Retinopathy in type 1 diabetes mellitus: Major differences between rural and urban dwellers in northwest Ethiopia

Aim: To audit levels of diabetes-related eye disease in Type 1 diabetes mellitus (T1DM) patients in northwest Ethiopia. In particular to establish whether, despite identical clinical goals, major differences between the physically demanding life-style of rural subsistence farmers and the sedentary life-style of urban dwellers would influence the prevalence of diabetes-related eye complications. 

Methods: A robust infrastructure for chronic disease management that comprehensively includes all rural dwellers was a pre-requisite for the investigation. A total of 544 T1DM were examined, representing 80% of all T1DM patients under regular review at both the urban and rural clinics and representative of patient age and gender (62.1% male, 37.9% female) of T1DM patients from this region; all were supervised by the same clinical team. Eye examinations were performed for visual acuity, cataract and retinal changes (retinal photography). HbA1c levels and the presence or absence of hypertension were recorded. 

Results/conclusions: Urban and rural groups had similar prevalences of severe visual impairment/blindness (7.0% urban, 5.2% rural) and cataract (7.3% urban, 7.1% rural). By contrast, urban dwellers had a significantly higher prevalence of retinopathy compared to rural patients, 16.1% and 5.0%, respectively (OR 2.9, p <. 0.02, after adjustment for duration, age, gender and hypertension). There was a 3-fold greater prevalence of hypertension in urban patients, whereas HbA1c levels were similar in the two groups. Since diabetic retinopathy is closely associated with microvascular disease and endothelial dysfunction, the possible influences of hypertension to increase and of sustained physical activity to reduce endothelial dysfunction are discussed.

Do persistent organic pollutants interact with the stress response? Individual compounds, and their mixtures, interaction with the glucocorticoid receptor

Persistent organic pollutants (POPs) are toxic substances, highly resistant to environmental degradation, which can bio-accumulate and have long-range atmospheric transport potential (UNEP 2001). The majority of studies on endocrine disruption have focused on interferences on the sexual steroid hormones and so have overlooked disruption to glucocorticoid hormones. Here the endocrine disrupting potential of individual POPs and their mixtures has been investigated in vitro to identify any disruption to glucocorticoid nuclear receptor transcriptional activity. POP mixtures were screened for glucocorticoid receptor (GR) translocation using a GR redistribution assay (RA) on a CellInsight(TM) NXT High Content Screening (HCS) platform. A mammalian reporter gene assay (RGA) was then used to assess the individual POPs, and their mixtures, for effects on glucocorticoid nuclear receptor transactivation. POP mixtures did not induce GR translocation in the GR RA or produce an agonist response in the GR RGA. However, in the antagonist test, in the presence of cortisol, an individual POP, p,p'-dichlorodiphenyldichloroethylene (DDE), was found to decrease glucocorticoid nuclear receptor transcriptional activity to 72.5% (in comparison to the positive cortisol control). Enhanced nuclear transcriptional activity, in the presence of cortisol, was evident for the two lowest concentrations of perfluorodecanoic acid (PFOS) potassium salt (0.0147mg/ml and 0.0294mg/ml), the two highest concentrations of perfluorodecanoic acid (PFDA) (0.0025mg/ml and 0.005mg/ml) and the highest concentration of 2,2',4,4'-tetrabromodiphenyl ether (BDE 47) (0.0000858mg/ml). It is important to gain a better understanding of how POPs can interact with GRs as the disruption of glucocorticoid action is thought to contribute to complex diseases.

