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1.
Mol Biol Rep ; 50(5): 4301-4307, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36922454

RESUMO

BACKGROUND: In a previous study, our group observed that 68% of the osteosarcoma (OS) samples presented PRAME (Preferentially Expressed Antigen in Melanoma) gene expression. In this work, we propose to investigate quantitatively gene expression of PRAME in distinct patients groups. METHODS AND RESULTS: 61 osteosarcoma samples, from 3 distinct patients groups were selected for this study: (1) Patients younger than 10 years old at diagnosis, (2) Patients that had poor evolution of disease and (3) Patients that were in remission of disease and had treatment with no intercurrences) PRAME gene expression levels were obtained using quantitative Real-Time Polymerase Chain Reaction method (qRT-PCR). Clinical parameters were collected from patient's medical charts. Results demonstrated an increase in PRAME gene expression in all samples, with high variation in expression levels, when considering all samples and when analyzed in each group. In addition, no statistical difference was found when considering clinical data collected or patients groups. CONCLUSION: PRAME gene expression quantitative investigation did not bring any complementary information beyond of what had already been observed in other qualitative investigations published by our group, there is no relation between PRAME gene expression levels and disease evolution. However, the findings in this work contribute for validation PRAME gene expression as a good biomarker to OS, which, in the future, may allow identification circulating tumor cell or molecules to contribute with early diagnostic of metastasis, a genuine problem in OS that determinate flattening in survival curves.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Criança , Antígenos de Neoplasias/genética , Reação em Cadeia da Polimerase em Tempo Real , Osteossarcoma/genética , Fatores de Transcrição/genética , Neoplasias Ósseas/genética , Biomarcadores Tumorais
2.
Int J Mol Sci ; 24(6)2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36982681

RESUMO

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. In recent decades, OS treatment has reached a plateau and drug resistance is still a major challenge. Therefore, the present study aimed to analyze the expression of the genes related to pharmacogenetics in OS. The expression of 32 target genes in 80 paired specimens (pre-chemotherapeutic primary tumor, post-chemotherapeutic primary tumor and pulmonary metastasis) obtained from 33 patients diagnosed with OS were analyzed by the real-time PCR methodology. As the calibrators (control), five normal bone specimens were used. The present study identified associations between the OS outcome and the expression of the genes TOP2A, DHFR, MTHFR, BCL2L1, CASP3, FASLG, GSTM3, SOD1, ABCC1, ABCC2, ABCC3, ABCC5, ABCC6, ABCC10, ABCC11, ABCG2, RALBP1, SLC19A1, SLC22A1, ERCC1 and MSH2. In addition, the expression of the ABCC10, GGH, GSTM3 and SLC22A1 genes were associated with the disease event, and the metastasis specimens showed a high expression profile of ABCC1, ABCC3 and ABCC4 genes and a low expression of SLC22A1 and ABCC10 genes, which is possibly an important factor for resistance in OS metastasis. Therefore, our findings may, in the future, contribute to clinical management as prognostic factors as well as possible therapeutic targets.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Criança , Adolescente , Humanos , Farmacogenética , Transcriptoma , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Osteossarcoma/patologia , Proteína 2 Associada à Farmacorresistência Múltipla , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Regulação Neoplásica da Expressão Gênica
3.
Nutr J ; 21(1): 66, 2022 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-36273143

RESUMO

BACKGROUND: A nutrient-poor and hypocaloric diet may be associated with lower handgrip strength (HGS), whereas a high-quality or balanced diet may be associated with higher HGS. However, no study has used the NOVA system for classifying food by their degree of processing. OBJECTIVE: To analyze the association between food consumption according to the degree of food processing and HGS in Brazilian teenagers. METHODS: This cross-sectional study included teenagers aged 18 and 19 years old from the 1997/98 São Luís' birth cohort, Maranhão, Brazil. HGS (kilogram-force) was measured via a Jamar Plus + dynamometer. Food consumption was assessed using a semiquantitative food frequency questionnaire. The energy intake of culinary preparations (unprocessed or minimally processed food and processed culinary ingredients), processed, and ultra-processed foods was evaluated in percentages and categorized in tertiles. The associations between each food group intake and HGS was estimated via crude and adjusted linear regression models. A directed acyclic graph was used to identify confounding factors. RESULTS: We evaluated 2,433 teenagers, 52.1% of which were girls. For boys, adjusted analysis showed an association between the highest HGS and the 3rd tertile of culinary preparation consumption (ß: 1.95; 95%CI: 0.80; 3.10) and between the lowest HGS and the 3rd tertile of ultra-processed food consumption (ß: -2.25; 95%CI: -3.40; -1.10). Among girls, the consumption of culinary preparations in the 3rd tertile was associated with higher HGS (ß: 0.76; 95%CI: 0.05; 1.46). CONCLUSIONS: Higher consumption of culinary preparations and lower consumption of ultra-processed foods can contribute to reduce the chance of lower HGS in adult life. Interventions to promote the development and preservation of muscle strength should include dietary recommendations.


