Comprehensive evaluation of methods for differential expression analysis of metatranscriptomics data.

Understanding the function of the human microbiome is important but the development of statistical methods specifically for the microbial gene expression (i.e. metatranscriptomics) is in its infancy. Many currently employed differential expression analysis methods have been designed for different data types and have not been evaluated in metatranscriptomics settings. To address this gap, we undertook a comprehensive evaluation and benchmarking of 10 differential analysis methods for metatranscriptomics data. We used a combination of real and simulated data to evaluate performance (i.e. type I error, false discovery rate and sensitivity) of the following methods: log-normal (LN), logistic-beta (LB), MAST, DESeq2, metagenomeSeq, ANCOM-BC, LEfSe, ALDEx2, Kruskal-Wallis and two-part Kruskal-Wallis. The simulation was informed by supragingival biofilm microbiome data from 300 preschool-age children enrolled in a study of childhood dental disease (early childhood caries, ECC), whereas validations were sought in two additional datasets from the ECC study and an inflammatory bowel disease study. The LB test showed the highest sensitivity in both small and large samples and reasonably controlled type I error. Contrarily, MAST was hampered by inflated type I error. Upon application of the LN and LB tests in the ECC study, we found that genes C8PHV7 and C8PEV7, harbored by the lactate-producing Campylobacter gracilis, had the strongest association with childhood dental disease. This comprehensive model evaluation offers practical guidance for selection of appropriate methods for rigorous analyses of differential expression in metatranscriptomics. Selection of an optimal method increases the possibility of detecting true signals while minimizing the chance of claiming false ones.

Metabolomics for dental caries diagnosis: Past, present, and future.

Dental caries, a prevalent global infectious condition affecting over 95% of adults, remains elusive in its precise etiology. Addressing the complex dynamics of caries demands a thorough exploration of taxonomic, potential, active, and encoded functions within the oral ecosystem. Metabolomic profiling emerges as a crucial tool, offering immediate insights into microecosystem physiology and linking directly to the phenotype. Identified metabolites, indicative of caries status, play a pivotal role in unraveling the metabolic processes underlying the disease. Despite challenges in metabolite variability, the use of metabolomics, particularly via mass spectrometry and nuclear magnetic resonance spectroscopy, holds promise in caries research. This review comprehensively examines metabolomics in caries prevention, diagnosis, and treatment, highlighting distinct metabolite expression patterns and their associations with disease-related bacterial communities. Pioneering in approach, it integrates singular and combinatory metabolomics methodologies, diverse biofluids, and study designs, critically evaluating prior limitations while offering expert insights for future investigations. By synthesizing existing knowledge, this review significantly advances our comprehension of caries, providing a foundation for improved prevention and treatment strategies.

Glycerol metabolism contributes to competition by oral streptococci through production of hydrogen peroxide.

