Short-Term Effects of 3D-Printed Occlusal Splints and Conventional Splints on Sleep Bruxism Activity: EMG-ECG Night Recordings of a Sample of Young Adults.

(1) Background: This study aims to compare the effects of 3D-printed splints and conventional manufactured splints on sleep bruxism (SB) EMG activity. (2) Methods: Twenty-six patients (19 M, 7 F, 25.8 ± 2.6 years) were randomly allocated to a study group (3D splints) and a control group (conventional manufactured splints) and followed for a period of three months with night EMG-ECG recordings. Samples of the involved materials were analyzed for nanoindentation. The outcomes of interest considered were the overall SB index, the total amount of surface masseter muscle activity (sMMA), and general and SB-related phasic and tonic contractions. A statistical evaluation was performed with a confidence interval (CI) between 2.5% and 97.5%. (3) Results: Differences between groups with OAs were observed for general tonic contraction (p = 0.0009), while differences between recording times were observed for general phasic contractions (p = 0.002) and general tonic contractions (p = 0.00001). Differences between recording times were observed for the total amount of sMMA (p = 0.01), for general phasic contractions (p = 0.0001), and for general tonic contractions (p = 0.000009) during night recordings without OAs. (4) Conclusions: Three-dimensional splints seem to have a higher impact on SB-related electromyographic activity but not on the overall sleep bruxism index. The more regular surfaces offered by 3D splints could be related to phasic contraction stabilization.

Impacted Permanent Mandibular Canines: Epidemiological Evaluation.

BACKGROUND: The aim of this study was to evaluate the epidemiology of impacted and transmigrated mandibular canines in a large orthodontic population referred to the University of Turin. METHODS: Panoramic radiographs, intraoral photographs, and dental casts of 2119 patients referred to the Department of Orthodontics at the University of Turin, Italy, between 1995 and 2022 were reviewed. These patients were divided into two groups. Group A included 1479 patients found in the Dental School archive before 2017, more specifically between 1995 and 2017. These patients were examined in order to calculate the prevalence of impacted and transmigrated mandibular canines. From 2017 to 2022, the records of 640 new patients were examined (GROUP B) in order to calculate the incidence of these occurrences. RESULTS: The prevalence of mandibular canine impaction in Group A was found to be 1.7%, with a total of 25 patients having mandibular canine impaction. A prevalence of 0.3% was found for mandibular canine transmigration (Group A). The incidence of mandibular canine impaction was found to be 2%, with a total of 13 patients with mandibular canine impaction (Group B). Mandibular canine transmigration was found in 1 of 640 participants (Group B). CONCLUSIONS: Twenty-five of 1479 patients had impacted mandibular canines, resulting in a prevalence value of 1.7%. The incidence was found to be 2%, with 13 of 640 patients having impacted mandibular canines. These results show higher prevalence and incidence rates of mandibular canine impaction when compared with previously published data.

Factors Affecting Patient Compliance during Orthodontic Treatment with Aligners: Motivational Protocol and Psychological Well-Being.

Objective: Compliance is critical for successful outcomes in orthodontics, and personality traits may play a role in determining patient adherence. This study aimed to monitor compliance during treatment with removable clear aligners (CA) [Align Technology Inc, San José, Calif ], and evaluate the influence of motivational techniques and the patient's profiles assessed through the psychological well-being (PWB) questionnaire on clinical outcomes. Methods: Thirty-nine consecutive patients in permanent dentition seeking treatment with CA were recruited from two universities. Casts were obtained before treatment and after 3, 6, and 12 months and the corresponding digital Clincheck©.STL files were used to calculate the discrepancy index to check for differences between virtual and real treatment stages. Patients were divided into two groups: the Case group, which received motivational techniques at each appointment, and the control group which received instructions only at the beginning. Psychological profiles were evaluated before treatment (T0) and after 3 (T1), 6 (T2), and 12 (T3) months. Results: There were no differences between the Case and Control groups regarding the use of motivational reminders. The analysis of the PWB showed that almost all values increased, and there was a strong correlation between dental casts and correspondent. STL files at every time point. The PWB showed increased values from T0 to T3 in the sample. Conclusion: Motivational techniques did not affect patient compliance, and treatment outcomes were achieved as planned. The PWB of all patients improved throughout the treatment with CA.

FKBP5, a Modulator of Stress Responses Involved in Malignant Mesothelioma: The Link between Stress and Cancer.

Malignant pleural mesothelioma (MPM) is a rare tumour characterized by a long latency period after asbestos exposure and poor survival [...].