Assuntos
Dieta Redutora , Força da Mão , Adulto , Masculino , Feminino , Adolescente , Humanos , Adulto Jovem , Inquéritos Nutricionais , Estudos Transversais , Obesidade , Fast Foods
4.
BMC Pregnancy Childbirth ; 22(1): 801, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319959

RESUMO

OBJECTIVE: To assess the direct, indirect, and total effects of violence during pregnancy on perinatal outcomes, and to evaluate the effect of violence as a moderator of the mediated relationship of depression with perinatal outcomes. METHODS: Data was collected from the prenatal study and follow-ups of the BRISA cohort, São Luís, Maranhão, Brazil. The perinatal outcomes investigated were: birth weight (BW), intrauterine growth restriction (IUGR) and gestational age (GA). Violence against women was evaluated using the World Health Organization Violence against Women instrument (Violence during pregnancy - regardless of the type of violence; Physical violence during pregnancy; Psychological violence during pregnancy). Depressive symptoms during pregnancy were evaluated as a mediating variable. Moderated mediation analysis was performed to estimate the effects of violence and depression on perinatal outcomes. RESULTS: Three types of violence analyzed by depression had an indirect effect in BW and GA. None of the types of violence showed an association with IUGR. All types of violence analyzed showed a moderated mediation effect with BW and GA. Only among women who experienced violence were birth weight and gestational age lower the higher the values of depressive symptoms. CONCLUSION: Violence and depression are only associated with lower BW and GA when they occur simultaneously.


Assuntos
Depressão , Análise de Mediação , Gravidez , Feminino , Humanos , Peso ao Nascer , Brasil , Retardo do Crescimento Fetal , Violência
5.
Global Health ; 18(1): 81, 2022 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-36123696

RESUMO

BACKGROUND: The use of telemedicine, or the provision of healthcare and communication services through distance-based technologies, has increased substantially since the 2019 novel coronavirus (COVID-19) pandemic. However, it is still unclear what are the innovative features of the widespread use of such modality, its forms of employment and the context in which it is used across pluralist health systems, particularly in low- and middle-income settings. We have sought to provide empirical evidence on the above issues by analysing the responses of medical doctors in a representative cross-sectional survey in two states in Brazil: São Paulo and Maranhão. METHODS: We analysed the responses of 1,183 physicians to a survey on the impact of COVID-19 on their livelihood and working practice. Two independent samples per state were calculated based on a total of 152,511 active medical registries in São Paulo and Maranhão. Proportional stratified sampling was performed and the distributions for gender, age, state and location of address (capital or countryside) were preserved. The survey contained questions on the frequency of physicians' employment of telemedicine services; the specific activities where these were employed, and; the forms in which the pandemic had influenced the adoption or consolidation of this technology. We performed descriptive and univariate analysis based on the chi-square test or Fisher's exact test for the qualitative data, and the Mann-Whitney test in the quantitative cases. Data were shown as absolute frequency and proportion with a 95% confidence interval. RESULTS: In our sample of physicians, telemedicine was employed as a form of clinical collaboration by most doctors (76.0%, 95 CI 73.6-78.5), but only less than a third of them (30.6%, 95 CI 28.0-33.3) used it as a modality to provide healthcare services. During the pandemic, telemedicine was used predominantly in COVID-19-related areas, particularly for hospital-based in-patient services, and in private clinics and ambulatory settings. Male, younger doctors used it the most. Doctors in São Paulo employed telemedicine more frequently than in Maranhão (p < 0.001), in urban settings more than in rural areas (p < 0.001). Approximately three-quarters of doctors in large hospitals reported using telemedicine services (78.3%, 95 CI 75.9-80.6), followed by doctors working for smaller private clinics (66.4%, 95 CI 63.7-69.1), and by a smaller proportion of primary care doctors (58.4%, 95 CI 55.6-61.2). CONCLUSIONS: Our study suggests that telemedicine may have helped ensure and expand the range of communication and healthcare services in low- and middle-income settings during the COVID-19 pandemic. However, the modality appears to lend itself to be disproportionally used by doctors working in specific, priviledged sections of pluralistic health systems, and presumably by patients seeking care there. Regulation and incentives will be required to support the use of the technology across health systems in low- and middle-income countries in order to increase access to services for less disadvantaged populations.


