RIG-I Uses an ATPase-Powered Translocation-Throttling Mechanism for Kinetic Proofreading of RNAs and Oligomerization.

RIG-I has a remarkable ability to specifically select viral 5'ppp dsRNAs for activation from a pool of cytosolic self-RNAs. The ATPase activity of RIG-I plays a role in RNA discrimination and activation, but the underlying mechanism was unclear. Using transient-state kinetics, we elucidated the ATPase-driven "kinetic proofreading" mechanism of RIG-I activation and RNA discrimination, akin to DNA polymerases, ribosomes, and T cell receptors. Even in the autoinhibited state of RIG-I, the C-terminal domain kinetically discriminates against self-RNAs by fast off rates. ATP binding facilitates dsRNA engagement but, interestingly, makes RIG-I promiscuous, explaining the constitutive signaling by Singleton-Merten syndrome-linked mutants that bind ATP without hydrolysis. ATP hydrolysis dissociates self-RNAs faster than 5'ppp dsRNA but, more importantly, drives RIG-I oligomerization through translocation, which we show to be regulated by helicase motif IVa. RIG-I translocates directionally from the dsRNA end into the stem region, and the 5'ppp end "throttles" translocation to provide a mechanism for threading and building a signaling-active oligomeric complex.

DDX58 variant triggers IFN-ß-induced autophagy in trabecular meshwork and influences intraocular pressure.

Singleton-Merten syndrome (SMS) is a rare immunogenetic disorder affecting multiple systems, characterized by dental dysplasia, aortic calcification, glaucoma, skeletal abnormalities, and psoriasis. Glaucoma, a key feature of both classical and atypical SMS, remains poorly understood in terms of its molecular mechanism caused by DDX58 mutation. This study presented a novel DDX58 variant (c.1649A>C [p.Asp550Ala]) in a family with childhood glaucoma. Functional analysis showed that DDX58 variant caused an increase in IFN-stimulated gene expression and high IFN-ß-based type-I IFN. As the trabecular meshwork (TM) is responsible for controlling intraocular pressure (IOP), we examine the effect of IFN-ß on TM cells. Our study is the first to demonstrate that IFN-ß significantly reduced TM cell viability and function by activating autophagy. In addition, anterior chamber injection of IFN-ß remarkably increased IOP level in mice, which can be attenuated by treatments with autophagy inhibitor chloroquine. To uncover the specific mechanism underlying IFN-ß-induced autophagy in TM cells, we performed microarray analysis in IFN-ß-treated and DDX58 p.Asp550Ala TM cells. It showed that RSAD2 is necessary for IFN-ß-induced autophagy. Knockdown of RSAD2 by siRNA significantly decreased autophagy flux induced by IFN-ß. Our findings suggest that DDX58 mutation leads to the overproduction of IFN-ß, which elevates IOP by modulating autophagy through RSAD2 in TM cells.

Diagnosing celiac disease in children using oral manifestations.

PURPOSE: Celiac disease (CD) may be frequently undiagnosed due to the absence of characteristic gastroenterologic symptoms in many CD patients. Our objective was to diagnose CD by utilizing documented oral manifestations such as Recurrent Aphthous Stomatitis (RAS) and Molar-Incisor Hypomineralization (MIH). METHODS: The study comprised sixty children who presented with complaints of RAS lesions. The MIH group consisted of 40 children, while the control group comprised 20 children without MIH lesions, ranging in age from 7 to 13 years. After the dental examination, all children were given a questionnaire to assess whether they had any previous history of general symptoms related to CD. Following that, diagnostic testing for celiac disease were conducted, including serological tests such as Tissue transglutaminase IgA (tTG-IgA), Endomysium Antibody (EMA), and Total IgA, as well as genetic tests for HLA-DQ2 and HLA-DQ8. RESULTS: The statistical analysis, conducted using Fisher's Exact, Yates' Continuity Correction, Fisher Freeman Halton, and Student's t tests, revealed no significant differences between the groups (p < 0.05). Within the MIH group, 3 children exhibited border tTG-IgA values, while another 3 had positive tTG-IgA results. Two of these 6 children had also positive EMA and HLA results. Following a biopsy procedure, these two children were ultimately diagnosed with celiac disease (CD). CONCLUSIONS: In this study, while children initially presented to the clinic with complaints of recurrent aphthous stomatitis (RAS), 2 children (5% of the MIH group) were diagnosed with CD shortly after the onset of MIH lesions. CD enhanced the likelihood of observing some oral manifestations particularly recurrent aphtous stomatitis and developmental enamel defects. We recommend that dentists be cautious about diagnosing CD when RAS lesions and DEDs and/or MIH lesions are present, whether or not other indications of this systemic disease exist.

