Elevated Liver Fibrosis Progression in Isolated PSC Patients and Increased Malignancy Risk in a PSC-IBD Cohort: A Retrospective Study.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease often associated with inflammatory bowel disease (IBD), particularly ulcerative colitis (CU), and rarely with Crohn's disease (CD). Various long-term analyses show different rates of cancer and the need for orthotopic liver transplantation (OLT) in patients with isolated PSC and with concomitant IBD, respectively. However, data on the detailed course of PSC with or without IBD are limited.

Phosphatidylserine Supplementation as a Novel Strategy for Reducing Myocardial Infarct Size and Preventing Adverse Left Ventricular Remodeling.

Phosphatidylserines are known to sustain skeletal muscle activity during intense activity or hypoxic conditions, as well as preserve neurocognitive function in older patients. Our previous studies pointed out a potential cardioprotective role of phosphatidylserine in heart ischemia. Therefore, we investigated the effects of phosphatidylserine oral supplementation in a mouse model of acute myocardial infarction (AMI).

Pre-procedural proton pump inhibition is associated with fewer peri-oesophageal lesions after cryoballoon pulmonary vein isolation.

Pulmonary vein isolation (PVI) using cryoenergy is safe and efficient for treatment of atrial fibrillation (AF). Pre-existing upper gastrointestinal (GI) pathologies have been shown to increase the risk for AF. Therefore, this study aimed at assessing incidental pathologies of the upper GI tract in patients scheduled for PVI and to analyse the impact of patients' characteristics on PVI safety outcome.

Impaired IFN-γ-dependent STAT3 Activation Is Associated With Dysregulation of Regulatory and Inflammatory Signaling in Monocytes of Ulcerative Colitis Patients.

Background: The Janus kinase/signal transducer and activator of transcription (JAK/STAT) inhibitor tofacitinib has been recently approved for the treatment of ulcerative colitis (UC) but not Crohn's disease (CD). Systematic analysis of the JAK/STAT pathway in inflammatory bowel disease is still missing. The aim of this study was to investigate JAK/STAT activation and adjacent signaling in monocytes of patients with inflammatory bowel diseases, which are key players in inflammatory responses.

Differential regulation of JAK/STAT-signaling in patients with ulcerative colitis and Crohn's disease.

In 2018, the pan-Janus kinase (JAK) inhibitor tofacitinib was launched for the treatment of ulcerative colitis (UC). Although tofacitinib has proven efficacious in patients with active UC, it failed in patients with Crohn's disease (CD). This finding strongly hints at a different contribution of JAK signaling in both entities.

MicroRNA-320a Monitors Intestinal Disease Activity in Patients With Inflammatory Bowel Disease.

Objectives: In patients with inflammatory bowel disease (IBD), a treat-to-target treatment strategy requires tight monitoring of disease activity. Noninvasive biomarkers may help to monitor the intestinal disease activity. We demonstrated recently that peripheral microRNA (miR)-320a expression in mice follows the course of experimental colitis.

Serum levels of ferritin and transferrin serve as prognostic factors for mortality and survival in patients with end-stage liver disease: A propensity score-matched cohort study.

Background: Patients with end-stage liver disease are known to suffer from a significantly high risk of mortality, but accurate prediction of the course of disease is challenging.

Objective: The study aim was to evaluate the independent prognostic and clinical importance of serum levels of ferritin and transferrin for 90-day survival of patients with liver disease.

Methods: Patients with end-stage liver disease treated during a 2-year period were enrolled retrospectively in a single-centre study.

Diagnosis and management of cold urticaria in cryoablation of atrial fibrillation: a case report.

Background: Cold-induced urticaria is triggered by exposure to local or environmental cold and manifests as localized or systemic pruritic papules, sometimes accompanied by angio-oedema and anaphylaxis representing a life-threatening condition. Therapy options of atrial fibrillation (AF) include catheter ablation with different energy sources, of which cryoenergy may be superior to other energy sources regarding safety and efficacy.

Case Summary: We report the case of a 60-year-old man suffering from symptomatic paroxysmal AF.

Distinct Disease Phenotype of Ulcerative Colitis in Patients With Coincident Primary Sclerosing Cholangitis: Evidence From a Large Retrospective Study With Matched Cohorts.

Background: Primary sclerosing cholangitis is a classical extraintestinal manifestation in patients with ulcerative colitis. However, the impact of primary sclerosing cholangitis on the disease course is incompletely understood.

Objective: This study aimed to assess the impact of primary sclerosing cholangitis on disease phenotype and its course in patients with ulcerative colitis.

Modest and nonessential roles of the endocannabinoid system in immature hematopoiesis of mice.

Endocannabinoids are lipid mediators that signal via several seven-transmembrane domain G protein-coupled receptors. The endocannabinoid receptor CB2 is expressed on blood cells, including stem cells, and mediates the effects of cannabinoids on the immune system. The role of the endocannabinoid system in immature hematopoiesis is largely elusive.

Tofacitinib Reprograms Human Monocytes of IBD Patients and Healthy Controls Toward a More Regulatory Phenotype.

Background: The inhibition of Janus kinases (JAKs) and subsequent signal transducers and activators of transcription (STATs) by tofacitinib represents a new therapeutic strategy in inflammatory bowel diseases (IBD) as clinical trials have led to approval of tofacitinib for ulcerative colitis (UC) and hint at a possible efficacy for Crohn`s disease (CD). However, the impact of tofacitinib on cellular response of monocytes, which are key players in inflammatory responses, has not been investigated so far. We aimed to analyze JAK/STAT-inhibition by tofacitinib in monocytes of IBD patients and healthy controls.

Endoscopic Radiofrequency Ablation Prolongs Survival of Patients with Unresectable Hilar Cholangiocellular Carcinoma - A Case-Control Study.