As a biological byproduct from both humans and microbes, glycerol's contribution to microbial homeostasis in the oral cavity remains understudied. In this study, we examined glycerol metabolism by Streptococcus sanguinis, a commensal associated with oral health. Genetic mutants of glucose-PTS enzyme II (manL), glycerol metabolism (glp and dha pathways), and transcriptional regulators were characterized with regard to glycerol catabolism, growth, production of hydrogen peroxide (H2O2), transcription, and competition with Streptococcus mutans. Biochemical assays identified the glp pathway as a novel source for H2O2 production by S. sanguinis that is independent of pyruvate oxidase (SpxB). Genetic analysis indicated that the glp pathway requires glycerol and a transcriptional regulator, GlpR, for expression and is negatively regulated by PTS, but not the catabolite control protein, CcpA. Conversely, deletion of either manL or ccpA increased the expression of spxB and a second, H2O2-non-producing glycerol metabolic pathway (dha), indicative of a mode of regulation consistent with conventional carbon catabolite repression (CCR). In a plate-based antagonism assay and competition assays performed with planktonic and biofilm-grown cells, glycerol greatly benefited the competitive fitness of S. sanguinis against S. mutans. The glp pathway appears to be conserved in several commensal streptococci and actively expressed in caries-free plaque samples. Our study suggests that glycerol metabolism plays a more significant role in the ecology of the oral cavity than previously understood. Commensal streptococci, though not able to use glycerol as a sole carbohydrate source for growth, benefit from the catabolism of glycerol through production of both ATP and H2O2. IMPORTANCE: Glycerol is an abundant carbohydrate in the oral cavity. However, little is understood regarding the metabolism of glycerol by commensal streptococci, some of the most abundant oral bacteria. This was in part because most streptococci cannot grow on glycerol as the sole carbon source. In this study, we show that Streptococcus sanguinis, a commensal associated with dental health, can degrade glycerol for persistence and competition through two pathways, one of which generates hydrogen peroxide at levels capable of inhibiting Streptococcus mutans. Preliminary studies suggest that several additional commensal streptococci are also able to catabolize glycerol, and glycerol-related genes are actively expressed in human dental plaque samples. Our findings reveal the potential of glycerol to significantly impact microbial homeostasis, which warrants further exploration.

Dental Caries, Race and Incident Ischemic Stroke, Coronary Heart Disease, and Death.

BACKGROUND: Dental caries is a highly prevalent disease worldwide. In the United States, untreated dental caries is present in >1 in 5 adults. The objective of this study was to determine the relationship between dental caries and incident ischemic stroke, coronary heart disease (CHD) events, and death. METHODS: The dental cohort (n=6351) of the ARIC study (Atherosclerosis Risk in Communities) was followed for incident ischemic stroke, CHD event, and all-cause mortality. Of all the participants at visit 4 (n=11 656), those who were unable to go through dental examination, or with prevalent ischemic stroke and CHD events, were excluded. The full-mouth dental examination was conducted at visit 4 (1996-1998), assessing dental caries. The dose response of decayed, missing, and filled surfaces due to caries was assessed and related to the outcome. Outcomes were assessed through the end of 2019. Additionally, the effect of regular dental care utilization on dental caries was evaluated. RESULTS: Participants with ≥1 dental caries had an increased risk of stroke (adjusted hazard ratio [HR], 1.40 [95% CI, 1.10-1.79]) and death (adjusted HR, 1.13 [95% CI, 1.01-1.26]) but not for CHD events (adjusted HR, 1.13 [95% CI, 0.93-1.37]). The association of dental caries and ischemic incident stroke was significantly higher in the African American population compared with the White subgroup (interaction term P=0.0001). Increasing decayed, missing, and filled surfaces were significantly associated with stroke (adjusted HR, 1.006 [95% CI, 1.001-1.011]) and death (adjusted HR, 1.003 [95% CI, 1.001-1.005]) but not CHD (adjusted HR, 1.002 [95% CI, 1.000-1.005]). Regular dental care utilization lowered (adjusted odds ratio, 0.19 [95% CI, 0.16-0.22]; P<0.001) the chance of caries. CONCLUSIONS: Among the cohort, dental caries was independently associated with the risk of ischemic stroke and death, with the effect higher in African American participants. Regular dental care utilization was associated with a lower chance of caries, emphasizing its relevance in the prevention of these events.

Salivary Diagnosis of Dental Caries: A Systematic Review.

