Utility of gingival crevicular fluid components for periodontal diagnosis.

Periodontal diseases are highly prevalent chronic diseases, and severe periodontitis creates functional and esthetic problems and decreases self-esteem for a large percentage of the older population worldwide. In many cases of periodontitis, there is no distinct tell-tale pain that motivates a patient to seek treatment, rather the signs become clinically detectable late, and typically when the disease has progressed to a problematic level for the life of the dentition. Early periodontal screening and diagnostics tools will provide early recognition of periodontal diseases and facilitate timely management of the disease to reduce tooth loss. To this goal, gingival crevicular fluid is easily sampled, can be repeatedly and non-invasively collected, and can be tested for potential biomarkers. Moreover, the site specificity of periodontal diseases enhances the usefulness of gingival crevicular fluid sampled from specific sites as a biofluid for diagnosis and longitudinal monitoring of periodontal diseases. The present review aimed to provide up-to-date information on potential diagnostic biomarkers with utility that can be assayed from gingival crevicular fluid samples, focusing on what is new and useful and providing only general historic background textually and in a tabulated format.

The role of acquired host immunity in periodontal diseases.

The aim of this narrative review is to relate the contribution of European researchers to the complex topic of the host immune system in periodontal disease, focusing on acquired immunity. Other chapters in this volume will address the genetics and autoantibody responses and other forms of immunity to periodontal disease. While the contribution of European authors is the focus, global literature is included in this descriptive narrative for contextual clarity, albeit many with European co-authors. The topic is relatively intense and is thus broken down into sections outlined below, tackled as descriptive narratives to enhance understanding. Any attempt at a systematic or scoping review was quickly abandoned given the descriptive nature and marked variation of approach in almost all publications. Even the most uniform area of this acquired periodontal immunology literature, antibody responses to putative pathogens in periodontal diseases, falls short of common structures and common primary outcome variables one would need and expect in clinical studies, where randomized controlled clinical trials (RCTs) abound. Addressing 'the host's role' in immunity immediately requires a discussion of host susceptibility, which necessitates consideration of genetic studies (covered elsewhere in the volume and superficially covered here).

Strategic approaches in oral squamous cell carcinoma diagnostics using liquid biopsy.

Liquid biopsy is a noninvasive diagnostic technique used for monitoring cancer utilizing specific genetic biomarkers present in bodily fluids, such as blood, saliva, or urine. These analyses employ multiple biomolecular sources including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomes (that contain DNA fragments) to detect genetic biomarkers that can predict, disclose, and/or monitor cancers. Levels of these biomarkers can inform on the presence of cancer, its genetic characteristics, and its potential treatment response and also provide predictive genetic predisposition information for specific cancers including oral squamous cell carcinomas (OSCC). Liquid biopsies can aid cancer management as they offer real-time dynamic information on the response to say chemotherapy or radiotherapy and recurrence following surgical excision. Unlike traditional tissue biopsies, which are invasive with a degree of morbidity and require specific tumor location sampling, liquid biopsies are noninvasive and can be repeated frequently. For oral squamous cell carcinoma, on which this review focuses, liquid biopsy of blood or saliva can be valuable in predicting susceptibility, providing early detection, and monitoring the disease's progression and response to therapy. This review gives a general narrative overview of the technology, its current medical usage, and advantages and disadvantages compared with current techniques and discusses a range of current potential biomarkers for disclosing OSCC and predicting its risk. Oral squamous cell carcinoma is all too often detected in the late stages. In future, liquid biopsy may provide an effective screening process such that cancers including OSCC will be detected in the early stages rather than later when prognosis is poor and morbidity and debilitation are greater. In this screening process, periodontists and hygienists have a critical role in that they are adept in examining mucosa, they see patients with shared risk factors for periodontitis and OSCC, namely smoking and poor oral hygiene, and they see patients frequently such that OSCC examinations should be a routine part of the recall visit. With this additional screening manpower, oral medicine and oral surgery colleagues will detect OSCC earlier and this coupled with new techniques such as liquid biopsy may greatly decrease global morbidity in OSCC.

