iTRAQ-based protein analysis provides insight into heterologous superinfection exclusion with TMV-43A against CMV in tobacco (Nicotiana benthamiana) plants.

Heterologous superinfection exclusion (HSE) is a phenomenon of an initial virus infection which prevents reinfection by a distantly related or unrelated challenger virus strain in the same host. Here, we demonstrate that a mild strain mutant of Tobacco mosaic virus (TMV-43A) can protect Nicotiana benthamiana plants against infection by a challenger Cucumber mosaic virus (CMV)-Fny strain. The isobaric tags for relative and absolute quantification (iTRAQ) technique was used to investigate proteome of N. benthamiana plant during HSE. Our results indicated that in superinfected plants, the PSI and PSII proteins in the photosynthetic pathway increased in abundance, providing sufficient energy to plants for survival. The fatty acid synthesis-related proteins acetyl-CoA carboxylase 1-like and fatty acid synthase were decreased in abundance, affecting the formation of virus replication complex, which in turn reduced CMV replication and lessen hijacking of basic building blocks of RNA transcription and protein synthesis required for normal host functions. This is the first analyses of host proteins that are correlated to HSE between two unrelated plant viruses TMV-43A and CMV in N. benthamiana plants. BIOLOGICAL SIGNIFICANCE: CMV is one of the most studied host-virus interaction models in plants. It infects both monocot and dicot crop plants, causing significant economic losses. Superinfection exclusion (also known as cross protection) is one of the methods to combat virus infection. However, there is lack of proteome information of heterologous superinfection exclusion between two taxonomically unrelated plant viruses (such as between CMV and TMV). An iTRAQ-based quantitative approach was used to study proteomics of superinfection, where TMV-43A acts as a protector of N. benthamiana plants against its challenger CMV. Results showed that TMV-43A protects host plants and prevents plant death from CMV infection. This study provided insights into host responses involving multiple host pathways: photosynthesis, plant defence, carbon metabolism, translation and protein processing, fatty acid metabolism and amino acid biosynthesis. The findings provide a reference database for other viruses and increase our knowledge in host proteins that are correlated to superinfection.

Cost-benefit analysis of the polypill in the primary prevention of myocardial infarction and stroke.

The primary prevention of cardiovascular disease is a public health priority. To assess the costs and benefits of a Polypill Prevention Programme using a daily 4-component polypill from age 50 in the UK, we determined the life years gained without a first myocardial infarction (MI) or stroke, together with the total service cost (or saving) and the net cost (or saving) per year of life gained without a first MI or stroke. This was estimated on the basis of a 50 % uptake and a previously published 83 % treatment adherence. The total years of life gained without a first MI or stroke in a mature programme is 990,000 each year in the UK. If the cost of the Polypill Prevention Programme were £1 per person per day, the total cost would be £4.76 bn and, given the savings (at 2014 prices) of £2.65 bn arising from the disease prevented, there would be a net cost of £2.11 bn representing a net cost per year of life gained without a first MI or stroke of £2120. The results are robust to sensitivity analyses. A national Polypill Prevention Programme would have a substantial effect in preventing MIs and strokes and be cost-effective.

Randomised trial comparing the recording ability of a novel, electronic emergency documentation system with the AHA paper cardiac arrest record.

