Estudo acústico de /a/ acentuado na fala bracarense: potenciais aplicações

Dissertação de mestrado em Ciências da Linguagem

Efficacy of a gas permeable contact lens to induce peripheral myopic defocus

Purpose. The purpose of this work was to evaluate the potential of a novel custom-designed rigid gas permeable (RGP) contact lens to modify the relative peripheral refractive error in a sample of myopic patients. Methods. Fifty-two right eyes of 52 myopic patients (mean [TSD] age, 21 [T2] years) with spherical refractive errors ranging from j0.75 to j8.00 diopters (D) and refractive astigmatism of 1.00 D or less were fitted with a novel experimental RGP (ExpRGP) lens designed to create myopic defocus in the peripheral retina. A standard RGP (StdRGP) lens was used as a control in the same eye. The relative peripheral refractive error was measured without the lens and with each of two lenses (StdRGP and ExpRGP) using an open-field autorefractometer from 30 degrees nasal to 30 degrees temporal, in 5-degree steps. The effectiveness of the lens design was evaluated as the amount of relative peripheral refractive error difference induced by the ExpRGP compared with no lens and with StdRGP conditions at 30 degrees in the nasal and temporal (averaged) peripheral visual fields. Results. Experimental RGP lens induced a significant change in relative peripheral refractive error compared with the nolens condition (baseline), beyond the 10 degrees of eccentricity to the nasal and temporal side of the visual field (p G 0.05). The maximum effect was achieved at 30 degrees. Wearing the ExpRGP lens, 60% of the eyes had peripheral myopia exceeding j1.00 D, whereas none of the eyes presented with this feature at baseline. There was no significant correlation (r = 0.04; p = 0.756) between the degree of myopia induced at 30 degrees of eccentricity of the visual field with the ExpRGP lens and the baseline refractive error. Conclusions. Custom-designed RGP contact lenses can generate a significant degree of relative peripheral myopia in myopic patients regardless of their baselin spherical equivalent refractive error.

Changes in peripheral refractive profile after orthokeratology for different degrees of myopia

Purpose: The purpose of this study was to evaluate the effect of orthokeratology for different degrees of myopia correction in the relative location of tangential (FT) and sagittal (FS) power errors across the central 70 of the visual field in the horizontal meridian. Methods: Thirty-four right eyes of 34 patients with a mean age of 25.2 ± 6.4 years were fitted with Paragon CRT (Mesa, AZ) rigid gas permeable contact lenses to treat myopia (2.15 ± 1.26D, range: 0.88 to 5.25D). Axial and peripheral refraction were measured along the central 70 of the horizontal visual field with the Grand Seiko WAM5500 open-field auto-refractor. Spherical equivalent (M), as well as tangential (FT) and sagittal power errors (FS) were obtained. Analysis was stratified in three groups according to baseline spherical equivalent: Group 1 [MBaseline = 0.88 to 1.50D; n = 11], Group 2 [MBaseline = 1.51 to 2.49D; n = 11], and Group 3 [MBaseline = 2.50 to 5.25D; n = 12]. Results: Spherical equivalent was significantly more myopic after treatment beyond the central 40 of the visual field (p50.001). FT became significantly more myopic for all groups in the nasal and temporal retina with 25 (p 0.017), 30 (p 0.007) and 35 (p 0.004) of eye rotation. Myopic change in FS was less consistent, achieving only statistical significance for all groups at 35 in the nasal and temporal retina (p 0.045). Conclusions: Orthokeratology changes significantly FT in the myopic direction beyond the central 40 of the visual field for all degrees of myopia. Changes induced by orthokeratology in relative peripheral M, FT and FS with 35 of eye rotation were significantly correlated with axial myopia at baseline. Keywords: Field

Segmentação do tecido tumoral cerebral em imagens de ressonância magnética

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Eletrónica Médica)

