The Severity of Human Peri-Implantitis Lesions Correlates with the Level of Submucosal Microbial Dysbiosis

AIM To cross-sectionally analyse the submucosal microbiome of peri-implantitis (PI) lesions at different severity levels. MATERIALS AND METHODS Microbial signatures of 45 submucosal plaque samples from untreated PI lesions obtained from 30 non-smoking, systemically healthy subjects were assessed by 16s sequencing. Linear mixed models were used to identify taxa with differential abundance by probing depth, after correction for age, gender, and multiple samples per subject. Network analyses were performed to identify groups of taxa with mutual occurrence or exclusion. Subsequently, the effects of peri-implant probing depth on submucosal microbial dysbiosis were calculated using the microbial dysbiosis index. RESULTS In total, we identified 337 different taxa in the submucosal microbiome of PI. Total abundance of 12 taxa correlated significantly with increasing probing depth; a significant relationship with lower probing depth was found for 16 taxa. Network analysis identified two mutually exclusive complexes associated with shallow pockets and deeper pockets, respectively. Deeper peri-implant pockets were associated with significantly increased dysbiosis. CONCLUSION Increases in peri-implant pocket depth are associated with substantial changes in the submucosal microbiome and increasing levels of dysbiosis

Re-evaluating genetic variants identified in candidate gene studies of breast cancer risk using data from nearly 280,000 women of Asian and European ancestry

BACKGROUND: We previously conducted a systematic field synopsis of 1059 breast cancer candidate gene studies and investigated 279 genetic variants, 51 of which showed associations. The major limitation of this work was the small sample size, even pooling data from all 1059 studies. Thereafter, genome-wide association studies (GWAS) have accumulated data for hundreds of thousands of subjects. It's necessary to re-evaluate these variants in large GWAS datasets. METHODS: Of these 279 variants, data were obtained for 228 from GWAS conducted within the Asian Breast Cancer Consortium (24,206 cases and 24,775 controls) and the Breast Cancer Association Consortium (122,977 cases and 105,974 controls of European ancestry). Meta-analyses were conducted to combine the results from these two datasets. FINDINGS: Of those 228 variants, an association was observed for 12 variants in 10 genes at a Bonferroni-corrected threshold of P<2.19x10(-4). The associations for four variants reached P<5x10(-8) and have been reported by previous GWAS, including rs6435074 and rs6723097 (CASP8), rs17879961 (CHEK2) and rs2853669 (TERT). The remaining eight variants were rs676387 (HSD17B1), rs762551 (CYP1A2), rs1045485 (CASP8), rs9340799 (ESR1), rs7931342 (CHR11), rs1050450 (GPX1), rs13010627 (CASP10) and rs9344 (CCND1). Further investigating these 10 genes identified associations for two additional variants at P<5x10(-8), including rs4793090 (near HSD17B1), and rs9210 (near CYP1A2), which have not been identified by previous GWAS. INTERPRETATION: Though most candidate gene variants were not associated with breast cancer risk, we found 14 variants showing an association. Our findings warrant further functional investigation of these variants. FUND: National Institutes of Health

In-vitro cytocompatibility and growth factor content of GBR/GTR membranes.

Objective. To assess the cytocompatibility of five commercially available xenogenic barrier membranes used for oral regenerative procedures and to determine the growth factor content of these membranes in-vitro.Methods. Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing. Cells were cultured with previously washed and unwashed membranes (n=4) and in the medium used for washing (eluate). Cell proliferation at 3 days (eluates) and at 7 days (membranes) was assessed using the WST-1 cell proliferation kit. Growth factor content of the membranes was measured using multiplex ELISA.Results. The eluate of BG and BM significantly inhibited proliferation of hMSCs, whereas DM and OX showed stimulating effects. The highest impact was observed for DM, its eluate doubled the cell proliferation of adherent cells when compared to the control (p&lt;0.001). The eluate of OG did not influence eluate cell cultures (p&gt;0.05). The presence of membranes had different impact on hMSCs and PDLs. hMSCs seem to be more resistant to the inhibitory effects of BG, OG and BM. hMSCs are only affected by OX, which actually stimulates hMSCs when the specimens are not washed previously. PDLs however proliferate significantly less once they are placed into culture with BM and OG as well as BG-not washed. Once BG is washed no inhibitory effect on PDLs was observed, however overall the washing of membrane samples prior to the placement into the cell culture did hardly have any effect on the outcome. The strongest inhibition of proliferation was shown with the BM and OG membrane in PDL-hTERTs (p&lt;0.001). Growth factor contents were quite similar quantitatively and qualitatively among the tested membranes with concentrations in the range of 50-500 pg/ml. Intriguingly DM contained considerably higher amounts of bFGF with up to 8000 pg/ml.Significance. The collagen membranes cross-linked with aldehydes show poor outcomes in PDLs while the collagen membrane cross-linked with polysaccharides generally shows promising results similar to the ECM-membrane DM in both membrane and eluate tests. The findings may be due to various factors, especially differences observed in composition, processing and bFGF content. (C) 2019 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved

Rethinking Job References: A Networking Challenge

Can job references play an active role in shaping your career plans? Would you consider your references as part of your personal and professional network? Although most professionals may respond with a resounding “Yes, of course!” to these questions, I realized that many of my students were skeptical about job references. To counter this, and to help improve their chances in the job market, I designed a multistep assignment that expanded students’ understanding of job references and required them to identify persons who were potential job references and members of their career network. This article provides the details for the assignment

Circulating endothelial progenitor cells in periodontitis.

BACKGROUND Several biologically plausible mechanisms have been proposed to mediate the association between periodontitis and atherosclerotic vascular disease (AVD), including adverse effects on vascular endothelial function. Circulating endothelial progenitor cells (cEPCs) are known to contribute to vascular repair, but limited data are available regarding the relationship between cEPC levels and periodontitis. The aims of this cross-sectional study are to investigate the levels of hemangioblastic and monocytic cEPCs in patients with periodontitis and periodontally healthy controls and to associate cEPC levels with the extent and severity of periodontitis. METHODS A total of 112 individuals (56 patients with periodontitis and 56 periodontally healthy controls, aged 26 to 65 years; mean age: 43 years) were enrolled. All participants underwent a full-mouth periodontal examination and provided a blood sample. Hemangioblastic cEPCs were assessed using flow cytometry, and monocytic cEPCs were identified using immunohistochemistry in cultured peripheral blood mononuclear cells. cEPC levels were analyzed in the entire sample, as well as in a subset of 50 pairs of patients with periodontitis/periodontally healthy controls, matched with respect to age, sex, and menstrual cycle. RESULTS Levels of hemangioblastic cEPCs were approximately 2.3-fold higher in patients with periodontitis than periodontally healthy controls, after adjustments for age, sex, physical activity, systolic blood pressure, and body mass index (P = 0.001). A non-significant trend for higher levels of monocytic cEPCs in periodontitis was also observed. The levels of hemangioblastic cEPCs were positively associated with the extent of bleeding on probing, probing depth, and clinical attachment loss. Hemangioblastic and monocytic cEPC levels were not correlated (Spearman correlation coefficient 0.03, P = 0.77), suggesting that they represent independent populations of progenitor cells. CONCLUSION These findings further support the notion that oral infections have extraoral effects and document that periodontitis is associated with a mobilization of EPCs from the bone marrow, apparently in response to systemic inflammation and endothelial injury