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Showing 381–400 of 2058 publications.
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Luo, Kaiming; Stocker, Roland; Britton, Warwick J.; Kikuchi, Kazu; Oehlers, Stefan H.Iron homeostasis is essential for both sides of the hostpathogen interface. Restricting access of iron slows bacterial growth while iron is also a necessary cofactor for host immunity. Haem oxygenase 1 (HMOX1) is a critical regulator of iron homeostasis that catalyses the liberation of iron during degradation of haem. It is also a stress-responsive protein that can be rapidly upregulated and confers protection to the host. Although a protective role of HMOX1 has been demonstrated in a variety of diseases, the role of HMOX1 in Mycobacterium tuberculosis infection is equivocal across experiments with different hostpathogen combinations. Here, we use the natural hostpathogen pairing of the zebrafish-Mycobacterium marinum infection platform to study the role of zebrafish haem oxygenase in mycobacterial infection. We identify zebrafish Hmox1a as the relevant functional paralog of mammalian HMOX1 and demonstrate a conserved role for Hmox1a in protecting the host from M. marinum infection. Using genetic and chemical tools, we show zebrafish Hmox1a protects the host against M. marinum infection by reducing infection-induced iron accumulation and ferrostatin-sensitive cell death. 2021 Federation of European Biochemical Societies
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Petrossian, Gregory; Ozdemir, Denizhan; Galougahi, Keyvan Karimi; Scheiner, Jonathan; Thomas, Susan V.; Shlofmitz, Richard Alan; Shlofmitz, Evan S.; Jeremias, Allen; Ali, Ziad A.Intravascular imaging with optical coherence tomography (OCT) and intravascular ultrasound provides superior visualization of the culprit plaques for acute coronary syndromes (ACS) compared with coronary angiography. Combined with angiography, intravascular imaging can be used to instigate 'precision therapy' for ACS. Post-mortem histopathology identified atherothrombosis at the exposed surface of a ruptured fibrous cap as the main cause of ACS. Further histopathological studies identified intact fibrous caps and calcified nodules as other culprit lesions for ACS. These plaque types were subsequently also identified on intravascular imaging, particularly with the high-resolution OCT. The less-common non-atherothrombotic causes of ACS are coronary artery spasm, coronary artery dissection, and coronary embolism. In this review, the authors provide an overview of clinical studies using intravascular imaging with OCT in the diagnosis and management of ACS. RADCLIFFE CARDIOLOGY 2022
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Kong, Wanwen; Ma, Junyi; Lin, Ying; Chen, WeiyuAim. Atherosclerosis is the major cause of acute coronary syndrome (ACS) which is a significant contributor to both morbidity and mortality in the world. The microbiome-derived metabolite trimethylamine-N-oxide (TMAO) has aroused great interest and controversy as a risk factor of atherosclerosis. Therefore, in this study, we aimed at investigating whether plasma TMAO can be a risk factor of atherosclerosis in coronary artery of patients with ACS and how this relates to lipids and proinflammatory cytokines in plasma. Methods. We enrolled consecutive patients with ACS who underwent percutaneous coronary intervention (PCI). Gensini scoring was used to evaluate angiographic atherosclerosis in the coronary artery of the patients. 13 patients were divided into low (Gensini score<25), 33 into intermediate (Gensini score 25-50), and 81 into severe atherosclerosis (Gensini score ?50). Plasma TMAO, vasculitis factors, and cardiovascular biomarkers were measured by clinical biochemistry, intima-media thickness (IMT) of carotid artery was determined by the Color Doppler ultrasound, and the atherosclerotic lesion in coronary artery was assessed in PCI. Results. Plasma TMAO concentrations were positively associated with Gensini score (OR=0.629, p<0.001) and Gensini subgroup (R=0.604, p<0.001). Plasma TMAO concentrations in patients with severe coronary atherosclerosis were higher than those of patients with moderate coronary atherosclerosis, and the plasma TMAO concentrations of patients with moderate coronary atherosclerosis were higher than those of patients with mild coronary atherosclerosis, the difference was statistically significant [4.73 (3.13, 4.62) versus 1.13 (0.63, 3.34) versus 0.79 (0.20, 1.29), p<0.001], respectively. Furthermore, ROC analysis showed that plasma TMAO could identify