ISGylation-independent protection of cell growth by USP18 following interferon stimulation.

Type 1 interferon stimulation highly up-regulates all elements of a ubiquitin-like conjugation system that leads to ISGylation of target proteins. An ISG15-specific member of the deubiquitylase family, USP18, is up-regulated in a co-ordinated manner. USP18 can also provide a negative feedback by inhibiting JAK-STAT signalling through protein interactions independently of DUB activity. Here, we provide an acute example of this phenomenon, whereby the early expression of USP18, post-interferon treatment of HCT116 colon cancer cells is sufficient to fully suppress the expression of the ISG15 E1 enzyme, UBA7. Stimulation of lung adenocarcinoma A549 cells with interferon reduces their growth rate but they remain viable. In contrast, A549 USP18 knock-out cells show similar growth characteristics under basal conditions, but upon interferon stimulation, a profound inhibition of cell growth is observed. We show that this contingency on USP18 is independent of ISGylation, suggesting non-catalytic functions are required for viability. We also demonstrate that global deISGylation kinetics are very slow compared with deubiquitylation. This is not influenced by USP18 expression, suggesting that enhanced ISGylation in USP18 KO cells reflects increased conjugating activity.

Balancing on life's ladder: A meta-ethnography of the existential experiences of siblings of children with complex care needs.

AIM: To synthesize and interpret existing qualitative research on the existential experiences of siblings of children with complex care needs. DESIGN: Noblit and Hare's interpretive meta-ethnography. METHODS: The study has been registered in the international prospective register for systematic reviews (PROSPERO). Noblit and Hare's 7-step procedure was followed and reciprocal translation was performed to analyse the data and develop a line of argument synthesis. DATA SOURCES: A comprehensive systematic literature search of five databases, along with extensive manual searches, was completed in November 2022. The final sample comprised 18 studies published between 2010 and 2022. RESULTS: A line of argument, expressed through an overarching metaphor, "balancing on life's ladder", illustrates the core findings of siblings' fluctuating experiences of existential well-being, and encapsulates four third-order themes: the emotional turmoil of siblings, interrupted family life, siblings strive to be themselves and siblings struggle to cope. CONCLUSION: Growing up with a sibling with complex care needs made children feel invisible, lonely and struggling to find the courage to cope. By adopting a lifeworld approach, nurses can become aware of healthy siblings' unmet needs. Future research is needed on how nurses can contribute to siblings' existential well-being, in primary - and secondary health care settings. IMPLICATIONS: The study provides insight into siblings' existential experiences and factors improving their well-being, enabling nurses to provide a more optimized lifeworld-led clinical practice. IMPACT: Healthcare, nursing education and practice should be informed by the knowledge of existential issues. Nurses are well-positioned to work alongside families to provide family-centered care. Our findings have implications for health policies tailored to the needs of children with chronically ill siblings. REPORTING METHOD: This review adheres to the Equator and improving reporting of meta-ethnography (eMERGe) guidelines. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution, because the data comprised previously published studies.

How do public health nurses in Norwegian school health services support siblings of children with complex care needs?

AIMS: There is a paucity of data regarding the care and support provided by Norwegian school health services to siblings of children with complex care needs. Public health nurses are an integral part of these universal services, which focus on health promotion and disease prevention in primary and secondary schools. This study aimed to explore health promotion interventions by public health nurses for siblings in Norwegian schools and to identify regional differences. METHODS: An online national questionnaire was distributed to Norwegian public health nurses and leaders of public health nursing services (N = 487). The questions were related to how the nurses support siblings of children with complex care needs. The quantitative data were analysed using descriptive statistics. An inductive thematic analysis of free-text comments was conducted. ETHICAL APPROVAL: The study was approved by the Norwegian Centre for Research Data. RESULTS: The majority of public health nursing leaders (67%) reported that the services in their municipality had no system to identify siblings or to provide them with routine care. However, 26% of public health nurses reported that routine support was provided to siblings. Regional differences were identified. STUDY LIMITATIONS: This study included responses from 487 PHNs from all four health regions in Norway. The study design is limited and gives a brief outline of the current situation. Further data are needed to provide in-depth knowledge. CONCLUSIONS: This survey provides important knowledge for health authorities and professionals working with siblings, about inadequate support and regional differences in care provided to siblings by school health services.

