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The increasing number of human biomonitoring (HBM) studies undertaken in recent decades has brought to light the need to harmonise procedures along all phases of the study, including sampling, data collection and analytical methods to allow data comparability. The first steps towards harmonisation are the identification and collation of HBM methodological information of existing studies and data gaps. Systematic literature reviews and meta-analyses have been traditionally put at the top of the hierarchy of evidence, being increasingly applied to map available evidence on health risks linked to exposure to chemicals. However, these methods mainly capture peer-reviewed articles, failing to comprehensively identify other important, unpublished sources of information that are pivotal to gather a complete map of the produced evidence in the area of HBM. Within the framework of the European Human Biomonitoring Initiative (HBM4EU) initiative—a project that joins 30 countries, 29 from Europe plus Israel, the European Environment Agency and the European Commission—a comprehensive work of data triangulation has been made to identify existing HBM studies and data gaps across countries within the consortium. The use of documentary analysis together with an up-to-date platform to fulfil this need and its implications for research and practice are discussed. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

The work presented in this thesis investigates the metabolic and functional benefits of metabolic modulatory treatment strategies in a rodent model of type 2 diabetes. The first strategy, using a fatty acid translocase (FAT/CD36) inhibitor was investigated, in an attempt to reduce fatty acid oxidation and force glucose uptake and glycolysis. A second strategy, using prolyl hydroxylase domain (PHD) inhibitors, was investigated, to activate hypoxia inducible factor 1 alpha (HIF-1–) to stimulate glycolysis and inhibit fatty acid oxidation. Type 2 diabetes was induced using high fat feeding and low dose streptozotocin in male Wistar rats. Hearts were excised for Langendorff perfusion, to assess substrate metabolism and cardiac function in the intact contracting organ. The use of ex vivo treatment with fatty acid uptake inhibitor sulfo-N-succinimidyl oleate (SSO) was investigated using a protocol of acute hypoxia and reoxygenation. The use of in vivo treatment with the prolyl hydroxylase domain inhibitors, dimethyloxalylglycine (DMOG) and Molidustat, (BAY85-3934) was investigated using a protocol of acute low-flow ischaemia and reperfusion. Diabetic hearts showed a significant impairment in functional recovery following both hypoxia-reoxygenation and ischaemia-reperfusion, and this was associated with lower glycolytic rates, and higher fatty acid oxidation rates, compared with controls. Metabolomics analysis revealed non-uniform changes to the Krebs cycle intermediates in diabetes, with a depletion of intermediates in the first span of the cycle, and accumulation of intermediates within the second span. When perfused hearts were given SSO just four minutes prior to the onset of hypoxia, a significant improvement in functional recovery was seen in diabetic hearts, which displayed similar recovery levels to control hearts. This improvement was associated with decreased fatty acid oxidation rates, increased glycolytic rates, and decreased triacylglyceride accumulation following hypoxia. Diabetic hearts from rats given three doses of DMOG (40 mg/kg) in vivo showed significantly improved functional recovery following ischaemia-reperfusion. However, this was not accompanied by the predicted improvement in susbtrate metabolism. No significant changes were seen in glycolytic rate, instead fatty acid oxidation was found to be significantly increased in DMOG-treated diabetics. Changes in several metabolites found through metabolomics suggested the metabolic effect seen with DMOG treatment was likely due to off-target effects on other –-ketoglutaratedependent enzymes. No evidence was found for significant upregulation of HIF-1 signalling with DMOG treatment, other than increased VEGFA mRNA. Additionally, hearts from control rats that received DMOG recovered to a much lesser extent than untreated control hearts following ischaemia-reperfusion. Diabetic hearts from rats treated with five daily oral doses of Molidustat (5 mg/kg) in vivo also showed significantly improved functional recovery following ischaemia-reperfusion. This was paired with increased baseline glycolytic rates, and decreased fatty acid oxidation rates. Molidustat treatment resulted in significantly increased blood haemoglobin levels in both control and diabetic rats, suggesting stimulation of HIF-1 signalling, although no increases in HIF-1– protein or downstream target glucose transporter 1 (GLUT1, SLC2A1) were found in cardiac tissue from treated rats. This work has validated the potential of metabolic modulation as a therapeutic avenue for the treatment of the diabetic heart, harnessing substrate metabolism as a driving force for functional improvement, and to improve function under stress conditions. We have shown that metabolic modulation improves the diabetic heart’s ability to recover in acute hypoxia, and that hypoxic signalling upregulation improves recovery in ischaemia. This provides a new opportunity for the investigation and development of drugs which can selectively target metabolism in the heart to relieve the long-term maladaptation caused by diabetes, allowing it to regain its inherent metabolic flexibility, which is critical for survival under stress.

