Results of Prevention of REStenosis with Tranilast and its Outcomes (PRESTO) trial

BACKGROUND: Restenosis after percutaneous coronary intervention (PCI) is a major problem affecting 15% to 30% of patients after stent placement. No oral agent has shown a beneficial effect on restenosis or on associated major adverse cardiovascular events. In limited trials, the oral agent tranilast has been shown to decrease the frequency of angiographic restenosis after PCI. METHODS AND RESULTS: In this double-blind, randomized, placebo-controlled trial of tranilast (300 and 450 mg BID for 1 or 3 months), 11 484 patients were enrolled. Enrollment and drug were initiated within 4 hours after successful PCI of at least 1 vessel. The primary end point was the first occurrence of death, myocardial infarction, or ischemia-driven target vessel revascularization within 9 months and was 15.8% in the placebo group and 15.5% to 16.1% in the tranilast groups (P=0.77 to 0.81). Myocardial infarction was the only component of major adverse cardiovascular events to show some evidence of a reduction with tranilast (450 mg BID for 3 months): 1.1% versus 1.8% with placebo (P=0.061 for intent-to-treat population). The primary reason for not completing treatment was > or =1 hepatic laboratory test abnormality (11.4% versus 0.2% with placebo, P<0.01). In the angiographic substudy composed of 2018 patients, minimal lumen diameter (MLD) was measured by quantitative coronary angiography. At follow-up, MLD was 1.76+/-0.77 mm in the placebo group, which was not different from MLD in the tranilast groups (1.72 to 1.78+/-0.76 to 80 mm, P=0.49 to 0.89). In a subset of these patients (n=1107), intravascular ultrasound was performed at follow-up. Plaque volume was not different between the placebo and tranilast groups (39.3 versus 37.5 to 46.1 mm(3), respectively; P=0.16 to 0.72). CONCLUSIONS: Tranilast does not improve the quantitative measures of restenosis (angiographic and intravascular ultrasound) or its clinical sequelae

An updated radiocarbon-based ice margin chronology for the last deglaciation of the North American Ice Sheet Complex

The North American Ice Sheet Complex (NAISC; consisting of the Laurentide, Cordilleran and Innuitian ice sheets) was the largest ice mass to repeatedly grow and decay in the Northern Hemisphere during the Quaternary. Understanding its pattern of retreat following the Last Glacial Maximum is critical for studying many facets of the Late Quaternary, including ice sheet behaviour, the evolution of Holocene landscapes, sea level, atmospheric circulation, and the peopling of the Americas. Currently, the most up-to-date and authoritative margin chronology for the entire ice sheet complex is featured in two publications (Geological Survey of Canada Open File 1574 [Dyke et al., 2003]; ‘Quaternary Glaciations – Extent and Chronology, Part II’ [Dyke, 2004]). These often-cited datasets track ice margin recession in 36 time slices spanning 18 ka to 1 ka (all ages in uncalibrated radiocarbon years) using a combination of geomorphology, stratigraphy and radiocarbon dating. However, by virtue of being over 15 years old, the ice margin chronology requires updating to reflect new work and important revisions. This paper updates the aforementioned 36 ice margin maps to reflect new data from regional studies. We also update the original radiocarbon dataset from the 2003/2004 papers with 1541 new ages to reflect work up to and including 2018. A major revision is made to the 18 ka ice margin, where Banks and Eglinton islands (once considered to be glacial refugia) are now shown to be fully glaciated. Our updated 18 ka ice sheet increased in areal extent from 17.81 to 18.37 million km2, which is an increase of 3.1% in spatial coverage of the NAISC at that time. Elsewhere, we also summarize, region-by-region, significant changes to the deglaciation sequence. This paper integrates new information provided by regional experts and radiocarbon data into the deglaciation sequence while maintaining consistency with the original ice margin positions of Dyke et al. (2003) and Dyke (2004) where new information is lacking; this is a pragmatic solution to satisfy the needs of a Quaternary research community that requires up-to-date knowledge of the pattern of ice margin recession of what was once the world’s largest ice mass. The 36 updated isochrones are available in PDF and shapefile format, together with a spreadsheet of the expanded radiocarbon dataset (n = 5195 ages) and estimates of uncertainty for each interval

Synthetic hydrogels as scaffolds for manipulating endothelium cell behaviors

Synthetic hydrogels can be used as scaffolds that not only favor endothelial cells (ECs) proliferation but also manipulate the behaviors and functions of the ECs. In this review paper, the effect of chemical structure, Young's modulus (E) and zeta potential (ζ) of synthetic hydrogel scaffolds on static cell behaviors, including cell morphology, proliferation, cytoskeleton structure and focal adhesion, and on dynamic cell behaviors, including migration velocity and morphology oscillation, as well as on EC function such as anti-platelet adhesion, are reported. It was found that negatively charged hydrogels, poly(2-acrylamido-2-methylpropanesulfonic sodium) (PNaAMPS) and poly(sodium p-styrene sulphonate) (PNaSS), can directly promote cell proliferation, with no need of surface modification by any cell-adhesive proteins or peptides at the environment of serum-containing medium. In addition, the Young's modulus (E) and zeta potential (ζ) of hydrogel scaffolds are quantitatively tuned by copolymer hydrogels, poly(NaAMPS-co-DMAAm) and poly(NaSS-co-DMAAm), in which the two kinds of negatively charged monomers NaAMPS and NaSS are copolymerized with neutral monomer, N,N-dimethylacrylamide (DMAAm). It was found that the critical zeta potential of hydrogels manipulating EC morphology, proliferation, and motility is ζcritical = -20.83 mV and ζcritical = -14.0 mV for poly(NaAMPS-co-DMAAm) and poly(NaSS-co-DMAAm), respectively. The above mentioned EC behaviors well correlate with the adsorption of fibronectin, a kind of cell-adhesive protein, on the hydrogel surfaces. Furthermore, adhered platelets on the EC monolayers cultured on the hydrogel scaffolds obviously decreases with an increase of the Young's modulus (E) of the hydrogels, especially when E > 60 kPa. Glycocalyx assay and gene expression of ECs demonstrate that the anti-platelet adhesion well correlates with the EC-specific glycocalyx. The above investigation suggests that understanding the relationship between physic-chemical properties of synthetic hydrogels and cell responses is essential to design optimal soft & wet scaffolds for tissue engineering