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The Nursing and Midwifery Council recognises that using simulated practice learning within the pre-registration nursing curriculum is a valuable way for students to develop nursing knowledge and skills. The University of Huddersfield developed simulated placements in the pre-registration nursing curriculum in 2021. Simulated placements are now embedded within all fields of the BSc and MSc programmes, providing structured, innovative learning experiences that embrace online technology in supporting the development of skills and knowledge relevant to all fields of nursing. Developing these placements has provided an opportunity for faculty staff to work collaboratively with clinical colleagues, service users and carers, academics and technologists. This article offers an overview of that work, addressing challenges, operational issues, and insight into some of the activities developed to support students' learning.

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PURPOSE: Service development to improve patient safety and experience, and improve staff safety and confidence when managing telephone calls from parents or carers of children with cancer in the UK. METHOD: A multi-layered mixed methods approach broadly based on sequential PDSA (plan, do, study, act) cycles, to a series of quality initiative projects spanning 14 years. Various project styles and methods are described. RESULTS: A Telephone Triage Toolkit for children's cancer services was piloted, reviewed and rolled out across the UK. Similarities were identified between adult and paediatric cancer services when identifying the case for need, enabling partnership working. A scheduled review completed in 2020 included new developments in cancer treatment, building on user experience, local audits and national feedback, leading to a 2nd edition being implemented. CONCLUSIONS: Ground up, quality initiatives and collaborative working across organisations can be complex but draws on a wider pool of expertise and can lead to improved parent and staff experience of services. This initiative has improved practice and has application outside the UK.

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Little is known about the role of the transcription factor peroxisome proliferator-activated receptor (PPAR) beta/delta in liver. Here we set out to better elucidate the function of PPARbeta/delta in liver by comparing the effect of PPARalpha and PPARbeta/delta deletion using whole genome transcriptional profiling and analysis of plasma and liver metabolites. In fed state, the number of genes altered by PPARalpha and PPARbeta/delta deletion was similar, whereas in fasted state the effect of PPARalpha deletion was much more pronounced, consistent with the pattern of gene expression of PPARalpha and PPARbeta/delta. Minor overlap was found between PPARalpha- and PPARbeta/delta-dependent gene regulation in liver. Pathways upregulated by PPARbeta/delta deletion were connected to innate immunity and inflammation. Pathways downregulated by PPARbeta/delta deletion included lipoprotein metabolism and various pathways related to glucose utilization, which correlated with elevated plasma glucose and triglycerides and reduced plasma cholesterol in PPARbeta/delta-/- mice. Downregulated genes that may underlie these metabolic alterations included Pklr, Fbp1, Apoa4, Vldlr, Lipg, and Pcsk9, which may represent novel PPARbeta/delta target genes. In contrast to PPARalpha-/- mice, no changes in plasma free fatty acid, plasma beta-hydroxybutyrate, liver triglycerides, and liver glycogen were observed in PPARbeta/delta-/- mice. Our data indicate that PPARbeta/delta governs glucose utilization and lipoprotein metabolism and has an important anti-inflammatory role in liver. Overall, our analysis reveals divergent roles of PPARalpha and PPARbeta/delta in regulation of gene expression in mouse liver.

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Peroxisome proliferator-activated receptor alpha (PPARalpha) is an important transcription factor in liver that can be activated physiologically by fasting or pharmacologically by using high-affinity synthetic agonists. Here we initially set out to elucidate the similarities in gene induction between Wy14643 and fasting. Numerous genes were commonly regulated in liver between the two treatments, including many classical PPARalpha target genes, such as Aldh3a2 and Cpt2. Remarkably, several genes induced by Wy14643 were upregulated by fasting independently of PPARalpha, including Lpin2 and St3gal5, suggesting involvement of another transcription factor. Using chromatin immunoprecipitation, Lpin2 and St3gal5 were shown to be direct targets of PPARbeta/delta during fasting, whereas Aldh3a2 and Cpt2 were exclusive targets of PPARalpha. Binding of PPARbeta/delta to the Lpin2 and St3gal5 genes followed the plasma free fatty acid (FFA) concentration, consistent with activation of PPARbeta/delta by plasma FFAs. Subsequent experiments using transgenic and knockout mice for Angptl4, a potent stimulant of adipose tissue lipolysis, confirmed the stimulatory effect of plasma FFAs on Lpin2 and St3gal5 expression levels via PPARbeta/delta. In contrast, the data did not support activation of PPARalpha by plasma FFAs. The results identify Lpin2 and St3gal5 as novel PPARbeta/delta target genes and show that upregulation of gene expression by PPARbeta/delta is sensitive to plasma FFA levels. In contrast, this is not the case for PPARalpha, revealing a novel mechanism for functional differentiation between PPARs.