Situated regional university incubation: A multi-level stakeholder perspective

From a macro perspective, it is widely acknowledged that University incubation models within a region are important stimulants of economic development through innovation and job creation. With the emergence of quadruple helix innovation ecosystems, universities have had re-evaluate their University incubation activity and models to engage more fully with industry and end users. However, within a given region, the type of University may influence their ability to engage with quadruple helix stakeholders and consequently impact their incubation activity. To date there is a scarcity of research which explores this 'meso' environment and its subsequent impact on University incubation models. Therefore, the aim of this paper is to use a stakeholder lens to explore University Incubation models within unique regional and organisational characteristics and constraints. The research methodology employed was based on a comparative case analysis of incubation of two different Universities within a UK peripheral region. It was found that variances existed in relation to the two universities incubation models which were found to result from both regional (macro environment) and organisational (meso environment) influences (i.e. university type). This research contributes to both regional and national agendas by empirically illustrating the need for appropriate design and tailoring of university incubation models (via acknowledgement of quadruple helix stakeholder influence) to incorporate contextual influences rather than adopting a best practise approach.

Extração e estrutura dos polissacarídeos do resíduo do café com atividade imunoestimuladora

As galactomananas das infusões de café apresentam atividade imunoestimuladora in vitro, sendo esta atividade semelhante à das mananas acetiladas extraídas de Aloe vera. As galactomananas presentes no resíduo de café também possuem atividade imunoestimuladora in vitro quando são parcialmente acetiladas. Como as galactomananas são o componente maioritário do resíduo de café e como o café é um produto de largo consumo a nível mundial, o reaproveitamento deste resíduo como fonte de galactomananas com atividade imunoestimuladora deve ser considerado. Esta dissertação procura dar resposta a duas questões: 1. Quais são as estruturas das galactomananas responsáveis pela atividade imunoestimuladora destes polissacarídeos; e 2. Como é que as galactomananas podem ser extraídas quantitativamente do resíduo de café de modo a serem solúveis em água à temperatura ambiente e, assim, poderem ser utilizadas como ingredientes alimentares com atividade imunoestimuladora. A questão 1 foi respondida pela caracterização estrutural de quatro galactomananas, de três origens: a) as galactomananas das infusões de café e do resíduo que apresentaram atividade imunoestimuladora; b) a galactomanana da goma de alfarroba (LBG), que não apresentou atividade imunoestimuladora; e c) a manana acetilada de Aloe vera, que apresentou atividade imunoestimuladora. Estes polissacarídeos foram submetidos à análise de açúcares e de ligações glicosídicas e a hidrólise por endo-β-D- (1→4)-mananase. Os fragmentos de oligossacarídeos mais pequenos foram ainda analisados por espetrometria de massa por ionização de electrospray e espetrometria de massa tandem. As galactomananas das infusões de café, do resíduo de café e do Aloe vera apresentaram grau de ramificação e peso molecular semelhantes, enquanto as galactomananas da LBG apresentaram grau de ramificação e de polimerização maiores. Todas as galactomananas apresentaram resíduos de arabinose como ramificação. O grau de acetilação das galactomananas da LBG foi vestigial enquanto as galactomananas do Aloe vera apresentaram um grau de acetilação de 2,08; para as galactomananas do resíduo de café o grau de acetilação foi de 0,98 e para as infusões foi de 0,08. A localização dos grupos acetilo foi irregular em todos os polímeros. Os resultados obtidos permitem inferir que baixos níveis de ramificação, cadeias pequenas e alguma acetilação parecem promover a atividade imunoestimuladora atribuída às galactomananas. Para responder à questão 2, foi testada uma metodologia que envolveu a torra do resíduo de café a 160 ºC e a 220 ºC e a sua extração com água quente e com soluções de 4 M NaOH à temperatura de 20, 60 e 120 ºC. A torra do resíduo a 160 ºC e a extração sequencial permitiu extrair 56% das galactomananas presentes no resíduo de café e, simultaneamente, 54% das arabinogalactanas. As galactomananas mantiveram a sua estrutura caraterística de polissacarídeo acetilado composto por uma cadeira principal de resíduos de manose em ligação β-(1→4) e resíduos de Gal e Ara nas cadeias laterais. A 220 ºC, as galactomananas foram parcialmente degradadas e o rendimento de extração foi muito menor do que a 160 ºC. No entanto, mesmo a esta temperatura as galactomananas apresentaram resíduos acetilados e a presença de pentoses nas cadeias laterais, o que permite inferir a elevada resistência destes polissacarídeos à temperatura e aos reagentes alcalinos. De forma a melhor compreender a estabilidade térmica das galactomananas do resíduo de café e a influência que a presença de arabinogalactanas pode ter na sua estabilidade, foi feita uma análise termogravimétrica aos polissacarídeos extraídos do resíduo de café assim como a polissacarídeos relacionados estruturalmente com estes, como a celulose, a galactomanana de LBG e a goma arábica, uma arabinogalactana. As galactomananas são termicamente estáveis durante 3 h a 200 ºC, enquanto as arabinogalactanas são estáveis a 180 ºC. De acordo com os perfis dos termogramas obtidos, e pelo cálculo das energias de ativação da degradação térmica, o resíduo de café apresenta uma estabilidade térmica menor do que a galactomanana, possivelmente devido à presença de arabinogalactanas. Apesar de não se ter verificado alterações no termograma da galactomanana do café submetida a um tratamento térmico de 200 ºC durante 3 h, verificam-se alterações estruturais que envolvem a formação de novas ligações glicosídicas, nomeadamente, a formação de resíduos de manose ligados em O-2 e em O-6, reações de transglicosilação, despolimerização, formação de resíduos de anidro-hexoses no terminal redutor e isomerização manose-glucose. Estas alterações promovem a solubilização das galactomananas. Os resultados obtidos permitem propor que o resíduo de café possa ser submetido a uma torra seguida de extração com reagentes alcalinos a quente para obtenção das galactomananas com rendimentos elevados. Estes polissacarídeos podem tornar-se solúveis em água após tratamento térmico a 200 ºC, permitindo assim a sua utilização em formulações alimentares, nomeadamente, por preparação de compostos acetilados com baixos níveis de ramificação e cadeias pequenas de modo a promover a sua atividade imunoestimuladora.

