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Prostate cancer (PCa) is a complex disease influenced by many factors, with the genetic contribution for this neoplasia having a great role in its risk. The literature brings an increased number of Genome-Wide Association Studies (GWAS's) that attempt to elucidate the genetic associations with PCa. However, these genome studies have a considerable rate of false-positive data whose results may be biased. Therefore, we aimed to apply Bayesian approaches on significant associations among polymorphisms and PCa from GWAS's data. A literature search was performed for data published before April 20, 2024, whereby two investigators used a specific combination of keywords and Boolean operators in the search ("prostate carcinoma or prostate cancer or PCa" and "polymorphism or genetic variation" and "Genome-Wide Association Study or GWAS"). The records were retrieved, and the data were extracted with further application of two different Bayesian approaches: The False Positive Report Probability (FPRP) and the Bayesian False-Discovery Probability (BFDP), both at the prior probabilities of 10 -3 and 10 -6 . The data were considered as noteworthy at the level of FPRP <0.2 and BFDP <0.8. Besides, in-silico analyses by gene-gene network and gene enrichment were performed to evaluate the role of the noteworthy genes in PCa. As results, 13 GWAS's were included, with 2,520 values for FPRP and 1,368 values for BFDP being obtained. Our study showed an extensive number of gene variations as noteworthy candidate biomarkers for PCa risk, with highlighting for those occurred in the 8q24 locus and in the MSMB, ITGA6, SUN2, FGF10, INCENP, MLPH, and KLK3 genes., 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 © 2024 Elsevier Inc. All rights reserved.)

The association between dystonia and early-onset epileptic encephalopathy (EOEE) may have a genetic basis. Phosphatidylinositol glycan biosynthesis class A protein (PIGA) germline mutations have been described in the last decade and associated with refractory EOEEs. Dysmorphisms and visceral abnormalities have also been reported. Here, we present the case of a now 8-month-old child who was evaluated for dystonia, visual impairment, and developmental delay at 2 months of age, followed by refractory focal seizures when he was 4 months old. The remaining examination was normal, besides an accelerated linear growth. His brain magnetic resonance and an extensive metabolic investigation failed to show any abnormalities. At 7 months of age, the exome sequencing found a hemizygous PIGA pathogenic variant-c.1352T > C (p.(Ile451Thr). Seizures improved after the association of carbamazepine with levetiracetam and the beginning of the ketogenic diet. To our knowledge, this is the first time the phenotype associated with this specific mutation is described. Our patient had the singularity of manifesting with remarkable dystonia, over 2 months before the onset of seizures. We also point to the utility of the gene sequencing approach in the diagnosis of patients with dystonia and EOEEs, since identification of the genetic cause may help in patient's management and families' empowerment., Competing Interests: None declared., (Thieme. All rights reserved.)

Delineating reference (i.e., baseline) riverine nutrient concentrations is essential to understand fundamental processes of biogeochemical transport from continents to the ocean, describe ecological conditions, and inform managers of best attainable conditions when attempting to control anthropogenic eutrophication. We used data from 434 Brazilian watersheds representative of major South American biomes covering over half the continental area, to estimate nutrient levels expected prior to anthropogenic development. We used a novel watershed-based approach to describe spatial patterns throughout Brazil and for the entire Amazon basin. This approach considered nitrogen (N) and phosphorus (P) independently and allowed removal of anthropogenic influences. The approach was useful where there were few unimpacted watersheds and low levels of urbanization had strong effects. We found reference total N concentrations were most closely related to biome, whereas total P levels related to percentage sand in soils in addition to climatic features influencing biomes. There was a wide range of N:P at this coarse level, suggesting P or co-limitation could occur in streams; many areas have intrinsically high background P and relatively low N, suggesting N-limitation of freshwaters could be widespread in South America, favoring nitrogen-fixing cyanobacterial blooms. We provide unique broad-scale analyses of spatial distribution of baseline nutrient levels for tropical and subtropical watersheds across continental scales., Competing Interests: Declaration of competing interest Authors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Rabbit production holds significant relevance in modern agriculture due to its potential as a sustainable source of high-quality protein and efficient feed conversion, contributing to food security and economic diversification. Nevertheless, studies incorporating feto-maternal monitoring in this species are uncommon. This review gathers research on the monitoring and evaluation of factors affecting rabbit gestation, providing a better understanding of the causes of prenatal development abnormalities. These include studies regarding how chronic maternal hypertension, gestational diabetes, maternal stress, ectopic gestation, maternal uterine ischemia and fetal hypoxia, intrauterine growth restriction, superfetation, maternal age, maternal nutritional status, maternal physical condition, maternal and embryonic genotype, and the intrauterine location of rabbit fetuses can potentially impact rabbits' reproduction and maternal and fetal health. Among other monitoring techniques, ultrasonography, considered one of the best tools for diagnosing pregnancy and conducting follow-up, is also reviewed. Details on measurable fetal-development parameters in rabbits and precautions to be considered before and during the examination are also provided. Additional studies are required to understand why some events occur and their consequences throughout gestation, allowing the determination of new biomarkers or cut-offs that can be helpful for early diagnosis and improve reproductive efficiency.

Castor ( Ricinus communis L.) is an important industrial crop with a wide range of industrial and pharmaceutical applications. Brazil is among the largest castor-producing countries. Between 2004 and 2010, castor cultivation was stimulated with an emphasis towards biodiesel production. However, this was not enough to leverage the production of castor in Brazil, mainly due to the lack of structured trade and the competition with other cheaper raw materials for the production of biodiesel. Despite this failure, the species presents itself as an excellent alternative for crop rotation in the second crop among soybean, corn, beans, and cotton cultivation areas as the oil is highly valuable for other products. Moreover, it has drawn the attention of producers and researchers in Brazil for this potential rotation as it is considered a plant tolerant of water-deficiency and is highly susceptible to gray mold, a disease favored by high humidity in the final stages of the crop. For instance, its cultivation in the second crop in Cerrado regions, where rains occur in the early stages of the crop and cease when the plants reach the final stage of production, has been successful and shows great promise. The current study aimed to evaluate the suitability of environments throughout Brazil to grow castor, incorporating variables associated with the incidence of gray mold and confirm these findings based on existing castor trial data obtained from the literature. The site suitability analysis determined that 74.99 million hectares - 8.8% of Brazilian territory - are highly suitable for castor production during second harvest, mostly located in the Northeastern and Midwestern regions. These results are surprising since Brazil currently has around 7.8% (∼66.81 million hectares) of its territory occupied with agriculture (grains, fruits, vegetables, and perennial crops). The findings of this study provide a method to perform site suitability for crops using data associated with agronomic and disease characteristics, as is the case with gray mold that often results in significant losses in castor production. Also, this analysis provides evidence for the great potential of Brazil to increase castor production and meet the world demand for its oil through utilization of second-crop cultivation., Competing Interests: 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.

The Euterpe genus (mainly Euterpe oleracea Martius, Euterpe precatoria Martius, and Euterpe edulis Martius) has recently gained commercial and scientific notoriety due to the high nutritional value of its fruits, which are rich in polyphenols (phenolic acids and anthocyanins) and have potent antioxidant activity. These characteristics have contributed to the increased number of neuropharmacological evaluations of the three species over the last 10 years, especially açaí of the species Euterpe oleracea Martius. The fruits of the three species exert neuroprotective effects through the modulation of inflammatory and oxidative pathways and other mechanisms, including the inhibition of the mTOR pathway and protection of the blood-brain barrier, all of them intimately involved in several neuropathologies. Thus, a better understanding of the neuropharmacological properties of these three species may open new paths for the development of therapeutic tools aimed at preventing and treating a variety of neurological conditions.

Hepatocellular carcinoma (HCC) is considered as the second cause of cancer-related deaths worldwide. Genetic variations are associated with HCC risk, an issue that has been the subject of several meta-analyses. However, meta-analyses have an important limitation on the likelihood of false positive data. Henceforth, this study aimed to assess the level of noteworthiness in the meta-analyses by means of a Bayesian approach. A systematic search was performed for meta-analyses with associations between gene polymorphisms and HCC. The calculations for the False-Positive Rate Probability (FPRP) and the Bayesian False Discovery Probability (BFDP) were performed to assess the noteworthiness with a statistical power of 1.2 and 1.5 of Odds Ratio at a prior probability of 10 -3 and 10 -5 . The quality of studies was evaluated by the Venice criteria. As additional analyses, the gene-gene and protein-protein networks were designed for these genes and products. As results, we found 33 meta-analytic studies on 45 polymorphisms occurring in 35 genes. A total of 1,280 values for FPRP and BFDP were obtained. Seventy-five for FPRP (5.86%) and 95 for BFDP (14.79%) were noteworthy. In conclusion, the polymorphisms in CCND1, CTLA4, EGF, IL6, IL12A, KIF1B, MDM2, MICA, miR-499, MTHFR, PNPLA3, STAT4, TM6SF2, and XPD genes were considered as noteworthy biomarkers for HCC risk., 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 © 2023 Elsevier B.V. All rights reserved.)

