Small molecule-mediated inhibition of CD40-TRAF6 reduces adverse cardiac remodelling in pressure overload induced heart failure.

Background: CD40 signalling is involved in chronic inflammation, a condition that plays an important role in non-ischemic heart failure (HF). Small molecule inhibitors of CD40-TRAF6 have shown to be effective in multiple animal-models of chronic inflammatory disease, such as obesity and atherosclerosis.

Methods & Results: Mice were subjected to transverse aortic constriction (TAC) and randomized to small molecule inhibition of CD40-TRAF6 or placebo.

A Proinflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis.

Rationale: Several studies have suggested a role for the gut microbiota in inflammation and atherogenesis. A causal relation relationship between gut microbiota, inflammation, and atherosclerosis has not been explored previously.

Objective: Here, we investigated whether a proinflammatory microbiota from Caspase1 ( Casp1) mice accelerates atherogenesis in Ldlr mice.

The Trusted Server: A secure computational environment for privacy compliant evaluations on plain personal data.

A growing framework of legal and ethical requirements limit scientific and commercial evaluation of personal data. Typically, pseudonymization, encryption, or methods of distributed computing try to protect individual privacy. However, computational infrastructures still depend on human system administrators.

Diabetes mellitus in pediatric solid organ recipients without and with cystic fibrosis: An analysis from the German-Austrian diabetes database (Diabetes Patienten Verlaufsdokumentation).

Introduction: Posttransplantation diabetes mellitus (PTDM) increases the risk of cardiovascular disease, graft loss, and decreased survival. Follow-up treatment after solid organ transplantation (SOT) needs to focus on, inter alia, maintaining balanced glucose metabolism. This study aimed to ascertain the prevalence of PTDM and describe patient characteristics in the large DPV (Diabetes Patienten Verlaufsdokumentation) pediatric diabetes database.

Recommendations for the diagnosis and treatment of patients with polycythaemia vera.

Objectives: To present the Central European Myeloproliferative Neoplasm Organisation (CEMPO) treatment recommendations for polycythaemia vera (PV).

Methods: During meetings held from 2015 through 2017, CEMPO discussed PV and its treatment and recent data.

Results: PV is associated with increased risks of thrombosis/thrombo-haemorrhagic complications, fibrotic progression and leukaemic transformation.

Incidence of tuberous sclerosis and age at first diagnosis: new data and emerging trends from a national, prospective surveillance study.

Background: Tuberous Sclerosis Complex (TSC) is a rare multisystem disorder. In 2012 diagnostic criteria for TSC were revised. However, data on the incidence of TSC are limited.

2016 Jeffrey M. Hoeg Award Lecture.

Innate and adaptive immune effector mechanisms, in conjunction with hyperlipidemia, are important drivers of atherosclerosis. The interaction between the different immune cells and the secretion of cytokines and chemokines determine the progression of atherosclerosis. The activation or dampening of the immune response is tightly controlled by immune checkpoints.

Common Coding Variants in Are Associated With the Nav1.8 Late Current and Cardiac Conduction.

Background: Genetic variants at the / locus are strongly associated with electrocardiographic PR and QRS intervals. While is the canonical cardiac sodium channel gene, the role of in cardiac conduction is less well characterized.

Methods: We sequenced the locus in 3699 European-ancestry individuals to identify variants associated with cardiac conduction, and replicated our findings in 21,000 individuals of European ancestry.

Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval.

Background: Electrical conduction from the cardiac sinoatrial node to the ventricles is critical for normal heart function. Genome-wide association studies have identified more than a dozen common genetic loci that are associated with PR interval. However, it is unclear whether rare and low-frequency variants also contribute to PR interval heritability.

Effects of mTOR-Is on malignancy and survival following renal transplantation: A systematic review and meta-analysis of randomized trials with a minimum follow-up of 24 months.

Background: mTOR-Is positively influence the occurrence and course of certain tumors after solid organ transplantation. The effect of mTOR-Is on the overall incidence of tumors irrespective of their origin is not entirely clear. Furthermore, conflicting data have been shown on mortality under mTOR-Is.

