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AimTo investigate whether there is an association between subgingival microbial diversity and reduced respiratory function.Materials and MethodsA group of dentate 58–72-year-old men in Northern Ireland had a comprehensive periodontal examination including subgingival plaque sampling. DNA was extracted from plaque samples and the V1–V3 regions of the 16S rRNA gene were analysed by high-throughput sequencing and a microbial diversity index (MDI) was derived. Spirometry measurements were made using a wedge bellows spirometer. The primary outcome variable of interest was the percentage of predicted forced expiratory volume in 1 s (% predicted FEV1). Analysis included multiple linear regression with adjustment for various confounders.ResultsFive-hundred and seven men were included in the analysis. The mean age was 63.6 years (SD = 3.1). Of these, 304 (60.0%) men had no or mild periodontitis, 105 (20.7%) had moderate periodontitis and 98 (19.3%) had severe periodontitis. Multiple linear regression analysis showed that a one unit increase in MDI was associated with a 0.71% loss (95% confidence interval: 0.06%–1.35%; p = .03) in % predicted FEV1 after adjustment for all confounders.ConclusionsIn this group of dentate men from Northern Ireland, subgingival microbial diversity was associated with reduced respiratory function.

There is a growing level of interest in the potential role inflammation has on the initiation and progression of malignancy. Notable examples include Helicobacter pylori-mediated inflammation in gastric cancer and more recently Fusobacterium nucleatum-mediated inflammation in colorectal cancer. Fusobacterium nucleatum is a Gram-negative anaerobic bacterium that was first isolated from the oral cavity and identified as a periodontal pathogen. Biofilms on oral squamous cell carcinomas are enriched with anaerobic periodontal pathogens, including F. nucleatum, which has prompted hypotheses that this bacterium could contribute to oral cancer development. Recent studies have demonstrated that F. nucleatum can promote cancer by several mechanisms; activation of cell proliferation, promotion of cellular invasion, induction of chronic inflammation and immune evasion. This review provides an update on the association between F. nucleatum and oral carcinogenesis, and provides insights into the possible mechanisms underlying it.

AIM The aim was to investigate the role of systemic inflammation in the relationship between periodontitis, edentulism, and all-cause mortality in a group of men in Northern Ireland aged 58-72 years. MATERIALS AND METHODS A representative sample of 1558 men had a detailed dental examination between 2001 and 2003. The primary end point was death from any cause. Cox's proportional hazards model was used to assess the longitudinal relationship between periodontitis, edentulism, and all-cause mortality. Accelerated failure time modelling was performed to investigate the mediating role of systemic inflammation. RESULTS Mean age of the men at baseline was 64.3 (standard deviation 2.9) years. During a median follow-up of 17 years, 500 (32.1%) men died. After adjustment for confounding variables, compared to men with no/mild periodontitis, edentulous men had a hazard ratio for all-cause mortality of 1.52 (95% confidence interval [CI] 1.16-1.99) p

Background A growing body of evidence suggests a role for oral bacteria in lung infections. This systematic review aimed to analyse the association between poor periodontal status and the frequency of chronic obstructive pulmonary disease (COPD) exacerbations. Methods PubMed, Embase, Web of Science, CINAHL and Medline were searched for studies published until May 2020, with no language restriction. Studies reporting periodontal condition, or periodontal treatment outcomes, with data on the frequency of exacerbations of COPD, were identified. The primary outcome was the frequency of exacerbations and secondary outcomes included quality of life (QoL) and hospitalisation. Quality and risk of bias assessment were carried out using the Newcastle Ottawa Scale for observational studies, Robins-1 tool for non-randomised intervention studies and Cochrane risk of bias assessment (RoB-2) tool for randomised clinical trials. Studies were assessed for eligibility and quality by two assessors independently. Results Searches identified 532 records and 8 met the inclusion criteria. Included studies were three clinical trials, one prospective cohort study, one case–control, and three cross-sectional studies. A narrative synthesis was performed. The data from intervention studies showed reduction in the frequency of exacerbations following periodontal treatment. Data from observational studies suggest association of worse plaque scores and fewer teeth with exacerbation, but not pocket depth or clinical attachment loss. Better periodontal health was also associated with reduced frequency of COPD exacerbations, hospitalisations and improved quality of life in COPD patients. Due to the high heterogeneity no meta-analysis was performed. The quality of some of the included studies was low and there was evidence of a high risk of bias. Conclusion The data supports possible association between poor periodontal health, the frequency of exacerbations, hospitalisation and quality of life in COPD patients. The evidence is of moderate to low certainty and is limited by high risk of bias suggesting the need for well-designed and adequately powered randomised controlled trials, to inform future research and clinical practice. The PROSPERO registration number CRD42020180328.

