Prenatal exposure to environmental phenols and phthalates and altered patterns of DNA methylation in childhood.

INTRODUCTION: Epigenetic marks are key biomarkers linking the prenatal environment to health and development. However, DNA methylation associations and persistence of marks for prenatal exposure to multiple Endocrine Disrupting Chemicals (EDCs) in human populations have not been examined in great detail. METHODS: We measured Bisphenol-A (BPA), triclosan, benzophenone-3 (BP3), methyl-paraben, propyl-paraben, and butyl-paraben, as well as 11 phthalate metabolites, in two pregnancy urine samples, at approximately 13 and 26 weeks of gestation in participants of the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study (N = 309). DNA methylation of cord blood at birth and child peripheral blood at ages 9 and 14 years was measured with 450K and EPIC arrays. Robust linear regression was used to identify differentially methylated probes (DMPs), and comb-p was used to identify differentially methylated regions (DMRs) in association with pregnancy-averaged EDC concentrations. Quantile g-computation was used to assess associations of the whole phenol/phthalate mixture with DMPs and DMRs. RESULTS: Prenatal BPA exposure was associated with 1 CpG among males and Parabens were associated with 10 CpGs among females at Bonferroni-level significance in cord blood. Other suggestive DMPs (unadjusted p-value < 1 × 10-6) and several DMRs associated with the individual phenols and whole mixture were also identified. A total of 10 CpG sites at least suggestively associated with BPA, Triclosan, BP3, Parabens, and the whole mixture in cord blood were found to persist into adolescence in peripheral blood. CONCLUSIONS: We found sex-specific associations between prenatal phenol exposure and DNA methylation, particularly with BPA in males and Parabens in females. Additionally, we found several DMPs that maintained significant associations with prenatal EDC exposures at age 9 and age 14 years.

Prenatal blood metals, per- and polyfluoroalkyl substances and antigen- or mitogen-stimulated cord blood lymphocyte proliferation and cytokine secretion.

BACKGROUND: Evidence suggests that prenatal per- and polyfluoroalkyl substances (PFAS) and metals, two classes of chemicals found ubiquitously in human populations, influence immune system development and response. OBJECTIVE: We evaluated whether first trimester blood PFAS and metals were associated with antigen- or mitogen-stimulated cord blood lymphocyte proliferation and cytokine secretion. METHODS: We measured six PFAS, as well as six nonessential and four essential metals, in first trimester blood from participants in the longitudinal pre-birth Project Viva cohort, recruited between 1999 and 2000 in eastern Massachusetts. We measured antigen- or mitogen-stimulated cord blood mononuclear cell proliferation responses (n = 269-314) and cytokine secretion (n = 217-302). We used covariate-adjusted least absolute shrinkage and selection operator (LASSO) for variable selection and multivariable regression to estimate associations with the immune markers. RESULTS: Each ng/mL of MeFOSAA was associated with a 3.6% (1.4, 5.8) higher lymphocyte proliferation response after stimulation with egg antigen, as well as 0.8 (0.7, 1.0) reduced odds of having IFN-γ detected in response to dust mite. Each ng/g increment of cesium was associated with 27.8% (-45.1, -4.9) lower IL-10 levels in response to dust mite. Each ng/g increment of mercury was associated with 12.0% (1.3, 23.8) higher IL-13 levels in response to mitogen PHA. Each ng/g increment of selenium and zinc was associated with 0.2% (0.01, 0.4) and 0.01% (0.002, 0.02) higher TNF-α in response to mitogen PHA, respectively. CONCLUSIONS: Prenatal metals and PFAS influence cord blood lymphocyte proliferation and cytokine secretion in ways that may increase risk for atopic disease in childhood.

