Publications

Showing 281–300 of 2058 publications.

• Algorithmic complexity stratification for congenital heart disease patients
  Chami, Jason; Strange, G. A.; Baker, David William; Cordina, Rachael Louise; Grigg, Leeanne Elizabeth; Celermajer, David S.; Nicholson, Calum
  International Journal of Cardiology Congenital Heart Disease (Vol. 11) – 2023
  Background: Congenital Heart Disease (CHD) encompasses a huge variety of rare diagnoses that range in complexity and comorbidity. To help build clinical guidelines, plan health services and conduct statistically powerful research on such a disparate set of diseases there have been various attempts to group pathologies into mild, moderate, or severe disease. So far, however, these complexity scores have required manual specialist input for every case, and are therefore missing in large databases where this is impractical, or quickly outdated when guidelines are revised. Methods: We used the up-to-date European Society of Cardiology guidelines to create an algorithm to assign complexity scores to CHD patients using only their diagnosis list. Two CHD specialists then independently assigned complexity scores to a random sample of patients. Results: Our algorithm was 96% accurate where both specialists agreed on a complexity score; this occurred 68% of the time overall, and 79% of the time in moderate or complex CHD. The algorithm failed mainly when diagnoses were insufficiently specific, usually for septal defects (where size was unspecified), or where complexity depends on the procedure performed (e.g. atrial/arterial switch for transposition of the great arteries). Conclusions: We were able to algorithmically determine the complexity scores of a majority of patients with CHD based on their diagnosis list alone. This could allow for automatic complexity scoring of most patients in large CHD databases, for example our own Registry of the Congenital Heart Alliance of Australia and New Zealand. This will facilitate targeted research into the management, outcomes and burden of CHD. 2022 The Authors
• Acute Vasoreactivity Testing and Outcomes in Pulmonary Arterial Hypertension: A Call for Increased Testing
  Chandrasekara, Sahan D.; Lau, Edmund M.T.; Anderson, James J.; Collins, Nicholas J.; Cordina, Rachael Louise; Corrigan, Carolyn; Dwyer, Nathan B.; Feenstra, John E.; Horrigan, Mark C.G.; Keogh, Anne M.; Kotlyar, Eugene; Lavender, Melanie A.; McWilliams, Tanya J.; Rhodes, Bronwen; Steele, Peter M.; Strange, G. A.; Thakkar, Vivek; Weintraub, Robert G.; Whitford, Helen M.; Whyte, Kenneth F.; Williams, Trevor J.; Wrobel, Jeremy P.; Keating, Dominic T.K.
  Heart Lung and Circulation (Vol. 32/2) – 2023
  Background: Pulmonary arterial hypertension (PAH) has a progressive, unremitting clinical course. Vasoreactivity testing (VdT) during right heart catheterisation (RHC) identifies a subgroup with excellent long-term response to calcium channel blockade (CCB). Reporting on these patients is limited. Established in 2011, the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) registry offers the opportunity to assess the frequency of VdT during RHC, treatment and follow up of PAH patients. Methods: Registry data from 3,972 PAH patients with index RHC revealed 1,194 VdT appropriate patients. Data was analysed in three groups: 1) VdT+CCB+: VdT positive, CCB treated; 2) VdT+CCB-: VdT positive, no CCB prescribed, 3) VdT-/noVdT: VdT negative, or VdT not tested. Data was reviewed for adherence to guidelines, clinical response (World Health Organization functional class [WHO FC], 6-minute-walk-distance [6MWD], RHC), and outcomes (survival or lung transplantation). Results: Patients included had idiopathic (IPAH=1,087), heritable (HPAH=67) and drug or toxin-induced PAH (DPAH=40). A VdT was performed in 22% (268/1,194), with incomplete data in 26% (70/268); 28% (55/198) were VdT+. Analysis group allocation was: VdT+CCB+ (33/55), VdT+CCB- (22/55), VdT- (143)/noVdT (996). From patients with 1-year data VdT+CCB+ and VdT-/noVdT patients improved WHO FC, 6MWD and cardiac index (CI); VdT+CCB- data remained similar. Within the VdT+CCB+ group, 30% (10/33) were long-term CCB responders with a 100% 5-year survival; non-responders had a 61% survival at 5.4 years. Long-term responders were younger at diagnosis (40 yrs vs 54 yrs). Conclusion: Use of VdT testing and documentation is poor in this contemporary patient cohort. Nonetheless, survival in VdT+CCB+ patients from the PHSANZ registry is excellent, supporting guidelines promoting VdT testing. Strategies to promote the use of VdT are warranted. 2022 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ)
• A placenta-on-a-chip model to determine the regulation of FKBPL and galectin-3 in preeclampsia
  Ghorbanpour, Sahar Masoumeh; Richards, Claire; Pienaar, Dillan; Sesperez, Kimberly; Aboulkheyr Es, Hamidreza; Nikoli?, Valentina N.; Karadov-Orli?, Nataa T.; Mikovi?, eljko D.; Stefanovi?, Milan; Cakic, Zoran; Alqudah, Abdelrahim M.A.; Cole, Louise; Gorrie, Catherine Anne; McGrath, Kristine C.Y.; Kavurma, Mary M.; Ebrahimi Warkiani, Majid; McClements, Lana
