Oral conditions are associated with salt taste disability among American adults.

AIM: To explore the association between oral conditions and their interaction with salt taste disability among American adults. METHODS: Data from the 2013-2014 NHANES cycle were used (n = 2373). The exposures were periodontitis, defined by the 2017 EFP-AAP classification, dental caries, missing teeth, and edentulism, as per the DMF-T index, and xerostomia. The outcome was salt taste disability, objectively assessed. Covariates included sex, age, educational level, poverty index, obesity, diabetes, smoking, alcohol consumption, and medications related to mouth dryness. Weighted multivariable logistic regression modeling was used to evaluate the relationship between oral conditions and their interaction and salt taste disability. RESULTS: Participants who reported xerostomia were more likely to have salt taste disability (OR 2.42; 95%CI 1.44-4.07), especially those older than 60 years (OR 3.63; 95%CI 1.72-7.63). Among participants aged 40-59, xerostomia increased the chance of salt taste disability; however, the confidence interval included the null value. The interactions between xerostomia and edentulism increased the chance of salt taste disability. CONCLUSION: Oral conditions seem to influence the ability to taste salt. Dental professionals may help identify individuals with taste alterations and raise their awareness of the risk of systemic diseases that require the reduction of salt intake.

Incidence, mortality and survival rates of lip, oral cavity and salivary glands cancers in Singapore: A half-century time trend analysis (1968-2017).

OBJECTIVES: To examine trends in incidence and mortality and evaluate overall survival (OS) of oral cancer in Singapore between 1968 and 2017. METHODS: All diagnosed oral cancers by anatomical sites and population size were extracted from the Singapore Cancer Registry and the Department of Statistics Singapore. The trend of age-standardized incidence rate (ASIR) and mortality rate (ASMR) (per 100 000 person-years) of the lip, oral cavity and salivary gland cancers were evaluated by Prais-Winsten regressions for each ethnicity and gender. Kaplan-Meier curves were performed to evaluate the OS by anatomical sites in each age group by ethnicity and sex. RESULTS: Overall, 49, 3494 and 1066 people were diagnosed, and 28, 2310 and 476 died from lip, oral cavity and salivary gland cancers, respectively. The oral cavity cancer ASIR and ASMR reduced from 3.07 (1968-1972) to 2.01(2008-2012) and from 2.06 (1978-1982) to 1.21 (2013-2017) per 100 000 person-years, respectively, with both highest in Indians throughout the whole period. Male:Female ratio ranged from 3.43 (1973-1977) to 1.75 (2013-2017) and from 3.41 (1978-1982) to 2.40 (2013-2017) for ASIR and ASMR, respectively. However, both salivary gland cancer ASIR and ASMR increased from 0.50 (1968-1972) to 0.80 (2008-2012) and from 0.18 (1968-1982) to 0.42 (1988-1992) per 100 000 person-years, respectively, with both higher in males since 1993. Oral cavity cancer ASIR decreased for males aged ≥60, and Indian females ≥25, but increased among Chinese females aged ≥60. Oral cavity cancer ASMR decreased among Chinese aged 25-59, and among Malay males and Indian females. Salivary gland cancer ASIR increased among Chinese males aged ≥60 and Malay males aged 25-59; while ASMR increased among Chinese males aged ≥60. The median OS for oral cavity, lip and salivary gland cancers were 3.0, 9.3 and 18.1 years, respectively, with females surviving longer than males. CONCLUSIONS: Singapore has experienced a decline in the incidence and mortality of lip, oral cancer, an increase in in the incidence and mortality of salivary gland cancer, with an increase in the median overall survival rate. Monitoring the magnitude of oral cancer burden and the demographic, and temporal variations is necessary for tailoring health planning and setting priorities for future clinical care and research.

Chewing Disability Is Associated With Cognitive Impairment Among Older Adults: A Population-Based Cohort Study.

