The therapeutic potential of losartan in lung metastasis of colorectal cancer

Colorectal cancer (CRC) is a common cancer with a high incidence rate. Components of the renin-angiotensin system (RAS) have been reported to be dysregulated in several malignancies including CRC. Here, we have explored the potential anti-metastatic effects of a RAS inhibitor, losartan, in an experimental model of lung metastasis in CRC. A murine model of lung metastasis of CRC was used, which involved the intravenous injection of CT26 cells via a tail vein. Four experimental groups comprised: an untreated group; a group that received 5-FU which was administered intraperitoneally; a losartan group that received a combination group that received 5-FU plus losartan . We evaluated the anti-inflammatory effects of losartan by histopathological method, and the measurement of oxidative or antioxidant markers including malondialdehyde (MDA) and total-thiols (T-SH) tissue levels, superoxide-dismutase (SOD) and catalase activity. We found that losartan inhibited lung metastasis of CRC and there was a reduction of the IL-6 expression level in the tissue sample. It was also associated with reduced levels of the anti-angiogenic factor Vascular endothelial growth factor (VEGF). Furthermore, we found that losartan induced oxidative stress as assessed by an elevation of MDA level, reduction of T-SH, SOD and catalase activities in lung tissue. Our findings demonstrated that losartan ameliorates angiogenesis, inflammation and the induction of oxidative stress via Angiotensin II type I receptor (AT1R). This may shine some lights on targeting the RAS pathway as a potential therapeutic approach in the treatment of metastatic CRC patients

Aligning assessment with the needs of work-integrated learning: the challenges of authentic assessment in a complex context

Work-integrated learning (WIL) is a feature of university courses, both in professional areas, where it is commonplace, but also across many different disciplines. Assessment of WIL can be complex as it involves parties and settings external to the university, and it can be problematic because of difficulties in aligning learning activities during placements with what is or can be assessed by the university. This paper explores the relationship between students’ placement experiences and accompanying assessments in contexts where activities are tightly coupled with the curriculum, and in those where it is not. It draws on a qualitative analysis of student interviews and drawings by the interviewees of their WIL experiences, supplemented with analysis of unit guides. Our findings highlight that students’ perceptions of authenticity of assessment were undermined by misalignments between the student, university and industry. Assessment authenticity was perceived by students as based on alignment between their current and future selves in the assessment process, involvement of industry supervisors and relevance of placement activities to assessment activities. The paper discusses the complexity of coordination of educational activities with external partners, especially when one party drives assessment. It then suggests a reframing of WIL assessment to promote alignment and authenticity

Hepatitis delta virus testing, epidemiology and management: A multicentre cross-sectional study of patients in London

AbstractBackgroundHepatitis delta virus (HDV) testing is recommended for all patients with hepatitis B virus (HBV) infection. HDV infection is associated with severe liver disease and interferon is the only available treatment.ObjectivesTo determine the rate of anti-HDV antibody testing in HBV patients; and to describe the epidemiology, clinical characteristics and management of HDV-infected patients at four hospitals in London.Study designThe anti-HDV testing rate was estimated by reviewing clinical and laboratory data. Cross-sectional data collection identified HDV-infected patients who had attended the study centres between 2005 and 2012.ResultsAt a centre with clinic-led anti-HDV testing, 40% (67/168) of HBV patients were tested. Recently diagnosed HBV patients were more likely to be screened than those under long-term follow-up (62% vs 36%, P=0.01). At a centre with reflex laboratory testing, 99.4% (3543/3563) of first hepatitis B surface antigen positive samples were tested for anti-HDV. Across the four study centres there were 55 HDV-infected patients, of whom 50 (91%) had immigrated to the UK and 27 (49%) had evidence of cirrhosis. 31 patients received interferon therapy for HDV with an end of treatment virological response observed in 10 (32%).ConclusionsThe anti-HDV testing rate was low in a centre with clinic-led testing, but could not be evaluated in all centres. The HDV-infected patients were of diverse ethnicity, with extensive histological evidence of liver disease and poor therapeutic responses. Future recommendations include reflex laboratory testing algorithms and a prospective cohort study to optimise the investigation and management of these patients

Recruitment, retention, and training of people with type 2 diabetes as diabetes prevention mentors (DPM) to support a healthcare professional-delivered diabetes prevention program: the Norfolk Diabetes Prevention Study (NDPS)

