Dietary nitrate intake and net nitrite-generating capacity of the oral microbiome interact to enhance cardiometabolic health: Results from the Oral Infections Glucose Intolerance and Insulin Resistance Study (ORIGINS).

Background: We investigated the association between dietary nitrate intake and early clinical cardiometabolic risk biomarkers, and explored whether the oral microbiome modifies the association between dietary nitrate intake and cardiometabolic biomarkers. Methods: Cross-sectional data from 668 (mean [SD] age 31 [9] years, 73% women) participants was analyzed. Dietary nitrate intakes and alternative healthy eating index (AHEI) scores were calculated from food frequency questionnaire responses and a validated US food database. Subgingival 16S rRNA microbial genes (Illumina, MiSeq) were sequenced, and PICRUSt2 estimated metagenomic content. The Microbiome Induced Nitric oxide Enrichment Score (MINES) was calculated as a microbial gene abundance ratio representing enhanced net capacity for NO generation. Cardiometabolic risk biomarkers included systolic and diastolic blood pressure, HbA1c, glucose, insulin, and insulin resistance (HOMA-IR), and were regressed on nitrate intake tertiles in adjusted multivariable linear models. Results: Mean nitrate intake was 190[171] mg/day. Higher nitrate intake was associated with lower insulin, and HOMA-IR but particularly among participants with low abundance of oral nitrite enriching bacteria. For example, among participants with a low MINES, mean insulin[95%CI] levels in high vs. low dietary nitrate consumers were 5.8[5.3,6.5] vs. 6.8[6.2,7.5] (p=0.004) while respective insulin levels were 6.0[5.4,6.6] vs. 5.9[5.3,6.5] (p=0.76) among partcipants with high MINES (interaction p=0.02). Conclusion: Higher dietary nitrate intake was only associated with lower insulin and insulin resistance among individuals with reduced capacity for oral microbe-induced nitrite enrichment. These findings have implications for future precision medicine-oriented approaches that might consider assessing the oral microbiome prior to enrollment into dietary interventions or making dietary recommendations.

Genetic/Protein Association of Atopic Dermatitis and Tooth Agenesis.

Atopic dermatitis and abnormalities in tooth development (including hypomineralization, hypodontia and microdontia) have been observed to co-occur in some patients. A common pathogenesis pathway that involves genes and protein interactions has been hypothesized. This review aims to first provide a description of the key gene mutations and signaling pathways associated with atopic dermatitis and tooth agenesis (i.e., the absence of teeth due to developmental failure) and identify the possible association between the two diseases. Second, utilizing a list of genes most commonly associated with the two diseases, we conducted a protein-protein network interaction analysis using the STRING database and identified a novel association between the Wnt/ß-catenin signaling pathway (major pathway responsible for TA) and desmosomal proteins (component of skin barrier that affect the pathogenesis of AD). Further investigation into the mechanisms that may drive their co-occurrence and underlie the development of the two diseases is warranted.

Oral Cancer Awareness of Tertiary Education Students and General Public in Singapore.

OBJECTIVES: Oral cancer confers high morbidity and mortality rates. Late diagnosis of oral cancer is linked to a lack of awareness of its existence and known risk factors. The purpose of this survey was to examine the knowledge and awareness of oral cancer amongst different groups in Singapore. METHODS: A self-administered questionnaire (including questions on awareness, risk factor knowledge, and health beliefs about oral cancer) was distributed to undergraduate students from the medical and dental schools and other faculties at the National University of Singapore, as well as the general public. RESULTS: A total of 470 responses were analysed. Both medical and dental students were almost universally aware of the disease and correctly identified recognised risk factors for oral cancers. Dental students had a significantly higher level of knowledge of chewing betel quid as a risk factor than medical students (98% vs 74%; P < .0001), although 1 in 10 dental students did not identify alcohol as a risk factor. In contrast, undergraduate students from other faculties were the least aware of oral cancer (62%). Within the general public, knowledge of the risk factors of oral cancer aside from smoking was low, with only 41% aware of viruses as a possible aetiology. However, the younger population group, aged 18 to 34 years old, in general had better knowledge of the risk factors of oral cancer compared with older participants. CONCLUSIONS: There is a general lack of awareness about oral cancer and its associated risk factors amongst certain cohorts of the Singapore population. There exists room for further targeted education.

