Delivering effective nursing care to children and young people outside of a hospital setting

This report may be reproduced for the purposes of private research and study; in addition, excerpts may be included in professional journals or conference presentations as long as acknowledgement is given and there is no association with advertisingOver the course of the last fifty years, there has been a reduction of approximately 75 per cent in the total number of children’s hospital beds in the United Kingdom [UK]; at the same time, there has been an increase in the amount and range of care now being provided in other environments that are located within outside of hospital settings. This shift in terms of the location and provision of care has meant that there has been an impact on the preparation and training that healthcare staff require. The Health Outcomes Forum specifically recommended: “That HEE [Health Education England] address the workforce education, training and development requirements (including capacity and capability) to refocus service provision at home or closer to home” (Department of Health, 2012: 52). This scoping project was financed and commissioned by Health Education North Central and East London Local Education and Training Board [HE NCEL LETB] in January 2014 and was undertaken by the University of Hertfordshire between February 2014 - August 2014. The project was funded to facilitate the consideration of the educational needs of the nursing workforce in relation to out of hospital care for children and young people, thus enabling the future potential development of out of hospital services to meet the health needs of the children and young people living in the HE NCEL geographical are

How the mammalian endoplasmic reticulum handles aggregation-prone β-sheet proteins

Misfolded proteins are prone to engage in aberrant intermolecular interactions that can lead to formation of large aggregate structures. Aggregation causes loss-of-function toxicity because the aggregating protein fails to reach its native fold and function. In addition, Protein aggregates may exert gain-of-toxicity, which is due to the shear presence of Aggregate conformations that sequester important cellular factors and disturb cell morphology. Protein aggregation is associated with a large number of human diseases. The endoplasmic reticulum (ER) is a membrane-bound cellular organelle andthe site of synthesis of one third of the eukaryotic proteome including secretory proteins and proteins destined for the endomembrane system. After co-translational translocation into the ER, nascent proteins are assisted to fold by molecular chaperones and are subject to post-translational modifications. Secretory proteins are retained in the ER lumen until they are correctly folded and are then delivered to the Golgi apparatus for further modifications. If a protein fails to fold properly after repeated folding cycles, it is instead targeted for degradation via the ER-associated degradation pathway (ERAD). The aim of the study presented in this thesis was to determine how the human ER quality control (ERQC) machinery deals with aggregation-prone proteins. This is of great interest because protein aggregates are differentially regulated by distinct cellular environments and many of the proteins that aggregate in diseases are in fact synthesised in the ER. To this end, we utilised de novo designed amyloidogenic β-proteins as generic models for protein aggregation. Due to their lack of evolved biological function, these model proteins allow the exclusive study of gain-of-function toxicity and enable us to dissect the effect of the ER environment on amyloidogenic proteins. We determined that ER-targeted versions of the model β-sheet proteins are significantly less toxic and more soluble than their non-targeted counterparts, which form toxic insoluble aggregates in the cytosol and nucleus. We found that the ER-targeted β-protein ER-β23 is recognised by ERQC machinery and efficiently retained in the ER lumen in a soluble polymeric state. Strikingly, ER-β23 interacted with factors of the ERAD pathway,even though it was not efficiently degraded. Instead, ER-β23 inhibited the degradation of other ERAD substrates by sequestering low-abundant ERAD factors. The presented results demonstrate a marked capacity of the ER to prevent the secretion of potentially toxic aggregation-prone proteins and to limit the formation of insoluble aggregates in the ER lumen. In addition, the data reveal a mechanism by which amyloidogenic proteins may disturb ER proteostasis. Another aim of this study was to analyse the effects of small molecule proteostasis modulators. We found that the anti-dopaminergic drugs fluphenazine and droperidolas well as the epidermal growth factor receptor (EGFR) inhibitors gefitinib and erlotinib improved proteostasis in the presence of Protein aggregates. In case of the former, this effect was most likely achieved via induction of the cytosol stress response. In summary, the work presented in this thesis provides novel insights into how aggregation-prone proteins behave in the environment of the ER and also demonstrates the potential of using small molecule modulators to improve cellular proteostasis in a disease context