Glyphosate-based herbicides can be harmful to the environment and human health. Especially in developing countries, these herbicides are often used indiscriminately in agricultural and urban areas. Here, we optimized a simple and efficient flow injection-based spectrophotometric method to monitor environmentally relevant glyphosate concentrations in surface waters. The method was then used to assess the environmental mobility of glyphosate in Southeast Brazil by monitoring surface runoff from experimental agricultural soil plots that received glyphosate applications in 2015. Further, water samples from low-order streams were collected in five agricultural, urban, and natural areas, as well as from the 5th-order Rio das Mortes during the rainy season. Finally, 20 drinking water sources were sampled in urban, rural, and agricultural areas. Runoff from reference plots without glyphosate application showed concentrations below the method's detection limit of 0.49 mg.L -1 , whereas runoff from plots with standard glyphosate application had concentrations between 1.24 and 6.1 mg.L -1 . Similarly, concentrations in natural stream water were below the detection limit, whereas agricultural streams had concentrations of up to 3.7 mg.L -1 (average: 0.97 mg.L -1 ). In an agricultural stream monitored weekly, concentration peaks were observed after glyphosate applications by farmers, and concentrations were correlated to stream discharge. Urban streams had concentrations of up to 5.8 mg.L -1 (average: 2.6 mg.L -1 ), but samples from the catchment's major river were mostly below detection limits, illustrating the dilution of urban and agricultural runoff in high-order rivers. In the sampled drinking water resources, glyphosate pollution occurred mainly in the rainy season, with detectable concentrations between 0.5 and 8.7 mg.L -1 in 80% of the sampled drinking water sources. In conclusion, our results suggest considerable environmental mobility of glyphosate in the studied Southeast Brazilian catchment. Substantial pollution, well above national and international limits, was detected in surface runoff, stream water, and drinking water resources., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Dengue fever is a clinical manifestation of dengue virus (DENV) infection well defined by the intense host immune response with the development of high fever, anorexia, headache and muscle pain. Several immune mediators are involved in the pathophysiology of DENV infection, in which polymorphisms in immune molecule genes contribute with the susceptibility and severity of the infection. Several meta-analyses are available with significant findings in the association between genetic variants in immune-mediator genes and dengue, though the results may be false positive. Hence, to solve this issue, we have performed a systematic revaluation with Bayesian approaches to verify the false positive rate in these results. A systematic search was performed for meta-analytic studies on the aforementioned issue. The calculations of false positive report probability (FPRP) and the Bayesian false-discovery probability (BFDP) at the prior probability of 10 -3 and 10 -6 have been performed. To verify the methodological quality of the studies included, the evaluation by the Venice criteria was applied. In addition, gene-gene and protein-protein networks were designed. As results, seven meta-analyses on genetic variants in several immune-inflammatory mediator genes and DENV infection comprise the results. Only the polymorphisms in the TNF, MICB, PLCE1, VDR, CD32 and HLA-A genes were considered as noteworthy. There was a heterogeneity profile for the results on Venice criteria indicating variability in the methodological quality. The gene-gene and protein-protein networks showed these immune mediators as relevant players in the disease. We suggest these polymorphisms as potential biomarkers for the pathogenesis and immune response against DENV., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To describe and compare the number of surgeries, mortality rate, length of hospital stay, and costs of transurethral resection of the prostate and open prostatectomy for the treatment of benign prostatic hyperplasia, between 2008 and 2018, in the Public Health System in São Paulo, Brazil., Methods: Ecological and retrospective study using data from the informatics department of the Brazilian Public Health System database. Procedure codes were "open prostatectomy" and "transurethral resection of the prostate." The outcomes analyzed were compared between transurethral resection of the prostate and open prostatectomy according to the hospital surgical volume and presence or absence of a residency program., Results: A total of 18,874 surgeries were analyzed (77% transurethral resection of the prostate) and overall mortality was not statistically different between procedures. Intermediate and high-volume centers had shorter length of hospital stay than low-volume centers for transurethral resection of the prostate (3.28, 3.02, and 6.58 days, respectively, p=0.01 and p=0.004). Length of hospital stay was also shorter for open prostatectomy in high-volume compared to low-volume centers (4.86 versus 10.76 days, p=0.036). Intrahospital mortality was inversely associated with surgical volume for transurethral resection of the prostate. Centers with residency program had shorter length of hospital stay considering open prostatectomy and less mortality regarding transurethral resection of the prostate. Open prostatectomy was 64% more expensive than transurethral resection of the prostate., Conclusion: The findings suggest the importance of investing in specialized centers, which could be potential referral centers for surgical cases.

Background: Several therapies have been used or proposed for the treatment of COVID-19, although their effectiveness and safety have not been properly evaluated. The purpose of this document is to provide recommendations to support decisions about the drug treatment of outpatients with COVID-19 in Brazil., Methods: A panel consisting of experts from different clinical fields, representatives of the Brazilian Ministry of Health, and methodologists (37 members in total) was responsible for preparing these guidelines. A rapid guideline development method was used, based on the adoption and/or adaptation of recommendations from existing international guidelines combined with additional structured searches for primary studies and new recommendations whenever necessary (GRADE-ADOLOPMENT). The rating of quality of evidence and the drafting of recommendations followed the GRADE method., Results: Ten technologies were evaluated, and 10 recommendations were prepared. Recommendations were made against the use of anticoagulants, azithromycin, budesonide, colchicine, corticosteroids, hydroxychloroquine/chloroquine alone or combined with azithromycin, ivermectin, nitazoxanide, and convalescent plasma. It was not possible to make a recommendation regarding the use of monoclonal antibodies in outpatients, as their benefit is uncertain and their cost is high, with limitations of availability and implementation., Conclusion: To date, few therapies have demonstrated effectiveness in the treatment of outpatients with COVID-19. Recommendations are restricted to what should not be used, in order to provide the best treatment according to the principles of evidence-based medicine and to promote resource savings by aboiding ineffective treatments., Competing Interests: Conflicts of interest The list of participants and the declaration of conflicts of interest are presented in the Supplementary Material., (Copyright © 2022 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: Several therapies are being used or proposed for COVID-19, and many lack appropriate evaluations of their effectiveness and safety. The purpose of this document is to develop recommendations to support decisions regarding the pharmacological treatment of patients hospitalized with COVID-19 in Brazil., Methods: A group of 27 experts, including representatives of the Ministry of Health and methodologists, created this guideline. The method used for the rapid development of guidelines was based on the adoption and/or adaptation of existing international guidelines (GRADE ADOLOPMENT) and supported by the e-COVID-19 RecMap platform. The quality of the evidence and the preparation of the recommendations followed the GRADE method., Results: Sixteen recommendations were generated. They include strong recommendations for the use of corticosteroids in patients using supplemental oxygen, the use of anticoagulants at prophylactic doses to prevent thromboembolism and the nonuse of antibiotics in patients without suspected bacterial infection. It was not possible to make a recommendation regarding the use of tocilizumab in patients hospitalized with COVID-19 using oxygen due to uncertainties regarding the availability of and access to the drug. Strong recommendations against the use of hydroxychloroquine, convalescent plasma, colchicine, lopinavir + ritonavir and antibiotics in patients without suspected bacterial infection and also conditional recommendations against the use of casirivimab + imdevimab, ivermectin and rendesivir were made., Conclusion: To date, few therapies have proven effective in the treatment of hospitalized patients with COVID-19, and only corticosteroids and prophylaxis for thromboembolism are recommended. Several drugs were considered ineffective and should not be used to provide the best treatment according to the principles of evidence-based medicine and promote economical resource use.