  Cellular and Molecular Life Sciences (Vol. 80/2) – 2023
  Preeclampsia is a pregnancy-specific cardiovascular disorder, involving significant maternal endothelial dysfunction. Although inappropriate placentation due to aberrant angiogenesis, inflammation and shallow trophoblast invasion are the root causes of preeclampsia, pathogenic mechanisms are poorly understood, particularly in early pregnancy. Here, we first confirm the abnormal expression of important vascular and inflammatory proteins, FK506-binding protein-like (FKBPL) and galectin-3 (Gal-3), in human plasma and placental tissues from women with preeclampsiaandnormotensive controls. We then employ a three-dimensional microfluidic placental model incorporating human umbilical vein endothelial cells (HUVECs) and a first trimester trophoblast cell line (ACH-3P) to investigate FKBPL and Gal-3 signaling in inflammatory conditions. In human samples, both circulating (n = 17 controls; n = 30 preeclampsia) and placental (n ? 6) FKBPL and Gal-3 levels were increased in preeclampsia compared to controls (plasma: FKBPL, p < 0.0001; Gal-3, p < 0.01; placenta: FKBPL, p < 0.05; Gal-3, p < 0.01), indicative of vascular dysfunction in preeclampsia. In our placenta-on-a-chip model, we show that endothelial cells are critical for trophoblast-mediated migration and that trophoblasts effectively remodel endothelial vascular networks. Inflammatory cytokine tumour necrosis factor-? (10ng/mL) modulates both FKBPL and Gal-3 signaling in conjunction with trophoblast migration and impairs vascular network formation (p < 0.005). Our placenta-on-a-chip recapitulates aspects of inappropriate placental development and vascular dysfunction in preeclampsia. 2023, The Author(s).
• FK506-Binding Protein like (FKBPL) Has an Important Role in Heart Failure with Preserved Ejection Fraction Pathogenesis with Potential Diagnostic Utility
  Chhor, Michael; Chen, Hao; Jerotic, Djurdja; Tei?, Milorad B.; Nikoli?, Valentina N.; Pavlovi?, Milan; Vu?i?, Rada M.; Rayner, Benjamin Saul; Watson, Chris J.; Ledwidge, Mark Thomas; McDonald, K. Michael; Robson, Tracy A.; McGrath, Kristine C.Y.; McClements, Lana
  Biomolecules (Vol. 13/2) – 2023
  Heart failure (HF) is the leading cause of hospitalisations worldwide, with only 35% of patients surviving the first 5 years after diagnosis. The pathogenesis of HF with preserved ejection fraction (HFpEF) is still unclear, impeding the implementation of effective treatments. FK506-binding protein like (FKBPL) and its therapeutic peptide mimetic, AD-01, are critical mediators of angiogenesis and inflammation. Thus, in this study, we investigatedfor the first timeFKBPLs role in the pathogenesis and as a biomarker of HFpEF. In vitro models of cardiac hypertrophy following exposure to a hypertensive stimulus, angiotensin-II (Ang-II, 100 nM), and/or AD-01 (100 nM), for 24 and 48 h were employed as well as human plasma samples from people with different forms of HFpEF and controls. Whilst the FKBPL peptide mimetic, AD-01, induced cardiomyocyte hypertrophy in a similar manner to Ang-II (p < 0.0001), when AD-01 and Ang-II were combined together, this process was abrogated (p < 0.010.0001). This mechanism appears to involve a negative feedback loop related to FKBPL (p < 0.05). In human plasma samples, FKBPL concentration was increased in HFpEF compared to controls (p < 0.01); however, similar to NT-proBNP and Gal-3, it was unable to stratify between different forms of HFpEF: acute HFpEF, chronic HFpEF and hypertrophic cardiomyopathy (HCM). FKBPL may be explored for its biomarker and therapeutic target potential in HFpEF. 2023 by the authors.
• Exercise as therapy for neurodevelopmental and cognitive dysfunction in people with a Fontan circulation: A narrative review
  Verrall, Charlotte E.; Tran, Derek L.; Yang, Joseph Yuan Mou; Lubans, David Revalds; Winlaw, David S.; Ayer, Julian Ganesh J.; Celermajer, David S.; Cordina, Rachael Louise
  Frontiers in Pediatrics (Vol. 11) – 2023
  People with a Fontan circulation are at risk of neurodevelopmental delay and disability, and cognitive dysfunction, that has significant implications for academic and occupational attainment, psychosocial functioning, and overall quality of life. Interventions for improving these outcomes are lacking. This review article discusses current intervention practices and explores the evidence supporting exercise as a potential intervention for improving cognitive functioning in people living with a Fontan circulation. Proposed pathophysiological mechanisms underpinning these associations are discussed in the context of Fontan physiology and avenues for future research are recommended. 2023 Verrall, Tran, Yang, Lubans, Winlaw, Ayer, Celermajer and Cordina.
