BACKGROUND: Simulation-based education (SBE) has many benefits for learners, but costs can limit embedding SBE in health professional curricula. Peer simulation involves students portraying patient roles, and may reduce costs while still providing the benefits of other SBE experiences. However, the quality of the SBE may be impacted if students cannot portray authentic and realistic patient roles. The aim of this study was to investigate whether targeted education was associated with observable changes to physiotherapy students' abilities to portray patient roles in SBE. METHODS: Second year pre-registration physiotherapy students (n = 40) participated. Students completed online and face-to-face education about SBE, patient portrayal skills, and how to portray a specific patient role. Students were video-recorded portraying patient roles in practical exams before and after the program. Three blinded independent assessors rated the overall quality of portrayals using a purpose-developed assessment instrument. RESULTS: Twenty-three sets of pre- and post-program videos were analysed. Correlations between assessor scores spanned 0.62 to 0.82 for analyses of interest, which justified using average assessor ratings in analysis. Statistically significant higher scores were seen for post-program assessments for overall portrayal scores (mean difference 6.5, 95%CI [1.51-11.45], p = 0.013), accuracy (mean difference 3.4, 95%CI [0.69-6.13], p = 0.016) and quality (mean difference 3.1, 95%CI [0.64-5.49], p = 0.016). CONCLUSIONS: Physiotherapy students appear capable of playing realistic patient roles. Peer simulation can be embedded into health professional programs, and education in patient role portrayal appears to be associated with improvements in portrayal quality and realism. Given these findings, further investigation, including testing program effects in a randomised study, is warranted.

<jats:sec><jats:title>Background</jats:title><jats:p>Healthcare simulation has been used as a pedagogical strategy in nursing education. Evidence has shown one of the positive impacts that simulations replace clinical placement. These wide-ranging initiatives are essential, and they can guide a nursing school’s simulation training. However, researching each innovation in the nursing field is beyond the scope.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>To focus our research and develop the capacity and capability to incorporate healthcare simulation in nursing education, we used a consensus building process to establish a school’s research agenda. A modified Delphi process was adopted to reach a consensus among 10 nursing faculty members in one university with a visiting professor’s support.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The three themes were identified as (1) embedding simulation into the baccalaureate in nursing curriculum, (2) designing effective simulation-based education and (3) simulating education in the broader world (adolescents). These themes were further categorised into two areas that used simulation in the educational and community settings. Sixty per cent of the faculty members agreed that the question, ‘How can simulation be incorporated into clinical placements to enhance students’ learning?' should be the highest research priority.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>This study adds understanding to incorporate simulation-based education in the nursing curriculum and community provides insights into future research.</jats:p></jats:sec>

Objectives: Endemic human coronaviruses (hCoVs) circulate worldwide but cause minimal mortality. Although seroconversion to hCoV is near ubiquitous during childhood, little is known about hCoV-specific T-cell memory in adults. Methods: We quantified CD4 T-cell and antibody responses to hCoV spike antigens in 42 SARS-CoV-2-uninfected individuals. Antigen-specific memory T cells and circulating T follicular helper (cTFH) cells were identified using an activation-induced marker assay and characterised for memory phenotype and chemokine receptor expression. Results: T-cell responses were widespread within conventional memory and cTFH compartments but did not correlate with IgG titres. SARS-CoV-2 cross-reactive T cells were observed in 48% of participants and correlated with HKU1 memory. hCoV-specific T cells exhibited a CCR6+ central memory phenotype in the blood, but were enriched for frequency and CXCR3 expression in human lung-draining lymph nodes. Conclusion: Overall, hCoV-specific humoral and cellular memory are independently maintained, with a shared phenotype existing among coronavirus-specific CD4 T cells. This understanding of endemic coronavirus immunity provides insight into the homeostatic maintenance of immune responses that are likely to be critical components of protection against SARS-CoV-2.

Recent studies reveal substantial species and regional differences in enteroendocrine cell (EEC) populations, including differences in patterns of hormone coexpression, which limit extrapolation between animal models and human. In this study, jejunal samples, with no histologically identifiable pathology, from patients undergoing Whipple's procedure were investigated for the presence of gastrointestinal hormones using double- and triple-labelling immunohistochemistry and high-resolution confocal microscopy. Ten hormones (5-HT, CCK, secretin, proglucagon-derived peptides, PYY, GIP, somatostatin, neurotensin, ghrelin and motilin) were localised in EEC of the human jejunum. If only single staining is considered, the most numerous EEC were those containing 5-HT, CCK, ghrelin, GIP, motilin, secretin and proglucagon-derived peptides. All hormones had some degree of colocalisation with other hormones. This included a population of EEC in which GIP, CCK and proglucagon-derived peptides are costored, and four 5-HT cell populations, 5-HT/GIP, 5-HT/ghrelin, 5-HT/PYY, and 5-HT/secretin cell groups, and a high degree of overlap between motilin and ghrelin. The presence of 5-HT in many secretin cells is consistent across species, whereas lack of 5-HT and CCK colocalisation distinguishes human from mouse. It seems likely that the different subclasses of 5-HT cells subserve different roles. At a subcellular level, we examined the vesicular localisation of secretin and 5-HT, and found these to be separately stored. We conclude that hormone-containing cells in the human jejunum do not comply with a one-cell, one-hormone classification and that colocalisations of hormones are likely to define subtypes of EEC that have different roles.

