RESUMO

Abstract Objective To assess a panel of cytokines and placental insufficiency with the risk of preterm delivery (PTD). Methods Nested case-control study into the BRISA birth cohort. Eighty-two mother-infant-placenta pairs were selected at 20+0 to 25+6 weeks. Circulating biomarker levels were performed using Luminex flowmetric xMAP technology. Cytokines classified as Th1, Th2 or Th17 and other biomarkers were selected. The ratio between birth weight and placental weight (BW/PW) was used as a proxy for placental efficiency. Spearman correlation, univariate analyses and logistic regression models were calculated. Sensitivity, specificity, positive and negative likelihood ratios were calculated using the Receiver Operating Characteristic curve. Results Mean gestational age was 250 days, 14,6% were small for gestational age, 4,8% large for gestational age and 13,4% stunted. Placental efficiency was higher for term newborns (p<0,001), and 18/22 (81%) preterm biomarker values were higher than the control group. Th1 cytokines were highly correlated, while the weakest correlation was observed in other biomarkers. Less education was associated with a higher risk of PTD (p = 0.046), while there was no appreciable difference in the risk of PTD for placental insufficiency. Biomarkers showed negligible adjusted OR of PTD (0.90 to 1.02). IL-6, IL-8, IL-1β, TNFβ, IL-4, IL-13, GCSF, MIP1A, VEGF, EGF, and FGF2 presented a higher sensitivity ranging from 75.56% to 91.11%. Conclusion IL-8, IL-12p40, IL-4, IL-13, GCSF, MIP1B, and GMSF in asymptomatic pregnant women were associated with PTD. This finding suggests an activation of maternal inflammatory response.

RESUMO

OBJECTIVE: To describe changes in sociodemographic, economic and variables related to the characterization of family, health and education during the COVID-19 pandemic in a birth cohort evaluated at 10-11 years of age. METHODS: Cross-sectional study involving 1,033 children from a cohort of children born in 2010/2011, in the city of Ribeirão Preto, SP, Brazil. Data were collected from July to October 2021 by telephone or video interview held with the person responsible for the child. The questionnaires discussed family organization, child behavior and health, school attendance, socioeconomic assessment and occurrence of COVID-19 during the period of social isolation due to the pandemic. Descriptive statistics were used to describe the data. The chi-square test was used to verify group differences by minimum wages (MW). RESULTS: Of the respondents, 47.6% reported worsening of their financial situation during the pandemic, which was more frequent in the group with a household income <3 MW compared to the group with >6 MW (59.1 vs. 15.7%; p<0.001). According to the respondents, 62% of the children exhibited behavioral changes during the period and anxiety was the most frequently reported condition. In addition, 61.4% of the children had learning difficulties and these problems were more prevalent among children from households with lower incomes compared to those with higher incomes (74.7 vs. 45.1%; p<0.001). CONCLUSION: The COVID-19 pandemic has changed different economic aspects of families, as well as educational, health and behavioral indicators of children. Lower-income families were the most affected both economically and in terms of other indicators.

Assuntos

RESUMO

Medulloblastoma is the most common type of pediatric malignant primary brain tumor, and about one-third of patients die due to disease recurrence and most survivors suffer from long-term side effects. MB is clinically, genetically, and epigenetically heterogeneous and subdivided into at least four molecular subgroups: WNT, SHH, Group 3, and Group 4. We evaluated common differentially expressed genes between a Brazilian RNA-seq GSE181293 dataset and microarray GSE85217 dataset cohort of pediatric MB samples using bioinformatics methodology in order to identify hub genes of the molecular subgroups based on PPI network construction, survival and functional analysis. The main finding was the identification of five hub genes from the WNT subgroup that are tumor suppressors, and whose lower expression is related to a worse prognosis for MB patients. Furthermore, the common genes correlated with the five tumor suppressors participate in important pathways and processes for tumor initiation and progression, as well as development and differentiation, and some of them control cell stemness and pluripotency. These genes have not yet been studied within the context of MB, representing new important elements for investigation in the search for therapeutic targets, prognostic markers or for understanding of MB biology.

