Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: Linker effects on the relaxivity

The relaxivity displayed by Gd3+ chelates immobilized onto gold nanoparticles is the result of complex interplay between nanoparticle size, water exchange rate and chelate structure. In this work we study the effect of the length of -thioalkyl linkers, anchoring fast water exchanging Gd3+ chelates onto gold nanoparticles, on the relaxivity of the immobilized chelates. Gold nanoparticles functionalized with Gd3+ chelates of mercaptoundecanoyl and lipoyl amide conjugates of the DO3A-N-(-amino)propionate chelator were prepared and studied as potential CA for MRI. High relaxivities per chelate, of the order of magnitude 28-38 mM-1s-1 (30 MHz, 25 ºC) were attained thanks to simultaneous optimization of the rotational correlation time and of the water exchange rate. Fast local rotational motions of the immobilized chelates around connecting linkers (internal flexibility) still limit the attainable relaxivity. The degree of internal flexibility of the immobilized chelates seems not to be correlated with the length of the connecting linkers. Biodistribution and MRI studies in mice suggest that the in vivo behavior of the gold nanoparticles is determined mainly by size. Small nanoparticles (HD= 3.9 nm) undergo fast renal clearance and avoidance of the RES organs while larger nanoparticles (HD= 4.8 nm) undergo predominantly hepatobiliary excretion. High relaxivities, allied to chelate and nanoparticle stability and fast renal clearance in vivo suggests that functionalized gold nanoparticles hold great potential for further investigation as MRI Contrast Agents. This study contributes to understand the effect of linker length on the relaxivity of gold nanoparticles functionalized with Gd3+ complexes. It is a relevant contribution towards “design rules” for nanostructures functionalized with Gd3+ chelates as Contrast Agents for MRI and multimodal imaging.

Recordando o Prof. Doutor José de Azevedo Ferreira 20 anos após a sua morte

Artigo de jornal (2015): «Recordando o Prof. Doutor José de Azevedo Ferreira 20 anos após a sua morte», in Diário do Minho, Caderno Cultura, pp. IV-VI, 10 de junho de 2015.

Aplicação da metodologia ROC na avaliação de desempenho de índices de gravidade clínica em unidades de neonatologia de Portugal

Tese de Doutoramento em Engenharia Industrial e de Sistemas

Design of bio-based supramolecular structures through self-assembly of α-lactalbumin and lysozyme

Bovine α-lactalbumin (α-La) and lysozyme (Lys), two globular proteins with highly homologous tertiary structures and opposite isoelectric points, were used to produce bio-based supramolecular structures under various pH values (3, 7 and 11), temperatures (25, 50 and 75 °C) and times (15, 25 and 35 min) of heating. Isothermal titration calorimetry experiments showed protein interactions and demonstrated that structures were obtained from the mixture of α-La/Lys in molar ratio of 0.546. Structures were characterized in terms of morphology by transmission electron microscopy (TEM) and dynamic light scattering (DLS), conformational structure by circular dichroism and intrinsic fluorescence spectroscopy and stability by DLS. Results have shown that protein conformational structure and intermolecular interactions are controlled by the physicochemical conditions applied. The increase of heating temperature led to a significant decrease in size and polydispersity (PDI) of α-La–Lys supramolecular structures, while the increase of heating time, particularly at temperatures above 50 °C, promoted a significant increase in size and PDI. At pH 7 supramolecular structures were obtained at microscale – confirmed by optical microscopy – displaying also a high PDI (i.e. > 0.4). The minimum size and PDI (61 ± 2.3 nm and 0.14 ± 0.03, respectively) were produced at pH 11 for a heating treatment of 75 °C for 15 min, thus suggesting that these conditions could be considered as critical for supramolecular structure formation. Its size and morphology were confirmed by TEM showing a well-defined spherical form. Structures at these conditions showed to be stable at least for 30 or 90 days, when stored at 25 or 4 °C, respectively. Hence, α-La–Lys supramolecular structures showed properties that indicate that they are a promising delivery system for food and pharmaceutical applications.

