Pharmacologic targeting of the p62 ZZ domain enhances both anti-tumor and bone-anabolic effects of bortezomib in multiple myeloma.

Multiple myeloma (MM) is a malignancy of plasma cells whose antibody secretion creates proteotoxic stress relieved by the N-end rule pathway, a proteolytic system that degrades Narginylated proteins in the proteasome. When the proteasome is inhibited, protein cargo is alternatively targeted for autophagic degradation by binding to the ZZ-domain of p62/sequestosome-1. Here, we demonstrate that XRK3F2, a selective ligand for the ZZ-domain, dramatically improved two major responses to the proteasome inhibitor bortezomib by increasing: 1) killing of human MM cells by stimulating both bortezomib mediated apoptosis and necroptosis, a process regulated by p62; and 2) preservation of bone mass by stimulating osteoblasts differentiation and inhibiting osteoclastic bone destruction. Co-administration of bortezomib and XRK3F2 inhibited both branches of the bimodal N-end rule pathway exhibited synergistic anti-MM effects on MM cell lines and CD138+ cells from MM patients, and prevented stromal-mediated MM cell survival. In mice with established human MM, coadministration of bortezomib and XRK3F2 decreased tumor burden and prevented the progression of MM-induced osteolytic disease by inducing new bone formation more effectively than either single agent alone. The results suggest that p62-ZZ ligands enhance the anti-MM efficacy of proteasome inhibitors and can reduce MM morbidity and mortality by improving bone health.

Undergraduate paramedic students and interpersonal communication development: a scoping review.

The objective of this review is to examine the current literature related to interpersonal communication skill development within undergraduate paramedicine. Interpersonal communication is a vital paramedic skill, with evidence demonstrating it leads to improved patient outcomes and satisfaction and reduces medical errors. Interpersonal communication is a core capability set by paramedicine regulatory bodies, and it is the responsibility of accredited universities to ensure graduates are ready for industry and possess all required skills and attributes. In order to be included in this scoping review, all articles were required to meet a pre-determined 'population, concept, context' (PCC) framework. The population was undergraduate paramedic students within the context of their undergraduate paramedicine programs, and the concept was interpersonal communication education/teaching/training. In June 2021, a search was conducted using CINAHL, Medline, Emcare and ERIC. The articles had to be written in English and published between 2011 and 2021 and non-research sources were excluded. 176 articles were identified in this search and after screening for duplicates and relevancy, 15 articles were found to be eligible. The literature highlighted 4 key themes, including graduate perception of 'work readiness', and a variety of learning experiences including alternative work integrated learning (WIL), interactions with specific patient groups and professional learning experiences. The literature demonstrated that interpersonal communication skills are fostered through human interactions, WIL and simulation, within undergraduate paramedicine programs. Findings from the literature review indicate that practising communication through human interactions, afford an increase in confidence, awareness of ability and empathy, and an increased awareness of preconceived biases. Intraprofessional and interprofessional simulation teaching methods demonstrate the potential to build students confidence in communication and awareness of what is required to function well in a team.

Nurse managers' learning facilitation practices: A philosophical hermeneutic study.

AIM(S): To understand how nurse managers facilitate learning in clinical workplaces. BACKGROUND: Meeting staff learning needs in the complex workplaces of contemporary health care is paramount to the delivery of safe patient care. Hospitals employ a range of strategies to address these needs. However, nurse managers' contribution to staff learning at the unit level is underexplored in contemporary literature. METHOD(S): A Gadamerian philosophical hermeneutic framework guided data collection and analysis. Thirteen nurse managers from two Australian hospitals each participated in two interviews and a period of observation. FINDINGS: Nurse managers' learning facilitation practices were enacted with staff individually, within teams, and through artefacts, and were shaped by their identities, perspectives on staff learning, knowledge of staff performance, and motivations. Power was revealed as a uniquely enacted driver of their learning facilitation practices. CONCLUSION(S): This paper illuminates an aspect of nurse managers' practice that has been poorly acknowledged in contemporary nursing literature. Nurse managers' learning facilitation practices were found to be complex, fluid, and embedded in their everyday work routines. IMPLICATIONS FOR NURSING MANAGEMENT: Given current concerns about safety and quality in health care, this research opens up possibilities for definition and enrichment of nurse managers' practice as facilitators of learning.