Fighting Talk: The Statements of 'The IRA/New IRA'

With the advent of the new violent dissident merger, ‘The IRA/New IRA’, the group and its affiliates have had to legitimise their new existence. They have utilised the maintenance of paramilitary activity to achieve this. However, they have also produced a number of organisational statements, justifying their position, tactics and strategies. This article analyses the evolution of these statements, both pre and post-merger from 2007 to 2015. 126 individual statements and 4 magazines are analysed using grounded theory. This analysis found that the statements have a dual strategy, aiming to foster trust in the movement and distrust in their perceived enemies. One of the dominant ways in which the group aims to foster trust, is by proposing their possession of an historical mandate from the republican forefathers of 1916, as well as the internally lauded paramilitaries from the Troubles era PIRA. The focus of the distrust narrative has been on the ‘constitutional nationalism’ of Sinn Féin. However, it also pours scorn on the PSNI, and capitalism, across the island of Ireland. The analysis of these statements can provide us with an understanding of the future direction of the group, as well as giving us insight, which can inform the development of any counter-narrative.

Turismo no Aït Bouguemmez (Alto Atlas Central, Marrocos) : representações sociais do turismo e dos seus impactes na perspetiva da comunidade local

Tese de doutoramento, Turismo (Planeamento dos Espaços Turísticos), Universidade de Lisboa, Instituto de Geografia e Ordenamento do Território, 2014

Principles and Practical Grouping for the Use of Drill and Practice Programs

A previous paper showed that young children performed better when working as individuals rather than in pairs on a drill and practice program. This paper reports an analysis of behaviour and talk for individuals and single sex pairs using a computer-based drill and practice activity to explain differences in performance. Results indicated that individuals were more likely to be task-focused and to complete tasks successfully than children working in pairs. Differences were found in off-task activity, behaviours and type of talk. Grouping and verbal interaction are discussed in relation to the type of task/program that children are asked to undertake, and how both task and peer presence may constrain the child's task focus and performance when reinforcing pre-existing knowledge.

