In Vitro Toxicity Evaluation of Carrageenan on Cells and Tissues of the Oral Cavity.

Carrageenan is a highly potent anti-human papillomavirus (HPV) agent with the potential for formulation as a mouthwash against oral HPV infection. However, its toxic effect on tissues of the oral cavity is currently unknown. This study aims to evaluate the safety of carrageenan on human cells and tissues of the oral cavity. Human salivary gland cells and reconstructed human oral epithelium (RHOE) were used for this in vitro study. The cells were subjected to 0.005-100 µg/mL of carrageenan for 4, 12, and 24 h in quadruplicate. RHOE were exposed to 100 µg/mL of carrageenan for 24 h in triplicate and stained with hematoxylin/eosin for histological analyses. All experiments had saline and 1% sodium dodecyl sulphate (SDS) as negative and positive controls, respectively. Carrageenan tissue toxicity was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to quantify cell viability. Tissue toxicity was further evaluated histologically by an oral pathologist to assess morphological changes. Our data showed that carrageenan did not significantly decrease cell and tissue viability when compared to the positive control. The histological evaluation of the RHOE also showed no loss of viability of the carrageenan-treated sample compared to untreated tissue. In contrast, 1% SDS-treated RHOE showed extensive tissue destruction. Our experiments suggest that carrageenan is safe for use in the oral cavity.

Association between periodontitis and severity of COVID-19 infection: A case-control study.

AIM: COVID-19 is associated with an exacerbated inflammatory response that can result in fatal outcomes. Systemic inflammation is also a main characteristic of periodontitis. Therefore, we investigated the association of periodontitis with COVID-19 complications. MATERIALS AND METHODS: A case-control study was performed using the national electronic health records of the State of Qatar between February and July 2020. Cases were defined as patients who suffered COVID-19 complications (death, ICU admissions or assisted ventilation), and controls were COVID-19 patients discharged without major complications. Periodontal conditions were assessed using dental radiographs from the same database. Associations between periodontitis and COVID 19 complications were analysed using logistic regression models adjusted for demographic, medical and behaviour factors. RESULTS: In total, 568 patients were included. After adjusting for potential confounders, periodontitis was associated with COVID-19 complication including death (OR = 8.81, 95% CI 1.00-77.7), ICU admission (OR = 3.54, 95% CI 1.39-9.05) and need for assisted ventilation (OR = 4.57, 95% CI 1.19-17.4). Similarly, blood levels of white blood cells, D-dimer and C Reactive Protein were significantly higher in COVID-19 patients with periodontitis. CONCLUSION: Periodontitis was associated with higher risk of ICU admission, need for assisted ventilation and death of COVID-19 patients, and with increased blood levels of biomarkers linked to worse disease outcomes.

Oscillating-rotating electric toothbrushes may have a better effect on gingivitis and plaque control than sonic and manual toothbrushes in adults.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Grender J, Adam R, Zou Y. The effects of oscillating-rotating electric toothbrushes on plaque and gingival health: A meta-analysis. Am J Dent. 2020 Feb;33(1):3-11. PMID: 32,056,408. SOURCE OF FUNDING: Industry (Procter & Gamble Company). TYPE OF STUDY/DESIGN: Systematic review with meta-analysis of data.

Stressed-Out Oral Immunity: A Gateway From Socioeconomic Adversity to Periodontal Disease.

