FERNANDA DE TOLEDO GONCALVES
Projetos de Pesquisa
Unidades Organizacionais
LIM/40 - Laboratório de Imunohematologia e Hematologia Forense, Hospital das Clínicas, Faculdade de Medicina
7 resultados
Resultados de Busca
Agora exibindo 1 - 7 de 7
- Ethnicity and Cutaneous Melanoma in the City of Sao Paulo, Brazil: A Case-Control Study(2012) LUIZ, Olinda C.; GIANINI, Reinaldo Jose; GONCALVES, Fernanda T.; FRANCISCO, Guilherme; FESTA-NETO, Cyro; SANCHES, Jose Antonio; GATTAS, Gilka J. F.; CHAMMAS, Roger; ELUF-NETO, JoseBackground: Over the last century the incidence of cutaneous melanoma has increased worldwide, a trend that has also been observed in Brazil. The identified risk factors for melanoma include the pattern of sun exposure, family history, and certain phenotypic features. In addition, the incidence of melanoma might be influenced by ethnicity. Like many countries, Brazil has high immigration rates and consequently a heterogenous population. However, Brazil is unique among such countries in that the ethnic heterogeneity of its population is primarily attributable to admixture. This study aimed to evaluate the contribution of European ethnicity to the risk of cutaneous melanoma in Brazil. Methodology/Principal Findings: We carried out a hospital-based case-control study in the metropolitan area of Sao Paulo, Brazil. We evaluated 424 hospitalized patients (202 melanoma patients and 222 control patients) regarding phenotypic features, sun exposure, and number of grandparents born in Europe. Through multivariate logistic regression analysis, we found the following variables to be independently associated with melanoma: grandparents born in Europe-Spain (OR = 3.01, 95% CI: 1.03-8.77), Italy (OR = 3.47, 95% CI: 1.41-8.57), a Germanic/Slavic country (OR = 3.06, 95% CI: 1.05-8.93), or >= 2 European countries (OR = 2.82, 95% CI: 1.06-7.47); eye color-light brown (OR = 1.99, 95% CI: 1.14-3.84) and green/blue (OR = 4.62; 95% CI 2.22-9.58); pigmented lesion removal (OR = 3.78; 95% CI: 2.21-6.49); no lifetime sunscreen use (OR = 3.08; 95% CI: 1.03-9.22); and lifetime severe sunburn (OR = 1.81; 95% CI: 1.03-3.19). Conclusions: Our results indicate that European ancestry is a risk factor for cutaneous melanoma. Such risk appears to be related not only to skin type, eye color, and tanning capacity but also to others specific characteristics of European populations introduced in the New World by European immigrants.
- Exploring the Role of Alcohol Metabolizing Genotypes in a 12-Week Clinical Trial of Naltrexone for Alcohol Use Disorder(2021) CASTALDELLI-MAIA, Joao M.; MALBERGIER, Andre; OLIVEIRA, Adriana B. P. de; AMARAL, Ricardo A.; NEGRAO, Andre B.; GONCALVES, Priscila D.; VENTRIGLIO, Antonio; BERARDIS, Domenico de; ANTONIO, Juliana de; FIRIGATO, Isabela; GATTAS, Gilka J. F.; GONCALVES, Fernanda de ToledoBackground: The efficacy of naltrexone in the treatment of alcohol use disorder (AUD) has been associated with a set of variables not directly related with the expression of opioid receptors. All the variables have been found to be highly associated with AUD itself or more severe clinical levels of AUD. Objectives: Given the high association between alcohol metabolizing enzymes (AME) and the outcome of AUD, the present study aims to investigate the role of AME genotype variants in the treatment of AUD with naltrexone. Methods: We carried out a 12-week longitudinal clinical trial based on the treatment of AUD patients with naltrexone (N = 101), stratified by different alcohol metabolization genotypes. Genotyping was performed after the inclusion of the patients in the study, based on the individual presence of single nucleotide polymorphisms (SNPs) in the ADH (alcohol dehydrogenase)1B (ADH1B*2 and ADH1B*3), ADH1C (ADHC*1) and ALDH (aldehyde dehydrogenase) 2 (ALDH2*2) genes. The outcome of alcohol use has been monitored employing the timeline follow-back during the treatment. Results: The ADH1C*1 (Ile350Val, rs698) and ALDH2*2 (Glu504Lys, rs671) polymorphisms were associated with a better response to naltrexone treatment, whereas the ADH1B*3 (Arg370Cys, rs2066702) allelic variant showed a negative outcome. Conclusions: The present study explores a genomic setting for the treatment of AUD with naltrexone. According to our findings, the association between ADH1C*1 and ALDH2*2 variants and better outcomes suggests a successful treatment, whereas the ADH1B*3 mutated allele might lead to an unsuccessful treatment. Further studies should be performed to investigate the relationship between alcohol metabolizing genotypes, the family history of alcohol use disorders and the effect of naltrexone on the outcomes. Genotyping may be a valuable tool for precision-medicine and individualized approach, especially in the context of alcohol use disorders. The small number of subjects was the main limitation of the present study.