• Molecularly targeted nanomedicine enabled by inorganic nanoparticles for atherosclerosis diagnosis and treatment
  Zhang, Xiuwen; Centurion, Franco; Misra, Ashish K.; Patel, Sanjay; Gu, Zi
  Advanced Drug Delivery Reviews (Vol. 194) – 2023
  Atherosclerosis, a chronic cardiovascular disease caused by plaque development in arteries, remains a leading cause of morbidity and mortality. Atherosclerotic plaques are characterized by the expression and regulation of key molecules such as cell surface receptors, cytokines, and signaling pathway proteins, potentially facilitating precise diagnosis and treatment on a molecular level by specifically targeting the characteristic molecules. In this review, we highlight the recent progress in the past five years on developing molecularly targeted nanomedicine for imaging detection and treatment of atherosclerosis with the use of inorganic nanoparticles. Through targeted delivery of imaging contrast nanoparticles to specific molecules in atherogenesis, atherosclerotic plaque development at different stages could be identified and monitored via various molecular imaging modalities. We also review molecularly targeted therapeutic approaches that target and regulate molecules associated with lipid regulation, inflammation, and apoptosis. The review is concluded with discussion on current challenges and future development of nanomedicine for atherosclerotic diagnosis and treatment. 2023 The Authors
• Finerenone and effects on mortality in chronic kidney disease and type 2 diabetes: a FIDELITY analysis
  Filippatos, Gerasimos S.; Anker, Stefan D.; August, Phyllis A.; Coats, Andrew J.S.; Januzzi, James Louis; Mankovsky, Boris N.; Rossing, Peter R.; Ruilope, Lu Miguel; Pitt, Bertram A.; Sarafidis, Pantelis A.; Teerlink, John R.; Kapelios, Chris J.; Gebel, Martin; Brinker, Meike D.; Joseph, Amer; Lage, Andrea; Bakris, George L.; Agarwal, Rajiv L.
  European Heart Journal - Cardiovascular Pharmacotherapy (Vol. 9/2) – 2023
  Aims Finerenone reduces the risk of cardiovascular events in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). We investigated the causes of mortality in the FIDELITY population. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Methods and The FIDELITY prespecified pooled data analysis from FIDELIO-DKD and FIGARO-DKD excluded patients with heart results failure and reduced ejection fraction. Outcomes included intention-to-treat and prespecified on-treatment analyses of the risk of all-cause and cardiovascular mortality. Of 13 026 patients [mean age, 64.8 years; mean estimated glomerular filtration rate (eGFR), 57.6 mL/min/1.73 m2], 99.8% were on reninangiotensin system inhibitors. Finerenone reduced the incidence of all-cause and cardiovascular mortality vs. placebo (8.5% vs. 9.4% and 4.9% vs. 5.6%, respectively) and demonstrated significant on-treatment reductions [hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.700.96; P = 0.014 and HR, 0.82; 95% CI, 0.670.99; P = 0.040, respectively]. Cardiovascular-related mortality was most common, and finerenone lowered the incidence of sudden cardiac death vs. placebo [1.3% (incidence rate 0.44/100 patient-years) vs. 1.8% (0.58/100 patient-years), respectively; HR, 0.75; 95% CI, 0.570.996; P = 0.046]. The effects of finerenone on mortality were similar across all Kidney Disease: Improving Global Outcomes risk groups. Event probability with finerenone at 4 years was consistent irrespective of baseline urine albumin-to-creatinine ratio, but seemingly more pronounced in patients with higher baseline eGFR. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusion In FIDELITY, finerenone significantly reduced the risk of all-cause and cardiovascular mortality vs. placebo in patients with T2D across a broad spectrum of CKD stages while on treatment, as well as sudden cardiac death in the intention-to-treat population. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Clinical trials FIDELIO-DKD and FIGARO-DKD are registered with ClinicalTrials.gov, numbers NCT02540993 and NCT02545049, registration respectively (funded by Bayer AG). 2023 Oxford University Press. All rights reserved.