OBJECTIVE: To investigate periodontitis as a risk factor for prevalent and incident coronary heart disease (CHD) in a group of middle-aged men from Northern Ireland.METHODS: A representative sample of 1400 dentate men had a comprehensive periodontal examination between 2001 and 2003. Prevalent and incident CHD events were validated by independent cardiologists. Logistic regression was used to assess the cross-sectional relationship between periodontitis and prevalent CHD and Cox's proportional hazards analysis to assess the longitudinal relationship between periodontitis and incident CHD.RESULTS: The mean age of the men at baseline was 63.7 (SD 3.0) years. Of the 1400 men examined, 126 (9%) had prevalent CHD. After adjusting for confounding variables, men with highest mean CAL (Q4) had an odds ratio of 2.15 (95% CI 1.15-4.02), p = 0.02 for prevalent CHD in comparison to men with the lowest CAL (Q1). During a median follow-up of 12.7 years, 137 (10.8%) of the 1274 men free of CHD at baseline had an incident CHD event. After adjusting for confounding variables, the hazard ratio for incident CHD in men in Q4 versus Q1 CAL categories was 1.36 (95% CI 0.81-2.29), p = 0.24.CONCLUSIONS: In this group of dentate men, periodontitis was associated with prevalent CHD. However, there was no association with incident CHD.

Introduction Like many tissues, the dental pulp is equipped with innate and adaptive immune responses, designed to defend against infection and limit its spread. The pulp’s innate immune response includes the synthesis and release of antimicrobial peptides by several dental pulp cell types. These naturally-occurring antimicrobial peptides have broad spectrum activity against bacteria, fungi and viruses. There is a resurgence of interest in the bioactivities of naturally-occurring antimicrobial peptides, largely driven by the need to develop alternatives to antibiotics. Methods This narrative review focused on the general properties of antimicrobial peptides, providing an overview of their sources and actions within the dental pulp. Results We summarized the relevance of antimicrobial peptides in defending the dental pulp, highlighting the potential for many of these antimicrobials to be modified or mimicked for prospective therapeutic use. Conclusion Antimicrobial peptides and novel peptide-based therapeutics are particularly attractive as emerging treatments for polymicrobial infections, such as endodontic infections, because of their broad activity against a range of pathogens.

BackgroundPeriodontitis is a major cause of tooth loss globally. Risk factors include age, smoking, and diabetes. Intake of specific nutrients has been associated with periodontitis risk but there has been little research into the influence of overall diet, potentially more relevant when formulating dietary recommendations.ObjectivesWe aimed to investigate potential associations between diet and periodontitis using novel statistical techniques for dietary pattern analysis.MethodsTwo 24-h dietary recalls and periodontal examination data from the cross-sectional US NHANES, 2009–2014 (n = 10,010), were used. Dietary patterns were extracted using treelet transformation, a data-driven hierarchical clustering and dimension reduction technique. Associations between each pattern [treelet component (TC)] and extent of periodontitis [proportion of sites with clinical attachment loss (CAL) ≥ 3 mm] were estimated using robust logistic quantile regression, adjusting for age, sex, ethnicity, education level, smoking, BMI, and diabetes.ResultsEight TCs explained 21% of the variation in diet, 1 of which (TC1) was associated with CAL extent. High TC1 scores represented a diet rich in salad, fruit, vegetables, poultry and seafood, and plain water or tea to drink. There was a substantial negative gradient in CAL extent from the lowest to the highest decile of TC1 (median proportion of sites with CAL ≥ 3 mm: decile 1 = 19.1%, decile 10 = 8.1%; OR, decile 10 compared with decile 1: 0.67; 95% CI: 0.46, 0.99).ConclusionsMost dietary patterns identified were not associated with periodontitis extent. One pattern, however, rich in salad, fruit, and vegetables and with plain water or tea to drink, was associated with lower CAL extent. Treelet transformation may be a useful approach for calculating dietary patterns in nutrition research.

Objectives The aim of this study was to investigate periodontitis as a risk factor for incident type 2 diabetes mellitus (T2DM) in a group of men aged 58–72 years. Methods One thousand three hundred and thirty-one dentate, diabetes-free men in Northern Ireland underwent a detailed periodontal examination during 2001–2003. Follow-up was by bi-annual questionnaire and for those reporting diabetes their general medical practitioner was contacted to validate diabetes type, treatment and diagnosis date. Cox's proportional hazard models were used to estimate the effect of periodontitis on incident diabetes. Multivariable analysis included adjustment for various known confounders. Results The mean age of the men was 63.7 (SD 3.0) years. There were 80 cases (6.0%) of incident T2DM. Follow-up was for a median period of 7.8 years (IQR 6.7–8.3). After adjusting for confounding variables, the hazard ratio (HR) for incident T2DM in men with moderate/severe periodontitis versus those with no/mild periodontitis was 1.69 (95% CI 1.06–2.69), p = 0.03. Conclusion There was evidence in this homogenous group of dentate men, that those with moderate to severe periodontitis had a significantly increased risk of incident T2DM.

