Combined mutation in Vhl, Trp53 and Rb1 causes clear cell renal cell carcinoma in mice.

Clear cell renal cell carcinomas (ccRCCs) frequently exhibit inactivation of the von Hippel-Lindau tumor-suppressor gene, VHL, and often harbor multiple copy-number alterations in genes that regulate cell cycle progression. We show here that modeling these genetic alterations by combined deletion of Vhl, Trp53 and Rb1 specifically in renal epithelial cells in mice caused ccRCC. These tumors arose from proximal tubule epithelial cells and shared molecular markers and mRNA expression profiles with human ccRCC.

A haplotype block downstream of plasminogen is associated with chronic and aggressive periodontitis.

Aim: The intronic variant rs4252120 in the plasminogen gene (PLG) is known to be associated with aggressive periodontitis (AgP) and atherosclerosis. Here, we examined the chromosomal region spanning PLG for associations with both chronic periodontitis (CP) and AgP.

Materials And Methods: The association of PLG candidate rs4252120 was tested in a German case-control sample of 1,419 CP cases using the genotyping assay hCV11225947 and 4,562 controls, genotyped with HumanOmni BeadChips.

The role of vaspin as a predictor of coronary angiography result in SCAD (stable coronary artery disease) patients.

Background: The role of vaspin in the pathogenesis of stable coronary artery disease (SCAD) have been repeatedly addressed in clinical studies. However, from the point of view of clinical practice, the results of earlier studies are still inconclusive.

Methods: The data of 106 SCAD patients who received coronary angiography and 85 coronary artery disease-free controls were collected and analysed.

Interferon-α for Induction and Maintenance of Remission in Eosinophilic Granulomatosis with Polyangiitis: A Single-center Retrospective Observational Cohort Study.

Objective: Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized by frequent relapses following induction therapy. Interferon-α (IFN-α) can reverse the underlying Th2-driven immune response and has successfully induced remission in previous reports. We undertook this study to investigate its efficacy and safety in patients with EGPA.

Model for End-stage Liver Disease excluding INR (MELD-XI) score in critically ill patients: Easily available and of prognostic relevance.

Purpose: MELD-XI, an adapted version of Model for End-stage Liver Disease (MELD) score excluding INR, was reported to predict outcomes e.g. in patients with acute heart failure.

Complications of liver resection in geriatric patients.

Unlabelled: Introduction and aims. Liver resection is the treatment of choice for many primary and secondary liver diseases. Most studies in the elderly have reported resection of primary and secondary liver tumors, especially hepatocellular carcinoma and colorectal metastatic cancer.

Soluble ST2 predicts 1-year outcome in patients undergoing transcatheter aortic valve implantation.

Background: Soluble ST2 (sST2) has been introduced as a novel biomarker in patients suffering from heart failure for risk stratification. In this study, we sought to investigate whether sST2 is useful for risk stratification and prediction of mortality in patients undergoing transcatheter aortic valve implantation (TAVI).

Materials And Methods: A total of 274 patients undergoing TAVI were included in this study (149 female; age 81 ± 1 years; EUROSCORE 25 ± 1; STS score 3·8 ± 0·2).

Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease.

Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; ∼75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified four new genome-wide significant loci. The most associated SNP at one locus affects splicing and expression of UBASH3A, with the protective allele (C) predicted to cause nonstop-mediated mRNA decay and lower expression of UBASH3A.

Hemodynamic Performance of a Novel Right Ventricular Assist Device (PERKAT).

Acute right ventricular failure (RVF) is an increasing clinical problem and a life-threatening condition. Right ventricular assist devices represent a reasonable treatment option for patients with refractory RVF. We here present a novel percutaneously implantable device for right ventricular support.

Correlation between CMV Infection and Post-transplantation New-onset Diabetes Mellitus.

Background: New-onset diabetes mellitus after transplantation (NODAT) is a well-known complication of transplantation.

Objective: To determine the correlation between CMV infection and NODAT.

Methods: Retrospectively, we detected CMV replication (PCR) in every month after renal transplantation in the first 12 months of the procedure in a homogenous group of patients from the immunosuppression point of view.

Differential Impact of Hyperglycemia in Critically Ill Patients: Significance in Acute Myocardial Infarction but Not in Sepsis?

Hyperglycemia is a common condition in critically ill patients admitted to an intensive care unit (ICU). These patients represent an inhomogeneous collective and hyperglycemia might need different evaluation depending on the underlying disorder. To elucidate this, we investigated and compared associations of severe hyperglycemia (>200 mg/dL) and mortality in patients admitted to an ICU for acute myocardial infarction (AMI) or sepsis as the two most frequent admission diagnoses.

Alterations in systemic levels of Th1, Th2, and Th17 cytokines in overweight adolescents and obese mice.

Background: Obesity represents a major problem for patients and health care systems in most industrialized countries. A chronic inflammatory state in obese individuals leads to disease conditions associated with activation of cellular immune mechanisms. Here, we sought to investigate the role of Th1-, Th2-, and Th17-related cytokines in overweight adolescents and mice on a high-fat diet.

Imaging in Colorectal Cancer: Progress and Challenges for the Clinicians.

The use of imaging in colorectal cancer (CRC) has significantly evolved over the last twenty years, establishing important roles in surveillance, diagnosis, staging, treatment selection and follow up. The range of modalities has broadened with the development of novel tracer and contrast agents, and the fusion of technologies such as positron emission tomography (PET) and computed tomography (CT). Traditionally, the most widely used modality for assessing treatment response in metastasised colon and rectal tumours is CT, combined with use of the RECIST guidelines.