Assuntos
COVID-19 , Médicos , Telemedicina , Brasil/epidemiologia , COVID-19/epidemiologia , Estudos Transversais , Humanos , Masculino , Pandemias
6.
J Neurooncol ; 155(1): 13-23, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34570300

RESUMO

PURPOSE: Ependymoma (EPN) accounts for approximately 10% of all primary central nervous system (CNS) tumors in children and in most cases, chemotherapy is ineffective and treatment remains challenging. We investigated molecular alterations, with a potential prognostic marker and therapeutic target in EPNs of childhood and adolescence, using a next-generation sequencing (NGS) panel specific for pediatric neoplasms. METHODS: We selected 61 samples with initial diagnosis of EPN from patients treated at Pediatric Oncology Institute-GRAACC/UNIFESP. All samples were divided according to the anatomical compartment of the CNS - 42 posterior fossa (PF), 14 supratentorial (ST), and five spinal (SP). NGS was performed to identify somatic genetic variants in tumor samples using the Oncomine Childhood Cancer Research Assay® (OCCRA®) panel, from Thermo Fisher Scientific®. RESULTS: Genetic variants were identified in 24 of 61 (39.3%) tumors and over 90% of all variants were pathogenic or likely pathogenic. The most commonly variants detected were in CIC, ASXL1, and JAK2 genes and have not been reported in EPN yet. MN1-BEND2 fusion, alteration recently described in a new CNS tumor type, was identified in one ST sample that was reclassified as astroblastoma. Additionally, YAP1-MAMLD1 fusion, a rare event associated with good outcome in ST-EPN, was observed in two patients diagnosed under 2 years old. CONCLUSIONS: Molecular profiling by the OCCRA® panel showed novel alterations in pediatric and adolescent EPNs, which highlights the clinical importance in identifying genetic variants for patients' prognosis and therapeutic orientation.


Assuntos
Ependimoma , Sequenciamento de Nucleotídeos em Larga Escala , Adolescente , Neoplasias do Sistema Nervoso Central/genética , Criança , Pré-Escolar , Ependimoma/genética , Humanos , Lactente , Neoplasias Supratentoriais , Fatores de Transcrição
7.
Neuropediatrics ; 52(1): 34-43, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33111304

RESUMO

BACKGROUND: Little information on gross motor function of congenital Zika syndrome (CZS) children is available. OBJECTIVES: To evaluate gross motor function in CZS children aged up to 3 years, and its associated factors and changes in a minimum interval of 6 months. METHODS: One hundred children with CZS and cerebral palsy (36 with confirmed and 64 with presumed CZS) were evaluated with the Gross Motor Function Classification System (GMFCS) and Gross Motor Function Measure (GMFM-88/GMFM-66). Forty-six were reevaluated. Wilcoxon tests, Wilcoxon tests for paired samples, percentile scores, and score changes were performed. RESULTS: Clinical and socioeconomic characteristics (except maternal age), GMFM scores and GMFCS classification of confirmed and probable cases, which were analyzed together, were similar. The mean age was 25.6 months (±5.5); the median GMFM-88 score was 8.0 (5.4-10.8); and the median GMFM-66 score was 20.5 (14.8-23.1); 89% were classified as GMFCS level V. Low economic class, microcephaly at birth, epilepsy, and brain parenchymal volume loss were associated with low GMFM-66 scores. The median GMFM-66 percentile score was 40 (20-55). On the second assessment, the GMFM-66 scores in two GMFCS level I children and one GMFCS level IV child improved significantly. In one GMFCS level III child, one GMFCS level IV child, and the group of GMFCS level V children, no significant changes were observed. CONCLUSIONS: Almost all CZS children had severe cerebral palsy; in the third year of life, most presented no improvement in gross motor function and were likely approaching their maximal gross motor function potential.


