University College Cork

About: University College Cork is a education organization based out in Cork, Ireland. It is known for research contribution in the topics: Population & Irish. The organization has 12056 authors who have published 28452 publications receiving 958414 citations. The organization is also known as: Coláiste na hOllscoile Corcaigh & National University of Ireland, Cork.

Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing

Abstract: Neurodegenerative disorders of ageing such as Alzheimer disease, Parkinson disease and Huntington disease are characterized by the presence of neurotoxic misfolded and aggregated proteins. One reason underlying the accumulation of these proteins is insufficient clearance by intracellular and extracellular pathways such as the autophagic–lysosomal network and the glymph system. This article reviews the potential for therapeutically enhancing the clearance of neurotoxic proteins to curtail the onset and slow the progression of neurodegenerative disorders of ageing. Neurodegenerative disorders of ageing (NDAs) such as Alzheimer disease, Parkinson disease, frontotemporal dementia, Huntington disease and amyotrophic lateral sclerosis represent a major socio-economic challenge in view of their high prevalence yet poor treatment. They are often called 'proteinopathies' owing to the presence of misfolded and aggregated proteins that lose their physiological roles and acquire neurotoxic properties. One reason underlying the accumulation and spread of oligomeric forms of neurotoxic proteins is insufficient clearance by the autophagic–lysosomal network. Several other clearance pathways are also compromised in NDAs: chaperone-mediated autophagy, the ubiquitin–proteasome system, extracellular clearance by proteases and extrusion into the circulation via the blood–brain barrier and glymphatic system. This article focuses on emerging mechanisms for promoting the clearance of neurotoxic proteins, a strategy that may curtail the onset and slow the progression of NDAs.

GPs' perspectives on the management of patients with multimorbidity: systematic review and synthesis of qualitative research.

Abstract: Objective To synthesise the existing published literature on the perceptions of general practitioners (GPs) or their equivalent on the clinical management of multimorbidity and determine targets for future research that aims to improve clinical care in multimorbidity. Design Systematic review and metaethnographic synthesis of primary studies that used qualitative methods to explore GPs’ experiences of clinical management of multimorbidity or multiple chronic diseases. Data sources EMBASE, MEDLINE, CINAHL, PsycInfo, Academic Search Complete, SocIndex, Social Science Full Text and digital theses/online libraries (database inception to September 2012) to identify literature using qualitative methods (focus groups or interviews). Review methods The 7-step metaethnographic approach described by Noblit and Hare, which involves cross-interpretation between studies while preserving the context of the primary data. Results Of 1805 articles identified, 37 were reviewed in detail and 10 were included, using a total of 275 GPs in 7 different countries. Four areas of difficulty specific to the management of multimorbidity emerged from these papers: disorganisation and fragmentation of healthcare; the inadequacy of guidelines and evidence-based medicine; challenges in delivering patient-centred care; and barriers to shared decision-making. A ‘line of argument’ was drawn which described GPs’ sense of isolation in decision-making for multimorbid patients. Conclusions This systematic review shows that the problem areas for GPs in the management of multimorbidity may be classified into four domains. There will be no ‘one size fits all’ intervention for multimorbidity but these domains may be useful targets to guide the development of interventions that will assist and improve the provision of care to multimorbid patients.

Cytokines: abnormalities in major depression and implications for pharmacological treatment

Abstract: The role of cytokines in depression was first considered when the cytokine interferon resulted in "sickness behaviour", the symptoms of which are similar to those of major depression. The latter is associated with an increase in pro-inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha). These cytokines are potent modulators of corticotropin-releasing hormone (CRH) which produces heightened hypothalamic-pituitary-adrenal axis (HPA) activity characterized by increases in ACTH and cortisol, both of which are reported elevated in major depression. Antidepressant treatment has immunomodulatory effects with increases in the production of IL-10, which is an anti-inflammatory cytokine. This review based on a Medline search from 1980-2003, focuses on the evidence available of cytokine changes in acute stress, chronic stress and major depression. It examines the effects of antidepressant treatment on immune parameters in both animal models and clinical trials. We suggest that future antidepressants may target the immune system by either blocking the actions of pro-inflammatory cytokines or increasing the production of anti-inflammatory cytokines.

Overcoming the technological hurdles in the development of probiotic foods

Abstract: While it is undoubted that clinical evidence supporting the health-promoting activity of probiotic cultures is of paramount importance, it is probably less well appreciated that the technological suitability of these strains is also critical to their exploitation. In this respect, it is not surprising that many human intestinal isolates, many of which are obligatively anaerobic grow very poorly outside their natural habitat, the human gut. Indeed, much of the human intestinal flora are at present unculturable and can only be studied using culture-independent approaches. Consequently, the large-scale cultivation and subsequent storage of probiotic lactobacilli and bifidobacteria in high numbers often presents a major bottleneck to the realization of their commercial potential. For this reason, intensive research efforts have recently focussed on protecting the viability of probiotic cultures both during product manufacture and storage and during gastric transit. These studies have demonstrated that cultures can be significantly protected via encapsulation in a variety of carriers, which include milk proteins and complex (prebiotic) carbohydrates. In many cases, the resultant products not only have better probiotic viability but can also be regarded as 'synbiotics' given the presence of probiotics and prebiotics (Roberfroid 1998). The physiological state of the probiotic cultures being added to a product can also be a major factor affecting overall culture viability. In this respect, the induction of stress responses in probiotic strains can have a dramatic effect on the ability of cultures to survive processing, such as freeze drying and spray drying and during gastric transit. Indeed, we have recently generated probiotic cultures that overexpress the heat shock proteins GroESL and have demonstrated improved performance of the culture under a variety of conditions including heat, spray drying and exposure to gastric acid (Desmond et al. 2004). The addition of various protective compounds to probiotic cultures can also improve their viability during manufacture - examples include glucose to energize cells on exposure to acid (Corcoran et al. 2005) and cryoprotectents such as inulin to improve survivability during freeze drying (Carvalho et al. 2004). In conclusion, a number of novel technologies are now emerging which can improve the viability of human intestinal strains for probiotic applications, which means that it may be possible to exploit many 'sensitive' cultures which hitherto have been difficult to propagate and maintain at high cell numbers.

Accounting, “economic citizenship” and the spatial reordering of manufacture☆

Abstract: This paper addresses the roles of accounting within one of the most extensive programs of advanced manufacture undertaken by an American corporation. Three distinct levels of analysis are pursued: firstly, the profound alterations that were to be effected in the identity and mode of operation of a key assembly plant, and in the ordering of its manufacturing spaces, as diverse calculative and managerial expertises were brought into complex and tentative alignments within a factory modernization process; secondly, the hopes and ideals for advanced manufacture and for American competitiveness that were to be constituted and made operable within this process; and thirdly, the links formed between this ambitious program of plant renewal and the various appeals to a “new economic citizenship” that have become prevalent in debates on advanced manufacture. By focusing on the relays and interconnections between these three levels of analysis, and the shifting ensembles thus formed, we are able to explore the dynamics of a specific attempt to govern the economic and personal dimensions of an enterprise. The concern is with all of those programs and technologies, including accounting, which seek to act upon and to transform the conduct of manufacture and the conduct of persons in a certain way. For it is, we argue, through such interventions that a new mode of seeking to govern economic life is set in place. And it is through such means that a novel type of economic citizen is called upon to play a new set of roles within the enterprise and within the nation.