Phosphorylation of Vasodilator-Stimulated Phosphoprotein (VASP) dampens hepatic ischemia-reperfusion injury

Recent work has demonstrated that the formation of platelet neutrophil complexes (PNCs) affects inflammatory tissue injury. Vasodilator-stimulated phosphoprotein (VASP) is crucially involved into the control of PNC formation and myocardial reperfusion injury. Given the clinical importance of hepatic IR injury we pursued the role of VASP during hepatic ischemia followed by reperfusion. We report here that VASP−/− animals demonstrate reduced hepatic IR injury compared to wildtype (WT) controls. This correlated with serum levels of lactate dehydrogenase (LDH), aspartate (AST) and alanine (ALT) aminotransferase and the presence of PNCs within ischemic hepatic tissue and could be confirmed using repression of VASP through siRNA. In studies employing bone marrow chimeric mice we identified hematopoietic VASP to be of crucial importance for the extent of hepatic injury. Phosphorylation of VASP on Ser153 through Prostaglandin E1 or on Ser235 through atrial natriuretic peptide resulted in a significant reduction of hepatic IR injury. This was associated with a reduced presence of PNCs in ischemic hepatic tissue. Taken together, these studies identified VASP and VASP phosphorylation as crucial target for future hepatoprotective strategies

Patient participation: A qualitative study of immigrant women and their experiences

Patient participation in healthcare is a neglected area of interest in the rather extensive amount of research on immigrant so-called Selma patients in Swedish health care as well as worldwide. The aim is to explore the phenomenon “patient participation” in the context of the Swedish health care from the perspective of immigrants non-fluent in Swedish. A phenomenological lifeworld approach was chosen. Data were collected from patients within a municipal home care setting in Sweden. Eight women agreed to participate. In seven interviews, an interpreter was necessary for the translation of the interview. Five authorized interpreters were used. Data were analysed in accordance to a descriptive phenomenological method for caring research. The analysis led to an essence of the phenomenon with three constituents, “to experience participation,” “to refrain from participation,” and “to be deprived of participation.” Patient participation from the perspective of immigrant women means that patients are involved and active in their own health and caring processes. For these women, it is particularly important to have the opportunity to express themselves. Patient participation presupposes professional caregivers who act in a way that increases the patients' opportunities to take part. A skilled interpreter is often necessary in order to enable the patient participation

Facilitating implementation of research evidence (FIRE): A randomised controlled trial and process evaluation of two models of facilitation informed by the promoting action on research implementation in health services (PARIHS) framework

Background: The PARIHS framework proposes that successful implementation of research evidence results from the complex interplay between the evidence to be implemented, the context of implementation and the facilitation processes employed. Facilitation is defined as a role (the facilitator) and a process (facilitation strategies/methods). Empirical evidence comparing different facilitation approaches is limited; this paper reports a trial of two different types of facilitation represented in the PARIHS framework. Methods: A pragmatic cluster randomised controlled trial with embedded process evaluation was undertaken in 24 long-term nursing care settings in four European countries. In each country, sites were randomly allocated to standard dissemination of urinary incontinence guideline recommendations and one of two types of external-internal facilitation, labelled Type A and B. Type A facilitation was a less resource intensive approach, underpinned by improvement methodology; Type B was a more intensive, emancipatory model of facilitation, informed by critical social science. The primary outcome was percentage documented compliance with guideline recommendations. Process evaluation was framed by realist methodology and involved quantitative and qualitative data collection from multiple sources. Findings: Quantitative data were obtained from reviews of 2313 records. Qualitative data included over 332 hours of observations of care; 39 hours observation of facilitation activity; 471 staff interviews; 174 resident interviews; 120 next of kin/carer interviews; and 125 stakeholder interviews. There were no significant differences in the primary outcome between study arms and all study arms improved over time. Process data revealed three core mechanisms that influenced the trajectory of the facilitation intervention: alignment of the facilitation approach to the needs and expectations of the internal facilitator and colleagues; engagement of internal facilitators and staff in attitude and action; and learning over time. Data from external facilitators demonstrated that the facilitation interventions did not work as planned, issues were cumulative and maintenance of fidelity was problematic. Implications for D&I Research: Evaluating an intervention - in this case facilitation - that is fluid and dynamic within the methodology of a randomised controlled trial is complex and challenging. For future studies, we suggest a theoretical approach to fidelity, with a focus on mechanisms, as opposed to dose and intensity of the intervention