A re-examination of the individual differences approach that explains occupational resilience and psychological adjustment among nurses.

AIMS: This study re-examines the validity of a model of occupational resilience for use by nursing managers, which focused on an individual differences approach that explained buffering factors against negative outcomes such as burnout for nurses. BACKGROUND: The International Collaboration of Workforce Resilience model (Rees et al., 2015, Frontiers in Psychology, 6, 73) provided initial evidence of its value as a parsimonious model of resilience, and resilience antecedents and outcomes (e.g., burnout). Whether this model's adequacy was largely sample dependent, or a valid explanation of occupational resilience, has been subsequently un-examined in the literature to date. To address this question, we re-examined the model with a larger and an entirely new sample of student nurses. METHODS: A sample of nursing students (n = 708, AgeM ( SD ) = 26.4 (7.7) years), with data examined via a rigorous latent factor structural equation model. RESULTS: The model upheld many of its relationship predictions following further testing. CONCLUSIONS: The model was able to explain the individual differences, antecedents, and burnout-related outcomes, of resilience within a nursing context. IMPLICATIONS FOR NURSING MANAGEMENT: The results highlight the importance of skills training to develop mindfulness and self-efficacy among nurses as a means of fostering resilience and positive psychological adjustment.

Dealing with end of life-New graduated nurse experiences.

AIMS AND OBJECTIVES: This article explores the perceptions of new graduate nurses around their readiness for practice when faced with death and dying within the workplace, particularly in rural hospital and community nursing settings. BACKGROUND: An essential consideration for nurses in the care of people with life-limiting illness is the extent of their preparation for this area of practice. Nurses need to be aware of a multitude of compounding factors that will influence how and where the person is cared for. Despite significant literature about how to provide end of life education to undergraduate nurses there is little in the literature that explores the experiences of new graduate nurses. DESIGN: This paper reports on a qualitative interpretative study with data collected in seven semi-structured interviews. METHOD: Participants were invited to be interviewed with an online mail-out to Alumni who had graduated between 1-2 years earlier. A thematic analysis of the interviews was then conducted. RESULTS: Four themes emerged from the thematic analysis of the interviews. These were; the role of the new graduate in palliative care, preparation for palliative care in undergraduate nursing curricula, readiness for dealing with death and dying, and gaps in educational preparation. CONCLUSIONS: While palliative care is viewed as an important aspect of undergraduate nursing education, it is recognised as an area of practice that undergraduate nurses feel they are not adequately prepared for. This study identifies the need to incorporate skills such as having conversations and communicating effectively with patients and families experiencing end of life issues. RELEVANCE TO CLINICAL PRACTICE: Graduate nurses feel they are not adequately prepared for end of life care which demonstrates the need for quality end of life care education in undergraduate nursing curricula.

Nurse participation in legal executions: An ethics round-table discussion.

A paper was published in 2003 discussing the ethics of nurses participating in executions by inserting the intravenous line for lethal injections and providing care until death. This paper was circulated on an international email list of senior nurses and academics to engender discussion. From that discussion, several people agreed to contribute to a paper expressing their own thoughts and feelings about the ethics of nurses participating in executions in countries where capital punishment is legal. While a range of opinions were presented, these opinions fell into two main themes. The first of these included reflections on the philosophical obligations of nurses as caregivers who support those in times of great need, including condemned prisoners at the end of life. The second theme encompassed the notion that no nurse ever should participate in the active taking of life, in line with the codes of ethics of various nursing organisations. This range of opinions suggests the complexity of this issue and the need for further public discussion.

Student participation in clinical handover-an integrative review.

