Association between periodontitis and depression severity - A cross-sectional study of the older population in Hamburg.

The aim of the current study is to investigate the association between periodontitis (exposure variable) and depression severity (outcome variable) in an older German population. We evaluated data from 6,209 participants (median age 62 years) of the Hamburg City Health Study (HCHS). The HCHS is a prospective cohort study and is registered at ClinicalTrial.gov (NCT03934957). Depression severity were assessed with the 9-item Patient Health Questionnaire (PHQ-9). Periodontal examination included probing depth, gingival recession, plaque index, and bleeding on probing. Descriptive analyses were stratified by periodontitis severity. Multiple linear regression models were adjusted for age, sex, diabetes, education, smoking, and antidepressant medication. Linear regression analyses revealed a significant association between log-transformed depression severity and periodontitis when including the interaction term for periodontitis * age, even after adjusting for age, sex, diabetes, education, smoking and antidepressant medication. We identified a significant association between severe periodontitis and elevated depression severity, which interacts with age. Additionally, we performed a linear regression model for biomarker analyses, which revealed significant associations between depression severity and severe periodontitis with log-transformed inflammatory biomarkers interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hsCRP). In order to identify new therapeutic strategies for patients with depression and periodontal disease, future prospective studies are needed to assess the physiological and psychosocial mechanisms behind this relationship and the causal directionality.

Association between C-Reactive protein and periodontitis in an obese population from the NHANES 2009-2010.

BACKGROUND: Various data have been obtained on the relationship between body mass index (BMI) and C-reactive protein (CRP) and periodontitis. The aim of this study was to determine whether CRP/BMI are associated with periodontitis using data from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: A cross-sectional analysis of data from 3602 participants in the 2009-2010 NHANES cycle was performed. The definition of periodontitis was used to divide participants into four groups according to the criteria of Eke. Correlations between CRP/BMI and periodontitis were tested for statistical significance by means of descriptive statistics, multivariate regression, and subgroup-stratified analyses, with and without adjustments for confounders (such as age and sex). RESULTS: There were no statistically significant differences (p > 0.05) regarding BMI and the development of periodontitis. After adjustment for age, sex, race, marital status, annual family income, alcohol consumption, hypertension, smoking, chronic pulmonary disease, cardiovascular disease, diabetes, flossing, and arthritis, CRP correlated significantly with the development of periodontitis in the subgroups stratified by obesity, with an odds ratio (OR) of 1.2 (95% CI, 1.0 to 1.5). CONCLUSION: Through data analysis, we found an association between CRP levels and periodontitis prevalence in the American population, although this association was only present in the obese population. While there are several hypotheses about the underlying mechanism, further studies are needed to validate these findings.

Association between an Anti-Inflammatory Dietary Score and Periodontitis-Evidence from the Population-Based Hamburg City Health Study.

While the effects of dietary patterns on cardiovascular risk and diabetes have been well studied, the evidence is scarce as to which diet has the greatest anti-inflammatory potential and how dietary patterns are associated with periodontitis. In the Hamburg City Health Study (HCHS), we developed an anti-inflammatory dietary score using a data-driven approach based on the relationship of relevant selected food groups with inflammatory biomarkers (hsCRP and IL-6). The aim of this cross-sectional study was to evaluate the association between the anti-inflammatory dietary score and the incidence of periodontitis in Hamburg, Germany. A total of n = 5642 participants fit the required inclusion criteria and were selected for analysis. Periodontal disease was assessed using probing depth, gingival recession, and bleeding on probing. Dietary intake was measured using a food frequency questionnaire (FFQ). A self-developed anti-inflammatory dietary score served as the key explanatory variable. Higher scores reflected lower inflammatory processes (measured through the biomarkers hsCRP and IL-6). Several covariates were included in the regression analysis. Regressions revealed that a higher anti-inflammatory dietary score was significantly associated with lower odds to be affected by periodontal disease in an unadjusted model (OR 0.86, 95% CI 0.82-0.89, p < 0.001) and in an adjusted model (age, sex, smoking, diabetes, hypertension, and physical activity) (OR 0.93, 95% CI 0.89-0.98, p = 0.003). Our study demonstrated a significant inverse association between an anti-inflammatory dietary score and periodontitis. Individuals with higher intake of proinflammatory nutrition should be specifically addressed to avoid periodontitis.