OBJECTIVE: It has been suggested that adverse socioeconomic conditions "get under the skin" by eliciting a stress response that can trigger periodontal inflammation. We aimed to a) estimate the extent to which socioeconomic position (SEP) is associated with periodontal disease (PD) and proinflammatory oral immunity, and b) determine the contribution of psychosocial stress and stress hormones to these relationships. METHODS: In this cross-sectional study (n = 102), participants (20-59 years old) completed financial and perceived stress questionnaires and underwent full-mouth periodontal examinations. SEP was characterized by annual household income and educational attainment. Cortisol, a biological correlate of chronic stress, was assessed in hair samples. Oral immunity was characterized by assessing oral inflammatory load and proinflammatory oral neutrophil function. Blockwise Poisson and logistic regression models were applied. RESULTS: Compared with lower SEP, individuals in the middle- and higher-income categories had a significantly lower probability of PD (incidence rate ratio [IRR] = 0.5 [confidence interval {CI} = 0.3-0.7] and IRR = 0.4 [95% CI = 0.2-0.7]) and oral inflammatory load (IRR = 0.6 [95% CI = 0.3-0.8] and IRR = 0.5 [95% CI = 0.3-0.7]) and were less likely to have a proinflammatory oral immune function (odds ratio [OR] = 0.1 [95% CI = 0.0-0.7] and OR = 0.1 [95% CI = 0.0-0.9]). PD and oral immune parameters were significantly associated with financial stress and cortisol. Adjusting for financial stress and cortisol partially attenuated the socioeconomic differences in PD to IRR = 0.7 (95% CI = 0.5-0.8) and IRR = 0.6 (95% CI = 0.5-0.7) for the middle- and higher-income categories, respectively. Similar results were observed for proinflammatory immunity (OR = 0.2 [95% CI = 0.0-1.8] and OR = 0.3 [95% CI = 0.0-2.3]). CONCLUSION: These findings suggest that psychosocial stress may contribute to a proinflammatory immunity that is implicated in PD pathobiology and provide insight into social-to-biological processes in oral health.

Maternal Mental Disorders before Delivery and the Risk of Dental Caries in Children.

Prevention of childhood caries is an ongoing public health challenge, but the possibility of an association with maternal mental disorders has received limited attention. We estimated the extent to which maternal mental disorders are associated with an increased risk of hospitalization due to dental caries. We conducted a longitudinal cohort study of 790,758 infants born in Quebec, Canada between 2006 and 2016, with follow-up extending to 2018. We identified women with mental disorders before or during pregnancy and computed the incidence of dental caries in their children. We estimated HR and 95% CI for the association of maternal mental disorders with the risk of dental caries, adjusted for personal characteristics. Infants of women with mental disorders before or during pregnancy had a higher incidence of dental caries compared to children of women with no mental disorder (56.1 vs. 27.2 per 10,000 person-years). Maternal stress and anxiety disorders (HR = 1.73; 95% CI 1.60-1.86), depression (HR = 1.81; 95% CI 1.60-2.03), schizophrenia and delusional disorders (HR = 1.69; 95% CI 1.29-2.22), and personality disorders (HR = 1.89; 95% CI 1.70-2.11) were associated with the risk of dental caries. The associations were present throughout childhood, including after 7 years (HR = 1.65; 95% CI 1.38-1.96). Maternal mental disorders were associated with caries of the enamel, dentin, and cementum and caries that reached the dental pulp. Maternal mental disorders before or during pregnancy, especially stress and anxiety, depression, schizophrenia, and personality disorders, are associated with the risk of childhood caries. Women with a history of mental disorders may benefit from enhanced strategies for prevention of dental caries in their children.

Oral Health Implications of Cannabis Smoking: A Rapid Evidence Review.

OBJECTIVES: To summarize evidence relating cannabis smoking and oral disease and highlight any potential influence of cannabis smoking on clinical care and dental public health. METHODS: Using rapid evidence review, a librarian facilitated a systematic search of 5 electronic databases in August and September 2018 and updated it in March 2019, yielding 581 publications. Two researchers screened the documents using pre-established inclusion criteria: article was based on primary or secondary data; cannabis smoking was an exposure; at least 1 cannabis-related oral health outcome was reported; participants were humans; and the article was available in English or French. Data from retained articles were analyzed for themes without meta-analysis. RESULTS: We synthesized and summarized 23 articles in 2 broad categories: cannabis and oral disease; and cannabis, clinical care and dental public health. Current evidence shows that smoking cannabis is harmful to the health of the periodontium. The association between smoking cannabis and other oral disease (dental caries, soft tissue lesions and oral cancers) is sparse and inconsistent, although studies suggest that cannabis smoking is an underlying risk factor. Cannabis smoking can lead to an altered mental state that can delay dental treatment of the patient. Further, interactions between smoked cannabis and adrenaline-containing local anesthetics can result in life-threatening consequences. CONCLUSIONS: Cannabis smoking is harmful to the periodontium. Further research is needed to fully understand how cannabis smoking affects oral disease and how dental professionals should integrate this knowledge into clinical care and dental public health.

