53 results on '"Mello CB"'
Search Results
2. Immune signaling pathways in Rhodnius prolixus in the context of Trypanosoma rangeli infection: cellular and humoral immune responses and microbiota modulation.
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Pereira SB, de Mattos DP, Gonzalez MS, Mello CB, Azambuja P, de Castro DP, and Vieira CS
- Abstract
Introduction: Rhodnius prolixus is a hematophagous insect and one of the main vectors for Trypanosoma cruzi and Trypanosoma rangeli parasites in Latin America. Gut microbiota and insect immune responses affect T. cruzi and T. rangeli infection within triatomines. Particularly the Toll and IMD signaling pathways activations and how they orchestrate the antimicrobial peptides (AMPs) expressions in R. prolixus , especially when infected by T. rangeli ., Objectives: Examine how T. rangeli infection modulates R. prolixus cellular and humoral immunity and its impacts on insect microbiota., Methods: R. prolixus was fed on blood containing epimastigotes of T. rangeli , and infection was quantified in insect tissues. The gene expression of dorsal , cactus , relish , PGRP , and AMPs was examined in the midgut, fat body, and salivary glands by quantitative real-time PCR. Microbiota composition was analyzed using RT-q PCR targeting specific bacterial species. Hemocyte numbers and phenoloxidase activity were quantified to assess cellular immune responses., Results: T. rangeli infection modulated triatomine immunity in midgut and hemocoel, activating the expression of the NF-kB gene dorsal , associated with the Toll pathway; increasing expression of the gene encoding PGRP receptor, a component involved in the IMD pathway, both in the intestine and fat body; repressing the expression of the relish transcription factor, mainly in salivary glands. Among the R. prolixus AMPs studied, T. rangeli infection repressed all AMP gene expression, other than defensin C which increased mRNA levels. The PO activity was enhanced in the hemolymph of infected insects. T. rangeli infection did not induce hemocyte number alterations compared to control insects. However, an increase in hemocyte microaggregation was detected in infected insects., Discussion: R. prolixus recognizes T. rangeli infection and triggers humoral and cellular immune responses involving Toll pathway activation, defensin C synthesis, increased phenoloxidase activity, and enhanced hemocyte aggregation. On the other hand, T. rangeli infection suppressed some IMD pathway components, suggesting that, in R. prolixus , this pathway is involved in defensins A and B gene regulation. Importantly, these immune responses altered the bacterial microbiota composition, potentially favoring T. rangeli establishment in the insect vector., 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 Pereira, Mattos, Gonzalez, Mello, Azambuja, Castro and Vieira.)
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- 2024
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3. Response to intervention as an identification strategy of the risk for dyslexia.
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Medda MG, Barbosa T, Rocco IS, and Mello CB
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- Humans, Child, Female, Male, Reading, Language Tests, Writing, Risk Factors, Phonetics, Memory, Short-Term physiology, Dyslexia diagnosis
- Abstract
Purpose: To develop on intervention process to identify children at risk of dyslexia, based on the Response to Intervention model. Specifically, to identify the pattern of changes in post-intervention performance in tasks of phonological awareness, working memory, lexical access, reading and writing; and to analyze which cognitive functions had a significant effect on the discriminating students at risk of dyslexia., Method: Sample of 30 participants with Reading and writing difficulties, aged 8-11, from public/private schools, students from 3rd to 5th grade. Participants were submitted to a battery of cognitive-linguistic tests, before and after 12 intervention sessions. To monitor their performance, five reading and writing lists of words and pseudowords were applied. We qualitatively and quantitatively analyzed the differences in pre- and post-intervention performance of each participant; and among participants in the post-assessment, to understand the patterns of dyslexia vs non-dyslexia groups., Results: There were statistically significant changes in: rapid automatized naming, narrative text comprehension, phonological awareness, rate and typology of hits/misses in reading and writing, and reading speed. Being the last three variables the most sensitive to discriminate the two groups, all with less post-intervention gains for the dyslexia group., Conclusions: The intervention focused on the stimulation of phonological skills and explicit and systematic teaching of graphophonemic correspondences contributed positively to the evolution of the group's participants. The intervention response approach favored the identification of children with a profile at risk for dyslexia, as distinct from children with other learning difficulties.
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- 2024
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4. Neuropsychological Profile of 25 Brazilian Patients with 22q11.2 Deletion Syndrome: Effects of Clinical and Socioeconomic Variables.
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Pimenta LSE, Mello CB, Benedetto LMD, Soares DCQ, Kulikowski LD, Dantas AG, Melaragno MI, and Kim CA
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- Humans, Male, Adolescent, Female, Child, Brazil epidemiology, Adult, Young Adult, Neuropsychological Tests, Socioeconomic Factors, Intelligence, Quality of Life, Social Class, DiGeorge Syndrome genetics, DiGeorge Syndrome psychology
- Abstract
The 22q11.2 deletion syndrome (22q11.2DS) is associated with a heterogeneous neurocognitive phenotype, which includes psychiatric disorders. However, few studies have investigated the influence of socioeconomic variables on intellectual variability. The aim of this study was to investigate the cognitive profile of 25 patients, aged 7 to 32 years, with a typical ≈3 Mb 22q11.2 deletion, considering intellectual, adaptive, and neuropsychological functioning. Univariate linear regression analysis explored the influence of socioeconomic variables on intellectual quotient (IQ) and global adaptive behavior. Associations with relevant clinical conditions such as seizures, recurrent infections, and heart diseases were also considered. Results showed IQ scores ranging from 42 to 104. Communication, executive functions, attention, and visuoconstructive skills were the most impaired in the sample. The study found effects of access to quality education, family socioeconomic status (SES), and caregiver education level on IQ. Conversely, age at diagnosis and language delay were associated with outcomes in adaptive behavior. This characterization may be useful for better understanding the influence of social-environmental factors on the development of patients with 22q11.2 deletion syndrome, as well as for intervention processes aimed at improving their quality of life.
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- 2024
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5. Immune Reactions of Vector Insects to Parasites and Pathogens.
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Ratcliffe NA, Mello CB, Castro HC, Dyson P, and Figueiredo M
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This overview initially describes insect immune reactions and then brings together present knowledge of the interactions of vector insects with their invading parasites and pathogens. It is a way of introducing this Special Issue with subsequent papers presenting the latest details of these interactions in each particular group of vectors. Hopefully, this paper will fill a void in the literature since brief descriptions of vector immunity have now been brought together in one publication and could form a starting point for those interested and new to this important area. Descriptions are given on the immune reactions of mosquitoes, blackflies, sandflies, tsetse flies, lice, fleas and triatomine bugs. Cellular and humoral defences are described separately but emphasis is made on the co-operation of these processes in the completed immune response. The paper also emphasises the need for great care in extracting haemocytes for subsequent study as appreciation of their fragile nature is often overlooked with the non-sterile media, smearing techniques and excessive centrifugation sometimes used. The potential vital role of eicosanoids in the instigation of many of the immune reactions described is also discussed. Finally, the priming of the immune system, mainly in mosquitoes, is considered and one possible mechanism is presented.
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- 2024
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6. Influence of blood phenylalanine level variations on the development of executive functions and social cognition in children with phenylketonuria.
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de Almeida Duarte CM, Piazzon FB, Rocco IS, and de Mello CB
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- Humans, Child, Cognition, Social Cognition, Neuropsychological Tests, Phenylalanine, Executive Function, Phenylketonurias complications
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Objective: To investigate the performance of 27 children with phenylketonuria (PKU) in tests of Executive Functions (EF) and Social Cognition (SC), and their associations with metabolic control inferred by phenylalanine (Phe) levels., Methods: The PKU group was dichotomized according to baseline Phe-levels into; "classical PKU"(n = 14), with Phe-levels above 1200 μmol/L (> 20 mg/dL); and "mild PKU" (n = 13) with Phe-between 360 and 1200 μmol/L (6-20 mg/dL). The neuropsychological assessment focused on the EF and SC subtests of the NEPSY-II battery and intellectual performance. Children were compared to age-matched healthy participants., Results: Participants with PKU presented significantly lower Intellectual Quotient (IQ) compared to controls (p = 0.001). Regarding EF analysis adjusted by age and IQ, significant differences between groups were observed only in the executive attention subtests (p = 0.029). The SC set of variables was significantly different between groups (p = 0.003), as in the affective recognition task (p < 0.001). In the PKU group, the relative variation of Phe-achieved 32.1 ± 21.0%. Relative Phe-variation was correlated only with measures of Working Memory (p < 0.001), Verbal Fluency (p = 0.004), Inhibitory Control (p = 0.035) and Theory of Mind (p = 0.003)., Conclusions: Phonological Verbal Fluency, Working Memory, Inhibitory Control, and Theory of Mind were shown to be most vulnerable when there is non-ideal metabolic control. Variations in the level of Phe-may have a selective negative effect on Executive Functions and Social Cognition, but not on intellectual performance., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2023 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)
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- 2023
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7. The impact of inflammatory and metabolic markers on depression, anxiety, and cognition after COVID-19: A narrative review.
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Diniz EJB, Scorza FA, Rodrigues FMS, de Mello CB, Bonetti TCS, Bortoluci KR, and Mari JJ
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Introduction: There has been growing concern about the long-term effects of COVID-19 on mental health. The biological factors common to psychiatric conditions and COVID-19 are not yet fully understood., Methodology: We narratively reviewed prospective longitudinal studies that measured metabolic or inflammatory markers and assessed psychiatric sequalae and cognitive impairment in individuals with COVID-19 at least 3 months after the infection. A literature search identified three relevant cohort studies., Results: Overall, depressive symptomatology and cognitive deficits persisted for up to one year after COVID-19; depression and cognitive changes were predicted by acute inflammatory markers, and changes in these markers correlated with changes in depressive symptomatology; female sex, obesity, and the presence of inflammatory markers were associated with more severe clusters of physical and mental health status in patients' self-perceived recovery; and plasma metabolic profiles of patients continued to differ from those of healthy controls three months after hospital discharge, which were associated with widespread alterations in neuroimaging, reflecting issues with white matter integrity. This is a non-systematic review and cautions should be made while interpreting the conclusions., Conclusion: In individuals affected by the COVID-19, prolonged exposure to stress and alterations in metabolic and inflammatory markers plays a central role in psychiatric sequalae and cognitive deficits in the long term., Competing Interests: JJM was a speaker for the following laboratories in topics not related to this article: EMS, Eurofarma, Janssen, Apsen, Abbot, and Biolab. No other conflicts of interest declared concerning the publication of this article.