Nitrite Generating and Depleting Capacity of the Oral Microbiome and Cardiometabolic Risk: Results from ORIGINS.

Background The enterosalivary nitrate-nitrite-nitric oxide (NO3-NO2-NO) pathway generates NO following oral microbiota-mediated production of salivary nitrite, potentially linking the oral microbiota to reduced cardiometabolic risk. Nitrite depletion by oral bacteria may also be important for determining the net nitrite available systemically. We examine if higher abundance of oral microbial genes favoring increased oral nitrite generation and decreased nitrite depletion is associated with a better cardiometabolic profile cross-sectionally. Methods and Results This study includes 764 adults (mean [SD] age 32 [9] years, 71% women) enrolled in ORIGINS (Oral Infections, Glucose Intolerance, and Insulin Resistance Study). Microbial DNA from subgingival dental plaques underwent 16S rRNA gene sequencing; PICRUSt2 was used to estimate functional gene profiles. To represent the different components and pathways of nitrogen metabolism in bacteria, predicted gene abundances were operationalized to create summary scores by (1) bacterial nitrogen metabolic pathway or (2) biochemical product (NO2, NO, or ammonia [NH3]) formed by the action of the bacterial reductases encoded. Finally, nitrite generation-to-depletion ratios of gene abundances were created from the above summary scores. A composite cardiometabolic Z score was created from cardiometabolic risk variables, with higher scores associated with worse cardiometabolic health. We performed multivariable linear regression analysis with cardiometabolic Z score as the outcome and the gene abundance summary scores and ratios as predictor variables, adjusting for sex, age, race, and ethnicity in the simple adjusted model. A 1 SD higher NO versus NH3 summary ratio was inversely associated with a -0.10 (false discovery rate q=0.003) lower composite cardiometabolic Z score in simple adjusted models. Higher NH3 summary score (suggestive of nitrite depletion) was associated with higher cardiometabolic risk, with a 0.06 (false discovery rate q=0.04) higher composite cardiometabolic Z score. Conclusions Increased net capacity for nitrite generation versus depletion by oral bacteria, assessed through a metagenome estimation approach, is associated with lower levels of cardiometabolic risk.

When e-learning takes centre stage amid COVID-19: Dental educators' perspectives and their future impacts.

INTRODUCTION: The COVID-19 pandemic has necessitated an unprecedented shift from face-to-face teaching to e-learning. Previous surveys revealed the negative impact of COVID-19 on dental education and the physical and psychological well-being of dental students. This qualitative study aimed to investigate the perspectives of dental educators towards e-learning during the pandemic and the impact of this experience on their future adoption of e-learning. MATERIALS AND METHODS: Semi-structured interviews with dental educators from the National University of Singapore were conducted over Zoom. Audio recordings were transcribed verbatim and subjected to thematic analysis. Data saturation was reached. Consolidated criteria for reporting qualitative research (COREQ) was followed. RESULTS: Fifteen out of 22 (68%) eligible dental educators were interviewed. Educators had minimal prior e-learning experience. They encountered difficulties in engaging students, assessing students' understanding and adapting their teaching. A practical challenge was to ensure the well-rounded training of competent dentists with adequate patient-interaction skills through e-learning. Self-motivation of the audience, class size, type of teaching and complexity of the material were perceived as factors influencing the suitability of the e-learning format. Educators reported an increased confidence after this emergency e-learning experience. Some considered sustaining or expanding e-learning in their future teaching practice and highlighted the need for continued investment and institutional support, training on the pedagogy of e-learning modalities and curriculum redesign to accommodate blended learning approaches. CONCLUSIONS: Although the shift to e-learning during the COVID-19 pandemic presented a myriad of challenges, dental educators gained experience and confidence which may accelerate the pace of future e-learning adoption and innovation.