Double-Stranded RNA Induces Mortality in an MDA5-Mediated Type I Interferonopathy Model.

Gain-of-function mutations in the viral dsRNA sensor melanoma differentiation-associated protein 5 (MDA5) lead to autoimmune IFNopathies, including Singleton-Merten syndrome (SMS) and Aicardi-Goutières syndrome. However, much remains unclear regarding the mechanism of disease progression and how external factors such as infection or immune stimulation with vaccination can affect the immune response. With this aim, we generated mice with human MDA5 bearing the SMS-associated mutation R822Q (hM-R822Q). hM-R822Q transgenic (Tg) mice developed SMS-like heart fibrosis, aortic valve enlargement, and aortic calcification with a systemic IFN-stimulated gene signature resulting in the activation of the adaptive immune response. Although administration of the viral dsRNA mimic polyinosinic-polycytidylic acid [poly(I:C)] did not have remarkable effects on the cardiac phenotype, dramatic inflammation was observed in the intestines where IFN production was most elevated. Poly(I:C)-injected hM-R822Q Tg mice also developed lethal hypercytokinemia marked by massive IL-6 levels in the serum. Interrupting the IFN signaling through mitochondrial antiviral signaling protein or IFN-α/ß receptor alleviated hM-R822Q-induced inflammation. Furthermore, inhibition of JAK signaling with tofacitinib reduced cytokine production and ameliorated mucosal damage, enabling the survival of poly(I:C)-injected hM-R822Q Tg mice. These findings demonstrate that the MDA5 R822Q mutant introduces a critical risk factor for uncontrollable inflammation on viral infection or vaccination.

Predictors of Developmental Defects of Enamel in Primary Maxillary Central Incisors Using Bayesian Model Selection.

INTRODUCTION: Localized non-inheritable developmental defects of tooth enamel (DDE) are classified as enamel hypoplasia (EH), opacity (OP), and post-eruptive breakdown (PEB) using the enamel defects index. To better understand the etiology of DDE, we assessed the linkages amongst exposome variables for these defects during the specific time duration for enamel mineralization of the human primary maxillary central incisor enamel crowns. In general, these two teeth develop between 13 and 14 weeks in utero and 3-4 weeks' postpartum of a full-term delivery, followed by tooth eruption at about 1 year of age. METHODS: We utilized existing datasets for mother-child dyads that encompassed 12 weeks' gestation through birth and early infancy, and child DDE outcomes from digital images of the erupted primary maxillary central incisor teeth. We applied a Bayesian modeling paradigm to assess the important predictors of EH, OP, and PEB. RESULTS: The results of Gibbs variable selection showed a key set of predictors: mother's prepregnancy body mass index (BMI); maternal serum concentrations of calcium and phosphorus at gestational week 28; child's gestational age; and both mother's and child's functional vitamin D deficiency (FVDD). In this sample of healthy mothers and children, significant predictors for OP included the child having a gestational period >36 weeks and FVDD at birth, and for PEB included a mother's prepregnancy BMI <21.5 and higher serum phosphorus concentration at week 28. CONCLUSION: In conclusion, our methodology and results provide a roadmap for assessing timely biomarker measures of exposures during specific tooth development to better understand the etiology of DDE for future prevention.

Which are the clinical consequences of Molar Incisor hypomineralization (MIH) in children and adolescents? Systematic review and meta-analysis.