the severity of atherosclerosis (p<0.001). The AUC of TMAO for severe atherosclerosis was 0.852 (95%CI=0.779-0.925). The sensitivity and specificity of TMAO for identifying severe atherosclerosis are 96.3% and 63.0% when the cut-off value of TMAO was set at 1.2715 pg/ml. Furthermore, logistic regression analysis showed plasma TMAO concentrations were positively associated with severity of atherosclerosis in coronary artery (OR=1.934, 95%CI=1.522-2.459, p<0.001). For all that, negatively association was observed between TMAO and age (OR=-0.224, p<0.05), B-Type natriuretic peptide (BNP) (OR=-0.175, p<0.05), and interleukin-8 (IL-8) (OR=-0.324, p<0.001), while positive association was observed between TMAO and nitric oxide (NO) (OR=0.234, p<0.01). However, there is no obvious association was observed between Gensini score and cardiovascular biomarkers, vasculitis factors, and carotid IMT, respectively. Conclusion. Our cross-sectional observation suggested that plasma TMAO concentrations positively associated with coronary atherosclerosis in ACS patients and serve as a risk factor for severe atherosclerosis. Plasma TMAO also correlated with age, BNP, IL-8, and NO. However, no obvious association was found between atherosclerosis with vasculitis factors and cardiovascular biomarkers in this study, and there was no conclusive evidence showing TMAO enhance atherosclerosis via regulation of inflammation or lipid. 2022 Wanwen Kong et al.
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Wadey, Curtis; Barker, Alan R.; Stuart, Graham A.; Tran, Derek L.; Laohachai, Karina; Ayer, Julian Ganesh J.; Cordina, Rachael Louise; Williams, Craig A.BACKGROUND: Peak oxygen consumption (peak?VO<inf>2</inf>) is traditionally divided (ratio-scaled) by body mass (BM) for clinical interpretation. Yet, it is unknown whether ratio-scaling to BM can produce a valid size-independent expression of peak?VO<inf>2</inf> in people with a Fontan circulation. Furthermore, people with a Fontan circulation have deficits in lean mass, and it is unexplored whether using different measures of body composition may improve scaling validity. The objective was to assess the validity of different scaling denominators (BM, stature, body surface area, fat-free mass, lean mass, and appendicular lean mass using ratio and allometric scaling). METHODS AND RESULTS: Eighty-nine participants (age: 23.36.7 years; 53% female) with a Fontan circulation had their cardiorespiratory fitness and body composition measured by cardiopulmonary exercise testing and dual-energy x-ray absorptiometry. Ratio and allometric (log-linear regression) scaling was performed and Pearson correlations assessed scaling validity. Scaling denominators BM (r=?0.25, P=0.02), stature (r=0.46, P<0.001), and body surface area (0.23, P=0.03) were significantly correlated with their respective ratio-scaled expressions of peak?VO<inf>2</inf>, but fat-free mass, lean mass, or appendicular lean mass were not (r?0.11; R2=1%). Allometrically expressed peak?VO<inf>2</inf> resulted in no significant correlation with any scaling denominator (r=?0.23; R2=?4%). CONCLUSIONS: The traditional and accepted method of ratio-scaling to BM is invalid because it fails to create a size-independent expression of peak?VO<inf>2</inf> in people with a Fontan circulation. However, ratio-scaling to measures of body composition (fat-free mass, lean mass, and appendicular lean mass) and allometric techniques can produce size-independent expressions of peak ?VO<inf>2</inf> in people with a Fontan circulation. 2022 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
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Liu, Joanna Shu Ting; Ding, Yiran; Schoenwaelder, Simone M.; Liu, XuyuAcute ischemic stroke is a consequence of disrupted blood flow to the brain, caused by thrombosisthe pathological formation of occlusive clots within blood vessels, which can embolize distally to downstream tissues and microvasculature. The highest priority of stroke treatment is the rapid removal of occlusive clots and restoration of tissue perfusion. Intravenous thrombolysis is the pharmacological standard-of-care for the dissolution of blood clots, wherein thrombolytic drugs are administered to restore vessel patency. While the introduction of recombinant tissue-plasminogen activator (rtPA) in 1996 demonstrated the benefit of acute thrombolysis for clot removal, this was countered by severe limitations in terms of patient eligibility, lytic efficacy, rethrombosis and safety implications. Development of safer and efficacious treatment strategies to