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordData availability statement: Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.Objective: Intensive lifestyle interventions reduce the risk of type 2 diabetes in populations at highest risk, but staffing levels are usually unable to meet the challenge of delivering effective prevention strategies to a very large at-risk population. Training volunteers with existing type 2 diabetes to support healthcare professionals deliver lifestyle interventions is an attractive option. Methods: We identified 141 973 people at highest risk of diabetes in the East of England, screened 12 778, and randomized 1764 into a suite of type 2 diabetes prevention and screen detected type 2 diabetes management trials. A key element of the program tested the value of volunteers with type 2 diabetes, trained to act as diabetes prevention mentors (DPM) when added to an intervention arm delivered by healthcare professionals trained to support participant lifestyle change. Results: We invited 9951 people with type 2 diabetes to become DPM and 427 responded (4.3%). Of these, 356 (83.3%) were interviewed by phone, and of these 131 (36.8%) were interviewed in person. We then appointed 104 of these 131 interviewed applicants (79%) to the role (mean age 62 years, 55% (n=57) male). All DPMs volunteered for a total of 2895 months, and made 6879 telephone calls to 461 randomized participants. Seventy-six (73%) DPMs volunteered for at least 6 months and 66 (73%) for at least 1 year. Discussion: Individuals with type 2 diabetes can be recruited, trained and retained as DPM in large numbers to support a group-based diabetes prevention program delivered by healthcare professionals. This volunteer model is low cost, and accesses the large type 2 diabetes population that shares a lifestyle experience with the target population. This is an attractive model for supporting diabetes prevention efforts.National Institute for Health Research (NIHR

Recruitment, retention, and training of people with type 2 diabetes as diabetes prevention mentors (DPM) to support a healthcare professional-delivered diabetes prevention program:The Norfolk Diabetes Prevention Study (NDPS)

Objective: Intensive lifestyle interventions reduce the risk of type 2 diabetes in populations at highest risk, but staffing levels are usually unable to meet the challenge of delivering effective prevention strategies to a very large at-risk population. Training volunteers with existing type 2 diabetes to support healthcare professionals deliver lifestyle interventions is an attractive option. Methods: We identified 141 973 people at highest risk of diabetes in the East of England, screened 12 778, and randomized 1764 into a suite of type 2 diabetes prevention and screen detected type 2 diabetes management trials. A key element of the program tested the value of volunteers with type 2 diabetes, trained to act as diabetes prevention mentors (DPM) when added to an intervention arm delivered by healthcare professionals trained to support participant lifestyle change. Results: We invited 9951 people with type 2 diabetes to become DPM and 427 responded (4.3%). Of these, 356 (83.3%) were interviewed by phone, and of these 131 (36.8%) were interviewed in person. We then appointed 104 of these 131 interviewed applicants (79%) to the role (mean age 62 years, 55% (n=57) male). All DPMs volunteered for a total of 2895 months, and made 6879 telephone calls to 461 randomized participants. Seventy-six (73%) DPMs volunteered for at least 6 months and 66 (73%) for at least 1 year. Discussion: Individuals with type 2 diabetes can be recruited, trained and retained as DPM in large numbers to support a group-based diabetes prevention program delivered by healthcare professionals. This volunteer model is low cost, and accesses the large type 2 diabetes population that shares a lifestyle experience with the target population. This is an attractive model for supporting diabetes prevention efforts

Assessment of HIF-1α expression and release following endothelial injury in-vitro and in-vivo