Introduction: Genitourinary tuberculosis is the fourth most common cause of extrapulmonary tuberculosis, although often underestimated by clinicians due to its rare and non-specific symptoms. One of the disease's complications is infertility. Although Portugal is one of the European countries with the highest prevalence of tuberculosis, its impact on Portuguese female fertility is unknown. With this study, we intend to evaluate the prevalence of genital tuberculosis, its presenting symptoms, and pregnancy outcomes in infertile women followed in a Portuguese tertiary hospital., Methods: Retrospective and descriptive study, performed using an electronic database and consultation of clinical files. Studied population: infertile women followed from 2000 until 2019 at the reproductive unit of a Portuguese tertiary hospital, who underwent endometrial biopsy/curettage in the context of their etiological investigation. The diagnosis of genital tuberculosis was based on histological criteria., Results: Over the 19 years, 2653 endometrial specimens were analyzed. Pathological evaluation was positive for tuberculosis in 19 cases (0.72%). There was a decrease in new diagnoses throughout the observation period., Conclusion: Despite being one of the European countries with the highest prevalence of tuberculosis, genital TB does not appear to have a significant impact on the etiology of female infertility in Portugal. Nevertheless, it is a diagnosis to be considered in selected patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Intoxication by heavy metals such as methylmercury (MeHg) is recognized as a global health problem, with strong implications in central nervous system pathologies. Most of these neuropathological conditions involve vascular, neurotransmitter recycling, and oxidative balance disruption leading to accelerated decline in fine balance, and learning, memory, and visual processes as main outcomes. Besides neurons, astrocytes are involved in virtually all the brain processes and perform important roles in neurological response following injuries. Due to astrocytes' strategic functions in brain homeostasis, these cells became the subject of several studies on MeHg intoxication. The most heterogenous glial cells, astrocytes, are composed of plenty of receptors and transporters to dialogue with neurons and other cells and to monitor extracellular environment responding tightly through fluctuation of cytosolic ions. The overall toxicity of MeHg might be determined on the basis of the balance between MeHg-mediated injury to neurons and protective responses from astrocytes. Although the role of neurons in MeHg intoxication is relatively well-established, the role of the astrocytes is only beginning to be understood. In this review, we update the information on astroglial modulation of the MeHg-induced neurotoxicity, providing remarks on their protective and deleterious roles and insights for future studies., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The metabolic syndrome (MetS) epidemic is a global challenge. Although developing countries (including Brazil, India, and South Africa) present a higher proportion of deaths by cardiovascular diseases than developed countries, most of our knowledge is from these developed countries. Amazonian riverine populations (ARP), as well as other vulnerable populations of the Southern Hemisphere, share low-income and traditional practices, among other features. This large cross-sectional study of ARP ( n = 818) shows high prevalence of hypertension (51%) and obesity (23%). MetS was diagnosed in 38% of participants (especially in women and 60-69 years-old individuals) without the influence of ancestry. Only 7-8% of adults had no cardio-metabolic abnormalities related to MetS. Atherogenic dyslipidemia (low HDL-cholesterol) was generally observed, including in individuals without MetS. Still, slight differences were detected between settings with a clear predominance of hypertension in Tucuruí. Hypotheses on possible genetic influence and factors (nutrition transition and environmental pollutants -mercury) are proposed for future studies. Moreover, a roadmap to MetS progression based on the most prevalent components is provided for the development of tailored interventions in the Amazon (initially, individuals would present low HDL-cholesterol levels, later progressing to increased blood pressure characterizing hypertension, and ultimately reaching MetS with obesity). Our alarming results support the need to improve our knowledge on these vulnerable populations.

Background: Migraine is a multifactorial disorder that is more frequent (two to four times) in women than in men. In recent years, our research group has focused on the role of neurotransmitter release and its regulation. Neurexin (NRXN2) is one of the components of the synaptic vesicle machinery, responsible for connecting intracellular fusion proteins and synaptic vesicles. Our aim was to continue exploring the role and interaction of proteins involved in the control and promotion of neurotransmission in migraine susceptibility., Methods: A case-control study was performed comprising 183 migraineurs (148 females and 35 males) and 265 migraine-free controls (202 females and 63 males). Tagging single nucleotide polymorphisms of NRXN2 were genotyped to assess the association between NRXN2 and migraine susceptibility. The χ 2 test was used to compare allele frequencies in cases and controls and odds ratios were estimated with 95% confidence intervals. Haplotype frequencies were compared between groups. Gene-gene interactions were analysed using the Multifactor Dimensionality Reduction v2.0., Results: We found a statistically significant interaction model (p = 0.009) in the female group between the genotypes CG of rs477138 (NRXN2) and CT of rs1158605 (GABRE). This interaction was validated by logistic regression, showing a significant risk effect [OR = 4.78 (95%CI: 1.76-12.97)] after a Bonferroni correction. Our data also supports a statistically significant interaction model (p = 0.011) in the female group between the GG of rs477138 in NRXN2 and, the rs2244325's GG genotype and rs2998250's CC genotype of CASK. This interaction was also validated by logistic regression, with a protective effect [OR = 0.08 (95%CI: 0.01-0.75)]. A weak interaction model was found between NRXN2-SYT1. We have not found any statistically significant allelic or haplotypic associations between NRXN2 and migraine susceptibility., Conclusions: This study unravels, for the first time, the gene-gene interactions between NRXN2, GABRE - a GABA A -receptor - and CASK, importantly it shows the synergetic effect between those genes and its relation with migraine susceptibility. These gene interactions, which may be a part of a larger network, can potentially help us in better understanding migraine aetiology and in development of new therapeutic approaches.

The Amazon is the largest tropical forest in the world and a source of healthy food, such as fruits and fish. Surprisingly, the Amazonian riverine population present an increased prevalence (as high as 58%) of non-communicable diseases, such as hypertension and insulin resistance, even higher than that described for the urban population of the Amazon. Therefore, this work aimed to analyze the nutritional status and associated risk of the riverine population. Body mass index, waist circumference (WC), waist-to-hip ratio, and neck circumference (NC) were evaluated, and risk analysis was assayed. Furthermore, data about occupation and the prevalence of consumers of the different groups of food were analyzed. All anthropometric parameters revealed high proportions of individuals at risk, WC and NC being the factors that had more high-risk women and men, respectively. Our data confirmed the characteristic profile of the riverine communities with a high number of fish consumers, but also observed different patterns probably associated to a phenomenon of nutrition transition. Based on our data, some nudge interventions that take into account the principles of behavior analysis are discussed and proposed for these populations, aiming to improve the nutritional status and avoid the long-term consequences of the results showed by this work.

Human exposure to mercury is a major public health concern, causing neurological outcomes such as motor and visual impairment and learning disabilities. Currently, human exposure in the Amazon is among the highest in the world. A recent systematic review (doi:10.1016/j.jtemb.2018.12.001), however, highlighted the lack of high-quality studies on mercury-associated neurotoxicity. There is, therefore, a need to improve research and much to still learn about how exposure correlates with disease. In this review, we discuss studies evaluating the associations between neurological disturbances and mercury body burden in Amazonian populations, to generate recommendations for future studies. A systematic search was performed during July 2020, in Pubmed/Medline, SCOPUS and SCIELO databases with the terms (mercury*) and (Amazon*). Four inclusion criteria were used: original article (1), with Amazonian populations (2), quantifying exposure (mercury levels) (3), and evaluating neurological outcomes (4). The extracted data included characteristics (as year or origin of authorship) and details of the research (as locations and type of participants or mercury levels and neurological assessments). Thirty-four studies, most concentrated within three main river basins (Tapajós, Tocantins, and Madeira) and related to environmental exposure, were found. Mercury body burden was two to ten times higher than recommended and main neurological findings were cognitive, vision, motor, somatosensory and emotional deficits. Important insights are described that support novel approaches to researching mercury exposure and intoxication, as well as prevention and intervention strategies. As a signatory country to the Minamata Convention, Brazil has the opportunity to play a central role in improving human health and leading the research on mercury intoxication., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction  Trapeziectomy and suture-button suspensionplasty (SBS) are a novel option to treat end-stage trapeziometacarpal (TMC) osteoarthritis. Our purpose is to evaluate our outcomes with this technique and in this setting, with a minimum of 18 months of follow-up. Materials and Methods  Twenty-eight patients were included, operated between 2016 and 2018. We recorded demographic data, preoperative Eaton stage, follow-up and operative times. The patients completed the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire and tip pinch, key pinch, and grip strength were measured. First metacarpal subsidence was calculated, and postoperative complications were documented. Results  The average follow-up was 34 months. The mean QuickDASH was 32 at the final follow-up. The average strength results were 20 kg for grip, 3.6 kg for tip pinch, and 4.2 kg for key pinch. The rate of first ray subsidence was 10.7%. We encountered three complications: a hardware intolerance, a second metacarpal fracture, and a suture rupture. There was one reoperation to remove an implant. Conclusion  Trapeziectomy and SBS functional results are similar to other techniques, with less subsidence of the first ray and allowing for early mobilization and fast recovery. This procedure is a safe and promising option in the treatment of TMC osteoarthritis, with good medium-term outcomes., Competing Interests: Conflict of Interest None declared., (Society of Indian Hand Surgery & Microsurgeons. All rights reserved.)

