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Identifying mutations in cancer-associated genes to guide patient treatments is essential for precision medicine. Circulating tumor DNA (ctDNA) offers valuable insights for early cancer detection, treatment assessment, and surveillance. However, a key issue in ctDNA analysis from the bloodstream is the choice of a technique with adequate sensitivity to identify low frequent molecular changes. Next-generation sequencing (NGS) technology, evolving from parallel to long-read capabilities, enhances ctDNA mutation analysis. In the present review, we describe different NGS approaches for identifying ctDNA mutation, discussing challenges to standardized methodologies, cost, specificity, clinical context, and bioinformatics expertise for optimal NGS application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Silva, Azevedo , Teixeira, Casseb, Moreira, Assumpção, Santos and Calcagno.)

The selection of proper reference genes is critical for accurate gene expression analysis in all fields of biological and medical research, mainly because there are many distinctions between different tissues and specimens. Given this variability, even in known classic reference genes, demands of a comprehensive analysis platform is needed to identify the most suitable genes for each study. For this purpose, we present an analysis tool for assisting in decision-making in the analysis of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) data. EndoGeneAnalyzer, an open-source web tool for reference gene analysis in RT-qPCR studies, was used to compare the groups/conditions under investigation. This interactive application offers an easy-to-use interface that allows efficient exploration of datasets. Through statistical and stability analyses, EndoGeneAnalyzer assists in the select of the most appropriate reference gene or set of genes for each condition. It also allows researchers to identify and remove unwanted outliers. Moreover, EndoGeneAnalyzer provides a graphical interface to compare the evaluated groups, providing a visually informative differential analysis., Competing Interests: The authors declare no conflict of interest. The funders had no role in the study’s design; in the collection, analyses, or data interpretation; in the writing of the manuscript, or in the decision to publish the results., (Copyright: © 2024 Teixeira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cervical cancer ranks among the most prevalent cancers globally with high-risk human papillomaviruses implicated in nearly 99% of cases. However, hidden players such as changes in the microbiota are now being examined as potential markers in the progression of this disease. Researchers suggest that changes in the vaginal microbiota might correlate with cervical cancer. This review provides a comprehensive look at the microbiota changes linked with the advancement of cervical cancer. It also scrutinizes the databases from past studies on the microbiota during healthy and cancerous stages, drawing connections between prior findings concerning the role of the microbiota in the progression of cervical cancer. Preliminary findings identify Fusobacterium spp., Peptostreptococcus spp., Campylobacter spp., and Haemophilus spp., as potential biomarkers for cervical cancer progression. Alloscardovia spp., Eubacterium spp., and Mycoplasma spp. were identified as potential biomarkers for HPVs (+), while Methylobacterium spp. may be indicative of HPV (-). However, the study's limitations, including potential biases and methodological constraints, underscore the need for further research to validate these findings and delve deeper into the microbiota's role in HPV development. Despite these limitations, the review provides valuable insights into microbiota trends during cervical cancer progression, offering direction for future research. The review summarizes key findings from previous studies on microbiota during healthy and cancerous stages, as well as other conditions such as CIN, SIL, HPV (+), and HPV (-), indicating a promising area for further investigation. The consistent presence of HPV across all reported cervical abnormalities, along with the identification of distinct bacterial genera between cancerous and control samples, suggests a potential link that merits further exploration. In conclusion, a more profound understanding of the microbial landscape could elucidate the pathogenesis of cervical diseases and inform future strategies for diagnosis, prevention, and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fong Amaris, Assumpção, Valadares and Moreira.)

Background: Approximately 3/4 of ovarian cancers are diagnosed in advanced stages, with the high-grade epithelial ovarian carcinoma (EOC) accounting for 90% of the cases. EOC present high genomic instability and somatic loss-of-function variants in genes associated with homologous recombination mutational repair pathway (HR), such as BRCA1 and BRCA2, and in TP53. The identification of germline variants in HR genes in EOC is relevant for treatment of platinum resistant tumors and relapsed tumors with therapies based in synthetic lethality such as PARP inhibitors. Patients with somatic variants in HR genes may also benefit from these therapies. In this work was analyzed the frequency of somatic variants in BRCA1, BRCA2, and TP53 in an EOC cohort of Brazilian patients, estimating the proportion of variants in tumoral tissue and their association with progression-free survival and overall survival., Methods: The study was conducted with paired blood/tumor samples from 56 patients. Germline and tumoral sequences of BRCA1, BRCA2, and TP53 were obtained by massive parallel sequencing. The HaplotypeCaller method was used for calling germline variants, and somatic variants were called with Mutect2., Results: A total of 26 germline variants were found, and seven patients presented germline pathogenic or likely pathogenic variants in BRCA1 or BRCA2. The analysis of tumoral tissue identified 52 somatic variants in 41 patients, being 43 somatic variants affecting or likely affecting protein functionality. Survival analyses showed that tumor staging was associated with overall survival (OS), while the presence of somatic mutation in TP53 was not associated with OS or progression-free survival., Conclusion: Frequency of pathogenic or likely pathogenic germline variants in BRCA1 and BRCA2 (12.5%) was lower in comparison with other studies. TP53 was the most altered gene in tumors, with 62.5% presenting likely non-functional or non-functional somatic variants, while eight 14.2% presented likely non-functional or non-functional somatic variants in BRCA1 or BRCA2., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Reference genes are used as internal reaction controls for gene expression analysis, and for this reason, they are considered reliable and must meet several important criteria. In view of the absence of studies regarding the best reference gene for the analysis of acute leukemia patients, a panel of genes commonly used as endogenous controls was selected from the literature for stability analysis: Glyceraldehyde-3-phosphate dehydrogenase ( GAPDH ), Abelson murine leukemia viral oncogene human homolog 1 ( ABL ), Hypoxanthine phosphoribosyl-transferase 1 ( HPRT1 ), Ribosomal protein lateral stalk subunit P0 ( RPLP0 ), β-actin ( ACTB ) and TATA box binding protein ( TBP ). The stability of candidate reference genes was analyzed according to three statistical methods of assessment, namely, NormFinder, GeNorm and R software (version 4.0.3). From this study's analysis, it was possible to identify that the endogenous set composed of ACTB , ABL , TBP and RPLP0 demonstrated good performances and stable expressions between the analyzed groups. In addition to that, the GAPDH and HPRT genes could not be classified as good reference genes, considering that they presented a high standard deviation and great variability between groups, indicating low stability. Given these findings, this study suggests the main endogenous gene set for use as a control/reference for the gene expression in peripheral blood and bone marrow samples from patients with acute leukemias is composed of the ACTB , ABL , TBP and RPLP0 genes. Researchers may choose two to three of these housekeeping genes to perform data normalization.

Since the discovery of the polymorphic nature of the IFNL4 gene, its variants have been investigated and associated with several viral diseases, with an emphasis on hepatitis C. However, the impacts of these variants on mixed-race and native populations in the northern region of Brazil are scarce. We investigated three variants of the IFNL4 gene in populations from this location, which were among the 14 most frequent variants in worldwide populations, and compared the frequencies obtained to populational data from the 1000 Genomes Project, gnomAD and ABraOM databases. Our results demonstrate that mixed-race and native populations from the northern region of Brazil present frequencies like those of European and Asian groups for the rs74597329 and rs11322783 variants, and like all populations presented for the rs4803221 variant. These data reinforce the role of world populations in shaping the genetic profile of Brazilian populations, indicate patterns of illness according to the expressed genotype, and infer an individual predisposition to certain diseases.