OBJECTIVE: This systematic review was conducted to address the following research question: "What are the clinical consequences (outcome) of Molar Incisor Hypomineralization (MIH) (exposure) in children and adolescents (population/patient)?". MATERIAL AND METHODS: After defining the strategy, a search was performed in different databases (MEDLINE via Pubmed, Cochrane Library, BBO, LILACS, Scopus, Web of Science, Embase) and Grey literature in August 2023. Cross-sectional observational studies that identified clinical consequences of MIH (dental caries, post-eruptive structural loss, atypical restorations, hypersensitivity and tooth extraction) were included. The risk of bias was assessed following the Joanna Briggs Institute protocol for cross-sectional studies. Meta-analyses were conducted for each outcome, taking into account the number of patients and teeth. The effect measure considered was the prevalence; random-effects model was adopted. Heterogeneity was assessed using I2 statistics and prediction intervals (PI). RESULTS: A total of 903 studies were identified; 41 were selected for qualitative analysis and 38 for quantitative analysis. Twenty eight studies were classified as presenting uncertain risk of bias, 11 as low risk and 3 as high risk of bias. The prevalence levels, ranked from highest to lowest and considering the tooth and patient units, respectively, were: caries lesions (0.252 - 95% CI 0.158-0.375; 0.512 - 95% CI 0.385-0.639); hypersensitivity (0.286 - 95% CI 0.190-0.407; 0.417 - 95% CI 0.197-0.674), post-eruptive fracture (0.125 - 95% CI 0.099-0.158; 0.257 - 95% CI 0.145-0.412); atypical restorations (0.048 - 95% CI 0.030-0.077; 0.167 - 95% CI 0.096 - 0.274); tooth extraction (0.012 - 95% CI 0.007-0.019; 0.090 - 95% CI 0.019 - 0.331). All meta-analyses resulted in heterogeneity greater than 85%, with the exception of the outcome "tooth extraction" according to the tooth unit (I2 = 57.83). This heterogeneity may be attributed to factors such as differences in the location where the study was realized, the socioeconomic conditions of the studied population, the asymmetric nature of MIH, and patient age. CONCLUSION: The most common consequences of MIH are caries lesions, hypersensitivity, and post-eruptive breakdown. (PROSPERO:CRD42020201410).

Cost-effectiveness of restorative treatments for permanent molars with severe molar incisor hypomineralization: perspectives for the Brazilian public health system.

OBJECTIVES: To undertake a cost-effectiveness analysis of restorative treatments for a first permanent molar with severe molar incisor hypomineralization from the perspective of the Brazilian public system. MATERIALS AND METHODS: Two models were constructed: a one-year decision tree and a ten-year Markov model, each based on a hypothetical cohort of one thousand individuals through Monte Carlo simulation. Eight restorative strategies were evaluated: high viscosity glass ionomer cement (HVGIC); encapsulated GIC; etch and rinse adhesive + composite; self-etch adhesive + composite; preformed stainless steel crown; HVGIC + etch and rinse adhesive + composite; HVGIC + self-etch adhesive + composite, and encapsulated GIC + etch and rinse adhesive + composite. Effectiveness data were sourced from the literature. Micro-costing was applied using 2022 USD market averages with a 5% variation. Incremental cost-effectiveness ratio (ICER), net monetary benefit (%NMB), and the budgetary impact were obtained. RESULTS: Cost-effective treatments included HVGIC (%NMB = 0%/ 0%), encapsulated GIC (%NMB = 19.4%/ 19.7%), and encapsulated GIC + etch and rinse adhesive + composite (%NMB = 23.4%/ 24.5%) at 1 year and 10 years, respectively. The benefit gain of encapsulated GIC + etch and rinse adhesive + composite in relation to encapsulated GIC was small when compared to the cost increase at 1 year (gain of 3.28% and increase of USD 24.26) and 10 years (gain of 4% and increase of USD 15.54). CONCLUSION: Within the horizon and perspective analyzed, the most cost-effective treatment was encapsulated GIC restoration. CLINICAL RELEVANCE: This study can provide information for decision-making.

Molar incisor hypomineralization and oral health-related quality of life: a sample of 8-12-years-old children.

