Current evidence strongly supports an association between periodontitis and rheumatoid arthritis (RA) in a subset of susceptible individuals. The relationship between these conditions is underpinned by a complex interplay between chronic inflammation and subgingival bacterial infection. Several hypotheses have been proposed to explain the mechanistic basis of this association. Among these, the "two-hit" model is particularly compelling, as it suggests that inflammation, infection, or a combination of both may contribute to the initiation and progression of RA in predisposed individuals. According to this model, the progression of gingivitis and periodontitis, together with associated microbial dysbiosis, may promote protein citrullination, carbamylation, and the formation of malondialdehyde-acetaldehyde (MAA) adducts. These post-translational modifications may subsequently induce the production of autoantibodies before the clinical onset of joint inflammation and RA. Once synovial inflammation develops, additional citrullination, carbamylation, and MAA adduct formation may occur within the joint microenvironment, further amplifying autoantibody production. In previously sensitized individuals, such as those with chronic gingivitis or periodontitis, this secondary immune response may be substantially enhanced, resulting in increased joint inflammation and tissue destruction. Subgingival bacteria may also contribute directly, or indirectly, to the periodontitis/RA axis through translocation to distant tissues, induction of protein citrullination and other protein post-translational modifications, stimulation of autoantibody production, and exacerbation of inflammatory responses. Central to the role bacteria play in the periodontitis/RA axis is the emergence of functional alterations in the microbiome. Dysbiosis in the subgingival microenvironment, and the emergence and proliferation of recognized periodontal pathobionts, underpins these key elements. This, along with bacterial-induced inflammation and direct influence on immune player trafficking, results in a complex synergy within the mechanistic processes involved in the relationship between periodontitis and RA. In this narrative review, we critically examine the inflammatory and microbial mechanisms implicated in the interaction between periodontitis and RA and propose an updated framework integrating inflammation, dysbiosis, and autoimmunity.

Mesenchymal stem cells (MSCs), characterized by their undifferentiated and multipotent nature, can be derived from various sources, including bone marrow, adipose, and dental tissues. Among these, dental MSCs (DSCs) exhibit universal MSC characteristics and are attracting considerable attention for regenerating oral and craniofacial tissues. This review provides a contemporary overview of recently published clinical studies using DSCs for various orodental and maxillofacial regenerative applications, including bone, periodontal, and endodontic regeneration. It also explores the utilization of DSCs in treating systemic conditions, exemplified by their application in managing conditions such as COVID-19 and osteoarthritis. The available evidence underscores the potential of DSCs and their secretome as efficacious tools in regenerative medicine for both dental and nondental clinical applications, supporting the continued promise of stem cell-based therapies. It is nevertheless evident that there are a number of important challenges that restrict the widespread utilization of DSCs, namely, difficulty in standardizing autologous preparations, insufficient cell surface marker characterization, high production costs, and regulatory compliance requirements. Further, the unique requirements of dental applications, especially complex structures such as the periodontium, where temporospatial control over the healing process is required, necessitate the combination of stem cells with appropriate scaffolds according to the principles of tissue engineering. There is currently insufficient evidence to support the clinical translation of DSCs into clinical practice, and phase 3 clinical trials with standardized protocols for cell sourcing, propagation, dosing, and delivery are required to move the field forward. In summary, this review provides a contemporary overview of the evolving landscape of stem cell therapy, offering insights into the latest developments and trends as well as the challenges that need to be addressed for the widespread application of DSC-based cell therapies.

Periodontitis (PD) is characterized by the host's inflammatory responses to microbial dental biofilm dysbiosis, potentially resulting in tooth loss if left untreated. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease leading to synovial inflammation and destruction of joint cartilage and bone. The suggested association between PD and RA is based on the potential of chronic inflammation present in periodontitis, which could induce alterations in proteins through post-translational modifications, leading to the formation of citrullinated and carbamylated protein antigens. Antibodies directed against these antigens can serve as biomarkers for the underlying immunological processes in RA. Recent studies have also focused on bacterial proteolytic enzymes released from PD-associated bacteria, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, which are also sources of these antibodies. Chronic inflammation in PD causes increased levels of inflammatory cytokines (interferon-α, interleukins-6 and 8, tumor necrosis factor-α) and neutrophil extracellular traps (NETs). The oral microbiota in PD is also associated with the release of NETs (a process known as NETosis). Elevated NET levels are a source of citrullinated and carbamylated proteins which highlights their role in an individual's risk of developing RA (pre-RA individuals) and the progression of chronic RA. This narrative review describes periodontitis and the dysbiotic subgingival microbiota and its role in NETosis as risk factors for inducing early RA and the prospects of identifying pre-RA individuals and seronegative RA patients with these risk factors.

