1. |
- Joshi, Peter K, et al.
(author)
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Directional dominance on stature and cognition in diverse human populations
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
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Journal article (peer-reviewed)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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2. |
- Pattaro, Cristian, et al.
(author)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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3. |
- Jepsen, Sören, et al.
(author)
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Primary prevention of peri-implantitis: Managing peri-implant mucositis.
- 2015
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In: Journal of clinical periodontology. - : Wiley. - 1600-051X .- 0303-6979. ; 42 Suppl 16
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Research review (peer-reviewed)abstract
- Over the past decades, the placement of dental implants has become a routine procedure in the oral rehabilitation of fully and partially edentulous patients. However, the number of patients/implants affected by peri-implant diseases is increasing. As there are - in contrast to periodontitis - at present no established and predictable concepts for the treatment of peri-implantitis, primary prevention is of key importance. The management of peri-implant mucositis is considered as a preventive measure for the onset of peri-implantitis. Therefore, the remit of this working group was to assess the prevalence of peri-implant diseases, as well as risks for peri-implant mucositis and to evaluate measures for the management of peri-implant mucositis.
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5. |
- Salvi, Giovanni E. E., et al.
(author)
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Clinical periodontal diagnosis
- 2023
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In: Periodontology 2000. - : WILEY. - 0906-6713 .- 1600-0757.
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Journal article (peer-reviewed)abstract
- Periodontal diseases include pathological conditions elicited by the presence of bacterial biofilms leading to a host response. In the diagnostic process, clinical signs such as bleeding on probing, development of periodontal pockets and gingival recessions, furcation involvement and presence of radiographic bone loss should be assessed prior to periodontal therapy, following active therapy, and during long-term supportive care. In addition, patient-reported outcomes such as increased tooth mobility, migration, and tilting should also be considered. More important to the patient, however, is the fact that assessment of signs of periodontal diseases must be followed by an appropriate treatment plan. Furthermore, it should be realized that clinical and radiographic periodontal diagnosis is based on signs which may not reflect the presence of active disease but rather represent the sequelae of a previous bacterial challenge. Hence, the aim of the present review is to provide a summary of clinical and radiographic diagnostic criteria required to classify patients with periodontal health or disease.
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6. |
- Fürst, Mirjam M, et al.
(author)
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Bacterial colonization immediately after installation on oral titanium implants.
- 2007
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In: Clinical Oral Implants Research. - 0905-7161 .- 1600-0501. ; 18:4, s. 501-8
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Journal article (peer-reviewed)abstract
- BACKGROUND: Information on bacterial colonization immediately after dental implant insertion is limited.AIMS: (1) To assess the early colonization on titanium implants immediately after placement and throughout the first 12 post-surgical weeks, (2) to compare the microbiota at interproximal subgingival implant and adjacent tooth sites.MATERIAL AND METHODS: Subgingival plaque samples from implant and neighbouring teeth were studied by checkerboard DNA-DNA hybridization before surgery, 30 min after implant placement, and 1, 2, 4, 8, and 12 weeks after surgery.RESULTS: Comparing bacterial loads at implant sites between 30 min after placement with 1-week data showed that only the levels of Veillonella parvula (P<0.05) differed with higher loads at week 1 post-surgically. Week 12 data demonstrated significantly higher bacterial loads for 15/40 species at tooth sites compared with pre-surgery (P-values varying between 0.05 and 0.01). Between the period immediately after surgery and 12 weeks at implant sites, 29/40 species was more commonly found at 12 weeks. Included among these bacteria at implant sites were Porphyromonas gingivalis (P<0.05), Tannerella forsythia, (P<0.01), and Treponema denticola (P<0.001). Immediately post-surgery 5.9% of implants, and 26.2% of teeth, and at week 12, 15% of implants, and 39.1% of teeth harbored Staphylococcus aureus. Comparing tooth and implant sites, significantly higher bacterial loads were found at tooth sites for 27/40 species after 30 min following implant placement. This difference increased to 35/40 species at 12 weeks post-surgically.CONCLUSIONS: Bacterial colonization occurred within 30 min after implant placement. Early colonization patterns differed between implant and tooth surfaces.
