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Behavioral problems of school children: impact of social vulnerability, chronic adversity, and maternal depression
No full textAbstract\ud
This study’s objective was to identify the predictive effect of indicators concerning social vulnerability, chronic adversity, and maternal depression on behavioral problems among school-aged children, according to the perceptions of mothers and teachers, considering the presence or absence of difficulties in the contexts of family and school. A total of 85 pairs of mothers and school children were distributed into three groups according to the behavioral problems identified. A General Questionnaire, the PHQ-9, the Chronic Adversity Scale, and the (Strengths and Difficulties Questionnaire) SDQ were applied to the mothers; the Raven’s Colored Progressive Matrices were applied to the children; and the SDQ was applied to the teachers. Data were analyzed with descriptive, predictive, and comparative statistical procedures (p ≤ 0.05). The results reveal the presence of cumulative risks for children with behavioral problems; mothers more frequently identified behavioral problems than teachers; and maternal depression was a predictor for behavioral problems. Such findings are relevant for devising mental health programs.To the development of this research, we counted on the financial support of\ud
the National Council for Scientific and Technological Development (CNPq/\ud
Brazil) under number 307394/2014-0
Augmentative and alternative communication in children with Down’s syndrome: a systematic review
No full textAbstract\ud
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Background\ud
The use of technology to assist in the communication, socialization, language, and motor skills of children with Down’s syndrome (DS) is required. The aim of this study was to analyse research findings regarding the different instruments of ‘augmentative and alternative communication’ used in children with Down’s syndrome.\ud
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Methods\ud
This is a systematic review of published articles available on PubMed, Web of Science, PsycInfo, and BVS using the following descriptors: assistive technology AND syndrome, assistive technology AND down syndrome, down syndrome AND augmentative and alternative communication. Studies published in English were selected if they met the following inclusion criteria: (1) study of children with a diagnosis of DS, and (2) assistive technology and/or augmentative and alternative communication analysis in this population.\ud
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Results\ud
A total of 1087 articles were identified. Thirteen articles met the inclusion criteria. The instruments most used by the studies were speech-generating devices (SGDs) and the Picture Exchange Communication System (PECS).\ud
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Conclusion\ud
Twelve instruments that provided significant aid to the process of communication and socialization of children with DS were identified. These instruments increase the interaction between individuals among this population and their peers, contributing to their quality of life and self-esteem.The authors would like to thank CAPES (Higher Education Personnel Training\ud
Coordination). Call Notice No. 59/2014 – PGPTA and the UNIEDU-SC postgraduate\ud
programme
Genome-wide screening of DNA methylation in bovine blastocysts with different kinetics of development
No full textAbstract\ud
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Background\ud
The timing of the first cell divisions may predict the developmental potential of an embryo, including its ability to establish pregnancy. Besides differences related to metabolism, stress, and survival, embryos with different speeds of development present distinct patterns of gene expression, mainly related to energy and lipid metabolism. As gene expression is regulated by epigenetic factors, and that includes DNA methylation patterns, in this study we compared the global DNA methylation profile of embryos with different kinetics of development in order to identify general pathways and regions that are most influenced by this phenotype. For this purpose, bovine embryos were in vitro produced using sexed semen (female), classified as fast (four or more cells) or slow (two cells) at 40 hpi and cultured until blastocyst stage, when they were analyzed.\ud
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Results\ud
Genome-wide DNA methylation analysis identified 11,584 differently methylated regions (DMRs) (7976 hypermethylated regions in fast and 3608 hypermethylated regions in slow embryos). Fast embryos presented more regions classified as hypermethylated distributed throughout the genome, as in introns, exons, promoters, and repeat elements while in slow embryos, hypermethylated regions were more present in CpG islands. DMRs were clustered by means of biological processes, and the most affected pathways were related to cell survival/differentiation and energy/lipid metabolism. Transcripts profiles from DM genes connected with these pathways were also assessed, and the most part disclosed changes in relative quantitation.\ud
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Conclusion\ud