First trimester prenatal metal mixtures, vitamins, and hypertensive disorders of pregnancy in the project viva cohort.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) such as preeclampsia and gestational hypertension are major contributors to maternal and child morbidity and mortality. Previous studies have reported associations with selected metals and vitamins but are limited in sample size and non-prospective study designs. We evaluated prospective associations of metal mixtures with HDP and tested interactions by vitamins. STUDY DESIGN: We measured first trimester (median = 10.1 weeks) concentrations of essential (copper, magnesium, manganese, selenium, zinc) and nonessential (arsenic, barium, cadmium, cesium, mercury, lead) metals in red blood cells (n = 1,386) and vitamins (B12 and folate) in plasma (n = 924) in Project Viva, a pre-birth US cohort. We collected diagnosis of HDP by reviewing medical records. We used multinomial logistic regression and Bayesian Kernel Machine Regression to estimate individual and joint associations of metals with HDP and interactions by vitamins, after adjusting for key covariates. RESULTS: The majority of participants were non-Hispanic white (72.5 %), never smokers (68.5 %) with a mean (SD) age of 32.3 (4.6) years. Fifty-two (3.8 %) developed preeclampsia and 94 (6.8 %) gestational hypertension. A doubling in first trimester erythrocyte copper was associated with 78 % lower odds of preeclampsia (OR=0.22, 95 % confidence interval: 0.08, 0.60). We also observed significant associations between higher erythrocyte total arsenic and lower odds of preeclampsia (OR=0.80, 95 % CI: 0.66, 0.97) and higher vitamin B12 and increased odds of gestational hypertension (OR=1.79, 95 % CI: 1.09, 2.96), but associations were attenuated after adjustment for dietary factors. Lower levels of the overall metal mixture and essential metal mixture were associated with higher odds of preeclampsia. We found no evidence of interactions by prenatal vitamins or between metals. CONCLUSION: Lower levels of a first-trimester essential metal mixture were associated with an increased risk of preeclampsia, primarily driven by copper. No associations were observed between other metals and HDP after adjustment for confounders and diet.

Telehealth Parenting Program and Salivary Epigenetic Biomarkers in Preschool Children With Developmental Delay: NIMHD Social Epigenomics Program.

Importance: Children with developmental delays are at a heightened risk of experiencing mental health challenges, and this risk is exacerbated among racially minoritized children who face disproportionate adversity. Understanding the impact of parenting interventions on biological markers associated with these risks is crucial for mitigating long-term health disparities. Objective: To examine the effect of 20 weeks of an internet-based parent-child interaction training (iPCIT) program on biomarkers associated with aging and chronic inflammation among preschoolers with developmental delay at 12-month follow-up. Design, Setting, and Participants: An observational secondary analysis of data from a randomized clinical trial conducted from March 17, 2016, to December 15, 2020, to assess changes in salivary DNA methylation (DNAm)-derived biomarkers following iPCIT intervention. Participants were recruited from 3 Part C early intervention sites in a large southeastern US city. Eligible participants included children recruited within 3 months of their third birthday who had a Child Behavior Checklist Externalizing Problems T score greater than 60 and provided saliva in at least 1 study wave. Data analysis was conducted May 2023 to April 2024. Intervention: Participants received either iPCIT (a telehealth therapeutic intervention focused on enhancing the parent-child relationship and addressing behavioral challenges in young children) or referrals as usual. Main Outcomes and Measures: DNAm at the 12-month follow-up was assessed using the Infinium HumanMethylationEPIC Bead Chip Assay to derive biomarkers DunedinPACE, C-reactive protein (CRP), and interleukin-6 (IL-6). Analyses were intent-to-treat and used path analysis. Results: A total of 71 children (mean [SD] age, 36.27 [0.61] months 51 male [71.8%] and 20 female [28.2%]) were analyzed, of whom 34 received iPCIT and 37 received referrals as usual. The iPCIT group had a slower pace of aging (ß = 0.26; 95% CI, 0.06 to 0.50; P = .03) and less DNAm-derived CRP (ß = 0.27; 95% CI, 0.05 to 0.49; P = .01) relative to the control condition at the 12-month follow-up. These associations remained significant after accounting for baseline DNAm score, child demographics, and symptom severity, and were independent of predicted buccal epithelial cell proportion for both DunedinPACE and CRP. There was no association with DNAm-derived IL-6 (ß = 0.14; 95% CI, -0.08 to 0.36; P = .21). Conclusions and Relevance: In this study of a parenting intervention, iPCIT, the association of intervention with decreased molecular markers of inflammation and biological aging suggests their potential to modify aspects of the biological embedding of stress. Understanding the systemic biological impact of such interventions offers insights into addressing health disparities and promoting resilience among vulnerable populations. Trial Registration: ClinicalTrials.gov Identifier: NCT03260816.

