The serum proteome of Atlantic salmon, Salmo salar, during pancreas disease (PD) following infection with salmonid alphavirus subtype 3 (SAV3)

Salmonid alphavirus is the aetological agent of pancreas disease (PD) in marine Atlantic salmon, Salmo salar, and rainbow trout, Oncorhynchus mykiss, with most outbreaks in Norway caused by SAV subtype 3 (SAV3). This atypical alphavirus is transmitted horizontally causing a significant economic impact on the aquaculture industry. This histopathological and proteomic study, using an established cohabitational experimental model, investigated the correlation between tissue damage during PD and a number of serum proteins associated with these pathologies in Atlantic salmon. The proteins were identified by two-dimensional electrophoresis, trypsin digest and peptide MS/MS fingerprinting. A number of humoral components of immunity which may act as biomarkers of the disease were also identified. For example, creatine kinase, enolase and malate dehydrogenase serum concentrations were shown to correlate with pathology during PD. In contrast, hemopexin, transferrin, and apolipoprotein, amongst others, altered during later stages of the disease and did not correlate with tissue pathologies. This approach has given new insight into not only PD but also fish disease as a whole, by characterisation of the protein response to infection, through pathological processes to tissue recovery. Biological significance: Salmonid alphavirus causes pancreas disease (PD) in Atlantic salmon, Salmo salar, and has a major economic impact on the aquaculture industry. A proteomic investigation of the change to the serum proteome during PD has been made with an established experimental model of the disease. Serum proteins were identified by two-dimensional electrophoresis, trypsin digest and peptide MS/MS fingerprinting with 72 protein spots being shown to alter significantly over the 12 week period of the infection. The concentrations of certain proteins in serum such as creatine kinase, enolase and malate dehydrogenase were shown to correlate with tissue pathology while other proteins such as hemopexin, transferrin, and apolipoprotein, altered in concentration during later stages of the disease and did not correlate with tissue pathologies. The protein response to infection may be used to monitor disease progression and enhance understanding of the pathology of PD

Social prescribing in cardiology : rediscovering the nature of and within us

Personalised care is integral to the delivery of the NHSE Long Term Plan. Enabling choice and supporting patients to make decisions predicated on what matters to them, rather than what is the matter with them, is a fundamental part of the NHS vision. Social prescribing uses nonmedical, asset based, salutogenic approaches to promote this personalised paradigm, and places the patient central to decision making. We discuss how Personalised care can be used to help people with Cardiovascular Disease (CVD) using socially prescribed ‘nature-based’ interventions to support the prehabilitation and rehabilitation of patients with CVD. The concept of Personalised care outlined and the significance of salutogenic principles as complementary approach to the pathogenic model is discussed. We argue that this seemingly novel approach to using nature-based interventions can help promote wellbeing for people with CVD as part of the wider personalised agenda

Influence of conjugated linoleic acid (CLA) or tetradecylthioacetic acid (TTA) on growth, lipid composition, fatty acid metabolism and lipid gene expression of rainbow trout (Oncorhynchus mykiss L.)