Socioeconomic inequalities in oral health-related quality of life in adolescents: a cohort study.

PURPOSE: Socioeconomic inequalities are recognized as a major problem with people in low socioeconomic groups having worse subjective oral health outcomes, including oral health-related quality of life (OHRQoL). However, only a few longitudinal studies assessed the impact of contextual and individual socioeconomic determinants in adolescents' OHRQoL. We estimate the impact of socioeconomic inequalities on adolescents' OHRQoL over a 2-year period. METHODS: This study followed up a random sample of 1134 12-year-old schoolchildren for 2 years in Brazil. OHRQoL was assessed by the Brazilian version of the Child Perceptions Questionnaire for 11- to 14-year-old Children (CPQ11-14) at baseline and follow-up. Participants were clinically examined for dental caries, gingival bleeding, and malocclusion. The schoolchildren's parents answered a questionnaire regarding socioeconomic status, social capital, and adolescents' use of dental service. Socioeconomic contextual variables were collected from official city publications. Multilevel linear regression models fitted the associations between socioeconomic factors and overall CPQ11-14 scores over time. RESULTS: A total of 747, 14-year-old adolescents were reassessed for OHRQoL (follow-up rate of 66%). Adolescents with lower mean income school's neighborhood (P < 0.05), household income (P < 0.05), and maternal schooling (P < 0.05) had higher overall CPQ11-14 scores. Female sex, attending a dentist by toothache, dental caries, and malocclusion were also associated with higher overall CPQ11-14 scores. CONCLUSIONS: Adolescents from low socioeconomic background reported worse OHRQoL at 2-year follow-up compared to those from high socioeconomic background. Actions toward health inequalities need to address socioeconomic factors in adolescence.

A Comprehensive Clinical Care Pathway for Microvascular Maxillofacial Reconstructive Surgery.

PURPOSE: Clinical care pathways (CCPs) for major surgical procedures are less developed. We describe the development of a comprehensive microvascular maxillofacial reconstruction CCP and evaluate the impact. MATERIALS AND METHODS: Our team developed a comprehensive CCP for patients undergoing microvascular free flap reconstruction for benign or malignant tumors. Patient data before (n = 48) and after (n = 47) implementation of the CCP were used to evaluate the impact. Bayesian negative binomial and logistic regression analyses were used to estimate the associations between the CCP and clinical outcomes (length of stay [LOS], readmission to the operating room, and readmission within 3 months of discharge). RESULTS: The average total hospital LOS was high in the pre-CCP group (16.9 days) compared with the post-CCP group (9.8 days). Being in the post-CCP group reduced the LOS in the intensive care unit and surgical ward and reduced the risk of readmission to the operating room. CONCLUSION: Our results underscore the importance of standardized evidence-based patient care through CCPs for complex patient populations.

Inconclusive Evidence Exists Regarding the Association Between Dental Caries and BMI in Children Under Age 18 Years.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Association between dental caries and BMI in children: a systematic review and meta-analysis. Chen D, Zhi Q, Zhou Y, Tao Y, Wu L, Lin H.Caries Res 2018;52:230-45. SOURCE OF FUNDING: None declared. TYPE OF STUDY/DESIGN: Systematic review with meta-analysis.

Periodontal diseases and risk of oral cancer in Southern India: Results from the HeNCe Life study.

Some studies suggest that periodontal diseases increase the risk of oral cancer, but contradictory results also exist. Inadequate control of confounders, including life course exposures, may have influenced prior findings. We estimate the extent to which high levels of periodontal diseases, measured by gingival inflammation and recession, are associated with oral cancer risk using a comprehensive subset of potential confounders and applying a stringent adjustment approach. In a hospital-based case-control study, incident oral cancer cases (N = 350) were recruited from two major referral hospitals in Kerala, South India, from 2008 to 2012. Controls (N = 371), frequency-matched by age and sex, were recruited from clinics at the same hospitals. Structured interviews collected information on several domains of exposure via a detailed life course questionnaire. Periodontal diseases, as measured by gingival inflammation and gingival recession, were evaluated visually by qualified dentists following a detailed protocol. The relationship between periodontal diseases and oral cancer risk was assessed by unconditional logistic regression using a stringent empirical selection of potential confounders corresponding to a 1% change-in-estimates. Generalized gingival recession was significantly associated with oral cancer risk (Odds Ratio = 1.83, 95% Confidence Interval: 1.10-3.04). No significant association was observed between gingival inflammation and oral cancer. Our findings support the hypothesis that high levels of periodontal diseases increase the risk of oral cancer.

