Endothelial HO-1 induction by model TG-rich lipoproteins is regulated through a NOX4-Nrf2 pathway

Circulating levels of chylomicron remnants (CMRs) increase postprandially and their composition directly reflects dietary lipid intake. These TG-rich lipoproteins likely contribute to the development of endothelial dysfunction, albeit via unknown mechanisms. Here, we investigated how the FA composition of CMRs influences their actions on human aortic endothelial cells (HAECs) by comparing the effects of model CMRs—artificial TG-rich CMR-like particles (A-CRLPs)—containing TGs extracted from fish, DHA-rich algal, corn, or palm oils. HAECs responded with distinct transcriptional programs according to A-CRLP TG content and oxidation status, with genes involved in antioxidant defense and cytoprotection most prominently affected by n-3 PUFA-containing A-CRLPs. These particles were significantly more efficacious inducers of heme oxygenase-1 (HO-1) than n-6 PUFA corn or saturated FA-rich palm CRLPs. Mechanistically, HO-1 induction by all CRLPs requires NADPH oxidase 4, with PUFA-containing particles additionally dependent upon mitochondrial reactive oxygen species. Activation of both p38 MAPK and PPARβ/δ culminates in increased nuclear factor erythroid 2-related factor 2 (Nrf2) expression/nuclear translocation and HO-1 induction. These studies define new molecular pathways coupling endothelial cell activation by model CMRs with adaptive regulation of Nrf2-dependent HO-1 expression and may represent key mechanisms through which dietary FAs differentially impact progression of endothelial dysfunction

Glastir Monitoring & Evaluation Programme. Second year annual report

What is the purpose of Glastir Monitoring and Evaluation Programme? Glastir is the main scheme by which the Welsh Government pays for environmental goods and services whilst the Glastir Monitoring and Evaluation Programme (GMEP) evaluates the scheme’s success. Commissioning of the monitoring programme in parallel with the launch of the Glastir scheme provides fast feedback and means payments can be modified to increase effectiveness. The Glastir scheme is jointly funded by the Welsh Government (through the Rural Development Plan) and the EU. GMEP will also support a wide range of other national and international reporting requirements. What is the GMEP approach? GMEP collects evidence for the 6 intended outcomes from the Glastir scheme which are focussed on climate change, water and soil quality, biodiversity, landscape, access and historic environment, woodland creation and management. Activities include; a national rolling monitoring programme of 1km squares; new analysis of long term data from other schemes combining with GMEP data where possible; modelling to estimate future outcomes so that adjustments can be made to maximise impact of payments; surveys to assess wider socio-economic benefits; and development of novel technologies to increase detection and efficiency of future assessments. How has GMEP progressed in this 2nd year? 90 GMEP squares were surveyed in Year 2 to add to the 60 completed in Year 1 resulting in 50% of the 300 GMEP survey squares now being completed. Squares will be revisited on a 4 year cycle providing evidence of change in response to Glastir and other pressures such as changing economics of the farm business, climate change and air pollution. This first survey cycle collects the baseline against which future changes will be assessed. This is important as GMEP work this year has demonstrated land coming into the scheme is different in some respects to land outside the scheme. Therefore, future analysis to detect impact of Glastir will be made both against the national backdrop from land outside the scheme and this baseline data from land in scheme. A wide range of analyses of longterm data has been completed for all Glastir Outcomes with the exception of landscape quality and historic features condition for which limited data is available. This has involved combining data with 2013/14 GMEP data when methods allow. Overall analysis of long term data indicates one of stability but with little evidence of improvement with the exception of headwater quality, greenhouse gas emissions and woodland area for which there has been improvement over the last 20 years. Some headline statistics include: 51% of historic features in excellent or sound condition; two thirds of public rights of way fully open and accessible; improvement in hedgerow management with 85% surveyed cut in the last 3 years but < 1% recently planted; 91% of streams had some level of modification but 60% retained good ecological quality; no change topsoil carbon content over last 25 years. What is innovative? GMEP has developed various new metrics to allow for more streamlined reporting in the future. For example a new Priority Bird species Index for Wales which combines data from 35 species indicates at least half have stable or increasing populations. The new GMEP Visual Quality Landscape Index has been tested involving over 2600 respondents. Results have demonstrated its value as an objective and repeatable method for quantifying change in visual landscape quality. A new unified peat map for Wales has been developed which has been passed to Glastir Contract Managers to improve targeting of payments when negotiating Glastir contracts. An estimate of peat soil contribution to current greenhouse gas emissions due to human modification has been calculated. Models have allowed quantification of land area helping to mitigate rainfall runoff. We are using new molecular tools to explore the effects of Glastir on soil organisms and satellite technologies to quantify e.g. small woody features and landcover change. Finally we are using a community approach to develop a consensus on how to define and report change in High Nature Value Farmland which will be reported in the Year 3 GMEP report