OBJECTIVES: The study aimed to evaluate the impact of molar incisor hypomineralization (MIH) and tooth sensitivity on the oral health in terms of the quality of life (OHRQoL). In addition, the impact of tooth maturity on tooth sensitivity was evaluated in the study. MATERIALS AND METHODS: Children aged 8-12 years with and without MIH participated in this descriptive cross-sectional study. They were chosen through the convenience sample technique. The Pediatric-Oral-Health-related-Quality-of-Life (POQL) scale was used to assess OHRQoL. The presence of the MIH and decayed, filled and missing teeth due to caries (using dmft/s, DMFT/S indexes) were recorded. The tooth sensitivity and dental maturity status were evaluated with the Shiff-Cold-Air-Sensitivity-Scale (SCASS) and Demirjian-method, respectively. Statistical analysis of the data was performed by Pearson Chi-Square Test and Mann-Whitney U test (p<0.05). RESULTS: In this study, the participants were a total of 260 children, half were affected by the MIH. Their mean POQL scores were higher than those of the children without MIH with a statistically significantly difference in the total child scale score (p=0.014). Among the children with the MIH, child total QoL score was found to be higher in SCASS positive response group (p=0.011). The teeth with MIH (p<0.001) showed higher response to the stimulus. According to the dental age and dental maturity categories of the children with MIH, the total child scale score was found to be higher in the SCASS category (p=0.011), and the response status to the SCASS was statistically significant (p=0.042 and p=0.05, respectively). CONCLUSIONS: Among the children with MIH, the OHRQoL was found to be negatively affected. The teeth with the MIH tend to reveal more tooth sensitivity than healthy teeth. Many conditions such as having MIH, and tooth sensitivity might have an impact on the OHRQoL. In addition, more sensitivity to the stimulus was observed in the teeth with lower tooth maturity status; the dental age and dental maturity might have effects on tooth sensitivity. CLINICAL RELEVANCE: Considering the negative impacts due to MIH, the evaluation of OHRQoL is critical for dentists to employ a well-defined guide in their clinical decisions.

Effect of photobiomodulation on the efficacy of anesthesia in maxillary permanent molar teeth with molar incisor hypomineralization: A randomized clinical trial.

BACKGROUND: Difficulty in anesthetizing teeth that have been diagnosed with molar incisor hypomineralization (MIH) is a frequently reported clinical problem. The effects of low-level laser application (photobiomodulation) on the efficacy of anesthesia during the dental treatment of patients with MIH have not yet been studied. AIM: To assess the effects of photobiomodulation therapy (PBMT) on the efficacy of anesthesia in maxillary permanent molar teeth with MIH. DESIGN: This prospective, parallel-arm control, randomized, triple-blind clinical trial included children aged 7-12 years. Maxillary permanent first molar teeth with MIH that required pulpotomy treatment were included. Seventy participants were randomly divided into two groups: experimental (with PBMT) and control (placebo). In the experimental group, before the administration of local infiltration anesthesia, PBMT (diode laser: 940 nm; continuous mode; 0.5 W; 78 J/cm2) was applied to the oral mucosa for 60 s each. In the control group, the laser probe was channeled toward the mucosa but was not activated. Pain scores were evaluated during the access cavity preparation of the pulpotomy treatment (when using the dentin cutting handpiece and while entering into the pulp) using the Face, Legs, Activity, Cry, Consolability (FLACC) scale. Additional anesthesia requirements were assessed in both groups. The data obtained were analyzed for statistical significance (p < .05). The chi-squared test was used to determine the effect of PBMT on categorical outcomes. RESULTS: The no-pain scores of the experimental group were higher than those of the control group (29% vs. 20%). Moderate-to-high pain was more frequent in the control group than in the experimental group (43% vs. 20%). While 31% of the experimental group required supplemental anesthesia, 49% of the control group required supplemental anesthesia during pulpotomy of the tooth with MIH. No statistical difference, however, was found between the two groups in terms of pain scores and the need for supplemental anesthesia (p = .235, p = .143). CONCLUSIONS: Anesthesia with and without PBMT caused no difference in pain during the treatment of maxillary molar teeth with MIH.

Assessment of the developmental defects of the enamel in children and adolescents with sickle cell disease: A comparative study.

BACKGROUND: Sickle cell disease (SCD) is the most important hemoglobinopathy in terms of frequency and social impact and can affect the stomatognathic system. AIM: To assess and compare the developmental defects of the enamel (DDE) in children and adolescents with and without SCD. DESIGN: This was a cross-sectional, analytical, and comparative study of 210 children and adolescents aged 5-18 years, who visited the Hematology and Hemotherapy Hospital of Pernambuco. RESULTS: Developmental defects of the enamel were observed in 55.2% of the SCD patients and 35.2% of the non-SCD patients (healthy group; p < .05). In the SCD group, DDE were more common in females than in males (69.1% vs. 40.0%; p < .05). The incidence of DDE in the permanent teeth was higher in the upper arch than in the lower arch (SCD group, 13.1% vs. 4.6%; healthy group, 8.9% vs. 3.6%; p < .05). CONCLUSION: Compared with the healthy group, the SCD patients were almost twice as likely to develop DDE, mostly affecting females and the permanent teeth. These findings suggest that individuals with SCD need early dental care to avoid future oral problems.