Chronic consumption of hyperpalatable and hypercaloric foods has been pointed out as a factor associated with cognitive decline and memory impairment in obesity. In this context, the integration between peripheral and central inflammation may play a significant role in the negative effects of an obesogenic environment on memory. However, little is known about how obesity-related peripheral inflammation affects specific neurotransmission systems involved with memory regulation. Here, we test the hypothesis that chronic exposure to a highly palatable diet may cause neuroinflammation, glutamatergic dysfunction, and memory impairment. For that, we exposed C57BL/6J mice to a high sugar and butter diet (HSB) for 12 weeks, and we investigated its effects on behavior, glial reactivity, blood-brain barrier permeability, pro-inflammatory features, glutamatergic alterations, plasticity, and fractalkine-CX3CR1 axis. Our results revealed that HSB diet induced a decrease in memory reconsolidation and extinction, as well as an increase in hippocampal glutamate levels. Although our data indicated a peripheral pro-inflammatory profile, we did not observe hippocampal neuroinflammatory features. Furthermore, we also observed that the HSB diet increased hippocampal fractalkine levels, a key chemokine associated with neuroprotection and inflammatory regulation. Then, we hypothesized that the elevation on glutamate levels may saturate synaptic communication, partially limiting plasticity, whereas fractalkine levels increase as a strategy to decrease glutamatergic damage., (© 2023. Springer Nature Limited.)

Gastric cancer (GC) is a highly prevalent and deadly malignant neoplasm worldwide. Currently, long non-coding RNAs (lncRNAs) have recently been identified as crucial regulators implicated in GC development and progression. Dysregulated expression of lncRNAs is commonly associated with enhanced tumor migration, invasiveness, and therapy resistance, highlighting their potential as promising targets for clinical applications. This review offers a comprehensive historical overview of lncRNAs in GC, describes the molecular mechanisms, and discusses the prospects and challenges of establishing lncRNAs as precision biomarkers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Silva, Teixeira, Mourão, Ferraz, Moreira, Assumpção and Calcagno.)

Due to their continuing geographic isolation, the Amerindian populations of the Brazilian Amazon present a different genetic profile when compared to other continental populations. Few studies have investigated genetic variants present in these populations, especially in the context of next-generation sequencing. Knowledge of the molecular profile of a population is one of the bases for inferences about human evolutionary history, in addition, it has the ability to assist in the validation of molecular biomarkers of susceptibility to complex and rare diseases, and in the improvement of specific precision medicine protocols applied to these populations and to populations with high Amerindian ancestry, such as Brazilians. DNA polymerases play essential roles in DNA replication, repair, recombination, or damage repair, and their influence on various clinical phenotypes has been demonstrated in the specialized literature. Thus, the aim of this study is to characterize the molecular profile of POLA1 , POLE , POLG , POLQ , and REV3L genes in Amerindian populations from the Brazilian Amazon, comparing these findings with genomic data from five continental populations described in the gnomAD database, and with data from the Brazilian population described in ABraOM. We performed the whole exome sequencing (WES) of 63 Indigenous individuals. Our study described for the first time the allele frequency of 45 variants already described in the other continental populations, but never before described in the investigated Amerindian populations. Our results also describe eight unique variants of the investigated Amerindians populations, with predictions of moderate, modifier and high clinical impact. Our findings demonstrate the unique genetic profile of the Indigenous population of the Brazilian Amazon, reinforcing the need for further studies on these populations, and may contribute to the creation of public policies that optimize not only the quality of life of this population, but also of the Brazilian population.

Gastric cancer (GC) is a multifactorial, complex, and aggressive disease with a prevalence of one million new cases and high global mortality. Factors such as genetic, epigenetic, and environmental changes contribute to the onset and progression of the disease. Identification of INDELs in miRNA and its target sites in current studies showed an important role in the development of cancer. In GC, miRNAs act as oncogenes or tumor suppressors, favoring important cancer pathways, such as cell proliferation and migration. This work aims to investigate INDELs in the coding region of miRNAs (hsa-miR-302c, hsa-miR-548AJ-2, hsa-miR-4274, hsa-miR-630, hsa-miR-516B-2, hsa-miR-4463, hsa-miR-3945, hsa-miR-548H_4, hsa-miR-920, has-mir-3171, and hsa-miR-3652) that may be associated with susceptibility and clinical variants of gastric cancer. For this study, 301 patients with GC and 145 individuals from the control group were selected from an admixed population in the Brazilian Amazon. The results showed the hsa-miR-4463, hsa-miR-3945, hsa-miR-548H_4, hsa-miR-920 and hsa-miR-3652 variants were associated with gastric cancer susceptibility. The hsa-miR-4463 was significantly associated with clinical features of GC such as diffuse gastric tumor histological type, "non-cardia" localization region, and early onset. Our findings indicated that INDELs could be potentially functional genetic variants for gastric cancer risk.

Hereditary gastric cancers (HGCs) are supposed to be rare and difficult to identify. Nonetheless, many cases of young patients with gastric cancer (GC) fulfill the clinical criteria for considering this diagnosis but do not present the defined pathogenic mutations necessary to meet a formal diagnosis of HGC. Moreover, GC in young people is a challenging medical situation due to the usual aggressiveness of such cases and the potential risk for their relatives when related to a germline variant. Aiming to identify additional germline alterations that might contribute to the early onset of GC, a complete exome sequence of blood samples from 95 GC patients under 50 and 94 blood samples from non-cancer patients was performed and compared in this study. The number of identified germline mutations in GC patients was found to be much higher than that from individuals without a cancer diagnosis. Specifically, the number of high functional impact mutations, including those affecting genes involved in medical diseases, cancer hallmark genes, and DNA replication and repair processes, was much higher, strengthening the hypothesis of the potential causal role of such mutations in hereditary cancers. Conversely, classically related HGC mutations were not found and the number of mutations in genes in the CDH1 pathway was not found to be relevant among the young GC patients, reinforcing the hypothesis that existing alternative germline contributions favor the early onset of GC. The LILRB1 gene variants, absent in the world's cancer datasets but present in high frequencies among the studied GC patients, may represent essential cancer variants specific to the Amerindian ancestry's contributions. Identifying non-reported GC variants, potentially originating from under-studied populations, may pave the way for additional discoveries and translations to clinical interventions for GC management. The newly proposed approaches may reduce the discrepancy between clinically suspected and molecularly proven hereditary GC and shed light on similar inconsistencies among other cancer types. Additionally, the results of this study may support the development of new blood tests for evaluating cancer risk that can be used in clinical practice, helping physicians make decisions about strategies for surveillance and risk-reduction interventions.

Introduction: Cancer research has significantly improved in recent years, primarily due to next-generation sequencing (NGS) technology. Consequently, an enormous amount of genomic and transcriptomic data has been generated. In most cases, the data needed for research goals are used, and unwanted reads are discarded. However, these eliminated data contain relevant information. Aiming to test this hypothesis, genomic and transcriptomic data were acquired from public datasets., Materials and Methods: Metagenomic tools were used to explore genomic cancer data; additional annotations were used to explore differentially expressed ncRNAs from miRNA experiments, and variants in adjacent to tumor samples from RNA-seq experiments were also investigated., Results: In all analyses, new data were obtained: from DNA-seq data, microbiome taxonomies were characterized with a similar performance of dedicated metagenomic research; from miRNA-seq data, additional differentially expressed sncRNAs were found; and in tumor and adjacent to tumor tissue data, somatic variants were found., Conclusions: These findings indicate that unexplored data from NGS experiments could help elucidate carcinogenesis and discover putative biomarkers with clinical applications. Further investigations should be considered for experimental design, providing opportunities to optimize data, saving time and resources while granting access to multiple genomic perspectives from the same sample and experimental run.