Coffee consumption and associations with blood pressure, LDL-cholesterol and echocardiographic measures in the general population.

Coffee, next to water the most widespread beverage, is attributed both harmful and protective characteristics concerning cardiovascular health. This study aimed to evaluate associations of coffee consumption with cardiac biomarkers, echocardiographic, electrocardiographic parameters and major cardiovascular diseases. We performed a cross-sectional analysis of 9009 participants of the population-based Hamburg City Health Study (HCHS), enrolled between 2016 and 2018 median age 63 [IQR: 55; 69] years. Coffee consumption was classified into three groups: < 3 cups/day (low), 3-4 cups/day (moderate), > 4 cups/day (high). In linear regression analyses adjusted for age, sex, body mass index, diabetes, hypertension, smoking, and additives, high coffee consumption correlated with higher LDL-cholesterol (ß = 5.92; 95% CI 2.95, 8.89; p < 0.001). Moderate and high coffee consumption correlated with lower systolic (ß = - 1.91; 95% CI - 3.04, - 0.78; p = 0.001; high: ß = - 3.06; 95% CI - 4.69, - 1.44; p < 0.001) and diastolic blood pressure (ß = - 1.05; 95% CI - 1.67, - 0.43; p = 0.001; high: ß = - 1.85; 95% CI - 2.74, - 0.96; p < 0.001). Different levels of coffee consumption did neither correlate with any investigated electrocardiographic or echocardiographic parameter nor with prevalent major cardiovascular diseases, including prior myocardial infarction and heart failure. In this cross-sectional analysis, high coffee consumption correlated with raised LDL-cholesterol levels and lower systolic and diastolic blood pressure. However, major cardiovascular diseases including heart failure and its diagnostic precursors were not associated with coffee consumption, connoting a neutral role of coffee in the context of cardiovascular health.

Effects of Infantile Hypophosphatasia on Human Dental Tissue.

Hypophosphatasia (HPP) is an inherited, systemic disorder, caused by loss-of-function variants of the ALPL gene encoding the enzyme tissue non-specific alkaline phosphatase (TNSALP). HPP is characterized by low serum TNSALP concentrations associated with defective bone mineralization and increased fracture risk. Dental manifestations have been reported as the exclusive feature (odontohypophosphatasia) and in combination with skeletal complications. Enzyme replacement therapy (asfotase alfa) has been shown to improve respiratory insufficiency and skeletal complications in HPP patients, while its effects on dental status have been understudied to date. In this study, quantitative backscattered electron imaging (qBEI) and histological analysis were performed on teeth from two patients with infantile HPP before and during asfotase alfa treatment and compared to matched healthy control teeth. qBEI and histological methods revealed varying mineralization patterns in cementum and dentin with lower mineralization in HPP. Furthermore, a significantly higher repair cementum thickness was observed in HPP compared to control teeth. Comparison before and during treatment showed minor improvements in mineralization and histological parameters in the patient when normalized to matched control teeth. HPP induces heterogeneous effects on mineralization and morphology of the dental status. Short treatment with asfotase alfa slightly affects mineralization in cementum and dentin. Despite HPP being a rare disease, its mild form occurs at higher prevalence. This study is of high clinical relevance as it expands our knowledge of HPP and dental involvement. Furthermore, it contributes to the understanding of dental tissue treatment, which has hardly been studied so far.

Cultivation of Cryopreserved Human Dental Pulp Stem Cells-A New Approach to Maintaining Dental Pulp Tissue.

Human dental pulp stem cells (hDPSCs) are multipotent mesenchymal stem cells (MSCs) that are capable of self-renewal with multilineage differentiation potential. After being cryopreserved, hDPSCs were reported to maintain a high level of proliferation and multi-differentiation abilities. In order to optimize cryopreservation techniques, decrease storage requirements and lower contamination risks, the feasibility of new whole-tooth cryopreservation and its effects on hDPSCs were tested. The survival rates, morphology, proliferation rates, cell activity, surface antigens and differentiation abilities of hDPSCs isolated from fresh teeth were compared with those of one-month cryopreserved teeth in 5% and 10% DMSO. The data of the present study indicated that the new cryopreservation approach did not reduce the capabilities or stemness of hDPSCs, with the exception that it extended the first appearance time of hDPSCs in the teeth that were cryopreserved in 10% DMSO, and reduced their recovery rate. With the novel strategy of freezing, the hDPSCs still expressed the typical surface markers of MSCs and maintained excellent proliferation capacity. Three consecutive weeks of osteogenic and adipogenic induction also showed that the expression of the key genes in hDPSCs, including lipoprotein lipase (LPL), peroxisome proliferator-activated receptor-γ (PPAR-γ), alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), type I collagen (COL I) and osteocalcin (OSC) was not affected, indicating that their differentiation abilities remained intact, which are crucial parameters for hDPSCs as cell-therapy candidates. These results demonstrated that the new cryopreservation method is low-cost and effective for the good preservation of hDPSCs without compromising cell performance, and can provide ideas and evidence for the future application of stem-cell therapies and the establishment of dental banks.