Rheumatoid arthritis (RA) is characterized by chronic inflammatory destruction of joint tissue and is caused by an abnormal autoimmune response triggered by interactions between genetics, environmental factors, and epigenetic and posttranslational modifications. RA has been suggested to be interrelated with periodontitis, a serious form or stage of chronic inflammatory periodontal disease associated with periodontopathic bacterial infections, genetic predisposition, environmental factors, and epigenetic influences. Over the last decade, a number of animal and clinical studies have been conducted to assess whether or not periodontitis and associated periodontopathic bacteria constitute risk factors for RA. The present review introduces recent accumulating evidence to support the associations of periodontitis and periodontopathic bacteria with the risk of RA or the outcome of RA pharmacological treatment with disease-modifying antirheumatic drugs. In addition, the results from intervention studies have suggested an improvement in RA clinical parameters after nonsurgical periodontal treatment. Furthermore, the potential causal mechanisms underlying the link between periodontitis and periodontopathic bacteria and RA are summarized.

OBJECTIVE:This study investigated the subgingival microbial profile of rheumatoid arthritis (RA) patients and its associations with disease parameters and the inflammation-related antimicrobial peptide, LL-37.METHODS:RA and non-RA (NRA) patients were assessed for periodontal status and divided into periodontitis (CP), gingivitis (G), and healthy (H) groups. Subgingival plaque 16s rRNA gene sequencing data was processed and analyzed using the CLC Genomic Workbench (Qiagen). Bacterial diversity and co-occurrence patterns were examined. Differential abundance between groups was also investigated. Associations between bacterial genera with disease parameters and LL-37 levels were explored qualitatively using canonical correlation analysis.RESULTS:Subgingival microbial community clustered in CP status. Co-occurrence network in NRA-H was dominated by health-associated genera, while the rest of the networks' key genera were both health- and disease-associated. RA-CP displayed highly inter-generic networks with a statistically significant increase in periodontal disease-associated genera (p<0.05). In NRA-H, disease parameters and LL-37 were correlated positively with disease-associated genera while negatively with health-associated genera. However, in the remaining groups, mixed positive and negative correlations were noted with genera.CONCLUSION:RA patients demonstrated subgingival microbial dysbiosis where the bacteria networks were dominated by health- and disease-associated genera. Mixed correlations with disease parameters and LL-37 levels were noted.CLINICAL RELEVANCE:The subgingival microbial dysbiosis in RA may predispose these patients to developing periodontal inflammation with an associated detrimental effect on host immune responses. Routine periodontal assessment may allow initiation of treatment strategies to minimize the effects of gingival inflammation on the existing heightened immune response present in RA patients.

Historically, there has been broad consensus that osseointegration represents a homeostasis between a titanium dental implant and the surrounding bone, and that the crestal bone loss characteristic of peri-implantitis is a plaque-induced inflammatory process. However, this notion has been challenged over the past decade by proponents of a theory that considers osseointegration an inflammatory process characterized by a foreign body reaction and peri-implant bone loss as an exacerbation of this inflammatory response. A key difference in these two schools of thought is the perception of the relative importance of dental plaque in the pathogenesis of crestal bone loss around implants, with obvious implications for treatment. This review investigates the evidence for a persistent foreign body reaction at osseointegrated dental implants and its possible role in crestal bone loss characteristic of peri-implantitis. Further, the role of implant-related material release within the surrounding tissue, particularly titanium particles and corrosion by-products, in the establishment and progression in peri-implantitis is explored. While it is acknowledged that these issues require further investigation, the available evidence suggests that osseointegration is a state of homeostasis between the titanium implant and surrounding tissues, with little evidence that a persistent foreign body reaction is responsible for peri-implant bone loss after osseointegration is established. Further, there is a lack of evidence for a unidirectional causative role of corrosion by-products and titanium particles as possible non-plaque related factors in the etiology of peri-implantitis.