Several neurodevelopmental and neuropsychiatric disorders are characterized by intermittent episodes of pathological activity. Although genetic therapies offer the ability to modulate neuronal excitability, a limiting factor is that they do not discriminate between neurons involved in circuit pathologies and "healthy" surrounding or intermingled neurons. We describe a gene therapy strategy that down-regulates the excitability of overactive neurons in closed loop, which we tested in models of epilepsy. We used an immediate early gene promoter to drive the expression of Kv1.1 potassium channels specifically in hyperactive neurons, and only for as long as they exhibit abnormal activity. Neuronal excitability was reduced by seizure-related activity, leading to a persistent antiepileptic effect without interfering with normal behaviors. Activity-dependent gene therapy is a promising on-demand cell-autonomous treatment for brain circuit disorders.

Native American populations from the Brazilian Amazon have a low genetic diversity and a different genetic profile when compared to people from other continents. Despite this, few studies have been conducted in this group, and there is no description of their genetic data in the various currently existent international databases. The characterization of the genomic profile of a population not only has an impact in studies of population genetics, but also helps to advance diagnostic and therapeutic response studies, leading to the optimization of clinical applicability. Genetic variations in DNA repair genes have been associated with the modulation of susceptibility to various pathologies, as well as in their prognosis and therapy. This is the first study to investigate DNA repair genes in Amerindians from the Brazilian Amazon region. We investigated 13 important DNA repair genes in the exome of 63 Native Americans, comparing our results with those found in 5 continental populations, whose data are available in the Genome Aggregation Database. Our results showed that 57 variants already described in literature were differentially distributed in the Amerindian populations in relation to the continental populations, 7 of which have significant clinical relevance. In addition, 9 new variants were described, suggesting that they are unique to these populations. Our study reinforces the understanding that the Amazonian Native American population presents a unique genetic profile, and our findings may collaborate with the creation of public policies that optimize the quality of life of these groups as well as the Brazilian population, which presents a high degree of interethnic mixing with Amerindian groups.

The circadian clock (CC) is a daily system that regulates the oscillations of physiological processes and can respond to the external environment in order to maintain internal homeostasis. For the functioning of the CC, the clock genes (CG) act in different metabolic pathways through the clock-controlled genes (CCG), providing cellular regulation. The CC's interruption can result in the development of different diseases, such as neurodegenerative and metabolic disorders, as well as cancer. Leukemias correspond to a group of malignancies of the blood and bone marrow that occur when alterations in normal cellular regulatory processes cause the uncontrolled proliferation of hematopoietic stem cells. This review aimed to associate a deregulated CC with the manifestation of leukemia, looking for possible pathways involving CG and their possible role as leukemic biomarkers.

Cancer is a multifactorial group of diseases, being highly incident and one of the leading causes of death worldwide. In Brazil, there is a great variation in cancer incidence and impact among the different geographic regions, partly due to the genetic heterogeneity of the population in this country, composed mainly by European (EUR), Native American (NAM), African (AFR), and Asian (ASN) ancestries. Among different populations, genetic markers commonly present diverse allelic frequencies, but in admixed populations, such as the Brazilian population, data is still limited, which is an issue that might influence cancer incidence. Therefore, we analyzed the allelic and genotypic distribution of 12 INDEL polymorphisms of interest in populations from the five Brazilian geographic regions and in populations representing EUR, NAM, AFR, and ASN, as well as tissue expression in silico. Genotypes were obtained by multiplex PCR and the statistical analyses were done using R, while data of tissue expression for each marker was extracted from GTEx portal. We highlight that all analyzed markers presented statistical differences in at least one of the population comparisons, and that we found 39 tissues to be differentially expressed depending on the genotype. Here, we point out the differences in genotype distribution and gene expression of potential biomarkers for risk of cancer development and we reinforce the importance of this type of study in populations with different genetic backgrounds.

Genetic variations in PCLO have been associated with different pathologies in global literature, but there are no data regarding this gene in Native American populations. The Amazonian Native American populations have lower genetic diversity and are more different from other continental groups. We investigated 18 genetic variants in the PCLO gene in Amazonian indigenous and compared our results with the ones found in global populations, which were publicly available in the 1000 Genomes Project, gnmAD and ABraOM databases. The results demonstrated that the variants of the PCLO , especially rs17156844, rs550369696, rs61741659 and rs2877, have a significantly higher frequency in Amerindian populations in comparison with other continental populations. These data outline the singular genetic profile of the Native American population from the Brazilian Amazon region.

piRNAs are a class of noncoding RNAs that perform functions in epigenetic regulation and silencing of transposable elements, a mechanism conserved among most mammals. At present, there are more than 30,000 known piRNAs in humans, of which more than 80% are derived from intergenic regions, and approximately 20% are derived from the introns and exons of pre-mRNAs. It was observed that the expression of the piRNA profile is specific in several organs, suggesting that they play functional roles in different tissues. In addition, some studies suggest that changes in regions that encode piRNAs may have an impact on their function. To evaluate the conservation of these regions and explore the existence of a seed region, SNP and INDEL variant rates were investigated in several genomic regions and compared to piRNA region variant rates. Thus, data analysis, data collection, cleaning, treatment, and exploration were implemented using the R programming language with the help of the RStudio platform. We found that piRNA regions are highly conserved after considering INDELs and do not seem to present an identifiable seed region after considering SNPs and INDEL variants. These findings may contribute to future studies attempting to determine how polymorphisms in piRNA regions can impact diseases.

Introduction  Tinnitus is experienced by a significant part of the patients suffering from otosclerosis. Objective  To assess the prevalence of tinnitus in otosclerosis, its main features, and the impact on the daily life. Methods  Patients diagnosed with otosclerosis in 2019 in a tertiary hospital were enrolled in the study. Demographic data were retrieved and, besides a regular audiometric evaluation, the patients underwent acuphenometry to assess the psychoacoustic measurements (pitch and loudness), and the Tinnitus Handicap Inventory (THI). Results  In total, 66 patients fulfilled the inclusion criteria, with a female predominance (63.6%; n = 42), and a mean age of 48.7 years. The mean air-bone gap was of 26.3 dB. A total of 72.7% complained of tinnitus; it was mostly unilateral, identified in the low frequencies, namely 500 Hz, with median loudness of 7.5 dB. The median score on the THI score was of 37; most patients had a mild handicap (33.3%, n = 16), followed by those with a severe handicap (22.9%; n = 11). The female gender had a statistically significant association with the presence of tinnitus. The THI scores were higher in middle-aged patients (age groups: 40 to 49 and 50 to 59 years), which was statistically significant. No correlation was found between audiometry results and the prevalence of tinnitus or score on the THI. On the other hand, high-pitched tinnitus, compared to low pitched-tinnitus, was associated with larger air-bone gaps. Conclusion  The prevalence of tinnitus in our population was in line with the prevalences reported in the literature. It caused a catastrophic handicap in 22.9% of the patients. High-pitched tinnitus was associated with higher handicap. Nonetheless, the existence of tinnitus and its severity were not associated with the degree of hearing loss., Competing Interests: Conflict of Interests The authors have no conflict of interests to declare., (Fundação Otorrinolaringologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

The Amazonian symbol fish Arapaima gigas is the only living representative of the Arapamidae family. Environmental pressures and illegal fishing threaten the species' survival. To protect wild populations, a national regulation must be developed for the management of A. gigas throughout the Amazon basin. Moreover, the reproductive genetic management and recruitment of additional founders by aquaculture farms are needed to mitigate the damage caused by domestication. To contribute to the sustainable development, we investigated the genetic diversity of wild and cultivated populations of A. gigas and developed a panel composed by 12 microsatellite markers for individual and population genetic tracing. We analyzed 368 samples from three wild and four farmed populations. The results revealed low rates of genetic diversity in all populations, loss of genetic diversity and high inbreeding rates in farmed populations, and genetic structuring among wild and farmed populations. Genetic tracing using the 12 microsatellite markers was effective, and presented a better performance in identifying samples at the population level. The 12-microsatellite panel is appliable to the legal aspects of the trade of the A. gigas , such as origin discrimination, reproductive genetic management by DNA profiling, and evaluation and monitoring of genetic diversity.