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7. |
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8. |
- Laugisch, Oliver, et al.
(author)
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Histologic evidence of periodontal regeneration in furcation defects : a systematic review
- 2019
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In: Clinical Oral Investigations. - : Springer. - 1432-6981 .- 1436-3771. ; 23:7, s. 2861-2906
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Research review (peer-reviewed)abstract
- Objective: To systematically review the available histologic evidence on periodontal regeneration in class II and III furcations in animals and humans. Materials and methods: A protocol including all aspects of a systematic review methodology was developed including definition of the focused question, defined search strategy, study inclusion criteria, determination of outcome measures, screening methods, data extraction and analysis, and data synthesis. The focused question was defined as follows: What is the regenerative effect obtained by using or not several biomaterials as adjuncts to open flap surgery in the treatment of periodontal furcation defects as evaluated in animal and human histological studies? Search strategy: Using the MEDLINE database, the literature was searched for articles published up to and including September 2018: combinations of several search terms were applied to identify appropriate studies. Reference lists of review articles and of the included articles in the present review were screened. A hand search of the most important dental journals was also performed. Criteria for study selection and inclusion: Only articles published in English describing animal and human histological studies evaluating the effect of surgical treatment, with or without the adjunctive use of potentially regenerative materials (i.e., barrier membranes, grafting materials, growth factors/proteins, and combinations thereof) for the treatment of periodontal furcation defects were considered. Only studies reporting a minimum of 8weeks healing following reconstructive surgery were included. The primary outcome variable was formation of periodontal supporting tissues [e.g., periodontal ligament, root cementum, and alveolar bone, given as linear measurements (in mm) or as a percentage of the instrumented root length (%)] following surgical treatment with or without regenerative materials, as determined histologically/histomorphometrically. Healing type and defect resolution (i.e., complete regeneration, long junctional epithelium, connective tissue attachment, connective tissue adhesion, or osseous repair) were also recorded. Results: In animals, periodontal regeneration was reported in class II and III defects with open flap debridement alone or combined with various types of bone grafts/bone substitues, biological factors, guided tissue regeneration, and different combinations thereof. The use of biological factors and combination approaches provided the best outcomes for class II defects whereas in class III defects, the combination approaches seem to offer the highest regenerative outcomes. In human class II furcations, the best outcomes were obtained with DFDBA combined with rhPDGF-BB and with GTR. In class III furcations, evidence from two case reports indicated very limited to no periodontal regeneration. Conclusions: Within their limits, the present results suggest that (a) in animals, complete periodontal regeneration has been demonstrated in class II and class III furcation defects, and (b) in humans, the evidence for substantial periodontal regeneration is limited to class II furcations. Clinical relevance: At present, regenerative periodontal surgery represents a valuable treatment option only for human class II furcation defects but not for class III furcations.
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9. |
- Persson, G. Rutger, et al.
(author)
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Antimicrobial therapy using a local drug delivery system (Arestin) in the treatment of peri-implantitis. I : Microbiological outcomes
- 2006
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In: Clinical Oral Implants Research. - 0905-7161 .- 1600-0501. ; 17:4, s. 386-393
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To assess the microbiological outcome of local administration of minocycline hydrochloride microspheres 1 mg (Arestin) in cases with peri-implantitis and with a follow-up period of 12 months.MATERIAL AND METHODS: After debridement, and local administration of chlorhexidine gel, peri-implantitis cases were treated with local administration of minocycline microspheres (Arestin). The DNA-DNA checkerboard hybridization method was used to detect bacterial presence during the first 360 days of therapy.RESULTS: At Day 10, lower bacterial loads for 6/40 individual bacteria including Actinomyces gerensceriae (P<0.1), Actinomyces israelii (P<0.01), Actinomyces naeslundi type 1 (P<0.01) and type 2 (P<0.03), Actinomyces odontolyticus (P<0.01), Porphyromonas gingivalis (P<0.01) and Treponema socranskii (P<0.01) were found. At Day 360 only the levels of Actinobacillus actinomycetemcomitans were lower than at baseline (mean difference: 1x10(5); SE difference: 0.34x10(5), 95% CI: 0.2x10(5) to 1.2x10(5); P<0.03). Six implants were lost between Days 90 and 270. The microbiota was successfully controlled in 48%, and with definitive failures (implant loss and major increase in bacterial levels) in 32% of subjects.CONCLUSIONS: At study endpoint, the impact of Arestin on A. actinomycetemcomitans was greater than the impact on other pathogens. Up to Day 180 reductions in levels of Tannerella forsythia, P. gingivalis, and Treponema denticola were also found. Failures in treatment could not be associated with the presence of specific pathogens or by the total bacterial load at baseline. Statistical power analysis suggested that a case control study would require approximately 200 subjects.