The life expectancy of unresectable hilar cholangiocellular carcinomas (CCCs) is very limited and endoscopic radiofrequency ablation (ERFA) of the biliary tract may prolong survival. Our single-center-study retrospectively analysed all CCC cases, in whom ERFAs of the biliary tract were performed between 2012 and 2017 and compared these to historical control cases who received the standard treatment of sole stent application. ERFA was performed in 32 patients with malignant biliary strictures that were mainly caused by Bismuth III and IV hilar CCCs (66%).

Time-to-isolation-guided cryoballoon ablation reduces oesophageal and mediastinal alterations detected by endoscopic ultrasound: results of the MADE-PVI trial.

Aims: Cryoballoon ablation is safe and efficient for achieving pulmonary vein isolation (PVI) in atrial fibrillation. Structural oesophago-mediastinal lesions, which seem to be associated with an increased risk of the lethal complication of an atrio-oesophageal fistula, have been described. MADE-PVI (Mediastino-oesophageal Alterations Detected by Endosonography after PVI) aimed at evaluating safety of cryoballoon PVI in relation to two different freeze protocols.

Anti-inflammatory Gold-Induced Autologous Cytokines treatment triggers heart failure after myocardial infarction.

Background: Gold-induced autologous cytokine (GOLDIC) treatment is usually used in the therapy of the inflammatory musculoskeletal disorders (e.g. osteoarthritis in humans) and is able to modulate the inflammatory reaction.

Fluorescence-mediated Tomography for the Detection and Quantification of Macrophage-related Murine Intestinal Inflammation.

Murine models of disease are indispensable to scientific research. However, many diagnostic tools such as endoscopy or tomographic imaging are not routinely employed in animal models. Conventional experimental readouts often rely on post mortem and ex vivo analyses, which prevent intra-individual follow-up examinations and increase the number of study animals needed.

The Impact of the Major Baltic Inflow of December 2014 on the Mercury Species Distribution in the Baltic Sea.

The Baltic Sea is a marginal sea characterized by stagnation periods of several years. Oxygen consumption in its deep waters leads to the buildup of sulfide from sulfate reduction. Some of the microorganisms responsible for these processes also transform reactive ionic mercury to neurotoxic methylmercury.

Detection and characterization of murine colitis and carcinogenesis by molecularly targeted contrast-enhanced ultrasound.

Aim: To study mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) and vascular endothelial growth factor (VEGF)-targeted contrast enhanced ultrasound (CEUS) for the assessment of murine colitis and carcinogenesis.

Methods: C57BL/6 mice were challenged with 3% dextran sodium-sulfate (DSS) for three, six or nine days to study the development of acute colitis. Ultrasound was performed with and without the addition of unspecific contrast agents.

MicroRNA-320a Strengthens Intestinal Barrier Function and Follows the Course of Experimental Colitis.

Background: Inflammatory bowel disease is a chronic-remittent disorder with the risk of disabling complications due to uncontrolled inflammation. Accurate biomarkers are needed to noninvasively monitor the disease course to tailor therapy. We evaluated the potential of the specific microRNA (miR)-320a to monitor disease activity in experimental colitis or patients with Crohn's disease and investigated its functional role in intestinal epithelial barrier formation.

Assessment of stricturing Crohn's disease: Current clinical practice and future avenues.

Crohn's disease (CD) is a chronic remittent idiopathic disease. Although the early phase of the disease is commonly characterized by inflammation-driven symptoms, such as diarrhea, the frequency of fibrostenotic complications in patients with CD increases over the long-term course of the disease. This review presents the current diagnostic options for assessing CD-associated strictures.

Selection and flexible optimization of binding modes from conformation ensembles.

This paper describes a new semi-flexible docking approach named Fado (flexible alignment and docking), which incorporates flexibility by using an ensemble of precomputed ligand conformers. A primary ligand is defined as a linear combination over all input conformers. An optimization with regard to the linear coefficients makes the ligand flexible.

Superposition of a tRNASer acceptor stem microhelix into the seryl-tRNA synthetase complex.

Aminoacyl-tRNA synthetases catalyze the formation of aminoacyl-tRNAs. Seryl-tRNA synthetase is a class II synthetase, which depends on rather few and simple identity elements in tRNA(Ser) to determine the amino acid specificity. tRNA(Ser) acceptor stem microhelices can be aminoacylated with serine, which makes this part of the tRNA a valuable tool for investigating the structural motifs in a tRNA(Ser)-seryl-tRNA synthetase complex.

Molecular model of a type III secretion system needle: Implications for host-cell sensing.

Type III secretion systems are essential virulence determinants for many Gram-negative bacterial pathogens. The type III secretion system consists of cytoplasmic, transmembrane, and extracellular domains. The extracellular domain is a hollow needle protruding above the bacterial surface and is held within a basal body that traverses both bacterial membranes.

Structure-function mapping of BbCRASP-1, the key complement factor H and FHL-1 binding protein of Borrelia burgdorferi.

Borrelia burgdorferi, a spirochaete transmitted to human hosts during feeding of infected Ixodes ticks, is the causative agent of Lyme disease, the most frequent vector-borne disease in Eurasia and North America. Sporadically Lyme disease develops into a chronic, multisystemic disorder. Serum-resistant B.

Bioinformatics approach to predicting HIV drug resistance.

The emergence of drug resistance remains one of the most challenging issues in the treatment of HIV-1 infection. The extreme replication dynamics of HIV facilitates its escape from the selective pressure exerted by the human immune system and by the applied combination drug therapy. This article reviews computational methods whose combined use can support the design of optimal antiretroviral therapies based on viral genotypic and phenotypic data.