Global validation of the WSES Sepsis Severity Score for patients with complicated intra-abdominal infections: a prospective multicentre study (WISS Study).

BACKGROUND To validate a new practical Sepsis Severity Score for patients with complicated intra-abdominal infections (cIAIs) including the clinical conditions at the admission (severe sepsis/septic shock), the origin of the cIAIs, the delay in source control, the setting of acquisition and any risk factors such as age and immunosuppression. METHODS The WISS study (WSES cIAIs Score Study) is a multicenter observational study underwent in 132 medical institutions worldwide during a four-month study period (October 2014-February 2015). Four thousand five hundred thirty-three patients with a mean age of 51.2 years (range 18-99) were enrolled in the WISS study. RESULTS Univariate analysis has shown that all factors that were previously included in the WSES Sepsis Severity Score were highly statistically significant between those who died and those who survived (p < 0.0001). The multivariate logistic regression model was highly significant (p < 0.0001, R2 = 0.54) and showed that all these factors were independent in predicting mortality of sepsis. Receiver Operator Curve has shown that the WSES Severity Sepsis Score had an excellent prediction for mortality. A score above 5.5 was the best predictor of mortality having a sensitivity of 89.2 %, a specificity of 83.5 % and a positive likelihood ratio of 5.4. CONCLUSIONS WSES Sepsis Severity Score for patients with complicated Intra-abdominal infections can be used on global level. It has shown high sensitivity, specificity, and likelihood ratio that may help us in making clinical decisions.

Diagnóstico e ensaio de carga de asnas tradicionais de madeira

Dissertação de mestrado Integrado em Engenharia Civil

Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication

Renal cell tumors (RCTs) are the most lethal of the common urological cancers. The widespread use of imaging entailed an increased detection of small renal masses, emphasizing the need for accurate distinction between benign and malignant RCTs, which is critical for adequate therapeutic management. Histone methylation has been implicated in renal tumorigenesis, but its potential clinical value as RCT biomarker remains mostly unexplored. Hence, the main goal of this study was to identify differentially expressed histone methyltransferases (HMTs) and histone demethylases (HDMs) that might prove useful for RCT diagnosis and prognostication, emphasizing the discrimination between oncocytoma (a benign tumor) and renal cell carcinoma (RCC), especially the chromophobe subtype (chRCC). We found that the expression levels of three genes-SMYD2, SETD3, and NO66-was significantly altered in a set of RCTs, which was further validated in a large independent cohort. Higher expression levels were found in RCTs compared to normal renal tissues (RNTs) and in chRCCs comparatively to oncocytomas. SMYD2 and SETD3 mRNA levels correlated with protein expression assessed by immunohistochemistry. SMYD2 transcript levels discriminated RCTs from RNT, with 82.1% sensitivity and 100% specificity (AUC=0.959), and distinguished chRCCs from oncocytomas, with 71.0% sensitivity and 73.3% specificity (AUC: 0.784). Low expression levels of SMYD2, SETD3, and NO66 were significantly associated with shorter disease-specific and disease-free survival, especially in patients with non-organ confined tumors. We conclude that expression of selected HMTs and HDMs might constitute novel biomarkers to assist in RCT diagnosis and assessment of tumor aggressiveness.

Myxoma of the mitral valve

Only rarely do myxomas originate from the mitral valve. This is the report of a 49-year-old woman presenting with congestive heart failure. The diagnosis of an intracardiac tumor involving the anterior cuspid of the mitral valve was made by transesophageal echocardiography. The patient underwent surgery for tumor resection and plasty of the valve was made with reconstruction and preservation of the valve. The diagnosis of myxoma was confirmed by histology. This is the 23rd case of myxoma of the mitral valve reported in the literature.