Assuntos

RESUMO

ABSTRACT Objective: To describe changes in sociodemographic, economic and variables related to the characterization of family, health and education during the COVID-19 pandemic in a birth cohort evaluated at 10-11 years of age. Methods: Cross-sectional study involving 1,033 children from a cohort of children born in 2010/2011, in the city of Ribeirão Preto, SP, Brazil. Data were collected from July to October 2021 by telephone or video interview held with the person responsible for the child. The questionnaires discussed family organization, child behavior and health, school attendance, socioeconomic assessment and occurrence of COVID-19 during the period of social isolation due to the pandemic. Descriptive statistics were used to describe the data. The chi-square test was used to verify group differences by minimum wages (MW). Results: Of the respondents, 47.6% reported worsening of their financial situation during the pandemic, which was more frequent in the group with a household income <3 MW compared to the group with >6 MW (59.1 vs. 15.7%; p<0.001). According to the respondents, 62% of the children exhibited behavioral changes during the period and anxiety was the most frequently reported condition. In addition, 61.4% of the children had learning difficulties and these problems were more prevalent among children from households with lower incomes compared to those with higher incomes (74.7 vs. 45.1%; p<0.001). Conclusion: The COVID-19 pandemic has changed different economic aspects of families, as well as educational, health and behavioral indicators of children. Lower-income families were the most affected both economically and in terms of other indicators.

RESUMO Objetivo: Descrever as alterações nas características sociodemográficas, econômicas e variáveis relacionadas à caracterização da família, saúde e educação durante a pandemia da COVID-19, em uma coorte de nascimento avaliada aos 10-11 anos de idade. Métodos: Estudo transversal envolvendo 1.033 crianças de uma coorte de nascidos em 2010/2011, na cidade de Ribeirão Preto, SP, Brasil. Os dados foram obtidos por meio de entrevistas por telefone ou videochamada com o responsável pela criança, no período de julho a outubro de 2021. Os questionários abordaram informações sobre a organização familiar, comportamento e saúde da criança, acompanhamento escolar, avaliação socioeconômica e ocorrência da COVID-19 durante o período de isolamento social. Foi realizada estatística descritiva. O teste qui-quadrado foi utilizado para verificar diferenças de grupos por salários-mínimos (SM). Resultados: Dos entrevistados, 47,6% relataram piora na condição financeira durante a pandemia, sendo a piora econômica mais frequente no grupo de renda familiar <3 SM em comparação ao grupo de >6 SM (59,1 vs. 15,7%; p<0,001). Segundo os responsáveis, 62% das crianças apresentaram mudança de comportamento durante o período, sendo a ansiedade relatada com mais frequência. Ainda, 61,4% das crianças apresentaram dificuldades de aprendizagem, e o prejuízo foi mais acentuado naquelas de menor renda familiar em comparação às de maior renda (74,7 vs. 45,1%; p<0,001). Conclusão: A pandemia da COVID-19 alterou diferentes aspectos econômicos das famílias, assim como indicadores educacionais, de saúde e de comportamento das crianças. As famílias de menor renda foram as mais prejudicadas tanto do ponto de vista econômico como nos demais indicadores.

