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Showing 681–700 of 2058 publications.
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Nidorf, Stefan Mark; Thompson, Peter LindsayPurpose: Colchicine is a widely available, inexpensive drug with a range of antiinflammatory properties that may make it suitable for the secondary prevention of atherosclerosis. This review examines how past and contemporary approaches to antiinflammatory therapy for atherosclerosis have led to a better understanding of the nature of the disease and sets out the reasons why colchicine has the potential to become a cornerstone therapy in its management. Methods: We performed a literature search using PubMed, the Cochrane library, and clinical trial registries to identify completed and ongoing clinical studies on colchicine in coronary artery disease, and a PubMed search to identify publications on the mechanism of action of colchicine relevant to atherosclerosis. Findings: A large body of data confirms that inflammation plays a pivotal role in atherosclerosis. The translation of this extensive knowledge into improved clinical outcomes has until recently been elusive. Findings from statin trials support the possibility that targeting inflammation may be beneficial, but this evidence has been inconclusive. Direct inhibition of atherosclerotic inflammation is being explored in current clinical trials. Targeted inhibition of interleukin 1? with canakinumab provided the proof of principle that limiting inflammation can improve outcomes in atherosclerotic vascular disease, but long-term treatment with a monoclonal antibody is unlikely to have widespread uptake. Other approaches using agents with a wider set of targets are being explored. Findings from observational studies suggest that methotrexate may reduce cardiovascular risk in patients with rheumatoid arthritis, but CIRT (Cardiovascular Inflammation Reduction Trial) demonstrated that methotrexate provided no cardiovascular benefit in patients with atherosclerotic vascular disease. Recent demonstration that cholesterol crystals trigger the NLRP3 (nucleotide oligomerization domain leucine-rich repeat and pyrin domaincontaining protein 3) inflammasome and the release of inflammatory cytokines that also drive uric acid crystalinduced inflammation indicates that the multiple actions of colchicine that make it effective in gout may be relevant to preventing inflammation and limiting inflammatory injury in atherosclerosis. The ongoing LoDoCo2 (Low Dose Colchicine2) and COLCOT (Colchicine Cardiovascular Outcomes Trial) trials and several other planned large-scale rigorous trials will determine the long-term tolerability and efficacy of low-dose colchicine for secondary prevention in patients with coronary disease. Implication: Colchicine holds promise as an important, accessible drug that could be successfully repurposed for the secondary prevention of atherosclerotic cardiovascular disease should its tolerability and cardiovascular benefits be confirmed in ongoing clinical trials. 2018 Elsevier Inc.
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Cohen, E. Myfanwy; Mohammed, Suja; Kavurma, Mary M.; Nedoboy, Polina E.; Cartland, Si; Farnham, M. M. J.; Pilowsky, Paul M.The RVLM of spontaneously hypertensive rats (SHR) contains over-active C1 neurons, which model the pathology of essential hypertension. Hypertension involves chronic low-grade neuroinflammation. Inflammation in the brain is produced and maintained primarily by microglia. We assessed microglial gene expression (P2Y12R and CX3CR1) and morphology in the RVLM of SHR compared to normotensive Wistar-Kyoto rats (WKY). The gene expression of the metabotropic purinergic receptor P2Y12 and the fractalkine receptor CX3CR1 was downregulated in the RVLM of SHR compared to WKY (by 37.3% and 30.9% respectively). P2Y12R and CX3CR1 are required for normal microglial function, and reduced P2Y12R expression is associated with changes in microglial activity. Histological analysis showed a 22.9% reduction in microglial cell density, along with 18.7% shorter microglial processes, a phenotypic indicator of activation, in the RVLM of SHR compared to WKY. These results indicate a subtle loss of function, or a mild state of inflammation, in the RVLM microglia of SHR. 2018
