Bioimpedance Analysis in CKD and HF Patients: A Critical Review of Benefits, Limitations, and Future Directions.

Bioimpedance analysis (BIA) is a validated non-invasive technique already proven to be useful for the diagnosis, prognosis, and management of body fluids in subjects with heart failure (HF) and chronic kidney disease (CKD). Although BIA has been widely employed for research purposes, its clinical application is still not fully widespread. The aim of this review is to provide a comprehensive overview of the state of the art of BIA utilization by analyzing the clinical benefits, limitations, and potential future developments in this clinically unexplored field.

In-hospital bioimpedance-derived total body water predicts short-term cardiovascular mortality and re-hospitalizations in acute decompensated heart failure patients.

Background: Hospital re-admissions in heart failure (HF) patients are mostly caused by an acute exacerbation of their chronic congestion. Bioimpedance analysis (BIA) has emerged as a promising non-invasive method to assess the volume status in HF. However, its correlation with clinically assessed volume status and its prognostic value in the acute intra-hospital setting remains uncertain.

Recombinant Acetylcholine Receptor Immunization Induces a Robust Model of Experimental Autoimmune Myasthenia Gravis in Mice.

Myasthenia gravis (MG) is a prototypical autoimmune disease of the neuromuscular junction (NMJ). The study of the underlying pathophysiology has provided novel insights into the interplay of autoantibodies and complement-mediated tissue damage. Experimental autoimmune myasthenia gravis (EAMG) emerged as a valuable animal model, designed to gain further insight and to test novel therapeutic approaches for MG.

Accessing three-branched high-affinity cereblon ligands for molecular glue and protein degrader design.

The Petasis borono-Mannich reaction was employed for an alternative entry towards three-branched cereblon ligands. Such compounds are capabable of making multiple interactions with the protein surface and possess a suitable linker exit vector. The high-affinity ligands were used to assemble prototypic new molecular glues and proteolysis targeting chimeras (PROTACs) targeting BRD4 for degradation.

Validation of TREK1 ion channel activators as an immunomodulatory and neuroprotective strategy in neuroinflammation.

Modulation of two-pore domain potassium (K) channels has emerged as a novel field of therapeutic strategies as they may regulate immune cell activation and metabolism, inflammatory signals, or barrier integrity. One of these ion channels is the TWIK-related potassium channel 1 (TREK1). In the current study, we report the identification and validation of new TREK1 activators.

Adsorption and Inactivation of SARS-CoV-2 on the Surface of Anatase TiO(101).

We investigated the adsorption of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), the virus responsible for the current pandemic, on the surface of the model catalyst TiO(101) using atomic force microscopy, transmission electron microscopy, fluorescence microscopy, and X-ray photoelectron spectroscopy, accompanied by density functional theory calculations. Three different methods were employed to inactivate the virus after it was loaded on the surface of TiO(101): (i) ethanol, (ii) thermal, and (iii) UV treatments. Microscopic studies demonstrate that the denatured spike proteins and other proteins in the virus structure readsorb on the surface of TiO under thermal and UV treatments.

The HSF1-CPT1a Pathway Is Differentially Regulated in NAFLD Progression.

Obesity and obesity-associated diseases represent one of the key health challenges of our time. In this context, aberrant hepatic lipid accumulation is a central pathological aspect of non-alcoholic fatty liver disease (NAFLD). By comparing methylation signatures of liver biopsies before and after bariatric surgery, we recently demonstrated the strong enrichment of differentially methylated heat shock factor 1 (HSF1) binding sites (>400-fold) in the process of liver remodeling, indicating a crucial role of HSF1 in modulating central aspects of NAFLD pathogenesis.

Cladribine treatment improves cortical network functionality in a mouse model of autoimmune encephalomyelitis.

Background: Cladribine is a synthetic purine analogue that interferes with DNA synthesis and repair next to disrupting cellular proliferation in actively dividing lymphocytes. The compound is approved for the treatment of multiple sclerosis (MS). Cladribine can cross the blood-brain barrier, suggesting a potential effect on central nervous system (CNS) resident cells.

Spillover and crossover effects of exposure to work-related aggression and adversities: A dyadic diary study.

The past two decades have produced extensive evidence on the manifold and severe outcomes for victims of aggression exposure in the workplace. However, due to the dominating individual-centered approach, most findings miss a social network perspective. Consequently, knowledge of negative spillover to different life-domains or crossover to uninvolved individuals alongside a detailed understanding of the involved transmission processes remains scarce.

Trans-[bis(benzimidazol-2-ylidene)dichlorido]platinum(II) complexes with peculiar modes of action and activity against cisplatin-resistant cancer cells.

Three series of cis- and trans-[bis(benzimidazol-2-ylidene)dichlorido]platinum(II) and cis-[(benzimidazol-2-ylidene)(DMSO)dichlorido]platinum(II) complexes were synthesised and screened for cytotoxicity against six human cancer cell lines. Depending on their N-alkyl and 5-alkoxycarbonyl substituents, two-digit nanomolar to single-digit micromolar IC values against cancer cell lines intrinsically resistant to or ill-responding to cisplatin were reached by both cis- and trans-configured complexes. The stability of the complexes under aqueous biotest conditions was shown via H and Pt NMR monitoring to be dependent on their configuration and their N-substituents.

Protocol to analyze the transmigration efficiency of T. brucei using an in vitro model of the blood-cerebrospinal fluid barrier.

At present, the only approach to investigate the transmigration of Trypanosoma brucei, the causative agent of human African trypanosomiasis, from blood to cerebrospinal fluid is through animal experiments. This protocol details how to analyze the transmigration efficiency using an in vitro model of the blood-cerebrospinal fluid (blood-CSF) barrier. We describe how to grow human choroid plexus epithelial cells on cell culture filter inserts to form the barrier, followed by isolating and quantifying genomic DNA of transmigrated parasites by qPCR.

