424 research outputs found

    Prion Protein Polymorphisms Affect Chronic Wasting Disease Progression

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    Analysis of the PRNP gene in cervids naturally infected with chronic wasting disease (CWD) suggested that PRNP polymorphisms affect the susceptibility of deer to infection. To test this effect, we orally inoculated 12 white-tailed deer with CWD agent. Three different PRNP alleles, wild-type (wt; glutamine at amino acid 95 and glycine at 96), Q95H (glutamine to histidine at amino acid position 95) and G96S (glycine to serine at position 96) were represented in the study cohort with 5 wt/wt, 3 wt/G96S, and 1 each wt/Q95H and Q95H/G96S. Two animals were lost to follow-up due to intercurrent disease. The inoculum was prepared from Wisconsin hunter-harvested homozygous wt/wt animals. All infected deer presented with clinical signs of CWD; the orally infected wt/wt had an average survival period of 693 days post inoculation (dpi) and G96S/wt deer had an average survival period of 956 dpi. The Q95H/wt and Q95H/G96S deer succumbed to CWD at 1,508 and 1,596 dpi respectively. These data show that polymorphisms in the PRNP gene affect CWD incubation period. Deer heterozygous for the PRNP alleles had extended incubation periods with the Q95H allele having the greatest effect

    The Keele community knee pain forum: action research to engage with stakeholders about the prevention of knee pain and disability

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    <p>Abstract</p> <p>Background</p> <p>Involvement of users in health care research is central to UK health care policy, and guidelines for involvement exist. However, there are limited examples in rheumatology research. The aim of this study was to establish a community knee pain forum aimed at engaging stakeholders in design, dissemination and prioritisation of knee pain research.</p> <p>Methods</p> <p>Ten people were recruited to the forum representing a wide range of agencies. These included Weight Watchers, the leisure industry, Beth Johnson Foundation, health and social care professionals and the public. Three two-hour meetings over a two-year period were held. Experienced qualitative researchers facilitated each meeting. Written feedback after each meeting was elicited, and a short evaluation form was mailed to all members after the final meeting.</p> <p>Results</p> <p>Establishing and maintaining a forum of mixed members required careful preparation and ongoing support. Meetings had to be well-structured in order to allow for balanced participation of lay and professional users. Users contributed to the design of methods, provided ideas for dissemination and set priorities for further research. Clear documentation of meetings ensured that users' contributions to the research cycle were transparent.</p> <p>Conclusion</p> <p>Our knee pain forum illustrates that community engagement can have a positive impact on the development, dissemination and implementation of health research. Engaging with non-academic partners enables mutual learning and this enhances the quality of NHS research.</p

    Mechanisms and physiological function of daily haemoglobin oxidation rhythms in red blood cells

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    Cellular circadian rhythms confer temporal organisation upon physiology that is fundamental to human health. Rhythms are present in red blood cells (RBCs), the most abundant cell type in the body, but their physiological function is poorly understood. Here, we present a novel biochemical assay for haemoglobin (Hb) oxidation status which relies on a redox-sensitive covalent haem-Hb linkage that forms during SDS-mediated cell lysis. Formation of this linkage is lowest when ferrous Hb is oxidised, in the form of ferric metHb. Daily haemoglobin oxidation rhythms are observed in mouse and human RBCs cultured in vitro, or taken from humans in vivo, and are unaffected by mutations that affect circadian rhythms in nucleated cells. These rhythms correlate with daily rhythms in core body temperature, with temperature lowest when metHb levels are highest. Raising metHb levels with dietary sodium nitrite can further decrease daytime core body temperature in mice via nitric oxide (NO) signalling. These results extend our molecular understanding of RBC circadian rhythms and suggest they contribute to the regulation of body temperature

    Factors affecting residency rank-listing: A Maxdiff survey of graduating Canadian medical students