Assuntos
Paralisia Cerebral/fisiopatologia , Epilepsia/fisiopatologia , Destreza Motora/fisiologia , Malformações do Sistema Nervoso/fisiopatologia , Infecção por Zika virus/congênito , Infecção por Zika virus/fisiopatologia , Paralisia Cerebral/etiologia , Pré-Escolar , Epilepsia/etiologia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Microcefalia/etiologia , Microcefalia/fisiopatologia , Malformações do Sistema Nervoso/etiologia , Índice de Gravidade de Doença , Classe Social , Infecção por Zika virus/complicações
8.
Childs Nerv Syst ; 37(1): 137-145, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32591873

RESUMO

PURPOSE: In neurogenesis, ASPM (abnormal spindle-like microcephaly-associated) gene is expressed mainly in the ventricular zone of posterior fossa and is the major determinant in the cerebral cortex. Besides its role in embryonic development, ASPM overexpression promotes tumor growth, including central nervous system (CNS) tumors. This study aims to investigate ASPM expression levels in most frequent posterior fossa brain tumors of childhood and adolescence: medulloblastoma (MB), ependymoma (EPN), and astrocytoma (AS), correlating them with clinicopathological characteristics and tumor solid portion size. METHODS: Quantitative reverse transcription (qRT-PCR) is used to quantify ASPM mRNA levels in 80 pre-treatment tumor samples: 28 MB, 22 EPN, and 30 AS. The tumor solid portion size was determined by IOP-GRAACC Diagnostic Imaging Center. We correlated these findings with clinicopathological characteristics and tumor solid portion size. RESULTS: Our results demonstrated that ASPM gene was overexpressed in MB (p = 0.007) and EPN (p = 0.0260) samples. ASPM high expression was significantly associated to MB samples from patients with worse overall survival (p = 0.0123) and death due to disease progression (p = 0.0039). Interestingly, two patients with AS progressed toward higher grade showed ASPM overexpression (p = 0.0046). No correlation was found between the tumor solid portion size and ASPM expression levels in MB (p = 0.1154 and r = - 0.4825) and EPN (p = 0.1108 and r = - 0.3495) samples. CONCLUSION: Taking in account that ASPM gene has several functions to support cell proliferation, as mitotic defects and premature differentiation, we suggest that its overexpression, presumably, plays a critical role in disease progression of posterior fossa brain tumors of childhood and adolescence.


Assuntos
Neoplasias Cerebelares , Neoplasias Infratentoriais , Microcefalia , Adolescente , Expressão Gênica , Humanos , Neoplasias Infratentoriais/diagnóstico por imagem , Neoplasias Infratentoriais/genética , Proteínas do Tecido Nervoso/genética
9.
Ann Diagn Pathol ; 46: 151482, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32145682

RESUMO

Osteosarcoma (OS) is a class of cancer originating from the bone, affecting mainly children and young adults. Our previous study showed that MAPK7 gene overexpression was significantly associated with tumor progression, poor treatment response, and worse overall survival, suggesting that MAPK7 could play an important role in OS tumorigenesis. We have investigated if MAPK7 overexpression was a result of any genomic changes in OS tumor specimens. We identified five SNPs (Single Nucleotide Polymorphism) previously described in databases, dbSNP and COSMIC, and identified two single nucleotide substitution not yet described. We found, in prechemotherapy specimens, a significant association of MAPK7 rs2233072G allele variant with metastasis at diagnosis and relapse (0.0909 and 0.0455, respectively). In post-chemotherapy, rs1054206GG specimen's genotype was associated with osteoblastic histological type (P= 0.0249) and presented decreased MAPK7 gene expression when compared with pre-chemotherapy specimens of same patients (P = 0.0095). Interestingly, it was observed some SNPs genotype exchange after chemotherapy. Our data indicated that MAPK7 gene expression associated with genotype exchange after chemotherapy, and these SNPs associated with important clinical parameters might be a valuable indicator for predicting in OS.


Assuntos
Neoplasias Ósseas/genética , Predisposição Genética para Doença/genética , Proteína Quinase 7 Ativada por Mitógeno/genética , Osteossarcoma/genética , Polimorfismo de Nucleotídeo Único/efeitos dos fármacos , Neoplasias Ósseas/tratamento farmacológico , Genótipo , Humanos , Osteossarcoma/tratamento farmacológico , Prognóstico
10.
Pediatr Blood Cancer ; 66(7): e27707, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30924609