Association between periodontitis and heart failure in the general population.

AIMS: Data on the association between periodontitis and preclinical cardiac alterations remain scarce. The aim of the current study is to determine if periodontitis is associated with morphological and functional cardiac changes measured by transthoracic echocardiography as well as different heart failure (HF) phenotypes. METHODS: Participants from the population-based Hamburg City Health Study [ClinicalTrial.gov (NCT03934957)], who underwent transthoracic echocardiography and periodontal screening were included. Periodontitis was classified according to Eke and Page (none/mild, moderate, severe). The 2021 ESC HF guidelines were applied and HF was classified into HF with preserved ejection fraction (HFpEF, ejection fraction ≥50%), HF with mid-range and reduced ejection fraction [HF(m)rEF, ejection fraction <50%], and HF in general [HFpEF and HF(m)rEF]. Due to limited size, all subjects with LVEF <50% and symptoms or signs of HF were classified as HF with reduced and mildly reduced ejection fraction [HF(m)rEF]. RESULTS: Within 6209 participants with full periodontal examination, we identified an overlap of n = 167 participants with periodontitis and HF. Participants with severe periodontitis showed a higher burden of cardiovascular risk factors (men at advanced age, diabetes mellitus, hypertension) when compared with participants with none/mild periodontitis. After adjustment for age, sex, body mass index, smoking, diabetes, hypertension, atrial fibrillation, and coronary artery disease, severe periodontitis was significantly associated with HF(m)rEF (odds ratio: 3.16; 95% CI: 1.21, 8.22; P = 0.019), although no association was found for HFpEF and HF in general. CONCLUSIONS: The current study demonstrated that severe periodontitis was significantly associated with HF(m)rEF, although no relevant associations were found with HFpEF and HF in general as well as echocardiographic variables. The results implicate a potential target group, who need special attention from cooperating physicians and dentists. Future studies are warranted to verify whether systemic inflammation could be the link between the two diseases.

Cross-sectional study on the association of periodontitis with arterial hypertension in the Hamburg City Health Study.

AIM: Aim of this study was to investigate the association between periodontitis and arterial hypertension, both of which show correlations with classical cardiovascular risk factors and inflammatory activity. MATERIALS AND METHODS: A cross-sectional analysis of data from a large population-based health survey (the Hamburg City Health Study, HCHS) including 5934 participants with complete periodontal examination and blood pressure data, of whom 5735 had medical records regarding anti-hypertensive medication, was performed. Probing depths, gingival recessions, bleeding on probing (BOP), dental plaque, and decayed-missing-filled teeth (DMFT) indices were recorded as measures of oral health. Clinical attachment loss (CAL) per tooth was calculated and periodontitis was staged into three groups (no/mild, moderate, severe). Arterial hypertension was diagnosed based on the participants' medication history and systolic and diastolic blood pressure values. Logistic regression models were constructed accounting for a set of potential confounders (age, sex, smoking, body mass index (BMI), diabetes, educational level, alcohol intake) and high sensitivity-C-reactive protein (hsCRP). RESULTS: The odds of arterial hypertension increased significantly along with periodontitis severity (OR for severe periodontitis: 2.19; 95% CI 1.85-2.59; p < 0.001; OR for moderate periodontitis: 1.65; 95% CI 1.45-1.87; p < 0.001). Participants with moderate or severe periodontitis also had significantly higher age- and sex-adjusted odds of arterial hypertension, which was slightly weakened when additionally adjusted for BMI, diabetes, smoking, educational level, and alcohol intake (OR for severe PD: 1.28, 95% CI 1.04-1.59, p = 0.02; OR for moderate PD: 1.30, 95% CI 1.11-1.52, p = 0.001). The fraction of participants with undertreated hypertension (untreated and poorly controlled hypertension) was considerably larger in participants with severe periodontitis than in those with no/mild periodontitis (50.1% vs. 37.4% for no/mild periodontitis). CONCLUSIONS: The study shows an association between periodontitis and arterial hypertension that is independent of age, sex, diabetes, BMI, smoking, educational level, and alcohol intake. In addition, undertreatment of hypertension was more common in people with severe periodontitis compared with periodontally more healthy people.

