Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

Continuous-Flow Bioseparation Using Microfabricated Anisotropic Nanofluidic Sieving Structures

The anisotropic nanofluidic-filter (nanofilter) array (ANAANAANA) is a unique molecular-sieving structure for separating biomolecules. In this protocol we describe the fabrication of planar and vertical ANAANAANA chips and how to perform continuous-flow bioseparation using them. This protocol is most useful for bioengineers who are interested in developing automated multistep chip-based bioanalysis systems and assumes previous cleanroom microfabrication knowledge. The ANAANAANA consists of a two-dimensional periodic nanofilter array, and the designed structural anisotropy of ANAANAANA causes different-sized or charged biomolecules to follow distinct trajectories under applied electric fields, leading to efficient continuous-flow separation. Using microfluidic channels surrounding the ANAANAANA, the fractionated biomolecule streams are collected and routed to different fluid channels or reservoirs for convenient sample recovery and downstream bioanalysis. The ANAANAANA is physically robust and can be reused repeatedly. Compared with the conventional gel-based separation techniques, ANAANAANA offers the potential for faster separation, higher throughput and more convenient sample recovery.National Institutes of Health (U.S.) (EB005743)Korea Institute of Science and Technology-Intelligent Microsystems CenterSingapore-MIT AllianceMassachusetts Institute of Technology. Microsystems Technology Laboratorie

Genomics and molecular markers for rice grain quality: a review

Rice grain quality is a benchmark of rice breeding success. Current rice breeding programs consider grain characteristics that are preferred by consumers in the rice value chain. Specific traits of quality that suit the demands of stakeholders must be targeted before, during and after breeding of new varieties. Therefore, screening tools that are environmentally independent, cheap, robust and easy to use, such as molecular markers, are needed to facilitate timely and accurate selection of traits. As a multifaceted overall phenotype and consisting of several parameters ranging from physical, textural, aroma and increasingly nutritional properties, the selection for quality has not only become about which trait(s) to focus on but is rather an issue of the combination of traits that can be incorporated into a dream variety. The more traits that are available, the more markers we need to capture these traits and feed them into the breeding and selection pipelines. This chapter reviews progress made on genomics and the molecular markers developed for quality traits of rice grains. In addition, this chapter presents the increasing need for novel phenotypes in the form of metabolites that can be traced back to the genome of rice