TLR1/2 Activation during Heterologous Prime-Boost Vaccination (DNA-MVA) Enhances CD8+ T Cell Responses Providing Protection against Leishmania (Viannia)

Leishmania (Viannia) are the predominant agents of leishmaniasis in Latin America. Given the fact that leishmaniasis is a zoonosis, eradication is unlikely; a vaccine could provide effective prevention of disease. However, these parasites present a challenge and we do not fully understand what elements of the host immune defense prevent disease. We examined the ability of vaccination to protect against L. (Viannia) infection using the highly immunogenic heterologous prime-boost (DNA-modified vaccinia virus) modality and a single Leishmania antigen (TRYP). Although this mode of vaccination can induce protection against other leishmaniases (cutaneous, visceral), no protection was observed against L. (V.) panamensis. However, we found that if the vaccination was modified and the innate immune response was activated through Toll-like receptor1/2(TLR1/2) during the DNA priming, vaccinated mice were protected. Protection was dependent on CD8 T cells. Vaccinated mice had higher CD8 T cell responses and decreased levels of cytokines known to promote infection. Given the long-term persistence of CD8 T cell memory, these findings are encouraging for vaccine development. Further, these results suggest that modulation of TLR1/2 signaling could improve the efficacy of DNA-based vaccines, especially where CD8 T cell activation is critical, thereby contributing to effective and affordable anti parasitic vaccines

Efect of maleated anhydride on mechanical properties of rice husk filler reinforced PLA Matrix Polymer Composite

Polylactic acid (PLA) formulated from corn starch has a bright potential to replace the non-renewable petroleum-based plastics. The combination of PLA and natural fbre has gained interest due to its unique performance, as reported in many researches and industries. Meanwhile, rice husk produced as the by-product of rice milling can be utilised, unless it is turned completely into waste. Therefore, in the present study, the rice husk powder (RHP) was used as a fller in the PLA, so to determine the infuence of the fller loading on the mechanical properties of the PLA composite. A coupling agent was selected for treatment from two options, i.e., maleic anhydride polypropylene (MAPP) and maleic anhydride polyethylene (MAPE), by applying the agents with various loading contents, such as 2, 4 and 6 wt%. The composite was fabricated by using the hot compression machine. Both the treated and untreated RHP–PLA composites were characterised via the tensile, fexural and impact strength tests. The increase in the RHP loading content led to the decrease in the tensile and fexural strengths. The applications of the coupling agents (MAPE and MAPP) did not improve the tensile and impact strengths, but the fexural strength was enhanced

A simplified (modified) Duke Activity Status Index (M-DASI) to characterise functional capacity: A secondary analysis of the Measurement of Exercise Tolerance before Surgery (METS) study

Background Accurate assessment of functional capacity, a predictor of postoperative morbidity and mortality, is essential to improving surgical planning and outcomes. We assessed if all 12 items of the Duke Activity Status Index (DASI) were equally important in reflecting exercise capacity. Methods In this secondary cross-sectional analysis of the international, multicentre Measurement of Exercise Tolerance before Surgery (METS) study, we assessed cardiopulmonary exercise testing and DASI data from 1455 participants. Multivariable regression analyses were used to revise the DASI model in predicting an anaerobic threshold (AT) >11 ml kg −1 min −1 and peak oxygen consumption (VO 2 peak) >16 ml kg −1 min −1, cut-points that represent a reduced risk of postoperative complications. Results Five questions were identified to have dominance in predicting AT>11 ml kg −1 min −1 and VO 2 peak>16 ml.kg −1min −1. These items were included in the M-DASI-5Q and retained utility in predicting AT>11 ml.kg −1.min −1 (area under the receiver-operating-characteristic [AUROC]-AT: M-DASI-5Q=0.67 vs original 12-question DASI=0.66) and VO 2 peak (AUROC-VO2 peak: M-DASI-5Q 0.73 vs original 12-question DASI 0.71). Conversely, in a sensitivity analysis we removed one potentially sensitive question related to the ability to have sexual relations, and the ability of the remaining four questions (M-DASI-4Q) to predict an adequate functional threshold remained no worse than the original 12-question DASI model. Adding a dynamic component to the M-DASI-4Q by assessing the chronotropic response to exercise improved its ability to discriminate between those with VO 2 peak>16 ml.kg −1.min −1 and VO 2 peak<16 ml.kg −1.min −1. Conclusions The M-DASI provides a simple screening tool for further preoperative evaluation, including with cardiopulmonary exercise testing, to guide perioperative management

Integration of the Duke Activity Status Index into preoperative risk evaluation: a multicentre prospective cohort study.

BACKGROUND: The Duke Activity Status Index (DASI) questionnaire might help incorporate self-reported functional capacity into preoperative risk assessment. Nonetheless, prognostically important thresholds in DASI scores remain unclear. We conducted a nested cohort analysis of the Measurement of Exercise Tolerance before Surgery (METS) study to characterise the association of preoperative DASI scores with postoperative death or complications. METHODS: The analysis included 1546 participants (≥40 yr of age) at an elevated cardiac risk who had inpatient noncardiac surgery. The primary outcome was 30-day death or myocardial injury. The secondary outcomes were 30-day death or myocardial infarction, in-hospital moderate-to-severe complications, and 1 yr death or new disability. Multivariable logistic regression modelling was used to characterise the adjusted association of preoperative DASI scores with outcomes. RESULTS: The DASI score had non-linear associations with outcomes. Self-reported functional capacity better than a DASI score of 34 was associated with reduced odds of 30-day death or myocardial injury (odds ratio: 0.97 per 1 point increase above 34; 95% confidence interval [CI]: 0.96-0.99) and 1 yr death or new disability (odds ratio: 0.96 per 1 point increase above 34; 95% CI: 0.92-0.99). Self-reported functional capacity worse than a DASI score of 34 was associated with increased odds of 30-day death or myocardial infarction (odds ratio: 1.05 per 1 point decrease below 34; 95% CI: 1.00-1.09), and moderate-to-severe complications (odds ratio: 1.03 per 1 point decrease below 34; 95% CI: 1.01-1.05). CONCLUSIONS: A DASI score of 34 represents a threshold for identifying patients at risk for myocardial injury, myocardial infarction, moderate-to-severe complications, and new disability

Efficacy of Quasi Agro Binding Fibre on the Hybrid Composite Used in Advance Application

The choice for natural fibre obtained from agricultural products is on the rise due to its solution to eco-friendly, environmental and improved mechanical properties concerns. Its abundant availability, low cost, emission reduction and adaptability to base material for composite make it a prime material for selection. This review explores diverse perspectives to the future trend of agro fibre in terms of the thermo-mechanical properties as it applies to advanced application in building structures. It is important to investigate the ecofriendliness of the products of composites from fibres in agricultural wastes so as to achieve a green and sustainable environment. This will come to fore by the combined efforts of both researchers and feedback from building stakeholders

Intentions and barriers to research activities among Australian and New Zealand anaesthetists: a survey

A voluntary, anonymous, cross-sectional online survey was conducted among 997 Fellows of the Australian and New Zealand College of Anaesthetists, using an electronic questionnaire. Details about their demographics, employment, research experience and barriers they had encountered, their perception about research and their future intentions to participate in research, were collected. The survey response rate was 24.6%. At the time of the survey, 29% of the survey respondents were involved in research. Respondents currently involved in research were more likely to be practising at a tertiary hospital, to have previously presented at conferences, to believe in the importance of research and to intend to undertake further research training (