• The influence of growth mindset, discipline, flow and creativity on innovation: Introducing the M.D.F.C. model of innovation
  Krskova, Hana; Breyer, Yvonne Alexandra
  Heliyon (Vol. 9/3) – 2023
  In times of change, such as during periods wrought by the COVID-19 pandemic, organisations must innovate, as otherwise, they will perish. The only acceptable way forward now is about exploring avenues for increasing innovation in order for businesses to survive. The purpose of our paper is to put forward a conceptual model of factors with the potential to positively influence innovations to assist aspiring leaders and managers in addressing challenges in the future when uncertainty may be the norm rather than the exception. The authors introduce a novel M.D.F.C. Innovation Model, comprising the concepts of a growth mindset (M) and flow (F) as well as the skills of discipline (D) and creativity (C). While the elements of the new M.D.F.C. conceptual model of innovation as separate areas of study - have been extensively researched in past studies, the authors have combined them into one model for the first time. The opportunities stemming from the proposed new model are numerous, with the implications for educators, industry and theory discussed. Developing the teachable skills outlined in the model can bring benefits for both educational institutions and employers, as more employees could be equipped to look forward, be innovative and bring new, creative solutions to ill-defined problems. The model is equally suitable for individuals wishing to embrace thinking outside of the box to reap the benefits of enhancing their capacity for innovation in all aspects of their lives. 2023 The Authors
• Personalized care of patients with heart failure: are we ready for a REWOLUTION? Insights from two international surveys on healthcare professionals' needs and patients' perceptions
  Jankowska, Ewa Anita; Liu, Peter P.; Cowie, Martin R.; Groenhart, Max; Cobey, K. D.; Howlett, Jonathan G.; Komajda, Michel; Lund, Lars H.; Maga-Serrano, JosAntonio; Mourilhe-Rocha, Ricardo Gonlves; Rosano, Giuseppe Massimo Claudio; Saldarriaga-Giraldo, Clara In; Schwartzmann, Pedro Vellosa; Zannad, Faiez; Zhang, Jian; Zhang, Yuhui; Coats, Andrew J.S.
  European Journal of Heart Failure (Vol. 25/3) – 2023
  Aims: Guidelines for the management of heart failure (HF) are evolving, and increasing emphasis is placed on patient-centred care. As part of the REWOLUTION HF (REal WOrLd EdUcaTION in HF) programme, we conducted two international surveys aimed at assessing healthcare professionals' (HCPs) educational needs and patients' perspectives on the care of HF. Methods and results: Anonymous online questionnaires co-developed by HF experts and patients assessed HCPs' educational needs (520 respondents, mostly cardiologists, in 67 countries) and patients' perceptions on HF impact and management (98 respondents in 18 countries). Among HCPs, 62.7% prioritized rapid initiation of all guideline-mandated medications over up-titration of some medications, and 87.7% always or frequently discussed treatment goals with patients. There was good agreement between HCPs and patients on key treatment goals, except for a greater emphasis on reducing hospitalizations among HCPs. The most frequently cited barriers to the provision of guideline-recommended pharmacological therapy were treatment side effects/intolerance, complex treatment regimens, low blood pressure, cost/reimbursement issues, and low estimated glomerular filtration rate. Most patients (81.6%) reported no difficulties taking medications as prescribed, although 21.4% felt they were taking too many pills. Patients wanted more information about HF and its consequences, prognosis, and treatments (70.4%, 74.5% and 76.6%, respectively). Cardiologists were the preferred source of information about HF, followed by general practitioners and HF nurses. Conclusions: These surveys provide valuable insights into HCPs' needs about personalized care for patients with HF, as well as patients' perceptions, expectations and preferences. These findings will be helpful to develop patient-centred, needs-driven quality improvement programmes. 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
• Yield of diagnosis and risk of stroke with screening strategies for atrial fibrillation: a comprehensive review of current evidence
  Corica, Bernadette; Bonini, Niccol Imberti, Jacopo Francesco; Romiti, Giulio Francesco; Vitolo, Marco; Attanasio, Lisa; Basili, Stefania; Freedman, Ben Ben; Potpara, Tatjana S.; Boriani, Giuseppe; Lip, Gregory Y.H.; Proietti, Marco
  European Heart Journal Open (Vol. 3/2) – 2023
  Atrial fibrillation (AF) is the most prevalent arrhythmia worldwide. The presence of AF is associated with increased risk of systemic thromboembolism, but with the uptake of oral anticoagulant (OAC) and implementation of a holistic and integrated care management, this risk is substantially reduced. The diagnosis of AF requires a 30-s-long electrocardiographic (ECG) trace, irrespective of the presence of symptoms, which may represent the main indication for an ECG tracing. However, almost half patients are asymptomatic at the time of incidental AF diagnosis, with similar risk of stroke of those with clinical AF. This has led to a crucial role of screening for AF, to increase the diagnosis of population at risk of clinical events. The aim of this review is to give a comprehensive overview about the epidemiology of asymptomatic AF, the different screening technologies, the yield of diagnosis in asymptomatic population, and the benefit derived from screening in terms of reduction of clinical adverse events, such as stroke, cardiovascular, and all-cause death. We aim to underline the importance of implementing AF screening programmes and reporting about the debate between scientific societies clinical guidelines recommendations and the concerns expressed by the regulatory authorities, which still do not recommend population-wide screening. This review summarizes data on the ongoing trials specifically designed to investigate the benefit of screening in terms of risk of adverse events which will further elucidate the importance of screening in reducing risk of outcomes and influence and inform clinical practice in the next future. The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.