RESUMO

Patients diagnosed with acute lymphoblastic leukemia (ALL) bearing t(4;11)/MLL-AF4 have aggressive clinical features, poor prognosis and there is an urgent need for new therapies to improve outcomes. Panobinostat (LBH589) has been identified as a potential therapeutic agent for ALL with t(4;11) and studies suggest that the antineoplastic effects are associated with reduced MLL-AF4 fusion protein and reduced expression of HOX genes. Here, we evaluated the in vitro effects of the combination of LBH589 with methotrexate (MTX) or 6-mercaptopurine (6MP) by cell proliferation assays and Calcusyn software in ALL cell line (RS4;11); the in vivo effects of LBH589 in xenotransplanted NOD-scid IL2Rgammanull mice measuring human lymphoblasts by flow cytometry; and the expression of HOX genes by qPCR after treatment in an adult model of ALL with t(4;11). LBH589 combination with MTX or 6MP did not promote synergistic effects in RS4;11 cell line. LBH589 treatment leads to increased overall survival and reduction of blasts in xenotransplanted mice but caused no significant changes in HOXA7, HOXA9, HOXA10, and MEIS1 expression. The LBH589, alone, showed promising antineoplastic effects in vivo and may represent a potential agent for chemotherapy in ALL patients with t(4;11).

Assuntos

RESUMO

Background: Preeclampsia is a serious pregnancy complication that affects 5%-10% of the obstetric population. Objective: To study inflammatory markers associated with preeclampsia. Search Strategy: Searches of articles on the topic published over a 10-year period (2009-2019) were performed in three databases (PubMed, Cochrane, and Embase) using the keywords preeclampsia and inflammatory markers. The PubMed search using 10 years and humans as filters retrieved 124 articles. Using an advanced search strategy, 0 articles were identified in Embase and 10 articles in Cochrane. After screening and eligibility assessment, 13 articles were included in the systematic review and meta-analysis. Meta-analysis and quality assessment of the studies were performed using the Review Manager 5.3 program. Results: For meta-analysis, women with preeclampsia were compared to control women, i.e., pregnancies without arterial hypertension. Leptin levels were significantly higher (p < 0.0002) in women with preeclampsia compared to controls. Total cholesterol was also significantly elevated in women with preeclampsia (p < 0.0001). There was no significant difference in HDL between groups, but women with preeclampsia had significantly increased LDL (p < 0.01). The same was observed for triglycerides, which were significantly increased in women with preeclampsia (p < 0.04) compared to controls. Analysis of TNF-alpha, an important inflammatory marker, showed higher levels in women with preeclampsia (p < 0.03) compared to controls. The same was observed for another important inflammatory marker, interleukin 6, which was significantly increased in women with preeclampsia (p < 0.0002). There was a significant increase of C-reactive protein in women with preeclampsia (p < 0.003) compared to controls. Conclusion: Women with preeclampsia have increased levels of inflammatory markers compared to control women.

RESUMO

PURPOSE: To evaluate the genetic variants related to polycystic ovary syndrome (PCOS) and its metabolic complications in girls born small for gestational age (SGA). DESIGN: Retrospective birth cohort study. MATERIALS AND METHODS: We evaluated 66 women of reproductive age born at term (37-42 weeks of gestational age) according to the birth weight in relation to gestational age: 26 SGA and 40 AGA (Adequate for gestational age). Anthropometric and biochemical characteristics were measured, as well as the PCOS prevalence. We analyzed 48 single nucleotide polymorphisms (SNPs) previously associated with PCOS and its comorbidities using TaqMan Low-Density Array (TLDA). miRNet and STRING databases were used to predict target and disease networks. RESULTS: Anthropometric and biochemical characteristics did not differ between the SGA and AGA groups, as well as insulin resistance and PCOS prevalence. Two SNPs were not in Hardy-Weinberg equilibrium, the rs2910164 (MIR146A C > G) and rs182052 (ADIPOQ G > A). The rs2910164 minor allele frequency (MAF) was increased in SGA (OR, 2.77; 95%; CI, 1.22-6.29), while the rs182052 was increased AGA (OR, 0.34; 95%; CI, 0.13 - 0.88). The alleles related to reduced miRNA-146a (C) and ADIPOQ (A) activity showed increased frequency in SGA. The mature miR-146a targets 319 genes, been the CXCR4, TMEM167A and IF144L common targets and contributes to PCOS. The ADIPOQ main protein interactions were ERP44, PPARGCIA and CDH13. CONCLUSIONS: The miR-146a (rs2910164) and ADIPOQ (rs182052) allelic variants are related to birth weight in SGA and may predict health-related outcomes, such as PCOS and obesity risk.