The activity of dental caries, combined with its multifactorial etiology, alters salivary molecule composition. The present systematic review was developed to answer the following question: "Are salivary biomarkers reliable for diagnosis of dental caries?". Following the "Preferred Reporting Item for Systematic Reviews and Meta-analysis" (PRISMA) guidelines, the review was conducted using multiple database research (Medline, Web of Science, and Scopus). Studies performed on healthy subjects with and without dental caries and providing detailed information concerning the clinical diagnosis of caries (Decayed, Missing, Filled Teeth-DMFT and International Caries Detection and Assessment System-ICDAS criteria) were included. The quality assessment was performed following a modified version of the Joanna Briggs Institute Prevalence Critical Appraisal Checklist. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, ID: CRD42022304505). Sixteen papers were included in the review. All studies reported statistically significant differences in the concentration of salivary molecules between subjects with and without caries (p < 0.05). Proteins were the most investigated molecules, in particular alpha-amylase and mucins. Some studies present a risk of bias, such as identifying confounding factors and clearly defining the source population. Nevertheless, the 16 papers were judged to be of moderate to high quality. There is evidence that some salivary compounds studied in this review could play an important diagnostic role for dental caries, such as salivary mucins, glycoproteins (sCD14), interleukins (IL-2RA, 4,-13), urease, carbonic anhydrase VI, and urea.

Plant-Derived Compounds: A Promising Tool for Dental Caries Prevention.

There is a growing shift from the use of conventional pharmaceutical oral care products to the use of herbal extracts and traditional remedies in dental caries prevention. This is attributed to the potential environmental and health implications of contemporary oral products. This comprehensive review aims at the analysis of plant-derived compounds as preventive modalities in dental caries research. It focuses on data collected from 2019 until recently, trying to emphasize current trends in this topic. The research findings suggest that several plant-derived compounds, either aqueous or ethanolic, exhibit notable antibacterial effects against Streptococcus mutans and other bacteria related to dental caries, with some extracts demonstrating an efficacy comparable to that of chlorhexidine. Furthermore, in vivo studies using plant-derived compounds incorporated in food derivatives, such as lollipops, have shown promising results by significantly reducing Streptococcus mutans in high-risk caries children. In vitro studies on plant-derived compounds have revealed bactericidal and bacteriostatic activity against S. mutans, suggesting their potential use as dental caries preventive agents. Medicinal plants, plant-derived phytochemicals, essential oils, and other food compounds have exhibited promising antimicrobial activity against oral pathogens, either by their anti-adhesion activity, the inhibition of extracellular microbial enzymes, or their direct action on microbial species and acid production. However, further research is needed to assess their antimicrobial activity and to evaluate the cytotoxicity and safety profiles of these plant-derived compounds before their widespread clinical use can be recommended.

Metabolomics reveals high fructose-1,6-bisphosphate from fluoride-resistant Streptococcus mutans.

BACKGROUND: Fluoride-resistant Streptococcus mutans (S. mutans) strains have developed due to the wide use of fluoride in dental caries prevention. However, the metabolomics of fluoride-resistant S. mutans remains unclear. OBJECTIVE: This study aimed to identify metabolites that discriminate fluoride-resistant from wild-type S. mutans. MATERIALS AND METHODS: Cell supernatants from fluoride-resistant and wild-type S. mutans were collected and analyzed by liquid chromatography-mass spectrometry. Principal components analysis and partial least-squares discriminant analysis were performed for the statistical analysis by variable influence on projection (VIP > 2.0) and p value (Mann-Whitney test, p < 0.05). Metabolites were assessed qualitatively using the Human Metabolome Database version 2.0 ( http://www.hmdb.ca ), or Kyoto Encyclopedia of Genes and Genomes ( http://www.kegg.jp ), and Metaboanalyst 6.0 ( https://www.metaboanalyst.ca ). RESULTS: Fourteen metabolites differed significantly between fluoride-resistant and wild-type strains in the early log phase. Among these metabolites, 5 were identified. There were 32 differential metabolites between the two strains in the stationary phase, 13 of which were identified. The pyrimidine metabolism for S. mutans FR was matched with the metabolic pathway. CONCLUSIONS: The fructose-1,6-bisphosphate concentration increased in fluoride-resistant strains under acidic conditions, suggesting enhanced acidogenicity and acid tolerance. This metabolite may be a promising target for elucidating the cariogenic and fluoride resistant mechanisms of S. mutans.