Our objective was to test the hypotheses that conjugated linoleic acid (CLA) and/or tetradecylthioacetic acid (TTA) would have beneficial effects on the nutritional quality of rainbow trout (Oncorhynchus mykiss) through decreased lipid content of flesh or viscera, and increased levels of beneficial fatty acids including accumulation of CLA or TTA themselves. The specific aims of this study were to determine the effects of CLA and TTA on growth performance, lipid and fatty acid metabolism, and selected gene expression in commercial sized trout grown in seawater. Trout were fed for eight weeks on fish meal and fish oil diets containing either 0.5% or 1% CLA, or 0.5% TTA. The effects of the supplemented fatty acids on growth, feed efficiency, lipid contents, class compositions and fatty acid compositions of flesh and liver were determined, along with liver highly unsaturated fatty acid synthesis, activities of key enzymes of fatty acid oxidation in liver and muscle, and expression of carnitine palmitoyltransferase-I (CPT-I) and fatty acyl desaturase and elongase genes. Neither functional fatty acid had any effect on growth parameters, condition factor, viscero- and hepato-somatic indices or fillet colour, and there were no mortalities in any of the treatments. Dietary CLA, but not TTA, decreased the lipid content of liver, but neither fatty acid had any significant effect on lipid class compositions of liver and flesh. Both CLA and TTA were incorporated into tissue lipids, with higher percentages found in flesh compared to liver. In addition, production of hexaene fatty acid by liver microsomes was increased by dietary CLA or TTA, and both functional fatty acids increased the proportion of n-3 fatty acids in liver mainly due to increased 20:5n-3 and 22:6n-3. However, the expression of fatty acyl Δ6 desaturase was significantly lower in fish fed CLA or TTA, whereas the expression of PUFA elongase was increased, significantly so in fish fed 1% CLA. CPT-I activity was increased by TTA in liver and red muscle, and acyl CoA oxidase activity was increased by TTA in liver and CLA at the higher dietary inclusion level in red muscle. There was a clear trend for CPT-I expression to be increased in fish fed 0.5% CLA or TTA in all tissues although this was only significant in white muscle. The results showed that both CLA and TTA had effects on lipid metabolism that partly support the hypotheses tested. Although CLA or TTA did not enhance growth parameters, feed conversion or potential yield, nutritional quality could be enhanced, and sea-run trout fed CLA or TTA could be beneficial in the human diet through provision of bioactive fatty acids, with no detrimental effects on 20:5n-3 or 22:6n-3 levels

Influence of dietary conjugated linoleic acid (CLA) and tetradecylthioacetic acid (TTA) on growth, lipid composition and key enzymes of fatty acid oxidation in liver and muscle of Atlantic cod (Gadus morhua L.)

The aim of the present study was to determine the effects of conjugated linoleic acid (CLA) and tetradecylthioacetic acid (TTA) on growth performance, and lipid and fatty acid metabolism in Atlantic cod. The overall objective being to test the hypotheses that CLA and TTA have beneficial effects in cod culture including decreased liver size and proportion through decreased lipid content, and increased nutritional quality through effects on fatty acid compositions including accumulation of bioactive fatty acids, CLA and TTA, in flesh. Juvenile cod were fed for three months on fish meal and fish oil diets of basically commercial formulation, but containing either 0.5% or 1% CLA, or 0.5% TTA. The effects of the functional fatty acids on growth, feed efficiency, body proximate composition, liver weight and lipid composition, fatty acid compositions of flesh and liver, and key enzymes of fatty acid oxidation were determined. Dietary CLA and TTA had no effect on growth parameters in cod juveniles, but viscero- and hepato-somatic indices were increased in fish fed 0.5% CLA and TTA, respectively. Proximate composition of whole fish was not affected by CLA or TTA, and there were no major effects of either functional fatty acid on lipid contents and compositions of liver and flesh. Dietary CLA and TTA were both incorporated into tissue lipids, with CLA deposited to a greater extent in liver, whereas TTA was deposited to a greater extent in flesh. In liver, acyl CoA oxidase (ACO) activity, but not carnitine palmitoyltransferase-I (CPT-I), was increased by CLA, whereas dietary TTA increased both ACO and CPT-I activities. In contrast, ACO activity was reduced by both CLA and TTA in red and white muscle, whereas CPT-I activity was generally not affected by CLA and TTA in either muscle tissue. Therefore, the results only partially supported the hypotheses tested, as CLA and TTA had few beneficial effects in Atlantic cod and did not enhance growth parameters, or improve feed conversion or potential yield through decreased adiposity or liver lipid deposition. However, nutritional quality could be enhanced, and cod fed CLA and/or TTA could be beneficial in the human diet, through provision of bioactive fatty acids with no detrimental effects on n-3 PUFA levels