Role of NOD1/NOD2 receptors in Fusobacterium nucleatum mediated NETosis.

Polymorphonuclear neutrophils (PMNs) are indispensable in fighting infectious microbes by adopting various antimicrobial strategies including phagocytosis and neutrophil extracellular traps (NETs). Although the role and importance of PMNs in periodontal disease are well established, the specific molecular mechanisms involved in NET formation are yet to be characterized. In the present study, we sought to determine the role of periodontal pathogen on NET formation by utilizing Fusobacterium nucleatum. Our data demonstrates that F. nucleatum activates neutrophils and induces robust NETosis in a time-dependent manner via the upregulation of the Nucleotide oligomerization domain 1 (NOD1) and NOD2 receptors. Furthermore, CRISPR/Cas9 knockout of HL-60 cells and the use of ligands/inhibitors confirmed the involvement of NOD1 and NOD2 receptors in F. nucleatum-mediated NET formation. When treated with NOD1 and NOD2 inhibitors, we observed a significant downregulation of peptidylarginine deiminase 4 (PAD4) activity. In addition, neutrophils showed a significant increase and decrease of myeloperoxidase (MPO) and neutrophil elastase (NE) when treated with NOD1/NOD2 ligands and inhibitors, respectively. Taken together, CRISPR/Cas9 knockout of NOD1/NOD2 HL-60 cells and inhibitors of NOD signaling confirmed the role of NLRs in F. nucleatum-mediated NETosis. Our data demonstrates an important pathway linking NOD1 and NOD2 to NETosis by F. nucleatum, a prominent microbe in periodontal biofilms. This is the first study to elucidate the role of NOD-like receptors in NETosis and their downstream signaling network.

Epigenetic and inflammatory events in experimental periodontitis following systemic microbial challenge.

AIM: The purpose of this study was to determine inflammatory and epigenetic features following induction of oral and gut dysbiosis in experimental periodontitis in order to examine the interplay between oral and systemic infection. MATERIALS AND METHODS: Periodontitis was induced in 6- to 8-week-old C57BL/6 mice by (a) Ligature placement (Lig group) (oral challenge); (b) P. gingivalis gavage (Pg group) (systemic challenge); and (c) the combination of the two models oral and systemic challenge (Pg + Lig). The duration of the experiment was 60 days, and the animals were then sacrificed for analyses. Alveolar bone loss was assessed, and a multiplex immunoassay was performed. Maxillae and gut tissues were immunostained for DNMT3b (de novo methylation marker), B and T lymphocyte attenuator (BTLA) and IL-18R1 (inflammation markers). RESULTS: Pg and Pg + Lig groups exhibited higher bone loss when compared to Sham. BAFF, VEGF, RANKL, RANTES and IP-10 were significantly higher with Pg gavage. Likewise, DNMT3b was overexpressed in both gut and maxilla after the Pg administration. The same pattern was observed for BTLA and IL-18R1 in gut tissues. CONCLUSIONS: The systemic microbial challenge either alone or in combination with local challenge leads to distinct patterns of inflammatory and epigenetic features when compared to simply locally induced experimental periodontitis.

Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions.

A new periodontitis classification scheme has been adopted, in which forms of the disease previously recognized as "chronic" or "aggressive" are now grouped under a single category ("periodontitis") and are further characterized based on a multi-dimensional staging and grading system. Staging is largely dependent upon the severity of disease at presentation as well as on the complexity of disease management, while grading provides supplemental information about biological features of the disease including a history-based analysis of the rate of periodontitis progression; assessment of the risk for further progression; analysis of possible poor outcomes of treatment; and assessment of the risk that the disease or its treatment may negatively affect the general health of the patient. Necrotizing periodontal diseases, whose characteristic clinical phenotype includes typical features (papilla necrosis, bleeding, and pain) and are associated with host immune response impairments, remain a distinct periodontitis category. Endodontic-periodontal lesions, defined by a pathological communication between the pulpal and periodontal tissues at a given tooth, occur in either an acute or a chronic form, and are classified according to signs and symptoms that have direct impact on their prognosis and treatment. Periodontal abscesses are defined as acute lesions characterized by localized accumulation of pus within the gingival wall of the periodontal pocket/sulcus, rapid tissue destruction and are associated with risk for systemic dissemination.