BACKGROUND: Chewing disability is associated with impaired quality of life, potentially leading to depression, and cognitive impairment. Although the chewing-ability-cognition relationship has been explored, examining whether depression mediates this relationship remains unclear. We investigated the association between chewing disability and cognitive impairment development and a potential mediation via depression among older persons. METHODS: Older persons without cognitive impairment at baseline (n = 973) from the 3 waves of the Panel on Health and Ageing of Singaporean Elderly were investigated. The outcome was incident cognitive impairment by the end of the study, while the exposure was chewing disability over the study period. Time-varying depression was the mediator. Time-fixed confounders included sex, ethnicity, education, marital status, living arrangement, and housing type, and time-varying confounders included age, smoking, cardiovascular diseases, diabetes, number of teeth, and denture wearing. We used marginal structural modeling to evaluate the effect of chewing disability on cognitive impairment development. RESULTS: After 6 years, 11% developed cognitive impairment, and chewing disability was reported by 33%. Chewing disability was associated with higher odds of developing cognitive impairment (OR 1.43, 95% CI: 1.09, 1.87), of which 85.3% was explained by the controlled direct effect of chewing disability, whereas the remaining 14.7% could be eliminated if there was no depression. CONCLUSIONS: Our findings indicate an association between chewing disability and cognitive impairment, while the role of depression could not be fully elucidated. Oral health should be incorporated as part of older persons' care for its potential to assess the risk for other systemic conditions.

Oral and systemic health in Singapore: Revisiting the past to define the future.

OBJECTIVES: This study aimed to identify studies exploring oral and systemic conditions using Singapore data. METHODS: Studies were searched using the databases PubMed, Embase and Web of Science, with no publication date or language restrictions. Studies analysing Singaporean data were included in this review. RESULTS: Six domains were identified: pregnancy and gingivitis; tooth eruption, dental caries and early-life factors; Crohn's disease and oral microbiome; diabetes and periodontal diseases; number of teeth, chewing ability and cognitive status; and oral health and pneumonia. Using data from Singapore, oral-systemic studies have prompted reflections on the aetiopathogenesis of oral disorders, such as common causes connecting oral and systemic chronic conditions. Moreover, it is speculated whether oral conditions could be used as a marker to predict future systemic diseases or whether early-life factors could affect the development of oral and systemic immune responses. CONCLUSIONS: While Singapore provides opportunities to explore challenges connected to healthy ageing, it also explores health development in many stages of life. Singapore has been prioritizing investigations on a healthier life, and new initiatives are paving the way for oral health research across the lifespan.

Advancing Universal Oral Health Coverage via Person-Centred Outcomes.

The World Health Organization member states proposed a comprehensive "Global Strategy on Oral Health," which includes achieving universal oral health coverage by 2030. Challenges and barriers, including persistent inequalities, will hamper the achievement of universal oral health coverage. In low- and middle-income countries, the oral health of a large proportion of the population has been neglected, increasing oral health inequalities. In high-income countries, some receive excessive dental treatment, whilst particularly those with higher needs receive too little dental care. Therefore, an analysis of individual countries' needs, encompassing the training of oral health professionals in a new philosophy of care and attention and the optimisation of the existing resources, is necessary. Distancing from a person-centred focus has prompted individual and societal issues, including under-/overdiagnosis and under-/overtreatment. The person-centred approach considers the perceptions, needs, preferences, and circumstances of individuals and populations. Patient-reported outcome measures, such as self-rated and -reported health, reflect an individual's overall perception of health and are designed to mediate human biology (ie, the disease) and psychology. The usage of patient-reported outcome measures in dentistry to place the individual at the centre of treatment is delayed compared to other areas. This paper discusses some challenges and potential solutions of patient-reported outcome measures in dentistry for achieving universal oral health coverage.

JAK/STAT as a Potential Therapeutic Target for Osteolytic Diseases.

Several cytokines with major biological functions in inflammatory diseases exert their functions through the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signal transduction pathway. JAKs phosphorylate the cytoplasmic domain of the receptor, inducing the activation of its substrates, mainly the proteins known as STATs. STATs bind to these phosphorylated tyrosine residues and translocate from the cytoplasm to the nucleus, further regulating the transcription of several genes that regulate the inflammatory response. The JAK/STAT signaling pathway plays a critical role in the pathogenesis of inflammatory diseases. There is also increasing evidence indicating that the persistent activation of the JAK/STAT signaling pathway is related to several inflammatory bone (osteolytic) diseases. However, the specific mechanism remains to be clarified. JAK/STAT signaling pathway inhibitors have gained major scientific interest to explore their potential in the prevention of the destruction of mineralized tissues in osteolytic diseases. Here, our review highlights the importance of the JAK/STAT signaling pathway in inflammation-induced bone resorption and presents the results of clinical studies and experimental models of JAK inhibitors in osteolytic diseases.