As we start 2021, a new cohort of dental graduates will commence their lifelong journey through dentistry. I wish them every success and hope their journey is as exciting as mine has been. It comes as no surprise that the practice of dentistry in 2021 is vastly different from what it was when I first started in 1979. In 1979, amalgam was still the material of choice for most posterior restorations and glass ionomer cements were being developed and only used in adults, dental implants were in their infancy and nowhere near the mainstream treatment option they are today, powered toothbrushes were available but considered a gimmick, oral health and systemic health were considered (and taught) as almost mutually exclusive entities and the world wide web and Dr Google were not available. How things have changed. In this first issue of the Australian Dental Journal for 2021, we have papers covering the demise of amalgam, use of glass ionmer cements in paediatric dentistry, the significant relationship between diabetes and oral health, utilization of powered toothbrushes and an assessment of dental treatment information contained within websites. All of these papers have arisen from research in the quest for attaining knowledge in the practice of dentistry. Without research, knowledge cannot advance. However, a research project is not complete until it is published and knowledge can be shared. The Australian Dental Journal is one of a large number of international peer-reviewed journals that provides a conduit for this sharing of knowledge. The responsibility of selecting material for publication in any professional journal is enormous and trying to identify material suitable for publication is an ever demanding problem for Editors. Did you know that in 2020, 1084 manuscripts were submitted to the Australian Dental Journal to be considered for publication yet only 53 were accepted for publication? This means that of all the manuscripts submitted to the Australian Dental Journal approximately 5% were deemed suitable for publication. Thus, there is a lot of dental research being carried out that is either substandard or struggles to find a suitable forum in which to be published. For the Australian Dental Journal, the selection sieve is small but the benefits for readers is that only material considered to be of an acceptable standard is presented for them in their information and knowledge base. What we do with research and knowledge then depends on our experience. For the neophyte practitioner, everything will seem new and so everything needs to be processed, stored and used according to a limited knowledge base. However, for the experienced practitioner, everything may not be so new anymore and so the information is processed in a different light that can only come with the benefit of years of clinical practice and practical experience. Indeed sometimes what is presented as ‘new’ is indeed ‘old’ and is just something that turned full circle in the life of the topic in question. For example, the relationship between diabetes and oral health is not new – indeed periodontal disease was proposed to be the sixth complication of diabetes as far back as 1993 but unless you were around in 1993 you may not know this and therefore consider the ‘new’ periodontal systemic connection, such as between diabetes and oral health, as a more contemporary development in dentistry. The topic of this editorial is research, knowledge and experience and how these form the cornerstones of our professional lives. We have all heard of the term the ‘Art and Science’ of dentistry and this reflects how research and knowledge (the ‘science’) are intimately interwoven in our experience (the ‘art’). What sets us apart as “professionals” in the true sense of the word is our ability to combine both art and science for the good of our patients and base the practice of our profession on sound research, knowledge and experience.

