Key elements for designing effective second victim support interventions: a focus group study in European clinical settings.

Background: The second victim (SV) experience limits the performance of health and care workers and places patients at risk. Peer support is recognised as the most effective, feasible and acceptable intervention to mitigate its impact.

Objective: To define a set of success factors when designing interventions to support SVs in health and care facilities based on expertise in different European countries.

Skeletal Phenotyping of Period-1-Deficient Melatonin-Proficient Mice.

In mice, variability in adult bone size and density has been observed among common inbred strains. Also, in the group of genes regulating circadian rhythmicity in mice, so called clock genes, changes in body size and skeletal parameters have been noted in knockout mice. Here, we studied the size and density of prominent bones of the axial and appendicular skeleton of clock gene Period-1-deficient (Per1) mice by means of microcomputed tomography.

Characterization of a novel SNP identified in Australian group A isolates derived from the M1 lineage.

Group A (GAS) is a human-adapted pathogen responsible for a variety of diseases. The GAS M1 lineage has contributed significantly to the recently reported increases in scarlet fever and invasive infections. However, the basis for its evolutionary success is not yet fully understood.

Pyroptotic cell corpses are crowned with F-actin-rich filopodia that engage CLEC9A signaling in incoming dendritic cells.

While apoptosis dismantles the cell to enforce immunological silence, pyroptotic cell death provokes inflammation. Little is known of the structural architecture of cells undergoing pyroptosis, and whether pyroptotic corpses are immunogenic. Here we report that inflammasomes trigger the Gasdermin-D- and calcium-dependent eruption of filopodia from the plasma membrane minutes before pyroptotic cell rupture, to crown the resultant corpse with filopodia.

Enhancement of a one-step membrane technique for the treatment of large bone defects by pre-seeding the membrane with CD8 lymphocyte depleted bone marrow mononuclear cells in a rat femoral defect model.

Background: The one-step membrane technique, using a human acellular dermal matrix (hADM), is an experimental method for treating large bone defects. This eliminates the need for the Masquelet membrane induction step, shortening the procedure while maintaining effectiveness. However, previous studies showed that colonizing hADM with bone marrow mononuclear cells (BMC) worsens healing, likely due to the presence of CD8+ lymphocytes, which negatively affect bone regeneration.

Physiologists as medical scientists: An early warning from the German academic system.

"Medical scientists" are postgraduate investigators who are engaged in biomedical research, and either hold a biomedical PhD or are qualified in medicine but do not participate in patient care. Medical scientists constitute ~40% of staff at medical faculties and >90% at nonuniversity medical research institutions in Germany. However, medical scientists in Germany face limited long-term career prospects and a lack of dedicated training and support programmes.

Redox Signaling in Endosomes Using the Example of EGF Receptors: A Graphical Review.

Early endosomes represent first-line sorting compartments or even organelles for internalized molecules. They enable the transport of molecules or ligands to other compartments of the cell, such as lysosomes, for degradation or recycle them back to the membrane by various mechanisms. Moreover, early endosomes function as signaling and scaffolding platforms to initiate or prolong distinct signaling pathways.

NoxO1 regulates EGFR signaling by its interaction with Erbin.

NADPH oxidase organizer 1 (NoxO1) is a scaffold cytoplasmic subunit of the reactive oxygen species (ROS) forming Nox1 complex and involved in angiogenesis, differentiation, and atherosclerosis. We found that overexpression of NoxO1 without simultaneous overexpression of any other component of the active Nox1 complex inhibited EGF-induced wound closure and signaling, while NoxO1 KO yielded the opposite effect. Accordingly, we hypothesize NoxO1 to exert Nox1 independent functions.

Ornithine lipid is a partial TLR4 agonist and NLRP3 activator.

Gram-negative bacterial lipopolysaccharides (LPSs) trigger inflammatory reactions through Toll-like receptor 4 (TLR4) and prime myeloid cells for inflammasome activation. In phosphate-limited environments, bacteria reduce LPS and other phospholipid production and synthesize phosphorus-free alternatives such as amino-acid-containing lipids like the ornithine lipid (OL). This adaptive strategy conserves phosphate for other essential cellular processes and enhances bacterial survival in host environments.

NoxO1 Determines the Level of ROS Formation by the Nox1-Centered NADPH Oxidase.

The Nox1-centered NADPH oxidase complex facilitates the transfer of electrons from intracellular NADPH across the cell membrane to extracellular molecular oxygen, resulting in the formation of superoxide. The complex is comprised of two membrane-bound subunits, namely Nox1 and p22phox, and the cytosolic subunits, namely NoxA1 and NoxO1. The presence of NoxO1 facilitates the proximity of all components, thereby enabling the complex to exhibit constitutive activity.

Inflammasome components as new therapeutic targets in inflammatory disease.

Inflammation drives pathology in many human diseases for which there are no disease-modifying drugs. Inflammasomes are signalling platforms that can induce pathological inflammation and tissue damage, having potential as an exciting new class of drug targets. Small-molecule inhibitors of the NLRP3 inflammasome that are now in clinical trials have demonstrated proof of concept that inflammasomes are druggable, and so drug development programmes are now focusing on other key inflammasome molecules.