Assuntos

RESUMO

Abdominal tumors (AT) in children account for approximately 17% of all pediatric solid tumor cases, and frequently exhibit embryonal histological features that differentiate them from adult cancers. Current molecular approaches have greatly improved the understanding of the distinctive pathology of each tumor type and enabled the characterization of novel tumor biomarkers. As seen in abdominal adult tumors, microRNAs (miRNAs) have been increasingly implicated in either the initiation or progression of childhood cancer. Moreover, besides predicting patient prognosis, they represent valuable diagnostic tools that may also assist the surveillance of tumor behavior and treatment response, as well as the identification of the primary metastatic sites. Thus, the present study was undertaken to compile up-to-date information regarding the role of dysregulated miRNAs in the most common histological variants of AT, including neuroblastoma, nephroblastoma, hepatoblastoma, hepatocarcinoma, and adrenal tumors. Additionally, the clinical implications of dysregulated miRNAs as potential diagnostic tools or indicators of prognosis were evaluated.

Assuntos

RESUMO

Even though the treatment of childhood cancer has evolved significantly in recent decades, aggressive central nervous system (CNS) tumors are still a leading cause of morbidity and mortality in this population. Consequently, the identification of molecular targets that can be incorporated into diagnostic practice, effectively predict prognosis, follow treatment response, and materialize into potential targeted therapeutic approaches are still warranted. Since the first evidence of the participation of miRNAs in cancer development and progression 20 years ago, notable progress has been made in the basic understanding of the contribution of their dysregulation as epigenetic driver of tumorigenesis. Nevertheless, among the plethora of articles in the literature, microRNA profiling of pediatric tumors are scarce. This article gives an overview of the recent advances in the diagnostic/prognostic potential of miRNAs in a selection of pediatric CNS tumors: medulloblastoma, ependymoma, pilocytic astrocytoma, glioblastoma, diffuse intrinsic pontine glioma, atypical teratoid/rhabdoid tumors, and choroid plexus tumors.

Assuntos

RESUMO

Medulloblastoma (MB) is the most common malignant brain tumor in children. Recent advances in molecular technologies allowed to classify MB in 4 major molecular subgroups: WNT, SHH, Group 3 and Group 4. In cancer research, cancer cell lines are important for examining and manipulating molecular and cellular process. However, it is important to know the characteristics of each cancer cell line prior to use, because there are some differences among them, even if they originate from the same cancer type. This study aimed to evaluate the similarities and differences among four human medulloblastoma cell lines, UW402, UW473, DAOY and ONS-76. The medulloblastoma cell lines were analyzed for (1) cell morphology, (2) immunophenotyping by flow cytometry for some specifics surface proteins, (3) expression level of adhesion molecules by RT-qPCR, (4) proliferative potential, (5) cell migration, and (6) in vivo tumorigenic potential. It was observed a relationship between cell growth and CDH1 (E-chaderin) adhesion molecule expression and all MB cell lines showed higher levels of CDH2 (N-chaderin) when compared to other adhesion molecule. ONS-76 showed higher gene expression of CDH5 (VE-chaderin) and higher percentage of CD144/VE-chaderin positive cells when compared to other MB cell lines. All MB cell lines showed low percentage of CD34, CD45, CD31, CD133 positive cells and high percentage of CD44, CD105, CD106 and CD29 positive cells. The DAOY cell line showed the highest migration potential, the ONS-76 cell line showed the highest proliferative potential and only DAOY and ONS-76 cell lines showed tumorigenic potential in vivo. MB cell lines showed functional and molecular differences among them, which it should be considered by the researchers in choosing the most suitable cellular model according to the study proposal.