Community interventions for people with complex emotional needs that meet the criteria for personality disorder diagnoses: systematic review of economic evaluations and expert commentary

Background: Diagnoses of personality disorder are prevalent among people using community secondary mental health services. Identifying cost-effective community-based interventions is important when working with finite resources. / Aims: To assess the cost-effectiveness of primary or secondary care community-based interventions for people with complex emotional needs who meet criteria for a diagnosis of personality disorder to inform healthcare policy-making. / Method: Systematic review (PROSPERO: CRD42020134068) of databases. We included economic evaluations of interventions for adults with complex emotional needs associated with a diagnosis of personality disorder in community mental health settings published before 18 September 2019. Study quality was assessed using the CHEERS statement. / Results: Eighteen studies were included. The studies mainly evaluated psychotherapeutic interventions. Studies were also identified that evaluated altering the setting in which care was delivered and joint crisis plans. No strong economic evidence to support a single intervention or model of community-based care was identified. / Conclusions: Robust economic evidence to support a single intervention or model of community-based care for people with complex emotional needs is lacking. The strongest evidence was for dialectical behaviour therapy, with all three identified studies indicating that it is likely to be cost-effective in community settings compared with treatment as usual. More robust evidence is required on the cost-effectiveness of community-based interventions on which decision makers can confidently base guidelines or allocate resources. The evidence should be based on consistent measures of costs and outcomes with sufficient sample sizes to demonstrate impacts on these

High fat diet-induced non alcoholic fatty liver disease in rats is associated with hyperhomocysteinemia caused by down regulation of the transsulphuration pathway

<p>Abstract</p> <p>Background</p> <p>Hyperhomocysteinemia (HHcy) causes increased oxidative stress and is an independent risk factor for cardiovascular disease. Oxidative stress is now believed to be a major contributory factor in the development of non alcoholic fatty liver disease, the most common liver disorder worldwide. In this study, the changes which occur in homocysteine (Hcy) metabolism in high fat-diet induced non alcoholic fatty liver disease (NAFLD) in rats were investigated.</p> <p>Methods and results</p> <p>After feeding rats a standard low fat diet (control) or a high fat diet (57% metabolisable energy as fat) for 18 weeks, the concentration of homocysteine in the plasma was significantly raised while that of cysteine was lowered in the high fat as compared to the control diet fed animals. The hepatic activities of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CGS), the enzymes responsible for the breakdown of homocysteine to cysteine via the transsulphuration pathway in the liver, were also significantly reduced in the high fat-fed group.</p> <p>Conclusions</p> <p>These results indicate that high fat diet-induced NAFLD in rats is associated with increased plasma Hcy levels caused by down-regulation of hepatic CBS and CGL activity. Thus, HHcy occurs at an early stage in high fat diet-induced NAFLD and is likely to contribute to the increased risk of cardiovascular disease associated with the condition.</p

Modelling Landscape-scale Species Response to Agri-Environment Schemes

Agri-environment schemes (AES) are the most significant environmental policy delivery mechanism in England, and include the conservation of biodiversity as a key objective. Provisional results from the ongoing Landscape-scale species monitoring of AES (LandSpAES) baseline field survey have shown some positive responses of mobile taxa to AES gradients at local (1km2) or landscape (3 × 3km) scales. However, it is not known whether these provisional results might be more broadly applicable outside the regions surveyed in the LandSpAES project, i.e. in other regions, or nationally. Here, we present the findings of an analytical project to explore the use of national Citizen Science (CitSci) scheme data, to investigate whether similar relationships with AES gradients would be found at a national scale in CitSci data to those shown with LandSpAES data, and whether integrated modelling was possible with combined CitSci and LandSpAES datasets. The design of LandSpAES has high power to detect AES effects, including the independent testing of the local and landscape AES gradients, but is restricted to six regions. The national CitSci are more representative of England as a whole, but have not been designed to detect AES effects. The aim of this project was to determine whether the provisional taxon responses to the AES gradients found in the LandSpAES project could be detected at a national scale using CitSci scheme data. To achieve this aim, three key questions were addressed through the analytical work: 1) Can addition of covariates account for environmental variation between survey squares in each dataset, to improve the comparability of AES gradient effects between LandSpAES and CitSci schemes? 2) Do the CitSci scheme datasets show similar relationships between taxa responses and the AES gradients, to those found with the LandSpAES data? 3) Can integrated approaches to combining datasets be used to jointly model CitSci and LandSpAES data, and does integrated modelling reduce uncertainty in quantifying the effects of AES gradients on taxa responses at a national scale across England