Evidence from the Hamburg City Health Study - association between education and periodontitis.

OBJECTIVE: Large-scale population-based studies regarding the role of education in periodontitis are lacking. Thus, the aim of the current study was to analyze the potential association between education and periodontitis with state of the art measured clinical phenotypes within a large population-based sample from northern Germany. MATERIAL & METHODS: The Hamburg City Health Study (HCHS) is a population-based cohort study registered at ClinicalTrial.gov (NCT03934957). Oral health was assessed via plaque-index, probing depth, gingival recession and gingival bleeding. Periodontitis was classified according to Eke & Page. Education level was determined using the International Standard Classification of Education (ISCED-97) further categorized in "low, medium or high" education. Analyses for descriptive models were stratified by periodontitis severity. Ordinal logistic regression models were stepwise constructed to test for hypotheses. RESULTS: Within the first cohort of 10,000 participants, we identified 1,453 with none/mild, 3,580 with moderate, and 1,176 with severe periodontitis. Ordinal regression analyses adjusted for co-variables (age, sex, smoking, diabetes, hypertension and migration) showed that the education level (low vs. high) was significantly associated with periodontitis (OR: 1.33, 95% CI: 1.18;1.47). CONCLUSION: In conclusion, the current study revealed a significant association between the education level and periodontitis after adjustments for a set of confounders. Further research is needed to develop strategies to overcome education related deficits in oral and periodontal health.

Antibacterial properties of functionalized silk fibroin and sericin membranes for wound healing applications in oral and maxillofacial surgery.

Oral wounds are among the most troublesome injuries which easily affect the patients' quality of life. To date, the development of functional antibacterial dressings for oral wound healing remains a challenge. In this regard, we investigated antibacterial silk protein-based membranes for the application as wound dressings in oral and maxillofacial surgery. The present study includes five variants of casted membranes, i.e., i) membranes-silver nanoparticles (CM-Ag), ii) membranes-gentamicin (CM-G), iii) membranes-control (without functionalization) (CM-C), iv) membranes-silk sericin control (CM-SSC), and v) membranes-silk fibroin/silk sericin (CM-SF/SS), and three variants of nonwovens, i.e., i) silver nanoparticles (NW-Ag), ii) gentamicin (NW-G), iii) control (without functionalization) (NW-C). The surface structure of the samples was visualized with scanning electron microscopy. In addition, antibacterial testing was accomplished using agar diffusion assay, colony forming unit (CFU) analysis, and qrt-PCR. Following antibacterial assays, biocompatibility was evaluated by cell proliferation assay (XTT), cytotoxicity assay (LDH), and live-dead assay on L929 mouse fibroblasts. Findings indicated significantly lower bacterial colony growth and DNA counts for CM-Ag with a reduction of bacterial counts by 3log levels (99.9% reduction) in CFU and qrt-PCR assay compared to untreated control membranes (CM-C and CM-SSC) and membranes functionalized with gentamicin (CM-G and NW-G) (p < 0.001). Similarly, NW-G yielded significantly lower DNA and colony growth counts compared to NW-Ag and NW-C (p < 0.001). In conclusion, CM-Ag represented 1log level better antibacterial activity compared to NW-G, whereas NW-G showed better cytocompatibility for L929 cells. As data suggest, these two membranes have the potential of application in the field of bacteria-free oral wound healing. However, provided that loading strategy and cytocompatibility are adjusted according to the antibacterial agents' characteristic and fabrication technique of the membranes.

Tissue Adhesives in Reconstructive and Aesthetic Surgery-Application of Silk Fibroin-Based Biomaterials.

