Search

Abstract After SARS-CoV-2 infection, strict recommendations for return-to-sport were published. However, data are insufficient about the long-term effects on athletic performance. After suffering SARS-CoV-2 infection, and returning to maximal-intensity trainings, control examinations were performed with vita-maxima cardiopulmonary exercise testing (CPET). From various sports, 165 asymptomatic elite athletes (male: 122, age: 20y (IQR: 17-24y), training:16 h/w (IQR: 12–20 h/w), follow-up:93.5 days (IQR: 66.8–130.0 days) were examined. During CPET examinations, athletes achieved 94.7 ± 4.3% of maximal heart rate, 50.9 ± 6.0 mL/kg/min maximal oxygen uptake (V̇O2max), and 143.7 ± 30.4L/min maximal ventilation. Exercise induced arrhythmias (n = 7), significant horizontal/descending ST-depression (n = 3), ischemic heart disease (n = 1), hypertension (n = 7), slightly elevated pulmonary pressure (n = 2), and training-related hs-Troponin-T increase (n = 1) were revealed. Self-controlled CPET comparisons were performed in 62 athletes: due to intensive re-building training, exercise time, V̇O2max and ventilation increased compared to pre-COVID-19 results. However, exercise capacity decreased in 6 athletes. Further 18 athletes with ongoing minor long post-COVID symptoms, pathological ECG (ischemic ST-T changes, and arrhythmias) or laboratory findings (hsTroponin-T elevation) were controlled. Previous SARS-CoV-2-related myocarditis (n = 1), ischaemic heart disease (n = 1), anomalous coronary artery origin (n = 1), significant ventricular (n = 2) or atrial (n = 1) arrhythmias were diagnosed. Three months after SARS-CoV-2 infection, most of the athletes had satisfactory fitness levels. Some cases with SARS-CoV-2 related or not related pathologies requiring further examinations, treatment, or follow-up were revealed.

In this single-arm clinical trial, the authors show that treatment of COVID-19 patients with bevacizumab, an anti-vascular endothelial growth factor drug, can improve PaO2/FiO2 ratios and oxygen-support status. Relative to an external control group, bevacizumab shows clinical efficacy by improving oxygenation.

ABCC9 encodes the SUR2 subunit of KATP channels and dominant genetic variants in ABCC9 have been associated with cardiac phenotypes. Here, the authors report recessive ABCC9 mutations in individuals with mild intellectual disability, myopathy and cardiac systolic dysfunction which is associated with loss of KATP channel function.

Abstract GLUT transgenic and knockout mice have provided valuable insight into the role of facilitative glucose transporters (GLUTs) in cardiovascular and metabolic disease, but compensatory physiological changes can hinder interpretation of these models. To determine whether adaptations occur in response to GLUT inhibition in the failing adult heart, we chronically treated TG9 mice, a transgenic model of dilated cardiomyopathy and heart failure, with the GLUT inhibitor ritonavir. Glucose tolerance was significantly improved with chronic treatment and correlated with decreased adipose tissue retinol binding protein 4 (RBP4) and resistin. A modest improvement in lifespan was associated with decreased cardiomyocyte brain natriuretic peptide (BNP) expression, a marker of heart failure severity. GLUT1 and −12 protein expression was significantly increased in left ventricular (LV) myocardium in ritonavir-treated animals. Supporting a switch from fatty acid to glucose utilization in these tissues, fatty acid transporter CD36 and fatty acid transcriptional regulator peroxisome proliferator-activated receptor α (PPARα) mRNA were also decreased in LV and soleus muscle. Chronic ritonavir also increased cardiac output and dV/dt-d in C57Bl/6 mice following ischemia-reperfusion injury. Taken together, these data demonstrate compensatory metabolic adaptation in response to chronic GLUT blockade as a means to evade deleterious changes in the failing heart.

Abstract The current research study evaluated the health and environmental risks issues associated with potentially toxic elements (PTEs) in the complex terminal aquifer located in the Algerian desert. The methods used included principal component and cluster (dendrogram) analysis to estimate source of ions and contamination. Various indices such as the Heavy Metal Pollution Index (HPI), Metal Index, hazard quotient, hazard index (HI), and cancer risk (CR) were applied to assess both environmental and human health risks. Furthermore, the Monte Carlo method was applied for probabilistic assessment of carcinogenic and non-carcinogenic risks through oral and dermal exposure routes in both adults and children. The results revealed that approximately 16% of the samples fell within the low pollution category (HPI

Abstract Mitral stenosis (MS) is a complex valvular pathology with significant clinical burden even today. Its effect on the right heart is often overlooked, despite it playing a considerable part in the symptomatic status. We enrolled 39 mitral valve stenosis patients and 39 age- and gender-matched healthy controls. They underwent conventional, speckle-tracking and 3D echocardiographic examinations. The 3D data was analyzed using the ReVISION software to calculate RV functional parameters. In the MS group, 3D RV ejection fraction (EF) (49 ± 7% vs. 61 ± 4%; p