• Intraplaque Myeloperoxidase Activity as Biomarker of Unstable Atheroma and Adverse Clinical Outcomes in Human Atherosclerosis
  Nadel, James; Tumanov, Sergey; Kong, Stephanie M.Y.; Chen, Weiyu; Giannotti, Nicola; Sivasubramaniam, Vanathi; Rashid, Imran M.; Ugander, Martin; Jabbour, Andrew; Stocker, Roland
  JACC: Advances (Vol. 2/3) – 2023
  Background: The detection of unstable atherosclerosis remains elusive. Intraplaque myeloperoxidase (MPO) activity causes plaque destabilization in preclinical models, holding promise for clinical translation as a novel imaging biomarker. Objectives: The purpose of this study was to assess whether MPO activity is greater in unstable human plaques, how this relates to cardiovascular events and current/emerging non-invasive imaging techniques. Methods: Thirty-one carotid endarterectomy specimens and 12 coronary trees were collected. MPO activity was determined in 88 individual samples through the conversion of hydroethidine to the MPO-specific adduct 2-chloroethidium and compared with macroscopic validation, histology, clinical outcomes, and computed tomographyderived high and low attenuation plaques and perivascular adipose tissue. Non-parametric statistical analysis utilizing Mann-Whitney U and Kruskal-Wallis tests for univariate and group comparisons were performed. Results: Unstable compared with stable plaque had higher MPO activity (carotid endarterectomy: n = 26, 4.2 3.1 vs 0.2 0.3 nmol/mgp; P < 0.0001; coronary: n = 17, 0.6 0.5 vs 0.001 0.003 nmol/mgp; P = 0.0006). Asymptomatic, stroke-free patients had lower MPO activity compared to those with symptoms or ipsilateral stroke (n = 12, 3.7 2.1 vs 0.1 0.2 nmol/mgp; P = 0.002). Computed tomographydetermined plaque attenuation did not differentiate MPO activity (n = 30, 0.1 0.1 vs 0.2 0.3 nmol/mgp; P = 0.23) and MPO activity was not found in perivascular adipose tissue. Conclusions: MPO is active within unstable human plaques and correlates with symptomatic carotid disease and stroke, yet current imaging parameters do not identify plaques with active MPO. As intraplaque MPO activity can be imaged non-invasively through novel molecular imaging probes, ongoing investigations into its utility as a diagnostic tool for high-risk atherosclerosis is warranted. 2023 The Authors
• Late outcomes in adults with atrial switch for transposition of the great arteries according to risk factor profile at 30 years of age
  Cherrett, Callum; Baker, David William; Dennis, Mark R.; Kotchetkova, Irina; Celermajer, David S.; Cordina, Rachael Louise
  International Journal of Cardiology Congenital Heart Disease (Vol. 11) – 2023
  Objective: To compare the late outcomes of adults who underwent atrial switch repair for dextro-transposition of the great arteries, based on their risk profile at age 30 years. Methods: We performed a retrospective study of 67 participants who had undergone atrial switch repair. Low risk people were defined as those who reached age 30 years or beyond with normal or mildly impaired systemic right ventricular (RV) function with no or mild tricuspid regurgitation (TR). High risk people were defined as those who had moderate or severe systemic RV dysfunction, or moderate or severe tricuspid regurgitation by age 30. The primary outcome was transplant-free survival and the secondary outcome was a composite end-point including hospitalisations for heart failure, inotrope requirement, referral for transplantation and transplantation. Results: 52/67 (78%) were classified as low risk and 15/67 (22%) were classified as high risk. At 45 years, transplant-free survival was 31% for the high risk group compared to 87% for low risk. All high risk people met the composite endpoint at 45 years compared to only 18% of the low risk group (hazard ratio 6.3, p = 0.03). Conclusion: Transplant-free survival is markedly reduced in high risk atrial switch patients. Risk stratification based on systemic right ventricular function and tricuspid regurgitation at age 30 may predict future health outcomes for atrial switch patients. 2022 The Authors
• An examination of the levels of work ethic in the university context across the United States of America, Korea and China
  Krskova, Hana; Breyer, Yvonne Alexandra
  International Journal of Educational Management (Vol. 37/2) – 2023
  Purpose: The purpose of this paper is to examine individuals' levels of work ethic amongst current and recent university attendees across three countries. This article presents the results of a survey of 537 respondents from the United States of America, Korea and China, thus extending the previous research into work ethic, often conducted from a Western perspective. The comparative study aims to enhance the understanding of cross-cultural and gender differences and similarities whilst probing for the levels of work ethic amongst the respondents. Design/methodology/approach: A comparative research method was adopted because the authors' aim was to probe similarities and differences across three societies. Multiple analysis of variance (ANOVA) and t-tests were utilised to explore gender and country-related differences. Cluster analysis was applied to probe for segments highly similar to each other in the levels of work ethic of the respondents. Findings: The results confirm the hypothesised differences between countries as well as across gender groups, with American females having the highest levels of work ethic, closely followed by Chinese males and females. Three distinct segments low, medium and high levels of work ethic were found in all three countries, indicating that there are individuals in each of the societies who could benefit from strategies for increasing the individuals' levels of work ethic. Originality/value: Novel gender comparisons of the three country groups revealed American females as having the highest levels of work ethic and Korean females the lowest, whilst the identification of clusters of low, medium and high levels of work ethic provides evidence of the need to increase levels of work ethic to enhance productivity, regardless of the country of origin. 2022, Emerald Publishing Limited.
