The Establishment of the Nordic Cardio-Oncology Society

Non peer reviewe

Role of Histone Acetylation in the Stimulatory Effect of Valproic Acid on Vascular Endothelial Tissue-Type Plasminogen Activator Expression

No grant i

Screen Time and Body Image in Icelandic Adolescents : Sex-Specific Cross-Sectional and Longitudinal Associations

Funding Information: Funding: This research was funded by The University of Iceland Research Fund, grant number. HI16120043, and the Icelandic Centre for research (RANNIS), grant number 152509-051. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Studies of adolescent body image and screen use are mostly limited to girls, and longitudinal data are scarce. We examined cross-sectional and longitudinal associations between these variables in mid-adolescent boys and girls. Data was collected when participants were at age 15 and 17, by questionnaire and objective measurements (n = 152 had complete data). Sex-specific linear regression was used to explore cross-sectional and longitudinal associations of self-reported screen use (total use, and time spent in gaming, TV/DVD/internet-based watching and internet use for communication) and body image, adjusting for vigorous physical activity, symptoms of depression, and body composition. Screen time was negatively associated with body image at both time points, although more strongly at age 15, and for girls only. Gaming and TV/DVD/internet watching was more strongly associated with body image than internet use for communication. Girls with above median screen time at both ages had 14% lower body image score at age 17 than girls with below median screen time at both time points. Our results suggest that screen use is likely to play a role in the development of body dissatisfaction among adolescent females. Limiting screen time may, therefore, help to mitigate body dissatisfaction in adolescent girls.Peer reviewe

Opposite effects of uracil and adenine nucleotides on the survival of murine cardiomyocytes

We previously showed that the human heart expresses all known P2X and P2Y receptors activated by extracellular adenine or uracil nucleotides. Despite evidence that, both in humans and rodents, plasma levels of ATP and UTP markedly increase during myocardial infarction, the differential effects mediated by the various adenine- and uracil-preferring myocardial P2 receptors are still largely unknown. Here, we studied the effects of adenine and uracil nucleotides on murine HL-1 cardiomyocytes. RT-PCR analysis showed that HL-1 cardiomyocytes express all known P2X receptors (except for P2X2), as well as the P2Y2,4,6,14 subtypes. Exposure of cardiomyocytes to adenine nucleotides (ATP, ADP or BzATP) induced apoptosis and necrosis, as determined by flow-cytometry. Cell death was exacerbated by tumour necrosis factor (TNF)-alpha, a cytokine implicated in chronic heart failure progression. Conversely, uracil nucleotides (UTP, UDP and UDPglucose) had no effect 'per se', but fully counteracted the deleterious effects induced by adenine nucleotides and TNF- alpha, even if added to cardiomyocytes after beginning exposure to these cell death-inducing agents. Thus, exposure of cardiomyocytes to elevated concentrations of ATP or ADP in the presence of TNF- alpha contributes to cell death, an effect which is counteracted by uracil-preferring P2 receptors. Cardiomyocytes do not need to be 'primed' by uracil nucleotides to become insensitive to adenine nucleotides-induced death, suggesting the existence of a possible 'therapeutic' window for uracil nucleotides-mediated protection. Thus, release of UTP during cardiac ischaemia and in chronic heart failure may protect against myocardial damage, setting the basis for developing novel cardioprotective agents that specifically target uracil-preferring P2Y receptors

Definitions of clinical study outcome measures for cardiovascular diseases: The European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart)

Background and Aims: Standardized definitions for outcome measures in randomized clinical trials and observational studies are essential for robust and valid evaluation of medical products, interventions, care, and outcomes. The European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart) project of the European Society of Cardiology aimed to create international data standards for cardiovascular clinical study outcome measures. Methods: The EuroHeart methods for data standard development were used. From a Global Cardiovascular Outcomes Consortium of 82 experts, five Working Groups were formed to identify and define key outcome measures for: cardiovascular disease (generic outcomes), acute coronary syndrome and percutaneous coronary intervention (ACS/PCI), atrial fibrillation (AF), heart failure (HF) and transcatheter aortic valve implantation (TAVI). A systematic review of the literature informed a modified Delphi method to reach consensus on a final set of variables. For each variable, the Working Group provided a definition and categorized the variable as mandatory (Level 1) or optional (Level 2) based on its clinical importance and feasibility. Results: Across the five domains, 24 Level 1 (generic: 5, ACS/PCI: 8, AF: 2; HF: 5, TAVI: 4) and 48 Level 2 (generic: 18, ACS-PCI: 7, AF: 6, HF: 2, TAVI: 15) outcome measures were defined. Conclusions: Internationally derived and endorsed definitions for outcome measures for a range of common cardiovascular diseases and interventions are presented. These may be used for data alignment to enable high-quality observational and randomized clinical research, audit, and quality improvement for patient benefit

Local regulation of the endogenous fibrinolytic system in man

The physiologically most important activator of intravascular fibrinolysis is tissue-type plasminogen activator (tPA). The endothelium synthesises and stores tPA and regulated release of the enzyme is an important mechanism for removal of fibrin from blood vessels. Plasminogen activator inhibitor type-1 (PAI-1) is the main inhibitor of tPA. The aim of the present thesis was to study how the local availability of free tPA is regulated under baseline conditions and during stimulated tPA release, to explore the potential role of extracellular nucleotides as potential mediators of tPA release in tissue injury and ischaemia, and to analyse if the capacity for tPA is decreased in hypertension and advanced chronic renal failure, and if so which mechanism may be involved.The studies were performed in 115 healthy subjects, seven patients with essential hypertension, and nine patients with advanced chronic renal failure. The release of tPA and PAI-1 was studied in a perfused-forearm model, at baseline and during stimulation with sodium nitroprusside, methacholine, desmopressin, or the extracellular nucleotides ATP and UTP. Also, the synthesis and secretion of tPA were studied in human conduit vessels perfused with high versus low intraluminal pressure ex vivo. During the morning hours the fibrinolytic activity increased secondary to an increase in the endothelial release of tPA and a decrease in the overall availability of its inhibitor PAI-1. The capacity for stimulated tPA release was not predicted from either plasma concentrations of the activator or its inhibitor, or from the basal release rate of these proteins. The local availability of free active tPA during stimulation of tPA release was dependent on the tPA release rate and not the inflow/release of inhibitors (PAI-1). The extracellular nucleotides ATP and UTP were found to induce regulated tPA release, which in the case of UTP was independent of NO and prostaglandin synthesis. Nucleotide stimulated tPA release may be a potential mechanism for activation of the thromboprotective programme.The capacity for regulated tPA release was found to be markedly impaired in patients with hypertension and advanced chronic renal failure. A potential mechanism is that high blood pressure in it self impairs regulated tPA release, as high intraluminal perfusions pressure inhibited tPA synthesis and release in endothelial cells ex vivo.In conclusion, these findings support the hypothesis that regulated tPA release is the major determinant of the local availability of active tPA. It was therefore of interest to find the capacity for stimulated tPA release to be reduced in patients with hypertension and advanced chronic renal failure, an impairment that potentially increases the susceptibility for atherothrombosis