A cohort study of neurodevelopmental disorders and/or congenital anomalies using high resolution chromosomal microarrays in southern Brazil highlighting the significance of ASD.

Chromosomal microarray (CMA) is the reference in evaluation of copy number variations (CNVs) in individuals with neurodevelopmental disorders (NDDs), such as intellectual disability (ID) and/or autism spectrum disorder (ASD), which affect around 3-4% of the world's population. Modern platforms for CMA, also include probes for single nucleotide polymorphisms (SNPs) that detect homozygous regions in the genome, such as long contiguous stretches of homozygosity (LCSH). These regions result from complete or segmental chromosomal homozygosis and may be indicative of uniparental disomy (UPD), inbreeding, population characteristics, as well as replicative DNA repair events. In this retrospective study, we analyzed CMA reading files requested by geneticists and neurologists for diagnostic purposes along with available clinical data. Our objectives were interpreting CNVs and assess the frequencies and implications of LCSH detected by Affymetrix CytoScan HD (41%) or 750K (59%) platforms in 1012 patients from the south of Brazil. The patients were mainly children with NDDs and/or congenital anomalies (CAs). A total of 206 CNVs, comprising 132 deletions and 74 duplications, interpreted as pathogenic, were found in 17% of the patients in the cohort and across all chromosomes. Additionally, 12% presented rare variants of uncertain clinical significance, including LPCNVs, as the only clinically relevant CNV. Within the realm of NDDs, ASD carries a particular importance, owing to its escalating prevalence and its growing repercussions for individuals, families, and communities. ASD was one clinical phenotype, if not the main reason for referral to testing, for about one-third of the cohort, and these patients were further analyzed as a sub-cohort. Considering only the patients with ASD, the diagnostic rate was 10%, within the range reported in the literature (8-21%). It was higher (16%) when associated with dysmorphic features and lower (7%) for "isolated" ASD (without ID and without dysmorphic features). In 953 CMAs of the whole cohort, LCSH (≥ 3 Mbp) were analyzed not only for their potential pathogenic significance but were also explored to identify common LCSH in the South Brazilians population. CMA revealed at least one LCSH in 91% of the patients. For about 11.5% of patients, the LCSH suggested consanguinity from the first to the fifth degree, with a greater probability of clinical impact, and in 2.8%, they revealed a putative UPD. LCSH found at a frequency of 5% or more were considered common LCSH in the general population, allowing us to delineate 10 regions as potentially representing ancestral haplotypes of neglectable clinical significance. The main referrals for CMA were developmental delay (56%), ID (33%), ASD (33%) and syndromic features (56%). Some phenotypes in this population may be predictive of a higher probability of indicating a carrier of a pathogenic CNV. Here, we present the largest report of CMA data in a cohort with NDDs and/or CAs from the South of Brazil. We characterize the rare CNVs found along with the main phenotypes presented by each patient and show the importance and usefulness of LCSH interpretation in CMA results that incorporate SNPs, as well as we illustrate the value of CMA to investigate CNV in ASD.

A novel approach for in-office tooth bleaching with 6% H2O2/TiO_N and LED/laser system-a controlled, triple-blinded, randomized clinical trial.

UNLABELLED: The purpose of this randomized, parallel, triple-blinded clinical trial was to compare efficacy and tooth sensitivity (TS) after use of an in-office bleaching agent of 6% hydrogen peroxide containing nanoparticles of nitrogen-doped titanium oxide (HP6) vs. 35% hydrogen peroxide (HP35). Forty-eight volunteers were randomly divided either a HP6 or HP35. Two clinical sessions were performed with an interval of 7 days between them for each group. In each session, two consecutive applications of each bleaching agent were performed and activated by a hybrid LED/laser light. Efficacy was determined by color alteration (ΔE), recorded with reflectance spectroscopy. It was assessed at baseline and after the first and second bleaching session. TS was characterized according to occurrence, intensity, duration, and type. Efficacy was analyzed by repeated measures analysis of variance (ANOVA) and post hoc Bonferroni test, and TS was analyzed by means of chi(2) test (α = 0.05). For HP35, highest and significant values of ΔE were found after bleaching when compared to HP6 (p = 0.002). However, HP35 showed a significantly higher occurrence of TS than HP6 (p = 0.008). Also, intensity and duration were higher in HP35. The majority of volunteers classified the type experienced in their sensitivity in the form of a "shock." The use of HP6 despite reducing efficacy when compared to an in-office bleaching in higher concentration (35%) produced less tooth sensitivity. CLINICAL RELEVANCE: In terms of tooth sensitivity, the use of lower concentrations of in-office bleaching should be the first choice, suggesting greater biocompatibility and safety compared to a conventional HP35.