Dual studies on autonomic function and cerebral autoregulation in ischemic stroke patients

Tese de mestrado, Neurociências, Faculdade de Medicina, Universidade de Lisboa, 2015

Impacto de andrógenos sobre a proliferação e atividade de fibroblastos e células epiteliais em cultura celular

Pós-graduação em Odontologia - FOAR

Abordagem prática para execução de taludes em obras rodoviárias com recurso a pré‐corte

Este trabalho é realizado no domínio das obras de engenharia, área onde o desmonte de rocha com recurso a explosivos em obras rodoviárias é uma actividade específica e consistiu no acompanhamento e execução de três obras rodoviárias de média e grande dimensão. A necessidade de executar escavações, recorrendo a técnicas de desmonte cuidadoso de contorno, onde o plano de corte do talude final deve obedecer a requisitos de localização, alinhamento, inclinação, estabilidade e também estéticos, acrescendo a isto a necessidade de optimizar os meios envolvidos, obriga a que esta actividade seja encarada de uma forma sistematizada, visando o racional aproveitamento de recursos. A execução desta actividade requer conhecimentos no domínio das técnicas de desmonte de contorno, dos explosivos, do mecanismo de rotura de rochas, da operação de perfuração e da geomecânica dos maciços. A abordagem deste trabalho incide sobre a técnica denominada de pré‐corte e tem como objectivo encontrar uma equação característica que permita relacionar diferentes parâmetros envolvidos nesta actividade. Este objectivo é alcançado recorrendo à correlação entre equações relativas à pressão de detonação, à pressão no furo e ao espaçamento entre furos consecutivos, desenvolvidas por outros autores. Desta forma obteve‐se uma equação que relaciona parâmetros relativos ao maciço rochoso (resistência à tracção), ao explosivo (velocidade de detonação e densidade) e ao diagrama de fogo (concentração de carga – volume de explosivo e comprimento do furo – volume do furo). A comparação entre os valores destes parâmetros obtidos na produção e os obtidos com recurso à equação característica permite concluir que a sua aplicação para execução de futuras obras possibilita uma optimização dos meios envolvidos.

Estudo económico das energias renováveis: o caso português

Dissertação de Mestrado apresentado ao Instituto de Contabilidade e Administração do Porto para a obtenção do grau de Mestre em Empreendedorismo e Internacionalização, sob orientação de Maria Clara Dias Pinto Ribeiro

Estudo sobre as diferenças interativas e comunicativas das educadoras e das mães

Dissertação apresentada na Escola Superior de Educação de Lisboa para obtenção do grau de Mestre em Ciências da Educação - Especialidade Intervenção Precoce

Utilização de tecnologias de apoio à comunicação com crianças com multideficiência

Dissertação apresentada à Escola Superior de Educação de Lisboa para obtenção do grau de Mestre em Educação Especial – ramo de Problemas de Cognição e Multideficiência

The role of the efflux mechanisms in multidrug resistance in Mycobacterium tuberculosis