Intake and serum levels of micronutrients and chronic oral diseases burden.

OBJECTIVE: To investigate pathways from micronutrient intake and serum levels to Chronic Oral Diseases Burden. METHODS: We analyzed cross-sectional data from NHANES III (n = 7936) and NHANES 2011-2014 (n = 4929). The exposure was the intake and serum levels of vitamin D, calcium, and phosphorus. Considering the high correlation of those micronutrients in the diet, they were analyzed as a latent variable dubbed Micronutrient intake. The outcome was the Chronic Oral Diseases Burden, a latent variable formed by probing pocket depth, clinical attachment loss, furcation involvement, caries, and missing teeth. Pathways triggered by gender, age, socioeconomic status, obesity, smoking, and alcohol were also estimated using structural equation modeling. RESULTS: In both NHANES cycles, micronutrient intake (p-value < 0.05) and vitamin D serum (p-value < 0.05) were associated with a lower Chronic Oral Diseases Burden. Micronutrient intake reduced the Chronic Oral Diseases Burden via vitamin D serum (p-value < 0.05). Obesity increased the Chronic Oral Diseases Burden by reducing vitamin D serum (p-value < 0.05). CONCLUSION: Higher micronutrient intake and higher vitamin D serum levels seem to reduce Chronic Oral Diseases Burden. Healthy diet policies may jointly tackle caries, periodontitis, obesity, and other non-communicable diseases.

Confounding in observational studies evaluating the association between Alzheimer's disease and periodontal disease: A systematic review.

Background: Studies investigating the association between periodontitis and Alzheimer's disease (AD) suggested indirect (periodontitis would increase the circulation of inflammation-inducible molecules) and direct (periodontopathogens might colonize brains affected by Alzheimer's disease) pathways. While there seems to be a positive relationship between periodontitis and AD, concerns have been raised about the role of confounding. Aim: To systematically review the literature to assess confounding and their level of heterogeneity in the association between periodontitis and AD. Also, to examine data reporting and interpretation regarding confounding bias. Methods: This review followed the PRISMA guidelines and was registered within PROSPERO. Electronic searches were performed in seven main databases and three others to capture the "grey literature". The PECO strategy was used to identify observational studies (cross-sectional, case-control, or cohort studies) assessing the association between periodontal disease and AD without restricting publication language and year. Critical appraisal was performed according to the Joanna Briggs Institute guidelines. Confounders were evaluated following a two-step approach. Results: A total of 3255 studies were found, of which 18 (13 case-control, four cross-sectional, and one cohort) met the eligibility criteria. Participants with AD were 1399 (mean age 64 ± 9 to 84.8 ± 5.6 years), whereas those without AD were 1730 (mean age 62.6 ± 7.1 to 81.4 ± 4.6). Female patients composed most of the sample for both groups. The confounding variables "age" and "sex" were present in all studies. Four studies used the 2017 AAP/EFP periodontal classification. Most studies had a low risk of bias. Fifty percent of the articles did not consider confounding; variation in the adjustment approaches was observed. Additionally, 62% of the studies did not mention bias, and 40% did not discuss any limitations about confounders. Conclusions: Given the study's limitations, caution must be taken to properly interpret the association between periodontitis and AD.Registration: CRD42022293884.

Salivary cytokine expression after non-surgical periodontal therapy in smokers: 12-month follow-up.

BACKGROUND: Diverse smoking trajectories may influence cytokine expression after non-surgical periodontal therapy and supportive periodontal care. Thus, we aimed to describe cytokine profiles in periodontal healing after periodontal therapy in smokers. METHODS: A smoking cessation program and non-surgical periodontal therapy were offered to 80 smokers with periodontitis. Smoking trajectories (quitters/light, moderate, heavy) were observed. The association of salivary interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) with smoking trajectories and periodontal outcomes was determined using mixed-effects linear regression. RESULTS: Among quitters/light smokers, IL-1ß was associated with an increase in mean periodontal pocket depth (PPD) and mean clinical attachment level (CAL). IL-6 was associated with a decrease in mean PPD and CAL in heavy smokers, whereas IL-8 was associated with a decrease in PPD among moderate smokers. TNFα was associated with a reduction in mean PPD and CAL among quitters/light smokers, while among moderate smokers, TNFα was associated with an increase in mean PPD and CAL. IL-12 and IL-13 were associated with a decrease in mean PPD in moderate smokers. CONCLUSION: Our findings suggest that distinctive smoking exposures induce differential cytokine expression, which, in turn, seems to influence periodontal repair.