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- 2023
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8. Reaching the Final Endgame for Constant Waves of COVID-19.
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Ratcliffe NA, Castro HC, Gonzalez MS, Mello CB, and Dyson P
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- Humans, Post-Acute COVID-19 Syndrome, SARS-CoV-2, Antiviral Agents therapeutic use, COVID-19 epidemiology, COVID-19 prevention & control
- Abstract
Despite intramuscular vaccines saving millions of lives, constant devastating waves of SARS-CoV-2 infections continue. The elimination of COVID-19 is challenging, but necessary in order to avoid millions more people who would suffer from long COVID if we fail. Our paper describes rapidly advancing and innovative therapeutic strategies for the early stage of infection with COVID-19 so that tolerating continuing cycles of infection should be unnecessary in the future. These therapies include new vaccines with broader specificities, nasal therapies and antiviral drugs some targeting COVID-19 at the first stage of infection and preventing the virus entering the body in the first place. Our article describes the advantages and disadvantages of each of these therapeutic options which in various combinations could eventually prevent renewed waves of infection. Finally, important consideration is given to political, social and economic barriers that since 2020 hindered vaccine application and are likely to interfere again with any COVID-19 endgame., Competing Interests: The authors have declared that there are no competing interests.
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- 2022
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9. Genetic polymorphisms and their effects on the severity of silicosis in workers exposed to silica in Brazil.
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Castro MCS, Nani ASF, Salum KCR, Rolando JM, Santos JFBD, Castro HA, Ribeiro PC, Costa W, Mello CB, and Kohlrausch FB
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- Humans, Genetic Predisposition to Disease, Brazil, Case-Control Studies, Polymorphism, Genetic, GTPase-Activating Proteins genetics, Silicon Dioxide toxicity, Silicon Dioxide analysis, Silicosis genetics
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Objective: Silicosis is a pneumoconiosis characterized by fibrosis of the lung parenchyma caused by inhalation of silica particles. Genetic factors might play a role in the severity silicosis. We sought to evaluate the influence of polymorphisms in the ACE, FAS, FASLG, NOS2, IL1RN, FAM13A, TGFB1, and TNF genes on the severity of silicosis., Methods: Nine polymorphisms were genotyped by PCR in a sample of 143 patients with silicosis in the state of Rio de Janeiro, Brazil., Results: Fifty-seven patients (40%) were classified as having simple silicosis and 86 (60%) were classified as having complicated silicosis. The TT genotype of rs1800469 in the TGFB1 gene showed a protective effect for complicated silicosis (OR = 0.35; 95% CI, 0.14-0.92; p = 0.028) when compared with the other two genotypes (CC+CT). The polymorphic T allele of rs763110 in the FASLG gene (OR = 0.56; 95% CI, 0.31-0.99; p = 0.047), as well as a dominant model for the T allele (TT+CT: OR = 0.37; 95% CI, 0.15-0.96; p = 0.037), also showed a protective effect. When patients with simple silicosis despite having been exposed to silica for a longer time (> 44,229 hours) were compared with patients with complicated silicosis despite having been exposed to silica for a shorter time, the T allele of rs763110 in the FASLG gene (OR = 0.20; 95% CI, 0.08-0.48; p < 0.0001), as well as dominant and recessive models (OR = 0.06; 95% CI, 0.00-0.49; p = 0.01 and OR = 0.22; 95% CI, 0.06-0.77; p = 0.014, respectively), showed a protective effect against the severity of silicosis., Conclusions: It appears that rs1800469 polymorphisms in the TGFB1 gene and rs763110 polymorphisms in the FASLG gene are involved in the severity of silicosis. Given the lack of studies relating genetic polymorphisms to the severity of silicosis, these results should be replicated in other populations.
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- 2022
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10. Overview of paratransgenesis as a strategy to control pathogen transmission by insect vectors.
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Ratcliffe NA, Furtado Pacheco JP, Dyson P, Castro HC, Gonzalez MS, Azambuja P, and Mello CB
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- Animals, Animals, Genetically Modified, Insect Vectors genetics, Mosquito Vectors, Culicidae, Tsetse Flies microbiology
- Abstract
This article presents an overview of paratransgenesis as a strategy to control pathogen transmission by insect vectors. It first briefly summarises some of the disease-causing pathogens vectored by insects and emphasises the need for innovative control methods to counter the threat of resistance by both the vector insect to pesticides and the pathogens to therapeutic drugs. Subsequently, the state of art of paratransgenesis is described, which is a particularly ingenious method currently under development in many important vector insects that could provide an additional powerful tool for use in integrated pest control programmes. The requirements and recent advances of the paratransgenesis technique are detailed and an overview is given of the microorganisms selected for genetic modification, the effector molecules to be expressed and the environmental spread of the transgenic bacteria into wild insect populations. The results of experimental models of paratransgenesis developed with triatomines, mosquitoes, sandflies and tsetse flies are analysed. Finally, the regulatory and safety rules to be satisfied for the successful environmental release of the genetically engineered organisms produced in paratransgenesis are considered., (© 2022. The Author(s).)
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- 2022
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11. Educational status, testosterone replacement, and intelligence outcomes in Klinefelter syndrome.
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Simonetti L, da Silva MRD, and de Mello CB
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Most male hypergonadotropic hypogonadism associated with infertility can be attributed to a single genetic condition such as Klinefelter syndrome (KS). This disease's wide phenotypic variability is frequently associated with mosaic 47,XXY lineages and testosterone replacement. Early diagnosis and treatment have been associated with better cognitive and intellectual outcomes, but the scope of this influence requires further investigation., Objective: This study aimed to investigate the intelligence profile of a cohort of patients with KS, considering the influence of educational level and clinical variables., Methods: Twenty-nine (9-65 years) individuals were submitted to the measures of intelligence quotient (IQ) (Wechsler's Scales) and adaptive behavior (Vineland-II). Linear regression analysis included the participants' educational level and clinical variables (i.e., comorbidities and use of testosterone) as predictors and intellectual performance and adaptive behavior as outcomes., Results: Scores varied from intellectual deficiency to average ranges (82.5+15.8). There were significant differences between adult's and children's IQ and between verbal and nonverbal indexes. The level of education predicted both IQ and adaptive behavior. Testosterone replacement therapy and absence of seizures predicted only adaptive behavior., Conclusions: The level of education and hormonal therapy can be selectively implicated in the intellectual variability in KS., Competing Interests: Disclosure: The authors report no conflicts of interest.
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- 2022
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12. Nasal therapy-The missing link in optimising strategies to improve prevention and treatment of COVID-19.
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Ratcliffe NA, Castro HC, Paixão IC, Evangelho VGO, Azambuja P, and Mello CB
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- Administration, Intranasal trends, Antiviral Agents administration & dosage, COVID-19 therapy, Humans, Receptors, Virus drug effects, Receptors, Virus metabolism, SARS-CoV-2 pathogenicity, Administration, Intranasal methods, COVID-19 prevention & control, COVID-19 transmission
- Abstract
Competing Interests: "The authors have declared that no competing interests exist."
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- 2021
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13. Intelligence Quotient Variability in Klinefelter Syndrome Is Associated With GTPBP6 Expression Under Regulation of X-Chromosome Inactivation Pattern.
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Simonetti L, Ferreira LGA, Vidi AC, de Souza JS, Kunii IS, Melaragno MI, de Mello CB, Carvalheira G, and Dias da Silva MR
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Klinefelter syndrome (KS) displays a broad dysmorphological, endocrinological, and neuropsychological clinical spectrum. We hypothesized that the neurocognitive dysfunction present in KS relies on an imbalance in X-chromosome gene expression. Thus, the X-chromosome inactivation (XCI) pattern and neurocognitive X-linked gene expression were tested and correlated with intelligence quotient (IQ) scores. We evaluated 11 KS patients by (a) IQ assessment, (b) analyzing the XCI patterns using both HUMARA and ZDHHC15 gene assays, and (c) blood RT-qPCR to investigate seven X-linked genes related to neurocognitive development ( GTPBP6 , EIF2S3 , ITM2A , HUWE1 , KDM5C , GDI1 , and VAMP7 ) and XIST in comparison with 14 (male and female) controls. Considering IQ 80 as the standard minimum reference, we verified that the variability in IQ scores in KS patients seemed to be associated with the XCI pattern. Seven individuals in the KS group presented a random X-inactivation (RXI) and lower average IQ than the four individuals who presented a skewed X-inactivation (SXI) pattern. The evaluation of gene expression showed higher GTPBP6 expression in KS patients with RXI than in controls ( p = 0.0059). Interestingly, the expression of GTPBP6 in KS patients with SXI did not differ from that observed in controls. Therefore, our data suggest for the first time that GTPBP6 expression is negatively associated with full-scale IQ under the regulation of the type of XCI pattern. The SXI pattern may regulate GTPBP6 expression, thereby dampening the impairment in cognitive performance and playing a role in intelligence variability in individuals with KS, which warrants further mechanistic investigations., 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 © 2021 Simonetti, Ferreira, Vidi, Souza, Kunii, Melaragno, Mello, Carvalheira and Dias da Silva.)
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- 2021
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14. When Leptin Is Not There: A Review of What Nonsyndromic Monogenic Obesity Cases Tell Us and the Benefits of Exogenous Leptin.
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Salum KCR, Rolando JM, Zembrzuski VM, Carneiro JRI, Mello CB, Maya-Monteiro CM, Bozza PT, Kohlrausch FB, and da Fonseca ACP
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- Energy Metabolism genetics, Hormone Replacement Therapy, Humans, Leptin deficiency, Leptin genetics, Mutation, Obesity congenital, Phenotype, Leptin therapeutic use, Obesity drug therapy, Obesity genetics
- Abstract
Obesity is a pandemic condition of complex etiology, resulting from the increasing exposition to obesogenic environmental factors combined with genetic susceptibility. In the past two decades, advances in genetic research identified variants of the leptin-melanocortin pathway coding for genes, which are related to the potentiation of satiety and hunger, immune system, and fertility. Here, we review cases of congenital leptin deficiency and the possible beneficial effects of leptin replacement therapy. In summary, the cases presented here show clinical phenotypes of disrupted bodily energy homeostasis, biochemical and hormonal disorders, and abnormal immune response. Some phenotypes can be partially reversed by exogenous administration of leptin. With this review, we aim to contribute to the understanding of leptin gene mutations as targets for obesity diagnostics and treatment strategies., 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 © 2021 Salum, Rolando, Zembrzuski, Carneiro, Mello, Maya-Monteiro, Bozza, Kohlrausch and da Fonseca.)
