TLR4 Inhibition Attenuated LPS-Induced Proinflammatory Signaling and Cytokine Release in Mouse Hearts and Cardiomyocytes.

Background: Sepsis is associated with myocardial injury and early mortality. The innate immune receptor Toll-like receptor 4 (TLR4) can recognize pathogen-associated-molecular-patterns (PAMPs) and damage-associated molecular patterns (DAMPs); the latter are released during tissue injury. We hypothesized that TLR4 inhibition reduces proinflammatory signaling and cytokine release in: (1) LPS or Escherichia coli-treated isolated mouse heart; (2) LPS-treated mouse primary adult cardiomyocytes; and (3) the isolated heart during ischemia-reperfusion.

Detection and characterization of Campylobacter in air samples from poultry houses using shot-gun metagenomics - a pilot study.

Background: Foodborne pathogens such as Campylobacter jejuni are responsible for a large proportion of the gastrointestinal infections worldwide associated with poultry meat. Campylobacter spp. can be found in the chicken fecal microbiome and can contaminate poultry meat during the slaughter process.

When Our Best Friend Becomes Our Worst Enemy: The Mitochondrion in Trauma, Surgery, and Critical Illness.

Common for major surgery, multitrauma, sepsis, and critical illness, is a whole-body inflammation. Tissue injury is able to trigger a generalized inflammatory reaction. Cell death causes release of endogenous structures termed damage associated molecular patterns (DAMPs) that initiate a sterile inflammation.

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The majority of Danish women are working, and many are standing/walking or lifting heavy objects at work. It is important for employers and employees to assess ergonomic risk factors in the work environment during pregnancy to avoid potential negative effects on the pregnancy. Studies show that walking/standing > 3-4 h/d may increase the risk of preterm delivery.

Energy substrate metabolism, mitochondrial structure and oxidative stress after cardiac ischemia-reperfusion in mice lacking UCP3.

Myocardial ischemia-reperfusion (IR) injury may result in cardiomyocyte dysfunction. Mitochondria play a critical role in cardiomyocyte recovery after IR injury. The mitochondrial uncoupling protein 3 (UCP3) has been proposed to reduce mitochondrial reactive oxygen species (ROS) production and to facilitate fatty acid oxidation.

Mitochondria-derived damage-associated molecular patterns and inflammation in the ischemic-reperfused heart.

Cardiac cell death after myocardial infarction release endogenous structures termed damage-associated molecular patterns (DAMPs) that trigger the innate immune system and initiate a sterile inflammation in the myocardium. Cardiomyocytes are energy demanding cells and 30% of their volume are mitochondria. Mitochondria are evolutionary endosymbionts originating from bacteria containing molecular patterns similar to bacteria, termed mitochondrial DAMPs (mDAMPs).

Reduced arterial elasticity after anabolic-androgenic steroid use in young adult males and mice.

High-doses of anabolic-androgenic steroids (AAS) is efficient for building muscle mass, but pose a risk of cardiovascular side effects. Little is known of the effect of AAS on vasculature, but previous findings suggest unfavorable alterations in vessel walls and vasoreactivity. Here, long-term effect of AAS on vascular function and morphology were examined in male weightlifters, and in a mimicking animal model.

Intracellular Complement Component 3 Attenuated Ischemia-Reperfusion Injury in the Isolated Buffer-Perfused Mouse Heart and Is Associated With Improved Metabolic Homeostasis.

The innate immune system is rapidly activated during myocardial infarction and blockade of extracellular complement system reduces infarct size. Intracellular complement, however, appears to be closely linked to metabolic pathways and its role in ischemia-reperfusion injury is unknown and may be different from complement activation in the circulation. The purpose of the present study was to investigate the role of intracellular complement in isolated, retrogradely buffer-perfused hearts and cardiac cells from adult male wild type mice (WT) and from adult male mice with knockout of complement component 3 (C3KO).

