Preparation and in vivo evaluation of insulin-loaded biodegradable nanoparticles prepared from diblock copolymers of PLGA and PEG

The aim of this study was to design a controlled release vehicle for insulin to preserve its stability and biological activity during fabrication and release. A modified, double emulsion, solvent evaporation, technique using homogenisation force optimised entrapment efficiency of insulin into biodegradable nanoparticles (NP) prepared from poly (dl-lactic-co-glycolic acid) (PLGA) and its PEGylated diblock copolymers. Formulation parameters (type of polymer and its concentration, stabiliser concentration and volume of internal aqueous phase) and physicochemical characteristics (size, zeta potential, encapsulation efficiency, in vitro release profiles and in vitro stability) were investigated. In vivo insulin sensitivity was tested by dietinduced type II diabetic mice. Bioactivity of insulin was studied using Swiss TO mice with streptozotocin-induced type I diabetic profile. Insulin-loaded NP were spherical and negatively charged with an average diameter of 200–400 nm. Insulin encapsulation efficiency increased significantly with increasing ratio of co-polymeric PEG. The internal aqueous phase volume had a significant impact on encapsulation efficiency, initial burst release and NP size. Optimised insulin NP formulated from 10% PEG-PLGA retained insulin integrity in vitro, insulin sensitivity in vivo and induced a sustained hypoglycaemic effect from 3 hours to 6 days in type I diabetic mice.

Malaria and tuberculosis co-infection:role for hemozoin immunosuppression?

Tese de doutoramento, Ciências Biomédicas (Microbiologia e Parasitologia), Universidade de Lisboa, Faculdade de Medicina, 2014

New method for the simultaneous identification of pathogenic human viruses using multiplex PCR

Tese de mestrado. Biologia (Biologia Molecular e Genética). Universidade de Lisboa, Faculdade de Ciências, 2014

Carers and Co-Production: Enabling Expertise through Experience?

Purpose To provide a brief overview of the literature to date which has focussed on co-production within mental healthcare in the UK, including service user and carer involvement and collaboration. Design The paper presents key outcomes from studies which have explicitly attempted to introduce co-produced care in addition to specific tools designed to encourage co-production within mental health services. The paper debates the cultural and ideological shift required for staff, service users and family members to undertake co-produced care and outlines challenges ahead with respect to service redesign and new roles in practice. Findings Informal carers (family and friends) are recognised as a fundamental resource for mental health service provision, as well as a rich source of expertise through experience, yet their views are rarely solicited by mental health professionals or taken into account during decision-making. This issue is considered alongside new policy recommendations which advocate the development of co-produced services and care. Research Limitations Despite the launch of a number of initiatives designed to build on peer experience and support, there has been a lack of attention on the differing dynamic which remains evident between healthcare professionals and people using mental health services. Co-production sheds a light on the blurring of roles, trust and shared endeavour (Slay and Stephens, 2013) but, despite an increase in peer recovery workers across England, there has been little research or service development designed to focus explicitly on this particular dynamic. Practical Implications Despite these challenges, coproduction in mental healthcare represents a real opportunity for the skills and experience of family members to be taken into account and could provide a mechanism to achieve the ‘triangle of care’ with input, recognition and respect given to all (service users, carers, professionals) whose lives are touched by mental distress. However, lack of attention in relation to carer perspectives, expertise and potential involvement could undermine the potential for coproduction to act as a vehicle to encourage person-centred care which accounts for social in addition to clinical factors. Social Implications The families of people with severe and enduring mental illness (SMI) assume a major responsibility for the provision of care and support to their relatives over extended time periods (Rose et al, 2004). Involving carers in discussions about care planning could help to provide a wider picture about the impact of mental health difficulties, beyond symptom reduction. The ‘co-production of care’ reflects a desire to work meaningfully and fully with service users and carers. However, to date, little work has been undertaken in order to coproduce services through the ‘triangle of care’ with carers bringing their own skills, resources and expertise. Originality/Value This paper debates the current involvement of carers across mental healthcare and debates whether co-production could be a vehicle to utilise carer expertise, enhance quality and satisfaction with mental healthcare. The critique of current work highlights the danger of increasing expectations on service providers to undertake work aligned to key initiatives (shared decision-making, person-centred care, co-production), that have common underpinning principles but, in the absence of practical guidance, could be addressed in isolation rather than as an integrated approach within a ‘triangle of care’.