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- 2021
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15. Azadirachtin interferes with basal immunity and microbial homeostasis in the Rhodnius prolixus midgut.
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Vieira CS, Figueiredo MB, Moraes CDS, Pereira SB, Dyson P, Mello CB, Castro DP, and Azambuja P
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- Animals, Drosophila Proteins metabolism, Gastrointestinal Microbiome, Homeostasis, Immunity, Humoral, Immunity, Innate, Molting, NF-kappa B metabolism, Serratia marcescens, Signal Transduction, Chagas Disease immunology, Ecdysone metabolism, Insect Proteins metabolism, Insect Vectors physiology, Insecticides administration & dosage, Intestinal Mucosa immunology, Limonins administration & dosage, Rhodnius physiology, Trypanosoma cruzi physiology, Trypanosoma rangeli physiology
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Rhodnius prolixus is an insect vector of two flagellate parasites, Trypanosoma rangeli and Trypanosoma cruzi, the latter being the causative agent of Chagas disease in Latin America. The R. prolixus neuroendocrine system regulates the synthesis of the steroid hormone ecdysone, which is essential for not only development and molting but also insect immunity. Knowledge for how this modulates R. prolixus midgut immune responses is essential for understanding interactions between the vector, its parasites and symbiotic microbes. In the present work, we evaluated the effects of ecdysone inhibition on R. prolixus humoral immunity and homeostasis with its microbiota, using the triterpenoid natural product, azadirachtin. Our results demonstrated that azadirachtin promoted a fast and lasting inhibitory effect on expression of both RpRelish, a nuclear factor kappa B transcription factor (NF-kB) component of the IMD pathway, and several antimicrobial peptide (AMP) genes. On the other hand, RpDorsal, encoding the equivalent NF-kB transcription factor in the Toll pathway, and the defC AMP gene were upregulated later in azadirachtin treated insects. The treatment also impacted on proliferation of Serratia marcescens, an abundant commensal bacterium. The simultaneous administration of ecdysone and azadirachtin in R. prolixus blood meals counteracted the azadirachtin effects on insect molting and also on expression of RpRelish and AMPs genes. These results support the direct involvement of ecdysone in regulation of the IMD pathway in the Rhodnius prolixus gut., (Copyright © 2020. Published by Elsevier Ltd.)
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- 2021
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16. A rhamnose-binding lectin from Rhodnius prolixus and the impact of its silencing on gut bacterial microbiota and Trypanosoma cruzi.
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Araújo CAC, Pacheco JPF, Waniek PJ, Geraldo RB, Sibajev A, Dos Santos AL, Evangelho VGO, Dyson PJ, Azambuja P, Ratcliffe NA, Castro HC, and Mello CB
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- Animals, Defensins metabolism, Disease Vectors, Fish Proteins genetics, Gene Silencing, Immunity, Innate, Insect Proteins metabolism, Lectins genetics, Molecular Docking Simulation, RNA, Ribosomal, 16S genetics, Structural Homology, Protein, Chagas Disease immunology, Defensins administration & dosage, Gastrointestinal Microbiome genetics, Insect Proteins genetics, Lectins metabolism, Rhodnius physiology, Trypanosoma cruzi physiology
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Lectins are ubiquitous proteins involved in the immune defenses of different organisms and mainly responsible for non-self-recognition and agglutination reactions. This work describes molecular and biological characterization of a rhamnose-binding lectin (RBL) from Rhodnius prolixus, which possesses a 21 amino acid signal peptide and a mature protein of 34.6 kDa. The in-silico analysis of the primary and secondary structures of RpLec revealed a lectin domain fully conserved among previous insects studied. The three-dimensional homology model of RpLec was similar to other RBL-lectins. Docking predictions with the monosaccharides showed rhamnose and galactose-binding sites comparable to Latrophilin-1 and N-Acetylgalactosamine-binding in a different site. The effects of RpLec gene silencing on levels of infecting Trypanosoma cruzi Dm 28c and intestinal bacterial populations in the R. prolixus midgut were studied by injecting RpLec dsRNA into the R. prolixus hemocoel. Whereas T. cruzi numbers remained unchanged compared with the controls, numbers of bacteria increased significantly. The silencing also induced the up regulation of the R. prolixus defC (defensin) expression gene. These results with RpLec reveal the potential importance of this little studied molecule in the insect vector immune response and homeostasis of the gut bacterial microbiota., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
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- 2021
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17. Malan syndrome in a patient with 19p13.2p13.12 deletion encompassing NFIX and CACNA1A genes: Case report and review of the literature.
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Bellucco FT, de Mello CB, Meloni VA, and Melaragno MI
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- Brazil, Chromosomes, Human, Pair 19 genetics, Genetic Association Studies, Humans, Intellectual Disability genetics, Male, Megalencephaly genetics, Seizures genetics, Young Adult, Calcium Channels genetics, Chromosome Deletion, NFI Transcription Factors genetics, Neurodevelopmental Disorders genetics
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Background: Malan syndrome is a recently introduced overgrowth disorder described in a limited number of individuals. Haploinsufficiency and also point mutations of NFIX gene have been proposed as its leading causative mechanism, however, due to the limited number of cases and different deletion sizes, genotype/phenotype correlations are still limited., Methods: Here, we report the first Brazilian case of Malan syndrome caused by a 990 kb deletion in 19p13.2p13.12, focusing on clinical and behavioral aspects of the syndrome., Results: The patient presented with macrocephaly, facial dysmorphisms, hypotonia, developmental delay, moderate thoracolumbar scoliosis, and seizures. The intellectual and behavioral assessments showed severe cognitive, language, and adaptive functions impairments. The 19p deleted region of our patient encompasses NFIX, CACNA1A, which seems to be related to a higher frequency of seizures among individuals with microdeletions in 19p13.2, and 15 other coding genes, including CC2D1A and NACC1, both known to be involved in neurobiological process and pathways., Conclusion: Deletions involving NFIX gene should be considered in patients with overgrowth during childhood, macrocephaly, developmental delay, and seizures, as well as severe intellectual disability., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)
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- 2019
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18. Executive functions in children with dyslexia.
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Barbosa T, Rodrigues CC, Mello CB, Silva MCSE, and Bueno OFA
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- Adolescent, Attention physiology, Case-Control Studies, Child, Disability Evaluation, Female, Humans, Male, Memory, Short-Term physiology, Neuropsychological Tests, Phonetics, Reference Values, Dyslexia physiopathology, Executive Function physiology
- Abstract
Introduction: This study aimed to verify whether children with dyslexia have difficulties in executive functions (shifting, working memory, inhibition)., Methods: A sample of 47 children (ages 8-13 years) participated in the study: 24 who were dyslexic and 23 controls with typical development. A battery of neuropsychological tests was used., Results: Results revealed executive function difficulties among the dyslexic children when compared with controls, encompassing selective attention modulation processes, shifting, and inhibitory control. These difficulties appeared to be affected by phonological working memory deficits, typically associated with dyslexia., Conclusion: Our findings support the consensus among scholars regarding the central involvement of phonological skill dysfunctions in dyslexia.
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- 2019
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19. Downregulation of genes outside the deleted region in individuals with 22q11.2 deletion syndrome.
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Dantas AG, Santoro ML, Nunes N, de Mello CB, Pimenta LSE, Meloni VA, Soares DCQ, Belangero SN, Carvalheira G, Kim CA, and Melaragno MI
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- Case-Control Studies, Down-Regulation, Follow-Up Studies, Gene Expression Profiling, Gene Expression Regulation, Gene Regulatory Networks, Humans, Phenotype, Prognosis, Biomarkers analysis, Chromosome Deletion, Chromosomes, Human, Pair 22 genetics, DiGeorge Syndrome genetics, GTP-Binding Protein alpha Subunits genetics, Tubulin genetics
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The 22q11.2 deletion syndrome (22q11.2DS) is caused by recurrent hemizygous deletions of chromosome 22q11.2. The phenotype of the syndrome is complex and varies widely among individuals. Little is known about the role of the different genes located in 22q11.2, and we hypothesized that genetic risk factors lying elsewhere in the genome might contribute to the phenotype. Here, we present the whole-genome gene expression data of 11 patients with approximately 3 Mb deletions. Apart from the hemizygous genes mapped to the 22q11.2 region, the TUBA8 and GNAZ genes, neighboring the deleted interval but in normal copy number, showed altered expression. When genes mapped to other chromosomes were considered in the gene expression analysis, a genome-wide dysregulation was observed, with increased or decreased expression levels. The enriched pathways of these genes were related to immune response, a deficiency that is frequently observed in 22q11.2DS patients. We also used the hypothesis-free weighted gene co-expression network analysis (WGCNA), which revealed the co-expression gene network modules with clear connection to mechanisms associated with 22q11.2DS such as immune response and schizophrenia. These findings, combined with the traditional gene expression profile, can be used for the identification of potential pathways and genes not previously considered to be related to the 22q11.2 deletion syndrome.
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- 2019
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20. Exploring the Insecticide and Acaricide Potential of Development Regulators obtained from Restinga vegetation from Brazil.
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Feder D, Gonzalez MS, Mello CB, Santos MG, Rocha L, Kelecom A, and Folly E
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- Agriculture, Animals, Brazil, Insecta drug effects, Monoterpenes chemistry, Reproducibility of Results, Sesquiterpenes chemistry, Acaricides chemistry, Insecticides chemistry, Oils, Volatile chemistry, Pest Control, Biological methods, Plant Extracts chemistry
- Abstract
As a part of our continuing search for insect and arthropod development regulators from Brazilian restinga vegetation of the Rio de Janeiro State, crude extracts, purified fractions and essential oils were submitted to screening tests seeking for biological activities on the development of the insects Rhodnius prolixus, Dysdercus peruvianus, Oncopeltus fasciatus and Rhipicephalus (Boophilus) microplus. Up to now, 102 secondary metabolites have been detected in the fractions, among them monoterpenes, sesquiterpenes and two triterpenes which were obtained from the species, Eugenia sulcata, Pilocarpus spicatus, Manilkara subsericea, Myrciaria floribunda and Zanthoxylum caribaeum. These secondary plant metabolites are considered of interest for the use of studies related to arthropod endocrinology, vector-parasite interaction system, and population control of vector insect and agricultural pest. The observed biological activities were surprisingly high, involving increased mortality, molting and metamorphosis inhibition, paralysis, corporeal deformities, apparition of permanent nymphs, of adultoids and juvenoids, partial or total inhibition of oviposition and egg hatching. These compounds are now being studied further to determine if they may or may not be useful in controlling insect populations and/or interfere with the life cycle and vector transmission of parasites to animal and human populations.