Public health nurses' experiences of ethical responsibility: A meta-ethnography.

Public health nursing is grounded in public health ideologies and fundamental nursing values. Researchers have argued that ethical responsibility from the perspective of the nurse is an understudied phenomenon. This meta-ethnography provides in-depth knowledge of how public health nurses (PHNs) experience ethical responsibility when working to prevent injury and disease, and promote health and well-being in children, young people and their families. There are reciprocal findings across the 10 included studies. The findings reveal that these nurses often feel alone, have worries and uncertainties and are afraid of doing wrong. They describe unclear boundaries in their work, creating a heightened sense of responsibility. PHNs fight lonely battles. Yet they show courage and commitment and are ready to stand up and fight for children and families who do not receive adequate care. A line of argument is developed and the metaphorical phrase Chivalrous knights in moral armour is used to express the authors' overall interpretations of the findings. Reflection on the findings shows how the different dimensions of ethical responsibility are interconnected. The nurses' ethical sensitivity enables them to feel compassion for others and they show indignation when vulnerable others are not treated with dignity and respect. Indignation and compassion are interrelated, and when human life and dignity are threatened, the ethical demand to respond emerges. Indignation is a precursor to moral courage, and the nurses' moral sensitivity and respect for their clients emboldens them to stand up for vulnerable others. The findings also illustrate the paradoxical nature of freedom. Freedom of choice due to unclear boundaries heightens the nurses' sense of responsibility. This research is an important step in theory development and has implications for further research, education and practice.

Health-related quality of life in inflammatory bowel disease: a comparison of patients receiving nurse-led versus conventional follow-up care.

BACKGROUND: Inflammatory bowel disease (IBD), consisting of Crohn's disease (CD) and ulcerative colitis (UC), is a chronic disorder with a considerable negative impact on health-related quality of life (HRQoL). During the past decade, IBD nurse specialists have been increasingly involved in follow-up care of IBD outpatients, in a consultative and coordinating role, closely cooperating with gastroenterologists. Whether patients' HRQoL differs between nurses' follow-up care (NF) and conventional follow-up care (CF) has not been widely researched and the aim of this study was to compare two different follow-up regimes with respect to patients' HRQoL. METHODS: This cross-sectional, multicenter study involved seven centers; five organized as CF, two as NF. RESULTS: A total of 304 patients aged 18-80 years, 174 females and 130 males, were included, of whom 140 received care under the NF model and 164 under the CF model. Participants in the NF group had a statistically significant higher median total score on the Inflammatory Bowel Disease Questionnaire (IBDQ) (p-value < .001). This pattern could also be seen in the sub-scores of the different IBDQ domains. Despite a trend of higher IBDQ score in all domains in the NF model, the overall result in our study did not reach the limit of 16 points, defined as clinically significant. A higher proportion of NF patients had IBDQ scores defined as remission, as well as a statistically significant higher frequency of outpatient check-ups during a two-year follow-up period. CONCLUSIONS: Nurse-led models are not inferior to conventional models with regards to patient reported HRQoL except in the social domain where the model showed to be clinically significant better. Further studies are needed to advance efforts to implement these models and increase access to IBD care.

An analysis of Norwegian public health nursing curricula: Where is the nursing literature?

BACKGROUND: Norwegian public health nurses prevent diseases and promote health in children and young people aged 0-20 and their families. Public health nursing programs prepare students for their practical role and provide relevant theoretical knowledge. OBJECTIVES: To gain knowledge of the literature in the Norwegian public health nursing curricula, and to examine further the nursing base in these curricula. DESIGN: An explorative and descriptive design was chosen. SAMPLE: Reading lists based on syllabus documents from the 10 higher educational institutions in Norway offering programs in public health nursing. MEASUREMENTS: A summative content analysis and a categorization of content from reading lists were performed. RESULTS: Numerical information on the content and categorization of reading lists shows that social science and humanities literature dominates, followed by psychology and medicine. Nursing texts, theories and philosophy comprise only a minor part of the curricula. CONCLUSION: The paper provides valuable data on the theoretical focus in Norwegian public health nursing and raises important questions about the paucity of nursing texts in the curriculum. The imbalance in reading lists in Norway should be studied further and similar studies conducted in other countries to encourage reflection on the theoretical content of public health nursing education globally.