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Vaidya, Kaivan; Martez, Gonzalo J.; Patel, SanjayPurpose: Because inflammation is a key process implicated in the pathogenesis of atherosclerosis at all stages, including plaque formation, progression, instability, and rupture, and because colchicine has unique anti-inflammatory properties, this review article summarizes the pathophysiologic mechanisms underpinning inflammation in atherosclerosis and acute coronary syndrome (ACS), outlines anti-inflammatory therapeutic approaches that have been tested thus far, and evaluates the evidence supporting the potential role of colchicine in improving outcomes and reducing cardiovascular morbidity and mortality in patients after ACS. Methods: PubMed was searched for publications on colchicine and ACSs and atherosclerosis, and www.clinicaltrials.org was searched for completed and ongoing trials of colchicine use in ACSs. Findings: Despite contemporary optimal medical therapy, patients remain at a high risk of future events after an ACS because of residual inflammation at culprit and nonculprit sites. Several attempts have been made to address this with targeted anti-inflammatory therapies, but until the recent promising results of canakinumab (an antiinterleukin-1? monoclonal antibody), most have failed to find any prognostic benefit in large clinical trials with hard end points. The pathogenic role of neutrophils and monocytes in atheroinflammation is well established, and a fundamental component in this process is the activation of the NOD-like receptor protein 3 inflammasome, a cytosolic multiprotein complex that, when activated by a stress signal such as cholesterol crystals, drives caspase-1dependent release of 2 key proinflammatory cytokines, which are predictive of future adverse cardiovascular events: interleukin-1? and interleukin-18. Colchicine is a widely available, inexpensive, and well-tolerated medication that, among several anti-inflammatory mechanisms of action, inhibits activation of the NOD-like receptor protein 3 inflammasome complex. A seminal trial has found the beneficial properties of colchicine in reducing adverse cardiovascular events in the stable coronary artery disease population. Implications: Despite promising results in small prospective observational and randomized trials, there is a need for more evidence evaluating the role of colchicine as a secondary preventive agent after ACSs. 2018
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Callaghan, Fraser Maurice; Bannon, Paul Gerard; Barin, Edward S.; Celemajer, David S.; Jeremy, Richmond William; Figtree, Gemma A.; Grieve, Stuart M.Background: Abnormal flow dynamics play an early and causative role in pathologic changes of the ascending aorta. Purpose: To identify: 1) the changes in flow, shape, and size that occur in the ascending aorta with normal human ageing and 2) the influence of these factors on aortic flow dynamics. Study Type: Retrospective. Subjects: In all, 247 subjects (age range 1986 years, mean 49 17.7, 169 males) free of aortic or aortic valve pathology were included in this study. Subjects were stratified by youngest (1833 years; n = 64), highest (>60 years, n = 67), and the middle two quartiles (3460 years, n = 116). Field Strength/Sequence: Subjects underwent a cardiac MRI (3T) exam including 4D-flow MRI of the aorta. Assessment: Aortic curvature, arch shape, ascending aortic angle, ascending aortic diameter, and the stroke volume normalized by the aortic volume (nSV) were measured. Velocity, vorticity, and helicity were quantified across the thoracic aorta. Statistical Tests: Univariate and multivariate regressions were used to quantify continuous relationships between variables. Results: Aortic diameter, ascending aortic angle, shape, and curvature all increased across age while nSV decreased (all P < 0.0001). Systolic vorticity in the mid arch decreased by 50% across the age range (P < 0.0001), while peak helicity decreased by 80% (P < 0.0001). Curvature tightly governs optimal flow in the youngest quartile, with an effect size 1.5 to 4 times larger than other parameters in the descending aorta, but had a minimal influence with advancing age. In the upper quartile of age, flow dynamics were almost completely determined by nSV, exerting an effect size on velocity and vorticity >10 times that of diameter and other shape factors. Data Conclusion: Aortic shape influences flow dynamics in younger subjects. Flow conditions become increasingly disturbed with advancing age, and in these conditions nSV has a more dominant effect on flow patterns than shape factors. Level of Evidence: 3. Technical Efficacy: Stage 1. J. Magn. Reson. Imaging 2019;49:90100. 2018 International Society for Magnetic Resonance in Medicine