This was the title of the final episode of the iconic and long running television series M*A*S*H. After 256 episodes this show came to an end. Likewise, after 22 years of being Editor of the Australian Dental Journal, my time has come to bid farewell. To say it has been an honour and privilege to serve as only the third Editor of the ADJ since its inception in 1956, is not only clichéd but is, in fact, the reality for me. This Editorial is a reflection on my term as ADJ Editor and, fortunately, unlike the star of M*A*S*H (Hawkeye Pearce), I do not leave my post shell-shocked but rather I leave it with a sense of gratitude to everyone who has joined me on this journey. Importantly, this includes my family who have had to endure my indulgence in tending to Journal business when I should have been better spending time serving them, all members of the Publication team over the years, members of the Editorial Advisory Board, manuscript reviewers, authors and, of course, the reason for the journal, our readers. A very big thank you to all of you. In my first Editorial, I referenced the following quote from Elspeth Huxley: Only man is not content to leave things as they are but must always be changing them, and when he has done so, is seldom satisfied with the result.1 Now after 88 consecutive Editorials, I can reflect and say that the changes we brought to the ADJ over the past 22 years have been done with our readers in mind and our primary aim of providing a vehicle for providing scientific and clinical articles of importance and relevance to dentistry as it is practiced in Australia. But we cannot be satisfied because knowledge is ever evolving and the need to share knowledge is central to ensuring contemporary practices are sustained. With this in mind, I would like to share my re-working of a very famous quote: Knowledge is right. Knowledge works. Knowledge clarifies, cuts through, and captures the essence of the evolutionary spirit. (Many thanks to Michael Douglas’ screen character Gordon Gekko for this one2 but I have to say I like this version rather than his.) I do not know who is right, but I do know that this comment captures the spirit of scientific endeavour and scientific publishing. Over my tenure, I have overseen a number of significant changes for the ADJ. When I commenced as the Editor in 1999, all manuscripts were processed manually and communication was via the snail mail postal system. Over time, the electronic age evolved and we were able to move to using email and eventually web-based processing and communication systems. We also progressed from ‘in-house publishing’ to becoming part of the global stable of dental journals published by the international publishing house – Wiley. The ADJ has seen its standing, in terms of world rankings and recognition, steadily increase over the years. For example, the Journal’s impact factor in 1999 was 0.297 and this has steadily improved over the years to reach a peak of 2.29 in 2020. Further evidence of the reach of the Journal is noting the increase in number of times papers published in the ADJ have been cited. For example, the papers considered for the 1999 Impact Factor ranking had been cited 454 times and for the 2020 ranking this had increased some 8-fold to 3723. There have been two major highlights for me as Editor. One was the very important task of overseeing and selecting manuscripts for publication and trying to ensure these reflected the high quality standards the Journal had set itself. The second has been the amazing liberty of being able to write an Editorial for each issue of the Journal. The amount of feedback on these Editorials has been remarkable and apart from only two occasions it has been all positive. To have been permitted to voice an opinion on a very wide range of topics and not once be admonished by the Australian Dental Association (ADA) is testimony to how our Association views the Journal and how the Association has allowed the Journal to be a voice for the profession. Not once did the ADA ever interfere or exert any influence on the content (editorial or papers) published. I cannot tell you how many people told me ‘the only thing I read is the Editorial’! To these people, I say thank you so much and I am glad that at least you opened the pages of the Journal. My two predecessors, Robert Harris and John Harcourt, have been icons in the Australian Dental Scene. To have been selected to follow in their footsteps was a daunting task. Over the years, I have tried to embrace their legacy and perpetuate their important and significant contributions to Australian dentistry and the ADJ. Now my time has come and I will hand over the Editorship to Professor Ivan Darby. I wish him all the best and I believe the journal will move to new heights under his stewardship. And so it is now, from me, ‘Goodbye, Farewell and Amen’. Or in the words of my favourite Nobel Laureate, Bob Dylan: ‘Its All Over Now Baby Blue’ (You must leave now, take what you need …..)

_Last year, the first carbon dioxide (CO2) laser, which is also suitable for hard-tissue indications, received approval by the Food and Drug Administration in the US. Could this be the next big thing in laser dentistry, in your opinion? A CO2 laser receiving FDA approval for hard-tissue indications looks promising and could definitely be a game changer, as it could alter the way we understand laser dentistry right now. We will have to wait and see how things develop in this regard.

Two recent items have caught my attention in recent months. The first is the role of oral health care for the aged and the second is artificial intelligence (AI). There was a general feeling of ‘reward for hard work’ by the dental profession following a number of submissions from interested oral health stakeholders that resulted in inclusion of oral health in the recommendations of the Royal Commission into Aged Care Quality and Safety. It was particularly pleasing to see the recommendation that at least one oral health practitioner be assigned to every aged care provider in Australia. An endorsement for a Seniors Dental Benefits Scheme to commence in 2023 was also encouraging news. However, the excitement was short-lived when the Federal Budget was delivered with no provision in it for oral health care for aged. Seems like one step forward and three steps backwards. Still, we should not give up and the call for greater funding and support for aged oral care. For any of us who have had the experience of having family members in aged care, the astounding lack of well-managed oral care at this very critical stage of life is all but a reality and a problem that seems to be poorly addressed in the overall medical management of people in aged care facilities. Perhaps this is exacerbated by an ongoing lack of understanding by the medical and aged care sectors that the mouth is connected to the rest of the body. I have often thought how could this issue be better embraced? We have some excellent examples where some inroads have been made for the provision of oral health care in the aged care sector but in general the problem of poor delivery and service persists. If the problem relates to lack of understanding of what goes on in an aged person’s mouth by the frontline aged care workers, then why not try to simplify it for them? Is one solution artificial intelligence? There is no doubt that AI has the potential to make oral health care accessible and effective but there is also the potential for errors to arise if the algorithms developed are not carefully designed and implemented. AI in dentistry is in its infancy but the potential for rapid development is high.1 It has been said that health care can be made more equitable by tailoring algorithms to specific patient populations (i.e. the aged). For example, knowing that delivery of oral health care for the aged has been underperforming for decades, and is a looming community disaster in the waiting, could we develop algorithms specifically targeted towards predicting the manifestations of age on oral diseases? As we move into the exciting age of personalized/precision medicine and dentistry where we will move from the ‘one size fits all’ paradigm to an individual focussed approach to oral health care, the potential for inclusion of AI in this processed should not be discounted. In the future, it should be possible to create algorithms that specifically target the aged and this could be the beginning of progression to an inclusive oral health care programmes for the aged and allow those not familiar with oral health care to participate in the triage and eventual implementation of treatment services as needed by this ever-increasing sector in our community. If the Royal Commission sees a need for inclusion of oral health care in the aged care sector, then we must look to innovative ways to implement this. AI may be one such way that could be harnessed to make aged oral health care more accessible, affordable and effective.