• Megakaryocyte buds are distinct from microvesicles and likely to represent platelet precursors
  Ellis, Marc L.; Alwis, Imala D.; Smythe, Rhyll E.; Yuan, Yuping; Jackson, Shaun P.
  Blood Advances (Vol. 7/6) – 2023
  [No abstract available]
• Destabilization of Atherosclerotic Plaque by Bilirubin Deficiency
  Chen, Weiyu; Tumanov, Sergey; Stanley, Christopher P.; Kong, Stephanie M.Y.; Nadel, James; Vigder, Niv; Newington, Darren L.; Wang, Xiaosuo; Dunn, Louise L.; Stocker, Roland
  Circulation Research (Vol. 132/7) – 2023
  Background: The rupture of atherosclerotic plaque contributes significantly to cardiovascular disease. Plasma concentrations of bilirubin - a byproduct of heme catabolism - inversely associate with risk of cardiovascular disease, although the link between bilirubin and atherosclerosis remains unclear. Methods: To assess the role of bilirubin in atherosclerotic plaque stability, we crossed Bvra-/-with Apoe-/-mice and used the tandem stenosis model of plaque instability. Human coronary arteries were obtained from heart transplant recipients. Analysis of bile pigments, heme metabolism, and proteomics were performed by liquid chromatography tandem mass spectrometry. MPO (myeloperoxidase) activity was determined by in vivo molecular magnetic resonance imaging, liquid chromatography tandem mass spectrometry analysis, and immunohistochemical determination of chlorotyrosine. Systemic oxidative stress was evaluated by plasma concentrations of lipid hydroperoxides and the redox status of circulating Prx2 (peroxiredoxin 2), whereas arterial function was assessed by wire myography. Atherosclerosis and arterial remodeling were quantified by morphometry and plaque stability by fibrous cap thickness, lipid accumulation, infiltration of inflammatory cells, and the presence of intraplaque hemorrhage. Results: Compared with Bvra+/+Apoe-/-tandem stenosis littermates, Bvra-/-Apoe-/-tandem stenosis mice were deficient in bilirubin, showed signs of increased systemic oxidative stress, endothelial dysfunction, as well as hyperlipidemia, and had a higher atherosclerotic plaque burden. Heme metabolism was increased in unstable compared with stable plaque of both Bvra+/+Apoe-/-and Bvra-/-Apoe-/-tandem stenosis mice and in human coronary plaques. In mice, Bvra deletion selectively destabilized unstable plaque, characterized by positive arterial remodeling and increased cap thinning, intraplaque hemorrhage, infiltration of neutrophils, and MPO activity. Proteomic analysis confirmed Bvra deletion enhanced extracellular matrix degradation, recruitment and activation of neutrophils, and associated oxidative stress in unstable plaque. Conclusions: Bilirubin deficiency, resulting from global Bvra deletion, generates a proatherogenic phenotype and selectively enhances neutrophil-mediated inflammation and destabilization of unstable plaque, thereby providing a link between bilirubin and cardiovascular disease risk. 2023 Lippincott Williams and Wilkins. All rights reserved.
• The Prognostic, Diagnostic, and Therapeutic Potential of TRAIL Signalling in Cardiovascular Diseases
  Kelland, Elaina; Patil, Manisha S.; Patel, Sanjay; Cartland, Si; Kavurma, Mary M.
  International Journal of Molecular Sciences (Vol. 24/7) – 2023
  TNF-related apoptosis-inducing ligand (TRAIL) was originally discovered, almost 20 years ago, for its ability to kill cancer cells. More recent evidence has described pleiotropic functions, particularly in the cardiovascular system. There is potential for TRAIL concentrations in the circulation to act as prognostic and/or diagnostic factors for cardiovascular diseases (CVD). Pre-clinical studies also describe the therapeutic capacity for TRAIL signals, particularly in the context of atherosclerotic disease and diseases of the myocardium. Because diabetes mellitus significantly contributes to the progression and pathogenesis of CVDs, in this review we highlight recent evidence for the prognostic, diagnostic, and therapeutic potential of TRAIL signals in CVDs, and where relevant, the impact of diabetes mellitus. A greater understanding of how TRAIL signals regulate cardiovascular protection and pathology may offer new diagnostic and therapeutic avenues for patients suffering from CVDs. 2023 by the authors.
