Lesões da substância branca por ressonância magnética: uma avaliação entre as ponderações DWI e T2 FLAIR

RESUMO: Objetivos – Determinar a sensibilidade e especificidade das ponderações Difusão (DWI) e T2 Fluid-Attenuated Inversion Recovery (FLAIR) na avaliação de lesões da substância branca (SB) e verificar em que medida se complementam, por forma a criar um conjunto de boas práticas na RM cranioencefálica de rotina. Metodologia – Recorrendo-se a uma metodologia quantitativa, efetuou-se uma análise retrospetiva da qual foram selecionados 30 pacientes, 10 sem patologia e 20 com patologia (2 com EM, 7 com Leucoencefalopatia, 6 com doença microangiopática e 5 com patologia da substância branca indefinida). Obteve-se uma amostra de 60 imagens, nomeadamente: 30 imagens ponderadas em DWI e 30 em T2 FLAIR. Recorrendo ao programa Viewdex®, três observadores avaliaram um conjunto de imagens segundo sete critérios: visibilidade, deteção, homogeneidade, localização, margens e dimensões da lesão e capacidade de diagnóstico. Com os resultados obtidos recorreu-se ao cálculo de sensibilidade e especificidade pelas Curvas ROC, bem como à análise estatística, nomeadamente, Teste-T, Índice de Concordância Kappa e coeficiente de correlação de Pearson entre as variáveis em estudo. Resultados – Os resultados de sensibilidade e de especificidade obtidos para a ponderação T2 FLAIR foram superiores (0,915 e 0,038, respetivamente) aos da ponderação DWI (0,08 e 0,100, respetivamente). Não se verificaram variâncias populacionais significativas. Obteve-se uma elevada correlação linear entre as variáveis com um valor r situado entre 0,8 e 0,99. Verificou-se também uma variabilidade considerável entre os observadores. Conclusões – Dados os baixos valores de sensibilidade e especificidade obtidos para a DWI, sugere-se que esta deva ser incluída no protocolo de rotina de crânio como auxiliar no diagnóstico diferencial com outras patologias.

In vivo and in vitro effects of RAD001 on bladder cancer

Objective: To evaluate the influence of Everolimus (RAD001) on chemically induced urothelial lesions in mice and its influence on in vitro human bladder cancer cell lines. Methods: ICR male mice were given N-butyl-N-(4-hydroxybutyl) nitrosamine in drinking water for a period of 12 weeks. Subsequently, RAD001 was administered via oral gavage, for 6 weeks. At the end of the experiment, all the animals were sacrificed and tumor development was determined by means of histopathologic evaluation; mammalian target of rapamycin (mTOR) expressivity was evaluated by immunohistochemistry. Three human bladder cancer cell lines (T24, HT1376, and 5637) were treated using a range of RAD001 concentrations. MTT assay, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and flow cytometry were used to assess cell proliferation, apoptosis index, and cell cycle analysis, respectively. Immunoblotting analysis of 3 cell line extracts using mTOR and Akt antibodies was performed in order to study the expression of Akt and mTOR proteins and their phosphorylated forms. Results: The incidence of urothelial lesions in animals treated with RAD001 was similar to those animals not treated. RAD001 did not block T24 and HT1376 cell proliferation or induce apoptosis. A reduction in cell proliferation rate and therefore G0/G1 phase arrest, as well as a statistically significant induction of apoptosis (P 0.001), was only observed in the 5637 cell line. Conclusion: RAD001 seems not to have a significant effect on chemically induced murine bladder tumors. The effect of RAD001 on tumor proliferation and apoptosis was achieved only in superficial derived bladder cancer cell line, no effect was observed in invasive cell lines.

A influência da reeducação vestibular nas medidas objetivas e subjetivas em pacientes com défice vestibular periférico unilateral

Mestrado em Fisioterapia.