Public health nursing education in Ireland and Norway: A comparative analysis.

BACKGROUND: Public health, primary health care, and nursing are founding principles of public health nursing. Thus, the underpinning curriculum needs to reflect these core principles. Public health nursing educators sought to delve deeper into curricula and training of public health nurse (PHNs) in Ireland and Norway OBJECTIVE: To compare PHNs' educational training in Ireland and Norway through a collaborative process DESIGN: This study used a descriptive comparative design SAMPLE: A panel of expert educators (the authors) compared national Public health nursing education strategies, guidelines, and curricula used to train PHN students RESULTS: Four core categories emerged from the analysis: general characteristics, theoretical and empirical knowledge base for PHNs practice, applying theory to clinical practice, and professional/ethical dimensions for practice. Results revealed more similarities than differences in both countries' educational models. The central difference related to the specialist role in Norway versus the generalist role in Ireland CONCLUSIONS: Workforce requirements drive the delivery of Public Health Nursing programs and educational curricula. However, it is imperative that educators evaluate their curricula in terms of fitness and practice, not just purpose.

The meaning of dignity for older adults: A meta-synthesis.

Dignified care is a central issue in the nursing care of older adults. Nurses are expected to treat older adults with dignity, and older adults wish to be treated in a dignified manner. Researchers have recommended investigating the concept of dignity based on specific contexts and population groups. This meta-synthesis study aims to explore the understandings of dignity from the perspective of older adults in the Nordic countries. Synthesising findings from qualitative studies on older adults' experiences of dignity has provided important insight into what can be essential for dignified care in a Nordic context. The importance of visibility and recognition for the experience of dignity is an overarching theme in all the studies. The participants' descriptions mostly implicated an existence dominated by a lack of recognition. The older adults do not feel valued as people or for their contribution to society and strive to tone down their illnesses in an attempt to become more visible and acknowledged as people. Toning down their illnesses and masking their needs can protect their independence. At the same time, becoming less visible can leave them without a voice. The metaphorical phrase protected and exposed by a cloak of invisibility is used to express the authors' overall interpretation of the findings. Lack of recognition and being socially invisible is a genuine threat to older adults' dignity.

The GET pathway can increase the risk of mitochondrial outer membrane proteins to be mistargeted to the ER.

Tail-anchored (TA) proteins are anchored to their corresponding membrane via a single transmembrane segment (TMS) at their C-terminus. In yeast, the targeting of TA proteins to the endoplasmic reticulum (ER) can be mediated by the guided entry of TA proteins (GET) pathway, whereas it is not yet clear how mitochondrial TA proteins are targeted to their destination. It has been widely observed that some mitochondrial outer membrane (MOM) proteins are mistargeted to the ER when overexpressed or when their targeting signal is masked. However, the mechanism of this erroneous sorting is currently unknown. In this study, we demonstrate the involvement of the GET machinery in the mistargeting of suboptimal MOM proteins to the ER. These findings suggest that the GET machinery can, in principle, recognize and guide mitochondrial and non-canonical TA proteins. Hence, under normal conditions, an active mitochondrial targeting pathway must exist that dominates the kinetic competition against other pathways.

δ-COP contains a helix C-terminal to its longin domain key to COPI dynamics and function.

Membrane recruitment of coatomer and formation of coat protein I (COPI)-coated vesicles is crucial to homeostasis in the early secretory pathway. The conformational dynamics of COPI during cargo capture and vesicle formation is incompletely understood. By scanning the length of δ-COP via functional complementation in yeast, we dissect the domains of the δ-COP subunit. We show that the µ-homology domain is dispensable for COPI function in the early secretory pathway, whereas the N-terminal longin domain is essential. We map a previously uncharacterized helix, C-terminal to the longin domain, that is specifically required for the retrieval of HDEL-bearing endoplasmic reticulum-luminal residents. It is positionally analogous to an unstructured linker that becomes helical and membrane-facing in the open form of the AP2 clathrin adaptor complex. Based on the amphipathic nature of the critical helix it may probe the membrane for lipid packing defects or mediate interaction with cargo and thus contribute to stabilizing membrane-associated coatomer.