RESUMO

BACKGROUND: The incidence of thyroid carcinoma has increased in most populations, including pediatric patients. The increase is almost exclusively due to an increase in the incidence of papillary thyroid carcinoma (PTC). Genetic alterations leading to mitogen-activated protein kinase (MAPK) pathway activation are highly prevalent in PTC, with BRAF V600E mutation being the most common event in adult PTC. Although a lower prevalence of BRAF V600E had been reported among pediatric patients, a higher prevalence of BRAF fusion has been identified in both radiation-exposed and sporadic pediatric PTC. However, little is known about the prognostic implications of BRAF fusions in pediatric PTC. PROCEDURE: In this study, we investigated the prevalence of BRAF alterations (AGK-BRAF fusion and BRAF V600E mutation) in a large set of predominantly sporadic pediatric PTC cases and correlate with clinicopathological features. Somatic AGK-BRAF fusion was investigated by RT-PCR and confirmed by FISH break-apart. The BRAF V600E mutation was screened using Sanger sequencing. RESULTS: AGK-BRAF fusion, found in 19% of pediatric PTC patients, was associated with distant metastasis and younger age. Conversely, the BRAF V600E, found in 15% of pediatric PTC patients, was correlated with older age and larger tumor size. CONCLUSION: Collectively, our results advance knowledge concerning genetic bases of pediatric thyroid carcinoma, with potential implications for diagnosis, prognosis, and therapeutic approaches.


Assuntos
Mutação de Sentido Incorreto , Proteínas de Fusão Oncogênica , Fosfotransferases (Aceptor do Grupo Álcool) , Proteínas Proto-Oncogênicas B-raf , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Adolescente , Fatores Etários , Substituição de Aminoácidos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Metástase Neoplásica , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Câncer Papilífero da Tireoide/epidemiologia , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia
11.
Mol Carcinog ; 56(6): 1630-1641, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28112450

RESUMO

Osteosarcoma (OS) is the most frequent primary bone tumor that affect children and adolescents. This tumor is highly aggressive with high risk of metastasis and the implementation of new drugs has not been successful. The search for biomarkers or new therapeutic targets is urgently needed and can help in advances of OS treatment. MAPKs are major signaling transduction molecules that play an important role in regulating a variety of cellular responses. DUSP1 is a phosphatase that dephosphorylates the MAPKs. Both MAPKs and DUSPs have been implicated as major modulators of critical signaling pathways that are dysregulated in various diseases. In a previous study, we found an increase in MAPK7 gene expression contributed for worst overall survival and treatment response. We analyzed gene expression of MAPK pathways that participate in MAPK7 regulation, and DUSP1 gene using paired 28 pre/post-chemotherapy and 12 metastasis OS samples. To understand the DUSP1 role in the pathogenesis of OS, we assessed the function of DUSP1 in four OS cell lines through a series of cellular assays combined with gene silencing technique. Our findings showed increased MAP2K6, MAP4K3, and DUSP1 gene expression in post-chemotherapy OS samples presenting poor prognosis. We also found that the suppression of DUSP1 gene expression resulted in decreased proliferation, migration, and invasion in OS cells. These results suggest that members of MAPK family may be possible prognostic markers in OS and DUSP1 has a relevant role in the OS pathogenesis and can be an attractive therapeutic target in new strategies of OS treatment.


Assuntos
Neoplasias Ósseas/genética , Osso e Ossos/patologia , Fosfatase 1 de Especificidade Dupla/genética , Regulação Neoplásica da Expressão Gênica , Sistema de Sinalização das MAP Quinases , Osteossarcoma/genética , Adolescente , Adulto , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Linhagem Celular Tumoral , Criança , Pré-Escolar , Fosfatase 1 de Especificidade Dupla/metabolismo , Feminino , Humanos , Lactente , MAP Quinase Quinase 6/genética , Masculino , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Invasividade Neoplásica/prevenção & controle , Osteossarcoma/diagnóstico , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Prognóstico , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais , Adulto Jovem
12.
Ann Vasc Surg ; 41: 214-224, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28163177