Migraine is highly prevalent and carries a significant personal, social and economic burden. It is the second cause of disability (years living with disability) worldwide and the first cause under 50 years of age. Chronic migraine (occurring for more than 15 days a month) and refractory migraine (treatment resistant), especially when there is also analgesic overuse, are the most disabling forms of migraine. These three disorders (chronic migraine, refractory migraine and medication overuse headache) are particularly difficult to treat. This article reviews their epidemiology, clinical presentation, diagnostic criteria, risk factors, comorbidities and social and personal impact. The therapeutic options available are discussed and focused on a multidisciplinary approach, non-pharmacological interventions treatment of comorbidities and avoiding analgesic overuse. Prophylactic treatments are mandatory and include the oral prophylactic treatments (topiramate), botulinum toxin type A and the novel monoclonal antibodies against calcitonin gene related peptide or its receptor, which are the first migraine preventive medicines developed specifically to target migraine pathogenesis. In refractory cases, multiple therapies are required including neurostimulation.

RGB digital cameras (RGB) compress the spectral information into a trichromatic system capable of approximately representing the actual colors of objects. Although RGB digital cameras follow the same compression philosophy as the human eye (OBS), the spectral sensitivity is different. To what extent they provide the same chromatic experiences is still an open question, especially with complex images. We addressed this question by comparing the actual colors derived from spectral imaging with those obtained with RGB cameras. The data from hyperspectral imaging of 50 natural scenes and 89 paintings was used to estimate the chromatic differences between OBS and RGB. The corresponding color errors were estimated and analyzed in the color spaces CIELAB (using the color difference formulas Δ E * ab and CIEDE2000), J z a z b z , and iCAM06. In CIELAB the most frequent error (using Δ E * ab ) found was 5 for both paintings and natural scenes, a similarity that held for the other spaces tested. In addition, the distribution of errors across the color space shows that the errors are small in the achromatic region and increase with saturation. Overall, the results indicate that the chromatic errors estimated are close to the acceptance error and therefore RGB digital cameras are able to produce quite realistic colors of complex scenarios.

Objective: A number of observations, including among our study population, have implicated variants in the syntaxin-1A, a component of the synaptic vesicles, in migraine susceptibility. Therefore, we hypothesize that variants in other components of the vesicle machinery are involved in migraine., Background: Migraine is a common and complex neurologic disorder that affects approximately 15-18% of the general population. The exact cause of migraine is unknown; however, genetic studies have made possible substantial progress toward the identification of underlying molecular pathways. Neurotransmitters have been for long considered to have a key role in migraine pathophysiology; so we investigated common variants in genes involved in the synaptic vesicle machinery and their impact in migraine susceptibility., Methods: We performed a case-control study comprising 188 unrelated patients with headache and 286 healthy controls in a population from the north of Portugal. Benefiting from the presence of linkage disequilibrium, we selected and genotyped 119 tagging single-nucleotide polymorphisms in 18 genes., Results: We found significant associations between single-nucleotide variants and migraine in 7 genes, SYN1, SYN2, SNAP25, VAMP2, STXBP1, STXBP5, and UNC13A, either conferring an increased risk or protection of migraine. Due to SYN1 X-chromosomal location, we performed the statistical analysis separated by gender and, in the female group, the C allele of rs5906435 increased the risk for migraine susceptibility (P = .021; OR = 1.69; 95% CI: 1.21-2.34). In contrast, the TT genotype of the same variant emerged as a potential protective factor (P = .003; OR = 0.45; 95% CI: 0.27-0.74). The SYN2 analysis supported the rs3773364's G allele (P = .014) as a risk factor for migraine, and although not statistically significant after correction, the AG genotype (P = .006; OR = 1.86; 95% CI: 1.20-2.90) reinforced the allelic findings. Additionally, we found the SNAP25-rs363039's CT genotype (P = .001; OR = 2.14; 95% CI: 1.36-3.34), the STXBP5-rs1765028's T allele (P = .041; OR = 1.46; 95% CI: 1.13-1.90), and the UNC13B-rs7851161's TT genotype (P = .001; OR = 2.14; 95% CI: 1.36-3.34) as statistically significant risk factors for migraine liability. VAMP2-rs1150's G allele revealed a risk association to migraine, not statistically significant after correction (P = .068). Additionally, we found haplotypes in SYN1, SYN2, STXBP1, and UNC13B to be associated with migraine., Conclusions: Overall, this study provides a new insight into migraine liability, identifying possible starting points for functional studies., (© 2020 American Headache Society.)

Two types of Epstein Barr virus (EBV1/EBV2) have been shown to infect humans. Although their genomes are similar, the regions containing the EBNA genes differ. This study aimed to characterize the EBV genotypes of infectious mononucleosis (IM) cases in the metropolitan region of Belém, Brazil, from 2005 to 2016. A total of 8295 suspected cases with symptoms/signs of IM were investigated by infectious disease physicians at Evandro Chagas Institute, Health Care Service, from January 2005 to December 2016. Out of the total, 1645 (19.8%) samples had positive results for EBV by enzyme immunoassay and 251 (15.3%) were submitted to polymerase chain reaction (PCR) technique, using the EBNA3C region, in order to determine the type of EBV. Biochemical testing involving aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase were also performed. EBV type was identified by PCR in 30.3% (76/251) of individuals; of those, 71.1% (54/76) were classified as EBV1, 17.1% (13/76) as EBV2, and 11.8% (9/76) as EBV1 + EBV2. The main symptoms/signs observed with EBV1 infection were cervical lymphadenopathy (64.8%, 35/54), fever (63%, 34/54), headache (20.4%, 11/54), arthralgia (20.4%, 11/54), and exanthema (18.5%, 10/54). EBV2 infection was detected in all but two age groups, with an average age of 24 years. The most common signs/symptoms of EBV2 were fever (76.9%, 10/13), average duration of 18 days, and lymphadenopathy (69.2%, 9/13). In contrast, EBV1 + EBV2 coinfections were more frequent in those aged five years or less (20.0%, 2/10). The symptoms of EBV1 + EBV2 coinfection included fever (66.7%, 6/9), and cervical lymphadenopathy and headache (33.3%, 3/9) each. The mean values of hepatic enzymes according to type of EBV was significantly different (p < 0.05) in those EBV1 infected over 14 years of age. Thus, this pioneering study, using molecular methods, identified the EBV genotypes in 30.3% of the samples, with circulation of EBV1, EBV2, and EBV1 + EBV2 co-infection in cases of infectious mononucleosis in the northern region of Brazil., (Copyright © 2020 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Methylmercury (MeHg) exposure is a serious problem of public health, especially in the Amazon. Exposure in riverine populations is responsible for neurobehavioral abnormalities. It was hypothesized that consumption of Amazonian fruits could protect by reducing mercury accumulation. This work analyzed the effects of commercial samples of Euterpe oleracea (EO) for human consumption (10 μL/g) against MeHg i.p. exposure (2.5 mg/Kg), using neurobehavioral (open field, rotarod and pole tests), biochemical (lipid peroxidation and nitrite levels), aging-related (telomerase reverse transcriptase (TERT) mRNA expression) and toxicokinetic (MeHg content) parameters in mice. Both the pole and rotarod tests were the most sensitive tests accompanied by increased lipid peroxidation and nitrite levels in brains. MeHg reduced TERT mRNA about 50% demonstrating a strong pro-aging effect. The EO intake, similar to that of human populations, prevented all alterations, without changing the mercury content, but avoiding neurotoxicity and premature aging of the Central Nervous System (CNS). Contrary to the hypothesis found in the literature on the possible chelating properties of Amazonian fruits consumption, the effect of EO would be essentially pharmacodynamics, and possible mechanisms are discussed. Our data already support the regular consumption of EO as an excellent option for exposed Amazonian populations to have additional protection against MeHg intoxication.

