XRCC3 THR241MET polymorphism influence on nuclear buds frequency in exposed to formaldehyde

Formaldehyde (FA), also known as formalin, formal and methyl aldehydes, is a colorless, flammable, strong-smelling gas. It has an important application in embalming tissues and that result in exposures for workers in the pathology anatomy laboratories and mortuaries. Occupational exposure to FA has been shown to induce nasopharyngeal cancer and has been classified as carcinogenic to humans (group 1) on the basis of sufficient evidence in humans and sufficient evidence in experimental animals. Manifold in vitro studies clearly indicated that FA is genotoxic. FA induced various genotoxic effects in proliferating cultured mammalian cells. The cytokinesis-block micronucleus (CBMN) assay was originally developped as an ideal system form easuring micronucleus (MN), however it can also be used to measure nucleoplasmic bridges (NBP) and nuclear buds (NBUD). Over the past decade another unique mechanism of micronucleus formation, known as nuclear budding has emerged. NBUDS is considered as a marker of gene amplification and/or altered gene dosage because the nuclear budding process is the mechanism by which cells removed amplified and/excess DNA.

Solid-state Marx based two-switch voltage modulator for the On-Line Isotope Mass Separator accelerator at the European Organization for Nuclear Research

A new circuit topology is proposed to replace the actual pulse transformer and thyratron based resonant modulator that supplies the 60 kV target potential for the ion acceleration of the On-Line Isotope Mass Separator accelerator, the stability of which is critical for the mass resolution downstream separator, at the European Organization for Nuclear Research. The improved modulator uses two solid-state switches working together, each one based on the Marx generator concept, operating as series and parallel switches, reducing the stress on the series stacked semiconductors, and also as auxiliary pulse generator in order to fulfill the target requirements. Preliminary results of a 10 kV prototype, using 1200 V insulated gate bipolar transistors and capacitors in the solid-state Marx circuits, ten stages each, with an electrical equivalent circuit of the target, are presented, demonstrating both the improved voltage stability and pulse flexibility potential wanted for this new modulator.

Genotoxicity biomarkers micronucleus, nucleoplasmic bridges and nuclear buds

The increase of mortality from cancer brought urgency in identification and validation of predictive markers of risk and therefore early diagnosis. There is evidence that cytogenetic biomarkers are positively correlated with risk of cancer, and this is validated by studies of cohort and case-control. Cytokinesis-blocked micronucleus (CBMN) assay is used extensively in molecular epidemiology, and can be considered as a “cytome” assay covering cell proliferation, apoptosis, necrosis and chromosomal changes. The chromosomal alterations most reported and studied by the CBMN are: micronucleus (MN), nucleoplasmic bridges (NPB) and nuclear buds (NBUDS). The use of the MN assay in biomonitoring studies had a large increase in the last 15 years and international projects such as the HUMN have helped to increase the applicability and reliability of these tests.

A medicina nuclear no diagnóstico dos tumores gastroenteropancreáticos

Objectivo do estudo - Demonstrar o contributo, essencial, que a Medicina Nuclear apresenta no diagnóstico dos Tumores Gastroenteropancreáticos e demonstrar a importância da precocidade diagnóstica recorrendo, maioritariamente, aos exames de medicina nuclear.

Some bounds of loss in classical semideterministic immunization

Since Samuelson, Redington and Fisher and Weil, duration and immunization are very important topics in bond portfolio analysis from both a theoretical and a practical point of view. Many results have been established, especially in semi-deterministic framework. As regards, however, the loss may be sustained, we do not think that the subject has been investigated enough, except for the results found in the wake of the theorem of Fong and Vasicek. In this paper we present some results relating to the limitation of the loss in the case of local immunization for multiple liabilities.

Viabilidade económica da implementação de um reactor nuclear para a produção de energia eléctrica em Portugal

O presente trabalho tem como objectivo avaliar economicamente e determinar a viabilidade da implementação de um reactor nuclear para produção de energia eléctrica. Faz-se uma abordagem a aspectos da energia nuclear no mundo e em particular a energia nuclear na união europeia, faz-se uma análise sobre a estrutura do sector nuclear em Espanha e o futuro da energia no mundo. É realizada uma análise sobre a energia nuclear em Portugal, são abordados aspectos como o planeamento energético, a localização da central nuclear, os recursos nacionais e internacionais, a inspecção e regulação nuclear e o impacto industrial. Por fim, faz-se uma análise sobre o mix energético português. Faz-se uma descrição do ciclo de combustível, isto é, um estudo a todas as fases pela qual o combustível nuclear passa desde a sua extracção, passando pela produção de energia e processamento dos resíduos. São descritos os principais componentes de uma central nuclear e o seu princípio de funcionamento. São analisados em detalhe os principais componentes de um reactor PWR (Objecto de estudo deste trabalho) e faz-se uma breve descrição de alguns modelos de reactores nucleares. É feita uma breve abordagem aos principais acidentes nucleares que ocorreram, e descrita a escala de ocorrências nucleares e as várias fases de desmantelamento de uma central. São apresentados os principais custos da central nuclear. Também é apresentado um estudo de viabilidade económica analisando três cenários diferentes e é apresentada uma análise de sensibilidade do VAL em função de algumas variáveis que têm grande influência na avaliação económica. São apresentadas as principais conclusões.