Periodontitis is an inflammatory disease, associated with a microbial dysbiosis. Early detection using salivary small extracellular vesicles (sEVs) biomarkers may facilitate timely prevention. sEVs derived from different species (i.e., humans, bacteria) are expected to circulate in saliva. This pilot study recruited 22 participants (seven periodontal healthy, seven gingivitis and eight periodontitis) and salivary sEVs were isolated using the size-exclusion chromatography (SEC) method. The healthy, gingivitis and periodontitis groups were compared in terms of salivary sEVs in the CD9+ sEV subpopulation, Gram-negative bacteria-enriched lipopolysaccharide (LPS+) outer membrane vesicles (OMVs) and global DNA methylation pattern of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) and N6-Methyladenosine (m6dA). It was found that LPS+ OMVs, global 5mC methylation and four periodontal pathogens (T. denticola, E. corrodens, P. gingivalis and F. nucleatum) that secreted OMVs were significantly increased in periodontitis sEVs compared to those from healthy groups. These differences were more pronounced in sEVs than the whole saliva and were more superior in distinguishing periodontitis than gingivitis, in comparison to healthy patients. Of note, global 5mC hypermethylation in salivary sEVs can distinguish periodontitis patients from both healthy controls and gingivitis patients with high sensitivity and specificity (AUC = 1). The research findings suggest that assessing global sEV methylation may be a useful biomarker for periodontitis.

BACKGROUND:Previous studies have reported conflicting findings between serum anti-citrullinated protein antibodies (ACPA) levels in rheumatoid arthritis (RA) participants with and without periodontitis (Pd). This study aimed to analyse possible correlations between serum ACPA levels and clinical parameters in Pd and RA participants. METHODS:Full mouth periodontal examination (probing pocket depth, clinical attachment levels, gingival bleeding index, visual plaque index) was conducted and serum samples obtained from 80 participants comprising RA, Pd, both RA and Pd (RAPd) and healthy individuals (HC). Erythrocyte sedimentation rates (ESR) and periodontal inflamed surface area (PISA) were obtained. Serum samples were analysed for ACPA quantification using enzyme-linked immunosorbent assay (ELISA). RESULTS:Median levels (IU/mL) of ACPA (interquartile range, IQR) in RAPd, RA, Pd and HC groups were 118.58(274.51), 102.02(252.89), 78.48(132.6) and 51.67(91.31) respectively. ACPA levels were significantly higher in RAPd and RA as compared to HC group (p < 0.05). However, ACPA levels of any of the groups were not correlated with any clinical periodontal and RA parameters within the respective groups. CONCLUSIONS:At individual level, the amount of serum ACPA seem to have an increasing trend with the diseased condition in the order of RAPd > RA > Pd > HC. However, lack of any significant correlation between the serum ACPA levels with the clinical Pd and RA parameters warrants further studies to investigate the causal link between RA and Pd for such a trend. Further studies involving more inflammatory biomarkers might be useful to establish the causal link between Pd in the development and progression of RA or vice versa.