The B Cell-Stimulatory Cytokines BLyS and APRIL Are Elevated in Human Periodontitis and Are Required for B Cell-Dependent Bone Loss in Experimental Murine Periodontitis.

B-lineage cells (B lymphocytes and plasma cells) predominate in the inflammatory infiltrate of human chronic periodontitis. However, their role in disease pathogenesis and the factors responsible for their persistence in chronic lesions are poorly understood. In this regard, two cytokines of the TNF ligand superfamily, a proliferation-inducing ligand (APRIL) and B-lymphocyte stimulator (BLyS), are important for the survival, proliferation, and maturation of B cells. Thus, we hypothesized that APRIL and/or BLyS are upregulated in periodontitis and contribute to induction of periodontal bone loss. This hypothesis was addressed in both human and mouse experimental systems. We show that, relative to healthy controls, the expression of APRIL and BLyS mRNA and protein was upregulated in natural and experimental periodontitis in humans and mice, respectively. The elevated expression of these cytokines correlated with increased numbers of B cells/plasma cells in both species. Moreover, APRIL and BLyS partially colocalized with κ L chain-expressing B-lineage cells at the epithelial-connective tissue interface. Ligature-induced periodontitis resulted in significantly less bone loss in B cell-deficient mice compared with wild-type controls. Ab-mediated neutralization of APRIL or BLyS diminished the number of B cells in the gingival tissue and inhibited bone loss in wild-type, but not in B cell-deficient, mice. In conclusion, B cells and specific cytokines involved in their growth and differentiation contribute to periodontal bone loss. Moreover, APRIL and BLyS have been identified as potential therapeutic targets in periodontitis.

Host response in aggressive periodontitis.

It is critical to understand the underlying host responses in aggressive periodontitis to provide a better appreciation of the risk and susceptibility to this disease. Such knowledge may elucidate the etiology and susceptibility to aggressive periodontitis and directly influence treatment decisions and aid diagnosis. This review is timely in that several widely held tenets are now considered unsupportable, namely the concept that Aggregatibacter actinomycetemycomitans is the key pathogen and that chemotactic defects in polymorphonuclear leukocytes are part of the etiopathology. This review also serves to put into context key elements of the host response that may be implicated in the genetic background of aggressive periodontitis. Furthermore, key molecules unique to the host response in aggressive periodontitis may have diagnostic utility and be used in chairside clinical activity tests or as population screening markers. It is becoming increasingly appreciated that the microbial etiology of aggressive periodontitis and the histopathology of this disease are more similar to than different from that of chronic periodontitis. An important therapeutic consideration from the lack of support for A. actinomycetemycomitans as a critical pathogen here is that the widely held belief that tetracycline had a role in aggressive periodontitis therapy is now not supported and that antibiotics such as those used effectively in chronic periodontitis (metronidazole and amoxicillin) are not contraindicated. Furthermore, A. actinomycetemycomitans-related molecules, such as cytolethal distending toxin and leukotoxin, are less likely to have utility as diagnosis agents or as therapeutic targets.

Porphyromonas gingivalis influences actin degradation within epithelial cells during invasion and apoptosis.

Porphyromonas gingivalis, a Gram-negative oral pathogen, has been shown to induce apoptosis in human gingival epithelial cells, yet the underlining cellular mechanisms controlling this process are poorly understood. We have previously shown that the P. gingivalis proteases arginine and lysine gingipains, are necessary and sufficient to induce host cell apoptosis. In the present study, we demonstrate that 'P. gingivalis-induced apoptosis' is mediated through degradation of actin leading to cytoskeleton collapse. Stimulation of human gingival epithelial cells with P. gingivalis strains 33277 and W50 at moi:100 induced ß-actin cleavage as early as 1 h and human serum inhibited this effect. By using gingipain-deficient mutants of P. gingivalis and purified gingipains, we demonstrate that lysine gingipain is involved in actin hydrolysis in a dose and time-dependent manner. Use of Jasplakinolide and cytochalasin D revealed that P. gingivalis internalization is necessary for actin cleavage. Further, we also show that lysine gingipain from P. gingivalis can cleave active caspase 3. Taken together, we have identified actin as a substrate for lysine gingipain and demonstrated a novel mechanism involved in microbial host cell invasion and apoptosis.