Aims Epidemiological evidence suggests that adipokines may be associated with the onset of type 2 diabetes, but the evidence to date is limited and inconclusive. This study examined the association between adiponectin and leptin and the subsequent diagnosis of type 2 diabetes in a UK population based cohort of non-diabetic middle-aged men. Methods Baseline serum levels of leptin and adiponectin were measured in 1839 non-diabetic men aged 50–60 years who were participating in the prospective population-based PRIME study. Over a mean follow-up of 14.7 years, new cases of type 2 diabetes were determined from self-reported clinical information with subsequent validation by general practitioners. Results 151 Participants developed type 2 diabetes during follow-up. In Cox regression models adjusted for age, men in the top third of the leptin distribution were at increased risk (hazard ratio (HR) 4.27, 95% CI 2.67–6.83) and men in the top third of the adiponectin distribution at reduced risk (HR 0.24, 95% CI 0.14–0.42) relative to men in the bottom third. However, significance was lost for leptin after additional adjustment for BMI, waist to hip ratio, lifestyle factors and biological risk factors, including C-reactive protein (CRP). Further adjustment for HOMA-IR also resulted in loss of significance for adiponectin. Conclusions This study provides evidence that adipokines are associated with men’s future type 2 diabetes risk but not independently of other risk factors.

AIMS: Our aims were to evaluate the distribution of troponin I concentrations in population cohorts across Europe, to characterize the association with cardiovascular outcomes, to determine the predictive value beyond the variables used in the ESC SCORE, to test a potentially clinically relevant cut-off value, and to evaluate the improved eligibility for statin therapy based on elevated troponin I concentrations retrospectively.METHODS AND RESULTS: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project, we analysed individual level data from 10 prospective population-based studies including 74 738 participants. We investigated the value of adding troponin I levels to conventional risk factors for prediction of cardiovascular disease by calculating measures of discrimination (C-index) and net reclassification improvement (NRI). We further tested the clinical implication of statin therapy based on troponin concentration in 12 956 individuals free of cardiovascular disease in the JUPITER study. Troponin I remained an independent predictor with a hazard ratio of 1.37 for cardiovascular mortality, 1.23 for cardiovascular disease, and 1.24 for total mortality. The addition of troponin I information to a prognostic model for cardiovascular death constructed of ESC SCORE variables increased the C-index discrimination measure by 0.007 and yielded an NRI of 0.048, whereas the addition to prognostic models for cardiovascular disease and total mortality led to lesser C-index discrimination and NRI increment. In individuals above 6 ng/L of troponin I, a concentration near the upper quintile in BiomarCaRE (5.9 ng/L) and JUPITER (5.8 ng/L), rosuvastatin therapy resulted in higher absolute risk reduction compared with individuals CONCLUSION: In individuals free of cardiovascular disease, the addition of troponin I to variables of established risk score improves prediction of cardiovascular death and cardiovascular disease.

The transient receptor potential (TRP) channels are unique cellular sensors that are widely expressed in many neuronal and nonneuronal cells. Among the TRP family members, TRPA1 and TRPV4 are emerging as candidate mechanosensitive channels that play a pivotal role in inflammatory pain and mechanical hyperalgesia. Odontoblasts are nonneuronal cells that possess many of the features of mechanosensitive cells and mediate important defense and sensory functions. However, the effect of inflammation on the activity of the odontoblast's mechanosensitive channels remains unknown. By using immunohistochemistry and calcium microfluorimetry, we showed that odontoblast-like cells express TRPA1 and TRPV4 and that these channels were activated by hypotonicity-induced membrane stretch. Short treatment of odontoblast-like cells with tumor necrosis factor (TNF)-α enhanced TRPA1 and TRPV4 responses to their chemical agonists and membrane stretch. This enhanced channel activity was accompanied by phospho-p38 mitogen-activated protein kinase (MAPK) expression. Treatment of cells with the p38 inhibitor SB202190 reduced TNF-α effects, suggesting modulation of channel activity via p38 MAPK. In addition, TNF-α treatment also resulted in an up-regulation of TRPA1 expression but down-regulation of TRPV4. Unlike TRPV4, enhanced TRPA1 expression was also evident in dental pulp of carious compared with noncarious teeth. SB202190 treatment significantly reduced TNF-α-induced TRPA1 expression, suggesting a role for p38 MAPK signaling in modulating both the transcriptional and non-transcriptional regulation of TRP channels in odontoblasts.

BACKGROUND AND AIMS: The scope of this working group was to review: (1) the effect of professional mechanical plaque removal (PMPR) on secondary prevention of periodontitis; (2) the occurrence of gingival recessions and non-carious cervical lesions (NCCL) secondary to traumatic tooth brushing; (3) the management of hypersensitivity, through professionally and self administered agents and (4) the management of oral malodour, through mechanical and/or chemical agents. RESULTS AND CONCLUSIONS: Patients undergoing supportive periodontal therapy including PMPR showed mean tooth loss rates of 0.15 ± 0.14 teeth/year for 5-year follow-up and 0.09 ± 0.08 teeth/year (corresponding to a mean number of teeth lost ranging between 1.1 and 1.3) for 12-14 year follow-up. There is no direct evidence to confirm tooth brushing as the sole factor causing gingival recession or NCCLs. Similarly, there is no conclusive evidence from intervention studies regarding the impact of manual versus powered toothbrushes on development of gingival recession or NCCLs, or on the treatment of gingival recessions. Local and patient-related factors can be highly relevant in the development and progression of these lesions. Two modes of action are used in the treatment of dentine hypersensitivity: dentine tubule occlusion and/or modification or blocking of pulpal nerve response. Dentifrices containing arginine, calcium sodium phosphosilicate, stannous fluoride and strontium have shown an effect on pain reduction. Similarly, professionally applied prophylaxis pastes containing arginine and calcium sodium phosphosilicate have shown efficacy. There is currently evidence from short-term studies that tongue cleaning has an effect in reducing intra-oral halitosis caused by tongue coating. Similarly, mouthrinses and dentifrices with active ingredients based on Chlorhexidine, Cetylpyridinium chloride and Zinc combinations have a significant beneficial effect. ispartof: Journal of Clinical Periodontology vol:42 issue:S16 pages:S214-S220 ispartof: location:SPAIN status: published

