Periodontitis and Outer Retinal Thickness: a Cross-Sectional Analysis of the United Kingdom Biobank Cohort.

Purpose: Periodontitis, a ubiquitous severe gum disease affecting the teeth and surrounding alveolar bone, can heighten systemic inflammation. We investigated the association between very severe periodontitis and early biomarkers of age-related macular degeneration (AMD), in individuals with no eye disease. Design: Cross-sectional analysis of the prospective community-based cohort United Kingdom (UK) Biobank. Participants: Sixty-seven thousand three hundred eleven UK residents aged 40 to 70 years recruited between 2006 and 2010 underwent retinal imaging. Methods: Macular-centered OCT images acquired at the baseline visit were segmented for retinal sublayer thicknesses. Very severe periodontitis was ascertained through a touchscreen questionnaire. Linear mixed effects regression modeled the association between very severe periodontitis and retinal sublayer thicknesses, adjusting for age, sex, ethnicity, socioeconomic status, alcohol consumption, smoking status, diabetes mellitus, hypertension, refractive error, and previous cataract surgery. Main Outcome Measures: Photoreceptor layer (PRL) and retinal pigment epithelium-Bruch's membrane (RPE-BM) thicknesses. Results: Among 36 897 participants included in the analysis, 1571 (4.3%) reported very severe periodontitis. Affected individuals were older, lived in areas of greater socioeconomic deprivation, and were more likely to be hypertensive, diabetic, and current smokers (all P < 0.001). On average, those with very severe periodontitis were hyperopic (0.05 ± 2.27 diopters) while those unaffected were myopic (-0.29 ± 2.40 diopters, P < 0.001). Following adjusted analysis, very severe periodontitis was associated with thinner PRL (-0.55 µm, 95% confidence interval [CI], -0.97 to -0.12; P = 0.022) but there was no difference in RPE-BM thickness (0.00 µm, 95% CI, -0.12 to 0.13; P = 0.97). The association between PRL thickness and very severe periodontitis was modified by age (P < 0.001). Stratifying individuals by age, thinner PRL was seen among those aged 60 to 69 years with disease (-1.19 µm, 95% CI, -1.85 to -0.53; P < 0.001) but not among those aged < 60 years. Conclusions: Among those with no known eye disease, very severe periodontitis is statistically associated with a thinner PRL, consistent with incipient AMD. Optimizing oral hygiene may hold additional relevance for people at risk of degenerative retinal disease. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Periodontal diseases and cardiovascular diseases, diabetes, and respiratory diseases: Summary of the consensus report by the European Federation of Periodontology and WONCA Europe.

BACKGROUND: Periodontitis is a chronic inflammatory non-communicable disease (NCD) characterised by the destruction of the tooth-supporting apparatus (periodontium), including alveolar bone, the presence of periodontal pockets, and bleeding on probing. OBJECTIVES: To outline, for family doctors, the implications of the association between periodontal and systemic diseases; to explore the role of family doctors in managing periodontitis as an ubiquitous non-communicable disease (NCD). METHODS: The consensus reports of previous focused collaborative workshops between WONCA Europe and the European Federation of Periodontology (using previously undertaken systematic reviews), and a specifically commissioned systematic review formed the technical papers to underpin discussions. Working groups prepared proposals independently, and the proposals were subsequently discussed and approved at plenary meetings. RESULTS: Periodontitis is independently associated with cardiovascular diseases, diabetes, chronic obstructive pulmonary disease, obstructive sleep apnoea, and COVID-19 complications. Treatment of periodontitis has been associated with improvements in systemic health outcomes. The article also presents evidence gaps. Oral health care professionals (OHPs) and family doctors should collaborate in managing these conditions, including implementing strategies for early case detection of periodontitis in primary medical care centres and of systemic NCDs in oral/dental care settings. There is a need to raise awareness of periodontal diseases, their consequences, and the associated risk factors amongst family doctors. CONCLUSION: Closer collaboration between OHPs and family doctors is important in the early case detection and management of NCDs like cardiovascular diseases, diabetes mellitus, and respiratory diseases. Strategies for early case detection/prevention of NCDs, including periodontitis, should be developed for family doctors, other health professionals (OHPs), and healthcare funders. Evidence-based information on the reported associations between periodontitis and other NCDs should be made available to family doctors, OHPs, healthcare funders, patients, and the general population.