Blood cell DNA methylation biomarkers in preclinical malignant pleural mesothelioma: The EPIC prospective cohort.

Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer mainly caused by asbestos exposure. Specific and sensitive noninvasive biomarkers may facilitate and enhance screening programs for the early detection of cancer. We investigated DNA methylation (DNAm) profiles in MPM prediagnostic blood samples in a case-control study nested in the European Prospective Investigation into Cancer and nutrition (EPIC) cohort, aiming to characterise DNAm biomarkers associated with MPM. From the EPIC cohort, we included samples from 135 participants who developed MPM during 20 years of follow-up and from 135 matched, cancer-free, controls. For the discovery phase we selected EPIC participants who developed MPM within 5 years from enrolment (n = 36) with matched controls. We identified nine differentially methylated CpGs, selected by 10-fold cross-validation and correlation analyses: cg25755428 (MRI1), cg20389709 (KLF11), cg23870316, cg13862711 (LHX6), cg06417478 (HOOK2), cg00667948, cg01879420 (AMD1), cg25317025 (RPL17) and cg06205333 (RAP1A). Receiver operating characteristic (ROC) analysis showed that the model including baseline characteristics (age, sex and PC1wbc) along with the nine MPM-related CpGs has a better predictive value for MPM occurrence than the baseline model alone, maintaining some performance also at more than 5 years before diagnosis (area under the curve [AUC] < 5 years = 0.89; AUC 5-10 years = 0.80; AUC >10 years = 0.75; baseline AUC range = 0.63-0.67). DNAm changes as noninvasive biomarkers in prediagnostic blood samples of MPM cases were investigated for the first time. Their application can improve the identification of asbestos-exposed individuals at higher MPM risk to possibly adopt more intensive monitoring for early disease identification.

Interleukin-3-Receptor-α in Triple-Negative Breast Cancer (TNBC): An Additional Novel Biomarker of TNBC Aggressiveness and a Therapeutic Target.

Tumour molecular annotation is mandatory for biomarker discovery and personalised approaches, particularly in triple-negative breast cancer (TNBC) lacking effective treatment options. In this study, the interleukin-3 receptor α (IL-3Rα) was investigated as a prognostic biomarker and therapeutic target in TNBC. IL-3Rα expression and patients' clinical and pathological features were retrospectively analysed in 421 TNBC patients. IL-3Rα was expressed in 69% human TNBC samples, and its expression was associated with nodal metastases (p = 0.026) and poor overall survival (hazard ratio = 1.50; 95% CI = 1.01-2.2; p = 0.04). The bioinformatics analysis on the Breast Invasive Carcinoma dataset of The Cancer Genome Atlas (TCGA) proved that IL-3Rα was highly expressed in TNBC compared with luminal breast cancers (p = 0.017, padj = 0.026). Functional studies demonstrated that IL-3Rα activation induced epithelial-to-endothelial and epithelial-to-mesenchymal transition, promoted large blood lacunae and lung metastasis formation, and increased programmed-cell death ligand-1 (PD-L1) in primary tumours and metastases. Based on the TCGA data, IL-3Rα, PD-L1, and EMT coding genes were proposed to discriminate against TNBC aggressiveness (AUC = 0.86 95% CI = 0.82-0.89). Overall, this study identified IL-3Rα as an additional novel biomarker of TNBC aggressiveness and provided the rationale to further investigate its relevance as a therapeutic target.

DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases.

We performed a multi-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). We find 1,511 independent differentially methylated loci associated with CRP. These CpG sites show correlation structures across chromosomes, and are primarily situated in euchromatin, depleted in CpG islands. These genomic loci are predominantly situated in transcription factor binding sites and genomic enhancer regions. Mendelian randomization analysis suggests altered CpG methylation is a consequence of increased blood CRP levels. Mediation analysis reveals obesity and smoking as important underlying driving factors for changed CpG methylation. Finally, we find that an activated CpG signature significantly increases the risk for cardiometabolic diseases and COPD.

Effects on Sleep Bruxism Activity of Three Different Oral Appliances: One Year Longitudinal Cohort Study.