BACKGROUND AND OBJECTIVES: There has been limited study of the bacterial species associated with aggressive periodontitis (AgP) in high-risk populations in Africa. The aim of this study was to investigate and quantify the presence of four putative periodontal pathogens in the subgingival plaque of Sudanese subjects with AgP. A secondary aim was to investigate the effect of varying the detection threshold on the reported prevalence of the bacterial species investigated.MATERIALS AND METHODS: Subgingival plaque samples were collected from AgP cases (n=73) and healthy controls (n=71). Bacterial DNA was extracted and analyzed by quantitative polymerase chain reaction for the detection and quantification of four putative periodontal pathogens: Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Treponema denticola and Tannerella forsythia.RESULTS: At the lowest detection threshold (>10(1) cells), P. gingivalis (p70%) in AgP cases at all detection levels. While T. forsythia was significantly more frequently identified in AgP than in controls at all detection thresholds, this was only the case for T. denticola at the intermediate threshold (>10(2) cells). A. actinomycetemcomitans was identified less frequently than the other bacterial species with no difference in its prevalence between AgP cases and controls.CONCLUSION: The prevalence of the putative periodontal pathogens investigated varied considerably in Sudanese subjects with AgP and in periodontally healthy controls depending on the detection thresholds applied. T. forsythia was identified as having the strongest association with AgP.

The aryl hydrocarbon receptor interacting protein (AIP) founder mutation R304* (or p.R304*; NM_003977.3:c.910C>T, p.Arg304Ter) identified in Northern Ireland (NI) predisposes to acromegaly/gigantism; its population health impact remains unexplored. We measured R304* carrier frequency in 936 Mid Ulster, 1000 Greater Belfast (both in NI) and 2094 Republic of Ireland (ROI) volunteers and in 116 acromegaly/gigantism patients. Carrier frequencies were 0.0064 in Mid Ulster (95%CI = 0.0027-0.013; P = 0.0005 vs. ROI), 0.001 in Greater Belfast (0.00011-0.0047) and zero in ROI (0-0.0014). R304* prevalence was elevated in acromegaly/gigantism patients in NI (11/87, 12.6%, P < 0.05), but not in ROI (2/29, 6.8%) vs. non-Irish patients (0-2.41%). Haploblock conservation supported a common ancestor for all the 18 identified Irish pedigrees (81 carriers, 30 affected). Time to most recent common ancestor (tMRCA) was 2550 (1275-5000) years. tMRCA-based simulations predicted 432 (90-5175) current carriers, including 86 affected (18-1035) for 20% penetrance. In conclusion, R304* is frequent in Mid Ulster, resulting in numerous acromegaly/gigantism cases. tMRCA is consistent with historical/folklore accounts of Irish giants. Forward simulations predict many undetected carriers; geographically-targeted population screening improves asymptomatic carrier identification, complementing clinical testing of patients/relatives. We generated disease awareness locally, necessary for early diagnosis and improved outcomes of AIP-related disease. This article is protected by copyright. All rights reserved.

Background Little is known about the financial costs that smoking adds to the lifetime treatment of periodontal disease. Methods The total lifetime cost of periodontal treatment was modeled using data from private periodontal practice. The costs of initial and supportive therapy, re‐treatment and tooth replacements (with bridgework or implants) were identified using average dental charges from the American Dental Association survey. Smoking costs at $6 and $10 for 20 cigarettes were compared to the costs of lifetime periodontal treatment for stable and unstable compliant patients. Results Smoking added 8.8% to the financial cost of the lifetime cost of periodontal therapy in stable maintenance patients, 40.1% in patients who needed one extra maintenance visit, and 71.4% in patients who needed two extra maintenance visits per year in addition to added retreatment. The cost of smoking far exceeded the cost of periodontal treatment; For patients who smoked 10 to 40 cigarettes per day at the cost of $6 or $10 a pack, the cost of smoking exceeded the cost of lifetime periodontal treatment by between 2.7 and 17.9 times. Smoking 40 cigarettes at $10 a packet for 3.4 years would pay for the entire lifetime cost of periodontal treatment. Conclusion Smoking adds considerable extra financial costs to the lifetime treatment of periodontal diseases. The cost of smoking itself exceeds the cost of periodontal therapy.