Periodontitis is independently associated with cardiovascular diseases, diabetes, chronic obstructive pulmonary disease, obstructive sleep apnoea, and COVID-19.Periodontal treatment for optimal outcomes improves diabetes outcomes and surrogate measures of cardiovascular risk.Closer collaboration between oral health care professionals and family doctors is important in the early case detection and management of non-communicable diseases.Information on the reported associations should be made available to family doctors, oral health professionals, healthcare funders, patients, and the general population.

Changes in Oral Health and Dental Esthetic in Smokers Switching to Combustion-Free Nicotine Alternatives: Protocol for a Multicenter and Prospective Randomized Controlled Trial.

BACKGROUND: Although the detrimental effects of conventional combustible cigarettes on oral health and dental esthetics are well known, there is limited information about the long-term impact of combustion-free nicotine alternatives (C-F NA) such as e-cigarettes or heated tobacco products. OBJECTIVE: This multicenter, prospective, 3-parallel-arm randomized controlled trial will investigate whether switching from combustible cigarettes to C-F NA will lead to measurable improvements in oral health parameters and dental esthetics over 18 months in adult smokers with limited gum disease. METHODS: Regular smokers not intending to quit and without clinical signs of periodontitis will be randomly assigned (1:4 ratio) to either standard of care with brief cessation advice (control group; arm A) or C-F NA use (intervention group; arm B). The study will also include a reference group of never smokers (reference group; arm C). The primary end point is the change in the Modified Gingival Index (MGI) score from baseline between the control arm (arm A) and the intervention arm (arm B) at the 18-month follow-up. In addition, the study will analyze the within- and between-group (arms A, B, and C) changes in MGI assessment, plaque imaging, dental shade quantitation, tooth stain scores, and oral health-related quality of life questionnaires measured at each study time point. All participants will attend a total of 7 clinic visits: screening, enrollment, and randomization (visit 0); baseline visit-day 14 (visit 1); day 90 (visit 2); day 180 (visit 3); day 360 (visit 4); and day 540 (visit 5). This multicenter study will be conducted in 4 dental clinics in 4 countries. The statistical analysis will involve descriptive statistics for continuous and categorical data. Primary end points will undergo tests for normality and, based on distribution, either a 2-sided t test or Mann-Whitney U test. Linear mixed model with random factors center and study arms by center will also be applied. Secondary end points, including MGI assessment and quality of life, will be subjected to similar tests and comparisons. Only if one value of the parameter MGI is missing after day 1, the last available observation will be carried forward. The analysis will be performed on the substituted data. Secondary parameters will not have missing value replacement. RESULTS: Participant recruitment began in October 2021, and enrollment was completed in June 2023. Results will be reported in 2025. CONCLUSIONS: This will be the first study to provide key insights into oral health benefits or risks associated with using C-F NA in smokers who are seeking alternatives to cigarette smoking. TRIAL REGISTRATION: ClinicalTrials.gov NCT04649645; https://clinicaltrials.gov/ct2/show/NCT04649645. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53222.

Genotype-Phenotype Correlation in Junctional Epidermolysis Bullosa: Signposts to Severity.