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- 2019
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21. Latent class analysis of attention and white matter correlation in children with attention-deficit/hyperactivity disorder.
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Rossi ASU, Moura LM, Miranda MC, Muszkat M, Mello CB, and Bueno OFA
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- Adolescent, Anisotropy, Attention Deficit Disorder with Hyperactivity diagnosis, Case-Control Studies, Child, Cognition physiology, Diffusion Tensor Imaging methods, Female, Humans, Male, Neuropsychological Tests, Reaction Time physiology, Reference Standards, Reference Values, Statistics as Topic methods, White Matter diagnostic imaging, Attention physiology, Attention Deficit Disorder with Hyperactivity physiopathology, White Matter physiopathology
- Abstract
This study aimed to explore attentional patterns among children with inattentive attention-deficit/hyperactivity disorder (ADHD-I) and children with typical development (TD), using a latent class analysis (LCA). Patterns of brain connectivity were also explored. The sample comprised 29 ADHD-I and 29 TD matched children. An LCA was conducted to reclassify subjects according to their attentional performance, considering cognitive measures of attention and behavioral symptoms, regardless of group of origin. The new clusters were then compared in respect to brain white matter measurements (extracted from diffusion tensor imaging). Participants were rearranged in 2 new latent classes, according to their performance in an attention task and the results of behavioral scales, resulting in groups with more homogeneous attentional profiles. A comparison of the 2 new classes using the white matter measurements revealed increased fractional anisotropy in the left inferior fronto-occipital fasciculus and left inferior longitudinal fasciculus for the class composed by participants with a higher risk of attentional problems. The findings indicated that it was possible to observe variability regarding neuropsychological profile, accompanied by underpinning neurobiological differences, even among individuals with the same disorder subtype - inattentive ADHD. This specific data-driven clustering analysis may help to enhance understanding of the pathophysiology of the disorder's phenotypes.
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- 2018
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22. Autonomic Modulation in Duchenne Muscular Dystrophy during a Computer Task: A Prospective Control Trial.
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Alvarez MP, Silva TD, Favero FM, Valenti VE, Raimundo RD, Vanderlei LC, Garner DM, and Monteiro CB
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- Adolescent, Blood Pressure physiology, Electrocardiography, Ambulatory, Games, Experimental, Humans, Male, Muscular Dystrophy, Duchenne psychology, Prospective Studies, Rest physiology, Stress, Psychological physiopathology, Video Games, Adaptation, Physiological physiology, Autonomic Nervous System physiopathology, Heart Conduction System physiopathology, Heart Rate physiology, Muscular Dystrophy, Duchenne physiopathology, Psychomotor Performance physiology, Vagus Nerve physiopathology
- Abstract
Introduction: Duchenne Muscular Dystrophy (DMD) is characterized by progressive muscle weakness that can lead to disability. Owing to functional difficulties faced by individuals with DMD, the use of assistive technology is essential to provide or facilitate functional abilities. In DMD, cardiac autonomic dysfunction has been reported in addition to musculoskeletal impairment. Consequently, the objective was to investigate acute cardiac autonomic responses, by Heart Rate Variability (HRV), during computer tasks in subjects with DMD., Method: HRV was assessed by linear and nonlinear methods, using the heart rate monitor Polar RS800CX chest strap Electrocardiographic measuring device. Then, 45 subjects were included in the group with DMD and 45 in the healthy Typical Development (TD) control group. They were assessed for twenty minutes at rest sitting, and five minutes after undergoing a task on the computer., Results: Individuals with DMD had a statistically significant lower parasympathetic cardiac modulation at rest when compared to the control group, which further declined when undergoing the tasks on the computer., Conclusion: DMD patients presented decreased HRV and exhibited greater intensity of cardiac autonomic responses during computer tasks characterized by vagal withdrawal when compared to the healthy TD control subjects., Competing Interests: The authors have declared that no competing interests exist.
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- 2017
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23. Pain characterization in Duchenne muscular dystrophy.
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Silva TD, Massetti T, Monteiro CB, Trevizan IL, Arab C, Caromano FA, Voos MC, Oliveira AS, and Favero FM
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- Chronic Pain physiopathology, Humans, Male, Pain Measurement, Quality of Life, Muscular Dystrophy, Duchenne physiopathology, Myalgia physiopathology
- Abstract
Objective: To investigate the relationship between DMD and pain., Methods: We conducted a systematic review in Medline/PubMed and BVS (virtual library in health) databases. We searched for articles that showed the terms "Muscular Dystrophy, Duchenne" and "Pain" in all fields. All studies included boys diagnosed with DMD and the occurrence/amount of pain on this population., Results: Initially, there were 175 studies. 167 articles were excluded for not meeting the inclusion criteria. The remaining eight eligible studies, involving pain assessment in DMD, were analyzed., Conclusion: Pain is a frequent problem in this population and this symptom is potentially tractable. Studies conclude that pain can directly influence the quality of life of this population.
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- 2016
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24. Brazilian Normative Data on Letter and Category Fluency Tasks: Effects of Gender, Age, and Geopolitical Region.
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Hazin I, Leite G, Oliveira RM, Alencar JC, Fichman HC, Marques PD, and de Mello CB
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Verbal fluency is a basic function of language that refers to the ability to produce fluent speech. Despite being an essentially linguistic function, its measurements are also used to evaluate executive aspects of verbal behavior. Performance in verbal fluency (VF) tasks varies according to age, education, and cognitive development. Neurodevelopmental disorders that affect the functioning of frontal areas tend to cause lower performance in VF tasks. Despite the relative consensus that has been reached in terms of the use of VF tasks for the diagnosis of dyslexia and attention-deficit/hyperactivity disorder, few studies have considered regional variations in Brazil. The present study sought to provide normative data on VF tasks in children by considering gender, age, education, and geopolitical region of origin with auxiliary purposes in neuropsychological diagnosis of disorders that occur with executive changes The study included 298 participants, 7-10 years of age of both genders, who performed three letter fluency tasks and three category fluency tasks. The data were subjected to correlational and variance analyses, with age and gender as factors. No effect of gender on the children's performance was found. However, significant differences between age groups were observed, with better performance in letter tasks in older children and better performance in letter tasks compared with category tasks. Significant regional differences in performance on the letter VF task were observed. These results reinforce the importance of regional normative data in countries with high regional cultural variations, such as Brazil.
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- 2016
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25. Everybody loves sugar: first report of plant feeding in triatomines.
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Díaz-Albiter HM, Ferreira TN, Costa SG, Rivas GB, Gumiel M, Cavalcante DR, Pavan MG, Gonzalez MS, de Mello CB, Dillon VM, Bruno RV, Garcia Ede S, Lima MM, de Castro DP, Dillon RJ, de Azambuja P, and Genta FA
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- Animals, Carbohydrates, Coloring Agents analysis, DNA, Plant analysis, Feeding Behavior, Solanum lycopersicum, Staining and Labeling, Insect Vectors, Rhodnius physiology
- Abstract
Background: Triatomines, which are the vectors of Trypanosoma cruzi, have been considered to be exclusive blood feeders for more than 100 years, since the discovery of Chagas disease., Methods: We offered artificial sugar meals to the laboratory model-insect Rhodnius prolixus, which is considered a strict haematophagous insect. We registered feeding by adding colorant to sugar meals. To assess putative phytophagy, fruits of the tomato Solanum lycopersicum were offered to R. prolixus and the presence of tomato DNA was assessed in the insects using PCR. We also assessed longevity, blood feeding and urine production of fruit-exposed triatomines and control insects., Results: All instars of R. prolixus ingested sugar from artificial sugar meals in laboratory conditions. First instar R. prolixus ingested plant tissue from S. lycopersicum fruits, and this increased the amount of blood ingested and urine excreted. Decreased mortality was also observed after blood feeding. Exposure to S. lycopersicum increased longevity and reduced weight loss caused by desiccation., Conclusions: We describe here the first report of sugar feeding and phytophagy in a species that was considered to be a strict blood-feeder for over a century. We suggest that local plants might be not merely shelters for insects and vertebrate hosts as previously described, but may have a nutritional role for the maintenance of the triatomine vectors. The description of sugar and plant meals in triatomines opens new perspectives for the study and control of Chagas Disease.
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- 2016
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26. Triflumuron Effects on the Physiology and Reproduction of Rhodnius prolixus Adult Females.
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Henriques BS, Genta FA, Mello CB, Silva LR, Codogno TF, Oliveira AF, Marinho LP, Valle D, Lima JB, Feder D, Gonzalez MS, and Azambuja P
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- Animals, Chitin metabolism, Diuresis drug effects, Eggs, Feeding Methods, Female, Immunity, Innate drug effects, Oocytes drug effects, Oviposition drug effects, Benzamides pharmacology, Insecticides pharmacology, Reproduction drug effects, Rhodnius drug effects
- Abstract
We evaluated the efficacy of the growth regulator triflumuron (TFM) in inducing mortality and disrupting both oviposition and egg hatching in Rhodnius prolixus adult females. TFM was administered via feeding, topically or by continuous contact with impregnated surfaces. Feeding resulted in mild biological effects compared with topical and impregnated surfaces. One day after treatment, the highest mortality levels were observed with topical surface and 30 days later both topical and impregnated surfaces induced higher mortalities than feeding. Oral treatment inhibited oviposition even at lower doses, and hatching of eggs deposited by treated females was similarly affected by the three delivery modes. Topical treatment of eggs deposited by nontreated females significantly reduced hatching. However, treatment per contact of eggs oviposited by untreated females did not disrupt eclosion. Additionally, oral treatment increased the number of immature oocytes per female, and topical treatment reduced the mean size of oocytes. TFM also affected carcass chitin content, diuresis, and innate immunity of treated insects. These results suggest that TFM acts as a potent growth inhibitor of R. prolixus adult females and has the potential to be used in integrated vector control programs against hematophagous triatomine species.