- Health-related quality of life and functionality in primary caregiver of surviving pediatric COVID-19(2023) MARTINS, Fernanda; GONCALVES, Fernanda T.; IMAMURA, Marta; BARBOZA, Daniela S.; MATHEUS, Denise; PEREIRA, Maria Fernanda B.; MARQUES, Heloisa H. S.; CORREA-SILVA, Simone; MONTENEGRO, Marilia M.; FINK, Thais T.; LINDOSO, Livia; BAIN, Vera; FERREIRA, Juliana C. O. A.; ASTLEY, Camilla; MATSUO, Olivia M.; SUGUITA, Priscila; TRINDADE, Vitor; PAULA, Camila S. Y.; LITVINOV, Nadia; PALMEIRA, Patricia; GUALANO, Bruno; DELGADO, Artur F.; CARNEIRO-SAMPAIO, Magda; FORSAIT, Silvana; ODONE-FILHO, Vicente; ANTONANGELO, Leila; BATTISTELLA, Linamara R.; SILVA, Clovis A.ObjectivesTo prospectively assess health-related quality of life (HRQoL), global functionality, and disability in primary caregivers of surviving children and adolescents after COVID-19. MethodsA longitudinal observational study was carried out on primary caregivers of surviving pediatric post-COVID-19 patients (n = 51) and subjects without COVID-19 (n = 60). EuroQol five-dimension five-level questionnaire (EQ-5D-5L) and 12-question WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) were answered for both groups. The univariate regression analysis was carried out using SPSS (v 20) and significance was established at 5%. ResultsThe median duration between COVID-19 diagnosis in children and adolescents and longitudinal follow-up visits was 4.4 months (0.8-10.7). The median age of children and adolescents caregivers with laboratory-confirmed COVID-19 was similar to primary caregivers of subjects without laboratory-confirmed COVID-19 [43.2 (31.6-60.9) vs. 41.5 (21.6-54.8) years, p = 0.08], as well as similar female sex (p = 1.00), level of schooling (p = 0.11), social assistance program (p = 0.28), family income/month U$ (p = 0.25) and the number of household's members in the residence (p = 0.68). The frequency of slight to extreme problems (level & GE; 2) of the pain/discomfort domain according to EQ-5D-5L score was significantly higher in the former group [74% vs. 52.5%, p = 0.03, OR = 2.57 (1.14-5.96)]. The frequency of disability according to WHODAS 2.0 total score was similar to those without disability and unknown (p = 0.79); however, with a very high disability in both groups (72.5% and 78.3%). Further analysis of primary caregivers of children and adolescents with post-COVID-19 condition (PCC) [n = 12/51 (23%)] compared to those without PCC [n = 39/51(77%)] revealed no differences between demographic data, EQ-5D-5L and WHODAS 2.0 scores in both groups (p > 0.05). ConclusionWe longitudinally demonstrated that pain/discomfort were predominantly reported in approximately 75% of primary caregiver of COVID-19 patients, with high disability in approximately three-quarters of both caregiver groups. These data emphasized the prospective and systematic caregiver burden evaluation relevance of pediatric COVID-19.
