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Showing 861–880 of 2058 publications.
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Leung, Christopher; Herath, C. B.; Jia, Zhiyuan; Andrikopoulos, Sofianos; Brown, Bronwyn E.; Davies, Michael J.; Rivera, Leni Rose; Furness, John B.; Forbes, Josephine Maree; Angus, PWAIM To determine if manipulation of dietary advanced glycation end product (AGE), intake affects nonalcoholic fatty liver disease (NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol (HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mRNA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content (a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, ?-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/- animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD. The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
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Geronimo, Francis Ruel B.; Barter, Philip J.; Rye, Kerry Anne; Heather, Alison Kay; Shearston, Kate D.; Rodgers, Kenneth JohnBackground and aims: Apolipoprotein (apo) A-IV, the third most abundant HDL-associated protein, is atheroprotective and shares similar properties as apoA-I. We have reported previously that apoA-I, the most abundant apolipoprotein in HDL, inhibits plaque disruption in a mouse model. We aimed at examining the effects of apoA-IV on markers of plaque stability in vivo. Methods: Plaques within brachiocephalic arteries of 16-week old apoE-knockout C57BL/6 mice were examined for changes in composition after 10 weeks on a high-fat diet (HFD). The animals received twice-weekly injections of human lipid-free apoA-IV (1 mg/kg, n = 31) or PBS (n = 32) during the 9th and 10th weeks of the HFD. Results: In the apoA-IV treated mice, there were significantly fewer hemorrhagic plaque disruptions (9/31 vs. 18/32, p < 0.05), thicker fibrous caps, smaller lipid cores, a lower macrophage:SMC ratio, less MMP-9 protein, more collagen, and fewer proliferating cells. In the plaques of mice given apoA-IV, MCP-1, VCAM-1, and inducible NOS were also significantly lower. Based on the percentage of cleaved PARP-positive and TUNEL-positive plaque nuclei, apoA-IV reduced apoptosis. in HMDMs, apoA-IV reduced MMP-9 mRNA expression by half, doubled mRNA levels of TIMP1 and decreased MMP-9 activity. Conclusions: ApoA-IV treatment is associated with a more stable plaque phenotype and a reduced incidence of acute disruptions in this mouse model. 2016.
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Degendorfer, Georg; Chuang, Christine Y.; Kawasaki, Hiroaki; Hammer, Astrid; Malle, Ernst; Yamakura, Fumiyuki; Davies, Michael J.Fibronectin is a large dimeric glycoprotein present in both human plasma and in basement membranes. The latter are specialized extracellular matrices underlying endothelial cells in the artery wall. Peroxynitrous acid (ONOOH) a potent oxidizing and nitrating agent, is formed in vivo from superoxide and nitric oxide radicals by stimulated macrophages and other cells. Considerable evidence supports ONOOH involvement in human atherosclerotic lesion development and rupture, possibly via extracellular matrix damage. Here we demonstrate that Tyr and Trp residues on human plasma fibronectin are highly sensitive to ONOOH with this resulting in the formation of 3-nitrotyrosine, 6-nitrotryptophan and dityrosine as well as protein aggregation and fragmentation. This occurs with equimolar or greater levels of oxidant, and in a dose-dependent manner. Modification of Tyr was quantitatively more significant than Trp (9.1% versus 1.5% conversion with 500?M ONOOH) after accounting for parent amino acid abundance, but only accounts for a small percentage of the total oxidant added. LC-MS studies identified 28 nitration sites (24 Tyr, 4 Trp) with many of these present within domains critical to protein function, including the cell-binding and anastellin domains. Human coronary artery endothelial cells showed decreased adherence and cell-spreading on ONOOH-modified fibronectin compared to control, consistent with cellular dysfunction induced by the modified matrix. Studies on human atherosclerotic lesions have provided evidence for co-localization of 3-nitrotyrosine and fibronectin. ONOOH-mediated fibronectin modification and compromised cell-matrix interactions, may contribute to endothelial cell dysfunction, a weakening of the fibrous cap of atherosclerotic lesions, and an increased propensity to rupture. 2016 Elsevier B.V.