Why orthodontists need to know about molar incisor hypomineralization.

Molar incisor hypomineralization (MIH) is a systemic developmental qualitative defect of the enamel that affects 1-4 first permanent molars with or without incisor involvement. Enamel hypomineralization is identified visually as a demarcated opacity with a clear border with varying extensions and can be white, yellow, or brown. This opacity is characterized by a reduced quality of enamel that is of normal thickness but not fully mineralized. It is very common for the affected teeth to present with posteruptive breakdown, making them susceptible to caries, leading to their subsequent loss. Thus, MIH is a significant dental problem with clinical, economic, and psychosocial implications. The planned extraction of compromised teeth is a valid alternative to complex restorative treatment. Orthodontists' involvement is essential in developing effective treatment strategies for children affected by MIH, contributing to their oral health and well-being.

Prenatal exposure to environmental toxins and comprehensive dental findings in a population cohort of children.

Environmental toxins are known to have many impacts on growth and development in humans, starting in utero. Alterations in amelogenesis, caused by chemical and physical trauma that occur during the antenatal, perinatal and postnatal time periods, may result in developmental defects in deciduous and permanent tooth enamel, as demonstrated in animal studies. These defects can be clinically visible and result in a variety of morphological and functional problems in the dentition. Since enamel does not remodel after formation, it may serve as a permanent record of insults during organ development.Our primary purpose was to investigate any possible relationship between intrauterine exposure to endocrine disrupting chemicals (phenols and phthalates) and developmental defects in enamel in children, while also accounting for fluoride exposure. Our secondary purpose was to report descriptively on findings from comprehensive dental examinations performed on 356 children that were drawn from the general paediatric population. A cohort of children from the Utah Children's Project (N = 356) that had full medical exams, comprehensive medical and family histories and available biospecimens were given extraoral and intraoral examinations. They also completed an oral health questionnaire. Standardized intraoral photographs were taken of the teeth and viewed by standardised examiners and the dental observations were recorded for a full inventory of findings, including: tooth morphology, caries, restorations, colorations, attrition, erosion, fractures and hypomineralization. Perinatal maternal urine samples were assessed for the concentration of fluoride, phenols and phthalates, including bisphenol A (BPA).Pairwise statistical analyses were done to correlate the dental findings with one another and with the presence of environment chemicals found in the urine samples. Hypomineralization was the most common finding (96% of children; 37% of deciduous teeth, 42% of permanent teeth), consistent with molar incisor hypomineralization (MIH) described in other human populations. No consistent correlations were seen between dental findings and the presence of phenols and phthalates in prenatal urine, but the number of samples available for the assessment was limited (n = 35).In conclusion, we found a high proportion of dental hypomineralization in a population based paediatric cohort, but did not find an association with prenatal exposure to phenols and phthalates.

Is there a rise of prevalence for Molar Incisor Hypomineralization? A meta-analysis of published data.

Since Molar Incisor Hypomineralization was first described as a pathologic entity, public perception often suggests a considerable rise in prevalence of the respective disease. Since there are still considerable doubts regarding the etiology and-accordingly-prevention of MIH and respective therapeutic approaches are difficult this question is of considerable clinical and public interest. Accordingly, a systematic literature search in accordance with the PRISMA guidelines for systematic reviews on Medline, Cochrane Database, EMBASE, LILACS, Web of Science, Google scholar, Scopus was performed to retrieve original articles reporting the prevalence of MIH as defined by the European Academy of Pediatric Dentistry (EAPD). From initially 2360 retrieved titles, 344 full texts were assessed for possible inclusion and finally 167 articles of mainly moderate to high quality and based on data of 46'613 individuals were included in the meta-analysis. All studies published before 2001 had to be excluded since it was not possible to align the findings with the EAPD classification. Studies varied considerably regarding cohort size (25 to 23'320, mean 1'235)) and age (5.6-19 y, mean 9.8 y). Over all studies, the weighted mean for the prevalence for MIH was 12.8% (95% CI 11.5%-14.1%) and no significant changes with respect to either publication year or birthyear were found. A sub-analysis of eleven studies reporting on the prevalence in different age groups, however, revealed strong evidence for an increasing prevalence between the years 1992 (3%) and 2013 (13%).Therefore, based on data from cross-sectional studies a possible rise in prevalence of MIH remains unclear. Future prospective large-scale studies under standardized examination conditions with an emphasis on examiner calibration are needed to gain better understanding in the evolution of the prevalence of MIH.