- IL28B Gene Polymorphism SNP rs8099917 Genotype GG Is Associated with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) in HTLV-1 Carriers(2014) ASSONE, Tatiane; SOUZA, Fernando Vieira de; GAESTER, Karen Oliveira; FONSECA, Luiz Augusto Marcondes; LUIZ, Olinda do Carmo; MALTA, Fernanda; PINHO, Joao Renato Rebello; GONCALVES, Fernanda de Toledo; DUARTE, Alberto Jose da Silva; OLIVEIRA, Augusto Cesar Penalva de; CASSEB, JorgeBackground: The polymorphisms of IL28B have been described as important in the pathogenesis of infections caused by some viruses. The aim of this research was to evaluate whether IL28B gene polymorphisms (SNP rs8099917 and SNP rs12979860) are associated with HAM/TSP. Methods: The study included 229 subjects, classified according to their neurological status in two groups: Group I (136 asymptomatic HTLV-1 carriers) and Group II (93 HAM/TSP patients). The proviral loads were quantified, and the rs8099917 and rs12979860 SNPs in the region of IL28B-gene were analyzed by StepOnePlus Real-time PCR System. Results: A multivariate model analysis, including gender, age, and HTLV-1 DNA proviral load, showed that IL28B polymorphisms were independently associated with HAM/TSP outcome in rs12979860 genotype CT (OR = 2.03; IC95% = 0.96-4.27) and in rs8099917 genotype GG (OR = 7.61; IC95% = 1.82-31.72). Conclusion: Subjects with SNP rs8099917 genotype GG and rs12979618 genotype CT may present a distinct immune response against HTLV-1 infection. So, it seems reasonable to suggest that a search for IL28B polymorphisms should be performed for all HTLV-1-infected subjects in order to monitor their risk for disease development; however, since this is the first description of such finding in the literature, we should first replicate this study with more HTLV-1-infected persons to strengthen the evidence already provided by our results.
- Polymorphisms of CHRNA3 and CHRNA5: Head and neck cancer and cigarette consumption intensity in a Brazilian population(2019) SILVA, Mariana R.; GATTAS, Gilka J. F.; ANTONIO, Juliana De; FIRIGATO, Isabela; CURIONI, Otavio A.; GONCALVES, Fernanda de ToledoBackground: Cigarette consumption has been identified as the main non-etiological factor in head and neck cancer (HNC) development. One of the main compounds in cigarettes is nicotine, which binds directly to nicotine acetylcholine receptors (nAchRs) in the body, which are encoded by different genes of the CHRNA family. Polymorphisms in some of these genes have been studied in relation to the risk of HNC and cigarette consumption intensity. The aim of this study was to evaluate whether there were associations between the CHRNA3 (rs578776) and CHRNA5 (rs16969968) polymorphisms and HNC risk and between the polymorphisms and the intensity of cigarette consumption. Methods: A total of 1,067 individuals from Heliopolis Hospital in Sao Paulo were investigated, including 619 patients with HNC and 448 patients without diagnosed tumors. All participants answered a questionnaire about sociodemographic information and cigarette consumption data. The polymorphisms were determined by TaqMan genotyping by real-time PCR. Results: The polymorphisms studied, rs578776 (CHRNA3) and rs16969968 (CHRNA5), did not have an association with HNC risk, but the rs16969968 homozygous genotype was associated with increased cigarette consumption intensity (OR 1.93, 95% CI 1.05-3.58). Conclusion: The polymorphism CHRNA5 can be considered an indirect risk factor for neoplasms in these Brazilian samples when cigarette consumption increased.
- Growth hormone insensitivity with immune dysfunction caused by a STAT5B mutation in the south of Brazil: evidence for a founder effect(2017) SCALCO, Renata C.; GONCALVES, Fernanda T.; SANTOS, Hadassa C.; CARDENA, Mari M. S. G.; TONELLI, Carlos A.; FUNARI, Mariana F. A.; ARACAVA, Rosana M.; PEREIRA, Alexandre C.; FRIDMAN, Cintia; JORGE, Alexander A. L.Homozygous STAT5B mutations causing growth hormone insensitivity with immune dysfunction were described in 10 patients since 2003, including two Brazilian brothers from the south of Brazil. Our objectives were to evaluate the prevalence of their STAT5B mutation in this region and to analyze the presence of a founder effect. We obtained DNA samples from 1,205 local inhabitants, 48 relatives of the homozygous patients and four individuals of another affected family. Genotyping forSTAT5B c.424_427del mutation and for two polymorphic markers around it was done through fragment analysis technique. We also determined Y-chromosome and mtDNA haplotypes and genomic ancestry in heterozygous carriers. We identified seven families with STAT5B c.424_427del mutation, with 33 heterozygous individuals. The minor allelic frequency of this mutation was 0.29% in this population (confidence interval 95% 0.08-0.5%), which is significantly higher than the frequency of other pathogenic STAT5B allele variants observed in public databases (p < 0.001). All heterozygous carriers had the same haplotype present in the homozygous patients, found in only 9.4% of non-carriers (p < 0.001), supporting the existence of a founder effect. The Y-chromosome haplotype, mtDNA and genomic ancestry analysis indicated a European origin of this mutation. Our results provide compelling evidence for a founder effect of STAT5B c.424_427del mutation.