• Clinical and Prognostic Relevance of Cardiac Wasting in Patients With Advanced Cancer
  Lena, Alessia; Wilkenshoff, Ursula M.; Hadzibegovic, Sara; Porthun, Jan; Rnick, Lukas; Frlich, Ann Kathrin; Zeller, Tanja; Karakas, Mahir; Keller, Ulrich Bernd; Ahn, Johann; Bullinger, Lars B.; Riess, Hanno B.; Rosen, Stuart D.; Lyon, Alexander Richard; Lcher, Thomas Felix; Totzeck, Matthias; Rassaf, Tienush; Burkhoff, Daniel; Mehra, M. R.; Bax, Jeroen Joost J.; Butler, Javed J.; Edelmann, Frank; Haverkamp, Wilhelm L.; Anker, Stefan D.; Packer, Milton P.; Coats, Andrew J.S.; von Haehling, Stephan; Landmesser, Ulf E.; Anker, Markus S.
  Journal of the American College of Cardiology (Vol. 81/16) – 2023
  Background: Body wasting in patients with cancer can affect the heart. Objectives: The frequency, extent, and clinical and prognostic importance of cardiac wasting in cancer patients is unknown. Methods: This study prospectively enrolled 300 patients with mostly advanced, active cancer but without significant cardiovascular disease or infection. These patients were compared with 60 healthy control subjects and 60 patients with chronic heart failure (ejection fraction <40%) of similar age and sex distribution. Results: Cancer patients presented with lower left ventricular (LV) mass than healthy control subjects or heart failure patients (assessed by transthoracic echocardiography: 177 47 g vs 203 64 g vs 300 71 g, respectively; P < 0.001). LV mass was lowest in cancer patients with cachexia (153 42 g; P < 0.001). Importantly, the presence of low LV mass was independent of previous cardiotoxic anticancer therapy. In 90 cancer patients with a second echocardiogram after 122 71 days, LV mass had declined by 9.3% 1.4% (P < 0.001). In cancer patients with cardiac wasting during follow-up, stroke volume decreased (P < 0.001) and resting heart rate increased over time (P = 0.001). During follow-up of on average 16 months, 149 patients died (1-year all-cause mortality 43%; 95% CI: 37%-49%). LV mass and LV mass adjusted for height squared were independent prognostic markers (both P < 0.05). Adjustment of LV mass for body surface area masked the observed survival impact. LV mass below the prognostically relevant cutpoints in cancer was associated with reduced overall functional status and lower physical performance. Conclusions: Low LV mass is associated with poor functional status and increased all-cause mortality in cancer. These findings provide clinical evidence of cardiac wastingassociated cardiomyopathy in cancer. 2023 The Authors
• Mechano-Redox Control of Mac-1 De-Adhesion by PDI Promotes Directional Movement under Flow
  Dupuy, Alexander; Aponte-Santamar, Camilo; Yeheskel, Adva; Hortle, Elinor J.; Oehlers, Stefan H.; Grer, Frauke; Hogg, Philip J.; Passam, Freda H.; Chiu, Joyce
  Circulation Research (Vol. 132/9) – 2023
  Background: Neutrophil migration is critical to the initiation and resolution of inflammation. Macrophage-1 antigen (Mac-1; CD11b/CD18, M?2) is a leukocyte integrin essential for firm adhesion to endothelial ICAM-1 (intercellular adhesion molecule 1) and migration of neutrophils in the shear forces of the circulation. PDI (protein disulfide isomerase) has been reported to influence neutrophil adhesion and migration. We aimed to elucidate the molecular mechanism of PDI control of Mac-1 affinity for ICAM-1 during neutrophil migration under fluid shear. Methods: Neutrophils isolated from whole blood were perfused over microfluidic chips coated with ICAM-1. Colocalization of Mac-1 and PDI on neutrophils was visualized by fluorescently labeled antibodies and confocal microscopy. The redox state of Mac-1 disulfide bonds was mapped by differential cysteine alkylation and mass spectrometry. Wild-type or disulfide mutant Mac-1 was expressed recombinantly in Baby Hamster Kidney cells to measure ligand affinity. Mac-1 conformations were measured by conformation-specific antibodies and molecular dynamics simulations. Neutrophils crawling on immobilized ICAM-1 were measured in presence of oxidized or reduced PDI, and the effect of PDI inhibition using isoquercetin on neutrophil crawling on inflamed endothelial cells was examined. Migration indices in the X- and Y-direction were determined and the crawling speed was calculated. Results: PDI colocalized with high-affinity Mac-1 at the trailing edge of stimulated neutrophils when crawling on ICAM-1 under fluid shear. PDI cleaved 2 allosteric disulfide bonds, C169-C176 and C224-C264, in the ?I domain of the ?2 subunit, and cleavage of the C224-C264 disulfide bond selectively controls Mac-1 disengagement from ICAM-1 under fluid shear. Molecular dynamics simulations and conformation-specific antibodies reveal that cleavage of the C224-C264 bond induces conformational change and mechanical stress in the ?I domain. This allosterically alters the exposure of an I domain epitope associated with a shift of Mac-1 to a lower-affinity state. These molecular events promote neutrophil motility in the direction of flow at high shear stress. Inhibition of PDI by isoquercetin reduces neutrophil migration in the direction of flow on endothelial cells during inflammation. Conclusions: Shear-dependent PDI cleavage of the neutrophil Mac-1 C224-C264 disulfide bond triggers Mac-1 de-adherence from ICAM-1 at the trailing edge of the cell and enables directional movement of neutrophils during inflammation. 2023 Lippincott Williams and Wilkins. All rights reserved.
