SMG1, a nonsense-mediated mRNA decay (NMD) regulator, as a candidate therapeutic target in multiple myeloma.

Early data suggested that CC-115, a clinical molecule, already known to inhibit the mammalian target of rapamycin kinase (TORK) and DNA-dependent protein kinase (DNA-PK) may have additional targets beyond TORK and DNA-PK. Therefore, we aimed to identify such target(s) and investigate a potential therapeutic applicability. Functional profiling of 141 cancer cell lines revealed inhibition of kinase suppressor of morphogenesis in genitalia 1 (SMG1), a key regulator of the RNA degradation mechanism nonsense-mediated mRNA decay (NMD), as an additional target of CC-115. CC-115 treatment showed a dose-dependent increase of SMG1-mediated NMD transcripts. A subset of cell lines, including multiple myeloma (MM) cell lines sensitive to the endoplasmic reticulum stress-inducing compound thapsigargin, were highly susceptible to SMG1 inhibition. CC-115 caused the induction of UPR transcripts and cell death by mitochondrial apoptosis, requiring the presence of BAX/BAK and caspase activity. Superior antitumor activity of CC-115 over TORK inhibitors in primary human MM cells and three xenograft mouse models appeared to be via inhibition of SMG1. Our data support further development of SMG1 inhibitors as possible therapeutics in MM.

Creating a transformative space for change: A qualitative evaluation of the RHS Wellbeing Programme for people with long term conditions.

PURPOSE: Our research aimed to evaluate the impact of the RHS Wellbeing (WB) Programme on people with long-term conditions. FINDINGS: A thematic analysis identified how the WB programme facilitated improved social connectivity, sense of wellbeing and purpose through the creation of a 'healthy, natural and safe space' predicated on 'person-centred approaches'. Participants felt they were 'part of something larger' which enabled 'transformation of their health and wellbeing'. CONCLUSIONS: The WB Programme offered space to grow, heal and reconnect. Losing oneself in a nature-based space can have a lasting transformative impact on individuals.

Ethical considerations referred to in child health research published in leading nursing journals: 2015-2019.

BACKGROUND: Child health research comprises complex ethical considerations. Understanding the extent to which the ethical process is reported in child health research is needed to improve reporting. AIMS: To identify reportage of ethical considerations in child health research in leading nursing and paediatric journals. METHODS: All child health research published between 2015 and 2019 in 10 leading nursing journals and two paediatric journals were retrieved and critically appraised for the reportage of informed consent and ethical approval. RESULTS: Eight hundred and fifty-one child health research papers were included. Although 544 (79.9%) of the prospective studies mentioned informed consent, only 300 (55.2%) reported that written informed consent was obtained from the participants. Overall, 748 (87.9%) of child health research papers noted obtaining research ethics committee approval. Articles that mentioned financial support were significantly more likely to report informed consent and ethical approval than unfunded studies (all P < 0.001). Prospective studies showed higher rates of reportage of ethical approval compared to retrospective studies (P = 0.027). Rates of child consent (assent) obtained in different age groups of children ranged from 29.6% to 66.3%. CONCLUSION: Despite improvements in the reportage of ethical review and approval processes in child health research, consistent and transparent reports are still lacking.

What is the evidence for the impact of gardens and gardening on health and well-being: a scoping review and evidence-based logic model to guide healthcare strategy decision making on the use of gardening approaches as a social prescription.