Diferenciação curricular para a inclusão de alunos com necessidades educativas especiais no 1º ciclo do Ensino Básico

Um dos grandes desafios da atualidade reside em construir uma escola inclusiva para todos, respeitando as diferenças entre os alunos e procurando dar resposta a todas as suas necessidades educativas, através do acesso igualitário a uma educação de qualidade, no sentido de uma preparação para a vida social e profissional ao longo da vida. Desta forma, é necessária uma mudança não só na maneira de pensar como também nas práticas dos agentes educativos, no sentido de adequarem o currículo às necessidades educativas especiais dos alunos. O presente estudo constitui, pois, uma tentativa de conhecer não apenas as conceções dos professores do 1º Ciclo do Ensino Básico sobre a inclusão e as adaptações curriculares para alunos com NEE, mas também as práticas curriculares que desenvolvem quando têm estes alunos nas suas turmas. O trabalho desenvolveu-se através de um estudo de caso, incidindo sobre 6 professores do 1º CEB e respetivas turmas com alunos com NEE incluídos. Como metodologia de recolha de dados utilizámos as técnicas da entrevista, da análise documental e da observação naturalista em contexto de sala de aula. Articulando os resultados das entrevistas com os das observações em sala de aula, podemos concluir que, para que a escola seja efetivamente inclusiva, não basta que os professores adotem este conceito. Algumas das maiores dificuldades que se colocaram aos professores foram a gestão do tempo e a adequação de estratégias no atendimento a todos os alunos, o que decorre da forma de organização do ensino, uma vez que os professores continuam a percecionar o seu papel como transmissores de conteúdos e executores de programas, apostando num ensino unilateral e homogéneo. No entanto, foi possível também verificar algumas formas de diferenciação pedagógica, sobretudo através da adequação da estrutura dos trabalhos individuais, do apoio individualizado do professor aos alunos com mais dificuldades ou da tutoria interpares e da realização de diferentes atividades consoante as necessidades específicas de cada aluno.

Cobalt and Zinc Compounds Bearing 1,10-Phenanthroline-5,6-dione or 1,3,5-Triaza-7-phosphaadamantane Derivatives - Synthesis, Characterization, Cytotoxicity, and Cell Selectivity Studies

The compounds [mPTA][CoCl4] (1, mPTA = N-methyl-1,3,5-triaza-7-phosphaadamantane cation), [CoCl(H2O)(DION)(2)][BF4] (2, DION = 1,10-phenanthroline-5,6-dione), [Zn(DION)(2)]Cl-2 (3) and [ZnCl(O-PTA=O)(DION)][BF4] (4) were synthesized by reaction of CoCl2 with [mPTA]I or DION and ZnCl2 with DION or 1,3,5-triaza-7-phosphaadamantane-7-oxide (PTA=O) and DION, respectively. All complexes are water soluble and have been characterized by IR, far-IR, H-1, C-13 and P-31{H-1} NMR spectroscopy, ESI-MS, elemental analyses and single-crystal X-ray diffraction structural analysis (for 1). They were screened against the human tumour cell lines HCT116, HepG2 and MCF7. Complexes 2 and 3 exhibit the highest in vitro cytotoxicity and show lower cytotoxic activities in normal human fibroblast cell line than in HCT116 tumour cell line, which demonstrates their slight specificity for this type of tumour cell.

Synthesis, characterization, electrochemical behavior and in vitro protein tyrosine kinase inhibitory activity of the cymene-halogenobenzohydroxamato [Ru(eta(6)-cymene)(bha)Cl] complexes

The ruthenium(II)-cymene complexes [Ru(eta(6)-cymene)(bha)Cl] with substituted halogenobenzohydroxamato (bha) ligands (substituents = 4-F, 4-Cl, 4-Br, 2,4-F-2, 3,4-F-2, 2,5-F-2, 2,6-F-2) have been synthesized and characterized by elemental analysis, IR, H-1 NMR, C-13 NMR, cyclic voltammetry and controlled-potential electrolysis, and density functional theory (DFT) studies. The compositions of their frontier molecular orbitals (MOs) were established by DFT calculations, and the oxidation and reduction potentials are shown to follow the orders of the estimated vertical ionization potential and electron affinity, respectively. The electrochemical E-L Lever parameter is estimated for the first time for the various bha ligands, which can thus be ordered according to their electron-donor character. All complexes exhibit very strong protein tyrosine kinase (PTK) inhibitory activity, even much higher than that of genistein, the clinically used PTK inhibitory drug. The complex containing the 2,4-difluorobenzohydroxamato ligand is the most active one, and the dependences of the PTK activity of the complexes and of their redox potentials on the ring substituents are discussed. (C) 2012 Elsevier B.V. All rights reserved.