Periodontitis is a highly prevalent multifactorial chronic inflammatory disease associated with a destructive host immune-inflammatory response to microbial dysbiosis. Current clinical diagnosis is reliant on measuring past periodontal tissue loss, with a lack of molecular biomarkers to accurately diagnose periodontitis activity in 'real-time'. Thus, discovery of new classes of diagnostic biomarkers is of critical importance in periodontology. Small extracellular vesicles (<200 nm in diameter; sEVs) from oral biofluids (saliva and gingival crevicular fluid-GCF) are lipid-encapsulated bilayered vesicles and have recently emerged as a potential source of biomarkers for periodontal disease (gingivitis and periodontitis), due to the cargo of protein, genetic material and lipids derived from their parent cells. There is limited information on the isolation and characterisation methods of saliva/GCF-sEVs or the characterisation of sEVs cargo as biomarkers for periodontitis. In this review, we detail the composition of sEVs and summarise their isolation and characterisation from saliva and GCF. The potential role of saliva and GCF-derived sEVs in periodontitis diagnosis is also explored. It is proposed that sEVs cargo, including protein, microRNA, message RNA and DNA methylation, are potential biomarkers for periodontitis with good diagnostic power (area under the curve-AUC > 0.9).

In this issue we publish an interesting article concerning prescribing of antibiotics by Australian dentists.1 The study covers the period 2005–2016 but is still of relevance to dentistry in 2021. The paper identifies excessive and sustained prescribing of moderate and broad-spectrum antibiotics by Australian dentists. This is contrary to national antimicrobial stewardship initiatives and guidelines and are of concern if Australian dentists, like their counterparts in the United Kingdom, have increased their antibiotic prescribing rates during the lockdowns imposed by COVID-19.2 Overprescribing antibiotics is concerning because facilitates increased antibiotic resistance. In this regard dentists have a significant role to play.3 Antibiotic resistance is a very significant concern for global health whereby delayed recovery from illnesses of bacterial origin and associated public health cost implications will emerge. Antibiotic resistance is exacerbated by excessive use of antibiotics. This is associated not only with prescription of antibiotics for humans but also their wide use in the food industry. The Walsh et al report noted that Australian dentists were responsible for an average of 24 prescriptions per dentists per year and this is considered high. For many years the dental profession has recognised its responsibility to prescribe antibiotics in a rational, professional and safe manner. Importantly the use of antibiotics for injudicious prophylaxis or “just in case” or due to patient requests undoubtedly leads to increased risk of emergence of antibiotic resistance. The these scenarios have increased during COVID-enforced restrictions. It is recognized that antibiotics are very often needed in “life or death” situations and resistance in such situations can be catastrophic. It is important to remember that for most oral infections very good outcomes can be achieved without resorting to the overuse of antibiotics. In many cases antibiotics should only be considered when there is clear evidence that the oral infection is not responding to conventional treatments aimed at removing or controlling the source of the infection. The Walsh et al paper notes that despite calls from bodies such as the FDI World Dental Federation and many national medical and dental associations for increased efforts in antimicrobial stewardship, this approach may have fallen on deaf ears within our profession. It is interesting to note that World Antimicrobial Awareness Week (AAW) is celebrated from 18–24 November each year. The overarching slogan for AWA 2021 is Antimicrobials: handle with care and the theme for 2021 is Spread Awareness, Stop Resistance for the food, animal, agriculture and human health sectors. By embracing events such as World Antimicrobial Awareness Week. By taking heed of publications in scientific journals we can optimise the rational use of antibiotics in compliance with global standards and this will surely have significant positive ramifications for all of us.

Extracellular vesicles (EVs) are membrane-bound lipid particles that are secreted by all cell types and function as cell-to-cell communicators through their cargos of protein, nucleic acid, lipids, and metabolites, which are derived from their parent cells. There is limited information on the isolation and the emerging therapeutic role of periodontal and dental pulp cell-derived small EVs (sEVs, <200 nm, or exosome). In this review, we discuss the biogenesis of three EV subtypes (sEVs, microvesicles and apoptotic bodies) and the emerging role of sEVs from periodontal ligament (stem) cells, gingival fibroblasts (or gingival mesenchymal stem cells) and dental pulp cells, and their therapeutic potential in vitro and in vivo. A review of the relevant methodology found that precipitation-based kits and ultracentrifugation are the two most common methods to isolate periodontal (dental pulp) cell sEVs. Periodontal (and pulp) cell sEVs range in size, from 40 nm to 2 μm, due to a lack of standardized isolation protocols. Nevertheless, our review found that these EVs possess anti-inflammatory, osteo/odontogenic, angiogenic and immunomodulatory functions in vitro and in vivo, via reported EV cargos of EV–miRNAs, EV–circRNAs, EV–mRNAs and EV–lncRNAs. This review highlights the considerable therapeutic potential of periodontal and dental pulp cell-derived sEVs in various regenerative applications.

