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

Collaborative knowledge sharing in developing and evaluating a training programme for health professionals to implement a social intervention in dementia research

Purpose: This study aims to explore the utility of collaborative knowledge sharing with stakeholders in developing and evaluating a training programme for health professionals to implement a social intervention in dementia research. Design/methodology/approach: The programme consisted of two phases: 1) development phase guided by the Buckley and Caple’s training model and 2) evaluation phase drew on the Kirkpatrick’s evaluation model. Survey and interview data was collected from health professionals, people with dementia and their supporters who attended the training programme, delivered or participated in the intervention. Qualitative data was analysed using the framework analysis. Findings: Seven health professionals participated in consultations in the development phase. In the evaluation phase, 20 intervention facilitators completed the post one-day training evaluations and three took part in the intervention interviews. Eight people with dementia and their supporters from the promoting independence in dementia feasibility study participated in focus groups interviews. The findings show that intervention facilitators were satisfied with the training programme. They learnt new knowledge and skills through an interactive learning environment and demonstrated competencies in motivating people with dementia to engage in the intervention. As a result, this training programme was feasible to train intervention facilitators. Practical implications: The findings could be implemented in other research training contexts where those delivering research interventions have professional skills but do not have knowledge of the theories and protocols of a research intervention. Originality/value: This study provided insights into the value of collaborative knowledge sharing between academic researchers and multiple non-academic stakeholders that generated knowledge and maximised power through building new capacities and alliances

An investigation into the fertilizer potential of slaughterhouse cattle paunch

In Australia, the red meat processing industry actively seeks approaches to improve the management of solid waste from processing operations and enhance the environmental performance. Recycling of paunch waste to farmland could be a cost-effective and practicable environmental option. However, little is known about the agronomic value of fresh and composted paunch, and the associated requirements for land application. Therefore, a short-term experimental work was undertaken to assess potential risks due to weed seed contamination and determine the agronomic response of ryegrass (Lolium perenne L.) to soil incorporation of paunch. The risk of weed contamination from soil application of paunch appeared to be low; however, methods that account for viability of seeds may be required to fully discard such a risk. Soil application of paunch at field equivalent rates of 150-300 kg ha-1 of N increased dry matter yield by ≈30% on average compared with untreated grass, but was approximately 35% lower than a mineral fertilizer treatment applied at the same rates. Dry matter yield of paunch-treated grass was between 2000 and 3000 kg per ha over four consecutive cuts at 25-day intervals. Nitrogen use-efficiency of paunch was approximately 10% (range: 3% to 20%, depending on paunch type), and total N in harvested plant material showed values, which were between 2% and 3%. Overall, there appears to be potential for paunch-derived products to be used as a source of carbon and nutrients in crop production. Areas that merit a research priority within this space are also outlined in this paper. Such work is required to inform soil-, climate- and crop-specific land application rates, optimize agronomic performance, and minimize environmental concerns. There is also a requirement for the value proposition to industry to be determined, including reduced cost of disposal of material via gate fees and fertilizer replacement value

Maintaining Social Connections in Dementia: A Qualitative Synthesis

The clinical symptoms of dementia include difficulty with speech, poor short-term memory, and changes in behavior. These symptoms can affect how the person with dementia understands and performs in social interactions. This qualitative review investigated how people with mild to moderate dementia managed social connections. A systematic search of social science databases retrieved 13 articles; data were synthesized using thematic analysis. Results established the work undertaken by people with dementia to maintain and present a social persona seen as socially acceptable. Interpretations are contextualized within Goffman and Sabat's theories on "self." People with dementia were agentic in impression management: undertaking work to maintain recognized social roles, while being aware of when their illness led to others discrediting them. Wider recognition of strategies used to maintain a social self could inform interventions designed to increase capability and confidence in co-managing social connections following dementia diagnosis

Concerted evolution of duplicated mitochondrial control regions in three related seabird species