A Comparison of Tools for Copy-Number Variation Detection in Germline Whole Exome and Whole Genome Sequencing Data.

Copy-number variations (CNVs) have important clinical implications for several diseases and cancers. Relevant CNVs are hard to detect because common structural variations define large parts of the human genome. CNV calling from short-read sequencing would allow single protocol full genomic profiling.

Clinical Outcomes in Patients with Multi-Hit Chronic Lymphocytic Leukemia Treated with Ibrutinib.

Purpose: aberration ( mutation and/or 17p deletion) is the most important predictive marker in chronic lymphocytic leukemia (CLL). Although each aberration is considered an equal prognosticator, the prognostic value of carrying isolated (single-hit) or multiple (multi-hit) aberrations remains unclear, particularly in the context of targeted agents.

Patients And Methods: We performed deep sequencing of using baseline samples collected from 51 aberrant patients treated with ibrutinib in a phase II study (NCT01500733).

Isolated Plin5-deficient cardiomyocytes store less lipid droplets than normal, but without increased sensitivity to hypoxia.

Plin5 is abundantly expressed in the heart where it binds to lipid droplets (LDs) and facilitates physical interaction between LDs and mitochondria. We isolated cardiomyocytes from adult Plin5 and Plin5 mice to study the role of Plin5 for fatty acid uptake, LD accumulation, fatty acid oxidation, and tolerance to hypoxia. Cardiomyocytes isolated from Plin5 mice cultured with oleic acid stored less LDs than Plin5, but comparable levels to Plin5 cardiomyocytes when adipose triglyceride lipase activity was inhibited.

Genomic profiling of newly diagnosed glioblastoma patients and its potential for clinical utility - a prospective, translational study.

Glioblastoma (GBM) is an incurable brain tumor for which new treatment strategies are urgently needed. Next-generation sequencing of GBM has most often been performed retrospectively and on archival tissue from both diagnostic and relapse surgeries with limited knowledge of clinical information, including treatment given. We sought to investigate the genomic composition prospectively in treatment-naïve patients, searched for possible targetable aberrations, and investigated for prognostic and/or predictive factors.

A Multicenter Proposal for a Fast Tool To Screen Biosecure Chicken Flocks for the Foodborne Pathogen .

The present multicenter study aimed at assessing the performance of air sampling as a novel method for monitoring in biosecure poultry farms. We compared, using a harmonized procedure, the bacteriological isolation protocol (ISO 10272-1:2017) and a real-time PCR method used on air filter samples. Air samples and boot swabs were collected from 62 biosecure flocks from five European countries during the summer of 2019.

Campylobacter in chicken - Critical parameters for international, multicentre evaluation of air sampling and detection methods.

The present pilot study aimed at evaluating air sampling as a novel method for monitoring Campylobacter in poultry farms. We compared the bacteriological isolation of Campylobacter from boot swabs and air filter samples using ISO 10272-1:2017. A secondary aim was to evaluate the use of molecular methods, i.

Occurrence of and risk factors for extended-spectrum cephalosporin-resistant Enterobacteriaceae determined by sampling of all Norwegian broiler flocks during a six month period.

All broiler flocks reared and slaughtered in Norway from May-October 2016 (n = 2110) were screened for the presence of extended-spectrum cephalosporin (ESC) -resistant Enterobacteriaceae. Furthermore, we investigated possible risk factors for occurrence of such bacteria in broiler flocks. The odds of a flock being positive for ESC-resistant Enterobacteriaceae increased if the previous flock in the same house was positive, and if the flock was reared during September-October.

Capture and Detection of Circulating Glioma Cells Using the Recombinant VAR2CSA Malaria Protein.

Diffuse gliomas are the most common primary malignant brain tumor. Although extracranial metastases are rarely observed, recent studies have shown the presence of circulating tumor cells (CTCs) in the blood of glioma patients, confirming that a subset of tumor cells are capable of entering the circulation. The isolation and characterization of CTCs could provide a non-invasive method for repeated analysis of the mutational and phenotypic state of the tumor during the course of disease.