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Koo, Kevin; Inglis, Sally C.; Freedman, Ben Ben; Thijs, Vincent N.S.; Ferguson, CalebThis is a protocol for a Cochrane Review (Intervention). The objectives are as follows:. To compare the benefits, harm and the atrial high-rate episode (AHRE) detection rate of implantable cardiac monitors against conventional methods (such as electrocardiogram, ambulatory Holter monitors, event monitors and real-time telemetry) in participants with embolic stroke of unknown source. 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Thompson, Peter Lindsay[No abstract available]
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Chen, Chaohao; Wang, Fan; Wen, Shihui; Su, Qian Peter; Wu, Mike C.L.; Liu, Yongtao; Wang, Baoming; Li, Du; Shan, Xuchen; Kianinia, Mehran; Aharonovich, Igor; Toth, M.; Jackson, Shaun P.; Xi, Peng; Jin, DayongMultiphoton fluorescence microscopy (MPM), using near infrared excitation light, provides increased penetration depth, decreased detection background, and reduced phototoxicity. Using stimulated emission depletion (STED) approach, MPM can bypass the diffraction limitation, but it requires both spatial alignment and temporal synchronization of high power (femtosecond) lasers, which is limited by the inefficiency of the probes. Here, we report that upconversion nanoparticles (UCNPs) can unlock a new mode of near-infrared emission saturation (NIRES) nanoscopy for deep tissue super-resolution imaging with excitation intensity several orders of magnitude lower than that required by conventional MPM dyes. Using a doughnut beam excitation from a 980 nm diode laser and detecting at 800 nm, we achieve a resolution of sub 50 nm, 1/20th of the excitation wavelength, in imaging of single UCNP through 93 ?m thick liver tissue. This method offers a simple solution for deep tissue super resolution imaging and single molecule tracking. 2018, The Author(s).
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Breukelaar, Isabella A.; Williams, Leanne M.; Antees, Cassandra; Grieve, Stuart M.; Foster, Sheryl L.; Gomes, Lavier J.; Korgaonkar, Mayuresh S.Cognitive control is one of the most important skills in day-to-day social and intellectual functioning but we are yet to understand the neural basis of the group of behaviors required to carry this out. Here, we probed changes over time in the brain network associated with cognitive control (the dorsolateral prefrontal cortex, the dorsal posterior parietal cortex, and the dorsal anterior cingulate cortex) using both behavioral assays and functional brain imaging during a selective working memory task in 69 healthy participants within the age range 1838 years (mean: 25, SD: 6), assessed twice, 2 years apart. We aimed to explore the relationship of changing network activation and connectivity with behavioral tasks associated with cognitive control in this otherwise neurodevelopmentally stable group. We found that increased connectivity between frontoparietal cognitive control network regions during the working memory task was associated with improved memory and executive functions over the 2-year period and that this association was not impacted by age, gender, or baseline performance. These results provide evidence that changes in the functional organization of the cognitive control brain network occur despite the absence of neurodevelopment, aging or targeted cognitive training effects, and could modulate cognitive performance in early to mid-adulthood. Understanding how and why this change is occurring could provide insights into the mechanisms through which cognitive control ability is cultivated over time. This could aid in the development of interventions in cases where cognitive control is impaired. 2018 Wiley Periodicals, Inc.