Effective nursing care of children and young people outside hospital

THIS ARTICLE presents an exploratory study that was financed and commissioned by Health Education, North Central and East London (NCEL), and the local education and training board (LETB); it was undertaken by the University of Hertfordshire between February and August 2014. The research was funded to explore the educational needs of the nursing workforce in relation to out-of-hospital care for children and young people in the UK. The data will be used to inform the development of service provision. Read More: http://journals.rcni.com/doi/10.7748/ncyp.27.5.28.e610 Open Access with Creative Commons Attribution 3.0 Unported (CC BY 3.0). Copyright © 2017 RCN Publishing Company Ltd.Aim To assess the preparation required to ensure a workforce of nurses who can provide high quality out-of-hospital services for children and young people. Methods Using mixed methods, questionnaires were sent to young people and community children’s nursing teams, interviews were conducted with academic staff and clinical nurses, and focus groups were undertaken with pre-registration children’s nursing students. Findings Nurses’ communication skills and clinical abilities were most important to young people. There is a range of opinions about optimum out-of-hospital clinical experience. Pre- and post-qualification education and recruitment in this area, therefore, need attention. Conclusion Out-of-hospital care presents problems, but is developing rapidly. Adequate, updated training, supervision and resources are needed.Peer reviewe

Children and young people’s health and wellbeing

© 2021 by John Wiley & Sons, Inc.Peer reviewe

How the mammalian endoplasmic reticulum handles aggregation-prone β-sheet proteins

Misfolded proteins are prone to engage in aberrant intermolecular interactions that can lead to formation of large aggregate structures. Aggregation causes loss-of-function toxicity because the aggregating protein fails to reach its native fold and function. In addition, Protein aggregates may exert gain-of-toxicity, which is due to the shear presence of Aggregate conformations that sequester important cellular factors and disturb cell morphology. Protein aggregation is associated with a large number of human diseases. The endoplasmic reticulum (ER) is a membrane-bound cellular organelle andthe site of synthesis of one third of the eukaryotic proteome including secretory proteins and proteins destined for the endomembrane system. After co-translational translocation into the ER, nascent proteins are assisted to fold by molecular chaperones and are subject to post-translational modifications. Secretory proteins are retained in the ER lumen until they are correctly folded and are then delivered to the Golgi apparatus for further modifications. If a protein fails to fold properly after repeated folding cycles, it is instead targeted for degradation via the ER-associated degradation pathway (ERAD). The aim of the study presented in this thesis was to determine how the human ER quality control (ERQC) machinery deals with aggregation-prone proteins. This is of great interest because protein aggregates are differentially regulated by distinct cellular environments and many of the proteins that aggregate in diseases are in fact synthesised in the ER. To this end, we utilised de novo designed amyloidogenic β-proteins as generic models for protein aggregation. Due to their lack of evolved biological function, these model proteins allow the exclusive study of gain-of-function toxicity and enable us to dissect the effect of the ER environment on amyloidogenic proteins. We determined that ER-targeted versions of the model β-sheet proteins are significantly less toxic and more soluble than their non-targeted counterparts, which form toxic insoluble aggregates in the cytosol and nucleus. We found that the ER-targeted β-protein ER-β23 is recognised by ERQC machinery and efficiently retained in the ER lumen in a soluble polymeric state. Strikingly, ER-β23 interacted with factors of the ERAD pathway,even though it was not efficiently degraded. Instead, ER-β23 inhibited the degradation of other ERAD substrates by sequestering low-abundant ERAD factors. The presented results demonstrate a marked capacity of the ER to prevent the secretion of potentially toxic aggregation-prone proteins and to limit the formation of insoluble aggregates in the ER lumen. In addition, the data reveal a mechanism by which amyloidogenic proteins may disturb ER proteostasis. Another aim of this study was to analyse the effects of small molecule proteostasis modulators. We found that the anti-dopaminergic drugs fluphenazine and droperidolas well as the epidermal growth factor receptor (EGFR) inhibitors gefitinib and erlotinib improved proteostasis in the presence of Protein aggregates. In case of the former, this effect was most likely achieved via induction of the cytosol stress response. In summary, the work presented in this thesis provides novel insights into how aggregation-prone proteins behave in the environment of the ER and also demonstrates the potential of using small molecule modulators to improve cellular proteostasis in a disease context

Predictors of an early death in patients diagnosed with colon cancer : A retrospective case-control study in the UK

Acknowledgements The authors gratefully appreciate the contribution of data abstractors: Donna Floyd, Rosemary Ward, Jacqui Napier, Kate Donnelly and Bríd Morris. The authors also thank Business Services Organisation, Health and Social Care NI for facilitating the note review. Finally, the authors would like to thank all patients whose data was used in this studyPeer reviewedPublisher PD

