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Showing 541–560 of 2058 publications.
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Levin, Rachel A.; Carnegie, Mark H.; Celermajer, David S.Elevated pulse pressure can cause blood-brain barrier dysfunction and subsequent adverse neurological changes that may drive or contribute to the development of dementia with age. In short, elevated pulse pressure dysregulates cerebral endothelial cells and increases cellular production of oxidative and inflammatory molecules. The resulting cerebral microvascular damage, along with excessive pulsatile mechanical force, can induce breakdown of the blood-brain barrier, which in turn triggers brain cell impairment and death. We speculate that elevated pulse pressure may also reduce the efficacy of other therapeutic strategies for dementia. For instance, BACE1 inhibitors and anti-amyloid-? biologics reduce amyloid-? deposits in the brain that are thought to be a cause of Alzheimers disease, the most prevalent form of dementia. However, upregulation of oxidative and inflammatory molecules and increased amyloid-? secretion by cerebral endothelial cells exposed to elevated pulse pressure may hinder cognitive improvements with these drugs. Additionally, stem or progenitor cell therapy has the potential to repair blood-brain barrier damage, but chronic oxidative and inflammatory stress due to elevated pulse pressure can inhibit stem and progenitor cell regeneration. Finally, we discuss current efforts to repurpose blood pressure medications to prevent or treat dementia. We propose that new drugs or devices should be developed to safely reduce elevated pulse pressure specifically to the brain. Such novel technologies may alleviate an entire downstream pathway of cellular dysfunction, oxidation, inflammation, and amyloidogenesis, thereby preventing pulse-pressure-induced cognitive decline. Furthermore, these technologies may also enhance efficacy of other dementia therapeutics when used in combination. Copyright 2020 Levin, Carnegie and Celermajer.
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Lam, Yuenting; Hsu, Chijen; Simpson, Philippa J.L.; Dunn, Louise L.; Chow, Renee W.Y.; Chan, Kim Hoe; Yong, Andy Sze Chiang; Yu, Young; Sieveking, Daniel P.; Lecce, Laura; Yuan, Jun; Celermajer, David S.; Wise, Steven G.; Ng, Martin K.C.Endothelial progenitor cells (EPCs) play a key role in neovascularization and have been linked to improved cardiovascular outcomes. Although there is a well-established inverse relationship between androgen levels and cardiovascular mortality in men, the role of androgens in EPC function is not fully understood. In this study, we investigated the effects of androgens on 2 subpopulations of EPCs, early EPCs (EEPCs) and late outgrowth EPCs (OECs), and their relationships with coronary collateralization. Early EPCs and OECs were isolated from the peripheral blood of young healthy men and treated with dihydrotestosterone (DHT) with or without androgen receptor (AR) antagonist, hydroxyflutamide, in vitro. Dihydrotestosterone treatment enhanced AR-mediated proliferation, migration, and tubulogenesis of EEPCs and OECs in a dose-dependent manner. Furthermore, DHT augmented EPC sensitivity to extracellular stimulation by vascular endothelial growth factor (VEGF) via increased surface VEGF receptor expression and AKT activation. In vivo, xenotransplantation of DHT pretreated human EPCs augmented blood flow recovery and angiogenesis in BALB/c nude male mice, compared to mice receiving untreated EPCs, following hindlimb ischemia. In particular, DHT pretreated human OECs exhibited higher reparative potential than EEPCs in augmenting postischemic blood flow recovery in mice. Furthermore, whole blood was collected from the coronary sinus of men with single vessel coronary artery disease (CAD) who underwent elective percutaneous intervention (n = 23). Coronary collateralization was assessed using the collateral flow index. Serum testosterone and EPC levels were measured. In men with CAD, circulating testosterone was positively associated with the extent of coronary collateralization and the levels of OECs. In conclusion, androgens enhance EPC function and promote neovascularization after ischemia in mice and are associated with coronary collateralization in men. Endocrine Society 2020. All rights reserved.