Analysis of health concerns not addressed by REACH for low tonnage chemicals and opportunities for new approach methodology

In Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) the criterion for deciding the studies that must be performed is the annual tonnage of the chemical manufactured or imported into the EU. The annual tonnage may be considered as a surrogate for levels of human exposure but this does not take into account the physico-chemical properties and use patterns that determine exposure. Chemicals are classified using data from REACH under areas of health concern covering effects on the skin and eye; sensitisation; acute, repeated and prolonged systemic exposure; effects on genetic material; carcinogenicity; and reproduction and development. We analysed the mandated study lists under REACH for each annual tonnage band in terms of the information they provide on each of the areas of health concern. Using the European Chemicals Agency (ECHA) REACH Registration data base of over 20,000 registered substances, we found that only 19% of registered substances have datasets on all areas of health concern. Information limited to acute exposure, sensitisation and genotoxicity was found for 62%. The analysis highlighted the shortfall of information mandated for substances in the lower tonnage bands. Deploying New Approach Methodologies (NAMs) at this lower tonnage band to assess health concerns which are currently not covered by REACH, such as repeat and extended exposure and carcinogenicity, would provide additional information and would be a way for registrants and regulators to gain experience in the use of NAMs. There are currently projects in Europe aiming to develop NAM-based assessment frameworks and they could find their first use in assessing low tonnage chemicals once confidence has been gained by their evaluation with data rich chemicals

Exploring relationships between land use intensity, habitat heterogeneity and biodiversity to identify and monitor areas of High Nature Value farming

Understanding how species richness is distributed across landscapes and which variables may be used as predictors is important for spatially targeting management interventions. This study uses finely resolved data over a large geographical area to explore relationships between land-use intensity, habitat heterogeneity and species richness of multiple taxa. It aims to identify surrogate landscape metrics, valid for a range of taxa, which can be used to map and monitor High Nature Value farmland (HNV). Results show that variation in species richness is distributed along two axes: land-use intensity and habitat heterogeneity. At low intensity land-use, species rich groups include wetland plants, plant habitat indicators, upland birds and rare invertebrates, whilst richness of other species groups (farmland birds, butterflies, bees) was associated with higher land-use intensity. Habitat heterogeneity (broadleaved woodland connectivity, hedgerows, habitat diversity) was positively related to species richness of many taxa, both generalists (plants, butterflies, bees) and specialists (rare birds, woodland birds, plants, butterflies). The results were used to create maps of HNV farmland. The proportion of semi-natural vegetation is a useful metric for identifying HNV type 1. HNV type 2 (defined as a mosaic of low-intensity habitats and structural elements) is more difficult to predict from surrogate variables, due to complex relationships between biodiversity and habitat heterogeneity and inadequacies of current remotely sensed data. This approach, using fine-scaled field survey data collected at regular intervals, in conjunction with remotely sensed data offers potential for extrapolating modelled results nationally, and importantly, can be used to assess change over time

The influence of chalk grasslands on butterfly phenology and ecology

The influence of large-scale variables such as climate change on phenology has received a great deal of research attention. However, local environmental factors also play a key role in determining the timing of species life cycles. Using the meadow brown butterfly Maniola jurtina as an example, we investigate how a specific habitat type, lowland calcareous grassland, can affect the timing of flight dates. Although protracted flight periods have previously been reported in populations on chalk grassland sites in the south of England, no attempt has yet been made to quantify this at a national level, or to assess links with population genetics and drought tolerance. Using data from 539 sites across the UK, these differences in phenology are quantified, and M. jurtina phenology is found to be strongly associated with both site geology and topography, independent of levels of abundance. Further investigation into aspects of M. jurtina ecology at a subset of sites finds no genetic structuring or drought tolerance associated with these same site conditions