AIM AND OBJECTIVES: To examine the literature exploring the current understanding of student nurse participation in clinical handover whilst they are enrolled in an undergraduate preregistration course. BACKGROUND: The importance of handing over the care of a patient to ensure continuity and safety of care is well-recognised. Effective preparation of student nurses to competently perform this critical task requires the use of appropriate teaching strategies to support this learning, within undergraduate preregistration nursing programs. DESIGN: An integrative literature review. METHOD: An integrative literature review was conducted to establish what is known about student nurse participation in relation to clinical handover. This resulted in 18 articles for inclusion in the literature review. An analysis was then undertaken of these 18 articles to extract key themes. RESULTS: Learning and teaching strategies need to address a variety of methods of the clinical handover process including verbal and written handovers. Participating in clinical handover prior to being given the responsibility of patient care prepares students for the workplace. Key themes identified within the literature included: learning strategies, limitations and challenges involved in putting theory into practice, handover structure and issues regarding confidentiality. CONCLUSION: Simulation and clinical practice are commonly used to prepare students for this role during their undergraduate education. The use of simulation and structured handover techniques prior to clinical placement increases student confidence to engage in clinical handovers during their clinical placements. RELEVANCE TO CLINICAL PRACTICE: This article raises the awareness of both clinical staff and educators as to the need for student nurses to develop their skills in clinical handover practice and suggests strategies to prepare student nurses to conduct clinical handover competently in the clinical setting.

Nursing bedside clinical handover - an integrated review of issues and tools.

AIMS AND OBJECTIVES: This article reviews the available literature that supports implementing bedside clinical handover in nursing clinical practice and then seeks to identify key issues if any. BACKGROUND: Clinical handover practices are recognised as being an essential component in the effective transfer of clinical care between health practitioners. It is recognised that the point where a patient is 'handed over' from one clinician to another is significant in maintaining continuity of care and that doing this poorly can have significant safety issues for the patient. DESIGN: An integrated literature review. METHOD: A literature review of 45 articles was undertaken to understand bedside clinical handover and the issues related to the implementation of this process. RESULTS: It was identified that there are a number of clinical handover mnemonics available that provide structure to the process and that areas such as confidentiality, inclusion of the patient/carer and involving the multidisciplinary team remain topical issues for practitioners in implementing good clinical handover practices. CONCLUSIONS: This literature review identified a lack of literature available about the transfer of responsibility and accountability during clinical handover and auditing practices of the clinical handover process. The nurses were more concerned about confidentiality issues than were patients. The use of a structured tool was strongly supported; however, no one singular tool was considered suitable for all clinical areas. RELEVANCE TO CLINICAL PRACTICE: Nursing clinicians seeking to implement best practice within their professional speciality should consider some of the issues raised within this article and seek to address these issues by developing strategies to overcome them.

Advice for running a successful research team.

AIM: To explore what is meant by a 'research team' and offer practical suggestions for supporting an effective and productive, collaborative research team. BACKGROUND: Collaborative research has become one of the main objectives of most higher education institutions and running effective research teams is central to achieving this aim. However, there is limited guidance in the literature about how to run or steer a research team. DATA SOURCES: Search engines/databases used: CINAHL, Nursing and Allied Health Source, Primo search, Google search and Health Collection to access research articles and publications to support this topic. Literature search was extended to the end of 2014. REVIEW METHODS: Publications were reviewed for relevance to the topic via standard literature search. DISCUSSION: Research teams vary in size and composition, however they all require effective collaboration if they are to establish successful and flexible working relationships and produce useful and trustworthy research outputs. This article offers guidance for establishing and managing successful collaborative research relationships, building trust and a positive research team culture, clarifying team member roles, setting the teams' research agenda and managing the teams' functions so that team members feel able to contribute fully to the research goals and build a culture of support and apply 'emotional intelligence' throughout the process of building and running a successful research team. CONCLUSION: Collaboration is a central component of establishing successful research teams and enabling productive research outputs. This article offers guidance for research teams to help them to function more effectively and allow all members to contribute fully to each team's goals. IMPLICATIONS FOR PRACTICE/RESEARCH: Research teams that have established trust and a positive team culture will result in more efficient working relationships and potentially greater productivity. The advice offered reinforces the value of having research teams with diverse members from different disciplines, philosophical roots and backgrounds. Each of these members should be able to contribute skills and expertise so that the parts of the team are able to develop 'synergy' and result in more productive, positive and rewarding research experiences, as well as more effective research.

Critical role of AKT protein in myeloma-induced osteoclast formation and osteolysis.

