1,091 research outputs found

    Communication in Clinical Practice, the Perspective of Patients with Cancer: Translation of the PACE (Patient Assessment of Cancer Communication Experiences) Questionnaire to European Portuguese

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    Introduction: Communication in clinical practice is essential to healthcare quality, especially in Oncology. The Patient Assessment of Communication Experiences questionnaire evaluates the perspective of cancer patients towards communication and identifies areas that can be improved. This study consists in its translation and validation to European Portuguese, to identify these areas. Material and methods: We performed a descriptive, observational, cross-sectional study. The translation was conducted according to the World Health Organization's guidelines. We applied the questionnaires to a convenience sample, in patients under systemic antineoplastic treatment at the Day Hospital of Centro Hospitalar Universitário do Porto, between January and March 2020. We calculated the Cronbach's Alpha for each phase of care, the bivariate and multiple correlations and, for each question, the percentage of "non applicable" and most positive answers. Results: We had 100 participants. The instrument we obtained ha good internal consistency, but the classification of some questions does not correlate sufficiently with the global opinion about the experiences with communication in the respective phase. The diagnosis phase revealed a lower proportion of positive experiences, particularly in terms of receiving the bad news. Conclusion: This study translates and validates part of the communication assessment instrument PACE to the Portuguese language and elicits the necessity to invest in the phase of diagnosis and disclosure of bad news.ste trabalho não recebeu qualquer tipo de suporte financeiro de nenhuma entidade no domínio público ou privado

    First-principles calculations of the electrical properties of LaAlO3 and its interface with Si

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    LaAlO3 is one of the potential candidates to replace SiO2 as a high permittivity dielectric for future generations of metal-oxide-semiconductor field effect transistors. Using first-principles plane-wave calculations within density functional theory, its bulk and surface electronic properties and the relative stability of cubic c-LaAlO3(001)/Si(001) interfaces are investigated. In agreement with experiment, our study shows that the dielectric constant of crystalline LaAlO3 (similar to 30) is comparable to that of hexagonal La2O3. To accurately calculate the c-LaAlO3(001) surface energy, several ways of eliminating the surface dipole moment of the polar surface are presented, with the transfer of an oxygen anion from one boundary surface to the other being identified as the energetically most favorable mechanism. We have found that lanthanum-terminated c-LaAlO3(001)/Si(001) interfaces are in general more stable than aluminum-terminated interfaces for both the oxidized and nonoxidized Si(001) surfaces. We have also identified a significant reduction of the c-LaAlO3(001)/Si(001) valence band offset due to the creation of interface dipoles for O-rich interfaces. Analysis of the density of interface states shows that La-Si bonds at the c-LaAlO3(001)/Si(001) interface do not create interface states in the silicon band gap, in contrast to Hf-Si bonds in m-HfO2(001)/Si(001) interfaces studied previously.722

    Dose-dependent effects of Allopurinol on human foreskin fibroblast cell and human umbilical vein endothelial cell under hypoxia

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    Allopurinol, an inhibitor of xanthine oxidase, has been used in clinical trials of patients with cardiovascular and chronic kidney disease. These are two pathologies with extensive links to hypoxia and activation of the transcription factor hypoxia inducible factor (HIF) family. Here we analysed the effects of allopurinol treatment in two different cellular models, and their response to hypoxia. We explored the dose-dependent effect of allopurinol on Human Foreskin Fibroblasts (HFF) and Human Umbilical Vein Endothelial Cells (HUVEC) under hypoxia and normoxia. Under normoxia and hypoxia, high dose allopurinol reduced the accumulation of HIF-1α protein in HFF and HUVEC cells. Allopurinol had only marginal effects on HIF-1α mRNA level in both cellular systems. Interestingly, allopurinol effects over the HIF system were independent of prolyl-hydroxylase activity. Finally, allopurinol treatment reduced angiogenesis traits in HUVEC cells in an in vitro model. Taken together these results indicate that high doses of allopurinol inhibits the HIF system and pro-angiogenic traits in cells

    Segregation trends of the metal alloys Mo-Re and Mo-Pt on HfO2: A first-principles study

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    Using first-principles calculations, we compared the segregation trends at the surface of metal alloys with those at an interface with HfO2. The choice of this oxide was motivated by its significance as a potential replacement for SiO2 in advanced transistors. We considered Mo-Re and Mo-Pt alloys as typical examples of disordered and ordered alloys, respectively. The segregation to the surface/interface was analyzed in terms of metal and oxygen adsorption energies. It is shown that chemical bonding at the metal/oxide interface strongly influences segregation both in Mo-Re and Mo-Pt alloys. In particular, bonding with oxygen atoms at the oxide/Mo-Re alloy interface depletes the Re content of the interfacial layer. In the case of Mo-Pt on HfO2 an oxygen-rich interface promotes the formation of one monolayer (but not two monolayers) of Mo separating PtMox from HfO2, while a stoichiometric interface favors an abrupt PtMox/HfO2 interface. This study also shows that the presence of Mo in the alloy stabilizes Pt which can potentially decrease the tendency of Pt to diffuse into the oxide matrix. The individual constituents of these intermetallic compounds exhibit high vacuum work functions, and therefore these alloys are also likely to have sufficiently high work functions to be considered as promising candidates for p-type gate electrodes in future generations of transistors. (c) 2006 American Institute of Physics.100