improve clot lysis has not significantly progressed over many decades, due to the challenge of maintaining the necessary efficacy-safety balance for these therapies. As such, rtPA has remained the sole approved acute therapeutic for ischemic stroke for over 25 years. Attempts to improve thrombolysis with coadministration of adjunct antithrombotics has demonstrated benefit in coronary vessels, but remain contraindicated for stroke, given all currently approved antithrombotics adversely impact hemostasis, causing bleeding. This Perspective provides a brief history of stroke drug development, as well as an overview of several groups of emerging drugs which have the potential to improve thrombolytic strategies in the future. These include inhibitors of the platelet receptor glycoprotein VI and the signaling enzyme PI3-Kinase, novel anticoagulants derived from hematophagous creatures, and proteolysis-targeting chimeras. 2022 Liu, Ding, Schoenwaelder and Liu.
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Freedman, Ben[No abstract available]
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Tran, Derek L.; Gibson, Hannah; Maiorana, Andrew John; Verrall, Charlotte E.; Baker, David William; Clode, Melanie; Lubans, David Revalds; Zannino, Diana; Bullock, Andrew M.; Ferrie, Suzie; Briody, Julie N.; Simm, Peter J.; Wijesekera, Vishva A.; D'Almeida, Michelle; Gosbell, Sally E.; Davis, Glen Macartney; Weintraub, Robert G.; Keech, Anthony C.; Puranik, Rajesh; Ugander, Martin; Justo, Robert N.; Zentner, Dominica; Majumdar, Avik; Grigg, Leeanne Elizabeth; Coombes, Jeff S.; d'Udekem, Yves A.; Morris, Norman R.; Ayer, Julian Ganesh J.; Celermajer, David S.; Cordina, Rachael LouiseBackground: Despite developments in surgical techniques and medical care, people with a Fontan circulation still experience long-term complications; non-invasive therapies to optimize the circulation have not been established. Exercise intolerance affects the majority of the population and is associated with worse prognosis. Historically, people living with a Fontan circulation were advised to avoid physical activity, but a small number of heterogenous, predominantly uncontrolled studies have shown that exercise training is safeand for unique reasons, may even be of heightened importance in the setting of Fontan physiology. The mechanisms underlying improvements in aerobic exercise capacity and the effects of exercise training on circulatory and end-organ function remain incompletely understood. Furthermore, the optimal methods of exercise prescription are poorly characterized. This highlights the need for large, well-designed, multi-center, randomized, controlled trials. Aims and Methods: The Fontan Fitness Intervention Trial (F-FIT)a phase III clinical trialaims to optimize exercise prescription and delivery in people with a Fontan circulation. In this multi-center, randomized, controlled study, eligible Fontan participants will be randomized to either a 4-month supervised aerobic and resistance exercise training program of moderate-to-vigorous intensity followed by an 8-month maintenance phase; or usual care (control group). Adolescent and adult (?16 years) Fontan participants will be randomized to either traditional face-to-face exercise training, telehealth exercise training, or usual care in a three-arm trial with an allocation of 2:2:1 (traditional:telehealth:control). Children (<16 years) will be randomized to either a physical activity and exercise program of moderate-to-vigorous intensity or usual care in a two-arm trial with a 1:1 allocation. The primary outcome is a change in aerobic exercise capacity (peak oxygen uptake) at 4-months. Secondary outcomes include safety, and changes in cardiopulmonary exercise testing measures, peripheral venous pressure, respiratory muscle and lung function, body composition, liver stiffness, neuropsychological and neurocognitive function, physical activity levels, dietary and nutritional status, vascular function, neurohormonal activation, metabolites, cardiac function, quality of life, musculoskeletal fitness, and health care utilization. Outcome measures will be assessed at baseline, 4-months, and 12-months. This manuscript will describe the pathophysiology of exercise intolerance in the Fontan circulation and the rationale and protocol for the F-FIT. 2022 Tran, Gibson, Maiorana, Verrall, Baker, Clode, Lubans, Zannino, Bullock, Ferrie, Briody, Simm, Wijesekera, D'Almeida, Gosbell, Davis, Weintraub, Keech, Puranik, Ugander, Justo, Zentner, Majumdar, Grigg, Coombes, d'Udekem, Morris, Ayer, Celermajer and Cordina.