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Abbott, Stephen B.G.; Machado, Natalia Lima; Geerling, Joel C.; Saper, Clifford B.Stimulation of glutamatergic neurons in the subfornical organ drives drinking behavior, but the brain targets that mediate this response are not known. The densest target of subfornical axons is the anterior tip of the third ventricle, containing the median preoptic nucleus (MnPO) and organum vasculosum of the lamina terminalis (OVLT), a region that has also been implicated in fluid and electrolyte management. The neurochemical composition of this region is complex, containing both GABAergic and glutamatergic neurons, but the possible roles of these neurons in drinking responses have not been addressed. In mice, we show that optogenetic stimulation of glutamatergic neurons in MnPO/OVLT drives voracious water consumption, and that optogenetic stimulation of GABAergic neurons in the same region selectively reduces water consumption. Both populations of neurons have extensive projections to overlapping regions of the thalamus, hypothalamus, and hindbrain that are much more extensive than those from the subfornical organ, suggesting that the MnPO/OVLT serves as a key link in regulating drinking responses. 2016 the authors.
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Kapoor, Komal; Bhandare, Amol M.; Nedoboy, Polina E.; Mohammed, Suja; Farnham, M. M. J.; Pilowsky, Paul M.Microglia are present throughout the central nervous system (CNS) and express receptors for every known neurotransmitter. During inflammation, microglia change into a state that either promotes removal of debris (M1), or into a state that promotes soothing (M2). Caudal- and rostral- ventrolateral medullary regions (CVLM and RVLM, respectively) of the brainstem are key nuclei involved in all aspects of the cardiovascular system. In this study, we investigate a novel role for microglia in cardiovascular control in the brainstem of adult male Sprague-Dawley (SD) rat. Here we show, that increases and decreases in blood pressure (BP) triggers alertness in the physiology of microglia in the brainstem region; inducing changes in microglial spatial distribution and the number of synapses in contact with microglial end processes. Following 6 h of acute hypertension, the number of synapses in contact with microglia increased by ?30% in both regions of the brainstem, CVLM and RVLM. Induction of acute hypotension for 6 h causes microglia to reduce the number of synaptic contacts by >20% in both, CVLM and RVLM, nuclei of the brainstem. Our analysis of the morphological characteristics of microglia, and expression levels of M1 and M2, reveals that the changes induced in microglial behavior do not require any obvious dramatic changes in their morphology. Taken together, our findings suggest that microglia play a novel, unexpected, physiological role in the uninjured autonomic nuclei of CNS; we therefore speculate that microglia act cooperatively with brainstem cardiovascular neurons to maintain them in a physiologically receptive state. 2016 IBRO.
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Wise, Steven G.; Liu, Hongjuan; Kondyurin, Alexey V.; Byrom, Michael John; Bannon, Paul Gerard; Edwards, Glenn Anthony; Weiss, Anthony Steven; Bao, Shishan San; Bilek, Marcela M.M.Expanded polytetrafluoroethylene (ePTFE) vascular conduits with less than or equal to 6 mm internal diameter typically occlude due to a combination of thrombus formation and neointimal hyperplasia. We hypothesized that by layering the polymerized elastin precursor, human tropoelastin, in the synthetic vessel lumen we could mimic the internal elastic lamina and so maintain low thrombogenicity while significantly reducing smooth muscle cell proliferation. The luminal surfaces of ePTFE conduits were activated with plasma immersion ion implantation (PIII) treatment to facilitate covalent attachment of tropoelastin. Multilayered tropoelastin vessels (2TE) enhanced endothelial cell attachment and proliferation in vitro and were superior to materials lacking the protein. In an ovine carotid interposition model of graft compatibility, partially tropoelastin coated vessels (1TE) thrombosed at a greater rate than control ePTFE, but 2TE maintained the same patency as controls. 2TE showed a significant reduction in neointimal area down to 9.7 5.2% (p < 0.05) in contrast to 32.3 3.9% for ePTFE alone. This reduction was due to a halving of the number of smooth muscle cells present and a corresponding reduction in their proliferation. 2TE, but not 1TE, enhanced the vascular compatibility of these materials: while both tropoelastin presentations increased in vitro endothelialization, only 2TE displayed the dual benefits of maintained hemocompatibility and simultaneously suppressed neointimal hyperplasia in vivo. We conclude that 2TE surface modification provides a significant improvement over ePTFE vascular conduits in a pilot large animal model study and presents an attractive path toward clinical applications for reduced diameter vessels. 2016 American Chemical Society.