OBJECTIVE: To systematically identify and describe studies that have evaluated the impact of gardens and gardening on health and well-being. A secondary objective was to use this evidence to build evidence-based logic models to guide health strategy decision making about gardens and gardening as a non-medical, social prescription. DESIGN: Scoping review of the impact of gardens and gardening on health and well-being. Gardens include private spaces and those open to the public or part of hospitals, care homes, hospices or third sector organisations. DATA SOURCES: A range of biomedical and health management journals was searched including Medline, CINAHL, Psychinfo, Web of Knowledge, ASSIA, Cochrane, Joanna Briggs, Greenfile, Environment Complete and a number of indicative websites were searched to locate context-specific data and grey literature. We searched from 1990 to November 2019. ELIGIBILITY CRITERIA: We included research studies (including systematic reviews) that assessed the effect, value or impact of any garden that met the gardening definition. DATA EXTRACTION AND SYNTHESIS: Three reviewers jointly screened 50 records by titles and abstracts to ensure calibration. Each record title was screened independently by 2 out of 3 members of the project team and each abstract was screened by 1 member of a team of 3. Random checks on abstract and full-text screening were conducted by a fourth member of the team and any discrepancies were resolved through double-checking and discussion. RESULTS: From the 8896 papers located, a total of 77* studies was included. Over 35 validated health, well-being and functional biometric outcome measures were reported. Interventions ranged from viewing gardens, taking part in gardening or undertaking therapeutic activities. The findings demonstrated links between gardens and improved mental well-being, increased physical activity and a reduction in social isolation enabling the development of 2 logic models. CONCLUSIONS: Gardens and gardening can improve the health and well-being for people with a range of health and social needs. The benefits of gardens and gardening could be used as a 'social prescription' globally, for people with long-term conditions (LTCs). Our logic models provide an evidence-based illustration that can guide health strategy decision making about the referral of people with LTCs to socially prescribed, non-medical interventions involving gardens and gardening.

Social prescribing: a 'natural' community-based solution.

This paper discusses social prescribing as part of the wider NHS England universal personalised care model, and it describes how community nurses can engage with social prescribing systems to support community resilience. A case study based on the example of gardening, as a nature-based social prescription provided by the RHS Bridgewater Wellbeing Garden, is provided to illustrate the scope, reach and impact of non-medical, salutogenic approaches for community practitioners. The authors argue that social prescribing and, in particular, nature-based solutions, such as gardening, can be used as a non-medical asset-based approach by all health professionals working in the community as a way to promote health and wellbeing. They consider how the negative impact of social distancing resulting from COVID-19 restrictions could be diluted through collaboration between a holistic, social prescribing system and community staff. The paper presents a unique perspective on how community nurses can collaborate with link workers through social prescribing to help combat social isolation and anxiety and support resilience.

Reporting of ethical approval and informed consent in clinical research published in leading nursing journals: a retrospective observational study.

BACKGROUND: Ethical considerations play a prominent role in the protection of human subjects in clinical research. To date the disclosure of ethical protection in clinical research published in the international nursing journals has not been explored. Our research objective was to investigate the reporting of ethical approval and informed consent in clinical research published in leading international nursing journals. METHODS: This is a retrospective observational study. All clinical research published in the five leading international nursing journals from the SCI Journal Citation Reports between 2015 and 2017 were retrieved to evaluate for evidence of ethical review. RESULTS: A total of 2041 citations have been identified from the contents of all the five leading nursing journals that were published between 2015 and 2017. Out of these, 1284 clinical studies have been included and text relating to ethical review has been extracted. From these, most of prospective clinical studies (87.5%) discussed informed consent. Only half of those (52.9%) reported that written informed consent had been obtained; few (3.6%) reported oral consent, and few (6.8%) used other methods such as online consent or completion and return of data collection (such as surveys) to denote assent. Notably, 36.2% of those did not describe the method used to obtain informed consent and merely described that "consent was obtained from participants or participants agreed to join in the research". Furthermore, whilst most of clinical studies (93.7%) mentioned ethical approval; 92.5% of those stated the name of ethical committee and interestingly, only 37.1% of those mentioned the ethical approval reference. The rates of reporting ethical approval were different between different study type, country, and whether financial support was received (all P < 0.05). CONCLUSION: The reporting of ethics in leading international nursing journals demonstrates progress, but improvement of the transparency and the standard of ethical reporting in nursing clinical research is required.

Reporting of ethical considerations in clinical trials in Chinese nursing journals.