Lipopolysaccharide Lowers Cholesteryl Ester Transfer Protein by Activating F4/80Clec4fVsig4Ly6C Kupffer Cell Subsets.

Background: Lipopolysaccharide (LPS) decreases hepatic CETP (cholesteryl ester transfer protein) expression albeit that the underlying mechanism is disputed. We recently showed that plasma CETP is mainly derived from Kupffer cells (KCs). In this study, we investigated the role of KC subsets in the mechanism by which LPS reduces CETP expression.

Extended Pancreas Donor Program-The EXPAND Study: A Prospective Multicenter Trial Testing the Use of Pancreas Donors Older Than 50 Years.

Background: Pancreas transplantation is the only curative treatment option for patients with juvenile diabetes. Organ shortage and restrictive allocation criteria are the main reasons for increasing waitlists, leading to severe morbidity and mortality. We designed a study to increase the donor pool with extended donor criteria (EDC) organs (donor age, 50-60 years; body mass index, 30-34 kg/m).

Exploring immune checkpoints as potential therapeutic targets in atherosclerosis.

In the past decades, the inflammatory nature of atherosclerosis has been well-recognized and despite the development of therapeutic strategies targeted at its classical risk factors such as dyslipidemia and hypertension, atherosclerosis remains a major cause of morbidity and mortality. Additional strategies targeting the chronic inflammatory pathways underlying the development of atherosclerosis are therefore required. Interactions between different immune cells result in the secretion of inflammatory mediators, such as cytokines and chemokines, and fuel atherogenesis.

Influence of irregular heart rhythm on radiation exposure, image quality and diagnostic impact of cardiac computed tomography angiography in 4,339 patients. Data from the German Cardiac Computed Tomography Registry.

Background: Coronary computed tomography angiography (coronary CTA) provides non-invasive evaluation of the coronary arteries with high precision for the detection of significant coronary artery disease (CAD).

Aim: To investigate whether irregular heart rhythm including atrial fibrillation and premature beats during data acquisition influences (i) radiation and contrast media exposure, (ii) number of non-evaluable coronary segments and (iii) diagnostic impact of coronary CTA.

Methods: Twelve tertiary care centers with ≥64 slice CT scanners and ≥5 years of experience with cardiovascular imaging participated in this registry.

Novel molecular imaging ligands targeting matrix metalloproteinases 2 and 9 for imaging of unstable atherosclerotic plaques.

Molecular imaging of matrix metalloproteinases (MMPs) may allow detection of atherosclerotic lesions vulnerable to rupture. In this study, we develop a novel radiolabelled compound that can target gelatinase MMP subtypes (MMP2/9) with high selectivity and inhibitory potency. Inhibitory potencies of several halogenated analogues of MMP subtype-selective inhibitors (N-benzenesulfonyliminodiacetyl monohydroxamates and N-halophenoxy-benzenesulfonyl iminodiacetyl monohydroxamates) were in the nanomolar range for MMP2/9.

CD40L controls obesity-associated vascular inflammation, oxidative stress, and endothelial dysfunction in high fat diet-treated and db/db mice.

Aims: CD40 ligand (CD40L) signaling controls vascular oxidative stress and related dysfunction in angiotensin-II-induced arterial hypertension by regulating vascular immune cell recruitment and platelet activation. Here we investigated the role of CD40L in experimental hyperlipidemia.

Methods And Results: Male wild type and CD40L-/- mice (C57BL/6 background) were subjected to high fat diet for sixteen weeks.

Helminth antigens counteract a rapid high-fat diet-induced decrease in adipose tissue eosinophils.

Brown adipose tissue (BAT) activation and white adipose tissue (WAT) beiging can increase energy expenditure and have the potential to reduce obesity and associated diseases. The immune system is a potential target in mediating brown and beige adipocyte activation. Type 2 and anti-inflammatory immune cells contribute to metabolic homeostasis within lean WAT, with a prominent role for eosinophils and interleukin (IL)-4-induced anti-inflammatory macrophages.

Clostridium difficile infection in returning travellers.

Background: There is increasing recognition of the contribution of community-acquired cases to the global burden of Clostridium difficile infection (CDI). The epidemiology of CDI among international travellers is poorly understood, and factors associated with international travel, such as antibiotic use and changes in gut microbiota, could potentially put travellers at higher risk.