Turning around the poorest neighbourhoods: learning the lessons from twenty years of neighbourhood-based regeneration strategies in England

In the past two decades governments in Britain have launched a series of initiatives designed to reduce the disparities between areas of affluence and deprivation. These initiatives were funded by central government and were delivered through a series of partnership boards operating at the neighbourhood level in areas with high levels of deprivation. Drawing on similar approaches in the US War on Poverty, the engagement of residents in the planning and delivery of projects was a major priority. This chapter draws on the national evaluations of three of these programmes in England: the Single Regeneration Budget, the New Deal for Communities and the Neighbourhood Management Pathfinders. The chapter begins by identifying the common characteristics of these programmes, known as area-based initiatives because they targeted areas of concentrated deprivation with a population of about 10,000 people each. It then goes on to discuss the three national programmes and summarises the main findings in relation to how far key indicators changed for the better. The final section sets out the ways in which policy objectives changed in 2010 after the election of a coalition government. This produced a shift to what was called the ‘Big Society’ where the rhetoric favoured a transfer of power away from central government towards the local, neighbourhood, level. This approach favoured self-help and a call to volunteering rather than channelling resources to the areas in greatest need. The chapter closes by reviewing the relatively modest achievements of this centralist, big-state approach to distressed neighbourhoods of 1990–2010.

Churchill as Chancellor of the Exchequer (1924–9) and the return to the gold standard

The general election of 29 October 1924 saw Winston Churchill return to Parliament as Constitutionalist MP for Epping after two years in the political wilderness. It also saw Stanley Baldwin swept back to Number 10 on a Conservative landslide. Speculation about whether Baldwin would cement Churchill’s drift from the Liberal fold by offering him office surfaced during the election campaign. Churchill nevertheless thought ‘it very unlikely that I shall be invited to join the Government, as owing to the size of the majority it will probably be composed only of impeccable Conservatives’. [ 1 ] Because of his anti-socialist credentials, his ability to reassure wavering Liberals through his opposition to protectionism – dropped by Baldwin after its rejection in the 1923 general election – and concern he could prove a rallying point for backbench malcontents, there was however much to commend giving Churchill a post. To his surprise, Baldwin offered Churchill the long-coveted office of Chancellor of the Exchequer, briefly held by his father before his ill-conceived resignation in 1887. Having arranged a meeting with his Labour predecessor, Philip Snowden, about outstanding business the new Chancellor set to work. Marking his political transition, a few days later Churchill resigned from the National Liberal Club.

Novel insights into the action of antimicrobial agents against human pathogens

Dissertation presented to obtain the Ph.D degree in Biochemistry

Non-cell autonomous neuroprotective effect of carbon monoxide : microglia-to-neuron communication