Junctional epidermolysis bullosa (JEB) is a rare autosomal recessive genodermatosis with a broad spectrum of phenotypes. Current genotype-phenotype paradigms are insufficient to accurately predict JEB subtype and characteristics from genotype, particularly for splice site variants, which account for over a fifth of disease-causing variants in JEB. This study evaluated the genetic and clinical findings from a JEB cohort, investigating genotype-phenotype correlations through bioinformatic analyses and comparison with previously reported variants. Eighteen unique variants in LAMB3, LAMA3, LAMC2, or COL17A1 were identified from 17 individuals. Seven had severe JEB, 9 had intermediate JEB, and 1 had laryngo-onycho-cutaneous syndrome. Seven variants were previously unreported. Deep phenotyping was completed for all intermediate JEB cases and demonstrated substantial variation between individuals. Splice site variants underwent analysis with SpliceAI, a state-of-the-art artificial intelligence tool, to predict resultant transcripts. Predicted functional effects included exon skipping and cryptic splice site activation, which provided potential explanations for disease severity and in most cases correlated with laminin-332 immunofluorescence. RT-PCR was performed for 1 case to investigate resultant transcripts produced from the splice site variant. This study expands the JEB genomic and phenotypic landscape. Artificial intelligence tools show potential for predicting the functional effects of splice site variants and may identify candidates for confirmatory laboratory investigation. Investigation of RNA transcripts will help to further elucidate genotype-phenotype correlations for novel variants.

A scoping review of new technologies for dental plaque quantitation: Benefits and limitations.

OBJECTIVES: To determine the validity and reliability of novel digitalized tools for dental plaque detection and explore the benefits and limitations connected to their use. DATA: Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews. All human clinical studies comparing dental plaque detection using digitalized systems against a standard reference were included. SOURCES: PubMed and Scopus were screened from 01 January 2013 to 28 September 2023. Bibliographies of primary studies and principal peer-reviewed scientific journals were manually searched. STUDY SELECTION: The initial search identified 576 articles, with a total of 13 included in the review, published between 2015 and 2023. Most of the studies included (77 %) were cross-sectional with three being prospective. Digital devices captured 2D and 3D images via cameras and intra-oral scanners, respectively. The Turesky's modified plaque index was the most frequent clinical index. Correlation with clinical examination was moderate to strong, with good to excellent intra- and inter-system agreement. CONCLUSIONS: Within the limitations of this scoping review, image analysis-based plaque detection systems demonstrated good correlations with clinical plaque indices, using both 2D and 3D imaging systems. Whilst digital plaque detection devices offer advantages in terms of procedural standardization and reproducibility, they also have limitations, therefore currently, their application should be underpinned by a comprehensive clinical examination. CLINICAL SIGNIFICANCE: Digital plaque detection tools, that provide standardized measurements and store acquired images, facilitate more informed feedback to patients. This objective analysis may enhance clinician confidence in their utility for clinical trials and other applications.

How to recognise a Behçet's ulcer from other types of oral ulceration? Defining Behçet's ulceration by an International Delphi Consultation.

OBJECTIVES: To define the clinical characteristics of oral ulceration (OU) in Behçet's disease (BD), to allow differentiation from other causes of OU, including aphthous ulcers, by an International Delphi consultation. To develop a clinical guideline on how to recognise BD ulcers. METHODS: Round 1. 40 clinical images of OU in BD, recurrent aphthous stomatitis (RAS), inflammatory bowel disease (IBD) and mucous membrane pemphigoid (MMP) were shown. Participants answered, independently, which images would be consistent with a BD ulcer. Round 2. The results from marking independently were shown. The panel remarked the questions through iteration process. The images not agreed to be a possible BD ulcer were discarded. Round 3. 10 clinical descriptors that may define BD ulcers were suggested. Participants ranked the level of importance for each descriptor on each image presented. Round 4. Participants re-ranked their level of agreement for each descriptor through iteration process. Whether the clinical pictures would be different from RAS was also explored. A final agreement was reached. RESULTS: This study has shown clear differentiation between BD, IBD and MMP ulcers when defining them by phenotype through clinical images only. On the other hand, no differentiation between RAS and BD ulcers was found. The most important clinical descriptors that define BD ulcers have been agreed. CONCLUSIONS: New clinical guidance for Health Care Professionals (HCP) on how to recognise a BD ulcer has been proposed. This should elucidate an earlier diagnosis, quicker access to treatment and control of the disease enhancing patient's quality of life.