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Yeung, Kristen R.; Sunderland, Neroli; Lind, Joanne Maree; Heffernan, Scott J.; Pears, Suzanne; Xu, Bei; Hennessy, Annemarie; Makris, AngelaPreeclampsia is a hypertensive disorder of pregnancy known to increase the risk of cardiovascular disease in mothers and offspring. Offspring exposed to a suboptimal intrauterine environment may experience altered fetal programming and subsequent long-term cardiovascular changes. This study investigated changes in the vascular response in offspring from experimental preeclampsia (EPE) induced by uterine artery ligation, in the absence of fetal growth restriction, compared to normal baboon pregnancies (controls), following a high salt diet challenge. After 1week of standard diet (containing <1% salt), animals were fed a high salt diet (6%) for 2weeks. Systolic and diastolic blood pressure (SBP, DBP), aldosterone, renin and creatinine clearance were evaluated in EPE (n=6, 50% male) and control (n=6, 50% male) offspring. A repeated measures analysis was performed, and P<0.05 was considered significant. At baseline, there were no differences between the groups in any parameter (EPE, mean age and weight 3.21.2years, 6.81.0kg, respectively; Control, 2.90.8years, 7.11.5kg). After salt loading the EPE group had significantly higher SBP (925mmHg) compared to the control group (834mmHg, P=0.03). Aldosterone concentration was higher in the EPE group despite the same salt excretion and no difference in renal function. Salt sensitivity may differ in offspring from hypertensive pregnancies due to fetal programming. This could have long-term consequences for cardiovascular health of EPE offspring and further research is required to determine the exact pathological mechanisms. 2018 John Wiley & Sons Australia, Ltd
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Rayner, Benjamin Saul; Zhang, Yunjia; Brown, Bronwyn E.; Reyes, Leila; Cogger, Victoria Carroll; Hawkins, Clare L.The infiltration of activated leukocytes, including macrophages, at sites of inflammation and the formation and presence of hypochlorous acid (HOCl) are interlinked hallmarks of many debilitating disease processes, including atherosclerosis, arthritis, neurological and renal disease, diabetes and obesity. The production of extracellular traps by activated leukocytes in response to a range of inflammatory stimuli is increasingly recognised as an important process within a range of disease settings. We show that exposure of human monocyte-derived macrophages to pathophysiological levels of HOCl results in the dose-dependent extrusion of DNA and histones into the cellular supernatant, consistent with extracellular trap formation. Concurrent with, but independent of these findings, macrophage exposure to HOCl also resulted in an immediate and sustained cytosolic accumulation of Ca2+, culminating in the increased production of cytokines and chemokines. Polarisation of the macrophages prior to HOCl exposure revealed a greater propensity for inflammatory M1 macrophages to produce extracellular traps, whereas alternatively-activated M2 macrophages were less susceptible to HOCl insult. M1 macrophages also produced extracellular traps on exposure to phorbol myristate acetate (PMA), interleukin-8 (IL-8) and tumour necrosis factor ? (TNF?). Taken together, these data indicate a potential role for macrophages in mediating extracellular trap formation, which may be relevant in pathological conditions characterised by chronic inflammation or excessive HOCl formation. 2018 Elsevier Inc.
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Xu, Xiaohong Ruby; Wang, Yiming; Adili, Reheman; Ju, Lining Arnold; Spring, Christopher M.; Jin, Joseph Wuxun; Yang, Hong; Neves, Miguel A.D.; Chen, Pingguo; Yang, Yan; Lei, Xi; Chen, Yunfeng; Gallant, Reid Carey; Xu, Miao; Zhang, Hailong; Song, Jina; Ke, Peifeng; Zhang, Dan; Carrim, Naadiya; Yu, Siyang; Zhu, Guangheng; She, Yimin; Cyr, Terry D.; Fu, Wenbin; Liu, Guoqing; Connelly, Philip W.; Rand, Margaret Lucille; Adeli, Khosrow; Freedman, John J.; Lee, Jeffrey E.; Tso, Patrick S.; Marchese, Patrizia; Davidson, William Sean; Jackson, Shaun P.; Zhu, Cheng; Ruggeri, Zaverio M.; Ni, HeyuPlatelet ?IIb?3 integrin and its ligands are essential for thrombosis and hemostasis, and play key roles in myocardial infarction and stroke. Here we show that apolipoprotein A-IV (apoA-IV) can be isolated from human blood plasma using platelet ?3 integrin-coated beads. Binding of apoA-IV to platelets requires activation of ?IIb?3 integrin, and the direct apoA-IV-?IIb?3 interaction can be detected using asingle-molecule Biomembrane Force Probe. We identify that aspartic acids 5 and 13 at the N-terminus of apoA-IV are required for binding to ?IIb?3 integrin, which is additionally modulated by apoA-IV C-terminus via intra-molecular interactions. ApoA-IV inhibits platelet aggregation and postprandial platelet hyperactivity. Human apoA-IV plasma levels show a circadian rhythm that negatively correlates with platelet aggregation and cardiovascular events. Thus, we identify apoA-IV as a novel ligand of ?IIb?3 integrin and an endogenous inhibitor of thrombosis, establishing a link between lipoprotein metabolism and cardiovascular diseases. 2018, The Author(s).
