The Courage to Care-An innovative arts-based event to engage students and the local community to reflect on Australian nurses' roles in the First World War and after.

There is a large body of work that documents the history of the nursing profession and the experiences of nurses during significant historical eras such as the First World War. Yet learning about nursing history is commonly a tiny, or absent, component in the undergraduate nursing curriculum. This paper discusses an innovative project that had multiple aims. A primary aim was to engage nursing students and educators in a project that valued nursing history by integrating it into an event to celebrate International Nurses Day. As the paper will explain, other aims were in organising the event so that it capitalised on particular creative arts strengths within the faculty, offering cross-disciplinary connections, engagement and appreciation. A Readers' Theatre event, involving academics and students in nursing, creative arts and education, was conceived, developed and performed for the community. The theme was the experiences of First World War nurses and how they encapsulated values important to nursing today - the 6 Cs - which guide high standards of nursing. The 6 Cs are care, compassion, competence, communication, courage and commitment. We called the Readers' Theatre "The Courage to Care", and this involved a 4month process of script development, event planning and a performance. This process and outcomes were evaluated, prompting a reflection on the strengths and challenges of working in this creative way to engage a wide group of stakeholders to advance the profession of nursing.

Illuminating and inspiring: using television historical drama to cultivate contemporary nursing values and critical thinking.

As the world prepares to commemorate the centenary of the First World War, it is timely to discuss meaningful learning activities that students of nursing could be engaged in to encourage them to reflect on the nurse's role then and now. Several films and television series about the war and featuring nursing have already been aired. No doubt there will be many more stories to come. Such stories have the potential to do more than eulogise nursing for students and practitioners. Stories, such as The crimson field, have potential to stimulate serious contemplation about values and cultural practices that have remained constant or have changed and to assist students to develop and articulate values that will be fitting for contemporary practice. Recently, excerpts from the series were examined with a group of nursing students and key learnings were found. These are shared in this paper for the benefit of educators planning to utilise public discourse as triggers to engage nursing students in discussions about nursing values, nursing history and representations of the profession.

An in vitro culture model to study the dynamics of colonic microbiota in Syrian golden hamsters and their susceptibility to infection with Clostridium difficile.

Clostridium difficile infections (CDI) are caused by colonization and growth of toxigenic strains of C. difficile in individuals whose intestinal microbiota has been perturbed, in most cases following antimicrobial therapy. Determination of the protective commensal gut community members could inform the development of treatments for CDI. Here, we utilized the lethal enterocolitis model in Syrian golden hamsters to analyze the microbiota disruption and recovery along a 20-day period following a single dose of clindamycin on day 0, inducing in vivo susceptibility to C. difficile infection. To determine susceptibility in vitro, spores of strain VPI 10463 were cultured with and without soluble hamster fecal filtrates and growth was quantified by quantitative PCR and toxin immunoassay. Fecal microbial population changes over time were tracked by 16S ribosomal RNA gene analysis via V4 sequencing and the PhyloChip assay. C. difficile culture growth and toxin production were inhibited by the presence of fecal extracts from untreated hamsters but not extracts collected 5 days post-administration of clindamycin. In vitro inhibition was re-established by day 15, which correlated with resistance of animals to lethal challenge. A substantial fecal microbiota shift in hamsters treated with antibiotics was observed, marked by significant changes across multiple phyla including Bacteroidetes and Proteobacteria. An incomplete return towards the baseline microbiome occurred by day 15 correlating with the inhibition of C. difficile growth in vitro and in vivo. These data suggest that soluble factors produced by the gut microbiota may be responsible for the suppression of C. difficile growth and toxin production.

Development of a recombinant toxin fragment vaccine for Clostridium difficile infection.