Introduction: Vestibular disorders in pediatric patients is still a controversial subject but has gained relevance over the years. In recent studies, its prevalence varied between 0.7% and 15%. Nevertheless, the true prevalence can be underestimated given that its clinical presentation is expressed compared to adults; it can present as rotatory vertigo, but It can also cause vision complaints, headaches, motor delay, and learning disability. Although middle ear effusion is considered the main cause of vestibular dysfunction in this age group, other diagnoses should be considered. The aim of this study was to describe clinical features of the pediatric population referred to a subspecialist Otorhinolaryngology vertigo clinic in a tertiary hospital between 2013 and 2017. We also aimed to compare the results and carry out a literature about the most common causes, diagnostic features and treatment approach., Material and Methods: Clinical records of patients referred to a subspecialist Otorhinolaryngology vertigo clinic with suspicion of vestibular dysfunction aged between 0 and 18 years old were reviewed. Patients with middle ear effusion were excluded., Results: Thirty-seven patients met the inclusion criteria. From these, 59% were female, with a mean age of 10.9 years old during the first consultation. The most common reason for referral was rotatory vertigo. Nausea and headache were also frequent complaints in our population. All patients performed audiometry; videonistagmography was performed in 41% of the cases; imaging studies were done in 59% of patients. The most common causes of vestibular dysfunction were vestibular migraine and benign paroxysmal vertigo of childhood (both in 27% of the cases), followed by vestibular neuritis (in 22% of the cases)., Discussion: Although our findings partially concur with the literature, compared with other specialist centers, the range of reasons for referral and of conditions is not as diverse, which may suggest that there is underdiagnosis of vestibular dysfunction in this age group., Conclusion: Vestibular dysfunction in the pediatric age can have several causes; pediatricians, neurologists, physiatrists, family doctors and otorhinolaryngologists must be aware of the different forms of presentation. Referral and evaluation protocols addressing pediatric patients should be created.

Identifying a microbiome pattern in gastric cancer (GC) is hugely debatable due to the variation resulting from the diversity of the studied populations, clinical scenarios, and metagenomic approach. H. pylori remains the main microorganism impacting gastric carcinogenesis and seems necessary for the initial steps of the process. Nevertheless, an additional non-H. pylori microbiome pattern is also described, mainly at the final steps of the carcinogenesis. Unfortunately, most of the presented results are not reproducible, and there are no consensual candidates to share the H. pylori protagonists. Limitations to reach a consistent interpretation of metagenomic data include contamination along every step of the process, which might cause relevant misinterpretations. In addition, the functional consequences of an altered microbiome might be addressed. Aiming to minimize methodological bias and limitations due to small sample size and the lack of standardization of bioinformatics assessment and interpretation, we carried out a comprehensive analysis of the publicly available metagenomic data from various conditions relevant to gastric carcinogenesis. Mainly, instead of just analyzing the results of each available publication, a new approach was launched, allowing the comprehensive analysis of the total sample amount, aiming to produce a reliable interpretation due to using a significant number of samples, from different origins, in a standard protocol. Among the main results, Helicobacter and Prevotella figured in the "top 6" genera of every group. Helicobacter was the first one in chronic gastritis (CG), gastric cancer (GC), and adjacent (ADJ) groups, while Prevotella was the leader among healthy control (HC) samples. Groups of bacteria are differently abundant in each clinical situation, and bacterial metabolic pathways also diverge along the carcinogenesis cascade. This information may support future microbiome interventions aiming to face the carcinogenesis process and/or reduce GC risk., (© 2021 S. Karger AG, Basel.)

Introduction: Computer-aided design and manufacturing (CAD-CAM) systems have assisted orthodontists to position brackets virtually. The purpose of this study was to evaluate if a CAD-CAM system could predict the orthodontic treatment outcome of patients with Angle Class I malocclusion with mild crowding or spacing and with no need for orthodontic extraction., Methods: Using the American Board of Orthodontics Cast-Radiograph Evaluation (ABO-CRE) and color map superimposition, the treated occlusion was compared with the virtual final occlusion of 24 young adults with Class I occlusion. Using eXceed software (eXceed, Witten, Germany), we created the final occlusion prediction for each patient (virtual set up group). A digital model of the final occlusion of each patient was created (treated occlusion group). ABO-CRE score was used to compare groups. In addition, a color map was created for all subjects to access the mean and range values between the virtual set up model and treated occlusion model of each patient. Random and systematic errors were calculated. In addition, chi-square and t test were used., Results: Comparisons between virtual set up occlusion and treated occlusion showed statistically significant differences in 3 out of 7 measurements: interproximal contact score was larger for treated than virtual occlusion (0.45 mm and 0.04 mm, respectively), and the treated occlusion showed larger values than the virtual occlusion for occlusal contacts (14.13 mm and 7.62 mm, respectively) and overjet (7.37 mm and 0.66 mm, respectively). Although the treated occlusion showed a larger score than the virtual occlusion (50.41 mm and 34.58 mm, respectively), there is no significant difference between both. Root angulation decreased (from 1.95 ± 1.29 to 0.65 ± 0.71) because of the treatment., Conclusions: ABO-CRE overall score presents no difference between groups. In addition, CAD-CAM setup occlusion closely predicts the final teeth alignment and leveling with interarch relationships showing less ABO-CRE score deduction., (Copyright © 2020 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