Prevalence and clinical presentation of molar incisor hypomineralisation among a population of children in the community of Madrid.

OBJECTIVE: The main objective of this study was to estimate the prevalence of molar incisor hypomineralisation (MIH), an alteration of tooth enamel with an estimated worldwide prevalence rate of 14%, among children using primary care services in the Community of Madrid, Spain. MATERIALS AND METHODS: This was a descriptive, cross-sectional and multicentre study. After calibrating all researchers and following the diagnostic criteria of the European Academy of Paediatric Dentistry (EAPD), children aged between 8 and 16 years who were users of the dental services at 8 primary oral health units of the Madrid Health Service (SERMAS) were included. The children underwent a dental examination, and the parents were asked to complete a questionnaire. RESULTS: The prevalence of MIH was 28.63% (CI: 24.61-32.65%). The age cohorts most affected by MIH were 8 years (21.4%) and 11 years (20.7%). The presence of MIH was greater among girls (85; 60.71%) than among boys (55; 39.28%). The mean number of affected teeth per patient was 4.46 ± 2.8. The most frequently affected molar was the upper right first molar (74.3%), and the upper left central incisor was the most affected incisor (37.85%). Opacities were the defects most frequently recorded (63.57%). CONCLUSIONS: The prevalence of MIH in this study is the highest of all relevant studies conducted in Spain.

Knowledge and perception regarding molar incisor hypomineralisation among dental students and dental hygienist students in Spain: a cross-sectional study.

BACKGROUND: Molar incisor hypomineralisation (MIH) has a high prevalence in the Spanish pediatric population and is a precursor of carious lesions in teeth in which it is present. Although this pathology is included in the curricula of the Degree in Dentistry and the Training Cycle in Oral Hygiene in our country, the contents currently taught seem to be insufficient in relation to the level of knowledge that we have today about this condition. METHODS: A digital questionnaire of 18 questions was sent to a sample of 448 students attending the 4th and 5th year of the Degree in Dentistry and 2nd year of the Training Cycle in Oral Hygiene from different universities and vocational training centers in the Valencian Community. Descriptive and multivariate statistical analysis of the data was subsequently performed. RESULTS: Of the 290 questionnaires that were obtained, 53.8% were from students attending the 2nd year of a training course in oral hygiene and 46.2% were from students pursuing a degree in dentistry. Most of the respondents had heard about MIH (75.2%), mainly through master classes. However, most students had difficulties distinguishing MIH lesions from other lesions (58.3%). The degree of knowledge about MIH was greater among dental students in all the aspects evaluated: prevalence, diagnosis, prevention, and treatment. Of all the students, 83.8% were interested in increasing their training on MIH, especially in the areas of diagnosis and treatment. CONCLUSION: The results of the present study justify the need to expand the content on MIH, both theoretical and practical, in the educational curricula of the Degree in Dentistry and Integrated Vocational Training Centers in Spain.

"Evaluation of Silver Diamine Fluoride Modified Atraumatic Restorative Treatment (SMART) on hypomineralized first permanent molar"- a randomized controlled clinical study.