No role for human papillomavirus infection in oral cancers in a region in southern India.

Oral cancer is a major public health issue in India with ∼ 77,000 new cases and 52,000 deaths yearly. Paan chewing, tobacco and alcohol use are strong risk factors for this cancer in India. Human papillomaviruses (HPVs) are also related to a subset of head and neck cancers (HNCs). We examined the association between oral HPV and oral cancer in a sample of Indian subjects participating in a hospital-based case-control study. We recruited incident oral cancer cases (N = 350) and controls frequency-matched by age and sex (N = 371) from two main referral hospitals in Kerala, South India. Sociodemographic and behavioral data were collected by interviews. Epithelial cells were sampled using Oral CDx® brushes from the oral cancer site and the normal mucosa. Detection and genotyping of 36 HPV genotypes were done using a polymerase chain reaction protocol. Data collection procedures were performed by qualified dentists via a detailed protocol with strict quality control, including independent HPV testing in India and Canada. HPV DNA was detected in none of the cases or controls. Associations between oral cancer and risk factors usually associated with HPV infection, such as oral sex and number of lifetime sexual partners, were examined by logistic regression and were not associated with oral cancer. Lack of a role for HPV infection in this study may reflect cultural or religious characteristics specific to this region in India that are not conducive to oral HPV transmission. A nationwide representative prevalence study is needed to investigate HPV prevalence variability among Indian regions.

Access to Dental Services for People Using a Wheelchair.

OBJECTIVES: We investigated the perspectives of people using a wheelchair and their difficulties in accessing dental services. METHODS: Our participatory research was on the basis of a partnership between people using a wheelchair, dental professionals, and academic researchers. Partners were involved in a committee that provided advice at all stages of the project. Our team adopted a qualitative descriptive design. Between October 2011 and October 2012 we conducted semistructured individual interviews with 13 adults who lived in Montreal, Québec, Canada, and used a wheelchair full time. We audio-recorded and transcribed verbatim interviews, and we interpreted data using an inductive thematic analysis. RESULTS: Oral health is of heightened importance to this group of people, who tend to use their mouth as a "third hand." We identified successive challenges in accessing dental services: finding a dentist and being accepted, organizing transportation, entering the building and circulating inside, interacting with the dental staff, transferring and overcoming discomfort on the dental chair, and paying for the treatments. CONCLUSIONS: Governments, dental professional bodies, dental schools, and researchers should work with groups representing wheelchair users to improve access to dental services.

Circulating undercarboxylated osteocalcin and gingival crevicular fluid tumour necrosis factor-α in children.

BACKGROUND: Osteocalcin, a protein secreted by osteoblasts during bone formation, is negatively associated with adult periodontal disease. Little is known about this association in children. AIM: To examine the extent to which plasma undercarboxylated osteocalcin (ucOC) is associated with gingival crevicular fluid tumour necrosis factor-alpha (GCF TNF-α) - a potential marker of gingival inflammation - in children. METHODS: We used data from the Quebec Adipose and Lifestyle InvesTigation in Youth cohort, an ongoing longitudinal study on the natural history of obesity among Caucasian children with a family history of obesity in Quebec, Canada. This cross-sectional analysis from the baseline visit includes 120 children aged 8-10 years. Plasma ucOC and GCF TNF-α levels were determined by enzyme-linked immunosorbent assay. Linear regression analyses, adjusting for age, gender, family income, sexual maturity stage, daily physical activity, obesity, and fasting glucose were conducted, with TNF-α level as the dependent variable. RESULTS: A 1-ng/ml increase in ucOC was associated with a 0.96% decrease (95% confidence interval (CI): -1.69, -0.23) in GCF TNF-α level. CONCLUSION: A negative association between a marker of bone formation and a marker of gingival inflammation was observed as early as childhood among Caucasian children with a family history of obesity.

