Impact of licit and illicit substances on the oral health-related quality of life in adolescents.

OBJECTIVE: To assess the impact of the consumption of licit and illicit substances on the oral health-related quality of life (OHRQoL) of adolescents from public schools in the south of Brazil. METHODS: This cross-sectional study was carried out with a random sample of adolescents aged between 17 and 18 years old from Santa Maria, Brazil. The consumption of licit and illicit substances was measured through a self-administered questionnaire with questions from the National Survey of Scholar Health. The OHRQoL was collected using the Brazilian short version of Child Perceptions Questionnaire 11-14 (CPQ11-14). Multilevel Poisson regression models were used to estimate the association between the outcome and the explanatory variables where the adolescents (first level) were nested in their schools (second level). RESULTS: A total of 768 adolescents were evaluated. Of these, about 15.6% have already used illegal substances. Adolescents who reported the use of illicit substances had 28% higher CPQ11-14 scores when compared to their counterparts. Alcohol use was also related to worse levels of OHRQoL, while the consumption of cigarettes acted as a protective factor. CONCLUSIONS: This study found an association between the use of alcohol and illicit drugs with worse levels of OHRQoL.

Fundamental Determinants of the Accuracy of Equilibrium Constants for Affinity Complexes.

The equilibrium constant of a chemical reaction is arguably the key thermodynamic parameter in chemistry; we naturally expect that equilibrium constants are determined accurately. The majority of equilibrium constants determined today are those of binding reactions that form affinity complexes, such as protein-protein, protein-DNA, and protein-small molecule. There is growing awareness that the determination of equilibrium constants for highly stable affinity complexes may be very inaccurate. However, fundamental (i.e., method-independent) determinants of accuracy are poorly understood. Here, we present a study that explicitly shows what the accuracy of equilibrium constants of affinity complexes depends on. This study reveals the critical importance of the choice of concentration of interacting components and creates a theoretical foundation for improving the accuracy of the equilibrium constants. The predicted influence of concentrations on accuracy was confirmed experimentally. The results of this fundamental study provide instructive guidance for experimentalists independently on the method they use.

Cycloguanil and Analogues Potently Target DHFR in Cancer Cells to Elicit Anti-Cancer Activity.

Dihydrofolate reductase (DHFR) is an established anti-cancer drug target whose inhibition disrupts folate metabolism and STAT3-dependent gene expression. Cycloguanil was proposed as a DHFR inhibitor in the 1950s and is the active metabolite of clinically approved plasmodium DHFR inhibitor Proguanil. The Cycloguanil scaffold was explored to generate potential cancer therapies in the 1970s. Herein, current computational and chemical biology techniques were employed to re-investigate the anti-cancer activity of Cycloguanil and related compounds. In silico modeling was employed to identify promising Cycloguanil analogues from NCI databases, which were cross-referenced with NCI-60 Human Tumor Cell Line Screening data. Using target engagement assays, it was found that these compounds engage DHFR in cells at sub-nanomolar concentrations; however, growth impairments were not observed until higher concentrations. Folinic acid treatment rescues the viability impairments induced by some, but not all, Cycloguanil analogues, suggesting these compounds may have additional targets. Cycloguanil and its most promising analogue, NSC127159, induced similar metabolite profiles compared to established DHFR inhibitors Methotrexate and Pyrimethamine while also blocking downstream signaling, including STAT3 transcriptional activity. These data confirm that Cycloguanil and its analogues are potent inhibitors of human DHFR, and their anti-cancer activity may be worth further investigation.

Impact of the use of dental services on dental pain according to adolescents' skin colour: a 10-year cohort.

OBJECTIVE: Evaluate the association of the interaction between the use of dental services and the skin colour on the occurrence of dental pain over time. MATERIAL AND METHODS: This study is a cohort with 10 years of follow-up, started in 2010 with a sample of 639 preschool children (1-5 years old). The use of dental services, race and the presence of dental pain were self-reported by the individuals according to predefined criteria. Multilevel logistic regression analysis was performed to assess the interaction between skin colour and use of dental services in the occurrence of dental pain over time. RESULTS: About 449 and 429 were reassessed in 2017 and 2020, respectively. The occurrence of dental pain across the cohort was 60.7%. Caucasian individuals who used dental services throughout the cohort had a 51% lower chance of having a dental pain than those who used dental services but were non-white (OR 0.49; 95% IC 0.27-0.90). CONCLUSION: There was a racial inequity in the occurrence of dental pain among individuals who managed to make use of dental services throughout the follow-ups. CLINICAL RELEVANCE: The differences found should serve as a warning to the way how individuals with different characteristics are treated and must be used to combat this inequity. Individuals should receive resolute and personalized treatments according to their clinical condition and not according to their socioeconomic characteristics.

Pathways between toothache and children's oral health-related quality of life.

BACKGROUND: Toothache is considered a multifactorial health problem that is associated with oral diseases and comorbidities. AIM: Evaluate the direct and indirect pathways between toothache and children's oral health-related quality of life (COHRQoL). DESIGN: This is a cross-sectional study conducted with a random sample of children from southern Brazil. The variables included demographic, socioeconomic, behavioral, and oral health characteristics. Toothache was collected through the question 'Have you had toothache in the last 12 months?'. COHRQoL was collected by the Child Perceptions Questionnaire 8-10 in his Brazilian version. The pathways between the associated variables, toothache, and COHRQoL were analyzed through structural equation modeling. RESULTS: A total of 449 schoolchildren were evaluated. The prevalence of toothache was 50.1% (95% confidence interval: 45.4%-54.8%). The poorer COHRQoL was directly affected by the presence of toothache. Considering the indirect pathways, the low household income, high household crowding, low age, the use of public health service, and the untreated dental caries influenced indirectly in the worst COHRQoL via toothache. CONCLUSION: This study determined that COHRQoL was directly influenced by toothache. Meanwhile, indirect pathways were observed. These findings justify initiatives that highlight the importance of the reduction of oral diseases that can lead to pain experiences.