Arne Jochens

Genetic evidence for PLASMINOGEN as a shared genetic risk factor of coronary artery disease and periodontitis

Background—Genetic studies demonstrated the presence of risk alleles in the genes ANRIL and CAMTA1/VAMP3 that are shared between coronary artery disease (CAD) and periodontitis. We aimed to identify further shared genetic risk factors to better understand conjoint disease mechanisms. Methods and Results—In-depth genotyping of 46 published CAD risk loci of genome-wide significance in the worldwide largest case–control sample of the severe early-onset phenotype aggressive periodontitis (AgP) with the Illumina Immunochip (600 German AgP cases, 1448 controls) and the Affymetrix 500K array set (283 German AgP cases and 972 controls) highlighted ANRIL as the major risk gene and revealed further associations with AgP for the gene PLASMINOGEN (PLG; rs4252120: P=5.9×10−5; odds ratio, 1.27; 95% confidence interval, 1.3–1.4 [adjusted for smoking and sex]; 818 cases; 5309 controls). Subsequent combined analyses of several genome-wide data sets of CAD and AgP suggested TGFBRAP1 to be associated with AgP (rs2679895: P=0.0016; odds ratio, 1.27 [95% confidence interval, 1.1–1.5]; 703 cases; 2.143 controls) and CAD (P=0.0003; odds ratio, 0.84 [95% confidence interval, 0.8–0.9]; n=4117 cases; 5824 controls). The study further provides evidence that in addition to PLG, the currently known shared susceptibility loci of CAD and periodontitis, ANRIL and CAMTA1/VAMP3, are subjected to transforming growth factor-&bgr; regulation. Conclusions—PLG is the third replicated shared genetic risk factor of atherosclerosis and periodontitis. All known shared risk genes of CAD and periodontitis are members of transforming growth factor-&bgr; signaling.

Influence of the drill material and method of cooling on the development of intrabony temperature during preparation of the site of an implant

Our aim was to evaluate the intrabony friction heat produced by implant drills, using different drill materials and methods of cooling. Four pilot drills and 4 form drills were used. The following combinations of drill material and cooling supply were tested: steel and external cooling; steel and internal cooling; steel coated with zirconium nitride and external cooling; and zirconium oxide and external cooling. The handpiece that supported the drill was fixed in a lifting device. Specimens of bovine ribs were fixed below the handpiece, and the drill speed was set to 1200 rpm. The vertical force was adjusted to 1 kg for pilot drills and 0.5 kg for implant drills. Intrabony temperature during drilling was measured at depths of 4, 8, and 12 mm parallel to the drill, and the depth was limited to 13 mm. There were no significant differences in heat generation between the drill materials (p>.05), but the differences between groups with internal or external cooling supplies were significant (p≤.05). The method of cooling affected the development of the intrabony temperature during preparation of the site of the implant, but the drill material seemed to play no particular role.

Long-term Survival of Straumann Dental Implants with TPS Surfaces: A Retrospective Study with a Follow-up of 12 to 23 Years.

PURPOSE The aim of this study was to evaluate the long-term dental implant survival rates of Straumann dental implants in a university hospital environment over 12 to 23 years. MATERIALS AND METHODS A total of 388 Straumann dental implants with titanium-sprayed surfaces (TPS) were inserted in 92 patients between 1988 and 1999 in the Department of Oral and Maxillofacial Surgery of the University Hospital Schleswig-Holstein in Kiel, and they were reevaluated with standardized clinical and radiological exams. Kaplan-Meier analyses were performed for individual factors. Cox proportional hazard regression analysis was used to detect the factors influencing long-term implant failure. RESULTS The long-term implant survival rate was 88.03% after an observation time of 12.2 to 23.5 years. Cox regression revealed statistically significant influences of the International Team for Implantology (ITI) implantation type (p = .00354) and tobacco smoking (p = .01264) on implant failure. A proportion 82.8% of the patients with implant losses had a medical history of periodontitis. Peri-implantitis was diagnosed in 9.7% of the remaining implants in the long-term survey. CONCLUSIONS This study emphasized the long-term rehabilitation capabilities of Straumann dental implants in complex cases. The survival rates after several years constitute important information for patients, as well as for clinicians, in deciding about different concepts of tooth replacement. Patient-related and technical factors - determined before implant placement - could help to predict the risk of implant loss.

A Markov chain description of the stepwise mutation model: Local and global behaviour of the allele process

The stepwise mutation model (SMM) is a simple, widely used model to describe the evolutionary behaviour of microsatellites. We apply a Markov chain description of the SMM and derive the marginal and joint properties of this process. In addition to the standard SMM, we also consider the normalised allele process. In contrast to the standard process, the normalised process converges to a stationary distribution. We show that the marginal stationary distribution is unimodal. The standard and normalised processes capture the global and the local behaviour of the SMM, respectively.

No shortcut solution to the problem of Y-STR match probability calculation

Match probability calculation is deemed much more intricate for lineage genetic markers, including Y-chromosomal short tandem repeats (Y-STRs), than for autosomal markers. This is because, owing to the lack of recombination, strong interdependence between markers is likely, which implies that haplotype frequency estimates cannot simply be obtained through the multiplication of allele frequency estimates. As yet, however, the practical relevance of this problem has not been studied in much detail using real data. In fact, such scrutiny appears well warranted because the high mutation rates of Y-STRs and the possibility of backward mutation should have worked against the statistical association of Y-STRs. We examined haplotype data of 21 markers included in the PowerPlex(®)Y23 set (PPY23, Promega Corporation, Madison, WI) originating from six different populations (four European and two Asian). Assessing the conditional entropies of the markers, given different subsets of markers from the same panel, we demonstrate that the PowerPlex(®)Y23 set cannot be decomposed into smaller marker subsets that would be (conditionally) independent. Nevertheless, in all six populations, >94% of the joint entropy of the 21 markers is explained by the seven most rapidly mutating markers. Although this result might render a reduction in marker number a sensible option for practical casework, the partial haplotypes would still be almost as diverse as the full haplotypes. Therefore, match probability calculation remains difficult and calls for the improvement of currently available methods of haplotype frequency estimation.