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Orchard, Jessica Joan; Freedman, Ben Ben; Lowres, Nicole; Neubeck, Lis[No abstract available]
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Chen, Yunfeng; Ju, Lining ArnoldArterial thrombosis is in part contributed by excessive platelet aggregation, which can lead to blood clotting and subsequent heart attack and stroke. Platelets are sensitive to the haemodynamic environment. Rapid haemodynamcis and disturbed blood flow, which occur in vessels with growing thrombi and atherosclerotic plaques or is caused by medical device implantation and intervention, promotes platelet aggregation and thrombus formation. In such situations, conventional antiplatelet drugs often have suboptimal efficacy and a serious side effect of excessive bleeding. Investigating the mechanisms of platelet biomechanical activation provides insights distinct from the classic views of agonist-stimulated platelet thrombus formation. In this work, we review the recent discoveries underlying haemodynamic force-reinforced platelet binding and mechanosensing primarily mediated by three platelet receptors: glycoprotein Ib (GPIb), glycoprotein IIb/IIIa (GPIIb/IIIa) and glycoprotein VI (GPVI), and their implications for development of antithrombotic mechano-medicine'. Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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Orchard, Jessica Joan; Orchard, John William; La Gerche, AndrCrossed D.Sign; Kountouris, Alex; Raju, Hariharan; Young, Mark; Puranik, Rajesh; Semsarian, ChristopherObjectives: To report the compliance and results of an electrocardiogram (ECG) cardiac screening program in male and female elite Australian cricketers. Design: cross-sectional study. Methods: Elite cricketers were offered screening in accordance with Cricket Australia policy. Players who consented provided a personal and family history, physical examination and resting 12-lead ECG. An audit (1 February 2019) examined all cardiac screening records for male and female players in all Australian Cricket state squads from 16 years upwards. Data extracted from the Cricket Australia database included the number of players who underwent screening; signed waivers opting out; and had follow-up tests. ECGs were re-reviewed according to the International Criteria. Results: 710 players were included in the cohort (mean age 20.4 4.9 years, 62% male). 692 (97.5%) players underwent recommended cardiac screening or signed a waiver opting out (1.1%). 173 (24.4%) players were screened (or signed a waiver) more than once. Follow-up testing was conducted for 59 (6.9%) cases. No players were excluded from sport due to a cardiac problem and no major cardiac incidents occurred to any player in the audit cohort. Review of 830 ECGs showed benign athlete heart changes, including sinus bradycardia (33.5%), left ventricular hypertrophy (16.3%), and incomplete/partial right bundle branch block (8.4%), were common but abnormal screening ECGs were uncommon (2.0%). Conclusions: An audit of a cardiac screening program in elite Australian cricketers found excellent compliance. A small proportion required follow-up testing and no player was excluded from sport due to a cardiac problem. ECG analysis suggested cricket is a sport of moderate cardiac demands, with benign athlete heart changes common. 2019 Sports Medicine Australia
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Chau, Katrina; Xu, Bei; Hennessy, Annemarie; Makris, AngelaPlacental growth factor (PlGF) is an important angiogenic factor which has an emerging role in the clinical management of suspected preeclampsia. The role of PlGF in normal placental development is not completely understood and it is uncertain whether PlGF influences trophoblast and endothelial cell interactions central to uterine spiral artery remodelling, especially in variable oxygen conditions. A two-cell model of endovascular invasion was used. Tissue culture plates were coated with Matrigel, on which fluorescent-labelled uterine microvascular endothelial cells (1 105/well) and HTR8/SVNeo cells were co-cultured (1 105/well) for 20h. Co-cultures were treated with recombinant human PlGF (rhPlGF) (10 or 100ng/mL) and incubated at either 21% O<inf>2</inf> or 2% O<inf>2</inf>. Images were captured by fluorescence microscopy and analysed using ImageJ (n = 7). Data was analysed using SPSSv24. Treatment with rhPlGF did not improve integration in co-cultures irrespective of oxygen conditions but increased proliferation in 2% O<inf>2</inf> of both trophoblast and endothelial cells. Expression of angiogenic factors VEGF, sFLT-1, PlGF and CXCL12 in both co-cultures and in isolated trophoblast cells was not altered by rhPlGF treatment. Expression of TLR-3 mRNA in co-cultures was increased by rhPlGF 100ng/mL at 21% O<inf>2</inf> (p = 0.03). PlGF contributes to trophoblast and endothelial cell proliferation in the setting of physiological hypoxia but does not influence trophoblast and endothelial cell interactions in an in vitro model of spiral artery remodelling. Upregulation of TLR-3 expression in co-cultures may indicate a role for PlGF in the placental inflammatory response. 2020, Society for Reproductive Investigation.