RESUMO: A isquémia cerebral é uma das doenças mais predominantes a nivel mundial, sendo uma das principais causas de mortalidade e invalidez. Parte da propagação de dano no cérebro é causado por inflamação descontrolada, causada principalmente por disfunção da microglia. Desta forma, existe a necessidade de tentar desenvolver estratégias para melhor compreender e modular as acções destas células. O monóxido de carbono (CO), é uma molécula endógena com provas dadas como anti-neuroinflamatório em vários modelos. Assim, o principal objectivo do trabalho foi o estudo do CO como um modulador da acção da microglia, com principal foco dado à comunicação entre estas células e neurónios, tentando entender se existe um efeito neuroprotector por inibição da inflamação. Um protocolo de meio condicionado foi estabelecido usando as linhas celulares BV2 e SH-SY5Y, de microglia e neurónio. A molécula CORM-A1, que liberta expontaniamente CO, foi usada como método de entrega da molécula às celulas. Demonstrámos que o pre-tratamento de células BV2 com CORM-A1 gera neuroprotecção já que reduz a morte celular de neurónios SH-SY5Y quando são incubados com meio condicionado de microglia activada em conjunto com o pró-oxidante t-BHP (tert-butil hidroperóxido). Assim, considerámos que o CO promove neuroprotecção ao inibir as acções inflamatórias da microglia. O papel anti-inflamatório da molécula CORM-A1 foi confirmado quando se verificou que pré-tratamento desta molécula em microglia BV2 limita a secreção de TNF-α mas estimula a secreção de IL-10. Por último, a CORM-A1 induziu a expressão do receptor da microglia CD200R1, molécula que participa na comunicação neurónio-microglia e fundamental para a modulação das acções inflamatórias destas últimas. Em suma, o nosso trabalho reforçou as propriedades anti-neuroinflamatórias do CO e uma capacidade de modular viabilidade neuronal através do seu efeito a nível de comunicação célula-célula. ---------------------------- ABSTRACT: Brain ischemia is a widespread disease worldwide, being one of the main causes of mortality and permanent disability. A portion of the damage that ensues following the ischemic event is caused by unrestrained inflammation, which is mainly orchestrated by exacerbated microglial activity. Hence, developing strategies for modulating microglial inflammation is a major concern nowadays. The endogenous molecule carbon monoxide (CO) has been shown to possess anti-neuroinflammatory properties using in vitro and in vivo approaches. Thus, our objective was to study CO as modulator of microglial activity, in particular in what concerns their communication with neurons, by promoting neuronal viability and limiting inflammatory output of activated microglia. A conditioned media strategy was established with BV2 microglia and SH-SY5Y neurons as cell models. CO-releasing molecule A1 (CORM-A1), a compound that releases CO spontaneously, was used as method of CO delivery to cells. We found that CORM-A1 pre-treatment in BV2 cells yields neuroprotective results, as it limits cell death when SH-SY5Y neurons are challenged with conditioned media from LPS-activated microglia and the pro-oxidant t-BHP (tert-butyl-hydroperoxide). Thus, we assumed carbon monoxide promotes neuroprotection via inhibition of microglial inflammation, displaying a non-cell autonomous role. CORM-A1 pre-treatment limited inflammation by inhibiting BV2 secretion of TNF-α and stimulating IL-10 production. These results reinforce that CO’s anti-inflammatory role confers neuroprotection, as the alterations in these cytokines occur concurrently with the increase in SH-SY5Y viability. Finally, we showed for the first time that carbon monoxide promotes the expression of CD200R1, a microglial receptor involved in neuron-glia communication and modulation of microglia inflammation. Further studies are necessary to clarify this role. Altogether, other than just highlighting CO as an anti-inflammatory and neuroprotective molecule, this work set the foundation for disclosing its involvement in cell-to-cell communication.

Registered nurses' perceptions of factors impacting on their continuing education /

This qualitative study examined the effects of hospital restructuring on a group of nurses at a community hospital. Eleven nurses were asked questions in order to gain insight into their experience in this situation. Ten of these participants were female, and one was male. The intent was to gather information about how restructuring has affected their lives, including, their motivational factors and barriers to participation in continuing education, and their descriptions of their workplace environment. Audiotaped interviews were conducted on two occasions to obtain this data. Emergent themes included the nurses' comments about continuing education, motivational factors, barriers that included geography and time, reactions of co-workers, restructuring, the College of Nurses' Quality Assurance Program including peer feedback, and performance appraisals. The literature review compares the barriers and motivational factors to the previous research findings. Thus, this study gave voice to the experience of this group of nurses, working in a healthcare setting that is involved in restructuring. This information is important to the healthcare system, since many areas are involved in restructuring. The whole process, if it is to be successful, depends on the frontline workers, namely the nurses. Thus, if there is anything to be learned from this group of people, that could be used to improve this progression, everyone would benefit from this information, were it to be implemented. Everyone is a stakeholder in the quality of healthcare in our province. The frontline workers are the ones that hold the vantage point to be able to provide suggestions for the changes needed to successful. These nurses are not just motivated by work issues however, and educating them and motivating them will also improve the care provided through increased knowledge and enhanced self-esteem.