Assessing the Relationship Between Nitrate-Reducing Capacity of the Oral Microbiome and Systemic Outcomes.

The significance of the oral microbiome in the generation of the nitric oxide (NO) via the enterosalivary nitrate-nitrite-nitric oxide pathway is increasingly recognized, directly linking the oral microbiome to cardiometabolic outcomes influenced by NO. The objective of this chapter is to outline a strategy of identifying pathway-specific bacterial taxa or predicted genes of interest from 16S rRNA data, specifically in the enterosalivary pathway of nitrate reduction, and analyzing their relationship with cardiometabolic outcomes using multivariable regression models.

Association Between Nitrate-Reducing Oral Bacteria and Cardiometabolic Outcomes: Results From ORIGINS.

Background The enterosalivary nitrate-nitrite-nitric oxide pathway is an alternative pathway of nitric oxide generation, potentially linking the oral microbiome to insulin resistance and blood pressure (BP). We hypothesized that increased abundance of nitrate-reducing oral bacteria would be associated with lower levels of cardiometabolic risk cross-sectionally. Methods and Results ORIGINS (Oral Infections, Glucose Intolerance, and Insulin Resistance Study) enrolled 300 diabetes mellitus-free adults aged 20 to 55 years (mean=34±10 years) (78% women). Microbial DNA was extracted from subgingival dental plaque (n=281) and V3-V4 regions of the 16S rRNA gene were sequenced to measure the relative abundances of 20 a priori-selected taxa with nitrate-reducing capacity. Standardized scores of each taxon's relative abundance were summed, producing a nitrate-reducing taxa summary score (NO3TSS) for each participant. Natural log-transformed homeostatic model assessment of insulin resistance, plasma glucose, systolic BP, and diastolic BP were regressed on NO3TSS in multivariable linear regressions; prediabetes mellitus and hypertension prevalence were regressed on NO3TSS using modified Poisson regression models. Nitrate-reducing bacterial species represented 20±16% of all measured taxa. After multivariable adjustment, a 1-SD increase in NO3TSS, was associated with a -0.09 (95% CI, -0.15 to -0.03) and -1.03 mg/dL (95% CI, -1.903 to -0.16) lower natural log-transformed homeostatic model assessment of insulin resistance and plasma glucose, respectively. NO3TSS was associated with systolic BP only among patients without hypertension; 1-SD increase in NO3TSS was associated with -1.53 (95% CI, -2.82 to -0.24) mm Hg lower mean systolic BP. No associations were observed with prediabetes mellitus and hypertension. Conclusions A higher relative abundance of oral nitrate-reducing bacteria was associated with lower insulin resistance and plasma glucose in the full cohort and with mean systolic BP in participants with normotension.

Neighborhood food environment, dietary fatty acid biomarkers, and cardiac arrest risk.

We explored links between food environments, dietary intake biomarkers, and sudden cardiac arrest in a population-based longitudinal study using cases and controls accruing between 1990 and 2010 in King County, WA. Surprisingly, presence of more unhealthy food sources near home was associated with a lower 18:1 trans-fatty acid concentration (-0.05% per standard deviation higher count of unhealthy food sources, 95% Confidence Interval [CI]: 0.01, 0.09). However, presence of more unhealthy food sources was associated with higher odds of cardiac arrest (Odds Ratio [OR]: 2.29, 95% CI: 1.19, 4.41 per standard deviation in unhealthy food outlets). While unhealthy food outlets were associated with higher cardiac arrest risk, circulating 18:1 trans fats did not explain the association.

Medical facilities in the neighborhood and incidence of sudden cardiac arrest.

