Proposta de Sistema de Monitorização da Estratégia Regional de Especialização Inteligente da Região Alentejo 2014-2020

A Unidade de Monitorização de Políticas Públicas (UMPP) da Universidade de Évora é uma estrutura técnica e científica dedicada à produção de conhecimento e informação sobre conceção, monitorização e avaliação de políticas públicas. Os UMPP Estudos são documentos de natureza sectorial e ou temática, elaborados com a preocupação de assegurar a concretização de análises em profundidade sobre políticas públicas concretas. Esta publicação destina-se a cumprir um dos objetivos da UMPP, nomeadamente a produção de conhecimento e de informação sobre a conceção, monitorização e avaliação das políticas públicas implementadas, ou em processo de implementação, na Região Alentejo, bem como promover a disseminação dessa informação no contexto regional e nacional. O UMPP Estudos nº 3 - 2015 é dedicado à apresentação de uma proposta de Sistema de Monitorização da Estratégia Regional de Especialização Inteligente da Região Alentejo 2014-2020.

Evaluation of serum lidocaine/monoethylglycylxylidide concentration to assess shunt closure in dogs with extrahepatic portosystemic shunts

Background: Liver function tests do not always normalize despite successful attenuation of extrahepatic portosystemic shunts (EHPSS). Objectives: Assess the lidocaine/monoethylglycylxylidide (MEGX) test to determine liver perfusion after EHPSS closure. Animals: Twenty dogs with EHPSS. Methods: A prospective cohort study was performed and all dogs were tested at diagnosis, 1, 3, and 6 months postoperatively. After collecting a baseline blood sample (T0), 1 mg/kg body weight of lidocaine was injected intravenously. Fifteen (T15) and 30 minutes (T30) later, blood was collected. Plasma concentrations of lidocaine and its metabolites MEGX and glycylxylidide (GX) were determined, using a high‐performance liquid chromatography with electrospray ionization tandem mass spectrometry method. Three months postoperatively, transsplenic portal scintigraphy was performed to determine EHPSS closure. Results: At T15, median MEGX concentrations were higher in dogs with closed EHPSS compared to diagnosis (33.73 ng/mL [21.11‐66.44 ng/mL] vs 13.74 ng/mL [7.25‐21.93 ng/mL]; P < .001), but were not different (12.28 ng/mL [10.62‐23.17 ng/mL] vs 13.74 ng/mL [7.25‐21.93 ng/mL]) in dogs with persistent shunting. Sensitivity to determine shunt closure for MEGX at T15 was 96.2% (95% confidence interval [CI]: 78.4‐99.8) and specificity 82.8% (95% CI: 63.5‐93.5). Conclusions and Clinical Importance: The lidocaine/MEGX test is a promising, rapid, and noninvasive blood test that seems helpful to differentiate dogs with closed EHPSS and dogs with persistent shunting after gradual attenuation

Validation of a commercial 1,2-o-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin) ester lipase assay for diagnosis of canine pancreatitis.

The objectives of this study were fourfold: technical validation of a commercial canine 1,2-o-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin) ester (DGGR) lipase assay, to calculate a reference interval for DGGR lipase by the indirect a posteriori method, to establish biological validity of the assay, and to assess agreement between DGGR lipase and specific canine pancreatic lipase (Spec cPL) assays. Dogs with histologically confirmed acute pancreatitis (n=3), chronic pancreatitis (n=8) and normal pancreatic tissue (n=7) with stored (-80°C) serum samples were identified. Relevant controls were selected. Precision, reproducibility and linearity of DGGR lipase, and the effect of sample haemolysis and freezing, were assessed. Sensitivity and specificity of DGGR lipase and Spec cPL were determined. Agreement between these two parameters was calculated using Cohen's kappa coefficient (κ). The DGGR lipase assay demonstrated excellent precision, reproducibility and linearity. Sample haemolysis and storage at -80°C for 12 months did not influence the assay. DGGR lipase (>245IU/l) and Spec cPL (>400µg/l) both showed poor sensitivity but excellent specificity for acute pancreatitis, and poor to moderate sensitivity but excellent specificity for chronic pancreatitis. Substantial agreement (κ=0.679) was found between DGGR lipase and Spec cPL. The validated DGGR lipase assay had similar sensitivity and specificity for the diagnosis of acute and chronic pancreatitis to Spec cPL. DGGR lipase is a reliable alternative to Spec cPL for the diagnosis of pancreatitis

A Negative Feedback Loop That Limits the Ectopic Activation of a Cell Type–Specific Sporulation Sigma Factor of Bacillus subtilis