OBJECTIVES:This study investigated changes induced by Porphyromonas gingivalis and on gastrointestinal histology and gut microbiome in a mouse model of experimental periodontitis. The effect of probiotic Lactobacillus rhamnosus GG (LGG) in altering these changes was also investigated.METHODS:IThirty-six mice were allocated into six groups. Experimental alveolar bone loss was induced by oral inoculation with P. gingivalis and F. nucleatum. LGG was orally inoculated or orally gavaged. Gastrointestinal tissue changes were assessed using histological analysis and immunohistochemistry. Caecal microbiome was analysed by sequencing 16S rRNA genes of caecal content.RESULTS:Inoculation with P. gingivalis and F. nucleatum induced inflammation throughout gastrointestinal tract (p less than 0.05), increased expression of IL-6 in ileum (p = 0.052) and altered composition of caecal microbiome (p less than 0.05) in experimental mice compared to controls. Mice treated with LGG had reduced tissue inflammation in duodenum (p = 0.044) and lowered levels of IL-6 in ileum (p = 0.048) when compared with disease. LGG therapy influenced gut microbiome changes.CONCLUSION:P. gingivalis and F. nucleatum inoculation induced significant changes in intestinal inflammation and caecal microbiome. Oral gavage with LGG exerted a protective effect against intestinal inflammation and limited gut microbiome changes associated with P. gingivalis and F. nucleatum.

The nexus between periodontal inflammation and the polymicrobial biofilm in the gingival sulcus is critical to understanding the pathobiology of periodontitis. Both play a major role in the etiology and pathogenesis of periodontal diseases and each reinforces the other. However, this nexus is also at the center of a significant conundrum for periodontology. For all mucosal polymicrobial biofilms, the most confounding issue is the paradoxical relationship between inflammation, infection and disease. Despite significant advances made in both periodontal microbiology and periodontal pathobiology, the issue of which comes first, the inflammatory response or the change to a dysbiotic subgingival microbiota, is still debated. In this paper, we present a model for the pathogenesis of periodontitis based on the central role of inflammation and how this modulates the polymicrobial biofilm within the context of the continuum of health, gingivitis and periodontitis. We propose a new model termed “Inflammation-Mediated Polymicrobial-Emergence and Dysbiotic-Exacerbation” (IMPEDE), which is designed to integrate into and complement the 2017 World Workshop Classification of Periodontitis.