Prenatal Maternal Occupation and Child Epigenetic Age Acceleration in an Agricultural Region: NIMHD Social Epigenomics Program.

Importance: Research on fetal epigenetic programming suggests that the intrauterine environment can have long-term effects on offspring disease susceptibility. Objective: To examine the association between prenatal maternal occupation and child epigenetic age acceleration (EAA) among a farmworker community. Design, Setting, and Participants: This cohort study included participants in the Center for the Health Assessment of Mothers and Children of Salinas, a prospective, Latino, prebirth cohort. Pregnant women were recruited from October 1, 1999, to October 1, 2000, from 6 community clinics in California's Salinas Valley agricultural region. Participants were 18 years or older, English or Spanish speaking, Medicaid eligible, and at 20 weeks' gestation or earlier at enrollment. Mother-child pairs who had blood DNA methylation measured at the ages of 7, 9, and 14 years were included. Data were analyzed from July 2021 to November 2023. Exposures: Prenatal maternal occupation was ascertained through study interviews conducted during prenatal visits and shortly after delivery. Main Outcomes and Measures: Child EAA at 7, 9, and 14 years of age was estimated using DNA methylation-based epigenetic age biomarkers. Three EAA measures were calculated: the Horvath EAA, skin and blood EAA, and intrinsic EAA. Linear mixed-effects models were used to estimate longitudinal associations of prenatal maternal occupation and child EAA, adjusting for confounders and prenatal organophosphate pesticide exposure. Results: Analyses included 290 mother-child pairs (mean [SD] maternal age at delivery, 26.5 [5.2] years; 152 [52.4%] female infants); 254 mothers (87.6%) were born in Mexico, 33 (11.4%) in the US, and 3 (1.0%) in other countries; and 179 families (61.7%) were below the federal poverty line during pregnancy. Mothers reported engaging in several types of work during pregnancy, including agricultural fieldwork (90 [31.0%]), other agricultural work (40 [13.8%]), nonagricultural work (53 [18.3%]), or no work (107 [36.9%]). Children whose mothers worked in agricultural fields during pregnancy had a mean of 0.66 (95% CI, 0.17-1.15) years of greater Horvath EAA, 0.62 (95% CI, 0.31-0.94) years of greater skin and blood EAA, and 0.45 (95% CI, 0.07-0.83) years of greater intrinsic EAA compared with children whose mothers did not work during pregnancy. Conclusions and Relevance: In this cohort study, prenatal maternal agricultural fieldwork was associated with accelerated childhood epigenetic aging independent of organophosphate pesticide exposure. Future research on which factors related to agricultural fieldwork accelerate aging in the next generation can inform targeted prevention programs and policies that protect children's health.

Ambient air pollution and urological cancer risk: A systematic review and meta-analysis of epidemiological evidence.

Exposure to ambient air pollution has significant adverse health effects; however, whether air pollution is associated with urological cancer is largely unknown. We conduct a systematic review and meta-analysis with epidemiological studies, showing that a 5 µg/m3 increase in PM2.5 exposure is associated with a 6%, 7%, and 9%, increased risk of overall urological, bladder, and kidney cancer, respectively; and a 10 µg/m3 increase in NO2 is linked to a 3%, 4%, and 4% higher risk of overall urological, bladder, and prostate cancer, respectively. Were these associations to reflect causal relationships, lowering PM2.5 levels to 5.8 µg/m3 could reduce the age-standardized rate of urological cancer by 1.5 ~ 27/100,000 across the 15 countries with the highest PM2.5 level from the top 30 countries with the highest urological cancer burden. Implementing global health policies that can improve air quality could potentially reduce the risk of urologic cancer and alleviate its burden.

Precision medicine for asthma treatment: Unlocking the potential of the epigenome and microbiome.