Amongst the recognized classes of naturally occurring antimicrobials, human host defense peptides are an important group with an advantage (given their source) that they should be readily translatable to medicinal products. It is also plausible that truncated versions will display some of the biological activities of the parent peptide, with the benefit that they are less costly to synthesize using solid-phase chemistry. The host defense peptide, LL-37, and two truncated mimetics, KE-18 and KR-12, were tested for their inhibitory effects and antibiofilm properties against Candida albicans, Staphylococcus aureus, and Escherichia coli, microorganisms commonly implicated in biofilm-related infections such as ventilator-associated pneumonia (VAP). Using in silico prediction tools, the truncated peptides KE-18 and KR-12 were selected for minimum inhibitory concentration (MIC) and antibiofilm testing on the basis of their favorable cationicity, hydrophobic ratio, and amphipathicity compared with the parent peptide. Two methods were analyzed for determining peptide efficacy against biofilms; a crystal violet assay and an XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assay. The biocidal activities (measured by MIC) and antibiofilm activities (measured by a crystal violet assay) appeared to be independent. LL-37 had no biocidal action against C. albicans (MIC > 250 μg/ml) but significant effects in both biofilm-prevention and biofilm-inhibition assays. KE-18 and KR-12 yielded superior MIC values against all three microorganisms. Only KE-18 had a significant effect in the biofilm-prevention assay, which persisted even at sub-MICs. Neither of the truncated peptides were active in the biofilm-inhibition assay. KE-18 was shown to bind lipopolysaccharide as effectively as LL-37 and to bind lipoteichoic acid more effectively. None of the peptides showed hemolytic activity against human erythrocytes at the concentrations tested. KE-18 should be considered for further development as a natural peptide-derived therapeutic for prevention of multi-species biofilm-related infections such as VAP.

Purpose of Review The aim was to assess recent evidence that diabetes, metabolic syndrome (MetS) and obesity impact the progression of periodontitis. Recent Findings Electronic searches using Embase, Medline, and Web of Science were carried out for epidemiological studies on humans, published between 2014 and 2016. A small number of prospective studies and systematic reviews were identified that in general provide further support for the hypothesis that diabetes, metabolic syndrome and obesity can adversely affect the periodontal condition. Summary Confounding remains the most challenging issue in the interpretation of the associations found between diabetes, MetS, obesity and periodontal disease. Recent research applying a Mendelian randomisation approach concluded that the association between obesity and periodontitis is confounded and questioned a role for obesity in causation. Further studies are warranted to assess the issue of causality.

Over the last two decades there has been a renewed interest around the possible effects of periodontal disease on both cardiovascular health and pregnancy outcome (among other diseases), a topic which has interested science for hundreds of years. These have led to a range of studies, workshops and consensus documents being published, with corresponding coverage in general and professional media. In this article the authors summarise the history and supporting theories behind such associations, whether clinical studies have been able to confirm these and what this might mean for general practitioners who are questioned on this topic by patients.

Background and Objective: The matrix metalloproteinases (MMPs) play a role in regulating turnover and metabolism of connective tissues in health but they have also been implicated in a wide variety of pathological conditions, including periodontal disease. MMP-8 has been extensively studied in periodontal health and disease using ELISA, although this technique is limited by its inability to determine enzyme activity. The aim was to develop an assay specifically to measure MMP-8 activity and to demonstrate its use in the analysis of gingival crevicular fluid samples.Material and Methods: A specific antibody was used to coat black 96-well microtitre plates to capture MMP-8 selectively. The activity of bound MMP-8 was measured using a fluorogenic substrate. Gingival crevicular fluid samples, from healthy and periodontally diseased sites, were collected using PerioPaper strips and tested for MMP-8 activity.Results: Significantly higher MMP-8 activity was demonstrated in gingival crevicular fluid from periodontally diseased sites compared with healthy sites that exhibited basal or no MMP-8 activity. No cross-reactivity with other MMPs was noted.Conclusion: We show, for the first time, that MMP-8 activity can be specifically detected and quantified in gingival crevicular fluid samples. Measurement of MMP-8 activity could prove to be useful in monitoring periodontal disease progression.

International audience; Introduction: The transient receptor potential (TRP) ion channels have emerged as important cellular sensors in both neuronal and non-neuronal cells, with TRPA1 playing a central role in nociception and neurogenic inflammation. The functionality of TRP channels has been shown to be modulated by inflammatory cytokines. The aim of this study was to investigate the effect of inflammation on odontoblast TRPA1 expression and to determine the effect of Biodentine (Septodent, Paris, France) on inflammatory-induced TRPA1 expression. Methods: Immunohistochemistry was used to study TRPA1 expression in pulp tissue from healthy and carious human teeth. Pulp cells were differentiated to odontoblastlike cells in the presence of 2 mmol/L beta-glycerophosphate, and these cells were used in quantitative polymerase chain reaction, Western blotting, calcium imaging, and patch clamp studies. Results: Immunofluorescent staining revealed. TRPA1 expression in odontoblast cell bodies and odontoblast processes, which was more intense in carious versus healthy teeth. TRPA1 gene expression was induced in cultured odontoblastlike cells by tumor necrosis factor alpha, and this expression was significantly reduced in the presence of Biodentine. The functionality of the TRPA1 channel was shown by calcium microfluorimetry and patch clamp recording, and our results showed a significant reduction in tumor necrosis factor alpha induced TRPA1 responses after Biodentine treatment. Conclusions: In conclusion, this study showed TRPA1 to be modulated by caries-induced inflammation and that Biodentine reduced TRPA1 expression and functional responses.