Home as a place for giving birth-A circumpolar study of the experiences of mothers and midwifes.

This article explores what home birth mothers and midwives say about the birth experience and the interaction between mother, partner and midwife. It is based on an explorative empirical study of the narratives of seven home birth mothers and the experiences of five midwives. The authors examine how these subjective experiences can help us to understand the phenomenon of home birth. The article is grounded in a philosophy of place and feminist theory, understood within a health promotion framework. Home birth manifests itself as a place-based esthetic experience characterized by gender, body, nature and culture. The participants spoke of the significance of giving birth at home. The authors discover that giving birth at home involves celebration, togetherness and ontological security. It also encompasses a broad understanding of risk, power structures, responsibility and co-determination. Openness about the challenges of home births can boost the position of home birth among both clinicians and the general public.

A competitive transcription factor binding mechanism determines the timing of late cell cycle-dependent gene expression.

Transcriptional control is exerted by the antagonistic activities of activator and repressor proteins. In Saccharomyces cerevisiae, transcription factor complexes containing the MADS box protein Mcm1p are key regulators of cell cycle-dependent transcription at both the G2/M and M/G1 transitions. The homeodomain repressor protein Yox1p acts in a complex with Mcm1p to control the timing of gene expression. Here, we show that Yox1p interacts with Mcm1p through a motif located N terminally to its homeodomain. Yox1p functions as a transcriptional repressor by competing with the forkhead transcription activator protein Fkh2p for binding to Mcm1p through protein-protein interactions at promoters of a subset of Mcm1p-regulated genes. Importantly, this competition is not through binding the same DNA site that is commonly observed. Thus, this study describes a different mechanism for determining the timing of cell cycle-dependent gene expression that involves competition between short peptide motifs in repressor and activator proteins for interaction with a common binding partner.

Unsung heroes, flying blind-A metasynthesis of parents' experiences of caring for children with special health-care needs at home.

AIMS AND OBJECTIVES: To aggregate, synthesise and interpret qualitative research studies of parents' experiences of caring for a child with special health-care needs at home. BACKGROUND: Advances in the field of medical and nursing science have ensured better survival rates for children with chronic illnesses. Many of these children have significant special health-care needs. Today parents assume a caregiver role, undertaking tasks previously provided by nurses in hospitals. As the complexity of care delivered by parents continues to develop, synthesised knowledge can provide an evidence base that will support and guide nurses when caring for these families. DESIGN: Metasynthesis. METHODS: Based upon a systematic search protocol, a structured literature search, covering the years 2003-2016, was conducted in five electronic databases. Ten studies were included and appraised using the Critical Appraisal Skills Program assessment tool. A metasummary and a metasynthesis were undertaken guided by the metasynthesis methodology as described by Sandelowski and Barroso (Handbook for synthesizing qualitative research. New York, NY: Springer, 2007). RESULTS: The results were interpreted and integrated under the overarching theme "unsung heroes, flying blind," supported by eight elucidating categories that illustrate aspects of the parents' life world. CONCLUSIONS: The enormous burden of care can weaken the parents' will to carry on and result in a decreased ability to provide care. This can have an impact on the parents' health, family functioning and the sick child's potential health outcomes. Nurses are in a unique position to help these families and should be better prepared for the role. RELEVANCE TO CLINICAL PRACTICE: Knowledge of how parents of children with special health-care needs experience their daily lives can promote trust in nurses and guide them in their efforts to support families with children living with chronic illness.

"Trapped in an Empty Waiting Room"-The Existential Human Core of Loneliness in Old Age: A Meta-Synthesis.