BACKGROUND: It is acknowledged that publishers now require all primary research papers to demonstrate that they have obtained ethical approval for their research. OBJECTIVES: To assess the rate of reporting of ethical approval in clinical trials in core nursing journals in mainland China. RESEARCH DESIGN: A retrospective observational study. PARTICIPANTS: All clinical trials published in all of the 12 core nursing periodicals from 2016 edition China Science and Technology Journal Citation Report (core version) between 2013 and 2016 were retrieved by hand to explicate rate of reporting ethical approval and informed consent. ETHICAL CONSIDERATIONS: The study did not require approval from the research ethics committee as it did not involve human subjects or records. RESULTS: In total, 40,278 papers were published in 12 nursing periodicals between 2013 and 2016. Out of these, 9488 (23.6%) focused on clinical trials. Informed consent obtained from patients or the legally authorized representative was reported in 51.8% of clinical trials. Notably, only 27.4% of clinical trials reported that they had obtained written consent. Furthermore, 25.9% of clinical trials described ethical approval; however, the rate of reporting informed consent and ethical approval in these 12 nursing journals in China during 4 years from 2013 to 2016 improved markedly, with 38.1%, 44.0%, 59.0% and 66.6%, respectively (p < 0.001), and 17.6%, 21.9%, 28.6% and 35.8%, respectively (p < 0.001). In addition, both reporting informed consent and reporting written informed consent had a positive significant correlation with the reporting ethical approval (p < 0.05 or < 0.01). CONCLUSION: Chinese scientific nursing journals have improved the rate of reporting informed consent and ethical approval in clinical trials during the last 4 years. However, it should be noted that nearly half of clinical trials still did not report either ethical approval or whether informed consent was obtained. Efforts from editors, researchers, sponsors and authors are needed to ensure the transparency of ethical scrutiny and adherence to ethical guidelines in publishing clinical trials in Chinese nursing journals.

Growing spaces: an evaluation of the mental health recovery programme using mixed methods.

BACKGROUND: Therapeutic horticulture is a nature-based method that includes a range of green activities, such as gardening, to promote wellbeing. It is believed that therapeutic horticulture provides a person-centred approach that can reduce social isolation for people with mental health problems. AIMS: The aim of the project was to evaluate the impact of a mental health recovery programme that used therapeutic horticulture as an intervention to reduce social inclusion and improve engagement for people with mental health problems. METHODS: A mixed-methods approach was used and data from four semi-structured focus group interviews, 11 exit interviews and 20 'recovery star' datasets were collected from September 2015 to October 2017. Qualitative data from the interviews were thematically analysed, and quantitative data based on a recovery star outcomes tool were analysed using descriptive statistics to demonstrate trends and progression. The findings were then triangulated to provide a rich picture of the impact of the mental health recovery programme. RESULTS: The recovery star data indicated that participants were working towards self-reliance. Qualitative data from the exit interview and semi-structured focus groups found similar results. The triangulated findings highlight that the mental health recovery programme enabled participant integration into the community through providing a space to grow and build self-confidence while re-engaging with society. The results suggest that using therapeutic horticulture as an intervention within the mental health recovery programme can support people with mental health problems to re-engage socially. Nature-based activities could be used within the 'social prescribing' movement to encourage partnership working between the NHS and voluntary sector organisations which can complement existing mental health services. CONCLUSION: The use of therapeutic horticulture as an intervention within a mental health recovery programme can support people with mental health problems to re-engage with the community and is integral to the rehabilitation process. The mental health recovery programme should be promoted within the social prescribing movement as an evidence-based opportunity to support people in the community.

Person-centred discharge education following coronary artery bypass graft: A critical review.

AIMS AND OBJECTIVES: To examine the extent that individualised education helps reduce depression and anxiety and improves self-care for people who have undergone coronary artery bypass graft surgery. BACKGROUND: Individualised discharge planning is increasingly important following cardiac surgery due to recurrent admissions as well as the issue of anxiety and depression, often due to lack of preparation. The hospital to home transition is fundamental in the recovery process. Individualised education and person-centred care ensure that patients' educational needs are met. This empowers patients, increasing self-efficacy or confidence, resulting in autonomy, a smoother discharge process and avoiding postdischarge problems and rehospitalisation. DESIGN: A critical review of published peer-reviewed literature was conducted. METHODS: Electronic databases searched included MEDLINE, CINAHL, the Cochrane Library and PsychInfo 2009-2015. RESULTS: Eight articles were identified for review, and a Critical Appraisal Skills Programme framework was used to determine the quality of the papers, all of the papers focussed on coronary artery bypass graft. The designs were typically experimental or quasi-experimental with two reviews. CONCLUSION: A greater understanding of the patients' needs allows tailored education to be provided, which promotes self-care management. This level of patient empowerment increases confidence and ultimately minimise anxiety and depression. Despite the varying teaching and learning methods associated with individualised education, patient-centred education has the potential to assist cardiac nurses in adequately preparing patients for discharge following their coronary artery bypass graft. RELEVANCE TO CLINICAL PRACTICE: Development of individualised education programmes is crucial in preparing patients for discharge. The reduction in readmission to hospital has a significant effect on already stretched resources, and the reduction in postoperative complications during the recovery period linked with depression and anxiety will have a positive effect on the individuals' ability to self-care, health and well-being.