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Freedman, Ben Ben; Potpara, Tatjana S.; Lip, Gregory Y.H.Atrial fibrillation is found in a third of all ischaemic strokes, even more after post-stroke atrial fibrillation monitoring. Data from stroke registries show that both unknown and untreated or under treated atrial fibrillation is responsible for most of these strokes, which are often fatal or debilitating. Most could be prevented if efforts were directed towards detection of atrial fibrillation before stroke occurs, through screening or case finding, and treatment of all patients with atrial fibrillation at increased risk of stroke with well-controlled vitamin K antagonists or non-vitamin K antagonist anticoagulants. The default strategy should be to offer anticoagulant thromboprophylaxis to all patients with atrial fibrillation unless defined as truly low risk by simple validated risk scores, such as CHA<inf>2</inf>DS<inf>2</inf>-VASc. Assessment of bleeding risk using the HAS-BLED score should focus attention on reversible bleeding risk factors. Finally, patients need support from physicians and various other sources to start anticoagulant treatment and to ensure adherence to and persistence with treatment in the long term. 2016 Elsevier Ltd
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Lam, Yuen Ting; Lecce, Laura; Clayton, Zoe E.; Simpson, Philippa J.L.; Karas, Richard H.; Ng, Martin K.C.Background: Aging is associated with impaired ischemia-induced neovascularization. However, the effects of aging on bone marrow-derived angiogenic cell (BMDAC)-mediated vasculogenesis and on angiogenesis at the ischemic sites remain incompletely understood. Methods and results: Two- and 24-month old male C57Bl/6J mice were subjected to hindlimb ischemia. The levels of Sca1 +/CXCR4 + BMDACs were determined post-ischemia by flow cytometry. In young mice, ischemia increased Sca1 +/CXCR4 + BMDAC levels in the bone marrow and spleen at day 3 (p < 0.001) and in the circulating blood at day 7 (p < 0.01) post-ischemia. However, ischemia-induced elevation of progenitor cells was attenuated in the bone marrow, spleen and blood of old mice despite a preserved HIF-1?-mediated angiogenic response in the ischemic tissues. Irradiated young recipient mice engrafted with old bone marrow displayed reduced levels of Sca1 +/CXCR4 + BMDACs in the bone marrow and circulating blood post-ischemia compared to recipients with young bone marrow. Ex vivo cultured BMDACs from old mice exhibited reduced SDF-1-stimulated migration (p < 0.01) and a decrease in JAK-2 and AKT activation. However, the intrinsic angiogenic function of BMDACs, including VEGF secretion and promotion of endothelial cell tubule formation, was preserved with aging. Furthermore, facilitated mobilization of old bone marrow-derived mononuclear cells to the ischemic hindlimb by intramuscular injection enhanced ischemia-induced neovascularization in old mice in vivo (p < 0.001). Conclusions: The age-related impairment in ischemia-induced neovascularization is largely attributable to a marked attenuation of BMDAC mobilization with a preservation of intrinsic angiogenic function with age. 2016.