Methods: We summarized demographic, travel-associated and geographic characteristics of travellers with CDI in the GeoSentinel database from 1997 to 2015.

Association of Higher CD4 CD25 CD127 , FoxP3 , and IL-2 T Cell Frequencies Early After Lung Transplantation With Less Chronic Lung Allograft Dysfunction at Two Years.

Regulatory T cells (Treg) can regulate alloantigens and may counteract chronic lung allograft dysfunction (CLAD) in lung transplantation. We analyzed Treg in peripheral blood prospectively and correlated percentages of subpopulations with the incidence of CLAD at 2 years. Among lung-transplanted patients between January 2009 and July 2011, only patients with sufficient Treg measurements were included into the study.

Multiparametric Functional MRI: A Tool to Uncover Subtle Changes following Allogeneic Renal Transplantation.

Purpose: To investigate multiparametric functional MRI to characterize acute rejection in a murine allogeneic renal transplant model and evaluate the effect of novel therapeutics.

Material And Methods: We performed allogeneic and syngeneic orthotopic transplantations (Balb/c to C57Bl/6 and C57Bl/6 to C57Bl/6). Allogeneic Groups (n = 5) were either treated with the anti-CCL2-Spiegelmer (mNOX-E36) in monotherapy or in combination with low doses of Ciclosporin-A (10mg/kgBW/d) for 10 days.

Chest electrical impedance tomography examination, data analysis, terminology, clinical use and recommendations: consensus statement of the TRanslational EIT developmeNt stuDy group.

Electrical impedance tomography (EIT) has undergone 30 years of development. Functional chest examinations with this technology are considered clinically relevant, especially for monitoring regional lung ventilation in mechanically ventilated patients and for regional pulmonary function testing in patients with chronic lung diseases. As EIT becomes an established medical technology, it requires consensus examination, nomenclature, data analysis and interpretation schemes.

Differential activation of afferent neuronal and inflammatory pathways during small bowel obstruction (SBO).

Background: Small bowel obstruction (SBO) is a potentially life-threatening condition which may be caused by a variety of pathologies such as postoperative adhesions or malignant diseases. Little is known on alterations in gut physiology during SBO, although its comprehension is essential to improve treatment which may help to prevent subsequent organ failure prior to surgical resolution. We aimed to investigate afferent nerve sensitivity and intestinal inflammatory response during SBO to identify possible targets of treatment.

BCG lowers plasma cholesterol levels and delays atherosclerotic lesion progression in mice.

Background And Aims: Bacille-Calmette-Guérin (BCG), prepared from attenuated live Mycobacterium bovis, modulates atherosclerosis development as currently explained by immunomodulatory mechanisms. However, whether BCG is pro- or anti-atherogenic remains inconclusive as the effect of BCG on cholesterol metabolism, the main driver of atherosclerosis development, has remained underexposed in previous studies. Therefore, we aimed to elucidate the effect of BCG on cholesterol metabolism in addition to inflammation and atherosclerosis development in APOE*3-Leiden.

Potent in vitro antiviral activity of Cistus incanus extract against HIV and Filoviruses targets viral envelope proteins.

Novel therapeutic options are urgently needed to improve global treatment of virus infections. Herbal products with confirmed clinical safety features are attractive starting material for the identification of new antiviral activities. Here we demonstrate that Cistus incanus (Ci) herbal products inhibit human immunodeficiency virus (HIV) infections in vitro.

Kawasaki Disease in Germany: A Prospective, Population-based Study Adjusted for Underreporting.

Background: National estimates of Kawasaki disease (KD) incidence often do not include incomplete cases (diagnosed based on only laboratory or echocardiographic criteria), and/or they rely on retrospective case reports and data registries where underreporting is known to be a problem.

Methods: We conducted a prospective nationwide KD surveillance study in children younger than 5 years through the hospital-based German Pediatric Surveillance Unit (ESPED). We accounted for underreporting through applying capture-recapture methodology in 2 federal states using hospital discharge records with KD International Statistical Classification of Diseases and Related Health Problems 10th revision code (ie, M30.