InCHARGE: Co-creating, implementing and evaluating interventions to utilize nurses' competence and achieve person-centred fundamental care-A research protocol describing an action research approach.

AIM AND OBJECTIVES: This research protocol presents an action research project with the aim to demonstrate the value of person-centred fundamental care to nurses and nurse managers in surgical care units to encourage a far-reaching change in this direction. The objectives are to describe this process and to evaluate the effects on missed nursing care and person-centred fundamental care. METHODS: In a novel collaboration between nursing science and medical humanities the action research design will be used to interact with nursing staff and leaders in three surgical care units and design interventions with the purpose to affect the direction of nursing. Initially, the care units will be presented with interactive workshops including evidence-based education on person-centered fundamental care, person-centredness, nurse role responsibility and leadership. This will be followed by cocreation of interventions to stimulate person-centered fundamental care. The Fundamentals of Care framework will be used as the overarching theoretical framework. Data on missed nursing care, person-centred climate and person-centered fundamental care will be collected repeatedly from patient- and nursing stakeholders through interviews and validated questionnaires. Additionally, data from written reflections following clinical observations and focus group interviews will be included. The duration of the study will be approximately five years from ethical approval. DISCUSSION: It has been previously reported that the current working environments of registered nurses are forcing them to ration their caring responsibilities, leading to a lack of fulfillment of patients' fundamental care needs, with possible severe consequences for patients. The action research design helps researchers gain an understanding of the contextual factors important for forthcoming interventions, enabling reflective processes and cocreation of interventions with stakeholders. This may lead to feasible interventions and strengthen nursing leadership in the involved units.

Targeted transgene expression in rat brain using lentiviral vectors.

Direct gene transfer to the adult brain is dependent on vectors that transduce non-dividing cells, such as lentiviral vectors. Another aspect of the development of gene therapy to the brain is the need for cell-specific transgene expression. Expression from vesicular stomatitis virus G-protein (VSV-G) pseudotyped lentiviral vectors has been reported to be mainly neuron specific in the brain. We constructed cell-specific lentiviral vectors using the neuron-specific enolase (rNSE) or the glial fibrillary acidic protein (hGFAP) promoters and compared them to the ubiquitous human cytomegalovirus promoter (hCMV), a hybrid CMV/beta-actin promoter (CAG) and the promoter for human elongation factor 1 alpha (EF1 alpha). Our results showed that the hGFAP promoter was expressed only in glial cells, whereas rNSE was purely neuron specific, showing that VSV-G is pantropic in the rat striatum. We conclude that the VSV-G allows transduction of both glial and neuronal cells and the promoter dictates in what cell type the transgene will be expressed. The expression of transgenes exclusively in astrocytes would allow for local delivery of secreted transgene products, such as glial cell line-derived neurotrophic factor (GDNF), circumventing the anterograde transport that may induce unwanted side effects.

Screening for gene mutations in a 500 kb neuroblastoma tumor suppressor candidate region in chromosome 1p; mutation and stage-specific expression in UBE4B/UFD2.

Deletion of a part of the short arm of chromosome 1 is one of the most common chromosomal rearrangements observed in neuroblastoma (NBL) tumors and it is associated with a poor prognosis. No NBL tumor suppressor gene has yet been identified in the region. Our shortest region of overlap of deletions, ranging from marker D1S80 to D1S244, was shown to partly overlap a 500 kb region that was homozygously deleted in a NBL cell line. We have screened seven genes known to reside in or very close to this overlap consensus region, UBE4B/UFD2, KIF1B, DFFA, PGD, CORT, PEX14, and ICAT, for coding mutations in NBL tumor DNA. A few deviations from the reference sequences were identified; most interestingly being a splice site mutation that was detected in UBE4B/UFD2 in a stage 3 NBL with a fatal outcome. This mutation was neither present in the patients constitutional DNA nor in any of 192 control chromosomes analysed. Also, the expression of UBE4B/UFD2 was markedly diminished in the high-stage/poor-outcome tumors as compared to the low-stage/favorable-outcome tumors. Overall, the number of amino-acid changes in the genes of the region was low, which shows that mutations in these genes are rare events in NBL development. Given the data presented here, UBE4B/UFD2 stands out as the strongest candidate NBL tumor suppressor gene in the region at this stage.