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Kim, Seung Jae; Pilowsky, Paul M.; Farnham, M. M. J.Intermittent hypoxia causes a persistent increase in sympathetic nerve activity (SNA), which progresses to hypertension in conditions such as obstructive sleep apnea. Orexins (A and B) are hypothalamic neurotransmitters with arousal-promoting and sympathoexcitatory effects. We investigated whether the sustained elevation of SNA, termed sympathetic long- Term facilitation, after acute intermittent hypoxia (AIH) is caused by endogenous orexin acting on spinal sympathetic preganglionic neurons. The role of orexin in the increased SNA response to AIH was investigated in urethane- Anesthetized, vagotomized, and artificially ventilated Sprague-Dawley rats (n 5 58). A spinally infused subthreshold dose of orexin-A (intermittent; 10 pmol X 10) produced long- Term enhancement in SNA (41.4% 6 6.9%) from baseline. This phenomenon was not produced by the same dose of orexin-A administered as a bolus intrathecal infusion (100 pmol; 7.3% 6 2.3%). The dual orexin receptor blocker, Almorexant, attenuated the effect of sympathetic long- Term facilitation generated by intermittent orexin-A (20.7% 6 4.5% for Almorexant at 30 mgkg21 and 18.5%61.2% for 75 mgkg21), but not in AIH. The peripheral chemoreflex sympathoexcitatory response to hypoxia was greatly enhanced by intermittent orexin-A and AIH. In both cases, the sympathetic chemoreflex sensitization was reduced by Almorexant. Taken together, spinally acting orexin-A is mechanistically sufficient to evoke sympathetic long- Term facilitation. However, AIH-induced sympathetic long- Term facilitation appears to rely on mechanisms that are independent of orexin neurotransmission. Our findings further reveal that the activation of spinal orexin receptors is critical to enhance peripheral chemoreceptor responses to hypoxia after AIH. 2016 by The American Society for Pharmacology and Experimental Therapeutics.
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Tsatralis, Tania; Ridiandries, Anisyah; Robertson, Stacy; Vanags, Laura Z.; Lam, Yuen Ting; Tan, Joanne Tsui Ming; Ng, Martin K.C.; Bursill, C. A.Background: The average population age is increasing and the incidence of age-related vascular complications is rising in parallel. Impaired wound healing and disordered ischemia-mediated angiogenesis are key contributors to age-impaired vascular complications that can lead to amputation. High-density lipoproteins (HDL) have vasculo-protective properties and augment ischemia-driven angiogenesis in young animals. We aimed to determine the effect of reconstituted HDL (rHDL) on aged mice in a murine wound healing model and the hindlimb ischemia (HLI) model. Methods: Murine wound healing model - 24-month-old aged mice received topical application of rHDL (50 ?g/wound/day) or PBS (vehicle control) for 10 days following wounding. Murine HLI model - Femoral artery ligation was performed on 24-month-old mice. Mice received rHDL (40 mg/kg) or PBS, intravenously, on alternate days, 1 week pre-surgery and up to 21 days post ligation. For both models, blood flow perfusion was determined using laser Doppler perfusion imaging. Mice were sacrificed at 10 (wound healing) or 21 (HLI) days post-surgery and tissues were collected for histological and gene analyses. Results: Daily topical application of rHDL increased the rate of wound closure by Day 7 post-wounding (25 %, p < 0.05). Wound blood perfusion, a marker of angiogenesis, was elevated in rHDL treated wounds (Days 4-10 by 22-25 %, p < 0.05). In addition, rHDL increased wound capillary density by 52.6 %. In the HLI model, rHDL infusions augmented blood flow recovery in ischemic limbs (Day 18 by 50 % and Day 21 by 88 %, p < 0.05) and prevented tissue necrosis and toe loss. Assessment of capillary density in ischemic hindlimb sections found a 90 % increase in rHDL infused animals. In vitro studies in fibroblasts isolated from aged mice found that incubation with rHDL was able to significantly increase the key pro-angiogenic mediator vascular endothelial growth factor (VEGF) protein (25 %, p < 0.05). Conclusion: rHDL can promote wound healing and wound angiogenesis, and blood flow recovery in response to ischemia in aged mice. Mechanistically, this is likely to be via an increase in VEGF. This highlights a potential role for HDL in the therapeutic modulation of age-impaired vascular complications. 2016 The Author(s).