INTRODUCTION: We aimed to perform a systematic review and meta-analysis on the long-term durability, incidence of complications, and patient satisfaction outcomes in ileal conduit (IC) and orthotopic neobladder (ONB). METHODS: A systematic electronic literature search was performed in Medline, Embase, Cochrane Library, and Scopus using MeSH and free-text search terms "Urinary diversion" AND "Ileal conduit" AND "Neobladder." The search concluded June 19, 2018. Inclusion criteria were those patients who had a cystectomy and required urinary diversion by either IC or neobladder. RESULTS: In total, 32 publications met the inclusion criteria. Data were available on 46 787 patients (n=36 719 for IC and n=10 068 for ONB). Meta-analyses showed that IC urinary diversions performed less favorably than ONB in terms of re-operation rates, Clavien-Dindo complications, and mortality rates; odds ratios (ORs) and 95% confidence intervals (CIs) were 1.76 (1.24, 2.50), p<0.01; 1.16 (1.09, 1.22), p<0.01; and 6.29 (5.30, 7.48), p<0.01, respectively. IC urinary diversion performed better than ONB in relation to urinary tract infection rates and ureteric stricture rates, OR and 95% CI 0.67 (0.58, 0.77), p<0.01; and 0.70 (0.55, 0.89), p<0.01, respectively. CONCLUSIONS: Our results show that there is no significantly increased morbidity with ONB compared to IC. Selection of either urinary diversion technique should be based on factors such as tumor stage, comorbidities, surgical experience, and patient acceptance of postoperative sequalae.

<jats:p>BACKGROUND: Little has been published regarding how doctors think and talk about prognosis and the potential benefits of adjuvant therapy. OBJECTIVE: We sought predictions of survival rates and survival times, for patients with and without adjuvant therapy, from the clinicians of patients participating in a randomised trial of adjuvant sorafenib after nephrectomy for renal cell carcinoma. METHODS: A subset of medical oncologists and urologists in the SORCE trial completed questionnaires eliciting their predictions of survival rates and survival times, with and without adjuvant sorafenib, for each of their participating patients. To compare predictions elicited as survival times versus survival rates, we transformed survival times to survival rates. To compare predicted benefits elicited as absolute improvements in rates and times, we transformed them into hazard ratios (HR), a measure of relative benefit.We postulated that a plausible benefit in overall survival (OS) should be smaller than that hypothesized for disease–free survival (DFS) in the trials original sample size justification (i.e. HR for OS should be ≥ 0.75). RESULTS: Sixty–one medical oncologists and 17 urologists completed questionnaires on 216 patients between 2007 and 2013. Predictions of survival without adjuvant sorafenib were similar whether elicited as survival rates or survival times (median 5–year survival rate of 61% vs 60%, p = 0.6). Predicted benefits of sorafenib were larger when elicited as improvements in survival rates than survival times (median HR 0.76 vs 0.83, p &lt; 0.0001). The proportion of HR for predicted OS with sorafenib that reflected a plausible benefit (smaller effect of sorafenib on OS than hypothesized on DFS, i.e. HR ≥ 0.75) was 51% for survival rates, and 65% for survival times. CONCLUSIONS: The predicted benefits of adjuvant sorafenib were larger when elicited as improvements in survival rates than as survival times, and were often larger than the sample size justification for the trial. These potential biases should be considered when thinking and talking about individual patients in clinical practice, and when designing clinical trials.</jats:p>

Here we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups of PanNETs, termed T1, T2 and T3, with distinct patterns of methylation. The T1 subgroup was enriched for functional tumors and ATRX, DAXX and MEN1 wild-type genotypes. The T2 subgroup contained tumors with mutations in ATRX, DAXX and MEN1 and recurrent patterns of chromosomal losses in half of the genome with no association between regions with recurrent loss and methylation levels. T2 tumors were larger and had lower methylation in the MGMT gene body, which showed positive correlation with gene expression. The T3 subgroup harboured mutations in MEN1 with recurrent loss of chromosome 11, was enriched for grade G1 tumors and showed histological parameters associated with better prognosis. Our results suggest a role for methylation in both driving tumorigenesis and potentially stratifying prognosis in PanNETs.