Reconstruction of the orbital floor with polydioxanone: a long-term clinical survey of up to 12 years

Fractures of the orbital floor are common in injured patients, who often require operation to prevent complications and, among other materials, polydioxanone is widely used. The aim of this study was to evaluate the long-term outcomes of fractures of the orbital floor that had been reconstructed with polydioxanone foil. A total of 101 patients (73 men and 28 women) who had reconstruction of the orbital floor for defects of 2cm(2) or smaller with polydioxanone implants, over a mean (SD) time period of 8 (2) years were evaluated. Sensitivity of the infraorbital nerve, ocular motility, and diplopia were evaluated and correlated with perioperative values. Persistent hyperaesthesia was found in 15 patients, whereas in another 15 the hyperaesthesia recovered completely over time. Three patients had double vision during follow-up. Twenty patients with preoperative diplopia had no persistent double vision postoperatively, and 15 patients with disturbed ocular motility recovered completely. Two patients had persistently disturbed motility, and one patient had enophthalmos. There was a significant association between hyperaesthesia preoperatively and postoperatively (p= 0.005). In most patients reconstruction of the orbital floor with polydioxanone was successful. Long-term complications such as diplopia, compromised bulbar motility, and hyperaesthesia of the cheek were seen in a few cases, but might not have been solely related to the use of polydioxanone.

Empirical Evaluation Reveals Best Fit of a Logistic Mutation Model for Human Y-Chromosomal Microsatellites

The rate of microsatellite mutation is dependent upon both the allele length and the repeat motif, but the exact nature of this relationship is still unknown. We analyzed data on the inheritance of human Y-chromosomal microsatellites in father–son duos, taken from 24 published reports and comprising 15,285 directly observable meioses. At the six microsatellites analyzed (DYS19, DYS389I, DYS390, DYS391, DYS392, and DYS393), a total of 162 mutations were observed. For each locus, we employed a maximum-likelihood approach to evaluate one of several single-step mutation models on the basis of the data. For five of the six loci considered, a novel logistic mutation model was found to provide the best fit according to Akaike’s information criterion. This implies that the mutation probability at the loci increases (nonlinearly) with allele length at a rate that differs between upward and downward mutations. For DYS392, the best fit was provided by a linear model in which upward and downward mutation probabilities increase equally with allele length. This is the first study to empirically compare different microsatellite mutation models in a locus-specific fashion.

Phenotypes of organ involvement in sarcoidosis

Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype–Phenotype Relationship in Sarcoidosis) project represents a European multicentre study to investigate the influence of genotype on disease phenotypes in sarcoidosis. The baseline phenotype module of GenPhenReSa comprised 2163 Caucasian patients with sarcoidosis who were phenotyped at 31 study centres according to a standardised protocol. From this module, we found that patients with acute onset were mainly female, young and of Scadding type I or II. Female patients showed a significantly higher frequency of eye and skin involvement, and complained more of fatigue. Based on multidimensional correspondence analysis and subsequent cluster analysis, patients could be clearly stratified into five distinct, yet undescribed, subgroups according to predominant organ involvement: 1) abdominal organ involvement, 2) ocular–cardiac–cutaneous–central nervous system disease involvement, 3) musculoskeletal–cutaneous involvement, 4) pulmonary and intrathoracic lymph node involvement, and 5) extrapulmonary involvement. These five new clinical phenotypes will be useful to recruit homogenous cohorts in future biomedical studies. Five new clinical phenotypes of sarcoidosis have been identified by analysing organ manifestations of 1932 patients http://ow.ly/UYLC30jpUkq

Stem/progenitor cell transplantation for pulpal regeneration: A systematic review and meta-analysis of animal studies

For treating pulpal pathological conditions, pulpal regeneration through transplanted stem/progenitor cells might be an alternative to conventional root canal treatment. A number of animal studies demonstrated beneficial effects of stem/progenitor cell transplantation for pulp-dentin complex regeneration, that is, pulpal tissue, neural, vascular, and dentinal regeneration. We systematically reviewed animal studies investigating stem/progenitor cell-mediated pulp-dentin complex regeneration. Studies quantitatively comparing pulp-dentin complex regeneration after transplantation of stem/progenitor cells versus no stem/progenitor cell transplantation controls in intraoral in vivo teeth animal models were analyzed. The following outcomes were investigated: regenerated pulp area per root canal total area, capillaries per total surface, regenerated dentinal area per total defect area, and nerves per total surface. PubMed and EMBASE were screened for studies published until July 2014. Cross-referencing and hand searching were used to identify further articles. Standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated using random-effects meta-analysis. To assess possible bias, SYRCLEs risk of bias tool for animal studies was used. From 1364 screened articles, five studies (representing 64 animals) were included in the quantitative analysis. Risk of bias of all studies was high. Stem/progenitor cell-transplanted pulps showed significantly larger regenerated pulp area per root canal total area (SMD [95% CI]: 2.28 [0.35-4.21]) and regenerated dentin area per root canal total area (SMD: 6.91 [5.39-8.43]) compared with no stem/progenitor cell transplantation controls. Only one study reported on capillaries per or nerves per total surface and found both significantly increased in stem/progenitor cell-transplanted pulps compared with controls. Stem/progenitor cell transplantation seems to enhance pulp-dentin complex regeneration in animal models. Due to limited data quantity and quality, current evidence levels are insufficient for further conclusions.