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OSullivan, John F.; Neylon, Antoinette M.; McGorrian, Catherine M.; Blake, Gavin J.Background MicroRNAs (miRNAs), small non-coding RNAs, have been implicated as regulators of all mediators of atherosclerosis, and some reports have suggested increased levels in coronary artery disease (CAD) and acute myocardial infarction (AMI). However, the potential of miRNAs as biomarkers or predictors of disease remains to be established. Methods We designed a study comprising 150 patients (50 Control, 50 Stable CAD, and 50 ST Elevation Myocardial Infarction (STEMI)), and measured plasma miRNAs in each. We then determined the ability of differential miRNAs, adjusting for Framingham Heart Study (FHS) risk factors, to discriminate between CAD vs Control, and STEMI vs Control. Results Three miRNAs (miR15a-5p, miR16-5p, and miR93-5p) were significantly increased in Stable CAD vs Control groups and one (miR146a-5p) was significantly decreased in Stable CAD vs Control. One miRNA miR499a-5p was significantly increased in the STEMI group compared to Controls. After adjustment for FHS risk factors, miR93-5p levels remained an independent predictor of the presence of CAD (Odds Ratio [OR]=8.76, P=0.002). All 4 miRNAs improved discriminatory power for CAD over FHS alone in ROC analysis. Similarly, after adjustment for risk factors miR499-5p remained an independent predictor of STEMI (OR=3.03, P=0.001) and improved discriminatory power for STEMI in ROC analyses. Conclusion We identified 4 miRNAs that were differentially expressed among stable CAD and control patients, and 1 miRNA that was elevated in STEMI patients vs controls. MiR93-5p was the strongest predictor of CAD after adjustment for traditional risk factors, suggesting potential diagnostic utility. 2016 Elsevier Ireland Ltd
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Schoenwaelder, Simone M.; Darbousset, Roxane; Cranmer, Susan L.; Ramshaw, Hayley S.; Orive, Stephanie L.; Sturgeon, Sharelle A.; Yuan, Yuping; Yao, Yu; Krycer, James Robert; Woodcock, Joanna M.; Maclean, Jessica A.A.; Pitson, Stuart M.; Zheng, Zhaohua; Henstridge, Darren Colin; van der Wal, Dianne E.; Gardiner, Elizabeth E.; Berndt, Michael C.; Andrews, Robert K.; James, David Ernest; Lopez, Angel F.; Jackson, Shaun P.The 14-3-3 family of adaptor proteins regulate diverse cellular functions including cell proliferation, metabolism, adhesion and apoptosis. Platelets express numerous 14-3-3 isoforms, including 14-3-3?, which has previously been implicated in regulating GPIb? function. Here we show an important role for 14-3-3? in regulating arterial thrombosis. Interestingly, this thrombosis defect is not related to alterations in von Willebrand factor (VWF)-GPIb adhesive function or platelet activation, but instead associated with reduced platelet phosphatidylserine (PS) exposure and procoagulant function. Decreased PS exposure in 14-3-3? -deficient platelets is associated with more sustained levels of metabolic ATP and increased mitochondrial respiratory reserve, independent of alterations in cytosolic calcium flux. Reduced platelet PS exposure in 14-3-3? -deficient mice does not increase bleeding risk, but results in decreased thrombin generation and protection from pulmonary embolism, leading to prolonged survival. Our studies define an important role for 14-3-3? in regulating platelet bioenergetics, leading to decreased platelet PS exposure and procoagulant function. The Author(s) 2016.
