Drug-eluting balloons with provisional bail-out or adjunctive stenting in de novo coronary artery lesions-a systematic review and meta-analysis.

Background: Efficacy of drug-eluting balloons (DEB) for treatment of de novo coronary lesions remains controversial. The present systematic review and meta-analysis of randomised controlled trials assessed DEB with bare-metal stents (BMS) and also DEB with provisional bail-out stents ('DEB-only' strategy), to other conventional options: plain-old balloon angioplasty (POBA), BMS and drug-eluting stents (DES). Methods: A systematic literature search from January 2000 until May 2017 was conducted. Primary outcome measure, late lumen loss (LLL); and secondary outcomes; binary restenosis, major adverse cardiac events (MACE), target lesion revascularization (TLR), myocardial infarction (MI), cardiovascular death and stent thrombosis were analysed. Results: Seventeen RCTs were included with 2,616 patients. Several comparative groups showed significant differences. DEB with BMS were inferior to DES for LLL [mean difference (MD) =0.12 mm; 95% confidence interval (CI), 0.03 to 0.22; P=0.01]; and binary restenosis [risk ratio (RR) =1.89; (CI, 1.13 to 3.18); P=0.02]. DEB with BMS was superior to BMS for LLL [MD =-0.27 mm; (-0.45 to -0.10); P=0.002]; and MACE [RR =0.64; (0.46 to 0.90); P=0.010]. Finally, DEB alone was superior to POBA for LLL [MD =-0.39 mm; (-0.67 to -0.11); P=0.006] and binary restenosis [RR =0.20; (0.05 to 0.85); P=0.03] in bifurcation lesions. Conclusions: The results of this meta-analysis showed that whilst DEB with BMS is superior to BMS alone, the combination is inferior to DES for treatment of de novo coronary lesions. Thus, DEB + BMS should not be applied in de novo lesions unless in patients who have absolute contraindications to DES. DEB alone, however, should be considered for relative contraindications to DES such as small vessel disease and bifurcation lesions

Effect of nanosilica addition on the fresh properties and shrinkage of mortars with fly ash and superplasticizer

The ongoing use of various mineral additions along with chemical admixtures such as superplasticizers justifies the need for further research. Understanding and quantifying their effects and possible synergies on the fresh and hardened properties of cement-based materials is necessary, especially if some of these components are known to have a pozzolanic effect. This paper describes and models the fresh and hardened properties of cement mortars including nanosilica and fly ash, and relates their properties to the proportioning of these materials and the superplasticizer dosage. Mini-slump, Marsh cone and Lombardi cone tests were used to examine the properties of the fresh mortars, and to assess density, plastic shrinkage, and drying shrinkage up to 20 days. The equations presented in this paper make it possible to optimize mortar proportionings to the required levels of performance in both fresh and hardened states

Longevity is determined by ETS transcription factors in multiple tissues and diverse species

Ageing populations pose one of the main public health crises of our time. Reprogramming gene expression by altering the activities of sequence-specific transcription factors (TFs) can ameliorate deleterious effects of age. Here we explore how a circuit of TFs coordinates pro-longevity transcriptional outcomes, which reveals a multi-tissue and multi-species role for an entire protein family: the E-twenty-six (ETS) TFs. In Drosophila, reduced insulin/IGF signalling (IIS) extends lifespan by coordinating activation of Aop, an ETS transcriptional repressor, and Foxo, a Forkhead transcriptional activator. Aop and Foxo bind the same genomic loci, and we show that, individually, they effect similar transcriptional programmes in vivo. In combination, Aop can both moderate or synergise with Foxo, dependent on promoter context. Moreover, Foxo and Aop oppose the gene-regulatory activity of Pnt, an ETS transcriptional activator. Directly knocking down Pnt recapitulates aspects of the Aop/Foxo transcriptional programme and is sufficient to extend lifespan. The lifespan-limiting role of Pnt appears to be balanced by a requirement for metabolic regulation in young flies, in which the Aop-Pnt-Foxo circuit determines expression of metabolic genes, and Pnt regulates lipolysis and responses to nutrient stress. Molecular functions are often conserved amongst ETS TFs, prompting us to examine whether other Drosophila ETS-coding genes may also affect ageing. We show that five out of eight Drosophila ETS TFs play a role in fly ageing, acting from a range of organs and cells including the intestine, adipose and neurons. We expand the repertoire of lifespan-limiting ETS TFs in C. elegans, confirming their conserved function in ageing and revealing that the roles of ETS TFs in physiology and lifespan are conserved throughout the family, both within and between species