Loneliness in old age has a negative influence on quality of life, health, and survival. To understand the phenomenon of loneliness in old age, the voices of lonely older adults should be heard. Therefore, the purpose of this meta-synthesis was to synthesize scientific studies of older adults' experiences of loneliness. Eleven qualitative articles that met the inclusion criteria were analyzed and synthesized according to Noblit and Hare's meta-ethnographic approach. The analysis revealed the overriding meaning of the existential human core of loneliness in old age expressed through the metaphor "trapped in an empty waiting room." Four interwoven themes were found: (a) the negative emotions of loneliness, (b) the loss of meaningful interpersonal relationships, (c) the influence of loneliness on self-perception, and (d) the older adults' endeavors to deal with loneliness. The joint contribution of family members, health care providers, and volunteers is necessary to break the vicious circle of loneliness.

Protein cofactor competition regulates the action of a multifunctional RNA helicase in different pathways.

A rapidly increasing number of RNA helicases are implicated in several distinct cellular processes, however, the modes of regulation of multifunctional RNA helicases and their recruitment to different target complexes have remained unknown. Here, we show that the distribution of the multifunctional DEAH-box RNA helicase Prp43 between its diverse cellular functions can be regulated by the interplay of its G-patch protein cofactors. We identify the orphan G-patch protein Cmg1 (YLR271W) as a novel cofactor of Prp43 and show that it stimulates the RNA binding and ATPase activity of the helicase. Interestingly, Cmg1 localizes to the cytoplasm and to the intermembrane space of mitochondria and its overexpression promotes apoptosis. Furthermore, our data reveal that different G-patch protein cofactors compete for interaction with Prp43. Changes in the expression levels of Prp43-interacting G-patch proteins modulate the cellular localization of Prp43 and G-patch protein overexpression causes accumulation of the helicase in the cytoplasm or nucleoplasm. Overexpression of several G-patch proteins also leads to defects in ribosome biogenesis that are consistent with withdrawal of the helicase from this pathway. Together, these findings suggest that the availability of cofactors and the sequestering of the helicase are means to regulate the activity of multifunctional RNA helicases and their distribution between different cellular processes.

Nursing staffs' attentiveness to older adults falling in residential care - an interview study.

AIMS AND OBJECTIVES: The focus of this study is to explore how nursing staff experience safety promotion and fall prevention in residential care settings for older adults. The article calls for attentiveness to fall prevention within a broader lifeworld context of well-being and health promotion. BACKGROUND: There is limited research on fall prevention and safety promotion where the lifeworld and well-being provide a direction for care. DESIGN: This interview study has a hermeneutic phenomenological design. METHODS: Fourteen interviews with nursing staff were carried out. The ethics of care and vulnerability within a lifeworld approach provide the theoretical framework and guide the interpretive process. RESULTS: The findings can indicate that there is a generalised understanding of the needs of older persons in residential care. The focus of the staff was more on protection and prevention than safety promotion and well-being. CONCLUSION: Risk prevention is not enough. The residents need protection against falls but they also need to be protected from situations that can be detrimental to their well-being and compromise their dignity. Acknowledging the complexities of safety promotion amongst older persons living in assisted care settings can prevent fall accidents and ensure attentiveness to a more fundamental sense of security that can promote the older person's well-being and health. RELEVANCE TO CLINICAL PRACTICE: This study is relevant to clinical nursing practice as it shows that risk management in fall prevention is not enough. The findings show the need for educated nursing home staff that can incorporate contemplative and scientific knowledge into injury prevention practice.

Meanings of knowledge and identity in public health nursing in a time of transition: interpretations of public health nurses' narratives.