Tissue adhesives have been successfully used in various kind of surgeries such as oral and maxillofacial surgery for some time. They serve as a substitute for suturing of tissues and shorten treatment time. Besides synthetic-based adhesives, a number of biological-based formulations are finding their way into research and clinical application. In natural adhesives, proteins play a crucial role, mediating adhesion and cohesion at the same time. Silk fibroin, as a natural biomaterial, represents an interesting alternative to conventional medical adhesives. Here, the most commonly used bioadhesives as well as the potential of silk fibroin as natural adhesives will be discussed.

Cross-sectional analysis of the association of periodontitis with carotid intima media thickness and atherosclerotic plaque in the Hamburg City health study.

BACKGROUND: Previous epidemiological studies regarding the association between chronic periodontitis (CP) and carotid intima-media thickness (cIMT) and subclinical atherosclerosis have been inconclusive. OBJECTIVE: The aim of this study was to determine whether CP is associated with subclinical atherosclerosis in a large population-based cohort study conducted in northern Germany (the Hamburg City Health study). METHODS: Baseline data from 5781 participants of the Hamburg City Health Study with complete oral health and carotid ultrasound data (50.7% female, mean age: 62.1 ± 8.4 years) were evaluated. A standardized duplex sonography of the carotid artery was performed with measurement of carotid intima-media thickness (cIMT) and atherosclerotic plaques. Oral health was assessed by recording the decayed, missing, and filled teeth (DMFT) index, clinical attachment loss (CAL), bleeding on probing (BOP), and the dental plaque index (PI). Correlations were tested for statistical significance by means of descriptive statistics and multivariate regression analyses. RESULTS: Moderate and severe CP were associated with the prevalence of cIMT ≥ 1 mm (none or mild CP: 5.1%, moderate CP: 6.1%, severe CP: 10%) and mean cIMT (none or mild CP: 0.72 mm, moderate CP: 0.75 mm, severe CP: 0.78 mm) in bivariate analyses (p < .001). Additionally, severe and moderate CP were associated with higher prevalence of carotid atherosclerotic plaques (plaque = yes: none or mild CP: 23.9%, moderate CP: 29%, severe CP: 40.2%,). After adjustment for age, sex, smoking, diabetes, hypertension, educational level, hypercholesterolemia, and hsCRP, severe CP still correlated significantly with cIMT and the prevalence of cIMT ≥1 mm and/or presence of carotid atherosclerotic plaques. CONCLUSION: In this study, severe CP was associated with increased cIMT and higher prevalence of carotid plaques independent of common risk factors.

Association between periodontitis and metabolic syndrome in the Hamburg City Health Study.

BACKGROUND: Previous studies demonstrated an association between severe chronic periodontitis (CP) and metabolic syndrome (MetS). However, these studies mostly used the outdated National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATP) III case definition of MetS. Additionally, CP was rarely diagnosed based on a full-mouth examination. Thus, the aim of the current study was to re-evaluate the potential association between CP and MetS in the Hamburg City Health Study (HCHS), a large population-based survey of middle-aged and elderly men and women in Germany, in view of more current definitions of MetS and CP. METHODS: A cross-sectional study was performed with baseline-data from participants of the HCHS. Periodontitis severity grades were determined in a random sample of 6,209 participants of which 5,456 had sufficient data to call absence or presence of MetS. Variables defining MetS according to the currently valid harmonized definition were determined and a full-mouth examination was performed, including determination of the clinical attachment loss, bleeding on probing, and dental plaque index. CP was classified in three grades of severity (none/mild, moderate, and severe). The Kruskal-Wallis test or the Chi-squared test were used for descriptive statistics and multivariate logistic regression models with and without adjustments for potential confounders (age, sex, smoking, high-sensitivity C-reactive protein [hsCRP], energy intake, and physical activity) were used to test for associations. RESULTS: The prevalence of MetS (39.0%) increased according to the severity grades of periodontitis (none/mild: 33.6%; moderate: 38.7%, and severe: 46.8%). Multivariate logistic regression analyses demonstrated that severe but not moderate CP was associated with MetS after adjusting for age and sex (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.03 to 1.48; P = 0.02). However, the association was attenuated after additional adjustment for smoking (OR, 1.19; 95% CI, 0.99 to 1.43; P = 0.058) and hsCRP, energy intake, and physical activity (OR, 1.11; 95% CI, 0.91 to 1.36; P = 0.294). CONCLUSIONS: The use of the more current definitions for MetS and CP confirmed previous observations of an age- and sex-adjusted association between severe CP and MetS. Smoking, high-energy intake, and low physical activity were identified as important lifestyle-related confounders. Abdominal obesity, as indicated by elevated waist circumference, was determined as the most important component of MetS in relationship to CP.