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Zhang, Yingqi; Jiang, Fengtao; Chen, Yunfeng; Ju, Lining ArnoldPlatelet function tests are essential to profile platelet dysfunction and dysregulation in hemostasis and thrombosis. Clinically they provide critical guidance to the patient management and therapeutic evaluation. Recently, the biomechanical effects induced by hemodynamic and contractile forces on platelet functions attracted increasing attention. Unfortunately, the existing platelet function tests on the market do not sufficiently incorporate the topical platelet mechanobiology at play. Besides, they are often expensive and bulky systems that require large sample volumes and long processing time. To this end, numerous novel microfluidic technologies emerge to mimic vascular anatomies, incorporate hemodynamic parameters and recapitulate platelet mechanobiology. These miniaturized and cost-efficient microfluidic devices shed light on high-throughput, rapid and scalable platelet function testing, hematological disorder profiling and antiplatelet drug screening. Moreover, the existing antiplatelet drugs often have suboptimal efficacy while incurring several adverse bleeding side effects on certain individuals. Encouraged by a few microfluidic systems that are successfully commercialized and applied to clinical practices, the microfluidics that incorporate platelet mechanobiology hold great potential as handy, efficient, and inexpensive point-of-care tools for patient monitoring and therapeutic evaluation. Hereby, we first summarize the conventional and commercially available platelet function tests. Then we highlight the recent advances of platelet mechanobiology inspired microfluidic technologies. Last but not least, we discuss their future potential of microfluidics as point-of-care tools for platelet function test and antiplatelet drug screening. 2022 Zhang, Jiang, Chen and Ju.
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Pankayatselvan, Varayini; Raber, Inbar; Playford, David A.; Stewart, S.; Strange, G. A.; Strom, Jordan B.Non-rheumatic aortic stenosis (AS) is among the most common valvular diseases in the developed world. Current guidelines support aortic valve replacement (AVR) for severe symptomatic AS, which carries high morbidity and mortality when left untreated. In contrast, moderate AS has historically been thought to be a benign diagnosis for which the potential benefits of AVR are outweighed by the procedural risks. However, emerging data demonstrating the substantial mortality risk in untreated moderate AS and substantial improvements in periprocedural and perioperative mortality with AVR have challenged the traditional risk/benefit paradigm. As such, an appraisal of the contemporary data on morbidity and mortality associated with moderate AS and appropriate timing of valvular intervention in AS is warranted. In this review, we discuss the current understanding of moderate AS, including the epidemiology, current surveillance and management guidelines, clinical outcomes, and future studies.