The complement system as a key modulator of the oral microbiome in health and disease.

In this review, we address the interplay between the complement system and host microbiomes in health and disease, focussing on oral bacteria known to contribute to homeostasis or to promote dysbiosis associated with dental caries and periodontal diseases. Host proteins modulating complement activities in the oral environment and expression profiles of complement proteins in oral tissues were described. In addition, we highlight a sub-set of bacterial proteins involved in complement evasion and/or dysregulation previously characterized in pathogenic species (or strains), but further conserved among prototypical commensal species of the oral microbiome. Potential roles of these proteins in host-microbiome homeostasis and in the emergence of commensal strain lineages with increased virulence were also addressed. Finally, we provide examples of how commensal bacteria might exploit the complement system in competitive or cooperative interactions within the complex microbial communities of oral biofilms. These issues highlight the need for studies investigating the effects of the complement system on bacterial behaviour and competitiveness during their complex interactions within oral and extra-oral host sites.

Competitive dynamics and balance between Streptococcus mutans and commensal streptococci in oral microecology.

Dental caries, as a biofilm-related disease, is closely linked to dysbiosis in microbial ecology within dental biofilms. Beyond its impact on oral health, bacteria within the oral cavity pose systemic health risks by potentially entering the bloodstream, thereby increasing susceptibility to bacterial endocarditis, among other related diseases. Streptococcus mutans, a principal cariogenic bacterium, possesses virulence factors crucial to the pathogenesis of dental caries. Its ability to adhere to tooth surfaces, produce glucans for biofilm formation, and metabolize sugars into lactic acid contributes to enamel demineralization and the initiation of carious lesions. Its aciduricity and ability to produce bacteriocins enable a competitive advantage, allowing it to thrive in acidic environments and dominate in changing oral microenvironments. In contrast, commensal streptococci, such as Streptococcus sanguinis, Streptococcus gordonii, and Streptococcus salivarius, act as primary colonizers and compete with S. mutans for adherence sites and nutrients during biofilm formation. This competition involves the production of alkali, peroxides, and antibacterial substances, thereby inhibiting S. mutans growth and maintaining microbial balance. This dynamic interaction influences the balance of oral microbiota, with disruptions leading to shifts in microbial composition that are marked by rapid increases in S. mutans abundance, contributing to the onset of dental caries. Thus, understanding the dynamic interactions between commensal and pathogenic bacteria in oral microecology is important for developing effective strategies to promote oral health and prevent dental caries. This review highlights the roles and competitive interactions of commensal bacteria and S. mutans in oral microecology, emphasizing the importance of maintaining oral microbial balance for health, and discusses the pathological implications of perturbations in this balance.

Comparative evaluation of anti-biofilm and anti- adherence potential of plant extracts against Streptococcus mutans: A therapeutic approach for oral health.

Dental caries predominantly attributed to the cariogenic nature of Streptococcus mutans, continue to pose a substantial global challenge to oral health. In response to this challenge, this study aimed to evaluate the effectiveness of leaf extracts (LEs) and essential oils (EOs) derived from different medicinal plants in inhibiting the growth of Streptococcus mutans biofilm. In vitro and in silico approaches were employed to identify active compounds and assess their inhibitory effects on S. mutans. Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were measured to determine the anti-biofilm and anti-adherence activity against S. mutans. Biofilm viability (CFU/mL) and extracellular polymeric substance (EPS) concentration were quantified. GC-MS analysis was utilized to identify active compounds in the most effective plant extracts exhibiting anti-S. mutans activity. A high-throughput screening focused on the interaction between these compounds and the target enzyme SortaseA (SrtA) using molecular docking was performed. Results indicated that Cymbopogon citratus displayed the highest efficacy in reducing S. mutans biofilm formation and adhesion activity, achieving 90 % inhibition at an MIC value of 12 µg/mL. Among the 12 bioactive compounds identified, trans-Carvyl acetate exhibited the lowest binding energy with SrtA (-6.0 Kcal/mole). Trans-Carvyl acetate also displayed favorable pharmacokinetic properties. This study provides novel insights into the anti-S. mutans properties of C. citratus and suggests its potential as a therapeutic approach for oral health. Further research is needed to explore the combined effect of plant extracts for enhanced protection against dental caries.