Simultaneous presentation of dual pathologies within the oral cavity: an unusual and diagnostically challenging presentation.

Necrotising sialometaplasia (NS) is a rare condition, with a limited scientific evidence base regarding its aetiology and pathophysiology. Diagnosing NS demands extensive investigatory tests. Their accuracy is vital in order to exclude oral malignancy and prevent unwarranted, invasive management.Within Birmingham Dental Hospital, a 22-year-old, South Asian woman presented with generalised pain from the lower right third molar extending to involve the palate, to which the patient's general medical practitioner previously attributed to a viral upper respiratory infection. Clinical examination revealed bilateral erythematous: non-ulcerated, palatal swellings (10 mm x 5 mm) at the greater palatine foramina. Following extensive investigations, the challenging definitive diagnoses of two distinct pathologies were made: non-ulcerative NS and pericoronitis.This case report describes the successful diagnosis and management of non-ulcerating NS, an 'atypical' presentation of a rare condition, that was confounded by a simultaneous episode of pericoronitis - a presentation not previously documented within scientific literature.

Saliva antiviral antibody levels are detectable but correlate poorly with serum antibody levels following SARS-CoV-2 infection and/or vaccination.

The importance of salivary SARS-CoV-2 antibodies, following infection and vaccination, has not been fully established. 875 healthcare workers were sampled during the first wave in 2020 and 66 longitudinally in response to Pfizer BioNTech 162b2 vaccination. We measured SARS-CoV-2 total IgGAM and individual IgG, IgA and IgM antibodies. IgGAM seroprevalence was 39.9%; however, only 34.1% of seropositive individuals also had salivary antibodies. Infection generated serum IgG antibodies in 51.4% and IgA antibodies in 34.1% of individuals. In contrast, the salivary antibody responses were dominated by IgA (30.9% and 12% generating IgA and IgG antibodies, respectively). Post 2nd vaccination dose, in serum, 100% of infection naïve individuals had IgG and 82.8% had IgA responses; in saliva, 65.5% exhibited IgG and 55.2% IgA antibodies. Prior infection enhanced the vaccine antibody response in serum but no such difference was observed in saliva. Strong neutralisation responses were seen for serum 6 months post 2nd-vaccination dose (median 87.1%) compared to low neutralisation responses in saliva (median 1%). Intramuscular vaccination induces significant serum antibodies and to a lesser extent, salivary antibodies; however, salivary antibodies are typically non-neutralising. This study provides further evidence for the need of mucosal vaccines to elicit nasopharyngeal/oral protection. Although saliva is an attractive non-invasive sero-surveillance tool, due to distinct differences between systemic and oral antibody responses, it cannot be used as a proxy for serum antibody measurement.

Quorum Sensing in Oral Biofilms: Influence on Host Cells.

Quorum sensing molecules (QSMs) in the oral cavity regulate biofilm formation, the acquisition of iron, stress responses, and the expression of virulence factors. However, knowledge of the direct QSM-host interactions in the oral environment is limited, although their understanding could provide greater insight into the cross-kingdom communication occurring during oral disease development. This review aims to explore the literature on oral QSM-host interactions and to highlight areas of advancement in this field. The studies included in this review encompass an array of cell types and oral QSMs, with particular emphasis on immune cells and their relationship to periodontal diseases. It can be inferred from the current literature that QSMs are utilised by host cells to detect bacterial presence and, in the majority of cases, elicit an immune response towards the environmental QSMs. This may provide a base to target QSMs as a novel treatment of oral diseases. However, N-acyl homoserine lactone (AHL) detection methods remain an area for development, through which a greater understanding of the influence of oral QSMs on host cells could be achieved.

Under pressure-mechanisms and risk factors for orthodontically induced inflammatory root resorption: a systematic review.