Precursors of insulin resistance underlying periodontitis in adolescents aged 17-18 years.

OBJECTIVE: To investigate the association between insulin resistance markers and periodontitis in adolescents, analyzing confounder variables and the adiposity as a mediator. METHODS: This is population-based study is representative of adolescents aged 17-18 years from public schools in São Luís, Brazil (n = 405). Insulin resistance was assessed using the Model of Assessment of the Homeostasis of the Insulin Resistance Index (HOMA-IR) and its percussor triglycerides/HDL-cholesterol ratio (TG/HDL-c). The outcome was Initial Periodontitis, a latent variable estimated by the common variance shared among bleeding on probing, probing depth ≥ 4 mm, and clinical attachment loss ≥ 4 mm. The association between insulin resistance and Initial Periodontitis was modeled via pathways triggered by socioeconomic status, smoking, alcohol, and Adiposity, using structural equation modeling. RESULTS: Higher TG/HDL-c was directly associated with higher Initial Periodontitis (standardized coefficient [SC] = 0.130, p < 0.001). HOMA-IR was not associated with periodontal outcome (SC = 0.023, p = 0.075), but it was with Adiposity (SC = 0.495, p < 0.001). Higher TG/HDL-c was associated with Adiposity (SC = 0.202, p < 0.001). CONCLUSION: The insulin resistance markers were associated with early signs of periodontal breakdown among adolescents, suggesting a possible relationship between diabetes and periodontitis commences early in life.

Dietary vitamin D and calcium and periodontitis: A population-based study.

Aim: This study aimed to explore the relationship between dietary vitamin D and calcium intake and periodontitis among adults and whether it differs from males to females. Methods: Cross-sectional analysis of a population-based cohort study with adults aged 20 to 60 from Southern Brazil. Intake of vitamin D and calcium were gathered in 2012 using two 24h-dietary recalls. Clinical examination assessed the clinical attachment level and bleeding on probing. Confounders included sex, age, family income, smoking, and obesity. The controlled direct effect of vitamin D and calcium on periodontitis was examined using marginal structural modeling. Analyses were also stratified by sex. Results: Of the 1,066 investigated adults (mean age 35 ± 11.7 years; 49% females), 12.3% (95%CI 10.2;14.7) had periodontitis. Calcium intake had a direct protective effect on periodontitis (risk ratio (RR) 0.61; 95%CI 0.45;0.83), whereas no association between vitamin D and periodontitis was observed (RR 1.13; 95%CI 0.82;1.56). Stratified analyses revealed a null association between both vitamin D and calcium intake and periodontitis among men, but a protective association between calcium and intake and periodontitis among women (RR 0.56; 95%CI 0.38;0.79), while vitamin D remained without any association (RR 1.07; 95%CI 0.72;1.61). Conclusion: Our findings suggest a protective association between dietary calcium intake and periodontitis among women.

Cytokine profiles and the dynamic of gingivitis development in humans.

AIM: To investigate the relationship between cytokine profiles and "fast" and "slow" patterns of gingival inflammation development. MATERIALS AND METHODS: Forty-two adults participated in an experimental gingivitis study, comprising a 2-week hygiene phase (clinical examination and professional cleaning); a 3-week induction phase (absence of oral hygiene); and a 2-week resolution phase (re-establishment of oral hygiene). Plaque and gingival inflammation scores were assessed. Interferon-gamma (IFN-γ), interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumour necrosis factor-alpha (TNF-α) from gingival crevicular fluid were collected and measured by multiplex ELISA. Group-based-trajectory-modelling (GBTM) was used to model cytokine profiles over the induction phase. The effect of gingival inflammation on cytokine levels over time was estimated with mixed-effects modelling. RESULTS: GBTM analysis revealed two cytokine profiles, "non-organized response" (IL-4, IL-6, IL-8, IL-12, and IL-13) and "organized response" (IL-2, IL-10, and TNF-α). Among the "slow" responders, neither cytokine profile was associated with gingivitis. In contrast, a "fast" response was associated with a higher "non-organized response" factor (coef. 0.14) and a lower "organized response" factor (coef. -0.03). CONCLUSION: A "fast" gingivitis development was associated with a higher "non-organized response" and a lower "organized response", which may elucidate the role of individual variability in gingivitis susceptibility.