Using next-generation sequencing for high resolution multiplex analysis of copy number variation from nanogram quantities of DNA from formalin-fixed paraffin-embedded specimens

The use of next-generation sequencing technologies to produce genomic copy number data has recently been described. Most approaches, however, reply on optimal starting DNA, and are therefore unsuitable for the analysis of formalin-fixed paraffin-embedded (FFPE) samples, which largely precludes the analysis of many tumour series. We have sought to challenge the limits of this technique with regards to quality and quantity of starting material and the depth of sequencing required. We confirm that the technique can be used to interrogate DNA from cell lines, fresh frozen material and FFPE samples to assess copy number variation. We show that as little as 5 ng of DNA is needed to generate a copy number karyogram, and follow this up with data from a series of FFPE biopsies and surgical samples. We have used various levels of sample multiplexing to demonstrate the adjustable resolution of the methodology, depending on the number of samples and available resources. We also demonstrate reproducibility by use of replicate samples and comparison with microarray-based comparative genomic hybridization (aCGH) and digital PCR. This technique can be valuable in both the analysis of routine diagnostic samples and in examining large repositories of fixed archival material

Effects of a demand-led evidence briefing service on the uptake and use of research evidence by commissioners of health services: protocol for a controlled before and after study

Background Clinical Commissioning Groups (CCGs) are mandated to use research evidence effectively to ensure optimum use of resources by the National Health Service (NHS), both in accelerating innovation and in stopping the use of less effective practices and models of service delivery. We intend to evaluate whether access to a demand-led evidence service improves uptake and use of research evidence by NHS commissioners compared with less intensive and less targeted alternatives. Methods/design This is a controlled before and after study involving CCGs in the North of England. Participating CCGs will receive one of three interventions to support the use of research evidence in their decision-making: 1) consulting plus responsive push of tailored evidence; 2) consulting plus an unsolicited push of non-tailored evidence; or 3) standard service unsolicited push of non-tailored evidence. Our primary outcome will be changed at 12 months from baseline of a CCGs ability to acquire, assess, adapt and apply research evidence to support decision-making. Secondary outcomes will measure individual clinical leads and managers’ intentions to use research evidence in decision making. Documentary evidence of the use of the outputs of the service will be sought. A process evaluation will evaluate the nature and success of the interactions both within the sites and between commissioners and researchers delivering the service. Discussion The proposed research will generate new knowledge of direct relevance and value to the NHS. The findings will help to clarify which elements of the service are of value in promoting the use of research evidence. Those involved in NHS commissioning will be able to use the results to inform how best to build the infrastructure they need to acquire, assess, adapt and apply research evidence to support decision-making and to fulfil their statutory duties under the Health and Social Care Act

What approaches to social prescribing work, for whom, and in what circumstances? A realist review

This is the final version. Available from Wiley via the DOI in this record.The use of non-medical referral, community referral or social prescribing interventions has been proposed as a cost-effective alternative to help those with long-term conditions manage their illness and improve health and well-being. However, the evidence base for social prescribing currently lags considerably behind practice. In this paper, we explore what is known about whether different methods of social prescribing referral and supported uptake do (or do not) work. Supported by an Expert Advisory Group, we conducted a realist review in two phases. The first identified evidence specifically relating to social prescribing in order to develop programme theories in the form of ‘if-then’ statements, articulating how social prescribing models are expected to work. In the second phase, we aimed to clarify these processes and include broader evidence to better explain the proposed mechanisms. The first phase resulted in 109 studies contributing to the synthesis, and the second phase 34. We generated 40 statements relating to organising principles of how the referral takes place (Enrolment), is accepted (Engagement), and completing an activity (Adherence). Six of these statements were prioritised using web-based nominal group technique by our Expert Group. Studies indicate that patients are more likely to enrol if they believe the social prescription will be of benefit, the referral is presented in an acceptable way that matches their needs and expectations, and concerns elicited and addressed appropriately by the referrer. Patients are more likely to engage if the activity is both accessible and transit to the first session supported. Adherence to activity programmes can be impacted through having an activity leader who is skilled and knowledgeable or through changes in the patient's conditions or symptoms. However, the evidence base is not sufficiently developed methodologically for us to make any general inferences about effectiveness of particular models or approaches.National Institute for Health Research (NIHR