Hospital Visits Associated With Oral Infections in Patients With Neurofibromatosis Type 1: A Register-Based Analysis.

Various forms of oral involvement have been reported in patients with neurofibromatosis 1 (NF1). Here, we analyze register-based associations between NF1 and hospital visits related to oral infections. The Finnish NF1 cohort encompasses all individuals with verified NF1 who have visited the Finnish central and university hospitals in 1987-2011. The Finnish Care Register for Health Care allowed the follow-up of 1349 individuals with NF1, their 1894 siblings without NF1, and 13,870 matched controls for diagnoses related to oral infections in 1998-2014. We observed clearly increased hazards for hospital visits associated with dental caries (ICD-10 K02; NF1 vs. controls, hazard ratio [HR] 4.42, 95% CI 3.23-6.04), diseases of pulp and periapical tissues (K04; HR 3.85, 95% CI 2.68-5.54), and gingivitis and periodontal diseases (K05; HR 3.63, 95% CI 2.37-5.56). In contrast, hospital visits related to diseases of salivary glands (K11), and stomatitis and related lesions (K12) did not show significantly increased hazard in NF1 compared with the controls or the non-NF1 siblings. In conclusion, the findings suggest that hospital visits related to oral infections are relatively common among individuals with NF1. The results highlight the need for early detection, proactive prevention, and timely treatment of oral infections in individuals with NF1.

Interplay between dental caries pathogens, periodontal pathogens, and sugar molecules: approaches for prevention and treatment.

Globally, oral diseases affect nearly 3.5 billion people, accounting for 4.6% of the healthcare expenditure. Common oral diseases include dental caries and periodontal disease, associated with biofilms formed by cariogenic pathogens. Epidemiological studies associate carbohydrates with these diseases due to  the sugars metabolized by cariogenic pathogens. This review focuses on dental caries and periodontal pathogens, quorum sensing, lectin-carbohydrate interactions, and various sugar molecules. Cariogenic sugars significantly influence biofilms by enhancing pathogen adhesion, viability, and gene expressions associated with biofilm formation. Moreover, lectin-carbohydrate interactions contribute to biofilm stability. Disrupting these interactions is a potential strategy for oral disease prevention. The use of nanoparticles, such as quantum dots, provides novel insights into lectin-sugar interactions and the development of inhibitors. Additionally, nanomaterials like calcium phosphate nanoparticles neutralize acids and inhibit microbial growth. This overview emphasizes understanding the relationships between oral diseases, microbial communities, and sugars to devise preventive and therapeutic strategies against oral diseases.

Dental Caries a Risk Factor for Intracerebral Hemorrhage.

INTRODUCTION: Streptococcus mutans is a known cause of dental caries that contains a collagen-binding protein, Cnm, and exhibits inhibition of platelet aggregation and matrix metalloproteinase-9 activation. This strain has been linked to aggravation of experimental intracerebral hemorrhage (ICH) and may be a risk factor for ICH. The purpose of this study was to test the association between dental caries and incident ICH. METHODS: The presence of dental caries and periodontal disease was assessed in subjects from the Dental Atherosclerosis Risk in Communities (DARIC) study without prior stroke or ICH. This cohort was followed for incident ICH over a period of 10 years. Cox regression was used to compute crude and adjusted hazards ratio from the dental assessment. RESULTS: Among 6,315 subjects, dental surface caries and/or root caries were recorded in 1,338 (27%) subjects. Of those, 7 (0.5%) had incident ICH over a period of 10 years following the visit 4 assessment. Of the remaining 4,977 subjects, 10 (0.2%) had incident ICH. Those with dental caries versus those without dental caries were slightly younger (mean age 62.0 ± 5.7 vs. 62.4 ± 5.6, p = 0.012), had a greater proportion of males (51 vs. 44%, p < 0.001), African Americans (44 vs. 10%, p < 0.001), and were hypertensive (42 vs. 31%, p < 0.001). The association between caries and ICH was significant (crude HR 2.69, 95% CI 1.02-7.06) and strengthened after adjustment for age, gender, race, education level, hypertension, and periodontal disease (adjusted HR 3.88, 95% CI 1.34-11.24). CONCLUSION: Dental caries is a potential risk for incident ICH after caries detection. Future studies are needed to determine if treatment of dental caries can reduce the risk of ICH.