Periodontitis, dental plaque, and atrial fibrillation in the Hamburg City Health Study.

BACKGROUND/AIM: Atrial fibrillation (AF) is a major health problem and causes heart failure and stroke. Pathophysiological mechanisms indicate a link with oral health including periodontitis (PD), but supporting data are scarce. The aim was to investigate the link between features of oral health and the prevalence of AF. METHODS: This cross-sectional analysis of the Hamburg City Health Study included 5,634 participants with complete data on their PD and AF status. AF was assessed via self-reported questionnaire or medically diagnosed by standard 12-lead resting ECG. The oral health examination included full-mouth measurements of the dental plaque index (PI), the clinical attachment loss (CAL) at 6 sites per tooth, the bleeding on probing (BOP) and the decayed, missing and filled teeth (DMFT) index. Descriptive analyses for all variables stratified by the status of PD were performed. To test for an association between prevalent PD and prevalent AF, multivariable logistic regression models were used. Mediation analysis was used to test if interleukin-6 (IL-6) and/or C-reactive protein (CRP) mediated the association between PD and AF. RESULTS: Atrial fibrillation (prevalence: 5.6%) and the severity of PD (prevalence: moderate: 57.7%, severe: 18.9%) increased with age in men and women. Prevalent severe PD, CAL ≥3 mm, PI, and BOP were all associated with prevalent AF in unadjusted regression analysis. However, no association except for PI (odds ratio (OR): 1.22, 95% confidence interval (CI): 1.1-1.35, p<0.001) could be observed after adjusting for age, sex, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), body mass index, diabetes, smoking, and educational level. Participants brushing their teeth at least twice daily had a lower AF prevalence compared with those brushing only once daily. Hs-CRP, IL-6, and the odds of AF increased as a function of PD severity grades in unadjusted analysis. However, neither the DMFT index nor IL-6 or CRP was associated with AF after adjusting for age and sex. Mediation analyses could not provide support for the hypothesis that IL-6 or CRP acted as mediator of the association between prevalent PD and prevalent AF. CONCLUSION: The study shows an association between prevalent AF and increased dental plaque levels indicated by a higher PI. In contrast, an association of prevalent PD with prevalent AF after adjustments for several confounders could not be demonstrated. Further studies are necessary to investigate the mechanisms underlying poor oral hygiene and AF as well as the influence of improved oral hygiene on AF onset.

The Association of Periodontitis and Peripheral Arterial Occlusive Disease in a Prospective Population-Based Cross-Sectional Cohort Study.

OBJECTIVES: Peripheral arterial occlusive disease (PAOD) and periodontitis are common chronic diseases, which together affect almost 1 billion people worldwide. There is growing evidence suggesting a relationship between chronic inflammatory conditions such as periodontitis and PAOD. This study aims to determine an association between both entities using high quality research data and multiple phenotypes derived from an epidemiological cohort study. DESIGN: This population-based cross-sectional cohort study included data from 3271 participants aged between 45 and 74 years enrolled in the Hamburg City Health Study (NCT03934957). MATERIAL & METHODS: An ankle-brachial-index below 0.9, color-coded ultrasound of the lower extremity arteries, and survey data was used to identify participants with either asymptomatic or symptomatic PAOD. Periodontitis data was collected at six sites per tooth and included the probing depth, gingival recession, clinical attachment loss, and bleeding on probing index. Multivariate analyses using logistic regression models were adjusted for variables including age, sex, smoking, education, diabetes, and hypertension. RESULTS: The baseline characteristics differed widely between participants neither affected by periodontitis nor PAOD vs. the group where both PAOD and severe periodontitis were identified. A higher rate of males, higher age, lower education level, smoking, diabetes, and cardiovascular disease was observed in the group affected by both diseases. After adjusting, presence of severe periodontitis (odds ratio 1.265; 97.5% CI 1.006-1.591; p = 0.045) was independently associated with PAOD. CONCLUSION: In this cross-sectional analysis of a prospective cohort study, an independent association between periodontitis and PAOD was revealed. The results of the current study emphasize a potential for preventive medicine in an extremely sensitive target population. Future studies should determine the underlying factors modifying the relationship between both diseases.