Development of self-compacting SIFCON

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Roundabout receptor 4 and its role in endothelial barrier dysfunction following cardiac surgery

Endothelial barrier dysfunction contributes to the systemic inflammatory response in patients undergoing cardiac surgery with surgery necessitating cardiopulmonary bypass. The bypass enables to perform complicated operations on static heart, but it comes with risks such as a damage to the endothelium which causes inflammation. Activation of endothelial cells by inflammatory mediators leads to changes in endothelial function. These changes include up-regulation of adhesion molecules, production and secretion of inflammatory mediators and chemo-attractant agents, as well as vasoactive compounds. These changes are central to the pathological processes leading to sepsis syndrome. The exaggerated release of pro- and anti-inflammatory cytokines leads to development of septic and vasoplegic syndromes which complicate recovery and can even cause a death. Currently, there are no specific therapies that target the endothelium, but greater insight into the pathogenesis of endothelial barrier dysfunction could lead to new biomarkers and therapies. Roundabout receptor 4 could be a novel biomarker and target for specific pharmacological intervention. Roundabout receptor 4 was originally identified as an axon guidance molecule but is now known to mediate various endothelial processes including cell migration and proliferation. At the outset of this thesis a role for Roundabout receptor 4 and its Slit 2 glycoprotein ligand as regulators of endothelial barrier function were also beginning to emerge; but there was little evidence of how Roundabout receptor 4 expression profiles and function might differ between endothelial cells; or of implications of Roundabout receptor 4 detected in human plasma. In patients (n=48) undergoing cardiac surgery, standard biomarkers of endothelial activation significantly increased 24h after surgery; by contrast, Roundabout receptor 4 increased immediately post-operatively, as did another novel biomarker of endothelial dysfunction - Syndecan-1. Roundabout receptor 4 could be a useful early marker of endothelial dysfunction in this patient group. There were significant associations between Roundabout receptor 4 plasma levels and prolonged length of stay in intensive care and hospital. Higher pre-operative plasma levels of Roundabout receptor 4 were also associated with the development of vasoplegia, a post-operative complication. Vasoplegia is caused by an imbalance of vasodilator and vasopressor mechanisms in the body, but the exact pathophysiology is not known. Vasoplegic patients are treated with high and prolonged doses of vasoconstrictor medications. This treatment can cause peripheral vasoconstriction and ischemia of limbs that can lead to metabolic acidosis and tissue necrosis. In vitro, Robo4 external expression decreased in endothelial cells treated with inflammatory cytokines. Robo4 plasma levels increased after cardiac surgery with snCPB. These results suggest that Robo4 might be cleaved or secreted by endothelial cells exposed to inflammation and released into the bloodstream. Roundabout receptor 4 expression was greater on human umbilical vein endothelial cells than on human pulmonary artery endothelial cells; and decreased following stimulation with tumour necrosis factor-alpha. In parallel, Slit2 increased barrier integrity in human umbilical vein endothelial cells but not in human pulmonary artery endothelial cells; difference could relate to differences in Roundabout receptor 4 expression levels, as Slit2 effects were inhibited with Roundabout receptor 4 short interfering RNA. The finding from these investigations inform greater understanding of the important role of Robo4 as an endothelial biomarker and its role in barrier function.Open Acces

Corporate Social Responsibility of Companies Producing PFOA Containing Waxes for Cross-Country Skiing