Collaborative reflection : supporting one practitioner's development of online learning communities /

This is a study of one participant's reflective practice as she worked to develop online communities in a face-to-face science course. Her process of reflective practice was examined in order to address factors that influenced her learning path, and the benefits and challenges of collaborative action research. These research goals were pursued using a collaborative action research methodology, initially chosen for its close match with Schon's (1983) model of reflective practice. The participant's learning fit vnth Mezirow's (1991) model of transformative learning. She began with beliefs that matched her goals, and she demonstrated significant learning in three areas. First, she demonstrated instrumental learning around the constraints of workload and time, and achieving online learning community indicators. Second, she demonstrated communicative learning that helped her to see her own needs for feedback and communication more clearly, and how other process partners had been a support to her. Third, her emancipatory learning saw her revisiting and questioning her goals. It was through the reflective conversation during the planned meetings and the researcher's reframing and interrogation of that reflection that the participant was able to clarify and extend her thinking, and in so doing, critically reflect on her practice as she worked to develop online learning communities. In this way, the collaborative action research methodology was an embodiment of co-constructivism through collaborative reflective practice. Schon's (1983) model of reflective practice positions a lone practitioners moving through cycles ofplan-act-observe-reflect. The results fi"om this study suggest that collaboration is an important piece of the reflective practice model.

A29 NMR spin-lattice relaxation study of paramagnetics -doped orthosilictes

A ~si MAS NMR study of spin-lattice relaxation behaviour in paramagnetic-doped crystalline silicates was undertaken, using synthetic magnesium orthosilicate (forsterite) and synthetic zinc orthosilicate (willemite) doped with 0.1% to 20% of Co(II), Ni(II), or CU(II), as experimental systems. All of the samples studied exhibited a longitudinal magnetization return to the Boltzmann distribution of nuclear spin states which followed a stretched-exponential function of time: Y=exp [- (tjTn) n], Oof deviation from 1/2power are for dopant concentrations equal to or exceeding 2.5 percent dopant. In some cases we find agreement with theory, and observe a direct proportionality between the spin-lattice relaxation time and paramagnetic dopant ion concentration, with Tni[M2+]i=Tnj[M2+]j for a given dopant and mineral. There are many cases where this correlation is not apparent, however, and this is attributed to the structural, phase, and ion distribution complexities inherent in many of these systems.

A comparison of self-determined motivational experiences between participants and non-participants following the physical activity component of the CATCH Kid Club

The CATCH Kids Club (CKC) is an after-school intervention that has attempted to address the growing obesity and physical inactivity concerns publicized in current literature. Using Self-Determination Theory (SDT: Deci & Ryan, 1985) perspective, this study's main research objective was to assess, while controlling for gender and age, i f there were significant differences between the treatment (CKC program participants) and control (non- eKC) groups on their perceptions of need satisfaction, intrinsic motivation and optimal challenge after four months of participation and after eight months of participation. For this study, data were collected from 79 participants with a mean age of9.3, using the Situational Affective State Questionnaire (SASQ: Mandigo et aI., 2008). In order to determine the common factors present in the data, a principal component analysis was conducted. The analysis resulted in an appropriate three-factor solution, with 14 items loading onto the three factors identified as autonomy, competence and intrinsic motivation. Initially, a multiple analysis of co-variance (MANCOY A) was conducted and found no significant differences or effects (p> 0.05). To further assess the differences between groups, six analyses of co-variance (ANeOY As) were conducted, which also found no significant differences (p >0 .025). These findings suggest that the eKC program is able to maintain the se1fdetermined motivational experiences of its participants, and does not thwart need satisfaction or self-determined motivation through its programming. However, the literature suggests that the CKe program and other P A interventions could be further improved by fostering participants' self-determined motivational experiences, which can lead to the persistence of healthy PA behaviours (Kilpatrick, Hebert & Jacobsen, 2002).

