Targeted disruption of the heat shock protein 20–phosphodiesterase 4D (PDE4D) interaction protects against pathological cardiac remodelling in a mouse model of hypertrophy

Phosphorylated heat shock protein 20 (HSP20) is cardioprotective. Using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and a mouse model of pressure overload mediated hypertrophy, we show that peptide disruption of the HSP20–phosphodiesterase 4D (PDE4D) complex results in attenuation of action potential prolongation and protection against adverse cardiac remodelling. The later was evidenced by improved contractility, decreased heart weight to body weight ratio, and reduced interstitial and perivascular fibrosis. This study demonstrates that disruption of the specific HSP20–PDE4D interaction leads to attenuation of pathological cardiac remodelling

Hospital patient experiences of contact isolation for antimicrobial resistant organisms in relation to health care–associated infections: A systematic review and narrative synthesis of the evidence

Laura Fregonese - ORCID: 0000-0002-8399-7074 https://orcid.org/0000-0002-8399-7074Background The alarming growth of antimicrobial resistance organisms (AMRs) and the threat caused by health care–associated infections require hospitalized individuals who are infected or colonized with AMRs to be cared for in isolation, predominantly in single rooms. None of the existing reviews focus on or specifically address the patient’s experience of being cared for in contact isolation when affected by AMRs exploring this specific context. Methods Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance for the conduct of systematic reviews was applied. Five databases were searched from inception to April 2019, with keywords related to adult patient experiences, AMR, and contact isolation. The evidence was certified by 2 reviewers. Principles of thematic analysis were used to produce a narrative synthesis of the findings. Results Eighteen eligible studies were identified. Narrative synthesis resulted in 3 overarching categories reflecting the patient experience: privacy versus loneliness; emotional responses to isolation; quality of care, recovery, and safety in isolation. Conclusions This review synthesizes existing evidence reflecting the patient experience of contact isolation. Study findings were often contradictory and may not reflect contemporary health care, such as shorter hospital stays, or societal preferences for greater privacy. Further research focusing on contemporary health care contexts is recommended.https://doi.org/10.1016/j.ajic.2023.04.01151pubpub1

Low-Background gamma counting at the Kimballton Underground Research Facility

The next generation of low-background physics experiments will require the use of materials with unprecedented radio-purity. A gamma-counting facility at the Kimballton Underground Research Facility (KURF) has been commissioned to perform initial screening of materials for radioactivity primarily from nuclides in the 238U and 232Th decay chains, 40K and cosmic-ray induced isotopes. The facility consists of two commercial low-background high purity germanium (HPGe) detectors. A continuum background reduction better than a factor of 10 was achieved by going underground. This paper describes the facility, detector systems, analysis techniques and selected assay results.Comment: 7 pages, 7 figures. Submitted to NIM

Attitudes towards the use and acceptance of eHealth technologies : a case study of older adults living with chronic pain and implications for rural healthcare

Acknowledgements The research described here is supported by the award made by the RCUK Digital Economy programme to the dot.rural Digital Economy Hub; award reference: EP/G066051/1. MC’s time writing the paper is funded by the Scottish Government’s Rural and Environmental Science and Analytical Services Division (RESAS) under Theme 8 ‘Vibrant Rural Communities’ of the Food, Land and People Programme (2011–2016). MC is also an Honorary Research Fellow at the Division of Applied Health Sciences, University of Aberdeen. The input of other members of the TOPS research team, Alastair Mort, Fiona Williams, Sophie Corbett, Phil Wilson and Paul MacNamee who contributed to be wider study and discussed preliminary findings reported here with the authors of the paper is acknowledged. We acknowledge the feedback on earlier versions of this paper provided by members of the Trans-Atlantic Rural Research Network, especially Stefanie Doebler and Carmen Hubbard. We also thank Deb Roberts for her comments.Peer reviewedPublisher PD

Spatial and temporal variability in recruitment of intertidal mussels around the coast of southern Africa

