MicroRNA-375 plays a dual role in prostate carcinogenesis

Background: Prostate cancer (PCa), a highly incident and heterogeneous malignancy, mostly affects men from developed countries. Increased knowledge of the biological mechanisms underlying PCa onset and progression are critical for improved clinical management. MicroRNAs (miRNAs) deregulation is common in human cancers, and understanding how it impacts in PCa is of major importance. MiRNAs are mostly downregulated in cancer, although some are overexpressed, playing a critical role in tumor initiation and progression. We aimed to identify miRNAs overexpressed in PCa and subsequently determine its impact in tumorigenesis. Results: MicroRNA expression profiling in primary PCa and morphological normal prostate (MNPT) tissues identified 17 miRNAs significantly overexpressed in PCa. Expression of three miRNAs, not previously associated with PCa, was subsequently assessed in large independent sets of primary tumors, in which miR-182 and miR-375 were validated, but not miR-32. Significantly higher expression levels of miR-375 were depicted in patients with higher Gleason score and more advanced pathological stage, aswellaswithregionallymph nodesmetastases. Forced expression of miR-375 in PC-3 cells, which display the lowest miR-375 levels among PCa cell lines, increased apoptosis and reduced invasion ability and cell viability. Intriguingly, in 22Rv1 cells, which displayed the highest miR-375 expression, knockdown experiments also attenuated the malignant phenotype. Gene ontology analysis implicated miR-375 in several key pathways deregulated in PCa, including cell cycle and cell differentiation. Moreover, CCND2 was identified as putative miR-375 target in PCa, confirmed by luciferase assay. Conclusions: A dual role for miR-375 in prostate cancer progression is suggested, highlighting the importance of cellular context on microRNA targeting.

Conformal symmetry of the critical 3D Ising model inside a sphere

We perform Monte-Carlo simulations of the three-dimensional Ising model at the critical temperature and zero magnetic field. We simulate the system in a ball with free boundary conditions on the two dimensional spherical boundary. Our results for one and two point functions in this geometry are consistent with the predictions from the conjectured conformal symmetry of the critical Ising model.

Critical analyses of the introduction of liquid-based cytology in a public health service of the state of São Paulo, Brazil

OBJECTIVE The aim of this study was to compare the performance of the current conventional Pap smear with liquid-based cytology (LBC) preparations. STUDY DESIGN Women routinely undergoing their cytopathological and histopathological examinations at Fundação Oncocentro de São Paulo (FOSP) were recruited for LBC. Conventional smears were analyzed from women from other areas of the State of São Paulo with similar sociodemographic characteristics. RESULTS A total of 218,594 cases were analyzed, consisting of 206,999 conventional smears and 11,595 LBC. Among the conventional smears, 3.0% were of unsatisfactory preparation; conversely, unsatisfactory LBC preparations accounted for 0.3%. The ASC-H (atypical squamous cells - cannot exclude high-grade squamous intraepithelial lesion) frequency did not demonstrate any differences between the two methods. In contrast, the incidence of ASC-US (atypical squamous cells of undetermined significance) was almost twice as frequent between LBC and conventional smears, at 2.9 versus 1.6%, respectively. An equal percentage of high-grade squamous intraepithelial lesions were observed for the two methods, but not for low-grade squamous intraepithelial lesions, which were more significantly observed in LBC preparations than in conventional smears (2.2 vs. 0.7%). The index of positivity was importantly enhanced from 3.0% (conventional smears) to 5.7% (LBC). CONCLUSIONS LBC performed better than conventional smears, and we are truly confident that LBC can improve public health strategies aimed at reducing cervical lesions through prevention programs.

Layer-by-layer technique to developing functional nanolaminate films with antifungal activity

The layer-by-layer (LbL) deposition method was used to build up alternating layers (five) of different polyelectrolyte solutions (alginate, zein-carvacrol nanocapsules, chitosan and chitosan-carvacrol emulsions) on an aminolysed/charged polyethylene terephthalate (A/C PET) film. These nanolaminated films were characterised by contact angle measurements and through the determination of water vapour (WVTR) and oxygen (O2TR) transmission rates. The effect of active nanolaminated films against the Alternaria sp. and Rhizopus stolonifer was also evaluated. This procedure allowed developing optically transparent nanolaminated films with tuneable water vapour and gas properties and antifungal activity. The water and oxygen transmission rate values for the multilayer films were lower than those previously reported for the neat alginate or chitosan films. The presence of carvacrol and zein nanocapsules significantly decreased the water transmission rate (up to 40 %) of the nanolaminated films. However, the O2TR behaved differently and was only improved (up to 45 %) when carvacrol was encapsulated, i.e. nanolaminated films prepared by alternating alginate with nanocapsules of zein-carvacrol layers showed better oxygen barrier properties than those prepared as an emulsion of chitosan and carvacrol. These films containing zein-carvacrol nanocapsules also showed the highest antifungal activity (30 %), which did not significantly differ from those obtained with the highest amount of carvacrol, probably due to the controlled release of the active agent (carvacrol) from the zein-carvacrol nanocapsules. Thus, this work shows that nanolaminated films prepared with alternating layers of alginate and zein-carvacrol nanocapsules can be considered to improve the shelf-life of foodstuffs.

