Failure to Downregulate the Epithelial Sodium Channel Causes Salt Sensitivity in Hsd11b2 Heterozygote Mice

In vivo, the enzyme 11β-hydroxysteroid dehydrogenase type 2 influences ligand access to the mineralocorticoid receptor. Ablation of the encoding gene, HSD11B2, causes the hypertensive syndrome of apparent mineralocorticoid excess. Studies in humans and experimental animals have linked reduced 11β-hydroxysteroid dehydrogenase type 2 activity and salt sensitivity of blood pressure. In the present study, renal mechanisms underpinning salt sensitivity were investigated in Hsd11b2(+/-) mice fed low-, standard-, and high-sodium diets. In wild-type mice, there was a strong correlation between dietary sodium content and fractional sodium excretion but not blood pressure. High sodium feeding abolished amiloride-sensitive sodium reabsorption, consistent with downregulation of the epithelial sodium channel. In Hsd11b2(+/-) mice, the natriuretic response to increased dietary sodium content was blunted, and epithelial sodium channel activity persisted. High-sodium diet also reduced renal blood flow and increased blood pressure in Hsd11b2(+/-) mice. Aldosterone was modulated by dietary sodium in both genotypes, and salt sensitivity in Hsd11b2(+/-) mice was associated with increased plasma corticosterone levels. Chronic administration of an epithelial sodium channel blocker or a glucocorticoid receptor antagonist prevented salt sensitivity in Hsd11b2(+/-) mice, whereas mineralocorticoid receptor blockade with spironolactone did not. This study shows that reduced 11β-hydroxysteroid dehydrogenase type 2 causes salt sensitivity of blood pressure because of impaired renal natriuretic capacity. This reflects deregulation of epithelial sodium channels and increased renal vascular resistance. The phenotype is not caused by illicit activation of mineralocorticoid receptors by glucocorticoids but by direct activation of glucocorticoid receptors

Comparing non-invasive surveying techniques for elusive, nocturnal mammals: a case study of the West European hedgehog (Erinaceus europaeus)

Monitoring changes in populations is fundamental for effective management. The West European hedgehog (Erinaceus europeaus) is of conservation concern in the UK because of recent substantial declines. Surveying hedgehogs is, however, problematic because of their nocturnal, cryptic behaviour. We compared the effectiveness of three methods (infra-red thermal camera, specialist search dog, spotlight) for detecting hedgehogs in three different habitats. Significantly more hedgehogs were detected, and at greater distance, using the camera and dog than the spotlight in amenity grassland and pasture; no hedgehogs were detected in woodland. Increasing ground cover reduced detection distances, with most detections (59.6%) associated with bare soil or mown grass; the dog was the only method that detected hedgehogs in vegetation taller than the target species’ height. The additional value of surveying with a detection dog is most likely to be realised in areas where badgers (Meles meles), an intra-guild predator, are and/or where sufficient ground cover is present; both would allow hedgehogs to forage further from refuge habitats such as hedgerows. Further consideration of the effectiveness of detection dogs for finding hedgehogs in nests, as well as developing techniques for monitoring this species in woodland, is warranted

Fetal and neonatal exposure to trans fatty acids impacts on susceptibility to atherosclerosis in apolipoprotein E*3 Leiden mice

Nutrition during pregnancy can impact on the susceptibility of the offspring to cardiovascular disease. Postnatal consumption of trans fatty acids (TFA), associated with partially hydrogenated vegetable oil (PHVO), increases the risk of atherosclerosis, while evidence for those trans fatty acids associated with ruminant-derived dairy and meat remain equivocal. Here, we investigate the impact of maternal consumption of dietary PHVO (P) and ruminant milk fat (R) on the development of atherosclerosis in their offspring, using the transgenic apoE*3 Leiden mouse. Dams were fed either chow (C) or one of three high fat diets: a diet reflecting the saturated fatty acid content of a ‘Western’ diet (W) or one enriched with either P or R. Diets were fed during either pregnancy alone or pregnancy and lactation. Weaned offspring were then transferred to an atherogenic diet for twelve weeks. Atherosclerosis was assessed as lipid staining in cross-sections of the aorta. There was a significant effect of maternal diet during pregnancy on development of atherosclerosis (p=0.013) in the offspring with those born of mothers fed R or P during pregnancy displaying smaller lesions that those fed C or W. This was not associated with changes in total or lipoprotein cholesterol. Continuing to feed P during lactation increased atherosclerosis compared to that seen in offspring of dams fed P only during pregnancy (p<0.001). No such effect was seen in those from mothers fed R (p=0.596) or W (p=901). We conclude that dietary TFA have differing effects on cardiovascular risk at different stages of the lifecycle