Abstract This study assessed the environmental and health risks associated with heavy metals in the water resources of Egypt's northwestern desert. The current approaches included the Spearman correlation matrix, principal component analysis, and cluster analysis to identify pollution sources and quality-controlling factors. Various indices (HPI, MI, HQ, HI, and CR) were applied to evaluate environmental and human health risks. Additionally, the Monte Carlo method was employed for probabilistic carcinogenic and non-carcinogenic risk assessment via oral and dermal exposure routes in adults and children. Notably, all water resources exhibited high pollution risks with HPI and MI values exceeding permissible limits (HPI > 100 and MI > 6), respectively. Furthermore, HI oral values indicated significant non-carcinogenic risks to both adults and children, while dermal contact posed a high risk to 19.4% of samples for adults and 77.6% of samples for children (HI > 1). Most water samples exhibited CR values exceeding 1 × 10–4 for Cd, Cr, and Pb, suggesting vulnerability to carcinogenic effects in both age groups. Monte Carlo simulations reinforced these findings, indicating a significant carcinogenic impact on children and adults. Consequently, comprehensive water treatment measures are urgently needed to mitigate carcinogenic and non-carcinogenic health risks in Siwa Oasis.

Abstract Choosing the optimal device during cardiac resynchronization therapy (CRT) upgrade can be challenging. Therefore, we sought to provide a solution for identifying patients in whom upgrading to a CRT-defibrillator (CRT-D) is associated with better long-term survival than upgrading to a CRT-pacemaker (CRT-P). To this end, we first applied topological data analysis to create a patient similarity network using 16 clinical features of 326 patients without prior ventricular arrhythmias who underwent CRT upgrade. Then, in the generated circular network, we delineated three phenogroups exhibiting significant differences in clinical characteristics and risk of all-cause mortality. Importantly, only in the high-risk phenogroup was upgrading to a CRT-D associated with better survival than upgrading to a CRT-P (hazard ratio: 0.454 (0.228–0.907), p = 0.025). Finally, we assigned each patient to one of the three phenogroups based on their location in the network and used this labeled data to train multi-class classifiers to enable the risk stratification of new patients. During internal validation, an ensemble of 5 multi-layer perceptrons exhibited the best performance with a balanced accuracy of 0.898 (0.854–0.942) and a micro-averaged area under the receiver operating characteristic curve of 0.983 (0.980–0.986). To allow further validation, we made the proposed model publicly available ( https://github.com/tokmarton/crt-upgrade-risk-stratification ).

Abstract Interleukin-1β (IL-1β) is a key mediator of non-alcoholic steatohepatitis (NASH), a chronic liver disease, and of systemic inflammation-driven aging. IL-1β contributes to cardio-metabolic decline, and may promote hepatic oncogenic transformation. Therefore, IL-1β is a potential therapeutic target in these pathologies. We aimed to investigate the hepatic and cardiac effects of an IL-1β targeting monoclonal antibody in an aged mouse model of NASH. 24 months old male C57Bl/6J mice were fed with control or choline deficient (CDAA) diet and were treated with isotype control or anti-IL-1β Mab for 8 weeks. Cardiac functions were assessed by conventional—and 2D speckle tracking echocardiography. Liver samples were analyzed by immunohistochemistry and qRT-PCR. Echocardiography revealed improved cardiac diastolic function in anti-IL-1β treated mice with NASH. Marked hepatic fibrosis developed in CDAA-fed group, but IL-1β inhibition affected fibrosis only at transcriptomic level. Hepatic inflammation was not affected by the IL-1β inhibitor. PCNA staining revealed intensive hepatocyte proliferation in CDAA-fed animals, which was not influenced by neutralization of IL-1β. IL-1β inhibition increased hepatic expression of Pd-1 and Ctla4, while Pd-l1 expression increased in NASH. In conclusion, IL-1β inhibition improved cardiac diastolic function, but did not ameliorate features of NASH; moreover, even promoted hepatic immune checkpoint expression, with concomitant NASH-related hepatocellular proliferation.

Abstract Doxorubicin (Dox), a widely used anticancer DNA-binding drug, affects chromatin in multiple ways, and these effects contribute to both its efficacy and its dose-limiting side effects, especially cardiotoxicity. Here, we studied the effects of Dox on the chromatin binding of the architectural proteins high mobility group B1 (HMGB1) and the linker histone H1, and the transcription factor retinoic acid receptor (RARα) by fluorescence recovery after photobleaching (FRAP) and fluorescence correlation spectroscopy (FCS) in live cells. At lower doses, Dox increased the binding of HMGB1 to DNA while decreasing the binding of the linker histone H1. At higher doses that correspond to the peak plasma concentrations achieved during chemotherapy, Dox reduced the binding of HMGB1 as well. This biphasic effect is interpreted in terms of a hierarchy of competition between the ligands involved and Dox-induced local conformational changes of nucleosome-free DNA. Combined, FRAP and FCS mobility data suggest that Dox decreases the overall binding of RARα to DNA, an effect that was only partially overcome by agonist binding. The intertwined interactions described are likely to contribute to both the effects and side effects of Dox.