Combined experience of six independent laboratories attempting to create an Ewing sarcoma mouse model.

Ewing sarcoma (ES) involves a tumor-specific chromosomal translocation that produces the EWS-FLI1 protein, which is required for the growth of ES cells both in vitro and in vivo. However, an EWS-FLI1-driven transgenic mouse model is not currently available. Here, we present data from six independent laboratories seeking an alternative approach to express EWS-FLI1 in different murine tissues. We used the Runx2, Col1a2.3, Col1a3.6, Prx1, CAG, Nse, NEFL, Dermo1, P0, Sox9 and Osterix promoters to target EWS-FLI1 or Cre expression. Additional approaches included the induction of an endogenous chromosomal translocation, in utero knock-in, and the injection of Cre-expressing adenovirus to induce EWS-FLI1 expression locally in multiple lineages. Most models resulted in embryonic lethality or developmental defects. EWS-FLI1-induced apoptosis, promoter leakiness, the lack of potential cofactors, and the difficulty of expressing EWS-FLI1 in specific sites were considered the primary reasons for the failed attempts to create a transgenic mouse model of ES.

Long noncoding RNA EWSAT1-mediated gene repression facilitates Ewing sarcoma oncogenesis.

Chromosomal translocation that results in fusion of the genes encoding RNA-binding protein EWS and transcription factor FLI1 (EWS-FLI1) is pathognomonic for Ewing sarcoma. EWS-FLI1 alters gene expression through mechanisms that are not completely understood. We performed RNA sequencing (RNAseq) analysis on primary pediatric human mesenchymal progenitor cells (pMPCs) expressing EWS-FLI1 in order to identify gene targets of this oncoprotein. We determined that long noncoding RNA-277 (Ewing sarcoma-associated transcript 1 [EWSAT1]) is upregulated by EWS-FLI1 in pMPCs. Inhibition of EWSAT1 expression diminished the ability of Ewing sarcoma cell lines to proliferate and form colonies in soft agar, whereas EWSAT1 inhibition had no effect on other cell types tested. Expression of EWS-FLI1 and EWSAT1 repressed gene expression, and a substantial fraction of targets that were repressed by EWS-FLI1 were also repressed by EWSAT1. Analysis of RNAseq data from primary human Ewing sarcoma further supported a role for EWSAT1 in mediating gene repression. We identified heterogeneous nuclear ribonucleoprotein (HNRNPK) as an RNA-binding protein that interacts with EWSAT1 and found a marked overlap in HNRNPK-repressed genes and those repressed by EWS-FLI1 and EWSAT1, suggesting that HNRNPK participates in EWSAT1-mediated gene repression. Together, our data reveal that EWSAT1 is a downstream target of EWS-FLI1 that facilitates the development of Ewing sarcoma via the repression of target genes.

Pain from the inside: understanding the theoretical underpinning of person-centered care delivered by pain teams.

Chronic back pain is globally acknowledged as a common reason why people seek help from health professionals. The complexity of persistent chronic pain can undermine the person's self-esteem and present a number of challenges to an individual's ability to manage their pain. Multi-professional person-centered care is advocated as a key strategy to support people with chronic back pain. However, the impact of these approaches on restoring the person's independence is unclear, and little is known about whether and how person-centered approaches restore autonomy and influence the person's ability to manage their pain. The aim of this grounded theory study was to generate understanding about person-centered care from the perspectives of people with chronic back pain and the multi-professional teams who cared for them. Semi-structured interviews were used to collect data from 17 people with chronic back pain over one year. A constant comparative analytical approach identified five key categories: the skeptical professional, validation, becoming a person, regaining control, and restoring faith. These categories formed the "conditional partnership" as a theory to explain person-centered care, which related to the way in which the partnership developed between the patients and teams. The findings suggest that person-centered care was influenced by the participants' need to be believed and the relationship developed with health care providers. Crucially, these findings suggest that legitimizing the pain experience through person-centered approaches to care can empower people with chronic back pain to regain control of their lives and their pain.