BACKGROUND: Different oral appliances (OAs) have been proposed to control sleep bruxism (SB) detrimental effects on the stomatognathic system. OBJECTIVE: The aim of the study was evaluate the effect of different OAs on SB activity and masticatory muscle activity (sMMA) measured by EMG. METHOD: This longitudinal cohort study was conducted on 51 patients (21 M, 30 F, mean age 26,5 ± 3,5) suffering from SB diagnosed with a validated portable EMG-ECG holter and wearing different OAs: occlusal splints, functional appliance with metallic bites and clear aligners followed after 1 week, 1 month, 3 months, 6 months and 12 months from delivery. A control group of 16 non-treated SB patients (6 M, 10 F mean age 27,1 ± 1,4) was used as reference. A multiple regression analysis was performed to estimate the differences between groups. Significance was set as P value <0,05. RESULTS: Occlusal splint reduced sleep bruxism index after 1 week, 3, 6 and 12 months from delivery while functional appliance only after 12 months. Occlusal splints reduced general phasic contractions only in the first week and sleep bruxism-related phasic contractions at 1 week, 3 and 6 months after delivery with no significant reductions after 12 months. Patients wearing clear aligners showed reduction in general tonic contractions after 6 and 12 months. CONCLUSION: Resin and metal bites can reduce sleep bruxism index, while resin bites can reduce sleep bruxism-related phasic contractions. Clear aligners do not influence sleep bruxism index but can reduce tonic contractions.

Variations in athletic performance with occlusal splint in track and field athletes: a randomized clinical trial.

BACKGROUND: Several studies have been proposed with the aim to demonstrate correlations between the dento-mandibular apparatus and the skeletal muscle system of the human body even in regions distant from the oral cavity. However, a definite conclusion cannot be drawn. The aim of this paper is to demonstrate a possible correlation between dental occlusion and sport performances in track and field athletes. METHODS: Sixteen track and field athletes were enrolled for the study and were randomly divided in three groups: Untreated control group, Placebo group (with a lower plaque without occlusal coverage) and Treated group (with occlusal splint). Changes in sprint and jump performance were assessed on a weekly basis for 5 consecutive weeks, during which athletes had to wear oral devices, except for the first week of baseline, for at least 3 trainings lasting 2 hours per week . All participants performed the countermovement jump (CMJ), the drop jump (DJ), the 10m and 30m sprint tests, always on the same day on the week. RESULTS: No statistically significant difference resulted between Control group and Placebo group and between Control group and Treated group. However, it was possible to observe a clinical improvement of measurements obtained, especially for CMJ, 10m and 30m sprint tests. No variation neither statistical neither clinical was observed in DJ test analysis. CONCLUSIONS: Even if statistically it was not possible to demonstrate an improvement in sport performance, most of the athlete analyzed showed better results during training session with occlusal splint compared to athlete without occlusal splint, in countermovement jump, in 10m and 30m sprint tests.

Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation.

Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype-phenotype map than previously anticipated.

New DNA Methylation Signals for Malignant Pleural Mesothelioma Risk Assessment.

Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm. Patients are usually diagnosed when current treatments have limited benefits, highlighting the need for noninvasive tests aimed at an MPM risk assessment tool that might improve life expectancy. Three hundred asbestos-exposed subjects (163 MPM cases and 137 cancer-free controls), from the same geographical region in Italy, were recruited. The evaluation of asbestos exposure was conducted considering the frequency, the duration and the intensity of occupational, environmental and domestic exposure. A genome-wide methylation array was performed to identify novel blood DNA methylation (DNAm) markers of MPM. Multiple regression analyses adjusting for potential confounding factors and interaction between asbestos exposure and DNAm on the MPM odds ratio were applied. Epigenome-wide analysis (EWAS) revealed 12 single-CpGs associated with the disease. Two of these showed high statistical power (99%) and effect size (>0.05) after false discovery rate (FDR) multiple comparison corrections: (i) cg03546163 in FKBP5, significantly hypomethylated in cases (Mean Difference in beta values (MD) = -0.09, 95% CI = -0.12|-0.06, p = 1.2 × 10-7), and (ii) cg06633438 in MLLT1, statistically hypermethylated in cases (MD = 0.07, 95% CI = 0.04|0.10, p = 1.0 × 10-6). Based on the interaction analysis, asbestos exposure and epigenetic profile together may improve MPM risk assessment. Above-median asbestos exposure and hypomethylation of cg03546163 in FKBP5 (OR = 20.84, 95% CI = 8.71|53.96, p = 5.5 × 10-11) and hypermethylation of cg06633438 in MLLT1 (OR = 11.71, 95% CI = 4.97|29.64, p = 5.9 × 10-8) genes compared to below-median asbestos exposure and hyper/hypomethylation of single-CpG DNAm, respectively. Receiver Operation Characteristics (ROC) for Case-Control Discrimination showed a significant increase in MPM discrimination when DNAm information was added in the model (baseline model, BM: asbestos exposure, age, gender and white blood cells); area under the curve, AUC = 0.75; BM + cg03546163 at FKBP5. AUC = 0.89, 2.1 × 10-7; BM + cg06633438 at MLLT1. AUC = 0.89, 6.3 × 10-8. Validation and replication procedures, considering independent sample size and a different DNAm analysis technique, confirmed the observed associations. Our results suggest the potential application of DNAm profiles in blood to develop noninvasive tests for MPM risk assessment in asbestos-exposed subjects.