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Giskes, Katrina; Hespe, Charlotte Mary; Freedman, Ben[No abstract available]
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Lowres, Nicole; Duckworth, Andrew; Redfern, Julie; Thiagalingam, Aravinda; Chow, Clara KayeiBackground: SMS text messaging programs are increasingly being used for secondary prevention, and have been shown to be effective in a number of health conditions including cardiovascular disease. SMS text messaging programs have the potential to increase the reach of an intervention, at a reduced cost, to larger numbers of people who may not access traditional programs. However, patients regularly reply to the SMS text messages, leading to additional staffing requirements to monitor and moderate the patients'SMS text messaging replies. This additional staff requirement directly impacts the cost-effectiveness and scalability of SMS text messaging interventions. Objective: This study aimed to test the feasibility and accuracy of developing a machine learning (ML) program to triage SMS text messaging replies (ie, identify which SMS text messaging replies require a health professional review). Methods: SMS text messaging replies received from 2 clinical trials were manually coded (1) into "Is staff review required?" (binary response of yes/no); and then (2) into 12 general categories. Five ML models (Nae Bayes, OneVsRest, Random Forest Decision Trees, Gradient Boosted Trees, and Multilayer Perceptron) and an ensemble model were tested. For each model run, data were randomly allocated into training set (2183/3118, 70.01%) and test set (935/3118, 29.98%). Accuracy for the yes/no classification was calculated using area under the receiver operating characteristics curve (AUC), false positives, and false negatives. Accuracy for classification into 12 categories was compared using multiclass classification evaluators. Results: A manual review of 3118 SMS text messaging replies showed that 22.00% (686/3118) required staff review. For determining need for staff review, the Multilayer Perceptron model had highest accuracy (AUC 0.86; 4.85% false negatives; and 4.63% false positives); with addition of heuristics (specified keywords) fewer false negatives were identified (3.19%), with small increase in false positives (7.66%) and AUC 0.79. Application of this model would result in 26.7% of SMS text messaging replies requiring review (true + false positives). The ensemble model produced the lowest false negatives (1.43%) at the expense of higher false positives (16.19%). OneVsRest was the most accurate (72.3%) for the 12-category classification. Conclusions: The ML program has high sensitivity for identifying the SMS text messaging replies requiring staff input; however, future research is required to validate the models against larger data sets. Incorporation of an ML program to review SMS text messaging replies could significantly reduce staff workload, as staff would not have to review all incoming SMS text messages. This could lead to substantial improvements in cost-effectiveness, scalability, and capacity of SMS text messaging-based interventions. 2020 JMIR Publications. All rights reserved.
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Peppou-Chapman, Sam; Hong, Jun Ki; Waterhouse, Anna; Neto, ChiaraLiquid-infused surfaces (or lubricant-infused surfaces) (LIS) are a new class of functional materials introduced in 2011. Their exceptional properties have earned them a place at the forefront of many fields including anti-biofouling, anti-icing, anti-corrosion, drag reduction, droplet manipulation and drop-wise condensation. Integral to their success is the infused lubricant layer which affords them their properties. In this review, we examine the current state of the literature relating to the lubricant layer. We consider the lubricant through all stages in the surface's lifecycle from design, to use, all the way through to depletion and eventual failure. First, we examine trends in lubricant choice and how to choose a lubricant, including environmental and medical considerations. We then look at the different methods used to infuse lubricant into surfaces and how lubricant depletes from the surface. We then report direct and indirect methods to characterise the thickness and distribution of the lubricant layer. Finally, we examine how droplets interact with LIS and the unique properties afforded by the lubricant before providing an outlook into where research centred on understanding the lubricant layer is heading in the new decade. 2020 The Royal Society of Chemistry.