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Hourigan, Samuel T.; Solly, Emma L.; Nankivell, Victoria A.; Ridiandries, Anisyah; Weimann, Benjamin M.; Henriquez, Rodney; Tepper, Edward R.; Zhang, Jennifer Q.J.; Tsatralis, Tania; Clayton, Zoe E.; Vanags, Laura Z.; Robertson, Stacy; Nicholls, Stephen J.; Ng, Martin K.C.; Bursill, C. A.; Tan, Joanne Tsui MingDiabetic vascular complications are associated with impaired ischaemia-driven angiogenesis. We recently found that reconstituted high-density lipoproteins (rHDL) rescue diabetes-impaired angiogenesis. microRNAs (miRNAs) regulate angiogenesis and are transported within HDL to sites of injury/repair. The role of miRNAs in the rescue of diabetes-impaired angiogenesis by rHDL is unknown. Using a miRNA array, we found that rHDL inhibits hsa-miR-181c-5p expression in vitro and using a hsa-miR-181c-5p mimic and antimiR identify a novel anti-angiogenic role for miR-181c-5p. miRNA expression was tracked over time post-hindlimb ischaemic induction in diabetic mice. Early post-ischaemia when angiogenesis is important, rHDL suppressed hindlimb mmu-miR-181c-5p. mmu-miR-181c-5p was not detected in the plasma or within HDL, suggesting rHDL specifically targets mmu-miR-181c-5p at the ischaemic site. Three known angiogenic miRNAs (mmu-miR-223-3p, mmu-miR-27b-3p, mmu-miR-92a-3p) were elevated in the HDL fraction of diabetic rHDL-infused mice early post-ischaemia. This was accompanied by a decrease in plasma levels. Only mmu-miR-223-3p levels were elevated in the hindlimb 3 days post-ischaemia, indicating that rHDL regulates mmu-miR-223-3p in a time-dependent and site-specific manner. The early regulation of miRNAs, particularly miR-181c-5p, may underpin the rescue of diabetes-impaired angiogenesis by rHDL and has implications for the treatment of diabetes-related vascular complications. 2018, The Author(s).
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Thompson, Peter Lindsay; Mark Nidorf, S.Purpose of review Inflammation has been shown to be central to the development and progression of atherosclerosis. Despite detailed understanding of its central role and the cellular dynamics, which contribute to atherosclerotic inflammation, there has been slow progress in finding suitable agents to treat it. The recent CANTOS trial showed that the interleukin-1b inhibitor canakinumab can improve outcomes after acute coronary syndromes. Being a monoclonal antibody, it is expensive and inconvenient to administer for long-term treatment. This review summarizes recent work in finding effective, affordable alternatives to canakinumab. Recent findings Statin drugs have anti-inflammatory properties but separating their LDL lowering effect from their antiinflammatory effect has been difficult. Drugs acting on targets outside of the interleukin-1b (IL-1b) pathway have been tested without finding a suitable candidate. Following the proof of principle provided by the success of canakinumab, other candidates targeting the IL-1b pathway are undergoing detailed evaluation. The most likely candidates are low-dose methotrexate and low-dose colchicine. The potential mechanisms and ongoing clinical trials are described. Summary Targeting the IL-1b pathway has already been successful with canakinumab but its expense and inconvenience of administration may limit its widespread uptake for controlling inflammation in atherosclerosis. Low-dose methotrexate and low-dose colchicine are affordable and more accessible alternatives, currently undergoing detailed evaluation for safety and efficacy in large randomized controlled trials. 2018 Lippincott Williams and Wilkins. All rights reserved.