This study focuses on the influence of major dissolved constituents naturally found in waters intended for human consumption on bromate (BrO 3 - ) reduction by heterogeneous photocatalysis. The individual and combined effect of chloride (Cl - ), bicarbonate/carbonic acid (HCO 3 - /H 2 CO 3 ), nitrate (NO 3 - ), sulphate (SO 4 2- ) and humic acids (HAs) on BrO 3 - reduction was evaluated in synthetic waters (SWs). Additionally, freshwaters (FWs) from a drinking water treatment plant (DWTP) were tested and directly compared to SWs. Cl - was beneficial for contents in the range 0.47-1.4 mM, with negligible influence for lower and higher contents. NO 3 - had a null effect regardless of its content (0.024-0.81 mM). HCO 3 - /H 2 CO 3 (0.061/0.45 mM), SO 4 2- (0.12-2.6 mM) and HAs (0.11-1.0 mM C) had a negative effect in the tested contents. The BrO 3 - reduction rate was 2.8 times lower in SW with a mixture of water constituents compared to SW without constituents addition. This decline on BrO 3 - reduction rate corresponded to the sum of the individual species contribution and so there was no evidence of synergetic effects. By contrast, the use of FWs provided BrO 3 - reduction rates only slightly lower than that found for SW without constituents addition (∼1.2-fold), which can be attributed to: (i) the distinct characteristics of the organic matter of FWs (HAs, fulvic acids and humins with distinct molecular weights and functional groups) compared to that of SW (pure HAs), and/or (ii) the presence in FWs of other inorganics in addition to those here addressed. The heterogeneous TiO 2 photocatalysis proved to be a promising process for BrO 3 - reduction in DWTPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The clinical condition COVID-19, caused by SARS-CoV-2, was declared a pandemic by the WHO in March 2020. Currently, there are more than 5 million cases worldwide, and the pandemic has increased exponentially in many countries, with different incidences and death rates among regions/ethnicities and, intriguingly, between sexes. In addition to the many factors that can influence these discrepancies, we suggest a biological aspect, the genetic variation at the viral S protein receptor in human cells, ACE2 (angiotensin I-converting enzyme 2), which may contribute to the worse clinical outcome in males and in some regions worldwide. We performed exomics analysis in native and admixed South American populations, and we also conducted in silico genomics databank investigations in populations from other continents. Interestingly, at least ten polymorphisms in coding, noncoding and regulatory sites were found that can shed light on this issue and offer a plausible biological explanation for these epidemiological differences. In conclusion, there are ACE2 polymorphisms that could influence epidemiological discrepancies observed among ancestry and, moreover, between sexes., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: Competing interests: None declared.

This study focuses on the development of a treatment train for a leachate from a hazardous industrial waste landfill (HIWL) previously treated by: (i) catalytic oxidation with hydrogen peroxide (H 2 O 2 ) for sulphide and sulphite conversion into oxidized sulphur species, including sulphate, and (ii) chemical precipitation of sulphate as barite. The complete treatment line counted on four more stages: (iii) 1 st biological oxidation for removal of biodegradable organic compounds and nitrogen species, (iv) coagulation with ferric chloride (coagulant dose of 100 mg Fe L -1 , pH 2.8) for removal of a fraction of recalcitrant organics and suspended solids, (v) photo-Fenton oxidation using ultraviolet A (UVA) radiation (PF-UVA) (pH 2.8, initial total dissolved iron content of 140 mg L -1 , treatment time of ~4 h) for recalcitrant organics degradation and biodegradability improvement, and (vi) 2 nd biological oxidation for removal of the biodegradable organic matter resulting from the PF-UVA process. The use of anodic oxidation or photoelectro-Fenton processes in stage (v) demonstrated to be unfeasible. A chemical oxygen demand (COD) below 1000 mg O 2 L -1 , a common limit imposed by municipal wastewater treatment plants (MWWTPs) to effluents discharged into the municipal sewer, was achieved after a feasible treatment time (~4 h) using the multistep approach. The remediation of the HIWL leachate proved to be a big challenge., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Gastric cancer (GC) represents a notable amount of morbidity and mortality worldwide. Understanding the molecular basis of CG will offer insight into its pathogenesis in an attempt to identify new molecular biomarkers to early diagnose this disease. Therefore, studies involving small non-coding RNAs have been widely explored. Among these, PIWI-interacting RNAs (piRNAs) are an emergent class that can play important roles in carcinogenesis. In this study, small-RNA sequencing was used to identify the global piRNAs expression profile (piRNome) of gastric cancer patients. We found 698 piRNAs in gastric tissues, 14 of which were differentially expressed (DE) between gastric cancer (GC), adjacent to gastric cancer (ADJ), and non-cancer tissues (NC). Moreover, three of these DE piRNAs (piR-48966*, piR-49145, piR-31335*) were differently expressed in both GC and ADJ samples in comparison to NC samples, indicating that the tumor-adjacent tissue was molecularly altered and should not be considered as a normal control. These three piRNAs are potential risk biomarkers for GC, especially piR-48966* and piR-31335*. Furthermore, an in-silico search for mRNAs targeted by the differentially expressed piRNAs revealed that these piRNAs may regulate genes that participate in cancer-related pathways, suggesting that these small non-coding RNAs may be directly and indirectly involved in gastric carcinogenesis.

The remediation of a real textile wastewater aiming its reuse in the textile industry was carried out by integrating two processes: (i) a chemical or electrochemical advanced oxidation process (AOP or EAOP) based on Fenton's reaction for organics degradation, and (ii) a cation exchange process using marine macroalgae for removal of the iron acting in the Fenton's reaction based processes. Four AOPs/EAOPs at acidic pH 2.8 were tested: Fenton, photo-Fenton with ultraviolet A (UVA) radiation (PF/UVA), electro-Fenton (EF) and photoelectro-Fenton with UVA radiation (PEF/UVA). These processes provided very high color removals. After a running time of 45 min, the color removals were 68-95% for the Fenton process, 76-94% for the EF process, 80-98% for the PF/UVA process and 85-100% for the PEF/UVA process. In contrast, the mineralization was negligible for all the processes, indicating the generation/presence of persistent colorless compounds. The PF process was selected as first treatment stage due to its ability for color removal and related lower costs. A set of six marine macroalgae (Gracilaria caudata, Gracilaria cervicornis, Ascophyllum nodosum, Fucus spiralis, Laminaria hyperborea and Pelvetia canaliculata) were tested for iron uptake. Laminaria hyperborea showed the highest ion exchange capacity and affinity for iron species. Its application allowed the removal of all the iron acting in the PF process (3.4 mg/L). The textile wastewater resulting from the application of PF process followed by cation exchange with Laminaria hyperborea was successfully reused in scouring, bleaching and dyeing processes., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Leprosy, which is caused by the human pathogen Mycobacterium leprae, causes nerve damage, deformity and disability in over 200,000 people every year. Because of the long doubling time of M. leprae (13 days) and the delayed onset of detectable symptoms, which is estimated to be approximately 3-7 years after infection, there is always a large percentage of subclinically infected individuals in the population who will eventually develop the disease, mainly in endemic countries. piRNAs comprise the largest group of small noncoding RNAs found in humans, and they are distinct from microRNAs (miRNAs) and small interfering RNAs (siRNAs). piRNAs function in transposon silencing, epigenetic regulation, and germline development. The functional role of piRNAs and their associated PIWI proteins have started to emerge in the development of human cancers and viral infections, but their relevance to bacterial diseases has not been investigated. The present study reports the piRNome of human skin, revealing that all but one of the piRNAs examined are downregulated in leprosy skin lesions. Considering that one of the best characterized functions of piRNAs in humans is posttranscriptional mRNA silencing, their functions are similar to what we have described for miRNAs, including acting on apoptosis, M. leprae recognition and engulfment, Schwann cell (SC) demyelination, epithelial-mesenchymal transition (EMT), loss of sensation and neuropathic pain. In addition to new findings on leprosy physiopathology, the discovery of relevant piRNAs involved in disease processes in human skin may provide new clues for therapeutic targets, specifically to control nerve damage, a prominent feature of leprosy that has no currently available pharmaceutical treatment.