Hypoxia-inducible factor 1α (HIF1α) is activated following myocardial infarction (MI), and is critical for cardiomyocyte survival in hypoxia. Patients with type 2 diabetes have poorer prognosis post-MI, which is associated with abnormal cardiac fatty acid (FA) metabolism. We questioned whether increased FA metabolism prevented HIF1α activation during myocardial ischemia and downstream adaptation in diabetes. Type 2 diabetic rat hearts had decreased HIF1α protein accumulation following ischemia, with ischemic HIF1α levels correlating negatively with plasma FAs. HIF1α accumulation and downstream metabolic adaptation to hypoxia were suppressed in insulin-resistant cardiomyocytes. This blunted adaptation to hypoxia was due to increased FAs, as long chain FAs palmitate and oleate prevented HIF1α accumulation in hypoxia in a concentration-dependent manner, which could be reversed by blocking FA uptake. FA exerted their effects by decreasing intracellular succinate, an inhibitor of the regulatory HIF hydroxylases. HIF1α stabilisation by succinate was derived from malate-aspartate shuttle activity coupled to glycolysis, and facilitated by reverse succinate dehydrogenase activity, as decreasing flux through these pathways during hypoxia decreased HIF1α levels. In contrast, supplementing succinate in insulin resistant cells increased HIF1α accumulation. Pharmacologic inhibition of the HIF hydroxylases using dimethyloxalylglycine (DMOG) promoted HIF1α accumulation in insulin resistance, and in vivo treatment with DMOG improved post-ischemic recovery of cardiac function in diabetes. In conclusion, elevated FAs prevent cardiac HIF1α activation by decreasing succinate concentrations, resulting in impaired adaptation to ischemia and hypoxia in diabetes. Pharmacologically overriding this HIF1α inhibition improves recovery of the diabetic heart following an ischemic insult.

A crise no sistema carcerário brasileiro, com presídios superlotados e deteriorados, índices elevados de presos reincidentes, muitas vezes em situações de maior gravidade, demonstram significativas falhas no processo de ressocialização desses indivíduos. É neste contexto que surge um modelo alternativo de sistema prisional proposto pela Associação de Proteção e Assistência aos Condenados (APAC). Essa instituição visa auxiliar a justiça na execução da pena e na recuperação do preso, através de sua corresponsabilidade no processo de ressocialização. O encarceramento, nesta perspectiva, deixa de ter o intuito exclusivamente punitivo e passa a exercer o papel de reeducador e fomentador de práticas de inclusão social. Neste contexto, no que tange ao processo de educação e inclusão social, um trabalho de extensão universitária realizado na APAC Viçosa/MG passou a adotara educação cooperativista como um dos fatores de contribuição para o desenvolvimento de valores e práticas necessárias para o processo de reinclusão do indivíduo ao convívio social. Desta forma, este artigo apresenta, através da experiência dos extensionistas, uma reflexão sobre como o cooperativismo através da educação cooperativista pode contribuir no processo de ressocialização de condenados e na remissão da pena pelos partícipes da APAC. Made available in DSpace on 2018-08-15T00:34:57Z (GMT). No. of bitstreams: 1 CNPASA2018hi1.pdf: 688229 bytes, checksum: b8d81294cb487d980580bd7bdee440f6 (MD5) Previous issue date: 2018-08-14

Submitted by Teresa Maria Fernandes Rodrigues Cabral Monteiro (tita@ua.pt) on 2012-01-19T14:28:56Z No. of bitstreams: 1 2012 Nuclear-Instruments-and-Methods-in-Physics-Research,-Section-B-Beam-Interactions-with-Materials-and-Atoms.pdf: 698565 bytes, checksum: d2dfb6a26e87815cfc52905be62c6fc6 (MD5) Made available in DSpace on 2012-01-27T11:35:57Z (GMT). No. of bitstreams: 1 2012 Nuclear-Instruments-and-Methods-in-Physics-Research,-Section-B-Beam-Interactions-with-Materials-and-Atoms.pdf: 698565 bytes, checksum: d2dfb6a26e87815cfc52905be62c6fc6 (MD5) Previous issue date: 2011 PTDC/CTM/100756/2008

AlxGa1-xN (0 axis for samples with AlN contents of 0.15 and 0.77 suggest a relation between the AlN content and Tm specific sites in the lattice. Rapid thermal annealing treatments under N2 ambient were performed to remove damage and promote optical activation of rare earth intra-4fn transitions. After annealing the observed intraionic emissions of Tm3+ ions were characterized by photoluminescence. © 2012 American Institute of Physics. published

x Suplemento. Edição dos Resumos do XLI Congresso Brasileiro de Fitopatologia, Belo Horizonte, MG, ago. 2008.

Os autores apresentam um caso clínico de encefalite crónica a enterovírus num rapaz de 9 anos com agamaglobulinémia congénita ligada ao cromossoma X (doença de Bruton). Apesar da terapêutica intraventricular com doses elevadas de gamaglobulina, registou-se uma progressão da doença com deterioração neurológica maciça e morte. Discutem-se os aspectos diagnósticos e terapêuticos desta situação.