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    <p>Abstract</p> <p>Background</p> <p>In Canada, graduating medical students consider many factors, including geographic, social, and academic, when ranking residency programs through the Canadian Residency Matching Service (CaRMS). The relative significance of these factors is poorly studied in Canada. It is also unknown how students differentiate between their top program choices. This survey study addresses the influence of various factors on applicant decision making.</p> <p>Methods</p> <p>Graduating medical students from all six Ontario medical schools were invited to participate in an online survey available for three weeks prior to the CaRMS match day in 2010. Max-Diff discrete choice scaling, multiple choice, and drop-list style questions were employed. The Max-Diff data was analyzed using a scaled simple count method. Data for how students distinguish between top programs was analyzed as percentages. Comparisons were made between male and female applicants as well as between family medicine and specialist applicants; statistical significance was determined by the Mann-Whitney test.</p> <p>Results</p> <p>In total, 339 of 819 (41.4%) eligible students responded. The variety of clinical experiences and resident morale were weighed heavily in choosing a residency program; whereas financial incentives and parental leave attitudes had low influence. Major reasons that applicants selected their first choice program over their second choice included the distance to relatives and desirability of the city. Both genders had similar priorities when selecting programs. Family medicine applicants rated the variety of clinical experiences more importantly; whereas specialty applicants emphasized academic factors more.</p> <p>Conclusions</p> <p>Graduating medical students consider program characteristics such as the variety of clinical experiences and resident morale heavily in terms of overall priority. However, differentiation between their top two choice programs is often dependent on social/geographic factors. The results of this survey will contribute to a better understanding of the CaRMS decision making process for both junior medical students and residency program directors.</p

    A randomised phase II study of pegylated arginine deiminase (ADI-PEG 20) in Asian advanced hepatocellular carcinoma patients

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    [[abstract]]Background:Human hepatocellular carcinoma (HCC) cells are largely deficient of argininosuccinate synthetase and thus auxotrophic for arginine. This study aims to investigate the efficacy and pharmacodynamics of pegylated arginine deiminase (ADI-PEG 20), a systemic arginine deprivation agent, in Asian HCC patients. Methods:Patients with advanced HCC who were not candidates for local therapy were eligible and randomly assigned to receive weekly intramuscular injections of ADI-PEG 20 at doses of 160 or 320 IU m-2. The primary end point was disease-control rate (DCR). Results:Of the 71 accruals, 43.6% had failed previous systemic treatment. There were no objective responders. The DCR and the median overall survival (OS) of the intent-to-treat population were 31.0% (95% confidence interval (CI): 20.5-43.1) and 7.3 (95% CI: 4.7-9.9) months respectively. Both efficacy parameters were comparable between the two study arms. The median OS of patients with undetectable circulating arginine for more than or equal to and <4 weeks was 10.0 (95% CI: 2.1-17.9) and 5.8 (95% CI: 1.4-10.1) months respectively (P=0.251, log-rank test). The major treatment-related adverse events were grades 1-2 local and/or allergic reactions. Conclusions:ADI-PEG 20 is safe and efficacious in stabilising the progression of heavily pretreated advanced HCC in an Asian population, and deserves further exploration.British Journal of Cancer advance online publication, 31 August 2010; doi:10.1038/sj.bjc.6605856 www.bjcancer.com

    The Oslo Health Study: Is bone mineral density higher in affluent areas?

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    <p>Abstract</p> <p>Background</p> <p>Based on previously reported differences in fracture incidence in the socioeconomic less affluent Oslo East compared to the more privileged West, our aim was to study bone mineral density (BMD) in the same socioeconomic areas in Oslo. We also wanted to study whether possible associations were explained by socio-demographic factors, level of education or lifestyle factors.</p> <p>Methods</p> <p>Distal forearm BMD was measured in random samples of the participants in The Oslo Health Study by single energy x-ray absorptiometry (SXA). 578 men and 702 women born in Norway in the age-groups 40/45, 60 and 75 years were included in the analyses. Socioeconomic regions, based on a social index dividing Oslo in two regions – East and West, were used.</p> <p>Results</p> <p>Age-adjusted mean BMD in women living in the less affluent Eastern region was 0.405 g/cm<sup>2 </sup>and significantly lower than in West where BMD was 0.419 g/cm<sup>2</sup>. Similarly, the odds ratio of low BMD (Z-score ≤ -1) was 1.87 (95% CI: 1.22–2.87) in women in Oslo East compared to West. The same tendency, although not statistically significant, was also present in men. Multivariate analysis adjusted for education, marital status, body mass index, physical inactivity, use of alcohol and smoking, and in women also use of post-menopausal hormone therapy and early onset of menopause, did hardly change the association. Additional adjustments for employment status, disability pension and physical activity at work for those below the age of retirement, gave similar results.</p> <p>Conclusion</p> <p>We found differences in BMD in women between different socioeconomic regions in Oslo that correspond to previously found differences in fracture rates. The association in men was not statistically significant. The differences were not explained by socio-demographic factors, level of education or lifestyle factors.</p
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