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Liu, Xuyu; Long, Marcus John Curtis; Hopkins, Benjamin D.; Luo, Chaosheng; Wang, Lingxi; Aye, YimonOff-target effects continue to impede disease interventions, particularly when targeting a specific protein within a family of similar proteins, such as kinase isoforms that play tumor-subtype-specific roles in cancers. Exploiting the specific electrophilic-metabolite-sensing capability of Akt3, versus moderate or no sensing, respectively, by Akt2 and Akt1, we describe a first-in-class functionally Akt3-selective covalent inhibitor [MK-H(F)NE], wherein the electrophilic core is derived from the native reactive lipid metabolite HNE. Mechanistic profiling and pathway interrogations point to retention of the metabolite's structure - as opposed to implicit electrophilicity - as being essential for biasing isoform preference, which we found translates to tumor-subtype specificity against pten-null triple-negative breast cancers (TNBCs). MK-H(F)NE further enables novel downstream target identification specific to Akt3-function in disease. In TNBC xenografts, MK-H(F)NE fares better than reversible pan-Akt-inhibitors and does not show commonly observed side-effects associated with Akt1-inhibition. Inhibitors derived from native-metabolite sensing are thus an enabling plan-of-action for unmasking kinase-isoform-biased molecular targets and tumor-subtype-specific interventions. 2020 American Chemical Society.
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An, Chenyi; Hu, Wei; Gao, Jie; Ju, Bing Feng; Obeidy, Peyman; Zhao, Yunduo Charles; Tu, Xiaoxuan; Fang, Weijia; Ju, Lining Arnold; Chen, WeiImmune checkpoint blockade with monoclonal antibodies (mAbs) that target programmed cell death protein-1 (PD-1) has remarkably revolutionized cancer therapy. Their binding kinetics measured by surface plasmon resonance does not always correlate well with their immunotherapeutic efficacies, mainly due to the lack of two-dimensional cell plasma membrane and the capability of force sensing and manipulation. In this regard, based on a more suitable and ultra-sensitive biomechanical nanotool, biomembrane force probe (BFP), we developed a Double-edge Smart Feedback control system as an ultra-stable platform to characterize ultra-long bond lifetimes of receptor-ligand binding on living cells. We further benchmarked the dissociation kinetics for three clinically approved PD-1 blockade mAbs (Nivolumab, Pembrolizumab, and Camrelizumab), intriguingly correlating well with the objective response rates in the hepatocellular carcinoma second-line treatment. This ultra-stable BFP potentially provides a compelling kinetic platform to direct the screening, optimization, and clinical selection of therapeutic antibodies in the future. 2020 American Chemical Society.
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Pacleb, Adrienne; Lowres, Nicole; Randall, Sue; Neubeck, Lis; Gallagher, Robyn D.Background: Non-adherence to medications is common in patients with atrial fibrillation (AF), increasing the risk of stroke, co-morbidities, and AF symptoms. Understanding factors influencing medication adherence is important in providing holistic care to patients with AF. This study aimed to explore medication adherence in patients with AF, and explore associations with health literacy, cognition, or AF knowledge. Methods: A single-centre pilot study, using survey questionnaires and open questions. Patients with a primary cardiac diagnosis, with AF as primary or secondary diagnosis, were eligible for recruitment. During hospitalisation, adherence to cardiac medications was assessed using the Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS). Health literacy, cognition, and AF knowledge were assessed through validated questionnaires. Facilitators and barriers for medication adherence were obtained through open-ended question and coded using a content analysis approach. Results: Fifty-four (54) patients were recruited (61% male, mean age 7111). Twenty-two (22) participants (41%) were classified as non-adherent using the BAASIS; with a corresponding self-reported adherence of 87.7% in non-adherent participants compared to 97.8% in adherent participants. No associations were identified between medication adherence and cognition, health literacy, or AF knowledge. Facilitators for adherence included external assistance, routines, and medication knowledge, and these were reported by both adherent and non-adherent participants. Non-adherent participants reported more barriers including medication concerns, forgetfulness, and lifestyle factors. Conclusions: Large numbers of AF patients are likely to be non-adherent to medications. Medication adherence is influenced by multiple factors, individual to each patient. Diverse strategies are required to ensure adherence to cardiac medications. 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ)