BACKGROUND: Restoring first permanent molars affected with molar incisor hypomineralization (MIH) is challenging. Focusing on improving the quality of life for children affected by MIH, at least until the complete eruption of first permanent molars to receive full coverage, to decrease the hypersensitivity and to be able to perform proper oral hygiene measures, the purpose of this study was to compare silver modified atraumatic restorative technique (SMART) versus the conventional restoration and fluoride varnish application on moderate to severe hypomineralized molars. The comparison considered the restoration survival, hypersensitivity, and digital surface area changes after one year follow up. METHODS: Twenty-eight children were selected (20 girls and 8 boys) with at least 2 MIH molars with the same defect severity. The study comprised 2 groups; MOD group (moderate hypomineralized molar severity) and SEV group (Severe hypomineralized molar severity) (n = 28 tooth). Each group was further subdivided into 2 subgroups according to the technique of restoration: SMART subgroup and CONV subgroup (high viscosity glass ionomer restoration and fluoride varnish application) (each = 14 tooth). Evaluation was done in terms of the restoration survival (6 months and 12 months), hypersensitivity at 1 weak, 6 months and 12 months and occlusal surface area changes at 12 months). Professional Fluoride varnish application and home prophylaxis using MI paste were the protocol for each child patient. RESULTS: There was no significant difference between the 4 subgroups, regarding tooth restoration integrity at 6-months vs. 12-months. However, a statistically significant difference in tooth restoration integrity between the 4 subgroups at 12-months (P = .049). Also, the hypersensitivity score, there was a statistically significant difference between the 4-time intervals (P < .001) and a statistically significant difference in surface area changes between the 4 subgroups. CONCLUSIONS: Selective removal of carious tissue and SMART restoration, combined with dental home and professional preventive measures every 3 months maintained the integrity of restorations in severely and moderately affected permanent molars up to 1 year. TRIAL REGISTRATION: The study protocol was retrospectively registered on Clinical Trials (NCT05931822-05/ 07/2023).

Development of undergraduate students' diagnostic accuracy for the classification of molar incisor hypomineralization.

INTRODUCTION: One of the major difficulties with respect to molar incisor hypomineralization (MIH) is its classification and differentiation from other enamel development defects (EDDs). The aim of this study was to evaluate diagnostic accuracy in dental students to classify MIH as well as its differentiation from other EDDs by combining conventional theoretical classes and e-learning-assisted pre-clinical practices. METHODS: In this one-group pre-test and post-test study, 59 second-year students assessed 115 validated photographs using the MIH Index on the Moodle learning platform. This index assesses the clinical features and extent of MIH, differentiating it from other EDDs. Students received automatic feedback after the pre-test. Two weeks later, students re-evaluated the same photographs. Both pairwise accuracy and overall diagnostic accuracy were estimated and compared for pre- and post-testing, with the area under the curve AUC, along with 95% confidence intervals (95% CI). RESULTS: The lowest diagnostic accuracy was for the ability to discriminate between white or cream-coloured demarcated opacities and hypomineralization-type defect that is not MIH. The overall pre-test accuracy was AUC = 0.83 and increased significantly post-test to AUC = 0.99 (p < .001). The overall accuracy to discriminate the extent of the lesion also increased significantly post-test (p < .001). CONCLUSION: Diagnostic skills to classify MIH can be developed by combining conventional theoretical classes and e-learning-assisted pre-clinical practices.

Is SDF better than the SMART (silver modified atraumatic restorative technique) in the management of molar incisor hypomineralisation molars with initial caries?