Agentes fitoquímicos como radio-sensibilizadores na terapêutica em medicina nuclear

Mestrado em Medicina Nuclear. Área de especialização: Radiofarmácia.

Cellular polarity in aging: role of redox regulation and nutrition

Cellular polarity concerns the spatial asymmetric organization of cellular components and structures. Such organization is important not only for biological behavior at the individual cell level, but also for the 3D organization of tissues and organs in living organisms. Processes like cell migration and motility, asymmetric inheritance, and spatial organization of daughter cells in tissues are all dependent of cell polarity. Many of these processes are compromised during aging and cellular senescence. For example, permeability epithelium barriers are leakier during aging; elderly people have impaired vascular function and increased frequency of cancer, and asymmetrical inheritance is compromised in senescent cells, including stem cells. Here, we review the cellular regulation of polarity, as well as the signaling mechanisms and respective redox regulation of the pathways involved in defining cellular polarity. Emphasis will be put on the role of cytoskeleton and the AMP-activated protein kinase pathway. We also discuss how nutrients can affect polarity-dependent processes, both by direct exposure of the gastrointestinal epithelium to nutrients and by indirect effects elicited by the metabolism of nutrients, such as activation of antioxidant response and phase-II detoxification enzymes through the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In summary, cellular polarity emerges as a key process whose redox deregulation is hypothesized to have a central role in aging and cellular senescence.

Translation termination and protein folding pathway genes are not correlated in gastric cancer

Background: The eukaryotic release factor 3 (eRF3) has been shown to affect both tubulin and actin cytoskeleton, suggesting a role in cytoskeleton assembly, mitotic spindle formation and chromosome segregation. Also, direct interactions between eRF3 and subunits of the cytosolic chaperonin CCT have been described. Moreover, both eRF3a and CCT subunits have been described to be up-regulated in cancer tissues. Our aim was to evaluate the hypothesis that eRF3 expression levels are correlated with the expression of genes encoding proteins involved in the tubulin folding pathways. Methods: Relative expression levels of eRF1, eRF3a/GSPT1, PFDN4, CCT2, CCT4, and TBCA genes in tumour samples relative to their adjacent normal tissues were investigated using real time-polymerase chain reaction in 20 gastric cancer patients. Results: The expression levels of eRF3a/GSPT1 were not correlated with the expression levels of the other genes studied. However, significant correlations were detected between the other genes, both within intestinal and diffuse type tumours. Conclusions: eRF3a/GSPT1 expression at the mRNA level is independent from both cell translation rates and from the expression of the genes involved in tubulin-folding pathways. The differences in the patterns of expression of the genes studied support the hypothesis of genetically independent pathways in the origin of intestinal and diffuse type gastric tumours.

Expression of YAP4 in Saccharomyces cerevisiae under osmotic stress

YAP4, a member of the yeast activator protein (YAP) gene family, is induced in response to osmotic shock in the yeast Saccharomyces cerevisiae. The null mutant displays mild and moderate growth sensitivity at 0.4 M and 0.8 M NaCl respectively, a fact that led us to analyse YAP4 mRNA levels in the hog1 (high osmolarity glycerol) mutant. The data obtained show a complete abolition of YAP4 gene expression in this mutant, placing YAP4 under the HOG response pathway. YAP4 overexpression not only suppresses the osmosensitivity phenotype of the yap4 mutant but also relieves that of the hog1 mutant. Induction, under the conditions tested so far, requires the presence of the transcription factor Msn2p, but not of Msn4p, as YAP4 mRNA levels are depleted by at least 75% in the msn2 mutant. This result was further substantiated by the fact that full YAP4 induction requires the two more proximal stress response elements. Furthermore we find that GCY1, encoding a putative glycerol dehydrogenase, GPP2, encoding a NAD-dependent glycerol-3-phosphate phosphatase, and DCS2, a homologue to a decapping enzyme, have decreased mRNA levels in the yap4 -deleted strain. Our data point to a possible, as yet not entirely understood, role of the YAP4 in osmotic stress response.