COVID-19. It is impossible to get away from this virus as it pervades all aspects of our lives. I am writing this Editorial on April 20, 2020 and by the time this is published in June 2020 I have no doubt that it will be out of date. I have had so many requests for papers on COVID-19 to be published in the Australian Dental Journal it is amazing – and everyone wants them fast tracked. At the moment I am taking a very cautious response and I am waiting on publishing any articles on this subject until the overall situation becomes clearer and well-founded evidence has been accumulated. It is obvious that the science and information about COVID-19 is evolving very rapidly. Did you know that as of today (April 20, 2020) PubMed lists 5284 papers, and Web of Science (WOS) lists 3473 papers, with ‘COVID-19’ in their title? All of these have been published this year. Yesterday, the figures were PubMed: 4882 and WOS: 3295!! The curve has not flattened for publications!!!!! This creates huge problems because what is current today might well be out of date tomorrow, or worse, wrong in a few months time. Thus, everything we know at the moment is extremely time sensitive and should be viewed accordingly. The quest for opportunistic rapid publication of hastily carried out research or general opinion pieces within the scientific community (including oral health) is risky. Clearly there has been little time for well planned, ethics-approved and properly controlled clinical studies to be carried out (at the time of writing) and so on many occasions we are forced to read observational studies. The problem is that observational studies are merely observational and opinion pieces are even worse as they can be based on very low evidence-based material. Observational studies are very limited because they report on findings of individuals in their everyday settings where there is very limited control over variable factors. Thus an individual becomes a ‘subject’ not controlled by the investigator, but controlled by specific features such as age, sex, disease status, etc., that are noted and recorded by the research team. Through observational studies, the investigator can study how individuals interact and assess behavior or relationships based on specific outcomes that are more reliable than self-reported metrics. Observational studies usually report on the outcome frequencies in terms of relative risks, rate ratios, hazard ratios and odds ratios. It is very important to understand that observational studies can identify associations; they cannot demonstrate a cause and effect relationship. This can only be done by carefully planned experimental studies such as randomized clinical trials. In the context of COVID-19 this means we need more time to move from observational studies to clinical trials, intervention studies and development of properly and well thought out intervention programmes. It is my sincere hope we never see a paper based on observation only that COVID-19 and oral health are associated and thus make a case for periodontal disease being related to COVID-19 just because COVID-19 patients might have more periodontal disease or elevated levels of P gingivalis. Notwithstanding the above there are several sources of very good information based on current and evolving evidence. For general information, the USA National Institutes for Health offer very comprehensive scientifically based information at: https://www.nih.gov/health-information/coronavirus For more specific dental related information, the International Association for Dental research offers excellent information at: https://www.iadr.org/COVID-19?utm_source=Real%20Magnet&utm_medium=email&utm_campaign=153212155 On another note, but in keeping with the theme of this Editorial of ‘Get the Facts First’, in my last editorial1 I alluded to the development and marketing of continuing professional education courses (CPD) that delve into trendy aspects of dentistry. I highlighted two such areas as being the business of dentistry and implants. In the case of implants, a course that provides advanced education and training in implantology was alluded to with regards to currently marketed implant CPD courses. To follow this theme of implant education it is important to note that there are two significant problems with implant education in dentistry in Australia. The first is that implant CPD courses are not very well regulated. Secondly, there is no formal specialty in Australia in ‘implantology’ to delineate what constitutes the outcome of high level and advanced training in implantology. One of the reasons for the lack of a specialist nomenclature of ‘implantologist’ is because the field of oral implantology is highly sophisticated and multidisciplinary. Accordingly, in order to be an ‘implantologist’ means that one must be an accomplished surgeon, prosthodontist and possibly periodontist. This is by no means a simple undertaking and to achieve this should take many years of full time advanced clinical training. Thus, back to the field of short-term CPD courses in implantology offering a one stop shop for incorporation of implants into everyday dental practice. This is a concerning trend in dentistry today involving individual oral health professionals, the commercial sector and even Universities. While it is true that there are many well-intentioned courses for individuals to choose from, before signing up one must decide if the course on offer provides an advanced level of training to allow one to become truly proficient for entry into, or participation in, the field of oral implantology. The course I alluded to in my previous Editorial1 is indeed run by qualified dentists who have experience in training and education in oral implantology. The course material appears to be comprehensive and the learning experience on offer has been successfully implemented for many years. It is presented as a comprehensive academic programme, that is delivered thorough a template that is monitored through graded outcomes. However, while such courses might be what individuals think they are looking for the real issue is whether such courses equip individuals sufficiently for the minefield of what we understand as the field of oral implantology. A very important point to be made here is that I am not saying such courses should not be held. In fact it is far from this. Dentists need to be able to get information, and CPD courses are a good starting point, but they are not the end of the story. Fortunately quality courses, and I am pleased to report that the course alluded to in this and a previous Editorial, recognize this and highlight the need for ongoing education, training and development to not only master the placement and restoration of implants, but also manage their (unfortunately not uncommon) complications. In my experience the success of implants is directly proportional to the level of training and unfortunately failure of implants is indirectly proportional to the level of training. Trendydontics in continuing professional development should stop, but in reality it is a boom business. I wish to place on record that this, and previous editorials, have not specifically identified or targeted any single individual or individuals to illustrate my wider point of view and that the Editorials I have written have been intended to be cautionary tales for ‘buyer beware’. Thus, whether it is COVID-19 or professional CPD, the message is clear, get the facts first and not the expert opinion before embarking on any course of clinical action.

While a number of reviews have been published in recent years covering all aspects of the relationship between rheumatoid arthritis and periodontitis, this review considers only the very most recent advances in the field by reporting on studies published from January 2018 to August 2019. The number of published studies that have investigated this relationship has increased dramatically in recent years. These studies have established a number of important biochemical, cellular, genetic and microbiological processes that link these two conditions at the clinical level. There is now very good evidence to support a relationship between RA and periodontitis. It is clear that very good progress is being made but there is need for continuing investigations to better identify the defining mechanism(s) that drive this intriguing relationship.