It is known that abnormal expression of miRNAs in the gastric cancer (GC) contributes to its carcinogenesis. Therefore, ingestion of commercial (usual) water on a daily basis may be a contributing factor for the occurrence of alterations in the gastric mucosal. In this study, it was evaluated the expression of the miRNAs miR-29c, miR-7, miR-155, and miR-135b in the gastric tissue of patients with gastritis before and after the consumption of alkaline water (pH range from 8.0 to 10.0), as well as the clinic pathological characteristics., Methods: 50 subjects from the Amazon region, diagnosed with gastritis that routinely used commercial (usual) water with a pH lower than 5.0, were enrolled to change the consume water to a pH of 8.5 to 10.0 for 5 months., Results: Endoscopic findings of gastritis were such different (less severe disease), P = 0.024; in 43% diagnosed with moderate gastritis upfront esophagogastroduodenoscopy (EGD) presented mild gastritis after the consumption of alkaline water, according to study methods; there were no worsening gastritis and there were a significant increase in the expression of miR-135b (P = 0.039) and miR-29c (P = 0.039)., Conclusion: Modified pH range water (from 8.0 to 10.0) ingested for 5 months was able lead to a less severe gastritis according to the Sidney classification system, suggesting that this lifestyle change represented a clinical benefit in patients with gastritis on the Amazon region. In addition, higher expression of miR-135b and miR-29c was observed after the consumption of alkaline water for 5 months., Competing Interests: None., (AJTR Copyright © 2020.)

Acute Lymphoblastic Leukemia (ALL) is the most common cancer in children. Differences are found among ethnic groups in the results of the treatment of pediatric ALL. In general, children with a high level of native American ancestry tend to respond less positively to ALL treatments, which may be related to specific genomic variants found in native American groups. Despite the evidence, few data are available on the distribution of the pharmacogenomic variants relevant to the treatment of ALL in traditional Amerindian populations, such the those of the Amazon region. Given this, the present study investigated 27 molecular markers related to the treatment of ALL in Amerindians from Brazilian Amazonia and compared the frequencies with those recorded previously on five continents, that are available in the 1,000 Genomes database. The variation in the genotype frequencies among populations was evaluated using Fisher's exact test. The False Discovery Rate method was used to correct the results of the multiple analyses. Significant differences were found in the frequencies of the majority of markers between the Amerindian populations and those of other regions around the world. These findings highlight the unique genetic profile of the indigenous population of Brazilian Amazonia, which may reflect a distinct therapeutic profile for the treatment of ALL in these populations.

Objective: The purpose of this study was to evaluate the effect of the Yd:YAG laser irradiation on orthodontic bracket base surface. Shear bond strength (SBS) values and sites of the bonding failure interfaces were quantified., Methods: Brackets were divided into two groups: OP (One Piece - integral sandblast base) and OPL (One Piece - laser irradiation). The brackets were randomly bonded on an intact enamel surface of 40 bovine incisors. The SBS tests were carry out using a universal test machine. A stereomicroscopy was used to evaluate the adhesive remnant index (ARI), and surface characterization was performed by scanning electron microscopy (SEM). Student's t-test was used to compare the SBS between the two groups (p< 0.05). Frequencies and chi-square analysis were applied to evaluate the ARI scores., Results: OPL group showed higher value (p< 0.001) of SBS than OP group (43.95 MPa and 34.81 MPa, respectively). ARI showed significant difference (p< 0.001) between OPL group (ARI 0 = 100%) and OP group (ARI 0 = 15%). SEM showed a higher affinity between the adhesive and the irradiated laser base surface., Conclusions: Yd:YAG laser irradiation on bracket base increased SBS values, showing that bonding failure occurs at the enamel/adhesive interface. Laser-etched bracket base may be used instead of conventional bases in cases where higher adhesion is required, reducing bracket-bonding failure.

We report the clinical case of a female patient who presented to our emergency department due to a septal abscess caused by the displacement of a dental implant into the nasal septum. The patient underwent surgical treatment for endoscopic foreign body excision and septal abscess drainage. Despite the presence of septal cartilage destruction, the L-shaped structure was preserved and no reconstruction was required. Postoperative healing was uneventful., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

This study is focused on the selection of the best piping arrangement for a pilot scale annular channel reactor intended for the remediation of waters and wastewaters. Two annular channel reactors composed of a single UV lamp and distinct piping arrangements were considered: (i) a novel reactor with tangential inlet/outlet pipes - the FluHelik reactor, and (ii) a conventional Jets reactor. These two reactors were manufactured at lab scale and characterized in terms of residence time distribution (RTD), radiant power and ability to degrade aqueous solutions spiked with a model compound - 3-amino-5-methylisoxazole (AMI) - by H 2 O 2 /UVC and UVC processes. Computational fluid dynamics (CFD) simulations were used to assess the hydrodynamics, RTD and UV radiation intensity distribution of both reactors at pilot scale. In general, experimental results at lab scale revealed quite similar RTDs, radiant powers and AMI degradation rates for both reactors. On the other hand, CFD simulations at pilot scale revealed the generation of a helical motion of fluid around the UVC lamp in the FluHelik reactor, inducing: (i) a longer contact time between fluid particles and UV light, (ii) more intense dynamics of macromixing as a result of larger velocity gradients, turbulent intensities and dispersion of RTD values around the peak, and (iii) a more homogeneous UV radiation distribution. In addition, the design of the FluHelik reactor can favor the implementation of various reactors in series, promoting its application at industrial scale. The FluHelik reactor was chosen for scaling-up. A pre-pilot scale treatment unit containing this reactor was constructed and its feasibility was proven., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This study aimed at developing an efficient multistage treatment strategy for a complex industrial landfill leachate: a leather tannery landfill leachate. Based on the leachate physicochemical characteristics, the following treatment train was delineated and tested: (i) initial biological process for removal of biodegradable organics, ammonium and alkalinity, (ii) coagulation/flocculation process for total removal of chromium and partial removal of recalcitrant organics and suspended solids, (iii) advanced oxidation process (AOP) or electrochemical AOP (EAOP) for degradation of recalcitrant organics and biodegradability enhancement, and (iv) final biological polishing step. Two initial biological treatment configurations were applied: one comprising nitrification and the other nitrification-denitrification. Coagulation/flocculation was optimized in terms of pH, coagulant dosage (iron(III) chloride) and flocculant nature and dosage. The following AOPs/EAOPs were tested: Fenton, photo-Fenton with UVA or UVC radiation (PF-UVA or PF-UVC), anodic oxidation (AO), electro-Fenton (EF) and photoelectro-Fenton with UVA radiation (PEF-UVA). The biological nitrification-denitrification was beneficial not only because it avoided the need for alkalinity addition during nitrification and decreased the amount of substrate added during denitrification, as expected. Over and above that, it reduced the acid consumption in the coagulation/flocculation, avoided the application of an additional stage comprising nitrites oxidation to nitrates prior to the AOP/EAOP, and improved the efficiency of Fenton's reaction based processes. Following nitrification-denitrification, the coagulation/flocculation was maximized at pH 3.0 and 400 mg Fe L -1 with no flocculant addition. The PEF-UVA process was the best AOP/EAOP. The final leachate fulfilled the discharge limits into waterbodies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

