Impact of TGF-ß1 -509C/T and 869T/C polymorphisms on glioma risk and patient prognosis

Transforming growth factor beta (TGF-ß) plays an important role in carcinogenesis. Two polymorphisms in the TGF-ß1 gene (-509C/T and 869T/C) were described to influence susceptibility to gastric and breast cancers. The 869T/C polymorphism was also associated with overall survival in breast cancer patients. In the present study, we investigated the relevance of these TGF-ß1 polymorphism in glioma risk and prognosis. A case-control study that included 114 glioma patients and 138 cancer-free controls was performed. Single nucleotide polymorphisms (SNPs) were evaluated by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP). Univariate and multivariate logistic regression analyses were used to calculate odds ratio (OR) and 95 % confidence intervals (95 % CI). The influence of TGF-ß1 -509C/T and 869T/C polymorphisms on glioma patient survival was evaluated by a Cox regression model adjusted for patients' age and sex and represented in Kaplan-Meier curves. Our results demonstrated that TGF-ß1 gene polymorphisms -509C/T and 869T/C are not significantly associated with glioma risk. Survival analyses showed that the homozygous -509TT genotype associates with longer overall survival of glioblastoma (GBM) patients when compared with patients carrying CC + CT genotypes (OR, 2.41; 95 % CI, 1.06-5.50; p = 0.036). In addition, the homozygous 869CC genotype is associated with increased overall survival of GBM patients when compared with 869TT + TC genotypes (OR, 2.62; 95 % CI, 1.11-6.17; p = 0.027). In conclusion, this study suggests that TGF-ß1 -509C/T and 869T/C polymorphisms are not significantly associated with risk for developing gliomas but may be relevant prognostic biomarkers in GBM patients.

Cotard syndrome without depressive symptoms in a schizophrenic patient

Cotard Syndrome without Depressive Symptoms in a Schizophrenic Patient

The bounds of education in the human brain connectome

Inter-individual heterogeneity is evident in aging; education level is known to contribute for this heterogeneity. Using a cross-sectional study design and network inference applied to resting-state fMRI data, we show that aging was associated with decreased functional connectivity in a large cortical network. On the other hand, education level, as measured by years of formal education, produced an opposite effect on the long-term. These results demonstrate the increased brain efficiency in individuals with higher education level that may mitigate the impact of age on brain functional connectivity.

KIAA1549: BRAF gene fusion and FGFR1 hotspot mutations are prognostic factors in pilocytic astrocytomas

Up to 20% of patients with pilocytic astrocytoma (PA) experience a poor outcome. BRAF alterations and Fibroblast growth factor receptor 1 (FGFR1) point mutations are key molecular alterations in Pas, but their clinical implications are not established. We aimed to determine the frequency and prognostic role of these alterations in a cohort of 69 patients with PAs. We assessed KIAA1549:BRAF fusion by fluorescence in situ hybridization and BRAF (exon 15) mutations by capillary sequencing. In addition, FGFR1 expression was analyzed using immunohistochemistry, and this was compared with gene amplification and hotspot mutations (exons 12 and 14) assessed by fluorescence in situ hybridization and capillary sequencing. KIAA1549:BRAF fusion was identified in almost 60% of cases. Two tumors harbored mutated BRAF. Despite high FGFR1 expression overall, no cases had FGFR1 amplifications. Three cases harbored a FGFR1 p.K656E point mutation. No correlation was observed between BRAF and FGFR1 alterations. The cases were predominantly pediatric (87%), and no statistical differences were observed in molecular alterations-related patient ages. In summary, we confirmed the high frequency of KIAA1549:BRAF fusion in PAs and its association with a better outcome. Oncogenic mutations of FGFR1, although rare, occurred in a subset of patients with worse outcome. These molecular alterations may constitute alternative targets for novel clinical approaches, when radical surgical resection is unachievable.

The role of IFNγ in higher brain function: in health and under chronic stress

Tese de Doutoramento em Ciências da Saúde

Synthesis and biological evaluation of mono and bis-naphthalimide derivatives against SH-SY5Y, human brain cancer cells

Dissertação de mestrado em Medicinal Chemistry

Pervasive patient timeline for intensive care units

This research work explores a new way of presenting and representing information about patients in critical care, which is the use of a timeline to display information. This is accomplished with the development of an interactive Pervasive Patient Timeline able to give to the intensivists an access in real-time to an environment containing patients clinical information from the moment in which the patients are admitted in the Intensive Care Unit (ICU) until their discharge This solution allows the intensivists to analyse data regarding vital signs, medication, exams, data mining predictions, among others. Due to the pervasive features, intensivists can have access to the timeline anywhere and anytime, allowing them to make decisions when they need to be made. This platform is patient-centred and is prepared to support the decision process allowing the intensivists to provide better care to patients due the inclusion of clinical forecasts.

A Real-Time intelligent system for tracking patient condition

Hospitals have multiple data sources, such as embedded systems, monitors and sensors. The number of data available is increasing and the information are used not only to care the patient but also to assist the decision processes. The introduction of intelligent environments in health care institutions has been adopted due their ability to provide useful information for health professionals, either in helping to identify prognosis or also to understand patient condition. Behind of this concept arises this Intelligent System to track patient condition (e.g. critic events) in health care. This system has the great advantage of being adaptable to the environment and user needs. The system is focused in identifying critic events from data streaming (e.g. vital signs and ventilation) which is particularly valuable for understanding the patient’s condition. This work aims to demonstrate the process of creating an intelligent system capable of operating in a real environment using streaming data provided by ventilators and vital signs monitors. Its development is important to the physician because becomes possible crossing multiple variables in real-time by analyzing if a value is critic or not and if their variation has or not clinical importance.

Pre-clinical trials for Machado-Joseph Disease: Hypothesis-based and hypothesis-free therapeutic approaches

Tese de Doutoramento em Ciências da Saúde