Sound evidence on the effectiveness of fluoride varnishes (FV) to reduce caries incidence in preschool children is lacking. Objective: To assess whether the application of FV in preschool children at 6-month intervals decreases the incidence of caries and produces any adverse effects. Methods: A randomized, examiner- and patient-blind, placebo-controlled, parallel-group design, clinical trial, comprising 1- to 4-year-old children, 100 in each group (FV or placebo varnish, PV), was conducted in Rio de Janeiro, Brazil. Two trained pediatric dentists performed the clinical examinations (kappa = 0.85). Dental caries was recorded at the d₂ (cavitated enamel) and d₃ (dentine) levels using the International Caries Diagnosis and Assessment System. Results: At baseline, the mean age of the participants was 2.4 years (SD 0.9) and the mean d₃mfs was 0.8 (SD 1.9). Most of the children brushed their teeth with fluoride toothpaste and consumed fluoridated tap water. After 24 months, 89 and 92 children of the test and the control groups were analyzed, respectively. A total of 32 (35.9%) children in the FV group and 43 (46.7%) in the PV group presented new dentine caries lesions (χ² test; p = 0.14), showing relative and absolute risk reductions of 23% (95% CI: -9.5 to 45.9) and 11% (95% CI: -3.5 to 25.0). The mean caries increment differences between the test and control groups were -0.8 (95% CI: -2.0 to 0.4) at the d₂ level and -0.7 (95% CI: -1.9 to 0.4) at the d₃ level. Only 2 minor complaints regarding the intervention were reported. Conclusion: Although safe and well accepted, twice-yearly professional FV application, during 2 years, did not result in a significant decrease in caries incidence.

Hypomyelinating leukodystrophies are genetic disorders characterized by insufficient myelin deposition during development. They are diagnosed on the basis of both clinical and MRI features followed by genetic confirmation. Here, we report on four unrelated affected individuals with hypomyelination and bi-allelic pathogenic variants in EPRS, the gene encoding cytoplasmic glutamyl-prolyl-aminoacyl-tRNA synthetase. EPRS is a bifunctional aminoacyl-tRNA synthetase that catalyzes the aminoacylation of glutamic acid and proline tRNA species. It is a subunit of a large multisynthetase complex composed of eight aminoacyl-tRNA synthetases and its three interacting proteins. In total, five different EPRS mutations were identified. The p.Pro1115Arg variation did not affect the assembly of the multisynthetase complex (MSC) as monitored by affinity purification-mass spectrometry. However, immunoblot analyses on protein extracts from fibroblasts of the two affected individuals sharing the p.Pro1115Arg variant showed reduced EPRS amounts. EPRS activity was reduced in one affected individual's lymphoblasts and in a purified recombinant protein model. Interestingly, two other cytoplasmic aminoacyl-tRNA synthetases have previously been implicated in hypomyelinating leukodystrophies bearing clinical and radiological similarities to those in the individuals we studied. We therefore hypothesized that leukodystrophies caused by mutations in genes encoding cytoplasmic aminoacyl-tRNA synthetases share a common underlying mechanism, such as reduced protein availability, abnormal assembly of the multisynthetase complex, and/or abnormal aminoacylation, all resulting in reduced translation capacity and insufficient myelin deposition in the developing brain.

The objective of this systematic review was to evaluate whether there is conclusive evidence that the professional application of fluoride varnish decreases the incidence of dental caries in preschool children. We searched the BBO, LILACS, MEDLINE and Cochrane electronic databases to identify controlled clinical trials that evaluated the development of cavitated caries lesions in children up to six years of age. Two researchers performed a critical appraisal of the studies selected for inclusion. Five-hundred and thirteen articles were found, but only eight met our inclusion criteria. Most of these eight studies were of poor methodological quality. They were also heterogeneous in relation to participants' previous caries experience, type of intervention performed on the control group, children's exposure to other sources of fluoride, and varnish application interval. The absolute differences between caries incidences in the control and test groups ranged from 0.30 to 1.64 and the preventive fractions varied from 5% to 63%. Fluoride varnish may be effective to decrease the incidence of dental caries in preschoolers, but more randomized clinical trials with better methodological quality are necessary to provide conclusive evidence in this respect.