Depression is a mental disorder that affects 300 million people of all ages worldwide, but fewer than half of those with the condition receive adequate treatment. In addition, the high pharmacological refractoriness (affecting 30%-50% of patients) and toxicity of some classical antidepressants support the pursuit of new therapies. People with this condition show depressed mood, loss of pleasure, high levels of oxidative stress, and accelerated biological aging (decreased telomere length and expression of the telomerase reverse transcriptase (TERT), the enzyme responsible for telomere maintenance). Because of the close relationship between depression and oxidative stress, nutraceuticals with antioxidant properties are excellent candidates for therapy. This study represents the first investigation of the possible antidepressant and antiaging effects of commercial samples of clarified açaí ( Euterpe oleracea ) juice (EO). This fruit is rich in antioxidants and widely consumed. In this study, mice were treated with saline or EO (10  μ L/g, oral) for 4 days and then with saline or lipopolysaccharide (0.5 mg/kg, i.p.) to induce depressive-like behavior. Only four doses of EO were enough to abolish the despair-like and anhedonia behaviors and alterations observed in electromyographic measurements. The antidepression effect of EO was similar to that of imipramine and associated with antioxidant and antiaging effects (preventing lipid peroxidation and increasing TERT mRNA expression, respectively) in three major brain regions involved in depression (hippocampus, striatum, and prefrontal cortex). Additionally, EO significantly protected hippocampal cells, preventing neuronal loss associated with the depressive-like state and nitrite level increases (an indirect marker of nitric oxide production). Moreover, EO alone significantly increased TERT mRNA expression, revealing for the first time a potent antiaging action in the brain that suggests neuroprotection against long-term age-related consequences., Competing Interests: Authors declare that no conflicts of interest exist. The donations from Amazon Dreams or Instituto Evandro Chagas do not imply any competing interests and they do not alter the authors' adherence to the policies of Oxidative Medicine and Cellular Longevity journal.

The biocontrol activity of some soil strains of Chromobacterium sp. against pathogenic fungi has been attributed to secreted chitinases. The aim of this work was to characterize biochemically a recombinant chitinase (CvChi47) from C. violaceum ATCC 12472 and to investigate its effects on phytopathogenic fungi. CvChi47 is a modular enzyme with 450 amino acid residues, containing a type I signal peptide at the N-terminal region, followed by one catalytic domain belonging to family 18 of the glycoside hydrolases, and two type-3 chitin-binding domains at the C-terminal end. The recombinant enzyme was expressed in Escherichia coli as a His-tagged protein and purified to homogeneity. The native signal peptide of CvChi47 was used to direct its secretion into the culture medium, from where the recombinant product was purified by affinity chromatography on chitin and immobilized metal. The purified protein showed an apparent molecular mass of 46 kDa, as estimated by denaturing polyacrylamide gel electrophoresis, indicating the removal of the signal peptide. CvChi47 was a thermostable protein, retaining approximately 53.7% of its activity when heated at 100 °C for 1 h. The optimum hydrolytic activity was observed at 60 °C and pH 5. The recombinant chitinase inhibited the conidia germination of the phytopathogenic fungi Fusarium oxysporum and F. guttiforme, hence preventing mycelial growth. Furthermore, atomic force microscopy experiments revealed a pronounced morphological alteration of the cell surface of conidia incubated with CvChi47 in comparison to untreated cells. Taken together, these results show the potential of CvChi47 as a molecular tool to control plant diseases caused by these Fusarium species., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Analysis that link hydrological processes with oceanographic dispersion offer a promising approach for assessing impacts of land-based activities on marine ecosystems. However, such an analysis has not yet been customised to quantify specific pressures from mining activities on marine biodiversity including those from spillages resulting from tailing dam failure. Here, using a Brazilian catchment in which a tailing dam collapsed (Doce river) as a case study, we provide a modelling approach to assess the impacts on key ecosystems and marine protected areas subjected to two exposure regimes: (i) a pulse disturbance event for the period 2015-2016, following the immediate release of sediments after dam burst, which witnessed an average increase of 88% in sediment exports; and (ii) a press disturbance phase for the period 2017-2029, when impacts are sustained over time by sediments along the river's course. We integrated four components into impact assessments: hydrological modelling, coastal-circulation modelling, ecosystem mapping, and biological sensitivities. The results showed that pulse disturbance causes sharp increases in the amount of sediments entering the coastal area, exposing key sensitive ecosystems to pollution (e.g. rhodolith beds), highlighting an urgent need for developing restoration strategies for these areas. The intensity of impacts will diminish over time but the total area of sensitive ecosystems at risk are predicted to be enlarged. We determined monitoring and restoration priorities by evaluating and comparing the extent to which sensitive ecosystems within marine protected areas were exposed to disturbances. The information obtained in this study will allow the optimization of recovery efforts in the marine area affected, and valuation of ecosystem services lost., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Dissemination of pathogenic multiresistant bacteria is of public health concern. Reliable data can be difficult to obtain, especially in developing countries. This work aimed to characterize the skin and oropharyngeal microbiota, as well as their antimicrobial resistance profiles, of East-Timor populations to identify potentially pathogenic Gram-positive cocci. In order to assess the prevalence of pathogenic bacteria in East-Timor, the oropharyngeal and skin microbiota of 74 individuals was characterized. Gram-positive cocci were evaluated and their antimicrobial resistance profiles were determined. A total of 228 oropharyngeal and 278 skin samples were obtained. The population consisted of 36.5% of asymptomatic carriers of Gram-positive cocci. Kocuria rosea (n = 7, 19.4%), Staphylococcus spp. (n = 6, 16.7%), and Micrococcus luteus (n = 6, 16.7%) were isolated, among others. Antimicrobial resistance levels ranged between 0% and 36.1%, and a multiresistance profile was observed in one third of the isolates. Gram-positive cocci colonization was associated with age group. Prevalence of multiresistant isolates was higher in males who were sampled at the refugee camp. Results show that the prevalence of antimicrobial resistance on East Timor may be underestimated. This study represents the first step toward the full characterization of potential pathogenic Gram-positive cocci present in the populations from East Timor.