Abnormal osteoclast formation and osteolysis are the hallmarks of multiple myeloma (MM) bone disease, yet the underlying molecular mechanisms are incompletely understood. Here, we show that the AKT pathway was up-regulated in primary bone marrow monocytes (BMM) from patients with MM, which resulted in sustained high expression of the receptor activator of NF-κB (RANK) in osteoclast precursors. The up-regulation of RANK expression and osteoclast formation in the MM BMM cultures was blocked by AKT inhibition. Conditioned media from MM cell cultures activated AKT and increased RANK expression and osteoclast formation in BMM cultures. Inhibiting AKT in cultured MM cells decreased their growth and ability to promote osteoclast formation. Of clinical significance, systemic administration of the AKT inhibitor LY294002 blocked the formation of tumor tissues in the bone marrow cavity and essentially abolished the MM-induced osteoclast formation and osteolysis in SCID mice. The level of activating transcription factor 4 (ATF4) protein was up-regulated in the BMM cultures from multiple myeloma patients. Adenoviral overexpression of ATF4 activated RANK expression in osteoclast precursors. These results demonstrate a new role of AKT in the MM promotion of osteoclast formation and bone osteolysis through, at least in part, the ATF4-dependent up-regulation of RANK expression in osteoclast precursors.

The right staffing mix for inpatient care in rural multi-purpose service health facilities.

CONTEXT: The Multipurpose Service (MPS) model has been in existence in rural and remote Australia for more than 20 years yet there is little guidance about developing an appropriate staffing structure. ISSUES: Managers of these facilities face issues related to isolation, safety, funding models and the need to provide a variety of services with limited resources and staffing. Because MPS are designed to meet unique community needs, a single staffing structure is not suitable for every site. Managers need to consider these issues in order to determine the most effective staffing structure for their particular environment. LESSONS LEARNED: Issues and concerns for managers are highlighted including discussion which may enhance the ability of managers to make appropriate decisions for their unique site.

A regional approach to the education of nurse practitioner candidates to meet the health needs of rural Australians.

BACKGROUND: Local health services expressed interest in supporting a nurse practitioner (NP) program specifically designed for rural practice environments. AIM: To develop and deliver a generalist NP program that prepares candidates for practice in rural contexts. METHODS: The Master of Clinical Nursing (Nurse Practitioner) program was designed with an understanding of the burden of disease impacting on rural Australians, application of the national health priorities, the Australian Government's refocus on preventative health care and rural health workforce shortages. RESULTS: This program offers nurses who work in rural and remote settings an opportunity to advance their careers. Increasing the numbers of rural NPs will improve rural populations access to healthcare and potentially improve health outcomes. CONCLUSION: This program will equip those seeking endorsement as a NP to effectively work in rural contexts.

Burnout in residential aged care managers: a scoping review.

Residential aged care managers play an important role which can influence outcomes for their staff, their residents, and the organisations they work for. Burnout in residential aged care employees has been researched however burnout in residential aged care managers has received little attention. This scoping review sought to identify literature examining burnout in residential aged care managers.To investigate the literature currently available on what stressors were experienced by residential aged care managers that led to burnout.This scoping review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) checklist.Five databases were searched, including CINAHL, MEDLINE, EMCARE, SCOPUS, and INFORMIT using primo search. The first review of title and abstracts was conducted by three authors to determine eligibility, using the program JBI SUMARI. Two authors were involved in the final screening of each full-text article. Where disagreement occurred, a collaborative discussion took place until consensus was reached. The review included peer-reviewed journal articles focusing on burnout, stress, fatigue, moral distress, exhaustion, or resilience in residential aged care managers or leaders published after 2012 in English.An initial search of the databases found 275 articles, of which 5 articles met the inclusion criteria for final review. Articles were categorised into the following groups Responsibilities, Reaction, and Regulation. These groups encapsulated risk factors for burnout in residential aged care managers.As a result of the scoping review, it is suggested that burnout in residential aged care managers can be attributed to environmental stressors, those being situational and organisational (Maslach, 2003), which are outside the control of the individual. Strategies that support residential aged care managers to manage and lessen the phenomenon of burnout require further exploration.

Navigating Mental Health Frontiers: A Scoping Review of Accessibility for Rural LGBTIQA+ Communities.