BackgroundExome and genome sequencing have been demonstrated to increase diagnostic yield in paediatric populations, improving treatment options and providing risk information for relatives. There are limited studies examining the clinical utility of these tests in adults, who currently have limited access to this technology.MethodsPatients from adult and cancer genetics clinics across Toronto, Ontario, Canada were recruited into a prospective cohort study evaluating the diagnostic utility of exome and genome sequencing in adults. Eligible patients were ≥18 years of age and suspected of having a hereditary disorder but had received previous uninformative genetic test results. In total, we examined the diagnostic utility of exome and genome sequencing in 47 probands and 34 of their relatives who consented to participate and underwent exome or genome sequencing.ResultsOverall, 17% (8/47) of probands had a pathogenic or likely pathogenic variant identified in a gene associated with their primary indication for testing. The diagnostic yield for patients with a cancer history was similar to the yield for patients with a non-cancer history (4/18 (22%) vs 4/29 (14%)). An additional 24 probands (51%) had an inconclusive result. Secondary findings were identified in 10 patients (21%); three had medically actionable results.ConclusionsThis study lends evidence to the diagnostic utility of exome or genome sequencing in an undiagnosed adult population. The significant increase in diagnostic yield warrants the use of this technology. The identification and communication of secondary findings may provide added value when using this testing modality as a first-line test.

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IntroductionGenomic sequencing has rapidly transitioned into clinical practice, improving diagnosis and treatment options for patients with hereditary disorders. However, large-scale implementation of genomic sequencing faces challenges, especially with regard to the return of incidental results, which refer to genetic variants uncovered during testing that are unrelated to the primary disease under investigation, but of potential clinical significance. High-quality evidence evaluating health outcomes and costs of receiving incidental results is critical for the adoption of genomic sequencing into clinical care and to understand the unintended consequences of adoption of genomic sequencing. We aim to evaluate the health outcomes and costs of receiving incidental results for patients undergoing genomic sequencing.Methods and analysisWe will compare health outcomes and costs of receiving, versus not receiving, incidental results for adult patients with cancer undergoing genomic sequencing in a mixed-methods randomised controlled trial. Two hundred and sixty patients who have previously undergone first or second-tier genetic testing for cancer and received uninformative results will be recruited from familial cancer clinics in Toronto, Ontario. Participants in both arms will receive cancer-related results. Participants in the intervention arm have the option to receive incidental results. Our primary outcome is psychological distress at 2 weeks following return of results. Secondary outcomes include behavioural consequences, clinical and personal utility assessed over the 12 months after results are returned and health service use and costs at 12 months and 5 years. A subset of participants and providers will complete qualitative interviews about utility of incidental results.Ethics and disseminationThis study has been approved by Clinical Trials Ontario Streamlined Research Ethics Review System that provides ethical review and oversight for multiple sites participating in the same clinical trial in Ontario.Results from the trial will be shared through stakeholder workshops, national and international conferences, and peer-reviewed journals.Trial registration numberNCT03597165.

Background: This paper aims to describe a case report about dentigerous cysts related to trauma in the primary teeth.Case report: An eight-year-old boy attended the Pediatric Dental Trauma Clinic. He had a delay in the eruption of the tooth 11 and when he was four years old suffered a trauma in the tooth 51. The radiograph showed a dentigerous cyst involving the tooth 11. The lesion was treated through enucleation and the permanent tooth erupted. Conclusions:A correlation was observed between the dentigerous cyst, trauma in the deciduous incisor and the successor teeth. Early diagnoses as well as clinical and radiographic follow-ups of traumatized primary teeth are important to minimize possible sequelae in the successor teeth.

Genomic sequencing (GS) can reveal secondary ndings (SFs), ndings unrelated to the reason for testing, that can be overwhelming to both patients and providers. An effective approach for communicating all clinically signi cant primary and secondary GS results is needed to effectively manage this large volume of results. The aim of this study was to develop a comprehensive approach to communicate all clinically signi cant primary and SF results. A genomic test report with accompanying patient and provider letters were developed in 3 phases: review of current clinical reporting practices, consulting with genetic and non-genetics experts, and iterative re nement through circulation to key stakeholders. The genomic test report and consultation letters present a myriad of clinically relevant GS results in distinct, tabulated sections, including primary and secondary ndings, with in-depth details of each nding. They provide detailed variant and disease information, personal and familial risk assessments, clinical management details, and additional resources to help support providers and patients with implementing healthcare recommendations related to their GS results. The report and consultation letters represent a comprehensive approach to communicate all clinically signi cant SFs to patients and providers, facilitating clinical management of GS results.