Micro computed tomography evaluation of Invisalign aligner thickness homogeneity.

OBJECTIVES: To measure the thickness homogeneity of Invisalign (Align Technology Inc, San José, Calif) aligners with micro-computed tomography (micro-CT) scans. MATERIALS AND METHODS: Starting from micro-CT scanning of 20 different aligners, multiplanar reconstructions were obtained. An orthodontist blinded about the study measured aligner thickness in different regions (molar, canine, incisor) and in different sites (gingival-buccal, buccal, occlusal, lingual, and gingival-lingual). To assess various thicknesses in different aligner sites and regions, the sample was stratified into subgroups and linear regression analysis was performed. RESULTS: Descriptive analysis showed that mean thickness of aligners in the incisor region ranged from 0.582 mm to 0.639 mm, in the canine region from 0.569 mm to 0.644 mm, and in the molar region from 0.566 mm to 0.634 mm. Student's t-tests showed no significant differences in the aligner thickness of different regions when data were stratified by different sites. Student's t-tests showed significant differences in thickness homogeneity for the molar region when the data were stratified by tooth (mean difference = 0.068 mm; 95% confidence interval, 0.009-0.126 mm; P = .024). CONCLUSIONS: Invisalign aligner thickness is characterized by small differences. The only significant difference was revealed in the molar region where thickness of the gingival-lingual edge is significantly thinner than that measured at the occlusal aspect. From a clinical perspective, the results of the present study could be considered to explain the reduced predictability of several orthodontic tooth movements in the molar region.

Functional and clinical implications of genetic structure in 1686 Italian exomes.

To reconstruct the phenotypical and clinical implications of the Italian genetic structure, we thoroughly analyzed a whole-exome sequencing data set comprised of 1686 healthy Italian individuals. We found six previously unreported variants with remarkable frequency differences between Northern and Southern Italy in the HERC2, OR52R1, ADH1B, and THBS4 genes. We reported 36 clinically relevant variants (submitted as pathogenic, risk factors, or drug response in ClinVar) with significant frequency differences between Italy and Europe. We then explored putatively pathogenic variants in the Italian exome. On average, our Italian individuals carried 16.6 protein-truncating variants (PTVs), with 2.5% of the population having a PTV in one of the 59 American College of Medical Genetics (ACMG) actionable genes. Lastly, we looked for PTVs that are likely to cause Mendelian diseases. We found four heterozygous PTVs in haploinsufficient genes (KAT6A, PTCH1, and STXBP1) and three homozygous PTVs in genes causing recessive diseases (DPYD, FLG, and PYGM). Comparing frequencies from our data set to other public databases, like gnomAD, we showed the importance of population-specific databases for a more accurate assessment of variant pathogenicity. For this reason, we made aggregated frequencies from our data set publicly available as a tool for both clinicians and researchers (http://nigdb.cineca.it; NIG-ExIT).

DNA Methylation of FKBP5 as Predictor of Overall Survival in Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive tumor with median survival of 12 months and limited effective treatments. The scope of this study was to study the relationship between blood DNA methylation (DNAm) and overall survival (OS) aiming at a noninvasive prognostic test. We investigated a cohort of 159 incident asbestos exposed MPM cases enrolled in an Italian area with high incidence of mesothelioma. Considering 12 months as a cut-off for OS, epigenome-wide association study (EWAS) revealed statistically significant (p value = 7.7 × 10-9) OS-related differential methylation of a single-CpG (cg03546163), located in the 5'UTR region of the FKBP5 gene. This is an independent marker of prognosis in MPM patients with a better performance than traditional inflammation-based scores such as lymphocyte-to-monocyte ratio (LMR). Cases with DNAm < 0.45 at the cg03546163 had significantly poor survival compared with those showing DNAm ≥ 0.45 (mean: 243 versus 534 days; p value< 0.001). Epigenetic changes at the FKBP5 gene were robustly associated with OS in MPM cases. Our results showed that blood DNA methylation levels could be promising and dynamic prognostic biomarkers in MPM.