Activation of non-classical NMDA receptors by glycine impairs barrier function of brain endothelial cells.

Blood-brain barrier (BBB) integrity is necessary to maintain homeostasis of the central nervous system (CNS). NMDA receptor (NMDAR) function and expression have been implicated in BBB integrity. However, as evidenced in neuroinflammatory conditions, BBB disruption contributes to immune cell infiltration and propagation of inflammatory pathways.

Microbiota-dependent activation of the myeloid calcineurin-NFAT pathway inhibits B7H3- and B7H4-dependent anti-tumor immunity in colorectal cancer.

Bacterial sensing by intestinal tumor cells contributes to tumor growth through cell-intrinsic activation of the calcineurin-NFAT axis, but the role of this pathway in other intestinal cells remains unclear. Here, we found that myeloid-specific deletion of calcineurin in mice activated protective CD8 T cell responses and inhibited colorectal cancer (CRC) growth. Microbial sensing by myeloid cells promoted calcineurin- and NFAT-dependent interleukin 6 (IL-6) release, expression of the co-inhibitory molecules B7H3 and B7H4 by tumor cells, and inhibition of CD8 T cell-dependent anti-tumor immunity.

Transmigration of across an blood-cerebrospinal fluid barrier.

is the causative agent of human African trypanosomiasis. The parasite transmigrates from blood vessels across the choroid plexus epithelium to enter the central nervous system, a process that leads to the manifestation of second stage sleeping sickness. Using an model of the blood-cerebrospinal fluid barrier, we investigated the mechanism of the transmigration process.

An optimized and validated protocol for inducing chronic experimental autoimmune encephalomyelitis in C57BL/6J mice.

Background: Myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalomyelitis (EAE) is the most commonly used animal model of multiple sclerosis. However, variations in the induction protocol can affect EAE progression, and may reduce the comparability of data.

Optimized Method: In the present study, we investigated the influence of the different components used for EAE induction in C57BL/6J mice on disease progression.

Dimethyl fumarate treatment restrains the antioxidative capacity of T cells to control autoimmunity.

Dimethyl fumarate, an approved treatment for relapsing-remitting multiple sclerosis, exerts pleiotropic effects on immune cells as well as CNS resident cells. Here, we show that dimethyl fumarate exerts a profound alteration of the metabolic profile of human CD4+ as well as CD8+ T cells and restricts their antioxidative capacities by decreasing intracellular levels of the reactive oxygen species scavenger glutathione. This causes an increase in mitochondrial reactive oxygen species levels accompanied by an enhanced mitochondrial stress response, ultimately leading to impaired mitochondrial function.

K18.1 translates T cell receptor signals into thymic regulatory T cell development.

It remains largely unclear how thymocytes translate relative differences in T cell receptor (TCR) signal strength into distinct developmental programs that drive the cell fate decisions towards conventional (Tconv) or regulatory T cells (Treg). Following TCR activation, intracellular calcium (Ca) is the most important second messenger, for which the potassium channel K18.1 is a relevant regulator.

A Nanoscaffolded Spike-RBD Vaccine Provides Protection against SARS-CoV-2 with Minimal Anti-Scaffold Response.

The response of the adaptive immune system is augmented by multimeric presentation of a specific antigen, resembling viral particles. Several vaccines have been designed based on natural or designed protein scaffolds, which exhibited a potent adaptive immune response to antigens; however, antibodies are also generated against the scaffold, which may impair subsequent vaccination. In order to compare polypeptide scaffolds of different size and oligomerization state with respect to their efficiency, including anti-scaffold immunity, we compared several strategies of presentation of the RBD domain of the SARS-CoV-2 spike protein, an antigen aiming to generate neutralizing antibodies.

One Brain-All Cells: A Comprehensive Protocol to Isolate All Principal CNS-Resident Cell Types from Brain and Spinal Cord of Adult Healthy and EAE Mice.

In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, the role of each central nervous system (CNS)-resident cell type during inflammation, neurodegeneration, and remission has been frequently addressed. Although protocols for the isolation of different individual CNS-resident cell types exist, none can harvest all of them within a single experiment. In addition, isolation of individual cells is more demanding in adult mice and even more so from the inflamed CNS.

Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABA receptor encephalitis.

Encephalitis associated with antibodies against the neuronal gamma-aminobutyric acid A receptor (GABA-R) is a rare form of autoimmune encephalitis. The pathogenesis is still unknown but autoimmune mechanisms were surmised. Here we identified a strongly expanded B cell clone in the cerebrospinal fluid of a patient with GABA-R encephalitis.

Consequences of Exposure to Violence, Aggression, and Sexual Harassment in Private Security Work: A Mediation Model.

While exposure to violence and aggression is well known for its detrimental effects on employees' health as well as organizational outcomes, certain high-risk work domains have scarcely been researched. Thus, this study set out to determine negative consequences of work-related exposure to four forms of harmful behaviors in private security. In a sample of 487 German-speaking security guards, 23% had experienced outsider-initiated violence, 56% aggressive acts, 30% vicarious violent acts, and 3% were sexually harassed over the past 12 months.

Intracellular fluoride influences TASK mediated currents in human T cells.

The expression of Kv1.3 and K channels in human T cells is essential for maintaining cell activation, proliferation and migration during an inflammatory response. Recently, an additional residual current, sensitive to anandamide and A293, compounds specifically inhibiting currents mediated by TASK channels, was observed after complete pharmacological blockade of Kv1.