This study focused on the removal of sulphur compounds from a high-strength leachate of a hazardous industrial waste landfill. Firstly, sulphides (0.5 g L -1 ) and sulphites (2.5 g L -1 ) were catalytic oxidised at natural pH (8.7). Air or H 2 O 2 were applied as oxidants and metals present in the leachate were used as catalysts. Distinct air flow rates and H 2 O 2 :sulphur molar ratios were tested. Concentrations of sulphide and sulphite lower than 1.0 mg L -1 (emission limit value - ELV) were obtained after 5-h oxygenation or 1-min peroxidation under the best conditions, i.e. air flow rate of 1 L air L leachate -1  min -1 and H 2 O 2 :sulphur stoichiometric ratio. Aeration was considered unsafe since >33 volatile organic compounds (VOCs) and hydrogen sulphide (H 2 S) were released to the atmosphere. Thus, only the H 2 O 2 -oxidised leachate pursued treatment. Sulphates (13 g L -1 ) were removed by chemical precipitation as ettringite or barite applying different reactants contents and pH values. Without pH correction, sulphate contents below 2.0 g L -1 (ELV) were achieved using a [Ca 2+ ]:[Al 3+ ]:[SO 4 2- ] molar ratio of 12:4:3 (2-fold stoichiometry) and a [Ba 2+ ]:[SO 4 2- ] molar ratio of 1.0:1.0 (1-fold stoichiometry). The analysis of precipitates by X-ray diffraction (XRD) showed a three-phase ettringite (only 67% corresponding to ettringite itself) and single-phase barite. Barite precipitation proved to be more appealing since a value-added product was obtained and, furthermore, less reactants were required. After sulphur compounds removal using H 2 O 2 -driven catalytic oxidation and chemical precipitation through barite, the leachate was suitable for biological treatment, despite the high salinity, and a high fraction of the organic load (46%) could be biologically oxidised., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The biological role of microRNAs (miRNAs) in field cancerization is unknown. To investigate the involvement of miRNAs in gastric field cancerization, we evaluated the expression profile of ten miRNAs and their diagnostic value. Methods: We used three groups of FFPE gastric samples: non-cancer (NC), cancer adjacent (ADJ) and gastric cancer (GC). The expression profiles of hsa-miR-10a , -miR-21, -miR-29c, -miR-135b , -miR-148a , -miR-150 , -miR-204 , -miR-215 , -miR-483 and -miR-664a were investigated using qRT-PCR. The results obtained by qRT-PCR were validated in Small RNA-Seq data from the TCGA database. The search for target genes of the studied miRNAs was performed in the miRTarBase public database and miRTargetLink tool, using experimentally validated interactions. In addition, we also performed the functional analysis of these genes using enrichment in KEGG pathways. The potential as biomarker was evaluated using a receiver operating characteristic (ROC) curve and the derived area under the curve (AUC>0.85) analysis. Results: The miRNAs hsa-miR-10a , -miR-21 , -miR-135b , hsa-miR-148a , -miR-150 , -miR-215 , -miR-204 , -miR-483 and -miR-664a were up-regulated in ADJ and GC compared to NC ( P <0.03); and hsa-miR-21 and -miR-135b were up-regulated in GC compared to ADJ ( P <0.01). Hsa-miR-148a , -miR-150 , -miR-215 , -miR-483 and -miR-664a were not differentially expressed between GC and ADJ, suggesting that both share similar changes ( P >0.1). The TS-miR hsa-miR-29c was up-regulated in ADJ compared to NC and GC ( P <0.01); we did not observe a significant difference in the expression of this miRNA between NC and GC. This feature may be an antitumor mechanism used by cancer-adjacent tissue because this miRNA regulates the BCL-2 , CDC42 and DMNT3A oncogenes. The expression level of hsa-miR-204 was associated with Helicobacter pylori infection status ( P <0.05) . Functional analysis using the genes regulated by the studied miRNAs showed that they are involved in biological pathways and cellular processes that are critical for the establishment of H. pylori infection and for the onset, development and progression of GC. hsa-miR-10a , -miR-21 , -miR-135b , -miR-148a , -miR-150 , -miR-215 , -miR-483 and -miR-664a were able to discriminate NC from other tissues with great accuracy (AUC>0.85). Conclusion: The studied miRNAs are closely related to field cancerization, regulate genes important for gastric carcinogenesis and can be potentially useful as biomarkers in GC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Estimates of different ancestral proportions in admixed populations are very important in population genetics studies, especially for the detection of population substructure effects in studies of case-control associations. Brazil is one of the most heterogeneous countries in the world, both from a socio-cultural and a genetic point of view. In this work, we investigated a previously developed set of 61 ancestry informative markers (AIM), aiming to estimate the proportions of four different ancestral groups (African, European, Native American and Asian) in Brazilian populations. To the best of our knowledge, this is the first study to use a set of AIM to investigate the genetic contribution of all four main parental populations to the Brazilian population, including Asian contribution. All selected markers were genotyped through multiplex PCR and capillary electrophoresis. The set was able to successfully differentiate the four ancestral populations (represented by 939 individuals) and identify their genetic contributions to the Brazilian population. In addition, it was used to estimate individual interethnic admixture of 1050 individuals from the Southeast region of Brazil and it showed that these individuals present a higher European ancestry contribution, followed by African, Asian and Native American ancestry contributions. Therefore, the 61 AIM set has proved to be a valuable tool to estimate individual and global ancestry proportions in populations mainly formed by these four groups. Our findings highlight the importance of using sets of AIM to evaluate population substructure in studies carried in admixed populations, in order to avoid misinterpretation of results., (Copyright © 2018 Andrade et al.)

The search for cancer biomarkers is frequently based on comparisons between tumors and adjacent-to-tumor samples. However, even after histological confirmation of been free of cancer cells, these adjacent-to-tumor samples might harbor molecular alterations which are not sufficient to cause them to look like cancer, but can differentiate these cells from normal cells. When comparing them, potential biomarkers are missed, and mainly the opportunity of finding initial aberrations presents in both tumors and adjacent samples, but not in true normal samples from non-cancer patients, resulting in misinterpretations about the carcinogenic process. Nevertheless, collecting adjacent-to-tumor samples brings trumps to be explored. The addition of samples from non-cancer patients opens an opportunity to increase the finds of the molecular cascade of events in the carcinogenic process. Differences between normal samples and adjacent samples might represent the first steps of the carcinogenic process. Adding samples of non-cancer patients to the analysis of molecular alterations relevant to the carcinogenic process opens a new window of opportunities to the discovery of cancer biomarkers and molecular targets.

Objective: To establish the prevalence of physical, cognitive and psychiatric disabilities, associated factors and their relationship with the qualities of life of intensive care survivors in Brazil., Methods: A prospective multicenter cohort study is currently being conducted at 10 adult medical-surgical intensive care units representative of the 5 Brazilian geopolitical regions. Patients aged ≥ 18 years who are discharged from the participating intensive care units and stay 72 hours or more in the intensive care unit for medical or emergency surgery admissions or 120 hours or more for elective surgery admissions are consecutively included. Patients are followed up for a period of one year by means of structured telephone interviews conducted at 3, 6 and 12 months after discharge from the intensive care unit. The outcomes are functional dependence, cognitive dysfunction, anxiety and depression symptoms, posttraumatic stress symptoms, health-related quality of life, rehospitalization and long-term mortality., Discussion: The present study has the potential to contribute to current knowledge of the prevalence and factors associated with postintensive care syndrome among adult intensive care survivors in Brazil. In addition, an association might be established between postintensive care syndrome and health-related quality of life.

Abstract., Objective: To present a cognitive map to support the radiological diagnosis of solitary bone tumors, as well as to facilitate the determination of the nature of the tumor (benign or malignant), in pediatric patients., Materials and Methods: We selected 28 primary lesions in pediatric patients, and we identified the findings typically associated with each of the diagnoses. The method used for the construction of the final cognitive map was the Bayesian belief network model with backward chaining., Results: We developed a logical, sequential structure, in the form of a cognitive map, based on the Bayesian belief network model, with the intention of simulating the sequence of human thinking, in order to minimize the number of unnecessary interventions and iatrogenic complications arising from the incorrect evaluation of bone lesions., Conclusion: With this map, it will be possible to develop an application that will provide support to physicians and residents, as well as contributing to training in this area and consequently to a reduction in diagnostic errors in patients with bone lesions.