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- 2016
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27. Face Scanning in Autism Spectrum Disorder and Attention Deficit/Hyperactivity Disorder: Human Versus Dog Face Scanning.
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Muszkat M, de Mello CB, Muñoz Pde O, Lucci TK, David VF, Siqueira Jde O, and Otta E
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This study used eye tracking to explore attention allocation to human and dog faces in children and adolescents with autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), and typical development (TD). Significant differences were found among the three groups. TD participants looked longer at the eyes than ASD and ADHD ones, irrespective of the faces presented. In spite of this difference, groups were similar in that they looked more to the eyes than to the mouth areas of interest. The ADHD group gazed longer at the mouth region than the other groups. Furthermore, groups were also similar in that they looked more to the dog than to the human faces. The eye-tracking technology proved to be useful for behavioral investigation in different neurodevelopmental disorders.
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- 2015
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28. NTPDase and 5'-nucleotidase activities in synaptosomes of rabbits experimentally infected with BoHV-5.
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da Silva CB, Paim FC, Wolkmer P, Abdalla FH, Carvalho FB, Palma HH, Mello CB, Flores EF, Andrade CM, and Lopes ST
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- Animals, Cerebral Cortex enzymology, Cerebral Cortex virology, Herpesvirus 5, Bovine, Hippocampus enzymology, Hippocampus virology, Rabbits, Encephalitis, Viral enzymology, Herpesviridae Infections enzymology, Meningoencephalitis enzymology, Nucleotidases metabolism, Synaptosomes enzymology
- Abstract
Bovine herpesvirus type 5 (BoHV-5) is the causative agent of herpetic meningoencephalitis in cattle. The purinergic system is described as a modulator of the immune response and neuroinflammation. These functions are related to the extracellular nucleotides concentration. NTPDase and 5'-nucleotidase are enzymes responsible for controlling the extracellular concentration of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine (ADO). The aim of this study is to determinate the ectonucleotidase activity in cortical synaptosomes and synaptosomes from the hippocampus of rabbits experimentally infected with BoHV-5. Rabbits were divided into four groups, two control groups (non-inoculated animals), and two infected groups (inoculated with BoHV-5). The infected groups received 0.5 ml of BoHV-5 suspension with 10(7.5)TCID50 of viral strain SV-507/99, per paranasal sinuses, and the control groups received 0.5 ml of minimum essential media per paranasal sinuses. Animals were submitted to euthanasia on days 7 and 12 post-inoculation (p.i.); cerebral cortex and hippocampus were collected for the synaptosomes isolation and posterior determination of the ectonucleotidase activities. The results showed a decrease (P < 0.05) in ectonucleotidase activity in synaptosomes from the cerebral cortex of infected rabbits, whereas an increased (P < 0.05) ectonucleotidase activity was observed in synaptosomes from the hippocampus. These differences may be related with the heterogeneous distribution of ectonucleotidases in the different brain regions and also with the viral infectivity. Therefore, it is possible to speculate that BoHV-5 replication results in changes in ectonucleotidase activity in the brain, which may contribute to the neurological signs commonly observed in this disease.
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- 2015
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29. Attentional Profiles and White Matter Correlates in Attention-Deficit/Hyperactivity Disorder Predominantly Inattentive Type.
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Rossi AS, de Moura LM, de Mello CB, de Souza AA, Muszkat M, and Bueno OF
- Abstract
Attention-deficit/hyperactivity disorder (ADHD) is a widely studied neurodevelopmental disorder. It is a highly heterogeneous condition, encompassing different types of expression. The predominantly inattentive type is the most prevalent and the most stable over the lifetime, yet it is the least-studied presentation. To increase understanding of its cognitive profile, 29 children with attention-deficit/hyperactivity disorder of predominantly inattentive type (ADHD-I) and 29 matched controls, aged 7-15 years, had their attentional abilities assessed through the Conners' continuous performance test. Diffusion tensor imaging data were collected for all of the participants using a 3.0-T MRI system. Fractional anisotropy (FA) values were obtained for 20 fiber tracts, and brain-behavior correlations were calculated for 42 of the children. The ADHD-I children differed significantly from the typically developing (TD) children with respect to attentional measures, such as the ability to maintain response-time consistency throughout the task (Hit RT SE and Variability), vigilance (Hit RT ISI and Hit RT ISI SE), processing speed (Hit RT), selective attention (Omissions), sustained attention (Hit RT Block Change), error profile (Response Style), and inhibitory control (Perseverations). Evidence of significant differences between the ADHD-I and the TD participants was not found with respect to the mean FA values in the fiber tracts analyzed. Moderate and strong correlations between performance on the attention indicators and the tract-average FA values were found for the ADHD-I group. Our results contribute to a better characterization of the attentional profile of ADHD-I individuals and suggest that in children and adolescents with ADHD-I, attentional performance is mainly associated with the white matter structure of the long associative fibers that connect anterior-posterior brain areas.
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- 2015
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30. Biocontrol evaluation of extracts and a major component, clusianone, from Clusia fluminensis Planch. & Triana against Aedes aegypti.
- Author
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Anholeti MC, Duprat RC, Figueiredo MR, Kaplan MA, Santos MG, Gonzalez MS, Ratcliffe NA, Feder D, Paiva SR, and Mello CB
- Subjects
- Animals, Time Factors, Aedes drug effects, Clusia chemistry, Insect Vectors drug effects, Larva drug effects, Plant Extracts pharmacology
- Abstract
Studies evaluated the effects of hexanic extracts from the fruits and flowers of Clusia fluminensis and the main component of the flower extract, a purified benzophenone (clusianone), against Aedes aegypti. The treatment of larvae with the crude fruit or flower extracts from C. fluminensis did not affect the survival ofAe. aegypti (50 mg/L), however, the flower extracts significantly delayed development of Ae. aegypti. In contrast, the clusianone (50 mg/L) isolate from the flower extract, representing 54.85% of this sample composition, showed a highly significant inhibition of survival, killing 93.3% of the larvae and completely blocking development of Ae. aegypti. The results showed, for the first time, high activity of clusianone against Ae. aegypti that both killed and inhibited mosquito development. Therefore, clusianone has potential for development as a biopesticide for controlling insect vectors of tropical diseases. Future work will elucidate the mode of action of clusianone isolated from C. fluminensis.
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- 2015
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31. Immunomodulatory effects of galectin-1 on an IgE-mediated allergic conjunctivitis model.
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Mello CB, Ramos L, Gimenes AD, Andrade TR, Oliani SM, and Gil CD
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- Animals, Blotting, Western, Chemokines metabolism, Conjunctiva drug effects, Conjunctiva immunology, Conjunctivitis, Allergic immunology, Conjunctivitis, Allergic metabolism, Disease Models, Animal, Immunohistochemistry, Male, Mice, Mice, Inbred BALB C, Microscopy, Electron, Recombinant Proteins, T-Lymphocytes immunology, Antibodies, Anti-Idiotypic immunology, Conjunctiva ultrastructure, Conjunctivitis, Allergic drug therapy, Galectin 1 pharmacology, Immunity, Cellular, Immunoglobulin E immunology, Immunomodulation immunology
- Abstract
Purpose: Galectin (Gal)-1, a lectin found at sites of immune privilege with critical role in the inflammation, has been poorly investigated in the ocular inflammatory diseases. Here, we evaluated the therapeutic potential of Gal-1 in ocular allergy using a model of ovalbumin (OVA)-induced AC., Methods: OVA-immunized BALB/c male mice were challenged with eye drops containing OVA on days 14 through 16 with a subset of animals pretreated intraperitoneally with recombinant Gal-1 (rGal-1) or dexamethasone (Dex)., Results: Recombinant Gal-1 and Dex administration on days 14 through 16 was effective in reducing the clinical signs of allergic conjunctivitis (AC), plasma anti-OVA IgE levels, Th2 (IL-4 and IL-13), and eotaxin/RANTES levels in the lymph nodes. Four hours after the last OVA challenge, rGal-1 markedly increased Gal-1 endogenous levels in the conjunctiva, and provoked eosinophilia, which persisted at 24 hours. Recombinant Gal-1 had no effect on eosinophil activation, as evidenced by the similar pattern of peroxidase eosinophil expression between cells of rGal-1-treated and untreated AC groups. Conjunctival migrated eosinophils and neutrophils exhibited high levels of Gal-1 and β2-integrin, with points of colocalization, in the rGal-1-treated groups. These different effects observed for rGal-1 were correlated with elevated levels of activated ERK and p38 at 4 hours, and diminished levels of activated JNK and p38 at 24 hours in the eyes., Conclusions: Gal-1 has an important role in ocular allergic inflammation and represents a potential target for the development of new therapeutic strategies in eye diseases., (Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.)
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- 2015
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32. Chronic obstructive pulmonary disease and heart rate variability: a literature update.
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Roque AL, Valenti VE, Massetti T, da Silva TD, Monteiro CB, Oliveira FR, de Almeida Junior ÁD, Lacerda SN, Pinasco GC, Nascimento VG, Granja Filho LG, de Abreu LC, Garner DM, and Ferreira C
- Abstract
Background: The literature indicates that chronic obstructive pulmonary disease (COPD) affects cardiac autonomic control. In this study, we conducted a literature review in order to investigate the heart rate variability (HRV) in COPD subjects., Methods: A search was performed in Medline database, using the link between the keywords: "autonomic nervous system", "cardiovascular system", "COPD" and "heart rate variability"., Results: The search resulted in a total of 40 references. Amongst these references, the first exclusion resulted in the barring of 29 titles and abstracts, which were not clearly related to the purpose of review. This resulted in a total of 11 articles that were then read and utilized in the review. The selected studies indicated that there is significant reduction of HRV in patients with COPD, characterized by reduction of indices that assess parasympathetic activity in addition to dealing with the global autonomic modulation. We also established that supervised exercise can reduce these harmful effects in COPD patients. Also, it was reported that the use of non-invasive ventilation in these patients may contribute to the improvement of respiratory symptoms, with no impairing, and may even induce positive responses in cardiac autonomic regulation., Conclusion: The studies indicate a need for further investigations to guide future therapies to improve the treatment of cardiovascular system in the respiratory diseases.
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- 2014
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33. Trisomy 1q32 and monosomy 11q25 associated with congenital heart defect: cytogenomic delineation and patient fourteen years follow-up.