BACKGROUND: Medical establishments in the neighborhood, such as pharmacies and primary care clinics, may play a role in improving access to preventive care and treatment and could explain previously reported neighborhood variations in sudden cardiac arrest (SCA) incidence and survival. METHODS: The Cardiac Arrest Blood Study Repository is a population-based repository of data from adult cardiac arrest patients and population-based controls residing in King County, Washington. We examined the association between the availability of medical facilities near home with SCA risk, using adult (age 18-80) Seattle residents experiencing cardiac arrest (n = 446) and matched controls (n = 208) without a history of heart disease. We also analyzed the association of major medical centers near the event location with emergency medical service (EMS) response time and survival among adult cases (age 18+) presenting with ventricular fibrillation from throughout King County (n = 1537). The number of medical facilities per census tract was determined by geocoding business locations from the National Establishment Time-Series longitudinal database 1990-2010. RESULTS: More pharmacies in the home census tract was unexpectedly associated with higher odds of SCA (OR:1.28, 95% CI: 1.03, 1.59), and similar associations were observed for other medical facility types. The presence of a major medical center in the event census tract was associated with a faster EMS response time (-53 s, 95% CI: -84, -22), but not with short-term survival. CONCLUSIONS: We did not observe a protective association between medical facilities in the home census tract and SCA risk, orbetween major medical centers in the event census tract and survival.

Association between Serum Folate and Insulin Resistance among U.S. Nondiabetic Adults.

Recent studies have suggested that epigenetic alterations, particularly DNA methylation, play a crucial role in the pathogenesis of insulin resistance. Folate is a key source of the one-carbon group for DNA methylation, whereas the association and mechanistic linkage between folate status and insulin resistance remains unclear with very limited experimental support. We performed a cross-sectional study of 1530 nondiabetic adults in the 2011-2012 National Health and Nutrition Examination Survey (NHANES). We examined associations between serum folate and insulin resistance using multiple linear regression models adjusted for potential confounders. We detected a significant inverse relationship for serum folate, where a 25% increase in serum folate was associated with a 3.06% (95% CI, -4.72, -1.37) and 2.77% (95% CI, -4.36, -1.77) decline in HOMA-IR and insulin respectively, and a 2.55% (95% CI, 0.93, 4.21) increase in G/I ratio. Our findings demonstrate that serum folate was inversely associated with insulin resistance in U.S. nondiabetic adults.

Association Between Serum Antibodies to Periodontal Bacteria and Rheumatoid Factor in the Third National Health and Nutrition Examination Survey.

OBJECTIVE: Alterations in the microbiome, including the periodontal microbiome, may be a risk factor for rheumatoid arthritis (RA). Most studies that have analyzed this association are relatively small, focus primarily on a single periodontal pathogen (Porphyromonas gingivalis), and are not population based. This study was undertaken to investigate the association between elevated serum levels of IgG antibodies to 19 periodontal species and the prevalence of rheumatoid factor (RF) in a large nationally representative sample of adults. METHODS: The Third National Health and Nutrition Examination Survey (NHANES-III) is a cross-sectional sample of the noninstitutionalized US population (n = 33,994). Our study population included all dentate participants who were 60 years and older, did not have RA as defined by a modified version of the American College of Rheumatology 1987 criteria, and had complete data for both serum IgG antibodies against periodontal bacteria and serum RF antibody titer (n = 2,461). RESULTS: Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) summarizing the relationship between the 19 periodontal serum IgG antibodies and RF seropositivity ranged from 0.53 (95% CI 0.29-0.97) to 1.27 (95% CI 0.79-2.06), and 17 of the 19 observed ORs were <1.0. The ORs for RF seropositivity among participants with elevated Prevotella intermedia (0.53 [95% CI 0.29-0.97]) and Capnocytophaga ochracea (0.54 [0.31-0.95]) IgG levels were statistically significant. CONCLUSION: Our findings indicate that elevated levels of IgG antibodies to periodontal bacteria are mostly unassociated with RF seropositivity in the nationally representative NHANES-III. Elevated levels of antibodies to P intermedia and C ochracea are associated with lower odds of RF seropositivity.