Asthma is a leading worldwide biomedical concern. Patients can experience life-threatening worsening episodes (exacerbations) usually controlled by anti-inflammatory and bronchodilator drugs. However, substantial heterogeneity in treatment response exists, and a subset of patients with unresolved asthma carry the major burden of this disease. The study of the epigenome and microbiome might bridge the gap between human genetics and environmental exposure to partially explain the heterogeneity in drug response. This review aims to provide a critical examination of the existing literature on the microbiome and epigenetic studies examining associations with asthma treatments and drug response, highlight convergent pathways, address current challenges, and offer future perspectives. Current epigenetic and microbiome studies have shown the bilateral relationship between asthma pharmacologic interventions and the human epigenome and microbiome. These studies, focusing on corticosteroids and to a lesser extent on bronchodilators, azithromycin, immunotherapy, and mepolizumab, have improved the understanding of the molecular basis of treatment response and identified promising biomarkers for drug response prediction. Immune and inflammatory pathways (eg, IL-2, TNF-α, NF-κB, and C/EBPs) underlie microbiome-epigenetic associations with asthma treatment, representing potential therapeutic pathways to be targeted. A comprehensive evaluation of these omics biomarkers could significantly contribute to precision medicine and new therapeutic target discovery.

Fabrication and characterization of physically crosslinked alginate/chitosan-based hydrogel loaded with neomycin for the treatment of skin infections caused by Staphylococcus aureus.

Staphylococcus aureus is a pathogen widely involved in wound infection due to its ability to release several virulence factors that impair the skin healing process, as well as its mechanism of drug resistance. Herein, sodium alginate and chitosan were combined to produce a hydrogel for topical delivery of neomycin to combat S. aureus associated with skin complications. The hydrogel was formulated by combining sodium alginate (50 mg/mL) and chitosan (50 mg/mL) solutions in a ratio of 9:1 (HBase). Neomycin was added to HBase to achieve a concentration of 0.4 mg/mL (HNeo). The incorporation of neomycin into the product was confirmed by scanning electron microscopy, FTIR and TGA analysis. The hydrogels produced are homogeneous, have a high swelling capacity, and show biocompatibility using erythrocytes and fibroblasts as models. The formulations showed physicochemical and pharmacological stability for 60 days at 4 ± 2 °C. HNeo totally inhibited the growth of S. aureus after 4 h. The antimicrobial effects were confirmed using ex vivo (porcine skin) and in vivo (murine) wound infection models. Furthermore, the HNeo-treated mice showed lower severity scores than those treated with HBase. Taken together, the obtained results present a new low-cost bioproduct with promising applications in treating infected wounds.

Epigenome-wide association study of lung cancer among never smokers in two prospective cohorts in Shanghai, China.

BACKGROUND: The aetiology of lung cancer among individuals who never smoked remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Epigenetic alterations, particularly DNA methylation (DNAm) changes, have emerged as potential drivers. Yet, few prospective epigenome-wide association studies (EWAS), primarily focusing on peripheral blood DNAm with limited representation of never smokers, have been conducted. METHODS: We conducted a nested case-control study of 80 never-smoking incident lung cancer cases and 83 never-smoking controls within the Shanghai Women's Health Study and Shanghai Men's Health Study. DNAm was measured in prediagnostic oral rinse samples using Illumina MethylationEPIC array. Initially, we conducted an EWAS to identify differentially methylated positions (DMPs) associated with lung cancer in the discovery sample of 101 subjects. The top 50 DMPs were further evaluated in a replication sample of 62 subjects, and results were pooled using fixed-effect meta-analysis. RESULTS: Our study identified three DMPs significantly associated with lung cancer at the epigenome-wide significance level of p<8.22×10-8. These DMPs were identified as cg09198866 (MYH9; TXN2), cg01411366 (SLC9A10) and cg12787323. Furthermore, examination of the top 1000 DMPs indicated significant enrichment in epithelial regulatory regions and their involvement in small GTPase-mediated signal transduction pathways. Additionally, GrimAge acceleration was identified as a risk factor for lung cancer (OR=1.19 per year; 95% CI 1.06 to 1.34). CONCLUSIONS: While replication in a larger sample size is necessary, our findings suggest that DNAm patterns in prediagnostic oral rinse samples could provide novel insights into the underlying mechanisms of lung cancer in never smokers.

Protocol for CARES-HAPIN: an ambidirectional cohort study on exposure to environmental tobacco smoke and risk of early childhood caries.

