Serum Urate Levels and Ultrasound Characteristics of Carotid Atherosclerosis across Obesity Phenotypes.

BACKGROUND: Existing evidence suggests a close link among high levels of serum urate (SU), obesity and carotid atherosclerosis. The aim of the present study was to evaluate the interrelations between SU levels and carotid atherosclerosis in subjects with different obesity phenotypes. METHODS: In this study, a total of 2076 subjects (mean age 48.1 ± 13.1 years; 1307 women) were recruited: 59 with general obesity, 616 with central obesity, 715 with mixed (general-central) obesity and 686 non-obese. Anthropometric measurements, vascular risk factors, blood biochemistry analysis (including SU levels), and carotid ultrasound were performed. Ultrasound assessment included evaluation of intima-media thickness (IMT) and plaque characteristics, including number, total area and type (vulnerable vs. stable) of plaques. RESULTS: After adjustment for potential confounders, the highest levels of SU were observed in subjects with mixed obesity, followed by subjects with central obesity, general obesity and the non-obese (309.4 ± 82.2 vs. 301.2 ± 73.1 vs. 272.9 ± 61.8 vs. 234.2 ± 59.8 µmol/L, respectively; F = 149.2, post hoc p < 0.001). Similarly, subjects with mixed and central obesity presented higher values of IMT compared to subjects with general obesity and the non-obese (0.68 ± 0.16 vs. 0.67 ± 0.16 vs. 0.62 ± 0.14 vs. 0.57 ± 0.13 mm, respectively; F = 54.2, post hoc p < 0.001). No difference in number, total area and type of plaques among obesity groups were attested (all p > 0.05). Significantly higher IMT values were observed in subjects with increased SU levels compared to subjects with normal SU levels (0.70 ± 0.10 vs. 0.62 ± 0.14 mm, p = 0.02) only within the central obesity group. Increasing levels of SU were associated with a higher frequency of increased IMT only in subjects with central obesity (OR 1.033, 95% CI 1.025-1.041). Similarly, SU levels yielded a satisfactory performance in detecting subjects with increased IMT (AUC 0.65, 95% CI 0.50-0.73, subjects with carotid plaques (0.62, 95% CI 0.55-0.68) and subjects with vulnerable plaque types (0.68, 0.59-0.76) only within the central obesity group. CONCLUSIONS: Among the studied obesity types, the association between SU levels and markers of carotid atherosclerosis was of particular significance in subjects with central obesity.

Calcification of Various Bioprosthetic Materials in Rats: Is It Really Different?

The causes of heart valve bioprosthetic calcification are still not clear. In this paper, we compared the calcification in the porcine aorta (Ao) and the bovine jugular vein (Ve) walls, as well as the bovine pericardium (Pe). Biomaterials were crosslinked with glutaraldehyde (GA) and diepoxide (DE), after which they were implanted subcutaneously in young rats for 10, 20, and 30 days. Collagen, elastin, and fibrillin were visualized in non-implanted samples. Atomic absorption spectroscopy, histological methods, scanning electron microscopy, and Fourier-transform infrared spectroscopy were used to study the dynamics of calcification. By the 30th day, calcium accumulated most intensively in the collagen fibers of the GA-Pe. In elastin-rich materials, calcium deposits were associated with elastin fibers and localized differences in the walls of Ao and Ve. The DE-Pe did not calcify at all for 30 days. Alkaline phosphatase does not affect calcification since it was not found in the implant tissue. Fibrillin surrounds elastin fibers in the Ao and Ve, but its involvement in calcification is questionable. In the subcutaneous space of young rats, which are used to model the implants' calcification, the content of phosphorus was five times higher than in aging animals. We hypothesize that the centers of calcium phosphate nucleation are the positively charged nitrogen of the pyridinium rings, which is the main one in fresh elastin and appears in collagen as a result of GA preservation. Nucleation can be significantly accelerated at high concentrations of phosphorus in biological fluids. The hypothesis needs further experimental confirmation.

Biological Studies of New Implant Materials Based on Carbon and Polymer Carriers with Film Heterostructures Containing Noble Metals.