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BACKGROUND: The effect of dietary fats on human health and disease are likely mediated by changes in gene expression. Several transcription factors have been shown to respond to fatty acids, including SREBP-1c, NF-kappaB, RXRs, LXRs, FXR, HNF4alpha, and PPARs. However, it is unclear to what extent these transcription factors play a role in gene regulation by dietary fatty acids in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Here, we take advantage of a unique experimental design using synthetic triglycerides composed of one single fatty acid in combination with gene expression profiling to examine the effects of various individual dietary fatty acids on hepatic gene expression in mice. We observed that the number of significantly changed genes and the fold-induction of genes increased with increasing fatty acid chain length and degree of unsaturation. Importantly, almost every single gene regulated by dietary unsaturated fatty acids remained unaltered in mice lacking PPARalpha. In addition, the majority of genes regulated by unsaturated fatty acids, especially docosahexaenoic acid, were also regulated by the specific PPARalpha agonist WY14643. Excellent agreement was found between the effects of unsaturated fatty acids on mouse liver versus cultured rat hepatoma cells. Interestingly, using Nuclear Receptor PamChip(R) Arrays, fatty acid- and WY14643-induced interactions between PPARalpha and coregulators were found to be highly similar, although several PPARalpha-coactivator interactions specific for WY14643 were identified. CONCLUSIONS/SIGNIFICANCE: We conclude that the effects of dietary unsaturated fatty acids on hepatic gene expression are almost entirely mediated by PPARalpha and mimic those of synthetic PPARalpha agonists in terms of regulation of target genes and molecular mechanism. Use of synthetic dietary triglycerides may provide a novel paradigm for nutrigenomics research.

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This paper reports the findings of a study which was carried out to evaluate the educational preparation of cancer and palliative care nurses in England. The study was carried out in three stages and covered the following areas; documentary analysis of curriculae, assessment of practice, patients and professionals views of threshold and expert practice. The findings suggested that although there was widespread compliance with a national standard for cancer nursing, this was not the case for palliative care nursing. There was uncertainty about what should be assessed in practice and ambiguity about what was actually assessed. Partnership with children and their parents, clinical skills, multi-disciplinary working, and personal attributes were the main foci for expectations of threshold practice but an expert panel had difficulty in describing the attributes of higher level practice. The paper also describes how some of recommendations from the study are being taken forward in current policy and practice.

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Cytochrome P450 (CYP) 2D6 is one of the most important enzymes involved in the metabolism of drugs. Multiple, clinically relevant, genetic variants of this gene have been identified and, among them, a gene deletion as well as multiplications of the gene. These large structural mutations in CYP2D6 occur at a relatively high frequency in several populations. Genotyping of CYP2D6 could therefore be applied to individualize drug therapy to improve therapeutic efficacy and decrease adverse effects in patients. However, a prerequisite for the pharmacogenetic screening of CYP2D6 in a clinical setting is the development of fast, reliable and cost-effective techniques for the routine genotyping of patients. In the case of CYP2D6, besides the general problems that arise in the detection of large gene deletions and multiplications, the presence of two highly homologous pseudogenes, CYP2D7 and CYP2D8, forms an extra challenge. This review provides an overview of the techniques that have been described to detect the CYP2D6 gene deletion and multiplication: Southern-blotting RFLP, long-template PCR, and real-time PCR. Of these techniques, real-time PCR is the only technique giving quantitative information about the exact copy number of the gene. Considering all of the other advantages of this method over other methods, such as cost-effectiveness and suitability for high throughput screening, real-time PCR is the most promising method for the genotyping of large structural alterations in the CYP2D6 gene in a routine clinical setting.

