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Aim: Periodontitis (PD) is influenced by genetic as well as lifestyle and socio-economic factors. Epidemiological studies show that men are at greater risk of severe forms of PD, suggesting interplay between sex and genetic factors. We aimed to systematically analyse patients with aggressive periodontitis (AgP) for gene-sex interactions., Materials and Methods: Three hundred and twenty-nine German AgP cases and 983 controls were genotyped with Affymetrix 500K Arrays and were analysed by logistic regression analysis. The most significant gene-sex interaction was replicated in an independent sample of 382 German/Austrian AgP cases and 489 controls., Results: Ten single-nucleotide polymorphisms (SNPs) in strong linkage disequilibrium (r(2)  > 0.85) upstream the gene neuropeptide Y (NPY) suggested gene-sex interaction (p < 5 × 10(-5) ). SNP rs198712 showed the strongest association in interaction with sex (p = 5.4 × 10(-6) ) with odds ratios in males and females of 1.63 and 0.69 respectively. In the replication, interaction of sex with rs198712 was verified with p = 0.022 (pooled p = 4.03 × 10(-6) ) and similar genetic effects. Analysis of chromatin elements from ENCODE data revealed tissue-specific transcription at the associated non-coding region., Conclusion: This study is the first to observe a sexually dimorphic role of alleles at NPY in humans and support previous genome-wide findings of a role of NPY in severe PD., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: Epidemiological and clinical studies indicated a relationship of periodontitis with rheumatoid arthritis (RA). We aimed to identify shared genetic susceptibility loci of RA and periodontitis., Materials and Methods: Forty-seven risk genes of genome-wide significance of RA and SLE were genotyped in a German case-control sample of aggressive periodontitis (AgP), using Immunochip genotyping arrays (Illumina, 600 cases, 1440 controls) and Affymetrix 500 K Genotyping Arrays (280 cases and 983 controls). Significant associations were replicated in 168 Dutch AgP cases and 679 controls and adjusted for the confounders smoking and sex., Results: Variants at IRF5 and PRDM1 showed association with AgP. Upon covariate adjustment for smoking and sex, the most strongly associated variant at IRF5 was the rare variant rs62481981 (ppooled  = 0.0012, odds ratio [OR] = 3.1, 95% confidence interval [95% CI] = 1.6-6.1; 801 cases, 1476 controls).Within PRDM1 it was rs6923419 (ppooled  = 0.004, OR = 0.7, 95% CI = 0.6-0.9; 833 cases, 1440 controls). The associations lost significance after correction for multiple testing in the replication. Both genes are implicated in beta-interferon signalling and are also genome-wide associated with SLE and inflammatory bowel disease., Conclusion: The study gives no definite evidence for a pathogenic genetic link of periodontitis and RA but suggests IRF5 and PRDM1 as shared susceptibility factors., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: The comparative cost-effectiveness of retaining or replacing molars with furcation involvement (FI) remains unclear. We assessed the cost-effectiveness of retaining FI molars via periodontal treatments versus replacing them via implant-supported crowns (ISCs)., Methods: Using tooth-level Markov models, we followed a molar with FI degree I or II/III in a 50-year-old patient over his lifetime. Tooth-retaining periodontal treatments (scaling and root planing, flap debridement, root resection, guided-tissue regeneration, tunnelling) were compared with tooth replacement using ISCs. We analysed costs, time until first re-treatment and total time of tooth or implant retention. The model adopted a private payer perspective within German health care. Transition probabilities were calculated based on current evidence. Monte-Carlo microsimulations were performed, and robustness of the model and effects of heterogeneity assessed using sensitivity analyses., Results: Despite requiring re-treatment later than other strategies, ISCs were the most costly therapy. Compared with most periodontal treatments, ISCs were retained for shorter time than natural teeth regardless of the degree of FI, the patients' age or risk profile (smoker/non-smoker)., Conclusions: Based on available data and within its limitations, our study indicates that retaining FI molars via periodontal treatments might be more cost-effective than replacing them via ISCs. Changes in the underlying evidence or the setting might alter these results., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Decisions in periodontal therapy for multirooted teeth are essentially based on accurate diagnosis of the furcation involvement (FI). Furcation probing (FP) is still the basic diagnostic measure, although the assessment may be difficult. The aim of this study is to evaluate the validity of FP and radiographic assessment of FI compared with visual assessment during open flap surgery (OFS)., Methods: In this retrospective clinical cohort study, 215 participants with periodontal disease and at least one molar treated with OFS were enrolled, and a total of 834 molars were assigned for FI by FP and in radiographs analyzed by an experienced (EE) and less experienced examiner (LE). For the investigation, 143 panoramic radiographs (OPGs) and 77 intra-oral radiographs (I-Os) were evaluated., Results: The Class of FI by FP was confirmed in 56%, whereas 15% were overestimated and 29% underestimated. FI Class 0 and I had been detected with high probability (74% and 54%, respectively). Of all FI Class III, 57% were detected correctly by radiographs and 32% by FP. FP and OFS revealed a weighted κ-coefficient (κw) = 0.588; radiographs and OFS had κw = 0.542 (OPG κw = 0.555 and I-O κw = 0.521). The interrater reliability for radiographs was dependent on the experience of the examiner (EE κw = 0.618; LE κw = 0.426)., Conclusions: Experience in analyzing conventional radiographs increases the potential of correct diagnosis of advanced FI. The reliability of FP compared with radiographic assessment depends on the anatomy and location of the tooth. Both diagnostic tools should be used in cases of suspected FI.

