The Distinct Regulation of the Vitamin D and Aryl Hydrocarbon Receptors in COVID-19.

(1) Background: SARS-CoV-2 affects several immune pathways, including the vitamin D (VDR) and the aryl hydrocarbon receptor pathways (AhR). The aim of the study was the evaluation of the VDR and AhR pathways in the blood of COVID-19 patients with regard to the severity of disease. (2) Methods: Observational, single-center, case-control design.

Ankle function after reconstruction of post-traumatic soft tissue defects with soleus and/or gastrocnemius local muscle flaps.

Local muscle flaps are especially advantageous when treating soft tissue defects, but one disadvantage is the potential functional deficits associated with the muscle transfer. In this study, we evaluated ankle function among patients (cases) who underwent reconstruction of soft tissue defects in the leg using local flaps of the gastrocnemius and/or soleus muscle. Function was compared between the affected and contralateral non-affected limb and against patients (controls) with open tibial fractures who required no soft tissue reconstruction.

Genetic Contribution to End-Stage Cardiomyopathy Requiring Heart Transplantation.

Background: Many cardiovascular disorders propel the development of advanced heart failure that necessitates cardiac transplantation. When treatable causes are excluded, studies to define causes are often abandoned, resulting in a diagnosis of end-stage idiopathic cardiomyopathy. We studied whether DNA sequence analyses could identify unrecognized causes of end-stage nonischemic cardiomyopathy requiring heart transplantation and whether the prevalence of genetic causes differed from ambulatory cardiomyopathy cases.

Angiotensin-converting enzyme 2-at the heart of the COVID-19 pandemic.

ACE2 is the indispensable entry receptor for SARS-CoV and SARS-CoV-2. Because of the COVID-19 pandemic, it has become one of the most therapeutically targeted human molecules in biomedicine. ACE2 serves two fundamental physiological roles: as an enzyme, it alters peptide cascade balance; as a chaperone, it controls intestinal amino acid uptake.

SARS-CoV-2 infection downregulates myocardial ACE2 and potentiates cardiac inflammation in humans and hamsters.

Myocardial pathologies resulting from SARS-CoV-2 infections are consistently rising with mounting case rates and reinfections; however, the precise global burden is largely unknown and will have an unprecedented impact. Understanding the mechanisms of COVID-19-mediated cardiac injury is essential toward the development of cardioprotective agents that are urgently needed. Assessing novel therapeutic strategies to tackle COVID-19 necessitates an animal model that recapitulates human disease.

Loss of ADAM15 Exacerbates Transition to Decompensated Myocardial Hypertrophy and Dilation Through Activation of the Calcineurin Pathway.

Background: Myocardial hypertrophy and dilation are key features of cardiomyopathies and involve several cellular and molecular events. ADAMs (a disintegrin and metalloproteinases) are membrane-bound proteinases with diverse functions whose role in heart disease remains underexplored. ADAM15 is expressed in the heart and is downregulated in the failing human heart.

Performance study of the anterior nasal AMP SARS-CoV-2 rapid antigen test in comparison with nasopharyngeal rRT-PCR.

Introduction: The gold standard for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection is real-time reverse transcription PCR (rRT-PCR), which is expensive, has a long turnaround time and requires special equipment and trained personnel. Nasopharyngeal swabs are uncomfortable, not suitable for certain patient groups and do not allow self-testing. Convenient, well-tolerated rapid antigen tests (RATs) for SARS-CoV-2 detection are called for.

Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies.

Pathogenic variants in genes that cause dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM) convey high risks for the development of heart failure through unknown mechanisms. Using single-nucleus RNA sequencing, we characterized the transcriptome of 880,000 nuclei from 18 control and 61 failing, nonischemic human hearts with pathogenic variants in DCM and ACM genes or idiopathic disease. We performed genotype-stratified analyses of the ventricular cell lineages and transcriptional states.

Impact of preoperative anemia, iron-deficiency and inflammation on survival after colorectal surgery-A retrospective cohort study.

Background: Anemia is present in up to two-thirds of patients undergoing colorectal surgery mainly caused by iron deficiency and inflammation. As anemia is associated with increased risk of perioperative death, diagnosis and treatment of preoperative anemia according to etiology have been recommended.

Objective: The aim of the present study was to assess if the association between anemia and survival in patients undergoing colorectal surgery was determined by the severity of anemia alone or also by anemia etiology.

Changes in the Left Ventricular Eicosanoid Profile in Human Dilated Cardiomyopathy.

Objective: Metabolites derived from -3 and -6 polyunsaturated fatty acids (PUFAs) have both beneficial and detrimental effects on the heart. However, contribution of these lipid mediators to dilated cardiomyopathy (DCM)-associated mitochondrial dysfunction remains unknown. This study aimed to characterize DCM-specific alterations in the PUFA metabolome in conjunction with cardiac mitochondrial quality in human explanted heart tissues.

Prognostic Factors for 10-Year Survival in Patients With Hepatocellular Cancer Receiving Liver Transplantation.

Background: Long-term survival after liver transplantation (LT) for hepatocellular cancer (HCC) continues to increase along with the modification of inclusion criteria. This study aimed at identifying risk factors for 5- and 10-year overall and HCC-specific death after LT.

Methods: A total of 1,854 HCC transplant recipients from 10 European centers during the period 1987-2015 were analyzed.