Evaluation of a host-protein signature score for differentiating between bacterial and viral infections: real-life evidence from a German tertiary hospital.

Purpose: A host-protein signature score, consisting of serum-concentrations of C-reactive protein, tumour necrosis factor-related apoptosis-inducing ligand, and interferon gamma-induced protein 10, was validated for distinguishing between bacterial and viral infections as an antimicrobial stewardship measure for routine clinical practice among adult patients in a German tertiary hospital.

Methods: This single-centre, explorative study prospectively assessed the host-protein signature score, comparing it with serum procalcitonin (PCT) in patients with blood stream infections (BSI) and evaluating its efficacy in patients with viral infections against the standard of care (SOC) to assess the need for antibiotics due to suspected bacterial super/coinfection. Manufacturer-specified threshold scores were used to differentiate viral (< 35) and bacterial (> 65) infections.

Biocompatibility and osteogenic capacity of additively manufactured biodegradable porous WE43 scaffolds: An in vivo study in a canine model.

Magnesium is the most promising absorbable metallic implant material for bone regeneration and alloy WE43 is already FDA approved for cardiovascular applications. This study investigates the cyto- and biocompatibility of novel additively manufactured (AM) porous WE43 scaffolds as well as their osteogenic potential and degradation characteristics in an orthotopic canine bone defect model. The cytocompatibility was demonstrated using modified ISO 10993-conform extract-based indirect and direct assays, respectively.

Stress-regulated Arabidopsis GAT2 is a low affinity γ-aminobutyric acid transporter.

The four-carbon non-proteinogenic amino acid γ-aminobutyric acid (GABA) accumulates to high levels in plants in response to various abiotic and biotic stress stimuli, and plays a role in C:N balance, signaling, and as a transport regulator. Expression in Xenopus oocytes and voltage-clamping allowed the characterization of Arabidopsis GAT2 (At5g41800) as a low affinity GABA transporter with a K0.5GABA ~8 mM.

Emydomyces testavorans Surveillance in Multiple Free-Ranging Terrestrial and Aquatic Chelonian Species in Illinois, USA.

The order Onygenales contains multiple fungal pathogens that affect free-ranging and zoo-housed reptilian species. Emydomyces testavorans, an onygenalean fungus associated with skin and shell disease, has been sporadically detected in aquatic chelonians. Because of the recent discovery of this organism, little is known about its prevalence in free-ranging chelonians.

[Interstitial lung diseases : From imaging to treatment].

Background: The role of radiology in the diagnosis of interstitial lung diseases (ILDs) has evolved over time, in part replacing histology. Radiology now represents a pillar of diagnostics and monitoring in ILDs.

Objective: To what extent does radiology influence diagnostics and treatment in ILDs?

Materials And Methods: A literature review was conducted, and current findings were discussed in the context of clinical data.

1.8-cineole prevents platelet activation and aggregation by activating the cAMP pathway via the adenosine A receptor.

Aims: Dysregulated platelet aggregation is a fatal condition in many bacterial- and virus-induced diseases. However, classical antithrombotics cannot completely prevent immunothrombosis, due to the unaddressed mechanisms towards inflammation. Thus, targeting platelet hyperactivation together with inflammation might provide new treatment options in diseases, characterized by immunothrombosis, such as COVID-19 and sepsis.

Specific signaling by nicotinamide adenine dinucleotide oxidases - Role of their site of action.

Nicotinamide adenine dinucleotide (NADPH) oxidases, known for their role in generating reactive oxygen species (ROS) have emerged as key regulators of specific cellular signaling pathways. While their primary function is ROS production, recent research has highlighted the significance of their site-specific activity in governing distinct cellular signaling events. NADPH oxidases (Nox) are found in various cell types, and both their expression and activities are tightly regulated.

The septin modifier, forchlorfenuron, activates NLRP3 via a potassium-independent mitochondrial axis.

The Nod-like receptor protein 3 (NLRP3) inflammasome is activated by stimuli that induce perturbations in cell homeostasis, which commonly converge on cellular potassium efflux. NLRP3 has thus emerged as a sensor for ionic flux. Here, we identify forchlorfenuron (FCF) as an inflammasome activator that triggers NLRP3 signaling independently of potassium efflux.

Mechanistic insights from inflammasome structures.

Inflammasomes are supramolecular complexes that form in the cytosol in response to pathogen-associated and damage-associated stimuli, as well as other danger signals that perturb cellular homoeostasis, resulting in host defence responses in the form of cytokine release and programmed cell death (pyroptosis). Inflammasome activity is closely associated with numerous human disorders, including rare genetic syndromes of autoinflammation, cardiovascular diseases, neurodegeneration and cancer. In recent years, a range of inflammasome components and their functions have been discovered, contributing to our knowledge of the overall machinery.

Fluorochrome-labeled inhibitors of caspase-1 require membrane permeabilization to efficiently access caspase-1 in macrophages.

Caspase-1 location in cells has been studied with fluorochrome-labeled inhibitors of caspase-1 (FLICA reagents). We report that FLICA reagents have limited cell-membrane permeability. This impacts experimental design as cells with intact membranes, including caspase-1 knockout cells, are not appropriate controls for cells with inflammasome-induced gasdermin D membrane pores.