Unlabelled: Infectious diseases endanger all dental personnel during treatment, especially when spatter and aerosols are produced. Therefore, there is a strong need for better infection control principles during all treatments. The purpose of this in-vitro pilot study was to measure the environmental spatter contamination through a fluorescence technique. Scaling was performed using different power-driven devices and high-volume evacuation combined with a newly developed cannula (PS), standard suction cannulas (STS) and saliva ejectors (CDS)., Material and Methods: One sonic (AIR) and two ultrasonic devices (TIG, VEC) were utilized to remove biofilm from 168 artificial teeth in a manikin head. Teeth were scaled for 120s supra- or subgingivally. The spatter contamination of an area of 1.5m2 around the manikin head was assessed., Results and Conclusions: The contaminated area (%) was significantly different for the AIR (median [25th; 75th percentiles]: 2.5 [1.16; 6.05]) versus TIG (0.25 [0.18; 0.88]) and VEC (0.08 [0.06; 0.1]) (p<0.001). Irrespective of the instrument, subgingival scaling led to a less contaminated area (0.18 [0.07; 1.05]) than supragingival scaling (0.34 [0.1; 2.24]) (p < 0.001). High-volume evacuation combined with STS (0.17 [0.07; 1.04]) and PS (0.18 [0.07; 1.14]) reduced the contamination similarly (p=0.302) and was more effective compared to CDS (1.01 [0.12-5.78]) (p<0.001; p=0.002). Beside the limitation of an in-vitro investigation, it can be conclude that only high-volume evacuation with an adequately calibrated cannula is capable of significantly reducing the amount of spatter contamination produced during power-driven scaling.

Aim: Identification of variants within genes SLC23A1 and SLC23A2 coding for vitamin C transporter proteins associated with aggressive (AgP) and chronic periodontitis (CP)., Material and Methods: Employment of three independent case-control samples of AgP (I. 283 cases, 979 controls; II. 417 cases, 1912 controls; III. 164 cases, 357 controls) and one sample of CP (1359 cases, 1296 controls)., Results: Stage 1: Among the tested single-nucleotide polymorphisms (SNPs), the rare allele (RA) of rs6596473 in SLC23A1 showed nominal significant association with AgP (p = 0.026, odds ratio [OR] 1.26, and a highly similar minor allele frequency between different control panels. Stage 2: rs6596473 showed no significant association with AgP in the replication with the German and Dutch case-control samples. After pooling the German AgP populations (674 cases, 2891 controls) to significantly increase the statistical power (SP = 0.81), rs6596473 RA showed significant association with AgP prior to and upon adjustment with the covariates smoking and gender with padj  = 0.005, OR = 1.35. Stage 3: RA of rs6596473 showed no significant association with severe CP., Conclusion: SNP rs6596473 of SLC23A1 is suggested to be associated with AgP. These results add to previous reports that vitamin C plays a role in the pathogenesis of periodontitis., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Periodontitis and Periimplantitis are oftentimes discussed as one entity, which is reflected by therapeutical as well as by scientific approaches. It is unclear, to which extent the similarity of the clinical characteristics is attributed to similarities in the underlying disease mechanisms., Purpose: The main objective of the study is to display if or how different periimplantitis and periodontitis are on the mRNA level, representing a high-resolution map of disease-associated events., Materials and Methods: Aiming to describe the pathophysiological mechanisms in vivo, primary gingival tissue from 7 periimplantitis patients, 7 periodontitis patients and 8 healthy controls was employed in order to generate genome wide transcriptome profiles., Results: On the basis of quantitative transcriptome analysis, we could show that periimplantitis and periodontitis exhibit significantly different mRNA signatures. Additionally we present a disease associated mRNA profile, which displays potential periimplantitis disease mechanisms. A gene ontology analysis revealed various pathways, supporting the hypothesis of periimplantitis being a complex inflammatory disorder with a unique pathophysiology. While in periimplantitis tissue the regulation of transcripts related to innate immune responses and defense responses were dominating, in periodontitis tissues bacterial response systems prevailed., Conclusions: Taken together, our results suggest considering periimplantitis and periodontitis as disease entities with shared as well as with distinct features, which should be reflected on the therapeutical as well as on the scientific level., (© 2012 Wiley Periodicals, Inc.)

