Role of major cardiovascular surgery-induced metabolic reprogramming in acute kidney injury in critical care.

Purpose: Major cardiovascular surgery imposes high physiologic stress, often causing severe organ dysfunction and poor outcomes. The underlying mechanisms remain unclear. This study investigated metabolic changes induced by major cardiovascular surgery and the potential role of identified metabolic signatures in postoperative acute kidney injury (AKI).

Immunomodulatory Effects and Protection in Sepsis by the Antibiotic Moxifloxacin.

Sepsis is a leading cause of death in Intensive Care Units. Despite its prevalence, sepsis remains insufficiently understood, with no substantial qualitative improvements in its treatment in the past decades. Immunomodulatory agents may hold promise, given the significance of TNF-α and IL-1β as sepsis mediators.

Physiologic disruption and metabolic reprogramming in infection and sepsis.

Effective responses against severe systemic infection require coordination between two complementary defense strategies that minimize the negative impact of infection on the host: resistance, aimed at pathogen elimination, and disease tolerance, which limits tissue damage and preserves organ function. Resistance and disease tolerance mostly rely on divergent metabolic programs that may not operate simultaneously in time and space. Due to evolutionary reasons, the host initially prioritizes the elimination of the pathogen, leading to dominant resistance mechanisms at the potential expense of disease tolerance, which can contribute to organ failure.

DNA damage independent inhibition of NF-κB transcription by anthracyclines.

Anthracyclines are among the most used and effective anticancer drugs. Their activity has been attributed to DNA double-strand breaks resulting from topoisomerase II poisoning and to eviction of histones from select sites in the genome. Here, we show that the extensively used anthracyclines Doxorubicin, Daunorubicin, and Epirubicin decrease the transcription of nuclear factor kappa B (NF-κB)-dependent gene targets, but not interferon-responsive genes in primary mouse () macrophages.

Role of Omega-6 Fatty Acid Metabolism in Cardiac Surgery Postoperative Bleeding Risk.

Unlabelled: Cardiac surgery is frequently associated with significant postoperative bleeding. Platelet-dysfunction is the main cardiopulmonary bypass (CPB)-induced hemostatic defect. Not only the number of platelets decreases, but also the remaining are functionally impaired.

Tetracycline Antibiotics Induce Host-Dependent Disease Tolerance to Infection.

Several classes of antibiotics have long been known to have beneficial effects that cannot be explained strictly on the basis of their capacity to control the infectious agent. Here, we report that tetracycline antibiotics, which target the mitoribosome, protected against sepsis without affecting the pathogen load. Mechanistically, we found that mitochondrial inhibition of protein synthesis perturbed the electron transport chain (ETC) decreasing tissue damage in the lung and increasing fatty acid oxidation and glucocorticoid sensitivity in the liver.

Polymerase δ deficiency causes syndromic immunodeficiency with replicative stress.

Polymerase δ is essential for eukaryotic genome duplication and synthesizes DNA at both the leading and lagging strands. The polymerase δ complex is a heterotetramer comprising the catalytic subunit POLD1 and the accessory subunits POLD2, POLD3, and POLD4. Beyond DNA replication, the polymerase δ complex has emerged as a central element in genome maintenance.

Diastolic Function and Peripheral Venous Pressure as Indices for Fluid Responsiveness in Cardiac Surgical Patients.

Objective: Identifying fluid responsiveness is critical to optimizing perfusion while preventing fluid overload. An experimental study of hypovolemic shock resuscitation showed the importance of ventricular compliance and peripheral venous pressure (PVP) on fluid responsiveness. The authors tested the hypothesis that reduced ventricular compliance measured using transesophageal echocardiography results in decreased fluid responsiveness after a fluid bolus.

Systematic genetic mapping of necroptosis identifies SLC39A7 as modulator of death receptor trafficking.

Regulation of cell and tissue homeostasis by programmed cell death is a fundamental process with wide physiological and pathological implications. The advent of scalable somatic cell genetic technologies creates the opportunity to functionally map such essential pathways, thereby identifying potential disease-relevant components. We investigated the genetic basis underlying necroptotic cell death by performing a complementary set of loss-of-function and gain-of-function genetic screens.

Gestational diabetes alters the fetal heart rate variability during an oral glucose tolerance test: a fetal magnetocardiography study.

Objective: Gestational diabetes mellitus (GDM) potentially harms the child before birth. We previously found GDM to be associated with developmental changes in the central nervous system. We now hypothesise that GDM may also impact on the fetal autonomic nervous system under metabolic stress like an oral glucose tolerance test (OGTT).

RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics.