Metabolic syndrome and gingival inflammation in Caucasian children with a family history of obesity.

AIM: To investigate whether metabolic syndrome (MetS) and its components are associated with gingival inflammation in children. MATERIALS AND METHODS: This is a cross-sectional analysis from the baseline visit of the QUebec Adipose and Lifestyle InvesTigation in Youth cohort, an ongoing longitudinal study investigating the natural history of obesity in children of Quebec, Canada. The analytic sample includes 448 children aged 8-10 years, 39% of whom were overweight or obese. MetS was defined according to the International Diabetes Federation recommendations. Gingival inflammation was defined by the level of gingival crevicular fluid (GCF) tumour necrosis factor alpha (TNF-α) and the extent of gingival bleeding. Sex-specific linear regression analyses estimated the associations between MetS and gingival inflammation, adjusting for potential confounders. RESULTS: Twenty-five children had MetS. Boys with MetS compared to those without, had a 49.5% (p-value = 0.001) higher GCF TNF-α level and 13.7% (p-value = 0.033) more sites with gingival bleeding. Moreover, for three of the five components of MetS - waist circumference, fasting plasma triglycerides, systolic blood pressure - an increase was associated with increased GCF TNF-α level in boys. No such findings were seen in girls. CONCLUSION: An association between MetS and gingival inflammation was observed as early as in childhood, and may differ by sex.

Tumor necrosis factor- α and interleukin-6: potential interorgan inflammatory mediators contributing to destructive periodontal disease in obesity or metabolic syndrome.

Obesity has become a worldwide health burden in the last two decades. Obesity has been associated with increased comorbidities, such as coronary artery disease, diabetes, and destructive periodontal disease. Obesity is also part of a group of risk factors occurring together in an individual, which is referred to as metabolic syndrome. Clinical studies have shown higher risk for destructive periodontal disease in obesity and metabolic syndrome. However, the role of obesity and metabolic syndrome in the onset and development of destructive periodontal disease has not yet been fully understood. In this review, we discuss a working model, which focuses on interorgan inflammation as a common etiological factor for destructive periodontal disease associated with obesity and metabolic syndrome. Specifically, we suggest that elevated levels of tumor necrosis factor- α (TNF- α ) or interleukin 6 (IL-6)--both adipokines and known risk factors for destructive periodontal disease--in obesity and metabolic syndrome contribute to the onset and development of destructive periodontal disease. The connections between destructive periodontal disease and systemic conditions, such as obesity or metabolic syndrome, are complex and potentially multidirectional. This review largely focuses on TNF- α and IL-6, inflammatory mediators, as potential common risk factors and does not exclude other biological mechanisms.

Protocol: carrageenan for the prevention of oral HPV infection - a feasibility randomised clinical trial.

INTRODUCTION: Head and neck cancers (HNCs) are a significant health burden worldwide. Oral human papillomavirus (HPV) infection is a major risk factor for HNCs. Unfortunately, currently available prophylactic vaccines have limited coverage and potential for HPV type replacement. Carrageenan, a natural product extracted from marine red algae, has demonstrated potency as an HPV inhibitor and could offer a potential alternative to prevent HPV-related diseases, including oral HPV infection. However, there is a lack of clinical studies on the effect of carrageenan on oral HPV infections. As a first step to address this gap, we propose a randomised controlled trial (RCT) to evaluate the feasibility of conducting a larger multicentric RCT to investigate the effect of a carrageenan mouthwash on oral HPV infection. METHODS AND ANALYSIS: We will conduct a placebo-controlled triple-blinded feasibility RCT with two parallel arms, each arm consisting of 20 participants. Participants will complete a single in-person visit at baseline and conduct biweekly follow-ups from home by completing a web-based questionnaire and sending saliva self-samples via mail. During the 6-month period trial, participants will gargle with the mouthwash morning and night, and around sexual activities. The study will evaluate several factors including recruitment and retention rates, the feasibility of data collection procedures, compliance with study procedures, acceptability of RCT procedures and intervention and safety data on carrageenan use in the oral cavity. We will estimate the standard deviation of outcome measures, including time to the incidence of oral HPV infection and time to clearance of prevalent oral HPV infection. The trial primary outcome is whether to proceed to a definitive trial based on prespecified progression criteria. ETHICS AND DISSEMINATION: The protocol was approved by the McGill University institutional review board. Study results will be presented at scientific conferences and published in academic journals. TRIAL REGISTRATION NUMBER: NCT05746988.