Two highly similar RNA polymerase sigma subunits, σF and σG, govern the early and late phases of forespore-specific gene expression during spore differentiation in Bacillus subtilis. σF drives synthesis of σG but the latter only becomes active once engulfment of the forespore by the mother cell is completed, its levels rising quickly due to a positive feedback loop. The mechanisms that prevent premature or ectopic activation of σG while discriminating between σF and σG in the forespore are not fully comprehended. Here, we report that the substitution of an asparagine by a glutamic acid at position 45 of σG (N45E) strongly reduced binding by a previously characterized anti-sigma factor, CsfB (also known as Gin), in vitro, and increased the activity of σG in vivo. The N45E mutation caused the appearance of a sub-population of pre-divisional cells with strong activity of σG. CsfB is normally produced in the forespore, under σF control, but sigGN45E mutant cells also expressed csfB and did so in a σG-dependent manner, autonomously from σF. Thus, a negative feedback loop involving CsfB counteracts the positive feedback loop resulting from ectopic σG activity. N45 is invariant in the homologous position of σG orthologues, whereas its functional equivalent in σF proteins, E39, is highly conserved. While CsfB does not bind to wild-type σF, a E39N substitution in σF resulted in efficient binding of CsfB to σF. Moreover, under certain conditions, the E39N alteration strongly restrains the activity of σF in vivo, in a csfB-dependent manner, and the efficiency of sporulation. Therefore, a single amino residue, N45/E39, is sufficient for the ability of CsfB to discriminate between the two forespore-specific sigma factors in B. subtilis

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

TREATMENT OF AMD EXSUDATIVE WITH RANIBIZUMAB - LONG-TERM RESULTS

Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de MedicinaObjectivos: Descrever a resposta estrutural e funcional do tratamento da Degenerescência Macular da Idade (DMI) exsudativa com ranibizumab, em doentes com follow up superior a 5 anos.Métodos: Estudo retrospetivo consecutivo de doentes tratados com injeções intra-vítreas de ranibizumab, em esquema pro-re-nata (PRN), com pelo menos 5 anos de seguimento. Foi analisada a melhor acuidade visual corrigida (MAVC) e quantificado o número de injeções realizadas. Foi realizada tomografia de coerência ótica spectral domain (OCT-SD) que permitiu a determinação da espessura foveal no milímetro central e de parâmetros estruturais qualitativos, nomeadamente a presença de atrofia macular (definida por 2DP abaixo da base normativa), fibrose ou fluido retiniano. Resultados: Foram incluídos 70 doentes com seguimento de 86.9 ± 17.9 meses (intervalo 60-119 meses). Verificou-se melhoria significativa da MAVC no primeiro ano (+3.91 ± 12.4 letras, p=0.010) e estabilidade no segundo ano de seguimento (+3.1 ± 14.9 letras, p=0.08). No final do follow up houve perda significativa de MAVC (-11.2 ± 22.1, p<0.001), sendo que 20 doentes (29%) perderam 15 ou mais letras e 26 doentes (37%) apresentaram uma melhoria de pelo menos 5 letras. Os fatores preditivos positivos para melhor MAVC final foram o maior número de injeções (p=0.002) e a amplitude de melhoria da MAVC nos primeiros 6 meses de tratamento (p=0.014), segundo um modelo de regressão multivariado. No primeiro ano o número médio de injeções foi de 3.7 ± 1.4 e ao longo do seguimento realizaram-se em média 12.3 ± 6.9 por cada doente. No que diz respeito à incidência de atrofia no fim do seguimento, foi significativamente menor quanto maior o número de injeções intravítreas realizadas. (OR=0.66, p=0.039).Conclusão: O maior número de injecções intra-vítreas administradas, assim como a resposta precoce favorável da MAVC ao tratamento, surgem como fatores de bom prognóstico funcional a longo prazo.Purpose: To describe the structural and functional response of treatment of exudative age macular degeneration (AMD) with ranibizumab, in patients with follow up superior than 5 years.Methods: Retrospective consecutive study enrolling patients submitted to ranibizumab intravitreal injections on pro-re-nata (PRN) regimen during at least five years of follow-up. The best corrected visual acuity (BCVA) and the number of injections performed were quantified. Structural optical coherence tomography spectral domain (SD-OCT) allowed the determination of the central macular thickness and of qualitative parameters, namely the presence of macular atrophy (defined by thickness below 2 SD of the normative database), retinal fibrosis or fluid. Results: We included 70 patients with a mean follow-up of 86.9 ± 17.9 months (range 60-119 months). At the end of the first year of treatment, BCVA significantly improved (+3.91 ± 12.4 letters, p=0.010), followed by BCVA stability at the end of the second year (+3.1±14.9 letters, p=0.08). At the end of follow up, there was a significantly decrease of the BCVA (-11.2±22.1 letters, p<0.001) and 20 of the patients (29%) lost 15 or more letters, and 26 of the patients (37%) improved at least 5 letters. The predictive factors for a greater improvement of the BCVA were the higher number of injections (p=0.002) and the amplitude of improvement of the BCVA during the first 6 months of treatment (p=0.014), in a multivariate regression model. In the first year of treatment, the mean number of injections was 3.7 ± 1.4 and during the follow-up an average of 12.3 ± 6.9 injections were performed. Regarding incidence of atrophy at the end of follow-up, was significantly lower with the greater the number of intravitreal injections performed (OR=0.66, p=0.039).Conclusion: The highest number of injections performed, as well as the most favorable BCVA response at the first 6 months of treatment, emerge as factors of a better long-term functional prognosis

