FERNANDA DE TOLEDO GONCALVES
Projetos de Pesquisa
Unidades Organizacionais
LIM/40 - Laboratório de Imunohematologia e Hematologia Forense, Hospital das Clínicas, Faculdade de Medicina
3 resultados
Resultados de Busca
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- Motor event-related synchronization as an inhibitory biomarker of pain severity, sensitivity, and chronicity in patients with knee osteoarthritis(2022) MARQUES, L. M.; BARBOSA, S. P.; PACHECO-BARRIOS, K.; GONCALVES, F. T.; IMAMURA, M.; BATTISTELLA, L. R.; SIMIS, M.; FREGNI, F.Objective: The study aimed to examine the clinical and neurophysiological predictors of motor event-related desynchronization (ERD) and synchronization (ERS) in patients with chronic pain due to knee osteoarthritis (KOA). Methods: We performed a cross-sectional analysis of our cohort study (DEFINE cohort), KOA arm, with 71 patients, including demographic, functionality, genetic and neurophysiological measures. ERD/ERS was evaluated during hand motor tasks (motor execution, active and passive observation, and imagery). Multivariate regression models were used to explore predictors of ERD/ERS. Results: Although we found an altered ERD/ERS pattern during motor execution and active observation, the ERS pattern could only be clearly differentiated after passive observation.‘. We found no predictors of ERD (excitatory biomarker). For ERS (inhibitory biomarker), our results showed that the main predictors differ across EEG frequency bands. Considering pain measures, we found that visual analogue scale (VAS, right knee) and chronicity of pain negatively predict low beta and high beta ERS, respectively. Pain threshold was positively correlated with alpha ERS, while 36-Item Short Form Survey (SF-36) emotional domain positively predicted beta ERS. Regarding transcranial magnetic stimulation (TMS) markers, intracortical inhibition (ICF) negatively predicted beta and low beta ERS, and left hemisphere cortical silent period (CSP) negatively predicted low beta ERS. Conclusion: Considering that higher power of ERS indicates a stronger cortical organization and inhibitory drive, our results show that limitation of activities due to emotional factors, lower pain threshold, higher VAS pain, and longer duration of pain are associated with lower ERS power (in alpha and beta frequencies), thus indicating a lower inhibitory drive. In the same direction, a lower inhibitory drive as indicated by higher ERS power is associated with higher ICF amplitude. Although there was a negative association between ERS and CSP, this may indicate that ICF values are adjusting CSP results. Our findings support the idea that a less organized cortical response as indicated by changes to the ERS is associated with higher pain correlates in subjects with KOA. © 2022
- 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.
- The copy number variation of GSTM1 as a promising prognostic factor of oral squamous cell carcinoma(2022) FIRIGATO, Isabela; LOPEZ, Rossana V. M.; CURIONI, Otavio A.; ANTONIO, Juliana De; GATTAS, Gilka J. F.; GONCALVES, Fernanda de ToledoObjective. The aim of this study was to investigate whether the copy number variation (CNV) of GSTM1 and GSTT1 is related to the occurrence of oral squamous cell carcinoma (OSCC) relapses, along the overall and progression-free survival of patients. Study Design. A total of 234 OSCC patients were recruited from the Heliopolis hospital and they were distributed among 4 groups according to the occurrence of OSCC relapses. Fisher exact test, odds ratio (OR), and 95% CI were determined to investigate the chances of OSCC progression. The overall and progression-free survival were analyzed by the Kaplan-Meier and Cox regression methods. Results. The CNV of GSTM1 analysis showed that one copy of the gene was associated with reduced chances of OSCC recurrences (OR 0.45; 95% CI 0.25-0.81) and decreased the risk of tumor progression (HR 0.50; 95% CI 0.33-0.75). Furthermore, one copy of GSTM1 was related to a better overall survival rate (HR 0.63; 95% CI 0.0.44-0.91). Regarding the CNV of GSTT1, no copies were associated with the chances of OSCC relapses, the overall survival, or the progression-free survival. Conclusions. The CNV of GSTM1 may be applied to predict OSCC relapses and aid the treatment management, which might improve the survival rates of patients.