Inhibiting nucleolin reduces inflammation induced by mitochondrial DNA in cardiomyocytes exposed to hypoxia and reoxygenation.

Background And Purpose: Cellular debris causes sterile inflammation after myocardial infarction. Mitochondria constitute about 30 percent of the human heart. Mitochondrial DNA (mtDNA) is a damage-associated-molecular-pattern that induce injurious sterile inflammation.

High frequency of pathogenic germline variants within homologous recombination repair in patients with advanced cancer.

Genomic screening of cancer patients for predisposing variants is traditionally based on age at onset, family history and type of cancer. Whereas the clinical guidelines have proven efficient in identifying families exhibiting classical attributes of hereditary cancer, the frequency of patients with alternative presentations is unclear. We identified and characterized germline variants in 636 patients with advanced solid cancer using whole exome sequencing.

Mammalian Target of Rapamycin (mTOR) and the Proteasome Attenuates IL-1β Expression in Primary Mouse Cardiac Fibroblasts.

IL-1β is a highly potent pro-inflammatory cytokine and its secretion is tightly regulated. Inactive pro-IL-1β is transcribed in response to innate immune receptors activating NFκB. If tissue damage occurs, danger signals released from necrotic cells, such as ATP, can activate NLRP3-inflammasomes (multiprotein complexes consisting of NLRP3, ASC, and active caspase-1) which cleaves and activates pro-IL-1β.

Glucose homeostasis in statin users-The LIFESTAT study.

Background: Statins are widely used to lower cholesterol concentrations in both primary and secondary prevention of cardiovascular disease. The treatment increases the risk of muscle pain (myalgia) and of type 2 diabetes. However, the underlying mechanisms remain disputed.

Re-oxygenation after anoxia induces brain cell death and memory loss in the anoxia-tolerant crucian carp.

Crucian carp () survive without oxygen for several months, but it is unknown whether they are able to protect themselves from cell death normally caused by the absence, and particularly return, of oxygen. Here, we quantified cell death in brain tissue from crucian carp exposed to anoxia and re-oxygenation using the terminal deoxy-nucleotidyl transferase dUTP nick-end labelling (TUNEL) assay, and cell proliferation by immunohistochemical staining for proliferating cell nuclear antigen (PCNA) as well as PCNA mRNA expression. We also measured mRNA and protein expression of the apoptosis executer protease caspase 3, in laboratory fish exposed to anoxia and re-oxygenation and fish exposed to seasonal anoxia and re-oxygenation in their natural habitat over the year.

Palmitate promotes inflammatory responses and cellular senescence in cardiac fibroblasts.

Palmitate triggers inflammatory responses in several cell types, but its effects on cardiac fibroblasts are at present unknown. The aims of the study were to (1) assess the potential of palmitate to promote inflammatory signaling in cardiac fibroblasts through TLR4 and the NLRP3 inflammasome and (2) characterize the cellular phenotype of cardiac fibroblasts exposed to palmitate. We examined whether palmitate induces inflammatory responses in cardiac fibroblasts from WT, NLRP3 and ASCmice (C57BL/6 background).

[Preoperative fasting: Instructions to patients and length of fasting - a prospective, descriptive survey].

Introduction: Fasting is an important safety precaution for patients before surgery but studies indicate that excessive fasting is common. Explanations for this, including patient education related factors, are not well known. The aim of this study was to explore how long patients fast before surgery and what instructions they received, one year after the introduction of new guidelines for patients and professionals.

Extracellular mtDNA activates NF-κB via toll-like receptor 9 and induces cell death in cardiomyocytes.

Acute myocardial infarction (AMI) causes sterile inflammation, which exacerbates tissue injury. Elevated levels of circulating mitochondrial DNA (mtDNA) have been associated with AMI. We hypothesized that mtDNA triggers an innate immune response via TLR9 and NF-κB activation, causing cardiomyocyte injury.