Objectives To improve understanding about the potential underlying biological mechanisms in the link between depression and all-cause mortality and to investigate the role that inflammatory and other cardiovascular risk factors may play in the relationship between depressive symptoms and mortality. Methods Depression and blood-based biological markers were assessed in the Belfast PRIME prospective cohort study (N = 2389 men, aged 50-59 years) in which participants were followed up for 18 years. Depression was measured using the 10-item Welsh Pure Depression Inventory. Inflammation markers (C-reactive protein [CRP], neopterin, interleukin [IL]-1 receptor antagonist [IL-1Ra], and IL-18) and cardiovascular-specific risk factors (N-terminal pro-b-type natriuretic peptide, midregion pro-atrial natriuretic peptide, midregion pro-adrenomedullin, C-terminal pro-endothelin-1 [CT-proET]) were obtained at baseline. We used Cox proportional hazards modeling to examine the association between depression and biological measures in relation to all-cause mortality and explore the mediating effects. Results During follow-up, 418 participants died. Higher levels of depressive symptoms were associated with higher levels of CRP, IL-1Ra, and CT-proET. After adjustment for socioeconomic and life-style risk factors, depressive symptoms were significantly associated with all-cause mortality (hazard ratio = 1.10 per scale unit, 95% confidence interval = 1.04-1.16). This association was partly explained by CRP (7.3%) suggesting a minimal mediation effect. IL-1Ra, N-terminal pro-b-type natriuretic peptide, midregion pro-atrial natriuretic peptide, midregion pro-adrenomedullin, and CT-proET contributed marginally to the association between depression and subsequent mortality. Conclusions Inflammatory and cardiovascular risk markers are associated with depression and with increased mortality. However, depression and biological measures show additive effects rather than a pattern of meditation of biological factors in the association between depression and mortality.

To investigate the association between periodontitis and mortality from all causes in a prospective study in a homogenous group of 60- to 70-year-old West European men.A representative sample of 1400 dentate men, (mean age 63.8, SD 3.0 years), drawn from the population of Northern Ireland, had a comprehensive periodontal examination between 2001 and 2003. Men were divided into thirds on the basis of their mean periodontal attachment loss (PAL). The primary endpoint, death from any cause, was analysed using Kaplan-Meier survival plots and Cox's proportional hazards model.In total, 152 (10.9%) of the men died during a mean follow-up of 8.9 (SD 0.7) years; 37 (7.9%) men in the third with the lowest PAL (1.8 mm) died compared with 73 (15.7%) in the third with the highest PAL (2.6 mm). The unadjusted hazard ratio (HR) for death in the men with the highest level of PAL compared with those with the lowest PAL was 2.11 (95% CI 1.42-3.14), p 0.0001. After adjustment for confounding variables (age, smoking, hypertension, BMI, diabetes, cholesterol, education, marital status and previous history of a cardiovascular event) the HR was 1.57 (1.04-2.36), p = 0.03.The European men in this prospective cohort study with the most severe loss of periodontal attachment were at an increased risk of death compared with those with the lowest loss of periodontal attachment.

In recent years there has been considerable interest in possible links between periodontal disease and systemic diseases. The general public are increasingly aware that such links may exist and in some cases are concerned about the implications for them as individuals. Nearly half of all adults in the United Kingdom have some form of periodontal disease,1 and as such present to dental practices every day. It is essential that all members of the dental team are aware of the periodontitis-systemic disease link, and can provide clear evidence-based advice and information to patients. The aim of this article is to summarise the current state of knowledge so that members of the dental team can convey appropriate advice and guidance to patients.

International audience; Protease-activated receptors (PARs) are G-proteincoupled receptors that are activated enzymatically by proteolysis of an N-terminal domain. The cleavage and activation of PARs by serine proteases represent a novel mechanism by which such enzymes could influence the host inflammatory response. The aim of this study was to determine whether PAR-2 expression and activation were increased in dental caries. Using immunohistochemistry, we showed PAR-2 to be localized to pulp cells subjacent to caries lesions, but minimally expressed by healthy pulp tissue. Trypsin and the PAR-2 agonist (PAR2-AP) activated PAR-2 in an in vitro functional assay. Endogenous molecules present in pulp cell lysates from carious teeth specifically activated PAR-2, but those from healthy teeth failed to do so. The activation of PAR-2 in vitro was shown to increase the expression of the pro-inflammatory mediator cyclo-oxygenase-2 (COX-2), providing a mechanism whereby PAR-2 could modulate pulpal inflammation.

Chronic periodontitis (CP) is a common inflammatory disease which is characterized by progressive destruction of the tooth supporting structures and ultimately, potential tooth loss. A relationship between CP and diabetes has been recognized for some time. Both diseases share several collective risk factors, however, recent research has provided greater insight into the relationship with evidence emerging for each disease being a co-factor in the pathogenesis of the other. The aim of this review is to examine recent epidemiological evidence for the impact of diabetes on CP, and in the reverse direction, the impact of CP on diabetes. Based on the available evidence to date, it seems likely that the level of metabolic control influences future periodontal disease risk. In the reverse direction, the presence of CP has the potential to adversely affect glycemic control in both diabetes-affected and diabetes-free individuals. CP may potentially be a risk factor for the development of type 2 diabetes in diabetes-free individuals. Interventional studies show that successful treatment of CP may improve metabolic control in people with diabetes in the short term.