The potential mutagenic and histopathological effects of the hexavalent chromium were investigated in Lithobates catesbeianus tadpoles. These larvae (GS 25-31) were exposed to three nominal concentrations of potassium dichromate (4, 12, and 36 mg L -1 ) and 5 mg L -1 of Cyclophosphamide as a positive control (PC), for 24 h. A negative control (NC) was also added to the experiment. Our results showed that, in general, the micronuclei (MN) were less frequent than the erythrocyte nuclear abnormalities (ENA); there was a significant difference in the frequency of MN between the NC and all treated groups (p < 0.05) in a concentration-dependent curve, in addition the PC did not differ from the chromium treatments. Also, only PC and the group treated with potassium dichromate at 36 mg L -1 showed significantly higher frequencies of ENA than NC (p < 0.05). Chromium treatments promoted cell retention in the Sub-G1 phase and a decrease of cells in the S and G2/M phases indicating inhibition of the cell cycle. All treatments with chromium led to liver and kidney histopathological lesions, especially with 36 mg L -1 (greater number of lesions). In conclusion, hexavalent chromium was mutagenic to L. catesbeianus tadpoles and its toxic effects also resulted in anti-mitotic activity, besides inducing histopathological alterations in liver and kidney. Amphibians have been proven to be useful bioindicators, and we suggest that tadpoles of different species can be used to represent the environmental impacts in aquatic ecosystems., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The Amazon River basin is the largest tropical forest in the world. Most of the Amazon belongs to Brazil, a developing country that currently faces huge challenges related to the consolidation of its universal healthcare system. Noncommunicable diseases (NCDs) are the leading cause of death in Brazil, accounting for 74% of all deaths, and NCDs are probably underestimated in Amazonian population because of their geographical isolation and the precariousness of riverine communities. Important risk factors, such as genetic susceptibility, remain undetermined in the riverine population. This study performed fasting blood sugar (FBS) and blood pressure measurements and investigated the presence of the ε4 allele of apolipoprotein E (APOE4) to determine the prevalence of diabetes, hypertension and the genetic risk of NCDs. FBS and APOE4 were measured in blood samples from 763 participants using spectrometry and real-time PCR; 67.5% showed altered measurements, and 57.9% had never been diagnosed or treated. Altered FBS was found in 28.3% of the participants, hypertension in 57.6% and APOE4 in 32.0%. The health profile of the riverine population appears to differ from that of urban population in the Amazon. Additional risk factors for NCDs, such as environmental contamination and nutritional transition, may contribute more than increased genetic susceptibility to the prevalence of altered FBS and hypertension. Our results will help guide the development of preventive strategies and governmental actions for more effective management of NCDs in the Amazon area., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Mercury is a heavy metal responsible for human intoxication worldwide and especially in the Amazon, where both natural and anthropogenic sources are responsible for exposure in riverine populations. Methylmercury is the most toxic specie of mercury with recognized neurotoxicity due to its affinity for the central nervous system. S100B protein is a well-established biomarker of brain damage and it was recently associated with mercury-related neurotoxicity. Accurate measurement is especially challenging in isolated/remote populations due to the difficulty of adequate sample conservation, therefore here we use S100B mRNA levels in blood as a way to assay mercury neurotoxicity. We hypothesized that individuals from chronically exposed populations showing mercury levels above the limit of 10 μg/g in hair would present increased levels of S100B mRNA, likely due to early brain damage. A total of 224 riverine individuals were evaluated for anthropometric data (age, body mass index), self-reported symptoms of mercury intoxication, c-reactive protein in blood, and mercury speciation in hair. Approximately 20% of participants showed mercury levels above the limit, and prevalence for most symptoms was not different between individuals exposed to high or low mercury levels. Rigorous exclusion criteria were applied to avoid confounding factors and S100B mRNA in blood was tested by RT-qPCR. Participants with ≥10 μg/g of mercury had S100B mRNA levels over two times higher than that of individuals with lower exposure. A significant correlation was also detected between mercury content in hair and S100B mRNA levels in blood, supporting the use of the latter as a possible candidate to predict mercury-induced neurotoxicity. This is the first report of an association between S100B mRNA and mercury exposure in humans. The combination of both exposure and intoxication biomarkers could provide additional support for the screening and early identification of high-risk individuals in isolated populations and subsequent referral to specialized centers., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The authors describe a 3-year-old female, diagnosed with GLUT1 deficiency Syndrome, with a previously unreported mutation in exon 7 of the SLC2A1 gene: c.968&#95;972 + 3del P. (Val323Alafs*53), characterized by a classic phenotypic of acquired microcephaly, developmental delay, ataxia, spasticity, and epilepsy. Ketogenic diet was started at the age of 30 months with epilepsy improvement. She presented paroxysmal ocular movements in the first 12 months of life, recently defined as "aberrant gaze saccades", that are present in the early phase of visual system development, being one of the first disease signs, but easily disregarded. Recognizing these particular ocular movements would allow an early diagnosis, followed by ketogenic diet implementation, improving significantly the prognosis and the neurological development of those children.

Human exposure to mercury is a serious problem of public health in Amazon. As in other vulnerable populations throughout the world, Amazonian riverine populations are chronically exposed to this metal and some symptoms of mercury intoxication were already detected in these populations. However, studies on the genetic susceptibility to mercury toxicity in the Amazon are scarce, and they tested a limited number of individuals. In this context, apolipoprotein E gene ( APOE ) is a key element with a well-established association among their alleles and the neurodegenerative consequences of mercury intoxication. However, no studies have addressed APOE genotyping in Amazonian exposed populations. Additionally, epidemiological studies with APOE genotyping in Amazon have been restricted to indigenous populations. Therefore, this work analyzed for the first time the genotypic and allelic profiles of APOE in Amazonian riverine populations chronically exposed to mercury. Eight hundred and twenty three individuals were enrolled in our study donating blood (794) and/or hair (757). APOE genotyping was analyzed by real-time PCR. Total mercury and mercury species were quantified by ICP-MS and GC-pyro-AFS, respectively. Genomic ancestry markers were evaluated by multiplex-PCR reaction, separated by capillary electrophoresis on the ABI 3130 Genetic Analyzer instrument and analyzed on GeneMapper ID v3.2. The 𝜀3 and 𝜀3/𝜀3 were the most frequent allele and genotype, respectively, followed by 𝜀4 allele and 𝜀3/𝜀4 genotype. Only 𝜀2/𝜀2 genotype was not found, suggesting that the absence of this genotype is a generalized phenomenon in Amazon. Also, our data supported an association between the presence of APOE4 and the Amerindian origin in these populations. Fifty-nine individuals were identified at maximum risk with levels of mercury above 10 μg/g and the presence of APOE4 . Interestingly, among individuals with high mercury content, APOE4 -carriers had high mercury levels than APOE2 -carriers, pointing to a different heavy metal accumulation according to the APOE allele. These data suggest that APOE4 , in addition to a possible pharmacodynamic effect, may influence pharmacokinetically the mercury exposure causing its higher accumulation and leading to worse deleterious consequences. Our results may aid in the development of prevention strategies and health policy decision-making regarding these at-risk vulnerable populations.

Objective: To describe the clinical manifestations of patients with pulmonary infection caused by mycobacteria of the Mycobacterium abscessus complex (MABSC), and to compare these manifestations with those of patients infected with other nontuberculous mycobacteria (NTM)., Methods: This was a retrospective cohort study involving 43 patients divided into two groups: the MABSC group, consisting of patients with pulmonary infection caused by MABSC (n = 17); and the NTM group, consisting of patients with pulmonary infection caused by NTM other than MABSC (n = 26). Patients were previously treated with a regimen of rifampin, isoniazid, pyrazinamide, and ethambutol before the diagnosis of NTM was confirmed by two culture-positive sputum samples. The nucleotide sequences of the hsp65, 16S rRNA, and/or rpoB genes were analyzed to identify the mycobacteria. Data were collected on demographic, clinical, and radiological characteristics, as well as on treatment responses and outcomes., Results: Loss of appetite was the only clinical manifestation that was significantly more common in the MABSC group than in the NTM group (p = 0.0306). The chance of having to use a second treatment regimen was almost 12 times higher in the MABSC group than in the NTM group. Treatment success was significantly higher in the NTM group than in the MABSC group (83.2% vs. 17.6%; p < 0.0001). The chance of recurrence was approximately 37 times higher in the MABSC group than in the NTM group., Conclusions: In the study sample, treatment response of pulmonary disease caused by MABSC was less favorable than that of pulmonary disease caused by other NTM.

Seizures affect about 50 million people around the world. Approximately 30% of seizures are refractory to the current pharmacological arsenal, so, the pursuit of new therapeutic alternatives is essential. Clarified Euterpe oleracea (EO) juice showed anticonvulsant properties similar to diazepam in an in vivo model with pentylenetetrazol, a GABA A receptor blocker. This study investigated the effects of EO on the main GABAergic targets for anticonvulsant drugs, analyzing the effect on the GABA receptor's benzodiazepine and picrotoxinin binding sites and the GABA uptake. Primary cultures of cortical neurons and astrocytes were treated with EO (0-25%) for up to 90 min. [ 3 H]Flunitrazepam and [ 3 H]TBOB binding, [ 3 H]GABA uptake, cell viability, and morphology were assayed. Nonlethal concentrations of EO increased agonist binding and decreased antagonist binding in cortical neurons. Low concentrations significantly inhibited GABA uptake, especially in astrocytes, suggesting an accumulation of endogenous GABA in the synaptic cleft. The results demonstrate, for the first time, that EO can improve GABAergic neurotransmission via interactions with GABA A receptor and modulation of GABA uptake. Understanding these molecular mechanisms will help in the treatment of seizures and epilepsy, especially in developing countries where geographic isolation and low purchasing power are the main barriers to access to adequate treatment.