Correlates of attitudes and perceived behavioural control towards oral care provision among trained and untrained nursing home caregivers in Singapore.

AIMS AND OBJECTIVES: To investigate the perspectives of nursing home caregivers towards oral care and the determinants of their attitudes and perceived behavioural control. BACKGROUND: There are few studies analysing nursing home caregivers' perspectives on the provision of oral care and factors correlated with these perspectives. DESIGN: Cross-sectional study. METHODS: Interviewer-administered survey questionnaires were completed by caregivers from five nursing homes in Singapore (n = 94). The rating-scale questionnaire items explored caregivers' attitudes, subjective norms and perceived behavioural control, as guided by the theory of planned behaviour. Demographic characteristics, oral care training received, years of work experience, oral hygiene behaviour and dental visit frequency of the caregivers, as well as organisational characteristics such as a requirement for oral care and the number of patients under their care, were obtained. RESULTS: Caregivers had very positive attitudes towards the provision of oral care. Half of the caregivers lacked confidence in providing oral care without harming the patients and this was not different by oral care training received. Multivariable linear regression analysis found that receiving oral care training and having a requirement by the nursing home to provide oral care were related to higher attitude scores but not perceived behaviour control. Having more residents under their care and on-the-job caregiver training were associated with lower perceived behavioural control. CONCLUSIONS: This study found that nursing home caregivers had positive attitudes towards providing oral care, but more modest perspectives about their ability to perform that behaviour. RELEVANCE TO CLINICAL PRACTICE: These findings have useful implications for the oral care training of nursing home caregivers. While attitudes towards the importance of oral care may be positive among nursing home caregivers, our study suggests that future interventions should include practical skills training for oral care management and consider organisational strategies for encouraging oral care provision.

The independent associations of recorded crime and perceived safety with physical health in a nationally representative cross-sectional survey of men and women in New Zealand.

OBJECTIVES: We investigated associations of officially recorded crime and perceived neighbourhood safety with physical health, evaluating potential effect modification by gender. SETTING: Nationally representative population-based survey in New Zealand. PARTICIPANTS: Individual-level data from 6995 New Zealand General Social Survey (2010-2011) participants with complete data on physical health status, perceived neighbourhood safety, sociodemographic characteristics and smoking. Crime rate for each participant's home census was estimated based on data from the New Zealand Police (2008-2010). PRIMARY OUTCOME MEASURE: The Transformed Physical Composite Score from the SF-12, a physical health summary score based on self-report ranging from 0 to 100. RESULTS: We used cluster robust multivariable regression models to examine the associations among neighbourhood crime rates, perceived neighbourhood safety and the physical health summary score. Crime rates predicted adults' perception that it was unsafe to walk in their neighbourhood at night: for each additional crime per 100 000 residents adults were 1.9% more likely to perceive their neighbourhood as unsafe (95% CI 1.2% to 2.5%). While relatively uncommon, the rate of crime with a weapon strongly predicted perceived safety: for each additional crime per 100 000 residents in this category, adults were 12.9% more likely to report the neighbourhood as unsafe (95% CI 8.8% to 17.0%). Police-recorded violent and night crime rates were associated with worse physical health among women: for each additional crime per 100 000 residents in these category women had a 0.3 point lower physical health score (95% CIs -0.6 to -0.1 for violent crime and -0.5 to -0.1 for crime at night, gender interaction p values 0.08 and 0.01, respectively). Perceiving the neighbourhood as unsafe was independently associated with 1.0 point lower physical health score (95% CI -1.5 to -0.5). CONCLUSIONS: Gender may modify the associations of officially recorded crime rates with physical health. Perceived neighbourhood safety was independently associated with physical health.