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Tan, Joanne Tsui Ming; Prosser, Hamish C.G.; Dunn, Louise L.; Vanags, Laura Z.; Ridiandries, Anisyah; Tsatralis, Tania; Leece, Laura; Clayton, Zoe E.; Yuen, Sui Ching G.; Robertson, Stacy; Ting Lam, Yuen; Celermajer, David S.; Ng, Martin K.C.; Bursill, C. A.Disordered neovascularization and impaired wound healing are important contributors to diabetic vascular complications. We recently showed that high-density lipoproteins (HDLs) enhance ischemia-mediated neovascularization, and mounting evidence suggests HDL have antidiabetic properties. We therefore hypothesized that HDL rescue diabetes-impaired neovascularization. Streptozotocin-induced diabetic mice had reduced blood flow recovery and neovessel formation in a hindlimb ischemia model compared with nondiabetic mice. Reconstituted HDL (rHDL) infusions in diabetic mice restored blood flow recovery and capillary density to nondiabetic levels. Topical rHDL application rescued diabetes-impaired wound closure, wound angiogenesis, and capillary density. In vitro, rHDL increased keymediators involved in hypoxia-inducible factor-1? (HIF-1?) stabilization, including the phosphoinositide 3-kinase/Akt pathway, Siah1, and Siah2, and suppressed the prolyl hydroxylases (PHD) 2 and PHD3. rHDL rescued high glucose-induced impairment of tubulogenesis and vascular endothelial growth factor (VEGF) A protein production, a finding associated with enhanced phosphorylation of proangiogenic mediators VEGF receptor 2 and endothelial nitric oxide synthase. Siah1/2 small interfering RNA knockdown confirmed the importance of HIF-1a stability in mediating rHDL action. Lentiviral short hairpin RNA knockdown of scavenger receptor class B type I (SR-BI) in vitro and SR-BI-/- diabetic mice in vivo attenuated rHDL rescue of diabetes-impaired angiogenesis, indicating a key role for SR-BI. These findings provide a greater understanding of the vascular biological effects of HDL, with potential therapeutic implications for diabetic vascular complications. 2016 by the American Diabetes Association.
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Freedman, Ben Ben; Lip, Gregory Y.H.[No abstract available]
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Orchard, Jessica Joan; Lowres, Nicole; Freedman, Ben Ben; Ladak, Laila Akbar; Lee, William; Zwar, Nicholas Arnold; Peiris, David P.; Kamaladasa, Yasith; Li, Jialin; Neubeck, LisBackground People with unknown atrial fibrillation (AF), who are often asymptomatic, have a substantially increased risk of stroke. Although recommended in European guidelines, AF screening is not routinely performed. Screening at the time of influenza vaccination presents an ideal opportunity to detect AF in large numbers in a primary care medical setting, with an existing annual recall system for patients aged ?65 years. Design Cross-sectional pilot study of handheld smartphone electrocardiogram (iECG) screening to identify unknown AF. Methods General practices in Sydney, Australia, were recruited during the influenza-vaccination period of April-June 2015. Practice nurses screened patients aged ?65 years with a 30-second iECG, which has a validated algorithm for detecting AF in real time. In order to confirm the accuracy of the algorithm, two research cardiologists reviewed de-identified iECGs. In order to explore barriers and enablers, semi-structured interviews were conducted with selected nurses, practice managers and general practitioners. Results Five general practices were recruited, and 973/2476 (39%) patients attending influenza vaccination were screened. Screening took an average of 5 minutes (range 1.5-10 minutes); however, abnormal iECGs required additional time. Newly identified AF was found in 8/973 patients (0.8%). The sensitivity of the iECG automated algorithm was 95% (95% confidence interval: 83-99%) and the specificity was 99% (95% confidence interval: 98-100%). Screening by practice nurses was well accepted by practice staff. Key enablers were the confidence and competence of nurses and a 'designated champion' to lead screening at the practice. Barriers were practice specific, and mainly related to staff time and funding. Conclusions Screening with iECG during influenza vaccination by primary care nurses is feasible and well accepted by practice staff. Addressing barriers is likely to increase uptake. European Society of Cardiology.