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Wallenhorst, Christopher; Martinez, Carlos; Freedman, Ben BenBackground It is uncertain whether stroke risk of asymptomatic ambulatory atrial fibrillation (AA-AF) incidentally detected in primary care is comparable with other clinical AF presentations in primary care or hospital. Methods The stoke risk of 22,035 patients with incident nonvalvular AF from the United Kingdom primary care Clinical Practice Research Datalink with linkage to hospitalization and mortality data was compared with 23,605 controls without AF (age- and sex-matched 5:1 to 5,409 AA-AF patients). Incident AF included 5,913 with symptomatic ambulatory AF (SA-AF); 4,989 with primary and 5,724 with nonprimary hospital AF discharge diagnosis (PH-AF and non-PH-AF); and 5,409 with AA-AF. Ischemic stroke adjusted subhazard ratios (aSHRs) within 3 years of AA-AF were compared with SA-AF, PH-AF, non-PH-AF, and no AF, accounting for mortality as competing risk and adjusted for ischemic stroke risk factors. Results There were 1,026 ischemic strokes in 49,544 person-years in patients with incident AF (crude incidence rate: 2.1 ischemic strokes/100 person-years). Ischemic stroke aSHR over 3 years showed no differences between AA-AF and SA-AF, PH-AF, and non-PH-AF groups (aSHR: 0.87-1.01 vs. AA-AF). All AF groups showed a significantly higher aSHR compared with no AF. Conclusion Ischemic stroke risk in patients with AA-AF incidentally detected in primary care is far from benign, and not less than incident AF presenting clinically in general practice or hospital. This provides justification for identification of previously undetected AF, e.g., by opportunistic screening, and subsequent stroke prevention with thromboprophylaxis, to reduce the approximately 10% of ischemic strokes related to unrecognized AF. 2022 American Institute of Physics Inc.. All rights reserved.
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Ju, Lining Arnold; Kossmann, Sabine; Zhao, Yunduo Charles; Moldovan, Laura; Zhang, Yingqi; de Zoysa Ramasundara, Savindi; Zhou, Fangyuan; Lu, Hang; Alwis, Imala D.; Schoenwaelder, Simone M.; Yuan, Yuping; Jackson, Shaun P.Microvascular thrombosis and inflammation (thromboinflammation) are major causes of morbidity and mortality in critically ill patients with limited therapeutic options. Platelets are central to thromboinflammation, and microvascular platelet thrombi are highly effective at recruiting and activating leukocytes at sites of endothelial injury. Whilst parallel-plate flow chambers, microslides and straight microchannel assays have been widely used to recapitulate leukocyte adhesive behavior on 2-dimensional (2D) surfaces, none of these methods achieve high fidelity 3-dimensional (3D) geometries emulating microvascular platelet thrombi. As a result, the role of hydrodynamic factors in regulating leukocyte interactions with platelet thrombi remains ill-defined. Here, we report a microfluidic post model that allows visualization and analysis of neutrophil-platelet interactions in a 3D flow field. We have utilized the unique mechanosensitive features of platelets to enable selective micropatterning of the 3D posts with human or mouse platelets. By modulating the activation status of platelets, our method enables precise control of platelet surface reactivity and neutrophil recruitment. In addition, our microfluidic post assay accurately recapitulated the rolling versus stationary adhesion behavior of single neutrophils and demonstrated the efficacy of the P-selectin and Mac-1 blocking antibodies to reduce neutrophil recruitment and stationary adhesion, respectively. Moreover, the geometry of posts had a major influence on the efficiency of neutrophil recruitment and adhesion stability. This new post method highlights the importance of platelet 3D geometries in facilitating efficient, localized neutrophil recruitment. These findings have potentially important implications for the potent proinflammatory function of microvascular platelet thrombi. This journal is The Royal Society of Chemistry
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Sun, Wen; Freedman, Ben Ben; Martinez, Carlos; Wallenhorst, Christopher; Yan, Bryan Ping YenObjective We evaluated stroke risk in patients with single time-point screen-detected atrial fibrillation (AF) and the effect of oral anticoagulants (OACs). Methods Consecutive patients aged ?65 years attending medical outpatient clinics were prospectively enrolled for AF screening using handheld single-lead electrocardiogram (ECG; AliveCor) from December 2014 to December 2017 (NCT02409654). Repeated screening was performed in patients with >1 visit during this period. Three cohorts were formed: screen-detected AF, clinically diagnosed AF, and no AF. Ischemic stroke risk was estimated using adjusted subdistribution hazard ratios (aSHRs) from multivariate regression and no AF as reference, and stratified according to OAC use. Results Of 11,972 subjects enrolled, 2,238 (18.7%) had clinically diagnosed AF at study enrollment. The yield of screen-detected AF on initial screening was 2.3% (n = 223/9,734). AF was clinically diagnosed during follow-up in 2.3% (n = 216/9,440) and during subsequent screening in 71 initially screen-negative patients. Compared with no AF, patients with screen-detected AF without OAC treatment had the highest stroke risk (aSHR: 2.63; 95% confidence interval: 1.46-4.72), while aSHR for clinically diagnosed AF without OAC use was 2.01 (1.54-2.62). Among screen-detected AF, the risk of stroke was significantly less with OAC (no strokes in 196 person-years) compared with those not given OAC (12 strokes in 429 person-years), p = 0.01. Conclusion The prognosis of single time-point ECG screen-detected AF is not benign. The risk of stroke is high enough to warrant OAC use, and reduced by OAC. 2022 American Institute of Physics Inc.. All rights reserved.