Recent large-scale association studies have identified over 100 MS risk loci. One of these MS risk variants is single-nucleotide polymorphism (SNP) rs17066096, located ~14 kb downstream of IL22RA2. IL22RA2 represents a compelling MS candidate gene due to the role of IL-22 in autoimmunity; however, rs17066096 does not map into any known functional element. We assessed whether rs17066096 or a nearby proxy SNP may exert pathogenic effects by affecting microRNA-to-mRNA binding and thus IL22RA2 expression using comprehensive in silico predictions, in vitro reporter assays, and genotyping experiments in 6,722 individuals. In silico screening identified two predicted microRNA binding sites in the 3'UTR of IL22RA2 (for hsa-miR-2278 and hsa-miR-411-5p) encompassing a SNP (rs28366) in moderate linkage disequilibrium with rs17066096 (r (2) = 0.4). The binding of both microRNAs to the IL22RA2 3'UTR was confirmed in vitro, but their binding affinities were not significantly affected by rs28366. Association analyses revealed significant association of rs17066096 and MS risk in our independent German dataset (odds ratio  = 1.15, P = 3.48 × 10(-4)), but did not indicate rs28366 to be the cause of this signal. While our study provides independent validation of the association between rs17066096 and MS risk, this signal does not appear to be caused by sequence variants affecting microRNA function.

Objectives: Psychosocial variables have received increased attention in periodontology. Attachment theory adds to known risk factors by linking early interactional experiences with adult tendencies of stress-regulation, health behaviour, symptom reporting, and healthcare utilization. The study investigates associations between attachment patterns and periodontal parameters., Methods: Within the context of a longitudinal study on periodontal diseases, 310 patients with aggressive (AgP) and chronic periodontitis (CP) filled out questionnaires on psychological attachment patterns. The influence of attachment style on health behaviour, treatment attendance and utilization, and periodontal variables was tested., Results: We found associations between psychological attachment anxiety on smoking and higher number of session use, independent of disease severity, which was more pronounced for women. Patients with higher attachment avoidance attended periodontal treatment later when diagnosed with CP and earlier with AgP. For men, we found differential associations for attachment avoidance and anxiety and number of teeth at beginning of treatment., Conclusion: Psychological attachment patterns are a promising target for understanding periodontal disease in addition to known psychosocial risk factors., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Long-term outcomes of conservative periodontal and prosthetic treatment of patients with moderate to severe periodontitis were to be evaluated. Groups of younger (YG) and middle-aged patients (MG) were to be compared regarding survival of fixed and removable dental prostheses (FDP, RDP) inserted after active periodontal therapy (APT). In addition, functional-occlusal status over more than 10 years of supportive periodontal therapy (SPT) was analysed., Methods: The present multi-case-series retrospectively analysed data of 68 patients (34 YG and 34 MG) who had received APT and regular SPT ≥10 years. Tooth loss, occlusal status and survival and complications of prosthetics were evaluated descriptively and comparatively (t-test)., Results: There was no statistical difference between YG and MG concerning tooth loss/year (p > 0.05). Functional-occlusal status was retained during SPT in 75% and 69% of YG and MG. Restorations inserted after APT showed high survival for both age groups (100%). Mean survival time until the last SPT visit was 15.2 and 11.6 years for FDP and RDP in YG, and 12.5 and 13.1 years in MG., Conclusions: Prosthetic restorations in both younger and middle-aged patients with severe periodontitis showed high survival, if pre-prosthetic APT and regular SPT had been performed., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: Many studies investigated the role of genetic variants in periodontitis, but few were established as risk factors. We aimed to validate the associations of recent candidate genes in aggressive periodontitis (AgP)., Material and Methods: We analysed 23 genes in 600 German AgP patients and 1441 controls on the Illumina custom