• Minimal Clinically Important Differences in 6-Minute Walk Test in Patients With HFrEF and Iron Deficiency: MCID for 6MWT in patients with HFrEF and iron deficiency
  Khan, Muhammad Shahzeb; Anker, Stefan D.; Friede, Tim; Jankowska, Ewa Anita; Metra, Marco; Pi, Ileana L.; Coats, Andrew J.S.; Rosano, Giuseppe Massimo Claudio; Roubert, Bernard; Goehring, Udo Michael; Dorigotti, Fabio; Com-Colet, Josep; Vanveldhuisen, Dirk J.; Filippatos, Gerasimos S.; Ponikowski, Piotr P.; Butler, Javed J.
  Journal of Cardiac Failure (Vol. 29/5) – 2023
  Background: The 6-minute walk test (6MWT) is widely used to measure exercise capacity; however, the magnitude of change that is clinically meaningful for individuals is not well established in heart failure with reduced ejection fraction (HFrEF). Objective: To calculate the minimal clinically important difference (MCID) for change in exercise capacity in the 6MWT in iron-deficient populations with HFrEF. Methods: In this pooled secondary analysis of the FAIR-HF and CONFIRM-HF trials, mean changes in the 6MWT from baseline to weeks 12 and 24 were calculated and calibrated against the Patient Global Assessment (PGA) tool (clinical anchor) to derive MCIDs in improvement and deterioration. Results: Of 760 patients included in the 2 trials, 6MWT and PGA data were available for 680 (89%) and 656 (86%) patients at weeks 12 and 24, respectively. The mean 6MWT distance at baseline was 281 103 meters. There was a modest correlation between changes in 6MWT and PGA from baseline to week 12 (r = 0.31; P < 0.0001) and week 24 (r = 0.43; P < 0.0001). Respective estimates (95% confidence intervals) of MCID in 6MWT at weeks 12 and 24 were 14 meters (5;23) and 15 meters (3;27) for a little improvement (vs no change), 20 meters (10;30) and 24 meters (12;36) for moderate improvement vs a little improvement,, -11 meters (-32;9.2) and -31 meters (-53;-8) for a little deterioration (vs no change), and -84 meters (-144;-24) and -69 meters (-118;-20) for moderate deterioration vs a little deterioration. Conclusions: The MCID for improvement in exercise capacity in the 6MWT was 14 meters15 meters in patients with HFrEF and iron deficiency. These MCIDs can aid clinical interpretation of study data. 2022 The Author(s)
• Autonomic and respiratory consequences of altered chemoreflex function: clinical and therapeutic implications in cardiovascular diseases
  Giannoni, Alberto; Borrelli, Chiara; Gentile, Francesco; Sciarrone, Paolo; Spiessher, Jens; PIEPOLI, MASSIMO Francesco; Richerson, George Bradley; Floras, John S.; Coats, Andrew J.S.; Javaheri, Shahrokh; Emdin, Michele; Passino, Claudio
  European Journal of Heart Failure (Vol. 25/5) – 2023
  The importance of chemoreflex function for cardiovascular health is increasingly recognized in clinical practice. The physiological function of the chemoreflex is to constantly adjust ventilation and circulatory control to match respiratory gases to metabolism. This is achieved in a highly integrated fashion with the baroreflex and the ergoreflex. The functionality of chemoreceptors is altered in cardiovascular diseases, causing unstable ventilation and apnoeas and promoting sympathovagal imbalance, and it is associated with arrhythmias and fatal cardiorespiratory events. In the last few years, opportunities to desensitize hyperactive chemoreceptors have emerged as potential options for treatment of hypertension and heart failure. This review summarizes up to date evidence of chemoreflex physiology/pathophysiology, highlighting the clinical significance of chemoreflex dysfunction, and lists the latest proof of concept studies based on modulation of the chemoreflex as a novel target in cardiovascular diseases. 2023 European Society of Cardiology.