Key content •Pregnancy has significant effects on the periodontal tissues and pregnancy gingivitis is a common manifestation of this. •The host response and oral flora are affected and tooth surface loss and mobility may develop. •Further research is required to establish the association between periodontal health and adverse pregnancy outcome. Learning objectives •To identify the main dental manifestations of pregnancy. •To be able to advise pregnant women on how to maintain good dental health. •To be aware of the need for effective communication between the dental and medical disciplines to ensure that pregnant women receive the best care possible for oral, obstetric and general health. Ethical issues •The treatment of gingivitis and periodontitis during pregnancy is safe and effective in treating gum disease. Please cite this article as: Pirie M, Cooke I, Linden G, Irwin C. Dental manifestations of pregnancy. The Obstetrician & Gynaecologist 2007;9:21–26.

BACKGROUND: Susceptibility to aggressive periodontitis (AgP) is influenced by genetic as well as environmental factors. Studies linking gene variants to AgP have been mainly centred in developed countries with limited data from Africa.AIM: To investigate whether previously reported candidate gene associations with AgP could be replicated in a population from Sudan.METHODS: The investigation was a case-control design. Cases with AgP (n = 132) and controls (n = 136) were identified from patients attending the Periodontal Department in Khartoum Dental Hospital. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. Analysis focused on gene variants with a minor allele frequency (MAF) > 25% in the Sudanese subjects that had previously been reported to be associated with AgP.RESULTS: One candidate gene rs1537415 (GLT6D1) was significantly associated with AgP, OR = 1.50 (95% CI 1.04-2.17), p = 0.0295 (increasing to p = 0.09 after correction for multiple testing). The association strengthened to OR = 1.56 (95% CI 1.15-2.16), p = 0.0042 when the controls were supplemented with data from the Hap map for the Yoruba in Ibadan (n = 147) and remained significant (p = 0.013) after correction for multiple testing.CONCLUSION: The study independently replicated the finding that rs1537415, a variant in glycosyl transferase gene GLT6D1, is associated with AgP and provided the first report of genetic associations with AgP in a Sudanese population.

Aim: To critically appraise recent research into associations between periodontal disease and systemic diseases and conditions specifically respiratory disease, chronic kidney disease, rheumatoid arthritis, cognitive impairment, obesity, metabolic syndrome and cancer. Methods: A MEDLINE literature search of papers published between 2002 and April 2012 was conducted. Studies that included periodontitis as an exposure were identified. Cross-sectional epidemiological investigations on large samples, prospective studies and systematic reviews formed the basis of the narrative review. A threshold set for the identification of periodontitis was used to identify those studies that contributed to the conclusions of the review. Results: Many of the investigations were cross-sectional secondary analyses of existing data sets in particular the NHANES studies. There were a small number of systematic reviews and prospective studies. There was substantial variability in the definitions of exposure to periodontitis. A small number of studies met the threshold set for periodontitis and supported associations; however, in some of the chronic diseases there were no such studies. There was strong evidence from randomized controlled trials that interventions, which improve oral hygiene have positive effects on the prevention of nosocomial pneumonias. Conclusions: There was substantial heterogeneity in the definitions used to identify periodontitis and very few studies met a stringent threshold for periodontitis. Published evidence supports modest associations between periodontitis and some, although not all, of the diseases and conditions reviewed. There is a need to reach a consensus on what constitutes periodontitis for future studies of putative associations with systemic diseases.

Odontoblasts form the outermost cellular layer of the dental pulp where they have been proposed to act as sensory receptor cells. Despite this suggestion, evidence supporting their direct role in mediating thermo-sensation and nociception is lacking. Transient receptor potential (TRP) ion channels directly mediate nociceptive functions, but their functional expression in human odontoblasts has yet to be elucidated. In the present study, we have examined the molecular and functional expression of thermo-sensitive TRP channels in cultured odontoblast-like cells and in native human odontoblasts obtained from healthy wisdom teeth. PCR and western blotting confirmed gene and protein expression of TRPV1, TRPA1 and TRPM8 channels. Immunohistochemistry revealed that these channels were localised to odontoblast-like cells as determined by double staining with dentin sialoprotein (DSP) antibody. In functional assays, agonists of TRPV1, TRPA1 and TRPM8 channels elicited [Ca2+]i transients that could be blocked by relevant antagonists. Application of hot and cold stimuli to the cells also evoked rises in [Ca2+]i which could be blocked by TRP-channel antagonists. Using a gene silencing approached we further confirmed a role for TRPA1 in mediating noxious cold responses in odontoblasts. We conclude that human odontoblasts express functional TRP channels that may play a crucial role in mediating thermal sensation in teeth. Cultured and native human odontoblasts express functional TRP channels that may play a crucial role in mediating thermal sensation in teeth.