The democracy of Green Infrastructure

With the understanding of nature in terms of ecosystem services and the recognition of the vital role these play for human wellbeing (Millennium Assessment, 2005), the value of the natural realm is scientifically and socially defined while at the same time institutionalised. Within this frame of interpretation, nature is a supplier of provision-ing, regulating, supporting welfare and cultural services, thus becoming not only a life-enabling factor for humanity but also a conceptual construct comparable to cornerstones of democracy, such as equality, freedom and citizenship. The idea of green infrastructure is another recently coined term envisioning nature in cities in the form of a net-work and enabling a broad life-furthering vision of society. Standards for green open spaces embedded in some planning frameworks further state the right for all to a common good. Yet, evidence shows that this common right is not always met. Within the current context of advanced and neoliberal capitalism, green areas are sometimes used as an added financial value for real estate, thus increasing restrictions to their free access and full utilization. In developing countries with young democracies, such as Brazil, this process implies another significant factor of social inequality insofar the restricted access to nature by the poorest people means also diminished food safety, and the jeopardizing of certain cultural practices. In developed countries, loss of land for food production and movements reclaiming the right to the city by squatting unoccupied open spaces to initiate community gar-dens, demonstrates that the access to green spaces is also problematic, although in different ways if compared to developing countries. This chapter contributes to this topic by discussing the inequality in provision of green spaces in informal settlements and social housing development in Brazil, as well as in the globalised north. The chapter concludes with recommendations to enhance democracy through a just provision of nature in cities

Routine gastric residual volume measurement and energy target achievement in the PICU: A comparison study

Critically ill children frequently fail to achieve adequate energy intake and some care practices, such as the measurement of gastric residual volume (GRV) may contribute to this problem. We compared outcomes in two similar European Pediatric Intensive Care Units (PICUs): one which routinely measures GRV (PICU-GRV) to one unit that does not (PICU-noGRV). An observational pilot comparison study was undertaken. 87 children were included in the study, 42 (PICU-GRV) and 45 (PICU-noGRV). There were no significant differences in the percentage of energy targets achieved in the first four days of PICU admission although PICU-noGRV showed more consistent delivery of median (and IQR) energy targets, and less under and over feeding for PICU-GRV and PICU-noGRV Day 1 37 (14-72) vs 44 (0-100); Day 2 97 (53-126) vs 100 (100-100), Day 3 84 (45-112) vs 100 (100-100) , Day 4 101 (63-124) vs 100 (100-100). The incidence of vomiting was higher in PICU-GRV. No necrotising enterocolitis was confirmed in either unit and ventilator acquired pneumonia rates were not significantly different (7.01 vs 12 5.31 per 1000 ventilator days; p=0.70) between PICU-GRV and PICU-noGRV units. Conclusions: The practice of routine gastric residual measurement did not significantly impair energy targets in the first four days of PICU admission. However, not measuring GRV did not increase vomiting, ventilator acquired pneumonia or necrotising enterocolitis, which is the main reason clinicians cite for measuring GRV. What is known?•The practice of routinely measuring gastric residual volume is widespread in critical care units•This practice is increasingly being questioned in critically ill patients, both as a practice that increases •the likelihood of delivering inadequate enteral nutrition amounts and as a tool to assess feeding tolerance What is new? •Not routinely measuring gastric residual volume did not increase adverse events of ventilator acquired pneumonia, necrotising enterocolitis or vomiting •In the first four days of PICU stay, energy target achievement was not significantly different, but the rates of under and over feeding were higher in the routine GRV measurement uni