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Karimi, Maryam; Crossett, Ben; Cordwell, Stuart James; Pattison, David I.; Davies, Michael J.Disulfide bonds play a key role in stabilizing proteins by cross-linking secondary structures. Whilst many disulfides are effectively unreactive, it is increasingly clear that some disulfides are redox active, participate in enzymatic reactions and/or regulate protein function by allosteric mechanisms. Previously (Karimi et al., Sci. Rep. 2016, 6, 38752) we have shown that some disulfides react rapidly with biological oxidants due to favourable interactions with available lone-pairs of electrons. Here we present data from kinetic, mechanistic and product studies for HOCl-mediated oxidation of a protected nine-amino acid model peptide containing a N- to C-terminal disulfide bond. This peptide reacts with HOCl with k<inf>2</inf> 1.8 106 M?1 s?1, similar to other highly-reactive disulfide-containing compounds. With low oxidant excesses, oxidation yields multiple oxidation products from the disulfide, with reaction predominating at the N-terminal Cys to give sulfenic, sulfinic and sulfonic acids, and disulfide bond cleavage. Limited oxidation occurs, with higher oxidant excesses, at Trp and His residues to give mono- and di- (for Trp) oxygenated products. Site-specific backbone cleavage also occurs between Arg and Trp, probably via initial side-chain modification. Treatment of the previously-oxidised peptide with thiols (GSH, N-Ac-Cys), results in adduction of the thiol to the oxidised peptide, with this occurring at the original disulfide bond. This gives an open-chain peptide, and a new mixed disulfide containing GSH or N-Ac-Cys as determined by mass spectrometry. Disulfide bond oxidation may therefore markedly alter the structure, activity and function of disulfide-containing proteins, and provides a potential mechanism for protein glutathionylation. 2020 Elsevier Inc.
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Cartland, Si; Lin, Ruby CY; Genner, Scott W.; Patil, Manisha S.; Martez, Gonzalo J.; Barraclough, Jennifer Y.; Gloss, Brian Stewart; Misra, Ashish K.; Patel, Sanjay; Kavurma, Mary M.Circulating plasma TRAIL levels are suppressed in patients with cardiovascular and diabetic diseases. To identify novel targets in vascular metabolic diseases, genome-wide transcriptome of aortic tissue from Trail?/? versus Trail+/+ mice were interrogated. We found 861 genes differentially expressed with TRAIL deletion. Gene enrichment analyses showed many of these genes were related to inflammation, cell-to-cell cytoskeletal interactions, and transcriptional modulation. We identified vascular protective and pathological gene clusters, with Ifi205 as the most significantly reduced vascular protective gene, whereas Glut1, the most significantly increased pathological gene with TRAIL deletion. We hypothesized that therapeutic targets could be devised from such integrated analysis and validated our findings from vascular tissues of diabetic mice. From the differentially expressed gene targets, enriched transcription factor (TF) and microRNA binding motifs were identified. The top two TFs were Elk1 and Sp1, with enrichment to eight gene targets common to both. miR-520d-3p and miR-377-3p were the top enriched microRNAs with TRAIL deletion; with four overlapping genes enriched for both microRNAs. Our findings offer an alternate in silico approach for therapeutic target identification and present a deeper understanding of gene signatures and pathways altered with TRAIL suppression in the vasculature. 2020 Federation of American Societies for Experimental Biology
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Galougahi, Keyvan Karimi; Petrossian, Gregory; Stone, Gregg Whitney; Ali, Ziad A.Purpose of reviewMajor studies in interventional cardiology in 2019 have added substantial new evidence for pharmaco-invasive management of coronary artery disease. The review highlights the main findings of a selection of these trials and summarizes their impact on clinical practice.Recent findingsRecent randomized studies examining the efficacy of revascularization or medical treatment in stable ischemic heart disease (SIHD), treatment of acute coronary syndromes, emerging interventional devices, adjunctive pharmacotherapy, and intravascular imaging and physiology guidance have substantially advanced the evidenced-based knowledge in interventional cardiology.SummaryPatients with SIHD and at least moderate myocardial ischemia have similar event-free survival after an initial conservative strategy of optimal medical therapy versus an upfront invasive strategy. Quality of life and angina-free status are significantly improved with revascularization. Percutaneous coronary intervention (PCI) and coronary artery bypass grafting provide similar 5-year outcomes in patients with left main coronary artery disease and low or intermediate disease complexity. An initially conservative management is equally effective as an early invasive approach in patients with out-of-hospital cardiac arrest without ongoing ischemia. Patients with ST-segment elevation myocardial infarction and multivessel disease benefit from staged complete revascularization after primary PCI. Post-PCI, patients with atrial fibrillation requiring anticoagulation can safely and effectively be treated with P2Y<inf>12</inf>inhibitor monotherapy without aspirin. Lastly, intravascular imaging guidance improves post-PCI outcomes, warranting increased use in clinical practice. 2020 Lippincott Williams and Wilkins. All rights reserved.