RESUMO

BACKGROUND: To evaluate the expression of immunohistochemical markers of tissue ischemia (iNOS, eNOS, and HSP70) in a vascular damage control experimental model to determine if a venous temporary vascular shunt insertion leads to a better limb perfusion when compared with the ligature of the injured vein. METHODS: Experimental study in male Sus Scrofa weighting 40 Kg. Animals were distributed into 5 groups: group 1 animals were submitted to right external iliac artery (EIA) shunting and right external iliac vein (EIV) ligation; group 2 animals were submitted to right EIA shunting and right EIV shunting; group 3 animals were submitted to right EIV ligation; group 4 animals were submitted to right EIV shunting; group 5 animals were not submitted to vascular shunting or venous ligation. Transonic Systems flowmeters were used to measure vascular flow on right and left external iliac vessels, and i-STAT (Abbot) portable blood analyzer was used for EIVs blood biochemical analysis. An initial baseline register of invasive arterial pressure, iliac vessels flow, and venous blood analysis was performed. Arterial pressure and iliac vessels flow were taken immediately after right iliac vessels shunting or ligation. Then, hemorrhagic shock was induced by continuous 20 mL/min blood withdraw from the external right jugular vein whereas arterial blood pressure and iliac vessels flow registers were taken every 10 min, and blood samples from EIVs were obtained every 30 min until the vascular flow through right EIA (or through the shunt inserted into the right EIV for group 4 animals) became inexistent or until the animal's death. After the end of the experiments, bilateral hind limb's biopsies were obtained for immunohistochemical analysis. Using image editing and analysis software, the expression of iNOS, eNOS, and HSP70 (3 well-known ischemic associated immunohistochemical markers) was assessed. The mean expression of each marker in the right hind limb was compared between groups. For statistical analysis, Microsoft Office Excel 2007 and BioEstat 5.0 (2007) were used. RESULTS: Immunohistochemical analysis showed no difference regarding the iNOS expression; nevertheless, both eNOS and HSP70 expression were statistically more intense (P < 0.05) on group 1 (eNOS = 1.32; HSP70 = 15.05) than on group 2 (eNOS = 0.018; HSP70 = 8.56). CONCLUSIONS: The higher expression of eNOS and HSP70 in the right hind limbs of group 1 animals (arterial shunt and venous ligature) than group 2 animals (arterial shunt and venous shunt) suggests that venous ligation is associated with more intense ischemic histological findings than venous shunting.


Assuntos
Artéria Ilíaca/cirurgia , Veia Ilíaca/cirurgia , Imuno-Histoquímica , Isquemia/cirurgia , Músculo Esquelético/irrigação sanguínea , Procedimentos Cirúrgicos Vasculares , Lesões do Sistema Vascular/cirurgia , Animais , Pressão Arterial , Velocidade do Fluxo Sanguíneo , Modelos Animais de Doenças , Proteínas de Choque Térmico HSP70/metabolismo , Membro Posterior , Artéria Ilíaca/patologia , Artéria Ilíaca/fisiopatologia , Veia Ilíaca/patologia , Veia Ilíaca/fisiopatologia , Isquemia/metabolismo , Isquemia/patologia , Isquemia/fisiopatologia , Ligadura , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fluxo Sanguíneo Regional , Choque Hemorrágico/fisiopatologia , Sus scrofa , Fatores de Tempo , Lesões do Sistema Vascular/metabolismo , Lesões do Sistema Vascular/patologia , Lesões do Sistema Vascular/fisiopatologia
13.
Emerg Infect Dis ; 22(11): 1953-1956, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27767931

RESUMO

We report the early growth and neurologic findings of 48 infants in Brazil diagnosed with probable congenital Zika virus syndrome and followed to age 1-8 months. Most of these infants had microcephaly (86.7%) and craniofacial disproportion (95.8%). The clinical pattern included poor head growth with increasingly negative z-scores, pyramidal/extrapyramidal symptoms, and epilepsy.


Assuntos
Malformações do Sistema Nervoso/epidemiologia , Malformações do Sistema Nervoso/etiologia , Complicações Infecciosas na Gravidez , Infecção por Zika virus/complicações , Zika virus , Peso ao Nascer , Pesos e Medidas Corporais , Brasil/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Malformações do Sistema Nervoso/diagnóstico , Avaliação de Resultados da Assistência ao Paciente , Fenótipo , Gravidez , Infecção por Zika virus/virologia
14.
BMC Med ; 14(1): 128, 2016 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-27580745

