ8–10 for children aged 8–10 years and the CPQ11–14 for those aged 11–14 years. The aim of this study was to develop a Danish version of the CPQ8–10 and the CPQ11–14 and to evaluate its validity for use among Danish-speaking children.
Methods
The instruments were translated from English into Danish in accordance with a recommended translation procedure. Afterwards, they were tested among children aged 8–10 (n = 120) and 11–14 years (n = 225). The validity was expressed by the correlation between overall CPQ scores and i) self-reported assessment of the influence of oral conditions on everyday life (not at all, very little, some, a lot, very much) and ii) the self-reported rating of oral health. Furthermore, groups of children with assumed decreased oral health-related quality of life were compared with children with healthy oral conditions. Finally, we examined the internal consistency.
Results
The correlation between overall CPQ scores and global assessments of the influence of oral conditions on everyday life showed Spearman correlation coefficients of 0.45, P < 0.001 for CPQ8–10 and 0.50, P < 0.001 for CPQ11–14. The correlation between overall CPQ scores and the self-reported rating of oral health showed Spearman correlation coefficients of 0.45, P < 0.001 for CPQ8–10 and 0.17, P = 0.010 for CPQ11–14.
The median overall CPQ8–10 scores were 7 for individuals with healthy oral conditions, 5 for individuals with cleft lip and palate, and 15 for individuals with rare oral diseases. The median overall CPQ11–14 scores were 9 for individuals with healthy oral conditions, 9 for individuals with cleft lip and palate, 17.0 for individuals with rare oral diseases, and 22.0 for individuals with fixed orthodontic appliances. There were statistically significant differences between the groups of children with healthy oral conditions and each of the subgroups, except for children with cleft lip and palate.
Chronbach'α were 0.82 for CPQ8–10 and 0.87 for CPQ11–14.
Conclusion
The results of this study reveal that the Danish CPQ8–10 and CPQ11–14, seem to be valid instruments for measuring oral health-related quality of life in children although its ability to discriminate between children with cleft lip and palate and healthy children seem to be limited.
doi:10.1186/1472-6831-9-11
PMCID: PMC2679003  PMID: 19383176
6.  Novel Loop-Mediated Isothermal Amplification Method for Detection of the JP2 Clone of Aggregatibacter actinomycetemcomitans in Subgingival Plaque▿  
Journal of Clinical Microbiology  2007;46(3):1113-1115.
We developed a loop-mediated isothermal amplification method that detects the JP2 clone of Aggregatibacter actinomycetemcomitans, which induces aggressive periodontitis in adolescents of North and West African descents. Being independent of special equipment, this specific and sensitive method offers significant advantages for screening of patients on a population basis and in clinical settings.
doi:10.1128/JCM.02107-07
PMCID: PMC2268348  PMID: 18160448
7.  Microevolution and Patterns of Dissemination of the JP2 Clone of Aggregatibacter (Actinobacillus) actinomycetemcomitans▿  
Infection and Immunity  2007;75(6):3080-3088.
The natural history, microevolution, and patterns of interindividual transmission and global dissemination of the JP2 clone of Aggregatibacter (Actinobacillus) actinomycetemcomitans were studied by population genetic analysis. The JP2 clone is strongly associated with aggressive periodontitis in adolescents of African descent and differs from other clones of the species by several genetic peculiarities, including a 530-bp deletion in the promoter region of the leukotoxin gene operon, which results in increased leukotoxic activity. Multilocus sequence analysis of 82 A. actinomycetemcomitans strains, 66 of which were JP2 clone strains collected over a period of more than 20 years, confirmed that there is a clonal population structure with evolutionary lineages corresponding to serotypes. Although genetically highly conserved, as shown by alignment of sequences of eight housekeeping genes, strains belonging to the JP2 clone had a number of point mutations, particularly in the pseudogenes hbpA and tbpA. Characteristic mutations allowed isolates from individuals from the Mediterranean area and from West Africa, including the Cape Verde Islands, to be distinguished. The patterns of mutations indicate that the JP2 clone initially emerged as a distinct genotype in the Mediterranean part of Africa approximately 2,400 years ago and subsequently spread to West Africa, from which it was transferred to the American continents during the transatlantic slave trade. The sustained exclusive colonization of individuals of African descent despite geographical separation for centuries suggests that the JP2 clone has a distinct host tropism. The colonization of family members by JP2 clone strains with unique point mutations provides strong evidence that there is intrafamilial transmission and suggests that dissemination of the JP2 clone is restricted to close contacts.
doi:10.1128/IAI.01734-06
PMCID: PMC1932881  PMID: 17353281
8.  Improved PCR for Detection of the Highly Leukotoxic JP2 Clone of Actinobacillus actinomycetemcomitans in Subgingival Plaque Samples 
Journal of Clinical Microbiology  2003;41(10):4829-4832.
The JP2 clone of Actinobacillus actinomycetemcomitans is associated with early-onset periodontitis in certain ethnic populations of African origin. Here, we describe and evaluate a set of primers for PCR to assay for the presence of A. actinomycetemcomitans and to discriminate between JP2-like strains and other genotypes in subgingival plaque samples.
doi:10.1128/JCM.41.10.4829-4832.2003
PMCID: PMC254341  PMID: 14532234

Results 1-8 (8)