Bayesian modeling of spatially differentiated multivariate enamel defects of the children's primary maxillary central incisor teeth.

BACKGROUND: The analysis of dental caries has been a major focus of recent work on modeling dental defect data. While a dental caries focus is of major importance in dental research, the examination of developmental defects which could also contribute at an early stage of dental caries formation, is also of potential interest. This paper proposes a set of methods which address the appearance of different combinations of defects across different tooth regions. In our modeling we assess the linkages between tooth region development and both the type of defect and associations with etiological predictors of the defects which could be influential at different times during the tooth crown development. METHODS: We develop different hierarchical model formulations under the Bayesian paradigm to assess exposures during primary central incisor (PMCI) tooth development and PMCI defects. We evaluate the Bayesian hierarchical models under various simulation scenarios to compare their performance with both simulated dental defect data and real data from a motivating application. RESULTS: The proposed model provides inference on identifying a subset of etiological predictors of an individual defect accounting for the correlation between tooth regions and on identifying a subset of etiological predictors for the joint effect of defects. Furthermore, the model provides inference on the correlation between the regions of the teeth as well as between the joint effect of the developmental enamel defects and dental caries. Simulation results show that the proposed model consistently yields steady inferences in identifying etiological biomarkers associated with the outcome of localized developmental enamel defects and dental caries under varying simulation scenarios as deemed by small mean square error (MSE) when comparing the simulation results to real application results. CONCLUSION: We evaluate the proposed model under varying simulation scenarios to develop a model for multivariate dental defects and dental caries assuming a flexible covariance structure that can handle regional and joint effects. The proposed model shed new light on methods for capturing inclusive predictors in different multivariate joint models under the same covariance structure and provides a natural extension to a nested hierarchical model.

Impact of public health and patient-centered prevention strategies on periodontitis and caries as causes of tooth loss in high-income countries.

In high-income countries, the oral health of the population is influenced by public health interventions, widespread use of oral care products, dental practice measures, and the cost of dental treatment. We compiled information on changes of the prevalence of proximal and upstream determinants of periodontitis, caries, and tooth loss over the last three decades to outline their potential effects on changes of oral health during this period. Information was retrieved from repeated cross-sectional studies and from published literature. While both the prevalence of edentulism and the number of missing teeth (from the DMF-T index) decreased, the number of sound teeth as well as the total number of teeth increased. The prevalence of severe periodontitis was unchanged, whereas the prevalence of periodontal health and moderate periodontitis may have increased to a minor extent. Concerning oral health risk factors, the proportion of individuals with tertiary education increased, while smoking prevalence declined. More and more people used oral care products. Whether one reimbursement system worked better than another one in terms of tooth retention could not be elucidated. In tooth retention, population-wide use of fluoridated toothpastes had the greatest impact. To some extent, the higher number of teeth present may be related to the more frequent use of interdental cleaning aids and powered toothbrushes. Since there was no decrease in severe periodontitis in most cohorts, periodontal interventions probably contributed little to improved tooth retention.

Diet-derived circulating antioxidants, periodontitis and dental caries: A Mendelian randomization study.