RESUMO

BACKGROUND: Risk prediction models for colorectal cancer (CRC) detection in symptomatic patients based on available biomarkers may improve CRC diagnosis. Our aim was to develop, compare with the NICE referral criteria and externally validate a CRC prediction model, COLONPREDICT, based on clinical and laboratory variables. METHODS: This prospective cross-sectional study included consecutive patients with gastrointestinal symptoms referred for colonoscopy between March 2012 and September 2013 in a derivation cohort and between March 2014 and March 2015 in a validation cohort. In the derivation cohort, we assessed symptoms and the NICE referral criteria, and determined levels of faecal haemoglobin and calprotectin, blood haemoglobin, and serum carcinoembryonic antigen before performing an anorectal examination and a colonoscopy. A multivariate logistic regression analysis was used to develop the model with diagnostic accuracy with CRC detection as the main outcome. RESULTS: We included 1572 patients in the derivation cohort and 1481 in the validation cohorts, with a 13.6 % and 9.1 % CRC prevalence respectively. The final prediction model included 11 variables: age (years) (odds ratio [OR] 1.04, 95 % confidence interval [CI] 1.02-1.06), male gender (OR 2.2, 95 % CI 1.5-3.4), faecal haemoglobin ≥20 µg/g (OR 17.0, 95 % CI 10.0-28.6), blood haemoglobin <10 g/dL (OR 4.8, 95 % CI 2.2-10.3), blood haemoglobin 10-12 g/dL (OR 1.8, 95 % CI 1.1-3.0), carcinoembryonic antigen ≥3 ng/mL (OR 4.5, 95 % CI 3.0-6.8), acetylsalicylic acid treatment (OR 0.4, 95 % CI 0.2-0.7), previous colonoscopy (OR 0.1, 95 % CI 0.06-0.2), rectal mass (OR 14.8, 95 % CI 5.3-41.0), benign anorectal lesion (OR 0.3, 95 % CI 0.2-0.4), rectal bleeding (OR 2.2, 95 % CI 1.4-3.4) and change in bowel habit (OR 1.7, 95 % CI 1.1-2.5). The area under the curve (AUC) was 0.92 (95 % CI 0.91-0.94), higher than the NICE referral criteria (AUC 0.59, 95 % CI 0.55-0.63; p < 0.001). On the basis of the thresholds with 90 % (5.6) and 99 % (3.5) sensitivity, we divided the derivation cohort into three risk groups for CRC detection: high (30.9 % of the cohort, positive predictive value [PPV] 40.7 %, 95 % CI 36.7-45.9 %), intermediate (29.5 %, PPV 4.4 %, 95 % CI 2.8-6.8 %) and low (39.5 %, PPV 0.2 %, 95 % CI 0.0-1.1 %). The discriminatory ability was equivalent in the validation cohort (AUC 0.92, 95 % CI 0.90-0.94; p = 0.7). CONCLUSIONS: COLONPREDICT is a highly accurate prediction model for CRC detection.


Assuntos
Antígeno Carcinoembrionário/análise , Neoplasias Colorretais , Fezes , Hemoglobinas/análise , Complexo Antígeno L1 Leucocitário/análise , Idoso , Biomarcadores/análise , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Estudos Transversais , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Imunoquímica/métodos , Masculino , Modelos Teóricos , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco/métodos
18.
J Neurooncol ; 117(2): 235-42, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24532263

RESUMO

Low-grade astrocytomas comprise about 30 % of the central nervous system tumors in children. Several investigations have searched a correlation between the BRAF gene fusions alterations and mutations at IDH1 and IDH2 genes in low grade pediatric astrocytomas. This study identified the expression of KIAA1549-BRAF fusion gene and BRAF V600E mutation, mutations at exon 4 of the IDH1 and IDH2 genes in samples of pilocytic astrocytomas (PA) and grade-II astrocytomas (A-II) pediatric patients. The correlation between these alterations and the clinical profile of the patients was also evaluated. Eighty-two samples of low-grade astrocytomas (65 PA and 17 A-II) were analyzed by PCR and sequencing for each of the targets identified. We identified the KIAA1549-BRAF fusion transcript in 45 % of the samples. BRAF V600E and BRAFins598T mutations were detected in 7 and 1 % of the samples, respectively. Mutations in the R132/R172 residues of the IDH1/IDH2 genes were detected in only two samples, and the G105G polymorphism (rs11554137:C>T) was identified in ten patients. Additionally, we observed two mutations out of the usual hotspots at IDH1 and IDH2 genes. We observed a smaller frequency of mutations in IDHs genes than previously described, but since the prior studies were composed of adult or mixed (adults and children) samples, we believe that our results represent a relevant contribution to the growing knowledge in low grade childhood astrocytomas.


Assuntos
Astrocitoma/genética , Isocitrato Desidrogenase/genética , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas B-raf/genética , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Gradação de Tumores , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
19.
BMC Pregnancy Childbirth ; 14: 266, 2014 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-25108701

