Characteristics of cases with poor outcomes of rendering medical care to children in six regions of the Russian Federation

Objective: to determine the characteristics of the outcome of the improper care for children, established during the commission of forensic examinations. Material and Methods. The material of this study was commission a forensic medical examination of the archives department of complex expertise of the Bureaus of Forensic Medicine of Moscow; the Moscow, Penza, Samara and Ulyanovsk regions, and the Republic of Mordovia, conducted from 1996 to 2006. The method of this study was a statistical database processing using Excel software application package. Results. The article presents the results of the analysis of 279 forensic medical examinations conducted by committees in the Bureaus of Forensic Medical Examination of Moscow; the Moscow, Penza, Samara and Ulyanovsk regions, and the Republic of Mordovia from 1996 to 2006. The examinations were conducted in connection with poor outcomes of rendering medical care to children. Conclusion. The number of conducted examinations correlates with the population of the region. The parents of the children affected by poor treatment mostly demand the medical staff to be prosecuted and more often make legal claims to the quality of emergency medical care; dissatisfaction with the quality of medical care is more often expressed by the parents of children under 3 years old. Legal claims are more often made against obstetricians-gynecologists, pediatricians, surgeons, infectious disease specialists and anesthesiologists-resuscitators. If the conclusion of the forensic medical examination committee on the nature of the pathological process coincides with the final clinical diagnosis, the provided medical care often turns out to be adequate; in cases of inadequate medical care the risks of moderate and grievous bodily harm as well as the patient's death are high.</p

Label-free sensitive detection of influenza virus using PZT discs with a synthetic sialylglycopolymer receptor layer

We describe rapid, label-free detection of Influenza A viruses using the first radial mode of oscillations of lead zirconate titanate (PZT) piezoelectric discs with a 2 mm radius and 100 µm thickness fabricated from a piezoelectric membrane. The discs are modified with a synthetic sialylglycopolymer receptor layer, and the coated discs are inserted in a flowing virus suspension. Label-free detection of the virus is achieved by monitoring the disc radial mode resonance frequency shift. Piezo transducers with sialylglycopolymer sensor layers exhibited a long lifetime, a high sensitivity and the possibility of regeneration. We demonstrate positive, label-free detection of Influenza A viruses at concentrations below 105 virus particles per millilitre. We show that label-free, selective, sensitive detection of influenza viruses by home appliances is possible in principle. © 2019 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited

Antifungal Thiazolidines: Synthesis and Biological Evaluation of Mycosidine Congeners

Novel derivatives of Mycosidine (3,5-substituted thiazolidine-2,4-diones) are synthesized by Knoevenagel condensation and reactions of thiazolidines with chloroformates or halo-acetic acid esters. Furthermore, 5-Arylidene-2,4-thiazolidinediones and their 2-thioxo analogs containing halogen and hydroxy groups or di(benzyloxy) substituents in 5-benzylidene moiety are tested for antifungal activity in vitro. Some of the synthesized compounds exhibit high antifungal activity, both fungistatic and fungicidal, and lead to morphological changes in the Candida yeast cell wall. Based on the use of limited proteomic screening and toxicity analysis in mutants, we show that Mycosidine activity is associated with glucose transport. This suggests that this first-in-class antifungal drug has a novel mechanism of action that deserves further study. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Synthesis and Biological Evaluation of PSMA Ligands with Aromatic Residues and Fluorescent Conjugates Based on Them

Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II (GCPII), is a suitable target for specific delivery of antitumor drugs and diagnostic agents due to its overexpression in prostate cancer cells. In the current work, we describe the design, synthesis, and biological evaluation of novel low-molecular PSMA ligands and conjugates with fluorescent dyes FAM-5, SulfoCy5, and SulfoCy7. In vitro evaluation of synthesized PSMA ligands on the activity of PSMA shows that the addition of aromatic amino acids into a linker structure leads to a significant increase in inhibition. The conjugates of the most potent ligand with FAM-5 as well as SulfoCy5 demonstrated high affinities to PSMA-expressing tumor cells in vitro. In vivo biodistribution in 22Rv1 xenografts in Balb/c nude mice of PSMA-SulfoCy5 and PSMA-SulfoCy7 conjugates with a novel PSMA ligand demonstrated good visualization of PSMA-expressing tumors. Also, the conjugate PSMA-SulfoCy7 demonstrated the absence of any explicit toxicity up to 87.9 mg/kg. © 2021 American Chemical Society. All rights reserved

Novel Copper-Containing Cytotoxic Agents Based on 2-Thioxoimidazolones

A series of 73 ligands and 73 of their Cu+2 and Cu+1 copper complexes with different geometries, oxidation states of the metal, and redox activities were synthesized and characterized. The aim of the study was to establish the structure-activity relationship within a series of analogues with different substituents at the N(3) position, which govern the redox potentials of the Cu+2/Cu+1 redox couples, ROS generation ability, and intracellular accumulation. Possible cytotoxicity mechanisms, such as DNA damage, DNA intercalation, telomerase inhibition, and apoptosis induction, have been investigated. ROS formation in MCF-7 cells and three-dimensional (3D) spheroids was proven using the Pt-nanoelectrode. Drug accumulation and ROS formation at 40-60 μm spheroid depths were found to be the key factors for the drug efficacy in the 3D tumor model, governed by the Cu+2/Cu+1 redox potential. A nontoxic in vivo single-dose evaluation for two binuclear mixed-valence Cu+1/Cu+2 redox-active coordination compounds, 72k and 61k, was conducted.

PSMA-targeted small-molecule docetaxel conjugate: Synthesis and preclinical evaluation

Prostate cancer is one of the most commonly diagnosed men's cancers and remains one of the leading causes of cancer death. The development of approaches to the treatment of this oncological disease is an ongoing process. In this work, we have carried out the selection of ligands for the creation of conjugates based on the drug docetaxel and synthesized a series of three docetaxel conjugates. In vitro cytotoxicity of these molecules was evaluated using the MTT assay. Based on the assay results, we selected the conjugate which showed cytotoxic potential close to unmodified docetaxel. At the same time, the molar solubility of the resulting compound increased up to 20 times in comparison with the drug itself. In vivo evaluation on 22Rv1 (PSMA+) xenograft model demonstrated a good potency of the synthesized conjugate to inhibit tumor growth: the inhibition turned out to be more than 80% at a dose of 30 mg/kg. Pharmacokinetic parameters of conjugate distribution were analyzed. Also, it was found that PSMA-targeted docetaxel conjugate is less toxic than docetaxel itself, the decrease of molar acute toxicity in comparison with free docetaxel was up to 20%. Obtained conjugate PSMA-DOC is a good candidate for further expanded preclinical trials because of high antitumor activity, fewer side toxic effects and better solubility. © 2021 Elsevier Masson SA