- Author
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Meloni VA, Takeno SS, Pilla AL, de Mello CB, Melaragno MI, and Kulikowski LD
- Abstract
Background: Partial duplication 1q is a rare cytogenetic anomaly frequently associated to deletion of another chromosome, making it difficult to define the precise contribution of the different specific chromosomal segments to the clinical phenotype., Case Presentation: We report a clinical and cytogenomic study of a patient with multiple congenital anomalies, heart defect, neuromotordevelopment delay, intellectual disability, who presents partial trisomy 1q32 and partial monosomy 11q25 inherited from a paternal balanced translocation identified by chromosome microarray and fluorescence in situ hybridization., Conclusion: Compared to patients from the literature, the patient's phenotype is more compatible to the 1q32 duplication's clinical phenotype, although some clinical features may also be associated to the deleted segment on chromosome 11. This is the smallest 11q terminal deletion ever reported and the first association between 1q32.3 duplication and 11q25 deletion in the literature.
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- 2014
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34. Humoral responses in Rhodnius prolixus: bacterial feeding induces differential patterns of antibacterial activity and enhances mRNA levels of antimicrobial peptides in the midgut.
- Author
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Vieira CS, Waniek PJ, Mattos DP, Castro DP, Mello CB, Ratcliffe NA, Garcia ES, and Azambuja P
- Subjects
- Animals, Escherichia coli immunology, Gastrointestinal Tract microbiology, Gene Expression Regulation immunology, Host-Pathogen Interactions, RNA, Messenger genetics, Staphylococcus aureus immunology, Antimicrobial Cationic Peptides metabolism, Escherichia coli physiology, Gastrointestinal Tract metabolism, RNA, Messenger metabolism, Rhodnius immunology, Staphylococcus aureus physiology
- Abstract
Background: The triatomine, Rhodnius prolixus, is a major vector of Trypanosoma cruzi, the causative agent of Chagas disease in Latin America. It has a strictly blood-sucking habit in all life stages, ingesting large amounts of blood from vertebrate hosts from which it can acquire pathogenic microorganisms. In this context, the production of antimicrobial peptides (AMPs) in the midgut of the insect is vital to control possible infection, and to maintain the microbiota already present in the digestive tract., Methods: In the present work, we studied the antimicrobial activity of the Rhodnius prolixus midgut in vitro against the Gram-negative and Gram-positive bacteria Escherichia coli and Staphylococcus aureus, respectively. We also analysed the abundance of mRNAs encoding for defensins, prolixicin and lysozymes in the midgut of insects orally infected by these bacteria at 1 and 7 days after feeding., Results: Our results showed that the anterior midgut contents contain a higher inducible antibacterial activity than those of the posterior midgut. We observed that the main AMP encoding mRNAs in the anterior midgut, 7 days after a blood meal, were for lysozyme A, B, defensin C and prolixicin while in the posterior midgut lysozyme B and prolixicin transcripts predominated., Conclusion: Our findings suggest that R. prolixus modulates AMP gene expression upon ingestion of bacteria with patterns that are distinct and dependent upon the species of bacteria responsible for infection.
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- 2014
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35. Development of an insecticidal nanoemulsion with Manilkara subsericea (Sapotaceae) extract.
- Author
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Fernandes CP, de Almeida FB, Silveira AN, Gonzalez MS, Mello CB, Feder D, Apolinário R, Santos MG, Carvalho JC, Tietbohl LA, Rocha L, and Falcão DQ
- Subjects
- Acetylcholinesterase metabolism, Animals, Emulsions toxicity, Female, Heteroptera physiology, Insecticides toxicity, Male, Mice, Plant Extracts toxicity, Solubility, Emulsions chemistry, Heteroptera drug effects, Insecticides chemistry, Manilkara chemistry, Plant Extracts chemistry
- Abstract
Background: Plants have been recognized as a good source of insecticidal agents, since they are able to produce their own defensives to insect attack. Moreover, there is a growing concern worldwide to develop pesticides with low impact to environment and non-target organisms. Hexane-soluble fraction from ethanolic crude extract from fruits of Manilkara subsericea and its triterpenes were considered active against a cotton pest (Dysdercus peruvianus). Several natural products with insecticidal activity have poor water solubility, including triterpenes, and nanotechnology has emerged as a good alternative to solve this main problem. On this context, the aim of the present study was to develop an insecticidal nanoemulsion containing apolar fraction from fruits of Manilkara subsericea., Results: It was obtained a formulation constituted by 5% of oil (octyldodecyl myristate), 5% of surfactants (sorbitan monooleate/polysorbate 80), 5% of apolar fraction from M. subsericea and 85% of water. Analysis of mean droplet diameter (155.2 ± 3.8 nm) confirmed this formulation as a nanoemulsion. It was able to induce mortality in D. peruvianus. It was observed no effect against acetylcholinesterase or mortality in mice induced by the formulation, suggesting the safety of this nanoemulsion for non-target organisms., Conclusions: The present study suggests that the obtained O/A nanoemulsion may be useful to enhance water solubility of poor water soluble natural products with insecticidal activity, including the hexane-soluble fraction from ethanolic crude extract from fruits of Manilkara subsericea.
- Published
- 2014
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36. Isolation and molecular characterization of a major hemolymph serpin from the triatomine, Panstrongylus megistus.
- Author
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Moreira CJ, Waniek PJ, Valente RH, Carvalho PC, Perales J, Feder D, Geraldo RB, Castro HC, Azambuja P, Ratcliffe NA, and Mello CB
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Mass Spectrometry, Models, Molecular, Molecular Sequence Data, Organ Specificity genetics, Protein Conformation, Proteome, Sequence Alignment, Serpins chemistry, Serpins genetics, Serpins isolation & purification, Transcription, Genetic, Hemolymph metabolism, Panstrongylus genetics, Panstrongylus metabolism, Serpins metabolism
- Abstract
Background: Chagas disease kills 2.5 thousand people per year of 15 million persons infected in Latin America. The disease is caused by the protozoan, Trypanosome cruzi, and vectored by triatomine insects, including Panstrongylus megistus, an important vector in Brazil. Medicines treating Chagas disease have unpleasant side effects and may be ineffective, therefore, alternative control techniques are required. Knowledge of the T. cruzi interactions with the triatomine host needs extending and new targets/strategies for control identified. Serine and cysteine peptidases play vital roles in protozoan life cycles including invasion and entry of T. cruzi into host cells. Peptidase inhibitors are, therefore, promising targets for disease control., Methods: SDS PAGE and chromatograpy detected and isolated a P. megistus serpin which was peptide sequenced by mass spectrometry. A full amino acid sequence was obtained from the cDNA and compared with other insect serpins. Reverse transcription PCR analysis measured serpin transcripts of P. megistus tissues with and without T. cruzi infection. Serpin homology modeling used the Swiss Model and Swiss-PDB viewer programmes., Results: The P. megistus serpin (PMSRP1) has a ca. 40 kDa molecular mass with 404 amino acid residues. A reactive site loop contains a highly conserved hinge region but, based on sequence alignment, the normal cleavage site for serine proteases at P1-P1' was translocated to the putative position P4'-P5'. A small peptide obtained corresponded to the C-terminal 40 amino acid region. The secondary structure of PMSRP1 indicated nine α-helices and three β-sheets, similar to other serpins. PMSRP1 transcripts occurred in all tested tissues but were highest in the fat body and hemocytes. Levels of mRNA encoding PMSRP1 were significantly modulated in the hemocytes and stomach by T. cruzi infection indicating a role for PMSRP1 in the parasite interactions with P. megistus., Conclusions: For the first time, a constitutively expressed serpin has been characterized from the hemolymph of a triatomine. This opens up new research avenues into the roles of serine peptidases in the T. cruzi/P. megistus association. Initial experiments indicate a role for PMSRP1 in T. cruzi interactions with P. megistus and will lead to further functional studies of this molecule.
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- 2014
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37. Recent advances in developing insect natural products as potential modern day medicines.
- Author
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Ratcliffe N, Azambuja P, and Mello CB
- Abstract
Except for honey as food, and silk for clothing and pollination of plants, people give little thought to the benefits of insects in their lives. This overview briefly describes significant recent advances in developing insect natural products as potential new medicinal drugs. This is an exciting and rapidly expanding new field since insects are hugely variable and have utilised an enormous range of natural products to survive environmental perturbations for 100s of millions of years. There is thus a treasure chest of untapped resources waiting to be discovered. Insects products, such as silk and honey, have already been utilised for thousands of years, and extracts of insects have been produced for use in Folk Medicine around the world, but only with the development of modern molecular and biochemical techniques has it become feasible to manipulate and bioengineer insect natural products into modern medicines. Utilising knowledge gleaned from Insect Folk Medicines, this review describes modern research into bioengineering honey and venom from bees, silk, cantharidin, antimicrobial peptides, and maggot secretions and anticoagulants from blood-sucking insects into medicines. Problems and solutions encountered in these endeavours are described and indicate that the future is bright for new insect derived pharmaceuticals treatments and medicines.
- Published
- 2014
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38. Trypanosoma cruzi TcSMUG L-surface mucins promote development and infectivity in the triatomine vector Rhodnius prolixus.
- Author
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Gonzalez MS, Souza MS, Garcia ES, Nogueira NF, Mello CB, Cánepa GE, Bertotti S, Durante IM, Azambuja P, and Buscaglia CA
- Subjects
- Animals, Chagas Disease parasitology, Chagas Disease transmission, Insect Vectors parasitology, Mucins metabolism, Rhodnius parasitology, Trypanosoma cruzi metabolism
- Abstract
Background: TcSMUG L products were recently identified as novel mucin-type glycoconjugates restricted to the surface of insect-dwelling epimastigote forms of Trypanosoma cruzi, the etiological agent of Chagas disease. The remarkable conservation of their predicted mature N-terminal region, which is exposed to the extracellular milieu, suggests that TcSMUG L products may be involved in structural and/or functional aspects of the interaction with the insect vector., Methodology and Principal Findings: Here, we investigated the putative roles of TcSMUG L mucins in both in vivo development and ex vivo attachment of epimastigotes to the luminal surface of the digestive tract of Rhodnius prolixus. Our results indicate that the exogenous addition of TcSMUG L N-terminal peptide, but not control T. cruzi mucin peptides, to the infected bloodmeal inhibited the development of parasites in R. prolixus in a dose-dependent manner. Pre-incubation of insect midguts with the TcSMUG L peptide impaired the ex vivo attachment of epimastigotes to the luminal surface epithelium, likely by competing out TcSMUG L binding sites on the luminal surface of the posterior midgut, as revealed by fluorescence microscopy., Conclusion and Significance: Together, these observations indicate that TcSMUG L mucins are a determinant of both adhesion of T. cruzi epimastigotes to the posterior midgut epithelial cells of the triatomine, and the infection of the insect vector, R. prolixus.