RASGRP1 is an important guanine nucleotide exchange factor and activator of the RAS-MAPK pathway following T cell antigen receptor (TCR) signaling. The consequences of RASGRP1 mutations in humans are unknown. In a patient with recurrent bacterial and viral infections, born to healthy consanguineous parents, we used homozygosity mapping and exome sequencing to identify a biallelic stop-gain variant in RASGRP1.

Biallelic loss-of-function mutation in NIK causes a primary immunodeficiency with multifaceted aberrant lymphoid immunity.

Primary immunodeficiency disorders enable identification of genes with crucial roles in the human immune system. Here we study patients suffering from recurrent bacterial, viral and Cryptosporidium infections, and identify a biallelic mutation in the MAP3K14 gene encoding NIK (NF-κB-inducing kinase). Loss of kinase activity of mutant NIK, predicted by in silico analysis and confirmed by functional assays, leads to defective activation of both canonical and non-canonical NF-κB signalling.

A role for the RNA pol II-associated PAF complex in AID-induced immune diversification.

Antibody diversification requires the DNA deaminase AID to induce DNA instability at immunoglobulin (Ig) loci upon B cell stimulation. For efficient cytosine deamination, AID requires single-stranded DNA and needs to gain access to Ig loci, with RNA pol II transcription possibly providing both aspects. To understand these mechanisms, we isolated and characterized endogenous AID-containing protein complexes from the chromatin of diversifying B cells.

Investigation of gold fluorides and noble gas complexes by matrix-isolation spectroscopy and quantum-chemical calculations.

Noble with a difference: Matrix-isolation experiments and quantum-chemical calculations have led to the characterization of two new compounds, namely first open-shell binary gold fluoride, AuF(2), and a NeAuF complex. Moreover, ArAuF, AuF(3), Au(2)F(6), and monomeric AuF(5) have been produced and identified under cryogenic conditions in neon and argon matrices.

High-fat taste challenge reveals altered striatal response in women recovered from bulimia nervosa: A pilot study.

Objectives: Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) tend to have disordered thinking and eating behaviours in regards to fat containing foods. This is the first study to investigate neuronal pathways that may contribute to altered fat consumption in eating disordered patients.

Methods: We used functional magnetic resonance imaging (fMRI) to compare responses to a high-fat cream stimulus, water, and a non-caloric viscous stimulus (CMC) to control for response to viscosity in individuals recovered from AN (N = 15), BN (N = 14) and a healthy control sample (CW, N = 18).

A comparison of SNAP II and bispectral index monitoring in patients undergoing sedation.

Clinical signs and patients' verbal responses have traditionally been used to assess patients' comfort and the depth of sedation. Recently, level-of-consciousness monitors have been used to guide sedation. The SNAP II(c) is a single-lead electroencephalogram device that displays a SNAP(c) Index - a derived value based on both high and low frequency electroencephalogram signals.

Wire-guided catheter exchange after failed direct laryngoscopy in critically ill adults.

Study Objective: To describe a technique for tracheal intubation after failed direct laryngoscopy using a Laryngeal Mask Airway (LMA) to secure the airway and to establish ventilation, and as a conduit for fiberoptic intubation utilizing a pre-packaged, convenient, and commercially available wire-guided catheter exchange kit.

Design: Retrospective case series.

Setting: University hospital.

A preliminary evaluation of a new derived EEG index monitor in anesthetized patients.

Background: An electroencephalogram (EEG) monitoring device, recently developed by Nicolet Biomedical, analyzes both high and low EEG frequencies. A processed derivative is obtained and displayed graphically and numerically on a monitor and may be used during anesthesia to indicate anesthetic "depth." However, radio-frequency interference from electrical equipment typically used in the operating room has the potential to interfere with the analysis of the high frequency components of the EEG.

A flow cytometric immune function assay for human peripheral blood dendritic cells.

CD11c+ and CD11c- (CD123+) dendritic cells (DCs) have been described in blood. Both cell types express high levels of HLA-DR and lack the lineage markers CD3, CD14, CD19, CD20, CD16, and CD56. These immunophenotypic properties were used along with analysis of activation-related surface antigens and intracellular staining of cytokines to characterize functional responses of these DC subsets to stimuli in whole human blood (WB).

Exercise in rats with liver injury induced by carbon tetrachloride or bile duct obstruction. Blood cholic acid and liver histology.

Unlabelled: Tolerance of exercise in rats with liver injury was evaluated by the response of plasma cholylglycine (CG) and by liver histology in two experiments with CCl4 hepatocellular damage and in two other experiments with cholestatic liver injury induced by obstruction of the common bile duct. (1) Rats swimming daily for 1 h while exposed to five successive doses of CCl4 and studied at rest, had a trend (P less than 0.06) to higher CG and a higher plasma SGPT (P less than 0.