After colonic surgery: The lived experience of participating in a fast-track programme

Postoperative recovery can be accelerated and hospitalization reduced through fast-track programmes. However, documented knowledge is limited and primarily focusing on a medical perspective whereas the patients' perspective lacks documentation. This study describes the lived experience of participating in a fast-track programme after colonic surgery. Sixteen patients were interviewed twice. The interviews were analysed using a descriptive phenomenological approach. Participating in a fast-track programme is characterized by a process where patients experience how the daily regimen works both with them and against them. To succeed in the overall goal of recovering fast according to the evidence-based care plan involves facing dilemmas and mobilizing courage and will to follow the regimen. Support from the professionals is crucial. The participants had a strong desire to comply and regain health; but this role of being a good and cooperative patient had a built-in asymmetric power relationship favouring the professionals' expectations. The complexities of this power relationship were related to both patient factors and contextual factors, e.g. the daily regimen and hospital norms. Although patient participation in care is an accepted ideal, it is demanding and difficult to accomplish. More studies on fast-track programmes are needed, with special attention to patient autonomy and partnership

Microparticle-mediated transfer of the viral receptors CAR and CD46, and the CFTR channel in a CHO cell model confers new functions to target cells

Cell microparticles (MPs) released in the extracellular milieu can embark plasma membrane and intracellular components which are specific of their cellular origin, and transfer them to target cells. The MP-mediated, cell-to-cell transfer of three human membrane glycoproteins of different degrees of complexity was investigated in the present study, using a CHO cell model system. We first tested the delivery of CAR and CD46, two monospanins which act as adenovirus receptors, to target CHO cells. CHO cells lack CAR and CD46, high affinity receptors for human adenovirus serotype 5 (HAdV5), and serotype 35 (HAdV35), respectively. We found that MPs derived from CHO cells (MP-donor cells) constitutively expressing CAR (MP-CAR) or CD46 (MP-CD46) were able to transfer CAR and CD46 to target CHO cells, and conferred selective permissiveness to HAdV5 and HAdV35. In addition, target CHO cells incubated with MP-CD46 acquired the CD46-associated function in complement regulation. We also explored the MP-mediated delivery of a dodecaspanin membrane glycoprotein, the CFTR to target CHO cells. CFTR functions as a chloride channel in human cells and is implicated in the genetic disease cystic fibrosis. Target CHO cells incubated with MPs produced by CHO cells constitutively expressing GFP-tagged CFTR (MP-GFP-CFTR) were found to gain a new cellular function, the chloride channel activity associated to CFTR. Time-course analysis of the appearance of GFP-CFTR in target cells suggested that MPs could achieve the delivery of CFTR to target cells via two mechanisms: the transfer of mature, membrane-inserted CFTR glycoprotein, and the transfer of CFTR-encoding mRNA. These results confirmed that cell-derived MPs represent a new class of promising therapeutic vehicles for the delivery of bioactive macromolecules, proteins or mRNAs, the latter exerting the desired therapeutic effect in target cells via de novo synthesis of their encoded proteins

A realist process evaluation within the Facilitating Implementation of Research Evidence (FIRE) cluster randomised controlled international trial: An exemplar