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- 2013
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39. Comparison between the six-minute walk test and the six-minute step test in post stroke patients.
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da Silva TD, Raimundo RD, Ferreira C, Torriani-Pasin C, Monteiro CB, Theodoro Júnior OA, Valenti VE, Adami F, de Oliveira EP, Barnabé V, and de Abreu LC
- Abstract
Background: The Stroke remains one of the major chronic diseases worldwide, and is considered a major cause of disability, which results not only in persistent neurological deficits, but also in the high physical deconditioning, nevertheless there are not many forms of assessing functional capacity in this population. We aimed to investigate the feasibility of the Six Minute Walk Teste and the Six-Minute Step Test (6MST) in post-stroke patients and compare the behavior of physiological variables during the 6MST and the Six-Minute Walk Test (6MWT), by correlating the functional performance obtained in both tests., Method: The 6MWT was carried out according to the American Thoracic Society (ATS) and the 6MST was performed in six minutes in order to compare it to the 6MWT in a 20 cm step. Was included post-stroke individuals able to walk without aid. All of them did the 6MWT and the 6MST., Results: 12 patients participated in the study. There was no statistical difference in the parameters analyzed when tests were compared. There was poor correlation between the functional performance in both tests., Conclusion: The 6MWT and the 6MST is feasible for post-stroke patients and physiological responses are equal during the performance of both tests. However, there was no correlation with respect to functional performance, which was assessed by the distance walked in the 6MWT and by the number of steps climbed in the 6MST.
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- 2013
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40. The biopsychosocial processes in autism spectrum disorder.
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Silva EB, Filipini R, Monteiro CB, Valenti VE, de Carvalho SM, Wajnsztejn R, de Farias Mdo C, Macedo CC, and de Abreu LC
- Abstract
Background: Autism is a disorder characterized by pervasive social and communicative impairments, repetitive and stereotyped behaviors and restricted interests. Its causes and effects have been researched from various neurocognitive theoretical perspectives and with the aid of neuroimaging technology. We aimed to describe biopsychosocial processes characteristic of the Autism Spectrum Disorders., Method: Literature review using Medline and Scopus databases published between 2001 and 2011, with the keywords "autism", "theory of mind", "executive functions", "central coherence" and "fMRI"., Results: The studies found were plotted and organized into tables and an explanatory diagram of the main findings was produced., Conclusions: The most popular neurocognitive theories are still unable to fully explain the characteristics of the complications that autistic spectrum disorder causes to the quality of life of individuals living with autism. The association of clinical research and neuroimaging may contribute to a better understanding of the functioning of the brain affected by the disorder.
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- 2013
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41. Pain and quality of life in patients undergoing radiotherapy for spinal metastatic disease treatment.
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Valesin Filho ES, de Abreu LC, Lima GH, de Cubero DI, Ueno FH, Figueiredo GS, Valenti VE, Monteiro CB, Wajnsztejn R, Fujiki EN, Neto MR, and Rodrigues LM
- Abstract
Background: Radiotherapy is an important tool in the control of pain in patients with spinal metastatic disease. We aimed to evaluate pain and of quality of life of patients with spinal metastatic disease undergoing radiotherapy with supportive treatment., Methods: The study enrolled 30 patients. From January 2008 to January 2010, patients selection included those treated with a 20 Gy tumour dose in five fractions. Patients completed the visual analogue scale for pain assessment and the SF-36 questionnaire for quality of life assessment., Results: The most frequent primary sites were breast, multiple myeloma, prostate and lymphoma. It was found that 14 spinal metastatic disease patients (46.66%) had restricted involvement of three or fewer vertebrae, while 16 patients (53.33%) had cases involving more than three vertebrae. The data from the visual analogue scale evaluation of pain showed that the average initial score was 5.7 points, the value 30 days after the end of radiotherapy was 4.60 points and the average value 6 months after treatment was 4.25 points. Notably, this final value was 25.43% lower than the value from the initial analysis. With regard to the quality of life evaluation, only the values for the functional capability and social aspects categories of the questionnaire showed significant improvement., Conclusion: Radiotherapy with supportive treatment appears to be an important tool for the treatment of pain in patients with spinal metastatic disease.
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- 2013
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42. Functional capacity and assistance from the caregiver during daily activities in Brazilian children with cerebral palsy.
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Malheiros SR, Monteiro CB, da Silva TD, Torriani-Pasin C, de Andrade M Sr, Valenti VE, Raimundo RD, Roosch A, Rodrigues L, Manhabusque KV, Camargo RC, Drezzet J, Quadrado VH, and de Abreu LC
- Abstract
Background: Cerebral Palsy (CP) presents changes in posture and movement as a core characteristic, which requires multiprofessional clinical treatments during children's habilitation or rehabilitation. Besides clinical treatment, it is fundamental that professionals use evaluation systems to quantify the difficulties presented to the individual and their families in their daily lives. We aimed to investigate the functional capacity of individuals with CP and the amount of assistance required by the caregiver in day-to-day activities., Methods: Twenty patients with CP, six-year-old on average, were evaluated. The Pediatric Evaluation Inventory of Incapacities was used (PEDI - Pediatric Evaluation Disability Inventory), a system adapted for Brazil that evaluates child's dysfunction in three 3 dimensions: self-care, mobility and social function. To compare the three areas, repeated measures analysis of variance (ANOVA) were used., Results: We found the following results regarding the functional capacity of children: self-care, 27.4%, ±17.5; mobility, 25.8%, ±33.3 and social function, 36.3%, ±27.7. The results of the demand of aid from the caregiver according to each dimension were: self-care, 9.7%, ±19.9; mobility, 14.1%, ± 20.9 and social function, 19.8%, ±26.1., Conclusion: We indicated that there was no difference between the performance of the subjects in areas of self-care, mobility and social function considering the functional skills and assistance required by the caregiver.
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- 2013
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43. Sensitivity, specificity and predictive values of linear and nonlinear indices of heart rate variability in stable angina patients.
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Pivatelli FC, Dos Santos MA, Fernandes GB, Gatti M, de Abreu LC, Valenti VE, Vanderlei LC, Ferreira C, Adami F, de Carvalho TD, Monteiro CB, and de Godoy MF
- Abstract
Background: Decreased heart rate variability (HRV) is related to higher morbidity and mortality. In this study we evaluated the linear and nonlinear indices of the HRV in stable angina patients submitted to coronary angiography., Methods: We studied 77 unselected patients for elective coronary angiography, which were divided into two groups: coronary artery disease (CAD) and non-CAD groups. For analysis of HRV indices, HRV was recorded beat by beat with the volunteers in the supine position for 40 minutes. We analyzed the linear indices in the time (SDNN [standard deviation of normal to normal], NN50 [total number of adjacent RR intervals with a difference of duration greater than 50ms] and RMSSD [root-mean square of differences]) and frequency domains ultra-low frequency (ULF) ≤ 0,003 Hz, very low frequency (VLF) 0,003 - 0,04 Hz, low frequency (LF) (0.04-0.15 Hz), and high frequency (HF) (0.15-0.40 Hz) as well as the ratio between LF and HF components (LF/HF). In relation to the nonlinear indices we evaluated SD1, SD2, SD1/SD2, approximate entropy (-ApEn), α1, α2, Lyapunov Exponent, Hurst Exponent, autocorrelation and dimension correlation. The definition of the cutoff point of the variables for predictive tests was obtained by the Receiver Operating Characteristic curve (ROC). The area under the ROC curve was calculated by the extended trapezoidal rule, assuming as relevant areas under the curve ≥ 0.650., Results: Coronary arterial disease patients presented reduced values of SDNN, RMSSD, NN50, HF, SD1, SD2 and -ApEn. HF ≤ 66 ms2, RMSSD ≤ 23.9 ms, ApEn ≤-0.296 and NN50 ≤ 16 presented the best discriminatory power for the presence of significant coronary obstruction., Conclusion: We suggest the use of Heart Rate Variability Analysis in linear and nonlinear domains, for prognostic purposes in patients with stable angina pectoris, in view of their overall impairment.
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- 2012
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44. Marfan syndrome with a complex chromosomal rearrangement including deletion of the FBN1 gene.
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Colovati ME, da Silva LR, Takeno SS, Mancini TI, N Dutra AR, Guilherme RS, de Mello CB, Melaragno MI, and A Perez AB
- Abstract
Background: The majority of Marfan syndrome (MFS) cases is caused by mutations in the fibrillin-1 gene (FBN1), mapped to chromosome 15q21.1. Only few reports on deletions including the whole FBN1 gene, detected by molecular cytogenetic techniques, were found in literature., Results: We report here on a female patient with clinical symptoms of the MFS spectrum plus craniostenosis, hypothyroidism and intellectual deficiency who presents a 1.9 Mb deletion, including the FBN1 gene and a complex rearrangement with eight breakpoints involving chromosomes 6, 12 and 15., Discussion: This is the first report of MFS with a complex chromosome rearrangement involving a deletion of FBN1 and contiguous genes. In addition to the typical clinical findings of the Marfan syndrome due to FBN1 gene haploinsufficiency, the patient presents features which may be due to the other gene deletions and possibly to the complex chromosome rearrangement.
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- 2012
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45. Cultivation-independent methods reveal differences among bacterial gut microbiota in triatomine vectors of Chagas disease.
