Physical Electronics

Contains reports on three research projects

Physical Electronics

Contains reports on three research projects

Designed Guanidinium-Rich Amphipathic Oligocarbonate Molecular Transporters Complex, Deliver and Release siRNA in Cells

The polyanionic nature of oligonucleotides and their enzymatic degradation present challenges for the use of siRNA in research and therapy; among the most notable of these is clinically relevant delivery into cells. To address this problem, we designed and synthesized the first members of a new class of guanidinium-rich amphipathic oligocarbonates that noncovalently complex, deliver, and release siRNA in cells, resulting in robust knockdown of target protein synthesis in vitro as determined using a dual-reporter system. The organocatalytic oligomerization used to synthesize these co-oligomers is step-economical and broadly tunable, affording an exceptionally quick strategy to explore chemical space for optimal siRNA delivery in varied applications. The speed and versatility of this approach and the biodegradability of the designed agents make this an attractive strategy for biological tool development, imaging, diagnostics, and therapeutic applications

Physical Electronics

Contains reports on three research projects

Physical Electronics

Contains reports on three research projects

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