BACKGROUND AND OBJECTIVE: Given the potential association between oxidative stress, periodontitis and dental caries, whether dietary supplementation with antioxidants is beneficial for periodontitis and dental caries has been widely reported, but remains controversial. This study aims to clarify these relationships through two-sample Mendelian randomization (MR) analysis. METHODS: Circulating antioxidants (copper, selenium, zinc, ascorbate, ß-carotene, lycopene, retinol and vitamin E) were derived from absolute circulating antioxidants and circulating antioxidant metabolites. Summary data of periodontitis and dental caries were obtained from two separate databases, respectively. We performed inverse-variance weighted (IVW) analysis separately in different databases, followed by meta-analysis. The robustness of results was examined by sensitivity analyses, including three complementary MR methods, heterogeneity and pleiotropy tests, and PhenoScanner query. RESULTS: IVW analysis showed that elevated levels of absolute circulating retinol reduced the risk of periodontitis (GLIDE: OR = 0.41, 95% CI = 0.18-0.95, p = .038, power = 100%; FinnGen: OR = 0.15, 95% CI = 0.04-0.54, p = .004, power = 100%). The pooled OR for periodontitis risk per unit increase of retinol is 0.30 (95% CI = 0.15-0.61, p = .001, I2 = 40.3%, power = 100%). No significant associations were noted for genetically predicted circulating antioxidants and dental caries risk. The sensitivity analyses yielded similar estimates. CONCLUSION: This study demonstrates that a negative causality between circulating retinol and periodontitis risk, and null linkage between circulating antioxidants and dental caries risk, suggesting potential strategies for the prevention and control of periodontitis.

Area-Level Factors of Dental Caries in Children and Adolescents in European Neighborhoods - a Systematic Review.

The WHO emphasizes the importance of taking area-level factors into account when formulating public health interventions. The aim of this systematic review was to identify which area-level factors are associated with children's dental caries in Europe and might therefore be a suitable starting point for public health interventions. We conducted a systematic review based on a search in PubMed, Web of Science, and Cochrane Library including all European studies on caries in children and their area-level factors published since the year 2000 in English or German. We included 39 studies and identified 13 area-level factors investigated in the literature: degree of urbanization, deprivation, mean housing price, gross-national product, mean level of education, unemployment proportion and income, density of supermarkets, snack bars and dental offices, health, diet, and crime. Rural residency and higher unemployment were weakly associated with poorer oral health regarding dental caries. Deprivation showed a stronger (inverse) association. For income, findings were ambiguous; studies showed associations in both directions. For the other determinants, the included studies found no association. Many studies reported associations between place of residence and children's dental caries, but the mediators on this causal path are still not clearly established. The area-level factors analyzed in this review seem to play a role, but more studies with designs that allow causal interpretation of findings are needed to establish solid robust evidence that can be used in the formulation of future health policies.

The association between dental caries and steroid-sensitive nephrotic syndrome in children.

BACKGROUND: Pathogenesis and relapse of steroid-sensitive nephrotic syndrome (SSNS) are primarily associated with infection. Dental caries is the most common chronic progressive oral infection in children. However, clinical studies of SSNS combined with dental caries in children are rare. METHODS: In our retrospective cohort study from January 2021 to June 2022, 145 children with SSNS were included in the baseline analysis and 105 in the follow-up analysis. The follow-up period was 1 year. The primary study endpoints were the relapse-free period and frequently relapsing nephrotic syndrome (FRNS). Secondary endpoints included the number and triggers of relapses and concomitant medications. RESULTS: The median age was 5.5 years, with a caries rate of 60.7%, the mean DMFT/dmft was 3.86, and the caries filling rate was 1.6%. Except for the lower proportion of high household income and high parental education observed in the caries group, no statistical differences were found when comparing the other baseline data with the non-caries group. The caries group had a shorter relapse-free period and a lower 1-year cumulative relapse-free survival rate (HR = 1.90, 95% CI 1.17-3.09, P = 0.009). Univariate regression analysis showed caries associated with FRNS (OR = 2.714, 95% CI 1.021-7.219, P = 0.045), but the correlation no longer remained in the multivariate analysis. Additionally, seven cases of caries-derived pulpal periapical inflammation triggered SSNS relapses. The caries group had more infection triggers and concomitant medication use. CONCLUSION: Dental caries and relapse of SSNS are potentially associated, but careful evaluation is needed.