genotyping array Immunochip. We tested a suggestive association in a Dutch and German/Austrian AgP case-control sample, and a German chronic periodontitis (CP) case-control sample using Sequenom iPlex assays. We additionally tested the common known risk variant rs1333048 of the gene ANRIL for its association in a Turkish and Italian population., Results: None of the analysed genes gave statistical evidence for association. Upon covariate adjustment for smoking and gender, in the pooled German-Austrian AgP sample, IL10 SNP rs6667202 was associated with p = 0.016, OR = 0.77 (95% CI = 0.6-0.95), and in the Dutch AgP sample, adjacent IL10 SNP rs61815643 was associated with p = 0.0009, OR = 2.31 (95% CI = 1.4-3.8). At rs61815643, binding of the transcription factor PPARG was predicted. ANRIL rs1333048 was associated in the Turkish sample (pallelic = 0.026, OR = 1.67 [95% CI = 1.11-2.60])., Conclusions: Previous candidate genes carry no susceptibility factors for AgP. Association of IL-10 rs61815643 with AgP is suggested. ANRIL is associated with periodontitis across different populations., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The aim of this study is to evaluate the efficiency of a recently developed smart digital toothbrush monitoring and training system (DTS) in terms of correct brushing motion and grip axis orientation in an at-home environment., Methods: Twenty-one participants (11 test individuals [DTSG] and 10 control individuals [COG]) received instructions on the modified Bass technique (MBT) after their toothbrushing performance was monitored and they received professional tooth cleaning (T0). After 36 hours (T1), without mechanical oral hygiene measures, plaque and gingival indices were recorded, and the brushing technique was reviewed. After randomization, participants individually performed oral hygiene for 6 weeks (T2) with the provided oral hygiene kits. The DTSG group additionally used DTS. During the following 8 weeks (T3), participants used their original brushing devices without any additional interference. Investigators at each visit were masked regarding group identity. Data were statistically evaluated using Mann-Whitney U, Friedman, Wilcoxon, and paired tests and Pearson correlation., Results: At T0, 27.27% of DTSG participants used the MBT correctly (COG, 50%), increasing to 54.55% (COG, 60%) after professional instruction (T1) and further to 90.91% at T2 (COG, 60%) (P <0.001). Plaque scores were reduced in DTSG (P <0.05). At T3, 80% of the DTSG (COG, 40%) totally adopted the MBT (P <0.05). The plaque scores on buccal surfaces of the DTSG showed an additional slight improvement between T2 and T3, in contrast to a decline on oral surfaces (P <0.001). At T2 and T3, the DTSG brushed >120 seconds (COG, 90% and 50%) (P <0.05)., Conclusion: Apparently, the tested DTS effectively improves the brushing technique and leads to a prolonged learning effect, including improved oral hygiene.

Aim: Involvement of TLR2 in the pathophysiology of periodontitis has widely been discussed, but hitherto, no validated genetic associations were reported. Previous association studies lacked sufficient statistical power and adequate haplotype information to draw unambiguous conclusions. The aim of this study was to comprehensively investigate TLR2 linkage disequilibrium (LD) regions for their potential associations with periodontitis in two large analysis populations of aggressive (AgP) and chronic periodontitis (CP) of North West European descent., Materials and Methods: The study population comprised 598 AgP patients, 914 CP patients and 1804 healthy controls. Analysis of TLR2 LD regions was performed with haplotype tagging SNPs (tagSNPs) using SNPlex and TaqMan genotyping assays. Genotypic, dominant, multiplicative, and recessive genetic models were tested. The genotypes were adjusted for the covariates smoking, diabetes, and gender. Resequencing was performed by Sanger technology., Results: Upon covariate adjustment and correction for multiple testing, no tagSNPs showed significant associations with AgP or CP. Targeted resequencing of exon 3 in 47 AgP cases identified carriership of two common and three rare variants., Conclusion: Common LD regions of TLR2 do not show genetic associations with periodontitis in the North West European population. Resequencing of exon 3 could not identify disease-associated rare variants in TLR2., (© 2012 John Wiley & Sons A/S.)