Non-oxidative modification of low density lipoprotein by ruptured myocytes

AbstractIn this study, the interaction of ruptured cardiac myocytes with low density lipoprotein (LDL) has been investigated and the consequent extent of uptake by macrophages. The results show that lysate released from ruptured myocytes is capable of inducing LDL oxidation and that the resulting modified form is recognised and degraded by macrophages. Peroxyl radical scavengers inhibit the LDL oxidation but not the macrophage uptake suggesting that LDL can be modified by mechanisms that are independent of oxidative processes by intracellular constituents of cardiac myocytes

Priorities for research during the Coronavirus SARS-CoV-2 (COVID-19) pandemic and beyond: a survey of nurses, midwives and health visitors in the United Kingdom

Background: The Coronavirus SARS-CoV-2 (COVID-19) pandemic has had a significant burden on global healthcare systems. Nurses, midwives and health visitors remain critical to the rapid responses and innovative solutions required. Their views, however, on priorities for research is mainly muted, necessitating greater clarity to inform research that benefits patients and families across the life course. Aims: To identify priorities for research in relation to the COVID-19 pandemic and ‘beyond’, as recommended by nurses, midwives and health visitors across the four countries of the United Kingdom (UK). Methods: A cross-sectional, web-based survey design was conducted (5th May-4th June 2020). In addition to the completion of demographic information, respondents identified up to three research areas important to their clinical care/practice in the context of COVID-19 and beyond. Data were imported for analysis into NVivo 12 (QSR International). Descriptive analysis was used to summarise the demographic variables. Free text responses were analysed using a semantic, inductive thematic analysis approach. Results: In total 1,296 responses were received from a self-selected sample of predominantly of female, registered nurses of white British ethnicity, located in England and working for acute care providers, providing 3,444 research priority recommendations. Four higher-order themes emerged, (1) New and unknown frontiers; (2) Care and treatment solutions; (3) Healthcare leadership and inclusive workforce; and (4) Emotional and mental health impact. Conclusions: At a time of significant global uncertainty, the collective voice of nursing, midwifery and health visiting is never more important to inform clinical research. Whilst generalisability is limited by the homogeneity of the sample, this is the first survey to elicit the priorities for research in relation to the COVID-19 pandemic and beyond from nurses, midwives and health visitors in the UK. Novel findings developed through a rigorous analytical approach illuminate areas that require both urgent and long-term attention and provide a platform to direct priority refinement, future research and the basis for evidence translation

From ocean sprawl to blue-green infrastructure:A UK perspective on an issue of global significance

Artificial structures are proliferating in the marine environment, resulting in ‘ocean sprawl’. In light of the potential environmental impacts of this, such as habitat loss and alteration, it is becoming increasingly important to incorporate ecologically-sensitive design into artificial marine structures. The principles of eco-engineering and green infrastructure are embedded in urban planning practice for terrestrial and freshwater development projects. In marine planning, however, eco-engineering of blue-green infrastructure remains an emerging concept. This note provides a UK perspective on the progress towards uptake of eco-engineering approaches for enhancing biodiversity on artificial marine structures. We emphasise that, despite a clear ‘policy pull’ to incorporate biodiversity enhancements in marine structures, a range of proof-of-concept evidence that it is possible to achieve, and strong cross-sectoral stakeholder support, there are still few examples of truly and purposefullydesigned blue-green artificial structures in the UK. We discuss the barriers that remain and propose a strategy towards effective implementation. Our strategy outlines a step-wise approach to: (1) strengthening the evidence base for what enhancements can be achieved in different scenarios; (2) improving clarity on the predicted benefits and associated costs of enhancements; (3) packaging the evidence in a useful form to support planning and decision-making; and (4) encouraging implementation as routine practice. Given that ocean sprawl is a growing problem globally, the perspective presented here provides valuable insight and lessons for other nations at their various states of progress towards this same goal