Abstract The emergence of multi and extensively drug resistant tuberculosis (MDRTB and XDRTB) has increased the concern of public health authorities around the world. The World Health Organization has defined MDRTB as tuberculosis (TB) caused by organisms resistant to at least isoniazid and rifampicin, the main first-line drugs used in TB therapy, whereas XDRTB refers to TB resistant not only to isoniazid and rifampicin, but also to a fluoroquinolone and to at least one of the three injectable second-line drugs, kanamycin, amikacin and capreomycin. Resistance in Mycobacterium tuberculosis is mainly due to the occurrence of spontaneous mutations and followed by selection of mutants by subsequent treatment. However, some resistant clinical isolates do not present mutations in any genes associated with resistance to a given antibiotic, which suggests that other mechanism(s) are involved in the development of drug resistance, namely the presence of efflux pump systems that extrude the drug to the exterior of the cell, preventing access to its target. Increased efflux activity can occur in response to prolonged exposure to subinhibitory concentrations of anti-TB drugs, a situation that may result from inadequate TB therapy. The inhibition of efflux activity with a non-antibiotic inhibitor may restore activity of an antibiotic subject to efflux and thus provide a way to enhance the activity of current anti-TB drugs. The work described in this thesis foccus on the study of efflux mechanisms in the development of multidrug resistance in M. tuberculosis and how phenotypic resistance, mediated by efflux pumps, correlates with genetic resistance. In order to accomplish this goal, several experimental protocols were developed using biological models such as Escherichia coli, the fast growing mycobacteria Mycobacterium smegmatis, and Mycobacterium avium, before their application to M. tuberculosis. This approach allowed the study of the mechanisms that result in the physiological adaptation of E. coli to subinhibitory concentrations of tetracycline (Chapter II), the development of a fluorometric method that allows the detection and quantification of efflux of ethidium bromide (Chapter III), the characterization of the ethidium bromide transport in M. smegmatis (Chapter IV) and the contribution of efflux activity to macrolide resistance in Mycobacterium avium complex (Chapter V). Finally, the methods developed allowed the study of the role of efflux pumps in M. tuberculosis strains induced to isoniazid resistance (Chapter VI). By this manner, in Chapter II it was possible to observe that the physiological adaptation of E. coli to tetracycline results from an interplay between events at the genetic level and protein folding that decrease permeability of the cell envelope and increase efflux pump activity. Furthermore, Chapter III describes the development of a semi-automated fluorometric method that allowed the correlation of this efflux activity with the transport kinetics of ethidium bromide (a known efflux pump substrate) in E. coli and the identification of efflux inhibitors. Concerning M. smegmatis, we have compared the wild-type M. smegmatis mc2155 with knockout mutants for LfrA and MspA for their ability to transport ethidium bromide. The results presented in Chapter IV showed that MspA, the major porin in M. smegmatis, plays an important role in the entrance of ethidium bromide and antibiotics into the cell and that efflux via the LfrA pump is involved in low-level resistance to these compounds in M. smegmatis. Chapter V describes the study of the contribution of efflux pumps to macrolide resistance in clinical M. avium complex isolates. It was demonstrated that resistance to clarithromycin was significantly reduced in the presence of efflux inhibitors such as thioridazine, chlorpromazine and verapamil. These same inhibitors decreased efflux of ethidium bromide and increased the retention of [14C]-erythromycin in these isolates. Finaly, the methods developed with the experimental models mentioned above allowed the study of the role of efflux pumps on M. tuberculosis strains induced to isoniazid resistance. This is described in Chapter VI of this Thesis, where it is demonstrated that induced resistance to isoniazid does not involve mutations in any of the genes known to be associated with isoniazid resistance, but an efflux system that is sensitive to efflux inhibitors. These inhibitors decreased the efflux of ethidium bromide and also reduced the minimum inhibitory concentration of isoniazid in these strains. Moreover, expression analysis showed overexpression of genes that code for efflux pumps in the induced strains relatively to the non-induced parental strains. In conclusion, the work described in this thesis demonstrates that efflux pumps play an important role in the development of drug resistance, namely in mycobacteria. A strategy to overcome efflux-mediated resistance may consist on the use of compounds that inhibit efflux activity, restoring the activity of antimicrobials that are efflux pump substrates, a useful approach particularly in TB where the most effective treatment regimens are becoming uneffective due to the increase of MDRTB/XDRTB.

Relatório de estágio curricular

The purpose of the current internship report is to share the opportunity I have had to learn during my stay in CMVM as an intern, specifically in relation to the exercise of private equity supervision in Portugal, in order to contribute to the study of private equity legal framework. Private equity is the activity to finance or acquire enterprises with growth potential (normally consider as genuine industry), for a limited period of time, in order to support the enterprise’s development to benefit from future profit sales of participations. By observing and studying the registration procedures, as well as the specific legislation and reality of other jurisdictions, it is concluded that supervision specifically related to private equity is one of the most important aspects in this industry, as it is the best way to know and control it. To improve the performance of supervisory functions, and the very development of private equity, it is essential to have a legislative review in order to simplify the rules enforcement necessary for the proper running of the industry as well as for more efficient supervision and control of this activity, thus developing it and making it more attractive in a national and international basis.