Cholesterol 24S-Hydroxylase overexpression inhibits the liver X receptor (LXR) pathway by activating small guanosine triphosphate-binding proteins (sGTPases) in neuronal cells

The neuronal-specific cholesterol 24S-hydroxylase (CYP46A1) is important for brain cholesterol elimination. Cyp46a1 null mice exhibit severe deficiencies in learning and hippocampal long-term potentiation, suggested to be caused by a decrease in isoprenoid intermediates of the mevalonate pathway. Conversely, transgenic mice overexpressing CYP46A1 show an improved cognitive function. These results raised the question of whether CYP46A1 expression can modulate the activity of proteins that are crucial for neuronal function, namely of isoprenylated small guanosine triphosphate-binding proteins (sGTPases). Our results show that CYP46A1 overexpression in SH-SY5Y neuroblastoma cells and in primary cultures of rat cortical neurons leads to an increase in 3-hydroxy-3-methyl-glutaryl-CoA reductase activity and to an overall increase in membrane levels of RhoA, Rac1, Cdc42 and Rab8. This increase is accompanied by a specific increase in RhoA activation. Interestingly, treatment with lovastatin or a geranylgeranyltransferase-I inhibitor abolished the CYP46A1 effect. The CYP46A1-mediated increase in sGTPases membrane abundance was confirmed in vivo, in membrane fractions obtained from transgenic mice overexpressing this enzyme. Moreover, CYP46A1 overexpression leads to a decrease in the liver X receptor (LXR) transcriptional activity and in the mRNA levels of ATP-binding cassette transporter 1, sub-family A, member 1 and apolipoprotein E. This effect was abolished by inhibition of prenylation or by co-transfection of a RhoA dominant-negative mutant. Our results suggest a novel regulatory axis in neurons; under conditions of membrane cholesterol reduction by increased CYP46A1 expression, neurons increase isoprenoid synthesis and sGTPase prenylation. This leads to a reduction in LXR activity, and consequently to a decrease in the expression of LXR target genes.

Avaliação da cultura de segurança num serviço de medicina nuclear

Mestrado em Gestão e Avaliação de Tecnologias em Saúde

Research practice development for nuclear medicine technologists: an innovative experience

Introduction - European nuclear medicine technologist’s education is delivered by Higher Education Institutions and students obtain a grade of Bachelor of Sciences (BSc), during which they are initiated to research during their studies. Once BSc nuclear medicine technologists are in professional practice, they have very few opportunities to develop a real research experience and they rather become passive users than active contributors the growth of scientific knowledge in nuclear medicine. Aim - To describe and discuss an innovative educational and professional experience aimed in strengthen research knowledge, skills and competencies of former nuclear medicine technologists student in the context of an international mobility stay.

A checklist for patient safety rounds at the care pathway level

Objective - To define a checklist that can be used to assess the performance of a department and evaluate the implementation of quality management (QM) activities across departments or pathways in acute care hospitals. Design - We developed and tested a checklist for the assessment of QM activities at department level in a cross-sectional study using on-site visits by trained external auditors. Setting and Participants - A sample of 292 hospital departments of 74 acute care hospitals across seven European countries. In every hospital, four departments for the conditions: acute myocardial infarction (AMI), stroke, hip fracture and deliveries participated. Main outcome measures - Four measures of QM activities were evaluated at care pathway level focusing on specialized expertise and responsibility (SER), evidence-based organization of pathways (EBOP), patient safety strategies and clinical review (CR). Results - Participating departments attained mean values on the various scales between 1.2 and 3.7. The theoretical range was 0-4. Three of the four QM measures are identical for the four conditions, whereas one scale (EBOP) has condition-specific items. Correlations showed that every factor was related, but also distinct, and added to the overall picture of QM at pathway level. Conclusion - The newly developed checklist can be used across various types of departments and pathways in acute care hospitals like AMI, deliveries, stroke and hip fracture. The anticipated users of the checklist are internal (e.g. peers within the hospital and hospital executive board) and external auditors (e.g. healthcare inspectorate, professional or patient organizations).

Nuclear medicine technologist education and training in Europe: literature and web-based findings

Purpose - The education and training of a nuclear medicine technologist (NMT) is not homogeneous among European countries, which leads to different scope of practices and, therefore, different technical skills are assigned. The goal of this research was to characterize the education and training of NMT in Europe. Materials and methods - This study was based on a literature research to characterize the education and training of NMT and support the historical evolution of this profession. It was divided into two different phases: the first phase included analysis of scientific articles and the second phase included research of curricula that allow health professionals to work as NMT in Europe. Results - The majority of the countries [N=31 (89%)] offer the NMT curriculum integrated into the high education system and only in four (11%) countries the education is provided by professional schools. The duration in each education system is not equal, varying in professional schools (2-3 years) and high education level system (2-4 years), which means that different European Credit Transfer and Accumulation System, such as 240, 230, 222, 210 or 180 European Credit Transfer and Accumulation System, are attributed to the graduates. The professional title and scope of the practice of NMT are different in different countries in Europe. In most countries of Europe, nuclear medicine training is not specific and curriculum does not demonstrate the Nuclear Medicine competencies performed in clinical practice. Conclusion - The heterogeneity in education and training for NMT is an issue prevalent among European countries. For NMT professional development, there is a huge need to formalize and unify educational and training programmes in Europe.