Trial Registration: Current Controlled Trials ISRCTN11598502Background Facilitation is a promising implementation intervention, which requires theory informed evaluation. This paper presents an exemplar of a multi-country realist process evaluation that was embedded in the first international randomised controlled trial evaluating two types of facilitation for implementing urinary continence care recommendations. We aimed to uncover what worked (and did not work), for whom, how, why and in what circumstances during the process of implementing the facilitation interventions in practice. Methods This realist process evaluation included theory formulation, theory testing and refining. Data were collected in 24 care home sites across four European countries. Data were collected over four time-points using multiple qualitative methods: observation (372 hours), interviews with staff (n=357), residents (n=152), next of kin (n=109) other stakeholders (n=128), supplemented by facilitator activity logs. A combined inductive and deductive data analysis process focused on realist theory refinement and testing. Results The content and approach of the two facilitation programmes prompted variable opportunities to align and realign support with the needs and expectations of facilitators and homes. This influenced their level of confidence in fulfilling the facilitator role, and ability to deliver the intervention as planned. The success of intervention implementation was largely dependent on whether sites prioritised their involvement in both the study and the facilitation programme. In contexts where the study was prioritised (including release of resources) and where managers and staff support was sustained, this prompted collective engagement (as an attitude and action). Internal facilitators’ (IF) personal characteristics and abilities, including personal and formal authority, in combination with a supportive environment prompted by managers triggered the potential for learning over time. Learning over time resulted in a sense of confidence and personal growth, and enactment of the facilitation role, which resulted in practice changes. Conclusion The scale and multi-country nature of this study provided a novel context to conduct one of the few trial embedded realist informed process evaluations. In addition to providing an explanatory account of implementation processes, a conceptual platform for future facilitation research is presented. Finally a realist informed process evaluation framework is outlined, which could inform future research of this nature.The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 223646. The funder had no role in designing, conducting, or interpreting study findings.https://implementationscience.biomedcentral.com/articles13pubpub13

FIRE (facilitating implementation of research evidence) : a study protocol

Research evidence underpins best practice, but is not always used in healthcare. The Promoting Action on Research Implementation in Health Services (PARIHS) framework suggests that the nature of evidence, the context in which it is used, and whether those trying to use evidence are helped (or facilitated) affect the use of evidence. Urinary incontinence has a major effect on quality of life of older people, has a high prevalence, and is a key priority within European health and social care policy. Improving continence care has the potential to improve the quality of life for older people and reduce the costs associated with providing incontinence aids

RNA extraction from self-assembling peptide hydrogels to allow qPCR analysis of encapsulated cells

Self-assembling peptide hydrogels offer a novel 3-dimensional platform for many applications in cell culture and tissue engineering but are not compatible with current methods of RNA isolation; owing to interactions between RNA and the biomaterial. This study investigates the use of two techniques based on two different basic extraction principles: solution-based extraction and direct solid-state binding of RNA respectively, to extract RNA from cells encapsulated in four β-sheet forming self-assembling peptide hydrogels with varying net positive charge. RNA-peptide fibril interactions, rather than RNA-peptide molecular complexing, were found to interfere with the extraction process resulting in low yields. A column-based approach relying on RNA-specific binding was shown to be more suited to extracting RNA with higher purity from these peptide hydrogels owing to its reliance on strong specific RNA binding interactions which compete directly with RNA-peptide fibril interactions. In order to reduce the amount of fibrils present and improve RNA yields a broad spectrum enzyme solution—pronase—was used to partially digest the hydrogels before RNA extraction. This pre-treatment was shown to significantly increase the yield of RNA extracted, allowing downstream RT-qPCR to be performed

Patients' independence of a nurse for the administration of subcutaneous anti-TNF therapy: A phenomenographic study

Rheumatology nursing supports patients to manage their lives and live as independently as possible without pain, stiffness and functional restrictions. When conventional drugs fail to delay the development of the rheumatic disease, the patient may require biological treatment such as self-administered subcutaneous anti-tumour necrosis factor (TNF) therapy. It is therefore important that the patient perspective focuses on the life-changing situation caused by the administration of regular subcutaneous injections. The aim of this study was to describe variations in how patients with rheumatic diseases experience their independence of a nurse for administration of subcutaneous anti-TNF therapy. The study had a descriptive, qualitative design with a phenomenographic approach and was carried out by means of 20 interviews. Four ways of understanding the patients' experience of their subcutaneous anti-TNF therapy and independence of a nurse emerged: the struggling patient; the learning patient; the participating patient; the independent patient. Achieving independence of a nurse for subcutaneous anti-TNF injections can be understood by the patients in different ways. In their strive for independence, patients progress by learning about and participating in drug treatment, after which they experience that the injections make them independent