Antineoplastic therapy is an independent risk factor for dental caries in childhood cancer patients: a retrospective cohort study.

PURPOSE: To evaluate the antineoplastic therapy (AT) as a risk factor for dental caries lesions independent of other risk factors such as income, family education, stimulated salivary flow rate, hygiene habits, frequency of sugar intake, and microbiota in childhood cancer (CC) patients. METHODS: 72 individuals were divided into CC patients (n=36) and healthy individuals (control group - CT n=36). Demographic data, hygiene habits, frequency of sugar intake, CC type, and AT were collected. Stimulated salivary flow rate was measured and the presence and concentration of Streptococcus mutans were assessed using a real-time polymerase chain reaction (qPCR) technique. Clinical evaluations included plaque index (PI) and decayed-missing-filled-teeth index (dmft/DMFT). Descriptive statistics, T-test, Mann-Whitney test, chi-square test, Fisher's exact test, and two-way analysis of variance were used for data analysis (p<0.05). RESULTS: At the time of oral evaluation, both groups exhibited similar ages with means of 12.0±3.9 years old for CC and 12.0±4.0 years old for CT patients. All CC patients underwent chemotherapy with nine also undergoing radiotherapy. Significant differences were observed between the groups in terms of color/race, income, family education, and hygiene habits. However, no statistically significant differences were found between groups regarding the frequency of sugar intake, stimulated salivary flow rate, or the concentration of Streptococcus mutans (qPCR technique). For clinical parameters, the DMF (CC:1.80, CT: 0.75), decayed (CC: 0.88, CT: 0.19), missing (CC: 0.25, CT:0), and PI (CC: 30.5%, CT: 22.6%) were higher in the CC group (p<0.05). CONCLUSION: Childhood cancer (CC) patients undergoing antineoplastic therapy (AT) exhibit a higher prevalence of dental caries, regardless of income/education, frequency of sugar intake, stimulated salivary flow rate, and microbiota.

Radiation-induced xerostomia and cariogenic dietary habits.

PURPOSE: Despite the availability of various prevention methods, dental caries continue to be diagnosed in patients receiving head and neck radiotherapy (RT). Since conventional approaches do not evaluate posttreatment alterations in dietary behaviors, we aimed to assess the influence of radiation-induced xerostomia on post-RT cariogenic dietary habits in patients. METHODS: Fifty-seven patients completed the Xerostomia Questionnaire (XQ) and answered questions regarding daily cariogenic food and beverage (CFB) intake, daily tooth brushing, fluoride application, and subjective total taste acuity (STTA). They also underwent evaluations to determine the Simplified Oral Hygiene Index (OHI-S) score, Saxon test score, number of decayed-missing-filled teeth (DMFT), and proportion of DMFT to the test teeth (DMFT rate). Clinical records were searched for information regarding RT modalities, including the median of the mean dose to the parotid glands, days after the completion of RT, submandibular gland resection, whole-neck irradiation, and the DMFT value and rate before RT. The patients were divided into low and high XQ score groups based on the median XQ score of 47.5 for the two sample tests. Univariable and multivariable regression analyses were used to identify independent factors for frequent CFB intake. RESULTS: Higher XQ scores were associated with a significantly greater frequency of CFB intake (p = 0.028*). Regression analysis also identified a higher XQ score (p = 0.017*) as an independent risk factor for frequent CFB intake. CONCLUSION: Radiation-induced xerostomia increased the frequency of CFB intake.