The Tucuruí Dam is one of the largest dams ever built in the Amazon. The area is not highly influenced by gold mining as a source of mercury contamination. Still, we recently noted that one of the most consumed fishes (Cichla sp.) is possibly contaminated with methylmercury. Therefore, this work evaluated the mercury content in the human population living near the Tucuruí Dam. Strict exclusion/inclusion criteria were applied for the selection of participants avoiding those with altered hepatic and/or renal functions. Methylmercury and total mercury contents were analyzed in hair samples. The median level of total mercury in hair was above the safe limit (10µg/g) recommended by the World Health Organization, with values up to 75µg/g (about 90% as methylmercury). A large percentage of the participants (57% and 30%) showed high concentrations of total mercury (≥ 10µg/g and ≥ 20µg/g, respectively), with a median value of 12.0µg/g. These are among the highest concentrations ever detected in populations living near Amazonian dams. Interestingly, the concentrations are relatively higher than those currently shown for human populations highly influenced by gold mining areas. Although additional studies are needed to confirm the possible biomagnification and bioaccumulation of mercury by the dams in the Amazon, our data already support the importance of adequate impact studies and continuous monitoring. More than 400 hydropower dams are operational or under construction in the Amazon, and an additional 334 dams are presently planned/proposed. Continuous monitoring of the populations will assist in the development of prevention strategies and government actions to face the problem of the impacts caused by the dams., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Leishmania (Leishmania) amazonensis and Leishmania infantum (=Leishmania chagasi) are protozoa that cause American cutaneous and visceral leishmaniasis, respectively. These diseases show a high incidence in developing countries such as Brazil. The treatments used for leishmaniasis are still limited due to their high cost and toxicity. Currently, some natural products are considered an important alternative source of new leishmanicidal agents. Euterpe oleracea Martius, a palm producing black fruits, is frequently consumed in the Amazon region, as a juice, known as açai, with potent antioxidant, anti-inflammatory and anticonvulsant properties. Interestingly, the biological activity of clarified açai juice (EO) on L. (L.) amazonensis and L. infantum (=L. chagasi) is unknown. Therefore, the mechanism of anti-leishmanial action of EO has been evaluated on L. (L.) amazonensis and L. infantum (=L. chagasi). EO reduced the number of promastigotes and caused morphological alterations, increased the production of reactive oxygen species (ROS) and induced cell death phenotypes probably seems by apoptosis in the promastigotes of L. (L.) amazonensis (IC 50  = 1:40) and L. infantum (=L. chagasi) (IC 50  = 1:38). EO also presented activity against Leishmania amastigotes. Treatment with EO for 72 h strongly reduced IL-17 cytokine levels at all tested concentrations and decreased the number of intracellular amastigotes in macrophages infected with L. (L.) amazonensis (IC 50  = 1:30) and L. infantum (=L. chagasi) (IC 50  = 1:38). Additionally, no cytotoxic effect was observed in murine macrophages treated with EO (72 h - CC 50  > 1:1). Our results demonstrated that EO has leishmanicidal activity against two different species that cause American visceral and cutaneous leishmaniasis without cytotoxic effects for the host cell., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective: Early neonatal thalamic lesions account for about 14% of continuous spike-wave of sleep (CSWS) syndrome, representing the most common etiology in this epileptic encephalopathy in children, and promise useful insights into the pathophysiology of the disease., Methods: We describe nine patients with unilateral neonatal thalamic lesions which progressed to CSWS. Longitudinal whole-night and high-density electroencephalograms (EEGs) were performed, as well as detailed imaging and clinical evaluation. Visual evoked potentials were used to probe cortical excitability., Results: Thalamic volume loss ranged from 19% to 94%, predominantly on medial and dorsal nuclei and sparing the ventral thalamus. Lesions produced white matter loss and ventricle enlargement on the same hemisphere, which in four patients was associated with selective loss of thalamic-cortical fibers. Cortical thickness quantification failed to reveal hemispheric asymmetries. Impact on EEG rhythms was mild, with a volume-loss-related decrease in alpha power and preservation of sleep spindles. The sleep continuous spiking was lateralized to the hemisphere with the lesion. Visual cortex stimulation in five patients with posterior cortex spiking revealed an abnormal frequency-dependent excitability at 10-20Hz on the side of the lesion., Significance: Unilateral selective thalamic-cortical disconnection is a common feature in our patients and is associated with both a focal pattern of CSWS and a pathological type of frequency-dependent excitability (peak: 10-20Hz). We propose that this excitability represents an abnormal synaptic plasticity previously described as the augmenting response. This synaptic plasticity has been described as absent in the corticocortical interactions in healthy experimental animals, emerging after ablation of the thalamus and producing a frequency-dependent potentiation with a peak at 10-20Hz. Because this response is potentiated by sleep states of reduced brainstem activation and by appropriate stimulating rhythms, such as sleep spindles, the simultaneous occurrence of these two factors in nonrapid-eye-movement sleep is proposed as an explanation for CSWS in our patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

M. paraffinicum , a slow-growing scotochromogenic mycobacterium that uses paraffinic hydrocarbons other than methane, i.e. inorganic carbon sources, was originally isolated from soil samples, but only in 2010 definitely achieved the species status. We have described here the first report of pulmonary disease due to M. paraffinicum in Amazon Region.

Background: Nosocomial pneumonia has correlated to dental plaque and to oropharynx colonization in patients receiving mechanical ventilation. The interruption of this process, by preventing colonization of pathogenic bacteria, represents a potential procedure for the prevention of ventilator-associated pneumonia (VAP)., Methods: The study design was a prospective, randomized trial to verify if oral hygiene through toothbrushing plus chlorhexidine in gel at 0.12% reduces the incidence of ventilatior-associated pneumonia, the duration of mechanical ventilation, the length of hospital stay and the mortality rate in ICUs, when compared to oral hygiene only with chlorhexidine, solution of 0.12%, without toothbrushing, in adult individuals under mechanical ventilation, hospitalized in Clinical/Surgical and Cardiology Intensive Care Units (ICU). The study protocol was approved by the Ethical Committee of Research of the Health Sciences Center of the Federal University of Pernambuco - Certificate of Ethical Committee Approval (CAAE) 04300012500005208. Because it was a randomized trial, the research used CONSORT 2010 checklist criteria., Results: Seven hundred sixteen patients were admitted into the ICU; 219 fulfilled the criteria for inclusion and 213 patients were included; 108 were randomized to control group and 105 to intervention group. Toothbrushing plus 0.12% chlorhexidine gel demonstrated a lower incidence of VAP throughout the follow up period, although the difference was not statistically significant (p = 0.084). There was a significant reduction of the mean time of mechanical ventilation in the toothbrushing group (p = 0.018). Regarding the length of hospital stay in the ICU and mortality rates, the difference was not statistically significant (p = 0.064)., Conclusions: The results obtained showed that, among patients undergoing toothbrushing there was a significant reduction in duration of mechanical ventilation, and a tendency to reduce the incidence of VAP and length of ICU stay, although without statistical significance., Trial Registration: Retrospectively registered in the Brazilian Clinical Trials Registry (Registro Brasileiro de Ensaios Clínicos) - RBR-4TWH4M (4 September 2016).