<p>Abstract</p> <p>Background</p> <p>Many population genetic and phylogenetic analyses of mitochondrial DNA (mtDNA) assume that mitochondrial genomes do not undergo recombination. Recently, concerted evolution of duplicated mitochondrial control regions has been documented in a range of taxa. Although the molecular mechanism that facilitates concerted evolution is unknown, all proposed mechanisms involve mtDNA recombination.</p> <p>Results</p> <p>Here, we document a duplication of a large region (cytochrome <it>b</it>, tRNA^Thr, tRNA^Pro, ND6, tRNA^Gluand the control region) in the mitochondrial genome of three related seabird species. To investigate the evolution of duplicate control regions, we sequenced both control region copies (CR1 and CR2) from 21 brown (<it>Sula leucogaster</it>), 21 red-footed (<it>S. sula</it>) and 21 blue-footed boobies (<it>S. nebouxii</it>). Phylogenetic analysis suggested that the duplicated control regions are predominantly evolving in concert; however, approximately 51 base pairs at the 5' end of CR1 and CR2 exhibited a discordant phylogenetic signal and appeared to be evolving independently.</p> <p>Conclusions</p> <p>Both the structure of the duplicated region and the conflicting phylogenetic signals are remarkably similar to a pattern found in <it>Thalassarche </it>albatrosses, which are united with boobies in a large clade that includes all procellariiform and most pelecaniform seabirds. Therefore we suggest that concerted evolution of duplicated control regions either is taxonomically widespread within seabirds, or that it has evolved many times.</p

The transcriptomic evolution of mammalian pregnancy:gene expression innovations in endometrial stromal fibroblasts

The endometrial stromal fibroblast (ESF) is a cell type present in the uterine lining of therian mammals. In the stem lineage of eutherian mammals, ESF acquired the ability to differentiate into decidual cells in order to allow embryo implantation. We call the latter cell type “neo-ESF” in contrast to “paleo-ESF” which is homologous to eutherian ESF but is not able to decidualize. In this study, we compare the transcriptomes of ESF from six therian species: Opossum (Monodelphis domestica; paleo-ESF), mink, rat, rabbit, human (all neo-ESF), and cow (secondarily nondecidualizing neo-ESF). We find evidence for strong stabilizing selection on transcriptome composition suggesting that the expression of approximately 5,600 genes is maintained by natural selection. The evolution of neo-ESF from paleo-ESF involved the following gene expression changes: Loss of expression of genes related to inflammation and immune response, lower expression of genes opposing tissue invasion, increased markers for proliferation as well as the recruitment of FOXM1, a key gene transiently expressed during decidualization. Signaling pathways also evolve rapidly and continue to evolve within eutherian lineages. In the bovine lineage, where invasiveness and decidualization were secondarily lost, we see a re-expression of genes found in opossum, most prominently WISP2, and a loss of gene expression related to angiogenesis. The data from this and previous studies support a scenario, where the proinflammatory paleo-ESF was reprogrammed to express anti-inflammatory genes in response to the inflammatory stimulus coming from the implanting conceptus and thus paving the way for extended, trans-cyclic gestation

Lack of evidence for the efficacy of enhanced surveillance compared to other specific interventions to control neonatal healthcare-associated infection outbreaks.

BACKGROUND: Despite current prevention efforts, outbreaks of healthcare-associated infections in neonatal units remain high globally, with a considerable burden of mortality and morbidity. METHODS: We searched Medline, Cochrane Library and Outbreak database to identify studies of neonatal healthcare-associated outbreaks between 2005 and 2015 that described interventions to control outbreaks. All studies were evaluated using the ORION guidance. RESULTS: Thirty studies were identified including 17 102 infants of whom 664 (3.9%) became infected. No single intervention was identified that reduced duration or mortality. Studies that introduced multiple interventions had significantly reduced case fatality ratio and outbreak duration compared to those that used basic surveillance only. Low and low-middle income countries reported the fewest interventions to control outbreaks and these studies were also associated with higher mortality than that found in middle and high income countries. CONCLUSIONS: Systematic reporting and formal evaluation of interventions used to reduce healthcare-associated neonatal infection outbreaks is key to identifying containment strategies worldwide