Reconhecimento de um caminho projectual : o trilho como elemento revelador da paisagem

Dissertação de mestrado integrado em Arquitectura, Universidade Lusíada de Lisboa, 2013.Exame público realizado em 16 de Outubro de 2013.A estrutura da presente dissertação desenvolve-se a partir de um itinerário conceptual progressivo que tem lugar em Projecto III - 5º ano. Surge como uma oportunidade de aprofundar alguns temas e de destacar metodologias, que permaneceram ténues até este momento. Enfatiza, sobretudo, matérias capazes de consolidar um caminho, encerrador no seu espaço e no seu tempo, um rasto que se torna linear. Não representa a materialização de um percurso adaptável a qualquer ideia projectual, constitui-se, antes, como específica, capaz de abranger matérias eminentes para o desenrolar de uma ideia. A importância do trilho como elemento revelador da paisagem surge como principal detonador desses conteúdos, que lhe são em parte inerentes, e representa um núcleo basilar que se expande e se aprofunda. A sua relevância encontra-se, em grande parte, relacionada com o papel crucial que exerce em Projecto III, ligado ao desenvolvimento do conceito operativo em arquitectura. São abordados temas sequenciais afectos, numa primeira fase, à questão da cidade e à relevância da sua estrutura subjectiva. Em parte, dentro desse conteúdo, surge a questão da poética do caminho, associada ao valor cinético de um percurso que se vivencia. Um ponto-chave deste trajecto depende da proposta arquitectónica que gere e gera a integração do edifício, encontrando a sua legitimidade e o respectivo contributo em três casos de estudo: Orlando Ribeiro, Dimitris Pikionis e Álvaro Siza. As suas experiências cognitivas e a sensibilidade que os caracteriza sugerem, à partida, atributos pertinentes para uma rigorosa leitura da paisagem. A componente sensível que decorre das personalidades em questão revela-se, ainda, determinante para o discernimento de outras matérias presentes neste desenvolvimento teórico. Atingimos um conteúdo relacionado com o sentido da cabana, associado às vivências do indivíduo. Explora, sobretudo, a intensidade que este vínculo constitui dando expressividade à memória que assume um papel crucial. Este factor, eminente na generalidade da dissertação, torna-se importante para a efectiva apreensão de um objecto, manifestando o impacto avassalador causado por uma imagem à qual se confere uma dimensão poética. Como desfecho, apresenta-se a componente prática, que se traduz no trabalho desenvolvido em Projecto III – 5º ano. Surge como elemento operativo deste trilho, elaborado segundo um conteúdo teórico, que aqui encontra um justo incremento, onde se revelam os prós e os contras do seu desenvolvimento. (Nuno Gonçalo Serrano Colaço

Repeated specific canine pancreatic lipase measurements do not identify multiple acquired portosystemic shunts in dogs after extrahepatic portosystemic shunt attenuation

AbstractBackgroundIn dogs with portal hypertension (PH), spec cPL is suggested to be increased despite normal pancreatic histology. After attenuation of congenital extrahepatic portosystemic shunts (cEHPSS), multiple acquired portosystemic shunt (MAPSS) can develop as consequence of sustained PH. Presence of MAPSS affects future therapeutic options and prognosis.ObjectiveEvaluate if spec cPL concentrations increase postoperatively in dogs that develop MAPSS and can thus serve as an indicator of PH.AnimalsTwenty‐four dogs with cEHPSS.MethodsDogs classified according to surgical outcome after cEHPSS attenuation (8 with MAPSS [group M], 9 with closed cEHPSS [group C] and 7 with patent blood flow through the original cEHPSS, without evidence of MAPSS [group P]). Spec cPL was measured in preoperative samples (T0), 4 days (T1) and 1 (T2) and 3‐ to 6‐months (T3) after surgery.ResultsSpec cPL was within reference interval (&lt;200 μg/L) at all timepoints except at T1. At T1, 2 dogs in group M (321 and &gt;2000 μg/L) and also 1 in group C (688 μg/L) and 1 in group P (839 μg/L) had increased spec cPL concentrations. No differences in spec cPL concentrations between groups or changes over time were identified.Conclusions and Clinical ImportanceSpec cPL is not consistently increased in dogs that develop MAPSS after cEHPSS attenuation and has no potential as a biomarker for the identification of MAPSS after cEHPSS attenuation.</jats:sec