The ethical dilemma of lifestyle change: designing for sustainable schools and sustainable citizenship

his paper explores how participation and sustainability are being addressed by architects within the Building Schools for the Future (BSF) programme in the UK. The intentions promoted by the programme are certainly ambitious, but the ways to fulfil these aims are ill-explored. Simply focusing on providing innovative learning technologies, or indeed teaching young people about physical sustainability features in buildings, will not necessarily teach them the skills they will need to respond to the environmental and social challenges of a rapidly changing world. However, anticipating those skills is one of the most problematic issues of the programme. The involvement of young people in the design of schools is used to suggest empowerment, place-making and to promote social cohesion but this is set against government design literature which advocates for exemplars, standard layouts and best practice, all leading to forms of standardisation. The potentials for tokenistic student involvement and conflict with policy aims are evident. This paper explores two issues: how to foster in young people an ethic towards future generations, and the role of co-design practices in this process. Michael Oakeshott calls teaching the conversation of mankind. In this paper, I look at the philosophy of Hannah Arendt, Emmanuel Levinas, Maurice Merleau-Ponty and Luce Irigaray to argue that investigating the ethical dilemmas of the programme through critical dialogue with students offers an approach to meeting government objectives, building sustainable schools, and fostering sustainable citizenship.

Effets de la purification d’alginate et de la co-encapsulation avec des cellules canaliculaires sur la survie et fonction d’îlots de Langerhans microencapsulés

La transplantation d’îlots chez des sujets diabétiques permet la normalisation de leur glycémie mais nécessite l’utilisation d’immunosuppresseurs. Afin d’éliminer l’utilisation de ceux-ci, une capsule d’alginate capable d’immunoprotéger l’îlot a été proposée. Cependant, un problème persiste : la survie de l’implant est limitée. Deux moyens afin d’améliorer ce facteur seront présentés dans ce mémoire: l’utilisation d’alginate purifié et la co-encapsulation des îlots avec des cellules canaliculaires pancréatiques. La première étude rapporte un aspect nouveau : les effets directs de l’alginate non-purifié, versus purifié, sur la survie d’îlots encapsulés. Ceci est démontré in vitro sur la viabilité à long terme des îlots, leur fonction et l’incidence de leur mort cellulaire par apoptose et nécrose. Ces investigations ont permis de conclure que l’alginate purifié permet de maintenir à long terme une meilleure survie et fonction des îlots. De plus, cette étude ajoute un autre rôle aux contaminants de l’alginate en plus de celui d’initier la réaction immunitaire de l’hôte; celle-ci étant indirectement reliée à la mort des îlots encapsulés. La deuxième étude consiste à déterminer les impacts possibles d’une co-encapsulation d’îlots de Langerhans avec des cellules canaliculaires pancréa-tiques. Les résultats obtenus démontrent que cette co-encapsulation n’améliore pas la survie des îlots microencapsulés, par des tests de viabilité et de morts cellulaires, ni leur fonction in vivo testée par des implantations chez un modèle murin immmunodéficient. Pour conclure, la survie des îlots encapsulés peut être améliorée par la purification de l’alginate mais reste inchangée lors d’une co-encapsulation avec des cellules canaliculaires pancréatiques.

La culture extrême, une approche à la co-construction de la culture organisationnelle

Ce mémoire propose de conceptualiser la culture organisationnelle d’un angle nouveau. Mary Jo Hatch (1993), dans son modèle de Cultural Dynamics, soutient que la culture d’une entreprise favorise la modulation de l’identité des individus y travaillant. Partant de cette affirmation, je me questionne à savoir si l’inverse est aussi possible. La culture de l’organisation et l’identité des individus y travaillant peuvent-ils évoluer dans une dynamique de co-construction? Afin d’étudier ce phénomène, j’ai mené une série d’entrevues selon la méthode du récit de vie au sein d’Empire Sports, une chaîne québécoise de boutiques de vente au détail d’articles de sports extrêmes. En me basant sur la théorie des communautés de pratiques, j’ai analysé et interprété les résultats obtenus lors des entrevues. J’arrive à identifier et à préciser ce phénomène de co-construction que j’interprète à l’aide d’un nouveau concept appelé la culture extrême. Comme cette recherche est exploratoire, les conclusions ouvrent la possibilité d’approfondir davantage les connaissances à propos de la culture extrême en l’examinant dans d’autres contextes organisationnels.