Escritas da utopia na literatura contemporânea – da utopia à distopia

Tese de Doutoramento em Ciências da Literatura (Especialidade em Literatura Comparada)

Gender, sex and sexuality in two open access communication journals published in Portugal: a critical overview of current discursive practices

The links between gender, sex and sexuality and their relevance are theoretically and politically problematic (Richardson, 2007). One of the difficulties in understanding their interconnections is that these terms are often used differently and ambiguously by different authors (and even by the same authors). This article reports the results of an analysis of the articles published in open access communication journals with known impact factor, edited in Portugal and published between 2005 and 2012. The diverse conceptualisations of those three basic concepts and of their (inter)relationships within communication research are identified. The complexity and the intricate (and often implicit) nature of both the meanings of these categories and their relationships underlie and justify our attention and further research. What the findings suggest about the current communication research into gender issues published in the two journals surveyed is that the ‘Gender differences discourse’ (Sunderland, 2004) is the most pervasive discourse (also) in academic practice. Additionally, they show that gender and sex are mainly taken for a fact, not a question that is worth being studied. The editors of these journals, as well as the scholars submitting manuscripts, need to be more aware of the traditional nature of the theoretical and methodological choices that they make regarding gender- and sex-related issues, as well as of the relative lack of attention to sexuality as a research subject.

Safety management of cranes on construction sites in Portugal: Critical factors of safety

The evolution of the construction caused a need to use more effective equipments, capable of meeting the increasingly demanding deadlines for the completion of works. In this context, the safety and efficiency of equipment have become key aspects in order to optimize the execution time of the works, as well as reducing labor costs and loss of materials. With the evolution of construction and construction processes, cranes have come to represent a signal of the construction of buildings, revealing to be, in most of the cases, the main equipment of construction sites. Currently, some engineers revels some apprehension regarding the use and handling of cranes which is natural and acceptable, since an equipment failure can lead to serious or fatal accidents. The factors affecting safety management of the cranes in construction sites were investigated, identified, classified and evaluated according to their degree of importance, through interviews with representatives of the general contractors of a set of selected construction sites.

Media(ted) discourse and society: rethinking the framework of critical discourse analysis

The analysis of journalistic discourse and its social embeddedness has known significant advances in the last two decades, especially due to the emergence and development of Critical Discourse Analysis. However, three important aspects remain under-researched: the time plane in discourse analysis, the discursive strategies of social actors, and the extra- and supra-textual effects of mediated discourse. Firstly, understanding the biography of public matters requires a longitudinal examination of mediated texts and their social contexts but most forms of analysis of journalistic discourse do not account for the time sequence of texts and its implications. Secondly, as the media representation of social issues is, to a large extent, a function of the discursive construction of events, problems and positions by social actors, the discursive strategies that they employ in a variety of arenas and channels ‘‘before’’ and ‘‘after’’ journalistic texts need to be examined. Thirdly, the fact that many of the modes of operation of discourse are extra- or supra-textual calls for a consideration of various social processes ‘‘outside’’ the text. This paper aims to produce a theoretical and methodological contribution to the integration of these issues in discourse analysis by proposing a framework that combines a textual dimension with a contextual one

Formação de professores: uma prática pedagógica frente aos desafios das necessidades educativas especiais: um estudo de caso numa IES Particular em Manaus-Am

Dissertação de mestrado em Educação Especial (área de especialização em Dificuldades de Aprendizagem Específicas)

A critical evaluation of methods for the reconstruction of tissue-specific models

Under the framework of constraint based modeling, genome-scale metabolic models (GSMMs) have been used for several tasks, such as metabolic engineering and phenotype prediction. More recently, their application in health related research has spanned drug discovery, biomarker identification and host-pathogen interactions, targeting diseases such as cancer, Alzheimer, obesity or diabetes. In the last years, the development of novel techniques for genome sequencing and other high-throughput methods, together with advances in Bioinformatics, allowed the reconstruction of GSMMs for human cells. Considering the diversity of cell types and tissues present in the human body, it is imperative to develop tissue-specific metabolic models. Methods to automatically generate these models, based on generic human metabolic models and a plethora of omics data, have been proposed. However, their results have not yet been adequately and critically evaluated and compared. This work presents a survey of the most important tissue or cell type specific metabolic model reconstruction methods, which use literature, transcriptomics, proteomics and metabolomics data, together with a global template model. As a case study, we analyzed the consistency between several omics data sources and reconstructed distinct metabolic models of hepatocytes using different methods and data sources as inputs. The results show that omics data sources have a poor overlapping and, in some cases, are even contradictory. Additionally, the hepatocyte metabolic models generated are in many cases not able to perform metabolic functions known to be present in the liver tissue. We conclude that reliable methods for a priori omics data integration are required to support the reconstruction of complex models of human cells.