Pulse contour cardiac output monitoring in acute heart failure patients : Assessment of hemodynamic measurements.

Background: Heart failure is known to be a major public health problem. Fluid redistribution contributes to acute heart failure; therefore, knowledge of hemodynamic parameters could be important for optimizing outcomes. The pulse contour cardiac output monitor PiCCO uses the single thermal indicator technique and pulse contour analysis to calculate hemodynamic parameters of preload, afterload, cardiac output, systemic vascular resistance and extravascular lung water.

Microparticles in patients undergoing transcatheter aortic valve implantation (TAVI).

Degenerative aortic stenosis (AS) is the most frequent form of acquired valvular heart disease. AS is known to entail endothelial dysfunction caused by increased mechanical shear stress leading to elevated circulatory levels of microparticles. Endothelial and platelet microparticles (EMP and PMP) are small vesicles that originate from activated cells and thrombocytes.

Predictive value of the augmentation index derived vascular age in patients with newly diagnosed atherosclerosis.

Early detection of atherosclerosis, i.e., in occupational health screening programs could reduce the rate of cardiovascular events in the working population.

Treatment sequence of synchronously (liver) metastasized colon cancer.

No standards for staging, systemic therapy or the timing of an operation are defined for patients newly diagnosed with synchronous metastases and a primary in the colon. An expert group of radiologists, medical, radiation and surgical oncologists therefore came together to discuss staging and treatment sequence for these patients and came up with a recommendation based on current evidence of potential therapeutic options. The discussion was organized to debate recommendations centred on 5 topics and therefore the position paper is built upon these titles and their subtitles.

Differential effects of high and low strength magnetic fields on mouse embryonic development and vasculogenesis of embryonic stem cells.

Man-made magnetic fields (MFs) may exert adverse effects on mammalian embryonic development. Herein, we analysed the effect of 10mT 50Hz sinusoidal (AC) or static (DC) MFs versus 1mT MFs on embryonic development of mice. Exposure for 20days during gestation to 10mT MFs increased resorptions and dead fetuses, decreased crown-rump length and fresh weight, reduced blood vessel differentiation and caused histological changes, accompanied with diminished vascular endothelial growth factor (VEGF) protein expression in several organs.

Effect of endothelin-1 and endothelin receptor blockade on the release of microparticles.

Background: Increased levels of endothelial cell microparticles (EMP) are known to reflect endothelial dysfunction (ED). In diabetes mellitus type 2 (T2DM), the expression of endothelin (ET)-1 is increased. As treatment with an ET-1 antagonist significantly inhibited atherosclerosis in animal models, we sought to investigate whether treatment with ET-1 antagonists affects EMP levels in vitro and in vivo in patients with T2DM.

Genome-wide association study of biologically informed periodontal complex traits offers novel insights into the genetic basis of periodontal disease.

Genome-wide association studies (GWAS) of chronic periodontitis (CP) defined by clinical criteria alone have had modest success to-date. Here, we refine the CP phenotype by supplementing clinical data with biological intermediates of microbial burden (levels of eight periodontal pathogens) and local inflammatory response (gingival crevicular fluid IL-1β) and derive periodontal complex traits (PCTs) via principal component analysis. PCTs were carried forward to GWAS (∼2.

The Intricate Network of Adipokines and Stroke.

Cerebrovascular disorders, particularly ischemic stroke, are one of the most common neurological disorders. High rates of overweight and obesity support an interest in the role of adipose tissue and adipose tissue releasing cytokines in inducing associated comorbidities. Adipokines can serve as a key messenger to central energy homeostasis and metabolic homeostasis.

High-Density Genetic Mapping Identifies New Susceptibility Variants in Sarcoidosis Phenotypes and Shows Genomic-driven Phenotypic Differences.

Rationale: Sarcoidosis is a multisystem disease of unknown cause. Löfgren's syndrome (LS) is a characteristic subgroup of sarcoidosis that is associated with a good prognosis in sarcoidosis. However, little is known about its genetic architecture or its broader phenotype, non-LS sarcoidosis.

Involvement of phosphoinositide 3-kinase class IA (PI3K 110α) and NADPH oxidase 1 (NOX1) in regulation of vascular differentiation induced by vascular endothelial growth factor (VEGF) in mouse embryonic stem cells.

The impact of reactive oxygen species and phosphoinositide 3-kinase (PI3K) in differentiating embryonic stem (ES) cells is largely unknown. Here, we show that the silencing of the PI3K catalytic subunit p110α and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (NOX1) by short hairpin RNA or pharmacological inhibition of NOX and ras-related C3 botulinum toxin substrate 1 (Rac1) abolishes superoxide production by vascular endothelial growth factor (VEGF) in mouse ES cells and in ES-cell-derived fetal liver kinase-1(+) (Flk-1(+)) vascular progenitor cells, whereas the mitochondrial complex I inhibitor rotenone does not have an effect. Silencing p110α or inhibiting Rac1 arrests vasculogenesis at initial stages in embryoid bodies, even under VEGF treatment, as indicated by platelet endothelial cell adhesion molecule-1 (PECAM-1)-positive areas and branching points.

In vitro evaluation of a novel pulsatile right heart assist device - the PERKAT system.

Purpose: Acute right ventricular failure is a life-threatening condition with poor prognosis. It occurs as a result of right ventricular infarction, postcardiac transplantation, or postimplantation of a left ventricular assist device. Temporary mechanical right ventricular support could be a reasonable treatment option.