The role of glycogen synthase kinase 3 in regulating IFN-ß-mediated IL-10 production.

The ability of IFN-ß to induce IL-10 production from innate immune cells is important for its anti-inflammatory properties and is believed to contribute to its therapeutic value in treating multiple sclerosis patients. In this study, we identified that IFN-ß stimulates IL-10 production by activating the JAK1- and PI3K-signaling pathways. JAK1 activity was required for IFN-ß to activate PI3K and Akt1 that resulted in repression of glycogen synthase kinase 3 (GSK3)-ß activity. IFN-ß-mediated suppression of GSK3-ß promoted IL-10, because IL-10 production by IFN-ß-stimulated dendritic cells (DC) expressing an active GSK3-ß knockin was severely reduced, whereas pharmacological or genetic inhibition of GSK3-ß augmented IL-10 production. IFN-ß increased the phosphorylated levels of CREB and STAT3 but only CREB levels were affected by PI3K. Also, a knockdown in CREB, but not STAT3, affected the capacity of IFN-ß to induce IL-10 from DC. IL-10 production by IFN-ß-stimulated DC was shown to suppress IFN-γ and IL-17 production by myelin oligodendrocyte glycoprotein-specific CD4(+) T cells, and this IL-10-dependent anti-inflammatory effect was enhanced by directly targeting GSK3 in DC. These findings highlight how IFN-ß induces IL-10 production and the importance that IL-10 plays in its anti-inflammatory properties, as well as identify a therapeutic target that could be used to increase the IL-10-dependent anti-inflammatory properties of IFN-ß.

Influence of periodontal disease, Porphyromonas gingivalis and cigarette smoking on systemic anti-citrullinated peptide antibody titres.

BACKGROUND: Anti-citrullinated protein antibody (ACPA) responses may precede clinical onset of rheumatoid arthritis. Porphyromonas gingivalis peptidylarginine deiminase can citrullinate proteins possibly inducing autoimmunity in susceptible individuals. AIM: To determine whether periodontitis, carriage of P. gingivalis, smoking and periodontal therapy influence ACPA titres. METHODS: Serum and plaque samples were collected from 39 periodontitis patients before and after non-surgical periodontal treatment, and from 36 healthy subjects. Carriage of P. gingivalis was determined by PCR of plaque DNA. ACPA was determined by anti-cyclic citrullinated peptide (CCP) enzyme-linked immunosorbent assay (ELISA). Anti-P. gingivalis titres were determined by ELISA. RESULTS: Untreated periodontitis patients had higher anti-CCP antibody titres than healthy controls [three patients (8%) greater than manufacturer suggested assay diagnostic threshold (5 Assay Units/AU) versus none (0%); mean ± SEM: 1.37 ± 0.23 versus 0.40 ± 0.10 AU, p < 0.0001]. Periodontitis patients who smoked demonstrated lower anti-P. gingivalis (15956 ± 4385 versus 2512 ± 1290 Units/ml, p < 0.05), but similar anti-CCP than non-smoking periodontitis patients (smokers: 1.31 ± 0.35; non-smokers: 1.41 ± 0.32 AU). Healthy smokers demonstrated elevated anti-CCP titres (0.75 ± 0.19 AU), at levels between healthy non-smokers (0.15 ± 0.05 AU) and non-smoker periodontitis patients. Six months after periodontal treatment, there were significant reductions in anti-CCP (non-smokers p < 0.05) and anti-P. gingivalis (all participants p < 0.01). CONCLUSION: In subjects with periodontitis, P. gingivalis infection may be responsible for inducing autoimmune responses that characterize rheumatoid arthritis.

