147 resultados para Bruce Sheldon


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Red meat is long established as an important dietary source of protein and essential nutrients including iron, zinc and vitamin B12, yet recent reports that its consumption may increase the risk of cardiovascular disease (CVD) and colon cancer have led to a negative perception of the role of red meat in health. The aim of this paper is to review existing literature for both the risks and benefits of red meat consumption, focusing on case-control and prospective studies. Despite many studies reporting an association between red meat and the risk of CVD and colon cancer, several methodological limitations and inconsistencies were identified which may impact on the validity of their findings. Overall, there is no strong evidence to support the recent conclusion from the World Cancer Research Fund (WCRF) report that red meat has a convincing role to play in colon cancer. A substantial amount of evidence supports the role of lean red meat as a positive moderator of lipid profiles with recent Studies identifying it as a dietary source of the anti-inflammatory long chain (LC) n-3 PUFAs and conjugated linoleic acid (CIA). In conclusion. moderate consumption of lean red meat as part of a balanced diet is unlikely to increase risk for CVD or colon cancer, but may positively influence nutrient intakes and fatty acid profiles, thereby impacting positively on long-term health. (C) 2009 Elsevier Ltd. All rights reserved

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The G-protein-coupled receptor free fatty acid receptor 1 (FFAR1), previously named GPR40, is a possible novel target for the treatment of type 2 diabetes. In an attempt to identify new ligands for this receptor, we performed virtual screening (VS) based on two-dimensional (2D) similarity, three-dimensional (3D) pharmacophore searches, and docking studies by using the structure of known agonists and our model of the ligand binding site, which was validated by mutagenesis. VS of a database of 2.6 million compounds followed by extraction of structural neighbors of functionally confirmed hits resulted in identification of 15 compounds active at FFAR1 either as full agonists, partial agonists, or pure antagonists. Site-directed mutagenesis and docking studies revealed different patterns of ligand-receptor interactions and provided important information on the role of specific amino acids in binding and activation of FFAR1.

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GPR40 was formerly an orphan G protein-coupled receptor whose endogenous ligands have recently been identified as free fatty acids (FFAs). The receptor, now named FFA receptor 1, has been implicated in the pathophysiology of type 2 diabetes and is a drug target because of its role in FFA-mediated enhancement of glucose-stimulated insulin release. Guided by molecular modeling, we investigated the molecular determinants contributing to binding of linoleic acid, a C18 polyunsaturated FFA, and GW9508, a synthetic small molecule agonist. Twelve residues within the putative GPR40-binding pocket including hydrophilic/positively charged, aromatic, and hydrophobic residues were identified and were subjected to site-directed mutagenesis. Our results suggest that linoleic acid and GW9508 are anchored on their carboxylate groups by Arg183, Asn244, and Arg258. Moreover, His86, Tyr91, and His137 may contribute to aromatic and/or hydrophobic interactions with GW9508 that are not present, or relatively weak, with linoleic acid. The anchor residues, as well as the residues Tyr12, Tyr91, His137, and Leu186, appear to be important for receptor activation also. Interestingly, His137 and particularly His86 may interact with GW9508 in a manner dependent on its protonation status. The greater number of putative interactions between GPR40 and GW9508 compared with linoleic acid may explain the higher potency of GW9508.

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Abstract OBJECTIVE: Accelerated atherosclerosis and premature coronary heart disease (CHD) are recognized complications of systemic lupus erythematosus (SLE), but the exact etiology remains unclear and is likely to be multifactorial. We hypothesized that SLE patients with CHD have increased exposure to traditional risk factors as well as differing disease phenotype and therapy-related factors compared to SLE patients free of CHD. Our aim was to examine risk factors for development of clinical CHD in SLE in the clinical setting. METHODS: In a UK-wide multicenter retrospective case-control study we recruited 53 SLE patients with verified clinical CHD (myocardial infarction or angina pectoris) and 96 SLE patients without clinical CHD. Controls were recruited from the same center as the case and matched by disease duration. Charts were reviewed up to time of event for cases, or the same "dummy-date" in controls. RESULTS: SLE patients with clinical CHD were older at the time of event [mean (SD) 53 (10) vs 42 (10) yrs; p

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In this study data generated by H-1 NMR spectroscopy were combined with chemometrics to analyse beef samples aged over a 21 day period. In particular, the amino acids, of which 12 were identified were found to increase over the ageing period with samples matured for 3 days having notably lower concentrations than carcasses aged for 21 days. This is believed to be a result of increased proteolysis within the muscle. This novel approach of using high resolution NMR spectrometry to analyse beef samples has not previously been reported and these findings demonstrate the potential of this technique linked with HPLC to be used as a suitable method for profiling meat samples.

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This article is based upon an analysis of 95 experimental, quasi-experimental, preexperimental and client-opinion studies of the effectiveness of social work. Three-quarters of these screened studies show positive results within their different methodological conventions. An examination is made of which methods and patterns of helping are correlated with positive outcomes and the implications for practice, training, and management explored.

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In this study a broadly representative sample of clients in the City of Westminster, receiving Care in the Community for reasons of mental ill-health, were interviewed regarding their experiences of, and levels of satisfaction with, services provided. The results reveal the vulnerability of services users, the benefits of community care, the high regard the majority have for their helpers, the limitations imposed by scarce resources, and the negative effects of only loose co-ordination between health and social services. Respondents also provide a rich source of data on how services might be improved.

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This article results from an analysis of 95 studies of the effectiveness of social work. The good news from this research, which features a wide range of demanding social problems, is that 75 per cent of results are positive. In this article the authors present their findings and consider their implications for practice.

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Considerable interest is being shown these days in evidence-based approaches to social work. In both health and social care there is increased emphasis on the quality of original research and reviews of research, and on the organized dissemination of findings. However, a number of formidable obstacles stand in the way of the achievement of such aims in our field. Some are organizational ; some are to do with the way in which the social work training is organised and managed, and some are psychological. Each of these sets of factors is reviewed in this article .

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The techniques and technologies currently being investigated to detect weapons and contraband concealed on persons under clothing are reviewed. The basic phenomenology of the atmosphere and materials that must be understood in order to realize such a system are discussed. The component issues and architectural designs needed to realize systems are outlined. Some conclusions with respect to further technology developments are presented.