Leprosy remains as a public health problem and its physiopathology is still not fully understood. MicroRNAs (miRNA) are small RNA non-coding that can interfere with mRNA to regulate gene expression. A few studies using DNA chip microarrays have explored the expression of miRNA in leprosy patients using a predetermined set of genes as targets, providing interesting findings regarding the regulation of immune genes. However, using a predetermined set of genes restricted the possibility of finding new miRNAs that might be involved in different mechanisms of disease. Thus, we examined the miRNome of tuberculoid (TT) and lepromatous (LL) patients using both blood and lesional biopsies from classical leprosy patients (LP) who visited the Dr. Marcello Candia Reference Unit in Sanitary Dermatology in the State of Pará and compared them with healthy subjects. Using a set of tools to correlate significantly differentially expressed miRNAs with their gene targets, we identified possible interactions and networks of miRNAs that might be involved in leprosy immunophysiopathology. Using this approach, we showed that the leprosy miRNA profile in blood is distinct from that in lesional skin as well as that four main groups of genes are the targets of leprosy miRNA: (1) recognition and phagocytosis, with activation of immune effector cells, where the immunosuppressant profile of LL and immunoresponsive profile of TT are clearly affected by miRNA expression; (2) apoptosis, with supportive data for an antiapoptotic leprosy profile based on BCL2, MCL1 , and CASP8 expression; (3) Schwann cells (SCs), demyelination and epithelial-mesenchymal transition (EMT), supporting a role for different developmental or differentiation gene families, such as Sox, Zeb, and Hox; and (4) loss of sensation and neuropathic pain, revealing that RHOA, ROCK1, SIGMAR1 , and aquaporin-1 ( AQP1 ) may be involved in the loss of sensation or leprosy pain, indicating possible new therapeutic targets. Additionally, AQP1 may also be involved in skin dryness and loss of elasticity, which are well known signs of leprosy but with unrecognized physiopathology. In sum, miRNA expression reveals new aspects of leprosy immunophysiopathology, especially on the regulation of the immune system, apoptosis, SC demyelination, EMT, and neuropathic pain.

The 7th edition of Union for International Cancer Control (UICC) staging system moved gastroesophageal junction (GEJ) cancers from gastric to esophageal group. Since clinical management is strongly influenced by this staging system, we looked at molecular fingerprints of GEJ tumors and compared to gastric and esophageal profiles. We aimed at elucidating whether GEJ cancers cluster with gastric or esophageal groups according to mRNA and microRNA expression pattern, since this might represent tumor identity. The clinical and expression data were downloaded from The Cancer Genome Atlas (TCGA) with 395 stomach, 184 esophagus and 521 colon samples for mRNA analyses and 392 stomach, 175 esophagus and 459 colon samples for microRNA comparisons. Both Principal Component Analysis (PCA) and Heat Map plots were performed in R platform, using Log 2 transformation of RPKM normalized data. Differential Expression Analysis was also performed in R, using RAW data and the DESeq2 package. The mRNAs and microRNAs were tagged as differentially expressed if they met the following criteria: i) FDR adjusted p-value < 0.05; and ii) |Log 2 (fold-change)| > 2. Esophagus squamous cell carcinoma (ESCC) clustered apart of the others tumors, while adenocarcinomas (AC) clustered all together according to both mRNAs and microRNAs expression patterns. The HMs of the differentially expressed mRNAs and microRNAs also demonstrated that ESCC belongs to a different group, while AC molecular signature of esophagus looks like AC of the cardia and non cardia regions. Even distal gastric cancers are quite similar to AC of the lower esophagus, demonstrating that esophagus AC relies much closer to gastric cancers than to esophagus cancers. By using robust molecular fingerprints, it was strongly demonstrated that GEJ tumors looks more like gastric cancers than esophageal cancers, despite of tumor heterogeneity., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.

Mutations in the HBB gene are responsible for several serious hemoglobinopathies, such as sickle cell anemia and β-thalassemia. Sickle cell anemia is one of the most common monogenic diseases worldwide. Due to its prevalence, diverse strategies have been developed for a better understanding of its molecular mechanisms. In silico analysis has been increasingly used to investigate the genotype-phenotype relationship of many diseases, and the sequences of healthy individuals deposited in the 1,000 Genomes database appear to be an excellent tool for such analysis. The objective of this study is to analyze the variations in the HBB gene in the 1,000 Genomes database, to describe the mutation frequencies in the different population groups, and to investigate the pattern of pathogenicity. The computational tool SNPEFF was used to align the data from 2,504 samples of the 1,000 Genomes database with the HG19 genome reference. The pathogenicity of each amino acid change was investigated using the databases CLINVAR, dbSNP and HbVar and five different predictors. Twenty different mutations were found in 209 healthy individuals. The African group had the highest number of individuals with mutations, and the European group had the lowest number. Thus, it is concluded that approximately 8.3% of phenotypically healthy individuals from the 1,000 Genomes database have some mutation in the HBB gene. The frequency of mutated genes was estimated at 0.042, so that the expected frequency of being homozygous or compound heterozygous for these variants in the next generation is approximately 0.002. In total, 193 subjects had a non-synonymous mutation, which 186 (7.4%) have a deleterious mutation. Considering that the 1,000 Genomes database is representative of the world's population, it can be estimated that fourteen out of every 10,000 individuals in the world will have a hemoglobinopathy in the next generation.

The present study aims to assess the removal of 3-amino-5-methylisoxazole (AMI), a recalcitrant by-product resulting from the biological breakdown of some pharmaceuticals, applying a solar photo-Fenton process assisted by ferrioxalate complexes (SPFF) (Fe 3+ /H 2 O 2 /oxalic acid/UVA-Vis) and classical solar photo-Fenton process (SPF) (Fe 2+ /H 2 O 2 /UVA-Vis). The oxidation ability of SPFF was evaluated at different iron/oxalate molar ratios (1:3, 1:6, and 1:9, with [total iron] = 3.58 × 10 -2  mM and [oxalic acid] = 1.07 × 10 -1 , 2.14 × 10 -1 and 3.22 × 10 -1  mM, respectively) and pH values (3.5-6.5), using low iron contents (2.0 mg Fe 3+ L -1 ). Additionally, the use of other organic ligands such as citrate and ethylenediamine-N,N'-disuccinic acid (EDDS) was tested. The oxidation power of the classical SPF was assessed at different pH values (2.8-4.0) using 2.0 mg Fe 2+ per liter. Furthermore, the effect of AMI concentration (2-20 mg L -1 ), presence of inorganic ions (Cl - , SO 4 2- , NO 3 - , HCO 3 - , NH 4 + ), and radical scavengers (sodium azide and D-mannitol) on the SPF method at pH 3.5 was also assessed. Experiments were done using a lab-scale photoreactor with a compound parabolic collector (CPC) under simulated solar radiation. A pilot-scale assay was conducted using the best operation conditions. While at near neutral pH, an iron/oxalate molar ratio of 1:9 led to the removal of 72 % of AMI after 90 min of SPFF, at pH 3.5, an iron/oxalate molar ratio of 1:3 was enough to achieve complete AMI degradation (below the detection limit) after 30 min of reaction. The SPF process at pH 3.5 underwent a slower AMI degradation, reaching total AMI degradation after 40 min of reaction. The scale up of SPF process showed a good reproducibility. Oxalic and oxamic acids were identified as the main low-molecular-weight carboxylic acids detected during the pilot-scale SPF reaction. Graphical abstract ᅟ.