INTRODUCTION: Prenatal and postnatal exposure to environmental tobacco smoke (ETS) has been linked with early childhood caries (ECC), but the specific molecular mechanisms and pathways remain largely unknown. The Caries Risk from exposure to Environmental tobacco Smoke (CARES) within the Household Air Pollution Intervention Network (HAPIN) study aims to establish the association between ETS and ECC by employing epidemiological and novel biomarker-based approaches. Here, we outline the overall design and rationale of the project. METHODS AND ANALYSIS: We will leverage the infrastructure and data from the HAPIN trial (India) to mount the CARES study. In this ambidirectional cohort study, children (n=735, aged: 3-5 years) will undergo ECC examination by a trained dentist using standard criteria and calibrated methods. Structured questionnaires will be used to gather information on sociodemographic variables, dietary habits, oral hygiene, oral health-related quality of life and current exposure to ETS. We will collect non-invasive or minimally invasive biospecimens (i.e., saliva, buccal cells, dried blood spots and urine) from a subset of HAPIN children (n=120) to assess a battery of biomarkers indicative of exposure to ETS, early biological effect and epigenetic modifications. Both self-reported and objective measures of ETS exposure collected longitudinally during in utero and early postnatal periods will be accessed from the HAPIN database. We will apply current science data techniques to assess the association and interrelationships between ETS, ECC, and multiple biomarkers. ETHICS AND DISSEMINATION: Information gathered in this research will be published in peer-reviewed journals and summaries will be shared with the key stakeholders as well as patients and their parents/guardians involved in this study. Sri Ramachandra Institute of Higher Education and Research Ethics Board has approved the study protocol (IEC-NI22/JUL/83/82). TRIAL REGISTRATION NUMBER: NCT02944682.

Maternal age is related to offspring DNA methylation: A meta-analysis of results from the PACE consortium.

Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta-analyzed epigenome-wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5-10 years old) from the Pregnancy and Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites in 13 loci with DNAm associated with maternal age (PFDR < 0.05). Eight of these CpGs were located near/in the MTNR1B gene, coding for a melatonin receptor. Regional analysis identified them together as a differentially methylated region consisting of 9 CpGs in/near MTNR1B, at which higher DNAm was associated with greater maternal age (PFDR = 6.92 × 10-8) in newborns. In childhood blood samples, these differences in blood DNAm of MTNR1B CpGs were nominally significant (p < 0.05) and retained the same positive direction, suggesting persistence of associations. Maternal age was also positively associated with higher DNA methylation at three CpGs in RTEL1-TNFRSF6B at birth (PFDR < 0.05) and nominally in childhood (p < 0.0001). Of the remaining 10 CpGs also persistent in childhood, methylation at cg26709300 in YPEL3/BOLA2B in external data was associated with expression of ITGAL, an immune regulator. While further study is needed to establish causality, particularly due to the small effect sizes observed, our results potentially support offspring DNAm as a mechanism underlying associations of maternal age with child health.

Evaluation of Microbiological Susceptibility and Long-term Adhesive Properties to Dentin of Primers with Terminalia catappa Linn.