Alterações da curvatura da coluna vertebral: influência da fisioterapia, a nível neuromuscular

Mestrado em Fisioterapia

Monte Carlo modeling and simulations of the High Definition (HD120) micro MLC and validation against measurements for a 6 MV beam

Purpose: The most recent Varian® micro multileaf collimator(MLC), the High Definition (HD120) MLC, was modeled using the BEAMNRCMonte Carlo code. This model was incorporated into a Varian medical linear accelerator, for a 6 MV beam, in static and dynamic mode. The model was validated by comparing simulated profiles with measurements. Methods: The Varian® Trilogy® (2300C/D) accelerator model was accurately implemented using the state-of-the-art Monte Carlo simulation program BEAMNRC and validated against off-axis and depth dose profiles measured using ionization chambers, by adjusting the energy and the full width at half maximum (FWHM) of the initial electron beam. The HD120 MLC was modeled by developing a new BEAMNRC component module (CM), designated HDMLC, adapting the available DYNVMLC CM and incorporating the specific characteristics of this new micro MLC. The leaf dimensions were provided by the manufacturer. The geometry was visualized by tracing particles through the CM and recording their position when a leaf boundary is crossed. The leaf material density and abutting air gap between leaves were adjusted in order to obtain a good agreement between the simulated leakage profiles and EBT2 film measurements performed in a solid water phantom. To validate the HDMLC implementation, additional MLC static patterns were also simulated and compared to additional measurements. Furthermore, the ability to simulate dynamic MLC fields was implemented in the HDMLC CM. The simulation results of these fields were compared with EBT2 film measurements performed in a solid water phantom. Results: Overall, the discrepancies, with and without MLC, between the opened field simulations and the measurements using ionization chambers in a water phantom, for the off-axis profiles are below 2% and in depth-dose profiles are below 2% after the maximum dose depth and below 4% in the build-up region. On the conditions of these simulations, this tungsten-based MLC has a density of 18.7 g cm− 3 and an overall leakage of about 1.1 ± 0.03%. The discrepancies between the film measured and simulated closed and blocked fields are below 2% and 8%, respectively. Other measurements were performed for alternated leaf patterns and the agreement is satisfactory (to within 4%). The dynamic mode for this MLC was implemented and the discrepancies between film measurements and simulations are within 4%. Conclusions: The Varian® Trilogy® (2300 C/D) linear accelerator including the HD120 MLC was successfully modeled and simulated using the Monte CarloBEAMNRC code by developing an independent CM, the HDMLC CM, either in static and dynamic modes.

The use of non-standard CT conversion ramps for Monte Carlo verification of 6 MV prostate IMRT plans

