Simulation of Diffusion-Controlled Growth of Interdependent Nuclei under Potentiostatic Conditions

The problem of diffusion-controlled growth following an instantaneous nucleation event was studied within the framework of a new numerical model, considering the spatial distribution of hemispherical nuclei on the electrode surface and the mutual influence of growing nuclei via the collision of 3D diffusion fields. The simulation of the diffusion-controlled growth of hexagonal and random ensembles was performed at the overpotential-dependent number density of nuclei. The diffusion flow to each nucleus within a random ensemble was simulated by the finite difference method using the derived analytical expressions for the surface areas and the volumes formed at the intersection of 3D diffusion fields with the side faces of a virtual right prism with a Voronoi polygon base. The implementation of this approach provides an accurate calculation of concentration profiles, time dependences of the size of nuclei, and current transients. The results, including total current density transients, growth exponents, and nucleus size distribution, were compared with models developed within the concept of planar diffusion zones, the mean-field approximation and the Brownian dynamics simulation method, as well as with experimental data from the literature. The prospects of the model for studying the initial stages of electrocrystallization were discussed.     

A Feasibility Study of High-Entropy Alloy Coating Deposition by Detonation Spraying Combined with Laser Melting

In this work, a new two-stage approach to the deposition of high-entropy alloy coatings is proposed. At the first stage, a composite precursor coating is formed by detonation spraying of the metal powder mixtures. At the second stage, the precursor coating is re-melted by a laser, and the formation of multi-component solid solution phases can be expected upon solidification. The feasibility of the proposed approach was validated using three different mixtures of Fe, Ni, Cu, Co and Al powders. It was shown that detonation spraying allows forming composite coatings with a uniform distribution of the lamellae of different metals. The results of the structural analysis of the laser-treated coatings suggest that complete alloying occurred in the melt and face-centered cubic solid solutions formed in the coatings upon cooling.     

Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin

The role of autophagy, a process in which the cell self-digests its own components, was investigated in glioma cell death induced by the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase-inhibiting drug simvastatin. Induction of autophagy and activation of autophagy-regulating signalling pathways were analyzed by immunoblotting. Flow cytometry/fluorescent microscopy was used to assess autophagy-associated intracellular acidification and apoptotic markers (phosphatidylserine exposure, DNA fragmentation and caspase activation). Cell viability was determined by crystal violet, MTT or LDH release assay. Simvastatin treatment of U251 and C6 glioma cell lines caused the appearance of autophagolysosome-like intracytoplasmic acidic vesicles. The induction of autophagy in U251 cells was confirmed by the upregulation of autophagosome-associated LC3-II and pro-autophagic beclin-1, as well as by the downregulation of the selective autophagic target p62. Simvastatin induced the activation of AMP-activated protein kinase (AMPK) and its target Raptor, while simultaneously downregulating activation of Akt. Mammalian target of rapamycin (mTOR), a major AMPK/Akt downstream target and a major negative autophagy regulator, and its substrate p70 S6 kinase 1 were also inhibited by simvastatin. Mevalonate, the product of HMG-CoA reductase enzymatic activity, AMPK siRNA or pharmacological inactivation of AMPK with compound C suppressed, while the inhibitors of Akt (10-DEBC hydrochloride) and mTOR (rapamycin) mimicked autophagy induction by simvastatin. Inhibition of autophagy with bafilomycin A1, 3-methyladenine and LC3β shRNA, as well as AMPK inhibition with compound C or AMPK siRNA, markedly increased apoptotic death of simvastatin-treated U251 cells. These data suggest that inhibition of AMPK-dependent autophagic response might sensitize glioma cells to statin-induced apoptotic death.     

Chronic biopsy proven post‐COVID myoendocarditis with SARS‐Cov‐2 persistence and high level of antiheart antibodies

PurposeTo study the clinical signs and mechanisms (viral and autoimmune) of myoendocarditis in the long‐term period after COronaVIrus Disease 2019 (COVID‐19).MethodsFourteen patients (nine male, 50.1 ± 10.2 y.o.) with biopsy proven post‐COVID myocarditis were observed. The diagnosis of COVID‐19 was confirmed by IgG seroconversion. The average time of admission after COVID‐19 was 5.5 [2; 10] months. An endomyocardial biopsy (EMB) of the right ventricle was obtained. The biopsy analysis included polymerase chain reaction diagnosis of viral infection, morphological, immunohistochemical (IHC) examination with antibodies to CD3, CD45, CD68, CD20, SARS‐Cov‐2 spike, and nucleocapsid antigens. Coronary atherosclerosis was ruled out in all patients over 40 years.ResultsThe new cardiac symptoms (congestive heart failure 3–4 New York Heart Association class with severe right ventricular involvement, various rhythm, and conduction disturbances) appeared 1–5 months following COVID‐19. Magnetic resonance imaging showed disseminated or focal subepicardial and intramyocardial late gadolinium enhancement, hyperemia, edema, and increased myocardial native T1 relaxation time. Antiheart antibodies levels were increased 3–4 times in 92.9% of patients. The mean left ventricular (LV) ejection fraction (EF) was 28% (24.5; 37.8). Active lymphocytic myocarditis was diagnosed in 12 patients, eosinophilic myocarditis in two patients. SARS‐Cov‐2 RNA was detected in 12 cases (85.7%), in association with parvovirus B19 DNA—in one. Three patients had also endocarditis (infective and nonbacterial, with parietal thrombosis). As a result of steroid and chronic heart failure therapy, the EF increased to 47% (37.5; 52.5).ConclusionsCOVID‐19 can lead to long‐term severe post‐COVID myoendocarditis, that is characterized by prolonged persistence of coronavirus in cardiomyocytes, endothelium, and macrophages (up to 18 months) in combination with high immune activity. Corticosteroids and anticoagulants should be considered as a treatment option of post‐COVID myoendocarditis.     