The isolation of Aspergillus spp from harvested maize in three Portuguese regions

In Portugal, maize is the cereal that involves more agriculture explorations. Aspergillus spp., among other species, are usually associated with this cereal, during drying and storage, making this commodity susceptible to mycotoxins (such as aflatoxins, ochratoxins, and cyclopiazonic acid). The aim of this study was to evaluate the mycotoxigenic potential of isolated Aspergillus strains from these maize samples and correlate it with the sampling place, the weather conditions, and local practices during drying and storage. The samples were collected between November 2008 and April 2009 in maize association of producers facilities in Coimbra, Santarém and Portalegre. The isolated strains were divided in three distinct groups, Aspergillus section Flavi, Aspergillus section Nigri and others Aspergillus. The preliminary results show that there are differences between the incidence of these groups in the three sampling places, especially in Coimbra, probably due to a lower mean temperatures and higher humidity levels. These data will be presented and discussed.

João de Guimarães Golias, o homem e o diplomata (1599-1653)

Dissertação de mestrado em História

Segmentação morfológica e dificuldades de leitura em crianças com perturbações de leitura e escrita

O presente estudo pretende verificar se existe uma correlação entre consciência morfológica e desempenho em leitura e escrita (mais precisamente, na componente de leitura) em crianças com e sem dificuldades ou perturbação de leitura e escrita. Para cumprir este objetivo, aplicou-se, numa amostra de crianças falantes de português europeu, dois instrumentos de avaliação: o “Teste de Idade de Leitura” e uma Prova de Consciência Morfológica, especificamente criada para o efeito. O grupo experimental (GE) inclui crianças com diagnóstico de dificuldades ou perturbação de leitura e escrita; o grupo de controlo (GC) não. Após a análise dos dados, conclui-se que existe uma diferença estatisticamente significativa entre os grupos de crianças em estudo, uma vez que o GC revela um desempenho superior ao GE em ambas as provas aplicadas. Os resultados obtidos demonstram ainda uma correlação estatisticamente significativa entre o desempenho das crianças no domínio de leitura e o desempenho das crianças ao nível da consciência morfológica. A correlação mostra-se consideravelmente mais forte no GE do que no GC. Deste modo, conclui-se que a estimulação da consciência morfológica pode efetivamente facilitar e auxiliar o desenvolvimento da aprendizagem leitora em crianças, sobretudo em crianças com dificuldades nestes domínios.

Factores de risco de abuso no relacionamento íntimo: Estudo de validação da versão portuguesa do questionário “Personal and Relationships Profile”

O presente artigo trata do estudo das características psicométricas da versão portuguesa do questionário “Personal and Relationships Profile" (PRP, Straus, Hamby, Boney-McCoy, & Sugarman, 1999). Este instrumento destina-se a avaliar os principais factores relacionados com a ocorrência de abuso no relacionamento com o companheiro; integra 21 sub-escalas substantivas e uma sub-escala de desejabilidade social. Foram participantes 551 estudantes universitários (60.3% do sexo feminino), na sua maioria com idades compreendidas entre os 19 e os 25 anos e com uma relação do tipo namoro. O questionário apresenta elevada consistência interna (α=.90), e as sub-escalas têm valores de alpha de Cronbach compreendidos entre .50 e .84. Confirma-se também a validade externa dado que um elevado número de sub-escalas do PRP, se encontra significativamente correlacionado com a escala de abuso físico sem sequelas (CT52). Os resultados obtidos confirmam a validade da versão portuguesa do questionário PRP, possibilitando a investigadores e práticos no âmbito das relações maritais um instrumento de screening para sinalização, aprofundamento e orientação das linhas de acção específicas no tratamento e/ou investigação dos principais factores associados à violência conjugal.

Multiple Embolism in a Female Patient with Infective Endocarditis: Low Back Pain and Hematuria as the Initial Clinical Manifestations

A 59-year-old female patient with mitral valve prolapse and a previous history of lumbosacral spondyloarthrosis and lumbar disk hernia had an episode of infective endocarditis due to Streptococcus viridans, which evolved with peripheral embolism to the left kidney, spleen, and left iliac artery, and intraventricular cerebral hemorrhage. Her clinical manifestations were low back pain and hematuria, which were initially attributed to an osteoarticular condition. Infective endocarditis is a severe polymorphic disease with multiple clinical manifestations and it should always be included in the differential diagnosis by clinicians.

Apresentação [a "Modernidades comparadas: estudos literários/estudos culturais revisitados"]

Coleção Hespérides. Literatura n.º 28