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10. |
- Salvi, Giovanni E, et al.
(author)
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Adjunctive local antibiotic therapy in the treatment of peri-implantitis II : clinical and radiographic outcomes.
- 2007
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In: Clinical Oral Implants Research. - 0905-7161 .- 1600-0501. ; 18:3, s. 281-285
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Journal article (peer-reviewed)abstract
- AIM: To monitor over 12 months clinical and radiographic changes occurring after adjunctive local delivery of minocycline microspheres for the treatment of peri-implantitis.MATERIAL AND METHODS: In 25 partially edentulous subjects, 31 implants diagnosed with peri-implantitis were treated. Three weeks after oral hygiene instruction, mechanical debridement and local antiseptic cleansing using 0.2% chlorhexidine gel, baseline (Day 0) parameters were recorded. Minocycline microspheres (Arestin) were locally delivered to each implant site with bone loss and a probing pocket depth (PPD) >or=5 mm. Rescue therapy with Arestin was allowed at Days 180 and 270 at any site exhibiting an increase in PPD>or=2 mm from the previous visit. The following clinical parameters were recorded at four sites/implant at Day 0, 10, 30, 60, 90, 180, 270 and 360: PPD, clinical attachment level (CAL), bleeding on probing (BOP) and plaque index (PlI).RESULTS: Six implants in six subjects were either rescued or exited because of persisting active peri-implantitis. Successful implants showed a statistically significant reduction in both PPD and percentage of sites with BOP between baseline and Day 360 (P<0.05). At mesial implant sites, the mean PPD reduction amounted to 1.6 mm (95% CI: 0.9-2.2 mm, P<0.001) and was accompanied by a statistically significant reduction of the BOP value (P<0.001). Binary regression analysis showed that the clinical parameters and smoking history could not discriminate between successfully treated and rescued or exited implants at any observation time point.CONCLUSION: Non-surgical mechanical treatment of peri-implantitis lesions with adjunctive local delivery of microencapsulated minocycline led to positive effects on clinical parameters up to 12 months.
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12. |
- Salvi, Giovanni E, et al.
(author)
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Experimental gingivitis in type 1 diabetics : a controlled clinical and microbiological study.
- 2005
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In: Journal of Clinical Periodontology. - 0303-6979 .- 1600-051X. ; 32:3, s. 310-316
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To monitor clinical and microbiological changes during experimental gingivitis in type 1 diabetics and non-diabetics.MATERIALS AND METHODS: Nine type 1 diabetics with good/moderate metabolic control and nine age-gender matched non-diabetics were recruited. Probing pocket depths in all subjects did not exceed 4 mm and none were affected by attachment loss. According to the original model, an experimental 3-week plaque accumulation resulting in experimental gingivitis development and a subsequent 2-week period of optimal plaque control were staged. Subgingival plaque samples were collected at days 0, 21 and 35 from one site per quadrant, pooled and analysed using checkerboard DNA-DNA hybridization.RESULTS: Diabetics (mean age 25.6+/-5.8 standard deviation (SD), range 16-35 years) had a mean HbA1c level of 8.1+/-0.7% (SD), while non-diabetics (mean age 24.8+/-5.7 (SD), range 15-36 years) were metabolically controlled (HbA1c< or =6.5%). Between Days 0, 21 and 35, no statistically significant differences in mean plaque and gingival index scores were observed between diabetics and non-diabetics. At days 7 and 21, however, diabetics showed statistically significantly higher percentages of sites with gingival index scores > or =2 compared with non-diabetics. Mean DNA probe counts of the red and orange complex species increased significantly (p<0.05) between days 0 and 21 and decreased significantly (p<0.05) between days 21 and 35 in both groups.CONCLUSION: Both diabetics and non-diabetics react to experimental plaque accumulation with gingival inflammation. Type 1 diabetics, however, develop an earlier and higher inflammatory response to a comparable bacterial challenge.