Evolving hallmarks in urothelial bladder cancer: unveiling potential biomarkers

Urothelial bladder carcinoma (UBC), the most frequent type (90%) of bladder cancer and the second most common malignancy of the urogenital region, is a relatively well understood type of cancer, with numerous studies concerning pathogenetic pathways, natural history and bladder tumor biology being reported. Despite this, it continues to remain a challenge in the oncology field, mostly due to its relapsing and progressive nature, and to the heterogeneity in the response to cisplatin-containing regimens. Although the formulae based on clinical staging and histopathological parameters are classically used as diagnostic and prognostic tools, they have proven insufficient to characterize the individual biological features and clinical behaviour of the tumours. Understanding the pathobiology of the disease can add important information to these classical criteria, and contribute to accurately predict outcome and individualize therapy for UBC patients. In this line of investigation, we found that tumour angiogenesis and lymphangiogenesis, the process of invasion and metastasis and the energy metabolism reprogramming/tumour microenvironment encompass several potential biomarkers that seem to infl bladder cancer aggressiveness and chemoresistance. We particularly highlight the roles of lymphovascular invasion, and of RKIP, CD147 and MCT1 immunoexpressions, as relevant prognostic and/or predictive biomarkers, and as promising areas of therapeutic intervention, eliciting for the development of additional studies that can validate and further explore these biomarkers.

Impact of mutated KRAS signalling on autophagy regulation in colorectal carcinoma

Programa Doutoral em Biologia Molecular e Ambiental

A glycolytic phenotype is associated with prostate cancer progression and aggressiveness: a role for Monocarboxylate Transporters as metabolic targets for therapy.

Metabolic adaptation is considered an emerging hallmark of cancer, whereby cancer cells exhibit high rates of glucose consumption with consequent lactate production. To ensure rapid efflux of lactate, most cancer cells express high levels of monocarboxylate transporters (MCTs), which therefore may constitute suitable therapeutic targets. The impact of MCT inhibition, along with the clinical impact of altered cellular metabolism during prostate cancer (PCa) initiation and progression, has not been described. Using a large cohort of human prostate tissues of different grades, in silico data, in vitro and ex vivo studies, we demonstrate the metabolic heterogeneity of PCa and its clinical relevance. We show an increased glycolytic phenotype in advanced stages of PCa and its correlation with poor prognosis. Finally, we present evidence supporting MCTs as suitable targets in PCa, affecting not only cancer cell proliferation and survival but also the expression of a number of hypoxia-inducible factor target genes associated with poor prognosis. Herein, we suggest that patients with highly glycolytic tumours have poorer outcome, supporting the notion of targeting glycolytic tumour cells in prostate cancer through the use of MCT inhibitors.

MET is required for the recruitment of anti-tumoural neutrophils

Mutations or amplification of the MET proto-oncogene are involved in the pathogenesis of several tumours, which rely on the constitutive engagement of this pathway for their growth and survival. However, MET is expressed not only by cancer cells but also by tumour-associated stromal cells, although its precise role in this compartment is not well characterized. Here we show that MET is required for neutrophil chemoattraction and cytotoxicity in response to its ligand hepatocyte growth factor (HGF). Met deletion in mouse neutrophils enhances tumour growth and metastasis. This phenotype correlates with reduced neutrophil infiltration to both the primary tumour and metastatic sites. Similarly, Met is necessary for neutrophil transudation during colitis, skin rash or peritonitis. Mechanistically, Met is induced by tumour-derived tumour necrosis factor (TNF)-a or other inflammatory stimuli in both mouse and human neutrophils. This induction is instrumental for neutrophil transmigration across an activated endothelium and for inducible nitric oxide synthase production upon HGF stimulation. Consequently, HGF/MET-dependent nitric oxide release by neutrophils promotes cancer cell killing, which abates tumour growth and metastasis. After systemic administration of a MET kinase inhibitor, we prove that the therapeutic benefit of MET targeting in cancer cells is partly countered by the pro-tumoural effect arising from MET blockade in neutrophils. Our work identifies an unprecedented role of MET in neutrophils, suggests a potential 'Achilles' heel' of MET-targeted therapies in cancer, and supports the rationale for evaluating anti-MET drugs in certain inflammatory diseases.

Síntese e testes in vitro de novas pirimido[5,4-d] pirimidinas em células resistentes do cancro coloretal

Dissertação de mestrado em Química Medicinal

Perceção e produção de sons consonânticos do português europeu por aprendentes chineses

Dissertação de mestrado em Português Língua Não Materna (PLNM): Português Língua Estrangeira (PLE) Português Língua Segunda (PL2)