Role of occlusal factors on probable bruxism and orofacial pain: Data from the 1982 Pelotas birth cohort study.

OBJECTIVES: This study aimed to explore the association between occlusal features and temporomandibular disorder (TMD) pain complaints and probable awake or sleep bruxism METHODS: Path analysis was used to estimate direct, indirect and total effects of occlusal features on probable bruxism and pain-related TMD in adults aged 31 years from the 1982 Pelotas Birth Cohort. A total of 539 cohort members had an oral examination in 2013. Occlusal features were assessed through the Dental Aesthetic Index (DAI), orofacial pain complaints through the TMD pain screener and probable bruxism based on self-reports in combination with clinical findings. RESULTS: Malocclusions were found in 28.8% of the participants, while awake bruxism was reported in 35.2%, sleep bruxism in 15.2%, and pain-related TMD in 52.5% of the sample. Occlusion had no direct effect on either awake bruxism [standardized coefficient (SC) -0.002; p = 0.995] or pain-related TMD (SC -0.06; p = 0.115). Conversely, probable awake bruxism was associated with pain-related TMD (SC 0.35; p < 0.001). Similar results were found when sleep bruxism was set as the mediator of interest, as malocclusion did not directly affect sleep bruxism (SC 0.05; p= 0.220) nor pain-related TMD (SC -0.06; p = 0.167). A direct effect of sleep bruxism on pain-related TMD was observed with an SC of 0.16 (p < 0.001). CONCLUSION: Our findings suggested that malocclusion during adulthood did not directly influence probable awake or sleep bruxism nor TMD pain complaints. Instead, probable awake and sleep bruxism was associated with TMD pain complaints. CLINICAL SIGNIFICANCE: Malocclusion did not impact the presence of bruxism nor TMD complaints in adulthood, but awake and sleep bruxism were associated with TMD pain complaints. The significance of malocclusion should be reconsidered in contemporary dentistry and oral rehabilitation.

The association between halitosis and oral-health-related quality of life: A systematic review and meta-analysis.

AIM: To investigate whether halitosis is associated with impaired oral-health-related quality of life (OHRQoL). MATERIALS AND METHODS: This is a systematic review of the literature. Electronic searches were performed in PubMed via Medline, Web of Science, Scopus, and EMBASE up to and including June 2021. Observational studies that assessed halitosis in association with OHRQoL were included. The pooled standardized mean difference (SMD) was estimated by meta-analysis. RESULTS: Thirteen studies were included in the review; however, the meta-analysis included only 10 studies, all cross-sectional, comprising 2692 individuals. The overall meta-analysis showed an association between halitosis and impaired OHRQoL (SMD 0.51; 95% confidence interval 0.27-0.75). Subgroup analyses, however, indicated that this association remained only among adults. Neither the OHRQoL instrument nor the halitosis assessment method, or the cultural background, influenced the pooled estimates. Meta-regression analyses revealed that the OHRQoL instrument, the halitosis assessment method, and the sample composition did not explain the between-study heterogeneity. Methodological quality appeared to explain 20% of the overall heterogeneity, as studies with high risk of bias overestimated the magnitude of the association. CONCLUSION: Our findings suggest that halitosis is associated with impaired OHRQoL.

Influence of Bacterial Profiles in Cytokine and Clinical Features of Endodontic Disease.

