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      Oral health’s inextricable connection to systemic health: Special populations bring to bear multimodal relationships and factors connecting periodontal disease to systemic diseases and conditions

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          Abstract

          The landscape in dentistry is changing as emerging studies continue to reveal that periodontal health impacts systemic health, and vice versa. Population studies, clinical studies, and in vitro animal studies underscore the critical importance of oral health to systemic health. These inextricable relationships come to the forefront as oral diseases, such as periodontal disease, take root. Special populations bring to bear the multimodal relationships between oral and systemic health. Specifically, periodontal disease has been associated with diabetes, metabolic syndrome, obesity, eating disorders, liver disease, cardiovascular disease, Alzheimer disease, rheumatoid arthritis, adverse pregnancy outcomes, and cancer. Although bidirectional relationships are recognized, the potential for multiple comorbidities, relationships, and connections (multimodal relationships) also exists. Proposed mechanisms that mediate this connection between oral and systemic health include predisposing and precipitating factors, such as genetic factors (gene polymorphisms), environmental factors (stress, habits—such as smoking and high‐fat diets/consumption of highly processed foods), medications, microbial dysbiosis and bacteremias/viremias/microbemias, and an altered host immune response. Thus, in a susceptible host, these predisposing and precipitating factors trigger the onset of periodontal disease and systemic disease/conditions. Further, high‐throughput sequencing technologies are shedding light on the dark matter that comprises the oral microbiome. This has resulted in better characterization of the oral microbial dysbiosis, including putative bacterial periodontopathogens and shifts in oral virome composition during disease. Multiple laboratory and clinical studies have illustrated that both eukaryotic and prokaryotic viruses within subgingival plaque and periodontal tissues affect periodontal inflammation, putative periodontopathogens, and the host immune response. Although the association between herpesviruses and periodontitis and the degree to which these viruses directly aggravate periodontal tissue damage remain unclear, the benefits to periodontal health found from prolonged administration of antivirals in immunocompromised or immunodeficient individuals demonstrates that specific populations are possibly more susceptible to viral periodontopathogens. Thus, it may be important to further examine the implications of viral pathogen involvement in periodontitis and perhaps it is time to embrace the viral dark matter within the periodontal environment to fully comprehend the pathogenesis and systemic implications of periodontitis. Emerging data from the coronavirus disease 2019 pandemic further underscores the inextricable connection between oral and systemic health, with high levels of the severe acute respiratory syndrome coronavirus 2 angiotensin‐converting enzyme 2 receptor noted on oral tissues (tongue) and an allostatic load or overload paradigm of chronic stress likely contributing to rapid breakdown of oral/dental, periodontal, and peri‐implant tissues. These associations exist within a framework of viremias/bacteremias/microbemias, systemic inflammation, and/or disturbances of the immune system in a susceptible host. A thorough review of systemic and oral diseases and conditions and their mechanistic, predisposing, and precipitating factors are paramount to better addressing the oral and systemic health and needs of our patients.

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          Most cited references29

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          High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa

          It has been reported that ACE2 is the main host cell receptor of 2019-nCoV and plays a crucial role in the entry of virus into the cell to cause the final infection. To investigate the potential route of 2019-nCov infection on the mucosa of oral cavity, bulk RNA-seq profiles from two public databases including The Cancer Genome Atlas (TCGA) and Functional Annotation of The Mammalian Genome Cap Analysis of Gene Expression (FANTOM5 CAGE) dataset were collected. RNA-seq profiling data of 13 organ types with para-carcinoma normal tissues from TCGA and 14 organ types with normal tissues from FANTOM5 CAGE were analyzed in order to explore and validate the expression of ACE2 on the mucosa of oral cavity. Further, single-cell transcriptomes from an independent data generated in-house were used to identify and confirm the ACE2-expressing cell composition and proportion in oral cavity. The results demonstrated that the ACE2 expressed on the mucosa of oral cavity. Interestingly, this receptor was highly enriched in epithelial cells of tongue. Preliminarily, those findings have explained the basic mechanism that the oral cavity is a potentially high risk for 2019-nCoV infectious susceptibility and provided a piece of evidence for the future prevention strategy in dental clinical practice as well as daily life.
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            Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies

            Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is the pathogen that causes coronavirus disease 2019 (COVID-19). As of 25 May 2020, the outbreak of COVID-19 has caused 347,192 deaths around the world. The current evidence showed that severely ill patients tend to have a high concentration of pro-inflammatory cytokines, such as interleukin (IL)-6, compared to those who are moderately ill. The high level of cytokines also indicates a poor prognosis in COVID-19. Besides, excessive infiltration of pro-inflammatory cells, mainly involving macrophages and T-helper 17 cells, has been found in lung tissues of patients with COVID-19 by postmortem examination. Recently, increasing studies indicate that the “cytokine storm” may contribute to the mortality of COVID-19. Here, we summarize the clinical and pathologic features of the cytokine storm in COVID-19. Our review shows that SARS-Cov-2 selectively induces a high level of IL-6 and results in the exhaustion of lymphocytes. The current evidence indicates that tocilizumab, an IL-6 inhibitor, is relatively effective and safe. Besides, corticosteroids, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, intravenous immunoglobulin, and antimalarial agents could be potentially useful and reliable approaches to counteract cytokine storm in COVID-19 patients.
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              Musculoskeletal Consequences of COVID-19

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                Author and article information

                Contributors
                yvonne.kapila@ucsf.edu
                Journal
                Periodontol 2000
                Periodontol 2000
                10.1111/(ISSN)1600-0757
                PRD
                Periodontology 2000
                John Wiley and Sons Inc. (Hoboken )
                0906-6713
                1600-0757
                31 August 2021
                October 2021
                : 87
                : 1 ( doiID: 10.1111/prd.v87.1 )
                : 11-16
                Affiliations
                [ 1 ] Department of Orofacial Sciences School of Dentistry University of California San Francisco San Francisco California USA
                Author notes
                [*] [* ] Correspondence

                Yvonne L. Kapila, Department of Orofacial Sciences, School of Dentistry, University of California San Francisco, San Francisco, CA, USA.

                Email: yvonne.kapila@ 123456ucsf.edu

                Article
                PRD12398
                10.1111/prd.12398
                8457130
                34463994
                3c41a635-1b1c-414b-8144-e72a6c37fc92
                © 2021 The Authors. Periodontology 2000 published by John Wiley & Sons Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                Page count
                Figures: 2, Tables: 0, Pages: 6, Words: 4487
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                October 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.7 mode:remove_FC converted:22.09.2021

                microbemias,oral health,periodontal disease,susceptible host,systemic disease,systemic inflammation

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