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Moore, Benjamin M.; Cao, Jacob Y.; Cordina, Rachael Louise; McGuire, Mark A.; Celermajer, David S.Aims: Sudden cardiac death (SCD) accounts for up to 25% of deaths in the adult congenital heart disease (ACHD) population. Current guidelines for defibrillator implantation are either extrapolated from acquired cardiac disease or are based upon single lesion studies, predominantly Tetralogy of Fallot (TOF). Defibrillator-related morbidity appears to be substantially higher in ACHD patients. Methods: We retrospectively evaluated all patients in our ACHD database who received an implantable cardioverter-defibrillator (ICD) between 2000 and 2019, and who were ?16 years old at time of implant. Patients were followed for appropriate shocks, inappropriate shocks, and complications. Results: Of 4748 patients in our database, 59 patients (1.2%) underwent ICD implantation. ICDs were for primary prevention in 63% and secondary prevention in 37%. Over a median follow-up of 6.6 years, 24% received an appropriate shock, 27% an inappropriate shock, and 42% suffered a device-related complication (annualized risks of 3.2%, 3.6%, and 5.7%, respectively). There were no significant predictors of appropriate shocks or inappropriate shocks. All appropriate shocks in primary prevention patients occurred in TOF or transposition of the great arteries (TGA) with atrial switch, typically in the presence of multiple SCD risk factors. The majority of inappropriate shocks were due to supraventricular arrhythmias. Device-related mortality was 1.7% (0.3% per annum). Conclusions: Appropriate shocks were relatively common in an ACHD ICD population followed in the long term. Device-related morbidity was significant. Although risk factors have been established for TOF, and to a lesser extent TGA, risk stratification for ICD implantation in ACHD remains challenging. 2020 Wiley Periodicals LLC
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Chen, Yi; Huang, Qifang; Sheng, Changsheng; Zhang, Wei; Shao, Shuai; Wang, Dian; Cheng, Yibang; Wang, Ying; Guo, Qianhui; Zhang, Dongyan; Li, Yan; Lowres, Nicole; Freedman, Ben Ben; Wang, JiguangBackground Atrial fibrillation (AF) is underdiagnosed and especially undertreated in China. We aimed to investigate the prevalence of unknown and untreated AF in community residents (?65 years old) and to determine whether an education intervention could improve oral anticoagulant (OAC) prescription. Methods and findings We performed a singletime point screening for AF with a handheld single-lead electrocardiography (ECG) in Chinese residents (?65 years old) in 5 community health centers in Shanghai from April to September 2017. Disease education and advice on referral to specialist clinics for OAC treatment were provided to all patients with actionable AF (newly detected or undertreated known AF) at the time of screening, and education was reinforced at 1 month. Follow-up occurred at 12 months. In total, 4,531 participants were screened (response rate 94.7%, mean age 71.6 6.3 years, 44% male). Overall AF prevalence was 4.0% (known AF 3.5% [n = 161], new AF 0.5% [n = 22]). The 183 patients with AF were older (p < 0.001), taller (p = 0.02), and more likely to be male (p = 0.01), and they had a higher prevalence of cardiovascular disease than those without AF (p < 0.001). In total, 85% (155/183) of patients were recommended for OAC treatment by the established guidelines (CHA<inf>2</inf>DS<inf>2</inf>-VASc ? 2 for men; ? 3 for women). OAC prescription rate for known AF was 20% (28/138), and actionable AF constituted 2.8% of all those screened. At the 12-month follow-up in 103 patients (81% complete), despite disease education and advice on specialist referral, only 17 attended specialist clinics, and 4 were prescribed OAC. Of those not attending specialist clinics, 71 chose instead to attend community health centers or secondary hospital clinics, with none prescribed OAC, and 15 had no review. Of the 17 patients with new AF and a class 1 recommendation for OAC, only 3 attended a specialist clinic, and none were prescribed OAC. Of the 28 AF patients taking OAC at baseline, OAC was no longer taken in 4. Ischemic