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Ayer, Anita; Fazakerley, Daniel J.; James, David Ernest; Stocker, RolandInsulin resistance is one of the earliest pathological features of a suite of diseases including type 2 diabetes collectively referred to as metabolic syndrome. There is a growing body of evidence from both pre-clinical studies and human cohorts indicating that reactive oxygen species, such as the superoxide radical anion and hydrogen peroxide are key players in the development of insulin resistance. Here we review the evidence linking mitochondrial reactive oxygen species generated within mitochondria with insulin resistance in adipose tissue and skeletal muscle, two major insulin sensitive tissues. We outline the relevant mitochondria-derived reactive species, how the mitochondrial redox state is regulated, and methodologies available to measure mitochondrial reactive oxygen species. Importantly, we highlight key experimental issues to be considered when studying the role of mitochondrial reactive oxygen species in insulin resistance. Evaluating the available literature on both mitochondrial reactive oxygen species/redox state and insulin resistance in a variety of biological systems, we conclude that the weight of evidence suggests a likely role for mitochondrial reactive oxygen species in the etiology of insulin resistance in adipose tissue and skeletal muscle. However, major limitations in the methods used to study reactive oxygen species in insulin resistance as well as the lack of data linking mitochondrial reactive oxygen species and cytosolic insulin signaling pathways are significant obstacles in proving the mechanistic link between these two processes. We provide a framework to guide future studies to provide stronger mechanistic information on the link between mitochondrial reactive oxygen species and insulin resistance as understanding the source, localization, nature, and quantity of mitochondrial reactive oxygen species, their targets and downstream signaling pathways may pave the way for important new therapeutic strategies. 2021 Elsevier Inc.