Monte Carlo (MC) dose calculation algorithms have been widely used to verify the accuracy of intensity-modulated radiotherapy (IMRT) dose distributions computed by conventional algorithms due to the ability to precisely account for the effects of tissue inhomogeneities and multileaf collimator characteristics. Both algorithms present, however, a particular difference in terms of dose calculation and report. Whereas dose from conventional methods is traditionally computed and reported as the water-equivalent dose (Dw), MC dose algorithms calculate and report dose to medium (Dm). In order to compare consistently both methods, the conversion of MC Dm into Dw is therefore necessary. This study aims to assess the effect of applying the conversion of MC-based Dm distributions to Dw for prostate IMRT plans generated for 6 MV photon beams. MC phantoms were created from the patient CT images using three different ramps to convert CT numbers into material and mass density: a conventional four material ramp (CTCREATE) and two simplified CT conversion ramps: (1) air and water with variable densities and (2) air and water with unit density. MC simulations were performed using the BEAMnrc code for the treatment head simulation and the DOSXYZnrc code for the patient dose calculation. The conversion of Dm to Dw by scaling with the stopping power ratios of water to medium was also performed in a post-MC calculation process. The comparison of MC dose distributions calculated in conventional and simplified (water with variable densities) phantoms showed that the effect of material composition on dose-volume histograms (DVH) was less than 1% for soft tissue and about 2.5% near and inside bone structures. The effect of material density on DVH was less than 1% for all tissues through the comparison of MC distributions performed in the two simplified phantoms considering water. Additionally, MC dose distributions were compared with the predictions from an Eclipse treatment planning system (TPS), which employed a pencil beam convolution (PBC) algorithm with Modified Batho Power Law heterogeneity correction. Eclipse PBC and MC calculations (conventional and simplified phantoms) agreed well (<1%) for soft tissues. For femoral heads, differences up to 3% were observed between the DVH for Eclipse PBC and MC calculated in conventional phantoms. The use of the CT conversion ramp of water with variable densities for MC simulations showed no dose discrepancies (0.5%) with the PBC algorithm. Moreover, converting Dm to Dw using mass stopping power ratios resulted in a significant shift (up to 6%) in the DVH for the femoral heads compared to the Eclipse PBC one. Our results show that, for prostate IMRT plans delivered with 6 MV photon beams, no conversion of MC dose from medium to water using stopping power ratio is needed. In contrast, MC dose calculations using water with variable density may be a simple way to solve the problem found using the dose conversion method based on the stopping power ratio.

Sequencing of a 17.6 kb segment on the right arm of yeast chromosome VII reveals 12 ORFs, including CCT, ADE3 and TR-I genes, homologues of the yeast PMT and EF1G genes, of the human and bacterial electron-transferring flavoproteins (beta-chain) and of the Escherichia coli phosphoserine phosphohydrolase, and five new ORFs.

A 17.6 kb DNA fragment from the right arm of chromosome VII of Saccharomyces cerevisiae has been sequenced and analysed. The sequence contains twelve open reading frames (ORFs) longer than 100 amino acids. Three genes had already been cloned and sequenced: CCT, ADE3 and TR-I. Two ORFs are similar to other yeast genes: G7722 with the YAL023 (PMT2) and PMT1 genes, encoding two integral membrane proteins, and G7727 with the first half of the genes encoding elongation factors 1gamma, TEF3 and TEF4. Two other ORFs, G7742 and G7744, are most probably yeast orthologues of the human and Paracoccus denitrificans electron-transferring flavoproteins (beta chain) and of the Escherichia coli phosphoserine phosphohydrolase. The five remaining identified ORFs do not show detectable homology with other protein sequences deposited in data banks. The sequence has been deposited in the EMBL data library under Accession Number Z49133.

Glucose-6-Phosphate dehydrogenase deficiency in children from 0 to 14 years hospitalized at the Pediatric Hospital David Bernardino, Luanda, Angola

The Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic defect in the world. The most common clinical manifestations are acute hemolytic anemia associated with drugs, infections, neonatal jaundice and hemolytic non-spherocytic chronic anemia. The main aim of this study was to determine the frequency of major genetic variants of G6PD leading to enzyme deficiency in children from 0 to 14 years at a Pediatric Hospital in Luanda, Angola. A cross-sectional and descriptive analytical study covered a total of 194 children aged from 0 to 14 years, of both genders and hospitalized at the Pediatric Hospital David Bernardino, Luanda between November and December, 2011. The G202A, A376G and C563T mutations of the G6PD gene were determined by real-time PCR with Taqman probes. The disabled A-/A- genotype was detected in 10 girls (10.9%). Among the boys, 21 (20.6%) presented the genotype A-. Considering all the samples, the A- variant was observed in 22.4% of cases. The Mediterranean mutation was not detected in the Angolan sample. Furthermore, no association was found between genotype and anemia, nutritional state and mucosa color. A significant association, however, was observed with jaundice. Based on the results obtained, there is a clear need to identify those with the disabled genotype in the Angolan population in order to avoid cases of drug-induced anemia, particularly in the treatment of malaria, so prevalent in Angola.