PURPOSE: To investigate the antibacterial effects of Terminalia catappa Linn (TCL) leaf extracts at different concentrations and the effects of these extracts used as primers on the long-term adhesive properties of two universal adhesives. MATERIALS AND METHODS: After extract preparation, the antimicrobial and antibacterial activities of TCL against Streptococcus mutans (UA 159) were assessed in microdilution assays to provide the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). Additionally, to provide quantitative data on the ability of TCL extract to reduce cell viability, colony forming units (CFU) were counted. To examine adhesive properties, 288 human molars were randomly assigned to 32 experimental conditions (n = 9) according to the following variables: (1) treatment agent: negative control (untreated surface), and primers at concentrations of 1xMIC, 5xMIC, and 10xMIC; (2) adhesives: Scotchbond Universal (SBU) and Futurabond Universal (FBU); (3) adhesive strategy: etch-and-rinse (ER) or self-etch (SE); and (4) storage time: 24 h or after 2 years. Primers were applied for 60 s, upon which the teeth were incrementally restored and sectioned into adhesive-dentin bonded sticks. These were tested for microtensile bond strength (µTBS) and nanoleakage (NL) after 24-h and 2-year water storage, as well as in-situ degree of conversion (DC) at 24 h. The chemical profile of the hybrid layer was determined via micro-Raman spectroscopy. Biofilm assay data were analyzed using the Kruskal-Wallis test; the pH of culture media and the chemical profile were analyzed by one-way ANOVA. The adhesive properties (µTBS, NL, DC) were evaluated using a four-way ANOVA and Tukey's test. Significance was set at 5%. RESULTS: Similar values of MIC and MBC were observed (2 mg/ml), showing bactericidal potential. CFU analysis demonstrated that concentrations of 5xMIC and 10xMIC significantly inhibited biofilm formation (p < 0.001). The application of the TCL primer at all concentrations significantly increased the immediate µTBS and DC, and decreased the immediate NL values when compared to the control group (p < 0.05), regardless of the adhesive and adhesive strategies. Despite an increase in the NL values for all groups after 2 years (p > 0.05), in groups where the TCL primer was applied, the µTBS remained constant after 2 years for both adhesives, while a decrease in the µTBS was observed in the control groups (p < 0.05). Usually, 10xMIC showed better results than 1xMIC and 5xMIC (p < 0.05). The application of TCL promoted cross-linking; cross-linking rates increased proportionally to the concentration of TCL (p < 0.05). CONCLUSION: Primers containing TCL promoted bactericidal and bacteriostatic action, as well as cross-linking with dentin, while maintaining the adhesive properties of the adhesive-dentin interface after 2 years of water storage.

Air pollution mixture associated with oxidative stress exacerbation and symptoms deterioration in allergic rhinitis patients: Evidence from a panel study.

With allergic rhinitis (AR) on the rise globally, there has been a growing focus on the role of environmental pollutants in the onset of AR. However, the potential mechanisms by how and which these pollutants exacerbate AR conditions remain unknown. This panel study of 49 patients diagnosed with AR over one year aimed to assess the individual and combined effects of short-term exposure to multiple ambient pollutants on oxidative stress, symptoms, and quality of life among patients with AR. All participants underwent four repeated assessments of health conditions and personal environmental exposures (PM2.5, O3, SO2, and NO2) over warm and cold seasons during 2017-2018. We evaluated two oxidative stress biomarkers (malondialdehyde [MDA], and superoxide dismutase [SOD]) via nasal lavage. We collected information on self-reported symptoms and quality of life using the Rhinitis Symptom Scale (SRS), the Visual Analog Scale (VAS), and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) through in-person interviews. Bayesian kernel machine regression (BKMR) was used to evaluate the joint effects of pollutant mixture and identify key contributors. The results revealed a significant association of the pollutant mixture when all four pollutants were at or above their median levels, with increased oxidative stress. This was evidenced by elevated MDA and reduced SOD. We found a joint detrimental effect of the pollutant mixture on AR symptoms with a strong association with increased SRS scores, but a non-significant positive association with VAS and RQLQ scores. PM2.5, O3, and SO2 presented as the potentially primary contributors to the adverse health effects associated with the pollutant mixture in Taiyuan city. Patients with AR exposed to short-term air pollutant mixture are more likely to have greater nasal symptoms and worse quality of life from increased oxidative stress and reduced antioxidant capacity. Further research is warranted to better elucidate the underlying mechanisms.

Influence of silver fluoride plus potassium iodine on adhesive properties of primary carious dentin-resin interface: An in vitro study.