Aim: The aim of this study was to determine the survival rates of questionable and hopeless teeth in patients with aggressive periodontitis (AgP) and chronic periodontitis (CP) during 15 years of supportive periodontal therapy (SPT)., Materials and Methods: Thirty-four AgP and 34 CP patients (SPT≥10 years) with bone loss of ≥50% at ≥2 teeth were consecutively recruited. Bone loss was measured on digitized radiographs and teeth were categorized as "questionable" (≥50 to <70% bone loss) or as "hopeless" (≥70%). Progression in pocket probing depths (PPD) during SPT, tooth loss and reasons for extraction were analysed., Results: In AgP patients, 262 teeth were considered as questionable and 63 as hopeless (CP: 149/51). During active periodontal therapy, 25 questionable and 26 hopeless teeth were extracted (CP: 12/16). During 15.3 ± 4.1 years of SPT of AgP 28 questionable and 15 hopeless teeth were removed (CP: 28/12). The mean tooth loss per patient during SPT in total was 0.14 (AgP) and 0.16 (CP) teeth/year. There were no significant differences in tooth loss or longitudinal progression of PPD between AgP and CP patients., Conclusions: In patients with AgP, 88.2% (209 of 237) of questionable and 59.5% (22 of 37) of hopeless teeth survived 15 years during regular SPT in a dental school department., (© 2011 John Wiley & Sons A/S.)

As peri-implantitis is an emerging problem, the development of validated animal models is mandatory. The aim of this pilot study was to provide a first step in describing the normal oral flora of minipigs. In five minipigs, samples of the oral flora were collected with sterile cotton swabs from the buccal gingiva of the lower jaw. Two swabs per animal were collected, followed by bacterial isolation under both aerobe and anaerobe conditions. Microbiological analyses included biochemical tests, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rDNA gene sequence analysis. A total of 61 taxa were detected, 14-21 different bacterial taxa from each minipig. Among the Gram-positive cocci, mainly staphylococcal and streptococcal species were identified. Different Actinomyces species were the most abundant taxa in the group of Gram-positive rods. Among the anaerobic bacteria, the Gram-negative genera Fusobacterium, Bacteroides and Prevotella were the most often observed taxa. This is the first study which begins to describe the normal oral flora in minipigs in cultures to allow for the detection of a broad spectrum. Several bacterial species identified are different from human ones. No specific species for peri-implantitis could be detected in that healthy sample.

Calcium-dependent cell death occurs in neurodegenerative diseases and ischemic or traumatic brain injury. We analyzed whether thioureylenes can act in a neuroprotective manner by pharmacological suppression of calcium-dependent pathological pathways. In human neuroblastoma (SK-N-SH) cells, thioureylenes (thiopental, carbimazole) inhibited the calcium-dependent neuronal protein phosphatase (PP)-2B, the activation of the proapoptotic transcription factor nuclear factor of activated T-cells, BAD-induced initiation of caspase-3, and poly-(ADP-ribose)-polymerase cleavage. Caspase-3-independent cell death was attenuated by carbimazole and the protein kinase C (PKC) delta inhibitor rottlerin by a PP-2B-independent mechanism. Neuroprotective effects were mediated by the redox-active sulfur of thioureylenes. Furthermore, we observed that the route of calcium mobilization was differentially linked to caspase-dependent or independent cell death and that BAD dephosphorylation did not necessarily induce intrinsic caspase activation. In addition, a new 30- to 35-kDa caspase-3 fragment with an unknown function was identified. In organotypic hippocampal slice cultures, thioureylenes inhibited caspase-3 activation or reduced N-methyl-d-aspartate and kainic acid receptor-mediated cell death that was independent of caspase-3. Because prolonged inhibition of caspase-3 resulted in caspase-independent cellular damage, different types of cell death must be taken under therapeutic consideration. Here we show that thioureylenes in combination with PKCdelta inhibitors might represent a promising therapeutic approach to attenuate neuronal damage.