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Zhu, Yingyan; Jackson, Dan J.; Hunter, Benjamin; Beattie, Lorna; Turner, Lisa; Hambly, Brett D.; Jeremy, Richmond William; Malecki, Cassandra; Robertson, Elizabeth N.; Li, Amy; Dos Remedios, Cris G.D.; Richmond, David R.; Semsarian, Christopher; OSullivan, John F.; Bannon, Paul Gerard; Lal, Sean P.Biobanking in health care has evolved over the last few decades from simple biological sample repositories to complex and dynamic units with multi-organizational infrastructure networks and has become an essential tool for modern medical research. Cardiovascular tissue biobanking provides a unique opportunity to utilize cardiac and vascular samples for translational research into heart failure and other related pathologies. Current techniques for diagnosis, classification, and treatment monitoring of cardiac disease relies primarily on interpretation of clinical signs, imaging, and blood biomarkers. Further research at the disease source (i.e. myocardium and blood vessels) has been limited by a relative lack of access to quality human cardiac tissue and the inherent shortcomings of most animal models of heart disease. In this review, we describe a model for cardiovascular tissue biobanking and databasing, and its potential to facilitate basic and translational research. We share techniques to procure endocardial samples from patients with hypertrophic cardiomyopathy, heart failure with reduced ejection fraction, and heart failure with preserved ejection fraction, in addition to aortic disease samples. We discuss some of the issues with respect to data collection, privacy, biobank consent, and the governance of tissue biobanking. The development of tissue biobanks as described here has significant scope to improve and facilitate translational research in multi-omic fields such as genomics, transcriptomics, proteomics, and metabolomics. This research heralds an era of precision medicine, in which patients with cardiovascular pathology can be provided with optimized and personalized medical care for the treatment of their individual phenotype. 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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Offen, Sophie M.; Baker, David William; Puranik, Rajesh; Celermajer, David S.Background: Significant right ventricular (RV) dilatation has long been considered integral to the pathogenesis of functional tricuspid regurgitation (FTR). Objectives: To explore the relationship of RV dilatation and FTR in patients with pure RV volume overload. Methods: Patients (>17yrs) with RV dilatation due to pre-tricuspid shunts (atrial septal defect; ASD and/or partial anomalous pulmonary venous drainage; PAPVD) referred to our service (20002019) were retrospectively identified. Those with pulmonary hypertension, primum ASD or left-heart disease were excluded. Using standard cardiac MRI protocols, RV, right atrial and TV parameters were measured and compared. Results: Of 52 consecutively eligible patients (42 15yrs, 25 males), 25 had ASDs, 13 had PAPVD and 14 had both conditions. All were in sinus rhythm and none had pulmonary regurgitation. Left and right ventricular ejection fractions were normal (LVEF 63 8%, RVEF 56 8%). Indexed RV end-diastolic volumes (RVEDVi) were moderately increased (males 148 33 mL/m2 and females 141 42 mL/m2, range 95267 mL/m2). Despite substantial RV volume overload, no patients had severe tricuspid regurgitation (TR). Only two had > mild TR. There was a weak correlation between tricuspid annular diameter and both degree of RV dilatation (r = 0.37; p = 0.01) and degree of TR (r = 0.38; p = 0.006). There was a similarly poor correlation between right atrial dimensions and the degree of TR (r = 0.34; p = 0.02). Conclusion: When RV dilatation is simply due to volume overload, we find that significant TR is extremely rare. This gives an important and novel insight; that RV dilatation per se does not result in FTR. 2021 The Authors
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Chan, Ngai Yin; Orchard, Jessica Joan; Agbayani, Michael Joseph F.; Boddington, Dean; Chao, Tzefan; Johar, Sofian; John, Bobby A.; Joung, Boyoung; Krishinan, Saravanan; Krittayaphong, Rungroj; Kurokawa, Sayaka; Lau, Chu Pak; Lim, Toon Wei; Linh, Pham Tran; Long, Vien Hoang; Naik, Ajay Madhukar; Okumura, Yasuo; Sasano, Tetsuo; Yan, Bernard; Raharjo, Sunu Budhi; Hanafy, Dicky Armein; Yuniadi, Yoga; Nwe, Nwe Htay Win; Awan, Zahid Aslam; Huang, He; Freedman, Ben Ben[No abstract available]
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Rivard, La; Friberg, Leif; Conen, David; Healey, Jeff S.; Berge, Trygve; Boriani, Giuseppe; Brandes, Axel; Calkins, Hugh G.; Camm, Alan John; Chen, Lin Y.; Clua-Espuny, J. L.; Collins, R D.; Connolly, Stuart J.; Dagres, Nikolaos; Elkind, Mitchell S.V.; Engdahl, Johan; Field, Thalia S.; Gersh, Bernard John; Glotzer, Taya V.; Hankey, Graeme J.; Harbison, Joseph A.; Georg Haeusler, Karl; Hills, Mellanie True; Johnson, Linda S.B.; Joung, Boyoung; Khairy Dr, Paul; Kirchhof, Paulus F.; Krieger, Derk Wolfgang; Lip, Gregory Y.H.; Lhen, Maja Lisa; Madhavan, Malini; Mairesse, Georges H.; Montaner, J. M.; Ntaios, George C.; Quinn, Terry J.; Rienstra, Michiel; Rosenqvist, Mten; Sandhu, Roopinder Kaur; Smyth, Breda; Schnabel, Renate B.; Stavrakis, Stavros; Themistoclakis, Sakis; van Gelder, Isabelle C.; Wang, Jiguang; Freedman, Ben BenGrowing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia. 2022 Lippincott Williams and Wilkins. All rights reserved.