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O'Brien, Emily Mary; Law, David; Celermajer, David S.; Grant, Peter Watson; Waites, Jonathon H.Objective: The number of adults with congenital heart disease has increased with improvements in surgical and medical management, posing a challenge for regional and rural settings, which might have difficulties accessing specialised professionals with congenital heart disease services. This study aims to ascertain the demographics and management of adults with congenital heart disease seen by a cardiology practice in regional Australia to better understand the needs of regional adults with congenital heart disease. Design: A descriptive study using data from clinical notes collected between April 2013 and April 2016. Setting: A private cardiology practice in Coffs Harbour, New South Wales. The practice has a treating cardiologist, senior sonographer, visiting cardiothoracic surgeon and visiting paediatric cardiologist. Participants: One-hundred-and-one adults with congenital heart disease (age: 1688 years; 55 women). Main outcome measures: Congenital heart disease defect, lesion severity, referral reason, past surgery, pulmonary hypertension, cardiac surgery during the study, mortality, adherence with follow-up plans and specialist referral. Results: Sixty-six patients had simple congenital heart disease, 24 had congenital heart disease of moderate complexity and 11 had congenital heart disease of great complexity. Most were referred for surveillance, seven were referred due to pregnancy and eight were new diagnoses. Six patients died, nine had cardiac operations and five were treated for pulmonary arterial hypertension. Overall adherence to the treating cardiologist's follow-up plans was 84%. All patients with congenital heart disease of great complexity were referred to congenital heart disease specialists. Conclusion: A substantial number of patients had complex pathology, new diagnoses or required surgery, highlighting the importance of developing integrated services with the close support of outside specialists in managing adults with congenital heart disease in regional settings. 2018 National Rural Health Alliance Ltd.
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Kakall, Zohra Mohtat; Nedoboy, Polina E.; Farnham, M. M. J.; Pilowsky, Paul M.Activation of neurons in the rostral ventrolateral medulla (RVLM) following glucoprivation initiates sympathoadrenal activation, adrenaline release, and increased glucose production. Here, we aimed to determine the role of RVLM ?-opioid receptors in the counterregulatory response to systemic glucoprivation. Experiments were performed in pentobarbital sodium anesthetized male Sprague-Dawley rats (n = 30). Bilateral activation of RVLM ?-opioid receptors with [ <inf>D</inf> -Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) (8 mM, 50 nl) depressed adrenal sympathetic nerve activity for ~60 min (n = 6; ?49.9 5.8%, P < 0.05). The counterregulatory response to glucoprivation (measured by adrenal sympathetic efferent nerve activity) induced by 2-deoxyglucose (2-DG) (n = 6; ?63.6 16.5%, P < 0.05) was completely blocked 60 min after DAMGO microinjections (n = 6; ?10.2 3.5%, P < 0.05). Furthermore, DAMGO pretreat-ment attenuated the increase in blood glucose levels after 2-DG infusion (n = 6; 6.1 0.7mmol/l vs. baseline 5.2 0.3mmol/l, P > 0.05) compared with 2-DG alone (n = 6; 7.6 0.4mmol/l vs. baseline 6.0 0.4mmol/l, P < 0.05). Thus, activation of RVLM ?-opioid receptors attenuated the neural efferent response to glucoprivation and reduced glucose production. 2018 the American Physiological Society.