BACKGROUND: A changing healthcare system affects the professional identity of nursing groups. Public health nursing has experienced challenges in balancing the paternalistic expert ideology and the empowerment participation ideology. A strong professional identity can legitimate nursing, and possibly influence the quality of nursing work. Narrations from practice can illuminate the nurses' theoretical and practical knowledge and help illustrate their collective professional identity. AIM: To illuminate the meaning of public health nursing knowledge and professional identity in a continuously changing public health nursing practice. METHOD: A qualitative interview study with a purposeful sample of 23 Norwegian public health nurses was carried out. Data were analysed using phenomenological hermeneutics, a descriptive method inspired by Ricoeur's philosophy of interpretation. FINDINGS: Three themes emerged (i) Being a generalist: emphasising the need for generalised knowledge and using clinical judgement, (ii) Being one who empowers: focusing on resources and coping strategies, (iii) Being occupied with individual problem solving: focusing on individuals with special needs, using standardised techniques and protocols, and lacking specialised knowledge. CONCLUSION: Interpretation of the nurses' stories illuminated their need for generalised evidence-based knowledge, but also the importance of using sound clinical judgement in a diverse complex practice, where service users need encouragement, support and expert advice. Time pressures can limit the nurses' involvement. Many had an individual problem-focus more than a primary prevention focus, in contrast to governmental regulations stating that Norwegian public health nurses should focus on health promotion and primary prevention. Public health nurses have a broad generalised knowledge of their special target group giving them a 'specialist generalist' role. Clarification of this role, in relation to jurisdictional borders, can create a strong identity at a time when healthcare policy promotes economic values, professional neutrality and increased collaboration.

The yeast oligopeptide transporter Opt2 is localized to peroxisomes and affects glutathione redox homeostasis.

Glutathione, the most abundant small-molecule thiol in eukaryotic cells, is synthesized de novo solely in the cytosol and must subsequently be transported to other cellular compartments. The mechanisms of glutathione transport into and out of organelles remain largely unclear. We show that budding yeast Opt2, a close homolog of the plasma membrane glutathione transporter Opt1, localizes to peroxisomes. We demonstrate that deletion of OPT2 leads to major defects in maintaining peroxisomal, mitochondrial, and cytosolic glutathione redox homeostasis. Furthermore, ∆opt2 strains display synthetic lethality with deletions of genes central to iron homeostasis that require mitochondrial glutathione redox homeostasis. Our results shed new light on the importance of peroxisomes in cellular glutathione homeostasis.

Contradictory discourses of health promotion and disease prevention in the educational curriculum of Norwegian public health nursing: a critical discourse analysis.

AIMS: Health care is under constant change creating new and demanding tasks for public health nurses. The curriculum for public health nursing students is controlled by governmental directives that decide the structure and content of their education. This paper analyses manifest and latent discourses in the curriculum, in order to reveal underlying governmental principles for how public health nurses should promote health and prevent diseases. METHODS: A critical discourse analysis of the Norwegian public health nursing curriculum was conducted. RESULTS: The study indicates i) 'a competing biomedical and social-scientific knowledge-discourse', with biomedical knowledge dominating the content of the curriculum; ii) 'a paternalistic meta-discourse', referring to an underlying paternalistic ideology despite a clear focus on user participation; and iii) 'a hegemonic individual discourse'. Even though the curriculum stipulates that public health nurses should work at both an individual and a societal level, there is very little population focus in the text. CONCLUSIONS: Recent political documents concerning public health nursing focus more on health promotion, however, this is not sufficiently explicit in the curriculum. The lack of emphasis on social scientific knowledge, and the blurred empowerment and population perspective in the curriculum, can lead to less emphasis on health promotion work in public health nursing education and practice. The curriculum should be revised in order to meet the recent governmental expectations.

Home as a health promotion setting for older adults.

BACKGROUND: The number and the proportion of older persons is growing in the Nordic Countries. The growth in the older population has a clear impact on the care system for older persons. One trend is to prioritise home care instead of care in institutions. Another trend is to emphasise preventive and health promotion care. As official guidelines in the Nordic countries state that home is the best place to grow old, it is essential that older persons keep their health and functional capacity in order to be able to live at home for as long as possible. As current policy emphasises living at home, home care, preventive work and health promotion it becomes essential to study the home as a health promotion setting. OBJECTIVE: The aim of this study was to reach a new understanding of home as a health promotion setting for older persons. STUDY DESIGN: The method used was a literature reflection and analysis with a hermeneutical approach. RESULTS: The results show that with increasing age the home environment becomes a crucial determinant for independence. The home environment supports the self as people age; it has associations with the past, can provide proximity to family, and a sense of being a part of neighbourhood life. CONCLUSIONS: Only by taking into consideration the meaning of home and the resources of the individual older person can home function as a true health promoting setting if health personnel focus solely on risk prevention, they can neglect the perspectives of the older person, resulting in dis-empowerment not health promotion.