Synonymous mutation in adenosine triphosphatase copper-transporting beta causes enhanced exon skipping in Wilson disease.

Wilson disease (WD) is caused by biallelic pathogenic variants in adenosine triphosphatase copper-transporting beta (ATP7B); however, genetic testing identifies only one or no pathogenic ATP7B variant in a number of patients with WD. Synonymous single-nucleotide sequence variants have been recognized as pathogenic in individual families. The aim of the present study was to evaluate the prevalence and disease mechanism of the synonymous variant c.

In-Cell Labeling Coupled to Direct Analysis of Extracellular Vesicles in the Conditioned Medium to Study Extracellular Vesicles Secretion with Minimum Sample Processing and Particle Loss.

Extracellular vesicles (EVs) are involved in a multitude of physiological functions and play important roles in health and disease. The largest proportion of studies on EVs is based on the analysis and characterization of EVs secreted in the cell culture medium. These studies remain challenging due to the small size of the EV particles, a lack of universal EV markers, and sample loss or technical artifacts that are often associated with EV labeling for single particle tracking and/or separation techniques.

Afamin predicts the prevalence and incidence of nonalcoholic fatty liver disease.

Objectives: In the general population, increased afamin concentrations are associated with the prevalence and incidence of metabolic syndrome as well as type 2 diabetes. Although metabolic syndrome is commonly associated with nonalcoholic fatty liver disease (NAFLD), there exist no information on afamin and NAFLD.

Methods: Afamin concentrations were cross-sectionally measured in 146 Austrian patients with NAFLD, in 45 patients without NAFLD, and in 292 age- and sex-matched healthy controls.

Sex- and age-specific regulation of ACE2: Insights into severe COVID-19 susceptibility.

Aged males disproportionately succumb to increased COVID-19 severity, hospitalization, and mortality compared to females. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2) facilitate SARS-CoV-2 viral entry and may have sexually dimorphic regulation. As viral load dictates disease severity, we investigated the expression, protein levels, and activity of ACE2 and TMPRSS2.

Evaluation of the AMP SARS-CoV-2 rapid antigen test in a hospital setting.

Objectives: Quick and inexpensive SARS-CoV-2 screening and frontline testing are in growing demand. Our study aimed to evaluate the performance of the immunochromatographic AMP rapid antigen test (AMP RAT) compared to the gold-standard real-time reverse transcription PCR (rRT-PCR) in a hospital cohort.

Methods: A total of 392 patients, who presented consecutively with COVID-19 symptoms in our emergency department, were included in this retrospective study.

MRI-Based Iron Phenotyping and Patient Selection for Next-Generation Sequencing of Non-Homeostatic Iron Regulator Hemochromatosis Genes.

Background And Aims: High serum ferritin is frequent among patients with chronic liver disease and commonly associated with hepatic iron overload. Genetic causes of high liver iron include homozygosity for the p.Cys282Tyr variant in homeostatic iron regulator (HFE) and rare variants in non-HFE genes.

Neurodegeneration in Hepatic and Neurologic Wilson's Disease.

Clinical presentation of Wilson disease (WD) includes hepatic and neurologic manifestations. This study compares subcortical brain regions by magnetic resonance imaging in patients with WD and without neurological symptoms. Distinct atrophy affecting the basal ganglia, accumbens, and hippocampus was present in neurological WD.

Hypophosphataemia after treatment of iron deficiency with intravenous ferric carboxymaltose or iron isomaltoside-a systematic review and meta-analysis.

Aims: Hypophosphataemia is an increasingly recognized side-effect of ferric carboxymaltose (FCM) and possibly iron isomaltoside/ferric derisomaltose (IIM), which are used to treat iron deficiency. The aim of this study was to determine frequency, severity, duration and risk factors of incident hypophosphataemia after treatment with FCM and IIM.

Methods: A systematic literature search for articles indexed in EMBASE, PubMed and Web of Science in years 2005-2020 was carried out using the search terms 'ferric carboxymaltose' OR 'iron isomaltoside'.

The Human Explanted Heart Program: A translational bridge for cardiovascular medicine.

The progression of cardiovascular research is often impeded by the lack of reliable disease models that fully recapitulate the pathogenesis in humans. These limitations apply to both in vitro models such as cell-based cultures and in vivo animal models which invariably are limited to simulate the complexity of cardiovascular disease in humans. Implementing human heart tissue in cardiovascular research complements our research strategy using preclinical models.

Autologous stem cell transplantation following simultaneous liver and kidney transplantation in severe amyloid light chain amyloidosis associated with multiple myeloma: a case report.

Introduction: The involvement of vital organs in multiple myeloma (MM) with systemic amyloid light-chain (AL) amyloidosis can lead to acute organ failure. In this case, the fear of recurrence or progression of multiple myeloma often excludes those patients from undergoing organ transplantation. Nevertheless, clinically fit patients might benefit from a different therapeutic approach.

The dual nature of obesity in metabolic programming: quantity versus quality of adipose tissue.

The global prevalence of obesity has been rising at an alarming rate, accompanied by an increase in both childhood and maternal obesity. The concept of metabolic programming is highly topical, and in this context, describes a predisposition of offspring of obese mothers to the development of obesity independent of environmental factors. Research published in this issue of Clinical Science conducted by Litzenburger and colleagues (Clin.

Cells of the adult human heart.

Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour.