Lipids in liver failure syndromes: a focus on eicosanoids, specialized pro-resolvinglipid mediators and lysophospholipids.

Lipids are organic compounds insoluble in water with a variety of metabolic and non-metabolic functions. They not only represent an efficient energy substrate but can also act as key inflammatory and anti-inflammatory molecules as part of a network of soluble mediators at the interface of metabolism and the immune system. The role of endogenous bioactive lipid mediators has been demonstrated in several inflammatory diseases (rheumatoid arthritis, inflammatory bowel disease, atherosclerosis, cancer). The liver is unique in providing balanced immunotolerance to the exposure of bacterial components from the gut transiting through the portal vein and the lymphatic system. This balance is abruptly deranged in liver failure syndromes such as acute liver failure and acute-on-chronic liver failure. In these syndromes, researchers have recently focused on bioactive lipid mediators by global metabonomic profiling and uncovered the pivotal role of these mediators in the immune dysfunction observed in liver failure syndromes explaining the high occurrence of sepsis and subsequent organ failure. Among endogenous bioactive lipids, the mechanistic actions of three classes (eicosanoids, pro-resolving lipid mediators and lysophospholipids) in the pathophysiological modulation of liver failure syndromes will be the topic of this narrative review. Furthermore, the therapeutic potential of lipid-immune pathways will be described

Sequence and structural patterns detected in entangled proteins reveal the importance of co-translational folding

Proteins must fold quickly to acquire their biologically functional three-dimensional native structures. Hence, these are mainly stabilized by local contacts, while intricate topologies such as knots are rare. Here, we reveal the existence of specific patterns adopted by protein sequences and structures to deal with backbone self-entanglement. A large scale analysis of the Protein Data Bank shows that loops significantly intertwined with another chain portion are typically closed by weakly bound amino acids. Why is this energetic frustration maintained? A possible picture is that entangled loops are formed only toward the end of the folding process to avoid kinetic traps. Consistently, these loops are more frequently found to be wrapped around a portion of the chain on their N-terminal side, the one translated earlier at the ribosome. Finally, these motifs are less abundant in natural native states than in simulated protein-like structures, yet they appear in 32% of proteins, which in some cases display an amazingly complex intertwining

Lattice model for cold and warm swelling of polymers in water

We define a lattice model for the interaction of a polymer with water. We solve the model in a suitable approximation. In the case of a non-polar homopolymer, for reasonable values of the parameters, the polymer is found in a non-compact conformation at low temperature; as the temperature grows, there is a sharp transition towards a compact state, then, at higher temperatures, the polymer swells again. This behaviour closely reminds that of proteins, that are unfolded at both low and high temperatures.Comment: REVTeX, 5 pages, 2 EPS figure

MIRU-VNTR genotyping of Mycobacterium tuberculosis strains using QIAxcel technology: a multicentre evaluation study

Molecular genotyping of M.tuberculosis is an important laboratory tool in the context of emerging drug resistant TB. The standard 24-loci MIRU-VNTR typing includes PCR amplification followed by the detection and sizing of PCR fragments using capillary electrophoresis on automated sequencers or using agarose gels. The QIAxcel Advanced system might offer a cost-effective medium-throughput alternative.Performance characteristics of the QIAxcel Advanced platform for the standard 24 VNTR loci panel was evaluated at two centres on a total of 140 DNA specimens using automated capillary electrophoresis as a reference method. Additionally 4 hypervariable MIRU-VNTR loci were evaluated on 53 crude DNA extracts. The sizing accuracy, interlaboratory reproducibility and overall instrument's performance were assessed during the study.An overall concordance with the reference method was high reaching 98.5% and 97.6% for diluted genomic and crude DNA extracts respectively. 91.4% of all discrepancies were observed in fragments longer than 700bp. The concordance for hypervariable loci was lower except for locus 4120 (96.2%). The interlaboratory reproducibility agreement rates were 98.9% and 91.3% for standard and hypervariable loci, respectively. Overall performance of the QIAxcel platform for M.tuberculosis genotyping using a panel of standard loci is comparable to that of established methods for PCR fragments up to 700bp. Inaccuracies in sizing of longer fragments could be resolved through using in-house size markers or introduction of offset values. To conclude, the QiaXcel system could be considered an effective alternative to existing methods in smaller reference and regional laboratories offering good performance and shorter turnaround times

The tyrosine kinase receptor c-met, its cognate ligand HGF and the tyrosine kinase receptor trasducers STAT3, PI3K and RHO in thyroid nodules associated with Hashimoto's thyroiditis: an immunohisto-chemical characterization

Hepatocyte growth factor (HGF) exerts proliferative activities in thyrocytes upon binding to its tyrosine kinase receptor c-met and is also expressed in benign thyroid nodules as well as in Hashimoto's thyroiditis (HT)

Sanitation: a set of interventions mandated by the Italian government to limit the spread of SARS-CoV-2 in non-medical facilities

There have been several concerns about the environmental persistence of SARS-CoV-2 virus. These concerns led to the formulation of sanitation measures that try to lower the risk of indirect transmission of SARS-CoV-2 in non-medical facilities. This manuscript will elucidate the topic of environmental persistence of SARS-CoV-2. This will benefit the occupational health professionals two-fold. It describes the proper techniques for an effective sanitation of the workplace. It also explains how to protect workers who are responsible for carrying out these interventions. Sanitation is an important measure for a safe workplace. Sanitation is legally established and referenced by all the decrees so far enacted by the Italian government. It is defined as a set of actions and procedures that aim to lower the risk of indirect transmission of SARS-CoV-2 virus

Evaluation of the Disk Diffusion Method Compared to the Microdilution Method in Susceptibility Testing of Anidulafungin against Filamentous Fungi

Susceptibility testing of anidulafungin (AFG) against 32 mold isolates showed an excellent correlation between disk diffusion (DD) and broth microdilution methods. Based on our data, a 2-microg disk of AFG and a 24-h reading time might represent the best parameters for AFG DD testing against filamentous fungi

Effects of oral citicoline in perimetric glaucoma defects

Abstract: Purpose: to study the neuroprotective effect of oral citicoline (CT) in patients with primary open-angle glaucoma (POAG). Methods: this study recruits 110 patients with stage IV POAG and well-controlled intraocular pressure (IOP). Enrollees were randomly allocated in two groups: therapy group (TG) or control group (CG). Subjects in TG were treated with citicoline 500 mg / die for 4 months. The treatment period was followed by a wash-out phase of 2 months. At the end of the washout phase, subjects in TG resumed CT in the same fashion. Both groups were treated with pressurelowering medications. Each subject was evaluated with standard automated perimetry (SAP) at baseline, and then again 12, 24, and 36 months after enrollment. Results: TG showed a statistically significant improvement in MD values at 12 months (∆ = 21%) and T24 (∆ = 35%), and gradual improvements of the stage, up to the 3rd stage with localized defects after 36 months of therapy. Conversely, in CG, both the MD and PSD indices continued to deteriorate throughout the duration of the study. Conclusion: long-term daily treatment with citicoline might have a neuroprotective effect. Patients treated with oral citicoline showed an improvement in perimetric indices. Additional studies with larger samples and longer follow-ups are needed to confirm these results