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da Mota FF, Marinho LP, Moreira CJ, Lima MM, Mello CB, Garcia ES, Carels N, and Azambuja P
- Subjects
- Animals, Cluster Analysis, DNA, Bacterial chemistry, DNA, Bacterial genetics, DNA, Ribosomal chemistry, DNA, Ribosomal genetics, Female, Gastrointestinal Tract microbiology, Humans, Male, Molecular Sequence Data, Phylogeny, RNA, Ribosomal, 16S genetics, Sequence Analysis, DNA, South America, Bacteria classification, Bacteria genetics, Biodiversity, Disease Vectors, Triatominae microbiology
- Abstract
Background: Chagas disease is a trypanosomiasis whose agent is the protozoan parasite Trypanosoma cruzi, which is transmitted to humans by hematophagous bugs known as triatomines. Even though insecticide treatments allow effective control of these bugs in most Latin American countries where Chagas disease is endemic, the disease still affects a large proportion of the population of South America. The features of the disease in humans have been extensively studied, and the genome of the parasite has been sequenced, but no effective drug is yet available to treat Chagas disease. The digestive tract of the insect vectors in which T. cruzi develops has been much less well investigated than blood from its human hosts and constitutes a dynamic environment with very different conditions. Thus, we investigated the composition of the predominant bacterial species of the microbiota in insect vectors from Rhodnius, Triatoma, Panstrongylus and Dipetalogaster genera., Methodology/principal Findings: Microbiota of triatomine guts were investigated using cultivation-independent methods, i.e., phylogenetic analysis of 16s rDNA using denaturing gradient gel electrophoresis (DGGE) and cloned-based sequencing. The Chao index showed that the diversity of bacterial species in triatomine guts is low, comprising fewer than 20 predominant species, and that these species vary between insect species. The analyses showed that Serratia predominates in Rhodnius, Arsenophonus predominates in Triatoma and Panstrongylus, while Candidatus Rohrkolberia predominates in Dipetalogaster., Conclusions/significance: The microbiota of triatomine guts represents one of the factors that may interfere with T. cruzi transmission and virulence in humans. The knowledge of its composition according to insect species is important for designing measures of biological control for T. cruzi. We found that the predominant species of the bacterial microbiota in triatomines form a group of low complexity whose structure differs according to the vector genus.
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- 2012
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46. A model for pediatric and neuropsychological screening assessment of children with learning disabilities.
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de Mello CB, Brunoni LRR, Pilla AL, Taddei JAAC, Barbosa T, Sinnes EG, Rodrigues CC, Miranda MC, Muzskat M, and Bueno OFA
- Abstract
Objectives: The high frequency of learning difficulties, attention disorders or developmental delay in children in the early years of schooling has resulted in a greater demand for pediatric services. Such services generally include assessments covering various specialties, are lengthy and often inaccessible to families due to prohibitively high cost. This paper presents an economically efficient model of interdisciplinary diagnosis., Methods: A group of 109 Brazilian students from public schools aged between 5 and 14 years old, referred by teachers for a history of learning disabilities, behavioral changes or language problems, was evaluated at the NANI (Nucleo de Atendimento Neuropsicologico Infantil). Assessments were performed simultaneously during a single day's attendance and comprised clinical-genetic examination, behavioral assessment and neuropsychological screening, specially developed for the process. The multiaxial system of DSM-IV was adopted for diagnostic description., Results: The results revealed heterogeneity in diagnoses which included specific learning disorders (25.7%), mild intellectual disabilities (17.43%), as well as suspected dysmorphic features (11.93%). Logistic regression showed good sensitivity of neuropsychological screening in the detection of predictive factors for specific developmental disorders, while working memory (p=0.05) and language (p=0.02) problems were found to be higher risk., Conclusions: The model adopted proved to be useful for defining the diagnosis of several conditions in infancy, and can be incorporated into specialized clinics such as psychiatric or developmental pediatric services., Competing Interests: Disclosure: The authors report no conflits of interest.
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- 2012
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47. Maintenance therapy with peginterferon alfa-2b does not prevent hepatocellular carcinoma in cirrhotic patients with chronic hepatitis C.
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Bruix J, Poynard T, Colombo M, Schiff E, Burak K, Heathcote EJ, Berg T, Poo JL, Mello CB, Guenther R, Niederau C, Terg R, Bedossa P, Boparai N, Griffel LH, Burroughs M, Brass CA, and Albrecht JK
- Subjects
- Antiviral Agents adverse effects, Biomarkers blood, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular virology, Disease Progression, Drug Administration Schedule, Europe, Female, Hepacivirus genetics, Hepatitis C, Chronic complications, Hepatitis C, Chronic diagnosis, Hepatitis C, Chronic mortality, Humans, Hypertension, Portal drug therapy, Hypertension, Portal virology, Interferon alpha-2, Interferon-alpha adverse effects, Kaplan-Meier Estimate, Liver Cirrhosis diagnosis, Liver Cirrhosis mortality, Liver Cirrhosis virology, Liver Neoplasms mortality, Liver Neoplasms virology, Male, Middle Aged, North America, Patient Selection, Polyethylene Glycols adverse effects, Proportional Hazards Models, Prospective Studies, RNA, Viral blood, Recombinant Proteins, Risk Assessment, Risk Factors, South America, Time Factors, Treatment Outcome, Viral Load, Antiviral Agents administration & dosage, Carcinoma, Hepatocellular prevention & control, Hepatitis C, Chronic drug therapy, Interferon-alpha administration & dosage, Liver Cirrhosis drug therapy, Liver Neoplasms prevention & control, Polyethylene Glycols administration & dosage
- Abstract
Background & Aims: Several studies have reported that low doses of interferon can delay the development of hepatocellular carcinoma (HCC) and progression of chronic hepatitis C. We investigated the incidence of clinical events among participants of the Evaluation of PegIntron in Control of Hepatitis C Cirrhosis (EPIC)3 program., Methods: Data were analyzed from an open-label randomized study of patients with chronic hepatitis C who had failed to respond to interferon alfa plus ribavirin. All patients had compensated cirrhosis with no evidence of HCC. Patients received peginterferon alfa-2b (0.5 μg/kg/week; n=311) or no treatment (controls, n=315) for a maximum period of 5 years or until 98 patients had a clinical event (hepatic decompensation, HCC, death, or liver transplantation). The primary measure of efficacy was time until the first clinical event., Results: There was no significant difference in time to first clinical event among patients who received peginterferon alfa-2b compared with controls (hazard ratio [HR], 1.452; 95% confidence interval [CI]: 0.880-2.396). There was no decrease in the development of HCC with therapy. The time to disease progression (clinical events or new or enlarged varices) was significantly longer for patients who received peginterferon alfa-2b compared with controls (HR, 1.564; 95% CI: 1.130-2.166). In a prospectively defined subanalysis of patients with baseline portal hypertension, peginterferon alfa-2b significantly increased the time to first clinical event compared with controls (P=.016). There were no new safety observations., Conclusions: Maintenance therapy with peginterferon alfa-2b is not warranted in all patients and does not prevent HCC. However, there is a potential clinical benefit of long-term suppressive therapy in patients with preexisting portal hypertension., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2011
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48. Motor and functional evaluation of patients with spastic paraplegia, optic atrophy, and neuropathy (SPOAN).
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Graciani Z, Santos S, Macedo-Souza LI, Monteiro CB, Veras MI, Amorim S, Zatz M, and Kok F
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- Adolescent, Adult, Aged, Child, Child, Preschool, Disease Progression, Female, Humans, Male, Middle Aged, Optic Atrophies, Hereditary physiopathology, Severity of Illness Index, Spastic Paraplegia, Hereditary physiopathology, Young Adult, Optic Atrophies, Hereditary complications, Psychomotor Performance physiology, Spastic Paraplegia, Hereditary complications
- Abstract
Spastic paraplegia, optic atrophy, and neuropathy (SPOAN) is an autosomal recessive complicated form of hereditary spastic paraplegia, which is clinically defined by congenital optic atrophy, infancy-onset progressive spastic paraplegia and peripheral neuropathy. In this study, which included 61 individuals (age 5-72 years, 42 females) affected by SPOAN, a comprehensive motor and functional evaluation was performed, using modified Barthel index, modified Ashworth scale, hand grip strength measured with a hydraulic dynamometer and two hereditary spastic paraplegia scales. Modified Barthel index, which evaluate several functional aspects, was more sensitive to disclose disease progression than the spastic paraplegia scales. Spasticity showed a bimodal distribution, with both grades 1 (minimum) and 4 (maximum). Hand grip strength showed a moderate inverse correlation with age. Combination of early onset spastic paraplegia and progressive polyneuropathy make SPOAN disability overwhelming.
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- 2010
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49. Categorization skills and recall in brain damaged children: a multiple case study.
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Mello CB, Muszkat M, Xavier GF, and Bueno OF
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- Adolescent, Age Factors, Brain Injuries physiopathology, Child, Humans, Male, Neuropsychological Tests, Brain Damage, Chronic physiopathology, Memory Disorders physiopathology, Mental Recall physiology
- Abstract
During development, children become capable of categorically associating stimuli and of using these relationships for memory recall. Brain damage in childhood can interfere with this development. This study investigated categorical association of stimuli and recall in four children with brain damages. The etiology, topography and timing of the lesions were diverse. Tasks included naming and immediate recall of 30 perceptually and semantically related figures, free sorting, delayed recall, and cued recall of the same material. Traditional neuropsychological tests were also employed. Two children with brain damage sustained in middle childhood relied on perceptual rather than on categorical associations in making associations between figures and showed deficits in delayed or cued recall, in contrast to those with perinatal lesions. One child exhibited normal performance in recall despite categorical association deficits. The present results suggest that brain damaged children show deficits in categorization and recall that are not usually identified in traditional neuropsychological tests.
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- 2009
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50. Clinical and neuropsychological profile in a sample of children with attention deficit hyperactivity disorders.
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Rizzutti S, Sinnes EG, Scaramuzza LF, Freitas L, Pinheiro D, Palma SM, Mello CB, Miranda MC, Bueno OF, and Muszkat M
- Subjects
- Adolescent, Child, Female, Humans, Male, Reference Values, Attention Deficit Disorder with Hyperactivity diagnosis, Neuropsychological Tests
- Abstract
Unlabelled: The aim of this study was to evaluate clinical and neuropsychological findings in children with suspicion of attention deficity hyperactivity disorder (ADHD). The assessment involved 150 children aged 7 to 14 referred to NANI at UNIFESP., Results: 75 children (55 M and 20 F) fulfilled the criteria for ADHD, among which 35 were of the inattentive type, 28 of combined type and 12 were hyperactive/impulsive. There was negative correlation between the digit score and the Corsi test. Children with hyperactivity and impulsivity had a low performance for functional memory. Children with oppositional defiant disorder presented pattern changes in adaptability when there was a change in the rhythm the stimuli were presented and lower adaptation to time variability (Hit RT), in addition to higher rates of omission in the continuous performance test., Conclusion: This study suggests multiple interrelations between the scores of neuropsychological battery useful for detailed delimitation of the clinical profile of children with ADHD.
- Published
- 2008
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