Does occlusal splint affect posture? A randomized controlled trial.

OBJECTIVE: The aim of this study was to evaluate the effect of an occlusal splint on body posture of intra-articular temporomandibular joint (TMJ) disorders patients. METHODS: The study was performed on 45 women affected by TMJ disorders divided into an occlusal splint group and a control group. Rasterstereographic recordings were performed at baseline and after 1, 3, and 6 months, in order to analyze the following postural parameters: trunk inclination, cervical and lumbar arrows, kyphotic and lordotic angles, trunk imbalance, pelvic tilt and torsion. RESULTS: Regarding the postural parameters in the intragroup analysis, no significant differences were detected. The analysis between the two groups revealed significant differences concerning the cervical arrow, the kyphotic and lordotic angles. DISCUSSION: Even if some differences were found between the control and the occlusal splint group, the low range of statistical significance made these results not significant from a clinical point of view.

DNA repair and cancer in colon and rectum: Novel players in genetic susceptibility.

Interindividual differences in DNA repair systems may play a role in modulating the individual risk of developing colorectal cancer. To better ascertain the role of DNA repair gene polymorphisms on colon and rectal cancer risk individually, we evaluated 15,419 single nucleotide polymorphisms (SNPs) within 185 DNA repair genes using GWAS data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), which included 8,178 colon cancer, 2,936 rectum cancer cases and 14,659 controls. Rs1800734 (in MLH1 gene) was associated with colon cancer risk (p-value = 3.5 × 10-6 ) and rs2189517 (in RAD51B) with rectal cancer risk (p-value = 5.7 × 10-6 ). The results had statistical significance close to the Bonferroni corrected p-value of 5.8 × 10-6 . Ninety-four SNPs were significantly associated with colorectal cancer risk after Binomial Sequential Goodness of Fit (BSGoF) procedure and confirmed the relevance of DNA mismatch repair (MMR) and homologous recombination pathways for colon and rectum cancer, respectively. Defects in MMR genes are known to be crucial for familial form of colorectal cancer but our findings suggest that specific genetic variations in MLH1 are important also in the individual predisposition to sporadic colon cancer. Other SNPs associated with the risk of colon cancer (e.g., rs16906252 in MGMT) were found to affect mRNA expression levels in colon transverse and therefore working as possible cis-eQTL suggesting possible mechanisms of carcinogenesis.

Scanning electron microscopy analysis of aligner fitting on anchorage attachments.

PURPOSE: The aims of the study were (1) to evaluate the fitting of three different aligners (Invisalign [Align Technology, Santa Clara, CA, USA], CA Clear Aligner [Scheu-Dental, Iserlohn, Germany] and F22 [Sweden&Martina, Due Carrare, Italy]) on anchorage attachments using scanning electron microscopy (SEM), and (2) to analyze the influence of 2 different types of resin used to build attachments on aligner fitting. METHODS: Using STL files of a patient, six resin casts were obtained and rectangular attachments were bonded on them. Conventional bulk-fill resin was used to build upper attachments while a flowable resin was used to build the lower ones. Passive aligners were adapted on each cast and then sectioned buccolingually. Microphotographs of the obtained sections were performed using a SEM and then micrometric measurements of aligner fitting on anchorage attachments were recorded. RESULTS: Analyzing the overall fitting of upper arch aligners, Invisalign provided a significantly better fitting with respect to F22 (P = 0.009); differences were not significant when comparing Invisalign with CA Clear Aligner, and CA Clear Aligner with F22. Analyzing the overall fitting of lower arch aligners, F22 provided a significantly better fitting with respect to CA Clear Aligner (P = 0.008) and Invisalign (P = 0.011). The analysis showed a significantly better fitting on upper attachments, built using conventional bulk-fill resin (P = 0.034). CONCLUSIONS: Invisalign, CA Clear Aligner and F22 have comparable performance in terms of fitting on anchorage attachments. Conventional bulk-fill resin provides the best fitting on anchorage attachments.