The kinetics of the first cleavages influences the DNA methylation and expression profiles of genes related to metabolism and differentiation pathways and may affect embryo viability.This work was supported by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) 2015/03381-0; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and EmbryoGENE Network
miR-29b enhances prostate cancer cell invasion independently of MMP-2 expression
No full textAbstract\ud
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Background\ud
The ability to metastasize is one of the most important characteristics of neoplastic cells. An imbalance between the action of some matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs drives the invasion process. Some studies have suggested that MMP-2 is involved in metastasis, while other studies have reported that collagen production by cancer cells might also contribute to motility. However, decreased expression of microRNA-29b (miR-29b), which may control MMP-2 and collagen gene expression, has been shown in prostate cancer (PCa). The objectives of the present study were to clarify whether MMP-2 as well as collagens I and III (encoded by COL1A1 and COL3A1, respectively) are controlled by miR-29b and to determine whether metastasis is altered by this relationship.\ud
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Methods\ud
PCa DU145 and PC-3 cells were transfected with 100 μL of OPTI-MEM I containing 100 nmol of miR-29b (or its inhibitor) along with 1.5 μL of lipofectamine. Positive and negative controls were prepared using the same protocol. MMP-2, COL1A1 and COL3A1 messenger RNA (mRNA) levels were evaluated via real-time polymerase chain reaction (qRT-PCR). For qRT-PCR, 6 × 104 cells were used. Invasion studies were conducted with Matrigel assays, which simulate invasion of the extracellular matrix by neoplastic cells. After transfection of 3 × 104 cells, invasion was allowed to proceed for 48 h. Invasive cells were counted under an optical microscope. Each experiment was performed in triplicate.\ud
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Results\ud
MMP-2 mRNA was not expressed in DU145 cells after transfection with miR-29b. After transfection of cells with the miR-29b inhibitor, COL1A1 (p = 0.02) and COL3A1 (p = 0.06) mRNA expression was increased in DU145 cells, and a large number of transfected DU145 and PC3 cells invaded the Matrigel membrane.\ud
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Conclusions\ud
In vitro studies showed that reducing the amount of miR-29b may lead to higher PCa cell invasion via a process that is independent of MMP-2. Collagen expression, controlled by miR-29b, may facilitate this motility process. Thus, the present study suggests that collagen production plays an active role in metastasis control and restoration of miR-29b levels may decrease metastasis. Altogether, these findings support further exploration of drug therapy targeting this aspect of the metastasis circuit.Funding was received from the State of Sao Paulo (FAPESP): 2012/21833-8; 2015/00845-6
Characterisation of Zika virus infection in primary human astrocytes
No full textAbstract\ud
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Background\ud
The recent Zika virus (ZIKV) outbreak has linked ZIKV with microcephaly and other central nervous system pathologies in humans. Astrocytes are among the first cells to respond to ZIKV infection in the brain and are also targets for virus infection. In this study, we investigated the interaction between ZIKV and primary human brain cortical astrocytes (HBCA).\ud
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Results\ud
HBCAs were highly sensitive to representatives of both Asian and African ZIKV lineages and produced high viral yields. The infection was associated with limited immune cytokine/chemokine response activation; the highest increase of expression, following infection, was seen in CXCL-10 (IP-10), interleukin-6, 8, 12, and CCL5 (RANTES). Ultrastructural changes in the ZIKV-infected HBCA were characterized by electron tomography (ET). ET reconstructions elucidated high-resolution 3D images of the proliferating and extensively rearranged endoplasmic reticulum (ER) containing viral particles and virus-induced vesicles, tightly juxtaposed to collapsed ER cisternae.\ud
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Conclusions\ud
The results confirm that human astrocytes are sensitive to ZIKV infection and could be a source of proinflammatory cytokines in the ZIKV-infected brain tissue.This work was supported by the Czech Science Foundation (Grants 16-20054S and 17-02196S); the Ministry of Education, Youth, and Sports of the Czech Republic, under the NPU I program (Grant LO1218); by Project “FIT” (Pharmacology, Immunotherapy, nanoToxicology), which was funded by the European Regional Development Fund; the National Subvention for the Development of Research Organizations (Grant RVO: 61388963); and the European Virus Archive Goes Global project, which has received funding from the European Union’s Horizon 2020 research and innovation program (Grant 653316). The Laboratory of EM supported by the Ministry of Education, Youth, and Sports of the Czech Republic (LM2015062 Czech-BioImaging) and Technology Agency of the Czech Republic (TE01020118)
Exosomes from patients with septic shock convey miRNAs related to inflammation and cell cycle regulation: new signaling pathways in sepsis?