stroke (n = 2) or death (n = 3) occurred in 5/126 (4%), with none receiving OAC. As screening was performed at a single time point, some paroxysmal AF cases may have been missed; thus, the rate of new AF may be underestimated. Conclusions We demonstrated a noticeable gap in AF detection and treatment in community-based elderly Chinese: actionable AF constituted a high proportion of those screened. Disease education and advice on specialist referral are insufficient to close the gap. Before more frequent or intensive screening for unknown AF could be recommended in China, greater efforts must be made to increase appropriate OAC therapy in known AF to prevent AF-related stroke. 2020 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Misra, Ashish K.; Fisher, Edward A.Many type 2 diabetes patients develop cardiovascular disease (CVD) while some are protected. Toyohara et al. (2020) find that elevated arylacetamide deacetylase (AADAC) expression in vascular smooth muscle cells (dVSMCs) differentiated from patient-derived induced pluripotent stem cells is associated with cardioprotection. AADAC overexpression alters multiple dVSMC properties and decreases murine CVD. 2020 Elsevier Inc.
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Lagrange, Jy; Finger, Stefanie; Kossmann, Sabine; Garlapati, Venkata S.; Ruf, Wolfram; Wenzel, PhilipMyeloid cells are crucial for the development of vascular inflammation. Low-density lipoprotein receptor-related protein 8 (LRP8) or Apolipoprotein E receptor 2 (ApoER2), is expressed by macrophages, endothelial cells and platelets and has been implicated in the development of cardiovascular diseases. Our aim was to evaluate the role of LRP8, in particular from immune cells, in the development of vascular inflammation. Methods. LRP8+/+ and LRP8?/? mice (on B6;129S background) were infused with angiotensin II (AngII, 1 mg/kg/day for 7 to 28 day) using osmotic minipumps. Blood pressure was recorded using tail cuff measurements. Vascular reactivity was assessed in isolated aortic segments. Leukocyte activation and infiltration were assessed by flow cytometry of aortic tissue and intravital videomicroscopy imaging. Histological analysis of aortic sections was conducted using sirius red staining. Results. AngII infusion worsened endothelial-dependent vascular relaxation and immune cells rolling and adherence to the carotid artery in both LRP8+/+ as well as LRP8?/? mice. However, only LRP8?/? mice demonstrated a drastically increased mortality rate in response to AngII due to aortic dissection. Bone marrow transplantation revealed that chimeras with LRP8 deficient myeloid cells phenocopied LRP8?/? mice. Conclusion. AngII-infused LRP8 deficient mice could be a useful animal model to study aortic dissection reflecting the lethality of this disease in humans. 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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Liu, Baolei; Chen, Chaohao; Di, Xiangjun; Liao, Jiayan; Wen, Shihui; Su, Qian Peter; Shan, Xuchen; Xu, Zaiquan; Ju, Lining Arnold; Mi, Chao; Wang, Fan; Jin, DayongVideo-rate super-resolution imaging through biological tissue can visualize and track biomolecule interplays and transportations inside cellular organisms. Structured illumination microscopy allows for wide-field super resolution observation of biological samples but is limited by the strong extinction of light by biological tissues, which restricts the imaging depth and degrades its imaging resolution. Here we report a photon upconversion scheme using lanthanide-doped nanoparticles for wide-field super-resolution imaging through the biological transparent window, featured by near-infrared and low-irradiance nonlinear structured illumination. We demonstrate that the 976 nm excitation and 800 nm upconverted emission can mitigate the aberration. We found that the nonlinear response of upconversion emissions from single nanoparticles can effectively generate the required high spatial frequency components in the Fourier domain. These strategies lead to a new modality in microscopy with a resolution below 131 nm, 1/7th of the excitation wavelength, and an imaging rate of 1 Hz. 2020 American Chemical Society.