OBJECTIVE: To evaluate the ability of an electronic system created at the University of Washington to accurately document prerecorded VF and pulseless electrical activity (PEA) cardiac arrest scenarios compared with the American Heart Association paper cardiac arrest record. METHODS: 16 anaesthesiology residents were randomly assigned to view one of two prerecorded, simulated VF and PEA scenarios and asked to document the event with either the paper or electronic system. Each subject then repeated the process with the other video and documentation method. Five types of documentation errors were defined: (1) omission, (2) specification, (3) timing, (4) commission and (5) noise. The mean difference in errors between the paper and electronic methods was analysed using a single factor repeated measures ANOVA model. RESULTS: Compared with paper records, the electronic system omitted 6.3 fewer events (95% CI -10.1 to -2.5, p=0.003), which represents a 28% reduction in omission errors. Users recorded 2.9 fewer noise items (95% CI -5.3 to -0.6, p=0.003) when compared with paper, representing a 36% decrease in redundant or irrelevant information. The rate of timing (Δ=-3.2, 95% CI -9.3 to 3.0, p=0.286) and commission (Δ=-4.4, 95% CI -9.4 to 0.5, p=0.075) errors were similar between the electronic system and paper, while the rate of specification errors were about a third lower for the electronic system when compared with the paper record (Δ=-3.2, 95% CI -6.3 to -0.2, p=0.037). CONCLUSIONS: Compared with paper documentation, documentation with the electronic system captured 24% more critical information during a simulated medical emergency without loss in data quality.

The virtual reality transurethral prostatic resection trainer: evaluation of discriminate validity.

PURPOSE: To understand how urologists acquire resection skills we analyzed factors correlating with favorable resection metrics in groups defined as experts, residents and novices. We then evaluated discriminate validity by determining factors correlating with proficiency among individuals in the expert, resident and novice groups. MATERIALS AND METHODS: A total of 136 subjects completed the protocol, including 72 urologists, 45 residents and 19 novices. After a pre-task questionnaire and training video subjects performed a standardized 5-minute resection task. Primary metrics were gm resected, blood loss, irrigant volume used, foot pedal use and differential time spent with orientation, cutting or coagulation. RESULTS: Among experts larger resection correlated with more time spent cutting (p <0.001). In contrast, increased coagulation time correlated with gm resected in the novice group (p = 0.001). The number of transurethral prostate resections that residents reported having done in the real operating room correlated with gm resected (p = 0.043), use of more irrigating fluid (p = 0.024) and less time spent coagulating (p = 0.027) on the simulator. In residents and experts exclusively primary resection efficiency metrics, fluid use and blood loss correlated with cuts at tissue and correlated inversely with coagulation and orientation time (p <0.05). CONCLUSIONS: Different factors determine transurethral prostate resection performance metrics among experts, residents and novices. These correlations reinforce discriminate validity and provide insight into specific factors that likely determine success at different training levels. Such data could be used to isolate and train skill subsets in the curriculum and they may elucidate the safest and most efficient approach to train resection skills.

Simulation of bleeding in endoscopic procedures using virtual reality.

BACKGROUND AND PURPOSE: An image-based approach has been developed to represent bleeding in a simulator for transurethral resection of the prostate (TURP). Whereas previous groups attempted to simulate bleeding mathematically over tissue surfaces or in blood vessels, our approach focused on macroscopic visualization of bleeding in a fluid environment. The TURP is an ideal procedure for simulator-based training because of its importance as a skill to acquire as well as its long learning curve. The most challenging step in creating a realistic TURP simulator is simulated bleeding. MATERIALS AND METHODS: We took an image-based approach in which we generated blood flow movies of bleeding vessels having different severity and position under variable fluid flow conditions and processed them to separate the blood flow from the background anatomy. We then organized the movies into a parametric database. During the running of the simulation, resection systematically triggers the playback of a blood flow movie (bleeding event). The movie is texture mapped onto a virtual surface that is positioned, oriented, morphed, composited, and looped into the virtual scene. RESULTS AND CONCLUSION: The technique produced an accurate depiction of bleeding vessels one would encounter during a TURP. The image changes readily according to the fluid flow state.

Virtual image grafting: image based generation and visualization of virtual skin defects.

We have developed methods for rapidly generating 3d dermatologic datasets for use in education, training simulations and procedure planning. By compositing local surface features of cutaneous wounds onto patient images and 3d models, one can flexibly generate large patient variability from a small initial 3d library. The wound database is generated from clinically captured photographic images. The wound image is extracted from the image of the surrounding tissue. The 3d anatomy database is generated from MRI scans and from multiple photographic views. Extracted wound images can be moved rotated and scaled and blended in the final composite.