Peripheral Blood DNA Methylation as Potential Biomarker of Malignant Pleural Mesothelioma in Asbestos-Exposed Subjects.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive tumor strongly associated with asbestos exposure. Patients are usually diagnosed when current treatments have limited benefits, highlighting the need for noninvasive early diagnostic tests to monitor asbestos-exposed people. METHODS: We used a genome-wide methylation array to identify, in asbestos-exposed subjects, novel blood DNA methylation markers of MPM in 163 MPM cases and 137 cancer-free controls (82 MPM cases and 68 controls, training set; replication in 81 MPM cases and 69 controls, test set) sampled from the same areas. RESULTS: Evidence of differential methylation between MPM cases and controls was found (more than 800 cytosine-guanine dinucleotide sites, false discovery rate p value (pfdr) < 0.05), mainly in immune system-related genes. Considering the top differentially methylated signals, seven single- cytosine-guanine dinucleotides and five genomic regions of coordinated methylation replicated with similar effect size in the test set (pfdr < 0.05). The top hypomethylated single-CpG (cases versus controls effect size less than -0.15, pfdr < 0.05 in both the training and test sets) was detected in FOXK1 (Forkhead-box K1) gene, an interactor of BAP1 which was found mutated in MPM tissue and as germline mutation in familial MPM. In the test set, comparison of receiver operating characteristic curves and the area under the curve (AUC) of two models, including or excluding methylation, showed a significant increase in case/control discrimination when considering DNA methylation together with asbestos exposure (AUC = 0.81 versus AUC = 0.89, DeLong's test p = 0.0013). CONCLUSIONS: We identified signatures of differential methylation in DNA from whole blood between asbestos exposed MPM cases and controls. Our results provide the rationale to further investigate, in prospective studies, the potential use of blood DNA methylation profiles for the identification of early changes related to the MPM carcinogenic process.

Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults.

BACKGROUND: DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health. METHODS: We meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n = 18,212). DNA methylation at the GFI1-locus was measured in whole-blood. Multivariable regression models were fitted to examine its association with exposure to prenatal and own adult smoking. DNA methylation levels were analysed in relation to body mass index (BMI), waist circumference (WC), fasting glucose (FG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), diastolic, and systolic blood pressure (BP). FINDINGS: Lower DNA methylation at three out of eight GFI1-CpGs was associated with exposure to maternal prenatal smoking, whereas, all eight CpGs were associated with adult own smoking. Lower DNA methylation at cg14179389, the strongest maternal prenatal smoking locus, was associated with increased WC and BP when adjusted for sex, age, and adult smoking with Bonferroni-corrected P < 0·012. In contrast, lower DNA methylation at cg09935388, the strongest adult own smoking locus, was associated with decreased BMI, WC, and BP (adjusted 1 × 10-7 < P < 0.01). Similarly, lower DNA methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 × 10-8 < P < 0.001). Lower DNA methylation at all the CpGs was consistently associated with higher TG levels. INTERPRETATION: Epigenetic changes at the GFI1 were linked to smoking exposure in-utero/in-adulthood and robustly associated with cardio-metabolic risk factors. FUND: European Union's Horizon 2020 research and innovation programme under grant agreement no. 633595 DynaHEALTH.

Scanning electron microscopy evaluation of aligner fit on teeth.

OBJECTIVES: The fitting of aligners on anchorage teeth is a crucial factor in clear aligner orthodontics. The purpose of this experimental study was to evaluate the fitting of two aligner systems, Invisalign and CA-Clear Aligner, using scanning electron microscopy (SEM). MATERIALS AND METHODS: Passive aligners (Invisalign and CA-Clear Aligner) were adapted on resin casts obtained by stereolithography (STL) files of a patient, and then sectioned buccolingually. Upper and lower central incisors, upper and lower first premolars, and upper and lower first molars were the regions analyzed. Representative microphotographs of sections were taken with a scanning electron microscope (SEM); a total of 160 micrometric measurements were obtained and analyzed with ANOVA tests. RESULTS: Invisalign provided an overall better fit on lower incisors ( F = 11.48, P = .0095) and on lower molars ( F = 19.93, P = .0012). Considering the different regions, Invisalign provided better fit at the gingival edge of the buccal aspect on lower incisors ( F = 11.33, P = 0.0056) and at the gingival edge of the lingual aspect on upper premolars ( F =5.34, P = 0.0047). On the upper molars, Invisalign provided better fit at the gingival edge of the buccal aspect, while CA-Clear Aligner provided better fit at the buccal maximum convexity, on the buccal cusp, on the occlusal groove and at the palatal cusp. On lower molars, Invisalign showed a more accurate fit at the buccal aspect points. CONCLUSIONS: Invisalign and CA-Clear Aligner exhibited comparable fit on anchorage teeth. Invisalign provided better fit at the gingival edges of aligners, while the CA-Clear Aligner provided better fit on complex occlusal surfaces.