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Ho, Kelvin Kam Fai; Joshi, Pragnesh V.; Wong, Daniel D.; Brusch, Anna M.; Hockley, Joseph Allan; Jansen, Shirley JaneTrue aneurysms of the internal thoracic artery (ITA) are rare and are associated with vasculitides, connective tissue diseases, and infections. We report a case of a 3-cm immunoglobulin G4-positive ITA aneurysm that was excised by a hybrid approach involving open ligation of the ITA origin and video-assisted thoracoscopic aneurysmectomy. This novel technique was able to acquire tissue for histopathologic diagnosis through a minimally invasive means. 2018
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Turanov, Anton A.; Lo, Agnes Shuk Yee; Hassler, Matthew R.; Makris, Angela; Ashar-Patel, Ami; Alterman, Julia F.; Coles, Andrew H.; Haraszti, Ra nes; Roux, Lo; Godinho, Bruno M.D.C.; Echeverria, Dimas; Pears, Suzanne; Iliopoulos, Jim N.; Shanmugalingam, Renuka; Ogle, Robert F.; Zsengell, Zsuzsanna K.; Hennessy, Annemarie; Karumanchi, Subbian Ananth; Moore, Melissa J.; Khvorova, Anastasia M.Preeclampsia is a placentally induced hypertensive disorder of pregnancy that is associated with substantial morbidity and mortality to mothers and fetuses. Clinical manifestations of preterm preeclampsia result from excess circulating soluble vascular endothelial growth factor receptor FLT1 (sFLT1 or sVEGFR1) of placental origin. Here we identify short interfering RNAs (siRNAs) that selectively silence the three sFLT1 mRNA isoforms primarily responsible for placental overexpression of sFLT1 without reducing levels of full-length FLT1 mRNA. Full chemical stabilization in the context of hydrophobic modifications enabled productive siRNA accumulation in the placenta (up to 7% of injected dose) and reduced circulating sFLT1 in pregnant mice (up to 50%). In a baboon preeclampsia model, a single dose of siRNAs suppressed sFLT1 overexpression and clinical signs of preeclampsia. Our results demonstrate RNAi-based extrahepatic modulation of gene expression with nonformulated siRNAs in nonhuman primates and establish a path toward a new treatment paradigm for patients with preterm preeclampsia. 2018, Nature Publishing Group. All rights reserved.
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Neidenbach, Rhoia Clara; Niwa, Kouichiro; Oto, Oeztekin; Oechslin, Erwin Notker; Aboulhosn, Jamil Anis; Celermajer, David S.; Schelling, Jg S.; Pieper, Lars; Sanftenberg, Linda; Oberhoffer, Renate; de Haan, Fokko; Weyand, Michael; Achenbach, Stephan S.; Schlensak, Christian; Lossnitzer, Dirk; Nagdyman, Nicole; von Kodolitsch, Yskert; Kallfelz, Hans Carlo; Pittrow, David Bernhard; Bauer, Ulrike Maria Margarethe; Ewert, Peter; Meinertz, Thomas; Kaemmerer, HaraldDespite relevant residua and sequels, follow-up care of adults with congenital heart disease (ACHD) is too often not performed by/in specialized and/or certified physicians or centers although major problems in the long-term course may develop. The most relevant encompass heart failure, cardiac arrhythmias, heart valve disorders, pulmonary vascular disease, infective endocarditis (IE), aortopathy and non-cardiac comorbidities. The present publication emphasizes current data on IE, pulmonary and pulmonary arterial hypertension and aortopathy in ACHD and underlines the deep need of an experienced follow-up care by specialized and/or certified physicians or centers, as treatment regimens from acquired heart disease can not be necessarily transmitted to CHD. Moreover, the need of primary and secondary medical prevention becomes increasingly important in order to reduce the burden of disease as well as the socioeconomic burden and costs in this particular patient group. Cardiovascular Diagnosis and Therapy. All rights reserved.
