Systemic Treatment with a miR-146a Mimic Suppresses Endotoxin Sensitivity and Partially Protects Mice from the Progression of Acute Graft-versus-Host Disease.

Acute GVHD (aGVHD) is driven by interactions between the allogenic T cell response, inflammation, tissue injury and microbial products that enter the circulation when protective barriers such as the intestinal epithelium become compromised. Mice with aGVHD become hypersensitive to LPS, secreting large quantities of inflammatory mediators that exacerbate tissue injury. We hypothesized that microRNA (miR) modulators could be used in vivo to mitigate LPS hypersensitivity, altering the course of aGVHD. Using the C57BL/6 → (C57BL/6 × DBA/2)F1 -hybrid model of aGVHD, we measured intestinal permeability over time and used a qPCR array to detect concomitant changes in the expression levels of certain microRNAs (miRs) in the intestine. Large increases in permeability were seen on day 15, when endotoxemia becomes detectable and GVHD-associated histopathological lesions develop. Amongst the miRs with altered expression levels were some that regulate sensitivity to endotoxin. We chose to focus on miR-146a and treated recipient mice systemically with a miR-146a mimic early in the GVH reaction. This led to a reduction in the burst of IFNγ that likely plays a priming role in the mechanism underlying heightened sensitivity to endotoxin. LPS-induced TNFα release and GVHD-associated weight loss were also diminished and survival was prolonged. In summary, systemic treatment with a miR-146a mimic dampens the heightened sensitivity to LPS that occurs concomitantly with increased intestinal permeability and provides partial protection from the progression of acute GVHD.

Bridging the theory--practice gap in the ITU with in-service education.

The use of an education programme within a busy intensive therapy unit has proved to be highly successful in providing a framework for learning for those taking up an appointment in the unit with no previous experience of intensive therapy. The creation of a supportive learning environment was vital for it to work, promoted by enthusiastic and motivated staff and led by a full-time education coordinator. New course members were allocated to teams and provided with a 4-week supernumerary status to work alongside the education coordinator or mentors who acted as role models. This provided an opportunity for junior nurses to build confidence in newly acquired skills and knowledge. Resources for learning included a room designated for teaching equipped with visual teaching and learning aids. It has been shown that a large percentage of the nurses who have completed the education programme have gone on to undertake the English National Board Course 100 or other related courses. The education programme has been effective in bridging the theory-practice gap and ultimately achieving excellence in patient care.