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Gray, Belinda R.; Klimis, Harry; Inam, Shafqat; Ariyarathna, Nilshan; Kumar, Shweta; Bailey, Brian P.; Patel, SanjayThe authors regret a misspelling of the fourth author name. The corrected author line is: Belinda Gray, FRACP a,b,d, Harry Klimis, MBBSa,b, Shafqat Inam, MBBSa, Nilshan Ariyarathna, MBBSa, Shweta Kumar, MBBSa, Brian Bailey, FRACPa, Sanjay Patel, FRACP PhDa,b,c* The authors would like to apologise for any inconvenience caused. 2016
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Lowres, Nicole; Neubeck, Lis; Freedman, Ben Ben[No abstract available]
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Tweeddale, Helen J.; Hawkins, Clare L.; Jamie, Joanne F.; Truscott, Roger John Willis; Davies, Michael J.Long-wavelength solar UV radiation is implicated in photodamage to the human eye. The human lens contains multiple tryptophan-derived compounds that have significant absorbance bands in the UVA region (? 315400 nm) that act as efficient physical filters for these wavelengths. The concentrations of many of these UV filter compounds decrease with increase in age, resulting in diminished protection, increased oxidative damage and the accumulation of modified proteins implicated in nuclear cataract formation. This damage may arise via the formation of ?,?-unsaturated carbonyls from the UV filter compounds, adduction to lens proteins and subsequent action as photosensitizers, and/or via the reactions of redox-active transition metal ions that accumulate in aged human lenses. The latter may promote the oxidation of free, or protein-bound, o-aminophenols, such as the UV filter compounds 3-hydroxykynurenine (3OHKyn) and 3-hydroxyanthranilic acid (3OHAA). It is shown here that Cu(II), and to a lesser extent Fe(III), enhance oxidation of free 3OHKyn, 3OHAA and 3OHKyn bound to specific amino acids and lens proteins, with this resulting in increased cross-linking of lens proteins. These data indicate that elevated levels of transition metal ions in aging lenses can enhance the loss of protective UV filter compounds, and contribute to the formation of high-molecular-mass dysfunctional crystallin proteins in a light-independent manner. These reactions may contribute to the formation of lens cataracts in humans. 2016 Informa UK Limited, trading as Taylor & Francis Group.
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Akhavan, Behnam; Wise, Steven G.; Bilek, Marcela M.M.Although plasma polymerization is traditionally considered as a substrate-independent process, we present evidence that the propensity of a substrate to form carbide bonds regulates the growth mechanisms of plasma polymer (PP) films. The manner by which the first layers of PP films grow determines the adhesion and robustness of the film. Zirconium, titanium, and silicon substrates were used to study the early stages of PP film formation from a mixture of acetylene, nitrogen, and argon precursor gases. The correlation of initial growth mechanisms with the robustness of the films was evaluated through incubation of coated substrates in simulated body fluid (SBF) at 37 for 2 months. It was demonstrated that the excellent zirconium/titanium-PP film adhesion is linked to the formation of metallic carbide and oxycarbide bonds during the initial stages of film formation, where a 2D-like, layer-by-layer (Frank-van der Merwe) manner of growth was observed. On the contrary, the lower propensity of the silicon surface to form carbides leads to a 3D, island-like (Volmer-Weber) growth mode that creates a sponge-like interphase near the substrate, resulting in inferior adhesion and poor film stability in SBF. Our findings shed light on the growth mechanisms of the first layers of PP films and challenge the property of substrate independence typically attributed to plasma polymerized coatings. 2016 American Chemical Society.
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Ridiandries, Anisyah; Tan, Joanne Tsui Ming; Bursill, C. A.Angiogenesis, the formation of new blood vessels, is critical for survival and in the regenerative response to tissue injury or ischemia. However, in diseases such as cancer and atherosclerosis, inflammation can cause unregulated angiogenesis leading to excessive neovascularization, which exacerbates disease. Current anti-angiogenic therapies cause complete inhibition of both inflammatory and ischemia driven angiogenesis causing a range of side effects in patients. Specific inhibition of inflammation-driven angiogenesis would therefore be immensely valuable. Increasing evidence suggests that the CC-chemokine class promotes inflammation-driven angiogenesis, whilst there is little evidence for a role in ischemia-mediated angiogenesis. The differential regulation of angiogenesis by CC-chemokines suggests it may provide an alternate strategy to treat angiogenesis associated pathological diseases. The focus of this review is to highlight the significant role of the CC-chemokine class in inflammation, versus ischemia driven angiogenesis, and to discuss the related pathologies including atherosclerosis, cancer, and rheumatoid arthritis. We examine the pros and cons of anti-angiogenic therapies currently in clinical trials. We also reveal novel therapeutic strategies that cause broad-spectrum inhibition of the CC-chemokine class that may have future potential for the specific inhibition of inflammatory angiogenesis. 2016 by the authors; licensee MDPI, Basel, Switzerland.