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13. |
- Salvi, Giovanni E, et al.
(author)
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One-year bacterial colonization patterns of Staphylococcus aureus and other bacteria at implants and adjacent teeth.
- 2008
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In: Clinical Oral Implants Research. - 0905-7161 .- 1600-0501. ; 19:3, s. 242-248
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Journal article (peer-reviewed)abstract
- AIMS: (i) To assess the pattern of early bacterial colonization on titanium oral implants after installation, at 12 weeks and at 12 months, (ii) to compare the microbiota at submucosal implant sites and adjacent subgingival tooth sites and (iii) to assess whether or not early colonization was predictive of 12-month colonization patterns.MATERIAL AND METHODS: Submucosal/subgingival plaque samples from 17 titanium oral implants and adjacent teeth were analyzed by checkerboard DNA-DNA hybridization 30 min, 12 weeks and 12 months after implant installation.RESULTS: At 12 months, none of the inserted implants had been lost or presented with signs of peri-implantitis. The distribution of sites at implants and teeth with bleeding on probing varied between 2% and 11%. Probing pocket depths < or =3 mm were found at 75% of implant sites. At 12 months, the sum of the bacterial counts of 40 species was statistically significantly higher at tooth compared with implant sites (mean difference: 34.4 x 10(5), 95% confidence interval -0.4 to 69.4, P<0.05). At 12 months, higher individual bacterial counts at tooth sites were found for 7/40 species compared with implant sites. Detection or lack of detection of Staphylococcus aureus at implant sites at 12 weeks resulted in the highest positive (e.g. 80%) and negative (e.g. 90%) predictive values, respectively. Between 12 weeks and 12 months, the prevalence of Tannerella forsythia increased statistically significantly at implant sites (P<0.05). Lack of detection of Porphyromonas gingivalis at 12 weeks yielded a negative predictive value of 93.1% of this microorganism being undetectable at implant sites at 12 months.CONCLUSIONS: Within the limits of this study, the findings showed (i) a few differences in the prevalence of bacterial species between implant and adjacent tooth sites at 12 months and (ii) high positive and negative predictive values for selected bacterial species.
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14. |
- Salvi, Giovanni E, et al.
(author)
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Pro-inflammatory biomarkers during experimental gingivitis in patients with type 1 diabetes mellitus : a proof-of-concept study.
- 2010
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In: Journal of Clinical Periodontology. - 0303-6979 .- 1600-051X. ; 37:1, s. 9-16
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Journal article (peer-reviewed)abstract
- AIM: To compare gingival crevicular fluid (GCF) biomarker levels and microbial distribution in plaque biofilm (SP) samples for subjects with type 1 diabetes (T1DM) versus healthy subjects without diabetes during experimental gingivitis (EG).MATERIALS AND METHODS: A total of nine T1DM patients and nine healthy controls of age and gender similar to the T1DM patients were monitored for 35 days during EG. Hygiene practices were stopped for 3 weeks, and GCF, SP, plaque index (PI) and gingival index were determined. IL-1beta, IL-8, MMP-8 and MMP-9 were quantified by enzyme-linked immunosorbent assay, and SP samples were assessed by DNA-DNA hybridization for a panel of 40 subgingival microbial species.RESULTS: IL-1beta levels in T1DM patients were elevated compared with healthy individuals, and showed differences between groups at 7-21 days while healthy patients showed IL-1beta increases from baseline to 14-21 days (p<0.05). Differences were observed in MMP-9 levels between patients with and without T1DM at 7-14 days (p<0.05). Orange complex species and PI measurements displayed a superior correlation with biomarker levels when compared with other complexes or clinical measurements during EG.CONCLUSIONS: The mean GCF biomarker levels for IL-1beta and MMP-8 were most significantly elevated in T1DM subjects compared with healthy individuals during EG, not resulting from differences in the mean PI or microbial composition.