Periodontal therapy in chronic periodontitis lowers gingival crevicular fluid interleukin-1beta and DAS28 in rheumatoid arthritis patients.

To evaluate clinical outcomes and effects of non-surgical periodontal therapy on serum, gingival crevicular fluid (GCF) interleukin-1beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) levels in chronic periodontitis patients with/without rheumatoid arthritis (RA), fifteen RA patients with chronic periodontitis (RA-P) and 15 systemically healthy non-RA chronic periodontitis patients (H-P) were recruited. Clinical periodontal recordings, GCF, and blood samples were obtained at baseline, 1, 3, and 6 months after periodontal treatment. GCF, serum IL-1ß, TNF-α levels were analyzed by ELISA. Disease activity score 28 (DAS28) was used to assess RA clinical morbidity. Study groups were compared by Mann-Whitney U test. Wilcoxon test was used to compare the data at baseline, 1, 3, and 6 months after periodontal therapy within the same group. DAS28 decreased significantly after periodontal therapy in RA-P group (p < 0.01). Serum TNF-α concentrations of H-P group were significantly higher than those of RA-P group (p < 0.01), whereas IL-1ß levels were similar. No significant change was observed in serum levels of these cytokines after periodontal therapy. GCF IL-1ß amounts decreased significantly in both groups following treatment (p < 0.01). At 6-months, H-P GCF IL-1ß concentrations were significantly lower than baseline. DAS28 and GCF IL-1ß correlated with clinical periodontal indices (p < 0.01). Significant decreases in DAS28 and GCF IL-1ß amounts after periodontal treatment suggest that periodontal therapy synergizes with systemic RA therapy to improve RA status.

Risk assessment and implementation of risk reduction measures is not associated with increased transmission of SARS-CoV-2 compared with standard isolation at professional golf events.

Objectives: The purpose of this prospective study was to report incidence and transmission of SARS-CoV-2, among professional golfers and essential support staff undergoing risk assessment and enhanced risk reduction measures when considered a close contact as opposed to standard isolation while competing on the DP World Tour during the 2021 season. Methods: This prospective cohort study included all players and essential support staff participating in 26 DP World Tour events from 18 April 2021 to 21 November 2021. High-risk contacts were isolated for 10 days. Moderate-risk contacts received education regarding enhanced medical surveillance, had daily rapid antigen testing for 5 days, with reverse transcriptase-polymerase chain reaction (RT-PCR) tesing on day 5, mandated mask use and access to outside space for work purposes only. Low-risk contacts typically received rapid antigen testing every 48 hours and RT-PCR testing on day 5. Results: The total study cohort compromised 13 394 person-weeks of exposure. There were a total of 30 positive cases over the study period. Eleven contacts were stratified as 'high risk'. Two of these subsequently tested positive for SARS-CoV-2. There were 79 moderate-risk contact and 73 low-risk contacts. One moderate-risk contact subsequently tested positive for SARS-CoV-2 but did not transmit the virus. All other contacts, remained negative and asymptomatic to the end of the tournament week. Conclusions: A risk assessment and risk reduction-based approach to contact tracing was safe in this professional golf event setting when Alpha and Delta were the predominant variants. It enabled professional golfers and essential support staff to work.

Gingival crevicular fluid IL-6, tPA, PAI-2, albumin levels following initial periodontal treatment in chronic periodontitis patients with or without type 2 diabetes.

OBJECTIVES: To evaluate initial periodontal treatment effects on gingival crevicular fluid (GCF) interleukin-6 (IL-6), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-2 (PAI-2), albumin levels in type 2 diabetic patients. DESIGN AND METHODS: GCF samples were collected from 20 type 2 diabetic, 22 non-diabetic non-smokers all with chronic periodontitis at baseline, 1-, 3-months following initial periodontal treatment. Biochemical analysis was performed by ELISA. Data were tested by Mann-Whitney U, Wilcoxon tests. RESULTS: The total amounts of albumin, IL-6, tPA, PAI-2 decreased significantly in diabetics after treatment (1- and 3-months) whereas, only PAI-2 decreased in non-diabetic group at 3-months (p < 0.05). There were statistically significant differences between the diabetics and non-diabetics at all time points for albumin, PAI-2 and at 1-, 3-months for GCF volume (p < 0.050) but only at baseline for IL-6 (p < 0.050). CONCLUSION: Present data suggest clinical improvements are less apparent in diabetic chronic periodontitis patients as reflected by disease markers in GCF and by an increase in concentrations of inflammatory proteins IL-6, tPA, and PAI-2 in GCF of this patient group following initial periodontal treatment.