Triterpene glycosides from Antarctic sea cucumbers. 1. Structure of liouvillosides A1, A2, A3, B1, and B2 from the sea cucumber Staurocucumis liouvillei: new procedure for separation of highly polar glycoside fractions and taxonomic revision

Five new triterpene glycosides, liouvillosides A1 (1), A2 (2), A3 (3), B1 (4), and B2 (5), have been isolated from the Antarctic sea cucumber Staurocucumis liouviellei along with the known liouvilloside A(6), isolated earlier from the same species, and hemoiedemosides A (7) and B (8), isolated earlier from the Patagonian sea cucumber Hemioedema spectabilis. The isolation was carried out using a new chromatographic procedure including application of ion-pair reversed-phase chromatography followed by chiral chromatography on a cyclodextrin ChiraDex column. The structures of the new glycosides were elucidated using extensive NMR spectroscopy (1H and 13C NMR spectrometry, DEPT, 1H-(1)H COSY, HMBC, HMQC, and NOESY), ESI-FTMS, and CID MS/MS, and chemical transformations. Glycosides 1-3 are disulfated tetraosides and glycosides 4 and 5 are trisulfated tetraosides. Glycosides 2 and 3 contain 3-O-methylquinovose, found for the first time as a natural monosaccharide in sea cucumber glycosides. On the basis of analyses of glycoside structures a taxonomic revision is proposed.     

One intrauterine device lost, two found

During a search for a recently inserted, lost intrauterine device (IUD), a pelvic x-ray found two devices. One of the IUDs had been inserted 9 years earlier and was thought expelled.     

Immunogenicity of two paediatric doses of monovalent hepatitis B or combined hepatitis A and B vaccine in 8-10-year-old children

Hepatitis A and B vaccines are highly immunogenic in three-dose schedules. To obtain an equivalent result in children with two paediatric doses would be of significant benefit. The purpose of this study was to measure the immunogenicity of a two-dose schedule in children with two licensed recombinant HBsAg containing vaccines given at paediatric doses, one of them combined with hepatitis A. Seven-hundred and four healthy school children aged 8-10 years were recruited in an open label study to receive either Twinrix Pediatric (360 El.U HAV antigen; 10 microg HBsAg) or Recombivax (2.5 microg HBsAg) vaccine intramuscularly 6 months apart. The seroconversion (>/=1 mIU/ml for anti-HBs antibodies and >/=33 mIU/ml for anti-HAV antibodies), seroprotection (anti-HBs >/=10 mIU/ml) rates and the geometric mean titers (GMTs) were determined 4-8 weeks after the second dose. The anti-HBs seroconversion rate was 97.1% with Twinrix and 97.2% with Recombivax. The seroprotection rates were 96.5 and 94.4%, respectively (P = 0.17). The GMT was higher with Twinrix than with Recombivax (3248 mIU/ml versus 742 mIU/ml, P < 0.0001). All the children vaccinated with Twinrix seroconverted to HAV and the GMT was 5168 mIU/ml. The obtained results suggest that two paediatric doses of hepatitis vaccines are highly immunogenic in 8-10-year-old children. This schedule could facilitate a greater vaccine acceptance and the addition of hepatitis A vaccine to existing adolescent universal hepatitis B virus immunization programs.     

Combination of endobronchial bronchoscopic debulking and bronchoplastic segmentectomy of an obstructive neuroendocrine tumour: probably the least invasive approach

We report the case of a female patient with an obstructing well-differentiated neuroendocrine tumour in the apical segment of the completely atelectatic right lower lobe. Bronchoscopic debulking of the tumour lead to re-ventilation of the remaining lobe, allowing to perform a lung-sparing bronchoplastic resection of the affected segment by uniportal video-assisted thoracic surgery.     

Secondary biogenic amine deficiencies: genetic etiology,therapeutic interventions,and clinical effects

neurogenetics - Monoamine neurotransmitter disorders present predominantly with neurologic features, including dystonic or dyskinetic cerebral palsy and movement disorders. Genetic conditions that...