RESUMO

BACKGROUND: Over the last decades there has been a reduction of social inequalities in Brazil, as well as a strong expansion of health services, including prenatal care. The objective of the present study was to estimate the rate of inadequate prenatal care utilization and its associated factors in São Luís, Brazil, in 2010 and to determine whether there was a reduction of inequity in prenatal care use by comparing the present data to those obtained from a previous cohort started in 1997/98. METHODS: Data from the BRISA (Brazilian birth cohort studies of Ribeirão Preto and São Luís) population-based cohort, which started in 2010 (5067 women), were used. The outcome variable was the inadequate utilization of prenatal care, classified according to the recommendations of the Brazilian Ministry of Health. The explanatory variables were organized into three hierarchical levels based on the Andersen's behavioral model of the use of health services: predisposing, enabling and need factors. RESULTS: Only 2.0% of the women did not attend at least one prenatal care visit. The rate of inadequate prenatal care utilization was 36.7%. Despite an improved adequacy of prenatal care use from 47.3% in 1997/98 to 58.2% in 2010, social inequality persisted: both low maternal schooling (prevalence ratio (PR) = 2.78; 95% confidence interval (95% CI) 2.23-3.47 for 0 to 4 years of study) and low family income, less than 0.5 monthly minimum wage per capita (PR = 1.37; 95% CI 1.22-1. 54), continued to be associated with higher rates of inadequate prenatal care utilization. Racial disparity regarding adequate utilization of prenatal services was detected, with black (PR = 1.19; 95% CI 1.04-1.36) and mulatto (PR = 1.14; 95% CI 1.02-1.26) women showing higher rates of inadequate use. On the other hand, women covered by the FHP - Family Health Program (PR = 0.92; 95% CI 0.85-0.98) showed a lower rate of inadequate prenatal care utilization. CONCLUSIONS: Despite strong expansion of health services and expressive improvements in adequate prenatal care use and social indicators, inequalities in prenatal care use still persist. The FHP seems to be effective in reducing inadequate prenatal care utilization.


Assuntos
Programas Governamentais , Disparidades em Assistência à Saúde/tendências , Cuidado Pré-Natal/estatística & dados numéricos , Cuidado Pré-Natal/tendências , Adulto , Consumo de Bebidas Alcoólicas , População Negra/estatística & dados numéricos , Brasil , Estudos Transversais , Feminino , Disparidades em Assistência à Saúde/etnologia , Humanos , Renda , Mães/educação , Gravidez , Fumar , Adulto Jovem
20.
BMC Pregnancy Childbirth ; 14: 66, 2014 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-24521235

RESUMO

BACKGROUND: Violence against pregnant women has been associated with gestational and perinatal disorders. Psychological violence is the type least investigated and its associated factors have been little studied. The present study was conducted in order to estimate prevalence rates and analyze the factors associated with exclusive and recurrent psychological violence in the municipality of São Luís, Brazil. METHODS: Data regarding 982 pregnant women, aged from 14 to 45 years, interviewed in 2010 and 2011 in a prenatal cohort were used. A self-applied questionnaire was used to screen for violence. Pregnant women submitted to physical and sexual violence were excluded from the analysis of factors associated with exclusive psychological violence. Prevalence ratios and 95% confidence intervals were estimated by a Poisson regression model with a hierarchical approach at three levels. At level 1 of the theoretical-conceptual model, we analyzed demographic and socioeconomic characteristics and variables that express gender inequalities; at level 2, we analyzed social support received by the women, and at level 3, the life experiences of the pregnant women. RESULTS: Prevalence rate of exclusive psychological violence was 41.6% and of recurrent violence was 32.6%. Exclusive psychological violence was associated with pregnant women's age of 14 to 18 years (PR: 1.32 95% CI: 1.04 - 1.70), pregnant women's schooling superior to that of her intimate partner (PR: 1.54 95% CI: 1.09 - 2.16), inadequate social affective support/positive social interaction (PR: 1.34 95% CI: 1.11 - 1.62), use of illicit drugs by the pregnant women (PR: 1.80 95% CI: 1.16 - 2.81) and having had six or more intimate partners in life (PR: 1.52 95% CI: 1.18 - 1.96). Recurrent exclusive psychological violence was associated with inadequate social affective support/positive social interaction (PR: 1.47 95% CI: 1.15 - 1.87), use of illicit drugs by the pregnant women (PR: 2,28 95% CI: 1,40 - 3,71) and having had six or more intimate partners in life (PR: 1.47 95% CI: 1.06 - 2.03). CONCLUSIONS: Psychological violence was a common phenomenon in this population of pregnant women that was associated with gender inequalities, inadequate social support and illicit drug use and should be routinely investigated during prenatal visits at health care services.


Assuntos
Violência Doméstica/psicologia , Violência Doméstica/estatística & dados numéricos , Gestantes/psicologia , Estresse Psicológico/epidemiologia , Adolescente , Adulto , Fatores Etários , Brasil/epidemiologia , Escolaridade , Feminino , Humanos , Drogas Ilícitas , Pessoa de Meia-Idade , Gravidez , Prevalência , Recidiva , Parceiros Sexuais , Apoio Social , Estresse Psicológico/psicologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Inquéritos e Questionários , Adulto Jovem
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