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Kott, Katharine A.; Bishop, Michael; Yang, Christina H.J.; Plasto, Toby M.; Cheng, Daniel Chih Yung; Kaplan, Adam I.; Cullen, Louise A.; Celermajer, David S.; Meikle, Peter J.; Vernon, Stephen Thomas; Figtree, Gemma A.Cardiac biomarkers have become pivotal to the clinical practice of cardiology, but there remains much to discover that could benefit cardiology patients. We review the discovery of key protein biomarkers in the fields of acute coronary syndrome, heart failure, and atherosclerosis, giving an overview of the populations they were studied in and the statistics that were used to validate them. We review statistical approaches that are currently in use to assess new biomarkers and overview a framework for biomarker discovery and evaluation that could be incorporated into clinical trials to evaluate cardiovascular outcomes in the future. 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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Luo, Kaiming; Ogawa, Masahito; Ayer, Anita; Britton, Warwick J.; Stocker, Roland; Kikuchi, Kazu; Oehlers, Stefan H.Heme oxygenase function is highly conserved between vertebrates where it plays important roles in normal embryonic development and controls oxidative stress. Expression of the zebrafish heme oxygenase 1 genes is known to be responsive to oxidative stress suggesting a conserved physiological function. In this study, we generate a knockout allele of zebrafish hmox1a and characterize the effects of hmox1a and hmox1b loss on embryonic development. We find that loss of hmox1a or hmox1b causes developmental defects in only a minority of embryos, in contrast to Hmox1 gene deletions in mice that cause loss of most embryos. Using a tail wound inflammation assay we find a conserved role for hmox1a, but not hmox1b, in normal macrophage migration to the wound site. Together our results indicate that zebrafish hmox1a has clearly a partitioned role from hmox1b that is more consistent with conserved functions of mammalian Heme oxygenase 1. Copyright 2022, Mary Ann Liebert, Inc., publishers 2022.
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Guan, Ivy A.; Williams, Kayla; Liu, Joanna Shu Ting; Liu, XuyuCells employ post-translational modifications (PTMs) as key mechanisms to expand proteome diversity beyond the inherent limitations of a concise genome. The ability to incorporate post-translationally modified amino acids into protein targets via chemical ligation of peptide fragments has enabled the access to homogeneous proteins bearing discrete PTM patterns and empowered functional elucidation of individual modification sites. Native chemical ligation (NCL) represents a powerful and robust means for convergent assembly of two homogeneous, unprotected peptides bearing an N-terminal cysteine residue and a C-terminal thioester, respectively. The subsequent discovery that protein cysteine residues can be chemoselectively desulfurized to alanine has ignited tremendous interest in preparing unnatural thiol-derived variants of proteogenic amino acids for chemical protein synthesis following the ligation-desulfurization logic. Recently, the 21st amino acid selenocysteine, together with other selenyl derivatives of amino acids, have been shown to facilitate ultrafast ligation with peptidyl selenoesters, while the advancement in deselenization chemistry has provided reliable bio-orthogonality to PTMs and other amino acids. The combination of these ligation techniques and desulfurization/deselenization chemistries has led to streamlined synthesis of multiple structurally-complex, post-translationally modified proteins. In this review, we aim to summarize the latest chemical synthesis of thiolated and selenylated amino-acid building blocks and exemplify their important roles in conquering challenging protein targets with distinct PTM patterns. 2022 Guan, Williams, Liu and Liu.