Mental healthcare for LGBTQIA+ populations in rural areas remains unequal, despite societal progress toward inclusivity. This review examines the specific obstacles faced in rural areas, such as limited services, workforce deficiencies, and travel burdens for treatment, which exacerbate existing mental health inequities. By following the Joanna Briggs Institute methodology, an exploration of SCOPUS, EBSCO Host (All), and Ovid databases yielded 2373 articles. After careful screening, 21 articles from five countries were selected, primarily using qualitative interviews and quantitative online surveys. Analysis through the Lévesque framework reveals the complex challenges faced by LGBTQIA+ individuals in rural mental healthcare. Discrepancies in approachability, acceptability, availability, affordability, and appropriateness were identified. Geographical isolation, discrimination, and a lack of LGBTQIA+-attuned professionals further compound these issues. Societal stigma, discrimination, and economic constraints hinder individuals from accessing and engaging in mental health services. This study highlights the need for purposeful interventions to improve rural mental health access for sexual and gender minorities.

The significance of paramedic communication during women's birth experiences: A scoping review.

BACKGROUND: Internationally, over one-third of women experience birth trauma, leading to adverse mental health outcomes. Poor communication with healthcare professionals is a primary contributing factor. Paramedics attend various clinical presentations, including childbirth, yet their potential impact on women's birth experiences has been largely overlooked. METHODS: A systematic literature search was conducted following the Joanna Briggs Institute methodological framework. The search identified 1015 potentially suitable articles, and 5 articles met the inclusion criteria. Data was analysed using reflexive thematic analysis from a feminist standpoint. RESULTS: Three themes were generated: 1. First Impressions Count: paramedic demeanour impacted the woman's sense of safety and perception of paramedic clinical competence. 2. Choice as a Pathway to Control: when paramedics involved women in decision-making, it led to empowerment, while non-involvement led to women becoming passive participants. 3. Exposed, Violated and Disempowered: some paramedics disrespected and abused women, treating them solely as objects for the purpose of producing a baby. CONCLUSIONS: This review highlights the influence of paramedic communication on women's birth experiences. While some paramedics communicated respectfully, other paramedics were the perpetrators of Obstetric Violence. Future research should inform paramedic education and improve outcomes for birthing women.

'DANMM that's good!': evaluating the feasibility and acceptability of the Deadly Aboriginal and Torres Strait Islander Nursing and Midwifery Mentoring (DANMM) Programme across rural, regional and metropolitan NSW-a collaborative study protocol.

INTRODUCTION: This paper will describe the research protocol for the Deadly Aboriginal and Torres Strait Islander Nursing and Midwifery Mentoring (DANMM) Project, which will determine the feasibility and acceptability of a cultural mentoring programme designed for Aboriginal and Torres Strait Islander nurses and midwives across five diverse local health districts in New South Wales, Australia. Government and health agencies highlight the importance of culturally appropriate and safe environments for Aboriginal people. Specifically, New South Wales Health prioritises workforce strategies that support Aboriginal people to enter and stay in the health workforce. However, retaining Aboriginal nurses and midwives remains challenging. The DANMM Project aligns with these local and state-wide health plans and strategies, addressing critical issues of workforce cultural safety and retention. METHODS AND ANALYSIS: A mixed-methods study design will be employed to assess feasibility, acceptability and preliminary efficacy of the DANMM Programme across five publicly funded local health districts in New South Wales, Australia. Adhering to cultural safety, a project cultural governance group will be formed. Quantitative outcome measures include the use of questionnaires (Nursing Workplace Satisfaction Questionnaire, Ganngaleh nga Yagaleh Cultural Safety assessment tool). Resource implications will be measured using the Organisational Commitment and Health Professional Program Readiness Assessment Compass. These will be triangulated with individual and group yarning circles to provide a holistic evaluation of the programme. ETHICS AND DISSEMINATION: The study has ethics approval: Aboriginal Health and Medical Research Council (#2054/23); New South Wales Health Human Research Committees (Greater Western Human Research Committee #2022/ETH01971, Murrumbidgee-site-specific approval, Sydney Local Health District-site-specific approval, Western Sydney Local Health District-site-specific approval and Mid North Coast-site-specific approval); and Charles Sturt University Human Research Committee (#2054/23). Findings will be disseminated through peer-reviewed articles, conferences and through roundtable discussions with key stakeholders.