    Gene Classification Based on Amino Acid Motifs and Residues: The DLX (distal-less) Test Case

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    BACKGROUND:Comparative studies using hundreds of sequences can give a detailed picture of the evolution of a given gene family. Nevertheless, retrieving only the sequences of interest from public databases can be difficult, in particular, when working with highly divergent sequences. The difficulty increases substantially when one wants to include in the study sequences from many (or less well studied) species whose genomes are non-annotated or incompletely annotated. METHODOLOGY/PRINCIPAL FINDINGS:In this work we evaluate the usefulness of different approaches of gene retrieval and classification, using the distal-less (DLX) gene family as a test case. Furthermore, we evaluate whether the use of a large number of gene sequences from a wide range of animal species, the use of multiple alternative alignments, and the use of amino acids aligned with high confidence only, is enough to recover the accepted DLX evolutionary history. CONCLUSIONS/SIGNIFICANCE:The canonical DLX homeobox gene sequence here derived, together with the characteristic amino acid variants here identified in the DLX homeodomain region, can be used to retrieve and classify DLX genes in a simple and efficient way. A program is made available that allows the easy retrieval of synteny information that can be used to classify gene sequences. Maximum likelihood trees using hundreds of sequences can be used for gene identification. Nevertheless, for the DLX case, the proposed DLX evolutionary is not recovered even when multiple alignment algorithms are used

    Piperidinols that show anti-tubercular activity as inhibitors of arylamine N-acetyltransferase: an essential enzyme for mycobacterial survival inside macrophages

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    Latent M. tuberculosis infection presents one of the major obstacles in the global eradication of tuberculosis (TB). Cholesterol plays a critical role in the persistence of M. tuberculosis within the macrophage during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids. Arylamine N-acetyltransferase (NAT) is encoded within a gene cluster that is involved in the cholesterol sterol-ring degradation and is essential for intracellular survival. The ability of the NAT from M. tuberculosis (TBNAT) to utilise propionyl-CoA links it to the cholesterol-catabolism pathway. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. TBNAT has been investigated as a potential target for TB therapies. From a previous high-throughput screen, 3-benzoyl-4-phenyl-1-methylpiperidinol was identified as a selective inhibitor of prokaryotic NAT that exhibited antimycobacterial activity. The compound resulted in time-dependent irreversible inhibition of the NAT activity when tested against NAT from M. marinum (MMNAT). To further evaluate the antimycobacterial activity and the NAT inhibition of this compound, four piperidinol analogues were tested. All five compounds exert potent antimycobacterial activity against M. tuberculosis with MIC values of 2.3-16.9 µM. Treatment of the MMNAT enzyme with this set of inhibitors resulted in an irreversible time-dependent inhibition of NAT activity. Here we investigate the mechanism of NAT inhibition by studying protein-ligand interactions using mass spectrometry in combination with enzyme analysis and structure determination. We propose a covalent mechanism of NAT inhibition that involves the formation of a reactive intermediate and selective cysteine residue modification. These piperidinols present a unique class of antimycobacterial compounds that have a novel mode of action different from known anti-tubercular drugs

    Neutrophil breaching of the blood vessel pericyte layer during diapedesis requires mast cell-derived IL-17A

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    Neutrophil diapedesis is an immediate step following infections and injury and is driven by complex interactions between leukocytes and various components of the blood vessel wall. Here, we show that perivascular mast cells (MC) are key regulators of neutrophil behaviour within the sub-endothelial space of inflamed venules. Using confocal intravital microscopy, we observe directed abluminal neutrophil motility along pericyte processes towards perivascular MCs, a response that created neutrophil extravasation hotspots. Conversely, MC-deficiency and pharmacological or genetic blockade of IL-17A leads to impaired neutrophil sub-endothelial migration and breaching of the pericyte layer. Mechanistically, identifying MCs as a significant cellular source of IL-17A, we establish that MC-derived IL-17A regulates the enrichment of key effector molecules ICAM-1 and CXCL1 in nearby pericytes. Collectively, we identify a novel MC-IL-17A-pericyte axis as modulator of the final steps of neutrophil diapedesis, with potential translational implications for inflammatory disorders driven by increased neutrophil diapedesis
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