BACKGROUND: The application of orthodontic forces causes root resorption of variable severity with potentially severe clinical ramifications. OBJECTIVE: To systematically review reports on the pathophysiological mechanisms of orthodontically induced inflammatory root resorption (OIIRR) and the associated risk factors based on in vitro, experimental, and in vivo studies. SEARCH METHODS: We undertook an electronic search of four databases and a separate hand-search. SELECTION CRITERIA: Studies reporting on the effect of orthodontic forces with/without the addition of potential risk factors on OIIRR, including (1) gene expression in in-vitro studies, the incidence root resorption in (2) animal studies, and (3) human studies. DATA COLLECTION AND ANALYSIS: Potential hits underwent a two-step selection, data extraction, quality assessment, and systematic appraisal performed by duplicate examiners. RESULTS: One hundred and eighteen articles met the eligibility criteria. Studies varied considerably in methodology, reporting of results, and variable risk of bias judgements.In summary, the variable evidence identified supports the notion that the application of orthodontic forces leads to (1) characteristic alterations of molecular expression profiles in vitro, (2) an increased rate of OIIRR in animal models, as well as (3) in human studies. Importantly, the additional presence of risk factors such as malocclusion, previous trauma, and medications like corticosteroids increased the severity of OIIRR, whilst other factors decreased its severity, including oral contraceptives, baicalin, and high caffeine. CONCLUSIONS: Based on the systematically reviewed evidence, OIIRR seems to be an inevitable consequence of the application of orthodontic forces-with different risk factors modifying its severity. Our review has identified several molecular mechanisms that can help explain this link between orthodontic forces and OIIRR. Nevertheless, it must be noted that the available eligible literature was in part significantly confounded by bias and was characterized by substantial methodological heterogeneity, suggesting that the results of this systematic review should be interpreted with caution. REGISTRATION: PROSPERO (CRD42021243431).

Prevention and treatment of peri-implant diseases-The EFP S3 level clinical practice guideline.

BACKGROUND: The recently published Clinical Practice Guidelines (CPGs) for the treatment of stages I-IV periodontitis provided evidence-based recommendations for treating periodontitis patients, defined according to the 2018 classification. Peri-implant diseases were also re-defined in the 2018 classification. It is well established that both peri-implant mucositis and peri-implantitis are highly prevalent. In addition, peri-implantitis is particularly challenging to manage and is accompanied by significant morbidity. AIM: To develop an S3 level CPG for the prevention and treatment of peri-implant diseases, focusing on the implementation of interdisciplinary approaches required to prevent the development of peri-implant diseases or their recurrence, and to treat/rehabilitate patients with dental implants following the development of peri-implant diseases. MATERIALS AND METHODS: This S3 level CPG was developed by the European Federation of Periodontology, following methodological guidance from the Association of Scientific Medical Societies in Germany and the Grading of Recommendations Assessment, Development and Evaluation process. A rigorous and transparent process included synthesis of relevant research in 13 specifically commissioned systematic reviews, evaluation of the quality and strength of evidence, formulation of specific recommendations, and a structured consensus process involving leading experts and a broad base of stakeholders. RESULTS: The S3 level CPG for the prevention and treatment of peri-implant diseases culminated in the recommendation for implementation of various different interventions before, during and after implant placement/loading. Prevention of peri-implant diseases should commence when dental implants are planned, surgically placed and prosthetically loaded. Once the implants are loaded and in function, a supportive peri-implant care programme should be structured, including periodical assessment of peri-implant tissue health. If peri-implant mucositis or peri-implantitis are detected, appropriate treatments for their management must be rendered. CONCLUSION: The present S3 level CPG informs clinical practice, health systems, policymakers and, indirectly, the public on the available and most effective modalities to maintain healthy peri-implant tissues, and to manage peri-implant diseases, according to the available evidence at the time of publication.

The role of the host-Neutrophil biology.