This paper presents pioneering results on the evaluation of noble metal film hetero-structures to improve some functional characteristics of carbon-based implant materials: carbon-composite material (CCM) and carbon-fiber-reinforced polyetheretherketone (CFR-PEEK). Metal-organic chemical vapor deposition (MOCVD) was successfully applied to the deposition of Ir, Pt, and PtIr films on these carriers. A noble metal layer as thin as 1 µm provided clear X-ray imaging of 1−2.5 mm thick CFR-PEEK samples. The coated and pristine CCM and CFR-PEEK samples were further surface-modified with Au and Ag nanoparticles (NPs) through MOCVD and physical vapor deposition (PVD) processes, respectively. The composition and microstructural features, the NPs sizes, and surface concentrations were determined. In vitro biological studies included tests for cytotoxicity and antibacterial properties. A series of samples were selected for subcutaneous implantation in rats (up to 3 months) and histological studies. The bimetallic PtIr-based heterostructures showed no cytotoxicity in vitro, but were less biocompatible due to a dense two-layered fibrous capsule. AuNP heterostructures on CFR-PEEK promoted cell proliferation in vitro and exhibited a strong inhibition of bacterial growth (p < 0.05) and high in vitro biocompatibility, especially Au/Ir structures. AgNP heterostructures showed a more pronounced antibacterial effect, while their in vivo biocompatibility was better than that of the pristine CFR-PEEK, but worse than that of AuNP heterostructures.

The Link between Activities of Hepatic 11beta-Hydroxysteroid Dehydrogenase-1 and Monoamine Oxidase-A in the Brain Following Repeated Predator Stress: Focus on Heightened Anxiety.

We investigated the presence of a molecular pathway from hepatic 11-ßHSD-1 to brain MAO-A in the dynamics of plasma corticosterone involvement in anxiety development. During 14 days following repeated exposure of rats to predator scent stress for 10 days, the following variables were measured: hepatic 11-ßHSD-1 and brain MAO-A activities, brain norepinephrine, plasma corticosterone concentrations, and anxiety, as reflected by performance on an elevated plus maze. Anxiety briefly decreased and then increased after stress exposure. This behavioral response correlated inversely with plasma corticosterone and with brain MAO-A activity. A mathematical model described the dynamics of the biochemical variables and predicted the factor(s) responsible for the development and dynamics of anxiety. In the model, hepatic 11-ßHSD-1 was considered a key factor in defining the dynamics of plasma corticosterone. In turn, plasma corticosterone and oxidation of brain ketodienes and conjugated trienes determined the dynamics of brain MAO-A activity, and MAO-A activity determined the dynamics of brain norepinephrine. Finally, plasma corticosterone was modeled as the determinant of anxiety. Solution of the model equations demonstrated that plasma corticosterone is mainly determined by the activity of hepatic 11-ßHSD-1 and, most importantly, that corticosterone plays a critical role in the dynamics of anxiety following repeated stress.

Clinical and Radiological Deterioration in a Case of Creutzfeldt-Jakob Disease following SARS-CoV-2 Infection: Hints to Accelerated Age-Dependent Neurodegeneration.

Systemic inflammation and the host immune responses associated with certain viral infections may accelerate the rate of neurodegeneration in patients with Creutzfeldt-Jakob disease (CJD), a rare, transmissible neurodegenerative disease. However, the effects of the newly emerged SARS-CoV-2 infection on the pathogenesis of CJD are unknown. In this study, we describe the case of an elderly female patient with sporadic CJD that exhibited clinical deterioration with the emergence of seizures and radiological neurodegenerative progression following an infection with SARS-CoV-2 and severe COVID-19. Despite efforts to control the progression of the disease, a dismal outcome ensued. This report further evidences the age-dependent neurological effects of SARS-CoV-2 infection and proposes a vulnerability to CJD and increased CJD progression following COVID-19.

Noble Metals for Modern Implant Materials: MOCVD of Film Structures and Cytotoxical, Antibacterial, and Histological Studies.