Being an effective nurse consultant in the English National Health Service: what does it take? A study of consultants specializing in safeguarding.

AIMS: This study established key attributes and perceived strengths, weaknesses, opportunities and threats (SWOT) of nurse consultants specializing in safeguarding children. BACKGROUND: The nurse consultant role in England spans four domains--clinical, leadership, education and research--and was intended to enable senior nurses to remain in clinical practice. METHOD: ata identifying the time spent by the nurse consultants in the four domains was collated and a thematic content analysis of the SWOT of the role was ascertained from semi-structured interviews with nurse consultants (n = 4) and stakeholders (n = 6). RESULTS: Strengths and opportunities in clinical (consultancy), leadership and educational functions were identified but some weaknesses and threats in terms of nurse consultant's contributions to research were also identified. The role was neither wholly strategic nor clinical. Role ambiguity meant that they were not always valued by managers, making the role potentially expendable. CONCLUSIONS: Nurse consultants are pivotal within health-care organizations because they span clinical practice and leadership enabling them to support managers in strategic planning, commissioning and implementation of policy. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse consultants can support strategic practice development and influence quality and effectiveness service-wide. To succeed they must be understood, supported and nurtured by managers.

"Let's stick together"--a grounded theory exploration of interprofessional working used to provide person centered chronic back pain services.

Chronic back pain is a global phenomenon and a common reason why patients seek help from health professionals. Person-centered interprofessional working is acknowledged as the main strategy for chronic back pain management; however, the complexity of chronic pain can present significant challenges for teams. Although methods used by interprofessional teams to collaborate have been previously explored, how they work together to deliver person-centered chronic back pain care has received limited attention. The aim of this study was to explore person-centered care from the perspectives of people with chronic back pain and the interprofessional teams who cared for them. A grounded theory methodology was used to capture the interprofessional team's perspectives of person-centered working. A purposive sample of four chronic back pain management teams participated in semi-structured face-to-face interviews and focus groups. Data were thematically analyzed using a constant comparative method. Three categories emerged, collective efficacy, negotiated space and team maturity, which illustrated the attributes of interprofessional teams that influenced person-centered working. The findings suggest that collective efficacy matures over time within a negotiated coalesced space and re-enforces the need for teams to stick together to ensure effective person-centered care.

Centralization and research governance: does it work?

AIM: This paper is a report of a study to evaluate the impact and success of the United Kingdom centralized Research Management and Governance model. BACKGROUND: Research is crucial to the generation of new knowledge and for the development of nursing services. However, poor research conduct has prompted a growing international impetus to govern and monitor research activity. In 2004, a centralized Research Management and Governance Model aimed at fostering a quality research culture through streamlining bureaucratic management processes was implemented across 14 primary care provider organizations in the United Kingdom. METHODS: A questionnaire survey was undertaken in 2004 to explore researchers' experiences (n = 76) of the model across the 14 organizations, and semi-structured interviews were conducted with five research and development managers. The interview transcripts were independently thematically analysed. FINDINGS: Governance processes were seen as useful or very useful by 36.8% (n = 28) of researchers viewed, and 47.3% (n = 36) thought they were a hindrance or not useful. Managers suggested that the model supported the research infrastructure and had reduced paperwork. The benefits of centralization were balanced against managers' perceptions of reduced autonomy and control. CONCLUSIONS: Centralizing research governance is an effective way of maximizing research resources, but researchers still may not value the process. Partnership working can streamline research governance mechanisms, but needs to be adequately resourced and transparent. This model could be of benefit to international colleagues who are charged with the management of research.

The use of simulation as a teaching and learning approach to support practice learning.

Simulation is an approach to teaching and learning which is gaining a greater emphasis within nurse education. This has been fueled by the Nursing and Midwifery Council's (NMC) decision to identify a baseline standard for using simulation safely and its inclusion as a contributory part to practice learning [Nursing and Midwifery Council (2006a). This paper presents some of the advantages and issues for consideration in relation to its effectiveness as a teaching and learning method. Of particular concern is the limited empirical evidence to support its effect on clinical practice. Debate and further research is needed to help consolidate our knowledge and develop an evidence base for its continued use.