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PPARalpha is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPARalpha in hepatic lipid metabolism, many PPARalpha-dependent pathways and genes have yet to be discovered. In order to obtain an overview of PPARalpha-regulated genes relevant to lipid metabolism, and to probe for novel candidate PPARalpha target genes, livers from several animal studies in which PPARalpha was activated and/or disabled were analyzed by Affymetrix GeneChips. Numerous novel PPARalpha-regulated genes relevant to lipid metabolism were identified. Out of this set of genes, eight genes were singled out for study of PPARalpha-dependent regulation in mouse liver and in mouse, rat, and human primary hepatocytes, including thioredoxin interacting protein (Txnip), electron-transferring-flavoprotein beta polypeptide (Etfb), electron-transferring-flavoprotein dehydrogenase (Etfdh), phosphatidylcholine transfer protein (Pctp), endothelial lipase (EL, Lipg), adipose triglyceride lipase (Pnpla2), hormone-sensitive lipase (HSL, Lipe), and monoglyceride lipase (Mgll). Using an in silico screening approach, one or more PPAR response elements (PPREs) were identified in each of these genes. Regulation of Pnpla2, Lipe, and Mgll, which are involved in triglyceride hydrolysis, was studied under conditions of elevated hepatic lipids. In wild-type mice fed a high fat diet, the decrease in hepatic lipids following treatment with the PPARalpha agonist Wy14643 was paralleled by significant up-regulation of Pnpla2, Lipe, and Mgll, suggesting that induction of triglyceride hydrolysis may contribute to the anti-steatotic role of PPARalpha. Our study illustrates the power of transcriptional profiling to uncover novel PPARalpha-regulated genes and pathways in liver.

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This paper reports on findings from an externally funded research study designed to map and analyse the educational preparation for cancer and palliative care nursing for children and adolescents. The courses reviewed in the whole study, were the English National Board for Nursing, Midwifery and Health Visiting (ENB) courses ENB240 (care of children with cancer) and the ENB R62 (paediatric oncology for nurses). The specific findings reported here are those relating to the investigation into the assessment of the clinical practice of students on the ENB 240 course in the eight universities, which offered that course. Twenty-six nurses, comprising both students and assessors were interviewed in this part of the study. Key issues arising from the study were the variety in what was assessed, in particular the lack of emphasis on the of assessment of clinical skills, the problem of student selected content of assessment, the different starting points of students and the lack of reliability and validity of the assessment process. Low priority was given to the assessment of clinical skills in these programmes, particularly using direct observation. The study was funded by the ENB and was carried out between 2001 and 2003.

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The results of part of a larger study to evaluate educational provision for paediatric oncology and palliative care nursing in England are presented here. Mapping of cancer care provision, based upon the English National Board 240 programme, was undertaken by analysis of relevant curriculum documents. Prescribed programme outcomes were reviewed against expected course outcomes proposed by the European Oncology Nursing Society. Particular attention was also paid to expected processes of assessment of clinical practice, consideration of adolescent patients, and opportunities for shared learning. Widespread compliance with the European Oncology Nursing Society standard was found, with only two of the 19 areas substantially neglected. These related to the prevention and early detection of cancer (less relevant in paediatric cancer than for adults), and understanding the principles of cancer clinical trials (probably due to lack of explicit statement in curriculum documents rather than actual failure to address the topic). A range of prescribed assessment practices were noted, but the degree to which direct observation was involved was variable, and indirect measures appeared to predominate. There was little specific recognition of adolescence as a discrete topic to be addressed in the programmes. Shared learning tended to be introduced for logistical reasons of small class numbers rather than for any perceived intrinsic value.

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