Autoantibodies against M5-muscarinic and beta1-adrenergic receptors in periodontitis patients.

Autoantibodies against muscarinic and beta1-adrenergic receptors are considered a potential cause and/or risk factor for chronic heart failure. Association of periodontitis with such autoantibodies and with impaired heart function has been observed in patients exposed to endemic Chagas' disease, which triggers by itself cardiomyopathy and receptor immunization.Here we studied the association between periodontitis, markers of cardiac injury and receptor autoimmunization in periodontitis patients (n = 147) not exposed to Chagas' disease. The autoantibodies were determined by IgG binding to native intact muscarinic and beta1-adrenergic receptors or to a cyclic peptide mimicking the disease-relevant conformational autoepitope presented by the active beta1-adrenergic receptor. Possible cardiac injury and inflammatory status were judged by serum levels of proBNP/Troponin I and CRP/IL-6, respectively. These parameters were analysed in healthy and periodontally diseased individuals as well as before and after periodontal therapy.Patients with periodontitis had significantly (p < 0.001) higher levels of autoantibodies against M5-muscarinic and beta1-adrenergic receptors, which further increased following periodontal therapy. Receptor autoantibodies were associated with increased inflammatory status but not with increased markers of cardiac injury. Thus, our data indicate that periodontitis triggers systemic inflammation, which is associated with receptor autoimmunization, and, independently thereof, with cardiac injury.

Rationale and Design of the Hamburg City Health Study.

The Hamburg City Health Study (HCHS) is a large, prospective, long-term, population-based cohort study and a unique research platform and network to obtain substantial knowledge about several important risk and prognostic factors in major chronic diseases. A random sample of 45,000 participants between 45 and 74 years of age from the general population of Hamburg, Germany, are taking part in an extensive baseline assessment at one dedicated study center. Participants undergo 13 validated and 5 novel examinations primarily targeting major organ system function and structures including extensive imaging examinations. The protocol includes validate self-reports via questionnaires regarding lifestyle and environmental conditions, dietary habits, physical condition and activity, sexual dysfunction, professional life, psychosocial context and burden, quality of life, digital media use, occupational, medical and family history as well as healthcare utilization. The assessment is completed by genomic and proteomic characterization. Beyond the identification of classical risk factors for major chronic diseases and survivorship, the core intention is to gather valid prevalence and incidence, and to develop complex models predicting health outcomes based on a multitude of examination data, imaging, biomarker, psychosocial and behavioral assessments. Participants at risk for coronary artery disease, atrial fibrillation, heart failure, stroke and dementia are invited for a visit to conduct an additional MRI examination of either heart or brain. Endpoint assessment of the overall sample will be completed through repeated follow-up examinations and surveys as well as related individual routine data from involved health and pension insurances. The study is targeting the complex relationship between biologic and psychosocial risk and resilience factors, chronic disease, health care use, survivorship and health as well as favorable and bad prognosis within a unique, large-scale long-term assessment with the perspective of further examinations after 6 years in a representative European metropolitan population.

Polyphenols in the prevention and treatment of periodontal disease: A systematic review of in vivo, ex vivo and in vitro studies.

Plant-derived polyphenols with antimicrobial and immunomodulatory characteristics appear to provide a variety of oral health benefits. Thus, the aim of the present study was to review the scientific literature to identify these effects of polyphenols on periodontal pathogens and inflammation. A MEDLINE search from 1st January 2013 to 18th January 2018 was performed to identify studies reporting polyphenol-containing plant extracts. Reports regarding pure compounds and essential oils, as well as effects on bacteria that are not defined as periodontal pathogens, were excluded. Thirty-eight studies matched the selection criteria. Studies on immunomodulatory effects included in vitro, ex vivo, and in vivo studies (n = 23), whereas studies reporting antibacterial effects against periodontal pathogens included only in vitro studies (n = 18). Three studies were included in both groups. The antibacterial effects were characterised by inhibition of bacterial growth, adhesion to oral cells, and enzymatic activity. Decreased secretion of pro-inflammatory and increased secretion of anti-inflammatory cytokines were demonstrated. Higher attachment levels, lower inflammation, and bone loss were reported by in vivo studies. Due to the high heterogeneity, it is difficult to draw clear conclusions for applicability; nevertheless, polyphenols have great potential as antimicrobial and immunomodulatory substances in the treatment and prevention of periodontal disease.