Introduction: There is disagreement whether white coat hypertensives (WCH) have different hemodynamic and structural characteristics compared to normotensives (NT) and hypertensives (HT)., Methods: We compared cardiovascular prognostic markers (pulse wave velocity [PWV] and aortic stiffness index [ASI]) and data on central hemodynamics and central pressures (augmentation index [AIx], augmentation pressure [AugP] and pulse pressure amplification [PPA]) from aortic pulse wave analysis between NT (n=175), WCH (n=315) and treated HT (n=691), all with 24-h blood pressure (BP) <130/80 and nocturnal BP <120/70 mmHg after matching for age, gender, body mass index (BMI) and and nocturnal BP. The groups were also compared separately in terms of 24-h systolic BP <120 mmHg and 120-129 mmHg., Results: The percentage of non-dippers was 40.1% in NT, 34.5% in WCH and 38.3 in HT. For similar 24-h and nocturnal systolic BP (NT 109/64±7/5, WCH 110/66±7/6, HT 109/64±7/5 mmHg), aortic stiffness was greater in HT (n=691, PWV 10.8±2.6 m/s and ASI 0.33±0.16, p<0.01) than in WCH (n=316, PWV 9.7±2.4 m/s and ASI 0.28±0.17) and NT (n=175, PWV 9.5±2.0 m/s and ASI 0.29±0.15); AugP and AIx were higher (p<0.01) in HT (13.9±8.2 and 29.6±12.6 mmHg) than in WCH (11.5±8.5 mmHg and 24.9±15.2) and NT (11.0±6.4 mmHg and 26.6±11.5). PPA was lower (p<0.01) in HT (11.3±5.5 mmHg) than in WCH (13.2±7.1 mmHg) and in NT (12.4±4.9 mmHg). The findings were similar when the 24-h systolic BP <120 mmHg and 120-129 mmHg subgroups were analyzed separately., Conclusion: Our data suggest that for similar age, gender distribution, BMI, and 24-h and nocturnal BP, aortic stiffness, central aortic pressures and wave reflection in WCH are closer to those of NT than to those with treated HT. This supports the idea that white coat hypertension may be a more benign condition than treated hypertension for similar 24-h and particularly nocturnal BP levels., (Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Convulsive seizures (CS) are deleterious consequences of acute cerebral insults and prejudicial events in epilepsy, affecting more than 50 million people worldwide. Molecular mechanisms of depression and epilepsy include an imbalance between excitatory and inhibitory neurotransmission provoking oxidative stress (OS). OS is intimately linked to the origin and evolution of CS and is modulated by antidepressant and anticonvulsant drugs. Although newer antidepressants have exhibited a possible protective role in CS, studies analyzing serotonin and norepinephrine reuptake inhibitors merit to be further investigated. Thus, this study challenged the traditional model of pentylenetetrazol-induced CS, with only one administration of duloxetine. Male Swiss mice were treated with duloxetine (dose corresponding to the therapeutic range for human depression or greater, by allometric calculation; 10, 20 or 40 mg/kg), 30 min before pentylenetetrazol. Behavioral and electroencephalographic alterations were monitored. Lipid peroxidation, nitrites and catalase and superoxidase activities were measured in cortex. Behavioral and electroencephalographic results suggested a possible biphasic effect of duloxetine on CS, with anticonvulsant actions at therapeutic doses and a proconvulsant effect at higher doses. Duloxetine (20 mg/kg) also prevented lipid peroxidation and decreased catalase and superoxide dismutase activities in the cerebral cortex, with no influence on nitrites levels. These data demonstrated an anticonvulsant effect of duloxetine in CS for the first time. This extra anticonvulsant effect may allow the doses of anticonvulsants to be reduced, causing fewer side effects and possibly decreasing morbidity and mortality due to drug interactions in polytherapy., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) manifests by migraine with aura, cerebral ischemic events, mood disturbances and dementia. Brain MRI lesions typically precede the symptoms from 10 to 15 years and previous evidence showed all CADASIL patients above 35 years old have an abnormal MRI, supporting the clinical diagnosis. Case results We present a 37-year-old female patient with migraine without aura, a family history of CADASIL, normal brain 3-Tesla MRI and normal skin biopsy, even though a pathogenic NOTCH3 gene mutation (allele 2, exon 11, c.1672 C\gtT, p.Arg558Cys) was detected. Conclusions When CADASIL is strongly suspected, a normal brain MRI, even in the fourth decade of life, does not rule out the diagnosis and should not discourage the genetic test.

Background: It is controversial whether high salt intake is directly associated with cardiovascular (CV) events and how far this relation is independent of blood pressure (BP). As Portugal has higher salt consumption and higher mortality by stroke than other European countries, we examined whether salt intake could predict the development of stroke and CV events in a hypertensive population., Methods: In a longitudinal retrospective study of a cohort of 608 adult treated hypertensive patients 54.1±14.3 years of age, BMI 29.3±8.3 kg/m, 56.3% women and 17.1% diabetics, we evaluate the long-term prognostic significance of urinary sodium (UNa) excretion measured in 24 h valid samples within the first 3 months after admission along with 24 h ambulatory blood pressure monitoring and pulse wave velocity [(PWV), complior)] measurements., Results: The mean follow-up duration was 7.2 years (0.5-11.1 years), during which 122 CV events occurred including 80 strokes and 36 coronary events. In 608 patients (group A=507 without events and group B=101 with events: 69 strokes, 26 coronary events, six others), the mean 24 h UNa was 208±79 mmol/day, corresponding to a salt intake of 12.1±4.6 g/day. Twenty-four hours UNa correlated positively with BMI, PWV and systolic blood pressure (SBP) particularly with night-time SBP. Group B versus A showed higher UNa (260+98 vs. 198+71 mmol/day, P<0.001) and higher PWV, BP office, 24 h, daytime and night-time SBP. Logistic regression analysis identified age, night-time SBP and 24 h UNa+ [HR=1.09 (95% CI, 1.06-1.12, P<0.001)] for each 10 mmol increase of UNa+ as the only independent predictors of CV events. UNa+ above the median (189 mmol sodium/day) predicted CV events with HR=2.99 (95% CI, 1.75-5.13, P<0.001) with worse CV event-free survival rates (log rank statistics of 17.44, P<0.001)., Conclusion: In a cohort of hypertensive patients, high salt intake independently predicts the occurrence of CV events, particularly of stroke.

Human exposure to relatively low levels of methylmercury is worrying, especially in terms of its genotoxicity. It is currently unknown as to whether exposure to low levels of mercury (below established limits) is safe. Genotoxicity was already shown in lymphocytes, but studies with cells of the CNS (as the main target organ) are scarce. Moreover, disturbances in the cell cycle and cellular proliferation have previously been observed in neuronal cells, but no data are presently available for glial cells. Interestingly, cells of glial origin accumulate higher concentrations of methylmercury than those of neuronal origin. Thus, the aim of this work was to analyze the possible genotoxicity and alterations in the cell cycle and cell proliferation of a glioma cell line (C6) exposed to a low, non-lethal and non-apoptotic methylmercury concentration. Biochemical (mitochondrial activity) and morphological (integrity of the membrane) assessments confirmed the absence of cell death after exposure to 3 μM methylmercury for 24 hours. Even without promoting cell death, this treatment significantly increased genotoxicity markers (DNA fragmentation, micronuclei, nucleoplasmic bridges and nuclear buds). Changes in the cell cycle profile (increased mitotic index and cell populations in the S and G2/M phases) were observed, suggesting arrest of the cycle. This delay in the cycle was followed, 24 hours after methylmercury withdrawal, by a decrease number of viable cells, reduced cellular confluence and increased doubling time of the culture. Our work demonstrates that exposure to a low sublethal concentration of MeHg considered relatively safe according to current limits promotes genotoxicity and disturbances in the proliferation of cells of glial origin with sustained consequences after methylmercury withdrawal. This fact becomes especially important, since this cellular type accumulates more methylmercury than neurons and displays a vital role protecting the CNS, especially in chronic intoxication with this heavy metal., Competing Interests: The authors have declared that no competing interests exist.

Background: In this paper, we describe a cohort of patients with short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), a rare trigeminal autonomic headache, managed in the outpatient clinic of a tertiary hospital., Methods: Patients were identified through review of individual records between January 1, 2008 and June 30, 2014., Results: Fifteen patients were identified (eight males:seven females), with mean age at onset of 49.7 years, mean number of attacks per day of 7.5 and mean attack duration of 54.6 seconds. Pain was mostly orbital, periorbital or temporal. Cranial autonomic signs/symptoms were universally present; one patient reported ipsilateral epistaxis. Two symptomatic cases were identified and treated surgically. Most patients responded to lamotrigine, one to topiramate and another to eslicarbazepine., Conclusion: Our case series is among the largest reported, with findings similar to others already published, but the first to report epistaxis during SUNCT attack and response to eslicarbazepine., (© International Headache Society 2015.)

Many tropical biomes are threatened by rapid land-use change, but its catchment-wide biogeochemical effects are poorly understood. The few previous studies on DOM in tropical catchments suggest that deforestation and subsequent land use increase stream water dissolved organic carbon (DOC) concentrations, but consistent effects on DOM elemental stoichiometry have not yet been reported. Here, we studied stream water DOC concentrations, catchment DOC exports, and DOM elemental stoichiometry in 20 tropical catchments at the Cerrado-Atlantic rainforest transition, dominated by natural vegetation, pasture, intensive agriculture, and urban land cover. Streams draining pasture could be distinguished from those draining natural catchments by their lower DOC concentrations, with lower DOM C:N and C:P ratios. Catchments with intensive agriculture had higher DOC exports and lower DOM C:P ratios than natural catchments. Finally, with the highest DOC concentrations and exports, as well as the highest DOM C:P and N:P ratios, but the lowest C:N ratios among all land-use types, urbanized catchments had the strongest effects on catchment DOM. Thus, urbanization may have alleviated N limitation of heterotrophic DOM decomposition, but increased P limitation. Land use-especially urbanization-also affected the seasonality of catchment biogeochemistry. While natural catchments exhibited high DOC exports and concentrations, with high DOM C:P ratios in the rainy season only, urbanized catchments had high values in these variables throughout the year. Our results suggest that urbanization and pastoral land use exerted the strongest impacts on DOM biogeochemistry in the investigated tropical catchments and should thus be important targets for management and mitigation efforts., (Copyright © 2016 Elsevier B.V. All rights reserved.)