No full textAbstract\ud
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Background\ud
Exosomes isolated from plasma of patients with sepsis may induce vascular apoptosis and myocardial dysfunction by mechanisms related to inflammation and oxidative stress. Despite previous studies demonstrating that these vesicles contain genetic material related to cellular communication, their molecular cargo during sepsis is relatively unknown. In this study, we evaluated the presence of microRNAs (miRNAs) and messenger RNAs (mRNAs) related to inflammatory response and redox metabolism in exosomes of patients with septic shock.\ud
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Methods\ud
Blood samples were collected from 24 patients with septic shock at ICU admission and after 7 days of treatment. Twelve healthy volunteers were used as control subjects. Exosomes were isolated by ultracentrifugation, and their miRNA and mRNA content was evaluated by qRT-PCR array.\ud
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Results\ud
As compared with healthy volunteers, exosomes from patients with sepsis had significant changes in 65 exosomal miRNAs. Twenty-eight miRNAs were differentially expressed, both at enrollment and after 7 days, with similar kinetics (18 miRNAs upregulated and 10 downregulated). At enrollment, 35 differentially expressed miRNAs clustered patients with sepsis according to survival. The pathways enriched by the miRNAs of patients with sepsis compared with control subjects were related mostly to inflammatory response. The comparison of miRNAs from patients with sepsis according to hospital survival demonstrated pathways related mostly to cell cycle regulation. At enrollment, sepsis was associated with significant increases in the expression of mRNAs related to redox metabolism (myeloperoxidase, 64-fold; PRDX3, 2.6-fold; SOD2, 2.2-fold) and redox-responsive genes (FOXM1, 21-fold; SELS, 16-fold; GLRX2, 3.4-fold). The expression of myeloperoxidase mRNA remained elevated after 7 days (65-fold).\ud
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Conclusions\ud
Exosomes from patients with septic shock convey miRNAs and mRNAs related to pathogenic pathways, including inflammatory response, oxidative stress, and cell cycle regulation. Exosomes may represent a novel mechanism for intercellular communication during sepsis.This study was supported by Fundação de Amparo à Pesquisa do Estado de\ud
São Paulo (FAPESP grant number 10/52554-1) and by the Research and\ud
Education Institute, Hospital Sirio-Libane
The ideal time of systemic metronidazole and amoxicillin administration in the treatment of severe periodontitis: study protocol for a randomized controlled trial
No full textAbstract\ud
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Background\ud
The combination of systemic metronidazole (MTZ) and amoxicillin (AMX) with scaling and root planing (SRP) has shown to be an effective periodontal treatment. However, some essential issues associated with the use of these antibiotics remain unanswered, such as the ideal time of administration during the course of periodontal treatment. Although these agents are often prescribed after the healing phase of the SRP procedure, there is biological plausibility to support its use in conjunction with the mechanical treatment. However, to date, no placebo controlled randomized clinical trial (RCT) has directly compared these two protocols. Therefore, the aim of this RCT is to compare the clinical, microbiological and immunological effects of the adjunctive systemic MTZ + AMX administered in different phases of the treatment of severe periodontitis.\ud
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Methods\ud
Subjects with severe periodontitis (n = 180) are being randomly assigned into three groups (n = 60/group): (i) SRP-only (control group), SRP in combination with 400 mg MTZ + 500 mg AMX, starting (ii) at the first SRP session (active phase group), or (iii) after 3 months of its completion (healing phase group). All volunteers are receiving clinical and microbiological evaluation at baseline, 3, 6 and 12 months, and immunological assessment at baseline and 12 months post-therapy. Nine subgingival biofilm samples are being collected per subject and analyzed for counts and proportions of 40 bacterial species by checkerboard DNA-DNA hybridization, and six gingival crevicular fluid samples are being collected and analyzed for the levels of 20 chemokines by multiplex immunoassay. The primary outcome variable is the number of volunteers reaching the clinical endpoint for treatment (≤ 4 sites with probing depth ≥5 mm) at 1 year post-therapy. Differences in clinical, microbiological and immunological parameters among groups and over time will be evaluated using analysis of variance, analysis of covariance and the Chi-square and Tukey tests. Microbiological and immunological analyses will be performed using adjustments for multiple comparisons. Statistical significance will be set at 5%.\ud
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Trial registration\ud
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ClinicalTrials.gov\ud
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NCT02954393\ud
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. Registered on 3 November 2016.The authors declare that this study is being supported by a research grant\ud
number 2016/10958–5 from São Paulo Research Foundation (FAPESP, Brazil).\ud
FAPESP (fapesp.br/en) is a public foundation, funded by the taxpayer in the\ud
State of São Paulo, with the mission to support research projects in higher\ud
education and research institutions, in all fields of knowledge. It is the main\ud