c-jun controls the ability of IL-12 to induce IL-10 production from human memory CD4+ T cells.

IL-12p70 is an immunoregulatory cytokine that has been shown to induce IL-10 production from CD4+ T cells, yet the underlying cellular mechanisms controlling this process are poorly understood. In the present study, we demonstrate that IL-12p70 induces IL-10 production from human memory CD4+ T cells via a PI3K-dependent signaling mechanism. Specifically, stimulation of human memory CD4+ T cells in the presence of IL-12p70 lead to increased PI3K activity and the subsequent phosphorylation and inactivation of the downstream constitutively active serine/threonine kinase, glycogen synthase kinase-3beta (GSK3beta). Inhibition of PI3K prevented the inactivation of GSK3beta by IL-12p70, as well as the subsequent ability of IL-12p70 to augment IL-10 levels by memory CD4+ T cells. Moreover, ectopic expression of a constitutively active form of GSK3beta abrogated the ability of IL-12p70 to increase IL-10 production by TCR-stimulated CD4+ T cells. In contrast, direct inhibition of GSK3 mimicked the effect of IL-12p70 on IL-10 production by memory CD4+ T cells. Analysis of downstream transcription factors identified that the ability of IL-12p70 to inactivate GSK3beta lead to increased levels of c-jun. The ability of IL-12p70 to inactivate GSK3beta and induce c-jun levels was required for IL-12 to augment IL-10 production by human memory CD4+ T cells, since small interfering RNA-mediated gene silencing of c-jun abrogated this process. These studies identify the cellular mechanism by which IL-12 induces IL-10 production from human memory CD4+ T cells.

Toll-like receptor-mediated production of IL-1Ra is negatively regulated by GSK3 via the MAPK ERK1/2.

IL-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1beta, has been shown to regulate the progression of a variety of inflammatory diseases. Although experimental studies and clinical trials have demonstrated the importance of IL-1Ra in chronic inflammatory diseases, the cellular mechanisms responsible for regulating the endogenous production of IL-1Ra by innate immune cells are currently unresolved. In the present study, we identify that glycogen-synthase kinase 3 (GSK3) regulates the production of the anti-inflammatory cytokine IL-1Ra via its ability to regulate the MAPK ERK1/2 in TLR-stimulated cells. Elucidation of the cell-signaling pathway by which GSK3 controlled ERK activity demonstrated that GSK3 inhibition resulted in an abrogation in the levels of the inhibitory residue serine 71 on Rac1 and increased the ability of Rac1 to interact with and activate p21-activated protein kinase. siRNA-mediated knockdown of Rac1 attenuated the ability of GSK3 inhibition to augment phospho-ERK1/2 levels in LPS-stimulated immune cells. Moreover, inhibiting the ability of GSK3 to augment ERK1/2 activity abrogated enhanced IL-1Ra production by GSK3-inhibited cells. Our findings identify that GSK3 negatively regulates the levels of IL-1Ra produced by LPS-stimulated innate immune cells.

Host-derived diagnostic markers related to soft tissue destruction and bone degradation in periodontitis.