Clostridium difficile infection (CDI) is the major cause of antibiotic-associated diarrhea and pseudomembranous colitis, a disease associated with significant morbidity and mortality. The disease is mostly of nosocomial origin, with elderly patients undergoing anti-microbial therapy being particularly at risk. C. difficile produces two large toxins: Toxin A (TcdA) and Toxin B (TcdB). The two toxins act synergistically to damage and impair the colonic epithelium, and are primarily responsible for the pathogenesis associated with CDI. The feasibility of toxin-based vaccination against C. difficile is being vigorously investigated. A vaccine based on formaldehyde-inactivated Toxin A and Toxin B (toxoids) was reported to be safe and immunogenic in healthy volunteers and is now undergoing evaluation in clinical efficacy trials. In order to eliminate cytotoxic effects, a chemical inactivation step must be included in the manufacturing process of this toxin-based vaccine. In addition, the large-scale production of highly toxic antigens could be a challenging and costly process. Vaccines based on non-toxic fragments of genetically engineered versions of the toxins alleviate most of these limitations. We have evaluated a vaccine assembled from two recombinant fragments of TcdB and explored their potential as components of a novel experimental vaccine against CDI. Golden Syrian hamsters vaccinated with recombinant fragments of TcdB combined with full length TcdA (Toxoid A) developed high titer IgG responses and potent neutralizing antibody titers. We also show here that the recombinant vaccine protected animals against lethal challenge with C. difficile spores, with efficacy equivalent to the toxoid vaccine. The development of a two-segment recombinant vaccine could provide several advantages over toxoid TcdA/TcdB such as improvements in manufacturability.

Development and optimization of a novel assay to measure neutralizing antibodies against Clostridium difficile toxins.

Clostridium difficile produces two major virulence toxins, toxin A (TcdA) and toxin B (TcdB). Antitoxin antibodies, especially neutralizing antibodies, have been shown to be associated with a lower incidence of C. difficile infection (CDI) recurrence, and antibody levels are predictive of asymptomatic colonization. The development of an assay to detect the presence of neutralizing antibodies in animal and human sera for the evaluation of vaccine efficacy is highly desired. We have developed such an assay, which allows for the quantification of the effect of toxins on eukaryotic cells in an automated manner. We describe here the optimization of this assay to measure toxin potency as well as neutralizing antibody (NAb) activity against C. difficile toxins using a design-of-experiment (DOE) methodology. Toxin concentration and source, cell seeding density, and serum-toxin preincubation time were optimized in the assay using Vero cells. The assay was shown to be robust and to produce linear results across a range of antibody concentrations. It can be used to quantify neutralizing antibodies in sera of monkeys and hamsters immunized with C. difficile toxoid vaccines. This assay was shown to correlate strongly with traditional assays which rely on labor-intensive methods of determining neutralizing antibody titers by visual microscopic inspection of intoxicated-cell monolayers. This assay has utility for the selection and optimization of C. difficile vaccine candidates.

A jugular bleeding technique in rabbits.

When studying pharmacokinetics in rabbits, researchers must often take multiple blood samples from conscious rabbits. Researchers usually collect these samples via the auricular vein, typically through a port or an indwelling catheter. The authors have developed an easy and efficient alternative method for obtaining multiple blood samples from conscious rabbits via the external jugular vein. This jugular bleeding technique serves as a refinement to blood sampling methods that require rabbits to undergo surgery (e.g., to insert a port) because it requires no alleviation of pain. During a 2-year period, the authors have taken multiple blood samples from more than 400 rabbits and have seen no adverse events attributed to this procedure.

Influence of Blood Collection Sites on Plasma Glucose and Insulin Concentration in Conscious C57BL/6 Mice.

Blood collection from conscious, unanesthetized mice is often performed during the drug development process. The site of collection may influence the parameter(s) of interest. To investigate the potential influence of collection site on plasma glucose and insulin, a study was conducted to compare plasma glucose and insulin concentrations in blood samples collected without anesthesia from the retroorbital sinus versus the tail vein in 10- to 12-week-old female C57BL/6 mice. Two experiments were performed. In the first experiment, mice were randomized to be bled from the tail vein then the retroorbital sinus or vice-versa in a balanced two-period crossover design. In this experiment, the retroorbital and tail vein bleeds were performed a few minutes apart. The second experiment was similar to the first, except the bleeds were performed 1 week apart. Overall, retroorbital collection yielded lower glucose levels (p, 0.001) and higher insulin levels (p, 0.001) than did tail vein collection. The minimum difference in measured glucose in a retroorbital collection versus a tail vein collection, after adjusting for the effect of sequential bleeding was -97 mg/dl; the maximum was 98 mg/dl. We estimate that about 98% of observations taken under similar conditions would fall in this interval. The minimum difference in measured insulin in a retroorbital collection versus a tail vein collection was -0.6 ng/ml; the maximum was 7.3 ng/ml. We estimate that about 98% of observations taken under similar conditions would fall in this interval.