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Neidenbach, Rhoia Clara; Niwa, Kouichiro; Oto, Oeztekin; Oechslin, Erwin Notker; Aboulhosn, Jamil Anis; Celermajer, David S.; Schelling, Jg S.; Pieper, Lars; Sanftenberg, Linda; Oberhoffer, Renate; de Haan, Fokko; Weyand, Michael; Achenbach, Stephan S.; Schlensak, Christian; Lossnitzer, Dirk; Nagdyman, Nicole; von Kodolitsch, Yskert; Kallfelz, Hans Carlo; Pittrow, David Bernhard; Bauer, Ulrike Maria Margarethe; Ewert, Peter; Meinertz, Thomas; Kaemmerer, HaraldToday most patients with congenital heart defects (CHD) survive into adulthood. Unfortunately, despite relevant residua and sequels, follow-up care of adults with congenital heart disease (ACHD) is not performed in specialized and/or certified physicians or centres. Major problems in the long-term course encompass heart failure, cardiac arrhythmias, heart valve disorders, pulmonary vascular disease, infective endocarditis, aortopathy and non-cardiac comorbidities. Many of them manifest themselves differently from acquired heart disease and therapy regimens from general cardiology cannot be transferred directly to CHD. It should be noted that even simple, postoperative heart defects that were until recently considered to be harmless can lead to problems with age, a fact that had not been expected so far. The treatment of ACHD has many special features and requires special expertise. Thereby, it is important that treatment regimens from acquired heart disease are not necessarily transmitted to CHD. While primary care physicians have the important and responsible task to set the course for adequate diagnosis and treatment early and to refer patients to appropriate care in specialized ACHD-facilities, they should actively encourage ACHD to pursue follow-up care in specialized facilities who can provide responsible and advanced advice. This medical update emphasizes the current data on epidemiology, heart failure and cardiac arrhythmia in ACHD. Cardiovascular Diagnosis and Therapy. All rights reserved.
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Stewart, Callum A.C.; Akhavan, Behnam; Hung, Juichien; Bao, Shishan San; Jang, Junhyeog; Wise, Steven G.; Bilek, Marcela M.M.Osseointegration is essential for ensuring optimal functioning and longevity of orthopedic implants. In a significant number of patients, the body does not fully integrate with the orthopedic implant, which opens the potential for the formation of bacterial biofilms and adverse foreign body reactions. Protein-functionalization of the implant surfaces can reduce this potential by stimulating rapid cell attachment or bone formation. Ideally, a multifunctional protein surface should simultaneously stimulate cell attachment and bone formation for optimal osseointegration. In this study, we utilized primary mouse osteoblasts to examine the osteogenic potential of a multifunctional fusion protein, combining the fibronectin (FN) attachment and osteocalcin (OCN) bone signaling sequences, compared against that of the individual proteins. These three biomolecules were immobilized on radical-functionalized plasma polymer films (rPPFs) that covalently bond proteins through interactions with embedded radicals that migrate to the surface. The fusion protein was also compared to a coimmobilized ratio of FN:OCN prepared through a two-step sequential exposure to OCN solution followed by FN solution. The preparation and characterization overhead for the two protein surfaces was substantial when compared to the fusion protein functionalization process. Significantly greater osteoblast attachment and spreading were observed for the FN, FN:OCN, and fusion protein surfaces compared to titanium (p < 0.05), while the calcium deposition after 17 days showed a significant increase (p < 0.01) on the fusion protein surface alone. The greater osseointegration potential of the fusion protein surface compared to the single and coimmobilized protein surfaces is attributed to the homogeneous distribution of the attachment and signaling sequences. Overall, the fusion protein-coated rPPFs produced easily functionalizable and highly osteogenic surfaces with the potential to greatly improve the tissue integration of orthopedic implants. 2018 American Chemical Society.