Neutrophilic polymorphonuclear leukocytes (neutrophils) are myeloid cells packed with lysosomal granules (hence also called granulocytes) that contain a formidable antimicrobial arsenal. They are terminally differentiated cells that play a critical role in acute and chronic inflammation, as well as in the resolution of inflammation and wound healing. Neutrophils express a dense array of surface receptors for multiple ligands, ranging from integrins to support their egress from bone marrow into the circulation and from the circulation into tissues, to cytokine/chemokine receptors that drive their navigation to the site of infection or tissue damage and also prime them for a second stimulus, to pattern recognition receptors and immunoglobulin receptors to facilitate the destruction and removal of infective agents or debridement of damaged tissues. When afferent neutrophil signals are proportionate and coordinated they will phagocytose opsonized and unopsonized bacteria, activating the nicotinamide adenine dinucleotide phosphate oxidase (respiratory burst) to generate reactive oxygen species, which augment the proteolytic destruction of microbes secured within the phagosome. A highly orchestrated process of apoptosis follows, forming membrane-bound substructures that are removed by macrophages. Neutrophils are capable of various other forms of programmed cell death, such as NETosis and pyroptotic cell death, as well as nonprogrammed cell death by necrosis. In recent years, research has revealed that neutrophils are capable of far more subtle cell-cell interactions than previously thought possible. This includes synthesis of various inflammatory mediators and also myeloid cell training within bone marrow, where epigenetic and metabolic signals associated with returning neutrophils that undergo reverse egress from tissues into the vasculature and back to bone marrow program a hyperreactive subset of neutrophils during myelopoiesis that are capable of hypersensitive reactions to microbial aggressors. These characteristics are evident in various neutrophil subsets/subpopulations, creating broad heterogeneity in the behavior and biological repertoire of these seemingly schizophrenic immune cells. Moreover, neutrophils are critical effector cells of adaptive and innate immunity, binding to opsonized bacteria and destroying them by extracellular and intracellular methods. The former creates substantial collateral host tissue damage, as they are less specific than T-cytotoxic cell-killing mechanisms, and in conditions such as peri-implantitis, where plasma cells and neutrophils dominate the immune infiltrate, bone and tissue destruction are rapid and appear relentless. Finally, the role of neutrophils as conduits for periodontal-systemic disease connections and for oxidative damage to act as a causal link between the two has only recently been realized. In this chapter, we attempt to expand on these issues, emphasizing the contributions of European scientists throughout a detailed appraisal of the benefits and side effects of neutrophilic inflammation and immune function.

Current concepts in the pathogenesis of periodontitis: from symbiosis to dysbiosis.

The primary etiological agent for the initiation and progression of periodontal disease is the dental plaque biofilm which is an organized aggregation of microorganisms residing within a complex intercellular matrix. The non-specific plaque hypothesis was the first attempt to explain the role of the dental biofilm in the pathogenesis of periodontal diseases. However, the introduction of sophisticated diagnostic and laboratory assays has led to the realisation that the development of periodontitis requires more than a mere increase in the biomass of dental plaque. Indeed, multispecies biofilms exhibit complex interactions between the bacteria and the host. In addition, not all resident microorganisms within the biofilm are pathogenic, since beneficial bacteria exist that serve to maintain a symbiotic relationship between the plaque microbiome and the host's immune-inflammatory response, preventing the emergence of pathogenic microorganisms and the development of dysbiosis. This review aims to highlight the development and structure of the dental plaque biofilm and to explore current literature on the transition from a healthy (symbiotic) to a diseased (dysbiotic) biofilm in periodontitis and the associated immune-inflammatory responses that drive periodontal tissue destruction and form mechanistic pathways that impact other systemic non-communicable diseases.

Association between periodontal diseases and cardiovascular diseases, diabetes and respiratory diseases: Consensus report of the Joint Workshop by the European Federation of Periodontology (EFP) and the European arm of the World Organization of Family Doctors (WONCA Europe).