Pharmacotherapies for the treatment of Benign Prostatic Hyperplasia (BPH) are targeted at reducing cellular proliferation (static component) or reducing smooth muscle tone (dynamic component), but response is unpredictable and many patients fail to respond. An impediment to identifying novel pharmacotherapies is the incomplete understanding of paracrine signalling. Oxytocin has been highlighted as a potential paracrine mediator of BPH. To better understand oxytocin signalling, we investigated the effects of exogenous oxytocin on both stromal cell proliferation, and inherent spontaneous prostate contractions using primary models derived from human prostate tissue. We show that the Oxytocin Receptor (OXTR) is widely expressed in the human prostate, and co-localises to contractile cells within the prostate stroma. Exogenous oxytocin did not modulate prostatic fibroblast proliferation, but did significantly (p < 0.05) upregulate the frequency of spontaneous contractions in prostate tissue, indicating a role in generating smooth muscle tone. Application of atosiban, an OXTR antagonist, significantly (p < 0.05) reduced spontaneous contractions. Individual tissue responsiveness to both exogenous oxytocin (R2 = 0.697, p < 0.01) and atosiban (R2 = 0.472, p < 0.05) was greater in tissue collected from older men. Overall, our data suggest that oxytocin is a key regulator of inherent spontaneous prostate contractions, and targeting of the OXTR and associated downstream signalling is an attractive prospect in the development of novel BPH pharmacotherapies.

Methods: Normal human proximal renal kidney cells (HK-2) were preconditioned with either increasing doses of ZnCl2 or control. Following this preconditioning, cells were exposed to increasing concentrations of Iohexol 300 mg I2/ml for four hours. Key outcome measures included cell survival (MTT colorimetric assay) and ROS generation (H2DCFDA fluorescence assay). Results: Contrast media induced a dose-dependent reduction in survival of HK-2 cells. Compared to control, contrast media at 150, 225, and 300 mg I2/ml resulted in 69.5% (SD 8.8%), 37.3% (SD 4.8%), and 4.8% (SD 6.6%) cell survival, respectively (p < 0.001). Preconditioning with 37.5 μM and 50 μM ZnCl2 increased cell survival by 173% (SD 27.8%) (p < 0.001) and 219% (SD 32.2%) (p < 0.001), respectively, compared to control preconditioning. Zinc preconditioning resulted in a reduction of ROS generation. Zinc pre-conditioning with 37.5 μM μM ZnCl2 reduced ROS generation by 46% (p < 0.001) compared to control pre-conditioning. Conclusions: Zinc preconditioning reduces oxidative stress following exposure to radiographic contrast media which in turn results in increased survival of renal cells. Translation of this in vitro finding in animal models will lay the foundation for future use of zinc preconditioning against contrast induced nephropathy.

Introduction: 3D printed patient-specific vascular phantoms provide superior anatomical insights for simulating complex endovascular procedures. Currently, lack of exposure to the technology poses a barrier for adoption. We offer an accessible, low-cost guide to producing vascular anatomical models using routine CT angiography, open source software packages and a variety of 3D printing technologies. Methods: Although applicable to all vascular territories, we illustrate our methodology using Abdominal Aortic Aneurysms (AAAs) due to the strong interest in this area. CT aortograms acquired as part of routine care were converted to representative patient-specific 3D models, and then printed using a variety of 3D printing technologies to assess their material suitability as aortic phantoms. Depending on the technology, phantoms cost $20-$1,000 and were produced in 12-48 h. This technique was used to generate hollow 3D printed thoracoabdominal aortas visible under fluoroscopy. Results: 3D printed AAA phantoms were a valuable addition to standard CT angiogram reconstructions in the simulation of complex cases, such as short or very angulated necks, or for positioning fenestrations in juxtarenal aneurysms. Hollow flexible models were particularly useful for device selection and in planning of fenestrated EVAR. In addition, these models have demonstrated utility other settings, such as patient education and engagement, and trainee and anatomical education. Further study is required to establish a material with optimal cost, haptic and fluoroscopic fidelity. Conclusion: We share our experiences and methodology for developing inexpensive 3D printed vascular phantoms which despite material limitations, successfully mimic the procedural challenges encountered during live endovascular surgery. As the technology continues to improve, 3D printed vascular phantoms have the potential to disrupt how endovascular procedures are planned and taught.