This work is aimed at developing the modification of the surface of medical implants with film materials based on noble metals in order to improve their biological characteristics. Gas-phase transportation methods were proposed to obtain such materials. To determine the effect of the material of the bottom layer of heterometallic structures, Ir, Pt, and PtIr coatings with a thickness of 1.4-1.5 µm were deposited by metal-organic chemical vapor deposition (MOCVD) on Ti6Al4V alloy discs. Two types of antibacterial components, namely, gold nanoparticles (AuNPs) and discontinuous Ag coatings, were deposited on the surface of these coatings. AuNPs (11-14 nm) were deposited by a pulsed MOCVD method, while Ag films (35-40 nm in thickness) were obtained by physical vapor deposition (PVD). The cytotoxic (24 h and 48 h, toward peripheral blood mononuclear cells (PBMCs)) and antibacterial (24 h) properties of monophase (Ag, Ir, Pt, and PtIr) and heterophase (Ag/Pt, Ag/Ir, Ag/PtIr, Au/Pt, Au/Ir, and Au/PtIr) film materials deposited on Ti-alloy samples were studied in vitro and compared with those of uncoated Ti-alloy samples. Studies of the cytokine production by PBMCs in response to incubation of the samples for 24 and 48 h and histological studies at 1 and 3 months after subcutaneous implantation in rats were also performed. Despite the comparable thickness of the fibrous capsule after 3 months, a faster completion of the active phase of encapsulation was observed for the coated implants compared to the Ti alloy analogs. For the Ag-containing samples, growth inhibition of S. epidermidis, S. aureus, Str. pyogenes, P. aeruginosa, and Ent. faecium was observed.

Cross-linking method using pentaepoxide for improving bovine and porcine bioprosthetic pericardia: A multiparametric assessment study.

Bioprosthetic heart valves made from bovine pericardium (BP) and porcine pericardium (PP) preserved with glutaraldehyde (GA) are commonly used in valve surgeries but prone to calcification in many patients. In this study, we compared BP and PP preserved with GA, ethylene glycol diglycidyl ether (DE), and 1,2,3,4,6-penta-O-{1-[2-(glycidyloxy)ethoxy]ethyl}-d-glucopyranose (PE). We studied the stabilities of DE and PE in preservation media along with the amino acid (AA) compositions, Fourier-transform infrared spectra, mechanical properties, surface morphologies, thermal stability, calcification, and the cytocompatibility of BP and PP treated with 0.625% GA, 5% DE, 2% PE, and alternating 5% DE and 2% PE for 3 + 11 d and 10 + 10 d, respectively. Both epoxides were stable in the water-buffer solutions (pH 7.4). DE provided high linkage densities in BP and PP owing to reactions with Hyl, Lys, His, Arg, Ser, and Tyr. PE reacted weakly with these AAs but strongly with Met. High cross-linking density obtained using the 10 d + 10 d method provided satisfactory thermal stability of biomaterials. The epoxy preservations improved cytocompatibility and resistance to calcification. PE enhanced the stress/strain properties of the xenogeneic pericardia, perhaps by forming nanostructures that were clearly visualised in BP using scanning electron microscopy. The DE + PE combination, in an alternating cross-linking manner, thus constitutes a promising option for developing bioprosthetic pericardia.

Botulinum Toxin-Chitosan Nanoparticles Prevent Arrhythmia in Experimental Rat Models.

Several experimental studies have recently demonstrated that temporary autonomic block using botulinum toxin (BoNT/A1) might be a novel option for the treatment of atrial fibrillation. However, the assessment of antiarrhythmic properties of BoNT has so far been limited, relying exclusively on vagal stimulation and rapid atrial pacing models. The present study examined the antiarrhythmic effect of specially formulated BoNT/A1-chitosan nanoparticles (BTN) in calcium chloride-, barium chloride- and electrically induced arrhythmia rat models. BTN enhanced the effect of BoNT/A1. Subepicardial injection of BTN resulted in a significant antiarrhythmic effect in investigated rat models. BTN formulation antagonizes arrhythmia induced by the activation of Ca, K and Na channels.