AIM: To explore the implications for dentists and family doctors of the association between periodontal and systemic diseases and the role of dentists and family doctors in managing non-communicable diseases (NCDs) and promoting healthy lifestyles. MATERIALS AND METHODS: The consensus reports of the previous Focused Workshops on the associations between periodontitis and diabetes (2017) and periodontitis and cardiovascular diseases (2019) formed the technical reviews to underpin discussions on both topics. For the association with respiratory diseases, a systematic review was specifically commissioned for the Workshop discussions. Working groups prepared proposals independently, and then the proposals were discussed and approved at plenary meetings. RESULTS: Periodontitis is independently associated with cardiovascular diseases, diabetes, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea and COVID-19 complications. Dentists and family doctors should collaborate in managing NCDs, implementing strategies for early detection of periodontitis in primary care centres and of cardiovascular diseases or diabetes in dental settings. Family doctors should be informed about periodontal diseases and their consequences, and oral health professionals (OHPs) should be informed about the relevance of NCDs and the associated risk factors. CONCLUSIONS: Closer collaboration between OHPs and family doctors is important in the early detection and management of NCDs and in promoting healthy lifestyles. Pathways for early case detection of periodontitis in family medicine practices and of NCDs in dental practices should be developed and evaluated.

Pre-conditioning of gingival epithelial cells with sub-apoptotic concentrations of curcumin prevents pro-inflammatory cytokine release.

BACKGROUND AND OBJECTIVE: Plaque-induced gingival inflammation (gingivitis) is ubiquitous in humans. The epithelial barrier reacts to the presence of oral bacteria and induces inflammatory cascades. The objective of this study was to investigate the mechanism by which the small molecule micronutrient curcumin could decrease inflammatory response in vitro to oral bacterium heat-killed Fusobacterium nucleatum as curcumin could be a useful compound for combatting gingivitis already consumed by humans. METHODS: H400 oral epithelial cell line was pre-conditioned with curcumin and the production of cytokines was measured by enzyme-linked immunosorbent assay (ELISA) and translocation of transcription factors was used to monitor inflammatory responses. Haem oxygenase (HO-1) expression and molecules that HO-1 releases were evaluated for their potential to reduce the quantity of cytokine production. Immunofluorescence microscopy and Western blotting were used to evaluate changes in transcription factor and enzyme location. RESULTS: Pre-conditioning of H400 cells with a sub-apoptotic concentration of curcumin (20 µM) attenuated secretion of Granulocyte-Macrophage - Colony-Stimulating Factor (GM-CSF) and reduced NFkB nuclear translocation. This pre-conditioning caused an increase in nuclear Nrf2; an initial drop (at 8 h) followed by an adaptive increase (at 24 h) in glutathione; and an increase in haem oxygenase (HO-1) expression. Inhibition of HO-1 by SnPPIX prevented the curcumin-induced attenuation of GM-CSF production. HO-1 catalyses the breakdown of haem to carbon monoxide, free iron and biliverdin: the HO-1/CO anti-inflammatory pathway. Elevations in carbon monoxide, achieved using carbon monoxide releasing molecule-2 (CORM2) treatment alone abrogated F. nucleatum-induced cytokine production. Biliverdin is converted to bilirubin by biliverdin reductase (BVR). This pleiotropic protein was found to increase in cell membrane expression upon curcumin treatment. CONCLUSION: Curcumin decreased inflammatory cytokine production induced by Fusobacterium nucleatum in H400 oral epithelial cells. The mechanism of action appears to be driven by the increase of haem oxygenase and the production of carbon monoxide.

Periodontal health and patient-reported outcomes: A longitudinal analysis of data from non-specialist practice settings.

AIM: To explore the associations between periodontal health and patient-reported outcomes (PROs), accounting for changes over time, in a large, non-specialist dental practice patient cohort. MATERIALS AND METHODS: This longitudinal study used data from 13,162 dentate patients, collected by 162 dentists at routine appointments between May 2013 and April 2020, in 238 non-specialist dental practices across the United Kingdom. Dentists collected data, as part of routine clinical care, on periodontal probing pocket depths, alveolar bone loss, bleeding on probing, as well as a range of covariates. Patients inputted data on outcomes (oral pain/discomfort, dietary restrictions, and dental appearance). Mixed-effects logistic regression analysis was used to investigate the associations between periodontal health and PROs. Models accounted for clustering at the patient and dentist level and were adjusted for time and variables which were thought to confound these associations. RESULTS: The odds of all PROs tended to increase with worsening periodontal parameters. For example, the odds of reporting pain in the worst periodontal health category were 1.99 (95% confidence interval: 1.57-2.53) times higher than in the best periodontal health category. CONCLUSIONS: This study confirms, using a large longitudinal dataset from a unique non-specialist setting, the associations between poorer periodontal health and poorer PROs.