How to use mixed methods in oral health research.

Wicked problems exist in the realm of oral health research. Due to their inherent complexity, using qualitative or quantitative methods alone may not be adequate for resolving them. Mixed methods approaches combine qualitative and quantitative methods, and thus, can provide a powerful tool for understanding and solving complex problems in dental public health. However, using mixed methods does not come without its challenges. This commentary outlines four main tips for researchers to consider when applying mixed methods to their research projects.

Chronotherapy in dentistry: A scoping review.

The circadian clock modulates almost all vital aspects of our physiology and metabolism, including processes relevant to dentistry, such as healing, inflammation and nociception. Chronotherapy is an emerging field aiming to improve therapeutic efficacy and decrease adverse effects on health outcomes. This scoping review aimed to systematically map the evidence underpinning chronotherapy in dentistry and to identify gaps in knowledge. We conducted a systematic scoping search using four databases (Medline, Scopus, CINAHL and Embase). We identified 3908 target articles screened by two blinded reviewers, and only original animal and human studies investigating the chronotherapeutic use of drugs or interventions in dentistry were included. Of the 24 studies included, 19 were human studies and five were animal studies. Chrono-radiotherapy and chrono-chemotherapy reduced treatment side effects and improved therapeutic response, leading to higher survival rates in cancer patients. Animal studies reported that tooth movement and periodontal tissue response to orthodontic forces follow a diurnal rhythm that might influence bone metabolism. Profound and prolonged local anesthesia could be achieved when injected in the evening. Although the overall quality of the included studies was low, chronotherapy applications in dentistry seem to have favourable outcomes, especially in head and neck cancer treatments.

Interaction of HPV16 and Cutaneous HPV in Head and Neck Cancer.

OBJECTIVES: Human papillomavirus 16 (HPV16) is an established risk factor for Head and Neck Cancer (HNC). Recent reports have shown that genotypes from the beta (ß) and gamma (γ) genera, also known as cutaneous HPV, can be found in the oral cavity, but their role is largely unidentified. We investigated the interaction between oral HPV16 and cutaneous HPV in HNC. METHODS: We use data on incident HNC cases (n = 384) and frequency-matched hospital-based controls (n = 423) from the HeNCe Life study in Montreal, Canada. Participants were tested for alpha HPV and cutaneous genera using oral mouth rinse and brush samples. We used unconditional logistic regression to obtain adjusted odds ratios (aOR) and 95% confidence interval (CI) as a measure of the effect between HPV and HNC and assessed the interaction between HPV genotypes on the multiplicative and additive scales. RESULTS: Prevalence of HPV infection was higher among cases (73%) than controls (63.4%), with cases more likely to be coinfected with more than a single genotype, 52.9% vs. 43.5%, respectively. Infection with HPV16 alone had a strong effect on HNC risk aOR = 18.2 [6.2, 53.2], while infection with any cutaneous HPV, but not HPV16, appeared to have the opposite effect aOR = 0.8 [0.6, 1.1]. The observed effect of joint exposure to HPV16 and any cutaneous HPV (aOR = 20.4 [8.3, 50.1]) was stronger than the expected effect based on an assumption of independent exposures but was measured with considerable imprecision. While the point estimate suggests a positive interaction between HPV16 and cutaneous HPV, results were imprecise with relative excess risk due to interaction (RERI) = 2.4 [-23.3, 28.2]. CONCLUSION: There could be biologic interaction between HPV16 and genotypes from cutaneous genera, which warrants further investigation. Although cutaneous HPVs are not usually found in tumor tissues, they are cofactors that could interact with HPV16 in the oral cavity and thus strengthen the latter's carcinogenic effect.