This paper evaluated the influence of different protocols of silver fluoride (SF) pretreatment of artificial carious lesions on the adhesive interface of composite resin restorations and remineralization of deciduous dentin compared to silver diamine fluoride (SDF). Sixty-four deciduous molar teeth were randomly divided into 8 groups (n = 8) according to the restoration time (immediately - IM; 30 days after SDF/SF treatment - 30 D) and treatment before restoration (SDF 38 %; SDF 38 % + potassium iodide - KI; SF 38 %; SF 38 % +KI). After SDF/SF application, teeth in the IM group were restored with self-etch universal adhesive system/composite resin. Samples in the 30D groups were stored in artificial saliva (37 °C) for 30 days before receiving the same restoring protocol. Beams were obtained from all groups and subjected to bond strength tests (µTBS), ultrastructural qualitative analysis (FEG) and mineral analysis (SEM/EDX; Micro-Raman spectroscopy). The µTBS data were subjected to three-factor ANOVA and multiple comparisons (Holm-Sidak method). Bond strength values (MPa) for IM groups were 16.9 ± 2.7 (SDF); 17.6 ± 3.5 (SDF + KI); 16.8 ± 5.5 (SF); 18.4 ± 4.1 (SF + KI); and 14.9 ± 4.2 (SDF); 16.0 ± 5.4 (SDF + KI); 14.1 ± 3.6(SF); 16.4 ± 5.4 (SF + KI) for 30D groups. Bond strength wasn't influenced by the moment of restoration (IM or 30D); the use of KI didn't alter adhesion characteristics; SDF/SF solutions resulted in similar adhesive strength; calcium and phosphate expressions were identified at the interfaces on IM and 30D moments. However, 30D presented qualitative increase in these ions, compatible with remineralization. It was concluded that the adhesion of composite resin restorations in artificial caries lesions of deciduous teeth treated with SDF (38 %) and SF (38 %) had similar effects in vitro; the use of KI or the moment when restorations were accomplished did not influence the adhesion and all tested protocols promoted remineralization of carious dentin.

Associations of prenatal one-carbon metabolism nutrients and metals with epigenetic aging biomarkers at birth and in childhood in a US cohort.

Epigenetic gestational age acceleration (EGAA) at birth and epigenetic age acceleration (EAA) in childhood may be biomarkers of the intrauterine environment. We investigated the extent to which first-trimester folate, B12, 5 essential, and 7 non-essential metals in maternal circulation are associated with EGAA and EAA in early life. Bohlin EGAA and Horvath pan-tissue and skin and blood EAA were calculated using DNA methylation measured in cord blood (N=351) and mid-childhood blood (N=326; median age = 7.7 years) in the Project Viva pre-birth cohort. A one standard deviation increase in individual essential metals (copper, manganese, and zinc) was associated with 0.94-1.2 weeks lower Horvath EAA at birth, and patterns of exposures identified by exploratory factor analysis suggested that a common source of essential metals was associated with Horvath EAA. We also observed evidence nonlinear associations of zinc with Bohlin EGAA, magnesium and lead with Horvath EAA, and cesium with skin and blood EAA at birth. Overall, associations at birth did not persist in mid-childhood; however, arsenic was associated with greater EAA at birth and in childhood. Prenatal metals, including essential metals and arsenic, are associated with epigenetic aging in early life, which might be associated with future health.

Experimental studies testing interventions to promote cultural safety, interculturality or antiracism in healthcare: protocol for a systematic review.

INTRODUCTION: Cultural safety, interculturality and antiracism are crucial concepts in addressing health disparities of minority and diverse groups. Measuring them is challenging, however, due to overlapping meanings and their highly contextual nature. Community engagement is essential for evaluating these concepts, yet the methods for social inclusion and protocols for participation remain unclear. This review identifies experimental studies that measure changes resulting from culturally safe, intercultural or antiracist healthcare. The review will describe outcomes and additional factors addressed in these studies. METHODS AND ANALYSIS: The study focuses on epidemiological experiments with counterfactual comparisons and explicit interventions involving culturally safe, intercultural or antiracist healthcare. The search strategy covers PubMed, CINAHL, Scopus, Web of Science, ProQuest, LILACS and WHO IRIS databases. We will use critical appraisal tools from the Joanna Briggs Institute to assess the quality of randomised and non-randomised experimental studies. Two researchers will screen references, select studies and extract data to summarise the main characteristics of the studies, their approach to the three concepts under study and the reported effect measures. We will use fuzzy cognitive mapping models based on the causal relationships reported in the literature. We will consider the strength of the relationships depicted in the maps as a function of the effect measure reported in the study. Measures of centrality will identify factors with higher contributions to the outcomes of interest. Illustrative intervention modelling will use what-if scenarios based on the maps. ETHICS AND DISSEMINATION: This review of published literature does not require ethical approval. We will publish the results in a peer-reviewed journal and present them at conferences. The maps emerging from the process will serve as evidence-based models to facilitate discussions with Indigenous communities to further the dialogue on the contributing factors and assessment of cultural safety, interculturality and antiracism. PROSPERO REGISTRATION NUMBER: CRD42023418459.