Supervisor trainees' and their supervisors' perceptions of attainment of knowledge and skills. An empirical evaluation of a psychotherapy supervisor training programme

Objectives. This study aimed to evaluate the success of a two-year, part-time training programme for psychotherapy supervisors. A second aim was to examine factors that might contribute to perceived knowledge and skills attainment during the training course. Design. This is a naturalistic, longitudinal study where several measures are used to examine group process and outcome. Methods. Supervisor trainees’ (n=21) and their facilitators’ (n=6) ratings of learning (knowledge and skills), relations to the supervisor and supervision group, usage of the group, and supervisor style were completed at three time points. Results. The findings suggested that both trainees and their supervisors perceived that the trainees attained a substantial amount of knowledge and skills during the course. In accordance with the literature and expectations, the regression analysis suggested a strong negative association between a strong focus on group processes in the initial and middle phases of the training and perceived knowledge and skills attainment in the final phase of the training. The expected, positive role of relations among trainees in the supervision group in the first half of the training and perceived knowledge and skills attainment in the final part of the training was obtained, whilst the hypothesized significance of the relationship between trainee and supervisor did not receive support. Conclusions The supervisory course seemed to provide a training that allowed trainees to attain knowledge and skills that are necessary for psychotherapy supervisors. The results of this pilot study also emphasize the need of more research on learning in the context of group supervision in psychotherapy

Fetal and neonatal exposure to trans fatty acids impacts on susceptibility to atherosclerosis in apolipoprotein E*3 Leiden mice

Nutrition during pregnancy can impact on the susceptibility of the offspring to cardiovascular disease. Postnatal consumption of trans fatty acids (TFA), associated with partially hydrogenated vegetable oil (PHVO), increases the risk of atherosclerosis, while evidence for those trans fatty acids associated with ruminant-derived dairy and meat remain equivocal. Here, we investigate the impact of maternal consumption of dietary PHVO (P) and ruminant milk fat (R) on the development of atherosclerosis in their offspring, using the transgenic apoE*3 Leiden mouse. Dams were fed either chow (C) or one of three high fat diets: a diet reflecting the saturated fatty acid content of a ‘Western’ diet (W) or one enriched with either P or R. Diets were fed during either pregnancy alone or pregnancy and lactation. Weaned offspring were then transferred to an atherogenic diet for twelve weeks. Atherosclerosis was assessed as lipid staining in cross-sections of the aorta. There was a significant effect of maternal diet during pregnancy on development of atherosclerosis (p=0.013) in the offspring with those born of mothers fed R or P during pregnancy displaying smaller lesions that those fed C or W. This was not associated with changes in total or lipoprotein cholesterol. Continuing to feed P during lactation increased atherosclerosis compared to that seen in offspring of dams fed P only during pregnancy (

Greening of grey infrastructure should not be used as a Trojan horse to facilitate coastal development

Climate change and coastal urbanization are driving the replacement of natural habitats with artificial structures and reclaimed land globally. These novel habitats are often poor surrogates for natural habitats. The application of integrated greening of grey infrastructure (IGGI) to artificial shorelines demonstrates how multifunctional structures can provide biodiversity benefits whilst simultaneously serving their primary engineering function. IGGI is being embraced globally, despite many knowledge gaps and limitations. It is a management tool to compensate anthropogenic impacts as part of the Mitigation Hierarchy. There is considerable scope for misuse and ‘greenwashing’ however, by making new developments appear more acceptable, thus facilitating the regulatory process. We encourage researchers to exercise caution when reporting on small-scale experimental trials. We advocate that greater attention is paid to when experiments ‘fail’ or yield unintended outcomes. We advise revisiting, repeating and expanding on experiments to test responses over broader spatio-temporal scales to improve the evidence base. Synthesis and applications. Where societal and economic demand makes development inevitable, particular attention should be paid to avoiding, minimizing and rehabilitating environmental impacts. Integrated greening of grey infrastructure (IGGI) should be implemented as partial compensation for environmental damage. Mutual benefits for both humans and nature can be achieved when IGGI is implemented retrospectively in previously developed or degraded environments. We caution, however, that any promise of net biodiversity gain from new developments should be scrutinized and any local ecological benefits set in the context of the wider environmental impacts. A ‘greened’ development will always impinge on natural systems, a reality that is much less recognized in the sea than on land.</p