- Systemic cytokines and GlycA discriminate disease status and predict corticosteroid response in HTLV-1-associated neuroinflammation(2022) ASSONE, Tatiane; MENEZES, Soraya Maria; GONCALVES, Fernanda de Toledo; FOLGOSI, Victor Angelo; PRATES, Gabriela da Silva; DIERCKX, Tim; BRAZ, Marcos; SMID, Jerusa; HAZIOT, Michel E.; MARCUSSO, Rosa M. N.; DAHY, Flavia E.; VANDERLINDEN, Evelien; CLAES, Sandra; SCHOLS, Dominique; BRUHN, Roberta; MURPHY, Edward L.; OLIVEIRA, Augusto Cesar Penalva de; DAELEMANS, Dirk; VERCAUTEREN, Jurgen; CASSEB, Jorge; WEYENBERGH, Johan VanBackground: HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is an incapacitating neuroinflammatory disorder for which no disease-modifying therapy is available, but corticosteroids provide some clinical benefit. Although HAM/TSP pathogenesis is not fully elucidated, older age, female sex and higher proviral load are established risk factors. We investigated systemic cytokines and a novel chronic inflammatory marker, GlycA, as possible biomarkers of immunopathogenesis and therapeutic response in HAM/TSP, and examined their interaction with established risk factors. Patients and methods: We recruited 110 People living with HTLV-1 (PLHTLV-1, 67 asymptomatic individuals and 43 HAM/TSP patients) with a total of 946 person-years of clinical follow-up. Plasma cytokine levels (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-gamma, TNF) and GlycA were quantified by Cytometric Bead Array and (NMR)-N-1, respectively. Cytokine signaling and prednisolone response were validated in an independent cohort by nCounter digital transcriptomics. We used multivariable regression, machine learning algorithms and Bayesian network learning for biomarker identification. Results: We found that systemic IL-6 was positively correlated with both age (r = 0.50, p < 0.001) and GlycA (r = 0.45, p = 0.00049) in asymptomatics, revealing an 'inflammaging "" signature which was absent in HAM/TSP. GlycA levels were higher in women (p = 0.0069), but cytokine levels did not differ between the sexes. IFN-gamma (p = 0.007) and IL-17A (p = 0.0001) levels were increased in untreated HAM/TSP Multivariable logistic regression identified IL-17A and proviral load as independent determinants of clinical status, resulting in modest accuracy of predicting HAM/TSP status (64.1%), while a machine learning-derived decision tree classified HAM/TSP patients with 90.7% accuracy. Pre-treatment GlycA and TNF levels significantly predicted clinical worsening (measured by Osame Motor Disability Scale), independent of proviral load. In addition, a poor prednisolone response was significantly correlated with higher post-treatment IFN-gamma levels. Likewise, a transcriptomic IFN signaling score, significantly correlated with previously proposed HAM/TSP biomarkers (CASP5/CXCL10/FCGR1A/STAT1), was efficiently blunted by in vitro prednisolone treatment of PBMC from PLHTLV-1 and incident HAM/TSP. Conclusions: An age-related increase in systemic IL-6/GlycA levels reveals inflammaging in PLHTLV-1, in the absence of neurological disease. IFN-gamma and IL-17A are biomarkers of untreated HAM/TSP, while pre-treatment GlycA and TNF predict therapeutic response to prednisolone pulse therapy, paving the way for a precision medicine approach in HAM/TSP.