Critical aortic stenosis in the neonate. Clinical assessment and surgical outcome in 18 patients

OBJECTIVE - To assess neonates with aortic stenosis with early decompensation operated upon. (LCO) (CHF). METHODS - A and retrospective study analyzing 6 neonates with LCO, group I (GI), and 12 neonates with CHF, group II (GII). Clinical radiographic, electrocardiographic and echocardiographic findings also provided comparative bases for the study, as did surgical and evolutional findings. RESULTS - The mean ages at hospitalization and surgery (p = 0.0031) were 14.3 and 14.8 days in GI and 35.4 and 42.8 days in GII, respectively. Cardiac murmurs were more intense in GII (p = 0.0220). The aortic ring was smaller in GI (8.0 ± 2.5mm) as compared to GII (11.4±1.4mm) (p = 0.2882). Ventricular function was reduced to 18±5.5% and 33.3±7.6% in GI and GII, respectively (p = 0.0162). Aortic atresia, however, was present only in 2 neonates in GI. Five of 6 patients in GI died but all patients in GII survived (p=0.0007). In the latter group, 84.6% of the patients were in functional class I (FC-I) in the long-term follow-up, with moderate residual lesions in 6 neonates, discrete residual lesions in 4, and reoperation in 2. CONCLUSION - Aortic stenosis is a severe anomaly of the neonate, whose immediate evolution depends on the pre-operative anatomic and functional findings, and the late evolution essentially depends on the anatomic features of the valve.

Fontan Operation and the Cavopulmonary Technique: Immediate and Late Results According to the Presence of Atrial Fenestration

OBJECTIVE: To compare immediate and late results in patients with or without fenestration who underwent cavopulmonary anastomosis so that we could assess the efficiency of the technique. METHODS: Sixty-two patients underwent surgery between 1988 and 1999, 41 with fenestration (group I -G I) and 21 without fenestration (group II -G II). Tricuspid atresia was prevalent in group I (23-56%) and single ventricle was prevalent in group II (14-66%). Mean ages at the time of operation were 7.3 years in group I and 7.6 in group II. At late follow-up, mean ages were 10.6 years in group I and 12.8 years in group II. RESULTS: Immediate and late mortality were 7.3% in G-I and 4.7% in G-II. Significant pleural effusion occurred in 41.4% of G-I patients and in 23.8% of G-II patients. Significant pericardial effusion occurred in 29.2% and 14.2%, respectively, in groups I and II. Central venous pressure was greater in G-II, 17.7 cm in H2O, as opposed to 15 cm in G-I. Hospital stay was similar between the groups, 26.3 and 21.8 days, respectively. Cyanosis and arterial insaturation occurred in 5 patients, and 4 patients were in functional class II, all from G-I. At late follow-up, 58 (93.5%) were in functional class I. Sinus rhythm was present in 94%, and pulmonary perfusion was similar in both groups. Eleven patients who underwent spirometry had good tolerance to physical effort. CONCLUSION: Atrial fenestration did not improve the immediate or late follow-up of patients who underwent cavopulmonary anastomosis, and is, therefore, dispensable.

Critical events in mechanically ventilated patients

Mechanical Ventilation is an artificial way to help a Patient to breathe. This procedure is used to support patients with respiratory diseases however in many cases it can provoke lung damages, Acute Respiratory Diseases or organ failure. With the goal to early detect possible patient breath problems a set of limit values was defined to some variables monitored by the ventilator (Average Ventilation Pressure, Compliance Dynamic, Flow, Peak, Plateau and Support Pressure, Positive end-expiratory pressure, Respiratory Rate) in order to create critical events. A critical event is verified when a patient has a value higher or lower than the normal range defined for a certain period of time. The values were defined after elaborate a literature review and meeting with physicians specialized in the area. This work uses data streaming and intelligent agents to process the values collected in real-time and classify them as critical or not. Real data provided by an Intensive Care Unit were used to design and test the solution. In this study it was possible to understand the importance of introduce critical events for Mechanically Ventilated Patients. In some cases a value is considered critical (can trigger an alarm) however it is a single event (instantaneous) and it has not a clinical significance for the patient. The introduction of critical events which crosses a range of values and a pre-defined duration contributes to improve the decision-making process by decreasing the number of false positives and having a better comprehension of the patient condition.