Intensity of intertidal mussel recruitment was compared across a range of different spatial and temporal scales around the coast of southern Africa between June 1995 and October 1996. Comparison of the east and west coasts revealed significantly higher recruit densities on the west coast, corresponding to larger adult densities. This difference between the two coasts reflects biogeographic disparities in mussel species composition, growth rates and spawning intensities, oceanographic conditions and productivity. Significant spatial variations in recruitment were recorded between regions 100–1000 km apart and between localities 1–25 km apart. Results suggest that the influence of dispersal processes on recruitment patterns acts at a relatively small scale, and may affect the distribution and abundance of adults among shores only a few kilometres apart. The high variability in recruitment intensities at a scale of metres indicates that larva! supply to the shore may be locally patchy, or that settlement preferences of recruits may be sensitive to subtle small-scale differences in adult density within mussel clumps. Small-scale differences in post-settlement mortality (e.g. owing to patchy predation pressure) may also play a role. This small-scale variability in recruitment is likely to reinforce the mosaic distribution of mussels evident on many of the shores. Significant temporal variability in recruit density was recorded, both between 3-monthly sampling intervals and interannually. Seasonal differences were absent for the north-west regions, whereas asynchronous seasonal patterns were displayed in the other regions. Results suggest that temporal cycles of recruitment are irregular and episodic, which may have important consequences for the dynamics of adults. Significant positive correlations were obtained between maximal recruitment and adult abundance, measured by density, or total number of adults on the shore (stock). This could be explained by the density-dependent role of adult conspecifics in providing suitable settlement habitat, or supply-side recruit limitation. These results have important implications for the management of exploited populations of mussels around the coast of southern Africa. Exploitation may influence recruitment success via at least two processes: reduction of larval supply by depletion of adult stock, and alteration of habitat suitable for settlement. Thus, overexploitation will compromise recruitment, which is itself the only mechanism of recovery. The west-coast mussel populations are likely to be more resilient to exploitation as recruitment is more predictable over time, stocks are larger and recruitment intensities high. This brings into question the present regulations for mussel harvesting because, paradoxically, more lenient regulations are applied on the east coast, where stocks and recruitment are low, than on the west coast, where biomass, recruitment and potential for recovery are high

Children's development and parental input: Evidence from the UK Millennium Cohort Study

In this study, we use the UK Millennium Cohort Study to estimate a dynamic factor model of child development. Our model follows the children from birth until 7 years of age and allows for both cognitive and noncognitive abilities in children. We find a significant self-productivity effect in both cognitive and noncognitive development, as well as some evidence of dynamic dependence across different abilities. The activities that parents carry out with children at home (parental investment) have a significant effect on children’s development; we find substantial evidence of two distinct latent parental investment variables with differential effects across the two abilities

The Challenges and Psychological Impact of Delivering Nursing Care within a War Zone

Background. Between 2001 and 2014, British military nurses served in Afghanistan caring for both Service personnel and local nationals of all ages. However, there have been few research studies assessing the psychological impact of delivering nursing care in a War Zone hospital. Purpose. To explore the challenges and psychological stressors facing military nurses in undertaking their operational role. Method. A Constructivist Grounded Theory was utilised. Semi-structured interviews were conducted with 18 British Armed Forces nurses at Camp Bastion Hospital, Afghanistan, in June - July 2013. Discussion. Military nurses faced prolonged periods of caring for seriously injured poly trauma casualties of all ages, and there were associated distressing psychological effects and prolonged periods of adjustment on returning home. Caring for children was a particular concern. The factors that caused stress, both on deployment and returning home, along with measures to address these issues such as time for rest and exercise, can change rapidly in response to the dynamic flux in clinical intensity common within the deployable environment. Conclusion. Clinical training, a good command structure, the requirement for rest, recuperation, exercise and diet were important in reducing psychological stress within a War Zone. No formal debriefing model was advocated for clinical staff who appear to want to discuss traumatic incidents as a group and this may have contributed to stigma and nurses' feeling isolated. On returning home, military nurses reported being disconnected from the civilian wards and departments. The study raised the question of who cares for the carers, as participants reported a perception that others felt that they should be able to cope without any emotional issues. It is envisioned that the results are transferable internationally to nurses from other Armed forces and will raise awareness with civilian colleagues

Comparison of the predictive nature of the genomic allergen rapid detection (GARD) assay with mammalian assays in determining the skin sensitisation potential of agrochemical active ingredients.

Alternatives to mammalian testing are highly desirable to predict the skin sensitisation potential of agrochemical active ingredients (AI). The GARD assay, a stimulated, dendritic cell-like, cell line measuring genomic signatures, was evaluated using twelve AIs (seven sensitisers and five non-sensitisers) and the results compared with historical results from guinea pig or local lymph node assay (LLNA) studies. Initial GARD results suggested 11/12 AIs were sensitisers and six concurred with mammalian data. Conformal predictions changed one AI to a non-sensitiser. An AI identified as non-sensitising in the GARD assay was considered a potent sensitiser in the LLNA. In total 7/12 GARD results corresponded with mammalian data. AI chemistries might not be comparable to the GARD training set in terms of applicability domains. Whilst the GARD assay can replace mammalian tests for skin sensitisation evaluation for compounds including cosmetic ingredients, further work in agrochemical chemistries is needed for this assay to be a viable replacement to animal testing. The work conducted here is, however, considered exploratory research and the methodology needs further development to be validated for agrochemicals. Mammalian and other alternative assays for regulatory safety assessments of AIs must provide confidence to assign the appropriate classification for human health protection

Post-millennial Literature

This chapter investigates the British novel since 2000 by thinking about how a range of novels demonstrate a concern with the ability of contemporary prose fiction to maintain the 'meanwhile' which, according to Benedict Anderson, has been crucial to the novel's representational techniques since its inception