Background: Endothelial injury is an early and enduring feature of cardiovascular disease. Inflammation and hypoxia may be responsible for this, and are often associated with the up-regulation of several transcriptional factors that include Hypoxia Inducible Factor-1 (HIF-1). Although it has been reported that HIF-1α is detectable in plasma, it is known to be unstable. Our aim was to optimize an assay for HIF-1α to be applied to in vitro and in vivo applications, and to use this assay to assess the release kinetics of HIF-1 following endothelial injury. Methods: An ELISA for the measurement of HIF in cell-culture medium and plasma was optimized, and the assay used to determine the best conditions for sample collection and storage. The results of the ELISA were validated using Western blotting and immunohistochemistry (IHC). In vitro, a standardized injury was produced in a monolayer of rat aortic endothelial cells (RAECs) and intracellular HIF-1α was measured at intervals over 24 hours. In vivo, a rat angioplasty model was used. The right carotid artery was injured using a 2F Fogarty balloon catheter. HIF-1α was measured in the plasma and in the arterial tissue (0, 1, 2, 3 and 5 days post injury). Results: The HIF-1α ELISA had a limit of detection of 2.7 pg/ mL and was linear up to 1000 pg/ mL. Between and within-assay coefficient of variation values were less than 15%. HIF-1α was unstable in cell lysates and plasma, and it was necessary to add a protease inhibitor immediately after collection, and to store samples at -800C prior to analysis. The dynamics of HIF-1α release were different for the in vitro and in vivo models. In vitro, HIF-1α reached maximum concentrations approximately 2h post injury, whereas peak values in plasma and tissues occurred approximately 2 days post injury, in the balloon injury model. Conclusion: HIF-1α can be measured in plasma, but this requires careful sample collection and storage. The carotid artery balloon injury model is associated with the transient release of HIF-1α into the circulation that probably reflects the hypoxia induced in the artery wall

Low oxygen tension primes aortic endothelial cells to the reparative effect of tissue-protective cytokines

Erythropoietin (EPO) has both erythropoietic and tissue-protective properties. The EPO analogues carbamylated EPO (CEPO) and pyroglutamate helix B surface peptide (pHBSP) lack the erythropoietic activity of EPO but retain the tissue-protective properties that are mediated by a heterocomplex of EPO receptor (EPOR) and the β common receptor (βCR). We studied the action of EPO and its analogues in a model of wound healing where a bovine aortic endothelial cells (BAECs) monolayer was scratched and the scratch closure was assessed over 24 h under different oxygen concentrations. We related the effects of EPO and its analogues on repair to their effect on BAECs proliferation and migration (evaluated using a micro-Boyden chamber). EPO, CEPO and pHBSP enhanced scratch closure only at lower oxygen (5%), while their effect at atmospheric oxygen (21%) was not significant. The mRNA expression of EPOR was doubled in 5% compared to 21% oxygen, and this was associated with increased EPOR assessed by immunofluorescence and Western blot. By contrast βCR mRNA levels were similar in 5% and 21% oxygen. EPO and its analogues increased both BAECs proliferation and migration, suggesting that both may be involved in the reparative process. The priming effect of low oxygen tension on the action of tissue-protective cytokines may be of relevance to vascular disease, including atherogenesis and restenosis

Functional foods and cardiometabolic diseases: International Task Force for Prevention of Cardiometabolic Diseases.

Mounting evidence supports the hypothesis that functional foods containing physiologically-active components may be healthful. Longitudinal cohort studies have shown that some food classes and dietary patterns are beneficial in primary prevention, and this has led to the identification of putative functional foods. This field, however, is at its very beginning, and additional research is necessary to substantiate the potential health benefit of foods for which the diet-health relationships are not yet scientifically validated. It appears essential, however, that before health claims are made for particular foods, in vivo randomized, double-blind, placebo-controlled trials of clinical end-points are necessary to establish clinical efficacy. Since there is need for research work aimed at devising personalized diet based on genetic make-up, it seems more than reasonable the latter be modeled, at present, on the Mediterranean diet, given the large body of evidence of its healthful effects. The Mediterranean diet is a nutritional model whose origins go back to the traditional diet adopted in European countries bordering the Mediterranean sea, namely central and southern Italy, Greece and Spain; these populations have a lower incidence of cardiovascular diseases than the North American ones, whose diet is characterized by high intake of animal fat. The meeting in Naples and this document both aim to focus on the changes in time in these two different models of dietary habits and their fall out on public health

Co-creation workshops for work life oriented ICT education

ICT Companies in Finland today are facing problems in recruiting the right skilled workforce to meet their needs [1]. There is particular shortage of application developers, application designers, web professionals and coders in the South Ostrobothnia area of Finland [2]. Typical degree courses offered by universities would not work because there is a mismatch between the university degrees offered and the needs of these companies. There is a need to develop a new approach to address this shortage. In response to this, local University of Applied Sciences has developed a new ICT education programme using co-creation methods. The new approach is based on the concepts of co-creation of value from service science. This paper discusses the importance of this new approach in education and how it can be implemented. Empirical data is gathered through observation of and reflection on the development of the ICT programme which follows the principles of co-creation