Treatment with bisphosphonates to mitigate calcification of elastin-containing bioprosthetic materials.

This study evaluated the ability of bisphosphonates (BPAs) of different molecular structures to mitigate the calcification of porcine aortic wall (PAW) and bovine jugular vein wall (BJVW). Tissues cross-linked with glutaraldehyde (GA) or diepoxide (DE) were modified with pamidronic acid (PAM), alendronic acid (ALE), neridronic acid (NER) (type 1 BPAs); 2-(2'-carboxyethylamino)ethylidene-1,1-bisphosphonic acid (CEABA), 2-(5-carboxypentylamino)ethylidene-1,1-bisphosphonic acid (CPABA) (type 2); and zoledronic acid (ZOL) (type 3). After implanting the tissue samples subcutaneously in 100 rats, calcification was examined using atomic absorption spectrophotometry (60-day explants) and light microscopy after von Kossa staining (10- and 30-day explants). The calcium contents in GA-BJVW and GA- and DE-PAW increased up to 100-120 mg/g after 60 days, while being 3 times lower in DE-BJVW. In modified and nonmodified PAW samples, calcium phosphates appeared by day 10 and were associated with elastic fibers and devitalized cellular elements. In all groups of BJVW samples, mineralization began in elastic fibers near the subendothelial layer. In addition, calcified collagen was found in the GA-BJVW samples. Minimal calcification was found in GA-PAW treated with type 1 BPAs and CEABA. For DE-PAW and GA-BJVW, the calcium level significantly decreased with PAM and CEABA. Meanwhile, ALE and NER were effective for DE-BJVW.

Translation of Human ß-Actin mRNA is Regulated by mTOR Pathway.

The mammalian target of rapamycin (mTOR) kinase is a well-known master regulator of growth-dependent gene expression in higher eukaryotes. Translation regulation is an important function of the mTORC1 pathway that controls the synthesis of many ribosomal proteins and translation factors. Housekeeping genes such as ß-actin (ACTB) are widely used as negative control genes in studies of growth-dependent translation. Here we demonstrate that translation of both endogenous and reporter ACTB mRNA is inhibited in the presence of mTOR kinase inhibitor (Torin1) and under amino acid starvation. Notably, 5'UTR and promoter of ACTB are sufficient for the mTOR-dependent translational response, and the degree of mTOR-sensitivity of ACTB mRNA translation is cell type-dependent.

Sporosalibacterium tautonense sp. nov., a thermotolerant, halophilic, hydrolytic bacterium isolated from a gold mine, and emended description of the genus Sporosalibacterium.

A novel strictly anaerobic, thermotolerant, moderately halophilic, organotrophic bacterium, strain MRo-4T, was isolated from a sample of a microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. Cells of the novel isolate stained Gram-positive and were motile, spore-forming rods, 0.2-0.3 µm in width and 5-20 µm in length. Strain MRo-4T grew at 25-50 °C, at pH 7.0-8.8 and at an NaCl concentration of 5-100 g l-1. The isolate was able to ferment yeast extract, peptone and mono-, oligo- and polysaccharides, including cellulose and chitin. Elemental sulfur, thiosulfate, sulfate, sulfite, nitrate, nitrite, fumarate and arsenate were not reduced. The major fatty acids were iso-C15 : 0, iso-C15 : 0 dimethyl acetyl and anteiso-C15 : 0. The G+C content of the DNA was 32.9 mol%. Phylogenetic analysis of 16S rRNA gene sequences of strain MRo-4T and its nearest relatives showed its affiliation to the genus Sporosalibacterium. Sporosalibacteriumfaouarense SOL3f37T, the only valid published representative of the genus, appeared to be its closest relative (96.8 % 16S rRNA gene sequence similarity). However, strains MRo-4T and S. faouarense SOL3f37T differed in temperature, pH and salinity ranges for growth, requirement for yeast extract and substrate profiles. Based on the phylogenetic analysis and physiological properties of the novel isolate, we propose a novel species, Sporosalibacterium tautonense sp. nov. The type strain is MRo-4T (=DSM 28179T=VKM B-2948T).