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16. |
- Sanz, Mariano, et al.
(author)
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Clinical research on peri-implant diseases : consensus report of Working Group 4.
- 2012
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In: Journal of Clinical Periodontology. - 0303-6979 .- 1600-051X. ; 39:Suppl 12, s. 202-6
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Journal article (peer-reviewed)abstract
- BACKGROUND: Two systematic reviews have evaluated the quality of research and reporting of observational studies investigating the prevalence of, the incidence of and the risk factors for peri-implant diseases and of experimental clinical studies evaluating the efficacy of preventive and therapeutic interventions.MATERIALS AND METHODS: For the improvement of the quality of reporting for both observational and experimental studies, the STROBE and the Modified CONSORT recommendations were encouraged.RESULTS: To improve the quality of research in peri-implant diseases, the following were recommended: the use of unequivocal case definitions; the expression of outcomes at the subject rather than the implant level; the implementation of study validation tools; the reporting of potential sources of bias; and the use of appropriate statistical methods.CONCLUSIONS: In observational studies, case definitions for peri-implantitis were agreed. For risk factor determination, the progressive use of cross-sectional and case-control studies (univariate analyses), to prospective cohorts (multilevel modelling for confounding), and ultimately to intervention studies were recommended. For preventive and interventional studies of peri-implant disease management, parallel arm RCTs of at least 6-months were encouraged. For studies of non-surgical and surgical management of peri-implantitis, the use of a composite therapeutic end point was advocated. The development of standard control therapies was deemed essential.
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17. |
- Sanz, Mariano, et al.
(author)
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Clinical research on peri-implant diseases : consensus report of Working Group 4.
- 2012
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In: Journal of Clinical Periodontology. - : Blackwell Munksgaard. - 0303-6979 .- 1600-051X. ; 39:Suppl 12, s. 202-6
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Journal article (peer-reviewed)abstract
- BACKGROUND: Two systematic reviews have evaluated the quality of research and reporting of observational studies investigating the prevalence of, the incidence of and the risk factors for peri-implant diseases and of experimental clinical studies evaluating the efficacy of preventive and therapeutic interventions. MATERIALS AND METHODS: For the improvement of the quality of reporting for both observational and experimental studies, the STROBE and the Modified CONSORT recommendations were encouraged. RESULTS: To improve the quality of research in peri-implant diseases, the following were recommended: the use of unequivocal case definitions; the expression of outcomes at the subject rather than the implant level; the implementation of study validation tools; the reporting of potential sources of bias; and the use of appropriate statistical methods. CONCLUSIONS: In observational studies, case definitions for peri-implantitis were agreed. For risk factor determination, the progressive use of cross-sectional and case-control studies (univariate analyses), to prospective cohorts (multilevel modelling for confounding), and ultimately to intervention studies were recommended. For preventive and interventional studies of peri-implant disease management, parallel arm RCTs of at least 6-months were encouraged. For studies of non-surgical and surgical management of peri-implantitis, the use of a composite therapeutic end point was advocated. The development of standard control therapies was deemed essential.
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18. |
- Schwarz, Frank, et al.
(author)
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Recommendations on the clinical application of air polishing for the management of peri-implant mucositis and peri-implantitis
- 2016
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In: Quintessence International. - : Quintessence Publishing Company. - 0033-6572 .- 1936-7163. ; 47:4, s. 293-296
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Journal article (peer-reviewed)abstract
- Air polishing was introduced as an alternative approach for the supra- and submucosal biofilm management at dental implants. An international expert meeting involving competent clinicians and researchers took place during the EUROPERIO 8 conference in London, UK, on 4 June 2015. Prior to this meeting a comprehensive systematic review dealing with the efficacy of air polishing in the treatment of peri-implant mucositis and peri-implantitis was prepared and served as a basis for the group discussions. This paper summarizes the consensus statements and practical recommendations on the clinical application of air polishing for the management of peri-implant mucositis and peri-implantitis.
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