STIR, SPIR and SPAIR techniques in magnetic resonance of the breast: a comparative study

The amount of fat is a component that complicates the clinical evaluation and the differential diagnostic between benign and malign lesions in the breast MRI examinations. To overcome this problem, an effective erasing of the fat signal over the images acquisition process, is essentials. This study aims to compare three fat suppression techniques (STIR, SPIR, SPAIR) in the MR images of the breast and to evaluate the best image quality regarding its clinical usefulness. To mimic breast women, a breast phantom was constructed. First the exterior contour and, in second time, its content which was selected based on 7 samples with different components. Finally it was undergone to a MRI breast protocol with the three different fat saturation techniques. The examinations were performed on a 1.5 T MRI system (Philips®). A group of 5 experts evaluated 9 sequences, 3 of each with fat suppression techniques, in which the frequency offset and TI (Inversion Time) were the variables changed. This qualitative image analysis was performed according 4 parameters (saturation uniformity, saturation efficacy, detail of the anatomical structures and differentiation between the fibroglandular and adipose tissue), using a five-point Likert scale. The statistics analysis showed that anyone of the fat suppression techniques demonstrated significant differences compared to the others with (p > 0.05) and regarding each parameter independently. By Fleiss’ kappa coefficient there was a good agreement among observers P(e) = 0.68. When comparing STIR, SPIR and SPAIR techniques it was confirmed that all of them have advantages in the study of the breast MRI. For the studied parameters, the results through the Friedman Test showed that there are similar advantages applying anyone of these techniques.

Strabismus, visual acuity, and uncorrected refractive error in Portuguese children aged 6 to 11 years

Introduction: Visual anomalies that affect school-age children represent an important public health problem. Data on the prevalence are lacking in Portugal but is needed for planning vision services. This study was conducted to determine the prevalence of strabismus, decreased visual acuity, and uncorrected refractive error in Portuguese children aged 6 to 11 years. Methods and materials: A cross-sectional study was carried out on a sample of 672 school-age children (7.69 ± 1.19 years). Children received an orthoptic assessment (visual acuity, ocular alignment, and ocular movements) and non-cycloplegic autorefraction. Results: After orthoptic assessment, 13.8% of children were considered abnormal (n = 93). Manifest strabismus was found in 4% of the children. Rates of esotropia (2.1%) were slightly higher than exotropia (1.8%). Strabismus rates were not statistically significant different per sex (p = 0.681) and grade (p = 0.228). Decreased visual acuity at distance was present in 11.3% of children. Visual acuity ≤20/66 (0.5 logMAR) was found in 1.3% of the children. We also found that 10.3% of children had an uncorrected refractive error. Conclusions: Strabismus affects a small proportion of the Portuguese school-age children. Decreased visual acuity and uncorrected refractive error affected a significant proportion of school-age children. New policies need to be developed to address this public health problem.

Reproducibility of simulated myocardial lesions simulated on a virtual phantom

Human virtual phantoms are being widely used to simulate and characterize the behavior of different organs, either in diagnosis stages but also to enable foreseeing the therapeutic effects obtained on a certain patient. In the present work a typical patient’s heart was simulated using XCAT2©, considering the possibility of a lesion and/or anatomical alteration being affecting the myocardium. These simulated images, were then used to carry out a set of parametric studies using Matlab©. Although performed in controlled sceneries, these studies are very important to understand and characterize the performance of the methodologies used, as well as to determine to what extent the relations between the perturbation introduced at the myocardium and the resulting simulated images can be considered conclusive.

Does 6-minutes walk test predict functional capacity in elderly people?

Portugal has an accentuated aging tendency, presenting an elderly population (individuals with more than 65 years old) of 19.2%. The average life expectancy is 79.2 years. Thus, it’s important to maintain autonomy and independency as long as possible. Functional ability concept rises from the need to evaluate the capacity to conduct daily activities in an independent way. It can be estimated with the 6-minute walk test (6MWT) and other validated test. This test is simple, reliable, valid and consists in a daily activity (walk). The goals of this study was to verify associations between functional capacity measured with two different instruments (6MWT and Composite Physical Function (CPF) scale) and between those results and characterization variables.