DESIGN: A prospective, randomized, split-mouth clinical study by the two previously trained and calibrated pediatric dentists without blinding operators and patients due to different protocols in both treatment groups. An SDF + potassium iodide (KI) and SDF + KI + glass ionmer cement (GIC) on International Caries Detection and Assessment System (ICDAS) 1/2 molar was received by each patient on either side of mouth. The local Ethics Committee approved this study. DATA SOURCE: Sample size calculation was not performed due to the lack of published studies on the longevity of SMART sealant on MIH-affected molars and the absence of research on the apparent difference between the effectiveness of SMART and SDF treatments in preventing further caries and sensitivity. STUDY SELECTION: These were children between the ages of 6 years to 13 years, who visited the Pediatric Dentistry Clinic at XX University School of Dentistry for routine exams and treatment between July 2019 to May 2020. They were in good health and had at least two fully erupted permanent first molars with MIH as per the European Academy of Pediatric Dentistry, ICDAS code 1/2. This study recorded 12 months of treatment outcomes on hypomineralised molars of 48 children with a follow-up of three years. Children were excluded with specific syndromes associated with enamel malformation, lack of cooperation, ongoing orthodontic treatment, and teeth with ICDAS 3/4/5/6 lesions, existing restorations, fluorosis, or pulpal symptoms. DATA ANALYSIS: Mann-Whitney U Test was used to assess differences between independent groups (SDF and SMART) and the Friedman Test between dependent groups at different time points. Kaplan-Meier analysis to evaluate the cumulative survival of SMART sealants and survival of caries-free hypomineralised molars in both groups. Chi-Square test was used to compare the success percentages of the SDF and SMART groups. To assess the changes in success percentages at three different time intervals for the caries preventive effect of SDF and SMART, and to evaluate the retention percentages for the SMART group. McNemar's test with a Bonferroni correction was used for significant differences. Cohen's kappa test indicated that the inter-examiner reliability determining the presence of MIH was 0.87. The intra-examiner reliability for US Public Health Service (USPHS)-Modified criteria was 0.90. The statistical significance level was set at p < 0.05 for all statistical analyses. RESULTS: At 12, 24 and 36 months the caries preventive effect was 100%, 67.9%, and 65.4% for SDF + KI-treated teeth; and 100%, 97.6%, and 94.7% for SMART (SDF + KI + GIC) respectively. During the recall period, there was no substantial difference in hypersensitivity scores between the groups. There was no hypersensitivity in teeth at 18 months and beyond. Compared to the baseline Schiff Cold Air Sensitivity Scale (SCASS) score 26 molar with initial hypersensitivity to hypomineralisation had a massive reduction at evaluation periods. The mean survival probabilities for the caries-preventive effect were considerably lower in SDF + KI-treated teeth (31.01 months) than in SMART-treated teeth (35.61 months) (p < 0.001). CONCLUSION: Considering the limitation of the study, both SMART (SDF + KI + GIC) sealants and 6-monthly application of SDF + KI, provided similar and substantial levels of desensitisation on the permanent MIH molars. When used as a sealing material on non-cavitated permanent MIH molars, the clinical retention rate for SMART was 88.7%, 73.1%, and 66.6% at 1, 2, and 3 years respectively. The caries preventive effect of SMART (SDF + KI + GIC) sealants was superior to SDF + KI application in hypomineralised teeth, however, a long-term monitoring and review is essential due to the gradual decrease in retention of SMART sealants.

Molar-incisor hypomineralisation in Norwegian children: Prevalence and associated factors.

This study investigated the prevalence and associations of molar-incisor hypomineralisation (MIH) in 8-9 year-old children in Oslo. A total of 3013 children in one age cohort participated in the study during their regular dental examination at the Public Dental Service. Hypomineralised enamel defects were recorded according to the European Academy of Paediatric Dentistry criteria for MIH. Information on health and medications used during pregnancy and in the child's first 3 years of life was obtained from a questionnaire administered to parents. The overall prevalence of MIH was 28.2%, with no gender difference. A higher prevalence of MIH was found in children who had been ill or had used medication in early life and in those whose mother had been ill during pregnancy. No association was found between MIH and prematurity or maternal use of medication during pregnancy. The multivariable analyses showed that children with MIH were more likely to have suffered from illness in early life (OR = 1.41, 95% CI: 1.17-1.70), used antibiotics during the first year of life (OR = 1.68, 95% CI: 1.19-2.35), experienced tooth pain (OR = 1.33, 95% CI: 1.03-1.72), and experienced pain while toothbrushing (OR = 2.17, 95% CI: 1.46-3.23) than children without MIH. The prevalence of MIH was high in the children participating in this study.

Epigenetics in developmental defects of enamel: A scoping review.

OBJECTIVES: The significant role of epigenetics has been revealed in normal enamel formation process and occurrence of developmental defects. This presented literature is aiming at summarizing the regulatory function of epigenetics in physiological amelogenesis process and reviewing the epigenetic mechanisms in occurrence of developmental defects of enamel (DDE), so as to provide biological foundation evidence to support early predication and clinical management of DDE. METHOD: An extensive literature review was conducted using electronic databases MEDLINE (through PubMed), Web of Science and EMBASE up to November 30, 2022. Studies about epigenetic effects on enamel tissue or cells associated with amelogenesis, including in vivo studies using human or animal models, and in vitro studies, are selected. RESULTS: A total of 22 studies were included. Epigenetic factors or effects specifically activate or silence certain genes, which may regulate related biological activities including cell proliferation, cell differentiation, enamel secretion, and mineralization during the process of amelogenesis. Once the status of epigenetic modification is altered, the quantity and quality of enamel may both be disturbed, which can finally result in DDE. CONCLUSION: Epigenetics plays a noteworthy role of regulating the amelogenesis process and DDE potentially by altering the expression levels of genes related to enamel formation, providing a new perspective of early predication and clinical management of DDE.