research foundation in Brazil and it works in close contact with the scientific\ud
community: all proposals are peer reviewed with the help of area panels\ud
composed of active researchers
Palmitate-induced Slc2a4/GLUT4 downregulation in L6 muscle cells: evidence of inflammatory and endoplasmic reticulum stress involvement
No full textAbstract\ud
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Background\ud
Obesity is strongly associated to insulin resistance, inflammation, and elevated plasma free fatty acids, but the mechanisms behind this association are not fully comprehended. Evidences suggest that endoplasmic reticulum (ER) stress may play a role in this complex pathophysiology. The aim of the present study was to investigate the involvement of inflammation and ER stress in the modulation of glucose transporter GLUT4, encoded by Slc2a4 gene, in L6 skeletal muscle cells.\ud
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Methods\ud
L6 cells were acutely (2 h) and chronically (6 and 12 h) exposed to palmitate, and the expression of several proteins involved in insulin resistance, ER stress and inflammation were analyzed.\ud
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Results\ud
Chronic and acute palmitate exposure significantly reduced GLUT4 protein (~ 39%, P < 0.01) and its mRNA (18%, P < 0.01) expression. Only acute palmitate treatment increased GRP78 (28%, P < 0.05), PERK (98%, P < 0.01), eIF-2A (35%, P < 0.01), IRE1a (60%, P < 0.05) and TRAF2 (23%, P < 0.05) protein content, and PERK phosphorylation (106%, P < 0.001), but did not elicit eIF-2A, IKK phosphorylation or increased XBP1 nuclear content. Additionally, acute and chronic palmitate increased NFKB p65 nuclear content (~ 30%, P < 0.05) and NFKB binding activity to Slc2a4 gene promoter (~ 45%, P < 0.05).\ud
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Conclusion\ud
Different pathways are activated in acute and chronic palmitate induced-repression of Slc2a4/GLUT4 expression. This regulation involves activation of initial component of ER stress, such as the formation of a IRE1a-TRAF2-IKK complex, and converges to NFKB-induced repression of Slc2a4/GLUT4. These results link ER stress, inflammation and insulin resistance in L6 cells.This research was supported by grants from FAPESP (São Paulo State\ud
Foundation for Research): 2010/09984-5, 2013/18841-1 and 2016/15603-1
The general Assembly of the International Association of Environmental Mutagenesis and Genomics Societies (IAEMGS) in 2017
No full textAbstract\ud
The International Association of Environmental Mutagenesis and Genomics Societies (IAEMGS) is a global organization that promotes applied and basic research on environmental mutagenesis and genomics. IAEMGS is composed of 13 national and regional societies of environmental mutagenesis and genomics and the total membership is approximately 4000. IAEMGS convenes the general assembly every four years during each International Conference on Environmental Mutagens (ICEM) for communication among members of participating societies and discussion on future directions. The latest general assembly was held during the 12th ICEM/5th Asian Conference on Environmental Mutagens (ACEM) in November 2017 in Incheon, Korea. This report summarizes the topics and discussions in the general assembly.JSPS KAKENHI Grant 26281029 for supporting travel expenses to attend\ud
ICEM2017 for T.N
High-resolution and high-precision correlation of dark and light layers in the Quaternary hemipelagic sediments of the Japan Sea recovered during IODP Expedition 346
No full textAbstract\ud
The Quaternary hemipelagic sediments of the Japan Sea are characterized by centimeter- to decimeter-scale alternation of dark and light clay to silty clay, which are bio-siliceous and/or bio-calcareous to a various degree. Each of the dark and light layers are considered as deposited synchronously throughout the deeper (> 500 m) part of the sea. However, attempts for correlation and age estimation of individual layers are limited to the upper few tens of meters. In addition, the exact timing of the depositional onset of these dark and light layers and its synchronicity throughout the deeper part of the sea have not been explored previously, although the onset timing was roughly estimated as ~ 1.5 Ma based on the result of Ocean Drilling Program legs 127/128. Consequently, it is not certain exactly when their deposition started, whether deposition of dark and light layers was synchronous and whether they are correlatable also in the earlier part of their depositional history.\ud
The Quaternary hemipelagic sediments of the Japan Sea were drilled at seven sites during Integrated Ocean Drilling Program Expedition 346 in 2013. Alternation of dark and light layers was recovered at six sites whose water depths are > ~ 900 m, and continuous composite columns were constructed at each site. Here, we report our effort to correlate individual dark layers and estimate their ages based on a newly constructed age model at Site U1424 using the best available paleomagnetic datum and marker tephras. The age model is further tuned to LR04 δ18O curve using gamma ray attenuation density (GRA) since it reflects diatom contents that are higher during interglacial high-stands. The constructed age model for Site U1424 is projected to other sites using correlation of dark layers to form a high-resolution and high-precision paleo-observatory network that allows to reconstruct changes in material fluxes with high spatio-temporal resolutions.This work was supported by a grant from IODP Exp. 346 After Cruise\ud
Research Program, JAMSTEC, awarded to TR, IK, Irino T, Itaki T, ST, KY, SS, and\ud
KA and from JSPS KAKENHI grant number 16H01765 awarded to TR