The chemical industry is a particularly sensitive sector that very often works with toxic, harmful and dangerous substances. This paper offers insight into the corporate socially responsible (CSR) behaviour of a specific segment of the chemical industry—the production of fluorinated ski waxes. Perfluorinated compounds, which excel in water and fat stability and repellency, are nowadays considered as harmful to human health and nature. During 2020, the basic compound, perfluorooctanoic acid (PFOA), will be banned, and finding its replacement will be a difficult task. So far, there are no alternatives in terms of environmentally friendly compounds that can maintain the desired properties of extreme ski glide. Based on a questionnaire distributed to twenty wax producers worldwide, we have concluded that, although the attitudes of companies towards CSR certification was rather negative (87.5%), and companies had not developed or documented any CSR policy/strategy with specific goals, they found CSR activities/instruments beneficial and important. The survey highlighted the fact that companies were aware that their products are dangerous for the environment, and that environmental issues are important for all of the responders, despite them being mostly without certified systems. The size of a company had no significant effect on their attitude. Micro and small producers were involved in raising awareness of environmental policies and responsibilities to the same extent (maybe even more) as medium or large companies. We also found varying behaviours between companies involved in environmental programs and those who were not. The companies involved felt a strong attitude towards all three pillars of CSR, which are the environment, as well as social and economic aspects. Those companies not involved had a strong attitude towards their customers, but not towards their employees, suppliers or the wider community. They also had stronger feelings about the quality of their products and economic profit, but without a strong approach to the related environmental issues. The Norwegian approach and the commitment of the company Swix to CSR are two positive examples leading to a fluorine-free future

Raised Plasma Robo4 and Cardiac Surgery-Associated Acute Kidney Injury

Endothelial dysfunction associated with systemic inflammation can contribute to organ injury/failure following cardiac surgery requiring cardiopulmonary bypass (CPB). Roundabout protein 4 (Robo4), an endothelial-expressed transmembrane receptor and regulator of cell activation, is an important inhibitor of endothelial hyper-permeability. We investigated the hypothesis that plasma levels of Robo4 are indicative of organ injury, in particular acute kidney injury (AKI), after cardiac surgery.Patients (n = 32) undergoing elective cardiac surgery with CPB were enrolled, prospectively. Plasma Robo4 concentrations were measured pre-, 2 and 24 h post-operatively, using a commercially available ELISA. Plasma and endothelial markers of inflammation [interleukin (IL) -6, -8, -10: von Willibrand factor (vWF) and angiopoeitin-2 (Ang-2)] and the AKI marker, neutrophil gelatinase-associated lipocalin (NGAL), were also measured by ELISA.Plasma Robo4 increased significantly (p<0.001) from pre-operative levels of 2515 ± 904 pg/ml to 4473 ± 1915 pg/ml, 2 h after surgery; and returned to basal levels (2682 ± 979 pg/ml) by 24 h. Plasma cytokines, vWF and NGAL also increased 2 h post-operatively and remained elevated at 24 h. Ang-2 increased 24 h post-operatively, only. There was a positive, significant correlation (r = 0.385, p = 0.0298) between Robo-4 and IL-10, but not other cytokines, 2 h post-operatively. Whilst raised Robo4 did not correlate with indices of lung dysfunction or other biomarkers of endothelial activation; there was a positive, significant correlation between raised (2 h) plasma NGAL and Robo4 (r = 0.4322, p = 0.0135). When patients were classed as AKI or non-AKI either using NGAL cut-off of 150 ng/ml, or the AKI Network (AKIN) clinical classification; plasma Robo4 was significantly higher (p = 0.0073 and 0.003, respectively) in AKI vs. non-AKI patients (NGAL cut-off: 5350 ± 2191 ng/ml, n = 16 vs. 3595 ± 1068 pg/ml, n = 16; AKIN: 6546 pg/ml, IQR 5025-8079, n = 6; vs. 3727 pg/ml, IQR 1962-3727, n = 26) subjects.Plasma Robo4 levels are increased, transiently, following cardiac surgery requiring CPB; and higher levels in patients with AKI suggest a link between endothelial dysregulation and onset of AKI