Regulator of Calcineurin 1 in Periodontal Disease.

Nuclear factor of activated T-cells (NFAT) and NF-kB pathway associated processes are involved in the pathogenesis of various inflammatory disorders, for example, periodontal disease. The activation of these pathways is controlled by the regulator of calcineurin 1 (RCAN1). The aim of this study was to elucidate the role of RCAN1 in periodontal disease. Healthy and inflamed periodontal tissues were analyzed by immunohistochemistry and immunofluorescence using specific rabbit polyclonal anti-RCAN1 antibodies. For expression analysis human umbilical vein endothelial cells (HUVEC) were used. HUVEC were incubated for 2 h with Vascular Endothelial Growth Factor (VEGF) or with wild type and laboratory strains of Porphyromonas gingivalis (P. gingivalis). Expression analysis of rcan1 and cox2 was done by real time PCR using specific primers for rcan1.4 and cox2. The expression of rcan1 was found to be significantly suppressed in endothelial cells of chronically inflamed periodontal tissues compared to healthy controls. Rcan1 and cox2 were significantly induced by VEGF and wild type and laboratory P. gingivalis strains. Interestingly, the magnitude of the rcan1 and cox2 induction was strain dependent. The results of this study indicate that RCAN1 is suppressed in endothelial cells of chronically inflamed periodontal tissues. During an acute infection, however, rcan1 seems to be upregulated in endothelial cells, indicating a modulating role in immune homeostasis of periodontal tissues.

Extract from Rumex acetosa L. for prophylaxis of periodontitis: inhibition of bacterial in vitro adhesion and of gingipains of Porphyromonas gingivalis by epicatechin-3-O-(4ß→8)-epicatechin-3-O-gallate (procyanidin-B2-Di-gallate).

BACKGROUND: The aerial parts of Rumex acetosa L. have been used in traditional European medicine for inflammatory diseases of the mouth epithelial tissue. The following study aimed to investigate the influence of a proanthocyanidin-enriched extract from R. acetosa extract against the adhesion of Porphyromonas gingivalis (P. gingivalis), a pathogen strongly involved in chronic and aggressive periodontitis. A further goal was to define the bioactive lead structures responsible for a potential antiadhesive activity and to characterize the underlying molecular mechanisms of the antiadhesive effects. METHODOLOGY: An extract of R. acetosa (RA1) with a defined mixture of flavan-3-ols, oligomeric proanthocyanidins and flavonoids, was used. Its impact on P. gingivalis adhesion to KB cells was studied by flow cytometry, confocal laser scanning microscopy and in situ adhesion assay using murine buccal tissue. RA1 and its compounds 1 to 15 were further investigated for additional effects on gingipain activity, hemagglutination and gene expression by RT-PCR. PRINCIPAL FINDINGS: RA1 (5 to 15 µg/mL) reduced P. gingivalis adhesion in a dose-dependent manner to about 90%. Galloylated proanthocyanidins were confirmed to be responsible for this antiadhesive effect with epicatechin-3-O-gallate-(4ß,8)-epicatechin-3'-O-gallate (syn. procyanidin B2-di-gallate) being the lead compound. Ungalloylated flavan-3-ols and oligomeric proanthocyanidins were inactive. RA1 and the galloylated proanthocyanidins strongly interact with the bacterial virulence factor Arg-gingipain, while the corresponding Lys-gingipain was hardly influenced. RA1 inhibited also hemagglutination. In silico docking studies indicated that epicatechin-3-O-gallate-(4ß,8)-epicatechin-3'-O-gallate interacts with the active side of Arg-gingipain and hemaglutinin from P. gingivalis; the galloylation of the molecule seems to be responsible for fixation of the ligand to the protein. In conclusion, the proanthocyanidin-enriched extract RA1 and its main active constituent procyanidin B2-di-gallate protect cells from P. gingivalis infection by inhibiting bacterial adhesion to the host cell. RA1 and procyanidin B2-di-gallate appear to be promising candidates for future cytoprotective preparations for oral mouth care products.