BACKGROUND: A major challenge in clinical periodontics is to find a reliable molecular marker of periodontal tissue destruction with high sensitivity, specificity and utility. OBJECTIVES: The aim of this systematic review is to evaluate available literature on 'the utility of molecular markers of soft and hard periodontal tissue destruction'. MATERIALS AND METHODS: Based on the focused question, 'What is the utility of molecular markers of soft and hard periodontal tissue destruction', an electronic and manual search was conducted for human studies presenting clinical data for the potential of molecular markers of tissue destruction in biofluids; gingival crevicular fluid (GCF), saliva, and serum. RESULTS: Papers fulfilling the inclusion criteria were selected. All relevant data from the selected papers were extracted and recorded in separate tables for molecules in GCF, saliva, and serum. CONCLUSION: Within the defined limits of the Problem/Population, Intervention, Comparison, Outcome, the present analysis reveals that (a) no single or combination of markers exists that can disclose periodontal tissue destruction adequately; (b) while the most fruitful source of biomarkers for periodontal destruction appears to be in molecules tightly related to bone and soft tissue destruction, this remains to be objectively demonstrated. Currently, clinical measurements are still the most reliable.

Host-response: understanding the cellular and molecular mechanisms of host-microbial interactions--consensus of the Seventh European Workshop on Periodontology.

BACKGROUND: Major challenges in periodontology include understanding the pathophysiology, the interplay between various components of the host response, parallels with other diseases and identifying biomarkers of the disease. OBJECTIVES: Four reviews were compiled with the aim of better understanding: (1) the role of polymorphic nuclear leucocytes (PMNs), i.e. neutrophils; (2) the function of cytokine networks in the host response; (3) whether parallels exist with rheumatoid arthritis (RA); and (4) whether useful biomarkers currently exist to help in the management of periodontal disease. MATERIAL AND METHODS: Based on the focused questions, electronic and manual searches were conducted for human, animal and cellular studies on the above topics. RESULTS: Papers fulfilling the inclusion criteria were selected and reviews were written and reviewed and corrected before the academy meeting to produce consensus statements. CONCLUSION: The following consensus statements were produced. PMNs are important in the pathophysiology of periodontal disease but there is limited evidence on their much quoted destructive potential. Cytokine networks are enormously complex and we are really at the beginning of understanding their role in the disease process. RA has both similarities and marked differences to periodontal disease although the existing utilization of anti-cytokine therapies and other molecules in its treatment may have importance in periodontal disease therapy. Biomarkers for periodontal disease have yet to be completely defined but the ratio of receptor activator of NF-κB ligand to osteoprotegerin appears to be a biomarker test with utility for detecting bone destruction.

Assessing the risk of SARS-CoV-2 transmission in international professional golf.

OBJECTIVES: There is no published data on the incidence or risk of SARS-CoV-2 transmission when playing golf, a sport played outdoors where social distancing is possible. The purpose of this prospective study was to report incidence and transmission regarding SARS-CoV-2, of professional golfers competing on the PGA European Tour across 23 events in 11 countries. METHODS: Daily symptom and temperature checks and weekly reverse transcriptase PCR (RT-PCR) screening were performed to determine potential carriage of SARS-CoV-2. Onset and type of symptomology were analysed. Gene expression and cycle thresholds (Cts) were reviewed for all positive cases. Repeat PCR testing was performed on all positive players. RT-PCR analysis included human housekeeping genes and various RNA genes specific for SARS-CoV-2. RESULTS: During the study period, there were 2900 RT-PCR tests performed on 195 professional golfers competing on the European Tour. Four players tested positive on-site during the study period (0.14% of tests; positive results were declared with Ct <40). Two positive tests were returned as part of routine protocols, while two reported a history of close contact with an individual who had tested positive for SARS-CoV-2 and were isolated and target tested. All were asymptomatic at time of testing, with three developing symptoms subsequently. None required hospital admission. There was no transmission from player to player. CONCLUSION: Golf is an outdoor sport where social distancing is possible, meaning risks can be low if guidance is followed by participants. Risk of transmission of SARS-CoV-2 can be mitigated by highly accurate RT-PCR testing of participants and by setting up a safe bubble that includes testing players and support staff, as well as all persons coming into contact with them during the course of the tournament, for example, drivers and hotel staff. This report can also provide reassurance for participants and policy makers regarding community golf, which can be encouraged for the health benefits it provides, in a relatively low-risk environment, with minimal risk of transmission by observing sensible viral hygiene protocols.