Outcomes of periodontal therapy in rheumatoid arthritis: The OPERA feasibility randomized trial.

AIM: Periodontitis is independently associated with rheumatoid arthritis (RA); however, there is limited data on whether periodontal treatment improves overall RA disease activity. We conducted a pilot feasibility randomized controlled clinical trial to test whether intensive periodontal therapy reduces RA disease activity in patients with active RA and periodontitis. MATERIALS AND METHODS: The following inclusion criteria were applied: patients with RA and periodontitis, aged 18+, stable on treatment with disease-modifying anti-rheumatic drugs for ≥3 months, disease activity score (DAS28) ≥3.2, and DAS28 >5.1 only if patient unwilling to take biologics. Participants meeting the inclusion criteria were randomized to immediate intensive periodontal therapy or to delayed therapy (control group) administered by a dental hygienist in a secondary care setting. Data were collected at baseline and at 3 and 6 months of follow-up. Participants randomized to the control group (delayed therapy) received the standard of care for the duration of the trial, including oral hygiene instructions delivered by a dental hygienist, and the same periodontal therapy as the intervention group after study completion (i.e., 6 months after randomization). The periodontal inflammation surface area was calculated using clinical attachment loss (CAL), periodontal probing pocket depth, and bleeding on probing. Cumulative probing depth was also measured. We examined the effect of periodontal therapy on periodontal outcomes and on clinical markers of disease activity in RA, as measured by the DAS28-C-reactive protein score as well as musculo-skeletal ultrasound grey scale and power Doppler scores. RESULTS: A total of 649 patients with RA were invited to participate in the study. Of these, 296 (46%) consented to participate in the screening visit. A sample of 201 patients was assessed for eligibility, of whom 41 (20%) did not meet the RA inclusion criteria and 100 (50%) did not meet the periodontal disease criteria. Among the 60 (30%) eligible participants, 30 were randomized to immediate periodontal therapy and 30 were allocated to the control group. The loss to follow-up was 18% at the end of the trial. There were no major differences with regard to baseline characteristics between the groups. Periodontal therapy was associated with reduced periodontal inflamed surface area, cumulative probing depths, RA disease activity scores, and ultrasound scores over the course of the trial. There was no change in CAL. CONCLUSIONS: Overall, the trial was feasible and acceptable to the study participants. Recruitment to and satisfactory retention in a randomized controlled trial on the effect of periodontal treatment on RA patients is possible, albeit challenging. In this feasibility study of patients with RA and periodontitis, periodontal treatment resulted in significant improvements in periodontal disease outcomes and overall RA disease activity, although complete resolution of periodontal inflammation was difficult to achieve in some cases.

Antioxidant Micronutrients and Oxidative Stress Biomarkers.

Chronic inflammatory diseases are the major causes of mortality in humans and recent research has improved our understanding of the major impact of lifestyle factors upon inflammatory diseases and conditions. One of the most influential of these is nutrition, which may drive both pro-inflammatory as well as anti-inflammatory cascades at molecular and cellular levels. There are a variety of model systems that may be employed to investigate the impact of micronutrients and macronutrients upon inflammatory pathways, many of which operate through oxidative stress, either at the level of controlling the redox state of the cell and downstream redox-regulated gene transcription factors, and other acting as free radical generating or scavenging agents. This chapter focuses upon biological sample preparation prior to assay and details methods for analyzing certain antioxidant micronutrients and biomarkers of oxidative stress.