Researching belonging with people with learning disabilities:Self-building active community lives in the context of personalisation

We wanted to understand more about how people with learning disabilities are building active community lives to help belonging. We spoke to 39 people from 29 different support organisations, 7 local authority representatives and 43 people with learning disabilities. They said belonging was about having the time to connect with other people in “everyday” places, being part of a supportive network and having the right choice and information. Belonging is like a cake. It needs the right ingredients. These ingredients include the right combination of people, places and times. Because of cuts to funding, many people with learning disabilities lack the right support, choice and information to access their communities. This is not belonging. ​. Abstract: Background This journal article draws on findings from a research project that examined how people with learning disabilities and their allies were seeking to build a sense of belonging. We wanted to focus on the concept of “belonging” in the context of personalisation and reduced government social care funding. Specifically, we sought to understand how people with learning disabilities and their supporters were coming together to “self-build” networks of support including friendship clubs and self-advocacy groups to enable a greater sense of belonging in their local communities. Methods Qualitative interviews were conducted with seven local authority representatives across four case study areas in the UK, as well as 39 staff across 29 organisations providing a range of day and evening support and activities. We also talked to 43 people with learning disabilities across the four areas about their experiences. Findings Our findings demonstrate how belonging involves a complex configuration of actors, places, times, relationships and institutional roles (much like the ingredients in a cake). The ways in which belonging intersects with agency and choice was also identified as an important and novel finding of our study. Conclusion While belonging is often presented to people as a desirable and realisable outcome of social inclusion policies, cuts in funding and a lack of appropriate support frustrate people's desires to meaningfully belong with other people in their local community. This demonstrates the importance of supporting social environments that meet people's needs for social connectedness and belonging

Inhibition of Gsk3β activity improves β-cell function in c-Kit\u3csup\u3eWv/+\u3c/sup\u3e male mice

Previous studies have shown that the stem cell marker, c-Kit, is involved in glucose homeostasis. We recently reported that c-KitWv/+ male mice displayed the onset of diabetes at 8 weeks of age; however, the mechanisms by which c-Kit regulates β-cell proliferation and function are unknown. The purpose of this study is to examine if c-KitWv/+ mutation-induced β-cell dysfunction is associated with downregulation of the phospho-Akt/Gsk3β pathway in c-KitWv/+ male mice. Histology and cell signaling were examined in C57BL/6J/KitWv/+ (c-Kit Wv/+) and wild-type (c-Kit+/+) mice using immunofluorescence and western blotting approaches. The Gsk3β inhibitor, 1-azakenpaullone (1-AKP), was administered to c-KitWv/+ and c-Kit+/+ mice for 2 weeks, whereby alterations in glucose metabolism were examined and morphometric analyses were performed. A significant reduction in phosphorylated Akt was observed in the islets of c-KitWv/+ mice (P\u3c0.05) along with a decrease in phosphorylated Gsk3β (P\u3c0.05), and cyclin D1 protein level (P\u3c0.01) when compared with c-Kit+/+ mice. However, c-KitWv/+ mice that received 1-AKP treatment demonstrated normal fasting blood glucose with significantly improved glucose tolerance. 1-AKP-treated c-KitWv/+ mice also showed increased β-catenin, cyclin D1 and Pdx-1 levels in islets, demonstrating that inhibition of Gsk3β activity led to increased β-cell proliferation and insulin secretion. These data suggest that c-KitWv/+ male mice had alterations in the Akt/Gsk3β signaling pathway, which lead to β-cell dysfunction by decreasing Pdx-1 and cyclin D1 levels. Inhibition of Gsk3β could prevent the onset of diabetes by improving glucose tolerance and β-cell function. © 2012 USCAP, Inc All rights reserved

Growing and Handling of Bacterial Cultures within a Shared Core Facility for Integrated Structural Biology Program

We have established and optimized standard operating procedures for growing and handling bacterial cultures in a shared core laboratory to support Integrative Structural Biology. The Integrative Structural Biology effort within the Biomolecular Research Center allows researchers to generate new knowledge about protein and RNA structure and function. We aim to understand how biomolecules assemble into stable structures and how structural dynamics impacts their function. Here we describe specific procedures for growing and handling bacterial cultures for overexpression and isolation of recombinant proteins, 15N/13C uniform labeling of recombinant proteins, protein isolation and purification, and analysis of protein solubility that are ideal for implementation in a shared research core laboratory that serves a multitude of diverse customers and research laboratories