INTRODUCTION: We verified the association between selected bacterial profiles and levels of cytokines, chemokines, and the expression of signs and symptoms of primary endodontic infection with apical periodontitis. METHODS: Samples were collected from 21 root canals, and macrophages were stimulated for 24 hours. Tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-10, IL-12p70, interferon gamma, and chemokine (C-C motif) ligand 2 (CCL2) were measured using cytometric bead array. We investigated the overlapping networks between cytokines and chemokines with regression analysis. Checkerboard DNA-DNA hybridization was used to assess 40 target bacteria species. Using factor analysis, bacterial species aggregated in 2 factors. The association of bacteria species-based factors on cytokine and chemokine levels and clinical features was estimated with regression analysis. RESULTS: A negative relationship between IL-10 (anti-inflammatory cytokine) and CCL2, TNF-α, and IFN-γ (proinflammatory cytokines) (all P < .05) was observed. CCL2 was positively correlated with TNF-α (P < .01). Thirty-eight bacteria species were detected in primary endodontic infection with apical periodontitis. The first bacteria species-based factor was associated with the size of the radiolucent area (coefficient = 15.42) and tenderness to percussion/pain on palpation (coefficient = 20.79). The second factor was associated with CCL2 levels (coefficient = 1.28). CONCLUSIONS: Different bacterial profiles can be differentially related to the expression of inflammatory proteins and the experience of clinical features.

Use of air polishing for supra- and subgingival biofilm removal for treatment of residual periodontal pockets and supportive periodontal care: a systematic review.

AIM: To systematically review the literature to compare the efficacy of air polishing to hand or ultrasonic instrumentation to reduce periodontal inflammation during treatment of residual pockets or supportive periodontal care. METHODS: Electronic searches were performed in five different databases, and two databases were used to capture the "grey literature partially." Clinical trials that compared the use of an air-polishing device to either conventional scaling and root planing (hand and/or ultrasonic instrumentation) or no treatment during periodontal therapy were included without restriction of year and publication status. The Joanna Briggs Institute instrument for clinical trials was used to appraise the studies critically. The results were submitted to qualitative descriptive analysis. The systematic review protocol was registered in PROSPERO (CRD420220156176). RESULTS: Electronic searches found 1100 hits published between 2008 and 2019. Thirteen studies were included in the review, out of which four had a follow-up longer than 180 days. Results indicated no differences between the efficacy of air polishing and hand or ultrasonic instruments to reduce periodontal inflammation. CONCLUSIONS: Our findings suggest that there is no difference in the efficacy of air polishing and hand or ultrasonic instrumentation to control biofilm and reduce periodontal inflammation. However, these findings must be carefully interpreted owing to methodological issues, including a short follow-up, and a potential conflict of interest related to industry funding. CLINICAL RELEVANCE: Air polishing for biofilm control may be used as an alternative to hand and ultrasonic instrumentation to reduce periodontal inflammation during treatment of residual pockets or supportive periodontal care.

The whitening effect of single brushing with blue-covarine containing toothpaste-A randomized controlled trial.

OBJECTIVE: To evaluate whether a blue covarine containing silica-based toothpaste promotes a whitening effect immediately after tooth brushing. METHODS: A triple-blind, parallel group, randomized design was used to compare the tooth color before and after brushing. Two silica-based toothpastes were chosen, one of them containing blue covarine (BCT) and the other one without pigment to serve as control (CT). Tooth color was measured using a spectrophotometer and expressed as CIEDE 2000 ΔE, CIELAB values, WIO index, WID index and VITA scale tooth shade. In addition, the participants' satisfaction with and perception of their own tooth color were registered using an aesthetic numeric analogue scale. RESULTS: No significant changes in color components or dimensions measured using CIEDE 2000 ΔE (CT: mean = 1.3, 95% CI 0.8, 1.7; BCT: mean = 1.6, 95% CI 1.2, 2.1), WIO, WID, VITA scale or CIELAB values were detected for the CT and BCT groups, comparing the results before and after brushing. Likewise, the participants' satisfaction with the treatment results (P = 0.31) and the participants' evaluation of tooth color (P = 0.71) did not differ significantly between groups. CONCLUSION: After a single application, no significant improvement in tooth whiteness by the presence of blue covarine in a silica-based toothpaste was detected in color dimensions or by assessing the participants' satisfaction and perception. CLINICAL SIGNIFICANCE: The present study does not show a clinically relevant increase in tooth whiteness after a single brushing with a blue covarine containing toothpaste, nor could the study participants observe a difference between treatment with blue covarine containing toothpaste and control treatment.