International audience; Introduction: Transient receptor potential (TRP) channels comprise a group of nonselective calcium-permeable cationic channels, which are polymodal sensors of environmental stimuli such as thermal changes and chemicals. TRPM8 and TRPA1 are cold-sensing TRP channels activated by moderate cooling and noxious cold temperatures, respectively. Both receptors have been identified in trigeminal ganglion neurones, and their expression in nonneuronal cells is now the focus of much interest. The aim of this study was to investigate the molecular and functional expression of TRPA1 and TRPM8 in dental pulp fibroblasts. Methods: Human dental pulp fibroblasts were derived from healthy molar teeth. Gene and protein expression was determined by polymerase chain reaction and Western blotting. Cellular localization was investigated by immunohistochemistry, and TRP functionality was determined by Ca 2+ microfluorimetry. Results: Polymerase chain reaction and Western blotting showed gene and protein expression of both TRPA1 and TRPM8 in fibroblast cells in culture. Immunohistochemistry studies showed that TRPA1 and TRPM8 immunoreactivity co-localized with the human fibroblast surface protein. In Ca 2+ microfluorimetry studies designed to determine the functionality of TRPA1 and TRPM8 in pulp fibroblasts, we showed increased intracellular calcium ([Ca 2+ ] i) in response to the TRPM8 agonist menthol, the TRPA1 agonist cinnamaldehyde, and to cool and noxious cold stimuli, respectively. The responses to agonists and thermal stimuli were blocked in the presence of specific TRPA1 and TRPM8 antagonists. Conclusions: Human dental pulp fibroblasts express TRPA1 and TRPM8 at the molecular, protein, and functional levels, indicating a possible role for fibroblasts in mediating cold responses in human teeth.

Background The human chromosomal region 9p21.3 has been shown to be strongly associated with Coronary Heart Disease (CHD) in several Genome-wide Association Studies (GWAS). Recently, this region has also been shown to be associated with Aggressive Periodontitis (AgP), strengthening the hypothesis that the established epidemiological association between periodontitis and CHD is caused by a shared genetic background, in addition to common environmental and behavioural risk factors. However, the size of the analyzed cohorts in this primary analysis was small compared to other association studies on complex diseases. Using our own AgP cohort, we attempted to confirm the described associations for the chromosomal region 9p21.3. Methods We analyzed our cohort consisting of patients suffering from the most severe form of AgP, generalized AgP (gAgP) (n = 130) and appropriate periodontally healthy control individuals (n = 339) by genotyping four tagging SNPs (rs2891168, rs1333042, rs1333048 and rs496892), located in the chromosomal region 9p21.3, that have been associated with AgP. Results The results confirmed significant associations between three of the four SNPs and gAgP. The combination of our results with those from the study which described this association for the first time in a meta-analysis of the four tagging SNPs produced clearly lower p-values compared with the results of each individual study. According to these results, the most plausible genetic model for the association of all four tested SNPs with gAgP seems to be the multiplicative one. Conclusion We positively replicated the finding of an association between the chromosomal region 9p21.3 and gAgP. This result strengthens support for the hypothesis that shared susceptibility genes within this chromosomal locus might be involved in the pathogenesis of both CHD and gAgP.

Patients' compliance with periodontal maintenance therapy is important for the treatment outcomes, however, most studies report compliance rates ranging from only 11%-45%. The aims of this study were to report on the acceptance of proposed treatment and the long-term compliance of patients treated in a specialist periodontal office in Norway. This was part of an internal quality control measure for this practice.152 consecutive patients who completed periodontal therapy in 1988 were retrospectively assessed after 10 years. In addition, the case records of 624 consecutive patients referred for periodontal assessment between 1989 and 1993 were examined to determine how many decided to accept the proposed therapy.The majority 132 (87%) of those who completed treatment in 1988 had attended for the prescribed maintenance therapy over a ten-year period. It was not possible to detect any differences between the compliers and non-compliers in terms of age, gender, severity of disease, cost and national insurance coverage. The 152 patients were originally referred by 18 general dental practitioners. The 'high referring' dentists (8 referrals) had significantly more non-complying patients than dentists who made less than 7 referrals. 20 (3%) of the 624 periodontal referrals over a 5-year period chose not to proceed with the proposed therapy.There was a high level of patient compliance in the population group studied in this specialist periodontal practice. Geographic and cultural factors as well as a stable rural population may be important factors in the high level of compliance with maintenance therapy in this practice. The referring general dental practitioners may also play an important role in patient compliance.

It is generally accepted that the nervous system contributes to the pathophysiology of peripheral inflammation, and a neurogenic component has been implicated in many inflammatory diseases, including periodontitis. Neurogenic inflammation should be regarded as a protective mechanism, which forms the first line of defense and protects tissue integrity. However, severe or prolonged noxious stimulation may result in the inflammatory response mediating injury rather than facilitating repair. This review focuses on the accumulating evidence suggesting that neuropeptides have a pivotal role in the complex cascade of chemical activity associated with periodontal inflammation. An overview of neuropeptide synthesis and release introduces the role of neuropeptides and their interactions with other inflammatory factors, which ultimately lead to neurogenic inflammation. The biological effects of the neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), and neuropeptide Y (NPY) are summarized, and evidence for their involvement in the localized inflammatory lesions which characterize periodontitis is presented. In this context, the role of CGRP in bone metabolism is described in more detail. Recent research highlighting the role of the nervous system in suppressing pain and inflammation is also discussed.